PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
SEPA
April 2024
United States Office of Chemical Safety and
Environmental Protection Agency Pollution Prevention
Draft Risk Evaluation for
Asbestos Part 2 -
Supplemental Evaluation Including Legacy Uses and
Associated Disposals of Asbestos
Systematic Review of Data Quality Evaluation Information for
Human Health Hazard Epidemiology
CASRN: 1332-21-4
April 2024
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
This supplemental file contains the data quality evaluation results for data sources that met the screening criteria for the Draft
Risk Evaluation for Asbestos Part 2: Supplemental Evaluation Including Legacy Uses and Associated Disposals of Asbestos.
Details regarding the data quality evaluation process implemented are described in the Draft Risk Evaluation for Asbestos Part
2: Supplemental Evaluation Including Legacy Uses and Associated Disposals of Asbestos - Systematic Review Protocol as well
as White Paper: Quantitative Human Health Approach to be Applied in the Risk Evaluation for Asbestos Part 2 - Supplemental
Evaluation including Legacy Uses and Associated Disposals of Asbestos.
As described in Section 4.6.2 of the Draft Risk Evaluation for Asbestos Part 2: Supplemental Evaluation Including Legacy
Uses and Associated Disposals of Asbestos - Systematic Review Protocol and Appendix B of the White Paper: Quantitative
Human Health Approach to be Applied in the Risk Evaluation for Asbestos Part 2 - Supplemental Evaluation including Legacy
Uses and Associated Disposals of Asbestos, additional screening was conducted based on whether the data source used stan-
dardized mortality ratios (SMR) or regression and whether the data source contained dose-response data. Specifically, following
full-text PECO-based screening, for those references that met PECO screening criteria and used SMR or regression, data quality
evaluation was conducted for data sources that received Medium or High metric ratings for Metrics 4 and 5. Data sources that
received either Low or Critically Deficient metric ratings for Metric 4 or Metric 5 did not proceed to data quality evaluation;
the metric ratings and comments for Metrics 4 and 5 are included in this supplemental file.
References that assessed the same cohort were linked and evaluated as a group of references or as multiple subgroups of
references from the same cohort. However, each health outcome assessed in a paper or cohort group of papers was evaluated
independently such that each reference or cohort group of references may have different overall quality determinations (OQD)
for different health outcomes. Additional comments providing a brief summary including strengths and weaknesses of the
study are presented adjacent to the OQD. If a reference also was evaluated for an evidence stream other than epidemiology,
those evaluations will be presented in a separate supplemental file with the Risk Evaluation. U.S. EPA conducted data quality
evaluation based on author-reported descriptions and results (including associated methods papers).
As described in Section 5.5.2 of the Draft Risk Evaluation for Asbestos Part 2: Supplemental Evaluation Including Legacy
Uses and Associated Disposals of Asbestos - Systematic Review Protocol and Appendix B of the White Paper: Quantitative
Human Health Approach to be Applied in the Risk Evaluation for Asbestos Part 2 - Supplemental Evaluation including Legacy
Uses and Associated Disposals of Asbestos, data quality evaluation forms from Asbestos Part 1 were modified to reflect the
change in scope for Asbestos Part 2. For mesothelioma, the mesothelioma data quality evaluation form used in Asbestos
Part 1 was used for Asbestos Part 2, with some modifications based on calibration. For other outcomes, the lung cancer
data quality evaluation form from Asbestos Part 1 was used with additional modifications to evaluate other outcomes that
were not considered in Asbestos Part 1. The Table of Contents lists data sources based on whether the endpoints were either
mesothelioma or other health outcome categories. In some circumstances, although a study assessed both mesothelioma and
other health outcomes, the mesothelioma data were not sufficient to undergo data quality evaluation (e.g., the reference might
not have met PECO screening criteria for mesothelioma), and the rationale for not evaluating mesothelioma is documented in the
"Additional Comments" field. Modifications to the forms are further described under Section 5.5.2 of the Draft Risk Evaluation
for Asbestos Part 2: Supplemental Evaluation Including Legacy Uses and Associated Disposals of Asbestos - Systematic Review
Protocol that accompanies the Draft Risk Evaluation for Asbestos Part 2: Supplemental Evaluation Including Legacy Uses and
Associated Disposals of Asbestos.
Page 2 of 606
-------
16
17
18
21
22
23
24
25
26
27
31
32
33
34
37
38
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Table of Contents
Reference
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. nan
NIOSH(1986): 19861986.
Armstrong, B. K., de Klerk, N. H., Musk, A. W., Hobbs, M. S. (1988). Mortality in miners and millers of crocidolite in Western Australia.
British Journal of Industrial Medicine 45(1988):13-May.
Berry, G., Pooley, F., Gibbs, A., Harris, J., Mcdonald, J. (2009). Lung fiber burden in the Nottingham gas mask cohort. Inhalation
Toxicology 21(2009):168-172.
Brims, F. J. H., Kong, K., Harris, E. J. A., Sodhi-Berry, N., Reid, A., Murray, C. P., Franklin, P. J., Musk, A. B., e Klerk, N. H. (2020).
Pleural plaques and the risk of lung cancer in asbestos-exposed subjects. American Journal of Respiratory and Critical Care Medicine
201(2020):57-62.
Churg, A., Vedal, S. (1994). Fiber burden and patterns of asbestos-related disease in workers with heavy mixed amosite and chrysotile
exposure. American Journal of Respiratory and Critical Care Medicine 150(1994):663-669.
Churg, A., Wright, J. L., Vedal, S. (1993). Fiber burden and patterns of asbestos-related disease in chrysotile miners and millers. American
Review of Respiratory Disease 148(1993):25-31.
Consonni, D., Calvi, C., De Matteis, S., Mirabelli, D., Landi, M. T., Caporaso, N. E., Peters, S., Vermeulen, R., Kromhout, H., Dallari, B.,
Pesatori, A. C., Riboldi, L., Mensi, C. (2019). Peritoneal mesothelioma and asbestos exposure: A population-based case-control study in
Lombardy, Italy. Occupational and Environmental Medicine 76(2019):545-553.
Cookson, W. O., Musk, A. W„ Glancy, J. J„ de Klerk, N. H„ Yin, R„ Mele, R„ Carr, N. G„ Armstrong, B. K„ Hobbs, M. S. (1985).
Compensation, radiographic changes, and survival in applicants for asbestosis compensation. British Journal of Industrial Medicine
42(1985):461-468.
Cuccaro, F., Nannavecchia, A. M., Silvestri, S., Angelini, A., Coviello, V., Bisceglia, L., Magnani, C. (2019). Mortality for mesothelioma
and lung cancer in a cohort of asbestos cement workers in BARI (Italy): Time related aspects of exposure. Journal of Occupational and
Environmental Medicine 61(2019):410-416.
Dawson, A., Gibbs, A. R., Pooley, F. D., Griffiths, D. M., Hoy, J. (1993). Malignant mesothelioma in women. Thorax 48(1993):269-274.
de Klerk, N. H., Armstrong, B. K., Musk, A. W., Hobbs, M. S. T. (1989). Cancer mortality in relation to measures of occupational exposure
to crocidolite at Wittenoom Gorge in Western Australia. British Journal of Industrial Medicine 46(1989):529-536.
de Klerk, N. H., Musk, A. W., Cookson, W. O., Glancy, J. J., Hobbs, M. S. (1993). Radiographic abnormalities and mortality in subjects
with exposure to crocidolite. British Journal of Industrial Medicine 50(1993):902-906.
Dunning, K. K., Adjei, S., Levin, L., Rohs, A. M., Hilbert, T., Borton, E., Kapil, V., Rice, C., Lemasters, G. K., Lockey, J. E. (2012).
Mesothelioma associated with commercial use of vermiculite containing Libby amphibole. Journal of Occupational and Environmental
Medicine 54(2012):1359-1363.
e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence
of digestive cancers and occupational exposure to asbestos. European Journal of Cancer Prevention ll(2002):523-528.
Farioli, A., Straif, K., Brandi, G., Curti, S., Kjaerheim, K., Martinsen, J. I., Sparen, P., Tryggvadottir, L., Weiderpass, E., Biasco, G.
(2018). Occupational exposure to asbestos and risk of cholangiocarcinoma: a population-based case-control study in four Nordic countries.
Occupational and Environmental Medicine 75(2018):191-198.
Ferrante, D., Mirabelli, D., Tunesi, S., Terracini, B., Magnani, C. (2015). Pleural mesothelioma and occupational and non-occupational
asbestos exposure: a case-control study with quantitative risk assessment. Occupational and Environmental Medicine 73(2015):147-153.
Page 3 of 606
-------
42
44
49
50
51
52
57
60
61
65
66
67
68
69
70
72
73
74
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Finkelstein, M. M. (1984). Mortality among employees of an Ontario asbestos-cement factory. American Review of Respiratory Disease
129(1984):754-761.
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of
Industrial Medicine 40(1983): 138-144.
Finkelstein, M. M. (1985). A study of dose-response relationships for asbestos associated disease. British Journal of Industrial Medicine
42(1985):319-325.
Franklin, P., Alfonso, H., Reid, A., Olsen, N., Shilkin, K. B., Brims, F., de Klerk, N., Musk, A. W. (2016). Asbestos exposure and
histological subtype of malignant mesothelioma. Occupational and Environmental Medicine 73(2016):749-752.
Gardner, M. J., Winter, R D., Pannett, B., Powell, C. A. (1986). Follow up study of workers manufacturing chrysotile asbestos cement
products. British Journal of Industrial Medicine 43(1986):726-732.
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015).
Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental
Medicine 73(2015):290-299.
Gilham, C., Rake, C., Hodgson, J., Darnton, A., Burdett, G., Peto Wild, J., Newton, M., Nicholson, A. G., Davidson, L., Shires, M. (2018).
Past and current asbestos exposure and future mesothelioma risks in Britain: The Inhaled Particles Study (TIPS). International Journal of
Epidemiology 47(2018):1745-1756.
Hagmar, L., Akesson, B., Nielsen, J., Andersson, C., Linden, K., Attewell, R., Moller, T. (1990). Mortality and cancer morbidity in
workers exposed to low levels of vinyl chloride monomer at a polyvinyl chloride processing plant. American Journal of Industrial Medicine
17(1990):553-565.
Hansen, J., de Klerk, N. H., Musk, A. W., Hobbs, M. S. T. (1998). Environmental exposure to crocidolite and mesothelioma: Exposure-
response relationships. American Journal of Respiratory and Critical Care Medicine 157(1998):69-75.
Howel, D., Gibbs, A., Arblaster, L., Swinburne, L., Schweiger, M., Renvoize, E., Hatton, P., Pooley, F. (1999). Mineral fibre analysis
and routes of exposure to asbestos in the development of mesothelioma in an English region. Occupational and Environmental Medicine
56(1999):51-58.
Hughes, J. M., Weill, H. (1991). Asbestosis as a precursor of asbestos related lung cancer: Results of a prospective mortality study. British
Journal of Industrial Medicine 48(1991):229-233.
Hughes, J. M., Weill, H., Hammad, Y. Y. (1987). Mortality of workers employed in two asbestos cement manufacturing plants. Occupa-
tional and Environmental Medicine 44(1987):161-174.
Hughes, J. M„ Weill, H„ Hammad, Y. Y. (1987). MORTALITY OF WORKERS EMPLOYED IN 2 ASBESTOS CEMENT MANUFAC-
TURING PLANTS. British Journal of Industrial Medicine 44(1987):161-174.
Iwatsubo, Y., Pairon, J. C., Boutin, C., Menard, O., Massin, N., Caillaud, D., Orlowski, E., Galateau-Salle, F., Bignon, J., Brochard, P.
(1998). Pleural mesothelioma: dose-response relation at low levels of asbestos exposure in a French population-based case-control study.
American Journal of Epidemiology 148(1998):133-142.
Jiang, Z., Xia, H., Wu, W., Chen, R., Morinaga, K., Lou, J., Zhang, X., Chen, T., Chen, J., Ying, S. (2018). Hand-spinning chrysotile
exposure and risk of malignant mesothelioma: A case-control study in Southeastern China. International Journal of Cancer 142(2018):514-
523.
Konen, T., Johnson, J. E., Lindgren, P., Williams, A. (2019). Cancer incidence and mortality associated with non-occupational and low
dose exposure to Libby vermiculite in Minnesota. Environmental Research 175(2019):449-456.
Kurumatani, N., Kumagai, S. (2008). Mapping the risk of mesothelioma due to neighborhood asbestos exposure. American Journal of
Respiratory and Critical Care Medicine 178(2008):624-629.
Lacourt, A., Gramond, C., Rolland, P., Ducamp, S., Audignon, S., Astoul, P., Chamming's, S., Gilg Soit Ilg, A., Rinaldo, M., Raherison,
C., Galateau-Salle, F., Imbernon, E., Pairon, J. C., Goldberg, M., Brochard, P. (2014). Occupational and non-occupational attributable risk
of asbestos exposure for malignant pleural mesothelioma. Thorax 69(2014):532-539.
Page 4 of 606
-------
75
76
80
83
86
87
90
91
92
93
95
98
99
100
101
103
105
109
110
111
114
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Larson, T. C., Antao, V. C., Bove, F. J. (2010). Vermiculite worker mortality: Estimated effects of occupational exposure to Libby
amphibole. Journal of Occupational and Environmental Medicine 52(2010):555-560.
Madkour, M. T., El Bokhary, M. S., Awad Allah, H. I., Awad, A. A., Mahmoud, H. F. (2009). Environmental exposure to asbestos and the
exposure-response relationship with mesothelioma. Eastern Mediterranean Health Journal 15(2009):25-38.
Mcdonald, J. C., Armstrong, B. G., Edwards, C. W., Gibbs, A. R., Lloyd, H. M., Pooley, F. D., Ross, D. J., Rudd, R. M. (2001). Case-
referent survey of young adults with mesothelioma: I. Lung fibre analyses. Annals of Occupational Hygiene 45(2001):513-518.
Mcdonald, J. C., Armstrong, B., Case, B., Doell, D., Mccaughey, W. T., Mcdonald, A. D., Sebastien, P. (1989). Mesothelioma and asbestos
fiber type. Evidence from lung tissue analyses. Cancer 63(1989):1544-1547.
Mcdonald, J. C., Mcdonald, A. D. (1997). Chrysotile, tremolite and carcinogenicity. Annals of Occupational Hygiene 41(1997):699-705.
Mcdonald, J. C., Mcdonald, A. D., Armstrong, B., Sebastien, P. (1986). Cohort study of mortality of vermiculite miners exposed to
tremolite. Occupational and Environmental Medicine 43(1986):436-444.
Menegozzo, S., Comba, P., Ferrante, D., De Santis, M., Gorini, G., Izzo, F., Magnani, C., Pirastu, R., Simonetti, A., Tunesi, S., Menegozzo,
M. (2011). Mortality study in an asbestos cement factory in Naples, Italy. Annali dell'Istituto superiore di sanit" 47(2011):296-304.
Metintas, S., Metintas, M., Ak, G., Kalyoncu, C. (2012). Environmental asbestos exposure in rural Turkey and risk of lung cancer.
International Journal of Environmental Health Research 22(2012):468-479.
Moshammer, H., Neuberger, M. (2009). Lung function predicts survival in a cohort of asbestos cement workers. International Archives of
Occupational and Environmental Health 82(2009):199-207.
Neuberger, M., Kundi, M. (1990). Individual asbestos exposure: Smoking and mortality"a cohort study in the asbestos cement industry.
British Journal of Industrial Medicine 47(1990):615-620.
Nicholson, W. J., Selikoff, I. J., Seidman, H., Lilis, R., Formby, P. (1979). Long-term mortality experience of chrysotile miners and millers
in Thetford Mines, Quebec. Annals of the New York Academy of Sciences, Vol. 330 330(1979):21-Nov.
Nokso-Koivisto, P., Pukkala, E. (1994). Past exposure to asbestos and combustion products and incidence of cancer among Finnish
locomotive drivers. Occupational and Environmental Medicine 51(1994):330-334.
Nuyts, V., Vanhooren, H., Begyn, S., Nackaerts, K., Nemery, B. (2017). Asbestos bodies in bronchoalveolar lavage in the 21st century: a
time-trend analysis in a clinical population. Occupational and Environmental Medicine 74(2017):59-65.
Offermans, N. S., Vermeulen, R., Burdorf, A., Goldbohm, R. A., Kauppinen, T., Kromhout, H., van den Brandt, P. A. (2014). Occupational
asbestos exposure and risk of pleural mesothelioma, lung cancer, and laryngeal cancer in the prospective Netherlands cohort study. Journal
of Occupational and Environmental Medicine 56(2014):19-Jun.
Peto, J. (1980). Lung cancer mortality in relation to measured dust levels in an asbestos textile factory. IARC Scientific Publications
nan(1980):829-836.
Peto, J., Seidman, H., Selikoff, I. J. (1982). Mesothelioma mortality in asbestos workers: implications for models of carcinogenesis and
risk assessment. British Journal of Cancer 45(1982):124-135.
Rogers, A. J., Leigh, J., Berry, G., Ferguson, D. A., Mulder, H. B., Ackad, M. (1991). Relationship between lung asbestos fiber type and
concentration and relative risk of mesothelioma. A case-control study. Cancer 67(1991):1912-1920.
Roggli, V. L., Pratt, P. C., Brody, A. R. (1986). Asbestos content of lung tissue in asbestos associated diseases: a study of 110 cases. British
Journal of Industrial Medicine 43(1986): 18-28.
Roggli, V. L., Vollmer, R. T., Butnor, K. J., Sporn, T. A. (2002). Tremolite and mesothelioma. Annals of Occupational Hygiene
46(2002):447-453.
Rubino, G. F., Piolatto, G., Newhouse, M. L., Scansetti, G., Aresini, G. A., Murray, R. (1979). Mortality of chrysotile asbestos workers at
the Balangero Mine, northern Italy. Occupational and Environmental Medicine 36(1979): 187-194.
Rodelsperger, K., Woitowitz, H. J., Briickel, B., Arhelger, R., Pohlabeln, H., Jockel, K. H. (1999). Dose-response relationship between
amphibole fiber lung burden and mesothelioma. Cancer Detection and Prevention 23(1999):183-193.
Page 5 of 606
-------
117
121
122
123
127
128
129
130
133
134
137
140
142
143
153
154
155
163
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Seidman, H., Selikoff, I. J., Gelb, S. K. (1986). Mortality experience of amosite asbestos factory workers: Dose-response relationships 5
to 40 years after onset of short-term work exposure. American Journal of Industrial Medicine 10(1986):479-514.
Smailyte, G., Kurtinaitis, J., Andersen, A. (2004). Cancer mortality and morbidity among Lithuanian asbestos-cement producing workers.
Scandinavian Journal of Work, Environment and Health 30(2004):64-70.
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study.
Environmental Health Perspectives 115(2007):579-585.
Szeszenia-D^browska, N., Wilczynska, U., Szymczak, W., Strzelecka, A. (2002). Mortality study of workers compensated for asbestosis
in Poland, 1970-1997. International Journal of Occupational Medicine and Environmental Health 15(2002):267-278.
Tuomi, T., Huuskonen, M. S., Virtamo, M., Tossavainen, A., Tammilehto, L., Mattson, K., Lahdensuo, A., Mattila, J., Karhunen, P.,
Liippo, K. (1991). Relative risk of mesothelioma associated with different levels of exposure to asbestos. Scandinavian Journal of Work,
Environment and Health 17(1991):404-408.
Visona, S. D., Capella, S., Bodini, S., Borrelli, P., Villani, S., Crespi, E., Frontini, A., Colosio, C., Belluso, E. (2021). Inorganic Fiber
Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An
SEM-EDS Study on Autoptic Samples. International Journal of Environmental Research and Public Health 18(2021):2053-2053.
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese
chrysotile asbestos textile workers. Lung Cancer 75(2012):151-155.
Abramson, M. J., Murambadoro, T., Alif, S. M., Benke, G. P., Dharmage, S. C., Glaspole, I., Hopkins, P., Hoy, R. F., Klebe, S., Moodley,
Y., Rawson, S., Reynolds, P. N., Wolfe, R., Corte, T. J., Walters, E. H. (2020). Occupational and environmental risk factors for idiopathic
pulmonary fibrosis in Australia: Case-control study. Thorax 75(2020):864-869.
Akkurt, I., Onal, B., Demir, A. U., Tiiziin, D., Sabir, H., Ulusoy, L., Karadag, K. O., Ersoy, N., Coplii, L. (2006). Respiratory health in
Turkish asbestos cement workers: the role of environmental exposure. American Journal of Industrial Medicine 49(2006):609-616.
Albin, M., Johansson, L., Pooley, F. D., Jakobsson, K., Attewell, R., Welinder, H. (1988). Mineral fibres, fibrosis, and asbestos bodies in
lung tissue from deceased asbestos-cement workers. Arhiv za Higijenu Rada i Toksikologiju 39(1988):447-453.
Alexander, B. H., Raleigh, K. K., Johnson, J., Mandel, J. H., Adgate, J. L., Ramachandran, G., Messing, R. B., Eshenaur, T., Williams,
A. (2012). Radiographic evidence of nonoccupational asbestos exposure from processing Libby vermiculite in Minneapolis, Minnesota.
Environmental Health Perspectives 120(2012):44-49.
Alfonso, H. S., Fritschi, L., de Klerk, N. H., Olsen, N., Sleith, J., Musk, A. W. (2004). Effects of asbestos and smoking on the levels and
rates of change of lung function in a crocidolite exposed cohort in Western Australia. Thorax 59(2004): 1052-1056.
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. nan
NIOSH(1986): 19861986.
Andrion, A., Colombo, A., Mollo, F. (1982). Lung asbestos bodies and pleural plaques at autopsy. Ricerca in Clinica e in Laboratorio
12(1982):461-468.
Anttila, S., Karjalainen, A., Taikina-Aho, O., Kyyronen, P., Vainio, H. (1993). Lung cancer in the lower lobe is associated with pulmonary
asbestos fiber count and fiber size. Environmental Health Perspectives 101(1993):166-170.
Arakawa, H., Kishimoto, T., Ashizawa, K., Kato, K., Okamoto, K., Honma, K., Hayashi, S., Akira, M. (2015). Asbestosis and
other pulmonary fibrosis in asbestos-exposed workers: high-resolution CT features with pathological correlations. European Radiology
26(2015): 1485-1492.
Armstrong, B. K., de Klerk, N. H., Musk, A. W., Hobbs, M. S. (1988). Mortality in miners and millers of crocidolite in Western Australia.
British Journal of Industrial Medicine 45(1988):13-May.
Page 6 of 606
-------
166
169
170
173
176
177
178
181
182
183
185
189
190
194
195
201
202
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Bagatin, E., Neder, J. A., Nery, L. E., Terra-Filho, M., Kavakama, J., Castelo, A., Capelozzi, V., Sette, A., Kitamura, S., Favero, M.,
Moreira-Filho, D. C., Tavares, R., Peres, C., Becklake, M. R. (2005). Non-malignant consequences of decreasing asbestos exposure in the
Brazil chrysotile mines and mills. Occupational and Environmental Medicine 62(2005):381-389.
Barbieri, P. G., Consonni, D., Somigliana, A. (2019). Relationship between pleural plaques prevalence and extension and biomarkers of
cumulative asbestos dose. A necropsy study. La Medicina del Lavoro nan(2019):353-362.
Beritic-Stahuljak, D., Valic, F., Zuskin, E. (1991). Relationship between cumulative occupational exposure to asbestos fibres and respiratory
symptoms. Acta Medica Croatica 45(1991):283-295.
Berry, G., Pooley, F., Gibbs, A., Harris, J., Mcdonald, J. (2009). Lung fiber burden in the Nottingham gas mask cohort. Inhalation
Toxicology 21(2009):168-172.
Bourgkard, E., Wild, P., Gonzalez, M., Fevotte, J., Penven, E., Paris, C. (2013). Comparison of exposure assessment methods in a lung
cancer case-control study: performance of a lifelong task-based questionnaire for asbestos and PAHs. Occupational and Environmental
Medicine 70(2013):884-891.
Brims, F. J. H., Kong, K., Harris, E. J. A., Sodhi-Berry, N., Reid, A., Murray, C. P., Franklin, P. J., Musk, A. B., e Klerk, N. H. (2020).
Pleural plaques and the risk of lung cancer in asbestos-exposed subjects. American Journal of Respiratory and Critical Care Medicine
201(2020):57-62.
Brown, D. P., Dement, J. M., Okun, A. (1994). Mortality patterns among female and male chrysotile asbestos textile workers. Journal of
Occupational Medicine 36(1994):882-888.
Carel, R., Boffetta, P., Kauppinen, T., Teschke, K., Andersen, A., Jappinen, P., Pearce, N., Rix, B. A., Bergeret, A., Coggon, D., Persson, B.,
Szadkowska-Stanczyk, I., Kielkowski, D., Henneberger, P., Kishi, R., Facchini, L. A., Sala, M., Colin, D., Kogevinas, M. (2002). Exposure
to asbestos and lung and pleural cancer mortality among pulp and paper industry workers. Journal of Occupational and Environmental
Medicine 44(2002):579-584.
Checkoway, H., Heyer, N. J., Demers, P. A., Gibbs, G. W. (1996). Reanalysis of mortality from lung cancer among diatomaceous
earth industry workers, with consideration of potential confounding by asbestos exposure. Occupational and Environmental Medicine
53(1996):645-647.
Chiazze, L., Jr, Watkins, D. K., Fryar, C., Kozono, J. (1993). A case-control study of malignant and non-malignant respiratory disease
among employees of a fiberglass manufacturing facility II Exposure assessment. Occupational and Environmental Medicine 50(1993):717-
725.
Christensen, K. Y., Kopylev, L. (2012). Localized pleural thickening: smoking and exposure to Libby vermiculite. Journal of Exposure
Science and Environmental Epidemiology 22(2012):320-323.
Churg, A., Vedal, S. (1994). Fiber burden and patterns of asbestos-related disease in workers with heavy mixed amosite and chrysotile
exposure. American Journal of Respiratory and Critical Care Medicine 150(1994):663-669.
Churg, A., Wright, J. L., Vedal, S. (1993). Fiber burden and patterns of asbestos-related disease in chrysotile miners and millers. American
Review of Respiratory Disease 148(1993):25-31.
Clin, B., Thaon, I., Boulanger, M., Brochard, P., Chamming's, S., Gislard, A., Lacourt, A., Luc, A., Ogier, G., Paris, C. (2017). Cancer of
the esophagus and asbestos exposure. American Journal of Industrial Medicine 60(2017):968-975.
Conforti, P. M., Kanarek, M. S., Jackson, L. A., Cooper, R. C., Murchio, J. C. (1981). Asbestos in drinking water and cancer in the San
Francisco Bay area: 1969-1974 incidence. Journal of Clinical Epidemiology 34(1981):211-224.
Cookson, W. O., Musk, A. W„ Glancy, J. J„ de Klerk, N. H„ Yin, R„ Mele, R„ Carr, N. G„ Armstrong, B. K„ Hobbs, M. S. (1985).
Compensation, radiographic changes, and survival in applicants for asbestosis compensation. British Journal of Industrial Medicine
42(1985):461-468.
Cuccaro, F., Nannavecchia, A. M., Silvestri, S., Angelini, A., Coviello, V., Bisceglia, L., Magnani, C. (2019). Mortality for mesothelioma
and lung cancer in a cohort of asbestos cement workers in BARI (Italy): Time related aspects of exposure. Journal of Occupational and
Environmental Medicine 61(2019):410-416.
Page 7 of 606
-------
203
204
205
209
212
213
214
215
217
218
225
233
237
244
251
252
253
254
255
256
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Cullen, M. R., Lopez-Carrillo, L., Alii, B., Pace, P. E., Shalat, S. L., Baloyi, R. S. (1991). Chrysotile asbestos and health in Zimbabwe: II.
Health status survey of active miners and millers. American Journal of Industrial Medicine 19(1991): 171-182.
Cvetanov, V., Karadzinska-Bislimovska, J., Vasevski, J., Ezova, N., Stikova, E. (1988). The relationship between asbestos bodies, serum
immunoglobulin levels and X-ray changes in asbestos workers. Arhiv za Higijenu Rada i Toksikologiju 39(1988):455-460.
Dahlqvist, M., Alexandersson, R., Hedenstierna, G. (1992). Lung function and exposure to asbestos among vehicle mechanics. American
Journal of Industrial Medicine 22(1992):59-68.
Dawson, A., Gibbs, A. R., Pooley, F. D., Griffiths, D. M., Hoy, J. (1993). Malignant mesothelioma in women. Thorax 48(1993):269-274.
de Klerk, N. H., Armstrong, B. K., Musk, A. W., Hobbs, M. S. T. (1989). Cancer mortality in relation to measures of occupational exposure
to crocidolite at Wittenoom Gorge in Western Australia. British Journal of Industrial Medicine 46(1989):529-536.
de Klerk, N. H., Cookson, W. O., Musk, A. W., Armstrong, B. K., Glancy, J. J. (1989). Natural history of pleural thickening after exposure
to crocidolite. British Journal of Industrial Medicine 46(1989):461-467.
de Klerk, N. H., Musk, A. W., Armstrong, B. K., Hobbs, M. S. (1991). Smoking, exposure to crocidolite, and the incidence of lung cancer
and asbestosis. British Journal of Industrial Medicine 48(1991):412-417.
de Klerk, N. H., Musk, A. W., Cookson, W. O., Glancy, J. J., Hobbs, M. S. (1993). Radiographic abnormalities and mortality in subjects
with exposure to crocidolite. British Journal of Industrial Medicine 50(1993):902-906.
de Klerk, N. H., Musk, A. W., Eccles, J. L., Hansen, J., Hobbs, M. S. (1996). Exposure to crocidolite and the incidence of different
histological types of lung cancer. Occupational and Environmental Medicine 53(1996): 157-159.
Dement, J. M. (1980). Estimation of dose and evaluation of dose-response in a retrospective cohort mortality study of chrysotile asbestos
textile workers, nan Doctoral Dissertation(1980):l-259.
Dement, J. M., Harris, R. L., Jr, Symons, M. J., Shy, C. M. (1983). Exposures and mortality among chrysotile asbestos workers: Part II:
Mortality. American Journal of Industrial Medicine 4(1983):421-433.
Deng, Q., Wang, X., Wang, M., Lan, Y. (2012). Exposure-response relationship between chrysotile exposure and mortality from lung
cancer and asbestosis. Occupational and Environmental Medicine 69(2012):81-86.
Dunning, K. K., Adjei, S., Levin, L., Rohs, A. M., Hilbert, T., Borton, E., Kapil, V., Rice, C., Lemasters, G. K., Lockey, J. E. (2012).
Mesothelioma associated with commercial use of vermiculite containing Libby amphibole. Journal of Occupational and Environmental
Medicine 54(2012):1359-1363.
e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence
of digestive cancers and occupational exposure to asbestos. European Journal of Cancer Prevention ll(2002):523-528.
Ehrlich, R., Lilis, R., Chan, E., Nicholson, W. J., Selikoff, I. J. (1992). Long term radiological effects of short term exposure to amosite
asbestos among factory workers. British Journal of Industrial Medicine 49(1992):268-275.
Eisenhawer, C., Felten, M. K., Tamm, M., Das, M., Kraus, T. (2014). Radiological surveillance of formerly asbestos-exposed power
industry workers: rates and risk factors of benign changes on chest X-ray and MDCT. Journal of Occupational Medicine and Toxicology
9(2014):18.
Elci, O. C., Akpinar-Elci, M., Blair, A., Dosemeci, M. (2002). Occupational dust exposure and the risk of laryngeal cancer in Turkey.
Scandinavian Journal of Work, Environment and Health 28(2002):278-284.
Farioli, A., Straif, K., Brandi, G., Curti, S., Kjaerheim, K., Martinsen, J. I., Sparen, P., Tryggvadottir, L., Weiderpass, E., Biasco, G.
(2018). Occupational exposure to asbestos and risk of cholangiocarcinoma: a population-based case-control study in four Nordic countries.
Occupational and Environmental Medicine 75(2018):191-198.
Finkelstein, M. (1986). Pulmonary function in asbestos cement workers: a dose-response study. British Journal of Industrial Medicine
43(1986):406-413.
Finkelstein, M. M. (1997). Radiographic asbestosis is not a prerequisite for asbestos-associated lung cancer in Ontario asbestos-cement
workers. American Journal of Industrial Medicine 32(1997):341-348.
Page 8 of 606
-------
259
263
274
275
276
278
302
303
304
310
317
318
319
322
324
325
327
330
331
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Finkelstein, M. M. (1984). Mortality among employees of an Ontario asbestos-cement factory. American Review of Respiratory Disease
129(1984):754-761.
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of
Industrial Medicine 40(1983): 138-144.
Finkelstein, M. M. (1985). A study of dose-response relationships for asbestos associated disease. British Journal of Industrial Medicine
42(1985):319-325.
Finkelstein, M. M. (1982). Asbestosis in long-term employees of an Ontario asbestos-cement factory. American Review of Respiratory
Disease 125(1982):496-501.
Finkelstein, M. M., Vingilis, J. J. (1984). Radiographic abnormalities among asbestos-cement workers. An exposure-response study.
American Review of Respiratory Disease 129(1984):17-22.
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory
Disease 119(1979):741-753.
Gardner, M. J., Winter, R D., Pannett, B., Powell, C. A. (1986). Follow up study of workers manufacturing chrysotile asbestos cement
products. British Journal of Industrial Medicine 43(1986):726-732.
Gautam, A. K., Yunus, M., Rahman, A., Reddy, S. S. (2003). Environmental monitoring of asbestos products manufacturing units-a case
study. Indian Journal of Environmental Health 45(2003):289-292.
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015).
Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental
Medicine 73(2015):290-299.
Green, F. H. Y., Harley, R., Vallyathan, V., Althouse, R., Fick, G., Dement, J., Mitha, R., Pooley, F. (1997). Exposure and mineralogical
correlates of pulmonary fibrosis in chrysotile asbestos workers. Occupational and Environmental Medicine 54(1997):549-559.
Gustavsson, P., Jakobsson, R., Johansson, H., Lewin, F., Norell, S., Rutkvist, L. E. (1998). Occupational exposures and squamous cell
carcinoma of the oral cavity, pharynx, larynx, and oesophagus: A case-control study in Sweden. Occupational and Environmental Medicine
55(1998):393-400.
Hagmar, L., Akesson, B., Nielsen, J., Andersson, C., Linden, K., Attewell, R., Moller, T. (1990). Mortality and cancer morbidity in
workers exposed to low levels of vinyl chloride monomer at a polyvinyl chloride processing plant. American Journal of Industrial Medicine
17(1990):553-565.
Hall, A., Kromhout, H., Schiiz, J., Peters, S., Portengen, L., Vermeulen, R., Agudo, A., Ahrens, W., Boffetta, P., Brennan, P. (2020). Laryn-
geal cancer risks in workers exposed to lung carcinogens: Exposure-effect analyses using a quantitative job exposure matrix. Epidemiology
31(2020):145-154.
Hansen, J., de Klerk, N. H., Musk, A. W., Hobbs, M. S. T. (1998). Environmental exposure to crocidolite and mesothelioma: Exposure-
response relationships. American Journal of Respiratory and Critical Care Medicine 157(1998):69-75.
Haque, A. K., Vrazel, D. M., Burau, K. D., Cooper, S. P., Downs, T. (1996). Is there transplacental transfer of asbestos? A study of 40
stillborn infants. Pediatric Pathology & Laboratory Medicine 16(1996):877-892.
Harless, K. W., Watanabe, S., Renzetti, A. D., Jr (1978). The acute effects of chrysotile asbestos exposure on lung function. Environmental
Research 16(1978):360-372.
Henderson, V. L., Enterline, P. E. (1979). Asbestos exposure: Factors associated with excess cancer and respiratory disease mortality.
Annals of the New York Academy of Sciences 330(1979): 117-126.
Hirsch, A., Di Menza, L., Dorbon, F., Carre, A., Bignon, J. (1980). Diaphragmatic straightness in 302 asbestos-exposed patients. IARC
Scientific Publications no. 30 nan(1980):523-526.
Howe, H. L., Wolfgang, P. E., Burnett, W. S., Nasca, P. C., Youngblood, L. (1989). Cancer incidence following exposure to drinking water
with asbestos leachate. Public Health Reports 104(1989):251-256.
Page 9 of 606
-------
332
336
339
344
348
350
351
352
353
354
355
356
363
364
366
367
368
374
375
378
379
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Huang, J. Q. (1990). A study on the dose-response relationship between asbestos exposure level and asbestosis among workers in a Chinese
chrysotile product factory. Biomedical and Environmental Sciences 3(1990):90-98.
Hughes, J. M., Weill, H. (1991). Asbestosis as a precursor of asbestos related lung cancer: Results of a prospective mortality study. British
Journal of Industrial Medicine 48(1991):229-233.
Hughes, J. M., Weill, H., Hammad, Y. Y. (1987). Mortality of workers employed in two asbestos cement manufacturing plants. Occupa-
tional and Environmental Medicine 44(1987):161-174.
Hughes, J. M„ Weill, H„ Hammad, Y. Y. (1987). MORTALITY OF WORKERS EMPLOYED IN 2 ASBESTOS CEMENT MANUFAC-
TURING PLANTS. British Journal of Industrial Medicine 44(1987):161-174.
liar, A., Klareskog, L., Saevarsdottir, S., Wiebert, P., Askling, J., Gustavsson, P., Alfredsson, L. (2019). Occupational exposure to asbestos
and silica and risk of developing rheumatoid arthritis: findings from a Swedish population-based case-control study, nan 5(2019):e000978.
Johnson, W. M., Lemen, R. A., Hurst, G. A., Spiegel, R. M., Liu, F. H. (1982). Respiratory morbidity among workers in an amosite
asbestos insulation plant. Journal of Occupational Medicine 24(1982):994-999.
Jarvholm, B., Larsson, S., Hagberg, S., Oiling, S., Ryd, W., Toren, K. (1993). Quantitative importance of asbestos as a cause of lung cancer
in a Swedish industrial city: A case-referent study. European Respiratory Journal 6(1993):1271-1275.
Karjalainen, A., Anttila, S., Vanhala, E., Vainio, H. (1994). Asbestos exposure and the risk of lung cancer in a general urban population.
Scandinavian Journal of Work, Environment and Health 20(1994):243-250.
Karjalainen, A., Karhunen, P. J., Lalu, K., Penttila, A., Vanhala, E., Kyyronen, P., Tossavainen, A. (1994). Pleural plaques and exposure to
mineral fibres in a male urban necropsy population. Occupational and Environmental Medicine 51(1994):456-460.
Kishimoto, T., Gemba, K., Fujimoto, N., Onishi, K., Usami, I., Mizuhashi, K., Kimura, K. (2010). Clinical study of asbestos-related lung
cancer in Japan with special reference to occupational history. Cancer Science 101 (2010): 1194-1198.
Kishimoto, T., Ono, T., Okada, K., Ito, H. (1989). Relationship between number of asbestos bodies in autopsy lung and pleural plaques on
chest X-ray film. Chest 95(1989):549-552.
Knox, J. F., Holmes, S., Doll, R., Hill, I. D. (1968). Mortality from lung cancer and other causes among workers in an asbestos textile
factory. Occupational and Environmental Medicine 25(1968):293-303.
Konen, T., Johnson, J. E., Lindgren, P., Williams, A. (2019). Cancer incidence and mortality associated with non-occupational and low
dose exposure to Libby vermiculite in Minnesota. Environmental Research 175(2019):449-456.
Kumagai, S., Kurumatani, N., Tsuda, T., Yorifuji, T., Suzuki, E. (2010). Increased risk of lung cancer mortality among residents near an
asbestos product manufacturing plant. International Journal of Occupational and Environmental Health 16(2010):268-278.
Lacquet, L. M., van der Linden, L., Lepoutre, J. (1980). Roentgenographic lung changes, asbestosis and mortality in a Belgian asbestos-
cement factory. IARC Scientific Publications -30(1980):783-793.
Larson, T. C., Antao, V. C., Bove, F. J. (2010). Vermiculite worker mortality: Estimated effects of occupational exposure to Libby
amphibole. Journal of Occupational and Environmental Medicine 52(2010):555-560.
Larson, T. C., Antao, V. C., Bove, F. J., Cusack, C. (2012). Association between cumulative fiber exposure and respiratory outcomes among
Libby vermiculite workers. Journal of Occupational and Environmental Medicine 54(2012):56-63.
Larson, T., Meyer, C., Kapil, V., Gurney, J., Tarver, R., Black, C., Lockey, J. (2010). Workers with Libby amphibole exposure: retrospective
identification and progression of radiographic changes. Radiology 255(2010):924-933.
Liddell, F. D., Gibbs, G. W., Mcdonald, J. C. (1982). Radiological changes and fibre exposure in chrysotile workers aged 60-69 years at
Thetford Mines. Annals of Occupational Hygiene 26(1982):889-898.
Liddell, F. D., Thomas, D. C., Gibbs, G. W., McDonald, J. C. (1984). Fibre exposure and mortality from pneumoconiosis, respiratory and
abdominal malignancies in chrysotile production in Quebec, 1926-75. Annals of the Academy of Medicine, Singapore 13(1984):340-344.
Lin, S., Wang, X., Yu, I. T., Yano, E., Courtice, M., Qiu, H., Wang, M. (2012). Cause-specific mortality in relation to chrysotile-asbestos
exposure in a Chinese cohort. Journal of Thoracic Oncology 7(2012): 1109-1114.
Page 10 of 606
-------
381
384
387
392
396
397
400
401
402
406
409
410
411
419
422
424
428
435
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Lockey, J. E., Brooks, S. M., Jarabek, A. M., Khoury, P. R., Mckay, R. T., Carson, A., Morrison, J. A., Wiot, J. F., Spitz, H. B.
(1984). Pulmonary changes after exposure to vermiculite contaminated with fibrous tremolite. American Review of Respiratory Disease
129(1984):952-958.
Loomis, D., Dement, J. M., Elliott, L., Richardson, D., Kuempel, E. D., Stayner, L. (2012). Increased lung cancer mortality among
chrysotile asbestos textile workers is more strongly associated with exposure to long thin fibres. Occupational and Environmental Medicine
69(2012):564-568.
Loomis, D., Richardson, D. B., Elliott, L. (2019). Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality.
American Journal of Industrial Medicine 62(2019):471-477.
Luberto, F., Ferrante, D., Silvestri, S., Angelini, A., Cuccaro, F., Nannavecchia, A. M., Oddone, E., Vicentini, M., Barone-Adesi, F., Cena,
T. (2019). Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts
in Italy. Environmental Health: A Global Access Science Source 18(2019):71.
Matrat, M., Guida, F., Cenee, S., Fevotte, J., Carton, M., Cyr, D., Menvielle, G., Paget-Bailly, S., Rado{
i}, L., Schmaus, A., Bara, S., Velten, M., Luce, D., Stiicker, I., The Icare Study Group, I. (2015). Occupational Exposure to Diesel Motor
Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study. Journal of
Cancer Epidemiology 2015(2015):879302.
Matrat, M., Pairon, J. C., Paolillo, A. G., Joly, N., Iwatsubo, Y., Orlowski, E., Letourneux, M., Ameille, J. (2004). Asbestos exposure and
radiological abnormalities among maintenance and custodian workers in buildings with friable asbestos-containing materials. International
Archives of Occupational and Environmental Health 77(2004):307-312.
McCredie, M., Stewart, J. H. (1993). Risk factors for kidney cancer in New South Wales. IV. Occupation. British Journal of Industrial
Medicine 50(1993):349-354.
Mcdonald, J. C., Mcdonald, A. D. (1997). Chrysotile, tremolite and carcinogenicity. Annals of Occupational Hygiene 41(1997):699-705.
Mcdonald, J. C., Mcdonald, A. D., Armstrong, B., Sebastien, P. (1986). Cohort study of mortality of vermiculite miners exposed to
tremolite. Occupational and Environmental Medicine 43(1986):436-444.
Mcdonald, J. C., Mcdonald, A. D., Sebastien, P., Moy, K. (1988). Health of vermiculite miners exposed to trace amounts of fibrous
tremolite. Occupational and Environmental Medicine 45(1988):630-634.
Mcdonald, J. C., Sebastien, P., Armstrong, B. (1986). Radiological survey of past and present vermiculite miners exposed to tremolite.
British Journal of Industrial Medicine 43(1986):445-449.
Mcelvenny, D. M., van Tongeren, M., Turner, M. C., Benke, G., Figuerola, J., Fleming, S., Hours, M., Kind, L., Krewski, D., Mclean, D.,
Parent, M. £., Richardson, L., Schlehofer, B., Schlaefer, K., Sadetzki, S., Schiiz, J., Siemiatycki, J., Cardis, E. (2018). The INTEROCC
case-control study: risk of meningioma and occupational exposure to selected combustion products, dusts and other chemical agents.
Occupational and Environmental Medicine 75(2018):22-Dec.
Menegozzo, S., Comba, P., Ferrante, D., De Santis, M., Gorini, G., Izzo, F., Magnani, C., Pirastu, R., Simonetti, A., Tunesi, S., Menegozzo,
M. (2011). Mortality study in an asbestos cement factory in Naples, Italy. Annali dellTstituto superiore di sanit" 47(2011):296-304.
Metintas, M., Metintas, S., Hillerdal, G., Ucgun, I., Erginel, S., Alatas, F., Yildirim, H. (2005). Nonmalignant pleural lesions due to
environmental exposure to asbestos: a field-based, cross-sectional study. European Respiratory Journal 26(2005):875-880.
Metintas, S., Metintas, M., Ak, G., Kalyoncu, C. (2012). Environmental asbestos exposure in rural Turkey and risk of lung cancer.
International Journal of Environmental Health Research 22(2012):468-479.
Mitchell, C. A., Charney, M., Schoenberg, J. B. (1978). Early lung disease in asbestos-product workers. Lung 154(1978):261-272.
Moshammer, H., Neuberger, M. (2009). Lung function predicts survival in a cohort of asbestos cement workers. International Archives of
Occupational and Environmental Health 82(2009):199-207.
Murai, Y., Kitagawa, M., Hiraoka, T. (1997). Fiber analysis in lungs of residents of a Japanese town with endemic pleural plaques. Archives
of Environmental Health 52(1997):263-269.
Page 11 of 606
-------
436
441
442
444
445
451
452
453
454
455
457
459
460
461
463
466
467
468
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Murphy, R. L. H., Ferris, B. G., Jr, Burgess, W. A., Worcester, J., Gaensler, E. A. (1971). Effects of low concentrations of asbestos: clinical,
environmental, radiologic and epidemiologic observations in shipyard pipe coverers and controls. New England Journal of Medicine
285(1971): 1271-1278.
Mandi, A., Posgay, M., Vadasz, P., Major, K., Rodelsperger, K., Tossavainen, A., Ungvary, G., Woitowitz, H. J., Galambos, E., Nemeth,
L., Soltesz, I., Egervary, M., Boszormenyi Nagy, G. (2000). Role of occupational asbestos exposure in Hungarian lung cancer patients.
International Archives of Occupational and Environmental Health 73(2000):555-560.
Neuberger, M., Kundi, M. (1990). Individual asbestos exposure: Smoking and mortality"a cohort study in the asbestos cement industry.
British Journal of Industrial Medicine 47(1990):615-620.
Newhouse, M. L., Sullivan, K. R. (1989). A mortality study of workers manufacturing friction materials: 1941-86. British Journal of
Industrial Medicine 46(1989): 176-179.
Nicholson, W. J., Selikoff, I. J., Seidman, H., Lilis, R., Formby, P. (1979). Long-term mortality experience of chrysotile miners and millers
in Thetford Mines, Quebec. Annals of the New York Academy of Sciences, Vol. 330 330(1979):21-Nov.
Nokso-Koivisto, P., Pukkala, E. (1994). Past exposure to asbestos and combustion products and incidence of cancer among Finnish
locomotive drivers. Occupational and Environmental Medicine 51(1994):330-334.
Nuyts, V., Vanhooren, H., Begyn, S., Nackaerts, K., Nemery, B. (2017). Asbestos bodies in bronchoalveolar lavage in the 21st century: a
time-trend analysis in a clinical population. Occupational and Environmental Medicine 74(2017):59-65.
Nyberg, F., Gustavsson, P., Jarup, L., Bellander, T., Berglind, N., Jakobsson, R., Pershagen, G. (2000). Urban air pollution and lung cancer
in Stockholm. Epidemiology ll(2000):487-495.
Offermans, N. S. M., Vermeulen, R., Burdorf, A., Goldbohm, R. A., Keszei, A. P., Peters, S., Kauppinen, T., Kromhout, H., van Den
Brandt, P. A. (2014). Occupational asbestos exposure and risk of oral cavity and pharyngeal cancer in the prospective Netherlands Cohort
Study. Scandinavian Journal of Work, Environment and Health 40(2014):420-427.
Offermans, N. S., Vermeulen, R., Burdorf, A., Goldbohm, R. A., Kauppinen, T., Kromhout, H., van den Brandt, P. A. (2014). Occupational
asbestos exposure and risk of pleural mesothelioma, lung cancer, and laryngeal cancer in the prospective Netherlands cohort study. Journal
of Occupational and Environmental Medicine 56(2014):19-Jun.
Ohlson, C. G., Bodin, L., Rydman, T., Hogstedt, C. (1985). Ventilatory decrements in former asbestos cement workers: a four year follow
up. British Journal of Industrial Medicine 42(1985):612-616.
Ohlson, C. G., Hogstedt, C. (1985). Lung cancer among asbestos cement workers. A Swedish cohort study and a review. British Journal
of Industrial Medicine 42(1985):397-402.
Ohlson, C. G., Klaesson, B., Hogstedt, C. (1984). Mortality among asbestos-exposed workers in arailroad workshop. Scandinavian Journal
of Work, Environment and Health 10(1984):283-291.
Ohlson, C. G., Rydman, T., Sundell, L., Bodin, L., Hogstedt, C. (1984). Decreased lung function in long-term asbestos cement workers: a
cross-sectional study. American Journal of Industrial Medicine 5(1984):359-366.
Paris, C., Benichou, J., Raffaelli, C., Genevois, A., Fournier, L., Menard, G., Broessel, N., Ameille, J., Brochard, P., Gillon, J. C. (2004).
Factors associated with early-stage pulmonary fibrosis as determined by high-resolution computed tomography among persons occupation-
ally exposed to asbestos. Scandinavian Journal of Work, Environment and Health 30(2004):206-214.
Paris, C., Martin, A., Letourneux, M., Wild, P. (2008). Modelling prevalence and incidence of fibrosis and pleural plaques in asbestos-
exposed populations for screening and follow-up: a cross-sectional study. Environmental Health: A Global Access Science Source
7(2008):30.
Pearce, N. (1988). Multistage modelling of lung cancer mortality in asbestos textile workers. International Journal of Epidemiology
17(1988):747-752.
Pesch, B., Taeger, D., Johnen, G., Gross, I. M., Weber, D. G., Gube, M., Miiller-Lux, A., Heinze, E., Wiethege, T., Neumann, V., Tannapfel,
A., Raithel, H. J., Briining, T., Kraus, T. (2010). Cancer mortality in a surveillance cohort of German males formerly exposed to asbestos.
International Journal of Hygiene and Environmental Health 213(2010):44-51.
Page 12 of 606
-------
469
472
500
501
505
512
514
515
516
519
522
523
527
532
536
537
538
540
541
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Peto, J. (1980). Lung cancer mortality in relation to measured dust levels in an asbestos textile factory. IARC Scientific Publications
nan(1980):829-836.
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos
miners in Balangero, northern Italy. British Journal of Industrial Medicine 47(1990):810-814.
Pira, E., Turbiglio, M., Maroni, M., Carrer, P., La Vecchia, C., Negri, E., Iachetta, R. (1999). Mortality among workers in the geothermal
power plants at Larderello, Italy. American Journal of Industrial Medicine 35(1999):536-539.
Plato, N., Tornling, G., Hogstedt, C., Krantz, S. (1995). An index of past asbestos exposure as applied to car and bus mechanics. Annals of
Occupational Hygiene 39(1995):441-454.
Polissar, L., Severson, R. K., Boatman, E. S. (1984). A case-control study of asbestos in drinking water and cancer risk. American Journal
of Epidemiology 119(1984):456-471.
Polissar, L., Severson, R. K., Boatman, E. S., Thomas, D. B. (1982). Cancer incidence in relation to asbestos in drinking water in the Puget
Sound region. American Journal of Epidemiology 116(1982):314-328.
Raffn, E., Villadsen, E., Engholm, G., Lynge, E. (1996). Lung cancer in asbestos cement workers in Denmark. Occupational and Environ-
mental Medicine 53(1996):399-402.
Raffn, E., Villadsen, E., Lynge, E. (1996). Colorectal cancer in asbestos cement workers in Denmark. American Journal of Industrial
Medicine 30(1996):267-272.
Richardson, D. B. (2009). Lung cancer in chrysotile asbestos workers: Analyses based on the two-stage clonal expansion model. Cancer
Causes and Control 20(2009):917-923.
Rodriguez-Roisin, R., Picado, C., Roca, J., Arrigo, S., Agusti-Vidal, A. (1986). Early lung function changes after short heavy exposure to
chrysotile asbestos in non-smoking women. Bulletin Europe"en de Physiopathologie Respiratoire 22(1986):225-229.
Roggli, V. L., Pratt, P. C., Brody, A. R. (1986). Asbestos content of lung tissue in asbestos associated diseases: a study of 110 cases. British
Journal of Industrial Medicine 43(1986): 18-28.
Rohs, A., Lockey, J., Dunning, K., Shukla, R., Fan, H., Hilbert, T., Borton, E., Wiot, J., Meyer, C., Shipley, R., Lemasters, G., Kapil,
V. (2008). Low-level fiber-induced radiographic changes caused by Libby vermiculite: a 25-year follow-up study. American Journal of
Respiratory and Critical Care Medicine 177(2008):630-637.
Rubino, G. F., Piolatto, G., Newhouse, M. L., Scansetti, G., Aresini, G. A., Murray, R. (1979). Mortality of chrysotile asbestos workers at
the Balangero Mine, northern Italy. Occupational and Environmental Medicine 36(1979): 187-194.
Ryan, P. H., Rice, C. H., Lockey, J. E., Black, B., Burkle, J., Hilbert, T. J., Levin, L., Cole, B., Mckay, R., Wolfe, C., Lemasters, G. K.
(2017). Childhood exposure to Libby amphibole asbestos and respiratory health in young adults. Environmental Research 158(2017):470-
479.
Santibanez, M., Vioque, J., Alguacil, J., Barber, X., de la Hera, G., Kauppinen, T. (2008). Occupational exposures and risk of oesophageal
cancer by histological type: a case-control study in eastern Spain. Occupational and Environmental Medicine 65(2008):774-781.
Santiba{
n}ez, M., Alguacil, J., de La Hera, M. G., Navarrete-Mu{
n}oz, E. M., Llorca, J., Aragones, N., Kauppinen, T., Vioque, J., PANESOES Study Group (2012). Occupational exposures and risk of
stomach cancer by histological type. Occupational and Environmental Medicine 69(2012):268-275.
Satta, G., Serra, T., Meloni, F., Lazzarato, A., Argiolas, A., Bosu, E., Coratza, A., Frau, N., Lai, M., Lecca, L. I., Mascia, N., Pilia, I., Piras,
V., Sferlazzo, G., Campagna, M., Cocco, P. (2019). Pulmonary Function and CT Scan Imaging at Low-Level Occupational Exposureto
Asbestos. International Journal of Environmental Research and Public Health 17(2019):50.
Schikowsky, C., Felten, M. K., Eisenhawer, C., Das, M., Kraus, T. (2017). Lung function not affected by asbestos exposure in workers
with normal Computed Tomography scan. American Journal of Industrial Medicine 60(2017):422-431.
Schnatter, A. R., Nicolich, M. J., Lewis, R. J., Thompson, F. L., Dineen, H. K., Drummond, I., Dahlman, D., Katz, A. M., Theriault, G.
(2012). Lung cancer incidence in Canadian petroleum workers. Occupational and Environmental Medicine 69(2012):877-882.
Page 13 of 606
-------
542
543
549
550
557
559
560
561
562
563
566
573
574
575
576
579
580
581
584
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Table of Contents
Seidler, A., Becker, N., Nieters, A., Arhelger, R., Mester, B., Rossnagel, K., Deeg, E., Eisner, G., Melis, M., Sesler, S., Avataneo, G.,
Meloni, M., Cocco, P. (2010). Asbestos exposure and malignant lymphoma: a multicenter case-control study in Germany and Italy.
International Archives of Occupational and Environmental Health 83(2010):563-570.
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Seidman, H., Selikoff, I. J., Gelb, S. K. (1986). Mortality experience of amosite asbestos factory workers: Dose-response relationships 5
to 40 years after onset of short-term work exposure. American Journal of Industrial Medicine 10(1986):479-514.
Seidman, H., Selikoff, I. J., Hammond, E. C. (1979). Short-term asbestos work exposure and long-term observation. Annals of the New
York Academy of Sciences 330(1979):61-89.
Selden, A. I., Berg, N. P., Lundgren, E. A., Hillerdal, G., Wik, N. G., Ohlson, C. G., Bodin, L. S. (2001). Exposure to tremolite asbestos
and respiratory health in Swedish dolomite workers. Occupational and Environmental Medicine 58(2001):670-677.
Sichletidis, L., Chloros, D., Spyratos, D., Haidich, A. B., Fourkiotou, I., Kakoura, M., Patakas, D. (2009). Mortality from occupational
exposure to relatively pure chrysotile: A 39-year study. Respiration 78(2009):63-68.
Sluis-Cremer, G. K., Hnizdo, E. (1989). Progression of irregular opacities in asbestos miners. British Journal of Industrial Medicine
46(1989):846-852.
Sluis-Cremer, G. K., Hnizdo, E., u Toit, R. S. J. (1990). Evidence for an amphibole asbestos threshold exposure for asbestosis assessed by
autopsy in South African asbestos miners. Annals of Occupational Hygiene 34(1990):443-451.
Smailyte, G., Kurtinaitis, J., Andersen, A. (2004). Cancer mortality and morbidity among Lithuanian asbestos-cement producing workers.
Scandinavian Journal of Work, Environment and Health 30(2004):64-70.
Soldan, K., Pooley, F. D., Hansen, J., Andersen, A., Chang-Claude, J., Ferro, G., Ohgaki, H., Skov, B. G., Cherrie, J. W., Saracci, R.,
Boffetta, P. (2006). Lung fibre burden in lung cancer cases employed in the rock and slag wool industry. Annals of Occupational Hygiene
50(2006):241-248.
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study.
Environmental Health Perspectives 115(2007):579-585.
Suraya, A., Nowak, D., Sulistomo, A. W., Ghanie Icksan, A., Syahruddin, E., Berger, U., Bose-O'Reilly, S. (2020). Asbestos-Related
Lung Cancer: A Hospital-Based Case-Control Study in Indonesia. International Journal of Environmental Research and Public Health
17(2020):591-591.
Szeszenia-D^browska, N., Wilczynska, U., Szymczak, W., Strzelecka, A. (2002). Mortality study of workers compensated for asbestosis
in Poland, 1970-1997. International Journal of Occupational Medicine and Environmental Health 15(2002):267-278.
Tamura, M., Okamoto, Y., Tokuyama, T., Yoneda, T., Kasuga, H., Miyazaki, R., Narita, N. (1998). Correlation of total amount of exposure
and dust concentration at first exposure to chest X-P course findings in asbestos plant employees. International Congress Series, vol. 1153
nan(1998):653-657.
Terra-Filho, M., Bagatin, E., Nery, L. E., Napolis, L. M., Neder, J. A., de Souza Portes Meirelles, G., Silva, C. I., Muller, N. L. (2015).
Screening of miners and millers at decreasing levels of asbestos exposure: comparison of chest radiography and thin-section computed
tomography. PLoS ONE 10(2015):e0118585.
van Cleemput, J., de Raeve, H., Verschakelen, J. A., Rombouts, J., Lacquet, L. M., Nemery, B. (2001). Surface of localized pleural plaques
quantitated by computed tomography scanning: No relation with cumulative asbestos exposure and no effect on lung function. American
Journal of Respiratory and Critical Care Medicine 163(2001):705-710.
Vathesatogkit, P., Harkin, T. J., Addrizzo-Harris, D. J., Bodkin, M., Crane, M., Rom, W. N. (2004). Clinical correlation of asbestos bodies
in BAL fluid. Chest 126(2004):966-971.
W. R. Grace & Co., (1988). Health of vermiculite miners exposed to trace amounts of fibrous tremolite with cover letter dated 022988.
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese
chrysotile asbestos textile workers. Lung Cancer 75(2012):151-155.
Page 14 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Table of Contents
2572504
730085
263
677716
626626
3080569
Wang, X., Lin, S., Yano, E., Qiu, H., Yu, I. T., Tse, L., Lan, Y., Wang, M. (2012). Mortality in a Chinese chrysotile miner cohort.
International Archives of Occupational and Environmental Health 85(2012):405-412.
Weiderpass, E., Pukkala, E., Kauppinen, T., Mutanen, P., Paakkulainen, H., Vasama-Neuvonen, K., Boffetta, P., Partanen, T. (1999). Breast
cancer and occupational exposures in women in Finland. American Journal of Industrial Medicine 36(1999):48-53.
Weill, H., Hughes, J., Waggenspack, C. (1979). Influence of dose and fiber type on respiratory malignancy risk in asbestos cement
manufacturing. American Review of Respiratory Disease 120(1979):345-354.
Wigle, D. T., Mao, Y., Semenciw, R., Smith, M. H., Toft, P. (1986). Contaminants in drinking water and cancer risks in Canadian cities.
Canadian Journal of Public Health 77(1986):335-342.
Wortley, P., Vaughan, T. L., Davis, S., Morgan, M. S., Thomas, D. B. (1992). A case-control study of occupational risk factors for laryngeal
cancer. British Journal of Industrial Medicine 49(1992):837-844.
Yano, E., Wang, Z. M., Wang, X. R., Wang, M. Z., Lan, Y. J. (2001). Cancer mortality among workers exposed to amphibole-free chrysotile
asbestos. American Journal of Epidemiology 154(2001):538-543.
599
600
601
604
605
606
Page 15 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3100838 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. NIOSH(1986):19861986.
Mesothelioma
Lung/Respiratory: mesothelioma; Cancer/Carcinogenesis: mesothelioma
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
3100838, 29839, 759132, 783513
3100838
Domain
Metric
Rating
Comments
Additional Comments:
None of the studies included in this cohort evaluated mesothelioma in a way that is appropriate for full evaluation (no SMRs or regression analyses)
(Amandus, 1986, 3100838; Amandus & Wheeler, 1987, 29839; Amandus et al., 1988, 783513). For Amandus & Wheeler, the authors describe that
there were two cases of mesothelioma observed, and they provided information on tenure, general exposure levels, and proportional mortality rate (1987,
29839).For Amandus et al., the authors only note the number of mesothelioma diagnoses indicated on death certificates, with no mortality rates or SMRs/
regressions (1988, 783513).For the Amandus study, the author provides some details about tenure, latency, and the number of cases of mesothelioma
detected. Proportional mortality rates are also reported (1986, 3100838).
* No biomarkers were identified for this evaluation.
Page 16 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083076 Table: 1 of 1
Armstrong, B. K., de Klerk, N. H., Musk, A. W., Hobbs, M. S. (1988). Mortality in miners and millers of crocidolite in Western Australia. British Journal
of Industrial Medicine 45(1988):13-May.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality; Mortality: Mesothelioma mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4
3083076, 6874474
3083076
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Dust concentration measurements were taken periodically at the mine and mill. A ko-
niometer, which is a device used to estimate the amount of dust in the air, was utilized
between 1948 and 1958. This only measured total dust per cubic centimeter (ppcc), and
it had an upper limit of 1,000 ppcc. This limit was often exceeded. A survey was under-
taken to determine the concentration of airborne crocidolite fibers greater than 5 microns
in length in 1966. A Casella long running thermal precipitator was used to generate the
data. A Casella gravimetric dust sampler and a Hexhelt were also used to estimate dust
mass. No impingers or PCM/TEM were utilized in this study.This metric is rated low
because the studies or any cited methods source does not explicitly mention the use of
PCM or TEM (Armstrong et al„ 1988, 3083076; Reid et al„ 2018, 6874474).
Medium The figure included in the Armstrong et al., 1988, (HERO ID: 3083076) paper displays
mesothelioma mortality amongst the miners and millers at various exposure levels.
They are split into groups as follows: <10 f/cc y, 10-100 f/cc y, and >100 f/cc y. They
also include all exposures combined, which includes unknown exposures.The levels of
exposure in the Reid et al. 2018 (HERO ID: 6874474) paper included <10 f/mL years,
10-50 f/mL years, and >50. These values allow for the development of an exposure-
response estimate.
Additional Comments: NOTE: This cohort was rated "Low" for Metric 4, and thus does not meet the criteria for usefulness for dose-response. Only outcome inventory, fiber types,
and Metrics 4 and 5 received a full QC.There are some concerns about the methods used to analyze mesothelioma outcomes. 32 mesothelioma deaths were
reported in this study, but there was no SMRs or associated confidence intervals reported. They did mention that there was a statistically significant excess
of mesothelioma deaths, but there is no information from the analysis to further support this.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 17 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709467 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Berry, G., Pooley, F., Gibbs, A., Harris, J., Mcdonald, J. (2009). Lung fiber burden in the Nottingham gas mask cohort. Inhalation Toxicology 21(2009): 168-
172.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma-pleural, Mesothelioma-peritoneal; Mortality: Mesothelioma-pleural, Mesothelioma-peritoneal; Lung/Respiratory:
Mesothelioma-pleural
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
709467
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Key elements of study design were reported in this retrospective case study of a subset
of the original Nottingham Gas Mask Cohort of n=l,154 mostly female employees who
assembled military gas masks, 1940-1945, using filter pads containing 20% crocidolite
asbestos. Within this cohort, a subset was selected of those with tissue samples. Lung
tissue samples were obtained from 50 (77% ) of the n=65 cases of mesothelioma, (and
n=20 deaths from other causes). Duration of employment was recorded in only 51 of the
70 deaths.
Medium Exclusions of subjects from the original cohort or analyses were adequately de-
scribed for the cases (n=70) with lung tissue samples selected out of the original cohort
(n=l,154) and those with employment duration data (n=-51 of n=70).
N/A This study focused upon mesothelioma outcomes.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Crocidolite asbestos fiber levels per microgram of dried lung were analyzed by transmis-
sion electron microscopy.
Medium The range and distribution of lung crocidolite fiber concentrations presented in Tables
1 and 2 by decade of death and categories (4 categories) of length (months) of exposure
are sufficient to develop an exposure response relationship.
High The study establishes appropriate temporality and the interval between exposure and
outcome is long enough for consideration of latency of the outcome. The period of
possible exposure to crocidolite was noted to be September 1940 to March 1945 with
follow-up for deaths through 1994.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or
Characterization
High ICD codes were not detailed within the main text, however data regarding deaths was
described in the referenced original Nottingham cohort study by McDonald et al., 2006
(HERO ID 709504) and indicate use of ICD-9 as well as employment and pathological
records for traced former workers with all deaths due to mesothelioma described as
confirmed by pathology.
Continued on next page ...
Page 18 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709467 Table: 1 of 1
... continued from previous page
Study Citation: Berry, G., Pooley, F., Gibbs, A., Harris, J., Mcdonald, J. (2009). Lung fiber burden in the Nottingham gas mask cohort. Inhalation Toxicology 21(2009): 168-
172.
Mesothelioma
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 709467
Cancer/Carcinogenesis: Mesothelioma-pleural, Mesothelioma-peritoneal; Mortality: Mesothelioma-pleural, Mesothelioma-peritoneal; Lung/Respiratory:
Mesothelioma-pleural
Asbestos - Crocidolite (riebeckite): 12001-28-4
Domain
Metric
Rating
Comments
Metric 8: Reporting Bias
High There were no concerns for selective reporting as all outcomes which were outlined
within methods were also reported within the results. Results for fiber concentrations
within lungs were reported across year of death and cause of death categories within
Table 1, and the regression equation was detailed in the text for the % fibers by year of
death in Figure 2.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Low
N/A
Medium
Other than stratification of fiber concentration results across year and cause of death
categories, no adjustments for gender, age or race appear to have been made and the
distribution of primary covariates and potential confounders was not reported.
Potential confounders were not detailed as considered.
The members of the cohort were workers at the Nottingham military gas mask factory
1940 through 1945. Although co-exposures were not addressed, there was no evidence
that there was an unbalanced provision of co-exposures among exposure groups. Con-
siderations for workers who might have initially left and worked elsewhere with ad-
ditional exposures but eventually returned to the gas mask factory for study were not
detailed. Authors noted that masks consisted of 20% crocidolite, but details regarding
the remaining composition of masks were not provided.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design was appropriate to address the main objective of analyzing lung fiber
burdens over time. The percentage of fibers longer than 6jUm was analyzed by logistic
regression with respect to year of death. Median geometric mean crocidolite fibers in
lung tissue were presented in Table 1 for year of death categories and cause of death.
Medium The number of participants (n=70 total with n=51 with duration of employment data)
was minimal for regression analyses, although additional covariates did not appear to
have been considered within modeling.
Medium The description of analysis is sufficient to understand how to generally reproduce the
analyses. Transformation of exposure variables was described in detail. Imputation of
exposures with zero values as one-half of the limit of detection was also detailed.
Low Model building was not described in terms of the reasoning for lack of considerations
for potential confounders.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric 16: Use of Biomarker of Exposure Low Evidence exists for a relationship between lung fiber concentrations and external ex-
posure, internal dose or target dose, but there has been no assessment of accuracy and
precision or none was reported.
Continued on next page ...
Page 19 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709467 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Berry, G., Pooley, F., Gibbs, A., Harris, J., Mcdonald, J. (2009). Lung fiber burden in the Nottingham gas mask cohort. Inhalation Toxicology 21(2009): 168-
172.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma-pleural, Mesothelioma-peritoneal; Mortality: Mesothelioma-pleural, Mesothelioma-peritoneal; Lung/Respiratory:
Mesothelioma-pleural
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
709467
Domain
Metric
Rating
Comments
Metric 17: Effect Biomarker
Metric 18: Method Sensitivity
Metric 19: Biomarker Stability
Metric 20: Sample Contamination
Metric 21: Method Requirements
Metric 22: Matrix Adjustment
N/A
Medium
Low
Medium
High
N/A
No biomarkers of effect were used.
Authors noted, "For three zero values, half of the detection limit (0.005, 0.005, 0.05
fibers/jUg) was substituted". Analytical method utilized transmission electron mi-
croscopy.
Lung fiber sample storage history and stability not detailed.
There is no information included regarding contamination.
Transmission electron microscopy utilized to provide identification and quantitation of
lung fibers.
A biomarker of exposure was utilized.
Additional Comments: This study focused upon post-mortem crocidolite lung fiber concentrations in a subset (n=70: n=50 mesothelioma and n=20 deaths from other causes) of
the Nottingham Gas Mask cohort of n=l,154 employees with lung tissue samples who had worked 1940-1945 on the manufacture of military gas masks
with filter pads containing 20% crocidolite and who were followed through 2003. Crocidolite asbestos fiber levels per microgram of dried lung were
presented by decade of death and cause of death (Table 1), duration of exposure (Table 2), and the percentage of fibers longer than 6/im was analyzed with
year of death by logistic regression (Figure 2). The crocidolite counts ranged from 0 to 1,949 (mean 234, median 47) fibers/jig.
Overall Quality Determination Medium
Page 20 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6868332 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Brims, F. J. H., Kong, K., Harris, E. J. A., Sodhi-Berry, N., Reid, A., Murray, C. P., Franklin, P. J., Musk, A. B., e Klerk, N. H. (2020). Pleural plaques and
the risk of lung cancer in asbestos-exposed subjects. American Journal of Respiratory and Critical Care Medicine 201(2020):57-62.
Mesothelioma
Lung/Respiratory: Malignant mesothelioma
Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): 733541, 709469, 3079298, 3520653, 3531364, 6868332
6868332
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not ex-
plicitly mention the use of PCM or TEM. Dust concentrations were measured using
koniometer between 1948 and 1958. In 1966, fiber counting was done using a Casella
long running thermal precipitator. Personal and fixed monitors were utilized in 1973.
Additional measurements were taken in 1977, 1978, 1980, 1984, 1986, and 1992, us-
ing interpolation to estimate concentrations for years that surveys were not conducted.
According to Hansen et al., 1997 2219991, all samples examined were analyzed using
the standard membrane filter method. Some exceptions were surveys in 1984 and 1986
which used SEM, and in 1992 which used TEM. Although later surveys utilized TEM,
the current study does not describe estimates in a way to know outcomes based on expo-
sures measured from 1992 and after.
Medium The distribution of exposure appears to be sufficient to develop an exposure-response
estimate. Cumulative exposure was utiliized in statistical models.
Additional Comments: None
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 21 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 758904 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Churg, A., Vedal, S. (1994). Fiber burden and patterns of asbestos-related disease in workers with heavy mixed amosite and chrysotile exposure. American
Journal of Respiratory and Critical Care Medicine 150(1994):663-669.
Mesothelioma
Lung/Respiratory: Mesothelioma
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Tremolite: 14567-73-8; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
758904
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
Methods for fiber count included fiber morphology and fiber chemistry determined
through energy-dispersive x-ray spectroscopy, followed by calculating fiber concentra-
tion using an algorithm that accounted for weight of lung tissue used in the study and
number of grid squares. However, authors did not utilize PCM or TEM, thus warranting
a low rating per the guidance.
Actual measured exposure data were not available for the cases and are estimations
based on historic data and calculations. Authors stated that exposure was not included
in their models as they felt combining years of exposure with fiber burden did not make
sense analytically nor is there a correlation between the two.
Additional Comments: 2/6/2023 UPDATE: DUE TO CHANGES IN THE GUIDANCE FOR SQE, ALL METRICS RATINGS EXCEPT FOR 4 AND 5 SHOULD BE IGNORED
BECAUSE METRIC 4 AND 5 WERE RATED "LOW".Authors stated crocidolite fibers were detected in a small number of cases but were excluded from
analyses. Examining the association between chrysotile or tremolite with disease was not conducted due to low concentrations, but concentrations are
reported.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 22 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1481523 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Churg, A., Wright, J. L., Vedal, S. (1993). Fiber burden and patterns of asbestos-related disease in chrysotile miners and millers. American Review of
Respiratory Disease 148(1993):25-31.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma, lung cancer; Lung/Respiratory: Asbestosis, airway fibrosis, pleural plaques, lung cancer, mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Tremolite: 14567-73-8
No linked references.
1481523
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Medium
Fiber concentrations were measured using analytic electron microscopy. Summary
statistics of exposure year and latency were reported. The nature of the study design
determined exposure measured at only one time period.
Metric 5:
Exposure Levels
Low
Very limited description of exposure range. The geometric means of asbestos concentra-
tion reported in cases (by disease type) and subjects without asbestos-related disease.
Additional Comments: The mesothelioma measurement is uninformative because no death certificate or ICD codes used. The participation selection lack of description of key
elements and attrition rate is high. Covariates were not sufficiently considered and comparison group is not ideal.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 23 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6868714 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Consonni, D., Calvi, C., De Matteis, S., Mirabelli, D., Landi, M. T., Caporaso, N. E., Peters, S., Vermeulen, R., Kromhout, H., Dallari, B., Pesatori, A. C.,
Riboldi, L., Mensi, C. (2019). Peritoneal mesothelioma and asbestos exposure: A population-based case-control study in Lombardy, Italy. Occupational
and Environmental Medicine 76(2019):545-553.
Mesothelioma
Lung/Respiratory: Peritoneal mesothelioma
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
6868714
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Neither PCM nor TEM were used for measuring exposure. The study measures asbestos
exposure in both a qualitative and quantitative approach. Quantitative measures came
from linking ISCO-68 codes to SYN-JEM which provided yearly exposure intensity
values for each job. From this, authors calculated individual lifetime cumulative expo-
sures to asbestos (ff/mL-years). The qualitative measure came from expert evaluations
of the ReNaM questionnaire (a standardized questionnaire that focuses on life-time
job-history) where asbestos exposure categories (never-exposed, extra-occupational, oc-
cupational probable/possible, and definite occupational exposure) were created. Recall
and interviewer bias is of concern since completing the questionnaire was done via an
interview by trained personnel (as opposed to occupational records) and assessment of
cases were non-blinded.
Medium Four levels of exposure are defined for cumulative asbestos exposure (ff/mL-years):
never exposed, <0.888, <3.158, 3.158 and over. Continuous cumulative and log-
transformed cumulative exposure are also calculated.
Additional Comments: While asbestos fiber type is not assessed in this study, authors state that chrysotile and amphiboles were often used in Italy.2/6/2023 UPDATE: DUE TO
CHANGES IN THE GUIDANCE FOR SQE, ALL METRICS RATINGS EXCEPT FOR 4 AND 5 SHOULD BE IGNORED BECAUSE METRIC 4 WAS
RATED "LOW".
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 24 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083452 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cookson, W. O., Musk, A. W., Glancy, J. J., de Klerk, N. H., Yin, R., Mele, R., Carr, N. G., Armstrong, B. K., Hobbs, M. S. (1985). Compensation,
radiographic changes, and survival in applicants for asbestosis compensation. British Journal of Industrial Medicine 42(1985):461-468.
Mesothelioma
Mortality: Respiratory neoplasms mortality; Lung/Respiratory: Respiratory neoplasms mortality; Cancer/Carcinogenesis: Respiratory neoplasms mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3083452
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated low because neither the study nor any cited methods sources explic-
itly mention the use of PCM or TEM to quantify asbestos fibers.
Medium Respiratory neoplasms, which included mesothelioma, were only assessed as "exposed"
vs. "unexposed" and thus have a limited range of exposure.
Additional Comments: This study was not fully evaluated because metric 4 was rated as low, due to no explicit mention in the study or cited sources about the use of PCM or
TEM.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 25 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6867273 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cuccaro, F., Nannavecchia, A. M., Silvestri, S., Angelini, A., Coviello, V., Bisceglia, L., Magnani, C. (2019). Mortality for mesothelioma and lung
cancer in a cohort of asbestos cement workers in BARI (Italy): Time related aspects of exposure. Journal of Occupational and Environmental Medicine
61(2019):410-416.
Mesothelioma
Peritoneal mesothelioma: Peritoneal mesothelioma mortality; Lung/Respiratory: Pleural mesothelioma mortality; Cancer/Carcinogenesis: Pleural
mesothelioma mortality, Peritoneal mesothelioma mortality; Mortality: Peritoneal mesothelioma, Pleural mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
6867273
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Between 1970 and 1974 several industrial hygiene investigations were carried out with
measurement of the concentration of the airborne fibers (Coviello, et al., 2002, HERO
ID 3080488). This metric is rated Low because authors in this paper do not explicitly
cite use of PCM or TEM, and the cited methods paper (Coviello et al. 2002, 3080488)
is not freely available or through HERO. PubMed also indicated that the article is in
Italian.
Medium The authors of this cohort study used an exposure index to evaluate individual cumu-
lative exposure as proxy of asbestos dose and reported 3 or more levels of exposure (3
tertiles).
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.Metric 4 is rated Low because authors in this paper do not explicitly cite use of PCM or TEM, and the cited methods paper (Coviello et al. 2002,
3080488) is not freely available. For Metric 5, this cohort study used an exposure index to evaluate individual cumulative exposure as proxy of asbestos
dose, and reported 3 or more levels of exposure (3 tertiles). Mesothelioma and other outcomes forms filled for Metrics 4 and 5 and evaluation stopped.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 26 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 718578 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dawson, A., Gibbs, A. R., Pooley, F. D., Griffiths, D. M., Hoy, J. (1993). Malignant mesothelioma in women. Thorax 48(1993):269-274.
Mesothelioma
Lung/Respiratory: Malignant mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5
No linked relerences.
718578
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3: Comparison Group
Medium Key elements of study design were reported. Participation is not likely biased and
exposure-outcome distribution of participants is likely representative of those eli-
gible for inclusion,. However, total number of patients, from which cases with post-
mortem evaluations were chosen, with malignant mesothelioma but with no postmortem
analyses records was not provided. Authors did acknowledged the potential non-
representativeness of this population due to the patient-referred nature of cases which
included wartime dockyard and gas mask workers known to have suffered from heavy
asbestos exposure. All available pathological, occupational and lung fiber mineralogical
data on n=177 female malignant mesothelioma cases from unspecified file records and
unspecified geographic residential origin 1963-1990 were reviewed and compared with
n=31 female controls from Exeter, Liverpool, Befast, Dublin, and Cardiff with post-
mortem examinations and no known history of exposure to dusts and no mesothelioma
or lung cancer. Source of data for controls not detailed but assumed to have been from
the same files as cases.
Medium Missing information was noted for several subsets of outcome and exposure, and authors
acknowledged the lack of completeness of exposure data, however it was unclear if
this was related to exposure and/or outcome. The total number of participants with
tumor tissue slides available (n=151) was a subset of the total number of mesothelioma
cases (n=177). Tumor tissue slides were available for n=151 of a total of n=177 cases.
Two cases of the total cases tested (n=103 of the n=151 with histologic slides available)
were positive for carcinoembryonic antigen and were excluded from further analyses.
Lung tissue fiber burden was examined by transmission electron microscopy for n=105
tumors of known sites (Table 2). Exposure classification according to Zielhuis et al.,
1978 (HERO ID 6910362) data was available for n= 93 cases.
Medium Inclusion criteria and methods of participant selection for cases and controls was re-
ported. Geographic residential origin of controls, but not cases (other than one case
from Antolia) was reported. Other than restriction of cases and controls to women and
reporting the mean (range) age of n=102 malignant mesothelioma cases (60.5 years (18-
89)) and n=31 controls (68.0 years (30-93)) for which age data was available, details
regarding other potentially relevant demographic and occupational covariate differences
between cases and controls were not considered. Statistical analyses of potential demo-
graphic or other relevant covariate differences between cases and controls was lacking,
and multivariate statistical control for differences, particularly age, between groups was
not detailed. It is unclear to what extent, if any, the healthy worker effect was involved
within results including those cases classified within Table 4 as having direct occupa-
tional exposure in comparison with the population controls.
Continued on next page ...
Page 27 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 718578 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
... continued from previous page
Dawson, A., Gibbs, A. R., Pooley, F. D., Griffiths, D. M., Hoy, J. (1993). Malignant mesothelioma in women. Thorax 48(1993):269-274.
Mesothelioma
Lung/Respiratory: Malignant mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5
Linked HERO ID(s): No linked relerences.
HERO ID:
718578
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement ol Exposure Medium Methods used to quantify exposure were well defined, with sources of methods reported.
Lung tissue fiber (106 fibers/g), fiber length and diameter analyses were assessed by
Transmission Electron Microscopy (TEM) with energy dispersive x ray analysis us-
ing an "EDAX" machine according to the methods within Pooley et al., 1979 (HERO
ID: 3084350). Asbestos exposure classification methods for cases only were conducted
as in Zielhuis et al., HERO ID 6910362. Exposure to asbestos was classified for n=93
(of total n=177 cases) malignant mesothelioma cases according to Zielhuisl8 into cat-
egories of (la) direct occupational exposure; (lb) indirect occupational exposure-for
example, workers in the vicinity of asbestos contaminated work situations; (2) paraoccu-
pational exposure-for example, the wives of men working with asbestos; (3) neighbor-
hood exposure-for example, people living in the vicinity of asbestos mines or processing
factories; (4) exposure in ambient air; and (5) no known exposure. Only n=74 (80% of
the total n=93 cases with Zielhuis classified exposure history data of the total n=177 ma-
lignant mesothelioma cases) cases had a history of known exposure to asbestos. Zielhuis
classification of potential historical exposure for controls was not detailed.
Metric 5: Exposure Levels Medium The range and distribution of exposure is sufficient to develop and exposure-response es-
timate. Table 4 presents fiber burden (x 10A 6 fibers/g lung) geometric mean (range) re-
sults for n=93 mesothelioma cases across five Zielhuis et al., 1978 (HERO ID 6910362)
exposure categories of direct occupational, indirect occupational, domestic, neighbor-
hood, ambient air and no known exposure categories. Table 3 reports lung fiber burden
(x 10A 6 fibers/g lung) across five fibrosis grade categories for n=116 cases.
Metric 6: Temporality Low This study reported cross-sectional results of fiber burdens in mesothelioma cases as
well as cross-sectional analyses of the relationship between postmortem fibrosis and
lung fiber burdens in mesothelioma cases and controls for which temporality cannot be
established.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or
Characterization
Medium Outcome of mesothelioma was assessed. Mesothelioma case histological subtypes were
confirmed by immunohistochemistry, although classification of n=26 cases for which
no tumor or tissue slides were available were described as classified as with previous
records from Dr JC Wagner.
Continued on next page ...
Page 28 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 718578 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dawson, A., Gibbs, A. R., Pooley, F. D., Griffiths, D. M., Hoy, J. (1993). Malignant mesothelioma in women. Thorax 48(1993):269-274.
Mesothelioma
Lung/Respiratory: Malignant mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5
No linked relerences.
718578
Domain
Metric
Rating
Comments
Metric 8:
Reporting Bias
Medium There were no concerns for selective reporting as all outcomes which were outlined
within methods were also reported within the results. Additional n=l,184 male cases of
mesothelioma were reported, but analyses of males was not a subset of reported objec-
tives and comparisons were only made within text with results from previous studies of
males. No formal statistical analyses between cases and controls was conducted, and no
effect estimates were reported,
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Low Analyses were restricted to female cases and controls. Additional statistical control for
potentially relevant demographic or other variables was not conducted.
Metric 10: Covariate Characterization Low Source of covariate data (age only) was not directly stated, nor validated, but assumed to
have been obtained from the files from which patient data were obtained.
Metric 11: Co-exposure Counfounding Low The patient population under study included mesothelioma case workers in Table 4 to
have had direct and indirect occupational exposure, however potential confounding due
to co-exposures was not reported as considered.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Medium
Medium
N/A
The study method chosen was appropriate for the cross-sectional data available.
The number of cases and controls are generally adequate to detect an effect in the over-
all population. Authors acknowledged the inadequacy of the sample size for analyses of
fiber types on outcomes of interest.
The description of analysis is sufficient to understand how to conceptually reproduce the
data within the presented tables, although raw data was not reported.
This study did not utilize multivariate statistical modeling methods.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric 16: Use of Biomarker of Exposure Low Asbestos bodies were assessed by light microscopy in the background lung of n=133
cases, with results indicating presence of asbestos bodies in n=70 (53% ) cases. Total
amphibole counts analyzed by transmission electron microscopy (TEM) of n=49 of
the n=70 specimens positive for asbestos bodies were less than the n=50 specimens
analyzed with no asbestos bodies.
Metric 17:
Effect Biomarker
N/A
Asbestos bodies were assessed in background lung as markers of exposure.
Metric 18:
Method Sensitivity
Low
LOD/LOQ was not detailed.
Metric 19:
Biomarker Stability
Low
Sample storage history and stability data were not detailed.
Metric 20:
Sample Contamination
Medium
No information was provided regarding sample contamination.
Metric 21:
Method Requirements
Medium
Asbestos bodies in background lung samples were assessed by light microscopy.
Continued on next page ...
Page 29 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 718578 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
... continued from previous page
Dawson, A., Gibbs, A. R., Pooley, F. D., Griffiths, D. M., Hoy, J. (1993). Malignant mesothelioma in women. Thorax 48(1993):269-274.
Mesothelioma
Lung/Respiratory: Malignant mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5
Linked HERO ID(s): No linked relerences.
HERO ID:
718578
Domain
Metric
Rating
Comments
Metric 22: Matrix Adjustment
N/A Matrix adjustment is not required for assessment of biomarker.
Additional Comments: This study reported cross-sectional results of postmortem fibrosis and lung fiber burdens from an initial total population of n=177 female malignant
mesothelioma cases 1963-1990 (geographic origin not detailed) and n=31 female controls from Exeter, Liverpool, Belfast, Dublin, and Cardiff with no
initially known exposure history to dusts and no mesothelioma or lung cancer. Cases (n=102 of total n=177) with age data were described as being of mean
(range) age 60.5 years (18-89 years) with n=31 controls aged 68 years (30-93 years). Mesothelioma cases had notably higher total amphibole counts than
controls. Fibrosis was noted within some controls.
Overall Quality Determination Low
Page 30 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 783917 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
de Klerk, N. H., Armstrong, B. K., Musk, A. W., Hobbs, M. S. T. (1989). Cancer mortality in relation to measures of occupational exposure to crocidolite
at Wittenoom Gorge in Western Australia. British lournal of Industrial Medicine 46(1989):529-536.
Mesothelioma
Lung/Respiratory: Mortality from malignant mesothelioma of the pleura; Mortality: Mortality from malignant mesothelioma of the pleura; Cancer/
Carcinogenesis: Mortality from malignant mesothelioma of the pleura
Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): 783917, 3079799, 3080174
783917
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low This metric is rated low because Klerk et al. 1989 783917, Reid et al. 2006 3079799,
and Reid et al. 2004 3080174 relied on historic dust measures (konimeters, thermal
precipitators) without documenting the use of appropriate conversions. These papers
cited the single time point membrane filter PCM fiber concentration measures that were
taken in 1966, shortly before the facility closed (publication not available in HERO or
other online sources, Major 1968 entitled the First Australian Pneumoconiosis Confer-
ence). However, they did not mention or cite a dust-to-fiber conversion factor, and no
such factors were identified in the literature. Concerns regarding the validity and utility
of occupational exposure measures used in Wittenoom studies have been expressed by
the industrial hygienist responsible for the membrane filter measures (e.g., Rogers and
Major 2002 HEROID 3080506).
Metric 5: Exposure Levels Low The distribution of exposure provided in de Klerk et al 783917 appears to be sufficient
to develop an exposure-response estimate. Cumulative exposure was used in analyses
either as a continuous variable or in 4 categories. As noted above, however, there are
important concerns remain regarding the validity of exposure estimates.
Additional Comments: Klerk et al. 1989 783917 was/were not evaluated for any metrics except Metric 4 and 5 and had no data extracted because it/they did not have sufficient
exposure information to be useful for dose-response analysis.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 31 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081932 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
de Klerk, N. H., Musk, A. W., Cookson, W. O., Glancy, J. J., Hobbs, M. S. (1993). Radiographic abnormalities and mortality in subjects with exposure to
crocidolite. British Journal of Industrial Medicine 50(1993):902-906.
Mesothelioma
Lung/Respiratory: Lung cancer mortality, mesothelioma mortality, pneumoconiosis mortality; Cancer/Carcinogenesis: Mesothelioma mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3081932
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
Study reports that estimates of crocidolite from Wittenoom Gorge were collected from
existing industry records of fibre. The exact tool utilized to measure the asbestos is not
mentioned, but methods state that fibers in the air >5mu in length from 1966 were used
to create cumulative exposure measures.
The exposure ranges are appropriate to the study using intensity (f/mL), days of expo-
sure (average), and cumulative exposure (f/mL-years).
Additional Comments: For the year of the study and the 5 different case-control analyses conducted, I agree with the rating. There are some discrepancies, such as how the
asbestos was measured and exposures to various forms of asbestos which were not regarded.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 32 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1066036 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Dunning, K. K., Adjei, S., Levin, L., Rohs, A. M., Hilbert, T., Borton, E., Kapil, V., Rice, C., Lemasters, G. K., Lockey, J. E. (2012). Mesothelioma
associated with commercial use of vermiculite containing Libby amphibole. Journal of Occupational and Environmental Medicine 54(2012):1359-1363.
Mesothelioma
Mortality: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Not specified: 1332-21-4; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7;
Asbestos - Tremolite: 14567-73-8
ID(s): No linked references.
1066036
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Analyses use cumulative fiber exposure. Additional details about exposure measurement
are reported in Lockey et al., 1984, HEROID 29685. Samples were collected via mem-
brane filters either by following an employee with a sampler (from 1972-1976) or by
breathing zone sampling (after 1976). Authors note that exposure of fiber was defined as
"particles with a length greater than 5 um, a diameter less than 3 um, and an aspect ra-
tio of 3:1 or greater". Thus, fiber type was unknown, and samples likely included fibers
other than asbestos. Samples were reviewed through polarized light microscopy, scan-
ning electron microscopy, and TEM. Indexes were created for each department within
the facility. Study authors used work histories reported by workers in 1980 to calcu-
late the cumulative fiber exposure level for each employee. Previous estimates were
revised to include additional data related to exposure collected in 2010, such as adjust-
ments for vermiculite source and changes in duration of work by season (Borton et al.,
2012, HEROID 1066035). Borton et al. also estimated exposures from 1957-1971 us-
ing estimates from 1972 with adjustments for dustier historical conditions. This study
also reported comparisons between personal and area samples and found approximately
equal means and ranges.
Metric 5: Exposure Levels Low For SMR analyses of mesothelioma, exposure is presented in two groups (exposed
workers and unexposed workers). Authors note the possibility that associations were
not observed due to the low exposure levels among the study population, which intro-
duces concern about the influence of the exposure distribution on the ability to detect an
effect.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-
response analysis.This retrospective occupational cohort study examined the association between asbestos exposure and mesothelioma mortality among
workers mining and milling contaminated vermiculite. There were no major concerns with the study, aside from limited exposure distributions among the
study population and concerns about the number of mesothelioma cases in the cohort. The approach for exposure measurement and statistical analysis was
strong, and there were no concerns about selection bias resulting from population recruitment approaches.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 33 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3520580 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence of digestive
cancers and occupational exposure to asbestos. European Journal of Cancer Prevention 11(2002):523-528.
Mesothelioma
Lung/Respiratory: Pleural and peritoneal mesothelioma; Gastrointestinal: Pleural and peritoneal mesothelioma; Cancer/Carcinogenesis: Pleural and peri-
toneal mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3520580, 3077730, 3078903, 3520549
3520580
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Clin et al. 2011, HERO ID: 3078903 analyzed the risk of mesotheliomas among salaried
and retired workers (men and women) from an asbestos reprocessing plant (textiles
and friction materials) in the Calvados department in Normandy, France. Eligibility
was based on: (i) working at the plant for at least 1 year; (ii) being alive in 1978 when
the regional cancer registry was established; (iii) having resided in Calvados during at
least part of the 1978 to 1995 initial follow-up period, with known vital status (de la
Provote et al al. 2002, HERO ID: 3520580). As noted by Clin et al. 2011, HERO ID:
3078903, "... since one of our inclusion criteria was that subjects had to be alive in 1978,
there may be a selection bias related to the "healthy worker effect"." Including retired
workers, however, would have helped to reduce this bias. The number of workers who
did not meet eligibility criteria was not provided; it is unknown whether a large number
of workers of similar age and employment duration as those in the cohort had cancer
diagnoses prior to 1978, which could bias results. The factories had operated using
asbestos in various capacities since 1928. All cancer cases from 1978 to 2004 were
included, resulting in 2024 subjects (1604 men).
High Clin et al. 2011, HERO ID: 3078903 reported that 107 subjects (5.3% ) had missing
vital status at the end of 2004 and were excluded from analysis. It is unclear why vital
status was missing, but given the relatively small share of subjects and that it would not
be expected to be related exposure and outcome make this a limited concern for bias.
Medium In calculating relative risk for mesothelioma, workers with varying concentrations of
exposures were compared amongst each other. There is no indication that groups were
similar but there is no indication of healthy worker effect.
Domain 2: Exposure Characterization
Continued on next page .
Page 34 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3520580 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence of digestive
cancers and occupational exposure to asbestos. European lournal of Cancer Prevention 11(2002):523-528.
Mesothelioma
Lung/Respiratory: Pleural and peritoneal mesothelioma; Gastrointestinal: Pleural and peritoneal mesothelioma; Cancer/Carcinogenesis: Pleural and peri-
toneal mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3520580, 3077730, 3078903, 3520549
3520580
Domain
Metric
Rating
Comments
Metric 4:
Measurement of Exposure
Metric 5:
Exposure Levels
Metric 6:
Temporality
Medium Exposure estimates were assigned to individuals based on job functions and timing/
duration of employment and fiber count measures. As described by de la Provote et
al. 2002, HERO ID: 3520580, fiber counts were measured at different locations in the
plant as follows: (i) 1973 -1995 data were collected by Casella pumps on a membrane
filter, with PCM (phase-contrast light microscopy) counts of fibers longer than 5 jU m,
less than 3jU m in diameter, with a length/diameter ratio greater than 3; (ii) 1960-1974
data were collected on soluble filters by an ARM (Avy"Raillere"Martin) apparatus,
with light microscopy fiber counts as particles per liter of air; and (iii) estimates prior to
1959/1960 were based on production reports for 1939-1945 [50% of 1960 levels], lin-
early extrapolated to 1960. Date cutoffs differed slightly across manuscripts [e.g. ARM
started in 1959 vs 1960 according to Clin et al. 2011, HERO ID: 3078903], Side-by-side
Casella vs. ARM method measures in 1974 were used to develop a conversion factor for
the different methods. A cumulative exposure index (CEI) for the entire career (fibers/
mL * year) was calculated as the sum of exposure * duration for each job position. A
mean exposure concentration (MEC), also referred to as averaged exposure (AEL) was
also calculated and expressed in fibers/mL). Clin et al. 2009, HERO ID: 3520549 and
Boulanger et al. 2017, HERO ID: 3077730 explain these same methods but in lesser de-
tail. Clin et al. 2011, HERO ID: 3078903 uses CEI and AEL exposure categories with a
10-year lag to account for latency.
Medium To estimate mesothelioma risk, only Clin et al. 2011, HERO ID: 3078903 categorized
asbestos exposure variables using 3 ordinal levels.In de la Provote et al. 2002, HERO
ID: 3520580, Clin et al. 2009, HERO ID: 3520549 and Boulanger et al. 2015, HERO
ID: 307773, SIRs are only calculated using 2 exposure categories of cumulative ex-
posure, such as exposed/unexposed or <= vs > 80 fibers/mL-year, all of which merit
a Low rating for this metric. Because of this, de la Provote et al. 2002, HERO ID:
3520580, Clin et al. 2009, HERO ID: 3520549, and Boulanger et al. 2015, HERO ID:
307773, are only evaluated for metrics 4 and 5.
High While Clin et al. 2011, HERO ID: 3078903 gives limited detail on temporality, de la
Provote et al. 2002, HERO ID: 3520580 shows that 69% of workers had at least 10 years
at work, and 50% had >= 20 years.
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
High Clin et al. 2011, HERO ID: 3078903 reported using ICD-O 3 codes to identify mesothe-
lioma cases, further stating that mesothelioma cases were assessed and validated by an
expert pathologist from the French mesothelioma panel. ICD-O 3 codes are not given.
Continued on next page ...
Page 35 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3520580 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence of digestive
cancers and occupational exposure to asbestos. European lournal of Cancer Prevention 11(2002):523-528.
Mesothelioma
Lung/Respiratory: Pleural and peritoneal mesothelioma; Gastrointestinal: Pleural and peritoneal mesothelioma; Cancer/Carcinogenesis: Pleural and peri-
toneal mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3520580, 3077730, 3078903, 3520549
3520580
Domain
Metric
Rating
Comments
Metric 8: Reporting Bias
High Clin et al. 2011, HERO ID: 3078903 reported findings in the abstract, results, and dis-
cussion sections adequately, where confidence intervals are provided for relative risk
estimates. P-values and numbers of cases were also presented in detail.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment High Clin et al. 2011, HERO ID: 3078903 adjusted models by sex and age (time dependent).
Data on smoking were not available. Race was not discussed, although it is likely that
the population was largely white.
Metric 10: Covariate Characterization Medium Information on covariates was obtained from the company's occupational health depart-
ment records.
Metric 11: Co-exposure Counfounding N/A For mesothelioma, there is not likely to be any co-exposures for these subjects or in their
settings, resulting in an "N/A" (not applicable) rating.
Domain 5: Analysis
Metric
12:
Study Design and Methods
Medium
Clin et al. 2011, HERO ID: 3078903 used a Cox hazard model to analyze the dose-
response relationship of occupational asbestos exposure and risk of mesothelioma.
Metric
13:
Statistical Power
Medium
Clin et al. 2011, HERO ID: 3078903 likely has adequate power to detect an association
(n cases=24, total n=2024).
Metric
14:
Reproducibility of Analyses
Medium
The descriptions of analyses are clear and sufficiently well-written to conceptually re-
produce analyses.
Metric
15:
Statistical Analysis
Medium
The authors describe appropriate methods, including using exposure lags, categorizing
exposure to avoid assumptions of linearity, and examining alternative time scales in Cox
models.
Additional Comments: Note that for de la Provote et al. 2002, HERO ID: 3520580, Clin et al. 2009, HERO ID: 3520549 and Boulanger et al. 2015, HERO ID: 307773, SIRs are
only calculated using 2 exposure categories of cumulative exposure, such as exposed/unexposed or <= vs > 80 fibers/mL-year, all of which merit a Low
rating for this metric. Because of this, de la Provote et al. 2002, HERO ID: 3520580, Clin et al. 2009, HERO ID: 3520549, and Boulanger et al. 2015,
HERO ID: 307773 are only evaluated for metrics 4 and 5, and QC was not performed for any other metrics. Only Clin et al. 2011, HERO ID: 3078903
was evaluated for all metrics. The only outcome evaluated here is pleural and peritoneal mesothelioma.
Overall Quality Determination High
* No biomarkers were identified for this evaluation.
Page 36 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 5029590 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Farioli, A., Straif, K., Brandi, G., Curti, S., Kjaerheim, K., Martinsen, J. I., Sparen, P., Tryggvadottir, L., Weiderpass, E., Biasco, G. (2018). Occupational
exposure to asbestos and risk of cholangiocarcinoma: a population-based case-control study in four Nordic countries. Occupational and Environmental
Medicine 75(2018):191-198.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma
Asbestos - Not specified: 1332-21-4
ID(s): 5029590,6875563
5029590
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low This metric is rated low because the study or any cited methods sources do not explicitly
mention the use of PCM or TEM (Plato et al., 2018, 6875563). Exposure in this study
was estimated using a generic job-exposure matrix that was specifically developed for
this cohort, but did not include personal measurements based on PCM or TEM (Kaup-
pinen et al., 2009, 699236).
Metric 5: Exposure Levels Medium A range of exposure levels is reported within the study. For Plato et al. (2018, 6875563)
these groupings include 0 fibers/ml, >0-0.2 fibers/ml, >0.2-1.25 fibers/ml, and >1.25-
2.0 fibers/ml.
Additional Comments: This evaluation was not completed because metric 4 was rated as low. This is due to no explicit mention of the use of PCM or TEM for exposure
measurements.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 37 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3008803 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Ferrante, D., Mirabelli, D., Tunesi, S., Terracini, B., Magnani, C. (2015). Pleural mesothelioma and occupational and non-occupational asbestos exposure:
a case-control study with quantitative risk assessment. Occupational and Environmental Medicine 73(2015):147-153.
Mesothelioma
Lung/Respiratory: Pleural malignant mesothelioma (PMM); Cancer/Carcinogenesis: Pleural malignant mesothelioma (PMM)
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3008803
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
High This population-based case-control study included the incident cases of pleural malig-
nant mesothelioma (PMM) diagnosed between 1 January 2001 and 30 June 2006 among
residents of the Casale Monferrato Local Health Authority (LHA) in Italy. Cases were
also recruited from a random sample of the corresponding general population. The LHA
included the town of Casale Monferrato, where an asbestos plan was operational for 80
years, and the surrounding area of approximately 60 towns and villages. Cases were
identified via units of pathology, pneumology, oncology, internal medicine, oncology,
internal medicine, thoracic surgery and radiotherapy of hospitals in the study area. The
authors report that 200 out of 223 eligible cases agreed to join the study and that the
ascertained cases represented 96% of all cases of PMM in the area. No inclusion or ex-
clusion criteria appear to be used. Participants were invited by their attending clinician.
High The authors do not report any subject withdrawal or attrition from the analysis sample
after formal recruitment. Outcome and exposure data appear to be complete.
High Controls were selected randomly from the population rosters of the Casale Monferatto
LHA. Cases and controls were matched by date of birth (±18 months) and gender. To
increase power in the younger age classes, the case control ratio was 1:2 for cases 60
years and older, and 1:4 for younger cases. Controls were invited by letter after their
general practitioners were informed. The authors report that 348 out of 552 controls
agreed to participate in the study. The distribution of cases and controls was similar by
sex, and cases were older than controls due to over-sampling of controls matched to
cases under 60 and "the different age distribution of non-participating controls." Infor-
mation on exposure and covariates was gathered directly via interviews from controls,
while 46% of interviews with cases were conducted with a close relative due to the case
being dead or being in poor health condition. All of these differences (gender, age, and
type of interview) were controlled for in statistical analysis. The potential for the healthy
worker effect is not discussed, but is unlikely to produce significant bias since both con-
trols and cases had occupational experience and exposure.
Domain 2: Exposure Characterization
Continued on next page .
Page 38 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3008803 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Ferrante, D., Mirabelli, D., Tunesi, S., Terracini, B., Magnani, C. (2015). Pleural mesothelioma and occupational and non-occupational asbestos exposure:
a case-control study with quantitative risk assessment. Occupational and Environmental Medicine 73(2015):147-153.
Mesothelioma
Lung/Respiratory: Pleural malignant mesothelioma (PMM); Cancer/Carcinogenesis: Pleural malignant mesothelioma (PMM)
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3008803
Domain
Metric
Rating
Comments
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium The authors do not directly reference PCM or TEM quantitative measures of exposure
in the methods. In the methods they cite various sources for where reference values for
fiber concentrations came from, but these references are in Italian and thus could not be
assessed for their usage of PCM or TEM by the QC team. However, in the discussion
section the authors state that the "information on airbone asbestos fiber concentration
in Casale Monferrato were presented by Maule et al and are only sumarised here." The
cited reference specifies that "fibers were counted on transmission electron microscope
(TEM, detection limit not provided) and were identified by EDXA" (Maule et al., 2007,
HERO ID: 3089896). However, other analyses from the Maule paper indicate that SEM
was used for some years and TEM in other years - it is not entirely clear which mea-
surements were used in the present analysis, although it may be reasonably assumed that
both were used for their respective years. The other sources of data, that were unable to
be retrieved in English, appear to be fiber measurements from the Balangero asbestos
mine, asbestos cement production, asbestos-textile works, and production of brake and
clutch linings.To assign exposure to individuals, asbestos exposure was assessed without
knowledge of case/control status. The assessment took into account the whole exposure
experience of each individual, including occupational and non-occupational sources
(environmental, familial, domestic). Individuals with multiple potential sources of oc-
cupational exposure were looked at separately. Study raters assessed the probability,
frequency, intensity, and duration of exposure for each potential source for each indi-
vidual based on existing literature and the subject's interview results in order to assign
an index value in fiber-ml years. There is some potential recall bias due to information
coming from personal interviews rather than company records. This is a larger concern
for the 46% of cases for whom interviews were conducted with close relatives rather
than the actual subject who may not know the exact tasks subjects performed on the job.
However, among participants who were directly interviewed recall bias is unlikely to
be significantly differential by outcome status. To account for the potential recall bias
among "proxy" interviewees, whether or not interviews were conducted with the actual
subject was an adjustment factor in statistical analysis.
Medium The range and distribution of exposure is sufficient or adequate to develop an exposure-
response estimate. Exposure was occupational or non-occupational and determined in
fibers/mL-years. Groups were <0.1, >0.1"<1, >1"<10, or >10. Mean and range of
fibre/mL-years are reported in Table 2.
Continued on next page ...
Page 39 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3008803 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Ferrante, D., Mirabelli, D., Tunesi, S., Terracini, B., Magnani, C. (2015). Pleural mesothelioma and occupational and non-occupational asbestos exposure:
a case-control study with quantitative risk assessment. Occupational and Environmental Medicine 73(2015):147-153.
Mesothelioma
Lung/Respiratory: Pleural malignant mesothelioma (PMM); Cancer/Carcinogenesis: Pleural malignant mesothelioma (PMM)
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3008803
Domain
Metric
Rating
Comments
Metric 6: Temporality
High There is an appropriate consideration of latency in this case-control study, as this study
was designed to assess outcomes 20 years after cessation of the industrial activity that
was responsible for asbestos exposure. Duration of exposure ranges are not provided for
the total population, but subjects with < 1 f/mL year exposure had a mean of 28 years of
exposure (SD 17) and subjects with >=10 f/mL year exposure had a mean of 53 years
(SD 17) of exposure.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High The study only included cases of pleural malignant mesothelioma with diagnosis con-
firmed after examination of histological and/or cytological samples, identified through
active search in the area referral hospitals.
Medium All of the study's findings that are discussed in the methods are clearly presented in
the results. However, p-values are not presented in the paper but are mentioned in the
abstract.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Analyses were conducted using unconditional logistic regression models adjusting for
gender, age at diagnosis and type of interview (direct or proxy respondents). There is no
discussion of why those specific variables were chosen and not others.
High Potential confounders were assessed using standardized questionnaires that were com-
pleted in interviews by trained professionals (residence at interview, no mention of other
confounders).
Low Potential co-exposures in occupational settings are otherwise not discussed.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study used unconditional logistic regression modeling to assess differences in PMM
diagnosis between cases and controls, which is an appropriate design.
Medium The final sample consisted of 548 individuals (200 cases and 348 controls), which is suf-
ficiently large to detect an effect. The authors do not calculate overall statistical power,
but mention using a 1:4 case:control ratio in younger cases to increase power.
Low Exposure estimation processes are not clearly defined, and would be difficult to repro-
duce given access to the analytic data. Other aspects of the study are well-described.
Medium Unconditional logistic regression modeling was used to calculate odds ratios and ratio-
nale around variables that were included were transparent.
Continued on next page ...
Page 40 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3008803 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Ferrante, D., Mirabelli, D., Tunesi, S., Terracini, B., Magnani, C. (2015). Pleural mesothelioma and occupational and non-occupational asbestos exposure:
a case-control study with quantitative risk assessment. Occupational and Environmental Medicine 73(2015):147-153.
Mesothelioma
Lung/Respiratory: Pleural malignant mesothelioma (PMM); Cancer/Carcinogenesis: Pleural malignant mesothelioma (PMM)
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3008803
Domain
Metric
Rating
Comments
Additional Comments:
Case-control study with 300 pleural malignant mesothelioma (PMM) cases and 348 controls. Asbestos type in this study is specific to 'amphibole'
but another methods paper that was referenced in methods ((Maule et al., 2007, 3089896) discusses chrysotile and crocidolite, so those were included.
Exposure was for occupational and non-occupational populations. Methods around the measurement of exposure and duration of exposure are unclear,
although another study was referenced in the methodology for measuring fibers which cited TEM, however since non-occupational exposed cases exposure
was not measured with TEM, Metric 4 was rated as Medium despite the large amount of uncertainty. The authors observed significant associations between
asbestos exposure and odds of PMM.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 41 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083612 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Finkelstein, M. M. (1984). Mortality among employees of an Ontario asbestos-cement factory. American Review of Respiratory Disease 129(1984):754-
761.
Mesothelioma
Lung/Respiratory: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality; Mortality: Mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3083612
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not ex-
plicitly mention the use of PCM or TEM.The estimated average cumulative exposure of
the production workers was about 60 fiber-years/mL (chrysotile and crocidolite). The
estimated mean cumulative exposure within the board shop, in which chrysotile was the
sole asbestos type utilized, was 39 f-y/mL. Air sampling data from government, insur-
ance and company hygienists initiated in late 1969 were utilized along with company
employment records to classify each production worker (n=186) according to estimated
annual cumulative asbestos exposure as described within Finkelstein et al., 1983 (HERO
ID 3100548), which also referenced Finkelstein, 1982 (HERO ID 76). Microscopic
method of fiber analysis (PCM or TEM) was not detailed in main or referenced text. Air
sampling data was obtained from only later factory years (late 1969 onward) and was
not representative of earlier years, although assumptions for exposure levels for those
earlier years were supported by impinger area sampling data. Air sampling data from
government, insurance and company hygienists initiated in late 1969 were utilized along
with company employment records to classify each production worker (n=186) accord-
ing to estimated annual cumulative asbestos exposure as described within Finkelstein
et al., 1983 (HERO ID 3100548) and Finkelstein, 1982 (HERO ID 76). Eighteen-year
cumulative exposures were calculated for the production workers (Table 7) by combin-
ing work histories and exposure estimates, with job-related exposures multiplied by the
time spent at each job and summed over the 18 years from first exposure. Workers were
assigned to an exposure category according to their 18-year exposure totals. Exposures
were assumed to have been unchanged from 1962 to 1970, to have been 30% higher
from 1955 to 1961, and to have been twice as high from 1948 to 1954, with assumptions
supported by impinger area sampling performed 1949 through the 1960"s. Raw mate-
rials in the production worker pipe manufacturing process included cement, silica and
both chrysotile and crocidolite asbestos, while the asbestos cement board production
utilized chrysotile asbestos only. Comparison control workers were primarily within the
rock wool/fiberglass insulation production area, although authors noted it was possible
for employees to be assigned to the pipe shop for brief clean-up duties, or re-assigned
from non-asbestos to asbestos work areas, such that some control workers were exposed
as well. Exposures for maintenance workers were not calculated due to inadequate data.
Medium The range and distribution of asbestos exposure in Table 7 presented across five expo-
sure categories ranging from <=30 fiber-years/mL through >150 fiber-years/mL for
production workers is sufficient to develop an exposure-response estimate.
Continued on next page ...
Page 42 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083612 Table: 1 of 1
... continued from previous page
Study Citation: Finkelstein, M. M. (1984). Mortality among employees of an Ontario asbestos-cement factory. American Review of Respiratory Disease 129(1984):754-
761.
Mesothelioma
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 3083612
Lung/Respiratory: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality; Mortality: Mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Domain
Metric
Rating
Comments
Additional Comments:
QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysisNOTE: this study was not evaluated for any metrics except Metric 4 and 5 and had no data extracted because it did not have sufficient exposure
information to be useful for dose-response analysis. Within this retrospective cohort study, mortality among asbestos exposed (n=535, production and
maintenance workers) and control (n=205) male employees (total n=740) of an asbestos cement pipe manufacturing factory with a minimum of one year
employment who had been hired prior to 1960 was compared with mortality of the Ontario, Canada male general population over a period of 10 to 34 years
of follow-up. Workers were divided into three groups for study: production workers involved in asbestos cement pipe manufacture, maintenance workers,
and those involved in rock wool and fiberglass insulation or other minimal exposure areas who were classified as non-exposed controls. Factory production
of asbestos cement pipe in one shed and rock wool (later fiberglass) insulation in another shed began in 1948, and asbestos cement board was produced in
a separate building from 1955 to 1970. Air sampling data from government, insurance and company hygienists initiated in late 1969 were utilized along
with company employment records to classify each production worker (n=186) according to estimated annual cumulative asbestos exposure. Air sampling
data was obtained from only later factory years (late 1969 onward) and was not representative of earlier years, although assumptions for exposure levels for
those earlier years were supported by impinger area sampling data. In the period 20 years from first exposure, the production workers had a standardized
mortality ratio of 181 for all causes of death, 320 for non-malignant respiratory disease, and 58 for ischemic heart disease.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 43 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3100548 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British lournal of Industrial Medicine
40( 1983): 138-144.
Mesothelioma
Mortality: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3100548
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Medium Key elements of the study design were reported within this retrospective cohort study
of long-term male workers in which n=339 male asbestos workers hired prior to 1960
and employed by the same company in Ontario, Canada for at least nine years were
followed until 31 October 1980 for mortality outcomes of interest. An additional n=ll
men (3.2% of the total) could not be properly classified from their work histories as
production, maintenance or rock wool/fiberglass workers and were excluded from the
current analysis. Participants were identified from company records of all hourly and
salaried employees who had worked at the plant of interest. Employees were excluded
if they did not work for at least nine years to account for the long latency of asbestos-
related diseases and difficulties of tracing short-term employees. There is no evidence
to suggest inclusion or exclusion from the sample differed significantly by outcome or
exposure status.
Low Official death certificates were obtained for all men who had died. However, a total of
five (2.7% ) of the n=186 production workers, three (5.5% ) of the n=55 maintenance
workers and five (5.7% ) of the n=87 unexposed or minimally exposed workers were
unable to be traced for mortality outcomes and were assumed still alive for analysis. A
group of 55 maintenance workers were originally included, but later excluded as the
study reported that it "was not thought possible to estimate exposures for the mainte-
nance men."
Continued on next page ...
Page 44 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 1 of 1
... continued from previous page
Study Citation:
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40( 1983): 138-144.
Mesothelioma
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 3100548
Mortality: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Domain
Metric
Rating
Comments
Metric 3: Comparison Group
Medium Inclusion criteria and methods of participant selection were reported. Workers within
the rock wool/fiber glass operations (n=87) were classified as minimally exposed, had
mortality described as similar to the general male Ontario population and were utilized
as the comparison control workers. SMR analyses results utilized the age and calendar
specific mortality experience of the male Ontario general population as a comparison
group for expected mortality rates. The mean age at the start of exposure or employment
was described as similar between the exposed and general populations. Comparison
control workers were primarily within the rock wool/fiberglass insulation production
area, although the author of the current study noted in another publication (Finkelstein
et al., 1983, HERO ID 3083612) of workers in the same factory that it was possible
for employees to be assigned to the pipe shop for brief clean-up duties, or re-assigned
from non-asbestos to asbestos work areas, such that some control workers may have
been exposed as well. There is potential for healthy worker effect in terms of left trunca-
tion bias, as the cohort for the current study was restricted to workers with at least nine
years of employment, such that all workers had to survive for at least nine years to be in-
cluded. However, Table 2 SMR results for non-malignant respiratory disease indicate no
evidence of healthy worker effect in terms of the healthy hire or healthy worker survivor
effect.
Domain 2: Exposure Characterization
Continued on next page ...
Page 45 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 1 of 1
... continued from previous page
Study Citation:
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40( 1983): 138-144.
Mesothelioma
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 3100548
Mortality: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium The microscopic method (PCM or TEM) of analysis of air sampling data reported in
Table 1 with outcome mortality rates was not detailed. The average estimated cumula-
tive exposure among production workers was reported for three groups of production
workers of 62 men each as 44 f-y/ml, 92 f-y/ml, and 180 f-y/mL (chrysotile and cro-
cidolite). Groups were created on the basis of ranking 18-year cumulative exposures.
Air sampling data from government, insurance and company hygienists initiated in late
1969 was utilized along with company employment records to classify each production
worker"s exposure, however production within the plant began in 1948 and measured
exposures for periods 1948-1970 were lacking and assumed as related to the quantita-
tive measurements made beginning in 1969. Exposures for maintenance workers was
described as not calculated due to inadequate data. Estimated cumulative exposure for
only the first 18 years of employment was utilized such that for men employed less than
18 years this parameter was used and for men employed more than 18 years, the po-
tential exposures after 18 years were excluded. Exposures were assumed to have been
unchanged from 1962 to 1970, to have been 30% higher from 1955 to 1961, and to have
been twice as high from 1948 to 1954, with assumptions supported by impinger area
sampling performed 1949 through the 1960"s. Based on subsequent discussion and
review of additional information, the rating was adjusted based on impinger data was
collected and personal membrane sampling was conducted beginning in late 1969 and
detailed employment records were used to construct exposure histories.
Medium The range and distribution of estimated exposures is reported within Table 1 for pro-
duction workers as 8 to 420 fiber-years/mL. Table 1 provides the mortality rates for
production workers across three groups of exposure categories.
High The study presents an appropriate temporality and the interval between exposure and
outcome is appropriate considering the latency of disease. Workers were required to
have been hired before 1960 and were followed up until 1980, ensuring at least 20 years
of follow-up for the cohort.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Medium Workers were followed up until 31 October 1980, and as such only pre-ICD 10 coding
was utilized as indicated for ICD codes reported in official death certificate data ob-
tained for all deaths in Table 2. Additional clinical, pathological and necropsy reports
were available for n=44 of the n=58 deaths among production workers.
Medium There were no concerns for selective reporting. SMR"s in Table 2 and mortality rates
across age and time since first exposure groups per man years in production workers
in Table 3 were reported as single values, with no measures of variation or confidence
intervals. Confidence intervals for specific outcomes were reported within the text.
Continued on next page ...
Page 46 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 1 of 1
... continued from previous page
Study Citation:
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40( 1983): 138-144.
Mesothelioma
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 3100548
Mortality: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Domain
Metric
Rating
Comments
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Other than stratification for years since first exposure and age, no additional adjustments
or consideration for differences between exposed and non-exposed groups regarding
distributions of relevant covariates were detailed. The cohort for study was restricted
to males. The authors mention that information for smoking was available for 70% of
the cohort, but this information is not used in statistical analyses. The authors state that
data was available for 9 of 11 men who had died of mesothelioma: 2 never smoked, 2
had quit for 10 or more years, and 5 were smokers. Based on subsequent discussion and
review of additional information, the rating was adjusted based on stratification by age
and only males being included in the study.
Medium Finkelstein, 1982 provides evidence of detailed personnel files use for TSFE, age, job
history, etc.
N/A This metric is not applicable for mesothelioma.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design was appropriate as an early study to address the research aims. Two
types of comparisons were performed, internal and external. Table 2 SMR results were
obtained through external comparisons by applying the Ontario general population mor-
tality rates as reference and presented for production, maintenance and control workers.
Table 3 mortality rate results were presented for production workers stratified across age
and years since first exposure groups. Tests for trend were not reported.
Medium The number of participants was adequate, however formal statistical comparisons be-
tween exposed and non-exposed workers, or across time since first exposure groups,
were not presented. SMR results in Table 2 were reported for the n=328 workers, while
results in Table 3 were reported only for the n=186 production workers.
Medium The data are presented in Table 1 that were used used in the 1986 analysis. Reporting
errors are present in Table 2, but these data are not used in the 1986 analysis.
Medium Model building was not conducted. The construction of SMRs appears appropriate.
Additional Comments: This was an occupational retrospective cohort study reporting SMRs of long-term male workers in which n=339 male asbestos workers hired prior to 1960
and employed by the same company in Ontario, Canada for at least nine years were followed until 31 October 1980 for mortality outcomes of interest.
Concerns included the assumption that workers unable to be traced for mortality outcomes were still alive at the end of follow-up, with no sensitivity
analyses conducted to examine results with and without these workers. Mesothelioma mortality was obtained utilizing pre-ICD 10 coding. Exposure
concentrations are provided for three groups of exposure in relation to a reference population of Ontario men by outcome - however, no statistical analysis
is done to compare mortality using exposure concentration data, limiting the study's usefulness for dose-response analysis.
Continued on next page ...
Page 47 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 1 of 1
Study Citation:
... continued from previous page
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40( 1983): 138-144.
Mesothelioma
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 3100548
Mortality: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Domain Metric
Rating
Comments
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 48 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709685 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Finkelstein, M. M. (1985). A study of dose-response relationships for asbestos associated disease. British Journal of Indus trial Medicine 42(1985):319-325.
Mesothelioma
Lung/Respiratory: Mesothelioma mortality; Mortality: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
709685
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not ex-
plicitly mention the use of PCM or TEM.Air sampling was conducted by different enti-
ties including the government, the asbestos cement company, and insurance hygienists
(Finkelstein, 1982, HEROID: 76). Measurements were primarily made through impinger
area sampling (Finkelstein, 1982, HEROID: 76). In 1969, personal membrane filters
were used (Finkelstein, 1982, HEROID: 76). Because of the infrequent consistency of
reporting exposure, extrapolations were needed for missing time frames (Finkelstein,
1982, HEROID: 76).Authors described the following for calculation expose and dose
estimation: "Cumulative exposures were calculated for each man by summing annual
exposures accumulated during the first 18 years from the start of exposure. Asbestos
dosages were calculated by assuming that a fixed proportion of the workplace air con-
centrations were deposited in the lungs, and each year's accumulation was weighted by
the residence time in lung tissue (the formulas used are given in the appendix). Cumula-
tive exposures had been estimated to be accurate to within a factor of 3 to 5."
Medium The distribution of exposure appears to be sufficient to develop an exposure-response
estimate. Cumulative exposure (f-y/ml) and dose (f/ml*yr-squared) for calculating cu-
mulative risk were utilized in statistical models. Range or other measure distribution is
not present in this paper, however Figure 3 shows values ranging from 0-6,500 fibers/mL
x yearA 2.
Additional Comments: Finklestein et al, 1985 709685 was not evaluated for any metrics except Metric 4 and 5 and had no data extracted because it did not have sufficient exposure
information to be useful for dose-response analysis. QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient
exposure information to be useful for dose-response analysis.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 49 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3520653 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Franklin, P., Alfonso, H., Reid, A., Olsen, N., Shilkin, K. B., Brims, F., de Klerk, N., Musk, A. W. (2016). Asbestos exposure and histological subtype of
malignant mesothelioma. Occupational and Environmental Medicine 73(2016):749-752.
Mesothelioma
Cancer/Carcinogenesis: malignant mesothelioma (cytology only), malignant mesothelioma (sarcomatoid), malignant mesothelioma (biphasic), malignant
mesothelioma (epithelioid); Lung/Respiratory: malignant mesothelioma (biphasic), malignant mesothelioma (epithelioid), malignant mesothelioma (cy-
tology only), malignant mesothelioma (sarcomatoid)
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4
733541, 709469, 3079298, 3520653, 3531364, 6868332
3520653
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low This metric is rated Low. The exposures used to calculate the effect estimates reported
in Table 2 stemmed from data that came from historical records like questionnaires
and clinical documents. Questions about asbestos exposure covered various charac-
teristics including "duration of exposure (for occupational cases only), time since first
exposure, source of asbestos exposure (occupational or non-occupational), form of as-
bestos handled (raw, processed or unclear), type of asbestos (crocidolite only or mixed
fibres) and cumulative exposure (for crocidolite only)." Measurements of these char-
acteristics did not suggest the use of PCM or TEM. "Additionally, cited methods for
exposure measurement based on historical records reported the following: Armstrong
et al., 1986 3083076 did not use either PCM or TEM. Counting method was with a
Casella long running thermal precipitator."Hansen et al., 1997 2219991 described that
the first survey to count fiber was in 1966, which was done by an industrial hygienist
using a Casella long running thermal precipitator. All samples examined in this partic-
ular study were analyzed using the standard membrane filter method. Some exceptions
were surveys in 1984 and 1986 which used SEM, and in 1992 which used TEM. So,
their latest samples were analyzed using TEM. However, the study being evaluated does
not describe estimates in a way to know outcomes based on exposures measured from
1992 and after. Based on Table 1, time since first exposure was over 40 years for this
sample of mesothelioma cases so I presume peak exposure for them was way before
1992."Lastly, these papers described methods for those tied to Wittenoom so it's still
not clear how exposure measurements were conducted for those who reported exposure
unrelated to Wittenoom."Analysis of lung specimens from select cases (n=122) did mea-
sure asbestos fibers via TEM, and estimates are reported in Table 4. However, they were
non-regression and non-SMR.
Metric 5: Exposure Levels Low Regression analyses only present exposure in terms of "exposed vs. unexposed" and thus
have a limited range of exposure.
Additional Comments: Due to "Low" ratings for both Metric 4 and Metric 5, this study was determined not to be useful for dose-response analysis and thus did not receive a full
evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 50 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083223 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gardner, M. J., Winter, P. D., Pannett, B., Powell, C. A. (1986). Follow up study of workers manufacturing chrysotile asbestos cement products. British
Journal of Industrial Medicine 43(1986):726-732.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3083223
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
Atmospheric fibre concentrations were made during period 1968-82 by company and
were assigned codes to job ittles to reflect levels of probable exposure (table 2). Over
70% of readings are based on use of personal samplers. "For the period before 1968 it
would be reasonable to assume that levels were higher because of less extensive exhaust
ventilation and more direct handling of raw asbestos".
"Since 10=970 fibre levels have generally bene low with mean levels under 1 f/ml
throughout factory. Only a few exposures over 2f/ml have been recorded and most mea-
sured concentrations have been under 0.5f/ml."
Additional Comments: Overall, information on the measurement of exposure metric (M4) to assess exposure was limited. Additionally, the exposure levels metric (M5) information
reported was limited to determine exposure-response relationships.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 51 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3077660 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015). Pleural
mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental Medicine 73(2015):290-
299.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma cases and mesothelioma mortality; Lung/Respiratory: Mesothelioma cases and mesothelioma mortality; Mortality:
Mesothelioma cases and mesothelioma mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3077660
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection Medium This study built on a case-control study referred to as the MALCS study (Rake et al.,
2009, HERO ID 733522). Telephone interviews of 622 mesothelioma patients and 1420
population controls in England, Wales, and Scotland were conducted between 2001
and 2006 as part of the MALCS study. Additionally, 420 patients with resected lung
cancer born since 1940 were interviewed as controls for the mesothelioma patients as
part of the present study (Gilham et al., 2015, HERO ID 3077660), though the dates of
these interviews were not specified.Patients with lung cancer and mesothelioma were
identified through physicians, nurses, and Hospital Episode Statistics (HES) notifica-
tions from 170 hospitals throughout Britain. Detailed selection methods are provided
in the MALCS paper (Rake et al., 2009, HERO ID 733522). In the cited MALCS case-
control study paper, it was reported that the exclusion criteria for both mesothelioma
cases and population controls were: being "physically or mentally unfit for interview",
not having access to a telephone, or not speaking English (Rake et al., 2009, HERO ID
733522).The MALCS paper reported "Overall 39% of 1396 notified mesothelioma pa-
tients (423 too ill or dead, 87 no GP or consultant permission and 31 ineligible or not
traced) and 18% of 2897 controls (169 too ill or dead, 169 no permission, 191 ineligible
or untraced) were not invited for interview. The proportion of those invited who were
interviewed, sometimes after several reminders, consisted of 73% (624 out of 857) of
mesothelioma cases and 60% (1420 out of 2368) of controls. As expected, response
rates in controls were higher in more affluent areas (69% in the top two quintiles of so-
cioeconomic status and 46% in the lowest)." The analysis of lung samples in the present
paper was conducted on mesothelioma patients and lung cancer patients, but not the
population controls from the MALCS study. The present paper (Gilham et al., 2015,
HERO ID 3077660) reported that written informed consent was obtained from 346 (77%
) patients with mesothelioma and their next of kin for postmortem samples to be ana-
lyzed and from 406 (96% ) patients with lung cancer for analysis of resected tissue."
Thus, although some elements were not present, the available information does not indi-
cate substantial risk of selection bias.
Continued on next page ...
Page 52 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077660 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015). Pleural
mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental Medicine 73(2015):290-
299.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma cases and mesothelioma mortality; Lung/Respiratory: Mesothelioma cases and mesothelioma mortality; Mortality:
Mesothelioma cases and mesothelioma mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3077660
Domain Metric Rating Comments
Metric 2: Attrition Medium The authors reported that "written informed consent was obtained from 346 (77% ) pa-
tients with mesothelioma and their next of kin for postmortem samples to be analyzed
and from 406 (96% ) patients with lung cancer for analysis of resected tissue." The use
of postmortem samples for mesothelioma patients indicates that the analyses could not
include samples from mesothelioma patients who were still alive. The use of resected
tissue for lung cancer patients implies that the lung cancer patients may have been alive
at the time of sample collection. The authors reported that samples were analyzed as
they became available, such that transmission electron microscopy (TEM) was per-
formed on 133 mesothelioma samples and 262 lung cancer samples. All of the analyzed
samples were from patients born since 1940, with the exception of 11 female mesothe-
lioma patients born between 1925-1939, who were excluded from most of the analyses.
Thus, lung samples were analyzed for 133/346 (38% ) of the mesothelioma patients and
262/406 (65% ) of the lung cancer patients for whom consent was obtained. Thus, there
was at least moderate exclusion from the analysis sample.
Metric 3: Comparison Group Medium The authors selected lung cancer patients as the control group for mesothelioma pa-
tients because "resected lung cancers provide the only adequate national source of lung
samples in people who can be identified systematically, are available for interview and
have an age distribution similar to mesothelioma. Only a small proportion of all lung
cancers are caused by asbestos, so the asbestos lung burdens of this national sample are
reasonably representative of the general population except for a few per cent with very
high burdens."The cited MALCS study indicated that information obtained via interview
included smoking histories and potential environmental exposures (Rake et al., 2009,
HERO ID 733522), but it is unclear whether the mesothelioma patients and the lung
cancer patients differed on these variables. The statistical analyses adjusted for period
of birth and sex, although neither was statistically significant. Several analyses were
restricted to only males due to the small number of females.In addition to comparison
of mesothelioma cases to lung cancer cases, "the lifetime risk (probability of dying by
age 90) was calculated actuarially in each lung burden category assuming current (2013)
UK rates for all other causes of death. These lifetime risks were standardized to the
projected probabilities of dying by age 90 for mesothelioma (0.86% ) and lung cancer
(4.67% ) of all British men born in 1945." SMRs in each lung burden category were de-
termined "for the cohort of British men whose central date of birth is the beginning of
1945, (The median date of birth of our mesothelioma cases was September 1944.)"Thus,
information about some demographic and exposure variables was not available to com-
pare between groups. For example, race was not mentioned. However, age and sex were
addressed in the analyses.
Continued on next page ...
Page 53 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077660 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015). Pleural
mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental Medicine 73(2015):290-
299.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma cases and mesothelioma mortality; Lung/Respiratory: Mesothelioma cases and mesothelioma mortality; Mortality:
Mesothelioma cases and mesothelioma mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3077660
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Medium
Metric 5: Exposure Levels
Metric 6: Temporality
Medium
Low
Lifetime occupational history was obtained from telephone interviews of 622 mesothe-
lioma patients, 1420 population controls, and 420 patients with resected lung cancer.
Then "job titles were assigned to Standard Occupational Classification 1990 (SOC 90)
and Standard Industrial Classification 1992 (SIC 92) codes and grouped into main job
categories" (Gilham et al., 2015, 733522). The authors reported that "subjects were as-
signed to the highest-ranking occupation they had worked in irrespective of duration".
Thus, although lifetime work history was obtained, the assignment of occupation was
based on only a portion of this history.Transmission electron microscopy (TEM) was
used to analyze 133 post-mortem lung tissue samples from a subset of the mesothelioma
patients and 262 resected lung tissue samples from a subset of the lung cancer patients.
The authors reported that "lung samples were anonymized and sent to the Health and
Safety Laboratory (HSL) for TEM counting of asbestos fibers longer than 5 um."Lung
tissue samples were analyzed as they became available. Because tissue samples, but
not environmental samples, were analyzed, the samples were only analyzed at one time
point for each individual, but this time point is representative of cumulative asbestos
lung fiber burden.
The range and distribution of exposure, expressed as million fibers longer than 5 um per
dry gram (mf/g) asbestos lung burden and displayed in Table 1, was sufficient to develop
an exposure-response relationship, as shown in Figure 2.
The exposure measurement of asbestos burden in lung tissue occurred post-mortem
for mesothelioma patients. Since the diagnosis of these patients was determined while
they were alive, the exposure measurement was obtained after the outcome measure-
ment. However, the study also included occupational history data, which indicates oc-
cupational exposures that occurred before death from mesothelioma. Some possibility
remains that some of the fiber accumulation that was assessed after death could have
occurred after disease development. Therefore, the temporality of exposure and outcome
is uncertain.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or High The authors state that lung cancer and mesothelioma patients were "identified through
Characterization chest physicians, lung cancer nurse specialists and Hospital Episode Statistics (HES)"
from 170 hospitals throughout Britain (Gilham et al., 2015, HERO ID 733522). The
MALCS study methods paper says that "histological confirmation was obtained for 92%
of interviewedmesothelioma cases" (Rake et al., 2009, HERO ID 733522).
Continued on next page ...
Page 54 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077660 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015). Pleural
mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental Medicine 73(2015):290-
299.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma cases and mesothelioma mortality; Lung/Respiratory: Mesothelioma cases and mesothelioma mortality; Mortality:
Mesothelioma cases and mesothelioma mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3077660
Domain
Metric
Rating
Comments
Metric 8:
Reporting Bias
Medium
Mesothelioma findings are reported throughout the paper. Some of the estimates are
reported with confidence intervals, such as in Table 1, while others are not, such as in
Table 3 (Gilham et al„ 2015, HERO ID 3077660).
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium The analyses adjusted for sex and age but did not adjust for race. In Table 1, the odds
ratios are adjusted for sex and period of birth (1940-1944, 1945-1949, 1950-1954, and
1955+), although neither was statistically significant.
Medium Although the authors did not discuss whether the questionnaires used to interview par-
ticipants were validated, there is no evidence to suggest any concerns about the validity
of the method. It is unlikely that the participants would have incorrectly reported sex or
age.
N/A The assessment of potential co-exposures was not necessary for mesothelioma because
there are few other causes of mesothelioma.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design used appropriate statistical methods including odds ratios and logistic
regression for case-control analyses, and SMR for comparison to the British population.
Medium Although the authors did not provide an explicit discussion of power, there was an ad-
equate number of participants such that an association was observed between asbestos
lung burden and mesothelioma.
Medium The analyses were described in sufficient detail in the paper and in "Appendix 1: Statis-
tical Methods" (Gilham et al„ 2015, 3077660).
Medium Although some details could have been explained better, the methods for calculating the
risk estimates were sufficiently transparent.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric 16: Use of Biomarker of Exposure High This study asbestos used fiber concentrations in lung tissue samples as a biomarker of
asbestos exposure, which has a clear relationship with target dose. Transmission elec-
tron microscopy (TEM) was used to measure this biomarker. In the lung cancer and
mesothelioma lung tissue samples assessed in this study, 75% of the counted fibers were
amosite, 18% were crocidolite, 1.9% were chrysotile, 1 % were tremolite, 2 % were
anthophyllite, 0.6% were actinolite, and 1.7% were uncharacterized amphiboles. Thus,
several different fiber types were identified in this study because TEM can distinguish
between fiber types, thus determining specific biomarkers of exposure (fiber concentra-
tions in lung tissue) for each specific fiber type.
Continued on next page ...
Page 55 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077660 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015). Pleural
mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental Medicine 73(2015):290-
299.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma cases and mesothelioma mortality; Lung/Respiratory: Mesothelioma cases and mesothelioma mortality; Mortality:
Mesothelioma cases and mesothelioma mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3077660
Domain
Metric
Rating
Comments
Metric 17: Effect Biomarker
Metric 18: Method Sensitivity
Metric 19: Biomarker Stability
Metric 20: Sample Contamination
Metric 21: Method Requirements
Metric 22: Matrix Adjustment
N/A The only biomarkers assessed were biomarkers of exposure. Biomarkers of effect were
not assessed.
Medium As described in Appendix 2, the analytical sensitivity for fiber counts was 0.01 million
fibers per dry gram. Only 2.8% of all samples, and 2/133 mesothelioma samples, did
not achieve this sensitivity due to low fiber concentrations and high amounts of other
particles. The sensitivity was later increased to 0.003 mf/g by using newer equipment
for a selected subgroup of samples.
Low All lung tissue samples were sent to a pathology laboratory in Leeds for an initial as-
sessment and preparation and then were sent to the Health and Safety Laboratory (HSL)
for TEM analysis. Specific preparation for storage and transport was not detailed,
though it was mentioned that blocks were waxed and de-waxed. The authors did not
specifically discuss the stability of the biomarker.
High The authors detail that "new disposable containers and filtration equipment were used
for each sample to avoid cross-contamination and a process blank was run with each
batch of analyses" (Gilham et al., 2015, 3077660)
High The use of transmission electron microscopy enabled appropriate identification and
quantification of asbestos fibers in the samples.
N/A Matrix adjustment is not required for assessment of this biomarker.
Additional Comments: This study built on the MALCS case-control study by comparing asbestos lung burden in a subset of the mesothelioma patients from the MALCS study
to that of a sample of patients with lung cancer. The study also assessed SMR in comparison to the British male population born in 1945. The strengths
of the study include the use of transmission electron microscopy for the quantification of asbestos fibers in lung tissue samples, and description of details
pertaining to method sensitivity and statistical methods. There were some limitations due to the comparison groups used (lung cancer cases and the British
male general population born in 1945). Some methodological details were unclear or were not described in sufficient detail. For example, the authors stated
that consent was obtained for postmortem samples from mesothelioma patients and resected tissue from lung cancer patients. It is unclear what proportion
of the lung cancer patients were alive at the time of sampling, or why the number of samples analyzed was substantially lower than the number of consent
forms received.
Overall Quality Determination Medium
Page 56 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6869402 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Gilham, C., Rake, C., Hodgson, I., Darnton, A., Burdett, G., Peto Wild, J., Newton, M., Nicholson, A. G., Davidson, L., Shires, M. (2018). Past and current
asbestos exposure and future mesothelioma risks in Britain: The Inhaled Particles Study (TIPS). International Journal of Epidemiology 47(2018): 1745-
1756.
Mesothelioma
Mortality: mesothelioma mortality; Cancer/Carcinogenesis: mesothelioma mortality; Lung/Respiratory: mesothelioma mortality
Asbestos - Tremolite: 14567-73-8; Asbestos - Not specified: 1332-21-4; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9;
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
6869402
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Medium
Metric 2:
Attrition
Medium
Metric 3: Comparison Group
Medium
This study estimated the average asbestos lung burden among all individuals in the
United Kingdom (UK) born in each of 5 time periods: 1940-44, 1945-49, 1950-54,
1955-59, and 1960-64. The study then estimates the association between the average
lung burden estimated among individuals in each time period (referred to as "birth co-
horts") and the corresponding national cumulative mesothelioma mortality rate by age
50. The unit of analyses is the birth cohort rather than the individual. Lung cancer and
mesothelioma patients in the Inhaled Particle Study (TIPS) were from a hospital-based
case-control study. Since each cohort includes all individuals born in the UK between
1940-1964 and this is a national study, bias due to selection criteria may not be a con-
cern.
The study interviewed and measured asbestos levels in lung samples from 257 patients
treated for pneumothorax and 262 with resected lung cancer. This resected lung cancer
and mesothelioma patients are from a national case-control study and they are born in
the United Kingdom during 1940-1964, with the analytic dataset constructed from ad-
ministrative data (e.g., birth records, death records). All eligible pneumothorax patients
recruited from 13 hospital centers in England and Wales Overall 42% of them them
replied agreeing to be interviewed, of whom 91% gave consent for their lung material
to be analyzed. The exclusion of subjects from analyses was adequately addressed, and
reasons were documented.
This aim of the Inhaled Particle Study (TIPS) were to determine whether the linear re-
lationship between mesothelioma risk and asbestos lung burden in individuals is also
seen in national mesothelioma death rates and population average burdens, and to pre-
dict future occupational and environmental mesothelioma rates from the lung burdens of
exposed workers and of the general population born since 1965. Analyses are stratified
by sex and year of birth, and groups are comparable with respect to age by definition
(i.e., the mortality rate by age 50 is computed for each group defined by birth year).
The authors do not discuss other potential factors that could be different between birth
cohorts and could be related to mesothelioma mortality. Given that this study involves
comparisons made over time, it is possible that improvements in treatment (such that
individuals born in later cohorts who develop mesothelioma are more likely to live past
the age of 50 than individuals born in earlier cohorts) could affect the results observed in
this study. However, there is no evidence to support or refute this possibility in the study.
Domain 2: Exposure Characterization
Continued on next page .
Page 57 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6869402 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Gilham, C., Rake, C., Hodgson, J., Darnton, A., Burdett, G., Peto Wild, J., Newton, M., Nicholson, A. G., Davidson, L., Shires, M. (2018). Past and current
asbestos exposure and future mesothelioma risks in Britain: The Inhaled Particles Study (TIPS). International lournal of Epidemiology 47(2018): 1745-
1756.
Mesothelioma
Mortality: mesothelioma mortality; Cancer/Carcinogenesis: mesothelioma mortality; Lung/Respiratory: mesothelioma mortality
Asbestos - Tremolite: 14567-73-8; Asbestos - Not specified: 1332-21-4; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9;
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
6869402
Domain
Metric
Rating
Comments
Metric 4:
Measurement of Exposure
Medium
This study estimated the association between average asbestos lung burdens among all
individuals born in the UK in 5-year increments between 1940-1964 and national rates
of mesothelioma mortality by age 50. Average asbestos lung burdens for the entire UK
population in each cohort was estimated via a job-exposure matrix developed from TEM
asbestos fiber counts in lung tissue in a sample of 262 lung cancer patients (resected
1999-2010), 133 pleural mesothelioma patients (resected postmortem), and 271 pneu-
mothorax patients (surgically treated 2002-2010). The justification for the "medium"
rating is due to the development of a JEM for the entire UK population based on fiber
counts in a small number of patients.
Metric 5:
Exposure Levels
Medium
Table 2 showed the male amphibole lung burden from occupational exposure at three
exposure levels (high risk, medium risk and any occupational exposure) in the year of
birth 1940-54.
Metric 6:
Temporality
Medium
The outcome measure in this study is the rate of mesothelioma mortality by age 50.
For individuals who are primarily exposed in the environment, particularly if exposure
occurs early in life or in young adulthood, this may reflect adequate follow-up time (e.g.,
> 20 years). For individuals who are primarily exposed in the workplace, the restriction
of the outcome measure to mortality by age 50 may not ensure adequate follow-up in
some cases, particularly if exposure occurred in mid-life.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High
High
The paper states that national mesothelioma death rates by age 50 were obtained from
the Health and Safety Executive (HSE) (Health and Safety Executive, 2017, no HERO
ID). Tables available from HSE indicate that mesothelioma cases were identified by
searching death records for mention of mesothelioma. The available information does
not state whether or not all death record fields were searched.
All findings described in the methods section and statistical appendix are reported on
in the results section and/or in the figures and tables. Effect estimates from regression
models include 95% confidence intervals.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Low While analyses are stratified by sex and age is accounted for by design, the study does
not describe whether other factors that differ between groups could be related to the out-
come, and no additional adjustment is made in regression models (i.e., there is indirect
evidence that considerations were not made for confounder adjustment).
Continued on next page ...
Page 58 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6869402 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gilham, C., Rake, C., Hodgson, J., Darnton, A., Burdett, G., Peto Wild, J., Newton, M., Nicholson, A. G., Davidson, L., Shires, M. (2018). Past and current
asbestos exposure and future mesothelioma risks in Britain: The Inhaled Particles Study (TIPS). International lournal of Epidemiology 47(2018): 1745-
1756.
Mesothelioma
Mortality: mesothelioma mortality; Cancer/Carcinogenesis: mesothelioma mortality; Lung/Respiratory: mesothelioma mortality
Asbestos - Tremolite: 14567-73-8; Asbestos - Not specified: 1332-21-4; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9;
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
6869402
Domain
Metric
Rating
Comments
Metric 10:
Covariate Characterization
High
The methods for assessing the covariates considered in this analysis (age, sex) were not
explicitly described, but can be reasonably assumed to have been assessed using either
birth or death records.
Metric 11:
Co-exposure Counfounding
N/A
Co-exposures are not discussed in this paper.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The method used to analyze data in this study was a linear regression of average as-
bestos lung burdens and cumulative mesothelioma mortality rates by age 50, where
the unit of analysis was the birth cohort rather than the individual. Lifetime occupa-
tional histories were obtained from resected lung cancer and mesothelioma patients in
a national case-conrol study. These methods are appropriate to the research question
described in the paper.
Uninformative The unit of analysis in the regression model constructed in this paper was the birth co-
hort rather than the individual. More specifically, for each of 5 birth cohorts consisting
of all individuals born in the UK within a 5-year period, the exposure entered into the
model was the average asbestos lung burden for the entire cohort, and the outcome en-
tered in the model was the cohort's cumulative mesothelioma mortality rate by age 50.
While each cohort consists of a large number of individuals, the total number of data
points in the regression model is n=5 due to aggregation to the cohort level. As such, the
statistical power of the regression model is likely limited.
Medium The description of the analysis is detailed enough to conceptually reproduce the analy-
sis.
Medium Detailed information regarding the form and variables of the linear regression model
are provided in the statistical appendix of this paper. The distribution of lung burden ins
approximately lognormal (Figure 1).
Additional Comments:
This paper uses linear regression to assess the relationship between average asbestos lung burden estimated across all individuals born in the United
Kingdom within each of 5 time windows (1940-44, 1945-49, 1950-54, 1955-59, and 1960-64) and each group's corresponding cumulative mesothelioma
mortality rate by age 50. In addition to this analysis of observed data, the paper develops predictions of future mesothelioma rates to age 90 in these groups,
as well as predictions of future mesothelioma rates among individuals born more recently. Chrysotile fibers were also analyzed in the lung tissue samples
used to develop exposure estimates but were excluded from regression analyses.
Overall Quality Determination
Uninformative
* No biomarkers were identified for this evaluation.
Page 59 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 675185 Table: 1 of 1
Hagmar, L., Akesson, B., Nielsen, J., Andersson, C., Linden, K., Attewell, R., Moller, T. (1990). Mortality and cancer morbidity in workers exposed to
low levels of vinyl chloride monomer at a polyvinyl chloride processing plant. American Journal of Industrial Medicine 17(1990):553-565.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Cancer/Carcinogenesis: mesothelioma mortality; Mortality: mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
675185
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
Estimates of asbestos exposure were obtained from breathing zone samples conducted in
1971 and 1975. Details on the sampling method were minimal. Other time periods were
not sampled, but industrial hygienists estimated job- and department-specific . Time-
weighted averages were assumed to be 40% lower after 1969 compared to prior years.
Cumulative exposure was determined by adding years of exposure.
For cancer mortality, SMRs were calculated without stratification, indicating two levels
of exposure (exposed and unexposed).
Additional Comments: This study utilized an occupational cohort to examine the relative mortality rates for mesothelioma compared to the general population. SMRs calculated
for mesothelioma were not specific to mesothelioma, including other lung cancer mortality. As a result, the results are difficult to interpret for mesothelioma
alone.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 60 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709618 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Hansen, J., de Klerk, N. H., Musk, A. W., Hobbs, M. S. T. (1998). Environmental exposure to crocidolite and mesothelioma: Exposure-response relation-
ships. American Journal of Respiratory and Critical Care Medicine 157(1998):69-75.
Mesothelioma
Lung/Respiratory: Lung cancer mortalityLung cancer incidenceRespiratory system mortalityMesothelioma incidenceMesothelioma mortality; Cancer/
Carcinogenesis: Mesothelioma incidenceMesothelioma mortalityLung cancer incidenceLung cancer mortalityCancer incidence, all and specific types (SIRs
for exposed/gen pop, no dose-reponse)Cancer mortality, all and specific types (SMRs for exposed/gen pop, no dose-response); Mortality: Mesothelioma
mortalityLung cancer mortality All-cause mortality (SMR for exposed/gen pop, no dose-response)Respiratory system mortality (SMR for exposed/gen
pop, no dose-response)Digestive system mortality (SMR for exposed/gen pop, no dose-response)Signs/symptoms ill-defined (SMR for exposed/gen pop,
no dose-response)Nervous system mortality (SMR, no dose-response)
Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): 709618, 709466, 709501, 2088306, 6869529
709618
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Medium As detailed in Hansen et al. 1998, 709618, the Wittenoom residents" cohort recruited
all individuals who: (i) lived in Wittenoom for >1 month between 1943 and 1993 and
(ii) had not been employed in the asbestos industry. Cohort size varied slightly with
updates over time, including 4,768 participants (2608 women, 2160 men) at the end of
2000 (Reid 2008 709466; Reid 2006 709501). Members were identified using multiple
sources to identification of former residents (e.g., doctors/hospitals, schools, vitamin A
trial participants, former asbestos workers), but inclusion rates cannot be determined.
The authors reduced the likelihood of "healthy resident" bias by including persons with
only 1 month of residence over a wide span of time. However, by 1993 when 27 cases
had been identified in residents, 17 additional mesotheliomas were identified among
individuals who resided in Wittenoom for less than one month. Although suggests that
exposure durations of less than one month are relevant, according to the authors, all of
these cases had reportedly worked with asbestos and likely had more intense exposure
(Hansen et al 1998 709618). The authors did not discuss the number of non-workers
identified who resided at Wittenoom for less than one month.
Medium In Hansen et al 1998 (709618), about 29% of the cohort could not be traced. The re-
maining studies, published after 2000, reported 20% loss to follow-up (e.g., Reid 2018
6869529). The extent to which this attrition may be selective is not known, since char-
acteristics of untraced subjects (e.g., age, sex) were not described. However, the authors
partially addressed attrition bias at the analysis stage in several papers (Reid et al. 2012,
2088306; Reid et al. 2018, 6869529) by comparing the impact of different censoring as-
sumptions for subjects lost to follow-up. Alternative analyses assumed these persons: (i)
were all still alive until censored at age 85y; vs. (ii) were eligible to contribute person-
years until the last date their status or age 85y. The first method likely overestimates and
the second underestimates person-years at risk.
Continued on next page ...
Page 61 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709618 Table: 1 of 1
... continued from previous page
Hansen, J., de Klerk, N. H., Musk, A. W., Hobbs, M. S. T. (1998). Environmental exposure to crocidolite and mesothelioma: Exposure-response relation-
ships. American lournal of Respiratory and Critical Care Medicine 157(1998):69-75.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Lung cancer mortalityLung cancer incidenceRespiratory system mortalityMesothelioma incidenceMesothelioma mortality; Cancer/
Carcinogenesis: Mesothelioma incidenceMesothelioma mortalityLung cancer incidenceLung cancer mortalityCancer incidence, all and specific types (SIRs
for exposed/gen pop, no dose-reponse)Cancer mortality, all and specific types (SMRs for exposed/gen pop, no dose-response); Mortality: Mesothelioma
mortalityLung cancer mortality All-cause mortality (SMR for exposed/gen pop, no dose-response)Respiratory system mortality (SMR for exposed/gen
pop, no dose-response)Digestive system mortality (SMR for exposed/gen pop, no dose-response)Signs/symptoms ill-defined (SMR for exposed/gen pop,
no dose-response)Nervous system mortality (SMR, no dose-response)
Asbestos - Crocidolite (riebeckite): 12001-28-4
709618, 709466, 709501, 2088306, 6869529
709618
Domain Metric Rating Comments
Metric 3: Comparison Group Medium Within-cohort analyses were used to estimate associations between mesothelioma and
exposure. Analysis samples included all identified eligible residents, avoiding bias
due to questionnaire non-response (47% non-response reported in Hansen et al. 1998,
709618). Because a high proportion (41% ) of the cohort identified from doctors, hos-
pitals, and schools or a vitamin A trial (14% ) there may have been some bias in favor
of including less healthy short-term residents (Reid et al., 2008 709466; Hansen et al.
1998, 709618). Western Australia data was used as a referent for SMRs; the authors
described ascertainment as almost complete (Reid et al., 2007, 2088306). Expected mor-
tality for 1950-1969 was extrapolated from 1970-74 as period specific rates were not
available.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium Residential exposure estimates were based on a series of fiber measures initiated in 1966
(Hansen et al. 1997, 2219991). A 1966 value of 0.5 f/mL was based on measures taken
prior to the mill/mine closure in 1966 (0.5 f/mL), and subsequent values were interpo-
lated through 1992 using measures from personal and/or fixed monitors: 1973 (median
0.22 f/mL), 1977, and 1978 using PCM counts; 1984 and 1986 using scanning elec-
tron microscopy (SEM); and 1992 using TEM. The 1966 outdoor fiber samples were
recounted in 1986 using PCM and updated guidelines according to Rogers and Major
2002 (3080506). Since 1948-1966 measures (1948-1966) were of dust by konimeter,
intensity prior to the 1958 new mill was extrapolated as 1.0 f/mL based on estimates
that the exposure was halved (Hansen 2219991). Concerns include the limited num-
ber, location, and quality of samples, as well as less precise SEM. Cumulative exposure
was calculated based on duration of residence, assuming 24 h a day, 7 d a week expo-
sure. Duration estimates used: (i) detailed mesothelioma registry data; (ii) questionnaire
responses, worker employment dates for relatives, or family member questionnaires
if available; (iii) records at hospitals, schools, etc; and (iv) a value of 6 months if still
unknown. Proportions estimated using each method were not shown. An important
concern is potential for differential measurement error by mesothelioma case status.
Another source of error includes the lack of information on specific locations and ac-
tivities that would affect individual exposure (only lived with, likely washed clothes of
an asbestos worker were estimated). The most recent study indicated that exposure was
missing for about 5% of the sample (Reid et al. 2018, 6869529).
Continued on next page ...
Page 62 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709618 Table: 1 of 1
... continued from previous page
Hansen, J., de Klerk, N. H., Musk, A. W., Hobbs, M. S. T. (1998). Environmental exposure to crocidolite and mesothelioma: Exposure-response relation-
ships. American lournal of Respiratory and Critical Care Medicine 157(1998):69-75.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Lung cancer mortalityLung cancer incidenceRespiratory system mortalityMesothelioma incidenceMesothelioma mortality; Cancer/
Carcinogenesis: Mesothelioma incidenceMesothelioma mortalityLung cancer incidenceLung cancer mortalityCancer incidence, all and specific types (SIRs
for exposed/gen pop, no dose-reponse)Cancer mortality, all and specific types (SMRs for exposed/gen pop, no dose-response); Mortality: Mesothelioma
mortalityLung cancer mortality All-cause mortality (SMR for exposed/gen pop, no dose-response)Respiratory system mortality (SMR for exposed/gen
pop, no dose-response)Digestive system mortality (SMR for exposed/gen pop, no dose-response)Signs/symptoms ill-defined (SMR for exposed/gen pop,
no dose-response)Nervous system mortality (SMR, no dose-response)
Asbestos - Crocidolite (riebeckite): 12001-28-4
709618, 709466, 709501, 2088306, 6869529
709618
Domain
Metric
Rating
Comments
Metric 5:
Exposure Levels
Medium
Cumulative exposure (f/mL-years) was analyzed with respect to mesothelioma as a
continuous variable in all 4 papers, and in some studies using 3 or more categories. The
estimated mean (SD) was on the order of 5.5 (8.0) f/mL year (Reid et al. 2007, 709501).
Variability was adequate overall and in sub-group analyses (e.g., in individuals exposed
as children median [IQR] = 3.3 [1.4-7.5], range 0.1 to 64.4; Reid et al., 2012 2088306).
Metric 6:
Temporality
High
All analyses had appropriate sequencing and lengthy follow-up. In the earliest analysis
with follow-up through 1993 (Hansen et al. 1998, 709618), only 12.5% of the cohort
had a lag of less than 20 years since first residence at Wittenoom. Subsequent analy-
ses had follow-up through 2002 or later (Reid et al. 2007, 709501). In the most recent
analysis (of mortality through 2014), the mean time since first exposure was 51 years in
children and 42 years in adults (Reid et al. 2018, 6869529).
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Medium
Record linkage to official sources was used was used to identify mesotheliomas; link-
age methods were not described. Mesotheliomas were identified by the Western Aus-
tralia Mesothelioma Registry (part of the regional cancer registry) and the Australian
Mesothelioma Surveillance Programme. ICD codes for mesothelioma were not pro-
vided, but a 2005 Western Australia Cancer Registry report ("Cancer in Western Aus-
tralia: Incidence and mortality 2003 and Mesothelioma 1960-2003") provided tables
indicating that over 95% of mesotheliomas were microscopically confirmed since 1960.
Metric 8:
Reporting Bias
High
Results for mesothelioma analyses were presented adequately and appropriately in all
papers.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
High
Associations between mesothelioma and cumulative asbestos exposure were adjusted
for age and sex; Hansen et al 1998 709618 also adjusted simultaneously for different
dimensions of exposure. Analyses also included appropriate interaction terms to test the
significance of hypothesized differences in gender and age at exposure (e.g., gender x
exposure in Reid et al. 2007, 709501).
Metric 10:
Covariate Characterization
High
Age and sex data was based on records and questionnaires.
Metric 11:
Co-exposure Counfounding
N/A
Per mesothelioma-specific guidance, concern about co-exposures is limited for mesothe-
lioma, meriting a "not applicable" rating.
Continued on next page ...
Page 63 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709618 Table: 1 of 1
... continued from previous page
Hansen, J., de Klerk, N. H., Musk, A. W., Hobbs, M. S. T. (1998). Environmental exposure to crocidolite and mesothelioma: Exposure-response relation-
ships. American lournal of Respiratory and Critical Care Medicine 157(1998):69-75.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Lung cancer mortalityLung cancer incidenceRespiratory system mortalityMesothelioma incidenceMesothelioma mortality; Cancer/
Carcinogenesis: Mesothelioma incidenceMesothelioma mortalityLung cancer incidenceLung cancer mortalityCancer incidence, all and specific types (SIRs
for exposed/gen pop, no dose-reponse)Cancer mortality, all and specific types (SMRs for exposed/gen pop, no dose-response); Mortality: Mesothelioma
mortalityLung cancer mortality All-cause mortality (SMR for exposed/gen pop, no dose-response)Respiratory system mortality (SMR for exposed/gen
pop, no dose-response)Digestive system mortality (SMR for exposed/gen pop, no dose-response)Signs/symptoms ill-defined (SMR for exposed/gen pop,
no dose-response)Nervous system mortality (SMR, no dose-response)
Asbestos - Crocidolite (riebeckite): 12001-28-4
709618, 709466, 709501, 2088306, 6869529
709618
Domain
Metric
Rating
Comments
Domain 5: Analysis
Metric 12: Study Design and Methods
Medium
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Medium
Medium
Analytic methods were appropriate. Hazard ratios or relative risks used Cox regression
models (Reid 2018 6869529, Hansen 1998 709618, Reid 2007 709501), and odds ratios
in an age-matched nested case-control analysis used conditional logistic regression
(Reid et al. 2008, 709466). SMRs/SIRs for mesothelioma were calculated using Western
Australia as an appropriate referent population (Reid et al. 2012, 2088306). To examine
the potential influence of loss to follow-up on results, some analyses studies compared
alternative censoring methods as described earlier (see Attrition comments).
With nearly 5,000 subjects, sample size was adequate overall as well as in analyses of
women (Reid et al. 2008, 709466) and individuals exposed as children (Reid et al. 2018,
6869529). There were a large number of mesothelioma cases (n=27 in the first analysis
by Hansen et al. 1998, 709618, n=119 in Reid et al. 2018, 6869529).
Descriptions of all analyses were clear and sufficient for reproduction.
The models and methods used were adequately described for both SMRs/SIRs and
regression models.
Additional Comments: These studies analyzed >5,000 individuals who had lived in Wittenoom, Australia for >1 month from 1943-1993 to evaluate associations between residen-
tial asbestos exposure and mesothelioma (all 4 studies). The cohort excluded asbestos workers. In the most recent study geometric mean (IQR) cumulative
exposure was 3.02 (1.4-7.70) f/mL-years in children and 2.05 (0.90-5.75) f/mL-years in adults, with 119 mesotheliomas identified by 2014. Increasing ex-
posure was consistently associated with risk of mesothelioma incidence and/or mortality. Though differences narrowed with longer follow-up, individuals
first exposed as adults had a higher risk vs. those exposed as children (Reid et al. 2007, 709501 vs. Reid et al. 2018, 6869529). Initial gender differences
were not significant after longer follow-up. SMRs for residents exposed as children were significantly higher for mesothelioma. Key concerns include
exposure measurement error, particularly prior to 1966 when mining ceased: a single value was extrapolated to the entire period as no fiber measures were
taken. Differential measurement error with respect to mesothelioma is a concern, since detailed residential and work histories were available for those
cases, while duration of residence was estimated from limited public records for half of the remaining cohort. There was also a 20% loss to follow-up,
addressed in some studies by comparing different assumptions on the status of these subjects. Associations with mesothelioma remained robust with
differing assumptions.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 64 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3081021 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Howel, D., Gibbs, A., Arblaster, L., Swinburne, L., Schweiger, M., Renvoize, E., Hatton, P., Pooley, F. (1999). Mineral fibre analysis and routes of exposure
to asbestos in the development of mesothelioma in an English region. Occupational and Environmental Medicine 56(1999):51-58.
Mesothelioma
Cancer/Carcinogenesis: malignant mesothelioma; Lung/Respiratory: malignant mesothelioma
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3081021
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
High Quantitative estimates of exposure were consistently assessed (i.e., using the same
method and sampling timeframe) during multiple time periods and using TEM. Samples
were obtained postmortem and prepared to be measured by TEM. All fibers >0.5um
were counted.
Low The range and distribution of exposure is limited. There are only 2 exposure groups,
high ("defined as being in the top third of values foundin all subjects for that fibre type")
and low, being reviewed for the odds ratios analyses.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 65 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2223821 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H. (1991). Asbestosis as a precursor of asbestos related lung cancer: Results of a prospective mortality study. British lournal of
Industrial Medicine 48(1991):229-233.
Mesothelioma
Lung/Respiratory: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality; Mortality: Mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
2223821
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low "This outcome is rated Low due to the lack of PCM or TEM being used in the
study.Authors refer to a different study for all information regarding to exposure to
asbestos (Hughes et al. 1987, 3583332) That paper notes that air sampling data was col-
lected by a mix of the government, industry, and insurance companies with a midget
impinger (recorded in millions of particles per cubic foot(mppcf)). This was done from
the 1950s-1960s. Membrane filter sampling (measured in fibers per milliliter) was also
noted to have been carried out starting in 1969. Authors note that because of the em-
ployment population occurring from 1940-1950, all exposure estimates were converted
into mppcf. These air sampling data in combination with job history data were used to
estimate cumulative exposure."
Metric 5: Exposure Levels Low SMRs for mesothelioma do not provide results by levels of exposure. Authors only pro-
vide categorical cumulative exposure levels for small opacities (<25, 25-99, 100-149,
and >=150 mppcf-y) and for lung cancer (<51, 51-85, 86-121, 122-169, and >=170
mppcf-y).
Additional Comments: Overall, this study is well-designed and references most methods to a previous paper (Hughes et al. 1987, 3583332).Note that the cancerous health
outcomes were not evaluated for any metrics except Metric 4 and 5 and had no data extracted because they did not have sufficient exposure information to
be useful for dose-response analysis.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 66 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 281 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H., Hammad, Y. Y. (1987). Mortality of workers employed in two asbestos cement manufacturing plants. Occupational and
Environmental Medicine 44(1987):161-174.
Mesothelioma
Lung/Respiratory: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality; Mortality: Mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
281
Domain
Metric Rating
Comments
Additional Comments: Mesothelioma was not analyzed in an SMR/Regression analysis.
Page 67 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3583332 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H„ Hammad, Y. Y. (1987). MORTALITY OF WORKERS EMPLOYED IN 2 ASBESTOS CEMENT MANUFACTURING
PLANTS. British Journal of Industrial Medicine 44(1987): 161-174.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3583332
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated as low because the study or any cited methods source does not ex-
plicitly mention the use of PCM or TEM.
Medium SMRs were calculated using 5 categories of employment duration that ranged from a
few months to >15 years (different values for each plant), and using 5 categories of
cumulative exposure (= 100 mppcf).
Additional Comments: NOTE: This study was not fully evaluated because the rating for metric 4 was low, due to no explicit mention of PCM or TEM. Analyses of the 10
mesotheliomas identified were not evaluated.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 68 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 308ii64 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Iwatsubo, Y., Pairon, J. C., Boutin, C., M&iard, O., Massin, N., Caillaud, D., Orlowski, E., Galateau-Salle, F., Bignon, J., Brochard, P. (1998). Pleural
mesothelioma: dose-response relation at low levels of asbestos exposure in a French population-based case-control study. American Journal of Epidemiol-
ogy 148(1998):133-142.
Mesothelioma
Lung/Respiratory: Pleural mesothelioma; Cancer/Carcinogenesis: Pleural mesothelioma
Asbestos - Not specified: 1332-21-4
ID(s): 3081164, 2569475, 3077945, 3078290, 3863052
3081164
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low These studies utilized a job exposure matrix to develop a semi-quantitative measurement
of exposure. Industrial hygienists evaluated the occupational exposure to asbestos, and
allowed for each job period of the subjects to be classified based on the probability,
frequency, and intensity of asbestos exposure (Iwatsubo et al., 1998, 3081164; Lacourt
et al., 2012, 2569475; Lacourt et al„ 2013, 3078290; Lacourt et al„ 2014, 3077945;
Lacourt et al., 2017, 3863052). This metric was rated as low because the study or any
cited methods source does not explicitly mention the use of PCM or TEM (Iwatsubo
et al., 1998, 3081164; Lacourt et al„ 2012, 2569475; Lacourt et al„ 2013, 3078290;
Lacourt et al., 2014, 3077945; Lacourt et al., 2017, 3863052).
Medium Each of the studies included in this cohort included a range of exposures based on the
JEMs, and three or more levels were reported in each study (Iwatsubo et al., 1998,
3081164; Lacourt et al., 2012, 2569475; Lacourt et al., 2013, 3078290; Lacourt et al.,
2014, 3077945; Lacourt et al„ 2017, 3863052).
Additional Comments: A complete evaluation of this cohort was not completed because they only utilized a job exposure matrix to semquantitatively determine asbestos exposure
levels. As this was based on professional judgment and did not include TEM or PCM, the metric pertaining to measurement of exposures was rated as
low (Iwatsubo et al., 1998, 3081164; Lacourt et al., 2012, 2569475; Lacourt et al., 2013, 3078290; Lacourt et al., 2014, 3077945; Lacourt et al., 2017,
3863052). Metric five was rated as high because there were several levels of exposure created in the JEM, representing a range of exposures.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 69 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6860340 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Jiang, Z., Xia, H., Wu, W., Chen, R., Morinaga, K., Lou, J., Zhang, X., Chen, T., Chen, J., Ying, S. (2018). Hand-spinning chrysotile exposure and risk of
malignant mesothelioma: A case-control study in Southeastern China. International Journal of Cancer 142(2018):514-523.
Mesothelioma
Lung/Respiratory: Cases of malignant mesothelioma; Cancer/Carcinogenesis: Cases of malignant mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
6860340
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Individual exposure was not directly measured, but was determined based on a cumula-
tive exposure index (CEI), which was based on job classification.lt is unclear whether
PCM or TEM or another method was used.Raw materials from 18 asbestos textile
plants were randomly sampled from the 1980s-2010s using X-Ray diffraction, which
determined that the raw materials were chrysotile mixed with other chemical impuri-
ties.Airborne asbestos samples from 1987-2011 from 49 hand-spinning asbestos plants
and 12 hand-spinning from home workplaces were analyzed using a weighting method.
Measurements were taken at a flow rate of 2 L/min for a duration of 15-20 minutes.
Mass concentrations were transformed into fiber number concentrations in fibers/ml
using a formula described in a paper that was not found in HERO (Huang I. 1994).
The estimated median concentration of asbestos was 8.0 fibers per milliliter (f/mL) for
hand-spinning at plants and 0.6 f/mL for hand-spinning at home.The study authors cited
several papers in their methods description, some of which were reviewed and were not
found to mention use of PCM or TEM, but at least one methods paper (Huang I. 1994)
wasn't readily accessible and the method for quantifying fiber counts is not fully known
based on the available information.To assess individual exposure levels, participants
were interviewed following a structured questionnaire, which included occupational
history. The occupations and industrial activities of all participants was classified using
the International Standard Classification of Occupation (ISCO) codes and the Interna-
tional Standard Industrial Classification (ISIC) codes, respectively. Two experts inde-
pendently assessed exposure probability based on fiber concentration measurements
(unclear whether PCM, TEM, or other) and expert judgement. The cumulative exposure
index (CEI) of asbestos was expressed as fibers per milliliter years (f/mL-years) and
was calculated based on the sum of the products of probability, frequency, intensity, and
duration of each job exposure.
Metric 5: Exposure Levels Medium The range and distribution of exposure is sufficient to develop an exposure-response es-
timate. Table 4 presents odds ratios for malignant mesothelioma stratified by asbestos
exposure levels. Asbestos exposure categories were defined in several different ways, in-
cluding categorization by cumulative exposure index (CEI). There were three categories
of CEI: >0"0.5, >0.5"29, and >29 fibers per milliliter years (f/mL-years).
Additional Comments: None
Continued on next page ...
Page 70 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6860340 Table: 1 of 1
... continued from previous page
Jiang, Z., Xia, H., Wu, W., Chen, R., Morinaga, K., Lou, J., Zhang, X., Chen, T., Chen, J., Ying, S. (2018). Hand-spinning chrysotile exposure and risk of
malignant mesothelioma: A case-control study in Southeastern China. International Journal of Cancer 142(2018):514-523.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Cases of malignant mesothelioma; Cancer/Carcinogenesis: Cases of malignant mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
6860340
Domain
Metric
Rating
Comments
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 71 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6866465 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Konen, T., Johnson, J. E., Lindgren, P., Williams, A. (2019). Cancer incidence and mortality associated with non-occupational and low dose exposure to
Libby vermiculite in Minnesota. Environmental Research 175(2019):449-456.
Mesothelioma
Lung/Respiratory: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality; Mortality: Mesothelioma mortality
Asbestos- Libby amphibole: 1318-09-8
No linked references.
6866465
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Asbestos exposure was estimated, and no quantitative measurements were taken. The
authors reported that the exposure estimates were calculated "based on total months
of residency (duration) and addresses in the study area and using results of modeled
ambient asbestos concentration levels during three different time periods during plant
operations (1938-1989)."
Medium The range of exposure was adequate to create an exposure-response estimate. The
study's analyses included 3 exposed groups (<50th percentile, 50th - 75th percentile,
and >75th percentile).
Additional Comments: METRIC 4 WAS RATED AS LOW - STOPPED EVALUATING BASED ON NEW GUIDANCE ON 1,27.23Information on the measurement of exposure
metric (M4) to assess exposure is limited (low rating) as no quantitative measurements were taken. However, the exposure levels metric (M5) information
reported is sufficient to determine exposure-response relationships.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 72 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2601091 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Kurumatani, N., Kumagai, S. (2008). Mapping the risk of mesothelioma due to neighborhood asbestos exposure. American Journal of Respiratory and
Critical Care Medicine 178(2008):624-629.
Mesothelioma
Mortality: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2601091
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Exposure was estimated utilizing professional judgement of plant concentration with
meteorological data to estimate "relative asbestos concentrations" for the population of
interest and no use of quantitative exposure measures. Authors noted in Supplemental
material that the "relative asbestos concentrations" for the population of interest sur-
rounding the plant were estimated using an assumed fiber concentration (professional
judgement) emitted from the plant because actual concentrations and emission rates of
airborne asbestos fibers during the period of interest were unknown. No quantitative
asbestos sampling was reported or utilized within calculations. Authors assumed the
emission point of asbestos was the center of the plant, and airborne asbestos emitted
from the plant was the sole industrial source of exposure.
Medium Dose-response relations between mesothelioma SMR"s and relative asbestos concentra-
tion levels divided into five exposure groups were presented within Figure 3.
Additional Comments:
HERO ID 2601091 Kurumatani (2008) was not evaluated for any metrics except Metrics 4 and 5 and had no data extracted because it did not have sufficient
exposure information to be useful for dose-response analysis.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 73 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3078046 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lacourt, A., Gramond, C., Rolland, P., Ducamp, S., Audignon, S., Astoul, P., Chamming's, S., Gilg Soitllg, A., Rinaldo, M., Raherison, C., Galateau-Salle,
F., Imbernon, E., Pairon, J. C., Goldberg, M., Brochard, P. (2014). Occupational and non-occupational attributable risk of asbestos exposure for malignant
pleural mesothelioma. Thorax 69(2014):532-539.
Mesothelioma
Lung/Respiratory: Pleural mesothelioma; Cancer/Carcinogenesis: Pleural mesothelioma
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3078046
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The assessment of asbestos exposure was done by two experts who examined the ques-
tionnaires of participants. Occupational exposure was broken down into four parameters,
including probability of exposure, frequency of exposure, intensity of exposure, and
route of exposure (Lacourt et al., 2014, 3078046). There was no indication of actual
tools or instruments used, and only professional judgment was used to estimate expo-
sure. This metric is rated low because the study or any cited methods source does not
explicitly mention the use of PCM or TEM (Lacourt et al., 2014, 3078046).
Medium The authors reported a range of exposure that is sufficient to develop an exposure-
response estimate. Table 1 presents the groupings for intensity of exposure, which is
reported in f/mL (Lacourt et al., 2014, 3078046).
Additional Comments: Due to the rating for measurement of exposure, this study was not evaluated fully. Utilization of professional judgment and a job exposure matrix, without
actual quantitative measurement of asbestos fibers, lead to a low rating. However, they did provide several levels of intensity of exposure which was
determined semiquantitatively (Lacourt et al., 2014, 3078046).
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 74 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 711560 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Larson, T. C., Antao, V. C., Bove, F. J. (2010). Vermiculite worker mortality: Estimated effects of occupational exposure to Libby amphibole. Journal of
Occupational and Environmental Medicine 52(2010):555-560.
Mesothelioma
Lung/Respiratory: Mesothelioma; Mortality: Mesothelioma
Asbestos- Libby amphibole: 1318-09-8
709497, 709457, 711560, 2238712
711560
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM to develop quantitative estimates of exposure.
Medium The distribution of exposure appears to be sufficient to develop an exposure-response
estimate. Cumulative exposure was utilized in dose-response calculations and were rep-
resented in four levels: <1.4 f/cc-y, 1.4 to <8.6 f/cc-y, 8.6 to <44.0 f/cc-y, and >=44.0
f/cc-y.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis. Metric 4 had a low level of confidence because the authors do not mention using PCM or TEM to develop quantitative estimates of exposure.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 75 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2593920 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Madkour, M. T., El Bokhary, M. S., Awad Allah, H. I., Awad, A. A., Mahmoud, H. F. (2009). Environmental exposure to asbestos and the exposure-response
relationship with mesothelioma. Eastern Mediterranean Health Journal 15(2009):25-38.
Mesothelioma
Cancer/Carcinogenesis: Malignant Pleural Mesothelioma; Lung/Respiratory: Malignant Pleural Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
2593920
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This study, conducted in 2003 and 2004 in Egypt, included two groups exposed to as-
bestos: (i) 2913 environmentally exposed individuals residing in 6 neighborhoods rang-
ing from 100 meters to 2.5 km from the Sigwart chrysotile asbestos manufacturing plant
in greater Cairo; and (ii) 487 workers currently employed at the asbestos plant (all de-
partments). The plant operated from 1948 to 2004. Participants were adults aged >20y.
An unexposed comparison group was also included. High confidence for environmen-
tally exposed: The environmentally exposed group is likely representative of environ-
mental exposure and health outcomes; individuals with "any history suggestive of any
occupational exposure to asbestos" were excluded. Health center workers recruited these
individuals, selecting from a target population identified using cluster sampling (not
specified if drawn from population or clinic registries). No other selection criteria were
mentioned (e.g. based on health status, employment status, duration of residence) that
could have biased the exposure-outcome distribution. Medium confidence for occu-
pationally exposed: The occupationally exposed group was limited to currently active
workers, which induced risk of a healthy worker bias (potential selection of less healthy
people out of the workforce). This is of concern as the study began after a 2002 report of
asbestos-related pleuropulmonary disorders at the plant.
High Participation rates were high in all three groups. Environmental: the authors report a
response rate of 95% (2913 of the 3059 invited). Occupational: 89% if the 543 current
employees participated (35 refused, 21 were lost to follow-up). Comparison group: 979
of 1041 invited (94% ) participated.
Low The comparison group comprised residents in an agricultural area (Banha city) 40 km
from the plant. None of the individuals had a history of occupational or environmental
exposure. No other selection criteria were mentioned. The appropriateness of compar-
isons with the two exposed groups is very uncertain as the authors do not provide any
information on the distribution of age, sex, socioeconomic indicators, employment sta-
tus, or health status in this group.
Domain 2: Exposure Characterization
Continued on next page .
Page 76 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2593920 Table: 1 of 1
... continued from previous page
Madkour, M. T., El Bokhary, M. S., Awad Allah, H. I., Awad, A. A., Mahmoud, H. F. (2009). Environmental exposure to asbestos and the exposure-response
relationship with mesothelioma. Eastern Mediterranean Health Journal 15(2009):25-38.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Malignant Pleural Mesothelioma; Lung/Respiratory: Malignant Pleural Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2593920
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Exposure was quantified based on: air sample concentrations; duration (of residence or
employment); and cumulative fiber-years (concentration x duration). 10-year categories
of exposure duration ranged from 0-10 to >40 years. Concentrations (fibers/cc) were
quantified based on PCM counts of fibers > 5 jUm using samples collected on membrane
filters using a known air flow rate (type of pump or impinger not specified), prepared
using OSHA methods. Exposure was estimated in each group, but there were differences
in the measures and methodologic information provided across groups, complicating
comparisons and making validity uncertain. Historic exposure measures were not in-
cluded. -Occupational exposure: Medium confidence. 45 air samples were taken at
breathing height (1.5 meters) from 8 areas including manufacturing, milling, and offices,
over 8h from 9:00-17:00h. Mean fiber concentration, but not mean fiber concentrations-
year or mean duration of employment, were shown for each of these 8 areas (Table 8;
overall mean 0.59 f/mL-years). Potential source of error: Measures were taken inside
the plant from January 2003 to March 2004 when it was fully functioning and after it
closed in November 2004. The paper does not specify when measures were taken in
each area, or whether measures after plant closure were included in the estimates. -
Environmental exposure: Medium confidence. Fiber counts were estimated using 5 air
samples collected in each of the 6 residential areas, which were characterized based on
mean distance from the plant. Mean concentrations were reported for each area (Table 9;
overall mean 0.38 f/mL), but not cumulative fiber-years or mean duration of residence.
Uncertainties: The authors did not specify sample collection height, flow rates, hours of
the day, or dates. -Control area exposure: Medium confidence. Air sample collection
was reported. The mean fiber concentration was reported as 0.0021 fibers/mL (Tables
8 and 9); mean duration of residence was not shown so mean fiber-years were uncer-
tain. Uncertainties: There was no description of the methods used to collect samples,
including: the number of samples; height, flow rate, hours of the day, dates of collection.
Medium In addition to any vs no known exposure, exposure levels associated with prevalent
mesothelioma were shown using: 5 categories of exposure duration; by area of resi-
dence/distance from the plant (n=6); location of work (n=8) with differing exposure
concentrations. For the study population as a whole (Table 10), the authors used two
categories of exposure concentration and three categories of cumulative exposure; it is
uncertain how cutoffs were selected as numbers were imbalanced.
Medium Temporality is established. Although outcomes and exposure were measured contem-
poraneously, exposure duration was estimated retrospectively using categories that
included >40 years of known exposure, an adequate timeframe for development of
mesothelioma.
Domain 3: Outcome Assessment
Continued on next page ...
Page 77 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2593920 Table: 1 of 1
... continued from previous page
Madkour, M. T., El Bokhary, M. S., Awad Allah, H. I., Awad, A. A., Mahmoud, H. F. (2009). Environmental exposure to asbestos and the exposure-response
relationship with mesothelioma. Eastern Mediterranean Health Journal 15(2009):25-38.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Malignant Pleural Mesothelioma; Lung/Respiratory: Malignant Pleural Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2593920
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
Metric 8:
Reporting Bias
Medium Malignant pleural mesothelioma (MPM) was identified using a four-step process: (1)
screening of all participants using mass miniature radiography (MMR, by qualified and
experienced readers for parenchymarous and pleural diseases); (2) standard chest radio-
graphs for cases with MMR abnrormalities; (3) high resolution computerized scans of
individuals with abnormal radiographs to localize lesions; (4) admission to chest hospi-
tal for pleural biopsy using methods that included CT-guided biopsy. ICD codes were
not provided, but procedures involved specialists and included biopsies. Screening of all
participants reduced the likelihood of differential misclassification related to detection
bias. The screening identified other pleuropulmonary disorders including pleural plaques
and diffuse pleural thickening. Potential source of bias: prevalence-incidence bias may
be present, since the most severe cases may not have been available for screening (e.g.
death, hospitalized, moved).
Medium The study presented findings in accordance with its aims: to evaluate the prevalence
of malignant pleural mesothelioma (MPM) among individuals with environmental and
occupational exposure; to examine the exposure response-curve for environmental ex-
posure. The statistical methods described in the methods section were used (t-tests or
chi-square tests for various descriptive tables; relative risk for any vs no exposure).
However, the paper did not include multivariable-adjusted estimates to account for con-
founding, relative risks for increasing exposure, or effect estimates with confidence
intervals or standard errors. In addition, the manuscript failed to present characteristics
of the comparison group.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Low Analyses did not adjust for any confounders, despite the differences shown in the age
and gender distribution among individuals with vs without malignant pleural mesothe-
lioma. Information on smoking habits and on SES was not discussed or shown.
Low The authors describe taking a "full history" of relevant background; however, assessment
of potential confounders such as age and SES was not discussed.
N/A For mesothelioma, there are no established risk factors other than exposure to asbestos.
Therefore, no known co-exposures are of concern.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Medium The authors present appropriate descriptive and statistical tests. However, there was
no consideration of confounding, and the relative risk shown did not examine dose-
response
Medium The sample size and the number of cases were both large.
Continued on next page ...
Page 78 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2593920 Table: 1 of 1
... continued from previous page
Madkour, M. T., El Bokhary, M. S., Awad Allah, H. I., Awad, A. A., Mahmoud, H. F. (2009). Environmental exposure to asbestos and the exposure-response
relationship with mesothelioma. Eastern Mediterranean Health Journal 15(2009):25-38.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Malignant Pleural Mesothelioma; Lung/Respiratory: Malignant Pleural Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2593920
Domain
Metric
Rating
Comments
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium Reproducing the analyses linking the prevalence of mesothelioma to exposure would be
straightforward.
Low The statistical analyses are not fully appropriate as they do not take into account poten-
tial confounding or evaluate dose-response.
Additional Comments: This study conducted in Egypt in 2003-04 screened three population groups to identify prevalent malignant pleural mesothelioma (MPM): residents living
at varying distanced from an urban chrysotile asbestos plant; active workers at the plant; and residents in a rural community with minimal/no exposure. A
total of 88 cases were identified, 83 in the environmentally exposed group. The study provides important insights on MPM risk in individuals with high
levels of environmental exposure. However, HWE bias is an important concern in analyses of occupational exposure based on current workers in a facility
where health risks had already been reported, that closed while the study was conducted. Other issues include the lack of accounting for confounding, the
lack of information on the comparison group, and some uncertainties in exposure assessment methods. Nonetheless, the study is well-powered to contribute
information on the dose-response relationship of high concentrations of environmental asbestos exposure and risk of MPM.
Overall Quality Determination nan
* No biomarkers were identified for this evaluation.
Page 79 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 758954 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Armstrong, B. G., Edwards, C. W., Gibbs, A. R., Lloyd, H. M., Pooley, F. D., Ross, D. J., Rudd, R. M. (2001). Case-referent survey of
young adults with mesothelioma: I. Lung fibre analyses. Annals of Occupational Hygiene 45(2001 ):513-518.
Mesothelioma
Lung/Respiratory: Mesothelioma diagnosis
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Tremolite: 14567-73-8; Asbestos - Not specified:
1332-21-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
758954
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium The current study noted that details regarding case selection were reported within Mc-
donald et al., 2001 (HERO ID 709579). Starting in 1989, approximately 85% of all
respiratory and occupational medicine consultants in the UK voluntarily reported new
cases of occupational respiratory disease to the national Surveillance of Work-related
and Occupational Respiratory Disease (SWORD) study. Eligibility was described as all
cases of malignant mesothelioma reported by physicians to SWORD between 1990 and
1996, born from 1943 onwards; these were selected for study and followed until the end
of 1997. Of the n=180 eligible cases, exclusions were made for n=18 reported twice,
n=14 described as too old, n=5 described as overseas, and n=3 for which diagnosis had
been changed to benign pleural disease, inflammatory disease or adenocarcinoma, leav-
ing n=140 men and women suitable for study. Of these, n=ll males and n=l female
was excluded due to lack of work history, leaving n=l 15 males and n=13 females for
study. Of these, those without autopsies and lung burden analysis were excluded, leav-
ing n=69 males and n=4 females for study. Final analyses for the current study excluded
the females and was restricted to n=69 male mesothelioma cases. Eligibility for n=57
potential controls was described as those with autopsies from accidental or sudden car-
diac deaths conducted by the same pathologists as cases, matched to cases by age and
geographic region. Distributions of relevant exposure, outcome, demographic and other
variables between those included and excluded were not detailed.
Medium Exposure and outcome data were complete for selected cases, although n=5 eligible
cases were originally noted as lost to follow-up ("overseas").
Medium Key elements of study design were reported (inclusion criteria and methods of partic-
ipant selection) and indicate subjects were recruited during the same time period from
the same eligible population. Differences in all potential confounding variables between
groups were not detailed, although cases and controls were compared across matching
variable categories of age and geographic region in Table 1.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
High Autopsied lung fiber burden within mesothelioma cases and controls was measured
utilizing Transmission Electron Microscopy (TEM).
Medium Exposure distribution is adequate for exposure-response analyses. Final regression mod-
els incorporated odds ratios across quartiles of fiber concentration per microgram (f/
ug) tissue within autopsied tissue samples including 0.0 f/ug, 0.1-0.9 f/ug, 1.0-9.9 f/ug,
>=10.0 f/ug, as well as linear models utilizing a continuous measure of exposure.
Continued on next page ...
Page 80 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 758954 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Armstrong, B. G., Edwards, C. W., Gibbs, A. R., Lloyd, H. M., Pooley, F. D., Ross, D. J., Rudd, R. M. (2001). Case-referent survey of
young adults with mesothelioma: I. Lung fibre analyses. Annals of Occupational Hygiene 45(2001 ):513-518.
Mesothelioma
Lung/Respiratory: Mesothelioma diagnosis
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Tremolite: 14567-73-8; Asbestos - Not specified:
1332-21-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
758954
Domain
Metric
Rating
Comments
Metric 6:
Temporality
Low
Temporality of exposure with outcome is uncertain within this cross-sectional study
where physician diagnosis of mesothelioma within original database was confirmed at
autopsy along with lung fiber analysis for the current study.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High Initial diagnoses were made by respiratory and occupational medicine consultants re-
ferring mesothelioma cases to the original SWORD study. Mcdonald et al., 2001 (ID
709259) indicates that research assistant confirmation of data was obtained from med-
ical records, occupational histories, coroners and subject general practitioners. Formal
validation of diagnoses was made through histological examination of lung tissue and
tumor samples for cases and controls described as conducted independently by two
pathologists considerably experienced in mesothelioma diagnosis.
High There were no concerns for selective reporting as all outcomes which were outlined
within methods were also reported within the results. Effect estimates within Tables
2 and 4 are reported as unadjusted and adjusted Odds Ratios (OR"s) and 95% confi-
dence intervals. The number of cases and controls within regression results was clearly
detailed.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10:
Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Controls were matched to cases on age and geographic region. Analysis was restricted
to males. Consideration for race was not detailed.
High Covariates were assessed using reliable methodologies, cases and controls were matched
on age and geographic region, but not race not discussed. Mcdonald et al., 2001 (ID
709259) indicates that research assistant confirmation of occupational data was obtained
from medical records, occupational histories, coroners and subject general practitioners.
N/A Per mesothelioma-specific guidance, concern about co-exposures is limited for mesothe-
lioma, meriting a "not applicable" rating.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Medium This cross-sectional design was appropriate for an initial investigation of exposure and
outcome. Conditional logistic regression was utilized for matched case control analyses.
Medium Analyses of n=69 mesothelioma cases with n=57 controls was minimal for this matched
case control analyses. Analyses within some higher exposure quartiles across asbestos
types was sometimes not possible due to the lack of cases and/or controls (Tables 2 and
4).
Medium Statistical tests and matching variables were described and general methods were de-
scribed in a way that would facilitate reproducibility with access to the analytic data.
Continued on next page ...
Page 81 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 758954 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Armstrong, B. G., Edwards, C. W., Gibbs, A. R., Lloyd, H. M., Pooley, F. D., Ross, D. J., Rudd, R. M. (2001). Case-referent survey of
young adults with mesothelioma: I. Lung fibre analyses. Annals of Occupational Hygiene 45(2001 ):513-518.
Mesothelioma
Lung/Respiratory: Mesothelioma diagnosis
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Tremolite: 14567-73-8; Asbestos - Not specified:
1332-21-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
758954
Domain Metric Rating Comments
Metric 15: Statistical Analysis Medium Conditional logistic regression models were adequately described and there were no
indications of a lack of adherence to model assumptions.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric
16:
Use of Biomarker of Exposure
High
Lung tissue fiber analyses was conducted by TEM and were presented for each fiber
type assessed (Table 2).
Metric
17:
Effect Biomarker
N/A
A biomarker of exposure was assessed in the current study.
Metric
18:
Method Sensitivity
Low
LOD/LOQ values were not stated.
Metric
19:
Biomarker Stability
Low
Storage history of samples was not detailed.
Metric
20:
Sample Contamination
Medium
Contamination information was not detailed.
Metric
21:
Method Requirements
Medium
Transmission electron microscopy provides a measure of degree of confidence for the
lung tissue samples selected from what was described as different parts of each lung.
Metric
22:
Matrix Adjustment
N/A
Matrix adjustment is not required.
Additional Comments: This cross-sectional study of a limited number (n=69 male mesothelioma cases and n=57 controls) with lung fiber analyses by transmission electron
microscopy (TEM)) indicated lung amosite and crocidolite fibers could account for about 80% of cases of mesothelioma, and tremolite for some 7% . A
steep linear trend in mesothelioma odds ratios (ORs) were noted for all amphiboles combined with an indication for additive effects.
Overall Quality Determination Medium
Page 82 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082766 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Armstrong, B., Case, B., Doell, D., Mccaughey, W. T., Mcdonald, A. D., S6bastien, P. (1989). Mesothelioma and asbestos fiber type.
Evidence from lung tissue analyses. Cancer 63(1989): 1544-1547.
Mesothelioma
Lung/Respiratory: mesothelioma; Mortality: mesothelioma
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite:
17068-78-9; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3082766
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
High This was a cross-sectional study design of asbestos fiber levels and the risk of mesothe-
lioma mortality. Lung samples from n=78 mesothelioma cases autopsied from 1982-
1983 were collected from registries from nine Canadian provinces. Cases were included
in the study if the pathologist deemed the diagnosis "more likely than not". Lung sam-
ples for deaths not caused by malignant or respiratory disease were collected from the
following years: 1979, 1980, 1981, and half of 1984. These controls (n=78) were se-
lected from the same autopsy register that cases were selected from. Controls were
matched by sex, date of death (within one year), type of tissue, and date of birth. Au-
thors note that British Columbia was excluded from the sample due to an existing study
occurring in the region.
High Authors report a total of 167 diagnosed mesothelioma cases in the study area during the
sampling period, with only a portion being fatal (n=83) and only 78 samples available.
There is no evidence of further restricting the sample for analyses. As the study was
conducted among subjects whose diseases were fatal, attrition and loss to follow up are
not of concern.
Medium Authors selected referent population from the same autopsy registry but during slightly
different years (1982 and 1983 for cases; 1979, 1980, 1981, and the first half of 1984 for
controls). Controls were matched for sex, date of death, type of tissue, and date of birth.
A full comparison of demographic characteristics of cases and controls is not provided,
thus other demographic differences cannot be completely ruled out.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Fiber levels in lung samples were assessed using analytic TEM to identify short (<8
um fiber length) and long (>=8 um fiber length) fibers. As samples were collected after
subject death, levels only represent one time period, which is anticipated to reasonably
represent the period of interest prior to subject death.
Medium Fiber concentrations ranged from <0.1 to 100 per ug dry weight of lung sample, which
represents a sufficient range to examine the exposure-outcome relationship.
Medium This study represents a cross-sectional analysis of a disease with a long latency period.
Fiber levels were measured after mesothelioma death, thus it can be assumed that the
latency period was accounted for in the study.
Domain 3: Outcome Assessment
Continued on next page ...
Page 83 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082766 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Armstrong, B., Case, B., Doell, D., Mccaughey, W. T., Mcdonald, A. D., S6bastien, P. (1989). Mesothelioma and asbestos fiber type.
Evidence from lung tissue analyses. Cancer 63(1989): 1544-1547.
Mesothelioma
Lung/Respiratory: mesothelioma; Mortality: mesothelioma
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite:
17068-78-9; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3082766
Domain
Metric
Rating
Comments
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High
Medium
Deaths from mesothelioma were assessed by examining information from the autopsy
registries in Canadian provinces. Fatal mesothelioma case samples were examined and
confirmed histologically (by biopsy or at autopsy).
While anticipated results of analyses are reported, the results do not always include all
information needed for dose-response analyses. Odds ratios are reported by fiber con-
centration in Table 1 along with case and referent numbers, but no measure of variance
accompanies the effect estimate. Additionally, the risk increment and 95% CI, along
with the attributable risk, are reported, but case and referent numbers are not reported.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Sex, year of death, type of tissue, and age were appropriately adjusted for using match-
ing of cases and referents. While age and sex are two important confounders, informa-
tion on other potential confounders is not provided, thus limiting the ability to assess is
adjustment was complete.
Low While it could be reasonably assumed that information on confounders was collected
from registries, the source of confounder information is not explicitly stated in the study.
N/A Per mesothelioma-specific guidance, concern about co-exposures is limited for mesothe-
lioma, meriting a "not applicable" rating.
Domain 5: Analysis
Metric
12:
Study Design and Methods
Medium
This cross-sectional assessment of the case and referent populations was appropriate,
as was the use of multivariate logistic regression to assess the relationship between the
exposure and outcome.
Metric
13:
Statistical Power
Medium
The number of cases (n=78) and matched referents (n=78) is adequate to detect an effect
in the population.
Metric
14:
Reproducibility of Analyses
Medium
The information provided about the analysis is sufficient to conceptually reproduce the
approach.
Metric
15:
Statistical Analysis
Medium
Authors explicitly provide information about the construction of statistical models and
why certain covariates were included.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric 16: Use of Biomarker of Exposure High Lung samples were analyzed to assess the number of asbestos fibers (by type) present
per ug dry weight tissue. Lung tissues are an appropriate matrix to accurately assess
asbestos fiber levels.
Metric 17: Effect Biomarker High Lung tissue samples were histologically examined to assess mesothelioma. Lung is an
appropriate matrix to accurately assess this health outcome.
Continued on next page ...
Page 84 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082766 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Armstrong, B., Case, B., Doell, D., Mccaughey, W. T., Mcdonald, A. D., S6bastien, P. (1989). Mesothelioma and asbestos fiber type.
Evidence from lung tissue analyses. Cancer 63(1989): 1544-1547.
Mesothelioma
Lung/Respiratory: mesothelioma; Mortality: mesothelioma
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite:
17068-78-9; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3082766
Domain
Metric
Rating
Comments
Metric 18:
Method Sensitivity
Medium
LOD <0.01 for fibers appears low enough to capture a wide range of exposure levels to
address the research hypothesis.
Metric 19:
Biomarker Stability
High
Stability and storage losses are not of concern for the lung samples collected in this
study.
Metric 20:
Sample Contamination
Medium
There is no information related to sample contamination, but there are no major con-
cerns about contamination of lung tissue samples with asbestos fibers.
Metric 21:
Method Requirements
Medium
Methods with high degrees of confidence are used to assess biomarkers of effect and of
exposure.
Metric 22:
Matrix Adjustment
N/A
Matrix adjustment was not required for any of the biomarkers assessed in this study.
Additional Comments: This cross-sectional study examines autopsy tissue from deceased mesothelioma patients to assess fiber levels and compare those levels to lung tissue from
a deceased referent population. While some information about consideration of confounders and details of results from statistical analyses are limited, the
study reasonably assesses the exposure-outcome relationship through appropriate participant selection, exposure analysis, statistical analysis, and outcome
ascertainment..
Overall Quality Determination Medium
Page 85 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 7836 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Mcdonald, J. C., Mcdonald, A. D. (1997). Chrysotile, tremolite and carcinogenicity. Annals of Occupational Hygiene 41(1997):699-705.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality; Mortality: Mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Tremolite: 14567-73-8
HERO ID:
7836
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Uninformative Details on exposure measurement methods were not reported in the present reference
or cited references (HERO ID 3081408 and 3651098). Men were compared by years of
employment.
Medium Participants were compared using logistic regression, suggesting a continuous measure
of exposure (years of employment).
Additional Comments: None
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessment for the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 86 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 29964 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Mcdonald, A. D., Armstrong, B., Sebastien, P. (1986). Cohort study of mortality of vermiculite miners exposed to tremolite. Occupational
and Environmental Medicine 43(1986):436-444.
Mesothelioma
Cancer/Carcinogenesis: mesothelioma mortality; Lung/Respiratory: mesothelioma mortality; Mortality: mesothelioma mortality
Asbestos- Libby amphibole: 1318-09-8
29964, 709547, 709695
29964
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium Description of study setting was provided, and other elements including inclusion cri-
teria and case ascertainment, primarily from McDonald et al. 1986, HERO ID: 29964,
with McDonald and Armstrong 2003, HERO ID: 709547 giving a briefer version of the
info. The study population includes male workers from a Libby mining company who
have been hired before 1963. In total, 406 males worked at the site for at least one net
year were included, 12 of which were employed before 1940. No other description of
additional inclusion or exclusion criteria. There is limited information on subjects not
included or participation rate, which introduces potential for selection bias.
High In McDonald et al. 1986, HERO ID: 29964, at the end of the follow-up period (July 1st,
1983), 226 were alive and 165 were dead. 14 men were found alive on 1981 but subse-
quent status was not available. In total, vital status of 405 out of 406 men included in
this study were traced. Death certificates were obtained for 163 of the 165 deceased. In
McDonald and Armstrong 2003, HERO ID: 709547, at the end of the follow-up period
(July 1st, 1983), the remaining 241 (vs 240 in McDonald et al. 1986, HERO ID: 29964)
known to be alive at the end of the 1983 follow up period were traced via the National
Death Index to 1998, where another 120 were confirmed dead.There is little loss to fol-
low up.
Medium In McDonald et al. 1986, HERO ID: 29964 mesothelioma case-referent analyses, "con-
trols for each case were chosen as men surviving beyond the age of death of the case,
who had been born and had started work at Libby mine within three years of the case. "In
McDonald and Armstrong 2003, HERO ID: 709547, comparison was made among other
workers. Age and sex were considered in the analyses.Thus, there is only indirect evi-
dence that groups are not similar to each other.
Domain 2: Exposure Characterization
Continued on next page .
Page 87 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29964 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Mcdonald, A. D., Armstrong, B., Sebastien, P. (1986). Cohort study of mortality of vermiculite miners exposed to tremolite. Occupational
and Environmental Medicine 43(1986):436-444.
Mesothelioma
Cancer/Carcinogenesis: mesothelioma mortality; Lung/Respiratory: mesothelioma mortality; Mortality: mesothelioma mortality
Asbestos- Libby amphibole: 1318-09-8
29964, 709547, 709695
29964
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Details on exposure assessment are primarily from McDonald et al. 1986, HERO ID:
29964, with McDonald and Armstrong 2003, HERO ID: 709547 citing this paper. The
measurement of exposure (a mix of personal and area) changed during the study period
but was ultimately based employment records and quantitative estimates of exposure
using a combination of midget impingers and PCM (cited as optical microscopy while
referencing Walton 1982, HERO ID: 29649, which clarifies it as phase contrast opti-
cal microscopy) for a portion of participant" s work history of exposure, requiring ex-
trapolation for earlier years. Air samples were collected using midget impinger before
1970 and using membrane filters after 1970. Samples before 1970 only measured dust
concentrations without conversion factors. Limited amount of samples were collected
before 1965, and the measurements were much higher after 1975 when the company
introduced a systematic air sampling program. Authors assumed that fiber exposure
measures made before 1965 (engineering controls installed at this point to reduce dust/
fiber levels), were a fraction of those measured afterwards. Authors further note: "For
the other operation locations fiber measurements were available only for the recent pe-
riods. When the data were considered inadequate to describe past conditions, because
of changes in process or control practice, arbitrary correction factors were applied. This
was done after discussion with the company's representatives and especially with a pre-
vious manager who had spent almost all his career with Libby and who had extensive
knowledge of the operations." Samples were taken until 1982. Cumulative exposure
levels were calculated based on job histories, operation locations, and estimated aver-
age fiber concentrations.In McDonald and Armstrong 2003, HERO ID: 709547, they
used three different indices for exposure: "...(A) average intensity over first five years of
employment (f/ml); (B) cumulative exposure (f/ml.y); and (C) residence weighted cu-
mulative exposure, for which each year"s exposure is weighted according to the number
of years since it was experienced (f/ml.y)."
Medium In McDonald et al. 1986, HERO ID: 29964, cumulative continuous exposure levels
were used for case-referent analysis of mesothelioma. In McDonald and Armstrong
2003, HERO ID: 709547, both continuous and categorical exposure levels were used in
Poisson regression analyses for mesothelioma.
High The follow-up period is greater than 20 years in this cohort for >2/3 of deaths (as shown
in McDonald et al. 1986, HERO ID: 29964), suggesting there is sufficient considera-
tion of latency of mesothelioma. The temporality is established and exposure occurred
before outcome.
Domain 3: Outcome Assessment
Continued on next page ...
Page 88 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29964 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Mcdonald, A. D., Armstrong, B., Sebastien, P. (1986). Cohort study of mortality of vermiculite miners exposed to tremolite. Occupational
and Environmental Medicine 43(1986):436-444.
Mesothelioma
Cancer/Carcinogenesis: mesothelioma mortality; Lung/Respiratory: mesothelioma mortality; Mortality: mesothelioma mortality
Asbestos- Libby amphibole: 1318-09-8
29964, 709547, 709695
29964
Domain
Metric
Rating
Comments
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High In McDonald et al. 1986, HERO ID: 29964, the cases were ascertained from death cer-
tificates and underlying cause of death was coded by a single qualified nosologist ac-
cording to ICD-8 codes (163, 199, and 515). In McDonald and Armstrong 2003, HERO
ID: 709547, the additional deaths were coded by State nosologists in ICD-9 (codes not
specified).
High Findings of the study were reported in abstract and results. Analyses show relative risk
with 95% CI (McDonald et al. 1986, HERO ID: 29964, McDonald and Armstrong 2003,
HERO ID: 709547). McDonald and Armstrong 2003, HERO ID: 709547 also reports a
p-trend. Reporting bias is not likely to be introduced.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Medium For case-referent analysis, age, sex, and date of hire were matched (McDonald et al.
1986, HERO ID: 29964), while in McDonald and Armstrong 2003, HERO ID: 709547,
there is no covariate adjustment, except for sex and race.
Metric 10: Covariate Characterization Medium The source of covariates were not described but likely collected from employment
records.
Metric 11: Co-exposure Counfounding N/A Co-exposure is not applicable for mesothelioma because there are no established risk
factors other than exposure to asbestos.
Domain 5: Analysis
Metric
12:
Study Design and Methods
Medium
The case-referent and Poisson analyses were appropriate method to evaluate the
exposure-outcome associations.
Metric
13:
Statistical Power
N/A
This metric is rated as not applicable according to EPA guidance for mesothelioma (i.e.,
mark not applicable when no analyses are performed for mesothelioma).
Metric
14:
Reproducibility of Analyses
Medium
The descriptions of the methods and analyses are sufficient and conceptually repro-
ducible.
Metric
15:
Statistical Analysis
Medium
Descriptions of case-referent and Poisson models are clear.
Additional Comments: This is a cohort of 2 studies (McDonald et al. 1986, HERO ID: 29964, McDonald and Armstrong 2003, HERO ID: 709547), with latter being a follow-up
on the same cohort of workers in a Libby asbestos mine, with more deaths added for analyses. Metrics 11 and 13 are marked as NA as per instructions
specific for mesothelioma.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 89 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 307878i Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Menegozzo, S., Comba, P., Ferrante, D., De Santis, M., Gorini, G., Izzo, F., Magnani, C., Pirastu, R., Simonetti, A., Tiinesi, S., Menegozzo, M. (2011).
Mortality study in an asbestos cement factory in Naples, Italy. Annali dell'Istituto superiore di sanit" 47(2011):296-304.
Mesothelioma
Lung/Respiratory: malignant neoplasms respiratory tract (160-165) mortality, malignant neoplasms pleura (163) mortality, malignant neoplasms peri-
toneum (158) mortality; Mortality: malignant neoplasms respiratory tract (160-165) mortality, malignant neoplasms pleura (163) mortality, malignant
neoplasms peritoneum (158) mortality; Cancer/Carcinogenesis: malignant neoplasms respiratory tract (160-165) mortality, malignant neoplasms pleura
(163) mortality, malignant neoplasms peritoneum (158) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3078781
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM.Authors provided a detailed history of asbestos
work in the plant, but methodology of exposure measurement is limited. Generic dust
measures were available from the 1960s and in 1979, 64 airborne asbestos fiber sam-
plings were available (crocidolite specific). No information is provided regarding how
measures were taken.
Medium The study cohort includes workers hired from 1950-1986, and follow-up is from 1965-
2005. Even though the environmental airborne generic asbestos fiber and crocidolite
sampling in different areas in 1979, this study only presented "duration of exposure" that
can be used as a surrogate of exposure assessment for several diseases and to determine
exposure-response relationships.
Additional Comments:
NOTE: This study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was mentioned in
the study or a cited source.This study provides a comprehensive analysis of SMRs from workers in the Bagnoli factory cohort. Overall, the study describes
metrics well, but lacks proper covariables and excluded smoking in their analyses. There is very little information regarding the measurements of asbestos
dusts within the factory, with no mention of what tools were used or measures for non-crocidolite asbestos exposures.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 90 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2325159 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Metintas, S., Metintas, M., Ak, G., Kalyoncu, C. (2012). Environmental asbestos exposure in rural Turkey and risk of lung cancer. International lournal of
Environmental Health Research 22(2012):468-479.
Mesothelioma
Lung/Respiratory: Malignant mesothelioma; Cancer/Carcinogenesis: Malignant mesothelioma
Asbestos - Tremolite: 14567-73-8
No linked references.
2325159
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium White soil exposure was assessed both indoors and outdoors (two samples for each
environment) in each village. Inclusion for indoor measurements included white-washed
walls with white soil. Outdoor samples were taken from the center of the village on the
main road. Samples were sent to specialists in the National Institute of Workers Health
and Security (ISGUM), Ankara. A PCM was used to count fibres longer than 5 um. This
has been marked medium as the authors don't clarify if multiple time periods were used
for measures.
Low Levels of exposure are by exposed and unexposed villages and by men and women. As
there are only two levels of exposure, the metric is rated Low.
Additional Comments:
HEROID 235159 was not evaluated for any metrics except Metric 4 and 5 and had no data extracted because it did not have sufficient exposure information
to be useful for dose-response analysis. Metric 5 only provided 2 exposure levels, thus receiving a Low rating. Comments can still be found for all metric,
but they are not rated.
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 91 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2079066 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Moshammer, H., Neuberger, M. (2009). Lung function predicts survival in a cohort of asbestos cement workers. International Archives of Occupational
and Environmental Health 82(2009):199-207.
Mesothelioma
Mortality: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
2079066
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Estimated cumulative exposure was described as based upon historical spot measure-
ments analyzed by light microscopy and exposure classifications assigned to each work
area. Workplace asbestos exposure spot measurement records were available from 1950
until 1981. Each worker was assigned a specific category of exposure for every year
that worker worked at the asbestos cement factory. Details regarding consideration for
changes in job area or task during that year were not provided. Authors did not discuss
the potential for exposure misclassification within these methods, but the misclassi-
fication was likely non-differential. Mean (IQR) estimated cumulative exposure was
reported in Table 2 as 72.62 fiber years (fibers x years/cmA 3) (70.81).
Metric 5: Exposure Levels Low The range and distribution of estimated exposure across five workplace areas in Table 1
is sufficient to develop exposure-response estimates. Separate mesothelioma mortality
analyses results within Table 4 utilized only binary (yes/no) amphibole exposure as an
exposure predictor variable.
Additional Comments: Metric 4 rating changed to low due to no mention of PCM/TEM in exposure assessmentMa
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 92 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082545 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Neuberger, M., Kundi, M. (1990). Individual asbestos exposure: Smoking and mortality"a cohort study in the asbestos cement industry. British Journal of
Industrial Medicine 47(1990):615-620.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3082545
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection Medium Eligibility criteria not described in detail (e.g., of the 2816 persons eligible for the
study), but other key details of participants described. A brief description of the study
setting and asbestos use was provided.
Metric 2: Attrition Medium A total of 121 persons lost to follow up. Authors note this was mostly due to emigration.
Metric 3: Comparison Group High A nested case-control analysis was completed for mesothelioma. Controls were matched
by year of first employment, duration of employment, and year of birth.
Domain 2: Exposure Characterization
Metric 4:
Metric 5:
Metric 6:
Measurement of Exposure
Exposure Levels
Temporality
Medium "Individual exposures were estimated (from 1973) from personal records onduration
of exposure at different workplaces, estimations of dust concentration until 1965, dust
measurements mainly by a conimeter method until 1975, and by personal air samplers
and membrane filter methods (Asbestos International Association, HERO 3648707) sub-
sequently. " The referenced study (HERO 3648707) cites the use of PCM methodology
to count fibres. Details on implementation for this study were limited, but it appears they
followed a standard protocol.
Medium Reports 4 exposure groups (high, high/medium, medium, and neglible).
Medium Study authors note that all persons who had not been observed for more than 15 years
from start of exposure were excluded.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Medium Follow up on vital status for participants was undertaken using government registration
offices, death registries, physicians, and pathologists. Mesothelioma was identified using
ICD-9 163.
High Table 3 indicates crocidolite exposure of four cases of mesothelioma verified by
necropsy and controls matched for sex, age, time of first employment, and duration of
employment. Chi-square results are provided in the discussion.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment High Cases and controls were matched on several factors: year of first employment, duration
of employment, and year of birth.
Metric 10: Covariate Characterization Medium Authors note they used a "standardised questionnaire on occupational exposures and
smoking." Age was presumably determined from personnel records.
Continued on next page ...
Page 93 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082545 Table: 1 of 1
... continued from previous page
Neuberger, M., Kundi, M. (1990). Individual asbestos exposure: Smoking and mortality"a cohort study in the asbestos cement industry. British lournal of
Industrial Medicine 47(1990):615-620.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3082545
Domain
Metric
Rating
Comments
Metric 11:
Co-exposure Counfounding
Low
In an occupational setting, potential co-exposures are not discussed.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium A chi-square test was used to compare exposure among the cases and controls.
Medium Only four confirmed mesothelioma cases were observed, and study authors made com-
parisons with a nested group of 16 controls.
Medium Simple comparisons were made between groups. No concerns for reproducibility.
Medium No concerns regarding use of chi-square to determine differences between groups.
Additional Comments: Historical prospective cohort study analyzing 49 lung cancer and 4 mesothelioma cases from asbestos-exposed cement factory workers. Methods were
generally standard, but some details were not present regarding selection and exposure measurement, however, this is not likely to appreciably impact the
results. Mesothelioma was analyzed in a nested case-control design with a small set of controls (n=16).
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 94 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 158 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Nicholson, W. J., Selikoff, I. J., Seidman, H., Lilis, R., Formby, P. (1979). Long-term mortality experience of chrysotile miners and millers in Thetford
Mines, Quebec. Annals of the New York Academy of Sciences, Vol. 330 33021-Nov.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma; Mortality: Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
158
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This study revolved around a cohort of men employed for at least 20 years in one of
four companies that mine and mill chrysotile, exclusively. This represented 544 indi-
viduals from four separate operations. These operations were examined in Thetford
Mines, Quebec, Canada. The participants included represented a variety of potential job
classifications. However, not many details beyond this were included pertaining to in-
clusion criteria, such as the total number of individuals that could have potentially been
included.
Medium There was moderate exclusion of participants from analyses. The aim of this study was
to determine mortality outcomes for participants enrolled from the asbestos mines. The
authors were able to obtain 172 of 178 certificates of death, and there were an additional
130 cases for which the authors obtained clinical, surgical, and pathological data to
supplement death certificate information.
Medium The expected number of deaths/illnesses included in this study were derived from the
age-specific death rate data for white Canadian males. It is important to note that they
did not use data specific to Quebec, but it is noted that "national rates are not impor-
tantly different from those of Quebec province but are likely to be significantly higher
than those of the rural mining counties in which these workers lived" (Nicholson et
al., 1979). The authors also explicitly discuss the potential for healthy worker effect,
but they mention that "the effects of asbestos exposure appear to overcome the bene-
ficial health status usually associated with employ ability" (Nicholson et al., 1979). As
mentioned, the participants were compared to white Canadian males, but there was no
discussion of the racial makeup of employees.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure High The authors report that 97 air samples were collected from various work locations within
five operating asbestos mines/mills. These samples were collected between 1973 and
1975, and a majority of them were personal samples. The concentrations varied greatly,
but it is reported that "in virtually all work categories average dust concentrations ex-
ceeded the asbestos standard then current in the United States of 5 fibers longer than 5
micrometers/milliliter (5 f/ml)" (Nicholson et al., 1979). The authors detail that they fol-
lowed the methods outlined by the National Institute of Occupational Safety and Health
to determine asbestos concentrations, which utilizes a microscope with phase contrast
optics (1972, 145).
Continued on next page ...
Page 95 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 158 Table: 1 of 1
... continued from previous page
Nicholson, W. J., Selikoff, I. J., Seidman, H., Lilis, R., Formby, P. (1979). Long-term mortality experience of chrysotile miners and millers in Thetford
Mines, Quebec. Annals of the New York Academy of Sciences, Vol. 330 33021-Nov.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma; Mortality: Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
158
Domain
Metric
Rating
Comments
Metric 5:
Metric 6:
Exposure Levels
Temporality
Medium
High
Multiple levels of asbestos exposure were presented in the study. Table 3 includes a
range, mean, and number of samples of asbestos in each of the mine/mill locations. It is
also further divided into various work areas/activities, including general mill air, bagging
asbestos, quality control laboratory, crusher, dryer, shops, and nonwork areas. This table
highlights that a majority of the cohort was employed in facility two, and concentrations
are reported in fibers longer than 5 micrometers/ml of air.
One of the requirements to be included in this study was that the workers must have
been employed for at least 20 years. This means that there is an appropriate temporality
between exposure and outcome such that exposure occurred prior to the outcome.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High
Medium
Death certificates were examined to determine the causes of death of participants. There
was no mention of ICD coding schemes present in this study.
The findings are reported at various points throughout the study. Expected and observed
deaths are reported, along with the O/E calculations. However, information such as
confidence intervals are not reported, contributing to the medium rating.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Low
N/A
N/A
No description is provided in this study that discusses considerations for potential con-
founders or their adjustment.
Covariates were not assessed in this study.
Because mesothelioma has few other causes than asbestos exposure, this metric was not
rated.
Domain 5: Analysis
Metric 12:
Metric 13:
Metric 14:
Metric 15:
Study Design and Methods
Statistical Power
Reproducibility of Analyses
Statistical Analysis
Medium
Medium
Low
Medium
The study design and methods are appropriate for the research question being examined.
Even though an explicit discussion of power was not included, the number of partici-
pants is adequate to detect an effect.
There is a very limited discussion of the analysis presented in this study.
SMRs were utilized, and it is clear why this analysis method was used.
Additional Comments:
This study had some strengths and limitations. One benefit was the temporality component, since one of the inclusion criteria was that employees must have
worked there for at least 20 years, providing a sufficient time from exposure to outcome. There was also an adequate number of participants included in the
study to determine an effect. However, these results could be limited. It would have also been beneficial for the authors to provide more information about
the causes of deaths, such as a discussion about diagnoses or specific indications, such as through cytological or histological means, for mesothelioma.
Continued on next page ...
Page 96 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 158 Table: 1 of 1
... continued from previous page
Study Citation:
Nicholson, W. J., Selikoff, I. J., Seidman, H., Lilis, R., Formby, P. (1979). Long-term mortality experience of chrysotile miners and millers in Thetford
Mines, Quebec. Annals of the New York Academy of Sciences, Vol. 330 33021-Nov.
Mesothelioma
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma; Mortality: Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5
HERO ID:
158
Domain Metric
Rating
Comments
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 97 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081842 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Nokso-Koivisto, P., Pukkala, E. (1994). Past exposure to asbestos and combustion products and incidence of cancer among Finnish locomotive drivers.
Occupational and Environmental Medicine 51(1994):330-334.
Mesothelioma
Gastrointestinal: Stomach cancer, Rectal cancer, Colon cancer, Oral cavity and pharynx cancer; Lung/Respiratory: Lung and trachea cancer, Mesothe-
lioma; Renal/Kidney: Kidney cancer, Bladder, ureter, urethra cancer; Skin/Connective Tissue: Skin (non-melanoma) cancer, Skin melanoma; Immune/
Hematological: Leukemia, Hodgkin's disease, Non-Hodgkin's lymphoma; Reproductive/Developmental: Prostate cancer; Cancer/Carcinogenesis: All site
cancer, Oral cavity and pharynx cancer, Stomach cancer, Colon cancer, Rectal cancer, Lung and trachea cancer, Mesothelioma, Prostate cancer, Kidney
cancer, Bladder, ureter, urethra cancer, Skin melanoma, Skin (non-melanoma), Non-Hodgkin's lymphoma, Hodgkin's disease, Leukemia
Asbestos - Anthophyllite: 17068-78-9; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3081842
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low To estimate pre-1970s steam engine maintenance exposures in Finland, working con-
ditions were reconstructed in two workshops with the assistance of workers who had
been exposed. During reconstructed dismantling of the outer covers of the boilers of
two engines, eight personal air samples were collected. The authors state that "asbestos
exposure was measured with standardized techniques," but they don't specify what these
techniques were. Therefore, it is unclear whether PCM, TEM, or another method was
used. The authors also reported that asbestos concentrations in cabins of diesel locomo-
tives with asbestos pipe insulation was measured.
Metric 5: Exposure Levels Low The range and distribution of exposure was limited. The authors reported that "the av-
erage number of fibres > 5 um was 5.0 (range 2.5-7.5)/cmA 3, indicating medium expo-
sure" (Nokso-Koivisto & Pukkala, 1994) for the reconstructed steam engine dismantling.
The number of fibers was undetectable for diesel locomotive cabins. Furthermore, al-
though different time periods were assessed, the study only assessed two exposure levels
- standardized incidence ratios were used to compare locomotive drivers (exposed) to
the Finnish population (presumed unexposed or lower exposed). Therefore, this study
does not include sufficient information for dose-response assessment.
Additional Comments: None
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 98 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3531256 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Nuyts, V., Vanhooren, H., Begyn, S., Nackaerts, K., Nemery, B. (2017). Asbestos bodies in bronchoalveolar lavage in the 21st century: a time-trend
analysis in a clinical population. Occupational and Environmental Medicine 74(2017):59-65.
Mesothelioma
Lung/Respiratory: mesothelioma; Cancer/Carcinogenesis: mesothelioma
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3531256
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Asbestos bodies were quantified in BAL samples using light microscopy.
Metric 5: Exposure Levels Medium The range and distribution of exposure is sufficient to develop an exposure-response
estimate, and an exposure-response model using a continuous measure of exposure was
used for the analysis. Exposures ranged from 0 to 164.5 asbestos bodies (AB)/mL, with
a median of 0.5 AB/mL and an arithmetic mean of 5 AB/mL.
Additional Comments: None
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 99 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3078062 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Offermans, N. S., Vermeulen, R., Burdorf, A., Goldbohm, R. A., Kauppinen, T., Kromhout, H., van den Brandt, P. A. (2014). Occupational asbestos
exposure and risk of pleural mesothelioma, lung cancer, and laryngeal cancer in the prospective Netherlands cohort study. Journal of Occupational and
Environmental Medicine 56(2014):19-Jun.
Mesothelioma
Cancer/Carcinogenesis: pleural mesothelioma, lung cancer, laryngeal cancer (glottis and supraglottis cancers); Lung/Respiratory: pleural mesothelioma,
lung cancer, laryngeal cancer (glottis and supraglottis cancers)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3078062
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The study employed two job exposure matrices - the DOMJEM (the Netherlands) and
the FINJEM (Finland) - however, only one matrix appears to leverage quantitative mea-
sures of exposure to asbestos, but it is unclear if TEM or PCM were used. It appears
that the DOMJEM uses expert judgment only to assign semiquantitative exposure val-
ues with corresponding weighting. The FINJEM uses expert judgment and exposure
measurement, though there is no discussion of the methodology used to make those
measurements.
Medium This study examines exposure by tertile of cumulative exposure, tertile of duration of
exposure, and, among the exposed only, tertile of duration of high exposure. Many of
the analyses use those who were not exposed to asbestos as the referent group. There
is an appropriate range of exposure among the study population to assess the exposure-
response relationship.
Additional Comments: This case-cohort study leverages the NLCS cohort to assess the association between occupational asbestos exposure and pleural mesothelioma cases. The
study design and methodological approaches are robust, and the study employed the ICD-O-3 to identify mesothelioma cases. There are no major concerns
about residual bias in the observed results.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 100 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: m Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Peto, J. (1980). Lung cancer mortality in relation to measured dust levels in an asbestos textile factory. IARC Scientific Publications (1980):829-836.
Mesothelioma
Cancer/Carcinogenesis: pleural mesothelioma mortality; Mortality: pleural mesothelioma mortality; Lung/Respiratory: pleural mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
163
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This study is an extended follow up of the same North England asbestos textile factory
worker cohort recruited from the work areas with highest expected asbestos exposure:
fiberizing, carding, spinning, weaving, and plaiting. (Knox et al. 1968, HEROID: 115;
Peto et al. 1977, HEROID: 3084525). Here, 679 men who had begun work after 1933
and who had accrued >10 total years of service by 1972 were included in the study.
There is limited detail on recruitment or other inclusion criteria. There may be some
selection bias, as only healthier workers would be able to complete >10 years of work in
select high-exposure areas.
High Follow up for mortality continued through 1978 by the National Health Central Register
and the factory personnel department. 41 of 679 (6% ) men were unable to be traced.
In this analysis, they were assumed to have been alive at the previous follow up date
(12/31/1974), but their subsequent man-years were not included here. Deaths of workers
over 85 are ignored. There is no other mention of drop-out or loss that was not included
in follow-up.
Low The study only mentions "unaffected controls" in the section on lung cancer mortality
and dust levels. Another study using the same cohort (Knox et al. 1968, HEROID: 115)
notes comparisons to "national rates," however it's not clear if this is the same compar-
ison group for this study. The study does compare in text results workers first exposed
before 1951 and those in 1951 and later (i.e., cohort 1 and 2).
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Asbestos fiber exposure concentrations were reportedly measured using a thermal pre-
cipitator in years between 1951-1961. Additional support for understanding past area
dust measures in particles/mL were taken in conversations with hygiene officers from
the factory. Static membrane filters in years after 1961. Authors state that for each area
of the factory, representative combinations of measures were used and averaged to be
converted to modern counting methods. "The revised estimates are based on preliminary
data abstracted from a detailed analysis that is currently being conducted by T.B.A. In-
dustrial Products Ltd and must be regarded as provisional. However, they indicate that
average dust levels were in the region of 30 fibre/ml in 1951 and remained high until
about 10 years ago."
Low Asbestos exposure appears to be continuous, however SMR analyses are stratified by
years since first exposure and year of first exposure, not by a quantitative measure of
asbestos exposure. This suggests the exposure for SMR analyses is dichotomous.
Continued on next page ...
Page 101 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 163 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Peto, J. (1980). Lung cancer mortality in relation to measured dust levels in an asbestos textile factory. IARC Scientific Publications (1980):829-836.
Mesothelioma
Cancer/Carcinogenesis: pleural mesothelioma mortality; Mortality: pleural mesothelioma mortality; Lung/Respiratory: pleural mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
HERO ID:
163
Domain
Metric
Rating
Comments
Metric 6: Temporality
Medium There is appropriate temporality reported (>10 years) to follow-up to establish
exposure-outcome, however it is not clear what share of workers has longer follow up
time, as only man-years are reported, not total workers by years of service. In the pa-
per on the same cohort published prior to this one, which had more subjects (Peto et al.
1977, HEROID: 3084525), 406/1085 (37% ) of workers had >20 years of service. It
seems reasonable to assume a similar proportion in the current study.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Medium No ICD codes were used to establish mortality, except for gastrointestinal cancer, how-
ever no version is explicitly listed. Authors report that follow-up was itself completed by
National Health Central Register (NHCR) and by the factory personnel department.
High Mesothelioma is reported in all parts of study. Rate of pleural mesothelioma mortal-
ity is reported without effect estimates (in tables). Some data is available in text with
confidence limits.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Low Sex is adjusted for based on inclusion of only men. There is brief mention of adjustment
for man-years in the analysis, but no other variables are discussed.
Metric 10: Covariate Characterization Low Covariate is assumed to have been collected from factory personnel records. No explicit
detail is provided.
Metric 11: Co-exposure Counfounding N/A There are no applicable co-exposures for mesothelioma.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design is appropriate for measuring relative risk and mortality rates of work-
ers from the textile factory.
Medium The number of subjects (n=679) should be sufficient to find any true relationships be-
tween exposure and outcome.
Medium The methods described in the paper are clear enough to be conceptually replicated.
Medium SMR analyses were appropriate, with no explicit assumptions to be met.
Additional Comments: Asbestos fiber types are detailed in an earlier iteration of the current study (Knox et al., 1968, HEROID: 115). There is limited detail on recruitment and
participation methods and rates, as well as how outcomes were ascertained by the National Health Central Register and factory personnel departments.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 102 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 165 Table: 1 of 1
Peto, J., Seidman, H., Selikoff, I. J. (1982). Mesothelioma mortality in asbestos workers: implications for models of carcinogenesis and risk assessment.
British lournal of Cancer 45(1982):124-135.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Mesothelioma; Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma
Asbestos - Not specified: 1332-21-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite
(riebeckite): 12001-28-4
No linked references.
165
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Low This study examined mesothelioma death rates among current and former 17,800 in-
sulation workers in North America, however this is not entirely certain given how the
study was written. Authors cite a previous work for details (Selikoff et al. 1979), but this
was not available at the time of evaluation. There is no information given on the study
population or its recruitment.
Low The number of participants were not reported at the different stages of the studies dis-
cussed in the manuscript.
Low The comparison groups belong to different studies (i.e., settings), exposed to different
asbestos fiber types in different locations (as suggested by the limited descriptions pro-
vided on Table III). It is uncertain if they belonged to the same eligible population.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Based on additional review of related publications and the 1986 assessment, asbestos
measurements were conducted using stand membrane filter technique of the US Public
Health Service, presented in Nicholson 1976. Membrane filters were counted using
PCM.
Medium Based on information presented in the 1986 assessment and Nicholson 1976, cumulative
exposures for workers were determined based on length of work history and asbestos
fiber counts presented in Nichols 1976.
High Selikoff, 1979 presents complete data on years from exposure onset including 35+ years
of follow-up. This study is part of the foundation establishing the latency of effect.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Medium The authors did not provide details about how the outcome was diagnosed in the re-
viewed studies. Medium is the most appropriate rating but still does not adequately
match with the study.
High The authors reported results for the outcomes mentioned in the abstract, allowing a
detailed extraction.
Domain 4: Potential Confounding / Variability Control
Continued on next page .
Page 103 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 165 Table: 1 of 1
... continued from previous page
Peto, J., Seidman, H., Selikoff, I. J. (1982). Mesothelioma mortality in asbestos workers: implications for models of carcinogenesis and risk assessment.
British lournal of Cancer 45(1982):124-135.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Mesothelioma; Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma
Asbestos - Not specified: 1332-21-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite
(riebeckite): 12001-28-4
No linked references.
165
Domain
Metric
Rating
Comments
Metric 9:
Metric 10:
Metric 11:
Covariate Adjustment
Covariate Characterization
Co-exposure Counfounding
Medium
Medium
N/A
Some adjustments were made (age, sex, years of exposure) but not described in detail.
There is indirect evidence that appropriate adjustments were also made, e.g., the foot-
note on p. 130 indicates that the authors made assumptions of white male rates for all
causes of death to adjust the authors "lifelong risk" estimates.
The methods used for confounder assessment are of unknown validity as details were
not provided. They are likely provided from company or employment records.
Not applicable (mesothelioma outcome).
Domain 5: Analysis
Metric 12:
Metric 13:
Metric 14:
Metric 15:
Study Design and Methods
Statistical Power
Reproducibility of Analyses
Statistical Analysis
Medium
Medium
Medium
Medium
The authors used appropriate statistical methods (SMRs, survival relative risk) to report
the distribution of mesothelioma mortality cases by age and years since first exposure.
The number of subjects analyzed (n=17,800 for North American insulation workers,
not including other cohorts in thi) is sufficiently large to detect the effect in the exposed
population (reporting 236 cases of mesothelioma deaths).
Reviewing the relevant information across publications and the 1986 assessment pro-
vides sufficient detail to conceptually understand the analysis.
Methods for calculating mortality risks are transparent.
Additional Comments:
This article is a review. While it may reanalyze or represent analyses of Selikoff et al. 1979, it does not appear to be original data in any way. The
measurement of exposure was uninformative as PCM or TEM were not mentioned, and details about exposure measurements were not provided. Fiber
types are those reported by any study in the review.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 104 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082405 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Rogers, A. J., Leigh, J., Berry, G., Ferguson, D. A., Mulder, H. B., Ackad, M. (1991). Relationship between lung asbestos fiber type and concentration and
relative risk of mesothelioma. A case-control study. Cancer 67(1991): 1912-1920.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4
No linked references.
3082405
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
High This study employed a case-control study design. Cases were obtained from the Aus-
tralian Mesothelioma Surveillance Program, which was in place from January 1, 1980 to
December 31, 1985. Notifications to this program helped the authors obtain participants,
and "voluntary notifications were sought from clinicians and pathologists throughout
Australia" (Rogers et al., 1991). Cancer registries in each Australian state were exam-
ined for cross-checking purposes. The only individuals allowed into the study were
those with a definite or probably mesothelioma diagnosis as determined by five experi-
enced pathologists appointed by the Royal College of Pathologists of Australasia. There
were 697 total cases with these diagnoses, but only 221 had lung tissue materials avail-
able. This included 209 individuals with a definite designation, and 12 with a probable
designation.
High While there were 697 potential participants identified as having definite or probable
mesothelioma diagnoses, only 221 cases were included in the analyses because of the
availability of lung tissue samples. The authors mention that "postmortem material from
five possible cases was also available but was excluded from the current study" (Rogers
et al., 1991). No information was provided as to why these samples were excluded;
however, this represented a minimal level of attrition.
Low This study utilized an unmatched method for obtaining controls. Formalin-preserved
lung tissue was obtained for another study from consecutive autopsies at the Royal
Prince Alfred Hospital in Sydney, Australia. These necropsies took place during the
same time period as the cases. Exclusion criteria for these controls included pneumo-
coniosis, emphysema, pneumonia, or gastrointestinal cancer. 359 control samples were
included in this study. They did mention that there was "reasonable frequency matching
for age and sex" (Rogers et al., 1991).
Domain 2: Exposure Characterization
Continued on next page .
Page 105 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082405 Table: 1 of 1
... continued from previous page
Rogers, A. J., Leigh, J., Berry, G., Ferguson, D. A., Mulder, H. B., Ackad, M. (1991). Relationship between lung asbestos fiber type and concentration and
relative risk of mesothelioma. A case-control study. Cancer 67(1991): 1912-1920.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Cancer/Carcinogenesis: Mesothelioma
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4
No linked references.
3082405
Domain
Metric
Rating
Comments
Metric 4:
Measurement of Exposure
Metric 5:
Metric 6:
Exposure Levels
Temporality
Medium Overall, 0.5 gram tissue samples were prepared and used for the examination of fiber
concentrations. Samples were filtered onto Millipore 0.8 um filters, which were then
examined using light microscopy. Nuclepore 0.4 um filters were used for the examina-
tion with transmission electron microscopy. The authors only counted fibers that were
> 2um (as determined by TEM), or > 5um (as determined by light microscopy). The
sensitivity was 15,000 fibers/g for light microscopy, and 200,000 fibers/g for TEM. It
is important to note that light microscopy fiber counts "were made on all 221 cases and
359 controls. Electron microscopic fiber counts, EDAX, and fiber length measurements
were made on all 221 cases and 103 male controls, drawn randomly from the total group
of 276" (Rogers et al., 1991). Because these samples were examined in necropsied lung
tissues, fiber concentrations were only determined at one point in time.
Medium The range of exposures is sufficient to develop an exposure-response estimate.
Low The temporality of exposure and outcome is uncertain. However, because asbestos con-
centrations were estimated from lung tissue samples, it can reasonably be assumed that
exposure preceded the outcome of mesothelioma.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High Mesothelioma diagnosis was determined by a panel of five experienced pathologists,
who were all appointed by the Royal College of Pathologists of Australasia. Potential
classifications included definite, probably, possible, and not mesothelioma based on
histologic classification. The scores for determining these classifications were 1, 0.75,
0.50, and 0, respectively. Only definite and probably classifications were included in the
study, and "the definite diagnosis was regarded as the category with score nearest to the
mean score" (Rogers et al., 1991).
High Mesothelioma findings are reported throughout the study, and odds ratios are provided
with their associated 95% confidence intervals.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment High The authors described in their discussion section that they included age as a confounding
variable, as it was a way to frequency match cases and controls.
Metric 10: Covariate Characterization Low The authors did not provide a description of the methods used for covariate characteriza-
tion.
Metric 11: Co-exposure Counfounding N/A As this was a mesothelioma study, there was no need to evaluate potential co-exposures,
as there are few other causes than asbestos exposure, meriting a "not applicable" rating.
Domain 5: Analysis
Continued on next page ...
Page 106 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082405 Table: 1 of 1
... continued from previous page
Rogers, A. J., Leigh, J., Berry, G., Ferguson, D. A., Mulder, H. B., Ackad, M. (1991). Relationship between lung asbestos fiber type and concentration and
relative risk of mesothelioma. A case-control study. Cancer 67(1991): 1912-1920.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Cancer/Carcinogenesis: Mesothelioma
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4
No linked references.
3082405
Domain
Metric
Rating
Comments
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design implemented is appropriate for the research question being examined.
Medium The authors did not provide an explicit discussion of the power for this study, but there
was an adequate number of participants to detect an effect in the exposed population.
Medium Given the amount of detail provided by the authors, this study is reproducible. Overall,
the authors calculated the relative risk, estimated by odds ratios. Fiber content levels
were used to group participants, and each level was compared with the zero-exposure
group, which was defined as <15,000 fibers by might microscopy, or <200,000 fibers
by TEM. The significance of linear trends was determined with the Mantel-Haenszel
chi-squared test. Multiple logistic regression models were also estimated.
Medium The model used for calculating the risk estimates is transparent. The logistics regression
model operates under the assumption that the distribution of the outcome is binomial.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric 16: Use of Biomarker of Exposure
Metric 17: Effect Biomarker
Metric 18: Method Sensitivity
Metric 19: Biomarker Stability
Metric 20: Sample Contamination
Metric 21: Method Requirements
Metric 22: Matrix Adjustment
High
N/A
Medium
Low
Medium
Medium
Low
The examination of fiber concentrations in lung tissue allow for a quantitative relation-
ship with external exposure. Even though there was the potential for multiple fiber types
to be present in the study, the authors were able to identify the specific fiber types by
"comparing the energy dispersive x-ray analysis (EDAX) spectrum of the fiber with
those of the International Union Against Cancer (UICC) asbestos specimens prepared in
the same manner" (Rogers et al., 1991).
The only biomarkers assessed in this study were biomarkers of exposure, as the authors
were examining fiber counts in lung tissue.
The authors detailed the analytical sensitivity for both light microscopy and TEM. The
sensitivity for light microscopy was 15,000 fibers per gram, and the limit was 200,000
fibers per gram for TEM.
The authors detail that the lung tissue was preserved in formalin, and they were gen-
erally comprised of a "5x5x5 cm blocks from the lower lobe of the uninvolved lung"
(Rogers et al., 1991). They did not describe the storage history further or information
pertaining to stability.
There is no information provided about the potential contamination of the samples.
The authors utilized light microscopy and transmission electron microscopy to deter-
mine fiber concentrations.
There was no description of matrix adjustments performed in this study.
Continued on next page ...
Page 107 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082405 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Rogers, A. J., Leigh, J., Berry, G., Ferguson, D. A., Mulder, H. B., Ackad, M. (1991). Relationship between lung asbestos fiber type and concentration and
relative risk of mesothelioma. A case-control study. Cancer 67(1991): 1912-1920.
Mesothelioma
ID(s):
Cancer/Carcinogenesis: Mesothelioma
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4
No linked references.
3082405
Domain Metric Rating Comments
Additional Comments: This study sought to examine the relationship between mesothelioma and asbestos fiber type and concentration found in postmortem lung tissue samples.
One of the strengths of this study was that the authors utilized a panel of pathologists to identify, on a scale, a histologic classification of mesothelioma.
Another strength was their use of TEM for the quantification of asbestos fibers. Some limitations included a lack of information surrounding storage and
contamination for the lung tissue samples, as well as the temporality. However, because this study examined postmortem samples, it can still be assumed
that exposure preceded the outcome.
Overall Quality Determination Medium
Page 108 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083350 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Roggli, V. L., Pratt, P. C., Brody, A. R. (1986). Asbestos content of lung tissue in asbestos associated diseases: a study of 110 cases. British Journal of
Industrial Medicine 43(1986):18-28.
Mesothelioma
Lung/Respiratory: mesothelioma; Cancer/Carcinogenesis: mesothelioma
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Anthophyllite: 17068-78-9; Asbestos - Tremolite:
14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3083350
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Metric 5:
Measurement of Exposure
Exposure Levels
Low Asbestos bodies in lung tissue samples were quantified by LM and SEM, post-mortem.
Medium The range and distribution of exposure is sufficient to develop an exposure-response
estimate, which was done using a continuous measure of exposure.Median and range
asbestos bodies (AB) exposures measured via LM were as follows:. Asbestosis: 106,000
(range: 2,400 " 684,000) AB/g. Mesothelioma: 550 (range: 0.2 " 13,3000) AB/g. Lung
cancer: 102 (0.8 " 46,000) AB/g. Idiopathic pulmonary fibrosis: 9 (0.8 " 148) AB/g.
Normal lungs: 3 (0.2 " 22) AB/g.
Additional Comments:
Overall, information on the measurement of exposure metric (M4) to assess exposure was limited or rated low (authors used Asbestos bodies in lung tissue
samples were quantified by LM and SEM, post-mortem). The exposure levels metric (M5) information reported was adequate to determine exposure-
response relationships.
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 109 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 758980 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Roggli, V. L., Vollmer, R. T., Butnor, K. J., Sporn, T. A. (2002). Tremolite and mesothelioma. Annals of Occupational Hygiene 46(2002):447-453.
Mesothelioma
Cancer/Carcinogenesis: mesothelioma
Asbestos - Tremolite: 14567-73-8; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-
78-9
No linked references.
758980
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Medium The authors indicated the use of scanning electron microscopy to analyze fiber presence
on lung tissue samples, estimating the quantity of fibers present per gram of wet lung
tissue.
Low The authors only reported the median and range of fiber concentrations in lung samples
as they related to the presence of mesothelioma (Table 1). Multivariate analyses were
conducted using continuous measures of talc and chrysotile, but only as they related
to the presence of tremolite and the presence of all three of tremolite, actinolite, and
anthophyllite in lung tissue, rather than the presence of mesothelioma (Table 4).
Additional Comments: None
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 110 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: m Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Rubino, G. F., Piolatto, G., Newhouse, M. L., Scansetti, G., Aresini, G. A., Murray, R. (1979). Mortality of chrysotile asbestos workers at the Balangero
Mine, northern Italy. Occupational and Environmental Medicine 36(1979):187-194.
Mesothelioma
Cancer/Carcinogenesis: Mesothelial malignancy occurrence; Lung/Respiratory: Mesothelial malignancy occurrence
Asbestos - Chrysotile (serpentine): 12001-29-5
178, 6861719
178
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
High The rating is based on asbestos part 1 evaluation description: "Subjects included men
from the Balangero mine worker cohort that were employed in an Italian asbestos mine.
The initial cohort ((Rubino et al., 1979, HEROID: 178), pg 188) consisted of 952 men
employed between 1/1/1930 and 12/31/1965, with at least 30 calendar days' employ-
ment during that period." and the description in the paper of interest (Ferrante et al.,
2020, HEROID: 6861719: "The cohort included 974 male workers employed for at least
6 months and active at the Balangero mine on 1st lanuary 1946 or hired subsequently
until the cessation of activity." While these accounts differ, it is likely meant to suggest
that only subjects with mortality, which began 1/1/46, are included in Ferrante et al.,
which extended mortality follow up to 5/31/2013.
High In Ferrante et al., 2020, HEROID: 6861719, only 21/974 (2% ) workers were lost by
follow up in 2013.
Medium As per asbestos part 1, this is rated high, however the paper in question Ferrante et al.,
2020, HEROID 6861719 does not explicitly address this metric. As per asbestos part
1: "The most complete data on comparison groups is available from the most recent
follow-up (Pira et al., 2017). General population mortality rates using the whole country
from 1955 until 1980 and specifically the Piedmont Region (where the mine is located)
from 1981 onwards (no regional rates available prior to 1981). The 1955-1959 rates
were applied to 1946-1954 period (no available data); this may have led to an underesti-
mate of expected deaths which may have showed and increased rate during this period.
Expected numbers of deaths (overall and selected cancers) were computed using age-
specific and calendar-year-specific (5-year categories) male death rates (Pira et al., 2017)
pg 559."
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium From asbestos part 1: "Most complete report of exposure assessment is in initial co-
hort study ((Rubino et al., 1979) pg 189). Chrysotile fiber counts were first measured
in 1969 using membrane filter collection and phase contrast microscopy (frequency
not reported). To estimate exposure from 1946-1969, factory records on daily produc-
tion, equipment used, characteristics of the job and number of hours/day were used
(this method has considerable limitations due to basis on mean values for large job cat-
egories and no allowance for changes in weather). Simulated and measured data were
made comparable by using weighting factors (e.g., more dusty operation for 1-2 hr/d
compared with longer working hours in the past)."
Continued on next page ...
Page 111 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 178 Table: 1 of 1
... continued from previous page
Rubino, G. F., Piolatto, G., Newhouse, M. L., Scansetti, G., Aresini, G. A., Murray, R. (1979). Mortality of chrysotile asbestos workers at the Balangero
Mine, northern Italy. Occupational and Environmental Medicine 36(1979):187-194.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Mesothelial malignancy occurrence; Lung/Respiratory: Mesothelial malignancy occurrence
Asbestos - Chrysotile (serpentine): 12001-29-5
178, 6861719
178
Domain
Metric
Rating
Comments
Metric 5:
Metric 6:
Exposure Levels
Temporality
Medium
High
The range and distribution of the cumulative exposure is sufficient to develop exposure-
response relations and the study reports 3 levels of exposure for analyses completed in
Ferrante et al„ 2020, HEROID: 6861719, table 3.
Ferrante et al., 2020, HEROID: 6861719 presents appropriate temporality between
the exposure to asbestos and the outcome of mesothelioma incidence, with follow up
spanning into 2013.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High
High
Ferrante et al., 2020, HEROID: 6861719 notes that mesothelioma cases were extracted
form a regional registry.
Ferrante et al., 2020, HEROID: 6861719 reports Poisson regression outcomes with
relative risks and 95% CIs.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium
High
Low
Ferrante et al., 2020, HEROID: 6861719 adjusted for age explicitly and sex and race
discretely based on the initial recruitment makeup of subjects, however there was no
adjustment for smoking.
Ferrante et al., 2020, HEROID: 6861719 used occupational data from employers: "The
list of cohort members and their working periods and job assignments were extracted
from the factory rosters, stored after the mine bankruptcy in the Turin section of the
Italian State Archives, where we had access to them."
Ferrante et al., 2020, HEROID: 6861719 did not adjust for coexposures.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design (cohort with follow up and analyses of mesothelioma incidence counts
by Poisson regression) was appropriate (Ferrante et al., 2020, HEROID: 6861719).
However it is unclear why authors did not complete a Cox survival model.
Medium The number of participants (n=953) are adequate to detect an effect in the exposed pop-
ulation (Ferrante et al., 2020, HEROID: 6861719).
Medium The description of the analysis is sufficient to understand how to conceptually reproduce
the analysis with access to the analytic data (Ferrante et al., 2020, HEROID: 6861719).
Low Relative risks were calculated for mesothelioma incidence using Poisson regression,
however model assumptions were not explicitly addressed (i.e., does outcome data fit
the Poisson distribution?). Authors state only: "95% CI were estimated assuming the
Poisson distribution of observed cases." However, it is unclear if they mean all outcomes
or a specific one (potentially only mesothelioma).
Continued on next page ...
Page 112 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 178 Table: 1 of 1
... continued from previous page
Rubino, G. F., Piolatto, G., Newhouse, M. L., Scansetti, G., Aresini, G. A., Murray, R. (1979). Mortality of chrysotile asbestos workers at the Balangero
Mine, northern Italy. Occupational and Environmental Medicine 36(1979):187-194.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Mesothelial malignancy occurrence; Lung/Respiratory: Mesothelial malignancy occurrence
Asbestos - Chrysotile (serpentine): 12001-29-5
178, 6861719
178
Domain
Metric
Rating
Comments
Additional Comments: Evaluations were only completed for Ferrante et al., 2020, HEROID: 6861719 for mesothelioma analyses with results shown in table 3.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 113 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081025 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Rodelsperger, K., Woitowitz, H. J., Briickel, B., Arhelger, R., Pohlabeln, H., Jockel, K. H. (1999). Dose-response relationship between amphibole fiber
lung burden and mesothelioma. Cancer Detection and Prevention 23(1999): 183-193.
Mesothelioma
Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Not specified: 1332-21-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite
(riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9
3081025, 3080703
3081025
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium 66 cases and 66 controls from five towns across seven clinical centers in West Germany
between January 1, 1988 and December 31, 1991. Cases had definite diagnosis of dif-
fuse malignant mesothelioma confirmed by a panel of pathologists. Inclusion criteria for
cases included the presence of a lung tissue sample, for which only 66 of the 324 con-
firmed mesothelioma cases. The 66 controls were selected from a combined pool of 315
hospital patients treated by surgical lung resection for something other than mesothe-
lioma and 182 population controls. Controls were matched to cases using age, sex, and
region of residence. Both cases and controls needed to be of German nationality. It is
unclear how many controls were sourced from the hospital patients and how many were
sourced from the population.
High There was no reported subject withdrawal from the study of the matched 66 cases with
lung tissue samples and controls and the outcome and exposure data were both largely
complete.
Medium Cases and controls had to be of German nationality, had to be willing and able to give an
interview, and had to provide written informed consent. Control group mostly had lung
cancer, and for some of these controls lung cancer might be caused by an asbestos expo-
sure, introducing possible bias. Controls were matched to cases according to age (± 5
years), sex, and region of residence. It is unclear how many controls were sourced from
hospital patients and how many were sourced from the population. Also, occupation was
not used in matching criteria.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium
Medium
Low
Lung tissue fiber analysis by TEM - single time point of measurement.
Unconditional logistic regression analysis of concentration of fibers longer than 5 jUm
from lung tissue on mesothelioma split the analysis sample into five categories of expo-
sure: <0.05, 0.05-<0.1, 0.1-<0.2, 0.2-<0.5, and >=0.5 f/jUg, and odds ratios compare
odds of mesothelioma in each of the four upper exposure categories to the to the lowest
exposure category.
The temporality of exposure and outcome is uncertain. Sources of data and details of
methods of assessment were not sufficiently reported for duration of follow-up and
periods of exposure.
Domain 3: Outcome Assessment
Continued on next page ...
Page 114 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3081025 Table: 1 of 1
... continued from previous page
Rodelsperger, K., Woitowitz, H. J., Briickel, B., Arhelger, R., Pohlabeln, H., Jockel, K. H. (1999). Dose-response relationship between amphibole fiber
lung burden and mesothelioma. Cancer Detection and Prevention 23(1999): 183-193.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Not specified: 1332-21-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite
(riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9
3081025, 3080703
3081025
Domain
Metric
Rating
Comments
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High
High
Out of 450 incident patients with a suspicious diagnosis of diffuse malignant mesothe-
lioma (DMM), 324 had a definite diagnosis confirmed by a panel of pathologists (66 of
which were cases in this study).
Mesothelioma findings are reported in the abstract, results, and discussion sections.
Odds ratios are reported with 95% confidence intervals, and the number of cases/
controls that fall into each exposure category are reported as well.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium
Medium
N/A
Confounding was addressed by controlling for a continuous variable for age and binary
variables for the clinical center (Hamburg/others) and sex. Race was not adjusted for in
the models, and it is unclear if the study participants were of multiple races as this was
not reported. Also, study authors had information on smoking habits but did not control
for this information in models.
It is assumed that confounder information was assessed from the standardized question-
naire to collect detailed occupational history that is mentioned in the methods section,
though it is not clear from the study details exactly where confounder information was
sourced.
Odds ratios related to Chrysotile and all "other mineral fibers" were adjusted for the
concentration of amphibole fibers longer than 5 jUm.
Domain 5: Analysis
Metric 12:
Metric 13:
Metric 14:
Study Design and Methods
Statistical Power
Reproducibility of Analyses
Medium
Medium
Medium
Case-control design was appropriate, and appropriate statistical methods (logistic regres-
sion) were used.
With only 66 cases and 66 controls split into five exposure groups, the sample size is rel-
atively small, but there is sufficient sample size to detect an effect. However, confidence
intervals are very wide, suggesting imprecise estimates of effect due to the small number
of cases/controls in each cell.
The description of the analysis is generally sufficient to understand how to conceptually
reproduce the analysis with access to the analytic data, however the authors note that
they perform a logarithmic transformation to asbestos and amphibole fiber concentra-
tions, but they did not specify the base that was used.
Continued on next
page...
Page 115 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3081025 Table: 1 of 1
... continued from previous page
Rodelsperger, K., Woitowitz, H. J., Briickel, B., Arhelger, R., Pohlabeln, H., Jockel, K. H. (1999). Dose-response relationship between amphibole fiber
lung burden and mesothelioma. Cancer Detection and Prevention 23(1999): 183-193.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Cancer/Carcinogenesis: Mesothelioma; Lung/Respiratory: Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Not specified: 1332-21-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite
(riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9
3081025, 3080703
3081025
Domain
Metric
Rating
Comments
Metric 15: Statistical Analysis
Medium The method for calculating risk estimates is transparent. Study authors estimated odds
ratios relating fiber concentrations in the lung to mesothelioma diagnoses. The authors
explained that they log transformed the fiber concentrations because they were inher-
ently right skewed distributions, and added 0.1 f/jUg to each concentrations to avoid
taking the logarithm of zero. Authors adjusted the odds ratios by age, sex, and region as
these variables were used to match cases to controls.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric 16: Use of Biomarker of Exposure
Metric 17:
Effect Biomarker
Metric 18: Method Sensitivity
Metric 19: Biomarker Stability
Metric 20: Sample Contamination
Metric 21: Method Requirements
Metric 22: Matrix Adjustment
High
N/A
Low
High
Medium
High
N/A
Fibers present in the lung tissue samples were able to be classified into asbestos-specific
categories of chrysotile and amphibole (with subcategories of amosite/crocidolite, acti-
nolite/tremolite, and anthophyllite), and also measured for length. Lung fibers them-
selves are derived from multiple parent chemicals, but the lung fibers were able to be
classified into asbestos-specific categories when appropriate.
Health outcome was measured by diagnosis from a panel of pathologists, rather than a
specific biomarker of effect.
Median detection limits were reported as 0.16 fibers/jUg of dried lung tissue for fibers
of all lengths and 0.029 fibers/jUg dry weight for fibers longer than 5 jUm. However,
median concentrations of 0.02 fibers/jUg dry weight are reported in Table III, calling into
question the actual limit of detection.
Detailed methodology for lung tissue fiber analysis by STEM were described in detail
including low temperature ashing. No known losses during storage were reported.
There is no information included in the study about contamination.
Scanning transmission electron microscope (TEM) was performed to examine asbestos
fiber species together with other mineral fibers in human lung tissue. TEM is considered
the best method for counting asbestos fibers.
Matrix adjustment is not required for assessment of lung fiber concentrations.
Additional Comments:
Study could have been improved with higher sample size, as well as additional details about logarithmic adjustment, but the study contains data that could
be potentially useful for dose-response in measuring the relationship between asbestos lung fiber concentrations and mesothelioma.
Overall Quality Determination
Medium
Page 116 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 257 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Mesothelioma
Mortality: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality; Lung/
Respiratory: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality; Cancer/
Carcinogenesis: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality
Asbestos - Amosite (grunerite): 12172-73-5
ID(s): No linked references.
257
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
High In this retrospective cohort study, Seidel et al 1984 (HEROID 257) examined cause-
specific mortality in a cohort of male workers at an amosite asbestos factory in Paterson,
NJ that operated from June 1941 to November 1954. The cohort was described as al-
most entirely white (mentioned in Seidman et al., 1979 HEROID 94625). This study
excluded deaths in the first five years, analyzing mortality occurring 5-40 years after
employment. Of all 933 men recruited to work from June 1941 to December 1945, this
study excluded 113: 35 who worked with asbestos elsewhere (21 before starting and 14
afterwards); 40 who died within 5 years; and 38 lost to follow-up shortly after leaving
the plant. The remaining 820 participants had worked at the facility for as little as one
month up to several years. The mean age at employment was 41.9 years (50.8% aged
>40 years). Three aspects of participant selection helped to limit bias. First, the study
avoided healthy worker selection bias because all workers were eligible for inclusion
regardless of date of initial employment, and regardless of duration of employment. In
addition, the study used an exposure lag to reduce potential bias by taking disease la-
tency into account: asbestos exposure at this plant may not have been causally related
to disease outcomes with latency periods of >5 years. Finally, participants exposed to
asbestos in other work settings were excluded.
High Only a few eligible workers (n=38) had been lost to follow-up at the start of this study.
There was little additional attrition of the 820 participants in this follow-up through
1982, which included: 4 additional men lost to follow-up, and 5 who contributed person-
time until starting asbestos work elsewhere (i.e., became ineligible; see p. 3). Of the 811
remaining men, 593 had died and 218 were still alive, accounting for the complete co-
hort. A later publication (Seidman et al., 1986, HEROID 290) reported similar numbers
(5 lost to follow-up, 6 who began asbestos work elsewhere, 216 alive). Table 1 shows,
for each 5-year period of follow-up, the number of workers at risk, the mean age of
those workers, and the number of deaths that occurred, along with the small number lost
to follow-up.
High Standardized mortality ratios were calculated comparing all eligible workers in the co-
hort to white male residents of New Jersey in the same 5-year age groups during the
same calendar periods. The authors reported elsewhere (Seidman et al., 1979 HEROID
94625) that death rates from cancer in New Jersey were "among the highest in the
United States". The choice of the state referent helped to account for the regional back-
ground rates of cancer mortality.
Domain 2: Exposure Characterization
Continued on next page .
Page 117 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 257 Table: 1 of 1
... continued from previous page
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Mesothelioma
Mortality: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality; Lung/
Respiratory: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality; Cancer/
Carcinogenesis: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality
Asbestos - Amosite (grunerite): 12172-73-5
ID(s): No linked references.
257
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Domain
Metric
Rating
Comments
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Low No fiber or dust count measures were available for this facility. Estimates were based
on measures taken in 1967, 1970 and 1971 at two other plants run by the same company
(in Tyler, TX; Port Allegany, PA) making the same products with the same machinery.
Details on sampling equipment and procedures, or references to obtain that informa-
tion, were not provided. Dr. William Nicholson helped to "assign plausible estimates" to
"particular jobs" (i.e., estimates were extrapolated from later measures at other facilities
using professional judgment). There were no details on how data were used, no discus-
sion of comparable ventilation/dust extraction, and no references cited. It is not possible
to ascertain the likely validity of fiber count estimates. Fiber-years/cc for each worker
were calculated by multiplying estimated fiber counts for each job duty by the duration
of work in that post. The median count of fibers > 5[i per cc across jobs was 50; counts
for a list of job titles were shown in Table 5 (e.g., 5 for office workers, 15 for inspectors
and foremen, 50 for production supervisors, 100 for pulverizers). Potential sources of
error noted by the authors included: (i) the tendency for industrial hygienists to over-
sample dustier areas (counts too high, underestimate dose-response); (ii) the possibility
that short-term workers "may have experienced an apprenticeship period in which they
did some of the dirtier work in their department" (counts too low, over-estimate effect of
short-term exposure); and (iii) lack of information on use of respirators (measurement
error, uncertain if a source of bias). The study reports that there was a "concerted ef-
fort to have the Paterson plant workers use respirator protectors" although no details on
compliance are provided.
Medium Exposure was analyzed using categories of fiber-years/cc and work duration. Data were
presented using 8 categories of fiber-years/cc (<6, 6-11.9, 12-24.9, 25-49.9, 50-99.9,
100-149.9, 150-249.9, 250+ fiber-years/cc), as well as dichotomized (<25 vs 25+
fiber-years/cc). Exposure duration was classified in 7 categories (<1 month, 1 month,
2 months, 3-5 months, 6-11 months, 1 year, 2+ years); boundaries for these periods
were not provided. In addition, some analyses calculated SMRs classified by depart-
ment of work (e.g., Table 11 in HEROID 257; see also Table XIII in Seidman et al, 1986
HEROID 290). Only incidence is provided for mesothelioma outcomes, with no statisti-
cal analysis.
High Temporality and duration of follow-up was appropriate for the outcomes evaluated (mul-
tiple cancers, mesothelioma, and asbestosis). Follow-up ranged from a minimum of 5 to
a maximum of 40 years.
Domain 3: Outcome Assessment
Continued on next page ...
Page 118 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 257 Table: 1 of 1
... continued from previous page
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Mesothelioma
Mortality: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality; Lung/
Respiratory: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality; Cancer/
Carcinogenesis: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality
Asbestos - Amosite (grunerite): 12172-73-5
ID(s): No linked references.
257
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
Medium ICD codes for mesotheliomas were not provided or discussed. The authors reported the
"best evidence (BE)" available to classify cause of death, in addition to death certificate
(DC) information. Tables comparing BE and DE indicated that additional information
increased the number of mesotheliomas identified, as well as knowledge of the site of
mesotheliomas. Best evidence included additional information from autopsy, surgical
specimens, x-ray films and clinical findings (Seidman et al., 1979 HEROID 94625).
Details on BE sources used to characterize mesotheliomas were not discussed, but in-
sights can be inferred from acknowledgements (e.g., see Seidman et al, 1986 HEROID
290), which mention receiving generous help from medical facilities including hospitals,
pathologists, and state health departments, with several facilities and clinicians listed by
name.
High Information is presented for all outcomes described. The authors present details on the
observed and expected numbers of deaths stratified by categories of exposure or time
period, along with the resulting SMRs; statistical significance is indicated. There is no
evidence of selective reporting.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Because of small numbers and limited data, analyses of mortality from mesothelioma
were based on death rates per million-man years overall, stratified by follow-up time,
and by indicators of exposure. Counts of mesotheliomas were also shown overall as well
as stratified by exposure and duration of follow-up.
Medium Analyses specific to mesothelioma did not include covariates; no confounding bias was
expected.
Low In this occupational setting, potential co-exposures are not discussed. There is no infor-
mation to suggest the presence of other important co-exposures in this setting. The fac-
tory supplied the US. Navy with asbestos insulation for the pipes, boilers, and turbines
of its ships. The manufacturing procedures carried out in the factory were described on
p. 5 of the manuscript (HEROID 257).
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Medium The retrospective cohort design was appropriate and mortality rates were calculated
appropriately.
Medium Based on best evidence, there were 17 mesotheliomas identified during the 5-to-40-year
follow-up (9 peritoneal, 8 pleural).
Medium The descriptions of analyses are brief but adequate. Tables included detailed counts of
deaths, including mesotheliomas.
Continued on next page ...
Page 119 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 257 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Mesothelioma
Mortality: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality; Lung/
Respiratory: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality; Cancer/
Carcinogenesis: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality, Mesothelioma (non-pleural and non-peritoneal) mortality
Asbestos - Amosite (grunerite): 12172-73-5
ID(s): No linked references.
257
Domain
Metric
Rating
Comments
Metric 15: Statistical Analysis
Medium Death rates per million person-years were calculated for mesothelioma. As the authors
note, person-years were limited due to the high mortality in the cohort.
Additional Comments: This retrospective cohort study evaluated mortality in 820 workers at an amosite factory in New Jersey that operated between 1941 and 1954. Workers
were almost exclusively white males. The authors reduced the likelihood of healthy worker selection bias by including all workers who were not exposed
to asbestos elsewhere regardless of date of initial employment, and regardless of duration of employment. The authors were able to access medical records
that appear to have improved the characterization of outcomes such as mesotheliomas (e.g., see Selikoff et al., 1992 HEROID 709720). With a high mean
age at initial employment (>40 years) mortality was high even after relatively short follow-up. Employment patterns facilitated the analysis of mortality
in workers with as little as one month of work. The study estimated death rates per million man-years for mesotheliomas overall and for two sites (pleural,
peritoneal) stratified by exposure in fiber-years/cc (observed as low as 6-11.9 fiber-years/cc) and by duration of time worked (observed as low as 2 months).
The major weakness of the study is that fiber count data were not available for this facility. Estimates were extrapolated based on measures taken at later
dates at other locations operated by the same company, based on professional judgment. Validity of these estimates cannot be ascertained.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 120 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 290 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Seidman, H., Selikoff, I. J., Gelb, S. K. (1986). Mortality experience of amosite asbestos factory workers: Dose-response relationships 5 to 40 years after
onset of short-term work exposure. American Journal of Industrial Medicine 10(1986):479-514.
Mesothelioma
Cancer/Carcinogenesis: All cancer, lung cancer, pleural mesothelioma, peritoneal mesothelioma, mesothelioma non-specified, larynx buccal and pharynx
cancer, esophagus cancer, stomach cancer, colon-rectum cancer, kidney cancer, bladder cancer, pancreas cancer, other and unspecified cancer mortality,
Pleural mesothelioma mortality, Mesothelioma (not specified) mortality; Mortality: Pleural mesothelioma mortality, Peritoneal mesothelioma mortality,
Mesothelioma (not specified) mortality; Lung/Respiratory: Peritoneal mesothelioma mortality, Mesothelioma (not specified) mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
290
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM.Authors state that there was "no direct observa-
tions of fiber counts in this factory". Instead, fiber counts from other Paterson factories
were used in this study. There is more information of the earlier version of this study,
which reports that that Paterson factory used the same fibers and followed the same
production process. Samples were made in October 1971 and followed "5u + fibers av-
eraged as high as 23 fibers/ml (Seidman et al., 1979). There is no defining of what tools
were used to measure fibers in either study.
Medium Range of exposure is appropriate, as it ranges in elapsed number of years since onset of
work as 5-9 years, 5-14 years, 5-19 years, 5-24 years, 5-29 years, 5-34 years, and 5-39
years. However, the exposure dose is not based on fiber concentration but on exposure
time.
Additional Comments: Please note that this study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was
mentioned in the study or a cited source.This study is a follow-up to RefID 94625 by the same authors. Comments referencing this study will be cited as
(Seidman et al., 1979).Overall, this study provides an analysis of workers from the Paterson factory to that of the general New lersey population. There is
some discrepancy when it comes to the race of the cohort and the comparison groups, and age is not provided in the study. Confidence intervals are also
not provided in the study results of SMRs and SIRs, but significant is noted when appropriate.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 121 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3080235 Table: 1 of 1
Smailyte, G., Kurtinaitis, J., Andersen, A. (2004). Cancer mortality and morbidity among Lithuanian asbestos-cement producing workers. Scandinavian
Journal of Work, Environment and Health 30(2004):64-70.
Mesothelioma
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Pleura cancer (mesothelioma); Lung/Respiratory: Pleura cancer (mesothelioma)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3080235
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
No measurements were taken at factory A, so no data is available. Factory B had an-
nual dust mass measurements from 1975-1993, and fibers per milliliter were available
for 1996-1998. There was no discussion of the tools used to ascertain these measure-
ments.This metric is rated low because the study or any cited methods source does not
explicitly mention the use of PCM or TEM.
The authors report the concentrations of asbestos in factory B varied from 1.9-4.0 mg/
mA 3 for 1975-89, and was 1.2-2.2 mg/mA 3 from 1990-1993. In 1996-1998, fiber mea-
surement shows the concentration 0.5-1.0 f/ml. These values are only available for fac-
tory B as no measurements were taken at facility A.
Additional Comments: With regards to mesothelioma outcomes, there is not a lot of information provided. Only one female participant had a case of mesothelioma, and the
authors included expected numbers of mesothelioma cases in men. The lack of data on asbestos concentrations in one of the factories examined may also
limit the results discussed in the paper.NOTE: Metric 4 was rated as low because there was no mention of PCM or TEM in the study or any cited source.
Under current guidelines, this would have resulted in the evaluation not being completed.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 122 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709497 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environmental
Health Perspectives 115(2007):579-585.
Mesothelioma
Mortality: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos - Tremolite: 14567-73-8
709497, 709457, 711560, 2238712
709497
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium Subjects were vermiculite miners, millers, and processors from a mine operating in
Libby, Montana. The authors specify that some subjects may have been "assigned jobs
in the screening plant, railroad loading dock, expansion plants, or an office located in the
town of Libby (several miles from the mine)." The cohort was designed to include all
white males hired at Libby from September 1935 to December 1981, and the total co-
hort was identified in May 1982 and subjects were followed through December 2001. It
is not clear exactly how subjects were recruited or identified, though it is likely that the
authors used data from an existing NIOSH database. Demographic data was collected
from a NIOSH database and then validated against microfilm company records. One
person originally identified (presumably from the NIOSH database) was removed due
to company records stating that the employee never actually worked. After excluding 9
participants for missing demographic data, there were 1,871 study subjects. However,
after additional exclusions based on missing outcome data and to limit the analysis sam-
ple to only white men, the final analytic sample consisted of 1,672 workers (Sullivan et
al. 2007 HERO ID: 709497).Moolgavkar et al. 2010 (HERO ID: 709457) used the same
cohort as Sullivan et al. 2007 (HERO ID: 709497) but they also excluded 10 individuals
were missing vital status and thus resulted in a final analytic sample of 1,662.
High In Sullivan et al. 2007 (HERO ID: 709497), after 1,871 subjects were identified for
inclusion, 104 were excluded due to not being white males, and 95 were exclude due
to dying or being lost to follow-up before 1960. Prior to 1960 comparison rates for
asbestosis in NIOSH Life Table Analysis system were not available, requiring exclusion
from the analysis sample. In Moolgavkar et al. 2010 (HERO ID: 709457) an additional
10 participants were excluded due to missing vital status, although it is not clear how
these cases were handled in the original study. There is overall a low rate of attrition and
it is unlikely to be influenced by both exposure and outcome.
Medium In Sullivan et al. 2007 (HERO ID: 709497) and SMRs were calculated as the primary
statistical analysis. Reference mortality rates were pulled from the NIOSH Life Table
Analysis system. It is not specified whether this reference population was the general
US population or an occupational-only population. Since the analysis samples only
contained white males, there was no need to adjust by race or sex. However, SMRs were
adjusted for age at risk and calendar-year of follow-up in Sullivan et al. 2007 (HERO
ID: 709497). Moolgavkar et al. 2010 (HERO ID: 709457) also performed a regression
analysis for mesothelioma that did not report any adjustments.
Domain 2: Exposure Characterization
Continued on next page .
Page 123 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709497 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environmental
Health Perspectives 115(2007):579-585.
Mesothelioma
Mortality: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos - Tremolite: 14567-73-8
709497, 709457, 711560, 2238712
709497
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium In this cohort, all studies used the exact same method of assessing exposure through
quantification using PCM and assignment to participants via a job-exposure matrix,
based on one used in an earlier NIOSH study (Amandus and Wheeler, 1987 HERO ID:
29839). In Sullivan et al. 2007 (HERO ID: 709497) and Moolgavkar et al. 2010 (HERO
ID: 709457) adjustments to the JEM were made, most notably to assign workers with
the "common laborer" job assignments or unknown job assignments the average esti-
mated exposure intensity for all unskilled jobs, as opposed to using the relatively low
exposure estimate for the mill yard in Libby. Thus, estimates of cumulative exposure
were higher in this cohort study than other studies using the same JEM. Additionally,
obtaining work histories for these studies resulted in additional jobs that were not de-
tailed in the original NIOSH JEM. Exposure estimates for these jobs and corresponding
calendar periods were extrapolated based on review of exposure records from other stud-
ies of Libby workers and professional judgment. Work history to assign exposure was
gathered from a NIOSH database created in the 1980"s and was validated against mi-
crofilm company records. The authors do not specify how many samples were analyzed
for use in the JEM. In statistical analysis results were presented in terms of cumulative
exposure (fiber/cc-years).
Medium All studies in the cohort have an adequate distribution of exposure to detect an effect.
All studies report at least three levels of exposure or use a continuous model of exposure
in their SMR analyses.
High In all studies there was a minimum of 20 years of follow-up since a participant"s first
exposure, and the workers hired earliest had >65 years of prior exposure data since the
study was designed to capture those employed between 1935 and 1981.
Domain 3: Outcome Assessment
Continued on next page .
Page 124 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709497 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environmental
Health Perspectives 115(2007):579-585.
Mesothelioma
Mortality: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos - Tremolite: 14567-73-8
709497, 709457, 711560, 2238712
709497
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
Medium Vital status was determined through 2001 by the National Death Index resources, the
Social Security Administration resources, the internet (Ancestry.com; RootsWeb.com,
and electronic links to state death records). And a tracking service. Workers found to
be alive on or after 1/1/1979, when the National Death Index tracking began, but not
found in the Index, were assumed to be alive as of 12/31/2001. Vital status follow-up
was successful for 97.8% of the cohort. While some of the resources have a high degree
of certainty, others such as the internet-based resources are of questionable quality.
There is no explanation of what percentage each resource was used to ascertain vital
status, but the more reliable method such as National Death Index are likely to be more
informative and thus used more often. Thus, while there is some uncertainty that the
vital status ascertainment was fully accurate, it is unlikely that a significant number of
participants would have their vital status changed or that this would be related to their
exposure status. .For 97% of the participants known to be deceased, exact cause of death
was pulled from death certificates and coded using the ICD codes relevant at the time
of death, ranging from ICD-8 to ICD-10. Deaths prior to 1979 were coded by a single
National Center for Health Statistics-trained nosologist; after 1979 ICD codes were
obtained from the National Death Index. Final results present ICD-9 codes, so it can be
assumed that all codes were converted to that system, although their methodology is not
explained.The ICD-10 code presented for mesothelioma was reported as C45.
High All stated outcomes are reported in the results.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium In Sullivan et al. 2007 (HERO ID: 709497) SMRs were calculated and the sample only
included white males, so there was no need to adjust for race and gender. Sullivan et
al. 2007 (HERO ID: 709497) state that they also adjusted for age at risk and calendar
year of follow-up. Moolgavkar et al. 2010 (HERO ID: 709457) also performed a Cox
proportional hazards model analysis in which they adjusted for year of birth. They state
that they used year of birth as a "rough surrogate" for smoking habits as well, which is
not a sufficient consideration for smoking.
Medium All covariate information was obtained from the NIOSH database and cross-checked
against microfilmed company records.
Low In this occupational setting, no co-exposures are adjusted for. Sullivan et al. 2007
(HERO ID: 709497) notes that there was insufficient data to estimate exposure to other
contaminants such as diesel particulate generated by mine machinery, or exposure to
silica.
Domain 5: Analysis
Continued on next page .
Page 125 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709497 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environmental
Health Perspectives 115(2007):579-585.
Mesothelioma
Mortality: Mesothelioma mortality; Lung/Respiratory: Mesothelioma mortality; Cancer/Carcinogenesis: Mesothelioma mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos - Tremolite: 14567-73-8
709497, 709457, 711560, 2238712
709497
Domain
Metric
Rating
Comments
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The use of SMRs and regression analyses to understand the long-term impact of as-
bestos exposure on mortality is appropriate. The use of a cohort design is also appropri-
ate to assess outcomes with a long latency such as lung cancer.
Medium The number of participants used in the analysis sample varies by study but is always
sufficiently large to detect an effect. Sullivan et al. 2007 (HERO ID: 709497) had a
final analysis sample of 1,672; Moolgavkar et al. 2010 (HERO ID: 709457) had a final
analysis sample of 1,662. There is not a significant discussion of power, but Sullivan
et al. 2007 (HERO ID: 709497) states that the study has low power for lung cancer
outcomes at lower exposure levels. There are some potential concerns for low power
since the overall incidence of mesothelioma was low (n=2).
Medium While several details are not explained in detail, such as how the ICD-8 through ICD-10
codes were converted to ICD-9 codes, overall the descriptions of methods across the
cohort are detailed enough that it would be possible to reproduce the results given access
to the analytic data.
Medium While there is no formal discussion of assumptions in statistical models in both Sullivan
et al. 2007 (HERO ID: 709497) and Bateson et al. 2014 (HERO ID: 2238712, there
are no assumptions in SMR or Cox proportional hazards model that would reasonably
expect to be unmet. Moolgavkar et al. 2010 (HERO ID: 709457) contains those same
analyses without a formal discussion of assumptions, but also analyses mesothelioma
using a maximum likelihood equation in which they assume a Poisson distribution.
Additional Comments: In these cohort studies of Libby, Montana employees exposure was measured via PCM and assigned using a JEM. Participants were followed up for a
minimum of 20 years from first exposure, and mortality outcomes were examined in relation to asbestos exposure through SMR and regression analysis.
While there is some potential for outcome and exposure misclassification, the impact of potential misclassification is unlikely to significantly bias the
results of the cohort. Significant effects were found mesothelioma mortality across the cohort.The measurement exposure (M4) and/or exposure levels
(M5) metrics are rated as medium upon review by both set of reviewers. Also, the overall quality determination (OQD) is rated medium. Extraction has
been completed and quality control reviewed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 126 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3080436 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Szeszenia-D^browska, N., Wilczyhska, U., Szymczak, W., Strzelecka, A. (2002). Mortality study of workers compensated for asbestosis in Poland,
1970-1997. International Journal of Occupational Medicine and Environmental Health 15(2002):267-278.
Mesothelioma
Lung/Respiratory: Pleural mesothelioma; Mortality: Pleural mesothelioma
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3080436
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low Study authors mentioned that weighted asbestos concentrations were typically used until
1981 for assessing exposure. They did not provide any information about measurement
tools such as midget impingers, TEM, or PCM.
Medium Table 4 displays the distribution of the cohort by cumulative dose of asbestos fibers
for most of the cohort. This distribution and range of exposure was sufficient to assess
exposure-outcome relationships.
Additional Comments: This study assessed the risk of asbestos-related malignancies (including mesothelioma) among persons with diagnosed asbestosis. In terms of exposure,
the authors used weighted asbestos concentrations to assessing exposures. They did not provide any information about measurement tools such as midget
impingers, TEM, or PCM. On the other hand, they used ICD-9 codes to ascertain health and mortality outcomes .While information on the measurement of
exposure metric (M4) to assess exposure was limited or rated low. The exposure levels metric (M5) information reported was adequate or rated medium to
determine exposure-response relationships. The overall rating for this outcome/study is medium.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 127 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082320 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Tuomi, T., Huuskonen, M. S., Virtamo, M., Tossavainen, A., Tammilehto, L., Mattson, K., Lahdensuo, A., Mattila, J., Karhunen, P., Liippo, K. (1991). Rel-
ative risk of mesothelioma associated with different levels of exposure to asbestos. Scandinavian Journal of Work, Environment and Health 17(1991):404-
408.
Mesothelioma
Lung/Respiratory: Mesothelioma; Cancer/Carcinogenesis: Mesothelioma
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3082320
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Exposure was assessed during one time period during diagnostic thoracotomy or au-
topsy. Though the authors stated that asbestos fibers in lung tissues were counted both
by TEM and SEM in the method section, the result section reported exposure data mea-
sured by SEM only.
Medium The study provided a range of exposure groups (overall 2 exposure groups: < 1 x 10A 6
and >= 1 x 10A 6 fibers/g dry tissue. For the ones >= 1 x 10A 6, 3 groups were further
reported: > 10 x 10A 6, 100 x 10A 6, and 1000 x 10A 6 fibers/g dry tissue).
Additional Comments:
QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis. The authors mentioned using TEM to develop quantitative estimates of exposure but only reported SEM results, resulting in a low confidence
level for metric 4,
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 128 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 7460031 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Visona, S. D., Capella, S., Bodini, S., Borrelli, P., Villani, S., Crespi, E., Frontini, A., Colosio, C., Belluso, E. (2021). Inorganic Fiber Lung Burden in
Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic
Samples. International Journal of Environmental Research and Public Health 18(2021):2053-2053.
Mesothelioma
Lung/Respiratory: Mesothelioma; Mortality: Mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos -
Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9
No linked references.
7460031
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Asbestos fiber concentration in lung tissue samples collected at forensic autopsy was
measured via Scanning Electron Microscope (SEM) and type of fiber was examined via
energy dispersive spectroscopy (EDS). Both fiber level and asbestos body (AB) load
was measured on a 2mmA 2 filter area at 2000M. In analyses, the following groupings
were made to assess type of fiber: chrysotile/asbestiform antigorite, tremolite/actinolite
asbestos. Exposure was measured in autopsied lungs, thus the measurements represent
a single time period but likely qualify cumulative asbestos exposures.Unfortunately,
the exposure was assessed using a quantitative method other than PCM or TEM and
conversion factors were not determined.
Low The range and distribution of exposure are not adequate to develop an exposure-
response estimate.
Additional Comments: This case-control study had largely adequate approaches to assessing the relationship between asbestos exposure and mesothelioma. A primary weakness
of the study is the approach to statistical analyses, as the Mann-Whitney test fails to allow for the inclusion of covariates. The methods for measuring
exposure and identifying mesothelioma mortality were appropriate.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 129 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2638749 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
Mesothelioma
Lung/Respiratory: lung cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality, mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Medium
Metric 2: Attrition
Metric 3: Comparison Group
High
High
This prospective occupational study examined the health effects of asbestos exposure
among a group of workers from an asbestos textile factory in China. Male workers were
included in the study if they were registered workers in the factory on January 1972
and did not have signs of malignant tumors. Follow up continued through 2008. 586
workers were recruited for the original cohort, and 577 workers remained through the
follow up period (98.5% participation rate at final follow up). While the study boasts a
high participation rate, it is unclear what percentage of the total eligible workers were
initially recruited in 1972, preventing a high rating in this domain.
This study had a participation rate of 98.5% at the final follow up, a high rate that mini-
mizes concerns about bias introduced via subject attrition. Analyses were limited to the
577 subjects that had complete follow up information. Outcome and exposure data are
complete for study subjects.
Authors provide a description of comparisons between the three exposure groups and
noted differences in age, exposure duration, and smoking in the three groups. These
variables were included as cofounders in Cox proportional hazard models, thus effec-
tively controlling for the differences between the groups.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Asbestos levels in the factory were quantitatively measured via TEM in 1982 and 2006,
with an assertion that levels remained over 2 mg/mA 3 during the study period. Personal
sampling was conducted to assess the levels in different areas of the factory, which
was ultimately used to construct three exposure groups (high, medium, low). Authors
note that 70% of the workers had stable positions in the factory for the duration of the
study. These positions were used to place workers into exposure categories. While these
exposure estimates were based on quantitative measures and the role in the factory,
there is still potential for nondifferential misclassification of exposure due to the limited
quantitative measuring and the lack of specificity about those who did have varying roles
during their employment.
Medium Exposure categories were high, medium, and low, based on the job description of work-
ers and sampling results from the factory.
High This study has over 30 years of follow-up, and subjects did not have signs of malignan-
cies during recruitment. This is an appropriate timeframe to assess mesothelioma with a
latency period of 20 years.
Continued on next page ...
Page 130 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
Mesothelioma
Lung/Respiratory: lung cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality, mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain
Metric
Rating
Comments
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Uninformative Authors note that two deaths from mesothelioma were identified among the study co-
hort. One case was pleural and one peritoneal. Deaths were identified through employ-
ment records and through municipal registries. There is no indication that ICD codes
were used to identify the cases, nor that death records captured non-site specific cases of
mesothelioma.
Medium Authors report two mesothelioma cases in the results and discussion, but do not report
quantitative results (effect estimates with confidence intervals, etc.) that would be useful
for extraction).
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High The authors appropriately adjust for variables that vary among the three exposure
groups. Age, duration of exposure, and smoking were included as covariates in Cox
proportional hazard models.
Medium Data on covariates was collected from factory records. Additionally, smoking informa-
tion was collected from individuals via interview or from family members via interview.
There was no indication of validation of factory records, though the records can be as-
sumed to be fairly accurate, thus meriting a medium rating.
N/A Per mesothelioma-specific guidance, concern about co-exposures is limited or likely not
relevant for mesothelioma, meriting a "not applicable" rating.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
N/A
N/A
N/A
This study used a prospective cohort design to assess mesothelioma, which has a long
latency period. This is an appropriate design for this health outcome. Additionally a Cox
proportional hazard model was used to compare the medium and high exposure groups
to the low exposure group (referent).
Per instructions, this metric was not rated for mesothelioma.
Per instructions, this metric was not rated for mesothelioma. Additionally, an analysis
was not conducted for mesothelioma cases.
Per instructions, this metric was not rated for mesothelioma. Additionally, a statistical
model was not built for mesothelioma cases.
Additional Comments:
This study is uninformative for mesothelioma outcomes, as the authors did not conduct statistical analyses for the two mesothelioma cases. Additionally,
the mesothelioma outcome was not assessed using ICD codes. The examination of mesothelioma through employee records seems to only assess pleural
and peritoneal cases, meriting and uninformative rating.
Continued on next page ...
Page 131 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 1 of 1
... continued from previous page
Study Citation: Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
Mesothelioma
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Lung/Respiratory: lung cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality, mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
HERO ID:
2638749
Domain
Metric
Overall Quality Determination
Rating
Comments
Uninformative
* No biomarkers were identified for this evaluation.
Page 132 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6869440 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Abramson, M. I., Murambadoro, T., Alif, S. M., Benke, G. P., Dharmage, S. C., Glaspole, I., Hopkins, P., Hoy, R. F., Klebe, S., Moodley, Y., Rawson, S.,
Reynolds, P. N., Wolfe, R., Corte, T. J., Walters, E. H. (2020). Occupational and environmental risk factors for idiopathic pulmonary fibrosis in Australia:
Case-control study. Thorax 75(2020):864-869.
Idiopathic pulmonary fibrosis
Lung/Respiratory: Idiopathic pulmonary fibrosis
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
6869440
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low It is unclear how the authors measured asbestos concentrations or how these data were
collected for their use in the manuscript.
Metric 5: Exposure Levels Medium The authors provided a wide range of fiber-years included in the analysis of 4 exposure
levels (Table 3).
Additional Comments: None
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 133 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2078953 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Akkurt, I., Onal, B., Demir, A. U., Tuzun, D., Sabir, H., Ulusoy, L., Karadag, K. O., Ersoy, N., Coplii, L. (2006). Respiratory health in Turkish asbestos
cement workers: the role of environmental exposure. American Journal of Industrial Medicine 49(2006):609-616.
Pulmonary Function/Spirometry Results; Small irregular parenchymal opacities
Lung/Respiratory: Forced vital capacity (FVC), Forced expiratory volume in 1 second (FEV1), Small irregular parenchymal opacities (>=1/0), Small
irregular parenchymal opacities (>=1/1), Forced expiratory volume in 1 second/Forced vital capacity (FEV1/FVC) % , Restrictive lung function (FVC
<80% of the predicted values based on age, sex and height), Obstructive lung function (FEV 1/FVC<70% of predicted values based on age, sex and height)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2078953
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3: Comparison Group
Low Among 474 active workers currently employed in any 6 cement factories spread
throughout Turkey, the study enrolled 424 (89% ). "The number of workers were 36,
42, 44, 62, 81 and 159, respectively" per asbestos factory. Authors do not describe re-
cruitment methods, the share of workers per factory recruited, or any additional inclu-
sion criteria. There is no discussion on whether exposure-outcome distribution may have
varied by those included vs. those excluded.
Low Of the initial 424 workers enrolled, authors reported that 406 responded to survey ques-
tions on birthplace, and among those, 334 (82.3% ) had chest x-rays of acceptable qual-
ity. Authors note that workers who had unusable chest x-rays were older and had longer
duration of work, resulting in bias of the sample, with younger subjects with lower du-
rations of exposure and presumably better respiratory health. There is no discussion of
this potential bias beyond stating the reason why subjects did not have usable x-rays. In
addition, only 260 workers have both workplace asbestos exposure and lung function
test results, allowing them to be included in models.
Medium Authors describe comparison groups as workers "who were titled with the jobs not re-
lated to asbestos dust". Age, duration of work, and radiological findings were used for
each outcome. Authors illustrate few differences (only in opacities and lung function
outcomes) among groups. There is limited detail on the comparison group with jobs not
related to asbestos exposure.
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium Authors report following the methods of the Asbestos International Association guid-
ance of 1982. Samples were "collected on 25 mm diameter cellulose ester membrane
filters with 1.2 mm pores in open face cowled casettes made of conductive plastic. Fil-
ters were mounted on glass slides and cleared with acetone vapor. One hundred fields
of a Walton Beckett granule were counted at 400 times magnification with phase con-
trast microscope." It is unclear how often these samples were taken (one time measure or
multiple times), when, or what duration. Asbestos fibers were reported in fibre/mL.
Medium Asbestos exposures are presented dichotomously (No/Possible), as well as continuously
(natural log transformed). The median and range of concentrations is 0.22 fiber/mL
and 0.02-0.76 fiber/mL. This distribution is likely sufficient to develop a dose-response
estimate.
Continued on next page ...
Page 134 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2078953 Table: 1 of 1
... continued from previous page
Akkurt, I., Onal, B., Demir, A. U., Tuzun, D., Sabir, H., Ulusoy, L., Karadag, K. O., Ersoy, N., Coplii, L. (2006). Respiratory health in Turkish asbestos
cement workers: the role of environmental exposure. American Journal of Industrial Medicine 49(2006):609-616.
Pulmonary Function/Spirometry Results; Small irregular parenchymal opacities
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Forced vital capacity (FVC), Forced expiratory volume in 1 second (FEV1), Small irregular parenchymal opacities (>=1/0), Small
irregular parenchymal opacities (>=1/1), Forced expiratory volume in 1 second/Forced vital capacity (FEV1/FVC) % , Restrictive lung function (FVC
<80% of the predicted values based on age, sex and height), Obstructive lung function (FEV 1/FVC<70% of predicted values based on age, sex and height)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2078953
Domain
Metric
Rating
Comments
Metric 6:
Temporality
Low
Authors note that 44.1% of subjects worked >10 years, making established temporality
between exposure and outcomes less certain.
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
High
Pulmonary Function/Spirometry Results: Spirometry was performed following the
American Thoracic Society, 1987 guidelines: "Each subject was seated while wearing a
nose clip. A portable spirometer (Gold Pulmonary Analysis Computer, and Pulmograph,
Holland) was used to measure the forced vital capacity (FVC) and forced expiratory vol-
ume in 1 s (FEV1). At least three forced expiratory maneuvers were completed with the
highest two FEV1 and FVC values within 5% of each other. The highest value of three
maneuvers was recorded and used in the analysis." Authors report using the spirome-
try results for "Predicted values of FEV1 and FVC based on gender, height, and age,
as adopted by Knudson et al. [1983], were used to calculate the predicted FEV1 and
FVC."; Other Non-Cancer Outcomes: Authors report obtaining standard posteroanterior
chest x-rays which were evaluated by two chest physicians individually. The physicians
were blinded and followed revised version of 1980 International Labour Organization
(ILO) Classifications. A third physician was brought in the case of inconsistency be-
tween two initial readers.
Metric 8:
Reporting Bias
High
The methods and results are reported throughout the paper, where regression coefficients
and standard errors or odds ratios and related confidence intervals and p-values are pro-
vided for analyses. The number of workers used in each analysis are reported in the
footnotes of tables.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
High
Lung function linear regression analyses were adjusted for age, sex, height, smoking
pack-years, and duration of work. Parenchymal opacities logistic regression analyses
were adjusted for age, ever smoking, finishing secondary school, and duration of work.
Metric 10:
Covariate Characterization
Medium
The questionnaire used for this study was conducted by an interviewer who collected
informed consent from all workers. "The questionnaire included information on demo-
graphics, occupational history, respiratory symptoms, and smoking habits." There was
no validation of smoking answers.
Metric 11:
Co-exposure Counfounding
Low
Authors do not discuss occupational co-exposures and if they may vary by factory. They
do discuss environmental or community exposures to naturally occuring asbestos in
soil (erionite) as based on birthplace. The questionnaire included a question about this
exposure, and only one worker noted that they were born in an area with high erionite
exposure. Authors note that this did not impact their findings.
Continued on next page ...
Page 135 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2078953 Table: 1 of 1
... continued from previous page
Akkurt, I., Onal, B., Demir, A. U., Tuzun, D., Sabir, H., Ulusoy, L., Karadag, K. O., Ersoy, N., Coplii, L. (2006). Respiratory health in Turkish asbestos
cement workers: the role of environmental exposure. American Journal of Industrial Medicine 49(2006):609-616.
Pulmonary Function/Spirometry Results; Small irregular parenchymal opacities
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Forced vital capacity (FVC), Forced expiratory volume in 1 second (FEV1), Small irregular parenchymal opacities (>=1/0), Small
irregular parenchymal opacities (>=1/1), Forced expiratory volume in 1 second/Forced vital capacity (FEV1/FVC) % , Restrictive lung function (FVC
<80% of the predicted values based on age, sex and height), Obstructive lung function (FEV 1/FVC<70% of predicted values based on age, sex and height)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2078953
Domain
Metric
Rating
Comments
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium Study design and methods are appropriate. The association of lung function and ranges
of exposure to asbestos were "adjusted for potential confounders by stepwise multiple
linear regression analysis with inclusion and exclusion criteria of 0.10 and 0.15, re-
spectively." Multiple logistic regression was used to adjust with radiological findings of
asbestosis. Analyses report p-value cutoffs of <0.05, 0.01, and 0.0001.
Medium Population size is adequate to analyze the outcomes for respiratory function and
parenchymal opacities (n=406 for full sample and n=260 for subsample analysis among
workers with workplace asbestos exposure during survey and lung function test).
Medium The methods and analysis sections are clear enough to understand and conceptually
reproduce the analyses.
Low The models for lung function and small irregular parenchymal opacities in asbestos
workers are transparent. No assumptions are explicitly discussed, however authors do
note they log-transformed asbestos exposure concentration to obtain a normal distribu-
tion.
Additional Comments:
Overall, this study is well designed to analyze respiratory function in occupational workers. PCM was used to count asbestos fibres, thus rating Metric 4 as
a medium. Major concerns for bias lie in lack of details on recruitment and higher attrition among older, likely higher-exposed workers. There is no detail
about sampling duration, timing, or frequency.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 136 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082921 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Albin, M., Johansson, L., Pooley, F. D., Jakobsson, K., Attewell, R., Welinder, H. (1988). Mineral fibres, fibrosis, and asbestos bodies in lung tissue from
deceased asbestos-cement workers. Arhiv za Higijenu Rada i Toksikologiju 39(1988):447-453.
fibrosis, mortality
Lung/Respiratory: fibrosis
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Antho-
phyllite: 17068-78-9; Asbestos - Amosite (grunerite): 12172-73-5
3082921, 3082513
3082921
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Some key elements of the study design were not present but available information indi-
cates a low risk of selection bias. Cases (n=89) were deceased individuals who worked
for more than three months between 1907 and 1977 (employed before the beginning of
1976) at an asbestos cement plant located in a small community in the south of Sweden
(Johansson et al., 1987 HeroID:3083094). The cohort that the cases came from appeared
to include both males and females (Johansson et al., 1987 HeroID:3083094) but the
distribution for this demographic characteristic is not provided in the study. Among
these, 69 has lung tissue that were further analyzed. Characteristics such as mean age,
year of first employment, employment duration, and time between end of exposure and
death are provided in Table 1. Exclusion criteria are not specified. Authors mentioned
non-random sampling of the tissue specimens is possible as asbestotic lesions tend to
be in a specific area of the lungs and have higher counts of fibres than other parts of the
lungs. Tissues from these parts of the lungs may have been observed in some of the ex-
posed workers, which could explain difference between the exposed workers and their
controls, although they say this is "highly unlikely."
High This study reports retrospective data of deceased individuals, thus subject withdrawal
from the study is not of concern. None of the cases were excluded for analyses. Out-
come and exposure data appear to be complete.
Medium There is indirect evidence that cases and controls are similar. Cases were matched with
controls by sex, age, and year and place of death. Necropsy files came from the Uni-
versity Hospital of Lund, which is one of the three departments where necropsy files
for the cases came from (Johansson et al., 1987 HeroID:3083094). The main occupa-
tion is not known or "was specified as labourer" for 46 controls (Johansson et al., 1987
HeroID:3083094), so healthy worker effect may not be of substantial concern if these 46
controls were in fact employed.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium Lung tissues were analyzed by TEM. Energy dispersive x ray spectrometry was used to
determine the type of asbestos fiber. These appear to be assessed during one time period
but meant to be reasonably representative of the entire study period.
Continued on next page ...
Page 137 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082921 Table: 1 of 1
... continued from previous page
Albin, M., Johansson, L., Pooley, F. D., Jakobsson, K., Attewell, R., Welinder, H. (1988). Mineral fibres, fibrosis, and asbestos bodies in lung tissue from
deceased asbestos-cement workers. Arhiv za Higijenu Rada i Toksikologiju 39(1988):447-453.
fibrosis, mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Lung/Respiratory: fibrosis
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Antho-
phyllite: 17068-78-9; Asbestos - Amosite (grunerite): 12172-73-5
3082921, 3082513
3082921
Domain
Metric
Rating
Comments
Metric 5:
Exposure Levels
Medium
Until 1952, the highest reported concentration was 10 fibres/ml. "During the 1970s
the highest exposure concentration was 4 f/ml." Average concentrations above 2 f/ml
applied to millers, mixers, and workers engaged in polishing and sawing operations.
Mean cumulative exposure is provided with a range of 0-230 f-y/ml and "the logarithm
of the fibre concentrations was used as the dependent variable in the multiple linear
regression." Additionally, Figure 3 illustrates the cumulative distribution of amphibole
content among workers without mesothelioma, while Figure 4 illustrates cumulative
distribution of chrysotile and tremolite content among workers and controls.
Metric 6:
Temporality
Medium
Based on the case data, a >15-year latency appears to be established if we can assume
that this study was conducted after 1984, which is 15 years after 1969 (the latest year
reported for year of first employment; see Table 1). However, it is unclear if fibrosis
preceded exposure which the authors admit to by saying "it cannot be judged whether
the fibres accumulated first, causing fibrosis, or if the fibrosis occurred first, causing a
deterioration of the alveolar clearance of fibre particles."
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Medium
Other Non-Cancer Outcomes: Authors examined lung tissue specimens and stated that
interstitial fibrosis was scored 0-4 according to the classification proposed by Hinson et
al." (Hinson et al., 1974 HeroID:3099579). Some analyses dichotomized the presence of
fibrosis.
Metric 8:
Reporting Bias
Medium
Most results seem to be reported in all aspects of the report, including p-values and
sample sizes. There is one instance where exact fiber concentrations are discussed in the
abstract text but not in the study. Some results are provided in text but not presented in
tables or figures.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
Medium
Final regression analyses adjusted for age and smoking. Although males and females
were included in the cohort, there is no discussion of adjusting for sex.
Metric 10:
Covariate Characterization
Medium
As an occupational study, it can be assumed that covariate data were collected from
personnel records. Information such as mean age, year of first employment, employment
duration, and time between end of exposure and death are provided in Table 1.
Metric 11:
Co-exposure Counfounding
Low
Co-exposures were not appropriated adjusted for in analyses. Authors stated that ex-
posed workers higher levels of the following non-asbestos fibres than controls: mullite,
iron, rutile, muscovite, aluminum, and silicon.
Domain 5: Analysis
Continued on next page .
Page 138 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082921 Table: 1 of 1
... continued from previous page
Albin, M., Johansson, L., Pooley, F. D., Jakobsson, K., Attewell, R., Welinder, H. (1988). Mineral fibres, fibrosis, and asbestos bodies in lung tissue from
deceased asbestos-cement workers. Arhiv za Higijenu Rada i Toksikologiju 39(1988):447-453.
fibrosis, mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: fibrosis
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Antho-
phyllite: 17068-78-9; Asbestos - Amosite (grunerite): 12172-73-5
ID(s): 3082921,3082513
3082921
Domain
Metric
Rating
Comments
Metric 12:
Study Design and Methods
Medium
The study design was appropriate to address the research question. "The Mann-Whitney
U test was used to compare concentrations of fibre or mass estimates between the groups
and Kendall's test was used to evaluate rank correlates between fibre concentration
or mass estimate and several variables (employment time, fibrosis grade, amount of
smoking, and counts of asbestos bodies)." As a case-control study, logistic regression
and multiple linear regression analyses were conducted.
Metric 13:
Statistical Power
Medium
The case-control study had small sample sizes (cases = 76; controls = 96); however,
authors were able to still detect effects. Despite lower measurements of exposure, effect
estimates among controls were more pronounced than cases, to the authors' surprise.
Metric 14:
Reproducibility of Analyses
Medium
The description of the analyses is sufficient to understand how to conceptually reproduce
the analysis with access to the analytic data.
Metric 15:
Statistical Analysis
Low
Description of assumptions made in the models are not provided.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric 16:
Use of Biomarker of Exposure
High
To confirm asbestos exposure, authors assessed lung tissue specimens for presence of
asbestos fibers.
Metric 17:
Effect Biomarker
N/A
Biomarkers of effect are not relevant to this study.
Metric 18:
Method Sensitivity
Medium
Fiber measurement was conducted through TEM. LOD/LOQ are not relevant for this
study's analyses.
Metric 19:
Biomarker Stability
Medium
Storage of lung specimens is not discussed. Stability of lung specimens are not a con-
cern for this study.
Metric 20:
Sample Contamination
Medium
Contamination of samples are not discussed nor is of concern.
Metric 21:
Method Requirements
High
TEM was conducted to measure asbestos fibers.
Metric 22:
Matrix Adjustment
N/A
Matrix adjustment is not applicable for this biomarker.
Additional Comments:
Biomarker evaluation was completed with assistance from project lead. Fiber counts among workers with mesothelioma; however, but no with SMR
or regression were used in analysis for mesothelioma. HeroID:3082921 and HeroID:3082513 are duplicates of the same study. Evaluation should be
considered applicable to both HERO IDs.
Overall Quality Determination
Medium
Page 139 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1005285 Table: 1 of 1
Study Citation: Alexander, B. H., Raleigh, K. K., Johnson, J., Mandel, J. H., Adgate, J. L., Ramachandran, G., Messing, R. B., Eshenaur, T., Williams, A. (2012). Radio-
graphic evidence of nonoccupational asbestos exposure from processing Libby vermiculite in Minneapolis, Minnesota. Environmental Health Perspectives
120(2012):44-49.
Pleural abnormalities (pleural thickening or pleural plaques)
Lung/Respiratory: Pleural abnormalities (pleural thickening or pleural plaques)
Asbestos- Libby amphibole: 1318-09-8
ID(s): No linked references.
1005285
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Low The exposure source was vermiculite ore originally from a mine near Libby, Montana
known to be contaminated with amphibole asbestos and sent for processing to plants
across the U.S., including the WM/WRG facility in Minneapolis, Minnesota. Potential
community member airborne asbestos fiber exposure was estimated through a combina-
tion of Minnesota Pollution Control Agency dispersion modeling estimates of air con-
centrations in the community resulting from plant operations and questionnaire-derived
activity-based modeling to establish exposure profiles for the enumerated cohort. Expo-
sures were estimated for the period of plant operations 1938-1989. To obtain a sample
representative of the range of community exposures, the population was stratified into
groups to represent three exposure scenarios: a) intense intermit"tent exposure, b) long-
term high ambient background exposure, and c) low ambient background exposure. We
classified people with a childhood history of playing in the piles of waste rock outside
the plant as the group with intense intermittent exposures to potentially high concen-
trations of asbes"tos fibers. The long-term high and low background exposure groups
were selected based on residential history and frequency matched to the age distribu-
tion of the intense intermit"tent exposure category Details of exposure assessments were
described as reported in full within Adgate et al., 2011 (HERO ID 105280). Adgate et
al., 2011 noted that potential activity-based exposure pathways were ascertained based
on previous Libby asbestos studies and questionnaire responses from the MDH/ATSDR
cohort members with direct contact with waste rock, waste piles or vermiculite insu-
lation. Background exposure for those with no reported activity-based exposure was
determined by length of residence in the affected community and estimates of airborne
fiber concentration. Adgate et al., 2011 noted that asbestos concentration data was re-
ported within previous publications, including Kelly et al., 2006 (HERO ID 709511).
Kelly et al., 2006 noted that exposure to Libby asbestos at the WRG plant was obtained
from 1970"s industrial hygiene data in air samples analyzed by phase-contrast light
microscopy. Regression models within the current study utilized categories of activity
exposure (f/cc x months), pile-playing exposure (f/cc x months), background exposure
(f/cc x months) and total exposure (f/cc x months). Authors noted that activity-based
exposure was derived from self-reported activities as assessed in 2001 when the cohort
was enumerated, with assumptions of activity duration likely introducing some exposure
misclassification. Furthermore, air dispersion models assumed an equivalent exposure
opportunity for all people, regardless of where they spent their day.
Continued on next page ...
Page 140 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1005285 Table: 1 of 1
... continued from previous page
Study Citation: Alexander, B. H., Raleigh, K. K., lohnson, J., Mandel, J. H., Adgate, J. L., Ramachandran, G., Messing, R. B., Eshenaur, T., Williams, A. (2012). Radio-
graphic evidence of nonoccupational asbestos exposure from processing Libby vermiculite in Minneapolis, Minnesota. Environmental Health Perspectives
120(2012):44-49.
Pleural abnormalities (pleural thickening or pleural plaques)
Lung/Respiratory: Pleural abnormalities (pleural thickening or pleural plaques)
Asbestos- Libby amphibole: 1318-09-8
ID(s): No linked references.
1005285
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Domain
Metric
Rating
Comments
Metric 5: Exposure Levels
Medium The range and distribution of estimated exposure is sufficient to develop exposure-
response estimates. Regression model results within the current study were reported
across three exposure f/cc x month categories based upon cut points at the 50th and 75th
percentile of the exposure distribution for each exposure category. Estimated exposure
levels in f/cc x months for regression categories of background exposure (<0.034, 0.034
to <0.077, and >=0.077 f/cc x months), exposure from pile playing (<0.158, 0.158 to
<0.549, and >=0.549 f/cc x months), total exposure (<0.0523, 0.0523 to 0.245, and
>= 0.245 f/cc x months), and total activity exposure (<0.082, 0.082 to <0.422, and
>=0.422 f/cc x months) were detailed.
Additional Comments: This study investigated the association between radiographic pleural abnormalities, parenchymal opacities and other evidence of asbestosis in 461 individu-
als with radiographic assessments and a history before 1980 of nonoccupational direct contact with, or ever playing with, Libby vermiculite ore processing
waste at the Western Minerals/W.R. Grace (WM/WRG) facility in Minneapolis, Minnesota who had never worked at the processing plant or never lived
with a plant worker. Residents were described as often hauling the freely offered rock from the waste piles and using it for gardening and as till material
for driveways and yards. Neighborhood children also played on the piles of vermiculite processing waste, as access to the site was not restricted. As part of
the Northeast Minneapolis Community Vermiculite Investigation (NMCVI), the Michigan Department of Health (MDH) and ATSDR surveyed over 1,600
properties and worked with the EPA to document contamination on more than 260 properties subsequently cleaned by EPA under the federal Superfund
program as part of an initial community exposure characterization. A history of direct contact with the waste and ever playing in the waste piles was
associated with pleural abnormalities, with a reported odds ratio of [OR] 2.78 [95% confidence inter"val (CI): 1.26, 6.10] and 2.17 (95% CI: 0.99, 4.78),
respectively, when adjusted for background exposure.NOTE: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have
sufficient exposure information to be useful for dose-response analysis
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 141 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 733567 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Alfonso, H. S., Fritschi, L., de Klerk, N. H., Olsen, N., Sleith, J., Musk, A. W. (2004). Effects of asbestos and smoking on the levels and rates of change of
lung function in a crocidolite exposed cohort in Western Australia. Thorax 59(2004):1052-1056.
Asbestosis; Pulmonary Function/Spirometry Results; Pleural Plaques; locus of control
Lung/Respiratory: Asbestosis, Pleural plaques and diffuse pleural thickening, carbon monoxide diffusing capacity, FEV1, FVC, FEV1/FVC; Neurological/
Behavioral: locus of control (LOC)
Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): 733567, 2079051, 3077939, 3079889
733567
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Neither PCM nor TEM were used for measuring exposure. Exposure data were esti-
mated from the 1966 survey of crocidolite fibers conducted by the Mines Department
of Western Australia. Measurements for former residents were based on periodic sur-
veys of fiber counts conducted by the Health Department of Western Australia made in
Wittenoom as well as personal monitors (Alfonso et al., 2004 733567). There is concern
that these measurements were not as precise as those done for former workers (Alfonso
et al., 2005 2079051).
Medium The distribution of exposure appears to be sufficient to develop an exposure-response
estimate. Cumulative exposure was utilized in statistical models (f/ml-y) (Alfonso et al.,
2004 733567, Alfonso et al„ 2005 2079051, Franklin & Robinson 2015 3077939).
Additional Comments: Authors admitted that the selected participants for final analyses may not be representative of the whole cohort. This might warrant further review by QC
to determine whether this is grounds for rating Metric 1 as uninformative. As QC reviewer, I agree with this concern from the initial reviewer that there
is potentially some issues with participants selection bias in this study, but overall, I think it has multiple strengths that adds to the body of literature.The
measurement exposure (M4) and/or is rated low upon review by both set of reviewers. However, exposure levels (M5) metrics is rated as medium. Also,
the overall quality determination (OQD) is rated medium.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 142 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3100838 Table: 1 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. NIOSH(1986): 19861986.
Lung Cancer; Stomach, digestive; Pleural Plaques; NMRD, pleural changes, all cause mortality, ischemic heart disease, diseases of the circulatory system
Lung/Respiratory: Small opacities with profusion greater >/= ILO category 1/0, Unilateral or bilateral pleural change, Unilater or bilateral pleural calcifi-
cation on the wall, diaphragm, or other site, Unilateral or bilateral pleural plaque or diffuse pleural thickening on the lung wall, Non-malignant respiratory
disease (NMRD) mortality, Pneumonia, Emphysema, Tuberculosis; Cardiovascular: All diseases of the circulatory system, Ischemic heart disease; Mortal-
ity: All diseases of the circulatory system, Ischemic heart disease, Non-malignant respiratory disease (NMRD) mortality, Pneumonia mortality, Emphysema
mortality, Tuberculosis mortality, All cause mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
3100838, 29839, 759132, 783513
3100838
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Low This study incorporated various sections, including both a morbidity and a mortality
study. For the morbidity study, the sample incorporated 191 men employed between
1975 and 1982 and had worked there for at least five years. This group was incorporated
because over 50% of workers did not have radiographs available, due to either working
less than five years or being terminated before 1975. The number of study participants
for the mortality analysis was larger, being comprised of 589 white male and female
employees. All of these individuals were hired before 1970 and had been employed for
at least one year. December 31, 1981 was the end of the follow-up period when vital
status was determined. 581 of these workers had their vital status determined, and 417
were alive. This means that there were 164 deceased workers, and death certificates
were obtained for 162 of them. The Social Security Administration records were used
to determine date of death for the two workers without death certificates available. More
details about the total number of potential employees within the vermiculite mine/mill,
participation rates, and specific inclusion/exclusion criteria would be beneficial for this
study.
High The attrition level in the mortality study was low, with many of the death certificates
available for 98.8% of the decedents. The attrition level was somewhat higher in the
morbidity study, with only 184 and 121 of the 191 men having radiographs and ques-
tionnaire results available, respectively. This rating would be medium for this portion of
the overall paper.
Medium To calculate the SMR, expected deaths were determined from the U.S. white male death
rates. For the morbidity study, the author utilized an external control group for smoking,
which was comprised of three groups without asbestos exposure. These groups included
blue-collar workers without pneumoconiosis, non-asbestos cement plant workers, and
coal miners with less than five years of employment. Control group members were
excluded for various reasons, including if they had worked in a dusty trade, had a radio-
graph with rounded opacities greater than 0/1, or never smoked regularly. There author
did not provide much of a discussion pertaining to similarities between the exposed and
control groups in this study, which would have been beneficial to ensure that analyses
were conducted appropriately.
Domain 2: Exposure Characterization
Continued on next page .
Page 143 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100838 Table: 1 of 3
... continued from previous page
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. NIOSH(1986): 19861986.
Lung Cancer; Stomach, digestive; Pleural Plaques; NMRD, pleural changes, all cause mortality, ischemic heart disease, diseases of the circulatory system
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Small opacities with profusion greater >/= ILO category 1/0, Unilateral or bilateral pleural change, Unilater or bilateral pleural calcifi-
cation on the wall, diaphragm, or other site, Unilateral or bilateral pleural plaque or diffuse pleural thickening on the lung wall, Non-malignant respiratory
disease (NMRD) mortality, Pneumonia, Emphysema, Tuberculosis; Cardiovascular: All diseases of the circulatory system, Ischemic heart disease; Mortal-
ity: All diseases of the circulatory system, Ischemic heart disease, Non-malignant respiratory disease (NMRD) mortality, Pneumonia mortality, Emphysema
mortality, Tuberculosis mortality, All cause mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
3100838, 29839, 759132, 783513
3100838
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
High For the morbidity study, the date of the most recent radiograph examination was used
to calculate the cumulative exposure levels. As detailed in the section for the mortal-
ity study, air dust samples were collected at various timepoints in different areas of the
mill/mine. Midget impingers were used to sample the dust in years prior to 1969, and
these values were reported as million particles per cubic foot of air (mppcf). After 1967,
membrane filter samples were collected, and values were instead reported as fibers per
cubic centimeter of air (f/cc). This information was used to generate a fiber-year esti-
mate for the individuals enrolled in the study. It is important to note that only samples
taken between 1965 and 1971 were used for these calculations. Several steps were un-
dertaken to determine job exposure estimates for the fiber-years accumulated for the
participants. These steps included coding the workers' jobs and abstracting fiber concen-
trations, dividing the facility into various location-operations, determining the arithmetic
mean to compute average f/cc concentrations, converting impingers measurements into
appropriate units, estimating the exposure level at the various location-operations, utiliz-
ing a plant manager to estimate the hours worked at these locations, determining work
histories, and computing the individual participant"s cumulative exposure index. The
authors also detail that some of the area samples of airborne dust were analyzed with
phase contrast microscopy (Amandus, 1986, 3100838).
Medium The authors reported a wide range of exposure levels in both the morbidity and the mor-
tality studies. Examples of this include the results of man-year analyses in the mortality
study were broken down into exposure groupings of <50, 50-99, 100-399, and >399 f-
y, and the radiographic findings by fiber-years in the morbidity study, where results were
reported in 0-15, 16-30, 31-85, and >86 fiber-year groupings.
Medium There was a range of latency groups included in the morbidity and mortality studies.
While temporality is established for the participants, it is unclear if there was an ade-
quate level of follow-up for the consideration of latency. For the mortality study, the
average tenure was 8.3 years, while the average tenure for the morbidity study was 14
years. Because the inclusion criteria required workers to have been employed for at least
one year, there is a wide range of potential latencies included in this study.
Domain 3: Outcome Assessment
Continued on next page .
Page 144 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100838 Table: 1 of 3
... continued from previous page
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. NIOSH(1986): 19861986.
Lung Cancer; Stomach, digestive; Pleural Plaques; NMRD, pleural changes, all cause mortality, ischemic heart disease, diseases of the circulatory system
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Small opacities with profusion greater >/= ILO category 1/0, Unilateral or bilateral pleural change, Unilater or bilateral pleural calcifi-
cation on the wall, diaphragm, or other site, Unilateral or bilateral pleural plaque or diffuse pleural thickening on the lung wall, Non-malignant respiratory
disease (NMRD) mortality, Pneumonia, Emphysema, Tuberculosis; Cardiovascular: All diseases of the circulatory system, Ischemic heart disease; Mortal-
ity: All diseases of the circulatory system, Ischemic heart disease, Non-malignant respiratory disease (NMRD) mortality, Pneumonia mortality, Emphysema
mortality, Tuberculosis mortality, All cause mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
3100838, 29839, 759132, 783513
3100838
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
High Lung Cancer: It is reported in the mortality study section that "death certificates
were obtained from the company and state vital statistics agencies" (Amandus, 1986,
3100838). Each of the underlying causes of death were recoded based on the Interna-
tional Classification of Diseases, Eighth Revision. Proper ICD codes were reported for
the lung cancer causes of death, and are mentioned in Table 3.1.; Other Cancer(s): The
underlying causes of death were reclassified and coded according to the International
Classification of Diseases, Eighth Revision. ICD codes respective to the various out-
comes are reported in Table 3.1. Death certificates were available for 98.8% of those
who were deceased.; Pleural Plaques: As noted in the morbidity study section, the avail-
able radiographs for 184 of the 191 men were examined by three "B" readers using
the ILO classification of 1980. The films were "taken in 1981-1982 for 134 workers,
in 1976-1980 for 49 workers, and prior to 1975 for only 1 worker" (Amandus, 1986,
3100838). The readers evaluated a number of outcomes, which are detailed on page 56.
It is important to note that the "profusion of small opacities was derived from a median
of the 3 readers, and for each pleural finding from a consensus of the readers" (Aman-
dus, 1986, 3100838).; Other Non-Cancer Outcomes: Information on causes of mortality
in the mortality study were determined from death certificates and vital statistic agen-
cies. The causes of death were coded "for statistical analysis according to the Eighth
Revision of the International Classification of Diseases, adapted" (Amandus, 1986,
3100838). NMRD included such things as pneumonia, emphysema, and tuberculosis.
These outcomes were reported with ICDA codes in Table 3.1.
Medium There are a number of findings reported at various points throughout this study. Con-
fidence intervals are reported in some tables for the mortality study, but not for all of
them. This is similar to results presented in the morbidity study, as some tables, such as
4.11, provide regression coefficients and their associated standard errors.
Domain 4: Potential Confounding / Variability Control
Continued on next page .
Page 145 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100838 Table: 1 of 3
... continued from previous page
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. NIOSH(1986): 19861986.
Lung Cancer; Stomach, digestive; Pleural Plaques; NMRD, pleural changes, all cause mortality, ischemic heart disease, diseases of the circulatory system
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Small opacities with profusion greater >/= ILO category 1/0, Unilateral or bilateral pleural change, Unilater or bilateral pleural calcifi-
cation on the wall, diaphragm, or other site, Unilateral or bilateral pleural plaque or diffuse pleural thickening on the lung wall, Non-malignant respiratory
disease (NMRD) mortality, Pneumonia, Emphysema, Tuberculosis; Cardiovascular: All diseases of the circulatory system, Ischemic heart disease; Mortal-
ity: All diseases of the circulatory system, Ischemic heart disease, Non-malignant respiratory disease (NMRD) mortality, Pneumonia mortality, Emphysema
mortality, Tuberculosis mortality, All cause mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
3100838, 29839, 759132, 783513
3100838
Domain
Metric
Rating
Comments
Metric 9: Covariate Adjustment
Low
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium
Low
While there was some discussion about the potential for confounding effects in the
mortality study, such as with smoking, adjustments were not always made appropriately.
There was an attempt to control for smoking in examinations of lung cancer, but there
was no mention of this adjustment for endpoints such as NMRD. It is important to note
that a small portion of the participants in the mortality study were female. Some results
were indicated for the total group, while some were for the male participants only. In the
morbidity study, radiographic findings and their relationship with f-y were controlled for
both smoking and age. However, it was noted by the author that the association was hard
to measure "because of the small number of cases among non-smokers and the tendency
for most cases to be older, to have smoked, and to have a high f-y" (Amandus, 1986,
3100838). In the remainder of analyses, only age was controlled for.
There was no information presented pertaining to the methods for validating the assess-
ment of potential confounders. However, there was no indication that the method had
poor validity.
Both studies conducted are examining asbestos exposure and health outcomes amongst
vermiculite workers. However, it does not appear that the author is controlling for ver-
miculite exposure itself. While they mention that "vermiculite has not been associated
with significant health effects" there is still a potential for some impact of vermiculite
dust on the workers (Amandus, 1986, 3100838), and it may have been beneficial to con-
trol for.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design implemented is appropriate for the research question being examined.
The use of SMRs was appropriate to examine the association between asbestos exposure
and the various mortality outcomes in the mortality study.
Medium The number of participants in both the morbidity and mortality studies was sufficient to
detect an effect in the exposed population. It is important to note that in the morbidity
study, when looking at respiratory symptoms, "the number of cases were small and
statistical power was low" (Amandus, 1986, 3100838).
Medium The description of the analysis is sufficient to understand how to conceptually reproduce
the analysis with access to the analytical data.
Low While some statistical models were used, there was no description of the model as-
sumptions present within this study. Assumptions for the regressions performed in the
morbidity study were not reported. However, the method for calculating SMRs in the
mortality analysis were described.
Continued on next page ...
Page 146 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100838 Table: 1 of 3
... continued from previous page
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. NIOSH(1986): 19861986.
Lung Cancer; Stomach, digestive; Pleural Plaques; NMRD, pleural changes, all cause mortality, ischemic heart disease, diseases of the circulatory system
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Small opacities with profusion greater >/= ILO category 1/0, Unilateral or bilateral pleural change, Unilater or bilateral pleural calcifi-
cation on the wall, diaphragm, or other site, Unilateral or bilateral pleural plaque or diffuse pleural thickening on the lung wall, Non-malignant respiratory
disease (NMRD) mortality, Pneumonia, Emphysema, Tuberculosis; Cardiovascular: All diseases of the circulatory system, Ischemic heart disease; Mortal-
ity: All diseases of the circulatory system, Ischemic heart disease, Non-malignant respiratory disease (NMRD) mortality, Pneumonia mortality, Emphysema
mortality, Tuberculosis mortality, All cause mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
3100838, 29839, 759132, 783513
3100838
Domain
Metric
Rating
Comments
Additional Comments: It is important to note that this study was a dissertation. While the author examined both morbidity and mortality, some metrics were rated differently
due to differences in outcome ascertainment, analysis etc. Another potential concern pertains to comparison groups, as they differed depending on the
outcome being examined. It is important to note that for the mortality study, there were some female participants included. Some results were reported
for the included cohort as a whole, while others were reported specifically for male participants. While this study was given a medium rating based on the
calculated scores, there is potential for that to be downgraded to a low.The measurement exposure (M4) and/or exposure levels (M5) metrics are rated as
medium upon review by both set of reviewers. Also, the overall quality determination (OQD) is rated medium. Extraction has been completed and quality
control reviewed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 147 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100838 Table: 2 of 3
Study Citation: Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. NIOSH(1986): 19861986.
Health Respiratory symptoms including cough, phlegm, dyspnea, and wheezing
Outcome:
Target Lung/Respiratory: Respiratory symptom: Cough, Respiratory symptom: Phlegm, Respiratory symptom: Dyspnea, Respiratory symptom: Wheezing
Organ(s):
Asbestos Fiber Asbestos-Libby amphibole: 1318-09-8; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
Type(s):
Linked HERO ID(s): 3100838, 29839, 759132, 783513
HERO ID: 3100838
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Low
Metric 2: Attrition
Metric 3: Comparison Group
Medium
Low
This study incorporated various sections, including both a morbidity and a mortality
study. For the morbidity study, the sample incorporated 191 men employed between
1975 and 1982 and had worked there for at least ten years. This group was incorporated
because over 50% of workers did not have radiographs available, due to either working
less than five years or being terminated before 1975. More details about the total number
of potential employees within the vermiculite mine/mill, participation rates, and specific
inclusion/exclusion criteria would be beneficial for this study.
The attrition level was somewhat higher in the morbidity study than in the mortality
study, with only 184 and 121 of the 191 men having radiographs and questionnaire
results available, respectively.
For the morbidity study, the author utilized an external control group for smoking, which
was comprised of three groups without asbestos exposure. These groups included blue-
collar workers without pneumoconiosis, non-asbestos cement plant workers, and coal
miners with less than five years of employment. Control group members were excluded
for various reasons, including if they had worked in a dusty trade, had a radiograph with
rounded opacities greater than 0/1, or never smoked regularly. It is important to note
that the coal miners were also excluded for the analysis examining a relationship be-
tween dyspnea and asbestos exposure. The author did not provide much of a discussion
pertaining to similarities between the exposed and control groups in this study, which
would have been beneficial to ensure that analyses were conducted appropriately.
Domain 2: Exposure Characterization
Continued on next page .
Page 148 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100838 Table: 2 of 3
... continued from previous page
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. NIOSH(1986): 19861986.
Respiratory symptoms including cough, phlegm, dyspnea, and wheezing
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Respiratory symptom: Cough, Respiratory symptom: Phlegm, Respiratory symptom: Dyspnea, Respiratory symptom: Wheezing
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
3100838, 29839, 759132, 783513
3100838
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
High
Metric 5: Exposure Levels
Metric 6: Temporality
Medium
Medium
For the morbidity study, the date of the most recent radiograph examination was used
to calculate the cumulative exposure levels. As detailed in the section for the mortal-
ity study, air dust samples were collected at various timepoints in different areas of the
mill/mine. Midget impingers were used to sample the dust in years prior to 1969, and
these values were reported as million particles per cubic foot of air (mppcf). After 1967,
membrane filter samples were collected, and values were instead reported as fibers per
cubic centimeter of air (f/cc). This information was used to generate a fiber-year esti-
mate for the individuals enrolled in the study. It is important to note that only samples
taken between 1965 and 1971 were used for these calculations. Several steps were un-
dertaken to determine job exposure estimates for the fiber-years accumulated for the
participants. These steps included coding the workers' jobs and abstracting fiber concen-
trations, dividing the facility into various location-operations, determining the arithmetic
mean to compute average f/cc concentrations, converting impingers measurements into
appropriate units, estimating the exposure level at the various location-operations, utiliz-
ing a plant manager to estimate the hours worked at these locations, determining work
histories, and computing the individual participant"s cumulative exposure index. The
authors also detail that some of the area samples of airborne dust were analyzed with
phase contrast microscopy (Pearce, 1998, 3100838).
The authors reported a wide range of exposure levels in both the morbidity and the mor-
tality studies. For example, Table 4.5 details radiographic findings by fiber-years, with
groupings of 0-15, 16-30, 31-85, and >86 f-y.
There was a range of latency groups included in the morbidity and mortality studies.
While temporality is established for the participants, it is unclear if there was an ad-
equate level of follow-up for the consideration of latency. The average tenure for the
morbidity study was 14 years. Because the inclusion criteria required workers to have
been employed for at least one year, there is a wide range of potential latencies included
in this study.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or
Characterization
Uninformative Other Non-Cancer Outcomes: For respiratory symptoms in the morbidity study, symp-
toms were considered present if the participant gave an affirmative answer to their ques-
tions pertaining to cough, phlegm, dyspnea, and wheezing. Because these were self-
reported, and there was no discussion of validation, the rating for this portion of the
morbidity study is uninformative.
Continued on next page ...
Page 149 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100838 Table: 2 of 3
... continued from previous page
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. NIOSH(1986): 19861986.
Respiratory symptoms including cough, phlegm, dyspnea, and wheezing
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Respiratory symptom: Cough, Respiratory symptom: Phlegm, Respiratory symptom: Dyspnea, Respiratory symptom: Wheezing
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
3100838, 29839, 759132, 783513
3100838
Domain
Metric
Rating
Comments
Metric 8:
Reporting Bias
Medium There are a number of findings reported at various points throughout this study. Where
appropriate, standard errors and associated confidence intervals are reported, and in
many instances, there are reports of the number of participants who fall within the re-
spective categories. However, the confidence intervals and standard errors are not re-
ported for every table and figure.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium In the morbidity study, some of the analyses included covariate adjustment. For the
respiratory symptoms examined, only dyspnea had covariates adjusted for, including
smoking and age.
Medium There was no information presented pertaining to the methods for validating the assess-
ment of potential confounders. However, there was no indication that the method had
poor validity.
Low Both studies conducted are examining asbestos exposure and health outcomes amongst
vermiculite workers. However, it does not appear that the author is controlling for ver-
miculite exposure itself. While they mention that "vermiculite has not been associated
with significant health effects" there is still a potential for some impact of vermiculite
dust on the workers (Amandus, 1986), and it may have been beneficial to control for.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design implemented is appropriate for the research question being examined.
Uninformative When looking at the respiratory symptoms outcomes, it is noted by the author that "the
number of cases were small and statistical power was low" (Amandus, 1986). This
presents some concern for the utility of results for these outcomes.
Medium The description of the analysis is sufficient to understand how to conceptually reproduce
the analysis with access to the analytical data.
Low While some statistical models were used, there was no description of the model as-
sumptions present within this study. Assumptions for the regressions performed in the
morbidity study were not reported. However, the method for calculating SMRs in the
mortality analysis were described.
Additional Comments: It is important to note that this study was a dissertation. While the author examined both morbidity and mortality, some metrics were rated differently
due to differences in outcome ascertainment, analysis etc. This particular outcome, respiratory symptoms, was rated as uninformative because of the
self-reported nature of the symptoms. There were also some concerns about this outcome because of the number of cases and low statistical power. While
the measurement exposure (M4) and/or exposure levels (M5) metrics are rated as medium upon review by both set of reviewers, the overall quality
determination (OQD) is rated uninformative due to lack confidence on the outcome measurement.
Continued on next page ...
Page 150 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100838 Table: 2 of 3
... continued from previous page
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. NIOSH(1986): 19861986.
Respiratory symptoms including cough, phlegm, dyspnea, and wheezing
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Respiratory symptom: Cough, Respiratory symptom: Phlegm, Respiratory symptom: Dyspnea, Respiratory symptom: Wheezing
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
3100838, 29839, 759132, 783513
3100838
Domain
Metric
Overall Quality Determination
Rating
Comments
Uninformative
* No biomarkers were identified for this evaluation.
Page 151 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100838 Table: 3 of 3
Amandus, H. (1986). The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite. NIOSH(1986):19861986.
Lung Cancer; digestive, respiratory cancer; Pleural Plaques; circulatory disease, NMRD
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Non-malignant respiratory disease (NMRD) mortality, Lung cancer, respiratory cancer, carcinoma trachea, bronchi, lung, small opaci-
ties, pleural thickening (plaques), pleural calcification; Cardiovascular: All diseases of the circulatory system; Mortality: Non-malignant respiratory disease
(NMRD) mortality, All cause mortality, Respiratory cancer, carcinoma trachea, bronchi, lung; Gastrointestinal: Digestive cancer; Cancer/Carcinogenesis:
Digestive cancer, Lung cancer, respiratory cancer, carcinoma trachea, bronchi, lung
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
3100838, 29839, 759132, 783513
3100838
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated low because the studies or any cited methods source do not explic-
itly mention the use of PCM or TEM (Amandus et al., 1988, 783513; Armstrong et al.,
1988, 759132).This metric was also rated low for (Amandus & Wheeler, 1987, 29839),
as the methods section or any cited source did not explicitly mention the use of PCM
or TEM. However, one of the cited sources mentions TEM for mineralogical purposes,
unrelated to the determination of exposure estimates (Mcdonald et al., 1986, 29964).
Medium The range and distribution of exposure is sufficient to develop an adequate exposure-
response estimate, and three or more levels of exposure are reported (Amandus et al.,
1988, 783513; Armstrong et al„ 1988, 759132; Amandus & Wheeler, 1987, 29839).
Additional Comments:
This portion of the cohort was not fully evaluated because the methods section or any cited sources did not explicitly mention the use of PCM or TEM
(Amandus et al., 1988, 783513; Armstrong et al., 1988, 759132).One of the cited sources mentions TEM for mineralogical purposes, unrelated to the
determination of exposure estimates (Mcdonald et al., 1986, 29964).While the measurement of exposure metric (M4) methods used to quantify the exposure
were not well defined, the exposure levels metric (M5) information reported was adequate to determine an exposure-response relationship.
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 152 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083914 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Andrion, A., Colombo, A., Mollo, F. (1982). Lung asbestos bodies and pleural plaques at autopsy. Ricerca in Clinica e in Laboratorio 12(1982):461-468.
Pleural Plaques
Lung/Respiratory: Pleural plaques
Asbestos - Not specified: 1332-21-4
3083914, 3083599
3083914
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Both studies used asbestos bodies from autopsied lung tissue for measurements of expo-
sure. Professional judgement was used to determine asbestos bodies. The parent study
observed "true asbestos bodies with well-defined morphological figures" (Andrion et
al. 1982, HERO ID: 3083914). The linked study observed both coated fibres (asbestos
bodies) and uncoated fibres and the concentration of asbestos was calculated by extrap-
olation and provided in number of fibres per gram of dry weight (Andrion et al. 1984,
HERO ID: 3083599).
Medium The parent study used asbestos bodies by number of asbestos bodies in 6.74mm. This
was further grouped into 0=no bodies, 1= 1-10 bodies, 11=11-100 bodies, and 111= over
100 bodies. (Andrion et al. 1982, HERO ID: 3083914). The linked study used both
coated and uncoated fibres. Uncoated fibres are grouped by 0, 1-10,000, 10,001-50,000,
and >50,000. Coated fibres are grouped by 0, 1-100, 101-1,000, and >1,000 (Andrion
et al. 1984, HERO ID: 3083599).
Additional Comments:
Overall, this cohort reviews asbestos bodies and pleural plaques from autopsies. The linked study (Andrion et al. 1984, HERO ID: 3083599) lacks statistical
analyses, but the paret study (Andrion et al. 1982, HERO ID: 3083914) provides associations. While this cohort is ranked as a medium, it may better fit as
a Low rating overall for its missing gaps in exposure assessment and limited analyses.
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 153 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081975 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Anttila, S., Karjalainen, A., Taikina-Aho, O., Kyyronen, P., Vainio, H. (1993). Lung cancer in the lower lobe is associated with pulmonary asbestos fiber
count and fiber size. Environmental Health Perspectives 101(1993): 166-170.
Lung Cancer; Asbestosis
Cancer/Carcinogenesis: Lung cancer, including squamous cell carcinomas, adenocarcinomas, small cell carcinomas, large cell carcinomas, and adenosqua-
mous carcinoma; Lung/Respiratory: Lung cancer
Asbestos - Anthophyllite: 17068-78-9; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Amosite (grunerite): 12172-73-5
No linked references.
3081975
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low Exposure to asbestos was determined to quantify concentration of asbestos fibers in lung
tissue samples. Since an interview structure was utilized to determine general classifica-
tions of asbestos exposure, there is no information on air concentrations of asbestos.
Low There was no direct of asbestos fibers using monitoring . Asbestos exposure information
was generated from asbestos fiber concentrations found in dried lung tissue samples
from the study participants.
Additional Comments: As the QC reviewer, I also rate this study medium for several reasons. This study used a job exposure matrix to estimate the level of asbestos exposure
into Definite Exposure, Probable Exposure, Possible Exposure, and Unlikely Exposure. The outcome of interest (lung cancer cases were confirmed by
histological means). However, even though no direct air measurements were taken, the authors examined lung tissue samples of the participants to determine
fibrosis, fiber type, etc. Those with signs of obstructive pneumonia were not included in the analysis. Table 3 includes information on the unadjusted and
adjusted odds ratios for various factors and their relation to lower lobe tumors.Overall, information on the measurement of exposure metric (M4) to assess
exposure was limited. Additionally, the exposure levels metric (M5) information reported was limited to determine exposure-response relationships.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 154 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3077721 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Arakawa, H., Kishimoto, T., Ashizawa, K., Kato, K., Okamoto, K., Honma, K., Hayashi, S., Akira, M. (2015). Asbestosis and other pulmonary fibrosis in
asbestos-exposed workers: high-resolution CT features with pathological correlations. European Radiology 26(2015):1485-1492.
Asbestosis
Lung/Respiratory: Asbestosis (CT asbestos score)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3077721
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Key elements of the study design were reported within this retrospective case study
of a subset of possible asbestosis cases obtained from a Japanese nationwide hospital
network that cares for asbestos workers. Of these cases (total number from hospital
network not detailed), only those with a lobectomy or autopsy specimen (total: n=33,
males: n=31, females: n=2; mean age at computed tomography (CT): 73 years) who
underwent high-resolution chest CT between May 2000 and July 2011 were selected
and enrolled for study. Of these, 30 cases underwent autopsy, and three cases had lobec-
tomies for lung cancer. Only those images of patients in stable condition and without
complications such as pneumonia or advanced lung cancer were evaluated. It is unclear
if the exposure-outcome distribution of those selected is representative of the target pop-
ulation as the total number of possible asbestosis cases within the hospital network was
not revealed, and only those cases with autopsy or pathology specimens, and potentially
higher exposures or more disease, were selected for study. Authors noted the potential
for selection bias.
Low Of the total hospital network possible asbestosis cases (number not detailed), only those
with lobectomy or autopsy specimens, in stable conditions and without complications,
were selected. The number of potential participants noted as possible asbestosis cases
but without lobectomy or autopsy specimens was not detailed.
Medium Inclusion criteria and methods of participant selection were reported and all subjects
were selected from the same eligible population within the same time frame. Demo-
graphic and other potentially relevant differences between subjects with differing levels
of asbestos body counts were not detailed, however Table 1 notes that age and work pe-
riod were not significantly different between asbestosis and non-asbestosis groups. It is
unclear to what extent various aspects (such as healthy hire, healthy worker survivor) of
the healthy worker effect might have been a factor in the cohort for study.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure High Asbestos body counts were analyzed by transmission electron microscopy.
Metric 5: Exposure Levels Medium The range and distribution of asbestos body (AB) counts presented in Table 1 (AB mean
(SD) for the Asbestosis group (n=15): 1,464,711 (1,974822); non-Asbestosis group
(n=18): 98,745 (174,492)) is sufficient to develop an exposure response relationship.
Correlation analyses utilized asbestos body counts as a continuous variable correlated
with asbestosis scores.
Continued on next page ...
Page 155 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077721 Table: 1 of 2
... continued from previous page
Arakawa, H., Kishimoto, T., Ashizawa, K., Kato, K., Okamoto, K., Honma, K., Hayashi, S., Akira, M. (2015). Asbestosis and other pulmonary fibrosis in
asbestos-exposed workers: high-resolution CT features with pathological correlations. European Radiology 26(2015):1485-1492.
Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Asbestosis (CT asbestos score)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3077721
Domain
Metric
Rating
Comments
Metric 6:
Temporality
Medium
This study establishes appropriate temporality within occupational histories, but it is
unclear if the interval between exposure and outcome is long enough for consideration
of latency of the outcome for those with 10 years of exposure as working years ranged
from 10 to 42 years (mean=24 years).
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Medium
Asbestosis: Outcomes of CT asbestosis score and pathological asbestosis score were
investigated. CT images of cases were reviewed by two independent, experienced (over
twenty years) radiologists aware of patient age and sex but blinded to pathological di-
agnoses and occupational histories, with disagreements resolved by a third experienced
(over twenty years) radiologist. Pleural disease scores were averaged across pulmonary
zones and the likelihood of asbestosis was designated for each case from a separate four-
point scale: 0=not asbestosis, l=possible asbestosis, 2=probably asbestosis, 3=definite
asbestosis. Summation of the pleural disease and asbestosis likelihood scores provided
the final CT-asbestosis score. Asbestosis diagnosis was made as in Akira et al., 2003
(HERO ID not available), and al-Jarad et al., (1992) (HERO ID not available). Authors
noted CT images were obtained in the supine position with potential for difficulty in
the analyses of ground-glass opacity and subpleural curvilinear lines. Radiologist inter-
observer agreements were 4.9 and 1.2 for ground glass opacity and curvilinear lines by
single determination standard deviation, respectively.
Metric 8:
Reporting Bias
High
There were no concerns for selective reporting as all outcomes which were outlined
within methods were also reported within the results. Correlations between asbestos
body counts and CT asbestosis and pathological asbestosis scores were reported as
correlation coefficients with corresponding p-values.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
Low
Other than stratification of mean ages across asbestosis and non-asbestosis groups in
Table 1, and the detail within the text regarding the total number of females (n=2), no
adjustments for gender, age or race appear to have been made within analyses and the
distribution of additional potentially relevant covariates and potential confounders was
not reported.
Metric 10:
Covariate Characterization
N/A
Covariates were not considered within final correlational analyses.
Continued on next page ...
Page 156 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077721 Table: 1 of 2
... continued from previous page
Arakawa, H., Kishimoto, T., Ashizawa, K., Kato, K., Okamoto, K., Honma, K., Hayashi, S., Akira, M. (2015). Asbestosis and other pulmonary fibrosis in
asbestos-exposed workers: high-resolution CT features with pathological correlations. European Radiology 26(2015):1485-1492.
Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Asbestosis (CT asbestos score)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3077721
Domain
Metric
Rating
Comments
Metric 11: Co-exposure Counfounding
Low The members of the cohort were workers with varying occupations. Occupational histo-
ries included: asbestos-manufacturing (n=9), shipyard workers (n=8), asbestos-spraying
(n=4), boiler repair (n=2), insulation worker (n=2), plumbing worker (n=2) and others
(n=5). Authors noted that non-asbestosis cases included workers exposed to asbestos
as well as other kinds of dust, however additional details regarding these other kinds of
dust were not provided and co-exposures were not addressed. Considerations for work-
ers who might have initially left and worked elsewhere with additional exposures but
eventually returned to asbestos work were not detailed. However, there was no evidence
that there was an unbalanced provision of co-exposures among exposure groups.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design was appropriate as an initial study to address the research aims. The
correlations of asbestos body count and CT/pathological scores were evaluated with the
Spearman rank correlation coefficient, however consideration for multivariate analyses
was not detailed. A value of p<0.05 was considered significant. Additional analyses
were detailed for the agreement of CT and pathological scores, calculated by weighted
kappa statistics. The difference in CT scores between asbestosis and non-asbestosis
cases was evaluated by a non-parametric test (IBM SPSS Statistics ver. 22, Tokyo,
Japan).
Medium The number of participants (n=33 total with n=15 asbestosis and n=18 non-asbestosis
cases) was minimal and described by the authors as small in number, but was adequate
for Spearman rank correlation.
Medium The description of analysis is sufficient to understand how to reproduce the analysis of
the correlation between asbestos body count and CT/pathological scores.
N/A Model building was not utilized.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric
16:
Use of Biomarker of Exposure
Low
Evidence was not detailed describing a relationship between asbestos body counts and
external occupational exposure specific for this population.
Metric
17:
Effect Biomarker
N/A
Biomarkers of effect were not assessed.
Metric
18:
Method Sensitivity
Low
LOD/LOQ was not stated. The analytical method was noted to be transmission electron
microscopy for asbestos body counts.
Metric
19:
Biomarker Stability
Low
Lung specimen sample storage history and stability not detailed.
Metric
20:
Sample Contamination
Medium
There is no information included regarding contamination.
Metric
21:
Method Requirements
High
Transmission electron microscopy utilized to provide identification and quantitation of
asbestos bodies.
Continued on next page ...
Page 157 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077721 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Arakawa, H., Kishimoto, T., Ashizawa, K., Kato, K., Okamoto, K., Honma, K., Hayashi, S., Akira, M. (2015). Asbestosis and other pulmonary fibrosis in
asbestos-exposed workers: high-resolution CT features with pathological correlations. European Radiology 26(2015):1485-1492.
Asbestosis
Lung/Respiratory: Asbestosis (CT asbestos score)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3077721
Domain
Metric
Rating
Comments
Metric 22: Matrix Adjustment
N/A
Matrix adjustment is not required.
Additional Comments: Cases of possible asbestosis were obtained from a lapanese nationwide hospital network that cares for asbestos workers in this retrospective case study.
Of these cases (total number from hospital network not detailed), only those with a pathologic lobectomy or autopsy specimen (total: n=33, males:
n=31, females: n=2; mean age at computed tomography (CT): 73 years) who underwent high-resolution chest CT between May 2000 and luly 2011
were selected and enrolled for study. Of these, 30 cases underwent autopsy, and three cases had lobectomies for lung cancer. Only those images of
patients in stable condition and without complications such as pneumonia or advanced lung cancer were evaluated. Outcomes of CT asbestosis score and
pathological asbestosis score were investigated. The number of asbestos bodies, not the number of asbestos fibers, were counted by experienced technicians
described as within participating institutions and utilizing transmission electron microscopy (TEM) asbestos counting methods as within Koyama et al.,
1991 (HERO ID 709715). Occupational histories included: asbestos-manufacturing (n=9), shipyard workers (n=8), asbestos-spraying (n=4), boiler repair
(n=2), insulation worker (n=2), plumbing worker (n=2) and others (n=5). Working years ranged from 10 to 42 years (mean=24 years). Asbestos body
count positively correlated with CT likelihood of asbestosis (r=0.503, p=0.003), and with the pathological asbestosis score (r=0.637, p<0.001) (Figures 4
and 5). CT-asbestosis score and pathological asbestosis score also showed a significant positive correlation (r=0.656, p<0.001).
Overall Quality Determination Medium
Page 158 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077721 Table: 2 of 2
Arakawa, H., Kishimoto, T., Ashizawa, K., Kato, K., Okamoto, K., Honma, K., Hayashi, S., Akira, M. (2015). Asbestosis and other pulmonary fibrosis in
asbestos-exposed workers: high-resolution CT features with pathological correlations. European Radiology 26(2015):1485-1492.
Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Asbestosis (pathological asbestos score)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3077721
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Key elements of the study design were reported within this retrospective case study
of a subset of possible asbestosis cases obtained from a Japanese nationwide hospital
network that cares for asbestos workers. Of these cases (total number from hospital
network not detailed), only those with a lobectomy or autopsy specimen (total: n=33,
males: n=31, females: n=2; mean age at computed tomography (CT): 73 years) who
underwent high-resolution chest CT between May 2000 and July 2011 were selected
and enrolled for study. Of these, 30 cases underwent autopsy, and three cases had lobec-
tomies for lung cancer. Only those images of patients in stable condition and without
complications such as pneumonia or advanced lung cancer were evaluated. It is unclear
if the exposure-outcome distribution of those selected is representative of the target pop-
ulation as the total number of possible asbestosis cases within the hospital network was
not revealed, and only those cases with autopsy or pathology specimens, and potentially
higher exposures or more disease, were selected for study. Authors noted the potential
for selection bias.
Low Of the total hospital network possible asbestosis cases (number not detailed), only those
with lobectomy or autopsy specimens, in stable conditions and without complications,
were selected. The number of potential participants noted as possible asbestosis cases
but without lobectomy or autopsy specimens was not detailed.
Medium Inclusion criteria and methods of participant selection were reported and all subjects
were selected from the same eligible population within the same time frame. Demo-
graphic and other potentially relevant differences between subjects with differing levels
of asbestos body counts were not detailed, however Table 1 notes that age and work pe-
riod were not significantly different between asbestosis and non-asbestosis groups. It is
unclear to what extent various aspects (such as healthy hire, healthy worker survivor) of
the healthy worker effect might have been a factor in the cohort for study.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure High Asbestos body counts were analyzed by transmission electron microscopy.
Metric 5: Exposure Levels Medium The range and distribution of asbestos body (AB) counts presented in Table 1 (AB mean
(SD) for the Asbestosis group (n=15): 1,464,711 (1,974822); non-Asbestosis group
(n=18): 98,745 (174,492)) is sufficient to develop an exposure response relationship.
Correlation analyses utilized asbestos body counts as a continuous variable correlated
with asbestosis scores.
Continued on next page ...
Page 159 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077721 Table: 2 of 2
... continued from previous page
Arakawa, H., Kishimoto, T., Ashizawa, K., Kato, K., Okamoto, K., Honma, K., Hayashi, S., Akira, M. (2015). Asbestosis and other pulmonary fibrosis in
asbestos-exposed workers: high-resolution CT features with pathological correlations. European Radiology 26(2015):1485-1492.
Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Asbestosis (pathological asbestos score)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3077721
Domain
Metric
Rating
Comments
Metric 6:
Temporality
Medium
This study establishes appropriate temporality within occupational histories, but it is
unclear if the interval between exposure and outcome is long enough for consideration
of latency of the outcome for those with 10 years of exposure as working years ranged
from 10 to 42 years (mean=24 years).
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
High
Asbestosis: Outcomes of CT asbestosis score and pathological asbestosis score were
investigated. Pathological asbestosis diagnoses of pulmonary tissues specimens from
autopsy and lobectomy were made based upon asbestosis diagnostic criteria as in Roggli
et al., 2010 (HERO ID 2587237) by two independent pulmonary pathologists blinded
to case occupational history with pathological asbestosis diagnoses based upon a three-
point scale: 0=fibrosis other than asbestosis, l=possible asbestosis, 2=definite asbesto-
sis. A pathological asbestosis score was obtained through the summation of the scores
given by each pathologist.
Metric 8:
Reporting Bias
High
There were no concerns for selective reporting as all outcomes which were outlined
within methods were also reported within the results. Correlations between asbestos
body counts and CT asbestosis and pathological asbestosis scores were reported as
correlation coefficients with corresponding p-values.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
Low
Other than stratification of mean ages across asbestosis and non-asbestosis groups in
Table 1, and the detail within the text regarding the total number of females (n=2), no
adjustments for gender, age or race appear to have been made within analyses and the
distribution of additional potentially relevant covariates and potential confounders was
not reported.
Metric 10:
Covariate Characterization
N/A
Covariates were not considered within final correlational analyses.
Metric 11:
Co-exposure Counfounding
Low
The members of the cohort were workers with varying occupations. Occupational histo-
ries included: asbestos-manufacturing (n=9), shipyard workers (n=8), asbestos-spraying
(n=4), boiler repair (n=2), insulation worker (n=2), plumbing worker (n=2) and others
(n=5). Authors noted that non-asbestosis cases included workers exposed to asbestos
as well as other kinds of dust, however additional details regarding these other kinds of
dust were not provided and co-exposures were not addressed. Considerations for work-
ers who might have initially left and worked elsewhere with additional exposures but
eventually returned to asbestos work were not detailed. However, there was no evidence
that there was an unbalanced provision of co-exposures among exposure groups.
Domain 5: Analysis
Continued on next page ...
Page 160 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077721 Table: 2 of 2
... continued from previous page
Arakawa, H., Kishimoto, T., Ashizawa, K., Kato, K., Okamoto, K., Honma, K., Hayashi, S., Akira, M. (2015). Asbestosis and other pulmonary fibrosis in
asbestos-exposed workers: high-resolution CT features with pathological correlations. European Radiology 26(2015):1485-1492.
Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Asbestosis (pathological asbestos score)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3077721
Domain
Metric
Rating
Comments
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design was appropriate as an initial study to address the research aims. The
correlations of asbestos body count and CT/pathological scores were evaluated with the
Spearman rank correlation coefficient, however consideration for multivariate analyses
was not detailed. A value of p<0.05 was considered significant. Additional analyses
were detailed for the agreement of CT and pathological scores, calculated by weighted
kappa statistics. The difference in CT scores between asbestosis and non-asbestosis
cases was evaluated by a non-parametric test (IBM SPSS Statistics ver. 22, Tokyo,
Japan).
Medium The number of participants (n=33 total with n=15 asbestosis and n=18 non-asbestosis
cases) was minimal and described by the authors as small in number, but was adequate
for Spearman rank correlation.
Medium The description of analysis is sufficient to understand how to reproduce the analysis of
the correlation between asbestos body count and CT/pathological scores.
N/A Model building was not utilized.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric
16:
Use of Biomarker of Exposure
Low
Evidence was not detailed describing a relationship between asbestos body counts and
external occupational exposure specific for this population.
Metric
17:
Effect Biomarker
N/A
Biomarkers of effect were not assessed.
Metric
18:
Method Sensitivity
Low
LOD/LOQ was not stated. The analytical method was noted to be transmission electron
microscopy for asbestos body counts.
Metric
19:
Biomarker Stability
Low
Lung specimen sample storage history and stability not detailed.
Metric
20:
Sample Contamination
Medium
There is no information included regarding contamination.
Metric
21:
Method Requirements
High
Transmission electron microscopy utilized to provide identification and quantitation of
asbestos bodies.
Metric
22:
Matrix Adjustment
N/A
Matrix adjustment is not required.
Continued on next page ...
Page 161 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077721 Table: 2 of 2
... continued from previous page
Arakawa, H., Kishimoto, T., Ashizawa, K., Kato, K., Okamoto, K., Honma, K., Hayashi, S., Akira, M. (2015). Asbestosis and other pulmonary fibrosis in
asbestos-exposed workers: high-resolution CT features with pathological correlations. European Radiology 26(2015):1485-1492.
Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Asbestosis (pathological asbestos score)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3077721
Domain
Metric
Rating
Comments
Additional Comments:
Cases of possible asbestosis were obtained from a lapanese nationwide hospital network that cares for asbestos workers in this retrospective case study.
Of these cases (total number from hospital network not detailed), only those with a pathologic lobectomy or autopsy specimen (total: n=33, males:
n=31, females: n=2; mean age at computed tomography (CT): 73 years) who underwent high-resolution chest CT between May 2000 and luly 2011
were selected and enrolled for study. Of these, 30 cases underwent autopsy, and three cases had lobectomies for lung cancer. Only those images of
patients in stable condition and without complications such as pneumonia or advanced lung cancer were evaluated. Outcomes of CT asbestosis score and
pathological asbestosis score were investigated. The number of asbestos bodies, not the number of asbestos fibers, were counted by experienced technicians
described as within participating institutions and utilizing transmission electron microscopy (TEM) asbestos counting methods as within Koyama et al.,
1991 (HERO ID 709715). Occupational histories included: asbestos-manufacturing (n=9), shipyard workers (n=8), asbestos-spraying (n=4), boiler repair
(n=2), insulation worker (n=2), plumbing worker (n=2) and others (n=5). Working years ranged from 10 to 42 years (mean=24 years). Asbestos body
count positively correlated with CT likelihood of asbestosis (r=0.503, p=0.003), and with the pathological asbestosis score (r=0.637, p<0.001) (Figures 4
and 5). CT-asbestosis score and pathological asbestosis score also showed a significant positive correlation (r=0.656, p<0.001).
Overall Quality Determination
Medium
Page 162 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083076 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Armstrong, B. K., de Klerk, N. H., Musk, A. W., Hobbs, M. S. (1988). Mortality in miners and millers of crocidolite in Western Australia. British Journal
of Industrial Medicine 45(1988):13-May.
Lung Cancer; Laryngeal Cancer; gastrointestinal, respiratory; infectious and parasitic diseases, mental disorders, accidents and injuries
Gastrointestinal: Stomach cancer mortality, Neoplasms of the prostate mortality, Other digestive neoplasms mortality (not stomach, intestines, or pancreas),
Neoplasms of the oesophagus mortality, Colorectal cancer mortality, Digestive diseases mortality, Neoplasms of intestines including rectum mortality, Neo-
plasms of pancreas mortality, Peptic ulceration mortality, Other digestive diseases mortality (not peptic ulceration or cirrhosis of the liver); nan: ; Cancer/
Carcinogenesis: Lung cancer mortality, Stomach cancer mortality, Neoplasms of the prostate mortality, Lymphoma and myeloma mortality, Other digestive
neoplasms mortality (not stomach, intestines, or pancreas), Neoplasms of the pancreas mortality, Neoplasms of the oesophagus mortality, Colorectal cancer
mortality, Cancer of the larynx/pharynx mortality, All cancers mortality, Neoplasms of upper aerodigestive tract mortality, Neoplasms of intestines includ-
ing rectum mortality, Neoplasms of larynx mortality, Neoplasms of trachea, bronchus, and lung, Other neoplasms mortality (not upper aerodigestive tract,
oesophagus, gastrointestinal, larynx, trachea, bronchus, lung, mesothelioma, prostate, lymphoma, or myeloma); Lung/Respiratory: Lung cancer mortality,
Pneumoconiosis mortality, Bronchitis and emphysema mortality, Respiratory diseases mortality, Tuberculosis mortality, Cancer of the larynx/pharynx mor-
tality, Neoplasms of larynx mortality, Neoplasms of trachea, bronchus, and lung, Other respiratory disease mortality (not pneumoconiosis, bronchitis, or
emphsyema); Mortality: Pneumoconiosis mortality, Bronchitis and emphysema mortality, Respiratory diseases mortality, Neoplasms of the prostate mor-
tality, Lymphoma and myeloma mortality, Other digestive neoplasms mortality (not stomach, intestines, or pancreas), Neoplasms of the pancreas mortality,
Neoplasms of the oesophagus mortality, Tuberculosis mortality, Colorectal cancer mortality, Liver cirrhosis mortality, Cardiovascular disease mortality,
Lung cancer mortality, Stomach cancer mortality, Cancer of the larynx/pharynx mortality, All cancers mortality, All causes mortality, Mental disorders
mortality, Nervous system and organ disease mortality, Infectious and parasitic diseases mortality, Digestive diseases mortality, Genitourinary diseases
mortality, Other infectious and parasitic diseases (not Tuberculosis) mortality, Neoplasms of upper aerodigestive tract mortality, Neoplasms of intestines
including rectum mortality, Neoplasms of larynx mortality, Neoplasms of trachea, bronchus, and lung, Other neoplasms mortality (not upper aerodigestive
tract, oesophagus, gastrointestinal, larynx, trachea, bronchus, lung, mesothelioma, prostate, lymphoma, or myeloma), Alcoholism mortality, Other mental
disorders mortality (non-alcoholism), Other respiratory disease mortality (not pneumoconiosis, bronchitis, or emphsyema), Peptic ulceration mortality,
Other digestive diseases mortality (not peptic ulceration or cirrhosis of the liver); Hepatic/Liver: Liver cirrhosis mortality; Cardiovascular: Cardiovascular
disease mortality; Neurological/Behavioral: Mental disorders mortality, Nervous system and organ disease mortality, Alcoholism mortality, Other mental
disorders mortality (non-alcoholism); Renal/Kidney: Genitourinary diseases mortality; Immune/Hematological: Lymphoma and myeloma mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4
3083076, 6874474
3083076
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Dust concentration measurements were taken periodically at the mine and mill. A ko-
niometer, which is a device used to estimate the amount of dust in the air, was utilized
between 1948 and 1958. This only measured total dust per cubic centimeter (ppcc), and
it had an upper limit of 1,000 ppcc. This limit was often exceeded. A survey was under-
taken to determine the concentration of airborne crocidolite fibers greater than 5 microns
in length in 1966. A Casella long running thermal precipitator was used to generate the
data. A Casella gravimetric dust sampler and a Hexhelt were also used to estimate dust
mass. No impingers or PCM/TEM were utilized in this study.This metric is rated low
because the studies or any cited methods source do not explicitly mention the use of
PCM or TEM (Armstrong et al„ 1988, 3083076; Reid et al„ 2018, 6874474).
Continued on next page ...
Page 163 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083076 Table: 1 of 1
... continued from previous page
Study Citation: Armstrong, B. K., de Klerk, N. H., Musk, A. W., Hobbs, M. S. (1988). Mortality in miners and millers of crocidolite in Western Australia. British Journal
of Industrial Medicine 45(1988):13-May.
Lung Cancer; Laryngeal Cancer; gastrointestinal, respiratory; infectious and parasitic diseases, mental disorders, accidents and injuries
Gastrointestinal: Stomach cancer mortality, Neoplasms of the prostate mortality, Other digestive neoplasms mortality (not stomach, intestines, or pancreas),
Neoplasms of the oesophagus mortality, Colorectal cancer mortality, Digestive diseases mortality, Neoplasms of intestines including rectum mortality, Neo-
plasms of pancreas mortality, Peptic ulceration mortality, Other digestive diseases mortality (not peptic ulceration or cirrhosis of the liver); nan: ; Cancer/
Carcinogenesis: Lung cancer mortality, Stomach cancer mortality, Neoplasms of the prostate mortality, Lymphoma and myeloma mortality, Other digestive
neoplasms mortality (not stomach, intestines, or pancreas), Neoplasms of the pancreas mortality, Neoplasms of the oesophagus mortality, Colorectal cancer
mortality, Cancer of the larynx/pharynx mortality, All cancers mortality, Neoplasms of upper aerodigestive tract mortality, Neoplasms of intestines includ-
ing rectum mortality, Neoplasms of larynx mortality, Neoplasms of trachea, bronchus, and lung, Other neoplasms mortality (not upper aerodigestive tract,
oesophagus, gastrointestinal, larynx, trachea, bronchus, lung, mesothelioma, prostate, lymphoma, or myeloma); Lung/Respiratory: Lung cancer mortality,
Pneumoconiosis mortality, Bronchitis and emphysema mortality, Respiratory diseases mortality, Tuberculosis mortality, Cancer of the larynx/pharynx mor-
tality, Neoplasms of larynx mortality, Neoplasms of trachea, bronchus, and lung, Other respiratory disease mortality (not pneumoconiosis, bronchitis, or
emphsyema); Mortality: Pneumoconiosis mortality, Bronchitis and emphysema mortality, Respiratory diseases mortality, Neoplasms of the prostate mor-
tality, Lymphoma and myeloma mortality, Other digestive neoplasms mortality (not stomach, intestines, or pancreas), Neoplasms of the pancreas mortality,
Neoplasms of the oesophagus mortality, Tuberculosis mortality, Colorectal cancer mortality, Liver cirrhosis mortality, Cardiovascular disease mortality,
Lung cancer mortality, Stomach cancer mortality, Cancer of the larynx/pharynx mortality, All cancers mortality, All causes mortality, Mental disorders
mortality, Nervous system and organ disease mortality, Infectious and parasitic diseases mortality, Digestive diseases mortality, Genitourinary diseases
mortality, Other infectious and parasitic diseases (not Tuberculosis) mortality, Neoplasms of upper aerodigestive tract mortality, Neoplasms of intestines
including rectum mortality, Neoplasms of larynx mortality, Neoplasms of trachea, bronchus, and lung, Other neoplasms mortality (not upper aerodigestive
tract, oesophagus, gastrointestinal, larynx, trachea, bronchus, lung, mesothelioma, prostate, lymphoma, or myeloma), Alcoholism mortality, Other mental
disorders mortality (non-alcoholism), Other respiratory disease mortality (not pneumoconiosis, bronchitis, or emphsyema), Peptic ulceration mortality,
Other digestive diseases mortality (not peptic ulceration or cirrhosis of the liver); Hepatic/Liver: Liver cirrhosis mortality; Cardiovascular: Cardiovascular
disease mortality; Neurological/Behavioral: Mental disorders mortality, Nervous system and organ disease mortality, Alcoholism mortality, Other mental
disorders mortality (non-alcoholism); Renal/Kidney: Genitourinary diseases mortality; Immune/Hematological: Lymphoma and myeloma mortality
Asbestos Fiber Asbestos - Crocidolite (riebeckite): 12001-28-4
Type(s):
Linked HERO ID(s): 3083076, 6874474
HERO ID: 3083076
Domain Metric Rating Comments
Metric 5: Exposure Levels Medium The figures included in the Armstrong et al., 1988, (HERO ID: 3083076) paper displays
several mortality outcomes amongst the miners and millers at various exposure levels.
They are split into groups as follows: <10 f/cc y, 10-100 f/cc y, and >100 f/cc y. They
also include all exposures combined, which includes unknown exposures.The levels of
exposure in the Reid et al. 2018 (HERO ID: 6874474) paper included <10 f/mL years,
10-50 f/mL years, and >50. These values allow for the development of an exposure-
response estimate.
Additional Comments: NOTE: This cohort was rated "Low" for Metric 4, and thus does not meet the criteria for usefulness for dose-response. Only outcome inventory, fiber
types, and Metrics 4 and 5 received a full QC.There were several limitations in this paper. One of the primary concerns pertains to the use of an appropriate
comparison group. The authors also did not discuss potential covariates to be included in the models, and the two different methods used to calculate SMRs
may also introduce bias into the results.
Continued on next page ...
Health
Outcome:
Target
Organ(s):
Page 164 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083076 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Armstrong, B. K., de Klerk, N. H., Musk, A. W., Hobbs, M. S. (1988). Mortality in miners and millers of crocidolite in Western Australia. British Journal
of Industrial Medicine 45(1988):13-May.
Lung Cancer; Laryngeal Cancer; gastrointestinal, respiratory; infectious and parasitic diseases, mental disorders, accidents and injuries
Gastrointestinal: Stomach cancer mortality, Neoplasms of the prostate mortality, Other digestive neoplasms mortality (not stomach, intestines, or pancreas),
Neoplasms of the oesophagus mortality, Colorectal cancer mortality, Digestive diseases mortality, Neoplasms of intestines including rectum mortality, Neo-
plasms of pancreas mortality, Peptic ulceration mortality, Other digestive diseases mortality (not peptic ulceration or cirrhosis of the liver); nan: ; Cancer/
Carcinogenesis: Lung cancer mortality, Stomach cancer mortality, Neoplasms of the prostate mortality, Lymphoma and myeloma mortality, Other digestive
neoplasms mortality (not stomach, intestines, or pancreas), Neoplasms of the pancreas mortality, Neoplasms of the oesophagus mortality, Colorectal cancer
mortality, Cancer of the larynx/pharynx mortality, All cancers mortality, Neoplasms of upper aerodigestive tract mortality, Neoplasms of intestines includ-
ing rectum mortality, Neoplasms of larynx mortality, Neoplasms of trachea, bronchus, and lung, Other neoplasms mortality (not upper aerodigestive tract,
oesophagus, gastrointestinal, larynx, trachea, bronchus, lung, mesothelioma, prostate, lymphoma, or myeloma); Lung/Respiratory: Lung cancer mortality,
Pneumoconiosis mortality, Bronchitis and emphysema mortality, Respiratory diseases mortality, Tuberculosis mortality, Cancer of the larynx/pharynx mor-
tality, Neoplasms of larynx mortality, Neoplasms of trachea, bronchus, and lung, Other respiratory disease mortality (not pneumoconiosis, bronchitis, or
emphsyema); Mortality: Pneumoconiosis mortality, Bronchitis and emphysema mortality, Respiratory diseases mortality, Neoplasms of the prostate mor-
tality, Lymphoma and myeloma mortality, Other digestive neoplasms mortality (not stomach, intestines, or pancreas), Neoplasms of the pancreas mortality,
Neoplasms of the oesophagus mortality, Tuberculosis mortality, Colorectal cancer mortality, Liver cirrhosis mortality, Cardiovascular disease mortality,
Lung cancer mortality, Stomach cancer mortality, Cancer of the larynx/pharynx mortality, All cancers mortality, All causes mortality, Mental disorders
mortality, Nervous system and organ disease mortality, Infectious and parasitic diseases mortality, Digestive diseases mortality, Genitourinary diseases
mortality, Other infectious and parasitic diseases (not Tuberculosis) mortality, Neoplasms of upper aerodigestive tract mortality, Neoplasms of intestines
including rectum mortality, Neoplasms of larynx mortality, Neoplasms of trachea, bronchus, and lung, Other neoplasms mortality (not upper aerodigestive
tract, oesophagus, gastrointestinal, larynx, trachea, bronchus, lung, mesothelioma, prostate, lymphoma, or myeloma), Alcoholism mortality, Other mental
disorders mortality (non-alcoholism), Other respiratory disease mortality (not pneumoconiosis, bronchitis, or emphsyema), Peptic ulceration mortality,
Other digestive diseases mortality (not peptic ulceration or cirrhosis of the liver); Hepatic/Liver: Liver cirrhosis mortality; Cardiovascular: Cardiovascular
disease mortality; Neurological/Behavioral: Mental disorders mortality, Nervous system and organ disease mortality, Alcoholism mortality, Other mental
disorders mortality (non-alcoholism); Renal/Kidney: Genitourinary diseases mortality; Immune/Hematological: Lymphoma and myeloma mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): 3083076, 6874474
3083076
Domain
Metric
Rating
Comments
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 165 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2078960 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Bagatin, E., Neder, J. A., Nery, L. E., Terra-Filho, M., Kavakama, J., Castelo, A., Capelozzi, V., Sette, A., Kitamura, S., Favero, M., Moreira-Filho, D.
C., Tavares, R., Peres, C., Becklake, M. R. (2005). Non-malignant consequences of decreasing asbestos exposure in the Brazil chrysotile mines and mills.
Occupational and Environmental Medicine 62(2005):381-389.
Pulmonary Function/Spirometry Results; Pleural Plaques
Lung/Respiratory: FEV1, FVC, FEF, Dyspnea, Parenchymal abnormalities, Pleural and/or parenchymal abnormalities, Pleural plaques
Asbestos - Tremolite: 14567-73-8; Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
2078960
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Metric 3:
Attrition
Comparison Group
Medium Cohort study, Ex-workers from a single asbestos mining and milling company who
worked for the company for at least one year were invited to participate. Study pop-
ulation was separated into 3 groups whose working conditions improved over time:
group I (1940"66, n = 180), group II (1967"76, n = 1317), and group III (1977"96, n =
2137). From the 6098 eligible subjects, 433 (7.1% ) were found to bedead (148, 184,
and 101 subjects for groups I, II, and III,respectively); 3634 of the remaining 5665 were
actuallyexamined (64.1% ). The rate of recruitment success variedbetween the differ-
ent groups: group 1=46.1% (180/390alive), group 11=67.5% (1317/1950), and group
111=64.2% (2137/3325) (table 1).
Medium 121 lung function tests did not meet quality criteria and were not included in the study.
Medium The demographic and occupational variables differed significantly among the groups.
Thus, group III subjects were younger and presented with a shorter latency than their
counterparts of groups I and II (table 1). Higher cumulative exposure was also found in
group I subjects compared to groups II and III. Subject numbers in group 1 n=180 com-
pared to group 2 n=1317 and group 3 n=2137. Difference reported between exposure
groups were controlled for.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Participants were split into three groups depending on when their exposure occurred.
Group III had routine measurements of asbestos fibers, which were obtained by airborne
samples from different areas of activity using a constant-flow sampler. A membrane
filter was used to collect the fibers and the counting was done with a phase contrast
microscope (PCM).
Medium Tables 2 and 3 use binary exposure groups (i.e. less than 10 fibers/y/cc, or greater than
or equal to 10 fibers/y/cc.) Tables 4 and 6 include a continuous measure of cumulative
exposure (but this is not a robust analysis due to not considering confounders). The
graphs in Figure 2 report three exposure levels (highest quartile, IQR, and lowest quar-
tile).
High Latency differed across groups, however at the time of the present evaluation, more than
half of group III workers already had a latency time of at least 20 years. Included in
analysis was Group I (1940"66, n = 107), group II (1967"76, n = 930), and group III
(1977"96, n = 713).
Continued on next page ...
Page 166 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2078960 Table: 1 of 1
... continued from previous page
Bagatin, E., Neder, J. A., Nery, L. E., Terra-Filho, M., Kavakama, J., Castelo, A., Capelozzi, V., Sette, A., Kitamura, S., Favero, M., Moreira-Filho, D.
C., Tavares, R., Peres, C., Becklake, M. R. (2005). Non-malignant consequences of decreasing asbestos exposure in the Brazil chrysotile mines and mills.
Occupational and Environmental Medicine 62(2005):381-389.
Pulmonary Function/Spirometry Results; Pleural Plaques
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Lung/Respiratory: FEV1, FVC, FEF, Dyspnea, Parenchymal abnormalities, Pleural and/or parenchymal abnormalities, Pleural plaques
Asbestos - Tremolite: 14567-73-8; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2078960
Domain
Metric
Rating
Comments
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Metric 8: Reporting Bias
High Pulmonary Function/Spirometry Results: FVC1, FEF, FVC measured through spiro-
metric tests, which were performed with a calibrated pneumo tacograph (Fleisch No. 3).
The subjects completed at least three acceptable maximal forced expiratory manoeuvres:
technical procedures, acceptability, and reproducibility criteria were those recommended
by the American Thoracic Society.; Pleural Plaques: Standard high-kilovoltage, pos-
teroanterior CRX were obtained, with radiographs classified by 3 chest physicians (2
B-readers and 1 A-reader) up to September 1999; after September 1999 one B-reader
was replaced by a radiologist with 18 years' experience. Readers were blinded as to
exposure status. Radiographs were interpreted using ILO standards; parenchymal opac-
ities were reported if ILO reading was 1/0 or more. Profusion readings were reported as
median values. Presence of pleural plaques also assessed.
High The authors wanted to examine mortality but report that they were unable to due to
a lack of reliability in death certificates. Additionally, the study reports information
graphically but has point estimates reported in either the footnotes of graphs or in the
text of the paper.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Low Covariates included smoking, latency time, cumulative exposure. Sex and race were not
adjusted for or analyzed.
Medium Collected via occupational interview.
Low Co-exposure was not analyzed.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The cohort uses a longitudinal design to study the long-term effects of asbestos expo-
sure, using statistical models such as linear and logistic regression.
Medium This study included the following number of participants in each group: Group I
(1940"66, n = 107), group II (1967"76, n = 930), and group III (1977"96, n = 713).
Medium All analyses appear reproducible.
Medium The discussion of normality implies they did assess one of the assumptions for linear
regression. A backward stepwise linear regression procedure was also used for analysing
the relation of the spirometric variables to latency, cumulative exposure, smoking (pack-
years), and radiographic abnormalities. Probability of type I error was established at
0.05 for all tests. Cumulative probability model in Figure 2
Continued on next page ...
Page 167 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2078960 Table: 1 of 1
... continued from previous page
Study Citation:
Bagatin, E., Neder, J. A., Nery, L. E., Terra-Filho, M., Kavakama, J., Castelo, A., Capelozzi, V., Sette, A., Kitamura, S., Favero, M., Moreira-Filho, D.
C., Tavares, R., Peres, C., Becklake, M. R. (2005). Non-malignant consequences of decreasing asbestos exposure in the Brazil chrysotile mines and mills.
Occupational and Environmental Medicine 62(2005):381-389.
Pulmonary Function/Spirometry Results; Pleural Plaques
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: FEV1, FVC, FEF, Dyspnea, Parenchymal abnormalities, Pleural and/or parenchymal abnormalities, Pleural plaques
Asbestos - Tremolite: 14567-73-8; Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
2078960
Domain
Metric
Rating
Comments
Additional Comments:
A standardized occupational history was administered by interview, detailing the start and end of exposure, the specific workplace(s), and the estimated
level of exposure (groups I and II) (Bagatin et al. 2004, HERO ID: 2078960). Groups I and II did not have routine systematic asbestos measurements, and
thus a "subjective, logarithmic scale" was used to estimate indices of exposure based on fiber measurements before the development of routine measures.
Participants self-identified their level of workplace dustiness as mild (0.3-3 fibers/cc), moderate (3-30 fibers/cc), or severe (more than 30 fibers/cc). Group
I differed significantly in terms of size, latency, cumulative exposure and age. Dyspnea, wheezing, cough, phlegm were also assessed as was radiographic
abnormalities (Bagatin et al. 2004, HERO ID: 2078960). Other study in other cohort revealed, however, that CXR compared to Thin-section CT was
associated with false-positives for interstitial abnormalities and false-negatives for pleural plaques, regardless of the intensity of asbestos exposure (Terra-
Filho et al. 2015, HERO ID: 3077807).
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 168 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6861350 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Barbieri, P. G., Consonni, D., Somigliana, A. (2019). Relationship between pleural plaques prevalence and extension and biomarkers of cumulative asbestos
dose. A necropsy study. La Medicina del Lavoro 353-362.
Asbestosis; Pleural Plaques
Lung/Respiratory: Pleural plaques, Asbestosis
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7
No linked references.
6861350
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The authors measured asbestos fibers in lung tissue of the subjects during necropsy,
which represented a measure of cumulative exposure to asbestos over the lifetime. The
authors did not collect primary or secondary data of asbestos fibers' concentration in
the occupational exposure environment. The authors used SEM and what appears to
be optical microscopy to quantify exposure, but this cannot be confirmed as the cited
method is in Italian (Istituto Superiore di Sanit", 2017).
Medium The authors reported summary statistics representing four different levels of exposure
associated with the pleural plaques' extension grades that are adequate for the devel-
opment of an exposure-response relationship. (Table 1; millions of asbestos fibres and
millions of amphibole fibres, per gram of dry lung tissue).
Additional Comments: The study authors may have had conflicts of interest in that they served as a consultants for victims" families in litigations concerning asbestos-related
diseases.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 169 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082482 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Beritid-Stahuljak, D., Valid, F., Zuskin, E. (1991). Relationship between cumulative occupational exposure to asbestos fibres and respiratory symptoms.
Acta Medica Croatica 45 (1991): 283-295.
Respiratory symptoms
Lung/Respiratory: Respiratory symptom-chronic cough, Respiratory symptom-chronic phlegm, Respiratory symptom-chronic bronchitis, Respiratory
symptom-dyspnea
Asbestos - Not specified: 1332-21-4
No linked references.
3082482
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This study examined the relationship between prevalent respiratory symptoms (chronic
cough, chronic phlegm, chronic bronchitis, dyspnea) assessed through standardized in-
terviews and asbestos exposure as represented by length of employment (years, range:
1-27 years), estimated cumulative exposure to total particles (particles/cc years), and
estimated cumulative exposure to asbestos fibers (fibers/cc years) in asbestos workers
(n=1127) engaged in asbestos mining, asbestos cement production, production of fric-
tion materials or the manufacture of asbestos textiles versus age-matched non-exposed
controls (n=593).
High Characteristics, in terms of relevant variables of those possibly excluded due to miss-
ing outcome or exposure data, were not reported, however there was no indication that
missing data or subject drop-out was an issue within this study.
Medium The control group (n=281) was described as having no known occupational exposure
to airborne particles or irritant gases. Control subjects were described as age-matched
(methods not specified) to asbestos male workers; however, text notes males and females
were part of the exposed worker group (n=230 female nonsmoking asbestos workers).
This study was restricted to employees working at the time of study and assessment of
prevalent outcomes. It is unclear if healthy hire or healthy worker survivor effects were
appreciable within this study which examined prevalent respiratory symptoms within a
population with 1-27 years of employment exposure.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure High Quantitative exposure measurements (1971-1974) of total airborne particulates and
asbestos fibers were performed simultaneously during typical work cycles and were
described in terms of equipment, procedures and referenced (Valic et al., 1988, foreign
reference number 15 in text). Number of samples varied and time of sample collection
ranged from 1 minute to three hours, depending on dust level. Asbestos exposure ana-
lytic methods utilized phase contrast illumination. Final estimated cumulative exposures
calculations were based on mean measured concentrations measured during typical work
cycles during all work shifts during two seasons, estimated duration of exposures, es-
timated weighted daily exposures for each typical work operation and complete work
histories for each worker. Exposures in control subjects not detailed, however controls
had no known occupational asbestos exposure.
Continued on next page ...
Page 170 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082482 Table: 1 of 1
... continued from previous page
Beritid-Stahuljak, D., Valid, F., Zuskin, E. (1991). Relationship between cumulative occupational exposure to asbestos fibres and respiratory symptoms.
Acta Medica Croatica 45 (1991): 283-295.
Respiratory symptoms
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Respiratory symptom-chronic cough, Respiratory symptom-chronic phlegm, Respiratory symptom-chronic bronchitis, Respiratory
symptom-dyspnea
Asbestos - Not specified: 1332-21-4
No linked references.
3082482
Domain
Metric
Rating
Comments
Metric 5:
Exposure Levels
Medium
Measured (1971-1974) asbestos fiber concentrations (f/cc) were reported within Table
1 for each mine and factory work category and ranged from 0.3 " 62.0 f/cc for six cate-
gories of exposure. Summary measures of estimated cumulative exposures were detailed
in Figure 1 footnote description of asbestos exposure categories and ranged from zero
fibers/cc years to greater than 80 fibers/cc years. The range and distribution of exposure
appeared adequate.
Metric 6:
Temporality
Low
This study was restricted to employees working at the time of study and outcomes were
those prevalent at time of assessment (dates of outcome assessment not provided). The
temporality of exposure-outcome relationships is uncertain due to the cross-sectional
nature of respiratory symptom outcome assessment within this study.
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Medium
Other Non-Cancer Outcomes: Respiratory symptom outcomes of interest included
prevalence of self-reported chronic cough, chronic phlegm, chronic bronchitis and
dyspnea as assessed by standardized interview questionnaire, which was noted to be
a modified form of the British Medical Research Council Questionnaire. Validation of
outcomes was not reported, and results were participant reported, however there is no
indication that methods had poor validity.
Metric 8:
Reporting Bias
Medium
There were no concerns for selective reporting as all outcomes which were outlined
within methods were also reported within the results. The results within Figure 1 were
reported only as p-values for each level of exposure specified within figure footnotes,
with details regarding number of participants, confidence intervals and standard errors
lacking.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
Medium
Controls were described as age-matched to male exposed workers. Text notes both male
and female asbestos workers were included within analyses, however considerations
for control of gender within analyses was lacking. Analyses within Tables 2-4 were
restricted to those within categories of smokers and non-smokers. A distribution of
demographic characteristics of exposed and control workers was presented.
Metric 10:
Covariate Characterization
Medium
While the methods utilized to obtain and validate data regarding potential confounders
were described only as obtained through interview, there is no indication that methods
had poor validity and the interview methods were described as standardized.
Metric 11:
Co-exposure Counfounding
Medium
Potential co-exposures somewhat considered by authors within assessment of total par-
ticles, however actual control of potential co-exposures potentially associated with in-
creased experience of respiratory symptoms within a multivariate analyses was lacking.
Continued on next page ...
Page 171 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082482 Table: 1 of 1
... continued from previous page
Beritid-Stahuljak, D., Valid, F., Zuskin, E. (1991). Relationship between cumulative occupational exposure to asbestos fibres and respiratory symptoms.
Acta Medica Croatica 45 (1991): 283-295.
Respiratory symptoms
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Respiratory symptom-chronic cough, Respiratory symptom-chronic phlegm, Respiratory symptom-chronic bronchitis, Respiratory
symptom-dyspnea
Asbestos - Not specified: 1332-21-4
No linked references.
3082482
Domain
Metric
Rating
Comments
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium Statistical analysis of the data within this study was not detailed within the text. Table 2
results for asbestos workers and controls indicate use of chi-square analyses for obtain-
ing p-values, however statistical analyses for Figure 1 results are not detailed.
Medium The number of subjects (n=1127 asbestos workers, n=593 controls) appeared adequate
for this analysis, although the number of subjects within each category of exposure
within Figure 1 was not detailed.
Low Statistical analysis methods were not reported and details such as rules for classification
of smoking categories, consideration of outliers, transformation of continuous variables
and methods for dealing with missing data were not detailed.
Low The description of statistical analysis was very brief and is only inferred from Table 2 as
consisting of chi-square analyses.
Additional Comments: This study examined the relationship between prevalent respiratory symptoms (chronic cough, chronic phlegm, chronic bronchitis, dyspnea) assessed
through standardized interviews and asbestos exposure as represented by length of employment (years, range: 1-27 years), estimated cumulative exposure
to total particles (particles/cc years), and estimated cumulative exposure to asbestos fibers (fibers/cc years) in asbestos workers (n=1127) engaged in
asbestos mining, asbestos cement production, production of friction materials or the manufacture of asbestos textiles versus age-matched non-exposed
controls (n=593). Exposure was measured 1971-1974 and estimates of cumulative exposure were calculated utilizing these measurements as well as
detailed complete work histories of each worker. Dates of assessment of respiratory outcomes through standardized interview questionnaire not specified.
Results indicated a statistically significant relationship between prevalence of respiratory symptoms and duration of employment (Fig. 1A, p<0.01), total
particles/cc years (Fig. IB, p<0.01). The relationship between prevalence of respiratory symptoms and exposure expressed by measured asbestos fibers/cc
years was not significant (Fig. 1C, P>0.05).
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 172 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709467 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Berry, G., Pooley, F., Gibbs, A., Harris, J., Mcdonald, J. (2009). Lung fiber burden in the Nottingham gas mask cohort. Inhalation Toxicology 21(2009): 168-
172.
mortality from other diseases and all cause mortality
Mortality: Other diseases, All cause mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
709467
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Key elements of study design were reported in this retrospective case study of a subset
of the original Nottingham Gas Mask Cohort of n=l,154 mostly female employees who
assembled military gas masks, 1940-1945, using filter pads containing 20% crocidolite
asbestos. Within this cohort, a subset was selected of those with tissue samples. Lung
tissue samples were obtained from 50 (77% ) of the n=65 cases of mesothelioma, and
n=20 deaths from other causes. Duration of employment was recorded in only 51 of the
70 deaths.
Medium Exclusions of subjects from the original cohort or analyses were adequately described
for the cases (n=70) with lung tissue samples selected out of the original cohort
(n=l,154) and those with employment duration data (n=-51 of n=70). Cause of death
was not detailed for these exclusions for missing data.
Medium Inclusion criteria and methods of participant selection were reported. All included sub-
jects came from the same original Nottingham cohort within the same time frame. It is
unclear to what extent various aspects (healthy hire, healthy worker survivor, left trunca-
tion bias, exposure-dependent right censoring) of the healthy worker effect might have
been a factor in the cohort for study.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
High Crocidolite asbestos fiber levels per microgram of dried lung were analyzed by transmis-
sion electron microscopy.
Medium The range and distribution of lung crocidolite fiber concentrations presented in Tables
1 and 2 by decade of death and categories (4 categories) of length (months) of exposure
are sufficient to develop an exposure response relationship.
High The study establishes appropriate temporality and the interval between exposure and
outcome is long enough for consideration of latency of the outcome. The period of
possible exposure to crocidolite was noted to be September 1940 to March 1945 with
follow-up for deaths through 1994.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or High Other Non-Cancer Outcomes: ICD codes were not detailed within the main text, how-
Characterization ever data regarding deaths was described in the referenced original Nottingham cohort
study by McDonald et al., 2006 (HERO ID 709504) and indicate use of ICD-9 as well
as employment and pathological records for traced former workers with all deaths due to
mesothelioma described as confirmed by pathology.
Continued on next page ...
Page 173 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709467 Table: 1 of 1
... continued from previous page
Berry, G., Pooley, F., Gibbs, A., Harris, J., Mcdonald, J. (2009). Lung fiber burden in the Nottingham gas mask cohort. Inhalation Toxicology 21(2009): 168-
172.
mortality from other diseases and all cause mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Mortality: Other diseases, All cause mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): No linked references.
709467
Domain
Metric
Rating
Comments
Metric 8:
Reporting Bias
High
There were no concerns for selective reporting as all outcomes which were outlined
within methods were also reported within the results. Results for fiber concentrations
within lungs were reported across year of death and cause of death categories within
Table 1.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Low Other than stratification of fiber concentration results across year and cause of death
categories, no adjustments for gender, age or race appear to have been made and the
distribution of primary covariates and potential confounders was not reported.
Medium The members of the cohort were workers at the Nottingham military gas mask factory
1940 through 1945. Although co-exposures were not addressed, there was no evidence
that there was an unbalanced provision of co-exposures among exposure groups. Con-
siderations for workers who might have initially left and worked elsewhere with ad-
ditional exposures but eventually returned to the gas mask factory for study were not
detailed. Authors noted that masks consisted of 20% crocidolite, but details regarding
the remaining composition of masks were not provided.
Medium The study design was appropriate to address the main objective of analyzing lung fiber
burdens over time. The percentage of fibers longer than 6jUm was analyzed by logistic
regression with respect to year of death. Median geometric mean crocidolite fibers in
lung tissue were presented in Table 1 for year of death categories and cause of death.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design was appropriate to address the main objective of analyzing lung fiber
burdens over time. The percentage of fibers longer than 6jUm was analyzed by logistic
regression with respect to year of death. Median geometric mean crocidolite fibers in
lung tissue were presented in Table 1 for year of death categories and cause of death.
Medium The number of participants (n=70 total with n=51 with duration of employment data)
was minimal for regression analyses, although additional covariates did not appear to
have been considered within modeling.
Medium The description of analysis is sufficient to understand how to generally reproduce the
analyses. Transformation of exposure variables was described in detail. Imputation of
exposures with zero values as one-half of the limit of detection was also detailed.
Low Model building was not described in terms of the reasoning for lack of considerations
for potential confounders within models of the percentage of fibers longer than 6jUm
analyzed by logistic regression with respect to year of death.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Continued on next page ...
Page 174 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709467 Table: 1 of 1
... continued from previous page
Berry, G., Pooley, F., Gibbs, A., Harris, J., Mcdonald, J. (2009). Lung fiber burden in the Nottingham gas mask cohort. Inhalation Toxicology 21(2009): 168-
172.
mortality from other diseases and all cause mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Other diseases, All cause mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
709467
Domain
Metric
Rating
Comments
Metric 16: Use of Biomarker of Exposure
Metric 17: Effect Biomarker
Metric 18: Method Sensitivity
Metric 19: Biomarker Stability
Metric 20: Sample Contamination
Metric 21: Method Requirements
Metric 22: Matrix Adjustment
Low
N/A
Medium
Low
Medium
High
N/A
Evidence exists for a relationship between lung fiber concentrations and external ex-
posure within models assessing the relationship between lung fiber concentrations and
length of exposure in years, but there has been no assessment of accuracy and precision
or none was reported.
No biomarkers of effect were used.
Authors noted, "For three zero values, half of the detection limit (0.005, 0.005, 0.05
fibers/jUg) was substituted". Analytical method utilized transmission electron mi-
croscopy.
Lung fiber sample storage history and stability not detailed.
There is no information included regarding contamination.
Transmission electron microscopy utilized to provide identification and quantitation of
lung fibers.
This study utilized a biomarker of exposure.
Additional Comments: This study focused upon post-mortem crocidolite lung fiber concentrations in a subset (n=70: n=50 mesothelioma and n=20 deaths from other causes) of
the Nottingham Gas Mask cohort of n=l,154 employees with lung tissue samples who had worked 1940-1945 on the manufacture of military gas masks
with filter pads containing 20% crocidolite and who were followed through 2003. Crocidolite asbestos fiber levels per microgram of dried lung were
presented by decade of death and cause of death (Table 1), duration of exposure (Table 2), and the percentage of fibers longer than 6/im was analyzed with
year of death by logistic regression (Figure 2). The crocidolite counts ranged from 0 to 1,949 (mean 234, median 47) fibers/jig.
Overall Quality Determination Medium
Page 175 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3078093 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Bourgkard, E., Wild, P., Gonzalez, M., F6votte, J., Penven, E., Paris, C. (2013). Comparison of exposure assessment methods in a lung cancer case-control
study: performance of a lifelong task-based questionnaire for asbestos and PAHs. Occupational and Environmental Medicine 70(2013):884-891.
Lung Cancer
Cancer/Carcinogenesis: Lung cancer; Lung/Respiratory: Lung cancer
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3078093
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
The study uses job-specific questionnaires (including JEM) to determine exposure;
however, the authors are not clear whether the categories of exposure were based on
PCM or TEM conversion factors. It appears that exposure was determined solely using
professional judgement.This metric is rated low because the study or any cited methods
source does not explicitly mention the use of PCM or TEM.
The authors provide the range of exposures; however, the information is very limited.
The distribution of exposures is only provided indirectly in comparing two of the differ-
ent exposure methods (i.e., Table 2).
Additional Comments:
NOTE: This study would not have been evaluated fully under the current guidelines. Metric 4 was rated as low because there was no mention of PCM or
TEM within the study or a cited methods source.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 176 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6868332 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Brims, F. J. H., Kong, K., Harris, E. J. A., Sodhi-Berry, N., Reid, A., Murray, C. P., Franklin, P. J., Musk, A. B., e Klerk, N. H. (2020). Pleural plaques and
the risk of lung cancer in asbestos-exposed subjects. American Journal of Respiratory and Critical Care Medicine 201(2020):57-62.
Lung Cancer; Ovarian Cancer; breast, cervical, corpus uterine, colorectal
Reproductive/Developmental: Breast cancer, Ovarian cancer, Cervical cancer, Corpus uterine cancer; Cancer/Carcinogenesis: Cancer in the lung, trachea
and bronchus, all cancers, Ovarian cancer, Breast cancer, Cervical cancer, Colorectal cancer, Corpus uterine cancer; Lung/Respiratory: Cancer in the lung,
trachea and bronchus; Gastrointestinal: Colorectal cancer
Asbestos - Crocidolite (riebeckite): 12001-28-4
733541, 709469, 3079298, 3520653, 3531364, 6868332
6868332
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not ex-
plicitly mention the use of PCM or TEM. dust concentrations were measured using
koniometer between 1948 and 1958. In 1966, fiber counting was done using a Casella
long running thermal precipitator. Personal and fixed monitors were utilized in 1973.
Additional measurements were taken in 1977, 1978, 1980, 1984, 1986, and 1992, us-
ing interpolation to estimate concentrations for years that surveys were not conducted.
According to Hansen et al., 1997 2219991, all samples examined were analyzed using
the standard membrane filter method. Some exceptions were surveys in 1984 and 1986
which used SEM, and in 1992 which used TEM. Although later surveys utilized TEM,
the current study does not describe estimates in a way to know outcomes based on expo-
sures measured from 1992 and after.
Medium The distribution of exposure appears to be sufficient to develop an exposure-response
estimate. Cumulative exposure was utiliized in statistical models.
Additional Comments: None
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 177 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081832 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Brown, D. P., Dement, J. M., Okun, A. (1994). Mortality patterns among female and male chrysotile asbestos textile workers. Journal of Occupational
Medicine 36(1994):882-888.
Pneumoconiosis and other respiratory disease mortality
Lung/Respiratory: Pneumoconiosis and other respiratory disease mortality; Mortality: Pneumoconiosis and other respiratory disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
3081832, 66, 2238696, 6860087
3081832
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
High The authors reference three previous studies of white male textile workers from a
chrysotile asbestos plant in South Carolina (Dement et al., 1982, HEROID: 65; Dement
et al., 1983, HEROID: 66; Dement et al., 1983, HEROID: 67). In the original analyses,
the white male workers were required to be employed for at least one month between
January 1, 1940-Decemeber 31, 1965. This study updates the cohort to include all work-
ers who were employed at least one month, and follow-up vital status extended by 15
years, updating from 1975-1990. The authors discuss using death files from "the Social
Security Administration, the National Death Index, and the files of the Internal Rev-
enue Service" (Brown et al., 1994, HEROID: 3081832). Black women employes were
excluded due to the small number (n=19). Overall, the updated cohort included 3,022
workers (1,229 white women, 1,247 white men, and 546 black men).
High Authors note that 22.8% of white women from the plant were lost to follow-up as their
vital status could not be confirmed. Authors found that most of these women were those
employed for a shorter amount of time: "54% worked less than 6 months, 17% worked
between 6 months and 1 year, and 29% worked longer than 1 year"(Brown et al., 1994,
HEROID: 3081832). Of the black men employed in the plant, 7.8% were lost to follow-
up, and 1.5% of white men were lost to follow-up. Additionally, 11% of white women,
7.6% of black men, and 2.8% of white men were presumed dead, but their death certifi-
cates were not obtained. These workers were assumed alive in the analyses.
High The South Carolina death rate was used to calculate expected deaths and the SMRs.
Additionally, outcomes are stratified by race/gender.
Domain 2: Exposure Characterization
Continued on next page .
Page 178 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3081832 Table: 1 of 1
... continued from previous page
Brown, D. P., Dement, J. M., Okun, A. (1994). Mortality patterns among female and male chrysotile asbestos textile workers. Journal of Occupational
Medicine 36(1994):882-888.
Pneumoconiosis and other respiratory disease mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Pneumoconiosis and other respiratory disease mortality; Mortality: Pneumoconiosis and other respiratory disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
3081832, 66, 2238696, 6860087
3081832
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Individual lifetime cumulative exposure to asbestos was estimated using data from De-
ment et al. (1983, HERO ID: 66), which clarifies that 5,952 environmental samples were
used covering the period of 1930-1975 using impingers until 1965, impingers and mem-
brane filter samples between 1965 and 1971, and membrane filter samples exclusively
from 1971-1975. Another study from the same cohort, Richardson et al. (2018, HERO
ID: 6860087) clarifies that the approach used phase-contrast microscopy (PCM) for fiber
counting (as evidenced by the citation of Edwards and Lynch, 1968, HEROID: 783893).
The impinger and membrane filter samples that were taken concurrently (n=l,106 pairs)
were used to create conversion between the two types of data, resulting in a conversion
factor of 2.9 fibers to one mpccf. Detailed job histories were also collected to calculate
individual exposure estimates, which took into account the dust concentration for the
job an individual worked at, the time spent in the job, and the number of jobs held. Data
came from personnel records.
Medium In SMR analysis, 7 different exposure levels are used which represent values of fibers/
cmA 3 days that range from <500 to >100,000.
High In the original study, workers had to be employed for at least one month at any time
from January 1940- December 1975 (Dement et al., 1982, HEROID: 65; Dement et al.,
1983, HEROID: 66; Dement et al., 1983, HEROID: 67). This study adds an additional
15 years of observation of mortality.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High Other Non-Cancer Outcomes: Authors used ICD-9 codes for pneumoconiosis and other
respiratory diseases (470-478 and 949-519).
High SMRs are reported in Table 5 for pneumoconiosis and other respiratory diseases, but
confidence intervals are not provided. P-values of <0.05 and <0.01 are reported. Ob-
served/expected mortality is also presented in Table 5
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium SMRs are adjusted by race and sex, but authors did not consider smoking as a covariate.
Medium While not mentioned in this study, Dement et al. (1982, HEROID: 65) writes "detailed
personnel records were first maintained beginning in approximately 1930. Therecord
system has remained remarkably unchanged since that time. For each worker,an em-
ployment card was completed at initial employment giving name, date of birth,sex, race,
social security number, marital status and address. This same card alsocontained the
detailed work history giving exact dates of employment by plantdepartment and specific
job. All information from these cards was entered onto acomputer data file."
Low In an occupational setting, potential co-exposures are not discussed.
Continued on next page ...
Page 179 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3081832 Table: 1 of 1
... continued from previous page
Brown, D. P., Dement, J. M., Okun, A. (1994). Mortality patterns among female and male chrysotile asbestos textile workers. Journal of Occupational
Medicine 36(1994):882-888.
Pneumoconiosis and other respiratory disease mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Pneumoconiosis and other respiratory disease mortality; Mortality: Pneumoconiosis and other respiratory disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
3081832, 66, 2238696, 6860087
3081832
Domain
Metric
Rating
Comments
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Medium
Medium
Medium
The study uses appropriate methods for calculating SMRs.
The sample size by sex and race is adequate to detect effect in the exposed worker's
mortality. Authors excluded previously employed black women as the numbers were to
calculate effect.
The methods are sufficient to conceptually reproduce this analysis, with reference to the
original studies (Dement et al., 1982, HEROID: 65; Dement et al., 1983, HEROID: 66;
Dement et al„ 1983, HEROID: 67).
Methods for calculating SMRs is transparent.
Additional Comments: This study is an extension of the retrospective cohort found in three studies (Dement et al., 1982, HEROID: 65; Dement et al., 1983, HEROID: 66; Dement
et al., 1983, HEROID: 67). The authors add 15 years of observation and include white women and black men to the analysis, which was previously limited
to white men. Overall, the study is well-designed but lacks covariates and adjustment for confounding for factors such as smoking.The measurement
exposure (M4) and/or exposure levels (M5) metrics are rated as medium upon review by both set of reviewers. Also, the overall quality determination
(OQD) is rated medium. Extraction has been completed and quality control reviewed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 180 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3080500 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Carel, R., Boffetta, P., Kauppinen, T., Teschke, K., Andersen, A., Jappinen, P., Pearce, N., Rix, B. A., Bergeret, A., Coggon, D., Persson, B., Szadkowska-
Stanczyk, I., Kielkowski, D., Henneberger, P., Kishi, R., Facchini, L. A., Sala, M., Colin, D., Kogevinas, M. (2002). Exposure to asbestos and lung and
pleural cancer mortality among pulp and paper industry workers. Journal of Occupational and Environmental Medicine 44(2002):579-584.
Lung Cancer; Pleural cancer
Cancer/Carcinogenesis: Pleural cancer mortality, Lung cancer mortality; Lung/Respiratory: Lung cancer mortality, Pleural cancer mortality
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3080500
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Exposure was estimated using a combination of job exposure matrices and available
measurements. A total of 1024 measurements of asbestos levels were available, along
with detailed information on processes and exposures in each department from industrial
hygienists and engineers from each mill. Both were used by an international team of in-
dustrial hygienists to quantitatively estimate exposure, who developed mill-, department-
, and time-specific assessments. Details on equipment used and measures from each mill
were not provided. The likelihood of substantial exposure misclassification cannot be
readily ascertained; there is no evidence suggesting differential error is likely.
Medium Exposure concentrations were quantified in three levels as low (average 0.001 fibers/
cm3), medium (0.01 f/cc) and high (0.10 f/cc). Cumulative exposure in f/cc-years was
then calculated by multiplying exposure intensity by the duration of exposure in years.
A weighted cumulative exposure measure incorporated prevalence of exposure.
Additional Comments: This study analyzed associations between occupational asbestos exposure and lung and pleural cancer mortality in a 13-country cohort of 62,937 male pulp
and paper workers employed for at least 1 year between 1945 and 1996. Exposure in this industry is predominantly from maintenance and repair work.
Exposure estimates used available dust measures and paper mill-specific information on exposure probabilities in each department. In internal analyses,
pleural but not lung cancer was significantly associated with ever exposure to asbestos, and non-significantly associated with higher years of exposure, years
since first exposure, and cumulative exposure. Higher cumulative exposure was also non-significantly associated with increased risk of lung cancer (n=450
in the cohort). Only 24 pleural cancers were identified, 10 in subjects classified as unexposed although several worked in departments where exposure may
occur. While there is no evidence of differential error, non-differential exposure misclassification may have attenuated associations. The authors also note
that the mean follow up of 23.5 years may not have been sufficient to fully identify pleural cancers, which have an extremely long latency.Information
on the measurement of exposure metric (M4) to assess exposure was limited and rated low. On the other hand, exposure levels metric (M5) information
reported was adequate/rated medium to determine exposure-response relationships. The overall rating for this outcome/study is medium.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 181 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081424 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Checkoway, H., Heyer, N. J., Demers, P. A., Gibbs, G. W. (1996). Reanalysis of mortality from lung cancer among diatomaceous earth industry workers,
with consideration of potential confounding by asbestos exposure. Occupational and Environmental Medicine 53(1996):645-647.
Lung Cancer
Cancer/Carcinogenesis: lung cancer mortality; Lung/Respiratory: lung cancer mortality; Mortality: lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): 3081424,4259501
3081424
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Both studies (Checkoway et al., 1996, HEROID: 3081424 and Checkoway et al., 1996,
HEROID: 4259501) reference Gibbs and Checkoway, 1994, HEROID: 3653704 for ex-
posure measurement information, which reports the use of midget impingers and mem-
brane filter sampling only without discussion of conversion factors or the use of PCM or
TEM methods, meriting a low rating. Gibbs and Checkoway, 1994 (HEROID: 3653704)
specifically note the inability to account for dust or other fibers that were erroneously
counted as asbestos fibers. In Gibbs and Checkoway, 1994, HEROID: 3653704, they do
reference a NIOSH report, which could offer additional information, but this was not
publicly available at the time of evaluation (NIOSH, 1977, "Health hazard evaluation de-
termination Report 77-2-404, Johns Manville Sales Corporation, Lompoc California").
Medium Both studies report four levels of exposure in their SMR analyses. Exposure groups in
both studies include unexposed as the lowest group and >=6.8 fiber-years as the highest
exposure group.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 182 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 30090 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Chiazze, L., Jr, Watkins, D. K., Fryar, C., Kozono, J. (1993). A case-control study of malignant and non-malignant respiratory disease among employees
of a fiberglass manufacturing facility II Exposure assessment. Occupational and Environmental Medicine 50(1993):717-725.
Lung Cancer; Non-malignant respiratory disease
Lung/Respiratory: Lung cancer, Non-malignant respiratory disease mortality; Cancer/Carcinogenesis: Lung cancer; Mortality: Non-malignant respiratory
disease mortality
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
30090
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low This metric is rated Low because the study or any cited methods source does not ex-
plicitly mention the use of PCM or TEM. Final regression modeling results in Table 4
included cumulative exposure estimates to respirable fibers (fibers/mL), asbestos (fibers/
mL), talc (fibers/mL), formaldehyde (ppm), respirable silica (mg/mA 3), and asphalt
fumes (mg/mA 3). Estimates of daily exposure to each of the substances over a worker"s
entire working lifetime were formulated from personal (proxy) interview occupational
history, detailed historical environmental reconstruction by year through engineering
process history (1938-1987), historical department job code titles, process-specific
chemical exposure analyses, industrial hygiene (IH) records (described as available
from about 1970 onwards) and employee work histories. The engineering process his-
tory was compiled by four Owens-Corning Fiberglass engineers and audited by process
division experts for validity. Assignment of department to process code was blinded to
case and control status. Authors noted few IH records existed for early, pre-1970 pro-
cesses and an exposure assessment committee of current and former Owens-Corning
Fiberglass employees with knowledge of IH, current and historical plant processes was
established to develop quantitative estimates of potential exposures to each substance
for each process by assigning each process to one of four ranges of estimated potential
exposure (eight-hour time weighted average (TWA) exposures specific to calendar time,
Table 1). Cumulative exposure to each substance for these employees was developed for
each employee as the product of the number of days in a process multiplied by the mid-
point of the exposure range and summed over all processes. Authors did not discuss the
potential for exposure misclassification within these methods, but the misclassification
was likely non-differential.
Metric 5: Exposure Levels Medium The range and distribution of estimated exposure (Table 4, four categories for asbestos
and three categories for talc estimated exposures) was sufficient to develop exposure-
response estimates.
Continued on next page ...
Page 183 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 30090 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Chiazze, L., Jr, Watkins, D. K., Fryar, C., Kozono, J. (1993). A case-control study of malignant and non-malignant respiratory disease among employees
of a fiberglass manufacturing facility II Exposure assessment. Occupational and Environmental Medicine 50(1993):717-725.
Lung Cancer; Non-malignant respiratory disease
Lung/Respiratory: Lung cancer, Non-malignant respiratory disease mortality; Cancer/Carcinogenesis: Lung cancer; Mortality: Non-malignant respiratory
disease mortality
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
30090
Domain Metric Rating Comments
Additional Comments: This occupational nested case-control study investigated the relationship between multiple exposures within cases of non-malignant (n=101) respiratory
disease mortality and matched controls (n=183) obtained from the Thermal Insulation Manufacturer"s Association (TIMA) historical cohort mortality
study of production and maintenance workers employed at the Newark, Ohio fiberglass manufacturing plant for at least one year between 1 lanuary 1940
and 31 December 1962 and followed up to the end of 1982. There is potential for Healthy Worker Survivor bias, indicated by results stratified by years
of employment. For non-malignant respiratory disease, only smoking was statistically significant with OR = 2.637 (95% CI, 1.146-6.069). None of the
exposure variables produced significant OR"s but higher OR"s were found for the higher ranked asbestos exposure levels.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 184 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1257859 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Christensen, K. Y., Kopylev, L. (2012). Localized pleural thickening: smoking and exposure to Libby vermiculite. lournal of Exposure Science and
Environmental Epidemiology 22(2012):320-323.
Pleural Plaques; Pleural thickening
Lung/Respiratory: Localized pleural thickening
Asbestos- Libby amphibole: 1318-09-8
No linked references.
1257859
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3: Comparison Group
Medium This study included workers from a Marysville, Ohio plant which used Libby amphibole
asbestos. There was a study that examined pulmonary effects in 512 workers, conducted
in 1980 (participation rates in Lockey et al., 1984 029685). The examination included
physical exams, spirometry, and chest x-rays. Information on smoking, work, and ex-
posure histories were collected. In 2002-2005, another follow-up study was conducted,
and included 280 of the original individuals. They participated in interviews and re-
ceived chest x-rays. The authors detail that they wanted to limit potential exposures in
other occupational settings, so the total number of individuals included in the analysis
was 118. They all began working in 1972 or later. The authors did not provide a ro-
bust description of the participation rate for this study, nor a comparison of participant
characteristics or the prevalence of pleural thickening in included vs excluded subjects.
However, there was no evidence of potential selection bias.
Medium To exclude potential error due to poorly measured occupational exposure prior to 1972,
this analysis limited the sample to workers hired after 1972, including 118 (42.1% ) of
280 workers included in a previous analysis of the same data (Rohs et al 2008, 709486).
In contrast to the earlier study, this paper did not compare characteristics of this subset
of participants vs. eligible living workers who were non-participants (e.g., age, exposure
level, smoking status). The earlier study also conducted sensitivity analyses to assess
the impact of attrition from the parent study (n=512) by adding the 151 eligible living
non-participants (assuming they had no pleural changes) to the model; conclusions did
not change. The potential impact of any attrition bias was not discussed here.
Medium Because of the nature of the analyses conducted in this study, subgroups were compared
against each other (i.e., a within-cohort analysis). Smoking and nonsmoking groups
were reported to be similar in age at x-ray and time from first exposure. However, fur-
ther discussion about similarities between the two groups was somewhat limited.
Domain 2: Exposure Characterization
Continued on next page .
Page 185 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1257859 Table: 1 of 1
... continued from previous page
Christensen, K. Y., Kopylev, L. (2012). Localized pleural thickening: smoking and exposure to Libby vermiculite. lournal of Exposure Science and
Environmental Epidemiology 22(2012):320-323.
Pleural Plaques; Pleural thickening
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Localized pleural thickening
Asbestos- Libby amphibole: 1318-09-8
No linked references.
1257859
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
High The authors detail that estimates of exposure through 2000 were developed through
several methods, including fiber measurements when available, and estimated fiber con-
centrations. For this cohort, the most accurate exposure data comes from 1972 onward,
because analytical measurements were used. According to the cited study (Rohs et al.,
2008, ID: 709486), airborne fibers were collected on membrane filters. The Rohs et al.
study cites another study in their methods section which details the use of transmission
electron microscopy for exposure measurements, contributing to the high rating for this
metric (Lockey et al., 1984, 29685). Prior to 1976, hygienists followed workers with a
sampling device to gather information about various departments. Information on the
year of hire and specific locations where individuals worked were used to determine a
cumulative exposure, reported in fibers/cc-year.
Medium The range and distribution of exposures presented in this study are sufficient to develop
an exposure-response estimate. Table 1 presents the mean as 0.42, with a standard devia-
tion of 0.77 fibers/cc-year. The range was reported as 0.001-5.51 fibers/cc-year.
High The interval between the exposure and the outcome is sufficiently long considering the
latency period for asbestos exposure. Table 1 reports that the average time since first
exposure was 28.2 years, with a standard deviation of 2.5 years. The range was reported
as 23.2-32.6 years since first exposure.
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Metric 8: Reporting Bias
High Pleural Plaques: See Other: Localized Pleural Thickening. From the manuscript: "In
the current International Labour Organization (ILO) classification, LPT includes both
pleural plaques (focal areas of pleural thickening generally present at the parietal pleura,
diaphragm or chest wall) and pleural thickening that does not involve blunting of the
costophrenic angle between the rib cage and the diaphragm."; Other Non-Cancer Out-
comes: The authors detail that "three board-certified radiologists blinded to any identi-
fying information, independently classified the radiographs using the ILO classification
system" (Christensen & Kopylev, 2012). The authors did not report the rate of agree-
ment between readers, but this is a well-established method. The authors did highlight
in the discussion section that one of the limitations of this study was a lack of BMI in-
formation for all participants. Some "fat pads may be mistaken for pleural thickening"
(Christensen & Kopylev, 2012).
Medium The results were presented in the text and included details on model fitting and evalua-
tion steps, p-values that informed decisions about variables included in the final model,
model fit indices, and the benchmark dose (BMC) calculated using the final model.
BMCs (the dose associated with a 10% increase in risk) were presented for the full sam-
ple, smokers, and non-smokers. However, coefficients from the models were not shown.
Continued on next page ...
Page 186 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1257859 Table: 1 of 1
... continued from previous page
Christensen, K. Y., Kopylev, L. (2012). Localized pleural thickening: smoking and exposure to Libby vermiculite. lournal of Exposure Science and
Environmental Epidemiology 22(2012):320-323.
Pleural Plaques; Pleural thickening
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Localized pleural thickening
Asbestos- Libby amphibole: 1318-09-8
No linked references.
1257859
Domain
Metric
Rating
Comments
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10:
Covariate Characterization
Metric 11: Co-exposure Counfounding
High The authors considered numerous covariates in their analyses. Time from first expo-
sure, age at x-ray, gender, and BMI were all considered for inclusion in the models; none
reached significance. The "covariates were evaluated according to the statistical signif-
icance of the covariate, and whether inclusion of the covariate improved model fit as
assessed by the AIC" (Christensen & Kopylev, 2012). Smoking history was included in
the final models, and interactions between smoking and asbestos exposure examined, in
keeping with the study aim of evaluating the impact of smoking on the asbestos BMC
for pleural thickening.
Medium There is no evidence to suggest poor validity of variables assessed as potential con-
founders . Confounders were characterized based on employee records, a screening
exam, and either in-person or telephone interviews. The potential influence of missing
data for BMI was considered in sensitivity analyses.
Medium The authors did not discuss potential co-exposures within the occupational setting in this
manuscript. However this issue was addressed in the manuscript analyzing the baseline
cohort: Lockey et al 1984, 029685 reported that a careful evaluation did not identify any
co-exposures that would cause pleural radiographic changes.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design and methods employed were appropriate for the research question
being examined. The candidate models used were provided, and the rationale for issues
such as the variables included and exposure lags selected was given.
Medium The analysis sample included only 12 cases and 106 non-cases. Power may have been
inadequate to detect statistically significant interactions.
Medium A thorough description of the analyses performed is included in this study. The descrip-
tion is sufficient to be able to conceptually understand how to reproduce the analyses
performed.
Medium The models included in this study are transparent, and it appears as though model as-
sumptions have been met.
Additional Comments: Overall, the authors provided a lot of detail within this study, and they were explicit about the analyses and model fit criteria used. The quality of both
exposure and outcome assessments was high, potential confounding was examined in depth, and there was lengthy follow-up. However, the small sample
size limited statistical power and results were presented only as benchmark doses, without additionally providing model coefficients. In addition, the
potential influence of any selection bias is uncertain: only 118 of the initial 512 workers in the cohort, and of the 431 alive at the time of X-rays, were
included due to the stringent criteria needed to minimize exposure measurement error.
Continued on next page ...
Page 187 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1257859 Table: 1 of 1
... continued from previous page
Christensen, K. Y., Kopylev, L. (2012). Localized pleural thickening: smoking and exposure to Libby vermiculite. lournal of Exposure Science and
Environmental Epidemiology 22(2012):320-323.
Pleural Plaques; Pleural thickening
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Localized pleural thickening
Asbestos- Libby amphibole: 1318-09-8
No linked references.
1257859
Domain Metric
Rating
Comments
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 188 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 758904 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Churg, A., Vedal, S. (1994). Fiber burden and patterns of asbestos-related disease in workers with heavy mixed amosite and chrysotile exposure. American
Journal of Respiratory and Critical Care Medicine 150(1994):663-669.
Lung Cancer; Asbestosis; Pleural Plaques; Airway fibrosis
Lung/Respiratory: Asbestosis, Airway fibrosis, pleural plaques, lung cancer; Cancer/Carcinogenesis: lung cancer
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Tremolite: 14567-73-8; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
758904
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
Methods for fiber count included fiber morphology and fiber chemistry determined
through energy-dispersive x-ray spectroscopy, followed by calculating fiber concentra-
tion using an algorithm that accounted for weight of lung tissue used in the study and
number of grid squares. However, authors did not utilize PCM or TEM, thus warranting
a low rating per the guidance.
Actual measured exposure data were not available for the cases and are estimations
based on historic data and calculations. Authors stated that exposure was not included
in their models as they felt combining years of exposure with fiber burden did not make
sense analytically nor is there a correlation between the two.
Additional Comments: 2/6/2023 UPDATE: DUE TO CHANGES IN THE GUIDANCE FOR SQE, ALL METRICS RATINGS EXCEPT FOR 4 AND 5 SHOULD BE IGNORED
BECAUSE METRIC 4 AND 5 WERE RATED "LOW".Authors stated crocidolite fibers were detected in a small number of cases but were excluded from
analyses. Examining the association between chrysotile or tremolite with disease was not conducted due to low concentrations, but concentrations are
reported.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 189 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1481523 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Churg, A., Wright, J. L., Vedal, S. (1993). Fiber burden and patterns of asbestos-related disease in chrysotile miners and millers. American Review of
Respiratory Disease 148(1993):25-31.
Lung Cancer; airway fibrosis
Cancer/Carcinogenesis: Mesothelioma, lung cancer; Lung/Respiratory: Asbestosis, airway fibrosis, pleural plaques, lung cancer, mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Tremolite: 14567-73-8
No linked references.
1481523
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Low
Low
Low
This study selected 300 autopsy lungs from workers in the Thetford Mines. The study
included 94 lung samples from miners and millers were included because data was
available. The selection criteria was not reported. Lack of information about the setting.
Only 94 out of 300 cases were included in analyses, over 2/3 of total subjects were lost
due to data unavailability. No discussion about excluded subjects and their relationship
with exposure or outcomes.
Comparison group was subjects without asbestos-related disease. The similarity of
groups was not described and demographic information for subjects without asbestos
related disease was not reported. There was very limited evidence indicated the groups
were similar.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Fiber concentrations were measured using analytic electron microscopy. Summary
statistics of exposure year and latency were reported. The nature of the study design
determined exposure measured at only one time period.
Medium The geometric means of asbestos concentration in cases by disease type and subjects
without asbestos-related disease were reported. Fiber concentration was treated as con-
tinuous variable in multiple linear regression
Medium The latency and exposure years were obtained from occupational histories. The reported
latency is sufficiently long. Uncertainty exists because exposure duration and latency
data not available to everyone; exposure years available for 91 subjects; latency data
available for 64 subjects.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Medium Lung Cancer: Lung cancer samples were identified but not reported using ICD codes or
confirmed by histological or cytological means.; Other Non-Cancer Outcomes: Airway
fibrosis identified through autopsy lung samples, but no ICD code or validation process
reported.
High Mesothelioma findings reported in the abstract and results section. Number of cases and
geometric mean of lung fiber burden were reported in table which allow extraction.
Domain 4: Potential Confounding / Variability Control
Continued on next page .
Page 190 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1481523 Table: 1 of 2
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Churg, A., Wright, J. L., Vedal, S. (1993). Fiber burden and patterns of asbestos-related disease in chrysotile miners and millers. American Review of
Respiratory Disease 148(1993):25-31.
Lung Cancer; airway fibrosis
Cancer/Carcinogenesis: Mesothelioma, lung cancer; Lung/Respiratory: Asbestosis, airway fibrosis, pleural plaques, lung cancer, mesothelioma
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Tremolite: 14567-73-8
No linked references.
1481523
Domain
Metric
Rating
Comments
Metric 9:
Metric 10:
Metric 11:
Covariate Adjustment
Covariate Characterization
Co-exposure Counfounding
Low
Low
Medium
The study mentioned covariates were adjusted but the age or smoking status were not
adjusted in models, and their distribution was not reported between groups. The covari-
ates controlled were concentration of another fiber and other disease.
Age and smoking status was checked for correlation with exposure concentration, but
not controlled in models. In multiple linear regression models of asbestos and disease,
concentration of another fiber and/or other asbestos related disease were sometimes
controlled in the model.
Co-exposures other than asbestos that would likely bias the results were not likely to be
present.
Domain 5: Analysis
Metric 12:
Metric 13:
Metric 14:
Metric 15:
Study Design and Methods
Statistical Power
Reproducibility of Analyses
Statistical Analysis
Medium
Uninformative
Medium
Medium
The study design is appropriate for the research question. t-Tests and linear regression
models were used to evaluate the association between fiber burden and asbestos related
disease.
The number of participants is small especially only n=6 subjects without asbestos re-
lated disease as reference group, which greatly limited the power of this study.
The description of the analysis is sufficient to understand how to conceptually reproduce
the analysis with access to the analytic data.
Statistical models and test method are transparent and appropriate
Additional Comments:
None
Overall Quality Determination
Uninformative
* No biomarkers were identified for this evaluation.
Page 191 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1481523 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Churg, A., Wright, J. L., Vedal, S. (1993). Fiber burden and patterns of asbestos-related disease in chrysotile miners and millers. American Review of
Respiratory Disease 148(1993):25-31.
Asbestosis; Pleural Plaques
Lung/Respiratory: Asbestosis, airway fibrosis, pleural plaques, lung cancer, mesothelioma; Cancer/Carcinogenesis: Mesothelioma, lung cancer
Asbestos - Tremolite: 14567-73-8; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
1481523
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Low
Low
Low
This study selected 300 autopsy lungs from workers in the Thetford Mines. The study
included 94 lung samples from miners and millers were included because data was
available. The selection criteria was not reported. Lack of information about the setting.
Only 94 out of 300 cases were included in analyses, over 2/3 of total subjects were lost
due to data unavailability. No discussion about excluded subjects and their relationship
with exposure or outcomes.
Comparison group was subjects without asbestos-related disease. The similarity of
groups was not described and demographic information for subjects without asbestos
related disease was not reported. There was very limited evidence indicated the groups
were similar.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Fiber concentrations were measured using analytic electron microscopy. Summary
statistics of exposure year and latency were reported. The nature of the study design
determined exposure measured at only one time period.
Medium The geometric means of asbestos concentration in cases by disease type and subjects
without asbestos-related disease were reported. Fiber concentration was treated as con-
tinuous variable in multiple linear regression
Medium The latency and exposure years were obtained from occupational histories. The reported
latency is sufficiently long. Uncertainty exists because exposure duration and latency
data not available to everyone; exposure years available for 91 subjects; latency data
available for 64 subjects.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Uninformative Asbestosis: Asbestosis assessment method was not reported. No imaging diagnosis or
validation or ICD code used.; Pleural Plaques: No established method usage reported for
pleural plaques measurement. No ICD code or validation process reported.
High Mesothelioma findings reported in the abstract and results section. Number of cases and
geometric mean of lung fiber burden were reported in table which allow extraction.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Low
The study mentioned covariates were adjusted when apply but the age or smoking status
were not adjusted in models, and their distribution was not reported between groups.
The covariates controlled were concentration of another fiber and other disease.
Continued on next page .
Page 192 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1481523 Table: 2 of 2
... continued from previous page
Study Citation: Churg, A., Wright, J. L., Vedal, S. (1993). Fiber burden and patterns of asbestos-related disease in chrysotile miners and millers. American Review of
Respiratory Disease 148(1993):25-31.
Asbestosis; Pleural Plaques
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Lung/Respiratory: Asbestosis, airway fibrosis, pleural plaques, lung cancer, mesothelioma; Cancer/Carcinogenesis: Mesothelioma, lung cancer
Asbestos - Tremolite: 14567-73-8; Asbestos - Chrysotile (serpentine): 12001-29-5
HERO ID:
1481523
Domain
Metric
Rating
Comments
Metric 10:
Metric 11:
Covariate Characterization
Co-exposure Counfounding
Low
Medium
Age and smoking status only checked for correlation with exposure concentration, but
not controlled in models. In multiple linear regression models of asbestos and disease,
concentration of another fiber and/or other asbestos related disease were sometimes
controlled in the model.
Co-exposures that other than asbestos that would likely bias the results were not likely to
be present.
Domain 5: Analysis
Metric 12:
Metric 13:
Metric 14:
Metric 15:
Study Design and Methods
Statistical Power
Reproducibility of Analyses
Statistical Analysis
Medium
Uninformative
Medium
Medium
The study design is appropriate for the research question. t-Tests and linear regression
models were used to evaluate the association between fiber burden and asbestos related
disease.
The number of participants is small especially only n=6 subjects without asbestos re-
lated disease as reference group, which greatly limited the power of this study.
The description of the analysis is sufficient to understand how to conceptually reproduce
the analysis with access to the analytic data.
Statistical models and test method are transparent and appropriate
Additional Comments: Lack of information on outcome measurements and small reference group size drastically limited the study's confidence and ability to detect an effect.
Overall Quality Determination
Uninformative
* No biomarkers were identified for this evaluation.
Page 193 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6863220 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Clin, B., Thaon, I., Boulanger, M., Brochard, P., Chamming's, S., Gislard, A., Lacourt, A., Luc, A., Ogier, G., Paris, C. (2017). Cancer of the esophagus
and asbestos exposure. American Journal of Industrial Medicine 60(2017):968-975.
esophageal cancer
Cancer/Carcinogenesis: Esophageal cancer mortality; Gastrointestinal: Esophageal cancer mortality; Mortality: Esophageal cancer mortality
Asbestos - Not specified: 1332-21-4
No linked references.
6863220
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low There is no detail regarding the measurement of exposure in this study, but a reference
to Paris et al., 2009 (Paris et al., 2009, HEROID 758968). There, authors describe the
use of a questionnaire and an a priori job-exposure matrix to calculate a cumulative
exposure index. This paper and the paper by Paris et al., 2009 lack and detail of as-
bestos sample measurements or quantification.Authors describe using four classes for
levels of exposure: "lowlevel (passive exposure), corresponding to a numerical value
of "O.Olequivalent fibers/mL"; low-intermediate, corresponding to a numericalvalue
of"0.1 equivalent fibers/mL"; high-intermediate, corresponding toa numerical value of
"1 equivalent fibers/mL"; and high exposure,corresponding to a numerical value of "10
equivalent fibers/mL" (Paris et al., 2009, HEROID 758968). A final cumulative exposure
index was calculated as the sum of each job's four-level CEI for each subject.
Medium Final models report 6 levels of exposure: unexposed, 0-3.3 f-y/mL, 3.3-13.5 f-y/ml,
13.6-32 f-y/ml, 32-64 f-y/ml, and >=64 f-y/ml. This data was calculated from cumula-
tive exposure indices.
Additional Comments:
HEROID 6863220 was not evaluated for any metrics except Metric 4 and 5 and had no data extracted because it did not have sufficient exposure information
to be useful for dose-response analysis.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 194 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 60556 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Conforti, P. M., Kanarek, M. S., Jackson, L. A., Cooper, R. C., Murchio, J. C. (1981). Asbestos in drinking water and cancer in the San Francisco Bay
area: 1969-1974 incidence. Journal of Clinical Epidemiology 34(1981):211-224.
Lung Cancer; Ovarian Cancer
Cancer/Carcinogenesis: Incidence of any cancer Incidence of 35 other system- and site-specific cancer outcomes, excluding skin and bone cancers:-
Digestive cancers (tract, esophagus, stomach, small intestine, colon, rectum, digestive organs, liver, gall bladder, pancreas, retroperitoneum)-Respiratory
cancers (larynx, trachea/bronchus/lung, pleura, lung small cell, lung squamous, lung adenocarcinoma)-Breast cancer-Female reproductive (cervix, cor-
pus uteri, ovary)-Male reproductive (prostate, urinary)-Kidney, bladder, brain, thyroid, Hodgkin's disease, leukemia; Lung/Respiratory: Incidence of
lung/respiratory cancer; Gastrointestinal: Incidence of gastrointestinal cancers; Hepatic/Liver: Incidence of liver cancer; Reproductive/Developmental:
Incidence of male (prostate, urinary) and female (cervix, corpus uteri, ovary) reproductive cancerslncidence of breast cancer; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
60556
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This ecological analysis in the San Francisco-Oakland Metropolitan Statistical Area
(SMSA) examined how standardized incidence ratios (SIRs) for cancer in 1969-1974
varied by level of chrysotile asbestos in residential water samples. Exposure was esti-
mated and cases identified for all 722 census tracts in the SMSA (1970 population > 3
million). The SMSA is characterized by distinct water supply sources, some of which
came from aquifers or reservoirs exposed to naturally occurring serpentine rock " the
official state rock of California and the parent form of chrysotile asbestos. Water supply
asbestos concentrations were estimated for 410 SMSA "super tracts" used to combine
the tracts used in 1960 and 1970 censuses. Newly diagnosed cancers were obtained from
surveys that comprehensively compiled data on cancers in the SMSA during the en-
tire period, which included census tract information. Possible ecological study biases:
Potential bias due to SES differences across super tracts was addressed by calculating
SIRs cross-classified by median income or education as well as by exposure. The au-
thors ensured that there were adequate numbers of tracts in each stratum (mostly n 50).
Confounding due to super tract group differences in potential occupational exposure was
addressed using models that adjusted for the percentage of construction, electrical and
textile workers in each tract.
Medium As this study was cross-sectional and ecological, attrition was not a concern. The au-
thors estimated the 1972 population - the midpoint of the period for which cancer inci-
dence data were used - using available census data.
High Both the expected and observed cancer rates used to derive SIRs were calculated us-
ing the estimated 1972 SMSA population, ensuring comparability. Expected cancer
incidence rates for the entire SMSA were calculated using an age, race (white vs non),
and sex-specific population estimate for January 1972, extrapolated from 1960 and
1970 censuses. Observed cases were compiled in 5-year age groups for each super tract.
These values were compared to the numbers of expected cancers based on the age, race,
and sex population of that super tract.
Domain 2: Exposure Characterization
Continued on next page .
Page 195 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 60556 Table: 1 of 1
... continued from previous page
Conforti, P. M., Kanarek, M. S., Jackson, L. A., Cooper, R. C., Murchio, J. C. (1981). Asbestos in drinking water and cancer in the San Francisco Bay
area: 1969-1974 incidence. Journal of Clinical Epidemiology 34(1981):211-224.
Lung Cancer; Ovarian Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Incidence of any cancer Incidence of 35 other system- and site-specific cancer outcomes, excluding skin and bone cancers:-
Digestive cancers (tract, esophagus, stomach, small intestine, colon, rectum, digestive organs, liver, gall bladder, pancreas, retroperitoneum)-Respiratory
cancers (larynx, trachea/bronchus/lung, pleura, lung small cell, lung squamous, lung adenocarcinoma)-Breast cancer-Female reproductive (cervix, cor-
pus uteri, ovary)-Male reproductive (prostate, urinary)-Kidney, bladder, brain, thyroid, Hodgkin's disease, leukemia; Lung/Respiratory: Incidence of
lung/respiratory cancer; Gastrointestinal: Incidence of gastrointestinal cancers; Hepatic/Liver: Incidence of liver cancer; Reproductive/Developmental:
Incidence of male (prostate, urinary) and female (cervix, corpus uteri, ovary) reproductive cancerslncidence of breast cancer; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
60556
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Exposure estimates used 353 water samples previously collected to represent the wa-
ter distribution systems along with 19 additional samples (Kanarek et al 1980, RefID
60569). The mean of samples from each distribution area was assigned to all super tracts
in that area. Exposure was assigned independently by personnel with no knowledge of
cancer incidence across census tracts. In addition to household taps, analyses were made
on raw and finished water at treatment plants and several stored historical samples to
reflect exposure over 40 years. Water districts were subdivided to the extent possible by
source, treatment process and/or pressure zones. Fibers were counted by filtering wa-
ter through 0.45 jUm filters and using TEM, with analysts blinded to the source of each
sample and several samples analyzed in duplicate. When results were below detectable
limits, the lowest detectable limit was used (usually 10A 4 fibers/liter), vs a fraction such
as half the detection limit. This approach likely inflated exposure estimates. Sources of
measurement error that could not be addressed include the lack of information on resi-
dential drinking water intake, water intake from other sources (e.g., work, school), and
use of bottled water or water filters (less common at the time than today). The authors
did not mention the prevalence of asbestos cement pipes, or the prevalence households
not connected to the public water supply. Possible ecological study biases: To evalu-
ate risk of bias due to heterogeneity in drinking water asbestos concentrations within
super tracts, the authors examined variability across random households within a se-
lected tract, within a distribution system (from treatment plant to household tap), and at
different times of day during high use. The authors described consistently finding very
little variability. Secondly, potential bias due to population mobility (i.e., changes in
residence and thus exposure) was examined in a sensitivity analysis limiting the sam-
ple to tracts in which more than 50% of the population aged >5y resided in the same
household in 1965 and 1970.
Medium The authors used 3 categories of exposure in most analyses, each including more than
100 super tracts. Multiple tracts had common water systems and identical fiber counts,
resulting in gaps in the boundary values defining these categories.
Medium The study was cross-sectional, using predominantly recent measures of drinking water
asbestos to characterize exposure. Given the long latency of many cancers, the authors
report that they incorporated a few historical water samples to estimate past exposure,
but no details were provided (number, timing, distribution, concentrations).
Domain 3: Outcome Assessment
Continued on next page .
Page 196 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 60556 Table: 1 of 1
... continued from previous page
Conforti, P. M., Kanarek, M. S., Jackson, L. A., Cooper, R. C., Murchio, J. C. (1981). Asbestos in drinking water and cancer in the San Francisco Bay
area: 1969-1974 incidence. Journal of Clinical Epidemiology 34(1981):211-224.
Lung Cancer; Ovarian Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Incidence of any cancer Incidence of 35 other system- and site-specific cancer outcomes, excluding skin and bone cancers:-
Digestive cancers (tract, esophagus, stomach, small intestine, colon, rectum, digestive organs, liver, gall bladder, pancreas, retroperitoneum)-Respiratory
cancers (larynx, trachea/bronchus/lung, pleura, lung small cell, lung squamous, lung adenocarcinoma)-Breast cancer-Female reproductive (cervix, cor-
pus uteri, ovary)-Male reproductive (prostate, urinary)-Kidney, bladder, brain, thyroid, Hodgkin's disease, leukemia; Lung/Respiratory: Incidence of
lung/respiratory cancer; Gastrointestinal: Incidence of gastrointestinal cancers; Hepatic/Liver: Incidence of liver cancer; Reproductive/Developmental:
Incidence of male (prostate, urinary) and female (cervix, corpus uteri, ovary) reproductive cancerslncidence of breast cancer; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
60556
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
High Lung Cancer: The outcome database included 51,314 incidence cases obtained from a
registry compiled by the San Francisco Bay Area Resource for Cancer Epidemiology
(RCE). The registry included all newly diagnosed cancers collected for the Third Na-
tional Cancer Survey (TNCS) 1969-1971 and subsequently for an RCE survey for 1972-
1974 that collected comparable data. Over 90% of the cancers were microscopically
confirmed. Codes for each cases included age, sex, race, body site, hospital, diagnosis
method and date, and census tract. ICD 8 codes were used to classify cancers. However,
the authors did not provide case counts. The number of cases available is relevant to
evaluate the robustness of findings for very rare outcomes such as pleural cancer. Lung
cancer: histological subtypes were assessed (lung small cell, squamous, and adenocar-
cinoma not otherwise specified).; Ovarian Cancer: See comments for all cancers shown
for lung cancer.; Other Cancer(s): See comments for all cancers shown for lung cancer.
Low The authors reported only statistically significant findings for most analyses. Conse-
quently, SES-stratified SIRs, regression/correlation coefficients, and p-values are se-
lectively available. In addition, most results were presented only for white men and
women, but the authors stated that results for the total population were almost identical
as the population was predominantly white.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Medium Selected SIRs were cross-classified by asbestos exposure categories and median in-
come or education. However, distributions of these variables across super tracts were not
shown, nor was the extent to which they related to exposure described. Along with un-
adjusted correlations, multivariate regression models were used to examine how asbestos
in water was associated with SIRs. These models adjusted for super tract medians for
family income, education, percentage married, and proportion employed in industries
with potential asbestos exposure. However, the authors were unable to adjust for the
distribution of other known cancer risk factors (e.g., smoking, alcohol, physical activity,
diet quality) which may vary by census tract.
Continued on next page ...
Page 197 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 60556 Table: 1 of 1
... continued from previous page
Conforti, P. M., Kanarek, M. S., Jackson, L. A., Cooper, R. C., Murchio, J. C. (1981). Asbestos in drinking water and cancer in the San Francisco Bay
area: 1969-1974 incidence. Journal of Clinical Epidemiology 34(1981):211-224.
Lung Cancer; Ovarian Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Incidence of any cancer Incidence of 35 other system- and site-specific cancer outcomes, excluding skin and bone cancers:-
Digestive cancers (tract, esophagus, stomach, small intestine, colon, rectum, digestive organs, liver, gall bladder, pancreas, retroperitoneum)-Respiratory
cancers (larynx, trachea/bronchus/lung, pleura, lung small cell, lung squamous, lung adenocarcinoma)-Breast cancer-Female reproductive (cervix, cor-
pus uteri, ovary)-Male reproductive (prostate, urinary)-Kidney, bladder, brain, thyroid, Hodgkin's disease, leukemia; Lung/Respiratory: Incidence of
lung/respiratory cancer; Gastrointestinal: Incidence of gastrointestinal cancers; Hepatic/Liver: Incidence of liver cancer; Reproductive/Developmental:
Incidence of male (prostate, urinary) and female (cervix, corpus uteri, ovary) reproductive cancerslncidence of breast cancer; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
60556
Domain
Metric
Rating
Comments
Metric 10:
Covariate Characterization
Medium
It is uncertain to what extent adjusting for a variable defined using the estimated per-
centage of construction, electrical and textile workers in each super tract addressed any
confounding by occupational exposure to asbestos. It is also uncertain to what extent
any confounding by individual level SES is addressed using area level SES measures.
SES may affect mobility and thus duration of exposure to water measured at current
residence; the authors attempted to address this using a sensitivity analysis that limited
the sample to persons remaining in the same census tract for 5y. However, 5 years is
relatively short.
Metric 11:
Co-exposure Counfounding
Low
Co-exposures to other pollutants, for example disinfectant by-products or other sub-
stances in the water supply (potential correlates of water quality), was not addressed.
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
The primary analyses, which compared how SIRs varied across super tract groups with
differing levels of drinking water asbestos, were appropriate to evaluate the study aims.
Metric 13:
Statistical Power
Medium
The population included more than 3,000,000 individuals, and the study accrued more
than 50,000 cases. However, no case numbers or confidence intervals were provided,
making power for analyses involving rare cancers uncertain. Most super tracts would
likely have had zero observed and expected cases for such outcomes.
Metric 14:
Reproducibility of Analyses
Medium
Analyses are for the most part described adequately, but key details were at times lack-
ing. For example, the authors present correlation coefficients between "asbestos val-
ues and cancer rates by site and sex for the white population". It is uncertain whether
outcome variables are in fact incidence rates (vs standardized incidence ratios), and
whether/how the rates used were adjusted. Additionally, the authors did not clearly spec-
ify whether the drinking water asbestos variable was categorized or used continuously
(despite its highly non-normal distribution) in either correlations or regression models.
Moreover, along with no case counts, the authors showed very few SIRs, which would
make it difficult to ascertain the extent to which results were replicated.
Continued on next
page...
Page 198 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 60556 Table: 1 of 1
... continued from previous page
Conforti, P. M., Kanarek, M. S., Jackson, L. A., Cooper, R. C., Murchio, J. C. (1981). Asbestos in drinking water and cancer in the San Francisco Bay
area: 1969-1974 incidence. Journal of Clinical Epidemiology 34(1981):211-224.
Lung Cancer; Ovarian Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Incidence of any cancer Incidence of 35 other system- and site-specific cancer outcomes, excluding skin and bone cancers:-
Digestive cancers (tract, esophagus, stomach, small intestine, colon, rectum, digestive organs, liver, gall bladder, pancreas, retroperitoneum)-Respiratory
cancers (larynx, trachea/bronchus/lung, pleura, lung small cell, lung squamous, lung adenocarcinoma)-Breast cancer-Female reproductive (cervix, cor-
pus uteri, ovary)-Male reproductive (prostate, urinary)-Kidney, bladder, brain, thyroid, Hodgkin's disease, leukemia; Lung/Respiratory: Incidence of
lung/respiratory cancer; Gastrointestinal: Incidence of gastrointestinal cancers; Hepatic/Liver: Incidence of liver cancer; Reproductive/Developmental:
Incidence of male (prostate, urinary) and female (cervix, corpus uteri, ovary) reproductive cancerslncidence of breast cancer; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
60556
Domain Metric Rating Comments
Metric 15: Statistical Analysis Low The authors described appropriate methods to calculate SIRs, accounting for age, race,
and sex distributions. However, in addition to no case counts, the authors did not provide
confidence intervals for the few SIR values shown. Particularly for very rare cancers,
understanding the level of precision for these estimates is important. Another impor-
tant concern is the use of Pearson"s product moment correlations vs. a non-parametric
method to characterize relationships with the non-normally distributed water asbestos
variable (whether used continuously without transformation or categorized " which
is unclear). Finally, the authors did not adequately describe the log-linear regression
models they used to evaluate associations after accounting for confounding. Log-linear
models are typically used for count/ordinal outcomes, and SIRs were continuous; par-
ticularly without specifying the link function it is unclear that regression models were
used appropriately.The measurement exposure (M4) and/or exposure levels (M5) met-
rics are rated as medium upon review by both set of reviewers. Also, the overall quality
determination (OQD) is rated medium. Extraction will be completed and quality control
reviewed.
Additional Comments: This ecologic study evaluated how standardized incidence ratios for cancers diagnosed in 1969-1974 varied across metropolitan San Francisco communi-
ties with differing levels of chrysotile asbestos " an issue due to natural occurrence - in residential drinking water. To address the limitations of ecological
study designs, the authors incorporated adjustments and sensitivity analyses to address potential biases such as confounding due to area-level SES differ-
ences. A comprehensive cancer incidence registry that included census tract information was used, along with more than 350 water samples to characterize
concentrations of asbestos in the drinking water of 410 census "super tracts". A minor concern is that exposure may have been overestimated by using
the detection limit, rather than half of the detection limit, to impute values below quantification. The authors found that areas with higher drinking water
asbestos consistently had higher standardized incidence ratios (SIRs) for digestive cancers in both men and women, but findings for some cancers were
inconsistent. For example, Pearson" s correlations with respiratory cancers (trachea, bronchus, lung) were significant only in men, while regression coeffi-
cients with these same cancers were significant only in women. Exposure was positively associated with pleural cancer in women using regression models
but not correlations; negative associations between exposure and female reproductive cancers were significant only using correlations. Methodological
issues such as using unadjusted Pearson correlations despite highly non-normal exposure data contributed to these inconsistencies. Neither case counts nor
confidence intervals were provided for rare outcomes such as pleural cancers, making it difficult to fully interpret those results.The measurement exposure
(M4) and/or exposure levels (M5) metrics are rated as medium upon review by both set of reviewers. Also, the overall quality determination (OQD) is
rated medium. Extraction has been completed and quality control reviewed.
Continued on next page ...
Page 199 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 60556 Table: 1 of 1
... continued from previous page
Conforti, P. M., Kanarek, M. S., Jackson, L. A., Cooper, R. C., Murchio, J. C. (1981). Asbestos in drinking water and cancer in the San Francisco Bay
area: 1969-1974 incidence. Journal of Clinical Epidemiology 34(1981):211-224.
Lung Cancer; Ovarian Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Incidence of any cancer Incidence of 35 other system- and site-specific cancer outcomes, excluding skin and bone cancers:-
Digestive cancers (tract, esophagus, stomach, small intestine, colon, rectum, digestive organs, liver, gall bladder, pancreas, retroperitoneum)-Respiratory
cancers (larynx, trachea/bronchus/lung, pleura, lung small cell, lung squamous, lung adenocarcinoma)-Breast cancer-Female reproductive (cervix, cor-
pus uteri, ovary)-Male reproductive (prostate, urinary)-Kidney, bladder, brain, thyroid, Hodgkin's disease, leukemia; Lung/Respiratory: Incidence of
lung/respiratory cancer; Gastrointestinal: Incidence of gastrointestinal cancers; Hepatic/Liver: Incidence of liver cancer; Reproductive/Developmental:
Incidence of male (prostate, urinary) and female (cervix, corpus uteri, ovary) reproductive cancerslncidence of breast cancer; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
60556
Domain Metric
Rating
Comments
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 200 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083452 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cookson, W. O., Musk, A. W., Glancy, J. J., de Klerk, N. H., Yin, R., Mele, R., Carr, N. G., Armstrong, B. K., Hobbs, M. S. (1985). Compensation,
radiographic changes, and survival in applicants for asbestosis compensation. British Journal of Industrial Medicine 42(1985):461-468.
mortality, radiographic profusions, pneumoconiosis
Mortality: All causes mortality, Pneumoconiosis mortality, Bronchitis and emphysema mortality, Tuberculosis mortality, Other respiratory disease, Gas-
trointestinal cancer mortality, Other cancers mortality, Heart disease mortality, Other circulatory disease mortality, Respiratory neoplasms mortality; Lung/
Respiratory: Profusion of radiographic opacities, Pneumoconiosis mortality, Bronchitis and emphysema mortality, Tuberculosis mortality, Other respi-
ratory disease mortality, Respiratory neoplasms mortality; Cancer/Carcinogenesis: Gastrointestinal cancer mortality, Other cancer mortality, Respiratory
neoplasms mortality; Gastrointestinal: Gastrointestinal cancer mortality; Cardiovascular: Heart disease mortality, Other circulatory disease mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3083452
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated low because neither the study nor any cited methods sources explic-
itly mention the use of PCM or TEM to quantify asbestos fibers.
Medium The distribution of exposure appears to be sufficient to develop an exposure-response
estimate for profusion of radiographic opacities since it is assessed continuously. How-
ever, all other outcomes are assessed as "exposed" vs. "unexposed" and thus have a
limited range of exposure.
Additional Comments: This study was not fully evaluated because metric 4 was rated as low, due to no explicit mention in the study or cited sources about the use of PCM or
TEM.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 201 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6867273 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cuccaro, F., Nannavecchia, A. M., Silvestri, S., Angelini, A., Coviello, V., Bisceglia, L., Magnani, C. (2019). Mortality for mesothelioma and lung
cancer in a cohort of asbestos cement workers in BARI (Italy): Time related aspects of exposure. Journal of Occupational and Environmental Medicine
61(2019):410-416.
Lung Cancer; "Even if the specific type of pneumoconiosis caused by exposure to asbestos is the, we decided to consider mortality for pneumoconiosis."
Cancer/Carcinogenesis: Lung cancer mortality; Lung/Respiratory: Lung cancer mortality, Mortality from pneumoconiosis; Mortality: Cardiovascular
disease, Pneumoconiosis, Lung cancer; Cardiovascular: Mortality from cardiovascular disease
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
6867273
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Between 1970 and 1974 several industrial hygiene investigations were carried out with
measurement of the concentration of the airborne fibers (Coviello, et al., 2002, HERO
ID 3080488). This metric is rated Low because authors in this paper do not explicitly
cite use of PCM or TEM, and the cited methods paper (Coviello et al. 2002, 3080488)
is not freely available or through HERO. PubMed also indicated that the article is in
Italian.
Medium The authors of this cohort study used an exposure index to evaluate individual cumu-
lative exposure as proxy of asbestos dose, and reported 3 or more levels of exposure (3
tertiles).
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.Metric 4 is rated Low because authors in this paper do not explicitly cite use of PCM or TEM, and the cited methods paper (Coviello et al. 2002,
3080488) is not freely available. For Metric 5, this cohort study used an exposure index to evaluate individual cumulative exposure as proxy of asbestos
dose and reported 3 or more levels of exposure (3 tertiles). Mesothelioma and other outcomes forms filled for Metrics 4 and 5 and evaluation stopped.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 202 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2078970 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cullen, M. R., Lopez-Carrillo, L., Alii, B., Pace, P. E., Shalat, S. L., Baloyi, R. S. (1991). Chrysotile asbestos and health in Zimbabwe: II. Health status
survey of active miners and millers. American Journal of Industrial Medicine 19(1991 ):171-182.
Pulmonary Function/Spirometry Results; pleural disease
Lung/Respiratory: FEV1, FVC, Pleural disease
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2078970
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Medium
Low
Concentration measurements were made in 1980 and were used to estimate exposures
during that time. Exposure estimates prior to 1980 were calculated based on profes-
sional judgement.
The authors reported two levels of exposure for FVCD (referent + 1 with 8 fibers/
cc*years or more). For the X-ray abnormalities, the study presented the relationship
between cumulative dose and radiographic category (0/1, 0/1, 1/0, 1/1) unadjusted for
age in Chrysotile miners and millers.
Additional Comments: None
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 203 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082920 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Cvetanov, V., Karadzinska-Bislimovska, J., Vasevski, J., Ezova, N., Stikova, E. (1988). The relationship between asbestos bodies, serum immunoglobulin
levels and X-ray changes in asbestos workers . Arhiv za Higijenu Rada i Toksikologiju 39(1988):455-460.
Serum immunoglobulin levels
Immune/Hematological: Serum immunoglobulin levels
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3082920
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
Exposure was directly measured and assessed using sputum samples taken from the
workers. The asbestos bodies were counted using native microscopic slides. Additional
information was not provided on the measurement of exposure.
The range of exposure in the population is limited because the study reports the expo-
sure using three categories: 1 to 5 asbestos bodies, 6 to 10 asbestos bodies, and over 10
asbestos bodies. One worker was cited to have over 20 asbestos bodies making it clear
that the categories cannot adequately display the range and distribution.
Additional Comments: None
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 204 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2248426 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Dahlqvist, M., Alexandersson, R., Hedenstierna, G. (1992). Lung function and exposure to asbestos among vehicle mechanics. American Journal of
Industrial Medicine 22(1992):59-68.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Forced vital capacity (FVC), Forced volume in 1 second (FEV1), FEV1 in percent of the largest vital capacity, Expiratory flow at 75%
of FVC (MEF25), Residual volume (RV), Total lung capacity (TLC), Nitrogen breath wash-out, Carbon monoxide single breath wash-out, Closing volume
(CV), Vital capacity (VC), Closing volume in percent of VC (CV% )
Asbestos- Exposure reported as PCM or TEM (including conversion factors for dust)
ID(s): No linked references.
2248426
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection Low This Swedish cross-sectional study included currently employed 99 auto mechanics ex-
posed to low levels of asbestos and 89 unexposed local controls. Only 101 of 259 (39%
) exposed subjects (from the "Motor Health organization" register, selection process not
described) were "approved to participate". Inclusion criteria were age >40y, and >15y
occupational asbestos exposure starting at least 20y prior. Selectivity is a concern given
the absence of details on why they were excluded (primarily unspecified "lung irritant"
exposure), and how excluded candidates differed from those excluded. Importantly,
excluding individuals with exposures common in mechanic workshops (ex. welding,
paint, or varnish fumes) could yield a sample unrepresentative of the target population1^
exposure-outcome distribution. Indeed, the authors noted in the discussion that healthy
worker selectivity was a concern since "subjects who left their jobs as a consequence of
lung disease were not included in the study".
Metric 2: Attrition Medium There was a moderate loss of subjects. Two of the 101 exposed and 6 of the 89 un-
exposed individuals were excluded from the initial study sample (unspecified health
disorders).
Metric 3: Comparison Group Medium The unexposed comparison group comprised of bus drivers and white-collar workers
drawn from Motor Health and Stockholm traffic registers (no further details, Ns for
each job not provided). Only 89 of 315 candidates (28% ) were approved to partici-
pate (reasons not specified beyond stating many had past occupational exposure to lung
irritants); the lack of details and comparisons with those included raises selectivity con-
cerns. Comparability of this group with the exposed mechanics may also be suboptimal
because: (i) current employment status is uncertain as participants were selected based
on their "last job description"; (ii) age and duration of employment restrictions used for
the exposed were not applied here. Other differences vs the exposed group which were
not addressed include higher body weight despite similar height (BMI not calculated),
and possible SES disparities.
Domain 2: Exposure Characterization
Continued on next page ...
Page 205 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2248426 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dahlqvist, M., Alexandersson, R., Hedenstierna, G. (1992). Lung function and exposure to asbestos among vehicle mechanics. American Journal of
Industrial Medicine 22(1992):59-68.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Forced vital capacity (FVC), Forced volume in 1 second (FEV1), FEV1 in percent of the largest vital capacity, Expiratory flow at 75%
of FVC (MEF25), Residual volume (RV), Total lung capacity (TLC), Nitrogen breath wash-out, Carbon monoxide single breath wash-out, Closing volume
(CV), Vital capacity (VC), Closing volume in percent of VC (CV% )
Asbestos- Exposure reported as PCM or TEM (including conversion factors for dust)
No linked references.
2248426
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Exposure was estimated for 95 of the 99 exposed mechanics, who had worked in 386
places, using: fiber exposure measurement and analysis, reviews of earlier reports, ques-
tionnaires, and interviews. For fiber measures, no details were provided on: collection
equipment; placement, duration or timing of sampling; data availability for past work-
places; or assumptions used in estimation (any published details in Swedish). Fiber
counts were described as using phase contrast light microscope (PCM). Measurement
error is a concern given the authors" report that asbestos dust from brakes - a major
source of exposure - comprise very short fibers (<0.4 jUm) not visible under these mi-
croscopes. They stated that concentrations were higher when analyzed using a STEM
(scanning transmission electron microscope) microscope but did not state whether or
how these STEM measures were used.
Medium The range of exposure was low by design: work environments below the Swedish con-
centration limit of 0.2 fibers/ml. The median fiber concentration over the years evaluated
was 0.08 (IQE 0.06-0.11) fibers/ml, and the median cumulative fiber dose 2.3 (IQR 1.5-
3.6) fiber-years/ml (8-hour time weighted average). Exposure variables were analyzed
continuously.
Medium Estimates accounting for past exposure were constructed (details not provided). Eligi-
bility criteria for the exposed included a history of 15 years working in similar envi-
ronments. Temporality is not a concern. However, as this study is cross-sectional, fiber
measures obtained by the investigators to help derive exposure estimates would have
been contemporaneous.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or High Pulmonary Function/Spirometry Results: Dynamic and static spirometry, along with a
Characterization carbon monoxide single breath wash-out and a nitrogen breath washout, were used to
assess lung function. Measures derived included FVC, FEV1, FEV% , MEF25, closing
volume percent (CV% ) from the nitrogen washout, and transfer factor (TL-co) from the
carbon monoxide washout. The authors cited references for the measures they derived
and reported weekly calibration of equipment. Smokers were asked to refrain from
smoking for 4 hours prior to testing. The authors did not, however, mention blinding
testers to exposure group status.
Continued on next page ...
Page 206 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2248426 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dahlqvist, M., Alexandersson, R., Hedenstierna, G. (1992). Lung function and exposure to asbestos among vehicle mechanics. American Journal of
Industrial Medicine 22(1992):59-68.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Forced vital capacity (FVC), Forced volume in 1 second (FEV1), FEV1 in percent of the largest vital capacity, Expiratory flow at 75%
of FVC (MEF25), Residual volume (RV), Total lung capacity (TLC), Nitrogen breath wash-out, Carbon monoxide single breath wash-out, Closing volume
(CV), Vital capacity (VC), Closing volume in percent of VC (CV% )
Asbestos- Exposure reported as PCM or TEM (including conversion factors for dust)
No linked references.
2248426
Domain
Metric
Rating
Comments
Metric 8: Reporting Bias
Medium Results (coefficients and SEs) from models analyzing how exposure status and other
predictors related to all lung function measure were presented (Table III), though co-
efficients were not shown when non-significant. However, partial correlations relating
increasing exposure to each lung function measure were presented only for the subgroup
of mechanics also exposed to diesel exhaust (Table IV). The association between lung
function and increasing exposure among all mechanics was shown only for CV% (Fig
1); the lack of a dose-response relationship with TLco was mentioned in the discussion,
p-values, but not confidence intervals, were provided.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Models adjusted for age, height, never/ever smoking and pack-years for current smok-
ers (not race or sex as participants were white males). Models did not adjust for body
weight or BMI, or for socioeconomic factors.
Medium Questionnaires and detailed interviews were used to obtain information from partici-
pants, including potential co-exposures. Details on the structure and content of inter-
views and interviewer qualifications were not provided. Biomarkers were not used.
Medium Diesel exhaust was included as a covariate in partial correlations associating asbestos
exposure to lung function measures in a subgroup of workers. Exposure to "lung irri-
tant" co-exposures was an exclusion criterion.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Medium The authors appropriately used multivariable linear regression and partial correlations to
analyze associations between asbestos exposure variables and lung function outcomes.
Minimally or unadjusted associations were not shown. The paper reported using "ap-
propriate transformations" if variables diverged from normality. In-transformed asbestos
exposure and diesel exhaust were noted in the results text. Testing of interactions be-
tween asbestos and smoking is mentioned in the discussion.
Medium The modest sample size (n=182), given the low range of exposure under study, might
have undermined sensitivity. The analysis incorporating diesel exhaust, which was lim-
ited to auto mechanics with this exposure, was especially small (n=50). However, the
use of continuous lung function outcome measures increased power.
Medium Though few details were provided in the description of analyses, information presented
in the tables facilitates reproducing results (variable coding is given, Ns and R-squared
values are provided). However, the main results table presents coefficients only for
variables with p<0.05 but does not state whether non-significant variables were included
in the models.
Continued on next page ...
Page 207 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2248426 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dahlqvist, M., Alexandersson, R., Hedenstierna, G. (1992). Lung function and exposure to asbestos among vehicle mechanics. American Journal of
Industrial Medicine 22(1992):59-68.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Forced vital capacity (FVC), Forced volume in 1 second (FEV1), FEV1 in percent of the largest vital capacity, Expiratory flow at 75%
of FVC (MEF25), Residual volume (RV), Total lung capacity (TLC), Nitrogen breath wash-out, Carbon monoxide single breath wash-out, Closing volume
(CV), Vital capacity (VC), Closing volume in percent of VC (CV% )
Asbestos- Exposure reported as PCM or TEM (including conversion factors for dust)
No linked references.
2248426
Domain Metric Rating Comments
Metric 15: Statistical Analysis Low The authors report appropriate models, correlations, and variable transformations. How-
ever, the analyses did not incorporate any methods aiming to reduce potential risk of
"healthy worker effect" bias, which can be induced by "the selection of unhealthy people
out of the workforce" (PMID: 17053019). The exposed population was restricted to per-
sons sufficiently healthy to remain actively employed as mechanics after >15y, without
comparable criteria for the unexposed group. Criteria such as the use of prevalent (but
not past or incident) employees is a well-known risk for healthy worker effect. Strategies
such as adjusting for employment status and duration could have helped to reduce risk of
bias by comparing lung function among subgroups with comparably shorter- or longer-
term employment durations - this was not done. Of note, "epidemiological studies of...
non-fatal outcomes" are especially prone to bias through aspects of the healthy worker
effect. The tendencies for sick workers to leave employment or transfer to less-exposed
jobs are two very commonly observed phenomena in occupational morbidity studies"
(PMID: 17053019).
Additional Comments: This study analyzed lung function among 99 auto mechanics exposed to low levels of asbestos (cumulative exposure 2.3 fiber-years/mL) vs. 89 unexposed
white-collar workers and bus drivers with normal lung function. Though asbestos exposure was not associated with several outcomes including FEV1,
exposure was associated with lower transfer factor (TLco from a CO washout) and with airway closure (CV% from a N washout), measures described
as perhaps more sensitive to early lung function decline. There are, however, several concerns. First, 61% of exposed and 72% of unexposed candidate
participants were excluded with few explanatory details. Exclusion of individuals with exposures very common in mechanic workshops (ex. welding or
paint fumes) could yield an unrepresentative sample with limited generalizability. Second, limiting the exposed sample to mechanics actively employed
for >15y, without comparable requirements that unexposed had similarly lengthy active employment, may have induced a healthy worker bias. Analyses
did not adjust for potential confounding by employment status or duration, BMI, or SES. Finally, exposure may have been estimated with error as the thin
fibers found in asbestos dust from automobile brakes are not captured by PCM. These issues may have affected validity of findings, potentially attenuating
any association between exposure and lung function.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 208 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 718578 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dawson, A., Gibbs, A. R., Pooley, F. D., Griffiths, D. M., Hoy, J. (1993). Malignant mesothelioma in women. Thorax 48(1993):269-274.
fibrosis in mesothelioma cases and controls
Lung/Respiratory: Fibrosis
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5
No linked relerences.
718578
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3: Comparison Group
Medium Key elements of study design were reported. Participation is not likely biased and
exposure-outcome distribution of participants is likely representative of those eligi-
ble for inclusion. However, the total number of patients, from which cases with post-
mortem evaluations were chosen, with malignant mesothelioma but with no postmortem
analyses records was not provided. Authors did acknowledged the potential non-
representativeness of this population due to the patient-referred nature of cases which
included wartime dockyard and gas mask workers known to have suffered from heavy
asbestos exposure. All available pathological, occupational and lung fiber mineralogical
data on n=177 female malignant mesothelioma cases from unspecified file records and
unspecified geographic residential origin 1963-1990 were reviewed and compared with
n=31 female controls from Exeter, Liverpool, Befast, Dublin, and Cardiff with post-
mortem examinations and no known history of exposure to dusts and no mesothelioma
or lung cancer. Source of data for controls not detailed but assumed to have been from
the same files as cases.
Medium Missing information was noted for several subsets of outcome and exposure, and authors
acknowledged the lack of completeness of exposure data, however it was unclear if
this was related to exposure and/or outcome. The total number of participants with
tumor tissue slides available (n=151) was a subset of the total number of mesothelioma
cases (n=177). Tumor tissue slides were available for n=151 of a total of n=177 cases.
Two cases of the total cases tested (n=103 of the n=151 with histologic slides available)
were positive for carcinoembryonic antigen and were excluded from further analyses.
Lung tissue fiber burden was examined by transmission electron microscopy for n=105
tumors of known sites (Table 2). Exposure classification according to Zielhuis et al.,
1978 (HERO ID 6910362) data was available for n= 93 cases.
Low Inclusion criteria and methods of participant selection for cases and controls was re-
ported. Geographic residential origin of controls, but not cases (other than one case
from Antolia) was reported. Other than restriction of cases and controls to women and
reporting the mean (range) age of n=102 malignant mesothelioma cases (60.5 years (18-
89)) and n=31 controls (68.0 years (30-93)) for which age data was available, details
regarding other potentially relevant demographic and occupational covariate differences
between cases and controls were not considered. Statistical analyses of potential demo-
graphic or other relevant covariate differences between cases and controls was lacking,
and multivariate statistical control for differences, particularly age, between groups was
not detailed. It is unclear to what extent, if any, the healthy worker effect was involved
within results including those cases classified within Table 4 as having direct occupa-
tional exposure in comparison with the population controls.
Continued on next page ...
Page 209 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 718578 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
ID(s):
Dawson, A., Gibbs, A. R., Pooley, F. D., Griffiths, D. M., Hoy, J. (1993). Malignant mesothelioma in women. Thorax 48(1993):269-274.
fibrosis in mesothelioma cases and controls
Lung/Respiratory: Fibrosis
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5
No linked relerences.
718578
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement ol Exposure
Medium
Metric 5: Exposure Levels
Metric 6: Temporality
Medium
Low
Methods used to quantify exposure were well defined, with sources of methods reported.
Lung tissue fiber (106 fibers/g), fiber length and diameter analyses were assessed by
Transmission Electron Microscopy (TEM) with energy dispersive x ray analysis us-
ing an "EDAX" machine according to the methods within Pooley et al., 1979 (HERO
ID: 3084350). Asbestos exposure classification methods for cases only were conducted
as in Zielhuis et al., HERO ID 6910362. Exposure to asbestos was classified for n=93
(of total n=177 cases) malignant mesothelioma cases according to Zielhuisl8 into cat-
egories of (la) direct occupational exposure; (lb) indirect occupational exposure-for
example, workers in the vicinity of asbestos contaminated work situations; (2) paraoccu-
pational exposure-for example, the wives of men working with asbestos; (3) neighbor-
hood exposure-for example, people living in the vicinity of asbestos mines or processing
factories; (4) exposure in ambient air; and (5) no known exposure. Only n=74 (80% of
the total n=93 cases with Zielhuis classified exposure history data of the total n=177 ma-
lignant mesothelioma cases) cases had a history of known exposure to asbestos. Zielhuis
classification of potential historical exposure for controls was not detailed.
The range and distribution of exposure is sufficient to develop and exposure-response
estimate. Table 3 reports lung fiber burden (x 10A 6 fibers/g lung) across five fibrosis
grade categories for n=l 16 mesothelioma cases.
The temporality of exposure and outcome is uncertain. This study reported cross-
sectional analyses of the relationship between postmortem fibrosis and lung fiber bur-
dens in mesothelioma cases and controls for which temporality cannot be established.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Medium Other Non-Cancer Outcomes: Fibrosis was assessed and graded for n=152 mesothe-
lioma cases and n=31 controls according to Hinson et al., 1973 (HERO ID 3101627).
Medium There were no concerns for selective reporting. No formal statistical analyses between
cases and controls was conducted, and no effect estimates were reported however lung
fiber concentration burdens as geometric means (range) were reported across categories
of fibrosis grade in Table 3.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10:
Covariate Characterization
Low
Low
Analyses were restricted to female cases and controls. Additional statistical control for
potentially relevant demographic or other variables was not conducted.
Source of covariate data (age only) was not directly stated, nor validated, but assumed to
have been obtained from the files from which patient data were obtained.
Continued on next page ...
Page 210 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 718578 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dawson, A., Gibbs, A. R., Pooley, F. D., Griffiths, D. M., Hoy, J. (1993). Malignant mesothelioma in women. Thorax 48(1993):269-274.
fibrosis in mesothelioma cases and controls
Lung/Respiratory: Fibrosis
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5
No linked relerences.
718578
Domain Metric Rating Comments
Metric 11: Co-exposure Counlounding Low The patient population under study included mesothelioma case workers in Table 4 to
have had direct and indirect occupational exposure, however potential confounding due
to co-exposures was not reported as considered.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Medium
Medium
N/A
The study method chosen was appropriate for the cross-sectional data available.
The number of cases and controls are generally adequate to detect an effect in the over-
all population, however it is unclear if the number of cases in fibrosis grade subgroups
would be adequate. Authors acknowledged the inadequacy of the sample size for analy-
ses of fiber types on outcomes of interest.
The description of analysis is sufficient to understand how to conceptually reproduce the
data within the presented tables, although raw data was not reported.
This study did not utilize multivariate statistical modeling methods.
Additional Comments: This study reported cross-sectional results of postmortem fibrosis and lung fiber burdens from an initial total population of n=177 female malignant
mesothelioma cases 1963-1990 (geographic origin not detailed) and n=31 female controls from Exeter, Liverpool, Belfast, Dublin, and Cardiff with no
initially known exposure history to dusts and no mesothelioma or lung cancer. Mesothelioma cases (n=102 of total n=177) with age data were described as
being of mean (range) age 60.5 years (18-89 years) with n=31 controls aged 68 years (30-93 years).
Overall Quality Determination Low
* No biomarkers were identified for this evaluation.
Page 211 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 783917 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
de Klerk, N. H., Armstrong, B. K., Musk, A. W., Hobbs, M. S. T. (1989). Cancer mortality in relation to measures of occupational exposure to crocidolite
at Wittenoom Gorge in Western Australia. British lournal of Industrial Medicine 46(1989):529-536.
Lung Cancer; Laryngeal Cancer; stomach cancer
Lung/Respiratory: Mortality from cancer of the trachea, bronchus, and lung, Lung cancer incidence; Cancer/Carcinogenesis: Lung cancer incidence,
Upper aerodigestive cancer (lip, tongue, pharynx, larynx), Mortality from cancer of the stomach, Mortality from cancer of the trachea, bronchus, and lung;
Gastrointestinal: Lower aerodigestive cancer (oesophagus, stomach, colon/rectum), Upper aerodigestive cancer (lip, tongue, pharynx, larynx) - incidence,
Mortality from cancer of the stomach; Mortality: Upper aerodigestive cancer (lip, tongue, pharynx, larynx) - mortality, Mortality from cancer of the trachea,
bronchus, and lung, Mortality from cancer of the stomach
Asbestos - Crocidolite (riebeckite): 12001-28-4
783917, 3079799, 3080174
783917
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated low because Klerk et al. 1989 783917, Reid et al. 2006 3079799,
and Reid et al. 2004 3080174 relied on historic dust measures (konimeters, thermal
precipitators) without documenting the use of appropriate conversions. These papers
cited the single time point membrane filter PCM fiber concentration measures that were
taken in 1966, shortly before the facility closed (publication not available in HERO or
other online sources, Major 1968 entitled the First Australian Pneumoconiosis Confer-
ence). However, they did not mention or cite a dust-to-fiber conversion factor, and no
such factors were identified in the literature. Concerns regarding the validity and utility
of occupational exposure measures used in Wittenoom studies have been expressed by
the industrial hygienist responsible for the membrane filter measures (e.g., Rogers and
Major 2002 HEROID 3080506).
Medium The distribution of exposure provided in de Klerk et al 783917 appears to be sufficient
to develop an exposure-response estimate. Cumulative exposure was used in analyses
either as a continuous variable or in 4 categories. As noted above, however, there are
important concerns remain regarding the validity of exposure estimates.
Additional Comments:
Klerk et al. 1989 783917, Reid et al. 2006 3079799, and Reid et al. 2004 3080174 were not evaluated for any metrics except Metric 4 and 5 and had no
data extracted because they did not have sufficient exposure information to be useful for dose-response analysis.
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 212 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082741 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
de Klerk, N. H., Cookson, W. O., Musk, A. W., Armstrong, B. K., Glancy, J. J. (1989). Natural history of pleural thickening after exposure to crocidolite.
British Journal of Industrial Medicine 46(1989):461-467.
Pleural Plaques
Lung/Respiratory: Diffuse pleural thickening
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3082741
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low The method of quantifying/counting fibers was not specified by the authors. They only
indicated that measurements had been taken "in a survey of the industry undertaken
on behalf of the Mines Department of Western Australia in 1966." The cited source
is not freely available at this time (Major, 1968, Proceedings of the first Australian
Pneumoconiosis Conference).
Medium The authors reported four levels of exposure: expressed as "intensity of exposure" in
fibers/cc (Table 4). They also reported 5 levels of "cumulative exposure" (Table 5)
Additional Comments: None
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 213 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082378 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
de Klerk, N. H., Musk, A. W., Armstrong, B. K., Hobbs, M. S. (1991). Smoking, exposure to crocidolite, and the incidence of lung cancer and asbestosis.
British Journal of Industrial Medicine 48(1991):412-417.
Lung Cancer; Asbestosis
Lung/Respiratory: Asbestosis, Lung cancer; Cancer/Carcinogenesis: Lung cancer
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3082378
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The authors did not use PCM or TEM to quantify fibers. "A survey of airborne res-
pirable fibres of crocidolite greater than 5um in length was carried out at various work
sites at Wittenoom in 1966. These measurements were used to obtain estimates of fi-
bre concentrations for all 87 job categories in the various worksites." This survey was
supplemented by subjective ranking of the degree of dustiness "provided by an ex-
superintendent of operations at Wittenoom, and verified by the industrial hygienist who
conducted the 1966 survey."
Low Mean cumulative exposure (f/ml-years) was 71 for cases, and 23 for controls for as-
bestosis (Table 4), reporting only 2 levels of exposure. Subjects could be controls for
more than one case and some cases could be control for other earlier cases (e.g., controls
may have been exposed and/or at risk for asbestosis/lung cancer).
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-
response analysis.Asbestosis was not assessed for all subjects thoroughly (only through death certificates or through reported workers compensation
claims). Wittenoom cohort the diagnosis of asbestosis for compensation purposes the of death is or as cause closely related to the degree of crocidolite to
exposure but not to smoking habits. Although study mentions 2400 men were included in the cohort, it appears that the cases and controls considered for
asbestosis were pulled from a larger cohort (N=2713).
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 214 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081932 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
de Klerk, N. H., Musk, A. W., Cookson, W. O., Glancy, J. J., Hobbs, M. S. (1993). Radiographic abnormalities and mortality in subjects with exposure to
crocidolite. British Journal of Industrial Medicine 50(1993):902-906.
Lung Cancer; Stomach cancer, other unspecified cancer; Asbestosis
Lung/Respiratory: Lung cancer mortality, mesothelioma mortality, pneumoconiosis mortality; Cancer/Carcinogenesis: Lung cancer mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3081932
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Study reports that estimates of crocidolite from Wittenoom Gorge were collected from
existing industry records of fibre. The exact tool utilized to measure the asbestos is
not mentioned, but methods state that fibers in the air >5mu in length from 1966 were
used to create cumulative exposure measures. However, the calculation for cumulative
exposure measures was not mentioned.
Metric 5: Exposure Levels Low The study only reported geometric means of asbestos exposure in terms of cumulative
exposure (f/ml-years), intensity (f/ml), and duration (days). There is no range and distri-
bution of exposure.
Additional Comments: For the year of the study and the 5 different case-control analyses conducted, I agree with the rating. There are some discrepancies, such as how the
asbestos was measured and exposures to various forms of asbestos which were not regarded.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 215 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081932 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
de Klerk, N. H., Musk, A. W., Cookson, W. O., Glancy, J. J., Hobbs, M. S. (1993). Radiographic abnormalities and mortality in subjects with exposure to
crocidolite. British Journal of Industrial Medicine 50(1993):902-906.
Pneumoconiosis, asbestosis, and all other causes
Other causes: Classified as all other causes of death (excluding malignant mesothelioma, lung cancer, stomach cancer, other cancer, and pneumoconiosis)
Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3081932
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Study reports that estimates of crocidolite from Wittenoom Gorge were collected from
existing industry records of fibre. The exact tool utilized to measure the asbestos is
not mentioned, but methods state that fibers in the air >5mu in length from 1966 were
used to create cumulative exposure measures. However, the calculation for cumulative
exposure measures was not mentioned.
Metric 5: Exposure Levels Low The study only reported geometric means of asbestos exposure in terms of cumulative
exposure (f/ml-years), intensity (f/ml), and duration (days). There is no range and distri-
bution of exposure.
Additional Comments: For the year of the study and the 5 different case-control analyses conducted, I agree with the rating. There are some discrepancies, such as how the
asbestos was measured and exposures to various forms of asbestos which were not regarded.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 216 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081494 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
de Klerk, N. H., Musk, A. W., Eccles, J. L., Hansen, J., Hobbs, M. S. (1996). Exposure to crocidolite and the incidence of different histological types of
lung cancer. Occupational and Environmental Medicine 53(1996):157-159.
Lung Cancer
Cancer/Carcinogenesis: Squamous cell carcinoma, Adenocarcinoma, Undifferentiated large cell cancer, Small cell cancer, All lung cancer; Lung/
Respiratory: Squamous cell carcinoma, Adenocarcinoma, Undifferentiated large cell cancer, Small cell cancer, All lung cancer
Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): No linked references.
3081494
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Authors do not describe how exposure was measured. Instead, measurements from a
different study were referenced for this paper (Armstrong, et al., 1988). The introduction
states that the median duration of employment (four months) and medium cumulative
exposure (six f/mL-y). They authors do not explain how the research in Armstrong et
al., 1988 measured this exposure.
Metric 5: Exposure Levels Medium The provided values from Armstrong, et al., 1988 seem sufficient to the analysis in this
paper. Duration since exposure to crocidolite is distributed by years:0-20 y, 21-25 y,26-
30 y, and >31 y
Additional Comments: Overall, this study did a good job in adjusting for smoking and providing various types of lung cancer following past exposure to crocidolite. The
study has some inconsistencies in how exposure was measured, only referencing a past study. Additionally, women were excluded from this study when
included in the original survey, and authors do not explain why.Overall, information on the measurement of exposure metric (M4) to assess exposure was
limited. However, the exposure levels metric (M5) information reported was adequate to determine exposure-response relationships. The overall quality
determination (OQD) for this study is rated medium.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 217 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6884448 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dement, J. M. (1980). Estimation of dose and evaluation of dose-response in a retrospective cohort mortality study of chrysotile asbestos textile workers.
Doctoral Dissertationl-259.
Lung Cancer; Digestive system cancer; All cause mortality, diseases of the circulatory system mortality, other nonmalignant respiratory diseases mortality
Mortality: All cause mortality, Diseases of the circulatory system mortality, Nonmalignant respiratory diseases (NMRD) mortality, Lung cancer mortality,
Digestive system cancer mortality; Lung/Respiratory: Nonmalignant respiratory disease (NMRD) mortality, Lung cancer mortality; Cardiovascular: Dis-
eases of the circulatory system mortality; Cancer/Carcinogenesis: Lung cancer mortality, Digestive system cancer mortality; Gastrointestinal: Digestive
system cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
6884448
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Medium A retrospective cohort design was used for this study. Inclusion in the cohort was lim-
ited to the male employees who had worked in the asbestos plant for 6 months or more,
and at least one month of that must have taken place between January 1, 1940 and De-
cember 31, 1965. It is important to note that the 1965 deadline was used to provide a
latency of 10 years for participants. The authors reported that a total of 768 white males
and 372 black males were included in the final cohort, however only white males were
used for the dose-response analysis. Some individuals were excluded for various rea-
sons including: lacking sufficient demographic data (8 individuals), and two individuals
were identified as war deaths, and were thus removed from the analysis once their em-
ployment was terminated. The eight individuals excluded for a lack of demographic
information were not believed to introduce bias because they "demonstrated no unusual
characteristics such as employment in specific departments or jobs or a racial composi-
tion different from the remainder of the cohort." A United States Public Health Service
study was conducted at the plant in 1968, and all employee records were microfilmed.
These records contained detailed information on demographic data, the employment
history, which was coded based on the job functions performed. This coding scheme
helped with determining fiber exposures. While some details are presented pertaining to
participant selection, information about participation rates at the various steps would be
beneficial.
High Of the 768 white males originally identified for this cohort, all of them were included
in final analyses. Several participants had an unknown vital status as of December 31,
1975 (n=22) - however, for those participants it was assumed that they were still alive to
ensure that they could still be used for analysis.
Continued on next page ...
Page 218 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6884448 Table: 1 of 2
... continued from previous page
Dement, J. M. (1980). Estimation of dose and evaluation of dose-response in a retrospective cohort mortality study of chrysotile asbestos textile workers.
Doctoral Dissertationl-259.
Lung Cancer; Digestive system cancer; All cause mortality, diseases of the circulatory system mortality, other nonmalignant respiratory diseases mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: All cause mortality, Diseases of the circulatory system mortality, Nonmalignant respiratory diseases (NMRD) mortality, Lung cancer mortality,
Digestive system cancer mortality; Lung/Respiratory: Nonmalignant respiratory disease (NMRD) mortality, Lung cancer mortality; Cardiovascular: Dis-
eases of the circulatory system mortality; Cancer/Carcinogenesis: Lung cancer mortality, Digestive system cancer mortality; Gastrointestinal: Digestive
system cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
6884448
Domain Metric Rating Comments
Metric 3: Comparison Group Medium For the standardized mortality ratio analysis conducted in this study, the expected num-
ber of deaths were determined using "cause-specific death rates for the total United
States to the person-years at risk of dying." The authors specify that the number of ex-
pected deaths were standardized for sex, age, race, and calendar time. The period of
follow-up for this study incorporated a time period when the Fifth through Eighth Re-
visions of the International Lists of Diseases and Causes of Death were being used.
"Death rates specific to the 89 Seventh Revision death groups were calculated form
yearly tallies of deaths and census data." U.S. deaths from 1940-1975 were obtained
from the "Vital Statistics of the United States," which was published yearly. The author
mentioned that they considered determining the expected death rates from counties sur-
rounding the county in which the plant was located. However, this was rejected because
a shipyard industry was present, which has been associated with potential asbestos ex-
posure. This was compounded by the potential increase in lung cancer and other health
outcomes resulting from asbestos plant workers, especially from the time when records
were not as well-maintained. It was also mentioned that the smoking rates among white
cohort members was nearly identical to the U.S. population. There is some potential
concern for healthy worker bias due to the comparison of an occupational population to
the general population, but this is not expected to have a substantial impact on the results
of the study.
Domain 2: Exposure Characterization
Continued on next page ...
Page 219 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6884448 Table: 1 of 2
... continued from previous page
Dement, J. M. (1980). Estimation of dose and evaluation of dose-response in a retrospective cohort mortality study of chrysotile asbestos textile workers.
Doctoral Dissertationl-259.
Lung Cancer; Digestive system cancer; All cause mortality, diseases of the circulatory system mortality, other nonmalignant respiratory diseases mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: All cause mortality, Diseases of the circulatory system mortality, Nonmalignant respiratory diseases (NMRD) mortality, Lung cancer mortality,
Digestive system cancer mortality; Lung/Respiratory: Nonmalignant respiratory disease (NMRD) mortality, Lung cancer mortality; Cardiovascular: Dis-
eases of the circulatory system mortality; Cancer/Carcinogenesis: Lung cancer mortality, Digestive system cancer mortality; Gastrointestinal: Digestive
system cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
6884448
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
High Due to the number of years that this plant was operational, there was a plethora of expo-
sure data available from a number of sources, including the company's insurance carrier,
the State Board of Health, the U.S. Public Health Service, and a sampling program that
was run by the company itself. It is noted that "prior to 1965 all samples were of the im-
pinger type; from 1965 until 1971 membrane filter samples were also taken. In 1971, the
impinger method was abandoned and the membrane filter method used exclusively." Im-
pinger samples were reported to be collected at the worker's "breathing level" and "oper-
ators were followed when there was considerable movement." Membrane filter samples
were collected via battery operated pumps worn by the workers being sampled. When
the midget impinger methods were utilized, a bright field optical microscope was used
to count the asbestos particles, at a magnification of lOOx. All concentrations calculated
using this method were reported in millions of particles per cubic foot of air (MPPCF).
When using the membrane filter method, phase contrast optical microscopy was used, at
a magnification of 400-450x. Paired sample analysis was used to compare the impinger
data to the membrane filter data, resulting in a conversion ratio of 3.0 generally and 8.0
for all activities related to fiber preparation, for final measurements presented in fibers/
cc. Cumulative fiber exposure for individual workers was calculated by using detailed
work histories and location-specific and job-specific estimates of fiber exposure.
Medium The authors report 4 levels of exposure in their SMR analysis to evaluate dose-response
relationships. Estimates of exposure are reported in fiber/cc days. The lowest com-
parator group represents exposures less than <10,000 fiber/cc days, while the highest
comparator group represents exposures between 100,000-200,000 fiber/cc days.
Medium The author mentions that the cutoff for follow-up, in 1965, was selected to allow for a
minimum latency of 10 years. The metric was rated as medium because of this indica-
tion from the author, although there were some individuals enrolled who had a longer
latency period, including intervals of 10-19, 20-29, and greater than or equal to 30.
However, summary statistics regarding latency are not provided, preventing a determina-
tion of the average latency for the cohort.
Domain 3: Outcome Assessment
Continued on next page .
Page 220 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6884448 Table: 1 of 2
... continued from previous page
Dement, J. M. (1980). Estimation of dose and evaluation of dose-response in a retrospective cohort mortality study of chrysotile asbestos textile workers.
Doctoral Dissertationl-259.
Lung Cancer; Digestive system cancer; All cause mortality, diseases of the circulatory system mortality, other nonmalignant respiratory diseases mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: All cause mortality, Diseases of the circulatory system mortality, Nonmalignant respiratory diseases (NMRD) mortality, Lung cancer mortality,
Digestive system cancer mortality; Lung/Respiratory: Nonmalignant respiratory disease (NMRD) mortality, Lung cancer mortality; Cardiovascular: Dis-
eases of the circulatory system mortality; Cancer/Carcinogenesis: Lung cancer mortality, Digestive system cancer mortality; Gastrointestinal: Digestive
system cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
6884448
Domain Metric Rating Comments
Metric 7: Outcome Measurement or High Lung Cancer: The authors examined death certificates to determine cause-specific mor-
Characterization tality. Requests for these certificates were submitted through the state vital statistics
offices. Also, "the entire death index (1935-1979) for the state in which the plant was
located was searched in an attempt to locate certificates missed by searches conducted
by state personnel." The follow-up period for this study incorporated a few different
versions of the International Lists of Diseases and Causes of Death, including the Fifth
through Eighth Revisions. A nosologist coded all of the death certificates according to
the ICDA revision that was being used at the time of the participants death, and were
then grouped into "89 death categories based on the Seventh Revision for purposes of
standardization." This was reported as ICDA 7th codes 162 and 163 for lung cancer.;
Other Cancer(s): (Digestive System Cancer) The authors examined death certificates
to determine cause-specific mortality. Requests for these certificates were submitted
through the state vital statistics offices. Also, "the entire death index (1935-1979) for
the state in which the plant was located was searched in an attempt to locate certificates
missed by searches conducted by state personnel." The follow-up period for this study
incorporated a few different versions of the International Lists of Diseases and Causes
of Death, including the Fifth through Eighth Revisions. A nosologist coded all of the
death certificates according to the ICDA revision that was being used at the time of the
participants death, and were then grouped into "89 death categories based on the Sev-
enth Revision for purposes of standardization." This was reported as ICDA 7th codes
150-159 for digestive system cancer.; Other Non-Cancer Outcomes: (All-cause mortal-
ity; Diseases of the Circulatory System, Other Nonmalignant Respiratory Diseases) The
authors examined death certificates to determine cause-specific mortality. Requests for
these certificates were submitted through the state vital statistics offices. Also, "the en-
tire death index (1935-1979) for the state in which the plant was located was searched in
an attempt to locate certificates missed by searches conducted by state personnel." The
follow-up period for this study incorporated a few different versions of the International
Lists of Diseases and Causes of Death, including the Fifth through Eighth Revisions.
A nosologist coded all of the death certificates according to the ICDA revision that was
being used at the time of the participants death, and were then grouped into "89 death
categories based on the Seventh Revision for purposes of standardization." This was re-
ported as ICDA 7th codes 400-468 for diseases of the circulatory system and 510-527
for other nonmalignant respiratory diseases.
Continued on next page ...
Page 221 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6884448 Table: 1 of 2
... continued from previous page
Dement, J. M. (1980). Estimation of dose and evaluation of dose-response in a retrospective cohort mortality study of chrysotile asbestos textile workers.
Doctoral Dissertationl-259.
Lung Cancer; Digestive system cancer; All cause mortality, diseases of the circulatory system mortality, other nonmalignant respiratory diseases mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: All cause mortality, Diseases of the circulatory system mortality, Nonmalignant respiratory diseases (NMRD) mortality, Lung cancer mortality,
Digestive system cancer mortality; Lung/Respiratory: Nonmalignant respiratory disease (NMRD) mortality, Lung cancer mortality; Cardiovascular: Dis-
eases of the circulatory system mortality; Cancer/Carcinogenesis: Lung cancer mortality, Digestive system cancer mortality; Gastrointestinal: Digestive
system cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
6884448
Domain
Metric
Rating
Comments
Metric 8: Reporting Bias
Medium SMRs are reported with both observed numbers of deaths and expected numbers of
deaths, along with indicators of statistical significance. Some outcomes are used in
an analysis of binary exposure (exposed vs. unexposed) but are then not used in dose-
response analysis. It is not explained why they were not analyzed for dose-response
data. SMRs for lung cancer and other nonmalignant respiratory diseases were also plot-
ted via least squares based on the Poisson distribution, and 95% confidence intervals
are presented, although the exact effect estimates from that analysis are only presented
graphically with no reporting of regression coefficients.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10:
Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Age, race, sex, and calendar time period were adjusted for via the calculation of stan-
dardized mortality rates based on those criteria.
Medium The author did not discuss the tools used to assess potential confounders among study
participants. However, because this was an occupational study, it can be assumed that
personnel records were used to obtain covariate data. Comparison population covari-
ates (via standardized mortality rates) were pulled from "Vital Statistics of the United
States."
Medium The author details in Chapter 2 that over the years of operation, various expansions
took place to allow for the production of rubber goods. It is important to note that many
of the asbestos textile productions took place in specific buildings. While this might
have presented a situation in which individuals were exposed to asbestos and various
materials involved in the creation of rubber products, this does not appear to be the
case. It was reported that "a departmental seniority system limited employee transfer
between rubber and textile departments." The separation of production facilities on the
plant grounds seems to be useful in limited potential exposures to substances other than
asbestos.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Medium The retrospective cohort design implemented by the author was appropriate for the
research question being examined. The calculation of SMRs is an appropriate method
for assessing the potential association between asbestos exposure and general or cause-
specific mortality.
Medium While there was no explicit discussion of the power for their calculations, the number of
participants analyzed (n=768) is adequate to detect an effect in the exposed population.
Continued on next page ...
Page 222 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6884448 Table: 1 of 2
... continued from previous page
Dement, J. M. (1980). Estimation of dose and evaluation of dose-response in a retrospective cohort mortality study of chrysotile asbestos textile workers.
Doctoral Dissertationl-259.
Lung Cancer; Digestive system cancer; All cause mortality, diseases of the circulatory system mortality, other nonmalignant respiratory diseases mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: All cause mortality, Diseases of the circulatory system mortality, Nonmalignant respiratory diseases (NMRD) mortality, Lung cancer mortality,
Digestive system cancer mortality; Lung/Respiratory: Nonmalignant respiratory disease (NMRD) mortality, Lung cancer mortality; Cardiovascular: Dis-
eases of the circulatory system mortality; Cancer/Carcinogenesis: Lung cancer mortality, Digestive system cancer mortality; Gastrointestinal: Digestive
system cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
6884448
Domain Metric Rating Comments
Metric 14: Reproducibility of Analyses Medium The authors clearly describe their methods; thus, it would be possible to recreate their
findings if given access to the analytic data.
Metric 15: Statistical Analysis Medium The method the authors report for the calculation of SMRs is transparent and well-
documented. There are less details provided for their use of a Poisson distribution and
they do not describe model assumptions, but it is reasonable to assume that model as-
sumptions were met.
Additional Comments: It is important to note that this study is a dissertation. The author provides extensive detail pertaining to the history of the plant, along with information
about engineering controls and how exposure data was collected over the years. Section 5 and 6 are the most relevant, discussing the mortality study
and dose-response analysis, respectively. There were some limitations noted for this study, including the information pertaining to participant selection.
Information about participation rates and a total number of employees would have been beneficial. This study also had some strengths, including the
author's discussion about limiting potential co-exposures from the rubber production at the plant, as well as their explanation about using broader U.S.
death rates as a comparison for SMR analysis because of characteristics of the surrounding counties. The separate mortality and dose-response analyses
were a benefit of this study, as the author is able to report results for various relationships between asbestos exposure and health outcomes.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 223 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6884448 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dement, J. M. (1980). Estimation of dose and evaluation of dose-response in a retrospective cohort mortality study of chrysotile asbestos textile workers.
Doctoral Dissertationl-259.
all cancers except lung and digestive; all non-cancer outcomes
Mortality: All cause mortality, Diseases of the circulatory system mortality, Diseases of the central nervous system mortality, Tuberculosis mortality,
Nonmalignant respiratory diseases (NMRD) mortality, Acute upper respiratory infection mortality, Influenza mortality, Pneumonia mortality, Bronchitis
mortality, Other respiratory diseases mortality, All other known causes mortality, All malignant neoplasms mortality, Trachea, bronchus & lung neoplasms
mortality, Other and unspecified sites neoplasms mortality, Digestive system neoplasms mortality; Lung/Respiratory: Nonmalignant respiratory disease
(NMRD) mortality, Acute upper respiratory infection mortality, Influenza mortality, Pneumonia mortality, Bronchitis mortality, Other respiratory diseases
mortality, Tuberculosis mortality, Trachea, bronchus & lung neoplasms mortality; Neurological/Behavioral: Diseases of the central nervous system mortal-
ity; Cardiovascular: Diseases of the circulatory system mortality; Cancer/Carcinogenesis: All malignant neoplasms mortality, Digestive system neoplasms
mortality, Trachea, bronchus & lung neoplasms mortality, Other and unspecified sites neoplasms mortality; Gastrointestinal: Digestive system neoplasms
mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
6884448
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure High Due to the number of years that this plant was operational, there was a plethora of expo-
sure data available from a number of sources, including the company's insurance carrier,
the State Board of Health, the U.S. Public Health Service, and a sampling program that
was run by the company itself. It is noted that "prior to 1965 all samples were of the im-
pinger type; from 1965 until 1971 membrane filter samples were also taken. In 1971, the
impinger method was abandoned and the membrane filter method used exclusively." Im-
pinger samples were reported to be collected at the worker's "breathing level" and "oper-
ators were followed when there was considerable movement." Membrane filter samples
were collected via battery operated pumps worn by the workers being sampled. When
the midget impinger methods were utilized, a bright field optical microscope was used
to count the asbestos particles, at a magnification of lOOx. All concentrations calculated
using this method were reported in millions of particles per cubic foot of air (MPPCF).
When using the membrane filter method, phase contrast optical microscopy was used, at
a magnification of 400-450x. Paired sample analysis was used to compare the impinger
data to the membrane filter data, resulting in a conversion ratio of 3.0 generally and 8.0
for all activities related to fiber preparation, for final measurements presented in fibers/
cc. Cumulative fiber exposure for individual workers was calculated by using detailed
work histories and location-specific and job-specific estimates of fiber exposure.
Metric 5: Exposure Levels Low All outcomes inventoried in this form are evaluated using an exposed vs. unexposed
exposure comparison.
Additional Comments: The outcome data represented here is not suitable for dose-response assessment due to a low rating for Metric 5
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 224 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 67 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dement, J. M., Harris, R. L., Jr, Symons, M. J., Shy, C. M. (1983). Exposures and mortality among chrysotile asbestos workers: Part II: Mortality.
American Journal of Industrial Medicine 4(1983):421-433.
Asbestosis; Mortality from non-malignant respiratory disease, mortality from circulatory system disease
Lung/Respiratory: Asbestosis or pulmonary fibrosis as underlying causes of mortality, Non-malignant respiratory disease mortality (non-infectious);
Mortality: All-cause mortality, Non-malignant respiratory disease mortality (non-infectious), Asbestosis or pulmonary fibrosis as underlying causes of
mortality, Circulatory system mortality; Cardiovascular: Circulatory system mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
67
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
High The cohort comprised 1,261 white males employed >1 month at a chrysotile asbestos
textile factory in South Carolina between 1940 an 1965, with vital status ascertained
through December 1975. Personnel records were maintained starting in 1930 " 10 years
prior to this study " with similar information collected since that time. Selection bias
should be limited since the study included a diverse sample of workers with both long
and very short employment duration and varying dates of initial employment.
High The cohort included all records that met eligibility criteria. Vital status was ascertained
for all but 26 (2.1% ) members of the cohort.
High SMRs were calculated using the total US white male population to define the number
of expected overall and cause-specific deaths. "The number of expected deaths, stan-
dardized for sex, age, race and calendar time, were calculated by application of cause-
specific death rates for the total United States to the person-years at risk of dying. Death
rates specific to the 89... death groups were calculated from yearly tallies of deaths and
census data." The US population referent was used because of very high mortality rates
in the county where the plant was located (75% higher than US white males), making
the general population a more suitable referent. The high rate may be due in part to a
large shipyard industry in the county (potential source of asbestos exposure). Mortality
was also elevated in neighboring counties.
Domain 2: Exposure Characterization
Continued on next page .
Page 225 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 67 Table: 1 of 2
... continued from previous page
Dement, J. M., Harris, R. L., Jr, Symons, M. J., Shy, C. M. (1983). Exposures and mortality among chrysotile asbestos workers: Part II: Mortality.
American lournal of Industrial Medicine 4(1983):421-433.
Asbestosis; Mortality from non-malignant respiratory disease, mortality from circulatory system disease
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Asbestosis or pulmonary fibrosis as underlying causes of mortality, Non-malignant respiratory disease mortality (non-infectious);
Mortality: All-cause mortality, Non-malignant respiratory disease mortality (non-infectious), Asbestosis or pulmonary fibrosis as underlying causes of
mortality, Circulatory system mortality; Cardiovascular: Circulatory system mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
67
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Cumulative exposure estimates used detailed work histories and air sampling data; time
exposed in each job and fiber conversions may be over-estimates as detailed below. In-
dividual exposure was obtained by summing the product of average concentrations for
each job at that time by the duration spent in that job. Time worked in each job/exposure
zone was estimated in days based on the difference in dates of job changes. This method
did not eliminate weekends and holidays, and did not account for overtime, both of
which introduced some measurement error. Estimated fiber concentrations, expressed
as fibers > 5 jUm per cubic center (i.e., milliliter), were derived using a total of 5,952
dust samples collected between 1930 and 1975 by the company, insurance carrier, state
health board and US public health service. Samples were collected by impinger prior
to 1965, by impinger and membrane filter from 1965-1971, and from 1971 onward by
membrane filter. Pre-1930 exposures were assigned the values measured prior to imple-
mentation of controls. Conversion of dust measures to estimated fiber concentrations
using concurrent impinger - membrane filter samples (120 in 1965 from the US Pub-
lic Health service, 968 from plant operations in 1968-71). No significant differences in
conversions were detected by calendar time or plant operation: mean conversions were
7.8 fibers/cc per MPPCF for fiber preparation, and 2.5 fibers per MPPCF for other oper-
ations. However, this study used conversion factors of 8 for fiber preparation and 3 for
other operations, described as "conservatively high conversion values".
Medium Several analyses (overall and cause-specific SMRs, incidence density for respiratory
outcomes) used 5 categories of cumulative exposure in fibers/cc-days (<1,000; 1,000-
10,000; 10,000-40,000; 40,000-100,000; and >100,000). In addition, some analyses
were stratified by exposure characterized using 4 categories of either years since initial
employment (<10, 10-19, 20-29, >30 years) or total years employed (same categories).
High The maximum follow up was >35 years (1940 to 1975, some employed prior to 1940),
and the minimum 10 years (1965-1975). With a total of 33,141 person years at risk
among 1,261 members, the mean follow-up was likely about 26 years. Additionally,
analyses of dose-response rates for respiratory outcomes were limited to men with 15 or
more years latency.
Domain 3: Outcome Assessment
Continued on next page .
Page 226 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 67 Table: 1 of 2
... continued from previous page
Dement, J. M., Harris, R. L., Jr, Symons, M. J., Shy, C. M. (1983). Exposures and mortality among chrysotile asbestos workers: Part II: Mortality.
American lournal of Industrial Medicine 4(1983):421-433.
Asbestosis; Mortality from non-malignant respiratory disease, mortality from circulatory system disease
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Asbestosis or pulmonary fibrosis as underlying causes of mortality, Non-malignant respiratory disease mortality (non-infectious);
Mortality: All-cause mortality, Non-malignant respiratory disease mortality (non-infectious), Asbestosis or pulmonary fibrosis as underlying causes of
mortality, Circulatory system mortality; Cardiovascular: Circulatory system mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
67
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
Medium Asbestosis: Death certificates were coded by a qualified nosologist, using ICD 7 codes
510-527 (523 and 527 are pneumoconioses) to identify non-infectious non-malignant
respiratory disease, which included asbestosis/pulmonary fibrosis (combined) as un-
derlying causes of disease (including among cardiovascular deaths). Overall, asbestosis
or pulmonary fibrosis were specified as the cause in 17 of 24 cases of non-infectious,
non-malignant respiratory disease. All of these cases had 15 or more years of latency
since first exposure. It was not feasible in this study design to obtain other information
(e.g., medical records) to confirm diagnoses reported on death certificates. Combining
asbestosis and pulmonary fibrosis limits specificity. However, asbestosis may have been
under-diagnosed/classified as pulmonary fibrosis.; Other Non-Cancer Outcomes: The
outcomes evaluated included all-cause mortality, mortality from other (non-infectious)
non-malignant respiratory disease (ONMRD), and circulatory system mortality, and
lung cancer mortality. The 24 deaths from other non-malignant respiratory disease (ON-
MRD) included asbestosis. Asbestosis or pulmonary fibrosis were underlying causes of
17 of these deaths (6 identified by examining contributory causes for the 105 individ-
uals with cardiovascular mortality). Vital status through 1975 was ascertained for all
but 26 (2.1% ) of the 1,261 cohort members. Multiple sources were used, including the
Social Security Administration (SSA), IRS, USPS, drivers" license records, and state
vital statistics offices, along with telephone listings, property, and voter records, among
others. Of 308 deaths, all but 17 death certificates were obtained. Death certificates
(which spanned ICD versions 5 to 8) were coded in 89 categories by a nosologist and
standardized using ICD 7 codes. Cause unknown was assigned for the 17 known deaths
for which no certificate was available.
Medium Numbers of expected and observed deaths were presented for all SMR analyses. How-
ever, SMRs did not include confidence intervals. Confidence intervals and the person-
years at risk denominator were reported for the incidence density of respiratory out-
comes, which was reported by cumulative exposure category. The authors did not report
the methods used for statistical significance testing.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Medium SMRs accounted for age, sex, race, and calendar period. Smoking data was only avail-
able for cohort members who completed a respiratory symptom questionnaire in 1964
and 1971 as part of a public health service study. However, the authors illustrated that
available estimates for current, past, and non-smoking for the cohort were extremely
similar to those for US white males in 1965. Incidence density analyses did not report
covariate adjustments. However, the study was limited to white males and incidence
density accounts for person-time.
Continued on next page ...
Page 227 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 67 Table: 1 of 2
... continued from previous page
Dement, J. M., Harris, R. L., Jr, Symons, M. J., Shy, C. M. (1983). Exposures and mortality among chrysotile asbestos workers: Part II: Mortality.
American lournal of Industrial Medicine 4(1983):421-433.
Asbestosis; Mortality from non-malignant respiratory disease, mortality from circulatory system disease
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Domain
Lung/Respiratory: Asbestosis or pulmonary fibrosis as underlying causes of mortality, Non-malignant respiratory disease mortality (non-infectious);
Mortality: All-cause mortality, Non-malignant respiratory disease mortality (non-infectious), Asbestosis or pulmonary fibrosis as underlying causes of
mortality, Circulatory system mortality; Cardiovascular: Circulatory system mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
67
Metric
Rating
Comments
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Data came primarily from personnel records and death certificates.
Medium Co-exposures (e.g., from earlier or subsequent work) were not taken into account. Silica
or other occupational exposures may have contributed to risk of deaths coded pulmonary
fibroses. However, there is no direct evidence that co-exposures might have confounded
the findings.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium Methods were appropriate. SMRs were calculated using a life-table method (reference is
cited) and Poisson regression was used to estimate incidence density.
Medium There were 308 deaths overall, including 24 from other non-malignant respiratory dis-
eases (22 with 15+ years latency). Of the 22, 17 deaths had codes for asbestosis and
pulmonary fibrosis as primary or underlying causes of death. Sparse numbers are not
unusual for outcomes such as asbestosis.
Medium The analyses presented should be readily reproducible as analyses were described and
cell sizes presented in adequate detail.
Medium The authors explained their rationale and methods in sufficient detail and methods were
appropriate. For SMRs, few confounders besides smoking are typically considered.
Additional Comments: This study analyzed mortality in a cohort of 1,261 white males employed > 1 month at a chrysotile asbestos textile factory in South Carolina between 1940
and 1965, followed through 1975. Vital status (98% ) and cause of death (94% ) ascertainment were nearly complete. Use of a dynamic cohort of individuals
employed at any time during a 25-year period reduced the likelihood of healthy worker survivor bias. Exposure was estimated using historical air samples,
applying dust-to-fiber conversion estimates for early years; methods may have over-estimated exposure. Based on person-years among participants with
>15 years of follow-up and converting cumulative exposure-days to years ("365), about 61% of the cohort had exposures >27.4 fiber/mL-years [10,000
fiber/cc-days]; 7% had exposures >109.6 fiber/mL-years [40,000 flber/cc-years], SMRs for non-malignant respiratory disease (excluding infectious)
increased from 362 to 2500 over 5 categories of increasing cumulative exposure. Incidence density for asbestos or pulmonary fibrosis mortality also
increased from 0.32/1000 person years to 15.98/1000 person-years with increasing exposure. SMRs were also stratified by years employed and years since
initial employment categories. SMRs for lung cancer increased from 140 to 1818 over 5 categories of increasing cumulative exposure. Limitations include
that asbestosis and pulmonary fibrosis were combined; it is not possible to ascertain if some cases might be fibroses attributable to other occupational
exposures. Although smoking adjustments were not possible, limited data suggested that smoking history in the cohort closely resembled the US white
male population.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 228 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 67 Table: 2 of 2
Dement, J. M., Harris, R. L., Jr, Symons, M. J., Shy, C. M. (1983). Exposures and mortality among chrysotile asbestos workers: Part II: Mortality.
American lournal of Industrial Medicine 4(1983):421-433.
Lung Cancer; digestive system cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Digestive system cancer mortality; Mortality: Lung cancer
mortality, Digestive system cancer mortality; Gastrointestinal: Digestive system cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
67
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
High The cohort comprised 1,261 white males employed >1 month at a chrysotile asbestos
textile factory in South Carolina between 1940 an 1965, with vital status ascertained
through December 1975. Personnel records were maintained starting in 1930 " 10 years
prior to this study " with similar information collected since that time. Selection bias
should be limited since the study included a diverse sample of workers with both long
and very short employment duration and varying dates of initial employment.
High The cohort included all records that met eligibility criteria. Vital status was ascertained
for all but 26 (2.1% ) members of the cohort.
High SMRs were calculated using the total US white male population to define the number
of expected overall and cause-specific deaths. "The number of expected deaths, stan-
dardized for sex, age, race and calendar time, were calculated by application of cause-
specific death rates for the total United States to the person-years at risk of dying. Death
rates specific to the 89... death groups were calculated from yearly tallies of deaths and
census data." The US population referent was used because of very high mortality rates
in the county where the plant was located (75% higher than US white males), making
the general population a more suitable referent. The high rate may be due in part to a
large shipyard industry in the county (potential source of asbestos exposure). Mortality
was also elevated in neighboring counties.
Domain 2: Exposure Characterization
Continued on next page .
Page 229 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 67 Table: 2 of 2
... continued from previous page
Dement, J. M., Harris, R. L., Jr, Symons, M. J., Shy, C. M. (1983). Exposures and mortality among chrysotile asbestos workers: Part II: Mortality.
American lournal of Industrial Medicine 4(1983):421-433.
Lung Cancer; digestive system cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Digestive system cancer mortality; Mortality: Lung cancer
mortality, Digestive system cancer mortality; Gastrointestinal: Digestive system cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
67
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Cumulative exposure estimates used detailed work histories and air sampling data; time
exposed in each job and fiber conversions may be over-estimates as detailed below. In-
dividual exposure was obtained by summing the product of average concentrations for
each job at that time by the duration spent in that job. Time worked in each job/exposure
zone was estimated in days based on the difference in dates of job changes. This method
did not eliminate weekends and holidays, and did not account for overtime, both of
which introduced some measurement error. Estimated fiber concentrations, expressed
as fibers > 5 jUm per cubic center (i.e., milliliter), were derived using a total of 5,952
dust samples collected between 1930 and 1975 by the company, insurance carrier, state
health board and US public health service. Samples were collected by impinger prior
to 1965, by impinger and membrane filter from 1965-1971, and from 1971 onward by
membrane filter. Pre-1930 exposures were assigned the values measured prior to imple-
mentation of controls. Conversion of dust measures to estimated fiber concentrations
using concurrent impinger - membrane filter samples (120 in 1965 from the US Pub-
lic Health service, 968 from plant operations in 1968-71). No significant differences in
conversions were detected by calendar time or plant operation: mean conversions were
7.8 fibers/cc per MPPCF for fiber preparation, and 2.5 fibers per MPPCF for other oper-
ations. However, this study used conversion factors of 8 for fiber preparation and 3 for
other operations, described as "conservatively high conversion values".
Medium Several analyses (overall and cause-specific SMRs, incidence density for respiratory
outcomes) used 5 categories of cumulative exposure in fibers/cc-days (<1,000; 1,000-
10,000; 10,000-40,000; 40,000-100,000; and >100,000). In addition, some analyses
were stratified by exposure characterized using 4 categories of either years since initial
employment (<10, 10-19, 20-29, >30 years) or total years employed (same categories).
High The maximum follow up was >35 years (1940 to 1975, some employed prior to 1940),
and the minimum 10 years (1965-1975). With a total of 33,141 person years at risk
among 1,261 members, the mean follow-up was likely about 26 years. Additionally,
analyses of dose-response rates for respiratory outcomes were limited to men with 15 or
more years latency.
Domain 3: Outcome Assessment
Continued on next page .
Page 230 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 67 Table: 2 of 2
... continued from previous page
Dement, J. M., Harris, R. L., Jr, Symons, M. J., Shy, C. M. (1983). Exposures and mortality among chrysotile asbestos workers: Part II: Mortality.
American lournal of Industrial Medicine 4(1983):421-433.
Lung Cancer; digestive system cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Digestive system cancer mortality; Mortality: Lung cancer
mortality, Digestive system cancer mortality; Gastrointestinal: Digestive system cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
67
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
High
Lung Cancer: Lung cancer mortality was assessed on death certificates by a nosologist
using the ICD revision that was in use at the time of death (which spanned ICD versions
5 to 8). Cause of death was coded into 89 categories standardized to ICD-7 for analy-
sis. Lung cancer mortality was defined as a 3-digit ICD-7 code of 162 or 163.; Other
Cancer(s): Digestive system cancer mortality was assessed on death certificates by a
nosologist using the ICD revision that was in use at the time of death (which spanned
ICD versions 5 to 8). Cause of death was coded into 89 categories standardized to ICD-
7 for analysis. Digestive system cancer mortality was defined as a 3-digit ICD-7 code of
150-159.
Metric 8:
Reporting Bias
Medium
Numbers of expected and observed deaths were presented for all SMR analyses. How-
ever, SMRs did not include confidence intervals. Confidence intervals and the person-
years at risk denominator were reported for the incidence density of respiratory out-
comes, which was reported by cumulative exposure category. The authors did not report
the methods used for statistical significance testing.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
Medium
SMRs accounted for age, sex, race, and calendar period. Smoking data was only avail-
able for cohort members who completed a respiratory symptom questionnaire in 1964
and 1971 as part of a public health service study. However, the authors illustrated that
available estimates for current, past, and non-smoking for the cohort were extremely
similar to those for US white males in 1965. Incidence density analyses did not report
covariate adjustments. However, the study was limited to white males and incidence
density accounts for person-time.
Metric 10:
Covariate Characterization
Medium
Data came primarily from personnel records and death certificates.
Metric 11:
Co-exposure Counfounding
Medium
Co-exposures (e.g., from earlier or subsequent work) were not taken into account. Silica
or other occupational exposures may have contributed to risk of deaths coded pulmonary
fibroses. However, there is no direct evidence that co-exposures might have confounded
the findings.
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
Methods were appropriate. SMRs were calculated using a life-table method (reference is
cited) and Poisson regression was used to estimate incidence density.
Metric 13:
Statistical Power
Medium
There were 308 deaths overall, including 24 from other non-malignant respiratory dis-
eases (22 with 15+ years latency). Of the 22, 17 deaths had codes for asbestosis and
pulmonary fibrosis as primary or underlying causes of death. Sparse numbers are not
unusual for outcomes such as asbestosis.
Continued on next
page...
Page 231 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 67 Table: 2 of 2
... continued from previous page
Dement, J. M., Harris, R. L., Jr, Symons, M. J., Shy, C. M. (1983). Exposures and mortality among chrysotile asbestos workers: Part II: Mortality.
American lournal of Industrial Medicine 4(1983):421-433.
Lung Cancer; digestive system cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Digestive system cancer mortality; Mortality: Lung cancer
mortality, Digestive system cancer mortality; Gastrointestinal: Digestive system cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
67
Domain Metric Rating Comments
Metric 14: Reproducibility of Analyses Medium The analyses presented should be readily reproducible as analyses were described and
cell sizes presented in adequate detail.
Metric 15: Statistical Analysis Medium The authors explained their rationale and methods in sufficient detail and methods were
appropriate. For SMRs, few confounders besides smoking are typically considered.
Additional Comments: This study analyzed mortality in a cohort of 1,261 white males employed > 1 month at a chrysotile asbestos textile factory in South Carolina between 1940
and 1965, followed through 1975. Vital status (98% ) and cause of death (94% ) ascertainment were nearly complete. Use of a dynamic cohort of individuals
employed at any time during a 25-year period reduced the likelihood of healthy worker survivor bias. Exposure was estimated using historical air samples,
applying dust-to-fiber conversion estimates for early years; methods may have over-estimated exposure. Based on person-years among participants with
>15 years of follow-up and converting cumulative exposure-days to years ("365), about 61% of the cohort had exposures >27.4 fiber/mL-years [10,000
fiber/cc-days]; 7% had exposures >109.6 fiber/mL-years [40,000 fiber/cc-years], SMRs for non-malignant respiratory disease (excluding infectious)
increased from 362 to 2500 over 5 categories of increasing cumulative exposure. Incidence density for asbestos or pulmonary fibrosis mortality also
increased from 0.32/1000 person years to 15.98/1000 person-years with increasing exposure. SMRs were also stratified by years employed and years since
initial employment categories. SMRs for lung cancer increased from 140 to 1818 over 5 categories of increasing cumulative exposure. Limitations include
that asbestosis and pulmonary fibrosis were combined; it is not possible to ascertain if some cases might be fibroses attributable to other occupational
exposures. Although smoking adjustments were not possible, limited data suggested that smoking history in the cohort closely resembled the US white
male population.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 232 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2573093 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Deng, Q., Wang, X., Wang, M., Lan, Y. (2012). Exposure-response relationship between chrysotile exposure and mortality from lung cancer and asbestosis.
Occupational and Environmental Medicine 69(2012):81-86.
Asbestosis
Lung/Respiratory: Asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
2573093, 3520560
2573093
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This fixed cohort comprised 586 male workers at an asbestos plant in Chongqing, China
employed in 1972 and followed through December 2006. The plant used chrysotile
asbestos to manufacture textiles, rubber plate and cement. This fixed cohort excluded
workers not employed for > 1 year at baseline and did not include either former workers
or new workers employed after 1972. These exclusions might induce the risk of healthy
worker survivor bias, shifting associations toward the null (e.g., Arrighi & Picciotto,
1996, HEROID 79805). Mean (SD) length of employment in the cohort was 25.4 (8.3)
years. Very long-term workers with low attrition likely over-represent those individuals
least vulnerable to adverse effects and to have accumulated high exposure. In contrast,
employees who may have self-selected out of employment after a shorter duration due
to poor health/symptoms are likely to be both under-represented in the cohort, and to
contribute person-time primarily to low exposure.
High Overall, only 49 workers " 7.7% of the 635 men employed at the factory in 1972 " were
excluded at baseline because they had worked for less than 1 year (shorter-term employ-
ees). In addition, 73 workers in the cohort were lost to follow-up, but job histories and
vital records were available from records.
Medium Analyses used workers in the same cohort with lower exposure as the comparison group.
This approach reduces healthy worker hire bias but may not address healthy worker sur-
vivor bias related to attrition. Because the cohort was fixed, lower exposure is primarily
a consequence of a relatively shorter employment duration: the comparison group may
over-represent individuals who stopped work due to poor health. To address this issue,
the authors incorporated exposure lag times, a method recommended to account for dis-
ease latency and help reduce healthy worker survivor bias by reducing reliance on the
participants with the shortest exposures. However, the effectiveness of applying this
approach cannot be ascertained (e.g., Arrighi & Picciotto, 1996 79805).
Domain 2: Exposure Characterization
Continued on next page .
Page 233 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2573093 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Deng, Q., Wang, X., Wang, M., Lan, Y. (2012). Exposure-response relationship between chrysotile exposure and mortality from lung cancer and asbestosis.
Occupational and Environmental Medicine 69(2012):81-86.
Asbestosis
Lung/Respiratory: Asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
2573093, 3520560
2573093
Domain
Metric
Rating
Comments
Metric 4:
Measurement of Exposure
Metric 5:
Metric 6:
Exposure Levels
Temporality
Medium Despite limitations (e.g., infrequent measures with sampling every 4 years), exposure
was estimated based on substantial quantitative data: a total of 556 measures, 223 us-
ing fiber counting with PCM. Estimated exposure intensity in this Chinese study was
considerably higher than in numerous studies in Western countries. Air monitoring data
from plant records was used for 1955-1970; the authors did not describe methods, equip-
ment, or frequency for this period. Exposure was measured every four years at the area
level (breathing zones) from 1970 to 2006 using a membrane filter (missing details e.g.,
on # hours). Paired dust and fiber concentrations (n=90) collected in 1999, 2002 and
2006 in each of the 7 factory workshops were used to develop a linear model to con-
vert dust measures to estimated fiber concentrations. No details were provided e.g., on
goodness-of-fit, or how measured and estimated fiber concentrations were combined for
1970-1994. Work areas were grouped into 4 categories based on work processes and
dust/fiber concentrations, with cumulative exposure for individuals estimated by sum-
ming the relevant concentration multiplied by duration. Exposure status in the cohort
was updated annually after baseline.
Medium Cumulative exposure was analyzed using a continuous fiber/mL-year variable.
High The follow-up time of 35 years was adequate for analyses of asbestosis. The authors
stated that none of the workers had a diagnosis of cardiopulmonary disease at baseline
(details not provided on any health examinations). All deaths from asbestosis occurred
10+ years after first exposure, the great majority after 15+ years.
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Metric 8:
Reporting Bias
High Asbestosis: Vital status and cause of death were obtained from death certificates and a
municipal hospital death registry, with ICD codes used to classify outcomes. Total mor-
tality was high (n=226 deaths). Asbestosis (n=37 cases) was determined by a special
panel based on criteria that included a job history confirming occupational exposure,
positive radiographic findings, and clinical signs and symptoms, as established by the
1986 Chinese Diagnosis Criteria of Pneumoconiosis by Radiograph. "Death from as-
bestosis was broadened to include asbestosis and any asbestosis complications, such as
cor pulmonale." Ascertainment of vital status involved annual follow-up at the plant and
with families (97%).
Medium The study presented results that included descriptive data on numbers and causes of
death stratified by smoking, fiber-to-dust conversions, and associations using alternative
model specifications. However, the authors did not present the distribution of deaths
over time or describe the number of deaths included when different exposure lag times
were applied in their analyses.
Continued on next page ...
Page 234 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2573093 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Deng, Q., Wang, X., Wang, M., Lan, Y. (2012). Exposure-response relationship between chrysotile exposure and mortality from lung cancer and asbestosis.
Occupational and Environmental Medicine 69(2012):81-86.
Asbestosis
Lung/Respiratory: Asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
2573093, 3520560
2573093
Domain
Metric
Rating
Comments
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Models adjusted for age, calendar time and smoking status. The article stated that the
majority of workers retired during the follow-up period; however, analyses did not
account for employment status changes as recommended (Arrighi & Picciotto, 1996
79805). Changes in employment status related to symptoms might be a confounder.
Medium Questionnaires, employment records and interviews with employees, family members
and coworkers were used to characterize covariates (e.g., smoking habits, job changes)
for both living and deceased workers.
Medium The study did not evaluate any co-exposures, but co-exposure confounding is unlikely
for asbestosis.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study compared associations using alternative models based on varying possible
exposure-response relationship. Models adjusted for potential confounders that included
calendar time and smoking, and incorporated exposure lag times in an effort to address
both disease latency and potential healthy worker survivor bias. As noted earlier models
did not adjust for employment status. NOTE: The online supplementary materials that
provided more details on these alternative models were requested but not yet available at
the time of this evaluation.
Medium There were 226 deaths in the cohort of 568 men, including 37 from asbestosis. Power
to detect interactions (tested with smoking) was likely limited given the small number
of cases and moderate overall sample size. Indeed, one model specification failed to
converge for asbestosis.
Medium The analyses presented are likely to be reproducible given the substantial detail provided
on model specifications. NOTE: Reproducibility of results in online supplementary
materials has not been evaluated as they are not yet available.
Medium The authors explained the rationale for their statistical methods used and covariates
examined. For example, they described the alternative model forms examined, discussed
interactions tested, and explained the use of exposure lagging.
Continued on next page ...
Page 235 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2573093 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Deng, Q., Wang, X., Wang, M., Lan, Y. (2012). Exposure-response relationship between chrysotile exposure and mortality from lung cancer and asbestosis.
Occupational and Environmental Medicine 69(2012):81-86.
Asbestosis
Lung/Respiratory: Asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
2573093, 3520560
2573093
Domain
Metric
Rating
Comments
Additional Comments:
This study evaluated the association between chrysotile asbestos exposure and mortality from asbestosis. The population comprised a fixed cohort of 586
workers employed for >1 year at a Chinese asbestos textile factory in 1972, followed to 2006. Neither former workers nor individuals employed after
1972 were not included. High exposure concentrations (attributed to legislation and management delays) and lengthy employment duration resulted in
higher cumulative exposure (126.1 f-y/mL) than in Western studies of chrysotile textile workers (e.g., 17.1 f/mL-year in a North Carolina study, Loomis
et al 2009). However, details on early exposure measurement methods were not provided, and monitoring was infrequent throughout the study. Mortality
(n=226 total) included 37 deaths from asbestosis. The authors evaluated alternative model forms and reported significant associations with asbestosis
mortality: the relative risk was 10.4 for 40 years of exposure to 1 f/mL of asbestos. Lung cancer mortality was also analyzed and the association with
cumulative asbestos exposure described as significant (additional details in online supplement not yet available). Given the use of a fixed cohort, healthy
worker survivor bias could have shifted associations towards the null. Low exposure may over-represent individuals selected out of employment duration
due in part to poorer health, while the more highly exposed long-term workers may over-represent less vulnerable "survivors". The authors incorporated
exposure lags of up to 10 years to help address this bias (Arrighi & Picciotto, 1996 79805), but effectiveness is uncertain. NOTE: Online supplementary
materials that included parameter estimates of key models not yet available.The measurement exposure (M4) and/or exposure levels (M5) metrics are rated
as medium upon review by both set of reviewers. Also, the overall quality determination (OQD) is rated medium. Extraction has been completed and
quality control reviewed.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 236 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1066036 Table: 1 of 7
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dunning, K. K., Adjei, S., Levin, L., Rohs, A. M., Hilbert, T., Borton, E., Kapil, V., Rice, C., Lemasters, G. K., Lockey, J. E. (2012). Mesothelioma
associated with commercial use of vermiculite containing Libby amphibole. Journal of Occupational and Environmental Medicine 54(2012):1359-1363.
Lung Cancer
Mortality: Mortality from cancer of trachea, bronchus, or lung; Cancer/Carcinogenesis: Mortality from cancer of trachea, bronchus, or lung; Lung/
Respiratory: Mortality from cancer of trachea, bronchus, or lung
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Not specified: 1332-21-4; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7;
Asbestos - Tremolite: 14567-73-8
No linked references.
1066036
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Analyses use cumulative fiber exposure. Additional details about exposure measurement
are reported in Lockey et al., 1984, HEROID 29685. Samples were collected via mem-
brane filters either by following an employee with a sampler (from 1972-1976) or by
breathing zone sampling (after 1976). Authors note that exposure of fiber was defined as
"particles with a length greater than 5 um, a diameter less than 3 um, and an aspect ra-
tio of 3:1 or greater". Thus, fiber type was unknown, and samples likely included fibers
other than asbestos. Samples were reviewed through polarized light microscopy, scan-
ning electron microscopy, and TEM. Indexes were created for each department within
the facility. Study authors used work histories reported by workers in 1980 to calcu-
late the cumulative fiber exposure level for each employee. Previous estimates were
revised to include additional data related to exposure collected in 2010, such as adjust-
ments for vermiculite source and changes in duration of work by season (Borton et al.,
2012, HEROID 1066035). Borton et al. also estimated exposures from 1957-1971 us-
ing estimates from 1972 with adjustments for dustier historical conditions. This study
also reported comparisons between personal and area samples and found approximately
equal means and ranges.
Metric 5: Exposure Levels Medium For SMR and SRR analyses of lung cancer, exposure is presented in three groups based
on cumulative fiber exposure estimates. Authors note the possibility that associations
were not observed due to the low exposure levels among the study population, which
raises some concern about the influence of the exposure distribution on the ability to
detect an effect.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.This retrospective occupational cohort study examined the association between asbestos exposure and all cancer mortality among workers mining
and milling contaminated vermiculite. There were no major concerns with the study, aside from limited exposure distributions among the study population
and concerns about fibrous co-exposures that were not characterized or quantified. Since these workers were exposed to fibers that were not asbestos, it
can be assumed that these exposures influenced the observed outcomes, but they were not characterized. The approach for exposure measurement and
statistical analysis was strong, and there were no concerns about selection bias resulting from population recruitment approaches.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 237 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1066036 Table: 2 of 7
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Dunning, K. K., Adjei, S., Levin, L., Rohs, A. M., Hilbert, T., Borton, E., Kapil, V., Rice, C., Lemasters, G. K., Lockey, J. E. (2012). Mesothelioma
associated with commercial use of vermiculite containing Libby amphibole. Journal of Occupational and Environmental Medicine 54(2012):1359-1363.
All cancer mortality
Cancer/Carcinogenesis: All cancer mortality; Mortality: All cancer mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Not specified: 1332-21-4; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7;
Asbestos - Tremolite: 14567-73-8
ID(s): No linked references.
1066036
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Analyses use cumulative fiber exposure. Additional details about exposure measurement
are reported in Lockey et al., 1984, HEROID 29685. Samples were collected via mem-
brane filters either by following an employee with a sampler (from 1972-1976) or by
breathing zone sampling (after 1976). Authors note that exposure of fiber was defined as
"particles with a length greater than 5 um, a diameter less than 3 um, and an aspect ra-
tio of 3:1 or greater". Thus, fiber type was unknown, and samples likely included fibers
other than asbestos. Samples were reviewed through polarized light microscopy, scan-
ning electron microscopy, and TEM. Indexes were created for each department within
the facility. Study authors used work histories reported by workers in 1980 to calcu-
late the cumulative fiber exposure level for each employee. Previous estimates were
revised to include additional data related to exposure collected in 2010, such as adjust-
ments for vermiculite source and changes in duration of work by season (Borton et al.,
2012, HEROID 1066035). Borton et al. also estimated exposures from 1957-1971 us-
ing estimates from 1972 with adjustments for dustier historical conditions. This study
also reported comparisons between personal and area samples and found approximately
equal means and ranges.
Metric 5: Exposure Levels Medium For SMR and SRR analyses of all cancer mortality, exposure is presented in three
groups based on cumulative fiber exposure estimates. Authors note the possibility that
associations were not observed due to the low exposure levels among the study popula-
tion, which raises some concern about the influence of the exposure distribution on the
ability to detect an effect.
Additional Comments: QC was not completed for metric other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.This retrospective occupational cohort study examined the association between asbestos exposure and all cancer mortality among workers mining
and milling contaminated vermiculite. There were no major concerns with the study, aside from limited exposure distributions among the study population
and concerns about fibrous co-exposures that were not characterized or quantified. Since these workers were exposed to fibers that were not asbestos, it
can be assumed that these exposures influenced the observed outcomes, but they were not characterized. The approach for exposure measurement and
statistical analysis was strong, and there were no concerns about selection bias resulting from population recruitment approaches.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 238 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1066036 Table: 3 of 7
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Dunning, K. K., Adjei, S., Levin, L., Rohs, A. M., Hilbert, T., Borton, E., Kapil, V., Rice, C., Lemasters, G. K., Lockey, J. E. (2012). Mesothelioma
associated with commercial use of vermiculite containing Libby amphibole. Journal of Occupational and Environmental Medicine 54(2012):1359-1363.
All cause mortality
Mortality: All cause mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Not specified: 1332-21-4; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7;
Asbestos - Tremolite: 14567-73-8
ID(s): No linked references.
1066036
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Analyses use cumulative fiber exposure. Additional details about exposure measurement
are reported in Lockey et al., 1984, HEROID 29685. Samples were collected via mem-
brane filters either by following an employee with a sampler (from 1972-1976) or by
breathing zone sampling (after 1976). Authors note that exposure of fiber was defined as
"particles with a length greater than 5 um, a diameter less than 3 um, and an aspect ra-
tio of 3:1 or greater". Thus, fiber type was unknown, and samples likely included fibers
other than asbestos. Samples were reviewed through polarized light microscopy, scan-
ning electron microscopy, and TEM. Indexes were created for each department within
the facility. Study authors used work histories reported by workers in 1980 to calcu-
late the cumulative fiber exposure level for each employee. Previous estimates were
revised to include additional data related to exposure collected in 2010, such as adjust-
ments for vermiculite source and changes in duration of work by season (Borton et al.,
2012, HEROID 1066035). Borton et al. also estimated exposures from 1957-1971 us-
ing estimates from 1972 with adjustments for dustier historical conditions. This study
also reported comparisons between personal and area samples and found approximately
equal means and ranges.
Metric 5: Exposure Levels Low For SMR analyses of all-cause mortality, exposure is presented in two groups only (ex-
posed workers and unexposed US general population). Authors note the possibility that
associations were not observed due to the low exposure levels among the study popula-
tion, which raises some concern about the influence of the exposure distribution on the
ability to detect an effect.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.This retrospective occupational cohort study examined the association between asbestos exposure and all cause mortality among workers mining
and milling contaminated vermiculite. There were no major concerns with the study, aside from limited exposure distributions among the study population
and concerns about fibrous co-exposures that were not characterized or quantified. Since these workers were exposed to fibers that were not asbestos, it
can be assumed that these exposures influenced the observed outcomes, but they were not characterized. The approach for exposure measurement and
statistical analysis was strong, and there were no concerns about selection bias resulting from population recruitment approaches.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 239 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1066036 Table: 4 of 7
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Dunning, K. K., Adjei, S., Levin, L., Rohs, A. M., Hilbert, T., Borton, E., Kapil, V., Rice, C., Lemasters, G. K., Lockey, J. E. (2012). Mesothelioma
associated with commercial use of vermiculite containing Libby amphibole. Journal of Occupational and Environmental Medicine 54(2012):1359-1363.
Chronic obstructive pulmonary disease
Mortality: Mortality from chronic obstructive pulmonary disease; Lung/Respiratory: Mortality from chronic obstructive pulmonary disease
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Not specified: 1332-21-4; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7;
Asbestos - Tremolite: 14567-73-8
ID(s): No linked references.
1066036
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Analyses use cumulative fiber exposure. Additional details about exposure measurement
are reported in Lockey et al., 1984, HEROID 29685. Samples were collected via mem-
brane filters either by following an employee with a sampler (from 1972-1976) or by
breathing zone sampling (after 1976). Authors note that exposure of fiber was defined as
"particles with a length greater than 5 um, a diameter less than 3 um, and an aspect ra-
tio of 3:1 or greater". Thus, fiber type was unknown, and samples likely included fibers
other than asbestos. Samples were reviewed through polarized light microscopy, scan-
ning electron microscopy, and TEM. Indexes were created for each department within
the facility. Study authors used work histories reported by workers in 1980 to calcu-
late the cumulative fiber exposure level for each employee. Previous estimates were
revised to include additional data related to exposure collected in 2010, such as adjust-
ments for vermiculite source and changes in duration of work by season (Borton et al.,
2012, HEROID 1066035). Borton et al. also estimated exposures from 1957-1971 us-
ing estimates from 1972 with adjustments for dustier historical conditions. This study
also reported comparisons between personal and area samples and found approximately
equal means and ranges.
Metric 5: Exposure Levels Low For SMR analyses of chronic obstructive pulmonary disease, exposure is presented in
two groups only (exposed workers vs. unexposed general population). Authors note the
possibility that associations were not observed due to the low exposure levels among
the study population, which raises some concern about the influence of the exposure
distribution on the ability to detect an effect.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.This retrospective occupational cohort study examined the association between asbestos exposure and chronic obstructive pulmonary disease
mortality among workers mining and milling contaminated vermiculite. There were concerns about the limited number of observed chronic obstructive
pulmonary disease cases in the study population (n=8) and the ability to detect an effect with a cohort of this sample size. Additionally, there were concerns
with the lack of consideration of co-exposures and the limited exposure distributions among the study population. Otherwise, the approach for exposure
measurement and statistical analysis was strong, and there were no concerns about selection bias resulting from population recruitment approaches.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 240 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1066036 Table: 5 of 7
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Dunning, K. K., Adjei, S., Levin, L., Rohs, A. M., Hilbert, T., Borton, E., Kapil, V., Rice, C., Lemasters, G. K., Lockey, J. E. (2012). Mesothelioma
associated with commercial use of vermiculite containing Libby amphibole. Journal of Occupational and Environmental Medicine 54(2012):1359-1363.
Asbestosis
Mortality: Asbestosis mortality; Lung/Respiratory: Asbestosis mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Not specified: 1332-21-4; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7;
Asbestos - Tremolite: 14567-73-8
No linked references.
1066036
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Analyses use cumulative fiber exposure. Additional details about exposure measurement
are reported in Lockey et al., 1984, HEROID 29685. Samples were collected via mem-
brane filters either by following an employee with a sampler (from 1972-1976) or by
breathing zone sampling (after 1976). Authors note that exposure of fiber was defined as
"particles with a length greater than 5 um, a diameter less than 3 um, and an aspect ra-
tio of 3:1 or greater". Thus, fiber type was unknown, and samples likely included fibers
other than asbestos. Samples were reviewed through polarized light microscopy, scan-
ning electron microscopy, and TEM. Indexes were created for each department within
the facility. Study authors used work histories reported by workers in 1980 to calcu-
late the cumulative fiber exposure level for each employee. Previous estimates were
revised to include additional data related to exposure collected in 2010, such as adjust-
ments for vermiculite source and changes in duration of work by season (Borton et al.,
2012, HEROID 1066035). Borton et al. also estimated exposures from 1957-1971 us-
ing estimates from 1972 with adjustments for dustier historical conditions. This study
also reported comparisons between personal and area samples and found approximately
equal means and ranges.
Metric 5: Exposure Levels Low For SMR analyses of asbestosis, exposure is presented in two groups only (exposed
workers vs. unexposed general population). Authors note the possibility that associ-
ations were not observed due to the low exposure levels among the study population,
which raises some concern about the influence of the exposure distribution on the ability
to detect an effect.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.This retrospective occupational cohort study examined the association between asbestos exposure and asbestosis mortality among workers mining
and milling contaminated vermiculite. There were concerns about the limited number of observed asbestosis cases in the study population (n=l) and the
ability to detect an effect with a cohort of this sample size. Additionally, there were limited exposure distributions among the study population. Otherwise,
the approach for exposure measurement and statistical analysis was strong, and there were no concerns about selection bias resulting from population
recruitment approaches.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 241 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1066036 Table: 6 of 7
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Dunning, K. K., Adjei, S., Levin, L., Rohs, A. M., Hilbert, T., Borton, E., Kapil, V., Rice, C., Lemasters, G. K., Lockey, J. E. (2012). Mesothelioma
associated with commercial use of vermiculite containing Libby amphibole. Journal of Occupational and Environmental Medicine 54(2012):1359-1363.
Other respiratory disease
Mortality: Mortality from other respiratory disease; Lung/Respiratory: Mortality from other respiratory disease
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Not specified: 1332-21-4; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7;
Asbestos - Tremolite: 14567-73-8
ID(s): No linked references.
1066036
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Analyses use cumulative fiber exposure. Additional details about exposure measurement
are reported in Lockey et al., 1984, HEROID 29685. Samples were collected via mem-
brane filters either by following an employee with a sampler (from 1972-1976) or by
breathing zone sampling (after 1976). Authors note that exposure of fiber was defined as
"particles with a length greater than 5 um, a diameter less than 3 um, and an aspect ra-
tio of 3:1 or greater". Thus, fiber type was unknown, and samples likely included fibers
other than asbestos. Samples were reviewed through polarized light microscopy, scan-
ning electron microscopy, and TEM. Indexes were created for each department within
the facility. Study authors used work histories reported by workers in 1980 to calcu-
late the cumulative fiber exposure level for each employee. Previous estimates were
revised to include additional data related to exposure collected in 2010, such as adjust-
ments for vermiculite source and changes in duration of work by season (Borton et al.,
2012, HEROID 1066035). Borton et al. also estimated exposures from 1957-1971 us-
ing estimates from 1972 with adjustments for dustier historical conditions. This study
also reported comparisons between personal and area samples and found approximately
equal means and ranges.
Metric 5: Exposure Levels Low For SMR analyses of other respiratory diseases, exposure is presented in two groups
only (exposed workers vs. unexposed general population). Authors note the possibility
that associations were not observed due to the low exposure levels among the study
population, which raises some concern about the influence of the exposure distribution
on the ability to detect an effect.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.This retrospective occupational cohort study examined the association between asbestos exposure and other respiratory disease mortality among
workers mining and milling contaminated vermiculite. There were concerns about the limited number of deaths from respiratory diseases in the study
population (n=2) and the ability to detect an effect with a cohort of this sample size. Additionally, there were concerns with the lack of consideration
of co-exposures and the limited exposure distributions among the study population. Otherwise, the approach for exposure measurement and statistical
analysis was strong, and there were no concerns about selection bias resulting from population recruitment approaches.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 242 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1066036 Table: 7 of 7
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Dunning, K. K., Adjei, S., Levin, L., Rohs, A. M., Hilbert, T., Borton, E., Kapil, V., Rice, C., Lemasters, G. K., Lockey, J. E. (2012). Mesothelioma
associated with commercial use of vermiculite containing Libby amphibole. Journal of Occupational and Environmental Medicine 54(2012):1359-1363.
Cancer of the digestive system and peritoneum
Mortality: Mortality from cancer of the digestive system and peritoneum; Cancer/Carcinogenesis: Mortality from cancer of the digestive system and
peritoneum; Gastrointestinal: Mortality from cancer of the digestive system and peritoneum
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Not specified: 1332-21-4; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7;
Asbestos - Tremolite: 14567-73-8
No linked references.
1066036
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Analyses use cumulative fiber exposure. Additional details about exposure measurement
are reported in Lockey et al., 1984, HEROID 29685. Samples were collected via mem-
brane filters either by following an employee with a sampler (from 1972-1976) or by
breathing zone sampling (after 1976). Authors note that exposure of fiber was defined as
"particles with a length greater than 5 um, a diameter less than 3 um, and an aspect ra-
tio of 3:1 or greater". Thus, fiber type was unknown, and samples likely included fibers
other than asbestos. Samples were reviewed through polarized light microscopy, scan-
ning electron microscopy, and TEM. Indexes were created for each department within
the facility. Study authors used work histories reported by workers in 1980 to calcu-
late the cumulative fiber exposure level for each employee. Previous estimates were
revised to include additional data related to exposure collected in 2010, such as adjust-
ments for vermiculite source and changes in duration of work by season (Borton et al.,
2012, HEROID 1066035). Borton et al. also estimated exposures from 1957-1971 us-
ing estimates from 1972 with adjustments for dustier historical conditions. This study
also reported comparisons between personal and area samples and found approximately
equal means and ranges.
Metric 5: Exposure Levels Medium For SMR and SRR analyses of digestive cancers, exposure is presented in three groups
based on cumulative fiber exposure estimates. Authors note the possibility that associ-
ations were not observed due to the low exposure levels among the study population,
which raises some concern about the influence of the exposure distribution on the ability
to detect an effect.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.This retrospective occupational cohort study examined the association between asbestos exposure and digestive and peritoneum cancer mortality
among workers mining and milling contaminated vermiculite. There were no major concerns with the study, aside from the low number of cases, the limited
exposure distributions among the study population and concerns about fibrous co-exposures that were not characterized or quantified. Since these workers
were exposed to fibers that were not asbestos, it can be assumed that these exposures influenced the observed outcomes, but they were not characterized.
The approach for exposure measurement and statistical analysis was strong, and there were no concerns about selection bias resulting from population
recruitment approaches.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 243 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3520580 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence of digestive
cancers and occupational exposure to asbestos. European Journal of Cancer Prevention 11(2002):523-528.
All digestive cancers
Cancer/Carcinogenesis: All digestive cancers; Gastrointestinal: All digestive cancers
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3520580, 3077730, 3078903, 3520549
3520580
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Clin et al. 2011, HERO ID: 3078903 analyzed the risk of cancers among salaried and
retired workers (men and women) from an asbestos reprocessing plant (textiles and fric-
tion materials) in the Calvados department in Normandy, France. Eligibility was based
on: (i) working at the plant for at least 1 year; (ii) being alive in 1978 when the regional
cancer registry was established; (iii) having resided in Calvados during at least part of
the 1978 to 1995 initial follow-up period, with known vital status (de la Provote et al
al. 2002, HERO ID: 3520580). As noted by Clin et al. 2011, HERO ID: 3078903, "...
since one of our inclusion criteria was that subjects had to be alive in 1978, there may be
a selection bias related to the "healthy worker effect"." Including retired workers, how-
ever, would have helped to reduce this bias. The number of workers who did not meet
eligibility criteria was not provided; it is unknown whether a large number of workers of
similar age and employment duration as those in the cohort had cancer diagnoses prior
to 1978, which could bias results. The factories had operated using asbestos in various
capacities since 1928. All cancer cases from 1978 to 1996 were included, resulting in
1820 subjects (1454 men).
High De la Provote et al al. 2002, HERO ID: 3520580 reported that 152 subjects (8.4% ) had
missing vital status at the end of 1995 and were excluded from analysis. It is unclear
why vital status was missing, but given the relatively small share of subjects and that it
would not be expected to be related exposure and outcome make this a limited concern
for bias.
Medium In calculating relative risk for cancers, workers with varying concentrations of exposures
were compared amongst each other. There is no indication that groups were similar, but
there is no indication of healthy worker effect.
Domain 2: Exposure Characterization
Continued on next page .
Page 244 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3520580 Table: 1 of 2
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence of digestive
cancers and occupational exposure to asbestos. European lournal of Cancer Prevention 11(2002):523-528.
All digestive cancers
Cancer/Carcinogenesis: All digestive cancers; Gastrointestinal: All digestive cancers
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3520580, 3077730, 3078903, 3520549
3520580
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Medium
Metric 5: Exposure Levels
Medium
Metric 6: Temporality
High
Exposure estimates were assigned to individuals based on job functions and timing/
duration of employment and fiber count measures. As described by de la Provote et
al. 2002, HERO ID: 3520580, fiber counts were measured at different locations in the
plant as follows: (i) 1973 -1995 data were collected by Casella pumps on a membrane
filter, with PCM (phase-contrast light microscopy) counts of fibers longer than 5jU m,
less than 3jU m in diameter, with a length/diameter ratio greater than 3; (ii) 1960-1974
data were collected on soluble filters by an ARM (Avy"Raillere"Martin) apparatus,
with light microscopy fiber counts as particles per liter of air; and (iii) estimates prior to
1959/1960 were based on production reports for 1939-1945 [50% of 1960 levels], lin-
early extrapolated to 1960. Date cutoffs differed slightly across manuscripts [e.g. ARM
started in 1959 vs 1960 according to Clin et al. 2011, HERO ID: 3078903], Side-by-side
Casella vs. ARM method measures in 1974 were used to develop a conversion factor for
the different methods. A cumulative exposure index (CEI) for the entire career (fibers/
mL * year) was calculated as the sum of exposure * duration for each job position. A
mean exposure concentration (MEC), also referred to as averaged exposure (AEL) was
also calculated and expressed in fibers/mL). Clin et al. 2009, HERO ID: 3520549 and
Boulanger et al. 2017, HERO ID: 3077730 explain these same methods but in lesser de-
tail. Clin et al. 2011, HERO ID: 3078903 uses CEI and AEL exposure categories with a
10-year lag to account for latency.
To estimate cancer risk, only de la Provote et al. 2002, HERO ID: 3520580 categorized
asbestos exposure variables using >=3 ordinal levels. Of note is that only mean cumu-
lative exposure, not cumulative exposure index values were used in adjusted models.In
Clin et al. 2009, HERO ID: 3520549 and Boulanger et al. 2015, HERO ID: 307773,
SIRs are only calculated using 2 exposure categories of cumulative exposure, such as
exposed/unexposed or <= vs > 80 fibers/mL-year, all of which merit a Low rating for
this metric. Because of this, Clin et al. 2009, HERO ID: 3520549 and Boulanger et al.
2015, HERO ID: 307773 are only evaluated for metrics 4 and 5 in this entry.
De la Provote et al. 2002, HERO ID: 3520580 shows that 69% of workers had at least
10 years at work, and 50% had >= 20 years.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Uninformative Other Cancer(s): The outcome is a combination of all digestive cancers, thus meriting an
uninformative rating.
High De la Provote et al. 2002, HERO ID: 3520580 reported findings in the abstract, results,
and discussion sections adequately, where confidence intervals are provided for relative
risk estimates. P-values and numbers of cases were also presented in detail.
Continued on next page ...
Page 245 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3520580 Table: 1 of 2
... continued from previous page
Study Citation: e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence of digestive
cancers and occupational exposure to asbestos. European lournal of Cancer Prevention 11(2002):523-528.
All digestive cancers
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): 3520580, 3077730, 3078903, 3520549
HERO ID: 3520580
Cancer/Carcinogenesis: All digestive cancers; Gastrointestinal: All digestive cancers
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Domain
Metric
Rating
Comments
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Low De la Provote et al. 2002, HERO ID: 3520580 adjusted models for age at recruitment,
latency (time dependent) and years at the company, but not sex. Data on smoking were
not available. Race was not discussed, although it is likely that the population was
largely white.
Medium Information on covariates was obtained from the company's occupational health depart-
ment records.
Low There was no discussion of coexposures at these factories.
Domain 5: Analysis
Metric
12:
Study Design and Methods
Medium
De la Provote et al. 2002, HERO ID: 3520580 used a Cox hazard model to analyze
the dose-response relationship of occupational asbestos exposure (mean cumulative
exposure only) and risk of digestive cancer.
Metric
13:
Statistical Power
Medium
De la Provote et al. 2002, HERO ID: 3520580 likely has adequate power to detect an
association (total n=1820, n cases=56).
Metric
14:
Reproducibility of Analyses
Medium
The descriptions of analyses are clear and sufficiently well-written to conceptually re-
produce analyses.
Metric
15:
Statistical Analysis
Medium
The authors describe appropriate methods and note that the assumption of proportional
hazards was checked graphically.
Additional Comments: Note that only De la Provote et al. 2002, HERO ID: 3520580 was evaluated for all metrics. The only outcome evaluated here is all digestive cancers. In
Clin et al. 2009, HERO ID: 3520549 and Boulanger et al. 2015, HERO ID: 307773, SIRs are only calculated using 2 exposure categories of cumulative
exposure, such as exposed/unexposed or <= vs > 80 fibers/mL-year, meaning these studies were not evaluated for this outcome.
Overall Quality Determination Uninformative
* No biomarkers were identified for this evaluation.
Page 246 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3520580 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence of digestive
cancers and occupational exposure to asbestos. European lournal of Cancer Prevention ll(2002):523-528.
Lung Cancer; colorectal, prostate, skin cancer, ear/nose/throat (ENT) cancer, bladder and kidney cancer, esophageal cancer, female genital tract cancer
Gastrointestinal: Colon-rectum cancer, Esophagus cancer; Cancer/Carcinogenesis: Colon-rectum cancer, Esophagus cancer, Prostate cancer, Skin can-
cer (excluding basal cell tumors), Ear nose throat (ENT) cancer, Bladder and kidney cancer, Female genital tract cancer, Lung cancer; Reproductive/
Developmental: Prostate cancer, Female genital tract cancer; Skin/Connective Tissue: Skin cancer (excluding basal cell tumors); nan: ; Renal/Kidney:
Bladder and kidney cancer; Lung/Respiratory: Lung cancer
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3520580, 3077730, 3078903, 3520549
3520580
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Clin et al. 2011, HERO ID: 3078903 analyzed the risk of cancers among salaried and
retired workers (men and women) from an asbestos reprocessing plant (textiles and fric-
tion materials) in the Calvados department in Normandy, France. Eligibility was based
on: (i) working at the plant for at least 1 year; (ii) being alive in 1978 when the regional
cancer registry was established; (iii) having resided in Calvados during at least part of
the 1978 to 1995 initial follow-up period, with known vital status (de la Provote et al
al. 2002, HERO ID: 3520580). As noted by Clin et al. 2011, HERO ID: 3078903, "...
since one of our inclusion criteria was that subjects had to be alive in 1978, there may be
a selection bias related to the "healthy worker effect"." Including retired workers, how-
ever, would have helped to reduce this bias. The number of workers who did not meet
eligibility criteria was not provided; it is unknown whether a large number of workers of
similar age and employment duration as those in the cohort had cancer diagnoses prior
to 1978, which could bias results. The factories had operated using asbestos in various
capacities since 1928. All cancer cases from 1978 to 2004 were included, resulting in
2024 subjects (1604 men).
High Clin et al. 2011, HERO ID: 3078903 reported that 107 subjects (5.3% ) had missing
vital status at the end of 2004 and were excluded from analysis. It is unclear why vital
status was missing, but given the relatively small share of subjects and that it would not
be expected to be related exposure and outcome make this a limited concern for bias.
Medium In calculating relative risk for cancers, workers with varying concentrations of exposures
were compared amongst each other. There is no indication that groups were similar, but
there is no indication of healthy worker effect.
Domain 2: Exposure Characterization
Continued on next page .
Page 247 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3520580 Table: 2 of 2
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence of digestive
cancers and occupational exposure to asbestos. European lournal of Cancer Prevention ll(2002):523-528.
Lung Cancer; colorectal, prostate, skin cancer, ear/nose/throat (ENT) cancer, bladder and kidney cancer, esophageal cancer, female genital tract cancer
Gastrointestinal: Colon-rectum cancer, Esophagus cancer; Cancer/Carcinogenesis: Colon-rectum cancer, Esophagus cancer, Prostate cancer, Skin can-
cer (excluding basal cell tumors), Ear nose throat (ENT) cancer, Bladder and kidney cancer, Female genital tract cancer, Lung cancer; Reproductive/
Developmental: Prostate cancer, Female genital tract cancer; Skin/Connective Tissue: Skin cancer (excluding basal cell tumors); nan: ; Renal/Kidney:
Bladder and kidney cancer; Lung/Respiratory: Lung cancer
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3520580, 3077730, 3078903, 3520549
3520580
Domain
Metric
Rating
Comments
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Exposure estimates were assigned to individuals based on job functions and timing/
duration of employment and fiber count measures. As described by de la Provote et
al. 2002, HERO ID: 3520580, fiber counts were measured at different locations in the
plant as follows: (i) 1973 -1995 data were collected by Casella pumps on a membrane
filter, with PCM (phase-contrast light microscopy) counts of fibers longer than 5[i m,
less than 3n m in diameter, with a length/diameter ratio greater than 3; (ii) 1960-1974
data were collected on soluble filters by an ARM (Avy"Raillere"Martin) apparatus,
with light microscopy fiber counts as particles per liter of air; and (iii) estimates prior to
1959/1960 were based on production reports for 1939-1945 [50% of 1960 levels], lin-
early extrapolated to 1960. Date cutoffs differed slightly across manuscripts [e.g. ARM
started in 1959 vs 1960 according to Clin et al. 2011, HERO ID: 3078903], Side-by-side
Casella vs. ARM method measures in 1974 were used to develop a conversion factor for
the different methods. A cumulative exposure index (CEI) for the entire career (fibers/
mL * year) was calculated as the sum of exposure * duration for each job position. A
mean exposure concentration (MEC), also referred to as averaged exposure (AEL) was
also calculated and expressed in fibers/mL). Clin et al. 2009, HERO ID: 3520549 and
Boulanger et al. 2017, HERO ID: 3077730 explain these same methods but in lesser de-
tail. Clin et al. 2011, HERO ID: 3078903 uses CEI and AEL exposure categories with a
10-year lag to account for latency.
Medium To estimate cancer risk, only Clin et al. 2011, HERO ID: 3078903 categorized asbestos
exposure variables using 3 ordinal levels.In Clin et al. 2009, HERO ID: 3520549 and
Boulanger et al. 2015, HERO ID: 307773, SIRs are only calculated using 2 exposure
categories of cumulative exposure, such as exposed/unexposed or <= vs > 80 fibers/
mL-year, all of which merit a Low rating for this metric. In de la Provote et al. 2002,
HERO ID: 3520580, only the "All digestive cancers" outcomes in analyzed with more
than dichotomous exposure categories, but is evaluated in a different entry because
the outcome is rated differently. All other outcomes in that study have dichotomous
exposure categories. Because of this, de la Provote et al. 2002, HERO ID: 3520580, Clin
et al. 2009, HERO ID: 3520549, and Boulanger et al. 2015, HERO ID: 307773, are only
evaluated for metrics 4 and 5 in this entry.
High While Clin et al. 2011, HERO ID: 3078903 gives limited detail on temporality, de la
Provote et al. 2002, HERO ID: 3520580 shows that 69% of workers had at least 10 years
at work, and 50% had >= 20 years.
Domain 3: Outcome Assessment
Continued on next page .
Page 248 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3520580 Table: 2 of 2
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence of digestive
cancers and occupational exposure to asbestos. European lournal of Cancer Prevention ll(2002):523-528.
Lung Cancer; colorectal, prostate, skin cancer, ear/nose/throat (ENT) cancer, bladder and kidney cancer, esophageal cancer, female genital tract cancer
Gastrointestinal: Colon-rectum cancer, Esophagus cancer; Cancer/Carcinogenesis: Colon-rectum cancer, Esophagus cancer, Prostate cancer, Skin can-
cer (excluding basal cell tumors), Ear nose throat (ENT) cancer, Bladder and kidney cancer, Female genital tract cancer, Lung cancer; Reproductive/
Developmental: Prostate cancer, Female genital tract cancer; Skin/Connective Tissue: Skin cancer (excluding basal cell tumors); nan: ; Renal/Kidney:
Bladder and kidney cancer; Lung/Respiratory: Lung cancer
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3520580, 3077730, 3078903, 3520549
3520580
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
High Lung Cancer: In Clin et al. 2011, HERO ID: 3078903, lung cancer incidence outcomes
were characterized by histology in a cancer registry: "The incidence of cancer was ac-
cordingly estimated for each anatomical cancer site (ICD-O 3 coding). Only primary
cancers were taken into account in our study, secondary cancer sites having been ex-
cluded. No subjects presented with secondary cancer at the same site. For subjects pre-
senting with primary cancers at different anatomical sites, each cancer was considered
independently in our analysis." "The table in the online supplementary appendix lists
(ICD-O 3 codes) the number of observed cancers for the entire cohort site by site and
separately for each sex, together with latency (time to diagnosis since first exposure) and
age at diagnosis." At the time of evaluation, the supplemental material was not freely
available and thus cannot be taken into account. However, because cases were diag-
nosed with histologies, this metric is rated High.; Other Cancer(s): In Clin et al. 2011,
HERO ID: 3078903, lung cancer incidence outcomes were characterized by histology in
a cancer registry: "The incidence of cancer was accordingly estimated for each anatom-
ical cancer site (ICD-O 3 coding). Only primary cancers were taken into account in our
study, secondary cancer sites having been excluded. No subjects presented with sec-
ondary cancer at the same site. For subjects presenting with primary cancers at different
anatomical sites, each cancer was considered independently in our analysis." "The table
in the online supplementary appendix lists (ICD-O 3 codes) the number of observed can-
cers for the entire cohort site by site and separately for each sex, together with latency
(time to diagnosis since first exposure) and age at diagnosis." At the time of evalua-
tion, the supplemental material was not freely available and thus cannot be taken into
account. However, because cases were diagnosed with histologies, this metric is rated
High.
High Clin et al. 2011, HERO ID: 3078903 reported findings in the abstract, results, and dis-
cussion sections adequately, where confidence intervals are provided for relative risk
estimates. P-values and numbers of cases were also presented in detail.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment High Clin et al. 2011, HERO ID: 3078903 adjusted models by sex and age (time dependent).
Data on smoking were not available. Race was not discussed, although it is likely that
the population was largely white.
Metric 10: Covariate Characterization Medium Information on covariates was obtained from the company's occupational health depart-
ment records.
Metric 11: Co-exposure Counfounding Low There was no discussion of coexposures at these factories.
Continued on next page ...
Page 249 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3520580 Table: 2 of 2
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
e La Provote, S., Desoubeaux, N., Paris, C., Letourneux, M., Raffaelli, C., Galateau-Salle, F., Gignoux, M., Launoy, G. (2002). Incidence of digestive
cancers and occupational exposure to asbestos. European lournal of Cancer Prevention ll(2002):523-528.
Lung Cancer; colorectal, prostate, skin cancer, ear/nose/throat (ENT) cancer, bladder and kidney cancer, esophageal cancer, female genital tract cancer
Gastrointestinal: Colon-rectum cancer, Esophagus cancer; Cancer/Carcinogenesis: Colon-rectum cancer, Esophagus cancer, Prostate cancer, Skin can-
cer (excluding basal cell tumors), Ear nose throat (ENT) cancer, Bladder and kidney cancer, Female genital tract cancer, Lung cancer; Reproductive/
Developmental: Prostate cancer, Female genital tract cancer; Skin/Connective Tissue: Skin cancer (excluding basal cell tumors); nan: ; Renal/Kidney:
Bladder and kidney cancer; Lung/Respiratory: Lung cancer
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3520580, 3077730, 3078903, 3520549
3520580
Domain
Metric
Rating
Comments
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium Clin et al. 2011, HERO ID: 3078903 used a Cox hazard model to analyze the dose-
response relationship of occupational asbestos exposure and risk of cancer.
Medium Clin et al. 2011, HERO ID: 3078903 likely has adequate power to detect an association
(total n=2024), with the cancer having the fewest cases being for female genital tract
cancer (n=15).
Medium The descriptions of analyses are clear and sufficiently well-written to conceptually re-
produce analyses.
Medium The authors describe appropriate methods, including using exposure lags, categorizing
exposure to avoid assumptions of linearity, and examining alternative time scales in Cox
models.
Additional Comments: Note that for de la Provote et al. 2002, HERO ID: 3520580, Clin et al. 2009, HERO ID: 3520549 and Boulanger et al. 2015, HERO ID: 307773, SIRs are
only calculated using 2 exposure categories of cumulative exposure, such as exposed/unexposed or <= vs > 80 fibers/mL-year, all of which merit a Low
rating for this metric. Because of this, de la Provote et al. 2002, HERO ID: 3520580, Clin et al. 2009, HERO ID: 3520549, and Boulanger et al. 2015,
HERO ID: 307773 are only evaluated for metrics 4 and 5, and QC was not performed for any other metrics. Only Clin et al. 2011, HERO ID: 3078903
was evaluated for all metrics. The only outcomes evaluated here are lung, colorectal, prostate, skin, ear/nose/throat (ENT), bladder and kidney, esophageal,
female genital tract cancers.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 250 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709723 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Ehrlich, R., Lilis, R., Chan, E., Nicholson, W. J., Selikoff, I. J. (1992). Long term radiological effects of short term exposure to amosite asbestos among
factory workers. British Journal of Industrial Medicine 49(1992):268-275.
Asbestosis
Lung/Respiratory: parenchymal abnormality, pleural abnormality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
709723
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Metric 5:
Measurement of Exposure
Exposure Levels
Low
Low
Exposure was estimated on professional judgement by using information on job tile and
duration of service for each subject. The fibre count estimates were used to derive the
average fibre concentration and cumulative exposure for each subject.
Range of exposure in the population is limited. The estimated counts ranged from 5
fibres/ml among office workers, to 120 fibres/ml among disintegrator operators.
Additional Comments: This is an occupational study with no appropriate mention of the comparison group. It looks for parenchymal and pleural abnormalities and asbestosis
among factory workers.Overall, the measurement of exposure metric (M4) methods used to quantify the exposure were not well defined. Additionally, the
exposure levels metric (M5) information reported was not adequate to determine an exposure-response relationship.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 251 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3077968 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Eisenhawer, C., Felten, M. K., Tamm, M., Das, M., Kraus, T. (2014). Radiological surveillance of formerly asbestos-exposed power industry workers:
rates and risk factors of benign changes on chest X-ray and MDCT. Journal of Occupational Medicine and Toxicology 918.
Asbestosis; Pleural Plaques; Diffuse pleural thickening, parenchymal or pleural changes
Lung/Respiratory: Asbestosis, Pleural plaques, Diffuse pleural thickening, Parenchymal or pleural changes
Asbestos - Not specified: 1332-21-4
ID(s): 3077968, 2584064
3077968
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low This study or any cited methods source does not explicitly mention the use of PCM or
TEM.Individual cumulative exposure level was determined by self-reported job history
and periods of exposure using a computer program based on ambient air monitoring
data of asbestos concentration, recall bias is likely to be present. The measurement and
quantifying methods were not specified. There is little information about exposure mea-
surement and mainly based on professional judgement. Exposure misclassification is
likely to exist according to the exposure measurement methods.Study cites another pa-
per (Felten et al., 2010, 2584064) that discusses ambient asbestos measuring techniques
with no indication of the use of PCM/TEM to measure fibers: "The ambient monitor-
ing data used in the report covered a period of four decades from the beginning of the
1950s until 1990. In the 1970s, the original technique of konimetrical measurements
was gradually replaced with membrane filter techniques applying a defined airflow. Both
methods were not specific for asbestos fibres. That deficit was overcome by combining
membranous filtering systems with the microscopical count of fibres."
Metric 5: Exposure Levels Medium The distribution of cumulative exposure level is sufficient to develop an exposure-
outcome estimate. The study used 3 levels of exposure.
Additional Comments: The main concern of this group of studies is exposure measurement, which is based on computer program and self-reported work history, could introduce
exposure misclassification to the analysis. In addition, high attrition plus missing exposure values could impact the accuracy of the results.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 252 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3080472 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Elci, O. C., Akpinar-Elci, M., Blair, A., Dosemeci, M. (2002). Occupational dust exposure and the risk of laryngeal cancer in Turkey. Scandinavian Journal
of Work, Environment and Health 28(2002):278-284.
Laryngeal Cancer; Supraglottic cancer, glottic cancer, other cancers
Throat: All laryngeal cancers, Supraglottic cancer, Glottic cancer; Cancer/Carcinogenesis: Supraglottic cancer, All laryngeal cancers, Other cancers,
Glottic cancer
Asbestos - Not specified: 1332-21-4
No linked references.
3080472
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Uninformative
Medium
This is marked as uninformative because there were no quantitative measure or estimate
of exposure. Study does not discuss any use of fibre measurements. Authors discuss
using a job-exposure matrix but provide no quantitative measures for this.
Job matrix exposure levels are provided by exposure intensity (low, medium, and high)
and exposure probability levels (low, medium, and high).
Additional Comments:
This study not evaluated for any metrics except Metric 4 and 5 and had no data extracted because it did not have sufficient exposure information to be
useful for dose-response analysis.Overall, The Measurement of Exposure Metric 4 (M4) is Uninformative for this Study.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessment for the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 253 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 5029590 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Farioli, A., Straif, K., Brandi, G., Curti, S., Kjaerheim, K., Martinsen, J. I., Sparen, P., Tryggvadottir, L., Weiderpass, E., Biasco, G. (2018). Occupational
exposure to asbestos and risk of cholangiocarcinoma: a population-based case-control study in four Nordic countries. Occupational and Environmental
Medicine 75(2018):191-198.
Cholangiocarcinoma
Cancer/Carcinogenesis: Cholangiocarcinoma, Intrahepatic cholangiocarcinoma, Extrahepatic cholangiocarcinoma; Hepatic/Liver: Cholangiocarcinoma,
Intrahepatic cholangiocarcinoma, Extrahepatic cholangiocarcinoma
Asbestos - Not specified: 1332-21-4
ID(s): 5029590,6875563
5029590
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated low because the study or any cited methods sources do not explicitly
mention the use of PCM or TEM (Farioli et al., 2018, 5029590). Exposure in this study
was estimated using a generic job-exposure matrix that was specifically developed for
this cohort, but did not include personal measurements based on PCM or TEM (Kaup-
pinen et al., 2009, 699236).
Medium A range of exposure levels are reported within the paper. The levels of maximum inten-
sity of exposure reported include 0 f/mL, <0.11 f/mL, 0.11-0.79 f/mL, >/=0.80 f/mL
(Farioli et al., 2018, 5029590). In Farioli et al. (2017, 5029590), the study reports cumu-
lative exposure split into groups of 0 f/mL x years, 0.1-4.9 f/mL x years, 5.0-9.9 f/mL x
years, 10.0-14.0 f/mL x years, and greater than or equal to 15.0 f/mL x years.
Additional Comments: This study was not fully evaluated because metric 4 was rated as low. Neither this study nor any cited sources papers explicitly mentioned the use of PCM
or TEM.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 254 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2248137 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Finkelstein, M. (1986). Pulmonary function in asbestos cement workers: a dose-response study. British Journal of Industrial Medicine 43(1986):406-413.
Pulmonary Function/Spirometry Results
Lung/Respiratory: FVC, FEV1, FEV1/FVC, FVC% , FEV1% , TLC, DLCO (mL/min/mmHg), DLCO (% predicted), KCO (mL/min/mmHg)
Asbestos - Not specified: 1332-21-4
HERO ID:
2248137
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low Exposure was measured using personal membrane filters. Authors assumed a fixed pro-
portion of workplace air concentrations deposited in the lungs of each subject, and each
year's accumulation was weighted by residence time in lung tissue. Asbestos dosages
were calculated as fibers/mL*years squared (yA 2). Authors note that exposure assess-
ment methods involved extrapolation, and that cumulative exposure values had been
previously estimated to within a factor of 3-5.
Medium Exposure distribution is not explicitly reported in text or table format, but is indicated
by scatterplot (Figure 2). Asbestos doses (f/mL*yA 2) appeared to vary from <500 to
nearly 8,000. Exposure was assessed as a continuous, quantitative variable.
Additional Comments: None
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 255 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081283 Table: 1 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Finkelstein, M. M. (1997). Radiographic asbestosis is not a prerequisite for asbestos-associated lung cancer in Ontario asbestos-cement workers. American
Journal of Industrial Medicine 32(1997):341-348.
Lung Cancer
Cancer/Carcinogenesis: lung cancer mortality; Lung/Respiratory: lung cancer mortality; Mortality: lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3081283
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Authors state that estimates of exposure were calculated through the use of a "model that
extrapolated measurements made by the personal membrane filter" and did not utilize
PCM or TEM. There appears to be a contradiction in time in that the personal membrane
filters was utilized by the industrial in 1969 (21 years after the plant opened in 1948).
The cohort includes workers hired prior to 1960 so it is unclear what exposure data was
used for workers who had worked for there before 1969.
Medium Estimates of 18-year cumulative exposure since first exposure is provided in Table 2 and
Figure 1 in fiber-years/ml for 5 groups.
Additional Comments: Majority of analyses were conducted to assess the lung cancer risk among those with and without asbestosis.2/6/2023 UPDATE: DUE TO CHANGES
IN THE GUIDANCE FOR SQE, ALL METRICS RATINGS EXCEPT FOR 4 AND 5 SHOULD BE IGNORED BECAUSE METRIC 4 WAS RATED
"LOW".
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 256 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081283 Table: 2 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Finkelstein, M. M. (1997). Radiographic asbestosis is not a prerequisite for asbestos-associated lung cancer in Ontario asbestos-cement workers. American
Journal of Industrial Medicine 32(1997):341-348.
digestive
Cancer/Carcinogenesis: digestive cancer mortality; Gastrointestinal: digestive cancer mortality; Mortality: digestive cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3081283
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Authors state that estimates of exposure were calculated through the use of a "model that
extrapolated measurements made by the personal membrane filter" and did not utilize
PCM or TEM. There appears to be a contradiction in time in that the personal membrane
filters was utilized by the industrial in 1969 (21 years after the plant opened in 1948).
The cohort includes workers hired prior to 1960 so it is unclear what exposure data was
used for workers who had worked there before 1969.
Medium Estimates of 18-year cumulative exposure since first exposure is provided in Table 2 and
Figure 1 in fiber-years/ml for 5 groups.
Additional Comments: 2/6/2023 UPDATE: DUE TO CHANGES IN THE GUIDANCE FOR SQE, ALL METRICS RATINGS EXCEPT FOR 4 AND 5 SHOULD BE IGNORED
BECAUSE METRIC 4 WAS RATED "LOW".
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 257 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081283 Table: 3 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Finkelstein, M. M. (1997). Radiographic asbestosis is not a prerequisite for asbestos-associated lung cancer in Ontario asbestos-cement workers. American
Journal of Industrial Medicine 32(1997):341-348.
circulatory disease, respiratory disease, pneumoconiosis
Mortality: all causes mortality, all malignancies mortality, respiratory disease mortality, pneumoconiosis mortality, Pleural mesothelioma mortality, circu-
latory disease mortality; Cardiovascular: circulatory disease mortality; Lung/Respiratory: respiratory disease mortality, pneumoconiosis mortality, Pleural
mesothelioma mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3081283
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Authors state that estimates of exposure were calculated through the use of a "model that
extrapolated measurements made by the personal membrane filter" and did not utilize
PCM or TEM. There appears to be a contradiction in time in that the personal membrane
filters was utilized by the industrial in 1969 (21 years after the plant opened in 1948).
The cohort includes workers hired prior to 1960 so it is unclear what exposure data was
used for workers who had worked for there before 1969.
Metric 5: Exposure Levels Medium Estimates of 18-year cumulative exposure since first exposure is provided in Table 2 and
Figure 1 in fiber-year/ml for 5 groups.
Additional Comments: While pleural mesothelioma is a reported outcome for Table 1, it did not seem to warrant a standalone data evaluation due to the lack of available findings.2/
6/2023 UPDATE: DUE TO CHANGES IN THE GUIDANCE FOR SQE, ALL METRICS RATINGS EXCEPT FOR 4 AND 5 SHOULD BE IGNORED
BECAUSE METRIC 4 WAS RATED "LOW".
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 258 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083612 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Finkelstein, M. M. (1984). Mortality among employees of an Ontario asbestos-cement factory. American Review of Respiratory Disease 129(1984):754-
761.
overall mortality, non-malignant respiratory disease mortality, and ischemic heart disease mortality
Mortality: overall mortality, non-malignant respiratory disease mortality, ischemic heart disease mortality; Lung/Respiratory: non-malignant respiratory
disease mortality; Cardiovascular: ischemic heart disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3083612
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM. The estimated average cumulative exposure of
the production workers was about 60 fiber-years/mL (chrysotile and crocidolite). The
estimated mean cumulative exposure within the board shop, in which chrysotile was the
sole asbestos type utilized, was 39 f-y/mL. Air sampling data from government, insur-
ance and company hygienists initiated in late 1969 were utilized along with company
employment records to classify each production worker (n=186) according to estimated
annual cumulative asbestos exposure as described within Finkelstein et al., 1983 (HERO
ID 3100548), which also referenced Finkelstein, 1982 (HERO ID 76). Microscopic
method of fiber analysis (PCM or TEM) was not detailed in main or referenced text. Air
sampling data was obtained from only later factory years (late 1969 onward) and was
not representative of earlier years, although assumptions for exposure levels for those
earlier years were supported by impinger area sampling data. Air sampling data from
government, insurance and company hygienists initiated in late 1969 were utilized along
with company employment records to classify each production worker (n=186) accord-
ing to estimated annual cumulative asbestos exposure as described within Finkelstein
et al., 1983 (HERO ID 3100548) and Finkelstein, 1982 (HERO ID 76). Eighteen-year
cumulative exposures were calculated for the production workers (Table 7) by combin-
ing work histories and exposure estimates, with job-related exposures multiplied by the
time spent at each job and summed over the 18 years from first exposure. Workers were
assigned to an exposure category according to their 18-year exposure totals. Exposures
were assumed to have been unchanged from 1962 to 1970, to have been 30% higher
from 1955 to 1961, and to have been twice as high from 1948 to 1954, with assumptions
supported by impinger area sampling performed 1949 through the 1960"s. Raw mate-
rials in the production worker pipe manufacturing process included cement, silica and
both chrysotile and crocidolite asbestos, while the asbestos cement board production
utilized chrysotile asbestos only. Comparison control workers were primarily within the
rock wool/fiberglass insulation production area, although authors noted it was possible
for employees to be assigned to the pipe shop for brief clean-up duties, or re-assigned
from non-asbestos to asbestos work areas, such that some control workers were exposed
as well. Exposures for maintenance workers were not calculated due to inadequate data.
Metric 5: Exposure Levels Medium The range and distribution of asbestos exposure in Table 7 presented across five expo-
sure categories ranging from <=30 fiber-years/ML through >150 fiber-years/mL for
production workers is sufficient to develop an exposure-response estimate.
Continued on next page ...
Page 259 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083612 Table: 1 of 2
... continued from previous page
Finkelstein, M. M. (1984). Mortality among employees of an Ontario asbestos-cement factory. American Review of Respiratory Disease 129(1984):754-
761.
overall mortality, non-malignant respiratory disease mortality, and ischemic heart disease mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: overall mortality, non-malignant respiratory disease mortality, ischemic heart disease mortality; Lung/Respiratory: non-malignant respiratory
disease mortality; Cardiovascular: ischemic heart disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3083612
Domain
Metric
Rating
Comments
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-
response analysis.NOTE: This study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM
or TEM was mentioned in the study or a cited source.Within this retrospective cohort study, mortality among asbestos exposed (n=535, production and
maintenance workers) and control (n=205) male employees (total n=740) of an asbestos cement pipe manufacturing factory with a minimum of one year
employment who had been hired prior to 1960 was compared with mortality of the Ontario, Canada male general population over a period of 10 to 34 years
of follow-up. Workers were divided into three groups for study: production workers involved in asbestos cement pipe manufacture, maintenance workers,
and those involved in rock wool and fiberglass insulation or other minimal exposure areas who were classified as non-exposed controls. Factory production
of asbestos cement pipe in one shed and rock wool (later fiberglass) insulation in another shed began in 1948, and asbestos cement board was produced in
a separate building from 1955 to 1970. Air sampling data from government, insurance and company hygienists initiated in late 1969 were utilized along
with company employment records to classify each production worker (n=186) according to estimated annual cumulative asbestos exposure. Air sampling
data was obtained from only later factory years (late 1969 onward) and was not representative of earlier years, although assumptions for exposure levels for
those earlier years were supported by impinger area sampling data. In the period 20 years from first exposure, the production workers had a standardized
mortality ratio of 181 for all causes of death, 320 for non-malignant respiratory disease, and 58 for ischemic heart disease.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 260 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083612 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Finkelstein, M. M. (1984). Mortality among employees of an Ontario asbestos-cement factory. American Review of Respiratory Disease 129(1984):754-
761.
Lung Cancer; gastrointestinal cancer
Lung/Respiratory: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Gastrointestinal cancer; Mortality: Lung cancer mortality,
Gastrointestinal cancer; Gastrointestinal: Gastrointestinal cancer
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3083612
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low This metric is rated Low because the study or any cited methods source does not ex-
plicitly mention the use of PCM or TEM.The estimated average cumulative exposure of
the production workers was about 60 fiber-years/mL (chrysotile and crocidolite). The
estimated mean cumulative exposure within the board shop, in which chrysotile was the
sole asbestos type utilized, was 39 f-y/mL. Air sampling data from government, insur-
ance and company hygienists initiated in late 1969 were utilized along with company
employment records to classify each production worker (n=186) according to estimated
annual cumulative asbestos exposure as described within Finkelstein et al., 1983 (HERO
ID 3100548), which also referenced Finkelstein, 1982 (HERO ID 76). Microscopic
method of fiber analysis (PCM or TEM) was not detailed in main or referenced text. Air
sampling data was obtained from only later factory years (late 1969 onward) and was
not representative of earlier years, although assumptions for exposure levels for those
earlier years were supported by impinger area sampling data. Air sampling data from
government, insurance and company hygienists initiated in late 1969 were utilized along
with company employment records to classify each production worker (n=186) accord-
ing to estimated annual cumulative asbestos exposure as described within Finkelstein
et al., 1983 (HERO ID 3100548) and Finkelstein, 1982 (HERO ID 76). Eighteen-year
cumulative exposures were calculated for the production workers (Table 7) by combin-
ing work histories and exposure estimates, with job-related exposures multiplied by the
time spent at each job and summed over the 18 years from first exposure. Workers were
assigned to an exposure category according to their 18-year exposure totals. Exposures
were assumed to have been unchanged from 1962 to 1970, to have been 30% higher
from 1955 to 1961, and to have been twice as high from 1948 to 1954, with assumptions
supported by impinger area sampling performed 1949 through the 1960"s. Raw mate-
rials in the production worker pipe manufacturing process included cement, silica and
both chrysotile and crocidolite asbestos, while the asbestos cement board production
utilized chrysotile asbestos only. Comparison control workers were primarily within the
rock wool/fiberglass insulation production area, although authors noted it was possible
for employees to be assigned to the pipe shop for brief clean-up duties, or re-assigned
from non-asbestos to asbestos work areas, such that some control workers were exposed
as well. Exposures for maintenance workers were not calculated due to inadequate data.
Metric 5: Exposure Levels Medium The range and distribution of asbestos exposure in Table 7 presented across five expo-
sure categories ranging from <=30 fiber-years/ML through >150 fiber-years/mL for
production workers is sufficient to develop an exposure-response estimate.
Continued on next page ...
Page 261 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083612 Table: 2 of 2
... continued from previous page
Finkelstein, M. M. (1984). Mortality among employees of an Ontario asbestos-cement factory. American Review of Respiratory Disease 129(1984):754-
761.
Lung Cancer; gastrointestinal cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Gastrointestinal cancer; Mortality: Lung cancer mortality,
Gastrointestinal cancer; Gastrointestinal: Gastrointestinal cancer
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3083612
Domain
Metric
Rating
Comments
Additional Comments:
QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.NOTE: this study was not evaluated for any metrics except Metric 4 and 5 and had no data extracted because it did not have sufficient exposure
information to be useful for dose-response analysis. Within this retrospective cohort study, mortality among asbestos exposed (n=535, production and
maintenance workers) and control (n=205) male employees (total n=740) of an asbestos cement pipe manufacturing factory with a minimum of one year
employment who had been hired prior to 1960 was compared with mortality of the Ontario, Canada male general population over a period of 10 to 34 years
of follow-up. Workers were divided into three groups for study: production workers involved in asbestos cement pipe manufacture, maintenance workers,
and those involved in rock wool and fiberglass insulation or other minimal exposure areas who were classified as non-exposed controls. Factory production
of asbestos cement pipe in one shed and rock wool (later fiberglass) insulation in another shed began in 1948, and asbestos cement board was produced in
a separate building from 1955 to 1970. Air sampling data from government, insurance and company hygienists initiated in late 1969 were utilized along
with company employment records to classify each production worker (n=186) according to estimated annual cumulative asbestos exposure. Air sampling
data was obtained from only later factory years (late 1969 onward) and was not representative of earlier years, although assumptions for exposure levels for
those earlier years were supported by impinger area sampling data. In the period 20 years from first exposure, the production workers had a standardized
mortality ratio of 181 for all causes of death, 320 for non-malignant respiratory disease, and 58 for ischemic heart disease.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 262 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3100548 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British lournal of Industrial Medicine
40( 1983): 138-144.
Lung Cancer
Mortality: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality; Lung/Respiratory: Lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3100548
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Medium Key elements of the study design were reported within this retrospective cohort study
of long-term male workers in which n=339 male asbestos workers hired prior to 1960
and employed by the same company in Ontario, Canada for at least nine years were
followed until 31 October 1980 for mortality outcomes of interest. An additional n=ll
men (3.2% of the total) could not be properly classified from their work histories as
production, maintenance or rock wool/fiberglass workers and were excluded from the
current analysis. Participants were identified from company records of all hourly and
salaried employees who had worked at the plant of interest. Employees were excluded
if they did not work for at least nine years to account for the long latency of asbestos-
related diseases and difficulties of tracing short-term employees. There is no evidence
to suggest inclusion or exclusion from the sample differed significantly by outcome or
exposure status.
Low Official death certificates were obtained for all men who had died. However, a total of
five (2.7% ) of the n=186 production workers, three (5.5% ) of the n=55 maintenance
workers and five (5.7% ) of the n=87 unexposed or minimally exposed workers were
unable to be traced for mortality outcomes and were assumed still alive for analysis. A
group of 55 maintenance workers were originally included, but later excluded as the
study reported that it "was not thought possible to estimate exposures for the mainte-
nance men."
Continued on next page ...
Page 263 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 1 of 2
... continued from previous page
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40( 1983): 138-144.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality; Lung/Respiratory: Lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3100548
Domain
Metric
Rating
Comments
Metric 3: Comparison Group
Medium Inclusion criteria and methods of participant selection were reported. Workers within
the rock wool/fiber glass operations (n=87) were classified as minimally exposed, had
mortality described as similar to the general male Ontario population and were utilized
as the comparison control workers. SMR analyses results utilized the age and calendar
specific mortality experience of the male Ontario general population as a comparison
group for expected mortality rates. The mean age at the start of exposure or employment
was described as similar between the exposed and general populations. Comparison
control workers were primarily within the rock wool/fiberglass insulation production
area, although the author of the current study noted in another publication (Finkelstein
et al., 1983, HERO ID 3083612) of workers in the same factory that it was possible
for employees to be assigned to the pipe shop for brief clean-up duties, or re-assigned
from non-asbestos to asbestos work areas, such that some control workers may have
been exposed as well. There is potential for healthy worker effect in terms of left trunca-
tion bias, as the cohort for the current study was restricted to workers with at least nine
years of employment, such that all workers had to survive for at least nine years to be in-
cluded. However, Table 2 SMR results for non-malignant respiratory disease indicate no
evidence of healthy worker effect in terms of the healthy hire or healthy worker survivor
effect.
Domain 2: Exposure Characterization
Continued on next page ...
Page 264 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 1 of 2
... continued from previous page
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40( 1983): 138-144.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality; Lung/Respiratory: Lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3100548
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium The microscopic method (PCM or TEM) of analysis of air sampling data reported in
Table 1 with outcome mortality rates was not detailed. The average estimated cumula-
tive exposure among production workers was reported for three groups of production
workers of 62 men each as 44 f-y/ml, 92 f-y/ml, and 180 f-y/mL (chrysotile and cro-
cidolite). Groups were created on the basis of ranking 18-year cumulative exposures.
Air sampling data from government, insurance and company hygienists initiated in late
1969 was utilized along with company employment records to classify each production
worker"s exposure, however production within the plant began in 1948 and measured
exposures for periods 1948-1970 were lacking and assumed as related to the quantita-
tive measurements made beginning in 1969. Exposures for maintenance workers was
described as not calculated due to inadequate data. Estimated cumulative exposure for
only the first 18 years of employment was utilized such that for men employed less than
18 years this parameter was used and for men employed more than 18 years, the po-
tential exposures after 18 years were excluded. Exposures were assumed to have been
unchanged from 1962 to 1970, to have been 30% higher from 1955 to 1961, and to have
been twice as high from 1948 to 1954, with assumptions supported by impinger area
sampling performed 1949 through the 1960"s. Based on subsequent discussion and
review of additional information, the rating was adjusted based on impinger data was
collected and personal membrane sampling was conducted beginning in late 1969 and
detailed employment records were used to construct exposure histories.
Medium The range and distribution of estimated exposures is reported within Table 1 for pro-
duction workers as 8 to 420 fiber-years/mL. Table 1 provides the mortality rates for
production workers across three groups of exposure categories.
High The study presents an appropriate temporality and the interval between exposure and
outcome is appropriate considering the latency of disease. Workers were required to
have been hired before 1960 and were followed up until 1980, ensuring at least 20 years
of follow-up for the cohort
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High Lung Cancer: ICD code 162 was utilized for lung cancer outcomes on official death
certificates for all men who had died. Additional clinical, pathological and necropsy
reports were available for n=44 of the n=58 deaths among production workers and are
used in analyses of exposure duration, but not of exposure concentration.
Medium There were no concerns for selective reporting. SMR"s in Table 2 and mortality rates
across age and time since first exposure groups per man years in production workers
in Table 3 were reported as single values, with no measures of variation or confidence
intervals. Confidence intervals for specific outcomes were reported within the text.
Continued on next page ...
Page 265 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 1 of 2
... continued from previous page
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40( 1983): 138-144.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality; Lung/Respiratory: Lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3100548
Domain
Metric
Rating
Comments
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Other than stratification for years since first exposure and age, no additional adjustments
or consideration for differences between exposed and non-exposed groups regarding
distributions of relevant covariates were detailed. The cohort for study was restricted to
males. The authors mention that information for smoking was available for 70% of the
cohort, but this information is not used in statistical analyses. The authors state that data
was available for 17 of 20 men who had died of lung cancer: 1 never smoked, 2 had quit
for 10 or more years, and 14 were smokers. Based on subsequent discussion and review
of additional information, the rating was adjusted based on stratification by age and only
males being included in the study.
Medium Finkelstein, 1982 provides evidence of detailed personnel files use for TSFE, age, job
history, etc.
Medium For lung cancer, there was no evidence of co-exposure or unbalanced provision of co-
exposures.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design was appropriate as an early study to address the research aims. Two
types of comparisons were performed, internal and external. Table 2 SMR results were
obtained through external comparisons by applying the Ontario general population mor-
tality rates as reference and presented for production, maintenance and control workers.
Table 3 mortality rate results were presented for production workers stratified across age
and years since first exposure groups. Tests for trend were not reported.
Medium The number of participants was adequate, however formal statistical comparisons be-
tween exposed and non-exposed workers, or across time since first exposure groups,
were not presented. SMR results in Table 2 were reported for the n=328 workers, while
results in Table 3 were reported only for the n=186 production workers.
Medium The data are presented in Table 1 that were used used in the 1986 analysis. Reporting
errors are present in Table 2, but these data are not used in the 1986 analysis.
Medium Model building was not conducted. The construction of SMRs appears appropriate.
Additional Comments: This was an occupational retrospective cohort study reporting SMRs of long-term male workers in which n=339 male asbestos workers hired prior to 1960
and employed by the same company in Ontario, Canada for at least nine years were followed until 31 October 1980 for mortality outcomes of interest.
Concerns included the assumption that workers unable to be traced for mortality outcomes were still alive at the end of follow-up, with no sensitivity
analyses conducted to examine results with and without these workers. Lung cancer mortality was obtained utilizing pre-ICD 10 coding. Exposure
concentrations are provided for three groups of exposure in relation to a reference population of Ontario men by outcome - however, no statistical analysis
is done to compare mortality using exposure concentration data, limiting the study's usefulness for dose-response analysis.
Continued on next page ...
Page 266 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 1 of 2
... continued from previous page
Study Citation:
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40( 1983): 138-144.
Lung Cancer
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Mortality: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality; Lung/Respiratory: Lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
HERO ID:
3100548
Domain Metric
Rating
Comments
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 267 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 2 of 2
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40(1983): 138-144.
gastrointestinal cancer mortality; all-cause mortality, non-malignant respiratory disease mortality, ischemic heart disease mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Mortality: All causes mortality, All malignancies mortality, Gastrointestinal cancer mortality, Non-malignant respiratory disease mortality, Ischemic heart
disease mortality; Cancer/Carcinogenesis: All malignancies mortality, Gastrointestinal cancer mortality; Gastrointestinal: Gastrointestinal cancer mortality;
Lung/Respiratory: Non-malignant respiratory disease mortality; Cardiovascular: Ischemic heart disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): No linked references.
3100548
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Medium Key elements of the study design were reported within this retrospective cohort study
of long-term male workers in which n=339 male asbestos workers hired prior to 1960
and employed by the same company in Ontario, Canada for at least nine years were
followed until 31 October 1980 for mortality outcomes of interest. An additional n=ll
men (3.2% of the total) could not be properly classified from their work histories as
production, maintenance or rock wool/fiberglass workers and were excluded from the
current analysis. Participants were identified from company records of all hourly and
salaried employees who had worked at the plant of interest. Employees were excluded
if they did not work for at least nine years to account for the long latency of asbestos-
related diseases and difficulties of tracing short-term employees. There is no evidence
to suggest inclusion or exclusion from the sample differed significantly by outcome or
exposure status.
Low Official death certificates were obtained for all men who had died. However, a total of
five (2.7% ) of the n=186 production workers, three (5.5% ) of the n=55 maintenance
workers and five (5.7% ) of the n=87 unexposed or minimally exposed workers were
unable to be traced for mortality outcomes and were assumed still alive for analysis. A
group of 55 maintenance workers were originally included, but later excluded as the
study reported that it "was not thought possible to estimate exposures for the mainte-
nance men."
Continued on next page ...
Page 268 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 2 of 2
... continued from previous page
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40(1983): 138-144.
gastrointestinal cancer mortality; all-cause mortality, non-malignant respiratory disease mortality, ischemic heart disease mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Mortality: All causes mortality, All malignancies mortality, Gastrointestinal cancer mortality, Non-malignant respiratory disease mortality, Ischemic heart
disease mortality; Cancer/Carcinogenesis: All malignancies mortality, Gastrointestinal cancer mortality; Gastrointestinal: Gastrointestinal cancer mortality;
Lung/Respiratory: Non-malignant respiratory disease mortality; Cardiovascular: Ischemic heart disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): No linked references.
3100548
Domain
Metric
Rating
Comments
Metric 3: Comparison Group
Medium Inclusion criteria and methods of participant selection were reported. Workers within
the rock wool/fiber glass operations (n=87) were classified as minimally exposed, had
mortality described as similar to the general male Ontario population and were utilized
as the comparison control workers. SMR analyses results utilized the age and calendar
specific mortality experience of the male Ontario general population as a comparison
group for expected mortality rates. The mean age at the start of exposure or employment
was described as similar between the exposed and general populations. Comparison
control workers were primarily within the rock wool/fiberglass insulation production
area, although the author of the current study noted in another publication (Finkelstein
et al., 1983, HERO ID 3083612) of workers in the same factory that it was possible
for employees to be assigned to the pipe shop for brief clean-up duties, or re-assigned
from non-asbestos to asbestos work areas, such that some control workers may have
been exposed as well. There is potential for healthy worker effect in terms of left trunca-
tion bias, as the cohort for the current study was restricted to workers with at least nine
years of employment, such that all workers had to survive for at least nine years to be in-
cluded. However, Table 2 SMR results for non-malignant respiratory disease indicate no
evidence of healthy worker effect in terms of the healthy hire or healthy worker survivor
effect.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low The microscopic method (PCM or TEM) of analysis of air sampling data reported in
Table 1 with outcome mortality rates was not detailed. The average estimated cumula-
tive exposure among production workers was reported for three groups of production
workers of 62 men each as 44 f-y/ml, 92 f-y/ml, and 180 f-y/mL (chrysotile and cro-
cidolite). Groups were created on the basis of ranking 18-year cumulative exposures.
Air sampling data from government, insurance and company hygienists initiated in late
1969 was utilized along with company employment records to classify each production
worker"s exposure, however production within the plant began in 1948 and measured
exposures for periods 1948-1970 were lacking and assumed as related to the quantita-
tive measurements made beginning in 1969. Exposures for maintenance workers was
described as not calculated due to inadequate data. Estimated cumulative exposure for
only the first 18 years of employment was utilized such that for men employed less than
18 years this parameter was used and for men employed more than 18 years, the po-
tential exposures after 18 years were excluded. Exposures were assumed to have been
unchanged from 1962 to 1970, to have been 30% higher from 1955 to 1961, and to have
been twice as high from 1948 to 1954, with assumptions supported by impinger area
sampling performed 1949 through the 1960"s.
Continued on next page ...
Page 269 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 2 of 2
... continued from previous page
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40(1983): 138-144.
gastrointestinal cancer mortality; all-cause mortality, non-malignant respiratory disease mortality, ischemic heart disease mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Mortality: All causes mortality, All malignancies mortality, Gastrointestinal cancer mortality, Non-malignant respiratory disease mortality, Ischemic heart
disease mortality; Cancer/Carcinogenesis: All malignancies mortality, Gastrointestinal cancer mortality; Gastrointestinal: Gastrointestinal cancer mortality;
Lung/Respiratory: Non-malignant respiratory disease mortality; Cardiovascular: Ischemic heart disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): No linked references.
3100548
Domain
Metric
Rating
Comments
Metric 5:
Metric 6:
Exposure Levels
Temporality
Medium
High
The range and distribution of estimated exposures is reported within Table 1 for pro-
duction workers as 8 to 420 fiber-years/mL. Table 1 provides the mortality rates for
production workers across three groups of exposure categories.
The study presents an appropriate temporality and the interval between exposure and
outcome is appropriate considering the latency of disease. Workers were required to
have been hired before 1960 and were followed up until 1980, ensuring at least 20 years
of follow-up for the cohort.
Domain 3: Outcome Assessment
Continued on next page .
Page 270 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 2 of 2
... continued from previous page
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40(1983): 138-144.
gastrointestinal cancer mortality; all-cause mortality, non-malignant respiratory disease mortality, ischemic heart disease mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Mortality: All causes mortality, All malignancies mortality, Gastrointestinal cancer mortality, Non-malignant respiratory disease mortality, Ischemic heart
disease mortality; Cancer/Carcinogenesis: All malignancies mortality, Gastrointestinal cancer mortality; Gastrointestinal: Gastrointestinal cancer mortality;
Lung/Respiratory: Non-malignant respiratory disease mortality; Cardiovascular: Ischemic heart disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): No linked references.
3100548
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
Metric 8:
Reporting Bias
Medium Other Cancer(s): Follow-up for mortality was described as conducted by a local trace
supplemented by a mortality search performed by Statistics Canada. Mortality rates
from mesothelioma, lung cancer, gastrointestinal cancer, and all malignancies deaths
were assessed in production workers and compared with the Ontario general population
rates in Table 1 (no ICD codes reported). Mortality rates in Table 2 from all-cause mor-
tality, all malignancies (ICD codes 140-209), lung cancer (ICD code 162), mesothelioma
(ICD codes 163, 158, 228), gastrointestinal cancer (ICD codes 150-154), non-malignant
respiratory disease (ICD codes 460-519) and ischemic heart disease (ICD codes 410-
414) deaths were reported for production workers, production plus maintenance workers
and control workers. Official death certificates were obtained for all men who had died.
For those production workers (n=5), maintenance workers (n=3) and control workers
(n=5) who were untraceable, authors assumed these workers were still alive at the end
of follow-up, 31 October 1980. Additional clinical, pathological and necropsy reports
were available for n=44 of the n=58 deaths among production workers and are used in
analyses of exposure duration, but not of exposure concentration.; Other Non-Cancer
Outcomes: Follow-up for mortality was described as conducted by a local trace sup-
plemented by a mortality search performed by Statistics Canada. Mortality rates from
mesothelioma, lung cancer, gastrointestinal cancer, and all malignancies deaths were
assessed in production workers and compared with the Ontario general population rates
in Table 1 (no ICD codes reported). Mortality rates in Table 2 from all-cause mortal-
ity, all malignancies (ICD codes 140-209), lung cancer (ICD code 162), mesothelioma
(ICD codes 163, 158, 228), gastrointestinal cancer (ICD codes 150-154), non-malignant
respiratory disease (ICD codes 460-519) and ischemic heart disease (ICD codes 410-
414) deaths were reported for production workers, production plus maintenance workers
and control workers. Official death certificates were obtained for all men who had died.
For those production workers (n=5), maintenance workers (n=3) and control workers
(n=5) who were untraceable, authors assumed these workers were still alive at the end
of follow-up, 31 October 1980. Additional clinical, pathological and necropsy reports
were available for n=44 of the n=58 deaths among production workers and are used in
analyses of exposure duration, but not of exposure concentration.
Medium There were no concerns for selective reporting. SMRs in Table 2 and mortality rates
across age and time since first exposure groups per man years in production workers
in Table 3 were reported as single values, with no measures of variation or confidence
intervals. Confidence intervals for specific outcomes were reported within the text.
Domain 4: Potential Confounding / Variability Control
Continued on next page ...
Page 271 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 2 of 2
... continued from previous page
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40(1983): 138-144.
gastrointestinal cancer mortality; all-cause mortality, non-malignant respiratory disease mortality, ischemic heart disease mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Mortality: All causes mortality, All malignancies mortality, Gastrointestinal cancer mortality, Non-malignant respiratory disease mortality, Ischemic heart
disease mortality; Cancer/Carcinogenesis: All malignancies mortality, Gastrointestinal cancer mortality; Gastrointestinal: Gastrointestinal cancer mortality;
Lung/Respiratory: Non-malignant respiratory disease mortality; Cardiovascular: Ischemic heart disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): No linked references.
3100548
Domain
Metric
Rating
Comments
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Low Other than stratification for years since first exposure and age, no additional adjustments
or consideration for differences between exposed and non-exposed groups regarding
distributions of relevant covariates were detailed. The cohort for study was restricted to
males. The authors mention that information for smoking was available for 70% of the
cohort, but this information is not used in statistical analyses. .
Low Although not specified within this occupational study, it is assumed that personnel files
were utilized to obtain age and time since first employed/exposed data.
Low The members of the cohort were employees of an Ontario asbestos cement pipe man-
ufacturing factory classified as production, maintenance and factory control workers.
In addition to chrysotile and crocidolite asbestos, authors noted production of asbestos
cement pipe included exposures to cement and silica, which were not accounted for.
Considerations for workers who might have initially left and worked elsewhere with ad-
ditional exposures but eventually returned to asbestos work were not detailed. However,
there was no evidence that there was an unbalanced provision of co-exposures among
exposure groups.
Domain 5: Analysis
Metric 12: Study Design and Methods
Medium
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Medium
Low
The study design was appropriate as an early study to address the research aims. Two
types of comparisons were performed, internal and external. Table 2 SMR results were
obtained through external comparisons by applying the Ontario general population mor-
tality rates as reference and presented for production, maintenance and control workers.
Table 3 mortality rate results were presented for production workers stratified across age
and years since first exposure groups. Tests for trend were not reported.
The number of participants was adequate, however formal statistical comparisons be-
tween exposed and non-exposed workers, or across time since first exposure groups,
were not presented. SMR results in Table 2 were reported for the n=328 workers, while
results in Table 3 were reported only for the n=186 production workers.
The only table presenting results and exposures was Table 1, which reported mortality
rates across each exposure group (A, B and C) and estimated mean and range of expo-
sures within each exposure group. However, no formal statistical analysis was conducted
to examine the statistical differences between the less exposed (Group A) and more
exposed (Group C) groups. The description of this, as well as SMR results in Table 2
and mortality rates in production workers in Table 3 is generally sufficient to under-
stand. Some of Table 2 observed /expected (SMR) results were unclear, as with the
non-malignant respiratory disease SMR for production workers within the 15-19 years
since first exposure group, where the observed mortality was 1, the expected was 0.4,
but the reported SMR is 1.0, rather than 2.5.
Continued on next page ...
Page 272 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3100548 Table: 2 of 2
... continued from previous page
Finkelstein, M. M. (1983). Mortality among long-term employees of an Ontario (Canada) asbestos-cement factory. British Journal of Industrial Medicine
40(1983): 138-144.
gastrointestinal cancer mortality; all-cause mortality, non-malignant respiratory disease mortality, ischemic heart disease mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: All causes mortality, All malignancies mortality, Gastrointestinal cancer mortality, Non-malignant respiratory disease mortality, Ischemic heart
disease mortality; Cancer/Carcinogenesis: All malignancies mortality, Gastrointestinal cancer mortality; Gastrointestinal: Gastrointestinal cancer mortality;
Lung/Respiratory: Non-malignant respiratory disease mortality; Cardiovascular: Ischemic heart disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3100548
Domain
Metric
Rating
Comments
Metric 15: Statistical Analysis
Medium Model building was not conducted. The construction of SMRs appears appropriate.
Additional Comments: This was an occupational retrospective cohort study reporting SMRs of long-term male workers in which n=339 male asbestos workers hired prior to 1960
and employed by the same company in Ontario, Canada for at least nine years were followed until 31 October 1980 for mortality outcomes of interest.
Concerns included the assumption that workers unable to be traced for mortality outcomes were still alive at the end of follow-up, with no sensitivity
analyses conducted to examine results with and without these workers. Mesothelioma mortality was obtained utilizing pre-ICD 10 coding. Exposure
concentrations are provided for three groups of exposure in relation to a reference population of Ontario men by outcome - however, no statistical analysis
is done to compare mortality using exposure concentration data, limiting the study's usefulness for dose-response analysis.
Overall Quality Determination Low
* No biomarkers were identified for this evaluation.
Page 273 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709685 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Finkelstein, M. M. (1985). A study of dose-response relationships for asbestos associated disease. British Journal of Indus trial Medicine 42(1985):319-325.
small opacities, pleural thickening
Lung/Respiratory: Small opacities >=1/0, Pleural thickening >=A, Small opacities >=1/1, Small opacities >=1/2, Pleural thickening >=B, Small opacities
>=0/1
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
HERO ID:
709685
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not ex-
plicitly mention the use of PCM or TEM.Air sampling was conducted by different enti-
ties including the government, the asbestos cement company and insurance hygienists
(Finkelstein, 1982, HEROID: 76). Measurements were primarily made through impinger
area sampling (Finkelstein, 1982, HEROID: 76). In 1969, personal membrane filters
were used (Finkelstein, 1982, HEROID: 76). Because of the infrequent consistency of
reporting exposure, extrapolations were needed for missing time frames (Finkelstein,
1982, HEROID: 76).Authors described the following for calculation expose and dose
estimation: "Cumulative exposures were calculated for each man by summing annual
exposures accumulated during the first 18 years from the start of exposure. Asbestos
dosages were calculated by assuming that a fixed proportion of the workplace air con-
centrations were deposited in the lungs, and each year's accumulation was weighted by
the residence time in lung tissue (the formulas used are given in the appendix). Cumula-
tive exposures had been estimated to be accurate to within a factor of 3 to 5."
Medium The distribution of exposure appears to be sufficient to develop an exposure-response
estimate. Cumulative exposure (f-y/ml) and dose (f/ml*yr-squared) for calculating cu-
mulative risk were utilized in statistical models. Range or other measure distribution is
not present in this paper, however Figures 1 and 2 show values ranging from 0-6,000
fibers/mL x yearA 2.
Additional Comments: Finkelstein, 1982, HEROID: 76 reported the dominant asbestos fibers were crocidolite and chrysotile. QCer may want to review Metric 9 to ensure
appropriate rating. QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be
useful for dose-response analysis.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 274 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 76 Table: 1 of 1
Study Citation: Finkelstein, M. M. (1982). Asbestosis in long-term employees of an Ontario asbestos-cement factory. American Review of Respiratory Disease
125(1982):496-501.
Asbestosis
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Lung/Respiratory: Asbestosis
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
HERO ID:
76
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not ex-
plicitly mention the use of PCM or TEM. Samples were collected using impingers and
membrane filters.
Medium The authors reported the incidence of certified asbestosis as a function of time and expo-
sure to asbestos. Authors utilize a continuous measure of exposure in the 18th year from
initial exposure to create 6 ordinal categories.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis. The method of fiber quantification was not mentioned or cited, resulting in Low rating for Metric 4.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 275 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083654 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Finkelstein, M. M., Vingilis, J. J. (1984). Radiographic abnormalities among asbestos-cement workers. An exposure-response study. American Review of
Respiratory Disease 129(1984):17-22.
Small irregular opacities on radiograph; bilateral pleural thickening on raidograph
Lung/Respiratory: Small irregular opacities on radiograph, Bilateral pleural thickening
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3083654
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
High Subjects included 181 asbestos-cement male workers hired prior to 1960 and who were
employed for 9 years or more at the factory (in Ontario) and who worked at least 12
months in asbestos exposure.
Medium Excluded participants was 5 subjects "who had died before or shortly after 18 years from
first exposure and who had not had a recent film". Men who were lost to follow up were
mentioned, but details on the number lost to follow up was not included.
Medium There is only indirect evidence stated by authors without description of methods that
groups are similar. "To investigate the influence of age and smoking habits on risk, the
cohort was stratified for exposure by the method described by Breslow (Breslow, 1979).
These include estimation of the survival curve, nonparametric tests to compare several
survival curves, tests for trend, and regression analysis.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
High "Cumulative exposures to asbestos were calculated using a model that extrapolated
measurements made by the personal membrane filter, a method that came into use 21
years after the plant opened... calculates estimated to be accurate to within a factor of 3
to 5." Earlier report on this cohort was referenced (Finkelstein, 1982).
Medium Results of the 5 exposure groups/exposure-response model were adequate (in f-y/ml:
A=0-49.9 (n=32); B=50-99.9 (n=68); C=100-149.9 (n=41); D=150-199.9 (n=25);
E=>=200 (n=15).)
High The study presents an appropriate temporality between exposure and outcome (radio-
graph taken 18 or more years since first exposure).
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or Medium Other Non-Cancer Outcomes: Chest radiographs (postanterior projections) were taken
Characterization annually as part of the routine medical surveillance. ICD-10CA codes were not men-
tioned.
Metric 8: Reporting Bias Medium Number of exposed workers by category clearly outlined in exposure-response analysis,
for smokers and non-smokers (Table 2).
Domain 4: Potential Confounding / Variability Control
Continued on next page ...
Page 276 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083654 Table: 1 of 1
... continued from previous page
Finkelstein, M. M., Vingilis, J. J. (1984). Radiographic abnormalities among asbestos-cement workers. An exposure-response study. American Review of
Respiratory Disease 129(1984):17-22.
Small irregular opacities on radiograph; bilateral pleural thickening on raidograph
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Small irregular opacities on radiograph, Bilateral pleural thickening
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3083654
Domain
Metric
Rating
Comments
Metric 9:
Covariate Adjustment
Medium
Stratification by age and smoking were mentioned, however methods not explicitly clear
on which stratification method was used from reference to the study by Breslow on
Statistical methods for censored survival data.
Metric 10:
Covariate Characterization
Low
Occupational study, it can be assumed that personnel records were used to obtain covari-
ate data, not otherwise mentioned.
Metric 11:
Co-exposure Counfounding
Medium
The authors mentioned co-exposure to silica which the study team "attempted no anal-
ysis" since quantitative measures for silica did not exist and "nor could we investigate
possible interaction between silica and asbestos."
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
Cohort design was appropriate for the exposure-response study. Methods for variable
stratification /regression analysis are difficult to determine.
Metric 13:
Statistical Power
Medium
The number of participants are adequate to detect an effect in the exposed population.
181 men, separated into 5 exposure groups (A=32, B=68, C=41, D=25, E=15)
Metric 14:
Reproducibility of Analyses
Low
The description of the analysis is insufficient to understand what has been done and to
be reproducible. Other papers are referenced for methods and mortality data, but not
entirely clear as to what methodology was used.
Metric 15:
Statistical Analysis
Medium
"Life-table analyses were performed using a computer program" and "risk was assessed
by calculating the 32-year cumulative probability of developing 'certified asbestosis'"
and "relative risk was calculated by assuming that if exposure were irrelevant to risk
of developing an abnormality, then at each examination the abnormalities would be
distributed among the exposure categories solely on the basis of the proportion of the
population at risk to be found in each category (the expected number). The expected
numbers were summed over the follow-up interval, and the number of abnormalities
actually observed in each exposure group was compared with the total expected. This
approach allowed statistical testing for equality of the "survival" distributions and for
trend with exposure" (Thomas et al., HERO ID 196727 ; Breslow, 1979).
Additional Comments: Studied the development of small irregular opacities and bilateral pleural thickening on radiograph in longitudinal cohort study of 181 asbestos and silica-
exposed male cement factory workers in Ontario. Co-exposure to silica not measured/analyzed but mentioned. Methods for stratifying by age and smoking
status not clearly outlined. Mortality data included and referenced from another earlier cohort, but not included in extraction as study did not appear to be
producing new results.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 277 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 29531 Table: 1 of 6
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Lung/Respiratory: FEV1
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium This cross-sectional study examined the relationship between pulmonary function and
exposures to talc containing anthophyllite and tremolite fibers in talc workers (n=93)
versus potash miners (n=l,077) and versus synthetic textile workers. A total of n=121
workers (78% of the n=156 total miller and miner workforce) participated, however
results were restricted to the n=93 males who had only worked at the talc mine and mill
under study. Participation rates were noted as similar across different work areas. Par-
ticipants and non-participants were noted to have had similar average exposure duration
in years (10.2 years for participants, 10.5 years for non-participants). Selection process
and participation rates for potash and synthetic textile comparison group worker data not
detailed.
Medium Talc millers and miner participants not working at the talc mine and mill under study
(n=28) were excluded, however sensitivity analyses revealed similar results when all
121 participants of the original n=156 male talc workforce were included in the anal-
yses. Comparison population consisted of n=l,077 potash mine workers and synthetic
textile workers (Table 10), however details on any exclusions involved in the creation
of the comparison populations not detailed. Missing data not detailed for talc miners or
comparison populations.
Medium Demographics between talc workers and potash workers noted as comparable with a
few exceptions for those with less than 15 years employment (non-smoking talc workers
were younger than potash workers, smoking talc workers smoked more than potash
workers) and for those with more than 15 years of exposure (potash non-smokers and
ex-smokers were slightly older than talc workers and smoking talc workers smoked
less daily but had more overall pack-years than potash workers). However, workers in
each population were grouped into or adjusted for categories of similar age, smoking
and duration of mining employment for stratified and regression analyses. Uncertainty
regarding potential healthy worker effects as prevalent hires comprised the available
population for study. Further uncertainty in utilizing potash workers and synthetic textile
workers as comparison groups with the potential for asbestos fibers within potash mines,
as well as the potential for pulmonary function changes in workers exposed to synthetic
fibers.
Domain 2: Exposure Characterization
Continued on next page ...
Page 278 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 1 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: FEV1
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5:
Exposure Levels
Metric 6:
Temporality
Medium Personal air samples were collected from miners and millers to determine the time-
weighted average (TWA) exposure to respirable dust, free silica, and asbestos fibers.
Sampling methods described in terms of sampling equipment, procedures and study site
characteristics for talc miners, with sampling equipment and procedures described for
potash miner exposures. Analytic methodology described in terms of instrumentation
(electron microscopy on a random sample) and standard (NIOSH phase contrast count-
ing technique) methods for talc miners and in terms of instrumentation (for total dust,
percent free silica, N02, but not area total respirable particulate sampling) for potash
miners. Estimated personal exposure to respirable particulates in potash miners was cal-
culated from averaged proportions of total particulate from area sampling within each
potash mine. Cumulative exposure for talc and potash miners described as calculated
from personal sampling and summation of historical time in each job. Uncertainty re-
garding cumulative exposure estimates as text notes no fiber sampling was done before
1970, exposures for each job were not well documented, representativeness of samples
described as "unknown" and estimates of cumulative exposures described as "probably
lower than actual cumulative exposures".
Medium Distribution of asbestos fiber exposure presented within Table 2 by age group and ade-
quate for analyses. Table 8 presented regression results utilizing estimated cumulative
fiber exposure calculated from historical exposures as continuous independent variables
predicting mean percent of predicted pulmonary function and changes in predicted pul-
monary function. Other analyses presented results across talc versus potash and textile
worker groups as exposed versus non-exposed categories without incorporation of mea-
sured or estimated cumulative exposures within models (Table 7).
Medium Uncertainty regarding temporality due to cross-sectional nature of study, however text
notes average duration of exposure to talc was 10.2 years. Range of employment dura-
tion not specified. Unclear number of years required for appearance of some pulmonary
function outcomes of interest.
Domain 3: Outcome Assessment
Continued on next page ...
Page 279 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 1 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: FEV1
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
Medium
Pulmonary Function/Spirometry Results: Pulmonary function outcomes of interest in-
cluded FEV1, FVC, FEV1/FVC% , Vmax50, Vmax75, pulmonary symptoms (cough,
phlegm, hemoptysis, dyspnea >= grade 2, pleural calcification, pneumoconiosis (opaci-
ties) and pleural thickening). Text notes use of respiratory questionnaire by the Medical
Research Council for smoking and total work data, however it is unclear if this ques-
tionnaire was also utilized for obtaining data for pulmonary symptom outcomes. Pleu-
ral thickening, opacities and calcification outcomes would have been obtainable from
the standard posteroanterior chest roentgenograms read independently without knowl-
edge of age, occupation and smoking history by three "B" readers using ILO standard
schemes. Pulmonary function outcomes obtained utilizing standard spirometry methods.
Metric 8:
Reporting Bias
Medium
No substantial concerns for selective reporting, although text noted blood samples col-
lected from talc workers for analyses of antinuclear antibodies and rheumatoid factor
which do not seem to have been analyzed, however these were not included as outcomes
of interest within original study objectives.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High Results reported as adjusted utilizing stratification and multivariate regression. Final
multivariate analysis (Table 6) adjusted for age, height, and smoking status. Additional
analyses (Table 8) adjusted for years of employment. Study restricted to males. Distribu-
tion of covariates presented for talc and potash workers presented within Table 5.
Medium Data regarding potential confounders seems to have been collected within the Medical
Research Council respiratory questionnaire, however it is unclear as source for indepen-
dent variable data not detailed directly in text.
Low Final analyses presented results without adjusting for co-exposures potentially relevant
to pulmonary function outcomes, such as silica.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13:
Statistical Power
Medium Study utilized stratification and multivariate regression for analyses of cross-sectional
data for lung function outcomes. Unclear amount of asbestos exposure in comparison
group potash workers. Unclear effect of utilizing synthetic textile workers as compar-
ison group, with their potential for increased risks of fiber exposure-related decreased
pulmonary function.
Medium Number of subjects adequate and reported as n=93 male talc miners and millers com-
pared with n=l,077 potash miners. Uncertainty regarding the number of comparison
group textile workers (Table 10).
Continued on next page ...
Page 280 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 1 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: FEV1
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Low
Statistical analyses reported as multivariate regression, however details of analyses
unclear for regression in terms of handling of missing data, consideration of outliers,
transformation of continuous variables and model assumptions.
Description of analysis brief with assumptions lacking.
Additional Comments: The relationship between pulmonary function (FEV1, FVC, FEV1/FVC% , Vmax50, Vmax75, pulmonary symptoms, pleural calcification, pneumoco-
niosis, pleural thickening) and exposures to talc containing anthophyllite and tremolite fibers in talc workers (n=93) versus potash miners (n=l,077) and
synthetic textile workers (Table 10) was examined in this cross-sectional study. Results indicated increased respiratory symptoms, radiographic abnor-
malities and decreased pulmonary function among these talc miners and millers with some findings noted as related to dose and duration of exposure.The
measurement exposure (M4) and/or exposure levels (M5) metrics are rated as medium upon review by both set of reviewers. Also, the overall quality
determination (OQD) is rated medium. Extraction has been completed and quality control reviewed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 281 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 2 of 6
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: FVC
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium The relationship between pulmonary function and exposures to talc containing antho-
phyllite and tremolite fibers in talc workers (n=93) versus potash miners (n=l,077) and
versus synthetic textile workers (Table 10) was examined in this cross-sectional study.
A total of n=121 workers (78% of the n=156 total miller and miner work force) partic-
ipated, however results were restricted to the n=93 males who had only worked at the
talc mine and mill under study. Participation rates were noted as similar across different
work areas. Participants and non-participants were noted to have had similar average
exposure duration in years (10.2 years for participants, 10.5 years for non-participants).
Selection process and participation rates for potash and synthetic textile comparison
group worker data not detailed.
Medium Talc millers and miner participants not working at the talc mine and mill under study
(n=28) were excluded, however sensitivity analyses revealed similar results when all
121 participants of the original n=156 male talc workforce were included in the anal-
yses. Comparison population consisted of n=l,077 potash mine workers and synthetic
textile workers (Table 10), however details on any exclusions involved in the creation
of the comparison populations not detailed. Missing data not detailed for talc miners or
comparison populations.
Medium Demographics between talc workers and potash workers noted as comparable with a
few exceptions for those with less than 15 years employment (non-smoking talc workers
were younger than potash workers, smoking talc workers smoked more than potash
workers) and for those with more than 15 years of exposure (potash non-smokers and
ex-smokers were slightly older than talc workers and smoking talc workers smoked
less daily but had more overall pack-years than potash workers). However, workers in
each population were grouped into or adjusted for categories of similar age, smoking
and duration of mining employment for stratified and regression analyses. Uncertainty
regarding potential healthy worker effects as prevalent hires comprised the available
population for study. Further uncertainty in utilizing potash workers and synthetic textile
workers as comparison groups with the potential for asbestos fibers within potash mines,
as well as the potential for pulmonary function changes in workers exposed to synthetic
fibers.
Domain 2: Exposure Characterization
Continued on next page ...
Page 282 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 2 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: FVC
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5:
Exposure Levels
Metric 6:
Temporality
Medium Personal air samples were collected from miners and millers to determine the time-
weighted average (TWA) exposure to respirable dust, free silica, and asbestos fibers.
Sampling methods described in terms of sampling equipment, procedures and study site
characteristics for talc miners, with sampling equipment and procedures described for
potash miner exposures. Analytic methodology described in terms of instrumentation
(electron microscopy on a random sample) and standard (NIOSH phase contrast count-
ing technique) methods for talc miners and in terms of instrumentation (for total dust,
percent free silica, N02, but not area total respirable particulate sampling) for potash
miners. Estimated personal exposure to respirable particulates in potash miners was cal-
culated from averaged proportions of total particulate from area sampling within each
potash mine. Cumulative exposure for talc and potash miners described as calculated
from personal sampling and summation of historical time in each job. Uncertainty re-
garding cumulative exposure estimates as text notes no fiber sampling was done before
1970, exposures for each job were not well documented, representativeness of samples
described as "unknown" and estimates of cumulative exposures described as "probably
lower than actual cumulative exposures".
Medium Distribution of asbestos fiber exposure presented within Table 2 by age group and ade-
quate for analyses. Table 8 presented regression results utilizing estimated cumulative
fiber exposure calculated from historical exposures as continuous independent variables
predicting mean percent of predicted pulmonary function and changes in predicted pul-
monary function. Other analyses presented results across talc versus potash and textile
worker groups as exposed versus non-exposed categories without incorporation of mea-
sured or estimated cumulative exposures within models (Table 7).
Medium Uncertainty regarding temporality due to cross-sectional nature of study, however text
notes average duration of exposure to talc was 10.2 years. Range of employment dura-
tion not specified. Unclear number of years required for appearance of some pulmonary
function outcomes of interest.
Domain 3: Outcome Assessment
Continued on next page ...
Page 283 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 2 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: FVC
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
Medium
Pulmonary Function/Spirometry Results: Pulmonary function outcomes of interest in-
cluded FEV1, FVC, FEV1/FVC% , Vmax50, Vmax75, pulmonary symptoms (cough,
phlegm, hemoptysis, dyspnea >= grade 2, pleural calcification, pneumoconiosis (opaci-
ties) and pleural thickening). Text notes use of respiratory questionnaire by the Medical
Research Council for smoking and total work data, however it is unclear if this ques-
tionnaire was also utilized for obtaining data for pulmonary symptom outcomes. Pleu-
ral thickening, opacities and calcification outcomes would have been obtainable from
the standard posteroanterior chest roentgenograms read independently without knowl-
edge of age, occupation and smoking history by three "B" readers using ILO standard
schemes. Pulmonary function outcomes obtained utilizing standard spirometry methods.
Metric 8:
Reporting Bias
Medium
No substantial concerns for selective reporting, although text noted blood samples col-
lected from talc workers for analyses of antinuclear antibodies and rheumatoid factor
which do not seem to have been analyzed, however these were not included as outcomes
of interest within original study objectives.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High Results reported as adjusted utilizing stratification and multivariate regression. Final
multivariate analysis (Table 6) adjusted for age, height, and smoking status. Additional
analyses (Table 8) adjusted for years of employment. Study restricted to males. Distribu-
tion of covariates presented for talc and potash workers presented within Table 5.
Medium Data regarding potential confounders seems to have been collected within the Medical
Research Council respiratory questionnaire, however it is unclear as source for indepen-
dent variable data not detailed directly in text.
Low Final analyses presented results without adjusting for co-exposures potentially relevant
to pulmonary function outcomes, such as silica.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13:
Statistical Power
Medium Study utilized stratification and multivariate regression for analyses of cross-sectional
data for lung function outcomes. Unclear amount of asbestos exposure in comparison
group potash workers. Unclear effect of utilizing synthetic textile workers as compar-
ison group, with their potential for increased risks of fiber exposure-related decreased
pulmonary function.
Medium Number of subjects adequate and reported as n=93 male talc miners and millers com-
pared with n=l,077 potash miners. Uncertainty regarding the number of comparison
group textile workers (Table 10).
Continued on next page ...
Page 284 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 2 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: FVC
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Low
Statistical analyses reported as multivariate regression, however details of analyses
unclear for regression in terms of handling of missing data, consideration of outliers,
transformation of continuous variables and model assumptions.
Description of analysis brief with assumptions lacking.
Additional Comments: The relationship between pulmonary function (FEV1, FVC, FEV1/FVC% , Vmax50, Vmax75, pulmonary symptoms, pleural calcification, pneumonoco-
niosis, pleural thickening) and exposures to talc containing anthophyllite and tremolite fibers in talc workers (n=93) versus potash miners (n=l,077) and
synthetic textile workers (Table 10) was examined in this cross-sectional study. Results indicated increased respiratory symptoms, radiographic abnor-
malities and decreased pulmonary function among these talc miners and millers with some findings noted as related to dose and duration of exposure.The
measurement exposure (M4) and/or exposure levels (M5) metrics are rated as medium upon review by both set of reviewers. Also, the overall quality
determination (OQD) is rated medium. Extraction has been completed and quality control reviewed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 285 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 3 of 6
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: FEV1%
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium The relationship between pulmonary function and exposures to talc containing antho-
phyllite and tremolite fibers in talc workers (n=93) versus potash miners (n=l,077) and
versus synthetic textile workers (Table 10) was examined in this cross-sectional study.
A total of n=121 workers (78% of the n=156 total miller and miner work force) partic-
ipated, however results were restricted to the n=93 males who had only worked at the
talc mine and mill under study. Participation rates were noted as similar across different
work areas. Participants and non-participants were noted to have had similar average
exposure duration in years (10.2 years for participants, 10.5 years for non-participants).
Selection process and participation rates for potash and synthetic textile comparison
group worker data not detailed.
Medium Talc millers and miner participants not working at the talc mine and mill under study
(n=28) were excluded, however sensitivity analyses revealed similar results when all
121 participants of the original n=156 male talc workforce were included in the anal-
yses. Comparison population consisted of n=l,077 potash mine workers and synthetic
textile workers (Table 10), however details on any exclusions involved in the creation
of the comparison populations not detailed. Missing data not detailed for talc miners or
comparison populations.
Medium Demographics between talc workers and potash workers noted as comparable with a
few exceptions for those with less than 15 years employment (non-smoking talc workers
were younger than potash workers, smoking talc workers smoked more than potash
workers) and for those with more than 15 years of exposure (potash non-smokers and
ex-smokers were slightly older than talc workers and smoking talc workers smoked
less daily but had more overall pack-years than potash workers). However, workers in
each population were grouped into or adjusted for categories of similar age, smoking
and duration of mining employment for stratified and regression analyses. Uncertainty
regarding potential healthy worker effects as prevalent hires comprised the available
population for study. Further uncertainty in utilizing potash workers and synthetic textile
workers as comparison groups with the potential for asbestos fibers within potash mines,
as well as the potential for pulmonary function changes in workers exposed to synthetic
fibers.
Domain 2: Exposure Characterization
Continued on next page ...
Page 286 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 3 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: FEV1%
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5:
Exposure Levels
Metric 6:
Temporality
Medium Personal air samples were collected from miners and millers to determine the time-
weighted average (TWA) exposure to respirable dust, free silica, and asbestos fibers.
Sampling methods described in terms of sampling equipment, procedures and study site
characteristics for talc miners, with sampling equipment and procedures described for
potash miner exposures. Analytic methodology described in terms of instrumentation
(electron microscopy on a random sample) and standard (NIOSH phase contrast count-
ing technique) methods for talc miners and in terms of instrumentation (for total dust,
percent free silica, N02, but not area total respirable particulate sampling) for potash
miners. Estimated personal exposure to respirable particulates in potash miners was cal-
culated from averaged proportions of total particulate from area sampling within each
potash mine. Cumulative exposure for talc and potash miners described as calculated
from personal sampling and summation of historical time in each job. Uncertainty re-
garding cumulative exposure estimates as text notes no fiber sampling was done before
1970, exposures for each job were not well documented, representativeness of samples
described as "unknown" and estimates of cumulative exposures described as "probably
lower than actual cumulative exposures".
Medium Distribution of asbestos fiber exposure presented within Table 2 by age group and ade-
quate for analyses. Table 8 presented regression results utilizing estimated cumulative
fiber exposure calculated from historical exposures as continuous independent variables
predicting mean percent of predicted pulmonary function and changes in predicted pul-
monary function. Other analyses presented results across talc versus potash and textile
worker groups as exposed versus non-exposed categories without incorporation of mea-
sured or estimated cumulative exposures within models (Table 7).
Medium Uncertainty regarding temporality due to cross-sectional nature of study, however text
notes average duration of exposure to talc was 10.2 years. Range of employment dura-
tion not specified. Unclear number of years required for appearance of some pulmonary
function outcomes of interest.
Domain 3: Outcome Assessment
Continued on next page ...
Page 287 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 3 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: FEV1%
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
Medium
Pulmonary Function/Spirometry Results: Pulmonary function outcomes of interest in-
cluded FEV1, FVC, FEV1/FVC% , Vmax50, Vmax75, pulmonary symptoms (cough,
phlegm, hemoptysis, dyspnea >= grade 2, pleural calcification, pneumoconiosis (opaci-
ties) and pleural thickening). Text notes use of respiratory questionnaire by the Medical
Research Council for smoking and total work data, however it is unclear if this ques-
tionnaire was also utilized for obtaining data for pulmonary symptom outcomes. Pleu-
ral thickening, opacities and calcification outcomes would have been obtainable from
the standard posteroanterior chest roentgenograms read independently without knowl-
edge of age, occupation and smoking history by three "B" readers using ILO standard
schemes. Pulmonary function outcomes obtained utilizing standard spirometry methods.
Metric 8:
Reporting Bias
Medium
No substantial concerns for selective reporting, although text noted blood samples col-
lected from talc workers for analyses of antinuclear antibodies and rheumatoid factor
which do not seem to have been analyzed, however these were not included as outcomes
of interest within original study objectives.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High Results reported as adjusted utilizing stratification and multivariate regression. Final
multivariate analysis (Table 6) adjusted for age, height, and smoking status. Additional
analyses (Table 8) adjusted for years of employment. Study restricted to males. Distribu-
tion of covariates presented for talc and potash workers presented within Table 5.
Medium Data regarding potential confounders seems to have been collected within the Medical
Research Council respiratory questionnaire, however it is unclear as source for indepen-
dent variable data not detailed directly in text.
Low Final analyses presented results without adjusting for co-exposures potentially relevant
to pulmonary function outcomes, such as silica.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13:
Statistical Power
Medium Study utilized stratification and multivariate regression for analyses of cross-sectional
data for lung function outcomes. Unclear amount of asbestos exposure in comparison
group potash workers. Unclear effect of utilizing synthetic textile workers as compar-
ison group, with their potential for increased risks of fiber exposure-related decreased
pulmonary function.
Medium Number of subjects adequate and reported as n=93 male talc miners and millers com-
pared with n=l,077 potash miners. Uncertainty regarding the number of comparison
group textile workers (Table 10).
Continued on next page ...
Page 288 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 3 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: FEV1%
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Low
Statistical analyses reported as multivariate regression, however details of analyses
unclear for regression in terms of handling of missing data, consideration of outliers,
transformation of continuous variables and model assumptions.
Description of analysis brief with assumptions lacking.
Additional Comments: The relationship between pulmonary function (FEV1, FVC, FEV1/FVC% , Vmax50, Vmax75, pulmonary symptoms, pleural calcification, pneumonoco-
niosis, pleural thickening) and exposures to talc containing anthophyllite and tremolite fibers in talc workers (n=93) versus potash miners (n=l,077) and
synthetic textile workers (Table 10) was examined in this cross-sectional study. Results indicated increased respiratory symptoms, radiographic abnor-
malities and decreased pulmonary function among these talc miners and millers with some findings noted as related to dose and duration of exposure.The
measurement exposure (M4) and/or exposure levels (M5) metrics are rated as medium upon review by both set of reviewers. Also, the overall quality
determination (OQD) is rated medium. Extraction has been completed and quality control reviewed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 289 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 4 of 6
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Vmax50
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium The relationship between pulmonary function and exposures to talc containing antho-
phyllite and tremolite fibers in talc workers (n=93) versus potash miners (n=l,077) and
versus synthetic textile workers (Table 10) was examined in this cross-sectional study.
A total of n=121 workers (78% of the n=156 total miller and miner work force) partic-
ipated, however results were restricted to the n=93 males who had only worked at the
talc mine and mill under study. Participation rates were noted as similar across different
work areas. Participants and non-participants were noted to have had similar average
exposure duration in years (10.2 years for participants, 10.5 years for non-participants).
Selection process and participation rates for potash and synthetic textile comparison
group worker data not detailed.
Medium Talc millers and miner participants not working at the talc mine and mill under study
(n=28) were excluded, however sensitivity analyses revealed similar results when all
121 participants of the original n=156 male talc workforce were included in the anal-
yses. Comparison population consisted of n=l,077 potash mine workers and synthetic
textile workers (Table 10), however details on any exclusions involved in the creation
of the comparison populations not detailed. Missing data not detailed for talc miners or
comparison populations.
Medium Demographics between talc workers and potash workers noted as comparable with a
few exceptions for those with less than 15 years employment (non-smoking talc workers
were younger than potash workers, smoking talc workers smoked more than potash
workers) and for those with more than 15 years of exposure (potash non-smokers and
ex-smokers were slightly older than talc workers and smoking talc workers smoked
less daily but had more overall pack-years than potash workers). However, workers in
each population were grouped into or adjusted for categories of similar age, smoking
and duration of mining employment for stratified and regression analyses. Uncertainty
regarding potential healthy worker effects as prevalent hires comprised the available
population for study. Further uncertainty in utilizing potash workers and synthetic textile
workers as comparison groups with the potential for asbestos fibers within potash mines,
as well as the potential for pulmonary function changes in workers exposed to synthetic
fibers.
Domain 2: Exposure Characterization
Continued on next page ...
Page 290 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 4 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Vmax50
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5:
Exposure Levels
Metric 6:
Temporality
Medium Personal air samples were collected from miners and millers to determine the time-
weighted average (TWA) exposure to respirable dust, free silica, and asbestos fibers.
Sampling methods described in terms of sampling equipment, procedures and study site
characteristics for talc miners, with sampling equipment and procedures described for
potash miner exposures. Analytic methodology described in terms of instrumentation
(electron microscopy on a random sample) and standard (NIOSH phase contrast count-
ing technique) methods for talc miners and in terms of instrumentation (for total dust,
percent free silica, N02, but not area total respirable particulate sampling) for potash
miners. Estimated personal exposure to respirable particulates in potash miners was cal-
culated from averaged proportions of total particulate from area sampling within each
potash mine. Cumulative exposure for talc and potash miners described as calculated
from personal sampling and summation of historical time in each job. Uncertainty re-
garding cumulative exposure estimates as text notes no fiber sampling was done before
1970, exposures for each job were not well documented, representativeness of samples
described as "unknown" and estimates of cumulative exposures described as "probably
lower than actual cumulative exposures".
Medium Distribution of asbestos fiber exposure presented within Table 2 by age group and ade-
quate for analyses. Table 8 presented regression results utilizing estimated cumulative
fiber exposure calculated from historical exposures as continuous independent variables
predicting mean percent of predicted pulmonary function and changes in predicted pul-
monary function. Other analyses presented results across talc versus potash and textile
worker groups as exposed versus non-exposed categories without incorporation of mea-
sured or estimated cumulative exposures within models (Table 7).
Medium Uncertainty regarding temporality due to cross-sectional nature of study, however text
notes average duration of exposure to talc was 10.2 years. Range of employment dura-
tion not specified. Unclear number of years required for appearance of some pulmonary
function outcomes of interest.
Domain 3: Outcome Assessment
Continued on next page ...
Page 291 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 4 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Vmax50
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
Medium
Pulmonary Function/Spirometry Results: Pulmonary function outcomes of interest in-
cluded FEV1, FVC, FEV1/FVC% , Vmax50, Vmax75, pulmonary symptoms (cough,
phlegm, hemoptysis, dyspnea >= grade 2, pleural calcification, pneumoconiosis (opaci-
ties) and pleural thickening). Text notes use of respiratory questionnaire by the Medical
Research Council for smoking and total work data, however it is unclear if this ques-
tionnaire was also utilized for obtaining data for pulmonary symptom outcomes. Pleu-
ral thickening, opacities and calcification outcomes would have been obtainable from
the standard posteroanterior chest roentgenograms read independently without knowl-
edge of age, occupation and smoking history by three "B" readers using ILO standard
schemes. Pulmonary function outcomes obtained utilizing standard spirometry methods.
Metric 8:
Reporting Bias
Medium
No substantial concerns for selective reporting, although text noted blood samples col-
lected from talc workers for analyses of antinuclear antibodies and rheumatoid factor
which do not seem to have been analyzed, however these were not included as outcomes
of interest within original study objectives.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High Results reported as adjusted utilizing stratification and multivariate regression. Final
multivariate analysis (Table 6) adjusted for age, height, and smoking status. Additional
analyses (Table 8) adjusted for years of employment. Study restricted to males. Distribu-
tion of covariates presented for talc and potash workers presented within Table 5.
Medium Data regarding potential confounders seems to have been collected within the Medical
Research Council respiratory questionnaire, however it is unclear as source for indepen-
dent variable data not detailed directly in text.
Low Final analyses presented results without adjusting for co-exposures potentially relevant
to pulmonary function outcomes, such as silica.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13:
Statistical Power
Medium Study utilized stratification and multivariate regression for analyses of cross-sectional
data for lung function outcomes. Unclear amount of asbestos exposure in comparison
group potash workers. Unclear effect of utilizing synthetic textile workers as compar-
ison group, with their potential for increased risks of fiber exposure-related decreased
pulmonary function.
Medium Number of subjects adequate and reported as n=93 male talc miners and millers com-
pared with n=l,077 potash miners. Uncertainty regarding the number of comparison
group textile workers (Table 10).
Continued on next page ...
Page 292 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 4 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Vmax50
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Low
Statistical analyses reported as multivariate regression, however details of analyses
unclear for regression in terms of handling of missing data, consideration of outliers,
transformation of continuous variables and model assumptions.
Description of analysis brief with assumptions lacking.
Additional Comments: The relationship between pulmonary function (FEV1, FVC, FEV1/FVC% , Vmax50, Vmax75, pulmonary symptoms, pleural calcification, pneumonoco-
niosis, pleural thickening) and exposures to talc containing anthophyllite and tremolite fibers in talc workers (n=93) versus potash miners (n=l,077) and
synthetic textile workers (Table 10) was examined in this cross-sectional study. Results indicated increased respiratory symptoms, radiographic abnor-
malities and decreased pulmonary function among these talc miners and millers with some findings noted as related to dose and duration of exposure.The
measurement exposure (M4) and/or exposure levels (M5) metrics are rated as medium upon review by both set of reviewers. Also, the overall quality
determination (OQD) is rated medium. Extraction has been completed and quality control reviewed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 293 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 5 of 6
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: VMax75
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium The relationship between pulmonary function and exposures to talc containing antho-
phyllite and tremolite fibers in talc workers (n=93) versus potash miners (n=l,077) and
versus synthetic textile workers (Table 10) was examined in this cross-sectional study.
A total of n=121 workers (78% of the n=156 total miller and miner work force) partic-
ipated, however results were restricted to the n=93 males who had only worked at the
talc mine and mill under study. Participation rates were noted as similar across different
work areas. Participants and non-participants were noted to have had similar average
exposure duration in years (10.2 years for participants, 10.5 years for non-participants).
Selection process and participation rates for potash and synthetic textile comparison
group worker data not detailed.
Medium Talc millers and miner participants not working at the talc mine and mill under study
(n=28) were excluded, however sensitivity analyses revealed similar results when all
121 participants of the original n=156 male talc workforce were included in the anal-
yses. Comparison population consisted of n=l,077 potash mine workers and synthetic
textile workers (Table 10), however details on any exclusions involved in the creation
of the comparison populations not detailed. Missing data not detailed for talc miners or
comparison populations.
Medium Demographics between talc workers and potash workers noted as comparable with a
few exceptions for those with less than 15 years employment (non-smoking talc workers
were younger than potash workers, smoking talc workers smoked more than potash
workers) and for those with more than 15 years of exposure (potash non-smokers and
ex-smokers were slightly older than talc workers and smoking talc workers smoked
less daily but had more overall pack-years than potash workers). However, workers in
each population were grouped into or adjusted for categories of similar age, smoking
and duration of mining employment for stratified and regression analyses. Uncertainty
regarding potential healthy worker effects as prevalent hires comprised the available
population for study. Further uncertainty in utilizing potash workers and synthetic textile
workers as comparison groups with the potential for asbestos fibers within potash mines,
as well as the potential for pulmonary function changes in workers exposed to synthetic
fibers.
Domain 2: Exposure Characterization
Continued on next page ...
Page 294 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 5 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: VMax75
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5:
Exposure Levels
Metric 6:
Temporality
Medium Personal air samples were collected from miners and millers to determine the time-
weighted average (TWA) exposure to respirable dust, free silica, and asbestos fibers.
Sampling methods described in terms of sampling equipment, procedures and study site
characteristics for talc miners, with sampling equipment and procedures described for
potash miner exposures. Analytic methodology described in terms of instrumentation
(electron microscopy on a random sample) and standard (NIOSH phase contrast count-
ing technique) methods for talc miners and in terms of instrumentation (for total dust,
percent free silica, N02, but not area total respirable particulate sampling) for potash
miners. Estimated personal exposure to respirable particulates in potash miners was cal-
culated from averaged proportions of total particulate from area sampling within each
potash mine. Cumulative exposure for talc and potash miners described as calculated
from personal sampling and summation of historical time in each job. Uncertainty re-
garding cumulative exposure estimates as text notes no fiber sampling was done before
1970, exposures for each job were not well documented, representativeness of samples
described as "unknown" and estimates of cumulative exposures described as "probably
lower than actual cumulative exposures".
Medium Distribution of asbestos fiber exposure presented within Table 2 by age group and ade-
quate for analyses. Table 8 presented regression results utilizing estimated cumulative
fiber exposure calculated from historical exposures as continuous independent variables
predicting mean percent of predicted pulmonary function and changes in predicted pul-
monary function. Other analyses presented results across talc versus potash and textile
worker groups as exposed versus non-exposed categories without incorporation of mea-
sured or estimated cumulative exposures within models (Table 7).
Medium Uncertainty regarding temporality due to cross-sectional nature of study, however text
notes average duration of exposure to talc was 10.2 years. Range of employment dura-
tion not specified. Unclear number of years required for appearance of some pulmonary
function outcomes of interest.
Domain 3: Outcome Assessment
Continued on next page ...
Page 295 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 5 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: VMax75
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
Medium
Pulmonary Function/Spirometry Results: Pulmonary function outcomes of interest in-
cluded FEV1, FVC, FEV1/FVC% , Vmax50, Vmax75, pulmonary symptoms (cough,
phlegm, hemoptysis, dyspnea >= grade 2, pleural calcification, pneumoconiosis (opaci-
ties) and pleural thickening). Text notes use of respiratory questionnaire by the Medical
Research Council for smoking and total work data, however it is unclear if this ques-
tionnaire was also utilized for obtaining data for pulmonary symptom outcomes. Pleu-
ral thickening, opacities and calcification outcomes would have been obtainable from
the standard posteroanterior chest roentgenograms read independently without knowl-
edge of age, occupation and smoking history by three "B" readers using ILO standard
schemes. Pulmonary function outcomes obtained utilizing standard spirometry methods.
Metric 8:
Reporting Bias
Medium
No substantial concerns for selective reporting, although text noted blood samples col-
lected from talc workers for analyses of antinuclear antibodies and rheumatoid factor
which do not seem to have been analyzed, however these were not included as outcomes
of interest within original study objectives.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High Results reported as adjusted utilizing stratification and multivariate regression. Final
multivariate analysis (Table 6) adjusted for age, height, and smoking status. Additional
analyses (Table 8) adjusted for years of employment. Study restricted to males. Distribu-
tion of covariates presented for talc and potash workers presented within Table 5.
Medium Data regarding potential confounders seems to have been collected within the Medical
Research Council respiratory questionnaire, however it is unclear as source for indepen-
dent variable data not detailed directly in text.
Low Final analyses presented results without adjusting for co-exposures potentially relevant
to pulmonary function outcomes, such as silica.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13:
Statistical Power
Medium Study utilized stratification and multivariate regression for analyses of cross-sectional
data for lung function outcomes. Unclear amount of asbestos exposure in comparison
group potash workers. Unclear effect of utilizing synthetic textile workers as compar-
ison group, with their potential for increased risks of fiber exposure-related decreased
pulmonary function.
Medium Number of subjects adequate and reported as n=93 male talc miners and millers com-
pared with n=l,077 potash miners. Uncertainty regarding the number of comparison
group textile workers (Table 10).
Continued on next page ...
Page 296 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 5 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: VMax75
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Low
Statistical analyses reported as multivariate regression, however details of analyses
unclear for regression in terms of handling of missing data, consideration of outliers,
transformation of continuous variables and model assumptions.
Description of analysis brief with assumptions lacking.
Additional Comments: The relationship between pulmonary function (FEV1, FVC, FEV1/FVC% , Vmax50, Vmax75, pulmonary symptoms, pleural calcification, pneumonoco-
niosis, pleural thickening) and exposures to talc containing anthophyllite and tremolite fibers in talc workers (n=93) versus potash miners (n=l,077) and
synthetic textile workers (Table 10) was examined in this cross-sectional study. Results indicated increased respiratory symptoms, radiographic abnor-
malities and decreased pulmonary function among these talc miners and millers with some findings noted as related to dose and duration of exposure.The
measurement exposure (M4) and/or exposure levels (M5) metrics are rated as medium upon review by both set of reviewers. Also, the overall quality
determination (OQD) is rated medium. Extraction has been completed and quality control reviewed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 297 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 6 of 6
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pleural Plaques
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Pleural thickening, Pleural calcification, Irregular opacities, Rounded opacities
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium This cross-sectional study examined the relationship between pulmonary function and
exposures to talc containing anthophyllite and tremolite fibers in talc workers (n=93)
versus potash miners (n=l,077) and versus synthetic textile workers. A total of n=121
workers (78% of the n=156 total miller and miner workforce) participated, however
results were restricted to the n=93 males who had only worked at the talc mine and mill
under study. Participation rates were noted as similar across different work areas. Par-
ticipants and non-participants were noted to have had similar average exposure duration
in years (10.2 years for participants, 10.5 years for non-participants). Selection process
and participation rates for potash and synthetic textile comparison group worker data not
detailed.
Medium Talc millers and miner participants not working at the talc mine and mill under study
(n=28) were excluded, however sensitivity analyses revealed similar results when all
121 participants of the original n=156 male talc workforce were included in the anal-
yses. Comparison population consisted of n=l,077 potash mine workers and synthetic
textile workers (Table 10), however details on any exclusions involved in the creation
of the comparison populations not detailed. Missing data not detailed for talc miners or
comparison populations.
Medium Demographics between talc workers and potash workers noted as comparable with a
few exceptions for those with less than 15 years employment (non-smoking talc workers
were younger than potash workers, smoking talc workers smoked more than potash
workers) and for those with more than 15 years of exposure (potash non-smokers and
ex-smokers were slightly older than talc workers and smoking talc workers smoked
less daily but had more overall pack-years than potash workers). However, workers in
each population were grouped into or adjusted for categories of similar age, smoking
and duration of mining employment for stratified and regression analyses. Uncertainty
regarding potential healthy worker effects as prevalent hires comprised the available
population for study. Further uncertainty in utilizing potash workers and synthetic textile
workers as comparison groups with the potential for asbestos fibers within potash mines,
as well as the potential for pulmonary function changes in workers exposed to synthetic
fibers.
Domain 2: Exposure Characterization
Continued on next page .
Page 298 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 6 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pleural Plaques
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Pleural thickening, Pleural calcification, Irregular opacities, Rounded opacities
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5:
Exposure Levels
Metric 6:
Temporality
Medium Personal air samples were collected from miners and millers to determine the time-
weighted average (TWA) exposure to respirable dust, free silica, and asbestos fibers.
Sampling methods described in terms of sampling equipment, procedures and study site
characteristics for talc miners, with sampling equipment and procedures described for
potash miner exposures. Analytic methodology described in terms of instrumentation
(electron microscopy on a random sample) and standard (NIOSH phase contrast count-
ing technique) methods for talc miners and in terms of instrumentation (for total dust,
percent free silica, N02, but not area total respirable particulate sampling) for potash
miners. Estimated personal exposure to respirable particulates in potash miners was cal-
culated from averaged proportions of total particulate from area sampling within each
potash mine. Cumulative exposure for talc and potash miners described as calculated
from personal sampling and summation of historical time in each job. Uncertainty re-
garding cumulative exposure estimates as text notes no fiber sampling was done before
1970, exposures for each job were not well documented, representativeness of samples
described as "unknown" and estimates of cumulative exposures described as "probably
lower than actual cumulative exposures".
Medium Distribution of asbestos fiber exposure presented within Table 2 by age group and ade-
quate for analyses. Table 8 presented regression results utilizing estimated cumulative
fiber exposure calculated from historical exposures as continuous independent variables
predicting mean percent of predicted pulmonary function and changes in predicted pul-
monary function. Other analyses presented results across talc versus potash and textile
worker groups as exposed versus non-exposed categories without incorporation of mea-
sured or estimated cumulative exposures within models (Table 7).
Medium Uncertainty regarding temporality due to cross-sectional nature of study, however text
notes average duration of exposure to talc was 10.2 years. Range of employment dura-
tion not specified. Unclear number of years required for appearance of some pulmonary
function outcomes of interest.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or High Pleural Plaques: Chest roentgenograms were examined by three "B" readers accord-
Characterization ing to the ILO U/C 1971 scheme. Each film was read independently, and the read-
ers were blinded to the age, occupation, and smoking history of the individuals the
roentgenograms belonged to. The median value from the three readings was included
and utilized for analyses. It is important to note that authors only examined prevalence
of pleural findings, such as in Tables 3 and 4.
Continued on next page ...
Page 299 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 6 of 6
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pleural Plaques
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Pleural thickening, Pleural calcification, Irregular opacities, Rounded opacities
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29531
Domain
Metric
Rating
Comments
Metric 8:
Reporting Bias
Medium
No substantial concerns for selective reporting, although text noted blood samples col-
lected from talc workers for analyses of antinuclear antibodies and rheumatoid factor
which do not seem to have been analyzed, however these were not included as outcomes
of interest within original study objectives.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High Results reported as adjusted utilizing stratification and multivariate regression. Final
multivariate analysis (Table 6) adjusted for age, height, and smoking status. Additional
analyses (Table 8) adjusted for years of employment. Study restricted to males. Distribu-
tion of covariates presented for talc and potash workers presented within Table 5.
Medium Data regarding potential confounders seems to have been collected within the Medical
Research Council respiratory questionnaire, however it is unclear as source for indepen-
dent variable data not detailed directly in text.
Low Final analyses presented results without adjusting for co-exposures potentially relevant
to pulmonary function outcomes, such as silica.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium Study utilized stratification and multivariate regression for analyses of cross-sectional
data for lung function outcomes. Unclear amount of asbestos exposure in comparison
group potash workers. Unclear effect of utilizing synthetic textile workers as compar-
ison group, with their potential for increased risks of fiber exposure-related decreased
pulmonary function.
Medium Number of subjects adequate and reported as n=93 male talc miners and millers com-
pared with n=l,077 potash miners. Uncertainty regarding the number of comparison
group textile workers (Table 10).
Medium Statistical analyses reported as multivariate regression, however details of analyses
unclear for regression in terms of handling of missing data, consideration of outliers,
transformation of continuous variables and model assumptions.
Low Description of analysis brief with assumptions lacking.
Additional Comments: The relationship between pulmonary function (FEV1, FVC, FEV1/FVC% , Vmax50, Vmax75, pulmonary symptoms, pleural calcification, pneumoco-
niosis, pleural thickening) and exposures to talc containing anthophyllite and tremolite fibers in talc workers (n=93) versus potash miners (n=l,077) and
synthetic textile workers (Table 10) was examined in this cross-sectional study. Results indicated increased respiratory symptoms, radiographic abnormal-
ities and decreased pulmonary function among these talc miners and millers with some findings noted as related to dose and duration of exposure.
Continued on next page ...
Page 300 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29531 Table: 6 of 6
Study Citation:
... continued from previous page
Gamble, J. F., Fellner, W., Dimeo, M. J. (1979). An epidemiologic study of a group of talc workers. American Review of Respiratory Disease
119(1979):741-753.
Pleural Plaques
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Lung/Respiratory: Pleural thickening, Pleural calcification, Irregular opacities, Rounded opacities
Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
HERO ID:
29531
Domain Metric
Rating
Comments
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 301 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083223 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gardner, M. J., Winter, P. D., Pannett, B., Powell, C. A. (1986). Follow up study of workers manufacturing chrysotile asbestos cement products. British
Journal of Industrial Medicine 43(1986):726-732.
Lung Cancer; All malignant neoplasms, other sites; Asbestosis; All other causes, circulatory disease, respiratory disease, accidents poisoning and violence,
other causes, all causes
Lung/Respiratory: Asbestosis; Cancer/Carcinogenesis: Lung cancer, All malignant neoplasms; Mortality: All other causes, circulatory diseases, respiratory
diseases, accidents poisoning and violence, other causes, all cause
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3083223
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
Atmospheric fibre concentrations were made during period 1968-82 by company and
were assigned codes to job ittles to reflect levels of probable exposure (table 2). Over
70% of readings are based on use of personal samplers. "For the period before 1968 it
would be reasonable to assume that levels were higher because of less extensive exhaust
ventilation and more direct handling of raw asbestos".
"Since 10=970 fibre levels have generally bene low with mean levels under 1 f/ml
throughout factory. Only a few exposures over 2f/ml have been recorded and most mea-
sured concentrations have been under 0.5f/ml."
Additional Comments: Cohort study, 2167 subjects employed between 1941-1983 at asbestos cement factory in England. One death from mesothelioma (pleural in the study
cohort during the follow-up period. A death, for which the underlying cause was reported as cancer of the lung mentioned as asbestosis as an associated
condition. Metric 4 and 5 were low for both mesothelioma and other outcomes, so stopped evaluating. Mention of "small amount of amosite during four
months in 1976," but not further analyzed.Overall, information on the measurement of exposure metric (M4) to assess exposure was limited. Additionally,
the exposure levels metric (M5) information reported was limited to determine an exposure-response relationships.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 302 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3080098 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gautam, A. K., Yunus, M., Rahman, A., Reddy, S. S. (2003). Environmental monitoring of asbestos products manufacturing units-a case study. Indian
Journal of Environmental Health 45(2003):289-292.
Pulmonary Function/Spirometry Results
Lung/Respiratory: VC, FVC, FEV1, % FEV1/FVC, Peak Expiratory Flow Rate (PEFR), Forced Expiratory Flow Rate (FEF2-12), Maximum Mid Expira-
tory Flow Rate (MEF25-75% )
Asbestos - Not specified: 1332-21-4
No linked references.
3080098
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Medium The authors described how the measurements were taken and the use of PCM to count
asbestos fibers, but do not provide details about the sampling procedure or detailed
quantitative estimates of exposure.
Low The range of exposure in the study's population is limited based on the data reported on
Figure 2.
Additional Comments: None
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 303 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3077660 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015). Pleural
mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental Medicine 73(2015):290-
299.
Lung Cancer
Cancer/Carcinogenesis: Lung cancer cases and lung cancer mortality; Lung/Respiratory: Lung cancer cases and lung cancer mortality; Mortality: Lung
cancer cases and lung cancer mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3077660
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection Low This study built on a case-control study referred to as the MALCS study (Rake et al.,
2009, HERO ID 733522), which included mesothelioma patients and population con-
trols. Telephone interviews of 622 mesothelioma patients and 1420 population controls
in England, Wales, and Scotland were conducted between 2001 and 2006 as part of the
MALCS study. Additionally, 420 patients with resected lung cancer born since 1940
were interviewed in the present study as controls for the mesothelioma patients as part
of the present study (Gilham et al., 2015, HERO ID 3077660), though the dates of these
interviews were not specified.Lung cancer patients were identified by "chest physicians,
lung cancer nurse specialists, and Hospital Episode Statistics (HES) notifications" from
170 hospitals throughout Britain "Oilman et al., 2015, 3077660). Out of 420 lung can-
cer patients who were interviewed, 406 (96% ) provided consent for resected tissue to
be analyzed.The lung cancer patients were selected to be a control group for the analy-
sis of mesothelioma patients because "resected lung cancers provide the only adequate
national source of lung samples in people who can be identified systematically, are avail-
able for interview and have an age distribution similar to mesothelioma. Only a small
proportion of all lung cancers are caused by asbestos, so the asbestos lung burdens of
this national sample are reasonably representative of the general population except for a
few per cent with very high burdens."The analysis of lung samples in the present paper
was conducted on mesothelioma patients and lung cancer patients, but not the popula-
tion controls from the MALCS study.Whereas reasons for exclusion were reported for
the mesothelioma patients in the MALCS publication (Gilham et al., 2015, HERO ID
3077660), the present study (Gilham et al., 2015, HERO ID 3077660) did not report
detailed inclusion and exclusion criteria for lung cancer cases, and did not report the
number of lung cancer patients who were contacted but declined to be interviewed. Of
those who were interviewed, "written informed consent was obtained from 346 (77% )
patients with mesothelioma and their next of kin for postmortem samples to be analyzed
and from 406 (96% ) patients with lung cancer for analysis of resected tissue. "Lifetime
excess lung cancer and SMR risks standardized to British males born in 1945 were also
determined.Thus, the paper did not report some relevant information about selection
criteria.
Continued on next page ...
Page 304 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077660 Table: 1 of 1
... continued from previous page
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015). Pleural
mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental Medicine 73(2015):290-
299.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Lung cancer cases and lung cancer mortality; Lung/Respiratory: Lung cancer cases and lung cancer mortality; Mortality: Lung
cancer cases and lung cancer mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3077660
Domain Metric Rating Comments
Metric 2: Attrition Medium The authors reported that "written informed consent was obtained from 346 (77% ) pa-
tients with mesothelioma and their next of kin for postmortem samples to be analyzed
and from 406 (96% ) patients with lung cancer for analysis of resected tissue." The use
of postmortem samples for mesothelioma patients indicates that the analyses could not
include samples from mesothelioma patients who were still alive. The use of resected
tissue for lung cancer patients implies that the lung cancer patients may have been alive
at the time of sample collection. The authors reported that samples were analyzed as
they became available, such that transmission electron microscopy (TEM) was per-
formed on 133 mesothelioma samples and 262 lung cancer samples. All of the analyzed
samples were from patients born since 1940, with the exception of 11 female mesothe-
lioma patients born between 1925-1939, who were excluded from most of the analyses.
Thus, lung samples were analyzed for 133/346 (38% ) of the mesothelioma patients and
262/406 (65% ) of the lung cancer patients for whom consent was obtained. Thus, there
was at least moderate exclusion from the analysis sample of lung cancer patients.
Metric 3: Comparison Group Low For the main analyses there was no control group for lung cancer because lung cancer
cases were included as a control group for mesothelioma cases. The paper also included
additional analyses of SMR, in which the comparison group was all British men born in
1945.The authors reported that "the lifetime risk (probability of dying by age 90) was
calculated actuarially in each lung burden category assuming current (2013) UK rates
for all other causes of death. These lifetime risks were standardized to the projected
probabilities of dying by age 90 for mesothelioma (0.86% ) and lung cancer (4.67% ) of
all British men born in 1945." SMRs in each lung burden category were determined "for
the cohort of British men whose central date of birth is the beginning of 1945, (The me-
dian date of birth of our mesothelioma cases was September 1944.)"The SMR analyses
were restricted to males, but the birth years of cases were not restricted to the one year
(1945) of birth of the comparison group. Race was not mentioned in the paper.
Domain 2: Exposure Characterization
Continued on next page ...
Page 305 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077660 Table: 1 of 1
... continued from previous page
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015). Pleural
mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental Medicine 73(2015):290-
299.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Lung cancer cases and lung cancer mortality; Lung/Respiratory: Lung cancer cases and lung cancer mortality; Mortality: Lung
cancer cases and lung cancer mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3077660
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Medium
Metric 5: Exposure Levels
Metric 6: Temporality
Medium
Low
Lifetime occupational history was obtained from telephone interviews of 622 mesothe-
lioma patients, 1420 population controls, and 420 patients with resected lung cancer.
Then "job titles were assigned to Standard Occupational Classification 1990 (SOC 90)
and Standard Industrial Classification 1992 (SIC 92) codes and grouped into main job
categories" (Gilham et al., 2015, 733522). The authors reported that "subjects were as-
signed to the highest-ranking occupation they had worked in irrespective of duration".
Thus, although lifetime work history was obtained, the assignment of occupation was
based on only a portion of this history.Transmission electron microscopy (TEM) was
used to analyze 133 post-mortem lung tissue samples from a subset of the mesothelioma
patients and 262 resected lung tissue samples from a subset of the lung cancer patients.
The authors reported that "lung samples were anonymized and sent to the Health and
Safety Laboratory (HSL) for TEM counting of asbestos fibers longer than 5 um."Lung
tissue samples were analyzed as they became available. Because tissue samples, but
not environmental samples, were analyzed, the samples were only analyzed at one time
point for each individual, but this time point is representative of cumulative asbestos
lung fiber burden.
The range and distribution of exposure was sufficient to develop an exposure-response
estimate. The asbestos fiber burden in lung tissue was grouped into six categories for the
analyses of SMR.
This study analyzed resected tissue from lung cancer patients. It is unclear whether all
of the resected tissue samples were from lung cancer patients who were alive or whether
some of the samples were obtained post-mortem. Regardless, the lung tissue samples
were taken after the diagnosis of lung cancer. Thus, the exposure measurement was
obtained after the outcome measurement. Therefore, the temporality of exposure and
outcome is uncertain.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
Medium Lung Cancer: The authors state that lung cancer cases were "identified through chest
physicians, lung cancer nurse specialists and Hospital Episode Statistics (HES)" from
170 hospitals throughout Britain (Gilham et al., 2015, HERO ID 733522). However, the
paper did not specify whether the cases were confirmed by histological or cytological
means, and did not specify ICD codes.
Medium Although lung cancer SMRs were reported, associated confidence intervals were not
reported.
Domain 4: Potential Confounding / Variability Control
Continued on next page ...
Page 306 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077660 Table: 1 of 1
... continued from previous page
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015). Pleural
mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental Medicine 73(2015):290-
299.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Lung cancer cases and lung cancer mortality; Lung/Respiratory: Lung cancer cases and lung cancer mortality; Mortality: Lung
cancer cases and lung cancer mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3077660
Domain
Metric
Rating
Comments
Metric 9:
Metric 10:
Covariate Adjustment
Covariate Characterization
Low
Medium
The SMR analyses were restricted to males. SMR were standardized to the population
of British males born in 1945, but the lung cancer cases were not restricted by birth year.
Race was not mentioned in the paper.
Although the authors did not discuss whether the questionnaires used to interview par-
ticipants were validated, there is no evidence to suggest any concerns about the validity
of the method. It is unlikely that the participants would have incorrectly reported sex or
age.
Potential co-exposures were not addressed.
Metric 11:
Co-exposure Counfounding
Low
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The main research question addressed the association between asbestos lung burden
and mesothelioma. The main study design and methods are uninformative for lung
cancer because lung cancer cases were used as a control group for mesothelioma cases.
Thus, the main study design is not appropriate for assessing the association between
asbestos exposure and lung cancer.However, the study also assessed lifetime excess lung
cancer risk and lung cancer SMRs for asbestos fiber burden categories standardized to
the population of British males born in 1945, which is an appropriate statistical method
for assessing the association between asbestos exposure and lung cancer mortality.
Medium Although the authors did not provide an explicit discussion of power, and did not pro-
vide p-values or confidence intervals for some of the results, there appears to be a suf-
ficient number of lung cancer cases for analyses of SMR by asbestos fiber burden cate-
gory.
Medium The analyses were described in sufficient detail in the paper and in "Appendix 1: Statis-
tical Methods" (Gilham et al„ 2015, 3077660).
Medium Although some details could have been explained better, the methods for calculating the
SMRs were sufficiently transparent.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Continued on next page ...
Page 307 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077660 Table: 1 of 1
... continued from previous page
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015). Pleural
mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental Medicine 73(2015):290-
299.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Lung cancer cases and lung cancer mortality; Lung/Respiratory: Lung cancer cases and lung cancer mortality; Mortality: Lung
cancer cases and lung cancer mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3077660
Domain
Metric
Rating
Comments
Metric 16: Use of Biomarker of Exposure
Metric 17: Effect Biomarker
Metric 18: Method Sensitivity
Metric 19: Biomarker Stability
Metric 20: Sample Contamination
Metric 21: Method Requirements
Metric 22: Matrix Adjustment
High This study asbestos used fiber concentrations in lung tissue samples as a biomarker of
asbestos exposure, which has a clear relationship with target dose. Transmission elec-
tron microscopy (TEM) was used to measure this biomarker. In the lung cancer and
mesothelioma lung tissue samples assessed in this study, 75% of the counted fibers were
amosite, 18% were crocidolite, 1.9% were chrysotile, 1 % were tremolite, 2 % were
anthophyllite, 0.6% were actinolite, and 1.7% were uncharacterized amphiboles. Thus,
several different fiber types were identified in this study because TEM can distinguish
between fiber types, thus determining specific biomarkers of exposure (fiber concentra-
tions in lung tissue) for each specific fiber type.
N/A The only biomarkers assessed were biomarkers of exposure. Biomarkers of effect were
not assessed.
Medium As described in Appendix 2, the analytical sensitivity for fiber counts was 0.01 million
fibers per dry gram. Only 2.8% of all samples, and 9/262 lung cancer samples, did not
achieve this sensitivity due to low fiber concentrations and high amounts of other parti-
cles. The sensitivity was later increased to 0.003 mf/g by using newer equipment for a
selected subgroup of samples.
Low All lung tissue samples were sent to a pathology laboratory in Leeds for an initial as-
sessment and preparation and then were sent to the Health and Safety Laboratory (HSL)
for TEM analysis. Specific preparation for storage and transport was not detailed,
though it was mentioned that blocks were waxed and de-waxed. The authors did not
specifically discuss the stability of the biomarker.
High The authors detail that "new disposable containers and filtration equipment were used
for each sample to avoid cross-contamination and a process blank was run with each
batch of analyses" (Gilham et al., 2015, 3077660)
High The use of transmission electron microscopy (TEM) enabled appropriate identification
and quantification of asbestos fibers in the samples.
N/A Matrix adjustment is not required for assessment of this biomarker.
Additional Comments: The main study design and methods are uninformative for lung cancer because lung cancer cases were used as a control group for mesothelioma cases.
The study also assessed lifetime excess lung cancer risk and standardized mortality ratios (SMR) for lung cancer standardized to all British men born in
1945, which may be informative, but there are several concerns about the potential usefulness of this study for assessing the association between asbestos
exposure and lung cancer. A strength is that researchers utilized transmission electron microscopy (TEM) to determine asbestos concentrations in resected
tissue samples from lung cancer patients. Concerns include insufficient details reported for participant selection, outcome measurement, and participant
characteristics including age and race.
Continued on next page ...
Page 308 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077660 Table: 1 of 1
... continued from previous page
Gilham, C., Rake, C., Burdett, G., Nicholson, A. G., Davison, L., Franchini, A., Carpenter, J., Hodgson, J., Darnton, A., Peto, J. (2015). Pleural
mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occupational and Environmental Medicine 73(2015):290-
299.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Lung cancer cases and lung cancer mortality; Lung/Respiratory: Lung cancer cases and lung cancer mortality; Mortality: Lung
cancer cases and lung cancer mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Not specified: 1332-21-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3077660
Domain Metric
Rating
Comments
Overall Quality Determination
Low
Page 309 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 7837 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Green, F. H. Y., Harley, R., Vallyathan, V., Althouse, R., Fick, G., Dement, J., Mitha, R., Pooley, F. (1997). Exposure and mineralogical correlates of
pulmonary fibrosis in chrysotile asbestos workers. Occupational and Environmental Medicine 54(1997):549-559.
Lung Cancer; Asbestosis
Lung/Respiratory: asbestosis (pathological pulmonary fibrosis grade), lung cancer, asbestosis mortality, lung cancer mortality; Cancer/Carcinogenesis:
lung cancer, lung cancer mortality; Mortality: asbestosis mortality, lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5; Asbestos - Anthophyllite: 17068-78-9
7837, 709498, 3081241
7837
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection Medium This retrospective cohort study included employees of a Charleston, South Carolina as-
bestos packing material and asbestos textile producing plant. As described in Green et
al. 1997 (RefID 7837), eligible participants included all employees employed in textile
production for at least one month (men) or six months (women) in the plant between 01
January 1940 and 31 December 1965 who were followed up until 31 December 1975.
A total of n=3744 employees were identified, with n=874 deaths. Necropsy records
were obtained for only n=87 (10% ) of these deaths, for which pathological material was
available for only n=59. Exclusion of five asbestos workers due to major confounding
diseases of chemotherapy fibrosis (n=2) and radiation fibrosis (n=3) left a total of n=54
asbestos workers for analysis (Green et al, 1997, 7837). Non-asbestos control work-
ers with available necropsy data were only described as matched to asbestos workers
in terms of age of death, sex, hospital of death, and year of death. Of the n=38 initially
identified controls, n=4 controls were excluded due to sarcoidosis (n=l), radiation fi-
brosis (n=l), tuberculosis (n=l), and scleroderma (n=l), leaving only n=34 matched
controls for analyses. Lung tissue suitable for mineralogical fiber analysis was only
available for n=39 former asbestos workers and n=31 non-exposed controls, however
authors noted no significant differences in demographic profile or exposure history be-
tween the whole cohort of asbestos workers and the subgroup with mineralogical fiber
data (Green et al., 1997, 7837). Due to the small number of asbestos workers with eli-
gible necropsy data (n=87, or 10% ) out of the total number of deaths (n=874) from the
original population, as well as the number of eligible non-exposed controls (n=34), it
is unclear if the exposure-outcome distribution of participants is representative of that
of the target population (Green et al., 1997, RefID 7837). Key elements of study design
are also reported for Stayner et al., 1997, RefID 3081241 and Hein et al., 2007, RefID
709498 for employees at the same asbestos plant employed at least one month between
1940 and 1975. However, follow-up for RefID 3081241 was extended up to 31 Decem-
ber 1990 and included an additional n=546 non-white men, n=l,229 white women, and
n=19 non-white women. Follow-up for RefID 709498 was extended through 2001 for a
total of 3,072 workers which included white and non-white males, white and non-white
female workers as well as additional n=29 workers previously excluded but for whom
updated demographic information was obtained.
Continued on next page ...
Page 310 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 7837 Table: 1 of 1
... continued from previous page
Green, F. H. Y., Harley, R., Vallyathan, V., Althouse, R., Fick, G., Dement, J., Mitha, R., Pooley, F. (1997). Exposure and mineralogical correlates of
pulmonary fibrosis in chrysotile asbestos workers. Occupational and Environmental Medicine 54(1997):549-559.
Lung Cancer; Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: asbestosis (pathological pulmonary fibrosis grade), lung cancer, asbestosis mortality, lung cancer mortality; Cancer/Carcinogenesis:
lung cancer, lung cancer mortality; Mortality: asbestosis mortality, lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5; Asbestos - Anthophyllite: 17068-78-9
7837, 709498, 3081241
7837
Domain
Metric
Rating
Comments
Metric 2:
Attrition
Medium
The text noted that for the outcome of fibrosis score, slides consisting predominantly
of tumor, bronchus, lymph nodes, abscess or infarct were excluded, but the number
of excluded slides was not detailed and any additional loss to follow-up or missing
data for outcome or exposure was not detailed for RefID 7837. Loss to follow-up and
missing data for outcome or exposure was not detailed within RefID 3081241. For Re-
fID 709498, authors noted nearly 10% of the cohort was considered lost to follow-up,
mostly because of high rates of loss to follow-up among females and n=120 workers
known to be dead as of 31 December 2001 were missing cause of death information
with an additional 426 workers who died or were lost to follow-up before 1 January
1960 excluded from analyses using South Carolina referent rates because rates were not
available before 1960.
Metric 3:
Comparison Group
Medium
Although a formal statistical evaluation of differences in baseline characteristics of
cases and controls was not conducted and reasons for choice of matching and potential
confounding variables were not explicitly stated within RefID 7837 and RefID 3081241,
all analyses between asbestos workers and non-exposed matched controls were adjusted
for matching variables of age at death, sex, hospital at death, and year of death for RefID
7837, and for age, sex, race and calendar time for RefID 3081241. Mortality results for
SMR analyses within RefID 709498 were not stratified for any additional covariates,
however results from Poisson analyses were adjusted for sex, race, age and calendar-
year.
Domain 2: Exposure Characterization
Continued on next page .
Page 311 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 7837 Table: 1 of 1
... continued from previous page
Green, F. H. Y., Harley, R., Vallyathan, V., Althouse, R., Fick, G., Dement, J., Mitha, R., Pooley, F. (1997). Exposure and mineralogical correlates of
pulmonary fibrosis in chrysotile asbestos workers. Occupational and Environmental Medicine 54(1997):549-559.
Lung Cancer; Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: asbestosis (pathological pulmonary fibrosis grade), lung cancer, asbestosis mortality, lung cancer mortality; Cancer/Carcinogenesis:
lung cancer, lung cancer mortality; Mortality: asbestosis mortality, lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5; Asbestos - Anthophyllite: 17068-78-9
7837, 709498, 3081241
7837
Domain
Metric
Rating
Comments
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium Exposure was summarized by estimated cumulative asbestos exposures, reported lung
fiber concentrations, and asbestos bodies in RefID 7837, and by estimated cumulative
chrysotile asbestos exposures within RefID 3081241 and RefID 709498. Exposure data
was not available for each worker and exposures were estimated in RefID 7837, RefID
3081241 and RefID 709498 as detailed within Dement et al., 1983 (HERO ID 66) and
described within the main text as utilizing a job coding scheme for each worker which
used detailed job histories and 5,952 industrial hygiene plant dust sampling (conversion
factor to fiber exposure details provided) results from the plant under study covering the
period 1930-1975. HERO ID 66 noted that all known industrial hygiene data were col-
lected utilizing midget impingers by the company insurance carrier, the State Board of
Health, the U.S. Public Health Service, and the Company sampling program. Impinger
dust concentrations were converted to fiber concentrations utilizing the reported conver-
sion factors. Concurrent paired sampling was utilized to assess possible differences in
conversion factors over time. Cumulative lifetime time weighted average exposure for
each worker was described as calculated by multiplying estimates of exposure for each
job held by the time spent in each job (fibers > 5 ^m/mL3 x years in job = fiber-years.
Estimations of exposure included considerations for engineering controls and historical
textile production process changes. Authors within referenced HERO ID 66 noted the
potential for exposure misclassification but asserted that it would be nondifferential as
exposures for both diseased and non-diseased individuals were calculated in the same
manner. Other than noting that controls were never employees of the one plant under
study and concentrations of mullite were statistically significantly greater in lungs of
non-exposed controls than in asbestos workers, no assessment of "non-exposed" con-
trol occupational exposure history was noted in 7837. Total lung asbestos fibers (fibers
x 106/g dry lung) were also reported within 7837 and lung tissue fiber mineralogical
analyses was conducted according to methods within Pooley et al., 1979 (HERO ID:
3084350) utilizing transmission electron microscopy. Asbestos bodies in 7837 were
graded by independently by three pathologists utilizing light microscopy and a scale
reported by Wagner et al., 1982 (HERO ID: 3083948).
Medium The range and distribution of estimated exposure is sufficient to develop exposure-
response estimates within RefID 7837, RefID 3081241 and RefID 709498. Estimates
of lifetime cumulative, peak and average exposure medians and quartiles are detailed
within Table 2 (and within referenced HERO ID 66 Tables IV-XII by textile production
area) of Ref ID 709498. Exposure summaries within RefID 3081241 were referenced
(HERO ID 66), but reported in main text for estimated cumulative exposures in Table 1
of RefID 709498. Cumulative lifetime exposure estimates in a log scale were utilized for
regression analyses within RefID 7837, as continuous estimated cumulative exposures
within RefID 3081241 and RefID 709498.
Continued on next page ...
Page 312 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 7837 Table: 1 of 1
... continued from previous page
Green, F. H. Y., Harley, R., Vallyathan, V., Althouse, R., Fick, G., Dement, J., Mitha, R., Pooley, F. (1997). Exposure and mineralogical correlates of
pulmonary fibrosis in chrysotile asbestos workers. Occupational and Environmental Medicine 54(1997):549-559.
Lung Cancer; Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: asbestosis (pathological pulmonary fibrosis grade), lung cancer, asbestosis mortality, lung cancer mortality; Cancer/Carcinogenesis:
lung cancer, lung cancer mortality; Mortality: asbestosis mortality, lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5; Asbestos - Anthophyllite: 17068-78-9
7837, 709498, 3081241
7837
Domain
Metric
Rating
Comments
Metric 6: Temporality
Medium Eligible participants were followed up until 31 December 1975 in RefID 7837, but it is
unclear if follow-up was sufficient for those who began work in the later years of study
as those hired around 1965 would have only been followed for approximately ten years
and Table 1 of main text indicates dates of death range from 1964-1975. Follow-up
for RefID 3081241 was extended through 1990, and follow-up for RefID 709498 was
extended through 2001.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or Medium Lung Cancer: In RefID 7837, both workers and control subjects for whom necropsy
Characterization lung tissue samples were evaluated for pulmonary fibrosis were additionally classi-
fied based on lung cancer status; the methods for doing so are not stated.; Asbestosis:
In RefID 7837, deaths were identified from hospital records, death certificates, and
state records. The extent of pulmonary fibrosis (referred to as "pulmonary fibrosis (as-
bestosis)") in necropsy samples was graded according to criteria established by a joint
National Institute for Occupational Safety and Health (NIOSH) and College of Amer-
ican Pathologists (CAP) Committee. The fibrosis scores for all slides from each case
were reviewed by three pathologists blinded to exposure status independently, averaged
to give an overall fibrosis score, only slides with recognizable lung parenchyma were
graded and those slides with predominantly tumor, bronchus, lymph notes abscess or
infarct were excluded. Pairwise reproducibility between pathologists in RefID 7837 was
assessed and for fibrosis severity was 71% for exact agreement and 98% for agreement
to ± one category and average pairwise reproducibility within pathologists for sever-
ity was 53% for exact agreement and 96% for agreement to one category. For RefID
3081241, deaths due to asbestosis were identified on death certificates using ICD codes.
Asbestosis deaths were identified using a multiple cause of death approach that included
a review of all death certificate fields as in Steenland et al., 1992 (HERO ID not avail-
able). A broad definition was used that included both deaths from asbestosis (ICD-9
501) and pneumoconiosis (ICD-9 505).For RefID 709498, deaths due to asbestosis were
identified using ICD codes in the National Death Index (via NDI Plus); codes used in the
definition of asbestosis are not provided but the methods are stated to be the same as in
prior studies of this cohort.
Continued on next page ...
Page 313 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 7837 Table: 1 of 1
... continued from previous page
Green, F. H. Y., Harley, R., Vallyathan, V., Althouse, R., Fick, G., Dement, J., Mitha, R., Pooley, F. (1997). Exposure and mineralogical correlates of
pulmonary fibrosis in chrysotile asbestos workers. Occupational and Environmental Medicine 54(1997):549-559.
Lung Cancer; Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: asbestosis (pathological pulmonary fibrosis grade), lung cancer, asbestosis mortality, lung cancer mortality; Cancer/Carcinogenesis:
lung cancer, lung cancer mortality; Mortality: asbestosis mortality, lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5; Asbestos - Anthophyllite: 17068-78-9
7837, 709498, 3081241
7837
Domain
Metric
Rating
Comments
Metric 8: Reporting Bias
Medium There were no concerns for selective reporting as all outcomes which were outlined
within methods were also reported within the results for RefID 7837, RefID 3081241
and RefID 709498. For RefID 7837, regression equation and correlation results from
the text and Figures 2 and 3 were summarized for the relationship between estimated
cumulative lifetime exposure, concentrations of lung fibers lung burden of asbestos and
lung fibrosis scores for asbestos textile workers. Results for RefID 7837 pleural plaques
were only reported within text as the proportion (percentage) of pleural plaque cases in
asbestos exposed workers versus non-exposed controls.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Final regression analyses in RefID 7837 were adjusted for age and sex for the outcome
of lung fibrosis score however it is unclear if all regression analyses results included
these covariates. All analyses between asbestos workers and non-exposed matched con-
trols in RefID 7837 were adjusted for matching variables of age at death, sex, hospital
at death, and year of death. Data regarding smoking status was not available, however
authors noted smoking history from a 1964 Public Health survey of the plant seemed
similar to the general population and it was surmised that there would not be significant
differences in smoking status between exposed workers and non-exposed controls, all
analyses were adjusted for age, sex, race and calendar time for RefID 3081241. Mortal-
ity results for SMR analyses within RefID 709498 were not stratified for any additional
covariates, however results from Poisson analyses were adjusted for sex, race, age and
calendar-year.
Medium While the methods in RefID 7837 utilized to obtain and validate data regarding potential
confounders were described only as obtained through computerized hospital records,
there is no indication that methods had poor validity. Methods for obtaining confounder
data within RefID 3081241 and RefID 709498 were not detailed, but assumed to be
obtained through similar hospital and national vital status records.
Medium Potential co-exposures to non-asbestos mullite, rutile and iron were considered within
analyses of fibrosis (Figure 3D) in RefID 7837. Assessment of potential co-exposures in
analyses within non-exposed controls in RefID 7837 was not detailed, although authors
noted that concentrations of mullite were statistically significantly greater in lungs of
non-exposed controls than in asbestos workers. Considerations of non-asbestos fibers
within RefID 3081241 and RefID 709498 was not detailed.
Domain 5: Analysis
Continued on next page ...
Page 314 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 7837 Table: 1 of 1
... continued from previous page
Green, F. H. Y., Harley, R., Vallyathan, V., Althouse, R., Fick, G., Dement, J., Mitha, R., Pooley, F. (1997). Exposure and mineralogical correlates of
pulmonary fibrosis in chrysotile asbestos workers. Occupational and Environmental Medicine 54(1997):549-559.
Lung Cancer; Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: asbestosis (pathological pulmonary fibrosis grade), lung cancer, asbestosis mortality, lung cancer mortality; Cancer/Carcinogenesis:
lung cancer, lung cancer mortality; Mortality: asbestosis mortality, lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5; Asbestos - Anthophyllite: 17068-78-9
7837, 709498, 3081241
7837
Domain
Metric
Rating
Comments
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium Multivariate linear regression was utilized for analysis of the relationship between esti-
mated occupational asbestos exposure and fibrosis score in RefID 7837. Authors several
regression models in RefID 7837, including addition of a quadratic term for exposure
and exploration of a threshold effect of exposure on lung fibrosis, were developed, how-
ever results were not detailed and authors noted the model was not precise enough to
determine a minimal or threshold level of exposure that would produce asbestosis. Anal-
yses within RefID 3081241 utilized Poisson regression and restricted cubic spline mod-
els, while RefID 709498 focused upon SMR, Poisson and cubic spline models.
Medium It is likely the number of subjects (n=54 total; n=44 male asbestos workers, n=10 fe-
male asbestos workers) was inadequate in RefID 7837 for analyses of fibrosis scores
with estimated exposures in asbestos workers only, or lung fiber content in asbestos and
non-asbestos workers (n=39 asbestos workers and n=31 non-exposed controls), partic-
ularly within results of multivariate analyses. Authors in RefID 7837 noted the lack of
statistical power was largely due to the small number of cases with low and intermediate
levels of exposure. The number of subjects within RefID 3081241 (n=l,848) and RefID
709498 (n=3,072) was adequate.
Medium Details were provided for exposure assessment within HERO ID 66 for RefID 7837,
RefID 3081241 and RefID 709498. Detailed statistical analysis methods for RefID 7837
were reported, however details such as rules for transformation of continuous variables
of age, assessment of non-linearity and missing data, other than smoking status, were
not detailed. The statistical analyses for RefID 3081241 and RefID 709498 were de-
scribed including variables within the analyses.
Medium The description of statistical analysis was fairly detailed in RefID 7837, RefID 3081241
and RefID 709498, however model details regarding consideration of non-linear effects
within reported exploration of quadratic exposure covariates and threshold effects of
exposure on lung fibrosis were reported in RefID 7837 but not in detail.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric 16: Use of Biomarker of Exposure
Metric 17:
Metric 18:
Metric 19:
Effect Biomarker
Method Sensitivity
Biomarker Stability
High Total lung asbestos fiber content in RefID 7837 was noted to have a highly significant
correlation with estimated cumulative asbestos exposure (Figure 1 and text). Additional
analyses indicated similar correlations with specific asbestos fiber types within lung tis-
sue. The mean number of asbestos bodies on tissue sections in RefID 7837 was strongly
associated with lifetime cumulative exposure (P< 0.01), total amphibole (P< 0.01), and
total chrysotile fibers (P< 0.05) in the lung.
N/A N/A. RefID 7837 reports a biomarker of exposure.
Low LOD/LOQ values were not stated in RefID 7837.
Low Storage history of samples not detailed in RefID 7837.
Continued on next page ...
Page 315 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 7837 Table: 1 of 1
... continued from previous page
Green, F. H. Y., Harley, R., Vallyathan, V., Althouse, R., Fick, G., Dement, J., Mitha, R., Pooley, F. (1997). Exposure and mineralogical correlates of
pulmonary fibrosis in chrysotile asbestos workers. Occupational and Environmental Medicine 54(1997):549-559.
Lung Cancer; Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: asbestosis (pathological pulmonary fibrosis grade), lung cancer, asbestosis mortality, lung cancer mortality; Cancer/Carcinogenesis:
lung cancer, lung cancer mortality; Mortality: asbestosis mortality, lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite: 14567-73-8; Asbestos - Amosite
(grunerite): 12172-73-5; Asbestos - Anthophyllite: 17068-78-9
7837, 709498, 3081241
7837
Domain
Metric
Rating
Comments
Metric 20: Sample Contamination
Metric 21: Method Requirements
Metric 22: Matrix Adjustment
Medium Contamination information was not detailed in RefID 7837.
Medium Transmission electron microscopy instrumentation within RefID 7837 methods pro-
vides unambiguous identification and quantitation of the biomarker, however text noted
analysis of samples from different unspecified sites yielded moderate variability in fiber
counts, but the proportions by fiber type were described as relatively constant. Asbestos
bodies in RefID 7837 were graded by independently by three pathologists utilizing light
microscopy and a scale reported by Wagner et al., 1982 (HERO ID: 3083948).
N/A N/A. RefID 7837 reports biomarker of exposure data.
Additional Comments: ReflDs 3081241 and 709498 report n=3 cases of mesothelioma, but authors in RefID 3081241 noted it was not possible to model this outcome due to the
low number of cases, and RefID 709498 did not include mesothelioma within SMR analyses outcomes. Pleural plaques were noted as an outcome in the
text of RefID 7837, but only reported as prevalent with lung cancer and not presented within results tables or analyzed with respect to levels of asbestos
exposure.RefID 709498 reported SMRs for a wide range of cancer and non-cancer outcomes in Table 2, but did not analyze these outcomes with respect to
levels of asbestos exposure.
Overall Quality Determination Medium
Page 316 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 626459 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Gustavsson, P., Jakobsson, R., Johansson, H., Lewin, F., Norell, S., Rutkvist, L. E. (1998). Occupational exposures and squamous cell carcinoma of the
oral cavity, pharynx, larynx, and oesophagus: A case-control study in Sweden. Occupational and Environmental Medicine 55(1998):393-400.
Laryngeal Cancer; oral cavity, pharynx, oesophagus, larynx , all sites (including head and neck)
Cancer/Carcinogenesis: cancer in all sites, cancer in larynx, cancer in oesophagus, cancer in pharynx, cancer in oral cavity; Lung/Respiratory: cancer in
larynx, cancer in pharynx; Gastrointestinal: cancer in oesophagus, cancer in oral cavity; head and neck: cancer in all sites
Asbestos - Not specified: 1332-21-4
No linked references.
626459
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Uninformative Neither PCM nor TEM were used for measuring exposure. The study measures asbestos
exposure and other selected exposures using occupational codes from the Swedish stan-
dard classification of occupations, NYK 1983, which were inputted by a blinded oc-
cupational hygienist. However, it appears that occupational history was collected via
interview which may be subject to recall bias and, thus, exposure misclassification.
Authors also stated "The classification of occupational exposures was based on occupa-
tional histories, and could not account for variation in the exposure that was not reflected
in the job titles or description of work tasks in the interviews. It is probable that there is
imprecision in the classification of the intensity of occupational exposures, even if the
histories were obtained directly from the men rather than from surrogates."
Metric 5: Exposure Levels Low Although cumulative exposure appeared to be collected for asbestos, levels of exposure
were separated into quartiles with no identification of the distribution of cumulative dose
(see Table 3). Additionally, Table 4 shows asbestos exposure treated as a dichotomized
variable. Authors also stated it was "not feasible to calculate dose-response in terms of
fibre concentrations or fibre-years from the data in its present form. Dose estimations
were based on quantitative assessments of the intensity of the exposure (annual average
fibre concentration) as well as the probability of exposure."
Additional Comments: Some target organs were categorized as either GI or respiratory. However, it might be worth considering them as overlapping since the authors stated they
were investigating " aetiological factors for cancer of the upper aerodigestive tract." Data were not extracted as the study was deemed uninformative in
Metric 4.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessment for the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 317 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 675185 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hagmar, L., Akesson, B., Nielsen, J., Andersson, C., Linden, K., Attewell, R., Moller, T. (1990). Mortality and cancer morbidity in workers exposed to
low levels of vinyl chloride monomer at a polyvinyl chloride processing plant. American Journal of Industrial Medicine 17(1990):553-565.
Lung Cancer; Laryngeal Cancer
Cancer/Carcinogenesis: malignant tumor mortality, gastrointestinal tumor mortality, respiratory tumor mortality, gastrointestinal tract tumor morbidity,
Liver and bile duct tumor morbidity, Respiratory tract tumor morbidity, nose and sinus tumor morbidity, larynx tumor morbidity, lung tumor morbidity,
prostate tumor morbidity, All cancer morbidity, Brain tumor morbidity; Cardiovascular: cardiovascular disease mortality, ischemic heart disease mortality;
Lung/Respiratory: bronchitis, emphysema, asthma mortality, respiratory tumor mortality, Respiratory tract tumor morbidity, nose and sinus tumor mor-
bidity, larynx tumor morbidity, lung tumor morbidity; Gastrointestinal: gastrointestinal disease mortality, gastrointestinal tumor mortality, gastrointestinal
tract tumor morbidity; Renal/Kidney: urinary tract disease mortality; Mortality: mortality from violence, All cause, gastrointestinal disease mortality, uri-
nary tract disease mortality, bronchitis, emphysema, asthma mortality, ischemic heart disease mortality, cardiovascular disease mortality, malignant tumor
mortality, gastrointestinal tumor mortality, respiratory tumor mortality; Hepatic/Liver: Liver and bile duct tumor morbidity; Reproductive/Developmental:
prostate tumor morbidity; Neurological/Behavioral: Brain tumor morbidity
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
675185
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Measurement of exposure was not mentioned using a combination of midget impinger,
PCM, or TEM, and conversion factors were not determined.Estimates of asbestos ex-
posure were obtained from breathing zone samples conducted in 1971. Details on the
sampling method were minimal. Other time periods were not sampled, but industrial
hygienists estimated job- and department-specific . Time-weighted averages were as-
sumed to be 40% lower after 1969 compared to prior years. Cumulative exposure was
determined by adding years of exposure.
Medium The mean exposure level among highly exposed workers was 1-3 fibers/ml, that among
moderately exposed workers was >0.1-0.5 fibers/ml, and that among workers exposed
to low levels was up to 0.1 fibers/ml. These measurements were performed for 108
hours in 1971. The study showed a relationship between three cumulative exposure
levels and SMR/SSMR of the respiratory tract, pleura of the lung, and all sites.
Additional Comments: This study utilized an occupational cohort in Sweden to examine rates of tumor mortality and morbidity. There was some concern regarding details of
exposure characterization, and the presence of other potential chemical hazards (e.g., VCM and plasticizers). Results indicated increased risk of mortality,
which was more apparent in 10-yr latency models.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 318 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6775698 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Hall, A., Kromhout, H., Schuz, J., Peters, S., Portengen, L., Vermeulen, R., Agudo, A., Ahrens, W., Boffetta, P., Brennan, P. (2020). Laryngeal cancer risks
in workers exposed to lung carcinogens: Exposure-effect analyses using a quantitative job exposure matrix. Epidemiology 31(2020):145-154.
Laryngeal Cancer
Cancer/Carcinogenesis: Laryngeal cancer; Lung/Respiratory: Laryngeal cancer
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
6775698
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium Subjects were male and female cases with diagnosed laryngeal cancer and drawn from
the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, de-
scribed as a "global collaboration established in 2004 among research groups currently
or recently conducting large molecular epidemiologic studies of head and neck cancer."
Subjects represented five INHANCE studies with occupational histories coded to the In-
ternational Standard Classification of Occupations (ISCO)-68, representing individuals
from Western Europe, Latin America, France, and Germany. Descriptive characteris-
tics of subjects are provided in Table 1. All subjects identified as blue-collar workers.
For studies to be included in this analysis, they needed to have a recruitment protocol
for cases and controls, and structured questionnaires to capture information on demo-
graphic factors, occupational history, tumor characteristics, alcohol consumption, and
tobacco use. The authors report that most studies were hospital based. Available infor-
mation indicates a low risk of selection bias as to which groups were included in the
present analysis.The final analytic sample consisted of 2256 laryngeal cancer cases (203
females; 2035 males) and 7857 controls (1604 females, 6263 males).
Medium There was moderate subject loss in the study. Participation rates across the five studies
ranged from 80% -96% and 62% -86% for cases and controls, respectively. However,
exposure and outcome data remain largely complete. Exclusion of subjects were also
adequately addressed, as 213 cases and 471 controls were excluded from the final ana-
lytical sample due to missing data on sex, age, occupational history, tobacco smoking,
and alcohol use. There is no evidence that this missingness is a significant source of
bias.
High Controls in the study were subject to the same inclusion and exclusion criteria as cases.
Additionally, controls were frequency-matched to cases based on factors such as age,
sex, and regional factors. However, in statistical analysis different exposure groups were
compared to each other rather than comparing cases to controls in logistic regression
analyses. Adjustment factors in those models included which study they originated
from, age, alcohol intake, and tobacco smoking. Results are also presented as stratified
by sex, thus allowing for an appropriate controlling for differences in exposure groups.
Difference in descriptive characteristics between cases and controls are also presented in
Table 1.
Domain 2: Exposure Characterization
Continued on next page .
Page 319 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6775698 Table: 1 of 1
... continued from previous page
Hall, A., Kromhout, H., Schuz, J., Peters, S., Portengen, L., Vermeulen, R., Agudo, A., Ahrens, W., Boffetta, P., Brennan, P. (2020). Laryngeal cancer risks
in workers exposed to lung carcinogens: Exposure-effect analyses using a quantitative job exposure matrix. Epidemiology 31(2020):145-154.
Laryngeal Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Cancer/Carcinogenesis: Laryngeal cancer; Lung/Respiratory: Laryngeal cancer
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
6775698
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Assessment of measures were completed using a SYN-JEM which used empirical mod-
els using individual personal measurements of occupational exposures from European
countries and Canada. Data represented measurements taken between the 1970s and
2009. For linear mixed-effect modeling, 27,958 measurements were recorded for as-
bestos (expressed in f/ml) and represented measurements that had a job code available
and a sampling duration between 60-600 minutes. Random effects terms in modeling in-
cluded region/country and job title, while fixed effects included measurement year, sam-
pling duration, and prior exposure rating that was based on a general population JEM.
Predictions provided an estimated annual mean exposure for a given job and region/
country for asbestos.According to Peters et al., 2016 (HERO ID: 3531308), asbestos
fiber concentrations were measured using PCM in over 95% of samples. One caveat is
that measurements conducted in Germany were predominantly (99% ) done using elec-
tron microscopy, which may make data from German participants (10% of cases and
11% of controls) somewhat biased relative to the rest of the participants. Additionally,
there is some risk for exposure misclassification when using JEMs since all individuals
in a given job category are given the same exposure measurement.
Medium The distribution of exposure appears to be sufficient to develop an exposure-response
estimate. Cumulative exposure was calculated and stratified by diameter and length.
<50th, 50"75th, 75"90th, and >90th percentiles were used to stratify cumulative expo-
sure. Because of the small sample size for females, the median exposure in controls was
used as the "cut-point" for categories of cumulative exposure.
Medium The authors report that the duration of exposure ranged from less than 10 years to
greater than 30 years, with a somewhat even distribution. The study appears to establish
appropriate temporality between exposure and outcome, but it"s unclear if this applied
for all subjects. Data on time since first exposure is not discussed; however, the study
applied "exposure lags of 10 and 20 years before diagnosis and interview to all agents
and metrics" in sensitivity analyses.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High Laryngeal Cancer: Laryngeal cancer status was ascertained in the original studies in-
cluded in this analysis using ICD-10 classification codes: C32.0-C32.3 and C32.8-
C32.9.
High All results seem to be reported in all aspects of the report. The authors provided suffi-
cient explanation for difference in methodology between male and female participants.
Effect estimates report confidence intervals. Footnotes are provided for additional clari-
fication on analyses. Links to supplemental results tables are available.
Continued on next page ...
Page 320 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6775698 Table: 1 of 1
... continued from previous page
Hall, A., Kromhout, H., Schuz, J., Peters, S., Portengen, L., Vermeulen, R., Agudo, A., Ahrens, W., Boffetta, P., Brennan, P. (2020). Laryngeal cancer risks
in workers exposed to lung carcinogens: Exposure-effect analyses using a quantitative job exposure matrix. Epidemiology 31(2020):145-154.
Laryngeal Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Cancer/Carcinogenesis: Laryngeal cancer; Lung/Respiratory: Laryngeal cancer
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
6775698
Domain
Metric
Rating
Comments
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Appropriate adjustments were made to account for potential confounding in final anal-
yses. In Model 1, the study adjusted for participant age and study. In Model 2, they
further adjusted for tobacco smoking and alcohol consumption which are well-known
risk factors for laryngeal cancer. There is no adjustment for socioeconomic status, and it
is not explicitly clear why all covariates were chosen.
Medium As an occupational study, it can be assumed that covariate data was collected from per-
sonnel records.
Low Co-exposures were not assessed in this study. Authors also recognized that potential
co-exposure to other carcinogenic agents can influence the precision of being able to
identify the agents of interest in the study as risk factors for laryngeal cancer.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design chosen was appropriate for the research question. Logistic regression
models were utilized in this case-control study.
Medium 2256 cases and 7857 controls were analyzed in this study. Sample sizes for female par-
ticipants tended to be smaller than males, but authors specified appropriate changes in
methodology to account for this. This included structuring percentile categories of cu-
mulative exposure based on the median exposure in controls as the cut-point and using
a continuous log-transformed pack-years variable to represent adjustment for tobacco
smoking.
Medium Methods and analyses were described sufficiently enough for reproducibility.
Medium Methods for calculating risk estimates are clear. The authors report the results of logistic
regression and there is no reason to suspect assumptions were not met.
Additional Comments:
This study assessed the association between several carcinogenic agents (including asbestos) and the risk of laryngeal cancer. For asbestos, it should be
noted that measurements conducted in Germany were predominantly (99% ) done using electron microscopy (Peters et al., 2016 3531308). However, the
paper does not report statistically significant results.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 321 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709618 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hansen, J., de Klerk, N. H., Musk, A. W., Hobbs, M. S. T. (1998). Environmental exposure to crocidolite and mesothelioma: Exposure-response relation-
ships. American Journal of Respiratory and Critical Care Medicine 157(1998):69-75.
Lung Cancer; Ovarian Cancer; Leukemia, colorectal cancer, digestive system cancers; Signs/symptoms ill defined mortality, nervous system mortality
Lung/Respiratory: Lung cancer mortalityLung cancer incidenceRespiratory system mortalityMesothelioma incidenceMesothelioma mortality; Cancer/
Carcinogenesis: Mesothelioma incidenceMesothelioma mortalityLung cancer incidenceLung cancer mortalityCancer incidence, all and specific types (SIRs
for exposed/gen pop, no dose-reponse)Cancer mortality, all and specific types (SMRs for exposed/gen pop, no dose-response); Mortality: Mesothelioma
mortalityLung cancer mortality All-cause mortality (SMR for exposed/gen pop, no dose-response)Respiratory system mortality (SMR for exposed/gen
pop, no dose-response)Digestive system mortality (SMR for exposed/gen pop, no dose-response)Signs/symptoms ill-defined (SMR for exposed/gen pop,
no dose-response)Nervous system mortality (SMR, no dose-response); nan:
Asbestos - Crocidolite (riebeckite): 12001-28-4
709618, 709466, 709501, 2088306, 6869529
709618
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium Exposure estimates for Wittenoom residents used intensities of 1.0 f/mL for 1943-1957
(old mill), 0.5 f/mL for 1958-1966 (new mill " mining ended), and declining values in-
terpolated to 0.01 f/mL in 1992 (see Hansen et al. 1997, HERO ID 2219991). These
values were based on measures of fibers > 5 jUm that began in 1966 using a Casella
thermal precipitator and PCM, cited as 0.5 f/mL (Armstrong et al. 1988, 3083076;
Rogers et al. 2001, 3080506). Earlier measures (1948-1966) were limited to dust col-
lected by konimeter; pre-1958 intensity was extrapolated based on estimates that the
new mill halved exposure (Hansen et al. 1997, 2219991; Rogers et al. 2002, 3080506).
Subsequent fiber measures were collected from personal and/or fixed monitors in 1973
(median 0.22 f/mL), 1977, and 1978 using PCM counts; in 1984 and 1986 using scan-
ning electron microscopy (SEM); and in 1992 using TEM. Concerns include the limited
number, location, and quality of samples, as well as use of less precise SEM counts.
Cumulative exposure was calculated based on duration of residence, assuming 24 h
a day, 7 d a week exposure, estimated with varying degrees of error and likely differ-
ing by mesothelioma case status. Duration estimated used available data as follows:
(i) mesothelioma registry data; (ii) questionnaire responses; (iii) worker employment
dates for relatives; (iv) family member questionnaires; (v) records at hospitals, schools,
etc; and finally (vi) a value of 6 months if still unknown. Details were not provided on
the proportion estimated using methods with increasing error. Another source of error
includes the lack of information on specific locations and activities that would affect
individual exposure (having lived with and/or likely washed the clothes of an asbestos
worker were estimated). The most recent publication indicated that cumulative exposure
data was missing for about 5% of the sample (Reid et al. 2018, 6869529).
Metric 5: Exposure Levels Low SMR and SIR analyses did not examine whether these rates varied over levels of expo-
sure. Lung cancer associations reported in Reid et al. 2008, 709466 used continuous
f/mL-years for cumulative exposure.
Continued on next page ...
Page 322 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709618 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Hansen, J., de Klerk, N. H., Musk, A. W., Hobbs, M. S. T. (1998). Environmental exposure to crocidolite and mesothelioma: Exposure-response relation-
ships. American lournal of Respiratory and Critical Care Medicine 157(1998):69-75.
Lung Cancer; Ovarian Cancer; Leukemia, colorectal cancer, digestive system cancers; Signs/symptoms ill defined mortality, nervous system mortality
Lung/Respiratory: Lung cancer mortalityLung cancer incidenceRespiratory system mortalityMesothelioma incidenceMesothelioma mortality; Cancer/
Carcinogenesis: Mesothelioma incidenceMesothelioma mortalityLung cancer incidenceLung cancer mortalityCancer incidence, all and specific types (SIRs
for exposed/gen pop, no dose-reponse)Cancer mortality, all and specific types (SMRs for exposed/gen pop, no dose-response); Mortality: Mesothelioma
mortalityLung cancer mortality All-cause mortality (SMR for exposed/gen pop, no dose-response)Respiratory system mortality (SMR for exposed/gen
pop, no dose-response)Digestive system mortality (SMR for exposed/gen pop, no dose-response)Signs/symptoms ill-defined (SMR for exposed/gen pop,
no dose-response)Nervous system mortality (SMR, no dose-response); nan:
Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): 709618, 709466, 709501, 2088306, 6869529
709618
Domain Metric Rating Comments
Additional Comments: These studies analyzed >5,000 individuals who had lived in Wittenoom, Australia for >1 month from 1943-1993 to evaluate associations between resi-
dential asbestos exposure and (i) mesothelioma (all studies); (ii) mortality in women and persons exposed as children (Reid et al. 2008, 709466; Reid et al.,
2012 2088306), and (iii) cancer incidence (Reid et al. 2012, 2088306). The cohort excluded asbestos workers. In the most recent study geometric mean
(IQR) cumulative exposure was 3.02 (1.4-7.70) f/mL-years in children and 2.05 (0.90-5.75) f/mL-years in adults. SMRs for residents exposed as children
were significantly higher for all causes, all neoplasms, mesothelioma, and the nervous system in males, but not for lung cancer (Reid et al. 2012, 2088306).
Cancer SIRs for childhood exposure were significant for mesothelioma, and for leukemia in males (Reid et al. 2012, 2088306). Among women, SMRs
but not HRs for lung cancer were significant (Reid et al. 2008, 709466). SMRs in women were also significant for pneumoconiosis, but there were only 2
cases. SMRs for both female childhood exposure and for women were large (>4) and significant for "symptoms/signed ill-defined". Key concerns include
exposure measurement error, particularly prior to 1966 when mining ceased: a single value was extrapolated to the entire period as no fiber measures were
taken. There is potential for differential measurement error by mesothelioma case status, since much more detailed occupational and residential history
information was available for cases. In contrast, duration of residence - used to calculate exposure - was estimated from limited public records for about
half of the cohort who did not return mailed questionnaires. There was also 20% loss to follow-up. This was addressed in some of the cohort papers by
comparing different assumptions on the status of these subjects. Several SMRs/SIRs calculated using alternate assumptions were inconsistent, significant
only with the censoring method that would tend to over-estimate effects.The measurement exposure (M4) metric is rated medium and exposure levels (M5)
metric is rated as low upon review by both set of reviewers. Also, the overall quality determination (OQD) is rated medium. Extraction has been completed
and quality control reviewed.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 323 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709626 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Haque, A. K., Vrazel, D. M., Burau, K. D., Cooper, S. P., Downs, T. (1996). Is there transplacental transfer of asbestos? A study of 40 stillborn infants.
Pediatric Pathology & Laboratory Medicine 16(1996):877-892.
stillbirth, placental pathology, fetal diseases, fetal masceration, gestational age
Mortality: stillbirth, placental pathology, fetal diseases, fetal masceration; Reproductive/Developmental: stillbirth, placental pathology, fetal diseases, fetal
masceration, gestational age
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Tremolite: 14567-73-8; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Actinolite:
12172-67-7; Asbestos - Anthophyllite: 17068-78-9
No linked references.
709626
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium Exposure was measured at a single time period (autopsy for stillbirth, birth for healthy
infants) via transmission electron microscopy (JOEL 100CX and Philips 525M). Energy
dispersive x-ray analysis was paired with selected area diffraction analyses to identify
asbestos fibers. For stillbirths, fiber burden was measured in lung, liver, placenta, and
skeletal muscle tissue, while fiber burden was measured in placental tissue only from
healthy live births. Before analysis, NC pore filters were measured to identify the back-
ground levels of asbestos. Exposure was measured at a single time period but can be rea-
sonably assumed to represent fetal exposure. Samples with calculated levels <=30,000
fibers/g were assigned a value of 0 for analyses.
Metric 5: Exposure Levels Low PRIMARY EVALUATION STOPPED AFTER METRIC 5 WAS RATED
LOW****Only two asbestos exposure levels are used in analyses of stillbirth infants.
Analyses use the presence or absence of fibers for their exposure levels. Mean fiber lev-
els are compared for stillbirth infants and healthy liveborn infants (report p-value for
significant difference).
Additional Comments: This study provided vague descriptions of statistical analyses which made it difficult to understand the results reported. Additionally, the study had a
small sample size with limited numbers of health live born infants and still births, limiting the likely sensitivity of analyses. The crude nature of statistical
analyses (Fisher's test and chi-square tests) prevented the consideration of confounders, though it appeared that the demographic variables differed among
the study population. Metric 10 received an NA rating, as covariates were not included in the analyses.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 324 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3084436 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Harless, K. W., Watanabe, S., Renzetti, A. D., Jr (1978). The acute effects of chrysotile asbestos exposure on lung function. Environmental Research
16(1978):360-372.
Pulmonary Function/Spirometry Results
Lung/Respiratory: FVC, FEV1, FEF(25-75% ), FRC
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3084436
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection High The authors provided sufficient details about the setting and study participants (n=23).
Metric 2: Attrition Low There was moderate subject loss (30% of all those evaluated in the initial visit) from the
study, but outcome and exposure data were largely complete.
Metric 3: Comparison Group Low The study only had an exposed group of participants and provided details about the
setting, suggesting the participants were similar. The authors did not include a clear
inclusion or exclusion criteria.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium The asbestos samples were not taken during regular operations or during the exposure of
the study participants. The sampling occurred after job closure using an OSHA method,
but it was not described in detail.
Medium The range of exposure is sufficient, albeit the measurements were taken during simu-
lated activities.
Low Temporality is established, but it is unclear whether there is adequate follow-up for
consideration of latency as spirometric measurements were taken within months of their
last exposure day.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High Pulmonary Function/Spirometry Results: The outcome was assessed using well estab-
lished methods that include standardized spirometric measurements (e.g., FEV1, FVC).
Medium The authors reported all results outlined in the methods section.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Medium The authors collected additional data on covariates e.g., age, weight, but they did not use
these data for adjustment in e.g., correlation analyses (not conducted).
Metric 10: Covariate Characterization Medium Data on potential confounders (excluding co-exposures) were collected, assuming accu-
rate personnel files were used.
Metric 11: Co-exposure Counfounding Medium The authors collected data on co-exposures i.e., tobacco smoke, and analyzed the study
results comparing smokers to nonsmokers and light smokers.
Domain 5: Analysis
Metric 12: Study Design and Methods Medium The authors used descriptive statistics to report their incidence findings.
Continued on next page ...
Page 325 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3084436 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Harless, K. W., Watanabe, S., Renzetti, A. D., Jr (1978). The acute effects of chrysotile asbestos exposure on lung function. Environmental Research
16(1978):360-372.
Pulmonary Function/Spirometry Results
Lung/Respiratory: FVC, FEV1, FEF(25-75% ), FRC
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3084436
Domain
Metric
Rating
Comments
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium While the sample size is low (n=16 participants who provided complete data), the occu-
pational setting and outcome measurements seem adequate to detect an effect in them.
Medium The description of the analysis is sufficient to reproduce the analysis conducted by the
authors.
Medium The use of descriptive statistics for this small study seems appropriate for the analysis
that was conducted.
Additional Comments: None
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 326 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 101 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Henderson, V. L., Enterline, P. E. (1979). Asbestos exposure: Factors associated with excess cancer and respiratory disease mortality. Annals of the New
York Academy of Sciences 330(1979): 117-126.
Lung Cancer; cancer mortality, digestive cancer, all other cancer mortality; Asbestosis; stroke mortality, heart disease mortality, pneumoconiosis and
pulmonary fibrosis mortality, all other cause mortality
Mortality: all cause mortality, cancer (140-205) mortality, digestive cancer (150-159) mortality, respiratory cancer (162-163) mortality, all other cancer
mortality, stroke (330-334) mortality, heart disease (400-443) mortality, respiratory disease (470-527) mortality, pneumoconiosis and pulmonary fibrosis
(523-525) mortality, asbestosis (523.2) mortality, all other cause mortality; Cancer/Carcinogenesis: cancer (140-205) mortality, digestive cancer (150-159)
mortality, respiratory cancer (162-163) mortality, all other cancer mortality; Gastrointestinal: digestive cancer (150-159) mortality; Lung/Respiratory:
respiratory cancer (162-163) mortality, respiratory disease (470-527) mortality, pneumoconiosis and pulmonary fibrosis (523-525) mortality, asbestosis
(523.2) mortality; Cardiovascular: stroke (330-334) mortality, heart disease (400-443) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
101
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Key elements of study design were reported within this retrospective cohort study of
n=1075 male asbestos workers who retired 1941-1967 with a pension from work within
U.S. asbestos manufacturing facilities and were followed for mortality outcomes dur-
ing the years 1941-1973. The retirees included those who retired normally at age 65,
those who retired before age 65 for personal reasons but lived to age 65, and those who
retired prior to age 65 due to a disability but also lived to age 65. The U.S. white male
population was used as a comparison population for standardized mortality ratio (SMR)
analyses. This study was an update to a previous study which only followed the origi-
nal cohort of this population (originally n=l,348 men) through December 31, 1969. Of
this original cohort of n=l,348 men, a total of n=273 employed only in Canada had to
be excluded as the current study deaths 1970-1973 through social security records. The
distribution of these exclusions with respect to exposure and outcomes was not detailed.
Medium Of the 781 deaths identified, death certificates were obtained for 749 individuals, and
authors noted exclusion of those with missing death certificates from analyses. No detail
regarding exposure or outcomes for these individuals was provided. Estimated cumula-
tive dust exposure was complete and described as calculated for each cohort member.
High Inclusion criteria and methods of participant selection were detailed. For SMR analyses,
the use of U.S. white males living at the same age and time periods was chosen as a
comparison population. This study was restricted to males.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium Section 3.9.12 of the 1986 assessment describes the application of a conversion factor
based on a study in a factory making asbestos cement pipes and sheets.
Metric 5: Exposure Levels Medium Fiber concentrations for 5 different exposure groups are presented in Section 3.9.12 of
the 1986 assessment.
Metric 6: Temporality High The study presents an appropriate temporality and the interval between exposure and
outcome is appropriate considering the latency of disease. The cohort was followed for
mortality 1941-1973. The average length of employment was 25 years.
Continued on next page ...
Page 327 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 101 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Henderson, V. L., Enterline, P. E. (1979). Asbestos exposure: Factors associated with excess cancer and respiratory disease mortality. Annals of the New
York Academy of Sciences 330(1979): 117-126.
Lung Cancer; cancer mortality, digestive cancer, all other cancer mortality; Asbestosis; stroke mortality, heart disease mortality, pneumoconiosis and
pulmonary fibrosis mortality, all other cause mortality
Mortality: all cause mortality, cancer (140-205) mortality, digestive cancer (150-159) mortality, respiratory cancer (162-163) mortality, all other cancer
mortality, stroke (330-334) mortality, heart disease (400-443) mortality, respiratory disease (470-527) mortality, pneumoconiosis and pulmonary fibrosis
(523-525) mortality, asbestosis (523.2) mortality, all other cause mortality; Cancer/Carcinogenesis: cancer (140-205) mortality, digestive cancer (150-159)
mortality, respiratory cancer (162-163) mortality, all other cancer mortality; Gastrointestinal: digestive cancer (150-159) mortality; Lung/Respiratory:
respiratory cancer (162-163) mortality, respiratory disease (470-527) mortality, pneumoconiosis and pulmonary fibrosis (523-525) mortality, asbestosis
(523.2) mortality; Cardiovascular: stroke (330-334) mortality, heart disease (400-443) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
101
Domain
Metric
Rating
Comments
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
High
Lung Cancer: Mortality data was coded by a qualified nosologist using codes in ICD-7.
Lung cancer was coded as 162-163.; Other Cancer(s): Mortality data was coded by a
qualified nosologist using codes in ICD-7, including any cancer (140-205) and digestive
cancer (150-159).; Asbestosis: Mortality data was coded by a qualified nosologist using
codes in ICD-7. Asbestosis was coded as 523.2.; Other Non-Cancer Outcomes: Mor-
tality data was coded by a qualified nosologist using codes in ICD-7, including stroke
(330-334), heart disease (400-443), respiratory disease (470-527), and pneumoconiosis
and pulmonary fibrosis (523-525).
Metric 8:
Reporting Bias
High
There were no concerns for selective reporting, with outcome counts reported in most
results and 95% CIs for some.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
Medium
Other than stratification for total estimated dust exposure, department in which most of
the worker"s life was spent, type of asbestos, and periods of follow-up, no additional
adjustments or consideration for differences between exposed and comparison groups
regarding distributions of relevant covariates were detailed. The cohort for study and the
comparison population for SMR analyses was restricted to white males.
Metric 10:
Covariate Characterization
Medium
Although not specified within this occupational study, it is assumed that personnel files
were utilized to obtain department, asbestos type, and years of follow-up data.
Metric 11:
Co-exposure Counfounding
Medium
Authors noted the potential for silica exposure within production of asbestos cement
pipe and asbestos cement shingles. Analyses did not account for these exposures, how-
ever authors noted no indication of unbalanced provision of these exposures across study
groups.
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
The study design was appropriate. Table 3 presented predicted SMR"s, derived from
linear regression from dose-response data, as well as observed SMR"s for respiratory
(lung) cancer.
Metric 13:
Statistical Power
Medium
The number of participants (n=1075) was adequate to detect an association.
Metric 14:
Reproducibility of Analyses
Medium
The description of SMR analyses and formation of rates for the comparison population
was presented in detail and generally sufficient to reproduce.
Continued on next
page...
Page 328 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 101 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Henderson, V. L., Enterline, P. E. (1979). Asbestos exposure: Factors associated with excess cancer and respiratory disease mortality. Annals of the New
York Academy of Sciences 330(1979): 117-126.
Lung Cancer; cancer mortality, digestive cancer, all other cancer mortality; Asbestosis; stroke mortality, heart disease mortality, pneumoconiosis and
pulmonary fibrosis mortality, all other cause mortality
Mortality: all cause mortality, cancer (140-205) mortality, digestive cancer (150-159) mortality, respiratory cancer (162-163) mortality, all other cancer
mortality, stroke (330-334) mortality, heart disease (400-443) mortality, respiratory disease (470-527) mortality, pneumoconiosis and pulmonary fibrosis
(523-525) mortality, asbestosis (523.2) mortality, all other cause mortality; Cancer/Carcinogenesis: cancer (140-205) mortality, digestive cancer (150-159)
mortality, respiratory cancer (162-163) mortality, all other cancer mortality; Gastrointestinal: digestive cancer (150-159) mortality; Lung/Respiratory:
respiratory cancer (162-163) mortality, respiratory disease (470-527) mortality, pneumoconiosis and pulmonary fibrosis (523-525) mortality, asbestosis
(523.2) mortality; Cardiovascular: stroke (330-334) mortality, heart disease (400-443) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
101
Domain
Metric
Rating
Comments
Metric 15: Statistical Analysis
Medium
The method for calculating SMRs is transparent and no assumptions need to be met.
Additional Comments: This study summarized the mortality experience of a cohort of 1075 men who attained age 65 years and retired with pensions from work in a U.S. asbestos
company during the period of 1941-1967 and was followed for deaths through 1973. Mortality was compared with the general U. S. white male population
within various SMR analyses. Exposure was only estimated for each worker as cumulative asbestos dust mppc-years and no measure of asbestos fiber
concentration was presented.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 329 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3084255 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hirsch, A., Di Menza, L., Dorbon, F., Carre, A., Bignon, J. (1980). Diaphragmatic straightness in 302 asbestos-exposed patients. IARC Scientific
Publications no. 30 (1980):523-526.
Pulmonary Function/Spirometry Results; Pleural Plaques; diaphragmatic straightness, fibrosis, bronchoalveolar cells
Lung/Respiratory: Diaphragmatic straightness, Pleural thickening, Pleural calcification, Fibrosis
Asbestos - Not specified: 1332-21-4
No linked references.
3084255
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
In this cohort, most groups had information on asbestos exposure generated through the
examination of ferruginous bodies counted in sputum or broncho-alveolar lavage fluid
samples (Hirsch et al., 1980, 3084255). A surgeon also examined the parietal pleura
in the costal and diaphragmatic regions. Specifics on how things were measured not
provided.
Exposure was categorized into definite, moderate, suspected, and absent. Quantitative
levels were not provided, very little information on actual exposure, however, they re-
ported 3 or more levels of exposure
Additional Comments: There wasn't anything relevant to dose response for extraction.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 330 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082764 Table: 1 of 1
Study Citation: Howe, H. L., Wolfgang, P. E., Burnett, W. S., Nasca, P. C., Youngblood, L. (1989). Cancer incidence following exposure to drinking water with asbestos
leachate. Public Health Reports 104(1989):251 -256.
Lung Cancer; Ovarian Cancer; Buccal, stomach, colon, rectum, liver, pancreas, melanoma, breast, uterus, cervix, prostate, testis, bladder, kidney, brain,
thyroid, lymphoma, leukemia
Cancer/Carcinogenesis: Standardized incidence ratios (SIR) of buccal cancer, Standardized incidence ratios (SIR) of stomach cancer, Standardized inci-
dence ratios (SIR) of colon cancer, Standardized incidence ratios (SIR) of rectum cancer, Standardized incidence ratios (SIR) of liver cancer, Standardized
incidence ratios (SIR) of pancreas cancer, Standardized incidence ratios (SIR) of lung cancer, Standardized incidence ratios (SIR) of melanoma, Standard-
ized incidence ratios (SIR) of breast cancer, Standardized incidence ratios (SIR) of uterus cancer, Standardized incidence ratios (SIR) of cervix cancer,
Standardized incidence ratios (SIR) of ovary cancer, Standardized incidence ratios (SIR) of prostate cancer, Standardized incidence ratios (SIR) of testis
cancer, Standardized incidence ratios (SIR) of bladder cancer, Standardized incidence ratios (SIR) of kidney cancer, Standardized incidence ratios (SIR) of
brain cancer, Standardized incidence ratios (SIR) of thyroid cancer, Standardized incidence ratios (SIR) of lymphoma, Standardized incidence ratios (SIR)
of leukemia; Gastrointestinal: Standardized incidence ratios (SIR) of buccal cancer, Standardized incidence ratios (SIR) of stomach cancer, Standardized
incidence ratios (SIR) of colon cancer, Standardized incidence ratios (SIR) of rectum cancer, Standardized incidence ratios (SIR) of pancreas cancer;
Hepatic/Liver: Standardized incidence ratios (SIR) of liver cancer; Lung/Respiratory: Standardized incidence ratios (SIR) of lung cancer; Skin/Connective
Tissue: Standardized incidence ratios (SIR) of melanoma; Reproductive/Developmental: Standardized incidence ratios (SIR) of breast cancer, Standardized
incidence ratios (SIR) of uterus cancer, Standardized incidence ratios (SIR) of cervix cancer, Standardized incidence ratios (SIR) of ovary cancer, Stan-
dardized incidence ratios (SIR) of prostate cancer, Standardized incidence ratios (SIR) of testis cancer; Renal/Kidney: Standardized incidence ratios (SIR)
of bladder cancer, Standardized incidence ratios (SIR) of kidney cancer; Neurological/Behavioral: Standardized incidence ratios (SIR) of brain cancer;
Thyroid: Standardized incidence ratios (SIR) of thyroid cancer; Immune/Hematological: Standardized incidence ratios (SIR) of lymphoma, Standardized
incidence ratios (SIR) of leukemia
Asbestos Fiber Asbestos - Not specified: 1332-21-4
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 3082764
Domain Metric Rating Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Uninformative The methods used to quantify the exposure were not well defined, and detailed methods
of exposure assessment were not reported.
Metric 5: Exposure Levels Uninformative The limited exposure data (only concentrations of 5 samples) that were reported are
not adequate to determine an exposure-response relationship between asbestos fibers in
drinking water and the different cancers evaluated in the study population.
Additional Comments: Overall, the measurement of exposure metric (M4) methods used to quantify the exposure were not well defined. Additionally, the exposure levels metric
(M5) information reported was not adequate to determine an exposure-response relationship.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessment for the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Health
Outcome:
Target
Organ(s):
Page 331 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 30826ii Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Huang, J. Q. (1990). A study on the dose-response relationship between asbestos exposure level and asbestosis among workers in a Chinese chrysotile
product factory. Biomedical and Environmental Sciences 3(1990):90-98.
Asbestosis
Lung/Respiratory: asbestosis
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3082611
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Metric 2:
Participant Selection
Attrition
Metric 3: Comparison Group
Medium Of the total 1059 workers (including retirees) at a Shanghai suburb chrysotile product
factory founded in 1958, 824 had been exposed to asbestos; all were employed prior
to 1980 for at least 3 years. Employees were identified and information obtained from
factory records. Including retirees as well as current workers in the target population of
workers reduced the likelihood of healthy worker bias.
Medium Of the 824 employees 48 (5.8% ) could not be followed up "for various reasons"; the
study sample therefore included 776 workers with complete records. In addition, of
the total of 277 workers diagnosed with asbestosis, 259 cases (93.5% ) had complete
occupational histories and were included in analyses examining the dose-response re-
lationship with exposure. Despite some losses, attrition was low, with no evidence of
bias.
Low Participant characteristics were not provided for the study population; it is therefore not
possible to evaluate to what extent associations might be confounded by factors such as
age or gender. In addition, the authors noted that in the study population "[a] portion of
the workers had been exposed to asbestos before this factory was founded in the early
1950s". The percentage of workers with unqualified prior exposure was not shown,
and analyses excluding these individuals to assess their influence on results were not
included. This issue can undermine the validity of analyses aiming to compare the risk
of asbestosis across levels of exposure.
Domain 2: Exposure Characterization
Continued on next page .
Page 332 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082611 Table: 1 of 1
... continued from previous page
Huang, J. Q. (1990). A study on the dose-response relationship between asbestos exposure level and asbestosis among workers in a Chinese chrysotile
product factory. Biomedical and Environmental Sciences 3(1990):90-98.
Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: asbestosis
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3082611
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Quantitative measures of dust levels for different workplaces in the factory were col-
lected from the facility records: "[t]he dust concentration of every workplace during
the subject"s employment was retrieved from the factory"s dust monitoring records."
Protocols (e.g., personal vs area sampling, number of hours) used historically were not
described. Exposure in the facility was measured using Chinese-made membrane filters
and gravimetry, which the authors report were rates as suitable by the Asbestos Insti-
tute of Canada. Paired dust-fiber samples were measured for 18 location-job function
groups; 7-26 samples were collected for each of these groups. Historical gravimetry
(dust) measures were converted to fiber concentrations using side by side sampling and
linear regression-derived conversion factors. Sampling protocols for the paired samples
were not described, but concentrations are shown for areas and specific job functions
(e.g., braiding round rope, braiding cubic rope); this suggests some personal samples
may have been collected. The fiber counting method cited was PCM [AIA (1979) Ref-
erence Method for the Determination of Airborne Asbestos Fibre Concentrations at
Workplaces by Light Microscopy (Membrane Filter Method)]. Asbestos exposure for
each worker was calculated using occupational history and fiber concentrations esti-
mated for that period. Since details on the sampling methods are lacking, the domain has
received a medium rating.
Medium Prevalence of asbestosis is reported cumulative exposure categorized in 8 levels, rep-
resenting a wide range of both high and low levels of exposure. The range of exposure
in the reference category was 0 to 99 f/ml-years, and thus included workers with large
disparities in exposure.
Medium Sequencing in this retrospective cohort was appropriate. The distribution of employment
dates was not presented, but the timing of initial exposure was described for the 101
asbestosis cases in the lowest exposure category. For 88 of these cases, exposure began
prior to 1958, i.e. 24 years prior to the end of cumulative exposure estimation in 1982.
While the proportion of the sample with adequate vs inadequate follow-up is unknown,
there is also no evidence that follow-up time was inadequate for a large proportion of the
sample.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or
Characterization
Medium Asbestosis: Asbestosis was identified by the Pneumoconiosis Diagnostic Panel of
Shanghai via chest x-rays. The panel used the "original Chinese standard system". Au-
thors note that this system has been compared with the ILO system, but the evaluator
could not access the cited study. As a comparison with the ILO coding system is not
available, the domain was rated medium.
Continued on next page ...
Page 333 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082611 Table: 1 of 1
... continued from previous page
Huang, J. Q. (1990). A study on the dose-response relationship between asbestos exposure level and asbestosis among workers in a Chinese chrysotile
product factory. Biomedical and Environmental Sciences 3(1990):90-98.
Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: asbestosis
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3082611
Domain
Metric
Rating
Comments
Metric 8: Reporting Bias
Medium Numbers of employees in each exposure group and number of diagnosed cases are re-
ported. The authors present coefficients from a regression model as well as a life table
analysis. Methods used for the latter were not detailed, and the reference cited was in
Chinese. It is uncertain whether the life table analysis method used was similar to the
NIOSH Life Table Analysis System (LTAS) approach, in which estimates may be stan-
dardized for variables such as age, sex, race and calendar year.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium No covariates were included in the regression model. However, there is no evidence to
suggest important differences by case status in the distribution of variables that might
have been considered (e.g., age or smoking history). Substantial confounding is not
likely an important issue for this association; many studies report little or no confound-
ing of associations between asbestos exposure and asbestosis (e.g., Paris et al 2009,
HERO ID: 758968).
Medium All variables were characterized from employment records; it is not certain whether age
adjustments were incorporated in the life table analysis.
Medium Asbestosis is explicitly linked to asbestos fibers and co-exposures are not an important
concern if disease ascertainment is adequate. In addition, the study was set in a Chinese
asbestos textile and friction material manufacturing facility, a setting where important
co-exposures are unlikely.
Domain 5: Analysis
Metric
12:
Study Design and Methods
Medium
Metric
13:
Statistical Power
Medium
Metric
14:
Reproducibility of Analyses
Medium
Metric
15:
Statistical Analysis
Medium
The retrospective cohort study design was appropriate to examine the exposure-outcome
relationship in this occupational setting.
The number of participants (n=776) was adequate to detect an effect in the study popula-
tion.
Results of the regression model are readily reproducible. Without access to the methods
reference, however, reproduction of the life table analysis might be difficult.
The authors presented results of "a linear regression model with the prevalence in logit
vs logarithm of the dose (f-y)", i.e. a logit model for asbestosis using a continuous log-
transformed asbestos exposure variable. Life table analyses were also used to analyze
the exposure-outcome association.
Continued on next page ...
Page 334 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082611 Table: 1 of 1
... continued from previous page
Huang, J. Q. (1990). A study on the dose-response relationship between asbestos exposure level and asbestosis among workers in a Chinese chrysotile
product factory. Biomedical and Environmental Sciences 3(1990):90-98.
Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: asbestosis
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3082611
Domain
Metric
Rating
Comments
Additional Comments:
This study examined the association between cumulative asbestos exposure and asbestosis in a Chinese factory manufacturing asbestos textile and friction
materials using chrysotile fiber. Participant selection, exposure measurement at the current facility, and outcome ascertainment appeared to be appropriate,
although details on sampling protocols were lacking (e.g., area vs personal samples, duration). Prior exposure to asbestos was reportedly an issue for an
unknown proportion of the sample; cumulative exposure could not be properly estimated for these individuals, as study information came solely from
factory records. The extent to which this issue undermined the validity of results cannot be determined.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 335 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2223821 Table: 1 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H. (1991). Asbestosis as a precursor of asbestos related lung cancer: Results of a prospective mortality study. British lournal of
Industrial Medicine 48(1991):229-233.
Lung Cancer; respiratory cancer mortality, larynx cancer mortality, buccal/pharynx cancer mortality, digestive cancer mortality, bladder/kidney cancer
mortality, lymphatic cancer mortality, miscellaneous cancer mortality, residual cancer mortality
Cancer/Carcinogenesis: All malignancies mortality, Respiratory cancer mortality, Larynx cancer mortality, Buccal/pharynx cancer mortality, Digestive
cancer mortality, Bladder and kidney cancer mortality, Lymphatic cancer mortality, Miscellaneous cancer mortality, Residual cancer mortality; Mortality:
All malignancies mortality, Respiratory cancer mortality, Larynx cancer mortality, Buccal/pharynx cancer mortality, Digestive cancer mortality, Bladder
and kidney cancer mortality, Lymphatic cancer mortality, Miscellaneous cancer mortality, Residual cancer mortality; Lung/Respiratory: Respiratory cancer
mortality, Larynx cancer mortality; Gastrointestinal: Buccal/pharynx cancer mortality, Digestive cancer mortality; Renal/Kidney: Bladder and kidney
cancer mortality; Immune/Hematological: Lymphatic cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
2223821
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This outcome is rated Low due to the lack of PCM or TEM being used in the
study.Authors refer to a different study for all information regarding to exposure to
asbestos (Hughes et al. 1987, 3583332) That paper notes that air sampling data was col-
lected by a mix of the government, industry, and insurance companies with a midget
impinger (recorded in millions of particles per cubic foot(mppcf)). This was done from
the 1950s-1960s. Membrane filter sampling (measured in fibers per milliliter) was also
noted to have been carried out starting in 1969. Authors note that because of the em-
ployment population occurring from 1940-1950, all exposure estimates were converted
into mppcf. These air sampling data in combination with job history data were used to
estimate cumulative exposure.
Low SMRs for cancer do not provide results by levels of exposure. Authors only provide
categorical cumulative exposure levels for small opacities (<25, 25-99, 100-149, and
>=150 mppcf-y) and for lung cancer (<51, 51-85, 86-121, 122-169, and >=170 mppcf-
y)-
Additional Comments:
Overall, this study is well-designed and references most methods to a previous paper (Hughes et al. 1987, 3583332).Note that the cancerous health
outcomes were not evaluated for any metrics except Metric 4 and 5 and had no data extracted because they did not have sufficient exposure information to
be useful for dose-response analysis.
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 336 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2223821 Table: 2 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H. (1991). Asbestosis as a precursor of asbestos related lung cancer: Results of a prospective mortality study. British lournal of
Industrial Medicine 48(1991):229-233.
cardiovascular mortality, non-malignant respiratory disease mortality, external causes mortality, pneumoconiosis mortality
Mortality: All-cause mortality, Cardiovascular mortality, Non-malignant respiratory diseases mortality, Pneumoconiosis mortality, External causes mor-
tality, Residual mortality; Cardiovascular: Cardiovascular mortality; Lung/Respiratory: Non-malignant respiratory diseases mortality, Pneumoconiosis
mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
2223821
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low This outcome is rated Low due to the lack of PCM or TEM being used in the
study.Authors refer to a different study for all information regarding to exposure to
asbestos (Hughes et al. 1987, 3583332) That paper notes that air sampling data was col-
lected by a mix of the government, industry, and insurance companies with a midget
impinger (recorded in millions of particles per cubic foot(mppcf)). This was done from
the 1950s-1960s. Membrane filter sampling (measured in fibers per milliliter) was also
noted to have been carried out starting in 1969. Authors note that because of the em-
ployment population occurring from 1940-1950, all exposure estimates were converted
into mppcf. These air sampling data in combination with job history data were used to
estimate cumulative exposure.
Metric 5: Exposure Levels Low SMRs for cancer do not provide results by levels of exposure. Authors only provide
categorical cumulative exposure levels for small opacities (<25, 25-99, 100-149, and
>=150 mppcf-y) and for lung cancer (<51, 51-85, 86-121, 122-169, and >=170 mppcf-
y)-
Additional Comments: Overall, this study is well-designed and references most methods to a previous paper (Hughes et al. 1987, 3583332).Note that the cancerous health
outcomes were not evaluated for any metrics except Metric 4 and 5 and had no data extracted because they did not have sufficient exposure information to
be useful for dose-response analysis.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 337 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2223821 Table: 3 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H. (1991). Asbestosis as a precursor of asbestos related lung cancer: Results of a prospective mortality study. British lournal of
Industrial Medicine 48(1991):229-233.
Pleural Plaques; small opacities
Lung/Respiratory: Small opacities mortality, Pleural plaques mortality; Mortality: Small opacities mortality, Pleural plaques mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
2223821
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This outcome is rated Low due to the lack of PCM or TEM being used in the
study.Authors refer to a different study for all information regarding to exposure to
asbestos (Hughes et al. 1987, 3583332) That paper notes that air sampling data was col-
lected by a mix of the government, industry, and insurance companies with a midget
impinger (recorded in millions of particles per cubic foot(mppcf)). This was done from
the 1950s-1960s. Membrane filter sampling (measured in fibers per milliliter) was also
noted to have been carried out starting in 1969. Authors note that because of the em-
ployment population occurring from 1940-1950, all exposure estimates were converted
into mppcf. These air sampling data in combination with job history data were used to
estimate cumulative exposure.
Medium Table 1 presents categorical cumulative exposure levels (<25, 25-99, 100-149, and
>=150 mppcf-y) paired with percentages of each group with normal and abnormal small
opacities.
Additional Comments: The purpose of this paper was to determine whether asbestos workers with small opacities had a higher risk of developing lung cancer, so it was not
completely focused on the relationship between asbestos exposure and pleural plaques, however the information collected for the purposes of answering
this question can be extracted to approach answering this other question. Table 1 contains a comparison between cumulative asbestos exposure groups
and percentage of the groups with >=1/0 and % 0/1 small opacities. The SMR analysis for small opacities does not compare groups by exposure
concentration.Note: QC was not completed for metrics other than metric 4 and metric 5 because the data are not amenable for dose-response modeling due
to metric 4 being rated low.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 338 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 281 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H., Hammad, Y. Y. (1987). Mortality of workers employed in two asbestos cement manufacturing plants. Occupational and
Environmental Medicine 44(1987): 161 -174.
Laryngeal Cancer; All, digestive, kidney or bladder, lymphatic, buccal, pharynx, and prostate
Cancer/Carcinogenesis: All malignancies mortality, Respiratory cancer mortality, Digestive cancer mortality, Kidney or bladder cancer mortality, Lym-
phatic cancer mortality, Residual cancer mortality (includes larynx, buccal, pharynx, and prostate cancer); Mortality: All malignancies mortality, Respi-
ratory cancer mortality, Digestive cancer mortality, Kidney or bladder cancer mortality, Lymphatic cancer mortality, Residual cancer mortality (includes
larynx, buccal, pharynx, and prostate cancer), Pneumoconiosis mortality; Lung/Respiratory: Respiratory cancer mortality, Pneumoconiosis mortality; Gas-
trointestinal: Digestive cancer mortality; Renal/Kidney: Kidney or bladder cancer mortality; Immune/Hematological: Lymphatic cancer mortality; larynx,
buccal, pharynx, and prostate cancer): Residual cancer mortality (includes larynx, buccal, pharynx, and prostate cancer)
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
281
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Medium Study participants included male workers (n = 6,931) from two asbestos cement fac-
tory plants in New Orleans, LA, USA. Participants were identified by abstracting all
job records on file in the two plants in 1970. Participants included those hired after
1942 (plant 1) or 1937 (plant 2) who worked at least one month prior to 1970 and had a
valid social security number. Employees hired before these dates were excluded due to
concerns about record keeping, which introduces the potential for healthy worker bias
(n=167). While the authors do note differences between the two plant populations (age
at employment, race, and location of plant) and analyses do not include adjustments
(SMR), the results are presented separately for each plant, minimizing concerns for
bias in the results. The authors attempted to validate their employment identification by
obtaining copies of Social Security Administration quarterly reporting forms for three
years of operation. They found that of the 1291 employees listed on those forms, 95.6%
were included in the study population. This analysis was not able to be performed on the
plant 1 participants. Overall this indicates a high level of participation, and there is no
reason to suspect that missingness would be related to exposure and outcome.
Medium Participants were followed through 1982 or to age 80, whichever was earlier, with only
a 4% loss to follow up rate. While information about the treatment of missing subjects
is not included, the extremely low attrition rate minimizes concerns about treatment of
these subjects introducing bias to the overall results. The authors do note that tracing
was more successful among those employed for more than year (97.7% ) compared
to other workers (95.1% ). However, this is not significant relative to the total amount
of participants who were successfully traced. Of the participants who were able to be
traced and identified as dead (n=2,143), death certificates to confirm cause of death were
obtained in 94% of cases. For the remaining 6% , causes of death were "allocated to
categories of cause of death in the same proportion as those with certificates." While this
is overall a low rate of missing outcome data an adequate way of addressing missing-
ness, there is some potential for bias of the true outcome data for the 6% without death
certificates.
Continued on next page ...
Page 339 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 281 Table: 1 of 2
... continued from previous page
Hughes, J. M., Weill, H., Hammad, Y. Y. (1987). Mortality of workers employed in two asbestos cement manufacturing plants. Occupational and
Environmental Medicine 44(1987): 161 -174.
Laryngeal Cancer; All, digestive, kidney or bladder, lymphatic, buccal, pharynx, and prostate
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: All malignancies mortality, Respiratory cancer mortality, Digestive cancer mortality, Kidney or bladder cancer mortality, Lym-
phatic cancer mortality, Residual cancer mortality (includes larynx, buccal, pharynx, and prostate cancer); Mortality: All malignancies mortality, Respi-
ratory cancer mortality, Digestive cancer mortality, Kidney or bladder cancer mortality, Lymphatic cancer mortality, Residual cancer mortality (includes
larynx, buccal, pharynx, and prostate cancer), Pneumoconiosis mortality; Lung/Respiratory: Respiratory cancer mortality, Pneumoconiosis mortality; Gas-
trointestinal: Digestive cancer mortality; Renal/Kidney: Kidney or bladder cancer mortality; Immune/Hematological: Lymphatic cancer mortality; larynx,
buccal, pharynx, and prostate cancer): Residual cancer mortality (includes larynx, buccal, pharynx, and prostate cancer)
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
281
Domain
Metric
Rating
Comments
Metric 3:
Comparison Group
Medium SMRs were reported to be adjusted for age (three categories for age at hire) and race
(black and white). However, these are only mentioned qualitatively in the text, as the
authors report "No effect of these factors was observed." The sample was limited to
only men. Rates from the Louisiana general population were used as the referent values,
which could introduce bias considering the employed population introduces the healthy
worker effect. Comparisons to the general United States population are also briefly
mentioned in the Results, but are a secondary analysis.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Factory measurements of fiber levels were taken using midget impingers from 1952-
1969. After 1969, membrane filter sampling was conducted for the remaining samples.
Job categories were used to relate quantitative measures to person-years of exposure in
order to establish a cumulative exposure measure. Anecdotal information was used to
group different jobs. For each category of jobs, the mean of the quantitative fiber mea-
sures was assigned to all individuals. The authors report a conversion factor of 1.4 f/ml
= 1 mppcf. Their citation for this conversion factor is Flammad et al. 1979, F1ERO ID:
91), which explains their use of paired samples of dust and fiber concentrations. Flam-
mad et al. 1979 cites NIOSF1 publication F1SM72-10267 for their method of counting
fibers, which is specified to have been conducted using PCM.
Medium Five levels of exposure are reported as ranges of cumulative asbestos exposure. The
levels appear to be adequate to develop exposure-response estimates.
High Measurement of outcomes occurred at least 20 years following the initial exposure.
Additionally, authors note that exposure measures 10-15 years prior to the outcome were
disregarded in the analyses. This follow-up period is adequate to establish temporality
and considers latency periods for cancer-related outcomes.
Domain 3: Outcome Assessment
Continued on next page .
Page 340 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 281 Table: 1 of 2
... continued from previous page
Hughes, J. M., Weill, H., Hammad, Y. Y. (1987). Mortality of workers employed in two asbestos cement manufacturing plants. Occupational and
Environmental Medicine 44(1987): 161 -174.
Laryngeal Cancer; All, digestive, kidney or bladder, lymphatic, buccal, pharynx, and prostate
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: All malignancies mortality, Respiratory cancer mortality, Digestive cancer mortality, Kidney or bladder cancer mortality, Lym-
phatic cancer mortality, Residual cancer mortality (includes larynx, buccal, pharynx, and prostate cancer); Mortality: All malignancies mortality, Respi-
ratory cancer mortality, Digestive cancer mortality, Kidney or bladder cancer mortality, Lymphatic cancer mortality, Residual cancer mortality (includes
larynx, buccal, pharynx, and prostate cancer), Pneumoconiosis mortality; Lung/Respiratory: Respiratory cancer mortality, Pneumoconiosis mortality; Gas-
trointestinal: Digestive cancer mortality; Renal/Kidney: Kidney or bladder cancer mortality; Immune/Hematological: Lymphatic cancer mortality; larynx,
buccal, pharynx, and prostate cancer): Residual cancer mortality (includes larynx, buccal, pharynx, and prostate cancer)
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
281
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
Medium Laryngeal Cancer: Deaths were identified in 96% of the population with vital status
tracing with the help of federal, state and local agencies. Of the 2143 who were iden-
tified as dead, death certificates were able to be obtained in 94% of cases. For the re-
maining 6% , causes of death were "allocated to categories of cause of death in the same
proportion as those with certificates." Death certificates were coded to ICD-8 codes by
a nosolgist.ICD-8 code 161 was used to identify laryngeal cancer.; Other Cancer(s):
Deaths were identified in 96% of the population with vital status tracing with the help
of federal, state and local agencies. Of the 2143 who were identified as dead, death cer-
tificates were able to be obtained in 94% of cases. For the remaining 6% , causes of
death were "allocated to categories of cause of death in the same proportion as those
with certificates." Death certificates were coded to ICD-8 codes by a nosolgist.ICD-8
codes 140-209 were used to determine all malignancies.ICD-8 codes 162-163 were used
to determine respiratory malignancies.ICD-8 codes 150-159 were used to determine di-
gestive malignancies.ICD-8 codes 188 and 189 were used to determine kidney/bladder
malignancies.ICD-8 codes 200-209 were used to determine lymphatic malignancies.;
Other Non-Cancer Outcomes: Deaths were identified in 96% of the population with
vital status tracing with the help of federal, state and local agencies. Of the 2143 who
were identified as dead, death certificates were able to be obtained in 94% of cases. For
the remaining 6% , causes of death were "allocated to categories of cause of death in
the same proportion as those with certificates." Death certificates were coded to ICD-8
codes by a nosolgist.ICD-8 code 515 was used to determine pneumoconiosis
Medium SMRs are reported, but a measure of variance is not included. The number of observed
and expected deaths for each plant are reported in a separate table.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Authors report that age and race stratified results did not show differences from the
unstratified results. The study population was restricted to males, which effectively
controls for sex in the study.
Medium While not explicitly stated, it is appropriate to assume that age, race, and sex informa-
tion was collected from personnel records at the two factories.
Medium While the study does not explicitly discuss the consideration of co-exposures, the oc-
cupational settings appear restricted to asbestos cement production, thus minimizing
concerns about other chemicals encountered in the factories.
Continued on next page ...
Page 341 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 281 Table: 1 of 2
... continued from previous page
Hughes, J. M., Weill, H., Hammad, Y. Y. (1987). Mortality of workers employed in two asbestos cement manufacturing plants. Occupational and
Environmental Medicine 44(1987): 161 -174.
Laryngeal Cancer; All, digestive, kidney or bladder, lymphatic, buccal, pharynx, and prostate
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: All malignancies mortality, Respiratory cancer mortality, Digestive cancer mortality, Kidney or bladder cancer mortality, Lym-
phatic cancer mortality, Residual cancer mortality (includes larynx, buccal, pharynx, and prostate cancer); Mortality: All malignancies mortality, Respi-
ratory cancer mortality, Digestive cancer mortality, Kidney or bladder cancer mortality, Lymphatic cancer mortality, Residual cancer mortality (includes
larynx, buccal, pharynx, and prostate cancer), Pneumoconiosis mortality; Lung/Respiratory: Respiratory cancer mortality, Pneumoconiosis mortality; Gas-
trointestinal: Digestive cancer mortality; Renal/Kidney: Kidney or bladder cancer mortality; Immune/Hematological: Lymphatic cancer mortality; larynx,
buccal, pharynx, and prostate cancer): Residual cancer mortality (includes larynx, buccal, pharynx, and prostate cancer)
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
281
Domain
Metric
Rating
Comments
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The cohort study design and SMR analyses were appropriate to assess associations
between asbestos exposure and cancer outcomes. The use of linear regression models to
estimate the dose-response effect on lung cancer is also an appropriate model.
Medium The study population size is adequate to detect an effect in the exposed population.
Some subgroups have a lower number of cases, but this does not introduce major con-
cerns about the power of the analyses.
Medium Authors report that mortality was compared using standardized mortality ratios and that
dose-response relationships were evaluated using weighted least squares regressions.
Enough conceptual information is reported to reproduce the analyses.
Medium The authors transparently report their use of SMR calculations, which does not have
specific model assumptions that would be expected to be violated in this study.
Additional Comments:
This retrospective occupational cohort study examined lung cancer mortality SMRs among male workers from two asbestos cement factories. While the
study had an adequate sample size, consideration of exposure, approach to outcome ascertainment, and follow-up time, the assignment of cause of death
based on proportions of causes on available death certificates introduces potential outcome misclassification.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 342 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 281 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H„ Hammad, Y. Y. (1987).
Environmental Medicine 44(1987):161-174.
Laryngeal Cancer
Mortality of workers employed in two asbestos cement manufacturing plants. Occupational and
Mortality: Larynx malignancies mortality, Buccal/pharynx malignancies mortality, Prostate malignancies mortality, Bladder malignancies mortality, Kid-
ney malignancies mortality, Cardiovascular malignancies mortality, Influenza, pneumonia, bronchitis, emphysema, and asthma mortality, Oesophagus
malignancies mortality, Stomach malignancies mortality, Colon, rectum malignancies mortality, Other digestive malignancies (not oesophagus, stomach,
colon, or rectum) mortality; Cancer/Carcinogenesis: Larynx malignancies mortality, Buccal/pharynx malignancies mortality, Prostate malignancies mortal-
ity, Bladder malignancies mortality, Kidney malignancies mortality, Cardiovascular malignancies mortality, Oesophagus malignancies mortality, Stomach
malignancies mortality, Colon, rectum malignancies mortality, Other digestive malignancies (not oesophagus, stomach, colon, or rectum) mortality; Lung/
Respiratory: Larynx malignancies mortality, Influenza, pneumonia, bronchitis, emphysema, and asthma mortality; Buccal: Buccal/pharynx malignancies
mortality; Gastrointestinal: Prostate malignancies mortality, Oesophagus malignancies mortality, Stomach malignancies mortality, Colon, rectum malig-
nancies mortality, Other digestive malignancies (not oesophagus, stomach, colon, or rectum) mortality; Renal/Kidney: Bladder malignancies mortality,
Kidney malignancies mortality; Cardiovascular: Cardiovascular malignancies mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
281
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium Factory measurements of fiber levels were taken using midget impingers from 1952-
1969. After 1969, membrane filter sampling was conducted for the remaining samples.
Job categories were used to relate quantitative measures to person-years of exposure in
order to establish a cumulative exposure measure. Anecdotal information was used to
group different jobs. For each category of jobs, the mean of the quantitative fiber mea-
sures was assigned to all individuals. The authors report a conversion factor of 1.4 f/ml
= 1 mppcf. Their citation for this conversion factor is Hammad et al. 1979, HERO ID:
91), which explains their use of paired samples of dust and fiber concentrations. Ham-
mad et al. 1979 cites NIOSH publication HSM72-10267 for their method of counting
fibers, which is specified to have been conducted using PCM.
Low Analyses for these outcomes are only presented as "exposed vs, unexposed."
Additional Comments: These outcomes were rated "Low" for Metric 5, and thus did not meet the criteria for usefulness in dose-response analysis.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 343 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3583332 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H„ Hammad, Y. Y. (1987). MORTALITY OF WORKERS EMPLOYED IN 2 ASBESTOS CEMENT MANUFACTURING
PLANTS. British Journal of Industrial Medicine 44(1987): 161-174.
Mortality (all cause, various causes)
Mortality: All cause mortality; Cardiovascular: Cardiovascular mortality; Cancer/Carcinogenesis: Cancer mortality; Lung/Respiratory: Respiratory mor-
tality (influenza, pneumonia, bronchitis, emphysema, asthma)Lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3583332
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Low This study on mortality among male workers at two asbestos cement manufacturing
plants in New Orleans. Overall, there were 6931 employed for at least one month prior
to 1970, according to job records, with mortality ascertained through 1982 or age 80
(whichever came first). However, analyses were restricted to the 5492 (79% ) employees
with >20 years since initial exposure (rationale not completely clear; see exposure). As
a result, the data analyzed represented only 477 of 886 (53.8% ) deaths at plant 1, and
874 of 1257 (69.5% ) deaths at plant 2 (Table 4 vs. Table 5). The authors did not dis-
cuss differences in causes of death among those included vs. excluded or note that the
large proportion excluded could have introduced bias. Other aspects of participant selec-
tion were good. A small number of workers employed prior to comprehensive record-
keeping dates (n=167 employed before 1942 or 1937) were also excluded; limited in-
formation on early workers meant these workers might be a "survivor population". The
sample included workers with variable hire dates (61% and 74% of workers at plants 1
and 2 respectively < 1950 vs. 1950-69) and employment duration (60.8% and 60.6% at
plants 1 and 2 employed <= 1 year, 19.3% and 19.6 employed >5 years).
High Tracing and mortality ascertainment were high. The estimated rates of inclusion were
95.6% enrolled based on plant 2 social security information, and mortality ascertainment
> 96% .
Medium This study calculated SMRs based on Louisiana mortality rates (preferable to US rates
given the higher mortality in that state). Nonetheless, as noted in the occupational epi-
demiology literature (e.g., Chowdhury et al 2017 PMID: 29391741; McMichael 1976
HEROID 73484), use of general population referents to calculate SMRs often induces
a healthy worker effect bias given that the working population is healthier than the gen-
eral population. Use of internal referents (i.e. within-cohort analyses), or a comparable
occupational population, are more appropriate approaches that reduce bias.
Domain 2: Exposure Characterization
Continued on next page .
Page 344 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3583332 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H„ Hammad, Y. Y. (1987). MORTALITY OF WORKERS EMPLOYED IN 2 ASBESTOS CEMENT MANUFACTURING
PLANTS. British lournal of Industrial Medicine 44(1987): 161-174.
Mortality (all cause, various causes)
Mortality: All cause mortality; Cardiovascular: Cardiovascular mortality; Cancer/Carcinogenesis: Cancer mortality; Lung/Respiratory: Respiratory mor-
tality (influenza, pneumonia, bronchitis, emphysema, asthma)Lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3583332
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Workers in these factories were exposed to both asbestos fibers and free silica dust (see
other manuscripts on this population e.g. Weill et al 1977, HEROID 3084634; Weill et
al 1975 HEROID 2079035). Both plants used chrysotile asbestos; some plant 2 workers
were also exposed to crocidolite. The measures analyzed were total dust concentrations
from impinger air sampling, updated in this study using additional samples (reduc-
ing extrapolation based on anecdotal data), totaling 100 at plant 1 and 1664 at plant 2
from 1952 to 1969, at which point membrane filter sampling began. Cumulative expo-
sure multiplied the mean of available dust measures for each job title (area and type of
work) by duration, excluding outliers ("In calculating this mean very high measurements
found to be statistical outliers based on a lognormal distribution were first recoded to
be equal to the highest non-outlying value"). Concern: It appears that recent exposures
(>1970) were omitted. The authors stated "In analysing risk " (20 or more years af-
ter initial exposure) each person contributed person-years to the cumulative exposure
category attained ten years previously. In this way relatively recent exposures (10-15
years previously) were disregarded in determining exposure category for each worker."
A conversion factor was provided to estimate dust mppcf measures as asbestos (f/mL)
equivalents: "Based on data collected in one of these plants, the best factor for con-
verting mppcf to f/ml will be assumed to be 1.4 f/mL = 1 mppcf." This factor was the
mean of dust-to-fibers >5 jUm ratio derived from impinger-filter pairs operated in 20- to
60-minute intervals in five "dust zones" (Hammad et al 1979, HEROID 91). Concern:
Ratios for individual dust zones varied, ranging from 0.63 to 2.5, which led the authors
to conclude in 1979 that "no one conversion factor can be used for all areas of this type
of operation".
Medium SMRs were calculated using 5 categories of employment duration that ranged from a
few months to >15 years (different values for each plant), and using 5 categories of
cumulative exposure (= 100 mppcf).
Medium Exposure was estimated retrospectively, and analyses included only employees with
>20 years since first exposure. Temporality was appropriate. However, the authors did
not adequately justify a 20-year latency or acknowledge that estimated latency time for
some outcomes are shorter.
Domain 3: Outcome Assessment
Continued on next page .
Page 345 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3583332 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H„ Hammad, Y. Y. (1987). MORTALITY OF WORKERS EMPLOYED IN 2 ASBESTOS CEMENT MANUFACTURING
PLANTS. British lournal of Industrial Medicine 44(1987): 161-174.
Mortality (all cause, various causes)
Mortality: All cause mortality; Cardiovascular: Cardiovascular mortality; Cancer/Carcinogenesis: Cancer mortality; Lung/Respiratory: Respiratory mor-
tality (influenza, pneumonia, bronchitis, emphysema, asthma)Lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3583332
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
Low Other Non-Cancer Outcomes: Death certificates available for 94% of the 2143 total
deaths were coded in categories by a nosologist; ICD codes were provided with detailed
codes for malignancies and pneumoconiosis. However, other causes were categorized
in ways that limited utility. All cardiovascular mortality was combined (vs. ischemic,
cerebrovascular, pulmonary heart disease [e.g. see asbestos-CVD analyses in Harding
et al 2012 HEROID 2564917]); respiratory mortality combined infectious and non-
infectious causes (influenza, pneumonia, bronchitis, emphysema, asthma); other broad
categories were "external" (ICD codes for injuries, poisoning) and unspecified "residual
(n=190)" causes. Some misclassification is likely: the authors stated that "deaths for
which certificates were not obtained were allocated to categories of causes of death in
the same proportion as those with certificates."
Low The authors presented analyses stratified by exposure and employment duration cate-
gories only for all-cause mortality and selected malignancies, where they demonstrated
how SMRs varied with greater exposure. Similar analyses were not reported for other
outcomes. The authors used linear regression models to analyze dose-response trends
in SMRs only for lung cancer (i.e., selectively). Only mesothelioma was analyzed using
logistic regression and within-cohort comparisons. As noted earlier, the authors also
failed to analyze deaths that occurred fewer than 20 years since first exposure, with no
discussion of potential bias.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium
Medium
Low
The manuscript stated "[standardised mortality ratio (SMR) analyses were carried out
using a computer program written in Britain (J Peto)." The authors describe using local
county-based death rates as a reference due to small numbers for age specific, race spe-
cific and cause specific rates, suggesting that their SMR calculations incorporated these
factors. SMRs were not adjusted for smoking.
Age and race were obtained from job records.
Co-exposure to silica, discussed elsewhere by the authors, was not taken into account in
this manuscript. Possible prior or subsequent exposure to asbestos from other sources
was also not discussed.
Domain 5: Analysis
Continued on next page ...
Page 346 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3583332 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Hughes, J. M., Weill, H„ Hammad, Y. Y. (1987). MORTALITY OF WORKERS EMPLOYED IN 2 ASBESTOS CEMENT MANUFACTURING
PLANTS. British lournal of Industrial Medicine 44(1987): 161-174.
Mortality (all cause, various causes)
Mortality: All cause mortality; Cardiovascular: Cardiovascular mortality; Cancer/Carcinogenesis: Cancer mortality; Lung/Respiratory: Respiratory mor-
tality (influenza, pneumonia, bronchitis, emphysema, asthma)Lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3583332
Domain
Metric
Rating
Comments
Metric 12: Study Design and Methods
Medium
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Medium
Low
The use of SMRs in occupational epidemiology is widely accepted in spite of concerns
regarding the use of general population mortality rates as a referent for relatively health-
ier worker populations. Adjustments have been suggested to address this limitation
including the calculation of relative SMRs as applied by Waggoner et al 2010 in the
Agricultural Health Study (PMID: 21084556): "we define the relative SMR (rSMR) as
the ratio of the cause-specific SMR to the SMR for all other causes, omitting the cause
of interest (i.e., rSMRx " SMRx/SMRnot x)" That study found an SMR of 0.61 and an
rSMR of 1.20 for all cancers. Other studies (e.g. Hwang et al 2021 PMID: 34525505)
report similarly that deriving rSMRs can provide additional insights over SMRs alone.
In addition to SMRs, a linear regression model ("an iteratively weighted least squares
regression line") was fit to examine the dose-response trend between exposure category
and odds of lung cancer. Details such as confirmation of age and race adjustments were
not given. A logistic regression model was also used to analyze employment duration
category and odds of mesothelioma (details lacking).
The analyses of nearly 5500 workers included 1,351 deaths from all causes.
Tables present both observed and expected deaths in detail, making SMR results readily
reproducible. The authors also adequately explained their application of the dust-to-fiber
conversion factor. However, details on the models used were lacking.
SMR methods were not described in detail, tables present observed and expected cell
sizes, and the text mentions considering age and race specific numbers for cause of
death.
Additional Comments: This paper analyzed mortality in a subset of workers from 2 asbestos cement factories. There were numerous concerns that undermine validity including:
selectively analying deaths that occurred >20 years after 1st exposure; analyzing primarily total dust measures and applying a summary conversion factor
of uncertain precision and validity; using a general population referent to calculate SMRs with no additional adjustments or efforts to take into account
possible effects of healthy worker effect bias. Analyses of the 10 mesotheliomas identified were not evaluated.NOTE: This study would not be fully
evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was mentioned in the study or a cited source.
Overall Quality Determination Low
* No biomarkers were identified for this evaluation.
Page 347 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6869216 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
liar, A., Klareskog, L., Saevarsdottir, S., Wiebert, P., Askling, J., Gustavsson, P., Alfredsson, L. (2019). Occupational exposure to asbestos and silica and
risk of developing rheumatoid arthritis: findings from a Swedish population-based case-control study. 5(2019):e000978.
Rheumatoid Arthritis
Immune/Hematological: Rheumatoid Arthritis
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
6869216
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Asbestos exposure was defined as occupational, inhalable exposure to any form of as-
bestos or asbestos-containing material. Silica exposure was defined as occupational ex-
posure to respirable (aerodynamic diameter less than 5 jUm) crystalline silica-containing
dusts (for example, granite). A detailed job exposure matrix (JEM) containing historical
exposure estimates was constructed for each study participant" s occupational title. Oc-
cupational titles were obtained through the Swedish Population and Housing Censuses
which were conducted every fifth year and described as containing data from ques-
tionnaires and various registries. For this study, occupational titles were available from
the Population and Housing Censuses carried out in 1960, 1970, 1975, 1980 and 1990.
Methods of occupational exposure measurement assessment (PCM or TEM) and propor-
tion of occupational history with historic measurements were not detailed, however the
JEM contained exposure estimates for the time periods 1955-1964, 1965-1972, 1973-
1977, 1978-1984, and 1985-1995, as well as intensity level and probability of exposure
for asbestos and silica for each occupation. Only workers with at least 50 percent proba-
bility of being exposed according to the JEM were considered exposed, and it is unclear
to what extent this might have been responsible for the exclusion of subjects with low
exposure but similar chance for development of RA outcome due to the understanding
that single asbestos fibers may cause significant inflammation and subsequent disease. It
is unclear if all changes in job title were captured within the censuses conducted every
five years and utilized for this study.This metric is rated low because the study or any
cited methods source does not explicitly mention the use of PCM or TEM.
Metric 5: Exposure Levels Low Median estimated asbestos exposure (Table 2) was noted as 0.10 fiber/cm3 for men, and
0.02 fiber/cm3 for women. Details on the range and distribution of estimated exposure
was lacking, and analyses utilized comparisons between workers ever versus never ex-
posed to asbestos, however some analyses (Table 4) utilized considerations for number
of exposed occupations (one " five occupations) within analyses.
Additional Comments: This study examined occupational exposure to asbestos and silica with risk of developing rheumatoid arthritis (RA) within a Swedish population-based
case-control study.Results indicated male workers exposed to asbestos had higher risks of seropositive RA and seronegative RA compared with workers
classified as non-exposed, with risks highest among workers exposed to asbestos from 1970, before a national ban was introduced. The highest risk
estimates were among smoking workers for seropositive RA, regardless of whether these workers had been exposed to asbestos or not.NOTE: This study
would not be reviewed in full under the current guidelines because of the low rating in metric 4.
Continued on next page ...
Page 348 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6869216 Table: 1 of 1
... continued from previous page
liar, A., Klareskog, L., Saevarsdottir, S., Wiebert, P., Askling, J., Gustavsson, P., Alfredsson, L. (2019). Occupational exposure to asbestos and silica and
risk of developing rheumatoid arthritis: findings from a Swedish population-based case-control study. 5(2019):e000978.
Rheumatoid Arthritis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Immune/Hematological: Rheumatoid Arthritis
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
6869216
Domain
Metric
Rating
Comments
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 349 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083873 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Johnson, W. M., Lemen, R. A., Hurst, G. A., Spiegel, R. M., Liu, F. H. (1982). Respiratory morbidity among workers in an amosite asbestos insulation
plant. Journal of Occupational Medicine 24(1982):994-999.
Asbestosis; Pulmonary Function/Spirometry Results
Lung/Respiratory: Asbestosis, Pulmonary function (FEV, FVC)
Asbestos - Amosite (grunerite): 12172-73-5
ID(s): No linked references.
3083873
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium The authors used years of exposure in five-year categories as a proxy for cumulative
asbestos exposure. Fiber concentrations in different locations at the plant were also
measured using personal breathing zone sampling; these concentration measures were
not used to estimate exposure levels of individual participants. Sampling equipment
and methods were not detailed; the manuscript states that PCM was used to count fibers
greater than 5 jUm in length using the OSHA standard methods. Measures were obtained
in 1967, 1970 and 1971. Mean concentrations were shown, and varied considerably in
different areas of the plant, particularly in earlier years.
Low The exposure measure used for analysis was duration of employment, in categories that
ranged from 1-4 to >15 years of employment. Duration of employment alone may im-
precisely classify cumulative exposure given the wide variation in intensity of exposures
at different locations in the plant (Table 1).
Additional Comments: This cross-sectional study described the prevalence of 5 asbestosis symptoms among 50 workers at an amosite asbestos insulation plant in East Texas.
Workers included had been employed for at least one year and were currently employed at the time of the study in 1971. The plant had been under
study by public health agencies and closed shortly after this study. Limiting the study to current workers, particularly since health risks were known,
may have induced some degree of healthy worker effect (HWE) bias in the form of employment changes among more susceptible workers. In fact, the
paper documented very high turnover among 850 workers. Based on multiple symptoms, the study identified possible asbestosis in 7 of the 18 workers
who had >=10 years of employment. In the sample as a whole, symptoms including measures of lung function tended to worsen with longer duration of
employment. However, there was an uptick in lung function among workers who remained employed for 15 years or more. Results were stratified by race,
but there were too few black workers to meaningfully assess trends. Overall, the small sample size, potential HWE, and use of employment duration alone
to classify exposure are limitations.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 350 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081928 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Jarvholm, B., Larsson, S., Hagberg, S., Oiling, S., Ryd, W., Tor6n, K. (1993). Quantitative importance of asbestos as a cause of lung cancer in a Swedish
industrial city: A case-referent study. European Respiratory Journal 6( 1993): 1271-1275.
Lung Cancer
Cancer/Carcinogenesis: Lung cancer; Lung/Respiratory: Lung cancer
Asbestos - Not specified: 1332-21-4
No linked references.
3081928
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Exposure was based on a questionnaire with the patients and referents focused on as-
bestos exposure and different occupational exposures; that information was used by
trained occupational hygienists to categorize cumulative asbestos exposure.This metric
is rated low because the study or any cited methods sources do not explicitly mention
the use of PCM or TEM.
Low Low. The study reports the estimated cumulative doses of asbestos (>25 fibre-year/mL,
1-24 fibre-years/mL, 0.05 - 0.9 fibre-years/mL, and <0.05 fibre-years/mL) along with
the number of cases and referents in each category of exposure. However, this does not
adequately represent a continuous range and distribution.
Additional Comments: Based upon the current guidance, this study would not be evaluated fully because of the metric 4 rating. This study, and any cited methods sources, did not
mention the use of PCM or TEM.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 351 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3081833 Table: 1 of 1
Karjalainen, A., Anttila, S., Vanhala, E., Vainio, H. (1994). Asbestos exposure and the risk of lung cancer in a general urban population. Scandinavian
Journal of Work, Environment and Health 20(1994):243-250.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: lung cancer; Lung/Respiratory: lung cancer
Asbestos - Anthophyllite: 17068-78-9; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3081833
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low Asbestos exposure (10A 6 f/g) was defined by scanning electron microscopic analysis of
pulmonary tissue of cases and referents.
Medium The range and distribution of exposure (Table 2) is sufficient to develop exposure-
response estimates. Multivariate logistic regression models incorporated three categories
(<1.0 x 10A 6 f/g, 1.0-4.99 x 10A 6 f/g, and >=5.0 x 10A 6 f/g).
Additional Comments: Karjalainen et al., 1994 (HERO ID 3081833) was not QC evaluated for any metrics except Metric 4 and 5 as it did not have sufficient exposure information
to be useful for dose-response analysis.Overall, information on the measurement of exposure metric (M4) to assess exposure was limited or rated low
(asbestos exposure was defined by SEM analysis of lung tissue of cases and referents). The exposure levels metric (M5) information reported was adequate
to determine exposure-response relationships.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 352 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081814 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Karjalainen, A., Karhunen, P. J., Lalu, K., Penttila, A., Vanhala, E., Kyyronen, P., Tossavainen, A. (1994). Pleural plaques and exposure to mineral fibres
in a male urban necropsy population. Occupational and Environmental Medicine 51(1994):456-460.
Pleural Plaques
Lung/Respiratory: Pleural plaques
Asbestos - Anthophyllite: 17068-78-9; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
3081814
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low Occupational exposure was classified according to four groups: Probable exposure, pos-
sible exposure, unlikely exposure, and unknown exposure. Individuals were grouped
according to the last occupation indicated on the necropsy records. The Nordic Classifi-
cation of Occupations was used to code the probability of exposure. One important note
pertains to the unknown exposure group, because this was for individuals who did not
have information on occupation and may have been listed as "retired." The researchers
also collected lung tissue samples so that they could conduct a fiber analysis with an
electron microscope. The procedure had an analytical sensitivity of 0.07 million fibers
per gram (f/g). The authors did not specify the use of PCM or TEM and mentioned de-
tecting chrysotile fibes with scanning electron microscopy.
Medium This metric is rated as medium because in Table 2, the authors present three levels of
exposure based on the concentration of asbestos fibers found in lung tissue samples.
These levels are reported in million f/g, and include: <0.1, 0.1-0.99, and >1.0.
Additional Comments: None
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 353 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3079077 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Kishimoto, T., Gemba, K., Fujimoto, N., Onishi, K., Usami, I., Mizuhashi, K., Kimura, K. (2010). Clinical study of asbestos-related lung cancer in Japan
with special reference to occupational history. Cancer Science 101(2010):1194-1198.
Lung Cancer
Cancer/Carcinogenesis: Lung cancer; Lung/Respiratory: Lung cancer
Asbestos - Not specified: 1332-21-4
No linked references.
3079077
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Metric 5:
Measurement of Exposure
Exposure Levels
Medium The number of asbestos particles in the lung were assessed using PCM.
Low The study only reports the number of asbestos particle using categories of exposure (i.e.,
1,000 - 4,999; 5,000 - 9,999) using a bar graph. The distribution information is limited.
Additional Comments: Note added 1/5/23 by Nathan Lothrop (ICF) - this study was reviewed and initially was part of a cohort, but upon further review determined it was not. In
process, it was noticed authors did a basic descriptive analysis of asbestosis.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 354 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082790 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Kishimoto, T., Ono, T., Okada, K., Ito, H. (1989). Relationship between number of asbestos bodies in autopsy lung and pleural plaques on chest X-ray
film. Chest 95(1989):549-552.
Pleural Plaques
Lung/Respiratory: Pleural plaques
Asbestos - Not specified: 1332-21-4
No linked references.
3082790
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Five gram samples of lung tissue were collected and lysed from the autopsied individ-
uals. Light microscopy was used to determine the number of asbestos bodies present in
the prepared samples. An occupational history was collected for the 71 cases with >500
asbestos bodies in their samples, but there were no quantitative measurements provided
for those locations.
Medium This metric was rated as "medium" because they displayed three different ranges of ex-
posure based on the type of plaque found by the x-ray readers. For plaques of type IIIB,
there were 960 +/- 104 asbestos bodies, for type IV there were 32,560 +/- 31,346, and
for type V there were 42,841 +/- 10,981. This information is also presented in Figure 3.
Additional Comments: This study focused on the relationship between the asbestos bodies in lung samples and pleural plaques. They did not provide any discussions of con-
founders that may be present in this study, and there was mention that this study cannot examine the relationship between time since first exposure and
pleural plaques/asbestos bodies because of a lack of asbestos exposure history for some participants. They did provide information on the range of asbestos
bodies found in the various groupings of pleural plaque determinations, but they had a wide variance within the groups. There are some qualitative state-
ments made in this study, such as "the cases with clear pleural plaques on chest x-ray film had many more asbestos bodies than unclear cases" (Kishimoto
etal., 1989).
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 355 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 115 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Knox, J. F., Holmes, S., Doll, R., Hill, I. D. (1968). Mortality from lung cancer and other causes among workers in an asbestos textile factory. Occupational
and Environmental Medicine 25(1968):293-303.
Lung Cancer; other neoplasms; Pulmonary Function/Spirometry Results; disease of the circulatory system mortality, diseases of the respiratory system
mortality
Mortality: cancer of the lung or pleura mortality, other neoplasms mortality, diseases of the circulatory system mortality, diseases of the respiratory system
mortality, all other causes mortality, all cause mortality; Lung/Respiratory: cancer of the lung or pleura mortality, diseases of the respiratory system
mortality, Forced expiratory volume (FEV), Forced vital capacity (FVC), Total lung capacity (TLC); Cancer/Carcinogenesis: cancer of the lung or pleura
mortality, other neoplasms mortality; Cardiovascular: diseases of the circulatory system mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
115, 46
115
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
High Key elements of study design are reported for Knox et al., 1968 (HERO ID 000115)
and Berry et al., 1979 (HERO ID 00046). Knox et al., 1968 included men and women
employed in scheduled areas (defined as parts of the factory to which 1931 regulations
which controlled asbestos dust exposure for the asbestos industry were applied by 1933)
for more than 20 years at any time since the asbestos textile factory opened in Eng-
land. Men and women who were employed for more than 10 years were also included
if they were first employed on or after January 1, 1933. A total of n=878 workers were
available for this study with follow-up over 50 years from 1916 through the end of June
1966. Table 1 detailed the numbers of men (Groups 1-4) and women (Group 5 only)
within categories of period of exposure (Groups 1-3: 20 males with or more years of
exposure; Group 4: men with 10-19 years exposure; Group 5: women with 10 or more
years of exposure) in scheduled areas and duration of exposure before 1933. Berry et
al., 1979 included n=379 men who had worked at the same asbestos textile factory in
England for at least 10 years and extended follow-up for 6.5 years beyond that of Knox
et al., 1968. Exclusions within Berry et al., 1979 were made for n=12 men who had also
worked at a subsidiary asbestos factory for several years where the asbestos dust con-
centrations were unknown, as well as n=l worker for whom a job history could not be
constructed, leaving the n=379 men for the final analysis.
Continued on next page ...
Page 356 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 115 Table: 1 of 1
... continued from previous page
Knox, J. F., Holmes, S., Doll, R., Hill, I. D. (1968). Mortality from lung cancer and other causes among workers in an asbestos textile factory. Occupational
and Environmental Medicine 25(1968):293-303.
Lung Cancer; other neoplasms; Pulmonary Function/Spirometry Results; disease of the circulatory system mortality, diseases of the respiratory system
mortality
Mortality: cancer of the lung or pleura mortality, other neoplasms mortality, diseases of the circulatory system mortality, diseases of the respiratory system
mortality, all other causes mortality, all cause mortality; Lung/Respiratory: cancer of the lung or pleura mortality, diseases of the respiratory system
mortality, Forced expiratory volume (FEV), Forced vital capacity (FVC), Total lung capacity (TLC); Cancer/Carcinogenesis: cancer of the lung or pleura
mortality, other neoplasms mortality; Cardiovascular: diseases of the circulatory system mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
115, 46
115
Domain Metric Rating Comments
Metric 2: Attrition Medium Outcome and exposure data were relatively complete for Knox et al., 1968 and Berry et
al., 1979. For Knox et al., Other than one man and one woman who could not be traced,
all other subjects were described as successfully traced. Death certificates were obtained
for all deaths but one, described as occurring abroad. Authors noted that three instances
of lung cancer were discovered post mortem that were not mentioned on death certifi-
cates and these deaths were not attributed to lung cancer. Asbestos dust quantitative
sampling data was not available prior to 1951, and quantitative measures of asbestos
fiber counts were not available until 1961 (Table I). Missing covariate information was
not detailed, although authors noted follow-up was facilitated by the restriction of the
main study to workers with more than 20 years exposure who would have been provided
pensions and thus were still in company personnel files. Berry et al., 1979 extended the
Knox et al., 1968 study to include n=89 men who had completed 10 years of service
between 30 June 1966 and 31 December 1972, as well as men who had left the factory
after 30 June 1966. Authors in Berry et al., 1979 noted 93% of the men in the study had
been medically examined or had a chest radiograph since 1969 or within three years of
death as the men working in scheduled occupations have periodic medical examinations
by a Pneumoconiosis Medical Panel under the Prescribed Diseases Regulations of the
National Insurance (Industrial Injuries) Act of 1946 and workers were given chest ra-
diographs every three years from 1951 until 1967 and every year since then. Berry et
al., 1979 noted information on asbestosis certification was complete up to 1975 for all
men, including those who had left the factory. For Berry et al., 1979, because pulmonary
function tests were not introduced until 1967 and were carried out every two years, these
data were available for only n=311 or 82% of the men in this study.
Continued on next page ...
Page 357 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 115 Table: 1 of 1
... continued from previous page
Knox, J. F., Holmes, S., Doll, R., Hill, I. D. (1968). Mortality from lung cancer and other causes among workers in an asbestos textile factory. Occupational
and Environmental Medicine 25(1968):293-303.
Lung Cancer; other neoplasms; Pulmonary Function/Spirometry Results; disease of the circulatory system mortality, diseases of the respiratory system
mortality
Mortality: cancer of the lung or pleura mortality, other neoplasms mortality, diseases of the circulatory system mortality, diseases of the respiratory system
mortality, all other causes mortality, all cause mortality; Lung/Respiratory: cancer of the lung or pleura mortality, diseases of the respiratory system
mortality, Forced expiratory volume (FEV), Forced vital capacity (FVC), Total lung capacity (TLC); Cancer/Carcinogenesis: cancer of the lung or pleura
mortality, other neoplasms mortality; Cardiovascular: diseases of the circulatory system mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
115, 46
115
Domain Metric Rating Comments
Metric 3: Comparison Group Medium Inclusion criteria and methods of subject selection were reported for Knox et al., 1968
(HERO ID 000115) and Berry et al., 1979 (HERO ID 00046). For Knox et al„ 1968, re-
sults were reported as observed and expected deaths for each outcome category, facilitat-
ing the calculation of Standardized Mortality Ratios (SMRs). Results in Table III were
reported stratified by designated Groups (1-5), which would have controlled for sex as
all Groups 1-4 were men only and Group 5 was only women, but were not stratified by
age. Additional analyses within subsequent tables IV, V and VI were standardized for,
or stratified by, age, but only Table IV was standardized by age and stratified by Groups
restricting to males and thus controlled for gender and age. Choice of reference popu-
lation was reported as the general population for expected deaths within Table III, and
as the internal worker population for expected deaths within Tables IV, V and VI. There
is potential and evidence for the Healthy Worker Effect (HWE) within results where
the ratio of observed total deaths versus expected deaths was <=1.0, including results
in Table III within some designated exposure period Group strata for cancer of the lung
or pleura, other neoplasms, disease of the respiratory system, all other causes, and all
causes. Substantial potential for the HWE is noted for the Table III results for cancer
outcomes where ratios of reported observed versus expected deaths would be <=1.0
as the general population was used as the referent for expected deaths in Table III and
smoking was not controlled for. Additional potential for HWE may be noted for Table
IV with an internal worker population was used as the referent for non-cancer outcomes
with lower observed versus expected deaths within some exposure group strata. Berry
et al., 1979 inclusion criteria and participation were reported. Differences in baseline
characteristics within the population were considered as potential confounding variables
in regression models-pulmonary function indices and cumulative asbestos exposure re-
gression models in Table 5 included age and height, but not smoking, and were restricted
to males first employed after 1950. The relationship between percentage developing
crepitations, possible asbestosis and certified asbestosis for men first employed after
1950 presented in Figure 4 of Berry et al., 1979 were described as obtained by life table
methods.
Domain 2: Exposure Characterization
Continued on next page ...
Page 358 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 115 Table: 1 of 1
... continued from previous page
Knox, J. F., Holmes, S., Doll, R., Hill, I. D. (1968). Mortality from lung cancer and other causes among workers in an asbestos textile factory. Occupational
and Environmental Medicine 25(1968):293-303.
Lung Cancer; other neoplasms; Pulmonary Function/Spirometry Results; disease of the circulatory system mortality, diseases of the respiratory system
mortality
Mortality: cancer of the lung or pleura mortality, other neoplasms mortality, diseases of the circulatory system mortality, diseases of the respiratory system
mortality, all other causes mortality, all cause mortality; Lung/Respiratory: cancer of the lung or pleura mortality, diseases of the respiratory system
mortality, Forced expiratory volume (FEV), Forced vital capacity (FVC), Total lung capacity (TLC); Cancer/Carcinogenesis: cancer of the lung or pleura
mortality, other neoplasms mortality; Cardiovascular: diseases of the circulatory system mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
115, 46
115
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium For Knox et al., 1968 quantitative measures of asbestos fiber levels were available only
after 1961, and dust sampling results were only available after 1951, however work-
ers were followed up for outcomes beginning in 1916. Table I reports average expo-
sure sampling results from routine dust (particles per c.c.; 1952, 1960) sampling using
the Casella Thermal Precipitator with analysis at a magnification of x 1,000, and fiber
(fibers per c.c.; 1961, 1966) sampling using the Long Running Thermal Precipitator
(magnification of x 500 with fibers 5-100 microns long and whose length was between
5 and 100 microns) or Cellulose Membrane sampler. Although Phase Contrast Mi-
croscopy (PCM) was not specified, the magnifications detailed indicate compatibility
with this standard. Authors noted substantial changes in asbestos dust levels following
introduction of asbestos industry control standards in 1931. Cumulative exposure to
asbestos in Berry et al., 1979 for analyses restricted to men employed after 1950 was
described as estimated from quantitative asbestos fiber sampling conducted beginning
in 1961, with the counts for 1951-1955 taken as those of 1961 multiplied by the ratio of
1952 to 1960 thermal precipitator measurements, and the counts for 1956-1960 assumed
as the same as 1961-1965 as there were no dust measurements prior to 1950.
Medium The range and distribution of exposure (Table I in both Knox et al., 1968 and Berry et
al., 1979) is sufficient to develop exposure-response estimates. Mortality was analyzed
as observed and expected deaths, but was stratified for periods of exposure in Knox et
al., 1968.
High The study establishes temporality by inclusion of workers with more than 20 (and more
than 10 years in Berry et al., 1979 and some analyses in Knox et al., 1968) years of
exposure and presentation of results (Table VI in Knox et al., 1968) stratified across
categories of years after completing twenty years of employment.
Domain 3: Outcome Assessment
Continued on next page .
Page 359 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 115 Table: 1 of 1
... continued from previous page
Knox, J. F., Holmes, S., Doll, R., Hill, I. D. (1968). Mortality from lung cancer and other causes among workers in an asbestos textile factory. Occupational
and Environmental Medicine 25(1968):293-303.
Lung Cancer; other neoplasms; Pulmonary Function/Spirometry Results; disease of the circulatory system mortality, diseases of the respiratory system
mortality
Mortality: cancer of the lung or pleura mortality, other neoplasms mortality, diseases of the circulatory system mortality, diseases of the respiratory system
mortality, all other causes mortality, all cause mortality; Lung/Respiratory: cancer of the lung or pleura mortality, diseases of the respiratory system
mortality, Forced expiratory volume (FEV), Forced vital capacity (FVC), Total lung capacity (TLC); Cancer/Carcinogenesis: cancer of the lung or pleura
mortality, other neoplasms mortality; Cardiovascular: diseases of the circulatory system mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
115, 46
115
Domain Metric Rating Comments
Metric 7: Outcome Measurement or Medium Lung Cancer: For Knox et al., 1968, mortality outcomes for workers followed up from
Characterization 1916 through 1966 included cancer of the lung or pleura (ICD codes 162,163), other
neoplasms (ICD codes 140-239, except 162 and 163), diseases of the circulatory sys-
tem (ICD codes 400-468), diseases of the respiratory system (ICD codes 470-527), all
other causes, and all causes (Table III), with Tables IV, V, and VI focusing on lung can-
cer deaths (ICD codes 162, 163). ICD codes were provided in Table III. Deaths were
described as assessed for all deaths but one (occurring abroad) through cause provided
on death certificate using the method of classification in use by the Registrar-General
at the relevant period, with ICD codes provided, and according to the best information
obtainable from all sources, although validation through histologic or cytologic means
was not described. For Berry et al., 1979, pulmonary function test results for FEV1,
FVC, TLC and TL, as well as diagnoses of crepitations, and possible asbestosis were
obtained from records in the factory" s medical department (ICD codes were not de-
tailed in text). Pneumoconiosis Medical Panel records were obtained for data regarding
asbestosis certification.; Other Cancer(s): For Knox et al., 1968, mortality outcomes
for workers followed up from 1916 through 1966 included cancer of the lung or pleura
(ICD codes 162, 163), other neoplasms (ICD codes 140-239, except 162 and 163), dis-
eases of the circulatory system (ICD codes 400-468), diseases of the respiratory system
(ICD codes 470-527), all other causes, and all causes (Table III), with Tables IV, V, and
VI focusing on lung cancer deaths (ICD codes 162, 163). ICD codes were provided in
Table III. Deaths were described as assessed for all deaths but one (occurring abroad)
through cause provided on death certificate using the method of classification in use by
the Registrar-General at the relevant period, with ICD codes provided, and according to
the best information obtainable from all sources, although validation through histologic
or cytologic means was not described. For Berry et al., 1979, pulmonary function test
results for FEV1, FVC, TLC and TL, as well as diagnoses of crepitations, and possible
asbestosis were obtained from records in the factory" s medical department (ICD codes
were not detailed in text). Pneumoconiosis Medical Panel records were obtained for data
regarding asbestosis certification.; Pulmonary Function/Spirometry Results: For Knox
et al., 1968, mortality outcomes for workers followed up from 1916 through 1966 in-
cluded cancer of the lung or pleura (ICD codes 162, 163), other neoplasms (ICD codes
140-239, except 162 and 163), diseases of the circulatory system (ICD codes 400-468),
diseases of the respiratory system (ICD codes 470-527), all other causes, and all causes
(Table III), with Tables IV, V, and VI focusing on lung cancer deaths (ICD codes 162,
163). ICD codes were provided in Table III. Deaths were described as assessed for all
deaths but one (occurring abroad) through cause provided on death certificate using the
method of classification in use by the Registrar-General at the relevant period, with ICD
codes provided, and according to the best information obtainable from all sources, al-
though validation through histologic or cytologic means was not described. For Berry
P 16ft f (Jftf* et al-. 1979, pulmonary function test results for FEV1, FVC, TLC and TL, as well as
rdge JOU Oi OUO diagnoses of crepitations, and possible asbestosis were obtained from records in the
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 115 Table: 1 of 1
... continued from previous page
Knox, J. F., Holmes, S., Doll, R., Hill, I. D. (1968). Mortality from lung cancer and other causes among workers in an asbestos textile factory. Occupational
and Environmental Medicine 25(1968):293-303.
Lung Cancer; other neoplasms; Pulmonary Function/Spirometry Results; disease of the circulatory system mortality, diseases of the respiratory system
mortality
Mortality: cancer of the lung or pleura mortality, other neoplasms mortality, diseases of the circulatory system mortality, diseases of the respiratory system
mortality, all other causes mortality, all cause mortality; Lung/Respiratory: cancer of the lung or pleura mortality, diseases of the respiratory system
mortality, Forced expiratory volume (FEV), Forced vital capacity (FVC), Total lung capacity (TLC); Cancer/Carcinogenesis: cancer of the lung or pleura
mortality, other neoplasms mortality; Cardiovascular: diseases of the circulatory system mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
115, 46
115
Domain
Metric
Rating
Comments
Metric 8: Reporting Bias
Medium There were no concerns in Knox et al., 1968 or Berry et al., 1979 for selective reporting
as all outcomes which were outlined within methods were also reported within the re-
sults. Observed and expected deaths were reported in tables as single values, rather than
ratios or SMRs for Knox et al., 1968, and regression results were reported as coefficients
(standard errors) for pulmonary function in Berry et al., 1979.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Final results for Knox et al., 1968 were reported in tables of observed and expected
deaths with no adjustments for sex, however results in Table III were stratified by des-
ignated exposure Group, which was males only for Groups 1-4 and females only for
Group 5. Additional tables IV, V and VI reported results standardized for age, period
of exposure Group, and time since completing 20 years exposure. Smoking status, es-
pecially for the lung cancer analyses with the general population as referent in Table
III, was not considered. Berry et al., 1979 pulmonary function indices and cumula-
tive asbestos exposure regression models in Table 5 included age and height, and were
restricted to males first employed after 1950. The relationship between percentage de-
veloping crepitations, possible asbestosis and certified asbestosis for men first employed
after 1950 presented in Figure 4 of Berry et al., 1979 were described as only as obtained
by life table methods.
Medium Covariates were described as assessed using data from personnel files, with no method
of validation for both Knox et al., 1968 and Berry et al., 1979.
Medium The members of the Knox et al., 1968 and Berry et al., 1979 cohorts for the main anal-
yses were workers with at least 20 years (10 years for Berry et al., 1979) of exposure at
an asbestos textile plant with no evidence of an unbalanced provision of co-exposures
among exposure groups.
Domain 5: Analysis
Metric 12: Study Design and Methods Medium The study design in Knox et al., 1968 was appropriate as a preliminary step to address
research questions on outcomes of interest. Results were reported as observed and ex-
pected deaths across gender and exposure period strata. Berry et al., 1979 included
n=379 men who had worked at the same asbestos textile factory in England for at least
10 years, with follow-up extended and analyses conducted utilizing multivariate regres-
sion and life table methods.
Continued on next page ...
Page 361 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 115 Table: 1 of 1
... continued from previous page
Knox, J. F., Holmes, S., Doll, R., Hill, I. D. (1968). Mortality from lung cancer and other causes among workers in an asbestos textile factory. Occupational
and Environmental Medicine 25(1968):293-303.
Lung Cancer; other neoplasms; Pulmonary Function/Spirometry Results; disease of the circulatory system mortality, diseases of the respiratory system
mortality
Mortality: cancer of the lung or pleura mortality, other neoplasms mortality, diseases of the circulatory system mortality, diseases of the respiratory system
mortality, all other causes mortality, all cause mortality; Lung/Respiratory: cancer of the lung or pleura mortality, diseases of the respiratory system
mortality, Forced expiratory volume (FEV), Forced vital capacity (FVC), Total lung capacity (TLC); Cancer/Carcinogenesis: cancer of the lung or pleura
mortality, other neoplasms mortality; Cardiovascular: diseases of the circulatory system mortality
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
115, 46
115
Domain Metric Rating Comments
Metric 13: Statistical Power Medium A total of n=878 workers were available for the Knox et al., 1968 study of observed
mortality with follow-up over 50 years from 1916 through the end of June 1966. A total
of n=379 men were utilized for the final analyses within Berry et al., 1979.
Metric 14: Reproducibility of Analyses Medium The methods utilized to estimate summarized exposures, as well as statistical analyses,
were described in a way that would facilitate general reproducibility in Knox et al., 1968
and Berry et al., 1979.
Metric 15: Statistical Analysis Medium N/A. for Knox et al., 1968. Medium for Berry et al., 1979 where methods utilized to
estimate regression coefficients were generally adequately described, although proce-
dures for outliers and missing data were not detailed. Multiple sensitivity models were
produced within Berry et al., 1979.
Additional Comments: These retrospective cohort studies investigated mortality from lung cancer and other causes (Knox et al., 1968) as well as pulmonary function and asbestosis
(Berry et al., 1979) in workers with at least 10 years of work in an asbestos textile factory in England. Results in Knox et al., 1968 indicated highly significant
increased mortality when compared with the general population for lung cancer, respiratory diseases and circulatory diseases associated with asbestosis
for men exposed for 10 or more years before 1933, but decreased mortality for those working greater than twenty years since 1933 for diseases of the
circulatory and respiratory system, and no change in mortality with the internal worker population as comparison for any cause of death for workers with
20 years of work. Results in Berry et al., 1979 indicated forced expiratory volume (FEV) and forced vital capacity (FVC), but not total lung capacity (TLC),
declined significantly with cumulative asbestos exposure for men first employed after 1950, and the relationship between exposure and 1% prevalence of
crepitations, possible asbestosis and certified asbestosis were detailed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 362 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6866465 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Konen, T., Johnson, J. E., Lindgren, P., Williams, A. (2019). Cancer incidence and mortality associated with non-occupational and low dose exposure to
Libby vermiculite in Minnesota. Environmental Research 175(2019):449-456.
Lung Cancer; All cancers; Asbestosis; COPD, NMRD, All causes of death
Lung/Respiratory: Asbestosis mortality, COPD mortality, Non-malignant respiratory disease (NMRD) mortality, All Respiratory Cancer mortality, Lung
Cancer mortality; Mortality: Mortality from asbestosis, Mortality from COPD, Mortality from NMRD, All respiratory cancer mortality, Lung Cancer mor-
tality, All causes mortality, All Cancer Mortality; Cancer/Carcinogenesis: All respiratory cancer mortality, Lung Cancer mortality, All Cancer Mortality;
All causes: All causes mortality
Asbestos- Libby amphibole: 1318-09-8
No linked references.
6866465
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Asbestos exposure was estimated, and no quantitative measurements were taken. The
authors reported that the exposure estimates were calculated "based on total months
of residency (duration) and addresses in the study area and using results of modeled
ambient asbestos concentration levels during three different time periods during plant
operations (1938-1989)."
Medium The range of exposure was adequate to create an exposure-response estimate. The
study's analyses included 3 exposed groups (<50th percentile, 50th - 75th percentile,
and >75th percentile).
Additional Comments:
METRIC 4 IS RATED AS LOW. EVALUATION FOR THIS STUDY WAS ALREADY IN PROGRESS, BUT AFTER LEARNING OF NEW GUIDANCE
(ABOUT METRICS 4/5) ON 1.27.23, STOPPED EVALUATIONInformation on the measurement of exposure metric (M4) to assess exposure is limited
(low rating) as no quantitative measurements were taken. However, the exposure levels metric (M5) information reported is sufficient to determine
exposure-response relationships.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 363 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2583283 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Kumagai, S., Kurumatani, N., Tsuda, T., Yorifuji, T., Suzuki, E. (2010). Increased risk of lung cancer mortality among residents near an asbestos product
manufacturing plant. International Journal of Occupational and Environmental Health 16(2010):268-278.
Lung Cancer; All body systems; All body system
Mortality: All causes, Infections (ICD10 - A,B), Neoplasm mortality (ICD 10 - C, D00-D48), Malignant neoplasm mortality (ICD 10 - C00-C97), Lip,
oral cavity, and pharynx neoplasm mortality (ICD 10 - C00-C14), Oesophagus neoplasm mortality (ICD10 - C15), Stomach neoplasm mortality (ICD10 -
C16), Colon and rectum neoplasm mortality (ICD10 C18-C20), Liver neoplasm mortality (ICD10 - C22), Gallbladder and biliary tract neoplasm mortality (
ICD10-C23-C24), Pancreas neoplasm mortality (ICD10 - C25), Lung and trachea excluding cases with occupational asbestos exposure, neoplasm mortality
(ICD10 - C33-C34), Lung and trachea excluding cases with occupational asbestos and silica exposure, neoplasm mortality (ICD10 - C33-C34), Skin
neoplasm mortality (ICD10 - C43-44), Breast neoplasm mortality (ICD10 - C50), Uterus neoplasm mortality (ICD10 - C53-C55), Prostate neoplasm
mortality (ICD10 - C61), Bladder neoplasm mortality (ICD10 - C67), Central nervous system neoplasm mortality (ICD10 - C70-C72, C75.1-C75.3),
Leukemia mortality (ICD10 - C91-C95), Other malignant neoplasm mortality, Endocrine mortality (ICD10 - E), Nervous system mortality (ICD10 - G),
Circulatory system mortality (ICD10 - I), Respiratory system mortality (ICD10 - J), Digestive system mortality (ICD10 - K), Musculoskeletal system
mortality (ICD10 - M), Genitourinary system mortality (ICD10 - N); Cancer/Carcinogenesis: Neoplasm mortality (ICD 10 - C, D00-D48), Malignant
neoplasm mortality (ICD 10 - C00-C97), Lip, oral cavity, and pharynx neoplasm mortality (ICD 10 - C00-C14), Oesophagus neoplasm mortality (ICD10
- C15), Stomach neoplasm mortality (ICD10 - C16), Colon and rectum neoplasm mortality (ICD10 C18-C20), Liver neoplasm mortality (ICD10 - C22),
Gallbladder and biliary tract neoplasm mortality ( ICD10-C23-C24), Pancreas neoplasm mortality (ICD10 - C25), Lung and trachea excluding cases
with occupational asbestos exposure, neoplasm mortality (ICD10 - C33-C34), Lung and trachea excluding cases with occupational asbestos and silica
exposure, neoplasm mortality (ICD10 - C33-C34), Skin neoplasm mortality (ICD10 - C43-44), Breast neoplasm mortality (ICD10 - C50), Uterus neoplasm
mortality (ICD10 - C53-C55), Prostate neoplasm mortality (ICD10 - C61), Bladder neoplasm mortality (ICD10 - C67), Central nervous system neoplasm
mortality (ICD10 - C70-C72, C75.1-C75.3), Leukemia mortality (ICD10 - C91-C95), Other malignant neoplasm mortality; Dermal: Lip, oral cavity, and
pharynx neoplasm mortality (ICD 10 - C00-C14); Gastrointestinal: Oesophagus neoplasm mortality (ICD10 - C15), Stomach neoplasm mortality (ICD10
- C16), Colon and rectum neoplasm mortality (ICD10 C18-C20), Gallbladder and biliary tract neoplasm mortality (ICD10-C23-C24), Pancreas neoplasm
mortality (ICD10 - C25), Digestive system mortality (ICD10 - K); Hepatic/Liver: Liver neoplasm mortality (ICD10 - C22); Lung/Respiratory: Lung and
trachea excluding cases with occupational asbestos exposure, neoplasm mortality (ICD10 - C33-C34), Lung and trachea excluding cases with occupational
asbestos and silica exposure, neoplasm mortality (ICD10 - C33-C34), Respiratory system mortality (ICD10 - J); Skin/Connective Tissue: Skin neoplasm
mortality (ICD10 - C43-44); Reproductive/Developmental: Breast neoplasm mortality (ICD10 - C50), Uterus neoplasm mortality (ICD10 - C53-C55),
Prostate neoplasm mortality (ICD10 - C61), Genitourinary system mortality (ICD10 - N); Renal/Kidney: Bladder neoplasm mortality (ICD10 - C67),
Genitourinary system mortality (ICD10 - N); Neurological/Behavioral: Central nervous system neoplasm mortality (ICD10 - C70-C72, C75.1-C75.3),
Nervous system mortality (ICD10 - G); Circulatory system: Leukemia mortality (ICD10 - C91-C95), Circulatory system mortality (ICD10 -1); Thyroid:
Endocrine mortality (ICD10 - E); Musculoskeletal: Musculoskeletal system mortality (ICD10 - M)
Asbestos - Not specified: 1332-21-4
2583283, 3541492
2583283
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Low Exposure was not directly measured using a quantitative method. Instead, the authors
estimated relative asbestos concentrations using meteorological parameters and asbestos
emission data. The assumptions and methodology were described in the paper. However,
exposure misclassification is likely to be present since no direct measurements using
well-established methods.Note: responses to other metrics beyond 4 and 5 were not
QC'ed because metric 4 was rated low.
Continued on next page ...
Page 364 ol 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2583283 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Kumagai, S., Kurumatani, N., Tsuda, T., Yorifuji, T., Suzuki, E. (2010). Increased risk of lung cancer mortality among residents near an asbestos product
manufacturing plant. International lournal of Occupational and Environmental Health 16(2010):268-278.
Lung Cancer; All body systems; All body system
Mortality: All causes, Infections (ICD10 - A,B), Neoplasm mortality (ICD 10 - C, D00-D48), Malignant neoplasm mortality (ICD 10 - C00-C97), Lip,
oral cavity, and pharynx neoplasm mortality (ICD 10 - C00-C14), Oesophagus neoplasm mortality (ICD10 - C15), Stomach neoplasm mortality (ICD10 -
C16), Colon and rectum neoplasm mortality (ICD10 C18-C20), Liver neoplasm mortality (ICD10 - C22), Gallbladder and biliary tract neoplasm mortality (
ICD10-C23-C24), Pancreas neoplasm mortality (ICD10 - C25), Lung and trachea excluding cases with occupational asbestos exposure, neoplasm mortality
(ICD10 - C33-C34), Lung and trachea excluding cases with occupational asbestos and silica exposure, neoplasm mortality (ICD10 - C33-C34), Skin
neoplasm mortality (ICD10 - C43-44), Breast neoplasm mortality (ICD10 - C50), Uterus neoplasm mortality (ICD10 - C53-C55), Prostate neoplasm
mortality (ICD10 - C61), Bladder neoplasm mortality (ICD10 - C67), Central nervous system neoplasm mortality (ICD10 - C70-C72, C75.1-C75.3),
Leukemia mortality (ICD10 - C91-C95), Other malignant neoplasm mortality, Endocrine mortality (ICD10 - E), Nervous system mortality (ICD10 - G),
Circulatory system mortality (ICD10 - I), Respiratory system mortality (ICD10 - I), Digestive system mortality (ICD10 - K), Musculoskeletal system
mortality (ICD10 - M), Genitourinary system mortality (ICD10 - N); Cancer/Carcinogenesis: Neoplasm mortality (ICD 10 - C, D00-D48), Malignant
neoplasm mortality (ICD 10 - C00-C97), Lip, oral cavity, and pharynx neoplasm mortality (ICD 10 - C00-C14), Oesophagus neoplasm mortality (ICD10
- C15), Stomach neoplasm mortality (ICD10 - C16), Colon and rectum neoplasm mortality (ICD10 C18-C20), Liver neoplasm mortality (ICD10 - C22),
Gallbladder and biliary tract neoplasm mortality ( ICD10-C23-C24), Pancreas neoplasm mortality (ICD10 - C25), Lung and trachea excluding cases
with occupational asbestos exposure, neoplasm mortality (ICD10 - C33-C34), Lung and trachea excluding cases with occupational asbestos and silica
exposure, neoplasm mortality (ICD10 - C33-C34), Skin neoplasm mortality (ICD10 - C43-44), Breast neoplasm mortality (ICD10 - C50), Uterus neoplasm
mortality (ICD10 - C53-C55), Prostate neoplasm mortality (ICD10 - C61), Bladder neoplasm mortality (ICD10 - C67), Central nervous system neoplasm
mortality (ICD10 - C70-C72, C75.1-C75.3), Leukemia mortality (ICD10 - C91-C95), Other malignant neoplasm mortality; Dermal: Lip, oral cavity, and
pharynx neoplasm mortality (ICD 10 - C00-C14); Gastrointestinal: Oesophagus neoplasm mortality (ICD10 - C15), Stomach neoplasm mortality (ICD10
- C16), Colon and rectum neoplasm mortality (ICD10 C18-C20), Gallbladder and biliary tract neoplasm mortality (ICD10-C23-C24), Pancreas neoplasm
mortality (ICD10 - C25), Digestive system mortality (ICD10 - K); Hepatic/Liver: Liver neoplasm mortality (ICD10 - C22); Lung/Respiratory: Lung and
trachea excluding cases with occupational asbestos exposure, neoplasm mortality (ICD10 - C33-C34), Lung and trachea excluding cases with occupational
asbestos and silica exposure, neoplasm mortality (ICD10 - C33-C34), Respiratory system mortality (ICD10 -1); Skin/Connective Tissue: Skin neoplasm
mortality (ICD10 - C43-44); Reproductive/Developmental: Breast neoplasm mortality (ICD10 - C50), Uterus neoplasm mortality (ICD10 - C53-C55),
Prostate neoplasm mortality (ICD10 - C61), Genitourinary system mortality (ICD10 - N); Renal/Kidney: Bladder neoplasm mortality (ICD10 - C67),
Genitourinary system mortality (ICD10 - N); Neurological/Behavioral: Central nervous system neoplasm mortality (ICD10 - C70-C72, C75.1-C75.3),
Nervous system mortality (ICD10 - G); Circulatory system: Leukemia mortality (ICD10 - C91-C95), Circulatory system mortality (ICD10 -1); Thyroid:
Endocrine mortality (ICD10 - E); Musculoskeletal: Musculoskeletal system mortality (ICD10 - M)
Asbestos - Not specified: 1332-21-4
ID(s): 2583283,3541492
2583283
Domain
Metric
Rating
Comments
Metric 5: Exposure Levels
Medium Subjects were categorized into 4 exposure levels according to their estimated exposure
level. The range and distribution of exposure is sufficient to detect an effect.
Additional Comments: The major concern of this study is no direct measurement of exposure, so potential exposure misclassification is likely to be present. Other part of the study
such as population selection and outcome measurements were appropriate and sufficiently described.Lung cancer SMR was assessed but not evaluated here
according to instruction from EPA.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 365 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3084226 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lacquet, L. M., van der Linden, L., Lepoutre, J. (1980). Roentgenograph^ lung changes, asbestosis and mortality in a Belgian asbestos-cement factory.
IARC Scientific Publications -30783-793.
Lung Cancer; gastrointestinal cancer, nervous cancer, lymphoid and haematopoietic cancer, other cancer, not specified cancer; Asbestosis; external cause,
cerebro-cardiovascular cancer, respiratory, gastrointestinal, other, unknow or poorly specified cause
Lung/Respiratory: Asbestosis, Respiratory cancer mortality, Respiratory non-malignant mortality; Mortality: All cause mortality, Respiratory cancer
mortality, Gastrointestinal cancer mortality, External cause mortality, Unknown of poorly specified cause mortality, Malignant cause mortality, Cerebro-
cardiovascular non-malignant mortality, Respiratory non-malignant mortality, Gastrointestinal non-malignant mortality, Other non-malignant mortality,
Nervous cancer mortality, Lymphoid and haematopoietic cancer mortality, Other cancer mortality, Not specified cancer mortality, All cancers mortality;
Cancer/Carcinogenesis: Respiratory cancer mortality, Gastrointestinal cancer mortality, Malignant cause mortality, Nervous cancer mortality, Lymphoid
and haematopoietic cancer mortality, Other cancer mortality, Not specified cancer mortality, All cancers mortality; Gastrointestinal: Gastrointestinal can-
cer mortality, Gastrointestinal non-malignant mortality; Cardiovascular: Cerebro-cardiovascular non-malignant mortality; Other non-malignant mortality:
Other non-malignant mortality; Neurological/Behavioral: Nervous cancer mortality; Immune/Hematological: Lymphoid and haematopoietic cancer mor-
tality; Other cancer mortality: Other cancer mortality; Not specified cancer mortality: Not specified cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
3084226
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated low because neither PCM nor TEM were explicitly mentioned as
a method for fiber quantification. Fiber measurements from 1970-1976 were obtained
with filter-membrane methods. This was specified as static sampling during peak instal-
lation activities in Van Cleemput et al., 2000 783706. Measurements prior to 1970 were
estimated using a formula that assumed dust concentrations followed a logistic decay,
but no apparent use of conversion factors.
Low The range and distribution of exposure was sufficient to develop and exposure-response
estimate. The cohort study reported up to 7 levels of exposure (number varied between
analyses), with estimates ranging from 0 to 3200 fiber-years. However, most analyses
have only dichotomous exposures, with the sole exception of respiratory and gastroin-
testinal cancer (table 8).
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 366 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 711560 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Larson, T. C., Antao, V. C., Bove, F. J. (2010). Vermiculite worker mortality: Estimated effects of occupational exposure to Libby amphibole. Journal of
Occupational and Environmental Medicine 52(2010):555-560.
Lung Cancer; digestive system cancer; non-malignant respiratory disease, cardiovascular disease
Mortality: cardiovascular disease, digestive system cancer, Lung cancer, Asbestosis, non-malignant respiratory disease; Cardiovascular: cardiovascu-
lar disease; Cancer/Carcinogenesis: Lung cancer, digestive system cancer; Gastrointestinal: digestive system cancer; Lung/Respiratory: non-malignant
respiratory disease, Lung cancer, Asbestosis
Asbestos- Libby amphibole: 1318-09-8
709497, 709457, 711560, 2238712
711560
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM to develop quantitative estimates of exposure.
Medium The distribution of exposure appears to be sufficient to develop an exposure-response
estimate. Cumulative exposure was utilized in dose-response calculations and were rep-
resented in four levels: <1.4 f/cc-y, 1.4 to <8.6 f/cc-y, 8.6 to <44.0 f/cc-y, and >=44.0
f/cc-y.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis. Metric 4 had a low level of confidence because the authors do not mention using PCM or TEM to develop quantitative estimates of exposure.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 367 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1005289 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Larson, T. C., Antao, V. C., Bove, F. J., Cusack, C. (2012). Association between cumulative fiber exposure and respiratory outcomes among Libby
vermiculite workers. Journal of Occupational and Environmental Medicine 54(2012):56-63.
Pulmonary Function/Spirometry Results; Pleural Plaques
Lung/Respiratory: Radiographic lung changes: diffuse or localized pleural thickening, parenchymal abnormalities. Respiratory symptoms: restrictive
spirometry, dyspnea/shortness of breath, excess cough, chronic bronchitis.
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos - Tremolite: 14567-73-8; Asbestos
- Actinolite: 12172-67-7
No linked references.
1005289
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Low Larson et al., 2012 1005289 analyzed data from 336 participants in a 2000-2001 ATSDR
community screening in Libby, MT who identified themselves as having worked at
the vermiculite mine. The screening included volunteers who had lived, worked, or
played in Libby for at least 6 months prior to 1991. The sample had fewer years since
first exposure (29 vs 48 years), lower cumulative fiber exposure (CFE), and more years
employed vs others in a complete registry of mine workers (>700 deceased workers
not excluded for that comparison). Concerns: Self-selection bias is an important con-
cern since voluntary participation is potentially related to both exposure and health
status. Along with losses due to mortality (healthy worker survivor effect), morbidity
may have affected interest in or ability to participate in the screening. As the authors
noted, "workers with greater cumulative exposure may have already been diagnosed
with asbestos-related health outcomes and opted not to participate." Only 18% of the
eligible population participated in the study.
Low Attrition was high relative to the target sample of more than 900 workers still alive,
according to mortality studies conducted by the authors at about the same time (see
Larson et al. 2010, 711560). Sensitivity analyses to evaluate the potential influence of
non-participants were not discussed. Loss to follow-up after enrollment was not an issue
as the study was cross-sectional, and 336 of 370 (91% ) of the self-selected screening
participants who reported working at mine were matched to company records.
Low This study compared workers within the cohort with higher vs. lower exposure. Self-
selection is a major concern, as noted above. For the comparison group, individuals with
lower exposure may have been more motivated to participate in the screening if they had
symptoms potentially linked to their work and had not yet been diagnosed with a related
condition.
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium This metric is rated medium because the Larson et al., 2012 1005289 study mentions
the use of PCM for analysis of personal air sampling data for all areas of the vermiculite
operation. Larson et al., 2012 1005289 estimated retrospective cumulative fiber expo-
sure (CFE) through 1980 using the methods described in the NIOSH cohort (Armstrong
et al., 709456). Exposure after 1980 was incorporated using updated job history data
collected by ATSDR (details not provided).
Medium Analyses used either CFE quartiles (<0.4, 0.4-3.5, 3.6-15.7, or >=15.7 f/cc-years) or a
continuous CFE measure, which was modeled used restricted cubic splines to allow for
non-linear associations.
Continued on next page ...
Page 368 ot 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1005289 Table: 1 of 2
... continued from previous page
Larson, T. C., Antao, V. C., Bove, F. J., Cusack, C. (2012). Association between cumulative fiber exposure and respiratory outcomes among Libby
vermiculite workers, lournal of Occupational and Environmental Medicine 54(2012):56-63.
Pulmonary Function/Spirometry Results; Pleural Plaques
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Radiographic lung changes: diffuse or localized pleural thickening, parenchymal abnormalities. Respiratory symptoms: restrictive
spirometry, dyspnea/shortness of breath, excess cough, chronic bronchitis.
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos - Tremolite: 14567-73-8; Asbestos
- Actinolite: 12172-67-7
No linked references.
1005289
Domain
Metric
Rating
Comments
Metric 6: Temporality
High Sequencing was appropriate as exposure was estimated retrospectively in Larson et
al., 2012 1005289. The median (IQR) follow-up time since date of hire was 29.4
(25.6"39.3) years, which was adequate for asbestos-related radiographic changes to
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Metric 8: Reporting Bias
High Pulmonary Function/Spirometry Results: Spirometry testing was conducted by a quali-
fied technician used American Thoracic Society guidelines and published references for
predicted values. Spirometry was defined as restrictive, obstructive, mixed, and normal
based on lower limits of normal (LLN) cutoffs, with restrictive defined as FEV1/FVC <
LLN. 16% had restrictive spirometry, 11% obstructive, and 4% mixed.; Pleural Plaques:
In Larson et al., 2012 1005289, posterior-anterior chest radiographs taken in accor-
dance with NIOSH guidelines were read by two primary readers using the 1980 ILO
classification. A third reader did an independent reading in case of disagreements. The
radiographic changes were classified as the presence or absence of parenchymal abnor-
malities, localized pleural abnormalities, and diffuse pleural thickening. No information
about whether the B readers were blinded to exposure status was included.
High Results were presented for all stated aims.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High Multivariable analyses adjusted for age. The authors also evaluated confounding by
employment before 1974 (exposure estimates prior to that time were less valid and ex-
posure was higher), smoking, sex, and BMI. Covariates ultimately included in models
were selected empirically based on changes of 10% or more in the odds ratio of the
exposure-response association with their inclusion.
Medium Employment records were used in this study; other studies reported some errors in
recorded smoking history (Rohs et al 2007, 709486). BMI was measured as part of
the community screening.
Medium Subsequent occupational exposure to commercial asbestos was considered in a sensitiv-
ity analysis. However, community/residential exposure was not taken into account.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Medium Appropriate analyses were used. In addition to descriptive tabulations, logistic regres-
sion models were used with adjustment for potential confounders.
Medium The number of cases was adequate for localized pleural thickening (n=l 17). However,
few cases had diffuse pleural thickening (n=18); parenchymal abnormalities (n=18); and
restrictive lung function (n=45) - statistical power was likely limited for these outcomes.
Continued on next page ...
Page 369 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1005289 Table: 1 of 2
... continued from previous page
Larson, T. C., Antao, V. C., Bove, F. J., Cusack, C. (2012). Association between cumulative fiber exposure and respiratory outcomes among Libby
vermiculite workers, lournal of Occupational and Environmental Medicine 54(2012):56-63.
Pulmonary Function/Spirometry Results; Pleural Plaques
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Radiographic lung changes: diffuse or localized pleural thickening, parenchymal abnormalities. Respiratory symptoms: restrictive
spirometry, dyspnea/shortness of breath, excess cough, chronic bronchitis.
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos - Tremolite: 14567-73-8; Asbestos
- Actinolite: 12172-67-7
No linked references.
1005289
Domain
Metric
Rating
Comments
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium Methods used were described clearly, and results tables included cell sizes for numbers
of cases.
Medium Methods were appropriate, and the authors explained their rationale for the methods they
used (e.g., splines used to increase power and examine non-linearities; 10% change-in-
estimate used to identify confounders). Model fit was examined.
Additional Comments: This analysis of radiologic lung changes and spirometry-based lung function among Libby vermiculite mine workers by Larson et al., 2012 1005289 had
a long follow-up time (median 29.4 years). Self-selection bias is a major concern: a voluntary community screening was the source of study participants.
This bias may explain the weak or null associations observed despite the long follow-up. As the authors noted, the prevalence of lung changes at higher
levels of exposure was lower than expected; this would occur if more highly exposed individuals who already had lung diagnoses were not interested in
or able to participate (i.e., suggestive of bias). Overall, they authors found a high (46% ) prevalence of pleural abnormalities (n=154 or 35% localized
pleural thickening, n=18 or 5% diffuse pleural thickening, n=74 or 22% pleural calcification); 18 or 5% had parenchymal abnormalities. The prevalence of
restrictive lung function was low. Although associations were weak and largely non-significant, the trend, particularly in spline models, was for generally
positive associations with increasing CFE. For some outcomes, however, the magnitude of association declined at the highest levels of exposure (again
consistent with self-selection bias). Despite major concerns regarding self-selection bias, the high prevalence of lung changes at relatively low exposure
observed in this study is noteworthy.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 370 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1005289 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Larson, T. C., Antao, V. C., Bove, F. J., Cusack, C. (2012). Association between cumulative fiber exposure and respiratory outcomes among Libby
vermiculite workers. Journal of Occupational and Environmental Medicine 54(2012):56-63.
Dyspnea/shortness of breath, excess cough, chronic bronchitis
Lung/Respiratory: Radiographic lung changes: diffuse or localized pleural thickening, parenchymal abnormalities. Respiratory symptoms: restrictive
spirometry, dyspnea/shortness of breath, excess cough, chronic bronchitis.
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos - Tremolite: 14567-73-8; Asbestos
- Actinolite: 12172-67-7
No linked references.
1005289
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection Low Larson et al., 2012 1005289 analyzed data from 336 participants in a 2000-2001 ATSDR
community screening in Libby, MT who identified themselves as having worked at
the vermiculite mine. The screening included volunteers who had lived, worked, or
played in Libby for at least 6 months prior to 1991. The sample had fewer years since
first exposure (29 vs 48 years), lower cumulative fiber exposure (CFE), and more years
employed vs others in a complete registry of mine workers (>700 deceased workers
not excluded for that comparison). Concerns: Self-selection bias is an important con-
cern since voluntary participation is potentially related to both exposure and health
status. Along with losses due to mortality (healthy worker survivor effect), morbidity
may have affected interest in or ability to participate in the screening. As the authors
noted, "workers with greater cumulative exposure may have already been diagnosed
with asbestos-related health outcomes and opted not to participate." Only 18% of the
eligible population participated in the study.
Metric 2: Attrition Low Attrition was high relative to the target sample of more than 900 workers still alive,
according to mortality studies conducted by the authors at about the same time (see
Larson et al. 2010, 711560). Sensitivity analyses to evaluate the potential influence of
non-participants were not discussed. Loss to follow-up after enrollment was not an issue
as the study was cross-sectional, and 336 of 370 (91% ) of the self-selected screening
participants who reported working at mine were matched to company records.
Metric 3: Comparison Group Low This study compared workers within the cohort with higher vs. lower exposure. Self-
selection is a major concern, as noted above. For the comparison group, individuals with
lower exposure may have been more motivated to participate in the screening if they had
symptoms potentially linked to their work and had not yet been diagnosed with a related
condition.
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium This metric is rated medium because the Larson et al., 2012 1005289 study mentions
the use of PCM for analysis of personal air sampling data for all areas of the vermiculite
operation. Larson et al., 2012 1005289 estimated retrospective cumulative fiber expo-
sure (CFE) through 1980 using the methods described in the NIOSH cohort (Armstrong
et al., 709456). Exposure after 1980 was incorporated using updated job history data
collected by ATSDR (details not provided).
Medium Analyses used either CFE quartiles (<0.4, 0.4-3.5, 3.6-15.7, or >=15.7 f/cc-years) or a
continuous CFE measure, which was modeled used restricted cubic splines to allow for
non-linear associations.
Continued on next page ...
Page 371 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1005289 Table: 2 of 2
... continued from previous page
Larson, T. C., Antao, V. C., Bove, F. J., Cusack, C. (2012). Association between cumulative fiber exposure and respiratory outcomes among Libby
vermiculite workers, lournal of Occupational and Environmental Medicine 54(2012):56-63.
Dyspnea/shortness of breath, excess cough, chronic bronchitis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Radiographic lung changes: diffuse or localized pleural thickening, parenchymal abnormalities. Respiratory symptoms: restrictive
spirometry, dyspnea/shortness of breath, excess cough, chronic bronchitis.
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos - Tremolite: 14567-73-8; Asbestos
- Actinolite: 12172-67-7
No linked references.
1005289
Domain
Metric
Rating
Comments
Metric 6:
Temporality
High
Sequencing was appropriate as exposure was estimated retrospectively in Larson et
al., 2012 1005289. The median (IQR) follow-up time since date of hire was 29.4
(25.6"39.3) years, which was adequate for asbestos-related radiographic changes to
occur.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Low
High
Other Non-Cancer Outcomes: Outcomes were self-reported without confirmation by a
clinician. A questionnaire was used to identify respiratory symptoms; the manuscript
does not state whether they adapted or used items from validated questionnaires. The
following three respiratory symptoms were analyzed: (i) dyspnea, defined as shortness
of breath "when walking up a slight hill or when hurrying on level ground") = 66 or
20% ; (ii) excess cough, defined as having a cough "on most days [at least 4 days of
the week]" = 49 or 15% ; and (iii) chronic bronchitis, defined as both excess cough and
excess phlegm [coughing up phlegm "for at least 3 months of the year for the past 2
years"] = 26 or 8% . The authors stated that "[a]s part of the definition of these respira-
tory symptoms and conditions, we excluded workers with radiographic abnormalities
consistent with pneumoconiosis or restrictive spirometry."
Results were presented for all stated aims.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High
Medium
Medium
Multivariable analyses adjusted for age. The authors also evaluated confounding by
employment before 1974 (exposure estimates prior to that time were less valid and ex-
posure was higher), smoking, sex, and BMI. Covariates ultimately included in models
were selected empirically based on changes of 10% or more in the odds ratio of the
exposure-response association with their inclusion.
Employment records were used in this study; other studies reported some errors in
recorded smoking history (Rohs et al 2007, 709486). BMI was measured as part of
the community screening.
Subsequent occupational exposure to commercial asbestos was considered in a sensitiv-
ity analysis. However, community/residential exposure was not taken into account.
Domain 5: Analysis
Metric 12:
Metric 13:
Metric 14:
Study Design and Methods
Statistical Power
Reproducibility of Analyses
Medium
Medium
Medium
Appropriate analyses were used. In addition to descriptive tabulations, logistic regres-
sion models were used with adjustment for potential confounders
The number of cases was adequate for respiratory outcomes.
Methods used were described clearly, and results tables included cell sizes for numbers
of cases.
Continued on next page ...
Page 372 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1005289 Table: 2 of 2
... continued from previous page
Larson, T. C., Antao, V. C., Bove, F. J., Cusack, C. (2012). Association between cumulative fiber exposure and respiratory outcomes among Libby
vermiculite workers, lournal of Occupational and Environmental Medicine 54(2012):56-63.
Dyspnea/shortness of breath, excess cough, chronic bronchitis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Radiographic lung changes: diffuse or localized pleural thickening, parenchymal abnormalities. Respiratory symptoms: restrictive
spirometry, dyspnea/shortness of breath, excess cough, chronic bronchitis.
Asbestos- Libby amphibole: 1318-09-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos - Tremolite: 14567-73-8; Asbestos
- Actinolite: 12172-67-7
No linked references.
1005289
Domain
Metric
Rating
Comments
Metric 15: Statistical Analysis
Medium Methods were appropriate, and the authors explained their rationale for the methods they
used (e.g., splines used to increase power and examine non-linearities; 10% change-in-
estimate used to identify confounders). Model fit was examined.
Additional Comments: Self-selection bias is a major concern, as discussed in the evaluation of radiologic lung change and spirometry outcomes. For respiratory symptoms, an
additional concern is reliance exclusively on self-report without physician validation. It was also not fully clear whether participants with radiologic lung
changes - but without the respiratory symptom of interest - were included in or excluded from the referent population used for estimating associations (i.e.,
was the referent group limited to healthy workers?).
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 373 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709456 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Larson, T., Meyer, C., Kapil, V., Gurney, J., Tarver, R., Black, C., Lockey, J. (2010). Workers with Libby amphibole exposure: retrospective identification
and progression of radiographic changes. Radiology 255(2010):924-933.
Pleural Plaques
Lung/Respiratory: Progression of radiographic lung changes.
Asbestos - Tremolite: 14567-73-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos- Libby amphibole: 1318-09-8
ID(s): No linked references.
709456
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium Cumulative fiber exposure was estimated retrospectively using available historic fiber
measures; PCM counts were used when membrane filter measures were initiated in
1974. Earlier measures included few measures from limited areas and used instruments
such as midget impingers. Measurement error is a concern especially before 1974. Em-
ployment records were used to calculate individual exposure. Methods were detailed
elsewhere (Amandus et al 1987 PMID: 3028135).
Low Distributions of participants or the prevalence of progressive lung changes was not
presented by category of cumulative fiber exposure. The cumulative fiber exposure
(CFE) variable used in logistic regression models was not specified, and results were
not shown. However, mean CFE was shown for the full sample and for subgroups with
different types of radiographic lung changes.
Additional Comments: The association between cumulative fiber exposure and odds of progressive lung abnormalities was not presented as it was not statistically significant. Con-
cerns regarding sample selectivity may have influenced this finding. Although the association between progression and fiber exposure was not presented,
this study provides very useful information on patterns of progression of radiographic lung changes, including the median latency time for progression to
occur.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 374 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083980 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Liddell, F. D., Gibbs, G. W., Mcdonald, J. C. (1982). Radiological changes and fibre exposure in chrysotile workers aged 60-69 years at Thetford Mines.
Annals of Occupational Hygiene 26(1982):889-898.
Pleural Plaques
Lung/Respiratory: small opacities, pleural changes
Asbestos - Chrysotile (serpentine): 12001-29-5
3083980, 3083580
3083980
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Liddel et al. RefID 3083980: Study population included all male Thetford Mines em-
ployees born 1891-1920 who had 20+ years of employment at the facility and were aged
60+ in November 1966 (when radiographs were taken) or at termination of their last
job, if earlier (n=515).Cordier et al. RefID 3083580: Study population included male
Thetford Mines employees beginning employment between 1954-1969 with 5+ years
cumulative exposure, excluding those who works 6+ months at another asbestos factory
and/or 1+ years at another asbestos mine (n=394).Inclusion/exclusion criteria for both
studies were generally appropriate. Key elements of study population were reported in
sufficient detail.
Medium Outcome assessment and exposure monitoring were both conducted onsite at the facility
for all active employees, so missing outcome information is not a large concern. Sub-
jects were included in both studies retroactively after both exposure and outcome status
had been measured. Exclusion criteria were adequately documented and appropriate. No
direct evidence of substantial bias by attrition.
Medium Comparison structure was appropriate. For both studies, all subjects were employees at
the facility. Outcome status(es) were compared across multiple quantitative exposure
level bins. Requirements for duration of employment/exposure (20+ years experience
for Liddel et al.; 5+ years cumulative exposure for Cordier et al.) may have introduced
healthy worker effect.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium Liddel et al:Exposure was consistently assessed quantitatively. Asbestos fibers were
using midget impingers and fiber/dust ratios were calculated for each main and sub-area
of the facility. Individual exposures were calculated based on job histories collected via
questionnaire by outcome-blinded researchers in 1977. Cumulative and average fiber
exposures were calculated using formulas from Gibbs and Lachance (1972).Cordier et
al:Exposure was consistently assessed quantitatively. Asbestos fibers were measured
using midget impingers from 1958-1976 and using membrane filters from 1976 onward.
Cumulative exposures for individuals were calculated using a job matrix and Gibbs
procedure. Due to incomplete monitoring data, cumulative exposure was only calculated
for 7 job locations.Both studies note likely incompletion of exposure monitoring data.
Continued on next page ...
Page 375 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083980 Table: 1 of 1
... continued from previous page
Liddell, F. D., Gibbs, G. W., Mcdonald, J. C. (1982). Radiological changes and fibre exposure in chrysotile workers aged 60-69 years at Thetford Mines.
Annals of Occupational Hygiene 26(1982):889-898.
Pleural Plaques
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: small opacities, pleural changes
Asbestos - Chrysotile (serpentine): 12001-29-5
3083980, 3083580
3083980
Domain
Metric
Rating
Comments
Metric 5:
Metric 6:
Exposure Levels
Temporality
Medium Liddel et al:Number of workers in each average fiber concentration category are re-
ported, stratified by gross service years (Table 1). Average fiber concentration ranged
from <=10 f/mL to >75 f/mL.Cordier et al:Number of workers in each cumulative ex-
posure category are reported (<30 f/cc*yr: 42 workers; 30-89 f/cc*yr: 155 workers;
>=90 f/cc*yr: 134 workers). In both studies, observed exposure ranges are adequate to
determine an exposure-response relationship.
Low Liddel et al:Outcomes were measured via the most recent chest radiograph for each
subject prior to 1966. Subjects were required to have 20+ years of service at the mine
before 1966 to be eligible for inclusion. Cordier et al:Timing of outcome measurement
is somewhat vague (chest radiographs were assembled beginning in 1975 and each sub-
ject's most recent radiograph was used, but the year of measurement is not reported).
Subjects were required to have begun employment between 1954-1969 and have 5+
years of cumulative exposure at the time of outcome assessment. There is some over-
lap in exposure assessment and outcome assessment window, but because exposure
index was estimated based on year-accurate measurements, temporality could be es-
tablished.For both studies, temporality is established between exposure and outcome
but the latency window is not clear or necessarily consistent among subjects. A shorter
latency window is less concerning for the outcomes of interest (small opacities of the
lung, plural changes) than for a cancer outcome.
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Metric 8: Reporting Bias
Medium Pleural Plaques: Liddel et al:Most recent radiograph for each employee prior to 1966
was read in 3 stages by an international group of 6 readers using the IUCC/Cincinnati
classification. Films were then randomly divided into 30 equal sets and each reader read
5 sets, providing 1 reading for each film. The 6 readers worked separately and inde-
pendently and were blinded to age, work history, and other personal details of subjects.
Readers were involved in development of classifications.Cordier et al:Annual chest ra-
diographs for asbestos mine workers in this geographic area were compiled beginning in
1975. The most recent chest radiograph for each man still working in the mine (through
1980) was used. Each radiograph was read by 5 readers according to the ILO U/C 1980
classification. Readers were all radiologists and pulmonary physicians experienced in
reading pneumoconiosis and certified by NIOSH. Readers worked independently and
received films in random order. Readers were blinded to occupation or exposure status
of subjects.Equipment details for chest radiographs are not reported, but reading classifi-
cation materials are included and there is no direct evidence of mis-measurement.
Medium Results for all anticipated analyses are included in the paper.
Domain 4: Potential Confounding / Variability Control
Continued on next page ...
Page 376 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083980 Table: 1 of 1
... continued from previous page
Liddell, F. D., Gibbs, G. W., Mcdonald, J. C. (1982). Radiological changes and fibre exposure in chrysotile workers aged 60-69 years at Thetford Mines.
Annals of Occupational Hygiene 26(1982):889-898.
Pleural Plaques
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: small opacities, pleural changes
Asbestos - Chrysotile (serpentine): 12001-29-5
3083980, 3083580
3083980
Domain
Metric
Rating
Comments
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Both papers were restricted to male employees only. Liddel et al. accounted for age
by calculating cumulative and average exposure indexes standardized to "by 45 years
of age." Cordier et al. accounted for age by including it as an independent variable in
multivariate analyses. Both papers included stratified analyses by dichotomized smok-
ing. Length and timing of employment were considered through calculation of exposure
indexes. Neither paper discusses additional covariates such as race/ethnicity or SES.
Medium Covariate information was collected from interviews (Liddel et al.) or medical records
(Cordier et al.). No direct evidence of misclassification.
Medium No direct evidence that co-exposures were likely to be present.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium Both studies compared prevalence of small irregular opacities and pleural changes
across ordinal cumulative and average exposure bins. Liddel et al. used a modified least
squares analysis (XA 2 values reported) and Cordier et al. used a multivariate analysis
that included age, smoking and exposure as independent terms (p-values discussed in
text). Both analytical approaches were generally appropriate for the subject matter, if not
overly robust.
Medium Sample size and observed exposure ranges are adequate to detect present relationships in
both studies.
Low Descriptions of analytical methods are lacking and could not be easily reproduced (e.g.,
type of multivariate analysis performed and comparison statistic calculated are not re-
ported in Cordier et al.).
Low Liddel et al. used a modified least square analysis and Cordier et al., used an unidenti-
fied "multivariate analysis" to characterize differences in prevalence of outcomes across
exposure groups. There is not direct evidence that these methods were inappropriate, but
full information is lacking.
Additional Comments: None
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 377 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083620 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Liddell, F. D., Thomas, D. C., Gibbs, G. W., McDonald, J. C. (1984). Fibre exposure and mortality from pneumoconiosis, respiratory and abdominal
malignancies in chrysotile production in Quebec, 1926-75. Annals of the Academy of Medicine, Singapore 13(1984):340-344.
Lung Cancer; Laryngeal Cancer; cancer of the esophagus and stomach, cancer of the colon and rectum, other abdominal cancers; pneumoconiosis
Lung/Respiratory: death from pneumoconiosis, death from lung cancer, death from cancer of larynx; Mortality: death from pneumoconiosis, death from
lung cancer, death from cancer of larynx, death from cancer of oesophagus and stomach, death from cancer of colon and rectum, death from other abdominal
cancers; Cancer/Carcinogenesis: death from lung cancer, death from cancer of larynx, death from cancer of oesophagus and stomach, death from cancer
of colon and rectum, death from other abdominal cancers; Gastrointestinal: death from cancer of oesophagus and stomach, death from cancer of colon and
rectum; Abdomen: death from other abdominal cancers
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3083620
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because authors in this paper do not explicitly cite use of PCM
or TEM. Authors suggest that side-by-side measurements of dust and fiber were made to
develop a conversion factor, but there is no detail on microscopy methods. The methods
paper cited is Gibbs and Lachance, 1972, HEROID: 3580825, but this does not clarify
fiber counting methods. Methods of sample collection included midget impinger dust
counts measured between 1949 and 1976 and membrane filters between 1969 and 1976.
Conversion factors were utilized but were based on other studies to convert mpcf to f-ml.
Exposure data was examined for both cases and referents and came from exposure work
histories. For measurements prior to 1949, estimates were based off of interviews from
long-service employees which could introduce recall bias.
Medium Four levels of exposure are provided in the analyses in (f/ml)*y. Mean exposure was
828.3 (f/ml)*y.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 378 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3078595 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lin, S., Wang, X., Yu, I. T., Yano, E., Courtice, M., Qiu, H., Wang, M. (2012). Cause-specific mortality in relation to chrysotile-asbestos exposure in a
Chinese cohort. Journal of Thoracic Oncology 7(2012):1109-1114.
Lung Cancer; all cancer mortality, GI cancer mortality; all cause mortality, non-malignant respiratory disease mortality
Gastrointestinal: GI cancer mortality; Cancer/Carcinogenesis: GI cancer mortality, lung cancer mortality, all cancer mortality; Mortality: GI cancer
mortality, lung cancer mortality, all cancer mortality, all cause mortality, non-malignant respiratory disease mortality; Lung/Respiratory: lung cancer
mortality, non-malignant respiratory disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
3078595, 3078782
3078595
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low In both Lin et al., 2012 (HERO ID 3078595) and Wang et al., 2012 (HERO ID 3078782)
worker job titles or workshops are utilized as surrogates for exposure within categories
of final SMR results (Lin et al., 2012) and Cox models (Wang et al., 2012). In Lin et
al., 2012 (HERO ID 3078595), SMR results were only presented across low, medium
and high exposure categories based on exposure measurements conducted only in 2002,
with only references to the Wang et al., 2012 (HERO ID 3078782) study. In Wang et al.,
2012, authors reference the 2002 measurements made using TEM (referencing a study
by Yano et al., 2001 with title "Longitudinal study of the mortality of lung cancer in
chrysotile workers", which does not exist and may be a misprint or has been replaced by
Yano et al., 2001, HERO ID 3080569, entitled "Cancer Mortality among Workers Ex-
posed to Amphibole-free ChrysotileAsbestos" and found in the same journal).It was not
until 2016 when Courtice et al., 2016 (HERO ID 3520560) was conducted with the spe-
cific purpose of estimating cumulative fiber exposures in this Chinese asbestos factory
worker cohort that exposure from historical dust measures and PCM-analyzed sampling
was combined within a formal analysis. In this study they note about the studies at hand:
"In the published studies, however, workers" job titles or workshops were used as sur-
rogates for exposure. This could have led to potential exposure misclassification and
over- or underestimation of the associations. These studies did not consider quantitative
estimates of individual exposures, with which one can test hypotheses concerning quan-
titative exposure"response relationships. The purpose of the present study is to estimate
cumulative fiber exposures in this Chinese asbestos factory worker cohort and determine
the exposure"response relationships with lung cancer mortality..." (page 370).
Metric 5: Exposure Levels Medium The range and distribution of exposures summarized within Table 1 of Wang et al.,
2012 (HERO ID 3079792) was adequate to develop an exposure response estimate,
however these were summary measures for only the year 2002 for a cohort follow-up for
outcomes for 37 years. These 2002 measures were only briefly summarized as median
levels within the text of in Lin et al., 2012 (HERO ID 3078595).
Additional Comments: Lin et al., 2012 (HERO ID 3078595) and Wang et al., 2012 (HERO ID 3078782) studied n=577 workers from a chrysotile asbestos textile plant in China,
1972-2008. Both Lin et al., 2012 (HERO ID 3078595) and Wang et al., 2012 (HERO ID 3078782) were not evaluated for any metrics except Metric 4 and
5 as they did not have sufficient exposure information to be useful for dose-response analysis.
Continued on next page ...
Page 379 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3078595 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Lin, S., Wang, X., Yu, I. T., Yano, E., Courtice, M., Qiu, H., Wang, M. (2012). Cause-specific mortality in relation to chrysotile-asbestos exposure in a
Chinese cohort. Journal of Thoracic Oncology 7(2012):1109-1114.
Lung Cancer; all cancer mortality, GI cancer mortality; all cause mortality, non-malignant respiratory disease mortality
Gastrointestinal: GI cancer mortality; Cancer/Carcinogenesis: GI cancer mortality, lung cancer mortality, all cancer mortality; Mortality: GI cancer
mortality, lung cancer mortality, all cancer mortality, all cause mortality, non-malignant respiratory disease mortality; Lung/Respiratory: lung cancer
mortality, non-malignant respiratory disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): 3078595,3078782
3078595
Domain
Metric
Rating
Comments
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 380 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 29685 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lockey, J. E., Brooks, S. M., Jarabek, A. M., Khoury, P. R., Mckay, R. T., Carson, A., Morrison, J. A., Wiot, J. F., Spitz, H. B. (1984). Pulmonary changes
after exposure to vermiculite contaminated with fibrous tremolite. American Review of Respiratory Disease 129(1984):952-958.
Pulmonary Function/Spirometry Results; Pleural Plaques; Pleural pain; asbestosis symptoms (dyspnea, rales, nail clubbing)
Lung/Respiratory: Dyspnea and pleural painLung function (spirometry, CO diffusing capacity)Rales (lung crackles)Nail clubbing
Asbestos - Tremolite: 14567-73-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos- Libby amphibole: 1318-09-8
ID(s): No linked references.
29685
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Metric 3:
Attrition
Comparison Group
Medium Lockey et al. 1984, 029685 is a retrospective cohort and cross-sectional study of 512
workers conducted in 1980 at a facility that processed Libby vermiculite contaminated
with tremolite as an inert carrier. All vermiculite-exposed employees and a group of
unexposed workers from the same plant were included (480 males, 32 females; 496
white) and stratified into three exposure groups. Group Ill/high exposure (n=194, 37.8%
) which included vermiculite expanders and plant maintenance workers) was older and
had longer duration of employment than the other groups. Concerns: No specific ev-
idence of bias but studying only current employees risks some HWE as susceptible
exposed individuals may have had a higher probability to transfer or leave.
High Of 530 workers asked to participate, 512 (97% ) were included.
Medium The comparison group comprised workers in the cohort with lower vermiculite expo-
sure. Other exposures were similar to those among the exposed group (particularly for
chemical workers in group II). The younger age and shorter duration of work in the
comparison vs. exposed group may warrant assessment of confounding.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Retrospective cumulative fiber exposure (CFE) was characterized using detailed job
histories and available fiber counts. Membrane filter samples and PCM was used, count-
ing particles > 5jUm in length, <9 [im in diameter, and aspect ratio of 3:1. Concerns:
(i) Exposure monitoring was initiated only in 1972; extrapolations to earlier years may
be underestimates as no data were available. Protocols were refined over time: mea-
sures prior to 1976, when personal breathing zone sampling began, may be less accurate.
(ii) Lack of information on extensive overtime worked may underestimate and/or mis-
classify exposures assigned to individuals. In addition, specific fiber types were not
characterized at that time.
Medium Three exposure groups were compared, either as CFE (<1, 1-10 and >10 fibers/mL-
year) or based on work groups (I, II and III). Mean exposure in these groups further
stratified by smoking ranged from 0.35 to 7.55 fibers/mL-year.
Medium Sequencing was appropriate. However, mean follow-up (6.6 to 13.3 years by work type
and smoking groups) was below the 20+ years estimated for some asbestos-associated
lung changes to occur. Only 48 employees were employed for >20 years.
Domain 3: Outcome Assessment
Continued on next page ...
Page 381 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29685 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Lockey, J. E., Brooks, S. M., Jarabek, A. M., Khoury, P. R., Mckay, R. T., Carson, A., Morrison, J. A., Wiot, J. F., Spitz, H. B. (1984). Pulmonary changes
after exposure to vermiculite contaminated with fibrous tremolite. American Review of Respiratory Disease 129(1984):952-958.
Pulmonary Function/Spirometry Results; Pleural Plaques; Pleural pain; asbestosis symptoms (dyspnea, rales, nail clubbing)
ID(s):
Lung/Respiratory: Dyspnea and pleural painLung function (spirometry, CO diffusing capacity)Rales (lung crackles)Nail clubbing
Asbestos - Tremolite: 14567-73-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos- Libby amphibole: 1318-09-8
No linked references.
29685
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
High Pulmonary Function/Spirometry Results: Lung function: spirometry and CO diffusing
capacity. Assessed by trained staff using ATS criteria and published reference. Mea-
sures were repeated if participants had a respiratory infection in the previous 3 weeks or
had smoked in the past hour.; Pleural Plaques: Radiographic lung changes (observed in
n=22): Chest radiographs were evaluated by two board-certified readers with no knowl-
edge of exposure using modified 1971 ILO criteria. A third reader resolved any lack of
consensus, and x-rays were retaken if necessary. Costophrenic angle blunting included
separately vs combined with diffuse pleural thickening as in later studies.; Other Non-
Cancer Outcomes: (1) Dyspnea: The American Thoracic Society (ATS) questionnaire
was modified to ask about pleuritic chest pain (reporting an evaluation by physician). (2)
Rales and nail clubbing: A physical exam including breath measures in 4 locations was
conducted.
Medium The study presented results for all aims and frequently showed details such as numbers
of cases and non-cases by exposure category. However, some results were presented
only in figures without population numbers.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Most associations were presented as unadjusted descriptive data, but confounding was
also considered. To address confounding, Lockey et al 029685: (i) provided an age-
matched case-control comparison of mean CFE for lung change outcomes; (ii) showed
pleuritic chest pain prevalence stratified by smoking history as well as asbestos expo-
sure; and (iii) reported results of discriminant analysis accounting for age and smoking
for some associations.
Medium Questionnaires and employment records were used.
Medium Lockey et al, RefID 029685 reported that a "careful review of all chemical and physi-
cal agents "did not identify any co-exposures at the plant that would be associated with
pleural radiographic changes. They also reported that "the study and control popula-
tions were evenly matched for exposure history except for the presence or absence of
exposure to vermiculite".
Domain 5: Analysis
Metric 12: Study Design and Methods
Medium Appropriate analyses were used for all studies. Lockey et al, RefID 029685 used dis-
criminant analysis for categorical analysis of covariance for continuous measures. The
statistical significance of differences in exposure for age-matched case-control pairs
was also evaluated using alternative tests given that the N was small (paired t-tests and
non-parametric Wilcoxon rank tests applied).
Continued on next page ...
Page 382 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29685 Table: 1 of 1
... continued from previous page
Lockey, J. E., Brooks, S. M., Jarabek, A. M., Khoury, P. R., Mckay, R. T., Carson, A., Morrison, J. A., Wiot, J. F., Spitz, H. B. (1984). Pulmonary changes
after exposure to vermiculite contaminated with fibrous tremolite. American Review of Respiratory Disease 129(1984):952-958.
Pulmonary Function/Spirometry Results; Pleural Plaques; Pleural pain; asbestosis symptoms (dyspnea, rales, nail clubbing)
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Dyspnea and pleural painLung function (spirometry, CO diffusing capacity)Rales (lung crackles)Nail clubbing
Asbestos - Tremolite: 14567-73-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos- Libby amphibole: 1318-09-8
ID(s): No linked references.
29685
Domain
Metric
Rating
Comments
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Medium
Medium
The overall N (512) was adequate, but power was limited because the prevalence of lung
radiographic changes was low in this first study, in which duration since first exposure
was short. Only 2.2% of the sample had significant pleural or parenchymal changes, and
2.2% had costophrenic blunting only.
The analyses presented are reproducible, sufficient detail was provided.
The authors explained the rationale for the statistical methods used (discriminant anal-
ysis, ANCOVA, age-matched case-control comparisons) and for the covariates exam-
ined (age, smoking). Non-parametric tests were used when Ns were small. It is unclear
whether they examined whether transformations to improve linearity or reduce skewness
of the cumulative fiber exposure variable would have better met model assumptions.
Additional Comments: This 1980 cohort begins a series of studies on 501 workers from facility that had been processing asbestos-contaminated vermiculite since 1957. The low
level of asbestos exposure at the plant was associated with radiographic lung changes, dyspnea, and pleuritic chest pain, but not lung function, rales, or
finger clubbing. The 8h time-weighted average exposure among the most exposed workers was 1.5 fibers/mL through 1973 and thereafter 0.375 fibers/mL.
Cumulative fiber exposure (CFE) was >10 flbers/mL-years in 9.6% of workers; 10.7% had a 20+-year work duration. Only 22 (4.4% ) workers had
radiographic lung changes at this time point: prevalence was 2.8% , 3.9% and 5.8% in the low, medium, and high exposure groups. Concerns: (1) Enrolling
only current workers limited employment duration and time since first exposure. HWE is possible if susceptible employees were more likely to change
jobs over time. Indeed, only 4 of the 7 workers with previously documented benign pleural effusions were enrolled in this study. (2) Misclassiflcation of
historic fiber exposure is likely as exposure measurement began only in 1972 and no information on considerable overtime hours was included.Note: Libby
ore was later found to contain winchite and richterite along with tremolite.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 383 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1257856 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Loomis, D., Dement, J. M., Elliott, L., Richardson, D., Kuempel, E. D., Stayner, L. (2012). Increased lung cancer mortality among chrysotile asbestos
textile workers is more strongly associated with exposure to long thin fibres. Occupational and Environmental Medicine 69(2012):564-568.
Lung Cancer
Lung/Respiratory: lung cancer mortality; Mortality: lung cancer mortality; Cancer/Carcinogenesis: lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
1257856
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium The study included pooled data from cohorts of people who were employed at any
of four textile mills in North Carolina (from 1950 - 1973) and South Carolina (from
1940-1965). This pooled study population included 3717 men and 2419 women. To
be included in this study, participants needed to have worked at least 30 days in textile
production departments. Recruitment methods are described in previous publications.
Additional demographic information such as race, gender, and duration of employment
is provided in Elliott et al. 2012 HERO ID: 1247861 (Table 1). Available information
does not indicate substantial risk of selection bias.
High Elliott et al. 2012 HERO ID: 1247861 stated that loss to follow-up was approximately
7% and that 5% of deaths had an undetermined cause, but this proportion of subjects
would not have significantly biased the exposure-outcome relationship.
High All participants were textile workers from North Carolina and South Carolina who were
included based on the same participant selection criteria. Differences in demographic
characteristics were considered as potential confounders and were adjusted for in statis-
tical models.
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium TEM was used to estimate the distributions of fibers for combinations of plant and de-
partment in categories defined by diameter and length, using a stratified random sample
of historical dust samples collected from the study plants. The samples were collected
from 1964-1971, which is only a small portion of the exposure period. The authors ac-
knowledge this limitation but note that methods of operation did not change during the
study period. Poisson regression modelling was used to estimate adjustment factors for
each length-diameter category, which were applied to a matrix of "fiber concentrations
estimated by the standard PCM method to generate fiber size-specific estimates of ex-
posure". Estimated exposures to fibers were linked to occupational histories to assign
individual cumulative exposure in fiber-years/ml.
Medium The range and distribution of exposure appear to be sufficient to develop an exposure-
response estimate. The distribution of fibers was classified into four diameter-based
categories and six length-based categories. Cumulative exposure was estimated as a
continuous variable.
Continued on next page ...
Page 384 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1257856 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Loomis, D., Dement, J. M., Elliott, L., Richardson, D., Kuempel, E. D., Stayner, L. (2012). Increased lung cancer mortality among chrysotile asbestos
textile workers is more strongly associated with exposure to long thin fibres. Occupational and Environmental Medicine 69(2012):564-568.
Lung Cancer
Lung/Respiratory: lung cancer mortality; Mortality: lung cancer mortality; Cancer/Carcinogenesis: lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
1257856
Domain
Metric
Rating
Comments
Metric 6: Temporality
High The exposure precedes the outcome of lung cancer mortality. Participants were followed
for vital status until December 31, 2001 and December 31, 2003 for South Carolina and
North Carolina workers, respectively. These dates provide more than 15 years of follow-
up after the employment end dates of 1973 and 1965, respectively. However, individuals
who died of other causes might not have survived long enough to develop lung cancer.
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Metric 8: Reporting Bias
Medium Lung Cancer: The authors stated "Causes of death, including underlying cause, immedi-
ate causes and other significant conditions, were coded to the International Classification
of Diseases in effect at the time of the death."
High Effect estimates are reported with standard errors.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10:
Covariate Characterization
Metric 11: Co-exposure Counfounding
High Appropriate adjustments were made to account for potential confounding in the analy-
ses. Models adjusted for age, sex, race, and calendar time.
High Elliott et al. 2012 1247861 stated that occupational histories stemmed from "several
sources, including employers" personnel records, records microfilmed by the USA
Public Health Service during the 1960s and records of a state occupational health pro-
gramme." Thus, it is likely that covariate data were obtained from these valid sources.
Medium Although co-exposures were not directly assessed in this study, the authors stated that
any variation in the strength of the association between asbestos fiber exposure and lung
cancer mortality is unlikely to be attributed to co-exposures. The authors stated that
mineral oils used for dust control were the only notable co-exposure, but that previous
studies indicated that mineral oil exposure was not a confounder of the association be-
tween asbestos and lung cancer.
Domain 5: Analysis
Metric
12:
Study Design and Methods
Metric
13:
Statistical Power
Metric
14:
Reproducibility of Analyses
Metric
15:
Statistical Analysis
Medium The study design chosen was appropriate for the research question. Poisson regression
models were utilized in this cohort study.
Medium The sample size was large enough to detect an association. Statistically significant re-
sults were found.
Medium Methods and analyses were described sufficiently to be reproducible.
Medium Methods for calculating risk estimates are clear and model assumptions appear to be
met.
Continued on next page ...
Page 385 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 1257856 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Loomis, D., Dement, J. M., Elliott, L., Richardson, D., Kuempel, E. D., Stayner, L. (2012). Increased lung cancer mortality among chrysotile asbestos
textile workers is more strongly associated with exposure to long thin fibres. Occupational and Environmental Medicine 69(2012):564-568.
Lung Cancer
Lung/Respiratory: lung cancer mortality; Mortality: lung cancer mortality; Cancer/Carcinogenesis: lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
1257856
Domain
Metric
Rating
Comments
Additional Comments:
The main fiber type in this study is chrysotile, but one plant processed limited amounts of amosite between 1973-1976 and one plant used limited amounts
of crocidolite from the 1950s - 1975. This study assessed cohorts from North Carolina and South Carolina that have been assessed in previous publications.
This study assessed the association between fiber dimensions (diameter and length) and lung cancer mortality. The study found that cumulative exposures
to total fibers and to fibers in every length and diameter category were significantly associated with lung cancer mortality, and the association was stronger
for long and thin fibers. The exposure estimation methods are the main limitation of the study, including that the TEM-based exposure estimates were
based on historical sampling that had occurred only for a small portion of the study period.
Overall Quality Determination
High
* No biomarkers were identified for this evaluation.
Page 386 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 5160027 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Loomis, D., Richardson, D. B., Elliott, L. (2019). Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality. American
Journal of Industrial Medicine 62(2019):471-477.
Pleural cancer
Cancer/Carcinogenesis: Mortality from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura); Lung/
Respiratory: Mortality from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura); Mortality: Mortality
from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura)
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
5160027
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3: Comparison Group
High This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The criteria for High are met for pleural cancer, because
as described in Asbestos Part 1 "Setting and methods of case ascertainment were re-
ported in (Loomis et al., 2009), p. 535-536. Participant selection and inclusion/exclusion
criteria varied by study and analysis. Although there were 4 plants in the cohort, expo-
sure data were available only for three of the four, so exposure-response analyses were
limited to these three plants. Original selection criteria reported in (Loomis et al., 2009)
p 536 (participants had to work at least 1 day between 1950 and 1973) and p 539 (par-
ticipants excluded due to missing data). (Elliott et al., 2012) evaluated a subset of the
cohort that worked >30 days during the same time frame, b. Selection in or out of the
study was based on 1) employment in production job during designated time frame and
b) availability of necessary data (birth and hire dates; work history; vital status). These
criteria are unlikely to result in biased subject participation."
Medium This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The criteria for Medium are met for pleural cancer, be-
cause as described in Asbestos Part 1 "Attrition/missing data exclusions were reported
in ((SRC, 2019a) p. 1), ((Loomis et al„ 2009) p. 539) and (Elliott et al„ 2012) pg 386.
The original cohort was 5770 persons; 373 workers at plant 2 were excluded due to lack
of exposure data at this plant, 1596 were excluded due to incomplete work histories (at
department level) or non-production jobs ((Loomis et al., 2009) p. 539). Final cohort
for exposure-response analyses was 3803. Vital status was unknown for 241 of the 3803
(6% ) cohort members (suggesting moderate loss to follow up). The subgroup evalu-
ated in (Elliott et al., 2012) consisted of 3082 subjects (excluded persons who worked
<30 days); the proportion for whom vital status was missing was not reported for the
subgroup."
High This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation and was rated as not applicable for mesothelioma. Key
elements of the study design for the North Carolina cohort study are reported in Loomis
et al., 2009, HERO ID 1257856. Men and women employed for at least one day be-
tween 1950 - 1973 in three North Carolina textile mills were included in the present
study. A fourth smaller plant that did not process raw fibers was excluded from the
present study due to a lack of adequate exposure data. Differences in demographic char-
acteristics were considered as potential confounders and were adjusted for in statistical
models.
Continued on next page ...
Page 387 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 5160027 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Loomis, D., Richardson, D. B., Elliott, L. (2019). Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality. American
lournal of Industrial Medicine 62(2019):471-477.
Pleural cancer
Cancer/Carcinogenesis: Mortality from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura); Lung/
Respiratory: Mortality from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura); Mortality: Mortality
from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
5160027
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The criteria for Medium are met for pleural cancer,
because as described in Asbestos Part 1 "(SRC, 2019a) reports air concentrations and
exposure duration by interval of TSFE. Air samples were available for 3 plants cover-
ing period from 1935 to 1986 (459 <1950; 1674 from 1950-1969, and 1287 from 1970
forward; (Loomis et al., 2009), p. 536). Measurements used impinger before 1964 and
PCM thereafter; paired and concurrent samples between 1964 and 1971 were used to re-
late impinger to PCM-equivalent concentrations. Air samples were not collected yearly,
so mean PCM-equivalent concentrations were estimated by plant, department, job, and
time period using multivariate mixed models ((Loomis et al., 2009), p. 536). Individual
cumulative exposure assessed using the modeled concentrations and JEM ((Loomis et
al., 2009) p 536); details of JEM reported in (Dement et al., 2008)."
Medium This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The criteria for Medium are met for pleural cancer,
because as described in Asbestos Part 1 "(SRC, 2019a) reports air concentrations and
exposure durations by interval of TSFE." The authors of the present study note that
the study includes "extensive individual exposure estimates, which facilitate a range of
exposure-response analyses."
High This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The criteria for High are met for pleural cancer, be-
cause as described in Asbestos Part 1 "Temporality was established (exposure preceded
death). (SRC, 2019a) reports cases by interval of TSFE ranging up to 72 years since first
exposure."
Domain 3: Outcome Assessment
Continued on next page ...
Page 388 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 5160027 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Loomis, D., Richardson, D. B., Elliott, L. (2019). Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality. American
lournal of Industrial Medicine 62(2019):471-477.
Pleural cancer
Cancer/Carcinogenesis: Mortality from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura); Lung/
Respiratory: Mortality from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura); Mortality: Mortality
from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
5160027
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
High Other Cancer(s): This paper was evaluated for mesothelioma as part of the North Car-
olina cohort in the Asbestos Part 1 risk evaluation, and was rated as High for mesothe-
lioma with a note that the "High rating applies to cases assessed with ICD10. For some
analyses, the authors pooled these cases with cases coded to cancer of the pleura in ICDs
6-9, which is not considered a reliable measure of mesothelioma outcome. (SRC, 2019a)
reports cases assessed with ICD10 by interval of TSFE". As described in the present
study, vital status of the cohort was ascertained using searches of the National Death
Index (NDI) and other sources. Cause of death information was coded to the 9th or 10th
revision of the ICD for information obtained from NDI-plus and to the ICD in force at
the time of death for deaths before 1979. This paper "fit models for the outcome of pleu-
ral cancer combined with mesothelioma (including deaths coded as either mesothelioma
or cancer of the pleura), as well as for the outcome of mesothelioma (including only
deaths with ICD" 10 codes for mesothelioma) in the subcohort of workers who survived
until at least 1999". Thus, the present study includes proper consideration of the coding
for pleural cancer and mesothelioma.
High This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The criteria for High are met for pleural cancer, be-
cause as described in Asbestos Part 1 "(SRC, 2019a) provides mesothelioma cases and
person-years at risk by interval of TSFE, including separate reporting of those assessed
by ICD10. Mesothelioma cases (with detail of those assessed by ICD10) reported by
employment duration in Table 4 of (Loomis et al., 2009) (2 coded cases with 5-10 years
employment and 1 coded case each with 10-20 and 20-30 years employment). SMR
with CI reported in Table 3 (Loomis et al., 2009). and in (SRC, 2019a). (Loomis et al.,
2009) reports number in cohort, total PY of follow-up, and median duration employ-
ment. In (Elliott et al., 2012), Table 1 reports cohort characteristics including age at
entry, age at first employment, person years at risk, cumulative exposures, for the sub-
set of workers who were employed at least 30 days (by NC plant and for the whole NC
cohort)."
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment High This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The cohort was not rated for mesothelioma for this met-
ric.In the present study, "all models were adjusted for age at risk (continuous) and race
(white or nonwhite)". The authors reported that "adjustment for gender had little impact
on any model and was omitted from" the final models. Thus, explicit considerations
were made for potential confounders.
Continued on next page ...
Page 389 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 5160027 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Loomis, D., Richardson, D. B., Elliott, L. (2019). Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality. American
lournal of Industrial Medicine 62(2019):471-477.
Pleural cancer
Cancer/Carcinogenesis: Mortality from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura); Lung/
Respiratory: Mortality from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura); Mortality: Mortality
from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
5160027
Domain
Metric
Rating
Comments
Metric 10:
Covariate Characterization
Metric 11: Co-exposure Counfounding
High This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The cohort was not rated for mesothelioma for this met-
ric.A previous paper from this cohort, Elliott et al. 2012 1247861, stated that occupa-
tional histories stemmed from "several sources, including employers" personnel records,
records microfilmed by the USA Public Health Service during the 1960s and records of
a state occupational health program." Thus, it is likely that covariate data were obtained
from these valid sources.
Low This paper was evaluated for mesothelioma as part of the North Carolina cohort in
the Asbestos Part 1 risk evaluation. The cohort was not rated for mesothelioma for
this metric because potential co-exposure confounding is generally not a concern for
mesothelioma because there are few potential confounders of the association between
asbestos and mesothelioma. In a previous publication from this cohort (Loomis et al.
2012, HERO ID 1257856), The authors stated that mineral oils used for dust control
were the only notable co-exposure. It is unclear whether mineral oils are a potential
confounder of the association between asbestos exposure and pleural cancer. But in the
present study, potential co-exposures were not discussed.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Medium This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The retrospective cohort design was appropriate to
address the research question. The present study used Poisson regression modeling to
estimate relationships between asbestos exposure and mortality from pleural cancer and
mesothelioma. Thus, the present paper used an appropriate statistical method to address
the research question.
Medium This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The cohort was not rated for mesothelioma for this met-
ric. The present analyses included 5397 workers included in analysis, which is a suffi-
ciently large sample size. Although pleural cancer and mesothelioma are rare outcomes,
which may have resulted in reduced precision in this study, there was sufficient power to
detect an association, as evidenced by the findings of statistically significant associations
between asbestos exposure and all pleural cancer (including mesothelioma).
Medium This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The cohort was not rated for mesothelioma for this
metric in Asbestos Part 1, but it was noted that "(SRC, 2019a) provides individual data
elements allowing independent analysis." The description of the analysis in the present
paper is sufficient to understand how to conceptually reproduce the analysis with access
to the analytic data.
Continued on next page ...
Page 390 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 5160027 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Loomis, D., Richardson, D. B., Elliott, L. (2019). Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality. American
lournal of Industrial Medicine 62(2019):471-477.
Pleural cancer
Cancer/Carcinogenesis: Mortality from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura); Lung/
Respiratory: Mortality from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura); Mortality: Mortality
from pleural cancer and mesothelioma combined (deaths coded as either mesothelioma or cancer of the pleura)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
5160027
Domain
Metric
Rating
Comments
Metric 15: Statistical Analysis
Medium This paper was evaluated for mesothelioma as part of the North Carolina cohort in the
Asbestos Part 1 risk evaluation. The cohort was not rated for mesothelioma for this
metric in Asbestos Part 1. The model for calculating the risk estimates in the present
paper is sufficiently transparent.
Additional Comments: This study assessed the outcomes of pleural cancer and mesothelioma. This study was evaluated for mesothelioma as part of the North Carolina cohort
in Asbestos Part 1. Therefore an evaluation form for the specific outcome of mesothelioma was not included in this evaluation. This evaluation is for
the broader category of pleural cancer, which includes mesothelioma. In Asbestos Part 1, this cohort was rated as High quality for mesothelioma. In
this particular study, models were fit "for the outcome of pleural cancer combined with mesothelioma (including deaths coded as either mesothelioma or
cancer of the pleura), as well as for the outcome of mesothelioma (including only deaths with ICD"10 codes for mesothelioma) in the subcohort of workers
who survived until at least 1999." This study assessed associations of mesothelioma and pleural cancer with exposure duration, time since first exposure
(TSFE) and cumulative fiber exposure. In addition to fitting Poisson regression models, this study also evaluated a mesothelioma risk model that was
developed in the 1980s and used by the EPA and OSHA. This study has several strengths. The authors noted that the study includes "extensive individual
exposure estimates, which facilitate a range of exposure-response analyses." The main limitations noted by the authors were reduced precision due to the
small number of informative deaths, and concerns about the quality of outcome assessment for mesothelioma. The latter concern was addressed in part
by the assessment of pleural cancer together with mesothelioma, and the assessment of mesothelioma only as identified by ICD-10. Thus, this study may
provide useful dose-response information for pleural cancer and mesothelioma, though most of this information has been captured in the Asbestos Part 1
assessment, of mesothelioma.
Overall Quality Determination High
* No biomarkers were identified for this evaluation.
Page 391 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6868486 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Luberto, F., Ferrante, D., Silvestri, S., Angelini, A., Cuccaro, F., Nannavecchia, A. M., Oddone, E., Vicentini, M., Barone-Adesi, F., Cena, T. (2019).
Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy. Environmental
Health: A Global Access Science Source 18(2019):71.
Lung Cancer; Ovarian Cancer; Laryngeal Cancer; stomach, colon, rectum, peritoneum, pleura, liver, pancreas, uterus, kidney, bladder, lip, oral cavity, phar-
ynx, esophagus, small intestine; Asbestosis; psychiatric diseases, neurological dieases, cardiovascular disease, bronchitis, emphysema, asthma, accidents,
and violence, genitourinary diseases, other pneumoconioses
Gastrointestinal: malignant neoplasm stomach mortality, malignant neoplasm colon mortality, malignant neoplasm rectum mortality, malignant neoplasm
peritoneum mortality, digestive disease mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum)
mortality, malignant neoplasm small intestine mortality; Cancer/Carcinogenesis: malignant neoplasm stomach mortality, malignant neoplasm colon mortal-
ity, malignant neoplasm rectum mortality, malignant neoplasm peritoneum mortality, malignant neoplasm respiratory organs mortality, malignant neoplasm
larynx mortality, malignant neoplasm lung mortality, malignant neoplasm pleura mortality, malignant neoplasm ovary mortality, malignant neoplasm lip,
oral cavity, and pharynx mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum) mortality, ma-
lignant neoplasm small intestine mortality, malignant neoplasm liver and intrahepatic bile ducts mortality, malignant neoplasm nose and paranasal sinuses
mortality, malignant neoplasm prostate mortality, malignant neoplasm bladder mortality, malignant neoplasm eye and nervous system mortality, malignant
neoplasm uterus mortality, malignant neoplasm ovaries mortality, Malignant neoplasm mortality, Leukemia and lymphoma mortality, Malignant neoplasm
unspecified site mortality; Mortality: malignant neoplasm stomach mortality, malignant neoplasm colon mortality, malignant neoplasm rectum mortal-
ity, malignant neoplasm peritoneum mortality, malignant neoplasm respiratory organs mortality, malignant neoplasm larynx mortality, malignant neoplasm
lung mortality, malignant neoplasm pleura mortality, Respiratory diseases mortality, Bronchitis, emphysema, asthma mortality, asbestosis mortality, cardio-
vascular disease mortality, digestive disease mortality, accidental and violent mortality, malignant neoplasm ovary mortality, malignant neoplasm lip, oral
cavity, and pharynx mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum) mortality, malignant
neoplasm small intestine mortality, malignant neoplasm liver and intrahepatic bile ducts mortality, malignant neoplasm nose and paranasal sinuses mor-
tality, malignant neoplasm prostate mortality, malignant neoplasm bladder mortality, malignant neoplasm kidney mortality, malignant neoplasm eye and
nervous system mortality, psychiatric diseases mortality, neurological diseases mortality, ischemic heart diseases mortality, myocardial infarction mortality,
malignant neoplasm uterus mortality, malignant neoplasm ovaries mortality, All causes mortality, Malignant neoplasm mortality, Unknown causes mortal-
ity, Leukemia and lymphoma mortality, Malignant neoplasm unspecified site mortality, Genitourinary diseases mortality, Other pneumoconioses mortality,
Poorly specified causes mortality; Lung/Respiratory: malignant neoplasm respiratory organs mortality, malignant neoplasm larynx mortality, malignant
neoplasm lung mortality, malignant neoplasm pleura mortality, Respiratory diseases mortality, Bronchitis, emphysema, asthma mortality, asbestosis mortal-
ity, malignant neoplasm nose and paranasal sinuses mortality, Other pneumoconioses mortality; Cardiovascular: cardiovascular disease mortality, ischemic
heart diseases mortality, myocardial infarction mortality; unspecified: accidental and violent mortality; Reproductive/Developmental: malignant neoplasm
ovary mortality, malignant neoplasm prostate mortality, malignant neoplasm uterus mortality, malignant neoplasm ovaries mortality, Genitourinary dis-
eases mortality; Head/face: malignant neoplasm lip, oral cavity, and pharynx mortality; Hepatic/Liver: malignant neoplasm liver and intrahepatic bile ducts
mortality; Renal/Kidney: malignant neoplasm bladder mortality, malignant neoplasm kidney mortality; Neurological/Behavioral: malignant neoplasm eye
and nervous system mortality, psychiatric diseases mortality, neurological diseases mortality; circulatory: Leukemia and lymphoma mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
6868486, 7460047
6868486
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Continued on next page .
Page 392 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6868486 Table: 1 of 1
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Study Citation: Luberto, F., Ferrante, D., Silvestri, S., Angelini, A., Cuccaro, F., Nannavecchia, A. M., Oddone, E., Vicentini, M., Barone-Adesi, F., Cena, T. (2019).
Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy. Environmental
Health: A Global Access Science Source 18(2019):71.
Lung Cancer; Ovarian Cancer; Laryngeal Cancer; stomach, colon, rectum, peritoneum, pleura, liver, pancreas, uterus, kidney, bladder, lip, oral cavity, phar-
ynx, esophagus, small intestine; Asbestosis; psychiatric diseases, neurological dieases, cardiovascular disease, bronchitis, emphysema, asthma, accidents,
and violence, genitourinary diseases, other pneumoconioses
Gastrointestinal: malignant neoplasm stomach mortality, malignant neoplasm colon mortality, malignant neoplasm rectum mortality, malignant neoplasm
peritoneum mortality, digestive disease mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum)
mortality, malignant neoplasm small intestine mortality; Cancer/Carcinogenesis: malignant neoplasm stomach mortality, malignant neoplasm colon mortal-
ity, malignant neoplasm rectum mortality, malignant neoplasm peritoneum mortality, malignant neoplasm respiratory organs mortality, malignant neoplasm
larynx mortality, malignant neoplasm lung mortality, malignant neoplasm pleura mortality, malignant neoplasm ovary mortality, malignant neoplasm lip,
oral cavity, and pharynx mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum) mortality, ma-
lignant neoplasm small intestine mortality, malignant neoplasm liver and intrahepatic bile ducts mortality, malignant neoplasm nose and paranasal sinuses
mortality, malignant neoplasm prostate mortality, malignant neoplasm bladder mortality, malignant neoplasm eye and nervous system mortality, malignant
neoplasm uterus mortality, malignant neoplasm ovaries mortality, Malignant neoplasm mortality, Leukemia and lymphoma mortality, Malignant neoplasm
unspecified site mortality; Mortality: malignant neoplasm stomach mortality, malignant neoplasm colon mortality, malignant neoplasm rectum mortal-
ity, malignant neoplasm peritoneum mortality, malignant neoplasm respiratory organs mortality, malignant neoplasm larynx mortality, malignant neoplasm
lung mortality, malignant neoplasm pleura mortality, Respiratory diseases mortality, Bronchitis, emphysema, asthma mortality, asbestosis mortality, cardio-
vascular disease mortality, digestive disease mortality, accidental and violent mortality, malignant neoplasm ovary mortality, malignant neoplasm lip, oral
cavity, and pharynx mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum) mortality, malignant
neoplasm small intestine mortality, malignant neoplasm liver and intrahepatic bile ducts mortality, malignant neoplasm nose and paranasal sinuses mor-
tality, malignant neoplasm prostate mortality, malignant neoplasm bladder mortality, malignant neoplasm kidney mortality, malignant neoplasm eye and
nervous system mortality, psychiatric diseases mortality, neurological diseases mortality, ischemic heart diseases mortality, myocardial infarction mortality,
malignant neoplasm uterus mortality, malignant neoplasm ovaries mortality, All causes mortality, Malignant neoplasm mortality, Unknown causes mortal-
ity, Leukemia and lymphoma mortality, Malignant neoplasm unspecified site mortality, Genitourinary diseases mortality, Other pneumoconioses mortality,
Poorly specified causes mortality; Lung/Respiratory: malignant neoplasm respiratory organs mortality, malignant neoplasm larynx mortality, malignant
neoplasm lung mortality, malignant neoplasm pleura mortality, Respiratory diseases mortality, Bronchitis, emphysema, asthma mortality, asbestosis mortal-
ity, malignant neoplasm nose and paranasal sinuses mortality, Other pneumoconioses mortality; Cardiovascular: cardiovascular disease mortality, ischemic
heart diseases mortality, myocardial infarction mortality; unspecified: accidental and violent mortality; Reproductive/Developmental: malignant neoplasm
ovary mortality, malignant neoplasm prostate mortality, malignant neoplasm uterus mortality, malignant neoplasm ovaries mortality, Genitourinary dis-
eases mortality; Head/face: malignant neoplasm lip, oral cavity, and pharynx mortality; Hepatic/Liver: malignant neoplasm liver and intrahepatic bile ducts
mortality; Renal/Kidney: malignant neoplasm bladder mortality, malignant neoplasm kidney mortality; Neurological/Behavioral: malignant neoplasm eye
and nervous system mortality, psychiatric diseases mortality, neurological diseases mortality; circulatory: Leukemia and lymphoma mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): 6868486,7460047
6868486
Domain Metric Rating Comments
Metric 4: Measurement of Exposure Low This metric is rated Low because neither study explicitly mentions the use of PCM or
TEM. In Luberto et al., 2019, HERO ID 6868486, there is no mention of microscopy
of citation of methods paper that would give details. In Magnani et al., 2020, HERO ID
7460047, authors mention optical microscopy: "The experts estimated for each plant
and year the proportion of exposed workers, the percentage of time in asbestos exposing
tasks and the minimum and maximumconcentrations of asbestos airborne fibres (f/ml,
from data measured in optical microscopy), for direct and indirect exposure separately."
In addition, both studies rely heavily on expert judgment to develop exposure estimates.
Continued on next page ...
Page 393 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6868486 Table: 1 of 1
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Study Citation: Luberto, F., Ferrante, D., Silvestri, S., Angelini, A., Cuccaro, F., Nannavecchia, A. M., Oddone, E., Vicentini, M., Barone-Adesi, F., Cena, T. (2019).
Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy. Environmental
Health: A Global Access Science Source 18(2019):71.
Lung Cancer; Ovarian Cancer; Laryngeal Cancer; stomach, colon, rectum, peritoneum, pleura, liver, pancreas, uterus, kidney, bladder, lip, oral cavity, phar-
ynx, esophagus, small intestine; Asbestosis; psychiatric diseases, neurological dieases, cardiovascular disease, bronchitis, emphysema, asthma, accidents,
and violence, genitourinary diseases, other pneumoconioses
Gastrointestinal: malignant neoplasm stomach mortality, malignant neoplasm colon mortality, malignant neoplasm rectum mortality, malignant neoplasm
peritoneum mortality, digestive disease mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum)
mortality, malignant neoplasm small intestine mortality; Cancer/Carcinogenesis: malignant neoplasm stomach mortality, malignant neoplasm colon mortal-
ity, malignant neoplasm rectum mortality, malignant neoplasm peritoneum mortality, malignant neoplasm respiratory organs mortality, malignant neoplasm
larynx mortality, malignant neoplasm lung mortality, malignant neoplasm pleura mortality, malignant neoplasm ovary mortality, malignant neoplasm lip,
oral cavity, and pharynx mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum) mortality, ma-
lignant neoplasm small intestine mortality, malignant neoplasm liver and intrahepatic bile ducts mortality, malignant neoplasm nose and paranasal sinuses
mortality, malignant neoplasm prostate mortality, malignant neoplasm bladder mortality, malignant neoplasm eye and nervous system mortality, malignant
neoplasm uterus mortality, malignant neoplasm ovaries mortality, Malignant neoplasm mortality, Leukemia and lymphoma mortality, Malignant neoplasm
unspecified site mortality; Mortality: malignant neoplasm stomach mortality, malignant neoplasm colon mortality, malignant neoplasm rectum mortal-
ity, malignant neoplasm peritoneum mortality, malignant neoplasm respiratory organs mortality, malignant neoplasm larynx mortality, malignant neoplasm
lung mortality, malignant neoplasm pleura mortality, Respiratory diseases mortality, Bronchitis, emphysema, asthma mortality, asbestosis mortality, cardio-
vascular disease mortality, digestive disease mortality, accidental and violent mortality, malignant neoplasm ovary mortality, malignant neoplasm lip, oral
cavity, and pharynx mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum) mortality, malignant
neoplasm small intestine mortality, malignant neoplasm liver and intrahepatic bile ducts mortality, malignant neoplasm nose and paranasal sinuses mor-
tality, malignant neoplasm prostate mortality, malignant neoplasm bladder mortality, malignant neoplasm kidney mortality, malignant neoplasm eye and
nervous system mortality, psychiatric diseases mortality, neurological diseases mortality, ischemic heart diseases mortality, myocardial infarction mortality,
malignant neoplasm uterus mortality, malignant neoplasm ovaries mortality, All causes mortality, Malignant neoplasm mortality, Unknown causes mortal-
ity, Leukemia and lymphoma mortality, Malignant neoplasm unspecified site mortality, Genitourinary diseases mortality, Other pneumoconioses mortality,
Poorly specified causes mortality; Lung/Respiratory: malignant neoplasm respiratory organs mortality, malignant neoplasm larynx mortality, malignant
neoplasm lung mortality, malignant neoplasm pleura mortality, Respiratory diseases mortality, Bronchitis, emphysema, asthma mortality, asbestosis mortal-
ity, malignant neoplasm nose and paranasal sinuses mortality, Other pneumoconioses mortality; Cardiovascular: cardiovascular disease mortality, ischemic
heart diseases mortality, myocardial infarction mortality; unspecified: accidental and violent mortality; Reproductive/Developmental: malignant neoplasm
ovary mortality, malignant neoplasm prostate mortality, malignant neoplasm uterus mortality, malignant neoplasm ovaries mortality, Genitourinary dis-
eases mortality; Head/face: malignant neoplasm lip, oral cavity, and pharynx mortality; Hepatic/Liver: malignant neoplasm liver and intrahepatic bile ducts
mortality; Renal/Kidney: malignant neoplasm bladder mortality, malignant neoplasm kidney mortality; Neurological/Behavioral: malignant neoplasm eye
and nervous system mortality, psychiatric diseases mortality, neurological diseases mortality; circulatory: Leukemia and lymphoma mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): 6868486,7460047
6868486
Domain
Metric
Rating
Comments
Metric 5: Exposure Levels
Medium The range and distribution of exposure is sufficient to develop an exposure-response
estimate and the included analyses are stratified by three levels of exposure (Luberto et
al„ 2019, HERO ID 6868486). In Magnani et al„ 2020, HERO ID 7460047, there are
only 2 exposure categories for SMR analyses.
Additional Comments:
HEROIDs 7460047 and 6868486 were not QC'd for any metrics except 4 and 5 and had no data extracted because they did not have sufficient information
to confirm the use of TEM or PCM and thus did not have sufficient information to be useful for dose-response analysis.
Continued on next page ...
Page 394 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6868486 Table: 1 of 1
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Study Citation: Luberto, F., Ferrante, D., Silvestri, S., Angelini, A., Cuccaro, F., Nannavecchia, A. M., Oddone, E., Vicentini, M., Barone-Adesi, F., Cena, T. (2019).
Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy. Environmental
Health: A Global Access Science Source 18(2019):71.
Lung Cancer; Ovarian Cancer; Laryngeal Cancer; stomach, colon, rectum, peritoneum, pleura, liver, pancreas, uterus, kidney, bladder, lip, oral cavity, phar-
ynx, esophagus, small intestine; Asbestosis; psychiatric diseases, neurological dieases, cardiovascular disease, bronchitis, emphysema, asthma, accidents,
and violence, genitourinary diseases, other pneumoconioses
Gastrointestinal: malignant neoplasm stomach mortality, malignant neoplasm colon mortality, malignant neoplasm rectum mortality, malignant neoplasm
peritoneum mortality, digestive disease mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum)
mortality, malignant neoplasm small intestine mortality; Cancer/Carcinogenesis: malignant neoplasm stomach mortality, malignant neoplasm colon mortal-
ity, malignant neoplasm rectum mortality, malignant neoplasm peritoneum mortality, malignant neoplasm respiratory organs mortality, malignant neoplasm
larynx mortality, malignant neoplasm lung mortality, malignant neoplasm pleura mortality, malignant neoplasm ovary mortality, malignant neoplasm lip,
oral cavity, and pharynx mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum) mortality, ma-
lignant neoplasm small intestine mortality, malignant neoplasm liver and intrahepatic bile ducts mortality, malignant neoplasm nose and paranasal sinuses
mortality, malignant neoplasm prostate mortality, malignant neoplasm bladder mortality, malignant neoplasm eye and nervous system mortality, malignant
neoplasm uterus mortality, malignant neoplasm ovaries mortality, Malignant neoplasm mortality, Leukemia and lymphoma mortality, Malignant neoplasm
unspecified site mortality; Mortality: malignant neoplasm stomach mortality, malignant neoplasm colon mortality, malignant neoplasm rectum mortal-
ity, malignant neoplasm peritoneum mortality, malignant neoplasm respiratory organs mortality, malignant neoplasm larynx mortality, malignant neoplasm
lung mortality, malignant neoplasm pleura mortality, Respiratory diseases mortality, Bronchitis, emphysema, asthma mortality, asbestosis mortality, cardio-
vascular disease mortality, digestive disease mortality, accidental and violent mortality, malignant neoplasm ovary mortality, malignant neoplasm lip, oral
cavity, and pharynx mortality, malignant neoplasm esophagus mortality, malignant neoplasm digestive organs (including peritoneum) mortality, malignant
neoplasm small intestine mortality, malignant neoplasm liver and intrahepatic bile ducts mortality, malignant neoplasm nose and paranasal sinuses mor-
tality, malignant neoplasm prostate mortality, malignant neoplasm bladder mortality, malignant neoplasm kidney mortality, malignant neoplasm eye and
nervous system mortality, psychiatric diseases mortality, neurological diseases mortality, ischemic heart diseases mortality, myocardial infarction mortality,
malignant neoplasm uterus mortality, malignant neoplasm ovaries mortality, All causes mortality, Malignant neoplasm mortality, Unknown causes mortal-
ity, Leukemia and lymphoma mortality, Malignant neoplasm unspecified site mortality, Genitourinary diseases mortality, Other pneumoconioses mortality,
Poorly specified causes mortality; Lung/Respiratory: malignant neoplasm respiratory organs mortality, malignant neoplasm larynx mortality, malignant
neoplasm lung mortality, malignant neoplasm pleura mortality, Respiratory diseases mortality, Bronchitis, emphysema, asthma mortality, asbestosis mortal-
ity, malignant neoplasm nose and paranasal sinuses mortality, Other pneumoconioses mortality; Cardiovascular: cardiovascular disease mortality, ischemic
heart diseases mortality, myocardial infarction mortality; unspecified: accidental and violent mortality; Reproductive/Developmental: malignant neoplasm
ovary mortality, malignant neoplasm prostate mortality, malignant neoplasm uterus mortality, malignant neoplasm ovaries mortality, Genitourinary dis-
eases mortality; Head/face: malignant neoplasm lip, oral cavity, and pharynx mortality; Hepatic/Liver: malignant neoplasm liver and intrahepatic bile ducts
mortality; Renal/Kidney: malignant neoplasm bladder mortality, malignant neoplasm kidney mortality; Neurological/Behavioral: malignant neoplasm eye
and nervous system mortality, psychiatric diseases mortality, neurological diseases mortality; circulatory: Leukemia and lymphoma mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): 6868486,7460047
6868486
Domain
Metric
Rating
Comments
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 395 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3077711 Table: 1 of 1
Study Citation:
Matrat, M., Guida, F., C6n6e, S., F6votte, J., Carton, M., Cyr, D., Menvielle, G., Paget-Bailly, S., Rado{
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
i}, L., Schmaus, A., Bara, S., Velten, M., Luce, D., Stilcker, I., The Icare Study Group, I. (2015). Occupational Exposure to Diesel Motor Exhaust and Lung
Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study, lournal of Cancer Epidemiology 2015879302.
Lung Cancer
Lung/Respiratory: Lung cancer; Cancer/Carcinogenesis: Lung cancer
Asbestos - Not specified: 1332-21-4
3077711, 6748863
3077711
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the studies or any cited methods source do not explic-
itly mention the use of PCM or TEM. Exposure for workers was assigned by a JEM
described in F"votte et al. 2011 (HERO ID: 2571088). However, the methods there do
not descibe how the exact IEM used in the present cohort was created, and do not cite
any sources providing data on sampling or quantification methods. The only sources
cited for details are in French and thus were not able to be evaluated by the EPA QC
team.
Medium The distribution of exposure appears to be sufficient to develop an exposure-response
estimate. Cumulative exposure was calculated in Matrat et al., 2015 307711 . L"v"que
et al., 2018 6748863 measured the association based on a "1 fiber/ml difference in the
annual average daily intensity each year of the specific exposure time-window."
Additional Comments: Matrat et al., 2015 307711 and L"v"que et al., 2018 6748863 were not evaluated for any metrics except Metric 4 and 5 and had no data extracted because
they did not have sufficient exposure information to be useful for dose-response analysis.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 396 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3080192 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Matrat, M., Pairon, J. C., Paolillo, A. G., Joly, N., Iwatsubo, Y., Orlowski, E., Letourneux, M., Ameille, J. (2004). Asbestos exposure and radiological
abnormalities among maintenance and custodian workers in buildings with friable asbestos-containing materials. International Archives of Occupational
and Environmental Health 77(2004):307-312.
Circumscribed pleural thickening, diffuse pleural thickening, Pleural thickening , small opacity profusions
Lung/Respiratory: Pleural thickening, Small opacities profusion, Circumscribed pleural thickening, Diffuse pleural thickening
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3080192
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Key elements of the study design are described in the Matrat et al., 2004 study (Matrat
et al. 2004, HERO ID: 3080192) which measures asbestos exposure and radiological
abnormalities in male and female maintenance workers. Male and female participants
(n=336) of (Matrat et al. 2004, HERO ID: 3080192) were aged an average of 44.1 +/
- 7.5 and latency began at less than or equal to 15 years since exposure, 16-22 years,
and greater than 22 years. Study participants complete a standardized questionnaire
regarding their work history, types of asbestos containing materials (ACMs), and other
work-related questions. All participants were volunteers.
High Studu functioned on a voluntary basis. (Matrat et al. 2004, HERO ID: 3080192) de-
scribed that 80% of eligible subjects participated, and that some subject loss occurred
due to poor quality x-ray imaging and previous asbestos exposure from other activities.
High 95 controls who were male workers in a public hospital with no known asbestos expo-
sures participated in the parent study (Matrat et al. 2004, HERO ID: 3080192). These
controls also received chest radiographs, same as the exposure group.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Matrat et al. referenced their measurements of exposure from the French Evalutil
database for specific occupational exposures to find fibre concentrations to estimate
the intensity and to create a cumulative exposure index (Matrat et al. 2004, HERO ID:
3080192). An article for the French Evalutil database describes all data from before
2012 as using studies which followed the standards of the time, expertise, and that most
air samples were taken with "membrane filters and analyzed by phase-contrast optical
microscopy (PCOM)" (Orlowski et al. 2015, HERO ID: 3089885).
Medium Matrat et al. reports a referent group and exposure group distributed by latency or cumu-
lative exposure index (f/mL*years) (Matrat et al. 2004, HERO ID: 3080192).
High Matrat et al. reports latency as <=15 years, 16-22 years, and >22 years, which is ade-
quate for the health outcomes evaluated (Matrat et al. 2004, HERO ID: 3080192).
Domain 3: Outcome Assessment
Continued on next page .
Page 397 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3080192 Table: 1 of 1
... continued from previous page
Study Citation:
Matrat, M., Pairon, J. C., Paolillo, A. G., Joly, N., Iwatsubo, Y., Orlowski, E., Letourneux, M., Ameille, J. (2004). Asbestos exposure and radiological
abnormalities among maintenance and custodian workers in buildings with friable asbestos-containing materials. International Archives of Occupational
and Environmental Health 77(2004):307-312.
Circumscribed pleural thickening, diffuse pleural thickening, Pleural thickening , small opacity profusions
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Pleural thickening, Small opacities profusion, Circumscribed pleural thickening, Diffuse pleural thickening
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3080192
Domain
Metric
Rating
Comments
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High
High
Other Non-Cancer Outcomes: Pleural thickening(s): Matrat et al. reports that all chest
radiographs were "classified independently by three expereicned readers according to
the International Labour Office (ILO) 1980" in random order. This includes profusions
of small opacities, circumscribed pleural thickening, and diffuse pleural thickening
(Matrat et al. 2004, HERO ID: 3080192).
Findings are appropriately reported (Matrat et al. 2004, HERO ID: 3080192) and ex-
traction is possible. Confidence intervals of 95% are reported where multivariate logistic
regression analysis was completed in the exposed groups for an adjusted odds ratio.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium
Medium
Low
For the multiple logistic regression in (Matrat et al. 2004, HERO ID: 3080192), three
models are created to analyze the exposure group. Model A measures by latency with
age, BMI and tobacco smoking; Model B measures duration of asbestos exposure by
age, BMI and tobacco smoking; and Model C measures cumulative exposure index by
age, BMI and tobacco smoking.
(Matrat et al. 2004, HERO ID: 3080192) report using a standardized questionnaire to
collect information on volunteers regarding their work history, including areas where
they worked, detailed list of tasks, duration (years), frequency (number of days a year
and number of hours a day) where exposure occurred.The authors only mentioned that
detailed information was obtained on tobacco consumption and height and weight were
measured to calculate BMI, but they did not describe the information source.
In an occupational setting, potential co-exposures are not discussed. This is relevant for
(Matrat et al. 2004, HERO ID: 3080192).
Domain 5: Analysis
Metric 12:
Metric 13:
Metric 14:
Metric 15:
Study Design and Methods
Statistical Power
Reproducibility of Analyses
Statistical Analysis
Medium
Medium
Medium
Medium
(Matrat et al. 2004, HERO ID: 3080192) used an appropriate study design to address the
research question with a multivariate logistic regression.
The number of participants was adequate to detect an effect in the exposure group.
(Matrat et al. 2004, HERO ID: 3080192) provided adequate methodology to understand
how to conceptually reproduce analyses.
(Matrat et al. 2004, HERO ID: 3080192) provided transparent methods for the multi-
variate logistic regression, organized by three models (A, B, and C) and provided the
covariates used in each analysis.
Additional Comments:
None
Continued on next
page...
Page 398 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3080192 Table: 1 of 1
... continued from previous page
Study Citation:
Matrat, M., Pairon, J. C., Paolillo, A. G., Joly, N., Iwatsubo, Y., Orlowski, E., Letourneux, M., Ameille, J. (2004). Asbestos exposure and radiological
abnormalities among maintenance and custodian workers in buildings with friable asbestos-containing materials. International Archives of Occupational
and Environmental Health 77(2004):307-312.
Circumscribed pleural thickening, diffuse pleural thickening, Pleural thickening , small opacity profusions
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Pleural thickening, Small opacities profusion, Circumscribed pleural thickening, Diffuse pleural thickening
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3080192
Domain Metric
Rating
Comments
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 399 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 630760 Table: 1 of 1
Study Citation: McCredie, M., Stewart, J. H. (1993). Risk factors for kidney cancer in New South Wales. IV. Occupation. British Journal of Industrial Medicine
50(1993):349-354.
Health Renal cell and renal pelvic cancer (kidney cancer)
Outcome:
Target Cancer/Carcinogenesis: Renal cell cancer, Renal pelvic cancer; Renal/Kidney: Renal cell cancer, Renal pelvic cancer
Organ(s):
Asbestos Fiber Asbestos - Not specified: 1332-21-4
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 630760
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
Measures of exposure were generated using professional judgment based on responses
to the interviews and questionnaires administered. Because there were no quantitative
measures of asbestos exposure, this metric was rated as uninformative. However, there
could be some utility for this study qualitatively.This metric is rated low because the
study or any cited methods sources does not use PCM or TEM.
Because the authors used professional judgment and responses to questionnaires to
determine asbestos exposure, individuals were only ranked as exposed or unexposed.
Additional Comments:
There are several limitations of this study that are important to note. For one, there were no quantitative measures of exposure to asbestos. The information
gathered through the self-report interviews may also be questionable, as even the authors highlight that there was no validation of the exposures reported.
This could introduce a certain level of bias to the results. While asbestos was one of the exposures examined, it was not the sole focus of this study.NOTE:
Based on the new guidance, this study would not have been evaluated past metric 4 and 5. There was no mention within the study or cited sources that
mentioned the use of PCM or TEM.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 400 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 7836 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Mcdonald, A. D. (1997). Chrysotile, tremolite and carcinogenicity. Annals of Occupational Hygiene 41(1997):699-705.
Lung Cancer; Laryngeal Cancer; stomach, colon and rectum
Cancer/Carcinogenesis: Lung cancer mortality, Laryngeal cancer mortality, Stomach cancer mortality, Colorectal cancer mortality; Lung/Respiratory:
Lung cancer mortality, Laryngeal cancer mortality; Mortality: Lung cancer mortality, Laryngeal cancer mortality, Stomach cancer mortality, Colorectal
cancer mortality; Gastrointestinal: Stomach cancer mortality, Colorectal cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Tremolite: 14567-73-8
No linked references.
7836
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Uninformative
Medium
Details on exposure measurement methods were not reported in the present reference
or cited references (HERO ID 3081408 and 3651098). Men were compared by years of
employment.
Participants were compared using logistic regression, suggesting a continuous measure
of exposure (years of employment).
Additional Comments: This study used a large occupational cohort to create a case-control study for several cancer types. Individuals were followed for a long period of time
(potentially >25 years). Some concerns included lack of description of exposure measurement in the current study and cited studies. Other minor concerns
included potential missing personnel records and lack of detail for outcome assessment (e.g., ICD codes used and/or case confirmation).
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessment for the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 401 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 29964 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Mcdonald, A. D., Armstrong, B., Sebastien, P. (1986). Cohort study of mortality of vermiculite miners exposed to tremolite. Occupational
and Environmental Medicine 43(1986):436-444.
Lung Cancer; all causes mortality, pneumoconiosis mortality, non-malignant respiratory disease mortality
Cancer/Carcinogenesis: respiratory cancer mortality; Lung/Respiratory: respiratory cancer mortality, pneumoconiosis mortality, non-malignant respiratory
disease mortality; Mortality: all cause mortality, pneumoconiosis mortality, respiratory cancer mortality, non-malignant respiratory disease mortality
Asbestos - Tremolite: 14567-73-8; Asbestos- Libby amphibole: 1318-09-8
29964, 709547, 709695
29964
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium Description of study setting was provided, and other elements including inclusion cri-
teria and case ascertainment, primarily from McDonald et al. 1986, HERO ID: 29964,
with McDonald and Armstrong 2003, HERO ID: 709547 giving a briefer version of the
info. The study population includes male workers from a Libby mining company who
have been hired before 1963. In total, 406 males worked at the site for at least one net
year were included, 12 of which were employed before 1940. No other description of
additional inclusion or exclusion criteria. There is limited information on subjects not
included or participation rate, which introduces potential for selection bias.
High In McDonald et al. 1986, HERO ID: 29964, at the end of the follow-up period (July 1st,
1983), 226 were alive and 165 were dead. 14 men were found alive on 1981 but subse-
quent status was not available. In total, vital status of 405 out of 406 men included in
this study were traced. Death certificates were obtained for 163 of the 165 deceased. In
McDonald and Armstrong 2003, HERO ID: 709547, at the end of the follow-up period
(July 1st, 1983), the remaining 241 (vs 240 in McDonald et al. 1986, HERO ID: 29964)
known to be alive at the end of the 1983 follow up period were traced via the National
Death Index to 1998, where another 120 were confirmed dead.There is little loss to fol-
low up.
Medium In McDonald et al. 1986, HERO ID: 29964 case-referent analyses, "controls for each
case were chosen as men surviving beyond the age of death of the case, who had been
born and had started work at Libby mine within three years of the case.'Tn McDonald
and Armstrong 2003, HERO ID: 709547, comparison was made among other workers.
Age and sex were considered in the analyses.Thus, there is only indirect evidence that
groups are not similar to each other.
Domain 2: Exposure Characterization
Continued on next page .
Page 402 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29964 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Mcdonald, A. D., Armstrong, B., Sebastien, P. (1986). Cohort study of mortality of vermiculite miners exposed to tremolite. Occupational
and Environmental Medicine 43(1986):436-444.
Lung Cancer; all causes mortality, pneumoconiosis mortality, non-malignant respiratory disease mortality
Cancer/Carcinogenesis: respiratory cancer mortality; Lung/Respiratory: respiratory cancer mortality, pneumoconiosis mortality, non-malignant respiratory
disease mortality; Mortality: all cause mortality, pneumoconiosis mortality, respiratory cancer mortality, non-malignant respiratory disease mortality
Asbestos - Tremolite: 14567-73-8; Asbestos- Libby amphibole: 1318-09-8
29964, 709547, 709695
29964
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Details on exposure assessment are primarily from McDonald et al. 1986, HERO ID:
29964, with McDonald and Armstrong 2003, HERO ID: 709547 citing this paper. The
measurement of exposure (a mix of personal and area) changed during the study period
but was ultimately based employment records and quantitative estimates of exposure
using a combination of midget impingers and PCM (cited as optical microscopy while
referencing Walton 1982, HERO ID: 29649, which clarifies it as phase contrast opti-
cal microscopy) for a portion of participant" s work history of exposure, requiring ex-
trapolation for earlier years. Air samples were collected using midget impinger before
1970 and using membrane filters after 1970. Samples before 1970 only measured dust
concentrations without conversion factors. Limited amount of samples were collected
before 1965, and the measurements were much higher after 1975 when the company
introduced a systematic air sampling program. Authors assumed that fiber exposure
measures made before 1965 (engineering controls installed at this point to reduce dust/
fiber levels), were a fraction of those measured afterwards. Authors further note: "For
the other operation locations fiber measurements were available only for the recent pe-
riods. When the data were considered inadequate to describe past conditions, because
of changes in process or control practice, arbitrary correction factors were applied. This
was done after discussion with the company's representatives and especially with a pre-
vious manager who had spent almost all his career with Libby and who had extensive
knowledge of the operations.""Samples were taken until 1982. Cumulative exposure
levels were calculated based on job histories, operation locations, and estimated aver-
age fiber concentrations.In McDonald and Armstrong 2003, HERO ID: 709547, they
used three different indices for exposure: "...(A) average intensity over first five years of
employment (f/ml); (B) cumulative exposure (f/ml.y); and (C) residence weighted cu-
mulative exposure, for which each year"s exposure is weighted according to the number
of years since it was experienced (f/ml.y)."
Medium In McDonald et al. 1986, HERO ID: 29964, cumulative continuous exposure levels were
used for case-referent analyses. In McDonald and Armstrong 2003, HERO ID: 709547,
both continuous and categorical exposure levels were used in Poisson regression analy-
ses. Dichotomous exposure SMR analyses in both papers merit a Low rating.
High The follow-up period is greater than 20 years in this cohort for >2/3 of deaths (as shown
in McDonald et al. 1986, HERO ID: 29964), suggesting there is sufficient considera-
tion of latency for a range of outcomes. The temporality is established and exposure
occurred before outcome.
Domain 3: Outcome Assessment
Continued on next page .
Page 403 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29964 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Mcdonald, A. D., Armstrong, B., Sebastien, P. (1986). Cohort study of mortality of vermiculite miners exposed to tremolite. Occupational
and Environmental Medicine 43(1986):436-444.
Lung Cancer; all causes mortality, pneumoconiosis mortality, non-malignant respiratory disease mortality
Cancer/Carcinogenesis: respiratory cancer mortality; Lung/Respiratory: respiratory cancer mortality, pneumoconiosis mortality, non-malignant respiratory
disease mortality; Mortality: all cause mortality, pneumoconiosis mortality, respiratory cancer mortality, non-malignant respiratory disease mortality
Asbestos - Tremolite: 14567-73-8; Asbestos- Libby amphibole: 1318-09-8
29964, 709547, 709695
29964
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
High Lung Cancer: In McDonald et al. 1986, HERO ID: 29964, the cases were ascertained
from death certificates and underlying cause of death was coded by a single qualified
nosologist according to ICD-8 codes (160-163). In McDonald and Armstrong 2003,
HERO ID: 709547, the additional deaths were coded by State nosologists in ICD-9
(160-165).; Other Non-Cancer Outcomes: In McDonald et al. 1986, HERO ID: 29964,
the cases were ascertained from death certificates and underlying cause of death was
coded by a single qualified nosologist according to ICD-8 codes: pneumoconiosis (515).
In McDonald and Armstrong 2003, HERO ID: 709547, the additional deaths were coded
by State nosologists in ICD-9: non-malignant respiratory disease (010-018, 460-519)
and all causes mortality (codes not specified but are implicit).
High Findings of the study were reported in abstract and results. Analyses show relative risk
with 95% CI (McDonald et al. 1986, HERO ID: 29964, McDonald and Armstrong 2003,
HERO ID: 709547). McDonald and Armstrong 2003, HERO ID: 709547 also reports a
p-trend. Reporting bias is not likely to be introduced.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Medium For case-referent analysis, age, sex, and date of hire were matched (McDonald et al.
1986, HERO ID: 29964), while in McDonald and Armstrong 2003, HERO ID: 709547,
there is no covariate adjustment, except for sex and race. Smoking is not addressed.
Metric 10: Covariate Characterization Medium The source of covariates were not described but likely collected from employment
records.
Metric 11: Co-exposure Counfounding Low There is no discussion of coexposures in these occupational studies.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The case-referent and Poisson analyses were appropriate method to evaluate the
exposure-outcome associations.
Medium Both studies likely have the statistical power to detect true associations, however there
are often more deaths in the latter study. The only exception may be pneumoconiosis,
which may be underpowered. Counts are as follows: for lung cancer (McDonald et al.
1986, HERO ID: 29964, n=23; McDonald and Armstrong 2003, HERO ID: 709547,
n=44); pneumoconiosis (McDonald et al. 1986, HERO ID: 29964, n=8); non-malignant
respiratory disease (McDonald and Armstrong 2003, HERO ID: 709547, n=51); all
causes of death (McDonald and Armstrong 2003, HERO ID: 709547, n=285).
Medium The descriptions of the methods and analyses are sufficient and conceptually repro-
ducible.
Medium Descriptions of case-referent and Poisson models are clear.
Continued on next page ...
Page 404 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29964 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Mcdonald, A. D., Armstrong, B., Sebastien, P. (1986). Cohort study of mortality of vermiculite miners exposed to tremolite. Occupational
and Environmental Medicine 43(1986):436-444.
Lung Cancer; all causes mortality, pneumoconiosis mortality, non-malignant respiratory disease mortality
Cancer/Carcinogenesis: respiratory cancer mortality; Lung/Respiratory: respiratory cancer mortality, pneumoconiosis mortality, non-malignant respiratory
disease mortality; Mortality: all cause mortality, pneumoconiosis mortality, respiratory cancer mortality, non-malignant respiratory disease mortality
Asbestos - Tremolite: 14567-73-8; Asbestos- Libby amphibole: 1318-09-8
29964, 709547, 709695
29964
Domain Metric Rating Comments
Additional Comments: Note that only outcomes with a rating higher than Low for Metric 5 were evaluated and QC'd. Many outcomes that only are analyzed by SMR (a
dichotomous exposure characterization) are thus not QC'd.This is a cohort of 2 studies (McDonald et al. 1986, HERO ID: 29964, McDonald and Armstrong
2003, HERO ID: 709547), with latter being a follow-up on the same cohort of workers in a Libby asbestos mine, with more deaths added for analyses. Of
note is that lung cancer shares slightly different ICD codings, however they are also from different ICDs (8 vs 9) but share the same total deaths, suggesting
that this difference has no impact.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 405 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 29998 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Mcdonald, A. D., Sebastien, P., Moy, K. (1988). Health of vermiculite miners exposed to trace amounts of fibrous tremolite. Occupational
and Environmental Medicine 45(1988):630-634.
Mortality from abdominal cancer, Mortality from other cancers; Mortality from circulatory disease, mortality from non-malignant respiratory disease, all
cause mortality
Mortality: Mortality from circulatory disease (ICD 390-458), Mortality from non-malignant respiratory disease (ICD 460-519), All causes mortality,
Mortality from respiratory cancer (ICD 160-163), mortality from abdominal cancer (ICD 150-159), and mortality from other cancers (140-149, 160,
164-208); Cardiovascular: Mortality from circulatory disease (ICD 390-458); Lung/Respiratory: Mortality from non-malignant respiratory disease (ICD
460-519); Cancer/Carcinogenesis: Mortality from respiratory cancer (ICD 160-163), mortality from abdominal cancer (ICD 150-159), and mortality from
other cancers (140-149, 160, 164-208); Gastrointestinal: Mortality from abdominal cancer (ICD 150-159); Other cancer sites (not specified): Mortality
from respiratory cancer (ICD 160-163), mortality from abdominal cancer (ICD 150-159), and mortality from other cancers (140-149, 160, 164-208)
Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29998
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium The study comprised 194 men employed by the company in South Carolina for 6
months or more who were hired before 1971. Criteria for inclusion in the cohort were
stated: all men who met the criteria were included. Exclusion criteria and other demo-
graphic characteristics were unclear. Some key elements of the study design were not
present but available information indicates a low risk of selection bias
High The study reported that the vital status of 189 men out of 194 men were obtained
through local inquiries. The remaining 5 men were traced only through social security
files.
Low "The mortality of the cohort was compared with that of white and black men in the
US using the person-years at risk method to compute the expected number of deaths
and hence standardized mortality ratios (SMRs)." SMR analysis adjusted for race but
not age. Workers are compared to an inappropriate general population, not a working
population.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium From 1969-1984, the company and Mine Safety and Health Administration took fiber
samples using personal and area measures in different work zones. No fiber counting is
explicitly stated for sampling in this period, and no comparison is made between com-
pany and MSHA samples. From 1985-1986, the study took dust samples and quantified
asbestos fibers using PCM and ATEM. ATEM is not defined in the study.
Medium Mean concentrations of airborne fibers were reported in Table 1 and 2. Estimates of
exposure intensity (expressed through f/cc) by zones and calendar years were reported in
Table 3 which were continuous measure. Exposure estimates were stratified by wet and
dry zones.
High The study presents an appropriate temporality between exposure and outcome. The
follow up was at least 15 years for the participants.
Domain 3: Outcome Assessment
Continued on next page ...
Page 406 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 29998 Table: 1 of 2
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Mcdonald, A. D., Sebastien, P., Moy, K. (1988). Health of vermiculite miners exposed to trace amounts of fibrous tremolite. Occupational
and Environmental Medicine 45(1988):630-634.
Mortality from abdominal cancer, Mortality from other cancers; Mortality from circulatory disease, mortality from non-malignant respiratory disease, all
cause mortality
Mortality: Mortality from circulatory disease (ICD 390-458), Mortality from non-malignant respiratory disease (ICD 460-519), All causes mortality,
Mortality from respiratory cancer (ICD 160-163), mortality from abdominal cancer (ICD 150-159), and mortality from other cancers (140-149, 160,
164-208); Cardiovascular: Mortality from circulatory disease (ICD 390-458); Lung/Respiratory: Mortality from non-malignant respiratory disease (ICD
460-519); Cancer/Carcinogenesis: Mortality from respiratory cancer (ICD 160-163), mortality from abdominal cancer (ICD 150-159), and mortality from
other cancers (140-149, 160, 164-208); Gastrointestinal: Mortality from abdominal cancer (ICD 150-159); Other cancer sites (not specified): Mortality
from respiratory cancer (ICD 160-163), mortality from abdominal cancer (ICD 150-159), and mortality from other cancers (140-149, 160, 164-208)
Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9
No linked references.
29998
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
High
Other Cancer(s): Mortality was characterized by registered causes of death, which were
coded according to the 8th revision of the International Classification of Diseases (ICD)
by a nosologist. Mortality from "other cancers" corresponded to codes 140-149, 160,
164-208.; Other Non-Cancer Outcomes: Mortality was characterized by registered
causes of death, which were coded according to the 8th revision of the International
Classification of Diseases (ICD). Mortality from circulatory disease corresponded to
ICD 390-458. Mortality from respiratory disease corresponded to ICD 460-519. Radio-
logic examination were assessed using ILO 1980 classification.
Metric 8:
Reporting Bias
High
Outcomes were outlined in all sections of the report. For SMR analyses, all relevant
findings were presented.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Low SMRs were reported. The authors stratified by race, but did not adjust for age.
Medium The study used personnel files which were assumed to be accurate.
Low The study was in an occupational setting with no discussion of co-exposures.
Domain 5: Analysis
Metric
12:
Metric
13:
Metric
14:
Metric
15:
Study Design and Methods
Statistical Power
Reproducibility of Analyses
Statistical Analysis
Medium The study design and method, SMR analyses in an occupational cohort, were appropri-
ate.
Medium The number of participants (n=194) was adequate to detect an effect in the exposed
population.
Medium The authors provided sufficient details to reproduce the analysis.
Medium The study conducted SMR analysis, which has no explicit assumptions to be met.
Additional Comments: Radiographic outcomes are shown (Table 8) but not analyzed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 407 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 29998 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Mcdonald, J. C., Mcdonald, A. D., Sebastien, P., Moy, K. (1988). Health of vermiculite miners exposed to trace amounts of fibrous tremolite. Occupational
and Environmental Medicine 45(1988):630-634.
Lung Cancer
Cancer/Carcinogenesis: Mortality from respiratory cancer (ICD 160-163), mortality from abdominal cancer (ICD 150-159), and mortality from other
cancers (140-149, 160, 164-208); Mortality: Mortality from respiratory cancer (ICD 160-163), mortality from abdominal cancer (ICD 150-159), and
mortality from other cancers (140-149, 160, 164-208)
Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9
ID(s): No linked references.
29998
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low From 1969-1984, the company and Mine Safety and Health Administration took fiber
samples using personal and area measures in different work zones. No fiber counting is
explicitly stated for sampling in this period, and no comparison is made between com-
pany and MSHA samples. From 1985-1986, the study took dust samples and quantified
asbestos fibers using PCM and ATEM. ATEM is not defined in the study.
Medium Mean concentrations of airborne fibers were reported in Table 1 and 2. Estimates of
exposure intensity (expressed through f/cc) by zones and calendar years were reported in
Table 3 which were continuous measure. Exposure estimates were stratified by wet and
dry zones.
Additional Comments: Radiographic outcomes are shown (Table 8) but not analyzed. Lung cancer is not assessed separately from respiratory cancer outcomes, meriting an
uninformative rating for this health outcome.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 408 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709695 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mcdonald, J. C., Sebastien, P., Armstrong, B. (1986). Radiological survey of past and present vermiculite miners exposed to tremolite. British Journal of
Industrial Medicine 43(1986):445-449.
small opacities, pleural thickening of chest wall
Lung/Respiratory: small opacities, pleural thickening
Asbestos - Tremolite: 14567-73-8
29964, 709547, 709695
709695
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Neither PCM or TEM was mentioned to be used to develop quantitative estimates of
exposure. The authors stated: "The mean airborne fibre concentrations for each location
operation, year by year, were estimated from all available midget impinger and mem-
brane filter measurements"
Metric 5: Exposure Levels Medium The range and distribution of cumulative exposure is sufficient to develop an exposure-
response estimate. Five exposure levels were reported as groups (<10, 10<=20,
20<=I00, 100<=200, and >=200 fibers/ml year).
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis. Metric 4 was deemed low because the authors did not indicate if exposure measurements were done with PCM or TEM.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 409 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 4165644 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Mcelvenny, D. M., van Tongeren, M., Turner, M. C., Benke, G., Figuerola, J., Fleming, S., Hours, M., Kind, L., Krewski, D., Mclean, D., Parent, M.
E., Richardson, L., Schlehofer, B., Schlaefer, K., Sadetzki, S., Schuz, J., Siemiatycki, J., Cardis, E. (2018). The INTEROCC case-control study: risk
of meningioma and occupational exposure to selected combustion products, dusts and other chemical agents. Occupational and Environmental Medicine
75(2018):22-Dec.
Meningioma
Cancer/Carcinogenesis: Meningioma
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
4165644
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Exposure was estimated using a job-exposure matrix; however, it is uncertain whether
PCM or TEM were used to construct the job-exposure matrix. The paper referenced
with more details (van Tongeren et al., 2013, HERO ID: 4142033) only mentions the
calculation of weighted means based on occupational codes.This study or any cited
methods source does not explicitly mention the use of PCM or TEM.
Metric 5: Exposure Levels Low The study reports the mean cumulative exposure between cases and controls overall and
then stratified by sex; the range of exposure in the population is limited to the means.
There are no other summary statistics provided for exposure.
Additional Comments: NOTE: This study would not be fully evaluated under the current guidelines. Metrics 4 and 5 were rated low due to a limited range of exposure and no
mention of the use of PCM or TEM for the determination of asbestos exposure.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 410 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 307878i Table: 1 of 8
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Menegozzo, S., Comba, P., Ferrante, D., De Santis, M., Gorini, G., Izzo, F., Magnani, C., Pirastu, R., Simonetti, A., Tiinesi, S., Menegozzo, M. (2011).
Mortality study in an asbestos cement factory in Naples, Italy. Annali dell'Istituto superiore di sanit" 47(2011):296-304.
Lung Cancer
Lung/Respiratory: malignant neoplasms respiratory tract (160-165) mortality, malignant neoplasms larynx (161) mortality, malignant neoplasms lung (162)
mortality, Respiratory diseases (460-519) mortality; Mortality: malignant neoplasms respiratory tract (160-165) mortality, malignant neoplasms larynx
(161) mortality, malignant neoplasms lung (162) mortality, malignant neoplasms pleura (163) mortality; Cancer/Carcinogenesis: malignant neoplasms
respiratory tract (160-165) mortality, malignant neoplasms larynx (161) mortality, malignant neoplasms lung (162) mortality, malignant neoplasms pleura
(163) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3078781
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM.Authors provided a detailed history of asbestos
work in the plant, but methodology of exposure measurement is limited. Generic dust
measures were available from the 1960s and in 1979, 64 airborne asbestos fiber sam-
plings were available (crocidolite specific). No information is provided regarding how
measures were taken.
Medium Study cohort includes workers hired from 1950-1986 and follow-up is from 1965-2005.
Even though the environmental airborne generic asbestos fiber and crocidolite sampling
in different areas in 1979, this study only presented "duration of exposure" that can
be used as a surrogate of exposure assessment for several diseases and to determine
exposure-response relationships.
Additional Comments:
NOTE: This study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was mentioned in
the study or a cited source.This study provides a comprehensive analysis of SMRs from workers in the Bagnoli factory cohort. Overall, the study describes
metrics well, but lacks proper covariables and excluded smoking in their analyses. There is very little information regarding the measurements of asbestos
dusts within the factory, with no mention of what tools were used or measures for non-crocidolite asbestos exposures.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 411 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3078781 Table: 2 of S
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Menegozzo, S., Comba, P., Ferrante, D., De Santis, M., Gorini, G., Izzo, F., Magnani, C., Pirastu, R., Simonetti, A., Tiinesi, S., Menegozzo, M. (2011).
Mortality study in an asbestos cement factory in Naples, Italy. Annali dell'Istituto superiore di sanit" 47(2011):296-304.
Asbestosis; Respiratory diseases, bronchitis, emphysema, asthma, pneumoconiosis
Mortality: Asbestosis (501) mortality, Pneumoconiosi (500-505) mortality, Bronchitis, emphysema, asthma (490-493) mortality, Respiratory diseases (460-
519) mortality; Lung/Respiratory: Asbestosis (501) mortality, Pneumoconiosi (500-505) mortality, Bronchitis, emphysema, asthma (490-493) mortality,
Respiratory diseases (460-519) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3078781
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM. Authors provided a detailed history of asbestos
work in the plant, but methodology of exposure measurement is limited. Generic dust
measures were available from the 1960s and in 1979, 64 airborne asbestos fiber sam-
plings were available (crocidolite specific). No information is provided regarding how
measures were taken.
Medium The study cohort includes workers hired from 1950-1986, and follow-up is from 1965-
2005. Even though the environmental airborne generic asbestos fiber and crocidolite
sampling in different areas in 1979, this study only presented "duration of exposure" that
can be used as a surrogate of exposure assessment for several diseases and to determine
exposure-response relationships.
Additional Comments:
NOTE: This study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was mentioned in
the study or a cited source.This study provides a comprehensive analysis of SMRs from workers in the Bagnoli factory cohort. Overall, the study describes
metrics well, but lacks proper covariables and excluded smoking in their analyses. There is very little information regarding the measurements of asbestos
dusts within the factory, with no mention of what tools were used or measures for non-crocidolite asbestos exposures.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 412 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 307878i Table: 3 of 8
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Menegozzo, S., Comba, P., Ferrante, D., De Santis, M., Gorini, G., Izzo, F., Magnani, C., Pirastu, R., Simonetti, A., Tiinesi, S., Menegozzo, M. (2011).
Mortality study in an asbestos cement factory in Naples, Italy. Annali dell'Istituto superiore di sanit" 47(2011):296-304.
malignant neoplasms of digestive organs and peritoneum, malignant neoplasms stomach, malignant neoplasm intesntine and rectum; digestive system
disease,
Cancer/Carcinogenesis: malignant neoplasms intestine and rectum (152-154) mortality, malignant neoplasms digestive organs and peritoneum (150-159)
mortality, malignant neoplasms stomach (151) mortality, malignant neoplasms rectum (154) mortality; Gastrointestinal: malignant neoplasms digestive
organs and peritoneum (150-159) mortality, malignant neoplasms stomach (151) mortality, malignant neoplasms rectum (154) mortality, Digestive sys-
tem disease (520-579) mortality, malignant neoplasms intestine and rectum (152-154) mortality; Mortality: malignant neoplasms digestive organs and
peritoneum (150-159) mortality, malignant neoplasms stomach (151) mortality, malignant neoplasms intestine and rectum (152-154) mortality, malignant
neoplasms rectum (154) mortality, Digestive system disease (520-579) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3078781
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM. Authors provided a detailed history of asbestos
work in the plant, but methodology of exposure measurement is limited. Generic dust
measures were available from the 1960s and in 1979, 64 airborne asbestos fiber sam-
plings were available (crocidolite specific). No information is provided regarding how
measures were taken.
Medium The study cohort includes workers hired from 1950-1986, and follow-up is from 1965-
2005. Even though the environmental airborne generic asbestos fiber and crocidolite
sampling in different areas in 1979, this study only presented "duration of exposure" that
can be used as a surrogate of exposure assessment for several diseases and to determine
exposure-response relationships.
Additional Comments: NOTE: This study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was mentioned
in the study or a cited source. This study provides a comprehensive analysis of SMRs from workers in the Bagnoli factory cohort. Overall, the study
describes metrics well, but lacks proper covariables and excluded smoking in their analyses. There is very little information regarding the measurements
of asbestos dusts within the factory, with no mention of what tools were used or measures for non-crocidolite asbestos exposures.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 413 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3078781 Table: 4 of S
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Menegozzo, S., Comba, P., Ferrante, D., De Santis, M., Gorini, G., Izzo, F., Magnani, C., Pirastu, R., Simonetti, A., Tiinesi, S., Menegozzo, M. (2011).
Mortality study in an asbestos cement factory in Naples, Italy. Annali dell'Istituto superiore di sanit" 47(2011):296-304.
malignant neoplasms (genitourinary, bladder); genitourinary diseases
Renal/Kidney: malignant neoplasms genitourinary (179-189) mortality, malignant neoplasms bladder (188) mortality, Genitourinary disease (580-629)
mortality; Mortality: malignant neoplasms genitourinary (179-189) mortality, malignant neoplasms bladder (188) mortality, Genitourinary disease (580-
629) mortality; Cancer/Carcinogenesis: malignant neoplasms genitourinary (179-189) mortality, malignant neoplasms bladder (188) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3078781
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM. Authors provided a detailed history of asbestos
work in the plant, but methodology of exposure measurement is limited. Generic dust
measures were available from the 1960s and in 1979, 64 airborne asbestos fiber sam-
plings were available (crocidolite specific). No information is provided regarding how
measures were taken.
Medium The study cohort includes workers hired from 1950-1986, and follow-up is from 1965-
2005. Even though the environmental airborne generic asbestos fiber and crocidolite
sampling in different areas in 1979, this study only presented "duration of exposure" that
can be used as a surrogate of exposure assessment for several diseases and to determine
exposure-response relationships.
Additional Comments:
NOTE: This study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was mentioned in
the study or a cited source.This study provides a comprehensive analysis of SMRs from workers in the Bagnoli factory cohort. Overall, the study describes
metrics well, but lacks proper covariables and excluded smoking in their analyses. There is very little information regarding the measurements of asbestos
dusts within the factory, with no mention of what tools were used or measures for non-crocidolite asbestos exposures.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 414 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3078781 Table: 5 off
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Menegozzo, S., Comba, P., Ferrante, D., De Santis, M., Gorini, G., Izzo, F., Magnani, C., Pirastu, R., Simonetti, A., Tiinesi, S., Menegozzo, M. (2011).
Mortality study in an asbestos cement factory in Naples, Italy. Annali dell'Istituto superiore di sanit" 47(2011):296-304.
malignant neoplasms (nervous system))
Neurological/Behavioral: malignant neoplasms nervous system (190-192) mortality; Mortality: malignant neoplasms nervous system (190-192) mortality;
Cancer/Carcinogenesis: malignant neoplasms nervous system (190-192) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3078781
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM. Authors provided a detailed history of asbestos
work in the plant, but methodology of exposure measurement is limited. Generic dust
measures were available from the 1960s and in 1979, 64 airborne asbestos fiber sam-
plings were available (crocidolite specific). No information is provided regarding how
measures were taken.
Medium The study cohort includes workers hired from 1950-1986, and follow-up is from 1965-
2005. Even though the environmental airborne generic asbestos fiber and crocidolite
sampling in different areas in 1979, this study only presented "duration of exposure" that
can be used as a surrogate of exposure assessment for several diseases and to determine
exposure-response relationships.
Additional Comments: NOTE: This study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was mentioned in
the study or a cited source.This study provides a comprehensive analysis of SMRs from workers in the Bagnoli factory cohort. Overall, the study describes
metrics well, but lacks proper covariables and excluded smoking in their analyses. There is very little information regarding the measurements of asbestos
dusts within the factory, with no mention of what tools were used or measures for non-crocidolite asbestos exposures.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 415 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3078781 Table: 6 of S
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Menegozzo, S., Comba, P., Ferrante, D., De Santis, M., Gorini, G., Izzo, F., Magnani, C., Pirastu, R., Simonetti, A., Tiinesi, S., Menegozzo, M. (2011).
Mortality study in an asbestos cement factory in Naples, Italy. Annali dell'Istituto superiore di sanit" 47(2011):296-304.
malignant neoplasms lynphohematopoietic system
Immune/Hematological: malignant neoplasms lynphohematopoietic system (200-208) mortality; Mortality: malignant neoplasms lynphohematopoietic
system (200-208) mortality; Cancer/Carcinogenesis: malignant neoplasms lynphohematopoietic system (200-208) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3078781
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM. Authors provided a detailed history of asbestos
work in the plant, but methodology of exposure measurement is limited. Generic dust
measures were available from the 1960s and in 1979, 64 airborne asbestos fiber sam-
plings were available (crocidolite specific). No information is provided regarding how
measures were taken.
Medium The study cohort includes workers hired from 1950-1986, and follow-up is from 1965-
2005. Even though the environmental airborne generic asbestos fiber and crocidolite
sampling in different areas in 1979, this study only presented "duration of exposure" that
can be used as a surrogate of exposure assessment for several diseases and to determine
exposure-response relationships.
Additional Comments: NOTE: This study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was mentioned in
the study or a cited source.This study provides a comprehensive analysis of SMRs from workers in the Bagnoli factory cohort. Overall, the study describes
metrics well, but lacks proper covariables and excluded smoking in their analyses. There is very little information regarding the measurements of asbestos
dusts within the factory, with no mention of what tools were used or measures for non-crocidolite asbestos exposures.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 416 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3078781 Table: 7 of S
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Menegozzo, S., Comba, P., Ferrante, D., De Santis, M., Gorini, G., Izzo, F., Magnani, C., Pirastu, R., Simonetti, A., Tiinesi, S., Menegozzo, M. (2011).
Mortality study in an asbestos cement factory in Naples, Italy. Annali dell'Istituto superiore di sanit" 47(2011):296-304.
Cardiovascular diseases, ischemic heart diseases
Cardiovascular: Cardiovascular diseases (390-459) mortality, Ischemic heart diseases (410-414) mortality; Mortality: Cardiovascular diseases (390-459)
mortality, Ischemic heart diseases (410-414) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3078781
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM. Authors provided a detailed history of asbestos
work in the plant, but methodology of exposure measurement is limited. Generic dust
measures were available from the 1960s and in 1979, 64 airborne asbestos fiber sam-
plings were available (crocidolite specific). No information is provided regarding how
measures were taken.
Medium The study cohort includes workers hired from 1950-1986, and follow-up is from 1965-
2005. Even though the environmental airborne generic asbestos fiber and crocidolite
sampling in different areas in 1979, this study only presented "duration of exposure" that
can be used as a surrogate of exposure assessment for several diseases and to determine
exposure-response relationships.
Additional Comments:
NOTE: This study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was mentioned in
the study or a cited source.This study provides a comprehensive analysis of SMRs from workers in the Bagnoli factory cohort. Overall, the study describes
metrics well, but lacks proper covariables and excluded smoking in their analyses. There is very little information regarding the measurements of asbestos
dusts within the factory, with no mention of what tools were used or measures for non-crocidolite asbestos exposures.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 417 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3078781 Table: 8 off
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Menegozzo, S., Comba, P., Ferrante, D., De Santis, M., Gorini, G., Izzo, F., Magnani, C., Pirastu, R., Simonetti, A., Tiinesi, S., Menegozzo, M. (2011).
Mortality study in an asbestos cement factory in Naples, Italy. Annali dell'Istituto superiore di sanit" 47(2011):296-304.
Diabetes
Nutritional/Metabolic: Diabetes (250) mortality; Mortality: Diabetes (250) mortality
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3078781
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM. Authors provided a detailed history of asbestos
work in the plant, but methodology of exposure measurement is limited. Generic dust
measures were available from the 1960s and in 1979, 64 airborne asbestos fiber sam-
plings were available (crocidolite specific). No information is provided regarding how
measures were taken.
Medium The study cohort includes workers hired from 1950-1986, and follow-up is from 1965-
2005. Even though the environmental airborne generic asbestos fiber and crocidolite
sampling in different areas in 1979, this study only presented "duration of exposure" that
can be used as a surrogate of exposure assessment for several diseases and to determine
exposure-response relationships.
Additional Comments: NOTE: This study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was mentioned in
the study or a cited source.This study provides a comprehensive analysis of SMRs from workers in the Bagnoli factory cohort. Overall, the study describes
metrics well, but lacks proper covariables and excluded smoking in their analyses. There is very little information regarding the measurements of asbestos
dusts within the factory, with no mention of what tools were used or measures for non-crocidolite asbestos exposures.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 418 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709524 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Metintas, M., Metintas, S., Hillerdal, G., Ucgun, I., Erginel, S., Alatas, F., Yildirim, H. (2005). Nonmalignant pleural lesions due to environmental exposure
to asbestos: a field-based, cross-sectional study. European Respiratory Journal 26(2005):875-880.
Pleural Plaques; mortality (circulation systems, COPD), Diffuse pleural fibrosis, asbestosis
Lung/Respiratory: Diffuse pleural fibrosis (Metintas et al. 2005 709524), Pleural plaques (Metintas et al. 2005 709524), Asbestosis (Metintas et al. 2005
709524); Mortality: Circulation systems (Metintas etal. 2012 2325159), COPD (Metintas etal. 2012 2325159)
Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9
No linked references.
709524
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
High The authors reported all key elements of the study, including location, and inclusion
criteria. In total, 991 individuals aged 30 years and more were selected from 10 villages
for the current study.
High Of the initial 991 individuals selected, 923 were included in the final analysis. Excluded
individuals (n=68) where those who did not either had complete outcome data or lack of
consensus among physician in ascertaining the outcome of interest.
High Key elements of the study design were reported, suggesting that the study subjects were
recruited from the same eligible population i.e., individuals living in villages known to
have asbestos-containing soil. The control population had similar demographic char-
acteristics and the authors mention that the study participants were farmers in both the
control and asbestos villages.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium The air sampling methodology was not described in detail, missing the description sam-
pling flowrate and sample processing for both publications (Metintas et al. 2005 709524
and Metintas et al. 2012 2325159). Nonetheless, both publications mentioned using
phase-contrast microscope (PCM) to count the asbestos fibers.
Medium The authors reported summary statistics representing multiple levels of exposure. Met-
intas et al. 2005 709524 reported indoor and outdoor concentrations and made assump-
tions to estimate the individual's exposure, reporting three different levels of exposure
as shown in Table 4. Metintas et al. 2012 2325159 reported exposure summary statistics
in the text, using a Cox model that considers exposure as a continuous variable. Both
studies include analyses that only consider exposure as a binary variable (exposed vs.
unexposed in Metintas et al. 2012 2325159, and greater or less than 5 f/y/mL for Met-
intas et al. 2005 709524).
Medium Temporality is established in both studies, but the consideration of latency may not be
sufficiently long in both studies as they had young study participants (20 years old and
above in Metintas et al. 2012 2325159, and 30 years old and above in Metintas 2005
709524).
Domain 3: Outcome Assessment
Continued on next page ...
Page 419 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709524 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Metintas, M., Metintas, S., Hillerdal, G., Ucgun, I., Erginel, S., Alatas, F., Yildirim, H. (2005). Nonmalignant pleural lesions due to environmental exposure
to asbestos: a field-based, cross-sectional study. European Respiratory Journal 26(2005):875-880.
Pleural Plaques; mortality (circulation systems, COPD), Diffuse pleural fibrosis, asbestosis
Lung/Respiratory: Diffuse pleural fibrosis (Metintas et al. 2005 709524), Pleural plaques (Metintas et al. 2005 709524), Asbestosis (Metintas et al. 2005
709524); Mortality: Circulation systems (Metintas etal. 2012 2325159), COPD (Metintas etal. 2012 2325159)
Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9
No linked references.
709524
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
High
Pleural Plaques: The mortality outcomes (i.e., circulatory systems and COPD SMRs)
were assessed using hospital records and household index cards (Metintas et al. 2012
2325159). In the study by Metintas et al. 2005 709524, all study participants completed
a questionnaire and went through clinical and radiological examination with chest x-rays
to evaluate if they had pleural plaques, diffuse pleural fibrosis or asbestosis. Study par-
ticipants were also examined using CT scans if the x-rays suggested possible abnormal
findings.; Other Non-Cancer Outcomes: The authors used hospital records to evaluate
the mortality cause in Metintas et al. 2012 2325159 (circulatory systems and COPD
SMRs). In Metintas et al. 2005 709524, the authors used x-rays followed by CT scans to
see if the study participants had diffuse pleural fibrosis or asbestosis.
Metric 8:
Reporting Bias
High
The authors reported results for all the outcomes mentioned in the methods section in
both publications (Metintas et al. 2005 709524 and Metintas et al. 2012 2325159).
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
Medium
Appropriate adjustments for age and sex were done in the analyses conducted in both
publications but the authors did not describe the methods in detail (Metintas et al. 2005
709524 and Metintas et al. 2012 2325159). Metintas et al. 2012 2325159 mentioned
data on smoker designation to study participants but it does not seem like the authors
used it to estimate the effect estimates.
Metric 10:
Covariate Characterization
High
The potential confounders (age, sex) data were collected through a questionnaire (Met-
intas et al. 2005 709524) or through medical records (Metintas et al. 2012 2325159).
Metric 11:
Co-exposure Counfounding
Medium
Data on co-exposures were not reported in either Metintas et al., 2005 709524 or Met-
intas et al. 2012 2325159.
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
The authors used appropriate statistical methods to evaluate the health outcomes in the
studies' participants; OR, prevalence and logistic regression analysis in Metintas et
al. 2005 709524, and standardized mortality ratios estimation in Metintas et al. 2012
2325159.
Metric 13:
Statistical Power
Medium
The sample size in both studies was sufficiently large to detect an effect in the exposed
population: n =943 individuals over 30 years old from 10 villages (Metintas et al. 2005
709524). n = 5318 individuals ages 20-70 and over from 15 villages (Metintas et al.
2012 2325159).
Metric 14:
Reproducibility of Analyses
Medium
The description of the analysis in both studies (Metintas et al. 2005 709524 and Met-
intas et al. 2012 2325159) is sufficient to understand how the data were analyzed in
order to reproduce the reported results.
Continued on next
page...
Page 420 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709524 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Metintas, M., Metintas, S., Hillerdal, G., Ucgun, I., Erginel, S., Alatas, F., Yildirim, H. (2005). Nonmalignant pleural lesions due to environmental exposure
to asbestos: a field-based, cross-sectional study. European Respiratory Journal 26(2005):875-880.
Pleural Plaques; mortality (circulation systems, COPD), Diffuse pleural fibrosis, asbestosis
Lung/Respiratory: Diffuse pleural fibrosis (Metintas et al. 2005 709524), Pleural plaques (Metintas et al. 2005 709524), Asbestosis (Metintas et al. 2005
709524); Mortality: Circulation systems (Metintas etal. 2012 2325159), COPD (Metintas etal. 2012 2325159)
Asbestos - Tremolite: 14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Anthophyllite: 17068-78-9
No linked references.
709524
Domain
Metric
Rating
Comments
Metric 15: Statistical Analysis
Medium The methods used to estimate ORs and SMRs are transparent in both studies (Metintas
et al. 2005 709524 and Metintas et al. 2012 2325159)
Additional Comments: The third study in this group (Akkurt et al. 2006, 2078953) does not belong to the cohort, as the location of the study cannot be identified as being the
same, and the study population are workers, instead of the general population evaluated in the other two studies by Metintas et al. in 2005 and 2012.The
measurement exposure (M4) and/or exposure levels (M5) metrics are rated as medium upon review by both set of reviewers. Also, the overall quality
determination (OQD) is rated medium. Extraction has been completed and quality control reviewed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 421 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2325159 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Metintas, S., Metintas, M., Ak, G., Kalyoncu, C. (2012). Environmental asbestos exposure in rural Turkey and risk of lung cancer. International lournal of
Environmental Health Research 22(2012):468-479.
COPD mortality, all-causes, circulation systems mortality
Mortality: All causes of mortality, Chronic obstructive pulmonary disease (COPD) mortality, Circulation systems mortality; Lung/Respiratory: Chronic
obstructive pulmonary disease (COPD) mortality; Cardiovascular: Circulation systems mortality
Asbestos - Tremolite: 14567-73-8
No linked references.
2325159
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium White soil exposure was assessed both indoors and outdoors (two samples for each
environment) in each village. Inclusion for indoor measurements included white-washed
walls with white soil. Outdoor samples were taken from the center of the village on the
main road. Samples were sent to specialists in the National Institute of Workers Health
and Security (ISGUM), Ankara. A PCM was used to count fibres longer than 5 um. This
has been marked medium as the authors don't clarify if multiple time periods were used
for measures.
Low Levels of exposure are by exposed and unexposed villages and by men and women. As
there are only two levels of exposure, the metric is rated Low.
Additional Comments: Overall, this study is robustly designed. There is not much information about the Household Detection Index Card, if the family self-reports cause of death
to their village Family Health Center to record, or if a doctor/autopsy confirmed cause of death. This provides little validity in the health outcomes. The
study also provides multiple analyses for cancer outcomes.Note: QC was not performed for any metrics except for Metric 4 and Metric 5 because Metric 5
was rated low.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 422 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2325159 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Metintas, S., Metintas, M., Ak, G., Kalyoncu, C. (2012). Environmental asbestos exposure in rural Turkey and risk of lung cancer. International lournal of
Environmental Health Research 22(2012):468-479.
Lung Cancer; GI system cancer, prostate cancer, larynx cancer, brain cancer, haemopeoitic system cancer, skin cancer and melanoma, bone cancer,
neuroblastoma, thyroid cancer, breast cancer, and female genital tract cancer
Lung/Respiratory: Lung cancer, Larynx cancer; Cancer/Carcinogenesis: Lung cancer, Gastrointestinal systems cancer, Prostate cancer, Larynx cancer,
Brain cancer, Haemopoietic system cancer, Skin cancers and melanoma, Bone cancer, Neuroblastoma cancer, Thyroid cancer, Breast cancer, Female
genital tract cancer; Gastrointestinal: Gastrointestinal systems cancer; Reproductive/Developmental: Prostate cancer, Breast cancer, Female genital tract
cancer; Neurological/Behavioral: Brain cancer, Neuroblastoma cancer; Immune/Hematological: Haemopoietic system cancer; Skin/Connective Tissue:
Skin cancers and melanoma; Musculoskeletal: Bone cancer; Thyroid: Thyroid cancer
Asbestos - Tremolite: 14567-73-8
No linked references.
2325159
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium White soil exposure was assessed both indoors and outdoors (two samples for each
environment) in each village. Inclusion for indoor measurements included white-washed
walls with white soil. Outdoor samples were taken from the center of the village on the
main road. Samples were sent to specialists in the National Institute of Workers Health
and Security (ISGUM), Ankara. A PCM was used to count fibres longer than 5 um. This
has been marked medium as the authors don't clarify if multiple time periods were used
for measures.
Low Levels of exposure are by exposed and unexposed villages and by men and women. As
there are only two levels of exposure, the metric is rated Low.
Additional Comments:
HEROID 235159 was not evaluated for any metrics except Metric 4 and 5 and had no data extracted because it did not have sufficient exposure information
to be useful for dose-response analysis. Metric 5 only provided 2 exposure levels, thus receiving a Low rating. Comments can still be found for all metric,
but they are not rated.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 423 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3084463 Table: 1 of 4
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mitchell, C. A., Charney, M., Schoenberg, J. B. (1978). Early lung disease in asbestos-product workers. Lung 154(1978):261-272.
Pulmonary Function/Spirometry Results
Lung/Respiratory: FVC, FEV1
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3084463
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Neither PCM nor TEM were used for measuring exposure. The study measures asbestos
exposure using the membrane filter method. Measurements were made available after
the authors conducted their study. Duration of asbestos exposure appears to be calcu-
lated from a modified British Medical Research Council questionnaire which collects
information about occupational history.
Medium Asbestos fibers were counted in different areas of the plant (corresponding with where
each group was primarily located) with ranges of exposure reported.
Additional Comments: The aim of the study was to assess the sensitivity of simple respiratory tests in detecting early stages of asbestos lung disease.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 424 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3084463 Table: 2 of 4
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mitchell, C. A., Charney, M., Schoenberg, J. B. (1978). Early lung disease in asbestos-product workers. Lung 154(1978):261-272.
chest auscultation
Lung/Respiratory: chest auscultation (Rales score)
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3084463
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Neither PCM nor TEM were used for measuring exposure. The study measures asbestos
exposure using the membrane filter method. Measurements were made available after
the authors conducted their study. Duration of asbestos exposure appears to be calcu-
lated from a modified British Medical Research Council questionnaire which collects
information about occupational history.
Medium Asbestos fibers were counted in different areas of the plant (corresponding with where
each group was primarily located) with ranges of exposure reported.
Additional Comments: The aim of the study was to assess the sensitivity of simple respiratory tests in detecting early stages of asbestos lung disease.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 425 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3084463 Table: 3 of 4
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mitchell, C. A., Charney, M., Schoenberg, J. B. (1978). Early lung disease in asbestos-product workers. Lung 154(1978):261-272.
cough, sputum, wheeze, dyspnea
Lung/Respiratory: Respiratory symptoms, loose cough test
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3084463
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Neither PCM nor TEM were used for measuring exposure. The study measures asbestos
exposure using the membrane filter method. Measurements were made available after
the authors conducted their study. Duration of asbestos exposure appears to be calcu-
lated from a modified British Medical Research Council questionnaire which collects
information about occupational history.
Medium Asbestos fibers were counted in different areas of the plant (corresponding with where
each group was primarily located) with ranges of exposure reported.
Additional Comments: The aim of the study was to assess the sensitivity of simple respiratory tests in detecting early stages of asbestos lung disease.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 426 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3084463 Table: 4 of 4
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mitchell, C. A., Charney, M., Schoenberg, J. B. (1978). Early lung disease in asbestos-product workers. Lung 154(1978):261-272.
abnormal radiographs
Lung/Respiratory: opacities from chest reading graphs
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Anthophyllite: 17068-78-9
No linked references.
3084463
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Neither PCM nor TEM were used for measuring exposure. The study measures asbestos
exposure using the membrane filter method. Measurements were made available after
the authors conducted their study. Duration of asbestos exposure appears to be calcu-
lated from a modified British Medical Research Council questionnaire which collects
information about occupational history.
Medium Asbestos fibers were counted in different areas of the plant (corresponding with where
each group was primarily located) with ranges of exposure reported.
Additional Comments: The aim of the study was to assess the sensitivity of simple respiratory tests in detecting early stages of asbestos lung disease.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 427 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2079066 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Moshammer, H., Neuberger, M. (2009). Lung function predicts survival in a cohort of asbestos cement workers. International Archives of Occupational
and Environmental Health 82(2009): 199-207.
Respiratory disease mortality, cardiovascular disease mortality, survival, total life expectancy
Mortality: Respiratory disease mortality, Cardiovascular disease mortality, Survival; Lung/Respiratory: Respiratory disease mortality, FEV1, FVC, PEF,
MEF75, MEF50, MEF25, Rounded small opacities, Irregular small opacities, Pleural thickening, Large opacities; Cardiovascular: Cardiovascular disease
mortality; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
2079066
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Key elements of study design were reported in this historical prospective study of n=309
asbestos cement factory workers who were in 1989/1990 aged 57.0 years (+/- 9.5 years)
in Vocklabruck, Upper Austria and were followed from 1974-2006. Estimated cumula-
tive exposure was based upon historical spot measurement data and exposure classifica-
tions assigned to each work area. Cohort formation began with workers in 1974 through
1981 when personal protective equipment became available to workers, and biannual
medical evaluations were available beginning in 1989 and vital status was updated until
the end of 2006. Workplace asbestos exposure spot measurement records were avail-
able from 1950 until 1981. The initial cohort of workers who agreed to participate in
extended biannual medical evaluations beginning in 1989 consisted of n=322 active and
retired workers. Of these, n=309 workers (n=270 males and n=39 females) with com-
plete asbestos exposure history and whose vital status could be followed until the end of
2006 were included.
High There was minimal subject loss to follow-up and exclusions during the study, and out-
come and exposure data were largely complete. Those workers (n=2) who had moved
out of the country and were lost to follow-up were excluded. Those (n=2) with no as-
bestos exposure history were also excluded. Smoking history data was not provided by
one worker. Radiological data was available for n=301 workers.
Medium Key elements of study design, such as inclusion and exclusion criteria and methods of
participant selection, were reported and indicate that subjects were similar. Participant
recruitment strategies were not detailed, but participating workers appear to have been
from the same eligible population within the same time frame. It is unclear to what ex-
tent various aspects (healthy hire, healthy worker survivor, left truncation bias, exposure-
dependent right censoring) of the healthy worker effect might have been a factor in the
cohort for study.
Domain 2: Exposure Characterization
Continued on next page .
Page 428 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2079066 Table: 1 of 2
... continued from previous page
Moshammer, H., Neuberger, M. (2009). Lung function predicts survival in a cohort of asbestos cement workers. International Archives of Occupational
and Environmental Health 82(2009): 199-207.
Respiratory disease mortality, cardiovascular disease mortality, survival, total life expectancy
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Respiratory disease mortality, Cardiovascular disease mortality, Survival; Lung/Respiratory: Respiratory disease mortality, FEV1, FVC, PEF,
MEF75, MEF50, MEF25, Rounded small opacities, Irregular small opacities, Pleural thickening, Large opacities; Cardiovascular: Cardiovascular disease
mortality; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
2079066
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Estimated cumulative exposure was described as based upon historical spot measure-
ments analyzed by light microscopy and exposure classifications assigned to each work
area. Workplace asbestos exposure spot measurement records were available from 1950
until 1981. Each worker was assigned a specific category of exposure for every year
that worker worked at the asbestos cement factory. Details regarding consideration for
changes in job area or task during that year were not provided. Authors did not discuss
the potential for exposure misclassification within these methods, but the misclassi-
fication was likely non-differential. Mean (IQR) estimated cumulative exposure was
reported in Table 2 as 72.62 fiber years (fibers x years/cmA 3) (70.81).
Medium In the Cox regression model asbestos exposure was modeled as a continuous variable,
but amphibole exposure was model as binary. The range and distribution of estimated
exposure across five workplace areas is presented in Table 1. Estimated cumulative
exposures were utilized and 70 fibre years were chosen because it approximated the IQR
Medium The study establishes appropriate temporality. Depending upon the date of hire and
outcome of interest, it is unclear if the interval between exposure and outcome was
adequate for all participants for all outcomes by the end of follow up in 2006 .
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Medium Other Non-Cancer Outcomes: Non-cancer outcomes of interest were mortality from
respiratory disease, cardiovascular disease, as well as survival and total life expectancy,.
Mortality data were obtained from official death certificates. Details regarding validity
of death certificate data were lacking. ICD coding utilized for death certificates was not
detailed.
High There were no concerns for selective reporting as all outcomes which were outlined
within methods were also reported within the results. Effect estimates were reported as
hazard ratios with corresponding 95% confidence intervals (CI"s) for results in Tables
4, 6 and 7 for mortality outcomes, as regression coefficients and 95% CI"s within Ta-
ble 8 for lung function outcomes and as odds ratios with 95% CI"s for x-ray analysis
outcomes.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Medium Mortality analyses appear to have been adjusted for age and smoking. Lung function
outcomes were adjusted for gender and age. Outcomes from x-ray analyses were ad-
justed for smoking history. The strategy for selection of potential confounders, as well
as the distribution of potential confounders, was not detailed, however authors noted the
use of stepwise regression with removal of model parameters with p>0.1 significance.
Continued on next page ...
Page 429 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2079066 Table: 1 of 2
... continued from previous page
Moshammer, H., Neuberger, M. (2009). Lung function predicts survival in a cohort of asbestos cement workers. International Archives of Occupational
and Environmental Health 82(2009): 199-207.
Respiratory disease mortality, cardiovascular disease mortality, survival, total life expectancy
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Respiratory disease mortality, Cardiovascular disease mortality, Survival; Lung/Respiratory: Respiratory disease mortality, FEV1, FVC, PEF,
MEF75, MEF50, MEF25, Rounded small opacities, Irregular small opacities, Pleural thickening, Large opacities; Cardiovascular: Cardiovascular disease
mortality; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
2079066
Domain
Metric
Rating
Comments
Metric 10:
Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium
Low
Method of assessment of covariate data was not detailed, although can be assumed to
have been from occupational personnel history and death certificate sources. Consid-
eration for validation of covariates not detailed. Analyses of some outcomes (x-ray
analyses outcomes) did not appear to have included all potential main confounders and
distributions of potential covariates across exposure groups was not reported.
The members of the cohort were workers at an asbestos cement factory in Austria. Po-
tential co-exposures were not discussed, although there was no evidence that there was
an unbalanced provision of potential co-exposures among exposure groups. Authors
noted use of personal protective equipment after 1981. Considerations for workers who
might have initially left and worked elsewhere with additional exposures but eventually
returned to the asbestos plant and cohort for study were not detailed.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study utilized appropriate study design and statistical methods to address the re-
search questions. Life expectancy and mortality outcomes were assessed using propor-
tional hazards regression, lung function outcomes were assessed using linear regression,
and presence of x-ray outcomes were assessed using logistic regression.
Medium The number of participants (n=309 for mortality and lung function, n=301 for x-ray
outcomes) was adequate to address the research questions. The number of non-smokers
within the cohort was not detailed.
Medium In general, the statistical analyses were described within the text in a way that might
facilitate reproducibility, although details regarding initial model covariates in each table
of regression analyses were lacking, transformation of continuous variables was not
detailed and there was no separate detailed section within the text for description of the
statistical analyses.
Medium The method used for calculating risk estimates was adequately described.
Additional Comments: Asbestosis was mentioned as an outcome only in the sense that the study text mentions that no cases of asbestosis was found as a cause of death.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 430 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2079066 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Moshammer, H., Neuberger, M. (2009). Lung function predicts survival in a cohort of asbestos cement workers. International Archives of Occupational
and Environmental Health 82(2009): 199-207.
Pulmonary Function/Spirometry Results; Pleural Plaques
Mortality: Respiratory disease mortality, Cardiovascular disease mortality, Survival; Lung/Respiratory: Respiratory disease mortality, FEV1, FVC, PEF,
MEF75, MEF50, MEF25, Rounded small opacities, Irregular small opacities, Pleural thickening, Large opacities; Cardiovascular: Cardiovascular disease
mortality; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): No linked references.
2079066
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection Medium Key elements of study design were reported in this historical prospective study of n=309
asbestos cement factory workers who were in 1989/1990 aged 57.0 years (+/- 9.5 years)
in Vocklabruck, Upper Austria and were followed from 1974-2006. Estimated cumula-
tive exposure was based upon historical spot measurement data and exposure classifica-
tions assigned to each work area. Cohort formation began with workers in 1974 through
1981 when personal protective equipment became available to workers, and biannual
medical evaluations were available beginning in 1989 and vital status was updated until
the end of 2006. Workplace asbestos exposure spot measurement records were avail-
able from 1950 until 1981. The initial cohort of workers who agreed to participate in
extended biannual medical evaluations beginning in 1989 consisted of n=322 active and
retired workers. Of these, n=309 workers (n=270 males and n=39 females) with com-
plete asbestos exposure history and whose vital status could be followed until the end of
2006 were included.
Metric 2: Attrition High There was minimal subject loss to follow-up and exclusions during the study, and out-
come and exposure data were largely complete. Those workers (n=2) who had moved
out of the country and were lost to follow-up were excluded. Those (n=2) with no as-
bestos exposure history were also excluded. Smoking history data was not provided by
one worker. Radiological data was available for n=301 workers.
Metric 3: Comparison Group Medium Key elements of study design, such as inclusion and exclusion criteria and methods of
participant selection, were reported and indicate that subjects were similar. Participant
recruitment strategies were not detailed, but participating workers appear to have been
from the same eligible population within the same time frame. It is unclear to what ex-
tent various aspects (healthy hire, healthy worker survivor, left truncation bias, exposure-
dependent right censoring) of the healthy worker effect might have been a factor in the
cohort for study.
Domain 2: Exposure Characterization
Continued on next page ...
Page 431 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2079066 Table: 2 of 2
... continued from previous page
Moshammer, H., Neuberger, M. (2009). Lung function predicts survival in a cohort of asbestos cement workers. International Archives of Occupational
and Environmental Health 82(2009): 199-207.
Pulmonary Function/Spirometry Results; Pleural Plaques
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Respiratory disease mortality, Cardiovascular disease mortality, Survival; Lung/Respiratory: Respiratory disease mortality, FEV1, FVC, PEF,
MEF75, MEF50, MEF25, Rounded small opacities, Irregular small opacities, Pleural thickening, Large opacities; Cardiovascular: Cardiovascular disease
mortality; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
2079066
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Estimated cumulative exposure was described as based upon historical spot measure-
ments analyzed by light microscopy and exposure classifications assigned to each work
area. Workplace asbestos exposure spot measurement records were available from 1950
until 1981. Each worker was assigned a specific category of exposure for every year
that worker worked at the asbestos cement factory. Details regarding consideration for
changes in job area or task during that year were not provided. Authors did not discuss
the potential for exposure misclassification within these methods, but the misclassi-
fication was likely non-differential. Mean (IQR) estimated cumulative exposure was
reported in Table 2 as 72.62 fiber years (fibers x years/cmA 3) (70.81).
Medium In the Cox regression model asbestos exposure was modeled as a continuous variable,
but amphibole exposure was model as binary. The range and distribution of estimated
exposure across five workplace areas is presented in Table 1. Estimated cumulative
exposures were utilized and 70 fibre years were chosen because it approximated the IQR
Medium The study establishes appropriate temporality. Depending upon the date of hire and
outcome of interest, it is unclear if the interval between exposure and outcome was
adequate for all participants for all outcomes by the end of follow up in 2006 .
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High Pulmonary Function/Spirometry Results: Pulmonary function outcomes of interest were
lung function (FEV1, FVC, PEF, MEF75, MEF50, MEF25). Lung function testing was
conducted by spirometry.; Pleural Plaques: Pleural plaque outcomes of interest were
from x-ray findings (rounded small opacities, irregular small opacities, pleural thicken-
ing, large opacities). Opacities in x-ray results were described as classified according to
ILO classification.
High There were no concerns for selective reporting as all outcomes which were outlined
within methods were also reported within the results. Effect estimates were reported as
hazard ratios with corresponding 95% confidence intervals (CI"s) for results in Tables
4, 6 and 7 for mortality outcomes, as regression coefficients and 95% CI"s within Ta-
ble 8 for lung function outcomes and as odds ratios with 95% CP's for x-ray analysis
outcomes.
Domain 4: Potential Confounding / Variability Control
Continued on next page ...
Page 432 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2079066 Table: 2 of 2
... continued from previous page
Moshammer, H., Neuberger, M. (2009). Lung function predicts survival in a cohort of asbestos cement workers. International Archives of Occupational
and Environmental Health 82(2009): 199-207.
Pulmonary Function/Spirometry Results; Pleural Plaques
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Respiratory disease mortality, Cardiovascular disease mortality, Survival; Lung/Respiratory: Respiratory disease mortality, FEV1, FVC, PEF,
MEF75, MEF50, MEF25, Rounded small opacities, Irregular small opacities, Pleural thickening, Large opacities; Cardiovascular: Cardiovascular disease
mortality; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
2079066
Domain
Metric
Rating
Comments
Metric 9: Covariate Adjustment
Metric 10:
Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Mortality analyses appear to have been adjusted for age and smoking. Lung function
outcomes were adjusted for gender and age. Outcomes from x-ray analyses were ad-
justed for smoking history. The strategy for selection of potential confounders, as well
as the distribution of potential confounders, was not detailed, however authors noted the
use of stepwise regression with removal of model parameters with p>0.1 significance.
Medium Method of assessment of covariate data was not detailed, although can be assumed to
have been from occupational personnel history and death certificate sources. Consid-
eration for validation of covariates not detailed. Analyses of some outcomes (x-ray
analyses outcomes) did not appear to have included all potential main confounders and
distributions of potential covariates across exposure groups was not reported.
Low The members of the cohort were workers at an asbestos cement factory in Austria. Po-
tential co-exposures were not discussed, although there was no evidence that there was
an unbalanced provision of potential co-exposures among exposure groups. Authors
noted use of personal protective equipment after 1981. Considerations for workers who
might have initially left and worked elsewhere with additional exposures but eventually
returned to the asbestos plant and cohort for study were not detailed.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study utilized appropriate study design and statistical methods to address the re-
search questions. Life expectancy and mortality outcomes were assessed using propor-
tional hazards regression, lung function outcomes were assessed using linear regression,
and presence of x-ray outcomes were assessed using logistic regression.
Medium The number of participants (n=309 for mortality and lung function, n=301 for x-ray
outcomes) was adequate to address the research questions. The number of non-smokers
within the cohort was not detailed.
Medium In general, the statistical analyses were described within the text in a way that might
facilitate reproducibility, although details regarding initial model covariates in each table
of regression analyses were lacking, transformation of continuous variables was not
detailed and there was no separate detailed section within the text for description of the
statistical analyses.
Medium The method used for calculating risk estimates was adequately described.
Additional Comments: Asbestosis was mentioned as an outcome only in the sense that the study text mentions that no cases of asbestosis was found as a cause of death.
Overall Quality Determination Medium
Continued on next page ...
Page 433 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2079066 Table: 2 of 2
... continued from previous page
Moshammer, H., Neuberger, M. (2009). Lung function predicts survival in a cohort of asbestos cement workers. International Archives of Occupational
and Environmental Health 82(2009): 199-207.
Pulmonary Function/Spirometry Results; Pleural Plaques
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Respiratory disease mortality, Cardiovascular disease mortality, Survival; Lung/Respiratory: Respiratory disease mortality, FEV1, FVC, PEF,
MEF75, MEF50, MEF25, Rounded small opacities, Irregular small opacities, Pleural thickening, Large opacities; Cardiovascular: Cardiovascular disease
mortality; nan:
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
2079066
Domain
Metric
Rating
Comments
* No biomarkers were identified for this evaluation.
Page 434 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081301 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Murai, Y., Kitagawa, M., Hiraoka, T. (1997). Fiber analysis in lungs of residents of a Japanese town with endemic pleural plaques. Archives of Environ-
mental Health 52(1997):263-269.
Pleural Plaques
Lung/Respiratory: Pleural plaque
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Actinolite: 12172-67-7; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Tremolite:
14567-73-8; Asbestos - Anthophyllite: 17068-78-9; Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
3081301
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
High Asbestos fiber levels were assessed by TEM and method details were described in the
study. The fiber quantification methods were applied for all samples. Comparison be-
tween asbestos bodies counted by optical microscope multiplied by the ratio of total
asbestos fibers to coated asbestos fibers and the TEM results was performed as quality
control step. There is minimal concern of exposure misclassification according to the
description.
Uninformative Mean fiber levels of each fiber type were reported and compared between patients with
pleural plaque and those without. Description of exposure distribution is limited and not
sufficient to determine an exposure-response relationship.
Additional Comments: None
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessment for the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 435 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 144 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Murphy, R. L. H., Ferris, B. G., Jr, Burgess, W. A., Worcester, J., Gaensler, E. A. (1971). Effects of low concentrations of asbestos: clinical, environmental,
radiologic and epidemiologic observations in shipyard pipe coverers and controls. New England Journal of Medicine 285(1971):1271-1278.
Asbestosis
Lung/Respiratory: Lung function (spirometry, respiratory questionnaires, physical exam, x-rays)., Asbestosis (3 or more of 5 symptoms: dyspnea, rales,
spirometry, finger clubbing, x-rays).
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
144
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium The authors included all 101 asbestos-exposed pipe coverers and 94 unexposed workers
employed at a New England shipyard in November 1965. Pipe coverers were exposed to
low levels of asbestos through work that involved preparing and applying insulating ma-
terials; materials and procedures had not varied appreciably since 1945. Ascertainment
of prevalent workers was complete. The main issue of note is that no former workers
were included, and no information on rates of or reasons for stopping pipe covering
work provided. As notedin the literature, occupational epidemiology studies limited to
prevalent workers are susceptible to healthy worker effect bias (Pearce et al 2007, HERO
ID: 713676). HWE can result from "the phenomenon that sicker or more sensitive indi-
viduals may choose work environments in which exposures are low" or once hired, they
may seek transfer to less exposed jobs or leave work" (Le Moual et al 2008 HERO ID:
1580313). Though there is no direct evidence of HWE, the authors mention the exis-
tence of company medical records that included information on cardiorespiratory health
(e.g. indicating more frequent dyspnea in pipe coverers, less frequent non-obstructive
lung disease).
High All currently employed pipe coverers participated in the study, along with 94 of the 101
initially selected controls (93% ).
High The comparison group comprised shiplifters and pipefitters employed at the same ship-
yard in November 1965. This group was selected to be comparable to the exposed work-
ers with the exception of asbestos-containing dust exposure. Controls were matched to
the exposed subjects by age (+/- ly), selecting the first eligible candidate on the list with
"approximately the same time at the yard". Mean age and years of employment in the
exposed vs. the comparison group were similar (age 41.5 vs 40.9y, duration employed
17.4 vs 17.ly), as were height, weight, and smoking history. Details on work activities
were not provided, but the authors stated that "cumulative years in dusty occupations
other than pipe covering did not differ in the two groups" (results paragraph 1).
Domain 2: Exposure Characterization
Continued on next page .
Page 436 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 144 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Murphy, R. L. H., Ferris, B. G., Jr, Burgess, W. A., Worcester, J., Gaensler, E. A. (1971). Effects of low concentrations of asbestos: clinical, environmental,
radiologic and epidemiologic observations in shipyard pipe coverers and controls. New England lournal of Medicine 285(1971):1271-1278.
Asbestosis
Lung/Respiratory: Lung function (spirometry, respiratory questionnaires, physical exam, x-rays)., Asbestosis (3 or more of 5 symptoms: dyspnea, rales,
spirometry, finger clubbing, x-rays).
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
144
Domain
Metric
Rating
Comments
Metric 4:
Measurement of Exposure
Medium
Quantitative exposure estimates were based on fiber concentrations from midget im-
pinger measures obtained in a single year - 1965 - using the Public Health Service
method, which involves PCM (see Edwards et al, 1968 HERO ID 783893). Details
such as numbers and timing of samples were not provided. Historical measures using
a konimeter from 1945, 1965 and 1966 counting "particles with a length-to-diameter
ratio greater than 3" were not used, as levels were considerably higher than simultaneous
impinger data. For example, weighted averages for 1965 incorporating multiple work
locations were 5.2 vs. 21.4 to 23.4 million particles per cubic foot (mppcf) (Table 1,
text). Konimeter measures from the three periods indicated variation in exposure over
time, with measures aboard ship decreasing (means = 49.2, 21.4 and 25.9 mppcf) and
measures in sewing and fabrication areas increasing (11.4, 23.4 and 23.1 mppcf).
Metric 5:
Exposure Levels
Medium
Exposure duration in years was categorized in 5 levels: 0-<5, 5-< 11, 11-<15, 15-<20,
and 20-35y. Quantification in millions of particles per cubic foot (mppcf) was estimated
using midget impinger measures from 1965; historical midget impinger data were not
available.
Metric 6:
Temporality
Medium
The study design was cross-sectional, as outcomes were measured at the time the study
was conducted. However, the use of historical exposure data and the long mean duration
of employment (17y) ensures appropriate temporality, that exposure preceded outcome
measures.
Domain 3: Outcome Assessment
Continued on next page .
Page 437 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 144 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Murphy, R. L. H., Ferris, B. G., Jr, Burgess, W. A., Worcester, J., Gaensler, E. A. (1971). Effects of low concentrations of asbestos: clinical, environmental,
radiologic and epidemiologic observations in shipyard pipe coverers and controls. New England lournal of Medicine 285(1971):1271-1278.
Asbestosis
Lung/Respiratory: Lung function (spirometry, respiratory questionnaires, physical exam, x-rays)., Asbestosis (3 or more of 5 symptoms: dyspnea, rales,
spirometry, finger clubbing, x-rays).
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
144
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
Metric 8:
Reporting Bias
High Asbestosis: Diagnosis of asbestosis is based on a physical exam and known exposure
to asbestos. Asbestosis was defined for this study as having 3 or more of the following
5 indications, all measured and evaluated by trained study staff: dyspnea, rales, finger
clubbing, reduced FVC and x-ray shadows. Assessment of each indication was de-
scribed briefly but adequately. (1) Habitual dyspnea, wheezing: self-reported using a
respiratory symptom questionnaire adapted from one extensively used in the literature
(one interviewer; reference cited. (2) Rales (breath sounds from 8 locations, recorded):
physical exam (one physician, reference cited). (3) Finger clubbing: physical exam with
frontal and lateral tracing outlines made used to measure hyponychial angle (fingernail)
of the right index finger (one physician, reference cited). (4) Spirometry: FEV1, FVC
and peak flow (PF) from tests administered in random order (calibration and analysis
reference cited). (5) Chest x-rays (roentgenogram): posterior and lateral views examined
and rated in random order by three radiologists blinded to exposure status, ratings based
on combined readings. Negative TB tests were confirmed, none of the workers had di-
agnosed asthma. All 11 cases of asbestosis in pipe coverers met x-ray criteria; each of
the other criteria was present in 8 or 9. Prevalence of each indication was correlated with
measures of impaired lung diffusing capacity (Figure 2). Moreover, all 8 cases who con-
sented to an independent medical exam were found to have symptoms consistent with
asbestosis, and 3 cases who subsequently died had asbestosis.
Medium Descriptive data comparing all outcomes exposed and unexposed workers were provided
(Tables 2 and 3); p-values were shown when significant. The proportion of subjects with
asbestosis and with each indication used to define asbestosis was shown stratified by
increasing duration of exposure (Figures 3 and 4). However, numbers of participants
by duration of exposure were not shown. For example, in Figure 3 there are data points
shown for 5 exposure duration categories, based on only 11-12 individuals with asbesto-
sis. Presenting only percentages masked the sparse sample available for these analyses.
Because impinger data were available only for a snapshot in time, figures do not further
quantify asbestos exposure in fiber-years. However, in the text they use the mean con-
centration measured by impinger to extrapolate cumulative exposure based on exposure
duration.
Domain 4: Potential Confounding / Variability Control
Continued on next page ...
Page 438 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 144 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Murphy, R. L. H., Ferris, B. G., Jr, Burgess, W. A., Worcester, J., Gaensler, E. A. (1971). Effects of low concentrations of asbestos: clinical, environmental,
radiologic and epidemiologic observations in shipyard pipe coverers and controls. New England lournal of Medicine 285(1971):1271-1278.
Asbestosis
Lung/Respiratory: Lung function (spirometry, respiratory questionnaires, physical exam, x-rays)., Asbestosis (3 or more of 5 symptoms: dyspnea, rales,
spirometry, finger clubbing, x-rays).
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
144
Domain
Metric
Rating
Comments
Metric 9:
Covariate Adjustment
Medium
Analyses did not adjust for potential confounders. However, potential confounding
by age and duration of employment was addressed by matching on these factors. The
authors further assessed confounding by age by demonstrating that the prevalence of al-
most all asbestosis indications increased with age in exposed but not unexposed workers
(Figure 5). The authors also showed that other potential confounders - smoking habits,
weight, and height" were similar among exposed and unexposed subjects. Job selection
for controls aimed to account for SES confounding: the authors state in the introduction
that their aim was to identify a "control group comparable in all respects except for dust
exposure". Race was not discussed; all participants were male.
Metric 10:
Covariate Characterization
Medium
Company records and an established questionnaire were used to characterize age, smok-
ing history, and job function.
Metric 11:
Co-exposure Counfounding
Medium
The authors stated that "cumulative years in dusty occupations other than pipe covering
did not differ in the two groups (results paragraph 1). Other potential co-exposures were
not discussed, but there is no evidence to suggest important co-exposure confounding.
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
Appropriate comparisons of outcomes in exposed workers vs unexposed controls were
presented as means with SDs and percentages in tables and figures. Methods used to
derive p-values were not provided. Statistical testing was not reported for the main anal-
yses shown in Figures 3 and 4. Note: there is an apparent labeling error in Figure 4.
The 5 duration of exposure categories appear to have been mislabeled using the 5 age
categories which are shown in relation to the same outcome measures in Figure 5.
Metric 13:
Statistical Power
Medium
The sample of 195 participants (101 exposed) seems sufficient for analyses of numerous
outcomes, including individual indications/symptoms of asbestosis. The prevalence of
the majority of indications was on the order of 20% (13% for x-rays coded 5 or 6). For
asbestosis, which is extremely rare, 12 cases were identified. The authors were able to
illustrate and increasing prevalence of asbestosis with increasing duration of exposure.
However, results were likely imprecise, and no confidence intervals or p-values were
provided.
Metric 14:
Reproducibility of Analyses
Medium
Information presented in tables and figures is sufficiently detailed to facilitate recon-
structing the analyses. However, the specific statistical tests used were not described.
Metric 15:
Statistical Analysis
Medium
Statistical modeling was not employed; confounding was addressed appropriately by
matching on age and duration of employment, as well as by selecting workers from the
same facility also employed doing skilled manual labor.
Continued on next page ...
Page 439 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 144 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Murphy, R. L. H., Ferris, B. G., Jr, Burgess, W. A., Worcester, J., Gaensler, E. A. (1971). Effects of low concentrations of asbestos: clinical, environmental,
radiologic and epidemiologic observations in shipyard pipe coverers and controls. New England lournal of Medicine 285(1971):1271-1278.
Asbestosis
Lung/Respiratory: Lung function (spirometry, respiratory questionnaires, physical exam, x-rays)., Asbestosis (3 or more of 5 symptoms: dyspnea, rales,
spirometry, finger clubbing, x-rays).
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
144
Domain Metric Rating Comments
Additional Comments: This study analyzed health effects of low-level exposure to asbestos among all 101 pipe coverers working at a New England shipyard in 1965, employed
for a mean of 17 years. Amosite and to a lesser extent chrysotile asbestos were used to insulate pipes. Exposed workers were compared with 94 unexposed
shiplifters and pipefitters who were matched on age and duration of employment at the same shipyard. The study measured pulmonary function and
physical exam indications used to diagnose asbestosis, defining asbestosis as 3 or more of the following 5 indications, measured by trained study staff:
dyspnea, rales, finger clubbing, reduced FVC and x-ray shadows. The validity of diagnosis was supported by internal consistency of symptoms and
independent medical exams. While duration of exposure was readily assessed, quantitative estimates based on fiber counts were crudely estimated based
on midget impinger data from a 1965 because historical data measured by konimeter were not comparable, and not readily converted. The weighted mean
concentration across locations was 5.2 million particles per cubic foot (mppcf), close to the threshold limit of 5 mppcf recommended at the time. Asbestosis
was not identified among individuals with fewer than 10 years of exposure. The authors provide data illustrating increases in each of the indications of
asbestosis, and of study-defined asbestosis, with increasing duration of this low level of exposure above that threshold. Issues of concern include the small
numbers of cases, as well as limiting the sample to prevalent workers, which has the potential to induce a healthy worker effect bias due to selective attrition
or transfer of individuals who are sicker or more susceptible to health effects of the occupational exposure.
Overall Quality Determination nan
* No biomarkers were identified for this evaluation.
Page 440 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3080762 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Mdndi, A., Posgay, M., VacMsz, P., Major, K., Rodelsperger, K., Tossavainen, A., Ungvdry, G., Woitowitz, H. J., Galambos, E., N&neth, L., Solt&z,
I., Egervdry, M., Boszorm&iyi Nagy, G. (2000). Role of occupational asbestos exposure in Hungarian lung cancer patients. International Archives of
Occupational and Environmental Health 73(2000):555-560.
Lung Cancer
Cancer/Carcinogenesis: Lung cancer, Mesothelioma; Lung/Respiratory: Diffuse pleural changes, Pleural plaques, Fibrosis, Mesothelioma, Lung cancer
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3080762
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Exposure status was self-reported retrospectively at the time of recruitment (after out-
come diagnosis). Exposure categories were never exposed, uncertain about exposure
history, <25 fiber-years, and >25 fiber years. Substantial concern for recall bias and
outcome misclassification due to reliance on retrospective self-reporting. Exposure esti-
mates for the majority of subjects are not quantitative in nature.The presence of asbestos
fibers in lung tissue was assessed by scanning transmission electron microscopy for 25/
300 patients. Fiber counts were strongly correlated with self-reported cumulative fiber
exposure values.
Low No description is provided on levels or range of exposure other than fiber-years category
(<25 or >25).The presence of asbestos fibers in lung tissue was assessed by scanning
transmission electron microscopy for 25/300 patients. Fiber counts were strongly corre-
lated with self-reported cumulative fiber exposure values.
Additional Comments: None
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 441 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082545 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Neuberger, M., Kundi, M. (1990). Individual asbestos exposure: Smoking and mortality"a cohort study in the asbestos cement industry. British Journal of
Industrial Medicine 47(1990):615-620.
Lung Cancer
Lung/Respiratory: Lung cancer; Cancer/Carcinogenesis: Lung cancer
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Not specified: 1332-21-4
No linked references.
3082545
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Metric 3:
Attrition
Comparison Group
Medium Eligibility criteria not described in detail (e.g., "of the 2816 persons eligible for the
study"), but other key details of participants described. "A possible reason for underesti-
mation of risk for lung cancer can be selection bias through a healthy worker effect, but
the total SMR (overall mortality) and the mortality from lung cancer of the low expo-
sure group (table 2) indicates that it did not play an important part in our study." A brief
description of the study setting and asbestos use was provided.
Medium A total of 121 persons lost to follow up. Authors note this was mostly due to emigration.
High SMRs were calculated using an "age and sex matched reference population" (Table 2)
from the same region-upper Austria.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium "Individual exposures were estimated (from 1973) from personal records onduration
of exposure at different workplaces, estimations of dust concentration until 1965, dust
measurements mainly by a conimeter method until 1975, and by personal air samplers
and membrane filter methods (Asbestos International Association, HERO 3648707) sub-
sequently. " The referenced study (HERO 3648707) cites the use of PCM methodology
to count fibres. Details on implementation for this study were limited, but it appears they
followed a standard protocol.
Medium The study reports two exposure groups <=25 fibres/ml-year and >25 fibres/ml-year, in
addition to the referent group.
High To investigate the latency of lung cancer induced by asbestos we removed from our
cohort all persons who had not been observed for more than 15 years from start of expo-
sure.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High Lung Cancer: Follow up on vital status for participants was undertaken using govern-
ment registration offices, death registries, physicians, and pathologists. Lung cancer was
identified using ICD-9 162.
High Table 2 indicates mortality from lung cancer for Austrian asbestos cement workers from
1950-1986 for the 2 exposure groups. The number of observed, expected, and confi-
dence intervals are provided.
Domain 4: Potential Confounding / Variability Control
Continued on next page ...
Page 442 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082545 Table: 1 of 1
... continued from previous page
Neuberger, M., Kundi, M. (1990). Individual asbestos exposure: Smoking and mortality"a cohort study in the asbestos cement industry. British lournal of
Industrial Medicine 47(1990):615-620.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Lung cancer; Cancer/Carcinogenesis: Lung cancer
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Not specified: 1332-21-4
No linked references.
3082545
Domain
Metric
Rating
Comments
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High Appropriate adjustments or explicit considerations were made for potential confounders
including age, sex, and smoking.
High Smoking was recorded using a "standardised questionnaire on occupational exposures
and smoking." Age and sex were presumably drawn from employment records.
Low In an occupational setting, potential co-exposures are not discussed.
Domain 5: Analysis
Metric 12: Study Design and Methods Medium SMRs were used to compare incidence of lung cancer mortality between the occupa-
tional group and the general population. Life-table analyses were used to compare rates
of mortality among the two exposed groups.
Metric
13:
Statistical Power
Medium
The overall population was 2,816, and authors observed 49 lung cancer cases, and 4
mesothelioma cases. No concerns.
Metric
14:
Reproducibility of Analyses
Medium
SMR and Life-table analysis methodology described sufficiently for reproduction.
Metric
15:
Statistical Analysis
Medium
Methods were standard. No concerns with SMRs or life-table analyses.
Additional Comments: Historical prospective cohort study analyzing 49 lung cancer and 4 mesothelioma cases from asbestos-exposed cement factory workers. Methods were
generally standard, but some details were not present regarding selection and exposure measurement, however, this is not likely to appreciably impact the
results. Study includes life table analysis, poison logistic regression, PCM, and SMR.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 443 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082792 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Newhouse, M. L., Sullivan, K. R. (1989). A mortality study of workers manufacturing friction materials: 1941-86. British Journal of Industrial Medicine
46(1989):176-179.
Lung Cancer; other cancers mortality; gastrointestinal cancer mortality; respiratory disease mortality, mortality from other causes
Lung/Respiratory: Respiratory disease mortality, Lung and pleural cancer mortality; Mortality: Mortality from other causes (other than lung and pleural
cancer, gastrointestinal cancer, other cancers, and respiratory disease), Respiratory disease mortality, Lung and pleural cancer mortality, Gastrointestinal
cancer mortality, Other cancers mortality; Cancer/Carcinogenesis: Lung and pleural cancer mortality, Gastrointestinal cancer mortality, Other cancers
mortality; Gastrointestinal: Gastrointestinal cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3082792
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This paper was evaluated for ovarian cancer mortality, lung cancer mortality, and laryn-
geal cancer mortality in Asbestos Part 1 and was rated Low for this metric. As described
in the Final Risk Evaluation for Asbestos Part 1 Systematic Review Supplemental File,
"Exposure assessed based solely on duration of employment at the plant. Job titles were
not available. Exposure levels are reported at the plant level (over 20 fibers/ml before
1931, 5-20 f/mL from 1931-1950, less than 5 f/mL after 1970)."
Medium This paper was evaluated for ovarian cancer mortality, lung cancer mortality, and la-
ryngeal cancer mortality in Asbestos Part 1 but was not rated for this metric. Exposure
levels at the plant ranged from less than 5 fibers/ml after 1970 to more than 20 fibers/ml
before 1931. The paper presents SMRs for five categories of year of start of employment
(pre-1940, 1941-1950, 1951-1960, 1961-1970, and 1971-). Year of start of employment
is a proxy for exposure levels, with exposure levels being lower for later start years.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis. This paper was evaluated for lung cancer mortality and laryngeal cancer mortality in Asbestos Part 1 and was rated Low for Metric 4 and was
not rated for Metric 5 for all three outcomes. The Overall Quality Determination for the study was Low for all three outcomes assessed in Asbestos Part 1.
The methods for the other outcomes assessed in this paper were the same as the methods assessed in Asbestos Part 1, indicating that the Overall Quality
Determination for this paper is likely to be Low.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 444 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 158 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Nicholson, W. J., Selikoff, I. J., Seidman, H., Lilis, R., Formby, P. (1979). Long-term mortality experience of chrysotile miners and millers in Thetford
Mines, Quebec. Annals of the New York Academy of Sciences, Vol. 330 33021-Nov.
Lung Cancer; Asbestosis
Lung/Respiratory: Asbestosis, Lung cancer; Mortality: All-cause mortality (excluding cancers), Lung cancer; Cancer/Carcinogenesis: Lung cancer
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
158
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This study revolved around a cohort of men employed for at least 20 years in one of
four companies that mine and mill chrysotile, exclusively. This represented 544 indi-
viduals from four separate operations. These operations were examined in Thetford
Mines, Quebec, Canada. The participants included represented a variety of potential job
classifications. However, not many details beyond this were included pertaining to in-
clusion criteria, such as the total number of individuals that could have potentially been
included.
Medium There was moderate exclusion of participants from analyses. The aim of this study was
to determine mortality outcomes for participants enrolled from the asbestos mines. The
authors were able to obtain 172 certificates of death, and there were an additional 130
cases for which the authors obtained clinical, surgical, and pathological data to supple-
ment death certificate information.
Medium The expected number of deaths/illnesses included in this study were derived from the
age-specific death rate data for white Canadian males. It is important to note that they
did not use data specific to Quebec, but it is noted that "national rates are not impor-
tantly different from those of Quebec province but are likely to be significantly higher
than those of the rural mining counties in which these workers lived" (Nicholson et
al., 1979). The authors also explicitly discuss the potential for healthy worker effect,
but they mention that "the effects of asbestos exposure appear to overcome the bene-
ficial health status usually associated with employ ability" (Nicholson et al., 1979). As
mentioned, the participants were compared to white Canadian males, but there was no
discussion of the racial makeup of employees.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure High The authors report that 97 air samples were collected from various work locations within
five operating asbestos mines/mills. These samples were collected between 1973 and
1975, and a majority of them were personal samples. The concentrations varied greatly,
but it is reported that "in virtually all work categories average dust concentrations ex-
ceeded the asbestos standard then current in the United States of 5 fibers longer than 5
micrometers/milliliter (5 f/ml)" (Nicholson et al., 1979). The authors detail that they fol-
lowed the methods outlined by the National Institute of Occupational Safety and Health
to determine asbestos concentrations, which utilizes a microscope with phase contrast
optics (1972, 145).
Continued on next page ...
Page 445 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 158 Table: 1 of 2
... continued from previous page
Nicholson, W. J., Selikoff, I. J., Seidman, H., Lilis, R., Formby, P. (1979). Long-term mortality experience of chrysotile miners and millers in Thetford
Mines, Quebec. Annals of the New York Academy of Sciences, Vol. 330 33021-Nov.
Lung Cancer; Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Asbestosis, Lung cancer; Mortality: All-cause mortality (excluding cancers), Lung cancer; Cancer/Carcinogenesis: Lung cancer
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
158
Domain
Metric
Rating
Comments
Metric 5:
Metric 6:
Exposure Levels
Temporality
Medium Multiple levels of asbestos exposure were presented in the study. Table 3 includes a
range, mean, and number of samples of asbestos in each of the mine/mill locations. It is
also further divided into various work areas/activities, including general mill air, bagging
asbestos, quality control laboratory, crusher, dryer, shops, and nonwork areas. This table
highlights that a majority of the cohort was employed in facility two, and concentrations
are reported in fibers longer than 5 micrometers/ml of air.
High One of the requirements to be included in this study was that the workers must have
been employed for at least 20 years. This means that there is an appropriate temporality
between exposure and outcome such that exposure occurred prior to the outcome.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or Medium Lung Cancer: To identify vital status of participants, the authors examined death certifi-
Characterization cates of those enrolled in the study. In instances where the authors were unable to obtain
death certificates due to not receiving permission from next of kin, they instead looked
at hospital records and autopsy protocols. In 130 cases (not necessarily lung cancer par-
ticipants), clinical, surgical, or pathological data was available.; Asbestosis: Vital status
for deceased participants were determined by examining death certificates. Some death
certificates were unable to be examined because the next of kin refused or contact could
not be made. There was no report of using imaging tests, but it is likely that a doctor
performed the autopsies to identify asbestosis. The authors did report that there were
some cases of misclassification of the health status. Due to asbestosis only developing
from asbestos exposure in the lungs, it "is an extremely rare cause of death in other than
occupational circumstances, the general population rates are not subject to error from its
misdiagnosis on certificated of death" (Nicholson et al., 1979).
Metric 8: Reporting Bias Medium The findings are reported at various points throughout the study. Expected and observed
deaths are reported, along with the O/E calculations. However, information such as
confidence intervals are not reported, contributing to the medium rating.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Low No description is provided in this study that discusses considerations for potential con-
founders or their adjustment.
Metric 10: Covariate Characterization N/A Covariates were not assessed in this study.
Metric 11: Co-exposure Counfounding Low Potential co-exposures were not explicitly discussed in this study. It was mentioned in
the discussion section that workers in some positions would work with materials other
than asbestos, but no examples were provided.
Domain 5: Analysis
Continued on next page ...
Page 446 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 158 Table: 1 of 2
... continued from previous page
Nicholson, W. J., Selikoff, I. J., Seidman, H., Lilis, R., Formby, P. (1979). Long-term mortality experience of chrysotile miners and millers in Thetford
Mines, Quebec. Annals of the New York Academy of Sciences, Vol. 330 33021-Nov.
Lung Cancer; Asbestosis
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Lung/Respiratory: Asbestosis, Lung cancer; Mortality: All-cause mortality (excluding cancers), Lung cancer; Cancer/Carcinogenesis: Lung cancer
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
158
Domain
Metric
Rating
Comments
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design and methods were appropriate for the research question being exam-
ined.
Medium The number of participants included in this study is appropriate to detect an effect in the
exposed population.
Low There was a very limited discussion of the analyses present in this study.
Medium SMRs were utilized, and it is clear why this analysis method was used.
Additional Comments: This study had some strengths and limitations. One benefit was the temporality component, since one of the inclusion criteria was that employees must have
worked there for at least 20 years, providing a sufficient time from exposure to outcome. There was also an adequate number of participants included in the
study to determine an effect. However, these results could be limited. It would have also been beneficial for the authors to provide more information about
the causes of deaths, such as a discussion about diagnoses or specific indications of lung cancer and asbestosis, such as with cytological or histological
means.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 447 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 158 Table: 2 of 2
Study Citation:
Nicholson, W. J., Selikoff, I. J., Seidman, H., Lilis, R., Formby, P. (1979). Long-term mortality experience of chrysotile miners and millers in Thetford
Mines, Quebec. Annals of the New York Academy of Sciences, Vol. 330 33021-Nov.
MISSING
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Cancer/Carcinogenesis: All other cancers; Mortality: All other cancers, All cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
HERO ID:
158
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This study revolved around a cohort of men employed for at least 20 years in one of
four companies that mine and mill chrysotile, exclusively. This represented 544 indi-
viduals from four separate operations. These operations were examined in Thetford
Mines, Quebec, Canada. The participants included represented a variety of potential job
classifications. However, not many details beyond this were included pertaining to in-
clusion criteria, such as the total number of individuals that could have potentially been
included.
Medium There was moderate exclusion of participants from analyses. The aim of this study was
to determine mortality outcomes for participants enrolled from the asbestos mines. The
authors were able to obtain 172 certificates of death, and there were an additional 130
cases were the authors obtained clinical, surgical, and pathological data to supplement
death certificate information.
Medium The expected number of deaths/illnesses included in this study were derived from the
age-specific death rate data for white Canadian males. It is important to note that they
did not use data specific to Quebec, but it is noted that "national rates are not impor-
tantly different from those of Quebec province but are likely to be significantly higher
than those of the rural mining counties in which these workers lived" (Nicholson et
al., 1979). The authors also explicitly discuss the potential for healthy worker effect,
but they mention that "the effects of asbestos exposure appear to overcome the bene-
ficial health status usually associated with employ ability" (Nicholson et al., 1979). As
mentioned, the participants were compared to white Canadian males, but there was no
discussion of the racial makeup of employees.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure High The authors report that 97 air samples were collected from various work locations within
five operating asbestos mines/mills. These samples were collected between 1973 and
1975, and a majority of them were personal samples. The concentrations varied greatly,
but it is reported that "in virtually all work categories average dust concentrations ex-
ceeded the asbestos standard then current in the United States of 5 fibers longer than 5
micrometers/milliliter (5 f/ml)" (Nicholson et al., 1979). The authors detail that they fol-
lowed the methods outlined by the National Institute of Occupational Safety and Health
to determine asbestos concentrations, which utilizes a microscope with phase contrast
optics (1972, 145).
Continued on next page ...
Page 448 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 158 Table: 2 of 2
... continued from previous page
Study Citation:
Nicholson, W. J., Selikoff, I. J., Seidman, H., Lilis, R., Formby, P. (1979). Long-term mortality experience of chrysotile miners and millers in Thetford
Mines, Quebec. Annals of the New York Academy of Sciences, Vol. 330 33021-Nov.
MISSING
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Cancer/Carcinogenesis: All other cancers; Mortality: All other cancers, All cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
HERO ID:
158
Domain
Metric
Rating
Comments
Metric 5:
Metric 6:
Exposure Levels
Temporality
Medium
High
Multiple levels of asbestos exposure were presented in the study. Table 3 includes a
range, mean, and number of samples of asbestos in each of the mine/mill locations. It is
also further divided into various work areas/activities, including general mill air, bagging
asbestos, quality control laboratory, crusher, dryer, shops, and nonwork areas. This table
highlights that a majority of the cohort was employed in facility two, and concentrations
are reported in fibers longer than 5 micrometers/ml of air.
One of the requirements to be included in this study was that the workers must have
been employed for at least 20 years. This means that there is an appropriate temporality
between exposure and outcome such that exposure occurred prior to the outcome.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High
Medium
Other Cancer(s): Death certificates and other vital records were used to ascertain the
cause of death for participants.; Other Non-Cancer Outcomes: In Table 4, the authors
include information pertaining to the "all other causes" that were classified on death
certificates.
The findings are reported at various points throughout the study. Expected and observed
deaths are reported, along with the O/E calculations. However, information such as
confidence intervals are not included, contributing to the medium rating.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Low
N/A
Low
No description is provided in this study that discusses considerations for potential con-
founders or their adjustment.
Covariates were not assessed in this study.
Potential co-exposures were not explicitly discussed in this study. It was mentioned in
the discussion section that workers in some positions would work with materials other
than asbestos, but no examples were provided.
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
The study design and methods were appropriate for the research question being exam-
ined.
The number of participants included in this study is appropriate to detect an effect in the
exposed population.
There was a very limited discussion of the analyses present in this study.
A statistical model was not used in this study.
Metric 13:
Metric 14:
Metric 15:
Statistical Power
Reproducibility of Analyses
Statistical Analysis
Medium
Low
N/A
Continued on next page ...
Page 449 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 158 Table: 2 of 2
... continued from previous page
Study Citation:
Nicholson, W. J., Selikoff, I. J., Seidman, H., Lilis, R., Formby, P. (1979). Long-term mortality experience of chrysotile miners and millers in Thetford
Mines, Quebec. Annals of the New York Academy of Sciences, Vol. 330 33021-Nov.
MISSING
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Cancer/Carcinogenesis: All other cancers; Mortality: All other cancers, All cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
HERO ID:
158
Domain
Metric
Rating
Comments
Additional Comments:
This study had some strengths and limitations. One benefit was the temporality component, since one of the inclusion criteria was that employees must
have worked there for at least 20 years, providing a sufficient time from exposure to outcome. There was also an adequate number of participants included
in the study to determine an effect. However, these results could be limited. For one, there was little information provided about the methods used to
ascertain asbestos concentrations. It would have also been beneficial for the authors to provide more information about the causes of deaths, such as a
discussion about diagnoses or specific indications of other cancers in the patients, such as through cytological or histological means.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 450 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081842 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Nokso-Koivisto, P., Pukkala, E. (1994). Past exposure to asbestos and combustion products and incidence of cancer among Finnish locomotive drivers.
Occupational and Environmental Medicine 51(1994):330-334.
Lung Cancer
Gastrointestinal: Stomach cancer, Rectal cancer, Colon cancer, Oral cavity and pharynx cancer; Lung/Respiratory: Lung and trachea cancer, Mesothe-
lioma; Renal/Kidney: Kidney cancer, Bladder, ureter, urethra cancer; Skin/Connective Tissue: Skin (non-melanoma) cancer, Skin melanoma; Immune/
Hematological: Leukemia, Hodgkin's disease, Non-Hodgkin's lymphoma; Reproductive/Developmental: Prostate cancer; Cancer/Carcinogenesis: All site
cancer, Oral cavity and pharynx cancer, Stomach cancer, Colon cancer, Rectal cancer, Lung and trachea cancer, Mesothelioma, Prostate cancer, Kidney
cancer, Bladder, ureter, urethra cancer, Skin melanoma, Skin (non-melanoma), Non-Hodgkin's lymphoma, Hodgkin's disease, Leukemia
Asbestos - Anthophyllite: 17068-78-9; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3081842
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low To estimate pre-1970s steam engine maintenance exposures in Finland, working con-
ditions were reconstructed in two workshops with the assistance of workers who had
been exposed. During reconstructed dismantling of the outer covers of the boilers of
two engines, eight personal air samples were collected. The authors state that "asbestos
exposure was measured with standardized techniques," but they don't specify what these
techniques were. Therefore, it is unclear whether PCM, TEM, or another method was
used. The authors also reported that asbestos concentrations in cabins of diesel locomo-
tives with asbestos pipe insulation was measured.
Metric 5: Exposure Levels Low The range and distribution of exposure was limited. The authors reported that "the av-
erage number of fibres > 5 um was 5.0 (range 2.5-7.5)/cmA 3, indicating medium expo-
sure" (Nokso-Koivisto & Pukkala, 1994) for the reconstructed steam engine dismantling.
The number of fibers was undetectable for diesel locomotive cabins. Furthermore, al-
though different time periods were assessed, the study only assessed two exposure levels
- standardized incidence ratios were used to compare locomotive drivers (exposed) to
the Finnish population (presumed unexposed or lower exposed). Therefore, this study
does not include sufficient information for dose-response assessment.
Additional Comments: None
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 451 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3531256 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Nuyts, V., Vanhooren, H., Begyn, S., Nackaerts, K., Nemery, B. (2017). Asbestos bodies in bronchoalveolar lavage in the 21st century: a time-trend
analysis in a clinical population. Occupational and Environmental Medicine 74(2017):59-65.
Lung Cancer; Asbestosis; Pleural Plaques
Lung/Respiratory: Pleural plaques, Asbestosis, lung cancer; Cancer/Carcinogenesis: lung cancer
Asbestos - Not specified: 1332-21-4
No linked references.
3531256
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Metric 5:
Measurement of Exposure
Exposure Levels
Low Asbestos bodies were quantified in BAL samples using light microscopy.
Medium The range and distribution of exposure is sufficient to develop an exposure-response
estimate, and an exposure-response model using a continuous measure of exposure was
used for the analysis.Exposures ranged from 0 to 164.5 asbestos bodies (AB)/mL, with a
median of 0.5 AB/mL and an arithmetic mean of 5 AB/mL.
Additional Comments: This retrospective study of clinical data quantified asbestos bodies in bronchoalveolar samples. The study found significant differences in concentrations
of asbestos bodies among groups of participants with pulmonary diseases compared to those with no known diagnoses. The Matrix Adjustment metric was
not rated for this study.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 452 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 12511 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Nyberg, F., Gustavsson, P., Jarup, L., Bellander, T., Berglind, N., Jakobsson, R., Pershagen, G. (2000). Urban air pollution and lung cancer in Stockholm.
Epidemiology ll(2000):487-495.
Lung Cancer
Lung/Respiratory: Lung cancer
Asbestos - Not specified: 1332-21-4
No linked references.
12511
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Uninformative The authors detail that asbestos exposure estimates were determined through a job expo-
sure matrix. An occupational hygienist was responsible for determining the cumulative
exposure, which was the "product of the intensity, the probability, and the duration of
exposure, summed over all work periods in occupational history" (Nyberg et al., 2000).
There was no information provided pertaining to actual quantitative measurements of
asbestos.
Metric 5: Exposure Levels Low Only two levels of asbestos exposure are reported in this study. These are "none or low,"
and "high (>/= 0.89 fiber-years/mL).
Additional Comments: None
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessment for the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 453 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3091862 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Offermans, N. S. M., Vermeulen, R., Burdorf, A., Goldbohm, R. A., Keszei, A. P., Peters, S., Kauppinen, T., Kromhout, H., van Den Brandt, P. A. (2014).
Occupational asbestos exposure and risk of oral cavity and pharyngeal cancer in the prospective Netherlands Cohort Study. Scandinavian Journal of Work,
Environment and Health 40(2014):420-427.
oral cavity cancer, pharyngeal cancer, oral cavity cancer and pharyngeal cancer combined
oral cavity: oral cavity cancer and pharyngeal cancer combined, oral cavity cancer; Cancer/Carcinogenesis: oral cavity cancer, oral cavity cancer and
pharyngeal cancer combined, pharyngeal cancer; Lung/Respiratory: pharyngeal cancer, oral cavity cancer and pharyngeal cancer combined
Asbestos - Not specified: 1332-21-4
No linked references.
3091862
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low In this study of participants in the population-based Netherlands Cohort Study (NLCS),
exposure was estimated using two different job-exposure matrices (JEMs) developed
for the general population: DOMJEM (described in Offermans NS et al. 2012, HERO
ID: 3091864) and FINJEM (Kauppinen T, Toikkanen J, Pukkala E. Am J Ind Med 1998,
33:409-417, not available in HERO). For both JEMs, asbestos exposures were assessed
for different occupations using either professional judgement (DOMJEM) or measure-
ment in a set of Finnish workplaces (FINJEM, exact methods not described). These
occupation-specific estimates were then assigned to NLCS participants based on oc-
cupational history. A metric rating of "low" was assigned because exposures were not
measured or otherwise assessed for the specific workplaces of NLCS participants.
Medium Exposure levels estimated from each of the two JEMs were grouped into four categories
(tertiles plus no exposure) for analysis. Exposures from each JEM were also evaluated
continuously. Median exposure levels of all study participants within tertiles 1-3 were as
follows - DOMJEM: 4, 20, 38 unit-years; FINJEM: 0.20, 1.59, 6.60 fiber-years/ml.
Additional Comments: None
* As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 454 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3078062 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Offermans, N. S., Vermeulen, R., Burdorf, A., Goldbohm, R. A., Kauppinen, T., Kromhout, H., van den Brandt, P. A. (2014). Occupational asbestos
exposure and risk of pleural mesothelioma, lung cancer, and laryngeal cancer in the prospective Netherlands cohort study. Journal of Occupational and
Environmental Medicine 56(2014):19-Jun.
Lung Cancer
Cancer/Carcinogenesis: pleural mesothelioma, lung cancer, laryngeal cancer (glottis and supraglottis cancers); Lung/Respiratory: pleural mesothelioma,
lung cancer, laryngeal cancer (glottis and supraglottis cancers)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3078062
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The study employed two job exposure matrices - the DOMJEM (the Netherlands) and
the FINJEM (Finland) - however, only one matrix appears to leverage quantitative mea-
sures of exposure to asbestos, but it is unclear if TEM or PCM were used. It appears
that the DOMJEM uses expert judgment only to assign semiquantitative exposure val-
ues with corresponding weighting. The FINJEM uses expert judgment and exposure
measurement, though there is no discussion of the methodology used to make those
measurements.
Medium This study examines exposure by tertile of cumulative exposure, tertile of duration of
exposure, and, among the exposed only, tertile of duration of high exposure. Many of
the analyses use those who were not exposed to asbestos as the referent group. There
is an appropriate range of exposure among the study population to assess the exposure-
response relationship.
Additional Comments: This case-cohort study leverages the NLCS cohort to assess the association between occupational asbestos exposure and lung cancer cases. The study
design and methodological approaches are robust, and the study employed the ICD-O-3 to identify lung cancer cases. There are no major concerns about
residual bias in the observed results.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 455 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3078062 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Offermans, N. S., Vermeulen, R., Burdorf, A., Goldbohm, R. A., Kauppinen, T., Kromhout, H., van den Brandt, P. A. (2014). Occupational asbestos
exposure and risk of pleural mesothelioma, lung cancer, and laryngeal cancer in the prospective Netherlands cohort study. Journal of Occupational and
Environmental Medicine 56(2014):19-Jun.
Laryngeal Cancer
Cancer/Carcinogenesis: pleural mesothelioma, lung cancer, laryngeal cancer (glottis and supraglottis cancers); Lung/Respiratory: pleural mesothelioma,
lung cancer, laryngeal cancer (glottis and supraglottis cancers)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3078062
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The study employed two job exposure matrices - the DOMJEM (the Netherlands) and
the FINJEM (Finland) - however, only one matrix appears to leverage quantitative mea-
sures of exposure to asbestos, but it is unclear if TEM or PCM were used. It appears
that the DOMJEM uses expert judgment only to assign semiquantitative exposure val-
ues with corresponding weighting. The FINJEM uses expert judgment and exposure
measurement, though there is no discussion of the methodology used to make those
measurements.
Medium This study examines exposure by tertile of cumulative exposure, tertile of duration of
exposure, and, among the exposed only, tertile of duration of high exposure. Many of
the analyses use those who were not exposed to asbestos as the referent group. There
is an appropriate range of exposure among the study population to assess the exposure-
response relationship.
Additional Comments: This case-cohort study leverages the NLCS cohort to assess the association between occupational asbestos exposure and laryngeal cancer cases of the
glottis and supraglottis. The study design and methodological approaches are robust, and the study employed the ICD-O-3 to identify laryngeal cancer
cases. There are no major concerns about residual bias in the observed results.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 456 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2238789 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Ohlson, C. G., Bodin, L., Rydman, T., Hogstedt, C. (1985). Ventilatory decrements in former asbestos cement workers: a four year follow up. British
Journal of Industrial Medicine 42(1985):612-616.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Pleural plaques, Forced vital capacity (FVC), Forced expiratory volume in one second (FEV1)
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
2238789, 758934
2238789
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The authors did not specify the methods used to determine asbestos concentrations in
the occupational settings. They did note that the information was limited, but the con-
centration was estimated to be 2 fibers/ml in the 1950s and 60s, and 1 fiber/ml during
the 1970s. It was also indicated that "a general dust level of 10 mg/m3" was found in
measurements before 1970 (Ohlson et al., 1985). Information on exposure measure-
ments ascertainment was also limited in the secondary study, although some levels of
exposure were reported (lakobsson et al., 1995, RefID 758934).
Medium In the methods section, it is mentioned that the workers at the asbestos plant were di-
vided into three groups depending on their cumulative exposure, in fiber-years. The
same groupings from the 1976 study were used. These fiber-year groupings include:
/= 23 fiber-years (Ohlson et al., 1985, Re-
fID 2238789). Three levels of cumulative asbestos dose were also reported in the sec-
ondary study: <10 f-y/ml, 10-30 f-y/ml, and >30 f-y/ml (Jakobsson et al., 1995, RefID
758934).
Additional Comments: While there were some differences in the ratings for some metrics between these two studies, there were no major ones that stood out. Both studies utilized
chest radiographs, although the (Jakobsson et al., 1995, 758934) study had more readers, which contributed to a high rating for that metric. Overall, both
studies had some strengths and limitations contributing to their medium overall judgment.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 457 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2238789 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Ohlson, C. G., Bodin, L., Rydman, T., Hogstedt, C. (1985). Ventilatory decrements in former asbestos cement workers: a four year follow up. British
Journal of Industrial Medicine 42(1985):612-616.
Pleural Plaques
Lung/Respiratory: Pleural plaques, Forced vital capacity (FVC), Forced expiratory volume in one second (FEV1)
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
2238789, 758934
2238789
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The authors did not specify the methods used to determine asbestos concentrations in
the occupational settings. They did note that the information was limited, but the con-
centration was estimated to be 2 fibers/ml in the 1950s and 60s, and 1 fiber/ml during
the 1970s. It was also indicated that "a general dust level of 10 mg/m3" was found in
measurements before 1970 (Ohlson et al., 1985). Information on exposure measure-
ments ascertainment was also limited in the secondary study, although some levels of
exposure were reported (lakobsson et al., 1995, RefID 758934).
Medium In the methods section, it is mentioned that the workers at the asbestos plant were di-
vided into three groups depending on their cumulative exposure, in fiber-years. The
same groupings from the 1976 study were used. These fiber-year groupings include:
/= 23 fiber-years (Ohlson et al., 1985,
2238789). Three levels of cumulative asbestos dose were also reported in the sec-
ondary study: <10 f-y/ml, 10-30 f-y/ml, and >30 f-y/ml (Jakobsson et al., 1995, RefID
758934).
Additional Comments: While there were some differences in the ratings for some metrics between these two studies, there were no major ones that stood out. Both studies utilized
chest radiographs, although the (Jakobsson et al., 1995, RefID 758934) study had more readers, which contributed to a high rating for that metric. Overall,
both studies had some strengths and limitations contributing to their medium overall judgment.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 458 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083459 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Ohlson, C. G., Hogstedt, C. (1985). Lung cancer among asbestos cement workers. A Swedish cohort study and a review. British Journal of Industrial
Medicine 42(1985):397-402.
Lung Cancer; gastrointestinal, pancreatic, intestinal, respiratory,; mortality by external causes, violent death, circulation, and respiratory tract
Lung/Respiratory: Lung cancer mortality, Respiratory cancer mortality, Non-malignant respiratory disease mortality, Diseases of the respiratory tract
mortality; Cancer/Carcinogenesis: Lung cancer mortality, Respiratory cancer mortality, Malignant tumors mortality, Gastric cancer mortality, Intestinal
cancer mortality, Pancreatic cancer mortality, Gastrointestinal cancer mortality; Mortality: Lung cancer mortality, Respiratory cancer mortality, Malignant
tumors mortality, Gastric cancer mortality, Intestinal cancer mortality, Pancreatic cancer mortality, Gastrointestinal cancer mortality, Non-malignant respi-
ratory disease mortality, Diseases of the respiratory tract mortality, Diseases of circulation mortality, All causes mortality, Violent death mortality, External
causes mortality; Gastrointestinal: Gastric cancer mortality, Intestinal cancer mortality, Pancreatic cancer mortality, Gastrointestinal cancer mortality;
Cardiovascular: Diseases of circulation mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
3083459, 3082919
3083459
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Neither study in this cohort indicated the method of quantifying/counting fibres Ohlson
and Hogstedt, 1985, HEROID: 3083459; Albin et al„ 1988, HEROID: 3082919).
Ohlson and Hogstedt state in the methods that a general dust level of 10 mg/m3 was
applied for pre-1970s data, and that fibre concentrations "averaged 1 fibre/ml based
on several hundred samples from five investigations between 1970 and 1976" (Ohlson
and Hogstedt, 1985, HEROID: 3083459). Albin et al. provides very little regarding
measurements of exposure, only stating, "Individual dose estimates were calculated for
two thirds of the cohort, the median intensity was around 1 f/ml" (Albin et al., 1988,
HEROID: 3082919). No methodology regarding how this was measured and calculated
is provided.This metric is rated Low because the studies or any cited methods source do
not explicitly mention the use of PCM or TEM.
Metric 5: Exposure Levels Medium Ohlson and Hogstedt provide exposure levels by employment time (<2 years, 2-<5
years, and >= 5 years) and latency time (0 or 20 years) (Ohlson and Hogstedt, 1985,
HEROID: 3083459). This study is a Medium. Albin et al. uses two levels of exposure
levels (exposed asbestos cement workers and the general population as referents (Albin
et al., 1988, HEROID: 3082919). This study would be rated Low in this regard.
Additional Comments: Overall, this cohort consists of two older studies (1980s) where there is lacking information and methods surrounding the measurement of exposure.
HEROIDs 3083459 and 3082919 were not evaluated for any metrics except Metric 4 and 5 and had no data extracted because they did not have sufficient
exposure information to be useful for dose-response analysis.QC was not completed for metrics other than Metrics 4 and 5 because the study does not have
sufficient exposure information to be useful for dose-response analysis.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 459 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083565 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Ohlson, C. G., Klaesson, B., Hogstedt, C. (1984). Mortality among asbestos-exposed workers in a railroad workshop. Scandinavian Journal of Work,
Environment and Health 10(1984):283-291.
Lung Cancer; Gastrointestinal; Chronic obstructive lung disease, other diseases of the respiratory tract
Mortality: All cause mortality, Lung cancer mortality, Gastric cancer mortality, Chronic obstructive lung disease mortality, Diseases of the respiratory tract
(excluding chronic obstructive lung disease) mortality; Lung/Respiratory: Lung cancer mortality, Chronic obstructive lung disease mortality, Diseases of
the respiratory tract (excluding chronic obstructive lung disease) mortality; Gastrointestinal: Gastric cancer mortality; Cancer/Carcinogenesis: Lung cancer
mortality, Gastric cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos -
Not specified: 1332-21-4
No linked references.
3083565
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM. In addition, while conversion factors for measure-
ments of dust are given in Table 1, these are based on professional judgement relying on
conversion factors from American insulators (Nicholson et al., 1982, HEROID 160).
Medium Five exposure levels (as dust scores ranging from 0-4) are presented in Table 1 with
crude conversions to fiber counts (ranging between 0-20 fibers/ml).Pre-1970, 5 expo-
sure levels are reported. Post-1970, fiber count measurements show adequate exposure
distribution to detect present associations (0-20 fibers/mL). However, of the 64 total
fiber count measurements available, only 8 were > 1 fibers/mL.SMR analyses incorpo-
rating relevant exposure concentrations are performed by 4 ordinal exposure intensity
categories (Table 4).
Additional Comments:
QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis. This study does contain dust exposure concentrations with a conversion factor, which allows it to technically meet PECO. However, the conversion
factor is based solely on professional judgement. In addition, there is no mention of PCM or TEM to quantify fibers.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 460 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2238788 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Ohlson, C. G., Rydman, T., Sundell, L., Bodin, L., Hogstedt, C. (1984). Decreased lung function in long-term asbestos cement workers: a cross-sectional
study. American Journal of Industrial Medicine 5(1984):359-366.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Forced vital capacity (FVC), Forced expiratory volume in one second (FEV1), Forced expiratory flow at 25-75% FVC, Pleural abnor-
malities
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
2238788
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The authors highlight that the exposure data available for the plant is limited, especially
for the 1950s and 60s. Some measurements "indicated a general dust level of 10 mg/m3
and half the amount during the 1970s" (Ohlson et al., 1984). Five investigations were
conducted between 1970 and 1976, and average fiber concentration was found to be 1
fiber/ml. Some assumptions were made by the authors due to less effective ventilation in
earlier decades, so a value of 2 fibers/ml was given. They also note that the highest value
recorded was 8 fibers/ml in 1970. However, the authors did not provide information
pertaining to the methods utilized to determine these fiber concentrations.The study or
any cited methods source does not explicitly mention the use of PCM or TEM.
Medium Exposed individuals were grouped into one of three categories based on the number
of fiber-years that they were exposed. These groupings included 0-14, 15-22, and 23+
fiber-years.
Additional Comments: Overall, this study had a number of strengths pertaining to their analyses performed, and their consideration of potential covariates. However, there were
also some limitations related to the exposure measurements taken, because there were no specifics given as to the methods used. The authors note that
there was no statistically significant dose-effect relationship between fiber-year estimates and lung function values.NOTE: Based on the new guidance, this
study would not have been evaluated fully. Metric 4 was rated as low because there was no mention within the study or a cited source about the use of
PCM or TEM.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 461 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2238788 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Ohlson, C. G., Rydman, T., Sundell, L., Bodin, L., Hogstedt, C. (1984). Decreased lung function in long-term asbestos cement workers: a cross-sectional
study. American Journal of Industrial Medicine 5(1984):359-366.
Pleural Plaques
Lung/Respiratory: Pleural abnormalities
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
2238788
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The authors highlight that the exposure data available for the plant is limited, especially
for the 1950s and 60s. Some measurements "indicated a general dust level of 10 mg/m3
and half the amount during the 1970s" (Ohlson et al., 1984). Five investigations were
conducted between 1970 and 1976, and average fiber concentration was found to be 1
fiber/ml. Some assumptions were made by the authors due to less effective ventilation in
earlier decades, so a value of 2 fibers/ml was given. They also note that the highest value
recorded was 8 fibers/ml in 1970. However, the authors did not provide information
pertaining to the methods utilized to determine these fiber concentrations.The study or
any cited methods source does not explicitly mention the use of PCM or TEM.
Medium Exposed individuals were grouped into one of three categories based on the number
of fiber-years that they were exposed. These groupings included 0-14, 15-22, and 23+
fiber-years.
Additional Comments: Overall, this study had a number of strengths pertaining to their analyses performed, and their consideration of potential covariates. However, there were
also some limitations related to the exposure measurements taken, because there were no specifics given as to the methods used. The authors note that
there was no statistically significant dose-effect relationship between fiber-year estimates and lung function values. There was no significant difference
between those with and without pleural plaques when the exposure was comparable.NOTE: This study would not have been fully evaluated under the
current guidance. This is due to metric 4 being rated as low because neither the study nor a cited methods source mentioned the use of PCM or TEM.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 462 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3080175 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Paris, C., Benichou, J., Raffaelli, C., Genevois, A., Fournier, L., Menard, G., Broessel, N., Ameille, J., Brochard, P., Gillon, J. C. (2004). Factors
associated with early-stage pulmonary fibrosis as determined by high-resolution computed tomography among persons occupationally exposed to asbestos.
Scandinavian Journal of Work, Environment and Health 30(2004):206-214.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Pulmonary Fibrosis
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3080175
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Low Tentative participants were pensioners or early retirees from companies in the Nomandy
region with known occupational asbestos exposure, recruited via mail from their former
employers or in local information meetings. Most had worked in a single asbestos textile
and friction material factory. Some had worked in other environments such as shipyards,
fossil fuel power stations, and industrial insulation contractors. Eligible individuals had
to have no previous involvement in systematic HRCT screening campaigns in their for-
mer companies and have no known asbestos-related diseases prior to inclusion. 706
retired workers were recruited from 1991-1999. Participation rates are not directly re-
ported, but authors note that participation varied widely among industries. Complete
interpretable functional test results were available for 630 of these participants.Healthy
worker selection bias is a concern because of the requirement for no known asbestos-
related disease at inclusion. Differential participation by knowledge of exposure and
outcome status is also a concern, as subjects with higher known occupational exposure
and known health problems may have been more likely to participate. The large dispari-
ties in participation rate across industries exacerbates this concern.
High Cross-sectional study design with outcome information available for 630 of 706 re-
cruited participants. No major concerns.
Medium Recruitment methods were consistent for subjects in all ecumulative asbestos xposure
categories (<25, 25-99.9 and >= 100 fibers/mL*years).
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium The study or any cited methods source does not explicitly mention the use of PCM or
TEM to quantify fibres.For participants who had worked in the asbetsos textile and
friction material plant, exposure was quantified using a job-exosure matrix determined
from airborne measurements collected annually from 1959-1999 in various areas of the
plant. For all other participants, exposure levels were assessed using published airborne
measurements available in the French database Evalutil according to calendar period
of exposure and typical reported tasks. Cumulative-exposure index (CEI) for asbestos
was calculated based on asbestos air measurements, job category, date of hire, date of
assignment end, and duration of exposure (fibers/mL*years). For analysis, CEI was
categorized at 3 levels: <25, 25-99.9, and >= 100 fibers/mL*years, with the lowest
level serving as the reference group.
Continued on next page ...
Page 463 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3080175 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Paris, C., Benichou, J., Raffaelli, C., Genevois, A., Fournier, L., Menard, G., Broessel, N., Ameille, J., Brochard, P., Gillon, J. C. (2004). Factors
associated with early-stage pulmonary fibrosis as determined by high-resolution computed tomography among persons occupationally exposed to asbestos.
Scandinavian lournal of Work, Environment and Health 30(2004):206-214.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Pulmonary Fibrosis
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3080175
Domain
Metric
Rating
Comments
Metric 5:
Metric 6:
Exposure Levels
Temporality
Medium
Low
3 levels of quantitative CEI are reported (<25, 25-99.9, and >= 100 fibers/mL*years,
with the lowest level serving as the reference group).
Dates of exposure assessment and outcome ascertainment are sufficiently documented.
However, length of latency period is not well established (exposure assessment lasted
until 1999, and outcome ascertainment began in 1990). Authors report that all subjects
were in retirement from their occupations at the time of inclusion, but an appropriate/
consistent latency period is not established.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High
High
Pulmonary Function/Spirometry Results: The outcome of interest was pulmonary fibro-
sis. CT exploration of the lungs with 6+ high-resolution millimetric sections were used
to assess clinical features of pulmonary fibrosis, including lesions, subpleural curvilinear
lines, and ground-glass opacity. A grading scale of 0-3 was used (0 = normal, 1 = mild
interstitial abnormalities, 2 = bilateral interstitial abnormalities with limited extent, 3 =
profuse interstitial abnormalities), with grades 2 and 3 diagnosed as pulmonary fibrosis.
All results are reported with sufficient detail for replication.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium 2 sets of adjustment factors were used for multivariate analyses. Model 1 included 5
dichotomous (yes/no or high/low) covariates: basilar crackles, observed-to-predicted
ratio for TLC, observed-to-predicted ratio for TLCO, small irregular opacities, and
pleural abnormalities in the X-ray. Model 2 employed a backward stepwise procedure
to all variables that appeared to be separately associated (10% change in estimate) with
pulmonary fibrosis in univariate analyses. BMI and smoking status were also included in
models 1 and 2 based on previous literature. Age and gender were adjusted for a priori.
High Covariates were assessed by standard interview or clinical examination performed by a
physician.
Low Occupational study with no discussion of potential co-exposures.
Domain 5: Analysis
Metric 12: Study Design and Methods Medium Study uses an appropriate statistical method (multiple logistic regression) for ordinal
exposure levels and a dichotomized outcome variable.
Metric 13: Statistical Power Medium Study population (n=630) and observed exposure ranges ((<25 - >=100 fibers/
mL*years) were adequate to detect present associations.
Metric 14: Reproducibility of Analyses Medium Description of analysis is sufficient for reproduction.
Continued on next page ...
Page 464 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3080175 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Paris, C., Benichou, J., Raffaelli, C., Genevois, A., Fournier, L., Menard, G., Broessel, N., Ameille, J., Brochard, P., Gillon, J. C. (2004). Factors
associated with early-stage pulmonary fibrosis as determined by high-resolution computed tomography among persons occupationally exposed to asbestos.
Scandinavian lournal of Work, Environment and Health 30(2004):206-214.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Pulmonary Fibrosis
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3080175
Domain
Metric
Rating
Comments
Metric 15: Statistical Analysis
Medium
Model for generating effect estimates is well documented and basic model assumptions
are met.
Additional Comments: 2/7/2023 UPDATE: DUE TO CHANGES IN THE GUIDANCE FOR SQE, ALL METRICS RATINGS EXCEPT FOR 4 AND 5 SHOULD BE IGNORED
BECAUSE METRTC 4 WAS R ATED "1 .OW".
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 465 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 758967 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Paris, C., Martin, A., Letourneux, M., Wild, P. (2008). Modelling prevalence and incidence of fibrosis and pleural plaques in asbestos-exposed populations
for screening and follow-up: a cross-sectional study. Environmental Health: A Global Access Science Source 730.
Asbestosis; Pleural Plaques
Lung/Respiratory: Asbestosis, Pleural plaques
Asbestos - Not specified: 1332-21-4
No linked references.
758967
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low This metric is rated Low because the study or any cited methods source does not ex-
plicitly mention the use of PCM or TEM. The cited method source entitled "Use of a
job-exposure matrix for the screening of occupational exposure to asbestos" by Fournier
2004 is not available on HERO nor accessible in public domains.Quantitative assess-
ment of exposure obtained by occupational hygiene measurements and job-exposure
matrix (JEM) elaborated from airborne measurements from 1959-1999 in various
workshops of the plant. A cumulative exposure index (CEI) was then calculated and
expressed in fibers/ml.years. Average exposure index calculated by dividing CEI by
duration of exposure.
Metric 5: Exposure Levels Medium 3 levels of exposure. Airborne measurements were collected annually 1959-1999 in
various workshops of plants, other subjects estimation of exposure was used based on
French Database Evalutil. Cumulative Exposure (y.f/ml) for healthy subjects was 88.9,
± 92.4; for pleural plaque subjects was 137.0, ± 140.8; and for asbestosis subjects was
143.3, ± 135.4. Other exposure metrics estimated in this study showed roughly similar
patterns as observed with cumulative exposure.
Additional Comments: 2/8/2023 UPDATE: DUE TO CHANGES IN THE GUIDANCE FOR SQE, ALL METRICS RATINGS EXCEPT FOR 4 AND 5 SHOULD BE IGNORED
BECAUSE METRIC 4 WAS RATED "LOW'.This study was a cross-sectional occupational study and it examined which exposure parameters are most
useful to the clinicians in the selection of asbestos-exposed subjectsto be submitted to a CT-Scan as part of a screening exercise. While it considered
adjusting for confounders and variables, potential confounders such as age were not included in the multiple regression models. It employed tests fit of data
while also highlighting assumptions and design flaws. Outcome/analysis of asbestosis vs. fibrosis terms used interchangeably throughout article. Overall, a
well-conducted study with ample information provided.Overall, information on the measurement of exposure metric (M4) to assess exposure was limited.
On the other hand, the exposure levels metric (M5) information reported was adequate to determine exposure-response relationships.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 466 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082886 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Pearce, N. (1988). Multistage modelling of lung cancer mortality in asbestos textile workers. International Journal of Epidemiology 17(1988):747-752.
Lung Cancer
Cancer/Carcinogenesis: Lung cancer; Lung/Respiratory: Lung cancer
Asbestos - Not specified: 1332-21-4
HERO ID:
3082886
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Exposure data was expressed in fibers per cc of air (fibers/cc), and was available from
1930-1975. However, the authors do not provide details about the equipment or methods
used to generate this data. All workers had an estimated cumulative exposure based
on "the summed products of air concentrations of asbestos and time (in days) spent in
various jobs" (Pearce, 1988). A dichotomous classification of exposure was utilized
because of the small numbers.
Low During the statistical analysis, exposure to asbestos was categorized into low or high,
with high being classified as 5000+ fibre/cc days and low as <5000 fibre/cc days. Table
2 also examined observed and expected number of lung cancer deaths among the work-
ers based on their cumulative exposure between <1 and 100+ in thousand fibre/cc days.
The authors indicated that this dichotomous classification of exposure was appropriate
because it provided "reasonable numbers in both exposure categories" (Pearce, 1988).
Additional Comments: Overall, information on the measurement of exposure metric (M4) to assess exposure was limited. Additionally, the exposure levels metric (M5) information
reported was limited to determine exposure-response relationships.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 467 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3079156 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Pesch, B., Taeger, D., Johnen, G., Gross, I. M., Weber, D. G., Gube, M., Milller-Lux, A., Heinze, E., Wiethege, T., Neumann, V., Tannapfel, A., Raithel,
H. J., Briining, T., Kraus, T. (2010). Cancer mortality in a surveillance cohort of German males formerly exposed to asbestos. International lournal of
Hygiene and Environmental Health 213(2010):44-51.
All cause mortality, Mortality from pneumoconioses and other lung diseases due to external agents
Lung/Respiratory: Mortality from pneumoconioses and other lung diseases due to external agents (ICD9: 500-208); Mortality: Mortality from pneumoco-
nioses and other lung diseases due to external agents (ICD9: 500-208), All causes (ICD9: 000-999)
Asbestos - Not specified: 1332-21-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3079156
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Metric 5:
Measurement of Exposure
Exposure Levels
Low
Low
Exposure was developed from expert input based on occupational history, job activity,
and other characteristics, but no measures of asbestos concentration.
Exposures are categorized into 3 ordinal groups of fiber years (< 25, 25-100, >100). It
is unclear if distributions are wide enough, given they are broken into 3 categories.
Additional Comments: No additional comments. Overall, the measurement of exposure metric (M4) methods used to assess the exposure were not well defined, there were
no quantitative measurements. Additionally, the exposure levels metric (M5) information reported was not adequate to determine an exposure-response
relationship.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 468 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: m Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Peto, J. (1980). Lung cancer mortality in relation to measured dust levels in an asbestos textile factory. IARC Scientific Publications (1980):829-836.
Lung Cancer; other cancers mortality; asbestosis mortality, other respiratory disease mortality, other causes mortality
Cancer/Carcinogenesis: lung cancer mortality, other cancers mortality; Mortality: lung cancer mortality, other cancers mortality, asbestosis mortality, other
respiratory disease mortality, other causes mortality; Lung/Respiratory: lung cancer mortality, asbestosis mortality, other respiratory disease mortality;
other causes: other causes mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
163
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This study is an extended follow up of the same North England asbestos textile factory
worker cohort recruited from the work areas with highest expected asbestos exposure:
fiberizing, carding, spinning, weaving, and plaiting. (Knox et al. 1968, HEROID: 115;
Peto et al. 1977, HEROID: 3084525). Here, 679 men who had begun work after 1933
and who had accrued >10 total years of service by 1972 were included in the study.
There is limited detail on recruitment or other inclusion criteria. There may be some
selection bias, as only healthier workers would be able to complete >10 years of work in
select high-exposure areas.
High Follow up for mortality continued through 1978 by the National Health Central Register
and the factory personnel department. 41 of 679 (6% ) men were unable to be traced.
In this analysis, they were assumed to have been alive at the previous follow up date
(12/31/1974), but their subsequent man-years were not included here. Deaths of workers
over 85 are ignored. There is no other mention of drop-out or loss that was not included
in follow-up.
Low The study only mentions "unaffected controls" in the section on lung cancer mortality
and dust levels. Another study using the same cohort (Knox et al. 1968, HEROID: 115)
notes comparisons to "national rates," however it's not clear if this is the same compar-
ison group for this study. The study does compare in text results workers first exposed
before 1951 and those in 1951 and later (i.e., cohort 1 and 2).
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Asbestos fiber exposure concentrations were reportedly measured using a thermal pre-
cipitator in years between 1951-1961. Additional support for understanding past area
dust measures in particles/mL were taken in conversations with hygiene officers from
the factory. Static membrane filters in years after 1961. Authors state that for each area
of the factory, representative combinations of measures were used and averaged to be
converted to modern counting methods. "The revised estimates are based on preliminary
data abstracted from a detailed analysis that is currently being conducted by T.B.A. In-
dustrial Products Ltd and must be regarded as provisional. However, they indicate that
average dust levels were in the region of 30 fibre/ml in 1951 and remained high until
about 10 years ago."
Low Asbestos exposure appears to be continuous, however SMR analyses are stratified by
years since first exposure and year of first exposure, not by a quantitative measure of
asbestos exposure. This suggests the exposure for SMR analyses is dichotomous.
Continued on next page ...
Page 469 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 163 Table: 1 of 1
... continued from previous page
Peto, J. (1980). Lung cancer mortality in relation to measured dust levels in an asbestos textile factory. IARC Scientific Publications (1980):829-836.
Lung Cancer; other cancers mortality; asbestosis mortality, other respiratory disease mortality, other causes mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: lung cancer mortality, other cancers mortality; Mortality: lung cancer mortality, other cancers mortality, asbestosis mortality, other
respiratory disease mortality, other causes mortality; Lung/Respiratory: lung cancer mortality, asbestosis mortality, other respiratory disease mortality;
other causes: other causes mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
163
Domain
Metric
Rating
Comments
Metric 6: Temporality
Medium There is appropriate temporality reported (>10 years) to follow-up to establish
exposure-outcome, however it is not clear what share of workers has longer follow up
time, as only man-years are reported, not total workers by years of service. In the pa-
per on the same cohort published prior to this one, which had more subjects (Peto et al.
1977, HEROID: 3084525), 406/1085 (37% ) of workers had >20 years of service. It
seems reasonable to assume a similar proportion in the current study.
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Metric 8: Reporting Bias
Medium Lung Cancer: No ICD codes were used to establish mortality, except for gastrointestinal
cancer, however no version is explicitly listed. Authors report that follow-up was itself
completed by National Health Central Register (NHCR) and by the factory personnel
department.; Other Cancer(s): No ICD codes were used to establish mortality, except for
gastrointestinal cancer (Codes 151-154), however no version is explicitly listed. Authors
report that follow-up was itself completed by National Health Central Register (NHCR)
and by the factory personnel department.; Other Non-Cancer Outcomes: No ICD codes
were used to establish mortality, except for gastrointestinal cancer, however no version is
explicitly listed. Authors report that follow-up was itself completed by National Health
Central Register (NHCR) and by the factory personnel department.
High Outcomes are reported in all parts of study along with p-values. Some data is available
in text with confidence limits.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Low Sex is adjusted for based on inclusion of only men. There is brief mention of adjustment
for man-years in the analysis, but no other variables are discussed.
Metric 10: Covariate Characterization Low Covariate is assumed to have been collected from factory personnel records. No explicit
detail is provided.
Metric 11: Co-exposure Counfounding Low Authors do not explicitly mention any co-exposures.
Domain 5: Analysis
Metric 12:
Metric 13:
Metric 14:
Metric 15:
Continued on next page ...
Study Design and Methods
Statistical Power
Reproducibility of Analyses
Statistical Analysis
Medium The study design is appropriate for measuring relative risk and mortality rates of work-
ers from the textile factory.
Medium The number of subjects (n=679) should be sufficient to find any true relationships be-
tween exposure and outcome.
Medium The methods described in the paper are clear enough to be conceptually replicated.
Medium SMR analyses were appropriate, with no explicit assumptions to be met.
Page 470 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 163 Table: 1 of 1
... continued from previous page
Peto, J. (1980). Lung cancer mortality in relation to measured dust levels in an asbestos textile factory. IARC Scientific Publications (1980):829-836.
Lung Cancer; other cancers mortality; asbestosis mortality, other respiratory disease mortality, other causes mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: lung cancer mortality, other cancers mortality; Mortality: lung cancer mortality, other cancers mortality, asbestosis mortality, other
respiratory disease mortality, other causes mortality; Lung/Respiratory: lung cancer mortality, asbestosis mortality, other respiratory disease mortality;
other causes: other causes mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
163
Domain
Metric
Rating
Comments
Additional Comments:
Asbestos fiber types are detailed in an earlier iteration of the current study (Knox et al., 1968, HEROID: 115). There is limited detail on recruitment and
participation methods and rates, as well as how outcomes were ascertained by the National Health Central Register and factory personnel departments.
Overall Quality Determination
Low
* No biomarkers were identified for this evaluation.
Page 471 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082492 Table: 1 of 3
Study Citation: Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British Journal of Industrial Medicine 47(1990):810-814.
Asbestosis
Lung/Respiratory: chronic obstructive pulmonary diseases mortality, asbestosis mortality, mortality from COPD+asbestosis, chronic respiratory disease
mortality; Cancer/Carcinogenesis: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate cancer mortality, bladder cancer
mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, colorectal, pancreas, prostate, bladder,
kidney, brain and CNS, lymphatic and hematopioetic; Mortality: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate
cancer mortality, bladder cancer mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, col-
orectal, liver, pancreas, prostate, bladder, kidney, brain and CNS, lymphatic and hematopioeticcerebrovascular diseases mortality, stroke mortality, chronic
obstructive pulmonary diseases mortality,mortality from COPD+asbestosis, asbestosis mortality, chronic respiratory disease mortality; Skin/Connective
Tissue: pleural and peritoneal cancer mortality; Neurological/Behavioral: cerebrovascular diseases mortality, stroke mortality, mortality from the following
neoplastic causes: brain and CNS; Cardiovascular: cerebrovascular diseases mortality, stroke mortality; Gastrointestinal: oro-pharyngeal cancer mor-
tality or oral cavity/pharynx cancer mortality, gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality,; Immune/Hematological:
lymphatic and haematopoietic cancer mortality; Reproductive/Developmental: prostate cancer mortality; Renal/Kidney: mortality from the following
neoplastic causes: kidney,
Asbestos Fiber Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Type(s):
Linked HERO ID(s): 3082492, 2592425, 5060134
HERO ID: 3082492
Domain Metric Rating Comments
Domain 1: Study Participation
Continued on next page ...
Health
Outcome:
Target
Organ(s):
Page 472 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 1 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
Asbestosis
Lung/Respiratory: chronic obstructive pulmonary diseases mortality, asbestosis mortality, mortality from COPD+asbestosis, chronic respiratory disease
mortality; Cancer/Carcinogenesis: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate cancer mortality, bladder cancer
mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, colorectal, pancreas, prostate, bladder,
kidney, brain and CNS, lymphatic and hematopioetic; Mortality: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate
cancer mortality, bladder cancer mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, col-
orectal, liver, pancreas, prostate, bladder, kidney, brain and CNS, lymphatic and hematopioeticcerebrovascular diseases mortality, stroke mortality, chronic
obstructive pulmonary diseases mortality,mortality from COPD+asbestosis, asbestosis mortality, chronic respiratory disease mortality; Skin/Connective
Tissue: pleural and peritoneal cancer mortality; Neurological/Behavioral: cerebrovascular diseases mortality, stroke mortality, mortality from the following
neoplastic causes: brain and CNS; Cardiovascular: cerebrovascular diseases mortality, stroke mortality; Gastrointestinal: oro-pharyngeal cancer mor-
tality or oral cavity/pharynx cancer mortality, gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality,; Immune/Hematological:
lymphatic and haematopoietic cancer mortality; Reproductive/Developmental: prostate cancer mortality; Renal/Kidney: mortality from the following
neoplastic causes: kidney,
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 1: Participant Selection Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Sup-
plemental File, "Subjects included men from the Balangero mine worker cohort that
were employed in an Italian asbestos mine. The initial cohort ((Rubino et al., 1979), pg
188) consisted of 952 men employed between 1/1/1930 and 12/31/1965, with at least
30 calendar days' employment during that period. Mortality data were collected from
1/1/1946 to 12/31/1975. Workers for which vital status could not be acertained and a
small number of contract workers employed intermittently were excluded. In the first
follow-up, 1058 workers were included that had worked at least one year between 1946
and 1987 and mortality follow-up was extended through 12/31/1987 ((Piolatto et al.,
1990), pg 810). In subsequent follow-ups ((Pira et al., 2009) pg 805, and (Pira et al.,
2017)), subjects included 1056 men from the Balangero mine worker cohort employed
between 1930 and 1990, and mortality records were evaluated though 2003 and 2014,
respectively. Records were not available between 1987 and 1990, when the mine closed,
so workers employed in 1987 were assumed to be employed through 1990 unless they
died during that period. Additional details in the most recent following indicated that
the initial cohort included 1182 men; the 126 excluded subjects were contract work-
ers, those employed <1 yr, those with inconsistencies in data, and those known to have
died prior to 1946 (Pira et al., 2017) pg 558." As described in the final Asbestos Part 1
Risk Evaluation Supplemental File for Laryngeal Cancers, "Subjects were drawn from
the employment records of an Italian asbestos mine (n=1056 men). Those eligible had
worked for the mine for at least one year between 1930 and 1989. Description of the
mine setting was described including some historical occupational measurements of dust
and asbestos."This metric was rated High in the Draft and Medium in the Final Asbestos
Part 1 Risk Evaluation.
Continued on next page ...
Page 473 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082492 Table: 1 of 3
... continued from previous page
Study Citation: Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British Journal of Industrial Medicine 47(1990):810-814.
Asbestosis
Lung/Respiratory: chronic obstructive pulmonary diseases mortality, asbestosis mortality, mortality from COPD+asbestosis, chronic respiratory disease
mortality; Cancer/Carcinogenesis: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate cancer mortality, bladder cancer
mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, colorectal, pancreas, prostate, bladder,
kidney, brain and CNS, lymphatic and hematopioetic; Mortality: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate
cancer mortality, bladder cancer mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, col-
orectal, liver, pancreas, prostate, bladder, kidney, brain and CNS, lymphatic and hematopioeticcerebrovascular diseases mortality, stroke mortality, chronic
obstructive pulmonary diseases mortality,mortality from COPD+asbestosis, asbestosis mortality, chronic respiratory disease mortality; Skin/Connective
Tissue: pleural and peritoneal cancer mortality; Neurological/Behavioral: cerebrovascular diseases mortality, stroke mortality, mortality from the following
neoplastic causes: brain and CNS; Cardiovascular: cerebrovascular diseases mortality, stroke mortality; Gastrointestinal: oro-pharyngeal cancer mor-
tality or oral cavity/pharynx cancer mortality, gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality,; Immune/Hematological:
lymphatic and haematopoietic cancer mortality; Reproductive/Developmental: prostate cancer mortality; Renal/Kidney: mortality from the following
neoplastic causes: kidney,
Asbestos Fiber Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Type(s):
Linked HERO ID(s): 3082492, 2592425, 5060134
HERO ID: 3082492
Domain Metric Rating Comments
Metric 2: Attrition High These three studies, along with Rubino etal. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Supple-
mental File, "In the most recent follow-up, study authors report that one of the strengths
of the study is low proportion of subjects lost to follow-up (Pira et al., 2017) pg 562.
Loss to follow-up was 2% in the initial cohort (Rubino et al., 1979), 3% in the first
follow-up ((Piolatto et al., 1990), pg 810), and 4% in the most recent follow-ups (Pira
et al., 2009) pg 805; (Pira et al., 2017) pg 559."As described in the Final Asbestos Part
1 Risk Evaluation Systematic Review Supplemental File for Laryngeal Cancer "The
study authors note that the cause of death could not be determined for a small sample
(n=6), and a small percentage (3.8% ) of participants emigrated or were otherwise lost
to follow-up. This level of attritionis not expected to appreciably bias the results."This
Metric was rated as High in both the Draft and Final Asbestos Part 1 Risk Evaluation.
Continued on next page ...
Health
Outcome:
Target
Organ(s):
Page 474 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 1 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
Asbestosis
Lung/Respiratory: chronic obstructive pulmonary diseases mortality, asbestosis mortality, mortality from COPD+asbestosis, chronic respiratory disease
mortality; Cancer/Carcinogenesis: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate cancer mortality, bladder cancer
mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, colorectal, pancreas, prostate, bladder,
kidney, brain and CNS, lymphatic and hematopioetic; Mortality: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate
cancer mortality, bladder cancer mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, col-
orectal, liver, pancreas, prostate, bladder, kidney, brain and CNS, lymphatic and hematopioeticcerebrovascular diseases mortality, stroke mortality, chronic
obstructive pulmonary diseases mortality,mortality from COPD+asbestosis, asbestosis mortality, chronic respiratory disease mortality; Skin/Connective
Tissue: pleural and peritoneal cancer mortality; Neurological/Behavioral: cerebrovascular diseases mortality, stroke mortality, mortality from the following
neoplastic causes: brain and CNS; Cardiovascular: cerebrovascular diseases mortality, stroke mortality; Gastrointestinal: oro-pharyngeal cancer mor-
tality or oral cavity/pharynx cancer mortality, gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality,; Immune/Hematological:
lymphatic and haematopoietic cancer mortality; Reproductive/Developmental: prostate cancer mortality; Renal/Kidney: mortality from the following
neoplastic causes: kidney,
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 3: Comparison Group Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Supple-
mental File, "The most complete data on comparison groups is available from the most
recent follow-up (Pira et al., 2017). General population mortality rates using the whole
country from 1955 until 1980 and specifically the Piedmont Region (where the mine is
located) from 1981 onwards (no regional rates available prior to 1981). The 1955-1959
rates were applied to 1946-1954 period (no available data); this may have led to an un-
derestimate of expected deaths which may have showed and increased rate during this
period. Expected numbers of deaths (overall and selected cancers) were computed us-
ing age-specific and calendar-year-specific (5-year categories) male death rates (Pira et
al., 2017) pg 559. The only deviation from this was in the first follow-up, which used
national mortality rates were for the entire follow-up period (through 1987) (Piolatto et
al., 1990) pg. 811). In the initial study on this cohort ((Rubino et al., 1979), pg. 189),
an additional case-control study was performed in which 5 age-matched controls were
selected at random; they were confirmed alive at the time of death for the matched case.
No details on what population provided controls. The evaluation is based on the cohort
mortality study only, as this was the analysis carried through the 3 follow-up studies
(Pira et al., 2017; Pira et al., 2009; Piolatto et al., 1990)."As described in the Final As-
bestos Part 1 Risk Evaluation Systematic Review Supplemental File for Laryngeal Can-
cer, "Mortality rates for males from the Piedmont Region were used as a comparison
group. This is a sufficiently similar group, however, the study authors note that mortality
rates were not available for certain periods (e.g., 1946-1954) and rates from adjacent
periods of time were used instead (1955-1959 rates applied to 1946-1954). "This metric
was rated as High in the Draft and Medium in the Final Asbestos Part 1 Risk Evaluation.
Continued on next page ...
Page 475 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082492 Table: 1 of 3
... continued from previous page
Study Citation: Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British Journal of Industrial Medicine 47(1990):810-814.
Asbestosis
Lung/Respiratory: chronic obstructive pulmonary diseases mortality, asbestosis mortality, mortality from COPD+asbestosis, chronic respiratory disease
mortality; Cancer/Carcinogenesis: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate cancer mortality, bladder cancer
mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, colorectal, pancreas, prostate, bladder,
kidney, brain and CNS, lymphatic and hematopioetic; Mortality: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate
cancer mortality, bladder cancer mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, col-
orectal, liver, pancreas, prostate, bladder, kidney, brain and CNS, lymphatic and hematopioeticcerebrovascular diseases mortality, stroke mortality, chronic
obstructive pulmonary diseases mortality,mortality from COPD+asbestosis, asbestosis mortality, chronic respiratory disease mortality; Skin/Connective
Tissue: pleural and peritoneal cancer mortality; Neurological/Behavioral: cerebrovascular diseases mortality, stroke mortality, mortality from the following
neoplastic causes: brain and CNS; Cardiovascular: cerebrovascular diseases mortality, stroke mortality; Gastrointestinal: oro-pharyngeal cancer mor-
tality or oral cavity/pharynx cancer mortality, gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality,; Immune/Hematological:
lymphatic and haematopoietic cancer mortality; Reproductive/Developmental: prostate cancer mortality; Renal/Kidney: mortality from the following
neoplastic causes: kidney,
Asbestos Fiber Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Type(s):
Linked HERO ID(s): 3082492, 2592425, 5060134
HERO ID: 3082492
Domain Metric Rating Comments
Health
Outcome:
Target
Organ(s):
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Supple-
mental File, "Most complete report of exposure assessment is in initial cohort study
((Rubino et al., 1979) pg 189). Chrysotile fiber counts were first measured in 1969 us-
ing membrane filter collection and phase contrast microscopy (frequency not reported).
To estimate exposure from 1946-1969, factory records on daily production, equipment
used, characteristics of the job and number of hours/day were used (this method has
considerable limitations due to basis on mean values for large job categories and no al-
lowance for changes in weather). Simulated and measured data were made comparable
by using weighting factors (e.g., more dusty operation for 1-2 hr/d compared with longer
working hours in the past). Less detailed information was included in follow-up reports
((Piolatto et al., 1990) pg. 810; (Pira et al., 2017), pg 558-559)."As described in the Fi-
nal Asbestos Part 1 Risk Evaluation for Laryngeal Cancer, "Descriptions of the mine and
occupational surveillance was described. Estimates of historical mean concentrations
were 37 fibre/mL up to 1950 and 5 fibre/mL between 1971 and 1976. Exposure was de-
termined by employment at the asbestos mine only."This metric was rated as Medium in
the Draft and Low in the Final Risk Evaluation for Asbestos Part 1. However, the cohort
meets the criteria for Medium as described above.
Continued on next page ...
Page 476 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082492 Table: 1 of 3
... continued from previous page
Study Citation: Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British Journal of Industrial Medicine 47(1990):810-814.
Asbestosis
Lung/Respiratory: chronic obstructive pulmonary diseases mortality, asbestosis mortality, mortality from COPD+asbestosis, chronic respiratory disease
mortality; Cancer/Carcinogenesis: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate cancer mortality, bladder cancer
mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, colorectal, pancreas, prostate, bladder,
kidney, brain and CNS, lymphatic and hematopioetic; Mortality: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate
cancer mortality, bladder cancer mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, col-
orectal, liver, pancreas, prostate, bladder, kidney, brain and CNS, lymphatic and hematopioeticcerebrovascular diseases mortality, stroke mortality, chronic
obstructive pulmonary diseases mortality,mortality from COPD+asbestosis, asbestosis mortality, chronic respiratory disease mortality; Skin/Connective
Tissue: pleural and peritoneal cancer mortality; Neurological/Behavioral: cerebrovascular diseases mortality, stroke mortality, mortality from the following
neoplastic causes: brain and CNS; Cardiovascular: cerebrovascular diseases mortality, stroke mortality; Gastrointestinal: oro-pharyngeal cancer mor-
tality or oral cavity/pharynx cancer mortality, gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality,; Immune/Hematological:
lymphatic and haematopoietic cancer mortality; Reproductive/Developmental: prostate cancer mortality; Renal/Kidney: mortality from the following
neoplastic causes: kidney,
Asbestos Fiber Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Type(s):
Linked HERO ID(s): 3082492, 2592425, 5060134
HERO ID: 3082492
Domain Metric Rating Comments
Metric 5: Exposure Levels Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Supple-
mental File, "In the initial cohort ((Rubino et al., 1979), Table 8), exposure was reported
as up to 100 fiber/yr or >100 fiber/year. In the follow-ups, exposure was reported as
<100 fiber/mL-yr, 100-<400 fiber/mL-yr, and >=400 fiber/ml-yr ((Piolatto et al., 1990),
Table 3; (Pira et al., 2009), Table 2; (Pira et al., 2017), Tables 3-4)." This metric was not
rated in the Final Asbestos Part 1 Risk Evaluation.
Metric 6: Temporality High These three studies, along with Rubino etal. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
The rating of High for other outcomes is based on the most recent publication, which
has the longest follow-up duration for this cohort (follow up of the 1946-1990 cohort
through 2014), as described in the Draft Risk Evaluation for Asbestos Part 1. The first
two studies in the cohort (Rubino et al., 1979 and Piolatto et al., 1990) have inadequate
follow-up durations (<15 years) considering the potential latency periods for some of
the outcomes assessed. As described in the Asbestos Part 1 Final Risk Evaluation for
Laryngeal Cancer, "Subjects were followed until loss to follow-up, their death, 85th
birthday, or through 2014. This is a sufficiently long follow-up period." This metric was
rated as High in both the Draft and Final Asbestos Part 1 Risk Evaluations.
Domain 3: Outcome Assessment
Continued on next page ...
Health
Outcome:
Target
Organ(s):
Page 477 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 1 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
Asbestosis
Lung/Respiratory: chronic obstructive pulmonary diseases mortality, asbestosis mortality, mortality from COPD+asbestosis, chronic respiratory disease
mortality; Cancer/Carcinogenesis: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate cancer mortality, bladder cancer
mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, colorectal, pancreas, prostate, bladder,
kidney, brain and CNS, lymphatic and hematopioetic; Mortality: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate
cancer mortality, bladder cancer mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, col-
orectal, liver, pancreas, prostate, bladder, kidney, brain and CNS, lymphatic and hematopioeticcerebrovascular diseases mortality, stroke mortality, chronic
obstructive pulmonary diseases mortality,mortality from COPD+asbestosis, asbestosis mortality, chronic respiratory disease mortality; Skin/Connective
Tissue: pleural and peritoneal cancer mortality; Neurological/Behavioral: cerebrovascular diseases mortality, stroke mortality, mortality from the following
neoplastic causes: brain and CNS; Cardiovascular: cerebrovascular diseases mortality, stroke mortality; Gastrointestinal: oro-pharyngeal cancer mor-
tality or oral cavity/pharynx cancer mortality, gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality,; Immune/Hematological:
lymphatic and haematopoietic cancer mortality; Reproductive/Developmental: prostate cancer mortality; Renal/Kidney: mortality from the following
neoplastic causes: kidney,
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 7: Outcome Measurement or High Other Cancer(s): These three studies, along with Rubino et al. 1979, HERO ID 000178,
Characterization were evaluated for lung cancer as part of the Balangero, Italy cohort in the Draft As-
bestos Part 1 Risk Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was
evaluated for lung cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Eval-
uation (Dec. 2020). In the Draft Asbestos Part 1 Risk Evaluation, the cohort was rated
as High for this Metric. In the Final Asbestos Part 1 Risk Evaluation this metric was
rated as Medium for laryngeal cancer because "Cause specific mortalities were obtained
from death certificates collected from population registers, municipal registration of-
fices, and local health authorities. Causes of death were coded using ICD-9, however,
the study authors did not report whether cancer cases were histologically confirmed.
It"s unclear if there may be any misclassification from obtaining vital status or cause of
death from various sources."Evaluation of all causes of death assessed in the cohort was
based on death certificates and population registers and coded according to the Interna-
tional Classification of Diseases (ICD). Rubino et al., 1979, HERO ID 000178 coded
causes of deaths according to ICD-7. Piolatto et al. 1990, HERO ID 3082492 did not
specify which version of the ICD was used. Pira et al., 2009, HERO ID 2592425 and
Pira et al., 2017, HERO ID 5060134 used ICD-9 codes. Numbers of certified deaths for
each cause for the general population were obtained from the Italian National Institute
of Statistics and the World Health Organization.; Asbestosis: These three studies, along
with Rubino et al. 1979, HERO ID 000178, were evaluated for lung cancer as part of
the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk Evaluation (March 2020).
Pira et al. 2017, HERO ID 5060134 was evaluated for lung cancer and laryngeal cancer
in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020). In the Draft Asbestos Part
1 Risk Evaluation, the cohort was rated as High for this Metric. In the Final Asbestos
Part 1 Risk Evaluation this metric was rated as Medium for laryngeal cancer because
"Cause specific mortalities were obtained from death certificates collected from popula-
tion registers, municipal registration offices, and local health authorities. Causes of death
were coded using ICD-9, however, the study authors did not report whether cancer cases
were histologically confirmed. It"s unclear if there may be any misclassification from
obtaining vital status or cause of death from various sources."Evaluation of all causes
Page 478 Of 606 death assessed in the cohort was based on death certificates and population regis-
ters and coded according to the International Classification of Diseases (ICD). Rubino
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082492 Table: 1 of 3
... continued from previous page
Study Citation: Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British Journal of Industrial Medicine 47(1990):810-814.
Asbestosis
Lung/Respiratory: chronic obstructive pulmonary diseases mortality, asbestosis mortality, mortality from COPD+asbestosis, chronic respiratory disease
mortality; Cancer/Carcinogenesis: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate cancer mortality, bladder cancer
mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, colorectal, pancreas, prostate, bladder,
kidney, brain and CNS, lymphatic and hematopioetic; Mortality: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate
cancer mortality, bladder cancer mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, col-
orectal, liver, pancreas, prostate, bladder, kidney, brain and CNS, lymphatic and hematopioeticcerebrovascular diseases mortality, stroke mortality, chronic
obstructive pulmonary diseases mortality,mortality from COPD+asbestosis, asbestosis mortality, chronic respiratory disease mortality; Skin/Connective
Tissue: pleural and peritoneal cancer mortality; Neurological/Behavioral: cerebrovascular diseases mortality, stroke mortality, mortality from the following
neoplastic causes: brain and CNS; Cardiovascular: cerebrovascular diseases mortality, stroke mortality; Gastrointestinal: oro-pharyngeal cancer mor-
tality or oral cavity/pharynx cancer mortality, gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality,; Immune/Hematological:
lymphatic and haematopoietic cancer mortality; Reproductive/Developmental: prostate cancer mortality; Renal/Kidney: mortality from the following
neoplastic causes: kidney,
Asbestos Fiber Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Type(s):
Linked HERO ID(s): 3082492, 2592425, 5060134
HERO ID: 3082492
Domain Metric Rating Comments
Metric 8: Reporting Bias Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
This metric was rated as High in the Draft Asbestos Part 1 Risk Evaluation for lung
cancer and High in the Draft Asbestos Part 1 Risk Evaluation for lung cancer and la-
ryngeal cancer.However, results for some of the other outcomes assessed in the paper
were reported in less detail than the results for lung cancer, resulting in a lower rating for
this Metric for these other outcomes. For example, Table 4 in Pira et al., 2017, HERO
ID 5060134 reports mortality rate ratios (MRR) for lung cancer for selected indicators
of asbestos exposure, and does not include reporting of MRR for other outcomes. All
three papers reported SMRs for several outcomes, though there were some differences
between papers in terms of which specific outcomes were included. The most recent
follow-up (Pira et al., 2017, HERO ID 5060134) had the most complete reporting with
95% confidence intervals. Some of the results reported in Piolatto et al., 1990, HERO
ID 3082492 and Pira et al., 2009, HERO ID 2592425 did not include reporting of confi-
dence intervals.
Domain 4: Potential Confounding / Variability Control
Continued on next page ...
Health
Outcome:
Target
Organ(s):
Page 479 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 1 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
Asbestosis
Lung/Respiratory: chronic obstructive pulmonary diseases mortality, asbestosis mortality, mortality from COPD+asbestosis, chronic respiratory disease
mortality; Cancer/Carcinogenesis: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate cancer mortality, bladder cancer
mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, colorectal, pancreas, prostate, bladder,
kidney, brain and CNS, lymphatic and hematopioetic; Mortality: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate
cancer mortality, bladder cancer mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, col-
orectal, liver, pancreas, prostate, bladder, kidney, brain and CNS, lymphatic and hematopioeticcerebrovascular diseases mortality, stroke mortality, chronic
obstructive pulmonary diseases mortality,mortality from COPD+asbestosis, asbestosis mortality, chronic respiratory disease mortality; Skin/Connective
Tissue: pleural and peritoneal cancer mortality; Neurological/Behavioral: cerebrovascular diseases mortality, stroke mortality, mortality from the following
neoplastic causes: brain and CNS; Cardiovascular: cerebrovascular diseases mortality, stroke mortality; Gastrointestinal: oro-pharyngeal cancer mor-
tality or oral cavity/pharynx cancer mortality, gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality,; Immune/Hematological:
lymphatic and haematopoietic cancer mortality; Reproductive/Developmental: prostate cancer mortality; Renal/Kidney: mortality from the following
neoplastic causes: kidney,
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 9: Covariate Adjustment Medium SMRs were stratified by age and five-year categories of calendar year. Only males were
included. There is no mention of adjustment for race, but from 1981 onwards mortality
ratios were standardized to male deaths from the Piedmont region where the mine was
located, which likely reduced the potential for confounding by race or SES. Prior to
1981 mortality ratios were standardized to national mortality for Italy because regional
data were not available. The authors noted that potential confounding by smoking and
alcohol consumption were limitations for some of the outcomes assessed. However,
as noted in the Draft Asbestos Part 1 Risk Evaluation, "In the most recent follow-up,
data on smoking was limited to 14.5% of the cohort, but the prevalence of smoking in
this subset of the cohort was comparable to that of the general male population." The
outcomes that are known to be associated with alcohol consumption are assessed in a
separate form. Alcohol is not likely to be a confounder for the outcomes assessed in this
form.
Metric 10: Covariate Characterization High These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
This metric was rated High in the Draft and Medium in the Final Asbestos Part 1 Risk
Evaluation.As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Re-
view Supplemental File, "Empirical data obtained from employment records. Smoking
information was obtained from medical records (when available)."
Continued on next page ...
Page 480 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082492 Table: 1 of 3
... continued from previous page
Study Citation: Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British Journal of Industrial Medicine 47(1990):810-814.
Asbestosis
Lung/Respiratory: chronic obstructive pulmonary diseases mortality, asbestosis mortality, mortality from COPD+asbestosis, chronic respiratory disease
mortality; Cancer/Carcinogenesis: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate cancer mortality, bladder cancer
mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, colorectal, pancreas, prostate, bladder,
kidney, brain and CNS, lymphatic and hematopioetic; Mortality: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate
cancer mortality, bladder cancer mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, col-
orectal, liver, pancreas, prostate, bladder, kidney, brain and CNS, lymphatic and hematopioeticcerebrovascular diseases mortality, stroke mortality, chronic
obstructive pulmonary diseases mortality,mortality from COPD+asbestosis, asbestosis mortality, chronic respiratory disease mortality; Skin/Connective
Tissue: pleural and peritoneal cancer mortality; Neurological/Behavioral: cerebrovascular diseases mortality, stroke mortality, mortality from the following
neoplastic causes: brain and CNS; Cardiovascular: cerebrovascular diseases mortality, stroke mortality; Gastrointestinal: oro-pharyngeal cancer mor-
tality or oral cavity/pharynx cancer mortality, gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality,; Immune/Hematological:
lymphatic and haematopoietic cancer mortality; Reproductive/Developmental: prostate cancer mortality; Renal/Kidney: mortality from the following
neoplastic causes: kidney,
Asbestos Fiber Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Type(s):
Linked HERO ID(s): 3082492, 2592425, 5060134
HERO ID: 3082492
Health
Outcome:
Target
Organ(s):
Domain Metric Rating Comments
Metric 11: Co-exposure Counfounding Low No adjustments for potential co-exposures were described. The authors mentioned the
possibility of confounding by other occupational exposures. Samples of chrysotile from
the mine were examined in detail for contamination from other materials (Piolatto et al.,
1990 3082492) and fibrous amphiboles were not detected. Crocidolite was occasion-
ally present at the mine. Balangeroite accounted for 0.2-0.5% of total mass chrysotile
samples from the mine. Balangeroite is a fibrous silicate that is not considered a true
asbestos fiber and has similar dimensions to amphiboles (Piolatto et al., 1990 3082492,
Pira et al„ 2009 2592425, Pira et al„ 2017 5060134).
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13:
Statistical Power
Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the his Metric was rated as Medium in both the Draft and Final
Risk Evaluations for Asbestos Part 1.Balangero, Italy cohort in the Draft Asbestos Part
1 Risk Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated
for lung cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec.
2020). TAs described in the Asbestos Part 1 Final Risk Evaluation Systematic Review
Supplemental File for laryngeal cancer, "SMRs were used to assess differences in cause
specific mortality rates between employees of an asbestos mine compared to a reference
population in the same region. This is an appropriate design for the study question."
Medium The cohort size was generally adequate, although some outcomes, particularly some of
the cancer outcomes, had low numbers of observed causes of death.
Continued on next page ...
Page 481 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082492 Table: 1 of 3
... continued from previous page
Study Citation: Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British Journal of Industrial Medicine 47(1990):810-814.
Asbestosis
Lung/Respiratory: chronic obstructive pulmonary diseases mortality, asbestosis mortality, mortality from COPD+asbestosis, chronic respiratory disease
mortality; Cancer/Carcinogenesis: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate cancer mortality, bladder cancer
mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, colorectal, pancreas, prostate, bladder,
kidney, brain and CNS, lymphatic and hematopioetic; Mortality: gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality, prostate
cancer mortality, bladder cancer mortality, lymphatic and haematopoietic cancer mortality, mortality from the following neoplastic causes: stomach, col-
orectal, liver, pancreas, prostate, bladder, kidney, brain and CNS, lymphatic and hematopioeticcerebrovascular diseases mortality, stroke mortality, chronic
obstructive pulmonary diseases mortality,mortality from COPD+asbestosis, asbestosis mortality, chronic respiratory disease mortality; Skin/Connective
Tissue: pleural and peritoneal cancer mortality; Neurological/Behavioral: cerebrovascular diseases mortality, stroke mortality, mortality from the following
neoplastic causes: brain and CNS; Cardiovascular: cerebrovascular diseases mortality, stroke mortality; Gastrointestinal: oro-pharyngeal cancer mor-
tality or oral cavity/pharynx cancer mortality, gastric cancer mortality or stomach cancer mortality, intestinal cancer mortality,; Immune/Hematological:
lymphatic and haematopoietic cancer mortality; Reproductive/Developmental: prostate cancer mortality; Renal/Kidney: mortality from the following
neoplastic causes: kidney,
Asbestos Fiber Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
Type(s):
Linked HERO ID(s): 3082492, 2592425, 5060134
HERO ID: 3082492
Domain Metric Rating Comments
Metric 14:
Reproducibility of Analyses
Medium
These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the his Metric was rated as Medium in both the Draft and Final
Risk Evaluations for Asbestos Part 1.Balangero, Italy cohort in the Draft Asbestos Part
1 Risk Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated
for lung cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec.
2020). This metric was rated Medium in both the Draft and the Final Asbestos Part 1
Risk Evaluations.As described in the Final Asbestos Part 1 Risk Evaluation Systematic
Review Supplemental File, "The analysis was well-described and could be reproduced
with original data."
Metric 15:
Statistical Analysis
Medium
The methods for calculating SMRs are transparent.
Additional Comments: These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated for lung cancer as part of the Balangero, Italy cohort in the Draft
Asbestos Part 1 Risk Evaluation (March 2020), with an overall quality determination of High for lung cancer. Pira et al. 2017, HERO ID 5060134
was evaluated for lung cancer and laryngeal cancer in the Final Risk Evaluation (Dec. 2020) with an overall quality determination of Medium for lung
cancer and Medium for laryngeal cancer. Some of the analyses that were reported for lung cancer were not reported for other outcomes. There might
not be sufficient information for dose-response assessment for the outcomes assessed on this form (in this row). Outcomes with sufficient dose-response
information were evaluated in a separate form (row).The main fiber type was chrysotile. Crocidolite was occasionally present at the mine. Balangeroite,
which is a fibrous silicate, accounted for 0.2-0.5% of total mass chrysotile samples from the mine.This study assessed a cohort who worked in an open-air
mine, and thus these outdoor exposures might be different than exposures in other environments.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Health
Outcome:
Target
Organ(s):
Page 482 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082492 Table: 2 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British Journal of Industrial Medicine 47(1990):810-814.
MISSING
Lung/Respiratory: pleural cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum,lung cancer
mortality (assessed in Asbestos Part 1), laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1); Cancer/Carcinogenesis: pleural
cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum, laryngeal cancer
mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer mortality (assessed in Asbestos Part 1), all cancer mortality; Cardiovascular:
ischemic heart disease; Mortality: pleural cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of
the pleura and peritoneum,ischemic heart disease mortality,laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer
mortality (assessed in Asbestos Part 1), all cancer mortality, all cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Sup-
plemental File, "Subjects included men from the Balangero mine worker cohort that
were employed in an Italian asbestos mine. The initial cohort ((Rubino et al., 1979), pg
188) consisted of 952 men employed between 1/1/1930 and 12/31/1965, with at least
30 calendar days' employment during that period. Mortality data were collected from
1/1/1946 to 12/31/1975. Workers for which vital status could not be acertained and a
small number of contract workers employed intermittently were excluded. In the first
follow-up, 1058 workers were included that had worked at least one year between 1946
and 1987 and mortality follow-up was extended through 12/31/1987 ((Piolatto et al.,
1990), pg 810). In subsequent follow-ups ((Pira et al., 2009) pg 805, and (Pira et al.,
2017)), subjects included 1056 men from the Balangero mine worker cohort employed
between 1930 and 1990, and mortality records were evaluated though 2003 and 2014,
respectively. Records were not available between 1987 and 1990, when the mine closed,
so workers employed in 1987 were assumed to be employed through 1990 unless they
died during that period. Additional details in the most recent following indicated that
the initial cohort included 1182 men; the 126 excluded subjects were contract work-
ers, those employed <1 yr, those with inconsistencies in data, and those known to have
died prior to 1946 (Pira et al., 2017) pg 558." As described in the final Asbestos Part 1
Risk Evaluation Supplemental File for Laryngeal Cancers, "Subjects were drawn from
the employment records of an Italian asbestos mine (n=1056 men). Those eligible had
worked for the mine for at least one year between 1930 and 1989. Description of the
mine setting was described including some historical occupational measurements of dust
and asbestos."This metric was rated High in the Draft and Medium in the Final Asbestos
Part 1 Risk Evaluation.
Continued on next page ...
Page 483 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 2 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Lung/Respiratory: pleural cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum,lung cancer
mortality (assessed in Asbestos Part 1), laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1); Cancer/Carcinogenesis: pleural
cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum, laryngeal cancer
mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer mortality (assessed in Asbestos Part 1), all cancer mortality; Cardiovascular:
ischemic heart disease; Mortality: pleural cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of
the pleura and peritoneum,ischemic heart disease mortality,laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer
mortality (assessed in Asbestos Part 1), all cancer mortality, all cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 2: Attrition High These three studies, along with Rubino etal. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Supple-
mental File, "In the most recent follow-up, study authors report that one of the strengths
of the study is low proportion of subjects lost to follow-up (Pira et al., 2017) pg 562.
Loss to follow-up was 2% in the initial cohort (Rubino et al., 1979), 3% in the first
follow-up ((Piolatto et al., 1990), pg 810), and 4% in the most recent follow-ups (Pira
et al., 2009) pg 805; (Pira et al., 2017) pg 559."As described in the Final Asbestos Part
1 Risk Evaluation Systematic Review Supplemental File for Laryngeal Cancer "The
study authors note that the cause of death could not be determined for a small sample
(n=6), and a small percentage (3.8% ) of participants emigrated or were otherwise lost
to follow-up. This level of attrition is not expected to appreciably bias the results."This
Metric was rated as High in both the Draft and Final Asbestos Part 1 Risk Evaluation.
Continued on next page ...
Page 484 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 2 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Lung/Respiratory: pleural cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum,lung cancer
mortality (assessed in Asbestos Part 1), laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1); Cancer/Carcinogenesis: pleural
cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum, laryngeal cancer
mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer mortality (assessed in Asbestos Part 1), all cancer mortality; Cardiovascular:
ischemic heart disease; Mortality: pleural cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of
the pleura and peritoneum,ischemic heart disease mortality,laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer
mortality (assessed in Asbestos Part 1), all cancer mortality, all cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 3: Comparison Group Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Supple-
mental File, "The most complete data on comparison groups is available from the most
recent follow-up (Pira et al., 2017). General population mortality rates using the whole
country from 1955 until 1980 and specifically the Piedmont Region (where the mine is
located) from 1981 onwards (no regional rates available prior to 1981). The 1955-1959
rates were applied to 1946-1954 period (no available data); this may have led to an un-
derestimate of expected deaths which may have showed and increased rate during this
period. Expected numbers of deaths (overall and selected cancers) were computed us-
ing age-specific and calendar-year-specific (5-year categories) male death rates (Pira et
al., 2017) pg 559. The only deviation from this was in the first follow-up, which used
national mortality rates were for the entire follow-up period (through 1987) (Piolatto et
al., 1990) pg. 811). In the initial study on this cohort ((Rubino et al., 1979), pg. 189),
an additional case-control study was performed in which 5 age-matched controls were
selected at random; they were confirmed alive at the time of death for the matched case.
No details on what population provided controls. The evaluation is based on the cohort
mortality study only, as this was the analysis carried through the 3 follow-up studies
(Pira et al., 2017; Pira et al., 2009; Piolatto et al., 1990)."As described in the Final As-
bestos Part 1 Risk Evaluation Systematic Review Supplemental File for Laryngeal Can-
cer, "Mortality rates for males from the Piedmont Region were used as a comparison
group. This is a sufficiently similar group, however, the study authors note that mortality
rates were not available for certain periods (e.g., 1946-1954) and rates from adjacent
periods of time were used instead (1955-1959 rates applied to 1946-1954). "This metric
was rated as High in the Draft and Medium in the Final Asbestos Part 1 Risk Evaluation.
Domain 2: Exposure Characterization
Continued on next page ...
Page 485 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 2 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Lung/Respiratory: pleural cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum,lung cancer
mortality (assessed in Asbestos Part 1), laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1); Cancer/Carcinogenesis: pleural
cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum, laryngeal cancer
mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer mortality (assessed in Asbestos Part 1), all cancer mortality; Cardiovascular:
ischemic heart disease; Mortality: pleural cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of
the pleura and peritoneum,ischemic heart disease mortality,laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer
mortality (assessed in Asbestos Part 1), all cancer mortality, all cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 4: Measurement of Exposure Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Supple-
mental File, "Most complete report of exposure assessment is in initial cohort study
((Rubino et al., 1979) pg 189). Chrysotile fiber counts were first measured in 1969 us-
ing membrane filter collection and phase contrast microscopy (frequency not reported).
To estimate exposure from 1946-1969, factory records on daily production, equipment
used, characteristics of the job and number of hours/day were used (this method has
considerable limitations due to basis on mean values for large job categories and no al-
lowance for changes in weather). Simulated and measured data were made comparable
by using weighting factors (e.g., more dusty operation for 1-2 hr/d compared with longer
working hours in the past). Less detailed information was included in follow-up reports
((Piolatto et al., 1990) pg. 810; (Pira et al., 2017), pg 558-559)."As described in the Fi-
nal Asbestos Part 1 Risk Evaluation for Laryngeal Cancer, "Descriptions of the mine and
occupational surveillance was described. Estimates of historical mean concentrations
were 37 fibre/mL up to 1950 and 5 fibre/mL between 1971 and 1976. Exposure was de-
termined by employment at the asbestos mine only."This metric was rated as Medium in
the Draft and Low in the Final Risk Evaluation for Asbestos Part 1. However, the cohort
meets the criteria for Medium as described above.
Metric 5: Exposure Levels Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Supple-
mental File, "In the initial cohort ((Rubino et al., 1979), Table 8), exposure was reported
as up to 100 fiber/yr or >100 fiber/year. In the follow-ups, exposure was reported as
<100 fiber/mL-yr, 100-<400 fiber/mL-yr, and >=400 fiber/ml-yr ((Piolatto et al., 1990),
Table 3; (Pira et al., 2009), Table 2; (Pira et al., 2017), Tables 3-4)." This metric was not
rated in the Final Asbestos Part 1 Risk Evaluation.
Continued on next page ...
Page 486 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 2 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Lung/Respiratory: pleural cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum,lung cancer
mortality (assessed in Asbestos Part 1), laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1); Cancer/Carcinogenesis: pleural
cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum, laryngeal cancer
mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer mortality (assessed in Asbestos Part 1), all cancer mortality; Cardiovascular:
ischemic heart disease; Mortality: pleural cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of
the pleura and peritoneum,ischemic heart disease mortality,laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer
mortality (assessed in Asbestos Part 1), all cancer mortality, all cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 6: Temporality High These three studies, along with Rubino etal. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
The rating of High for other outcomes is based on the most recent publication, which
has the longest follow-up duration for this cohort (follow up of the 1946-1990 cohort
through 2014), as described in the Draft Risk Evaluation for Asbestos Part 1. The first
two studies in the cohort (Rubino et al., 1979 and Piolatto et al., 1990) have inadequate
follow-up durations (<15 years) considering the potential latency periods for some of
the outcomes assessed. As described in the Asbestos Part 1 Final Risk Evaluation for
Laryngeal Cancer, "Subjects were followed until loss to follow-up, their death, 85th
birthday, or through 2014. This is a sufficiently long follow-up period." This metric was
rated as High in both the Draft and Final Asbestos Part 1 Risk Evaluations.
Domain 3: Outcome Assessment
Continued on next page ...
Page 487 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 2 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Lung/Respiratory: pleural cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum,lung cancer
mortality (assessed in Asbestos Part 1), laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1); Cancer/Carcinogenesis: pleural
cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum, laryngeal cancer
mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer mortality (assessed in Asbestos Part 1), all cancer mortality; Cardiovascular:
ischemic heart disease; Mortality: pleural cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of
the pleura and peritoneum,ischemic heart disease mortality,laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer
mortality (assessed in Asbestos Part 1), all cancer mortality, all cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 7: Outcome Measurement or High Other Cancer(s): These three studies, along with Rubino et al. 1979, HERO ID 000178,
Characterization were evaluated for lung cancer as part of the Balangero, Italy cohort in the Draft As-
bestos Part 1 Risk Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was
evaluated for lung cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evalu-
ation (Dec. 2020). In the Draft Asbestos Part 1 Risk Evaluation, the cohort was rated as
High for this Metric. In the Final Asbestos Part 1 Risk Evaluation this metric was rated
as Medium for laryngeal cancer because "Cause specific mortalities were obtained from
death certificates collected from population registers, municipal registration offices, and
local health authorities. Causes of death were coded using ICD-9, however, the study
authors did not report whether cancer cases were histologically confirmed. It"s unclear
if there may be any misclassification from obtaining vital status or cause of death from
various sources."Evaluation of all causes of death assessed in the cohort was based
on death certificates and population registers and coded according to the International
Classification of Diseases (ICD). Rubino et al., 1979, HERO ID 000178 coded causes
of deaths according to ICD-7. Piolatto et al. 1990, HERO ID 3082492 did not specify
which version of the ICD was used. Pira et al., 2009, HERO ID 2592425 and Pira et al.,
2017, HERO ID 5060134 used ICD-9 codes. Numbers of certified deaths for each cause
for the general population were obtained from the Italian National Institute of Statistics
and the World Health Organization.; Other Non-Cancer Outcomes: These three stud-
ies, along with Rubino et al. 1979, HERO ID 000178, were evaluated for lung cancer as
part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk Evaluation (March
2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung cancer and laryngeal
cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020). In the Draft Asbestos
Part 1 Risk Evaluation, the cohort was rated as High for this Metric. In the Final As-
bestos Part 1 Risk Evaluation this metric was rated as Medium for laryngeal cancer
because "Cause specific mortalities were obtained from death certificates collected from
population registers, municipal registration offices, and local health authorities. Causes
of death were coded using ICD-9, however, the study authors did not report whether
cancer cases were histologically confirmed. It"s unclear if there may be any misclassi-
fication from obtaining vital status or cause of death from various sources."Evaluation
of all causes of death assessed in the cohort was based on death certificates and popula-
tion registers and coded according to the International Classification of Diseases (ICD).
Rubino et al., 1979, HERO ID 000178 coded causes of deaths according to ICD-7. Pi-
olatto et al. 1990, HERO ID 3082492 did not specify which version of the ICD was
used. Pira et al„ 2009, HERO ID 2592425 and Pira et al„ 2017, HERO ID 5060134 used
ICD-9 codes. Numbers of certified deaths for each cause for the general population were
Page 488 of 606 obtained from the Italian National Institute of Statistics and the World Health Organiza-
tion.
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 2 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Lung/Respiratory: pleural cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum,lung cancer
mortality (assessed in Asbestos Part 1), laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1); Cancer/Carcinogenesis: pleural
cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum, laryngeal cancer
mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer mortality (assessed in Asbestos Part 1), all cancer mortality; Cardiovascular:
ischemic heart disease; Mortality: pleural cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of
the pleura and peritoneum,ischemic heart disease mortality,laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer
mortality (assessed in Asbestos Part 1), all cancer mortality, all cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 8: Reporting Bias High These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
This metric was rated as High in the Draft Asbestos Part 1 Risk Evaluation for lung can-
cer and High in the Draft Asbestos Part 1 Risk Evaluation for lung cancer and laryngeal
cancer.All three papers reported SMRs for several outcomes, though there were some
differences between papers in terms of which specific outcomes were included. The
most recent follow-up (Pira et al., 2017, HERO ID 5060134) had the most complete re-
porting with 95% confidence intervals. Some of the results reported in Piolatto et al.,
1990, HERO ID 3082492 and Pira et al„ 2009, HERO ID 2592425 did not include re-
porting of confidence intervals.Dose-response information was reported for laryngeal
cancer, lung cancer, pleural and peritoneal cancer, all cancer, and all causes in Table 2
of Pira et al., 2009, HERO ID 2592425 and for laryngeal cancer, lung cancer, pleural
cancer, and ischemic heart disease in Table 3 of Pira et al., 2017, HERO ID 5060134.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Medium SMRs were stratified by age and five-year categories of calendar year. Only males were
included. There is no mention of adjustment for race, but from 1981 onwards mortality
ratios were standardized to male deaths from the Piedmont region where the mine was
located, which likely reduced the potential for confounding by race or SES. Prior to
1981 mortality ratios were standardized to national mortality for Italy because regional
data were not available. The authors noted that potential confounding by smoking and
alcohol consumption were limitations for some of the outcomes assessed. However,
as noted in the Draft Asbestos Part 1 Risk Evaluation, "In the most recent follow-up,
data on smoking was limited to 14.5% of the cohort, but the prevalence of smoking in
this subset of the cohort was comparable to that of the general male population." The
outcomes that are known to be associated with alcohol consumption are assessed in a
separate form. Alcohol is not likely to be a confounder for the outcomes assessed in this
form.
Continued on next page ...
Page 489 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 2 of 3
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Lung/Respiratory: pleural cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum,lung cancer
mortality (assessed in Asbestos Part 1), laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1); Cancer/Carcinogenesis: pleural
cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum, laryngeal cancer
mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer mortality (assessed in Asbestos Part 1), all cancer mortality; Cardiovascular:
ischemic heart disease; Mortality: pleural cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of
the pleura and peritoneum,ischemic heart disease mortality,laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer
mortality (assessed in Asbestos Part 1), all cancer mortality, all cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain
Metric
Rating
Comments
Metric 10:
Covariate Characterization
High
These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
This metric was rated High in the Draft and Medium in the Final Asbestos Part 1 Risk
Evaluation.As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Re-
view Supplemental File, "Empirical data obtained from employment records. Smoking
information was obtained from medical records (when available)."
Metric 11:
Co-exposure Counfounding
Low
No adjustments for potential co-exposures were described. The authors mentioned the
possibility of confounding by other occupational exposures. Samples of chrysotile from
the mine were examined in detail for contamination from other materials (Piolatto et al.,
1990 3082492) and fibrous amphiboles were not detected. Crocidolite was occasion-
ally present at the mine. Balangeroite accounted for 0.2-0.5% of total mass chrysotile
samples from the mine. Balangeroite is a fibrous silicate that is not considered a true
asbestos fiber and has similar dimensions to amphiboles (Piolatto et al., 1990 3082492,
Pira et al„ 2009 2592425, Pira et al„ 2017 5060134).
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
This Metric was rated as Medium in both the Draft and Final Risk Evaluations for As-
bestos Part l.As described in the Asbestos Part 1 Final Risk Evaluation Systematic
Review Supplemental File for laryngeal cancer, "SMRs were used to assess differences
in cause specific mortality rates between employees of an asbestos mine compared to
a reference population in the same region. This is an appropriate design for the study
question."
Metric 13:
Statistical Power
Medium
The cohort size was generally adequate, although some outcomes, particularly some of
the cancer outcomes, had low numbers of observed causes of death.
Continued on next
page...
Page 490 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 2 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Lung/Respiratory: pleural cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum,lung cancer
mortality (assessed in Asbestos Part 1), laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1); Cancer/Carcinogenesis: pleural
cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of the pleura and peritoneum, laryngeal cancer
mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer mortality (assessed in Asbestos Part 1), all cancer mortality; Cardiovascular:
ischemic heart disease; Mortality: pleural cancer mortality, peritoneal cancer mortality, mortality from cancer of the pleura only, mortality from cancer of
the pleura and peritoneum,ischemic heart disease mortality,laryngeal cancer mortality or larynx cancer mortality (assessed in Asbestos Part 1), lung cancer
mortality (assessed in Asbestos Part 1), all cancer mortality, all cause mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 14: Reproducibility of Analyses Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the his Metric was rated as Medium in both the Draft and Final
Risk Evaluations for Asbestos Part 1.Balangero, Italy cohort in the Draft Asbestos Part
1 Risk Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated
for lung cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec.
2020). This metric was rated Medium in both the Draft and the Final Asbestos Part 1
Risk Evaluations.As described in the Final Asbestos Part 1 Risk Evaluation Systematic
Review Supplemental File, "The analysis was well-described and could be reproduced
with original data."
Metric 15: Statistical Analysis Medium The methods for calculating SMRs are transparent.
Additional Comments: These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated for lung cancer as part of the Balangero, Italy cohort in the Draft
Asbestos Part 1 Risk Evaluation (March 2020), with an overall quality determination of High for lung cancer. Pira et al. 2017, HERO ID 5060134 was
evaluated for lung cancer and laryngeal cancer in the Final Risk Evaluation (Dec. 2020) with an overall quality determination of Medium for lung cancer
and Medium for laryngeal cancer. Dose-response information was reported for laryngeal cancer, lung cancer, pleural and peritoneal cancer, all cancer, and
all causes in Table 2 of Pira et al., 2009, HERO ID 2592425 and for laryngeal cancer, lung cancer, pleural cancer, and ischemic heart disease in Table 3 of
Pira et al., 2017, HERO ID 5060134.The main fiber type was chrysotile. Crocidolite was occasionally present at the mine. Balangeroite, which is a fibrous
silicate, accounted for 0.2-0.5% of total mass chrysotile samples from the mine.This study assessed a cohort who worked in an open-air mine, and thus
these outdoor exposures might be different than exposures in other environments.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 491 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082492 Table: 3 of 3
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British Journal of Industrial Medicine 47(1990):810-814.
MISSING
Hepatic/Liver: liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality,; Cancer/Carcinogenesis: oro-pharyngeal cancer mortality or
oral cavity/pharynx cancer mortality, esophageal cancer, liver cancer; Mortality: oro-pharyngeal cancer mortality or oral cavity/pharynx cancer mortality,
esophageal cancer, liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality, accidents and violence mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection High These three studies were evaluated for lung cancer as part of the Balangero, Italy cohort
in Asbestos Part 1. As described in the Asbestos Part 1 Risk Evaluation Systematic
Review Supplemental File, "Subjects included men from the Balangero mine worker
cohort that were employed in an Italian asbestos mine. The initial cohort ((Rubino et al.,
1979), pg 188) consisted of 952 men employed between 1/1/1930 and 12/31/1965, with
at least 30 calendar days' employment during that period. Mortality data were collected
from 1/1/1946 to 12/31/1975. Workers for which vital status could not be acertained
and a small number of contract workers employed intermittently were excluded. In the
first follow-up, 1058 workers were included that had worked at least one year between
1946 and 1987 and mortality follow-up was extended through 12/31/1987 ((Piolatto et
al., 1990), pg 810). In subsequent follow-ups ((Pira et al., 2009) pg 805, and (Pira et al.,
2017)), subjects included 1056 men from the Balangero mine worker cohort employed
between 1930 and 1990, and mortality records were evaluated though 2003 and 2014,
respectively. Records were not available between 1987 and 1990, when the mine closed,
so workers employed in 1987 were assumed to be employed through 1990 unless they
died during that period. Additional details in the most recent following indicated that
the initial cohort included 1182 men; the 126 excluded subjects were contract workers,
those employed < 1 yr, those with inconsistencies in data, and those known to have died
prior to 1946 (Pira et al., 2017) pg 558."
Metric 2: Attrition High These three studies, along with Rubino etal. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Supple-
mental File, "In the most recent follow-up, study authors report that one of the strengths
of the study is low proportion of subjects lost to follow-up (Pira et al., 2017) pg 562.
Loss to follow-up was 2% in the initial cohort (Rubino et al., 1979), 3% in the first
follow-up ((Piolatto et al., 1990), pg 810), and 4% in the most recent follow-ups (Pira
et al., 2009) pg 805; (Pira et al., 2017) pg 559."As described in the Final Asbestos Part
1 Risk Evaluation Systematic Review Supplemental File for Laryngeal Cancer "The
study authors note that the cause of death could not be determined for a small sample
(n=6), and a small percentage (3.8% ) of participants emigrated or were otherwise lost
to follow-up. This level of attrition is not expected to appreciably bias the results."This
Metric was rated as High in both the Draft and Final Asbestos Part 1 Risk Evaluation.
Continued on next page ...
Page 492 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 3 of 3
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Hepatic/Liver: liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality,; Cancer/Carcinogenesis: oro-pharyngeal cancer mortality or
oral cavity/pharynx cancer mortality, esophageal cancer, liver cancer; Mortality: oro-pharyngeal cancer mortality or oral cavity/pharynx cancer mortality,
esophageal cancer, liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality, accidents and violence mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 3: Comparison Group High These three studies were evaluated for lung cancer as part of the Balangero, Italy co-
hort in Asbestos Part 1. As described in the Asbestos Part 1 Risk Evaluation Systematic
Review Supplemental File, "The most complete data on comparison groups is avail-
able from the most recent follow-up (Pira et al., 2017). General population mortality
rates using the whole country from 1955 until 1980 and specifically the Piedmont Re-
gion (where the mine is located) from 1981 onwards (no regional rates available prior
to 1981). The 1955-1959 rates were applied to 1946-1954 period (no available data);
this may have led to an underestimate of expected deaths which may have showed and
increased rate during this period. Expected numbers of deaths (overall and selected can-
cers) were computed using age-specific and calendar-year-specific (5-year categories)
male death rates (Pira et al., 2017) pg 559. The only deviation from this was in the
first follow-up, which used national mortality rates were for the entire follow-up period
(through 1987) (Piolatto et al., 1990) pg. 811). In the initial study on this cohort ((Ru-
bino et al., 1979), pg. 189), an additional case-control study was performed in which 5
age-matched controls were selected at random; they were confirmed alive at the time of
death for the matched case. No details on what population provided controls. The evalu-
ation is based on the cohort mortality study only, as this was the analysis carried through
the 3 follow-up studies (Pira et al., 2017; Pira et al., 2009; Piolatto et al., 1990)."
Domain 2: Exposure Characterization
Continued on next page ...
Page 493 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 3 of 3
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Hepatic/Liver: liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality,; Cancer/Carcinogenesis: oro-pharyngeal cancer mortality or
oral cavity/pharynx cancer mortality, esophageal cancer, liver cancer; Mortality: oro-pharyngeal cancer mortality or oral cavity/pharynx cancer mortality,
esophageal cancer, liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality, accidents and violence mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 4: Measurement of Exposure Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Supple-
mental File, "Most complete report of exposure assessment is in initial cohort study
((Rubino et al., 1979) pg 189). Chrysotile fiber counts were first measured in 1969 us-
ing membrane filter collection and phase contrast microscopy (frequency not reported).
To estimate exposure from 1946-1969, factory records on daily production, equipment
used, characteristics of the job and number of hours/day were used (this method has
considerable limitations due to basis on mean values for large job categories and no al-
lowance for changes in weather). Simulated and measured data were made comparable
by using weighting factors (e.g., more dusty operation for 1-2 hr/d compared with longer
working hours in the past). Less detailed information was included in follow-up reports
((Piolatto et al., 1990) pg. 810; (Pira et al., 2017), pg 558-559)."As described in the Fi-
nal Asbestos Part 1 Risk Evaluation for Laryngeal Cancer, "Descriptions of the mine and
occupational surveillance was described. Estimates of historical mean concentrations
were 37 fibre/mL up to 1950 and 5 fibre/mL between 1971 and 1976. Exposure was de-
termined by employment at the asbestos mine only."This metric was rated as Medium in
the Draft and Low in the Final Risk Evaluation for Asbestos Part 1. However, the cohort
meets the criteria for Medium as described above.
Metric 5: Exposure Levels Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Review Supple-
mental File, "In the initial cohort ((Rubino et al., 1979), Table 8), exposure was reported
as up to 100 fiber/yr or >100 fiber/year. In the follow-ups, exposure was reported as
<100 fiber/mL-yr, 100-<400 fiber/mL-yr, and >=400 fiber/ml-yr ((Piolatto et al., 1990),
Table 3; (Pira et al., 2009), Table 2; (Pira et al., 2017), Tables 3-4)." This metric was not
rated in the Final Asbestos Part 1 Risk Evaluation.
Continued on next page ...
Page 494 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 3 of 3
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Hepatic/Liver: liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality,; Cancer/Carcinogenesis: oro-pharyngeal cancer mortality or
oral cavity/pharynx cancer mortality, esophageal cancer, liver cancer; Mortality: oro-pharyngeal cancer mortality or oral cavity/pharynx cancer mortality,
esophageal cancer, liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality, accidents and violence mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 6: Temporality High These three studies, along with Rubino etal. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
The rating of High for other outcomes is based on the most recent publication, which
has the longest follow-up duration for this cohort (follow up of the 1946-1990 cohort
through 2014), as described in the Draft Risk Evaluation for Asbestos Part 1. The first
two studies in the cohort (Rubino et al., 1979 and Piolatto et al., 1990) have inadequate
follow-up durations (<15 years) considering the potential latency periods for some of
the outcomes assessed. As described in the Asbestos Part 1 Final Risk Evaluation for
Laryngeal Cancer, "Subjects were followed until loss to follow-up, their death, 85th
birthday, or through 2014. This is a sufficiently long follow-up period." This metric was
rated as High in both the Draft and Final Asbestos Part 1 Risk Evaluations.
Domain 3: Outcome Assessment
Continued on next page ...
Page 495 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 3 of 3
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Hepatic/Liver: liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality,; Cancer/Carcinogenesis: oro-pharyngeal cancer mortality or
oral cavity/pharynx cancer mortality, esophageal cancer, liver cancer; Mortality: oro-pharyngeal cancer mortality or oral cavity/pharynx cancer mortality,
esophageal cancer, liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality, accidents and violence mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Metric 7: Outcome Measurement or High Other Cancer(s): These three studies, along with Rubino et al. 1979, HERO ID 000178,
Characterization were evaluated for lung cancer as part of the Balangero, Italy cohort in the Draft As-
bestos Part 1 Risk Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was
evaluated for lung cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evalu-
ation (Dec. 2020). In the Draft Asbestos Part 1 Risk Evaluation, the cohort was rated as
High for this Metric. In the Final Asbestos Part 1 Risk Evaluation this metric was rated
as Medium for laryngeal cancer because "Cause specific mortalities were obtained from
death certificates collected from population registers, municipal registration offices, and
local health authorities. Causes of death were coded using ICD-9, however, the study
authors did not report whether cancer cases were histologically confirmed. It"s unclear
if there may be any misclassification from obtaining vital status or cause of death from
various sources."Evaluation of all causes of death assessed in the cohort was based
on death certificates and population registers and coded according to the International
Classification of Diseases (ICD). Rubino et al., 1979, HERO ID 000178 coded causes
of deaths according to ICD-7. Piolatto et al. 1990, HERO ID 3082492 did not specify
which version of the ICD was used. Pira et al., 2009, HERO ID 2592425 and Pira et al.,
2017, HERO ID 5060134 used ICD-9 codes. Numbers of certified deaths for each cause
for the general population were obtained from the Italian National Institute of Statistics
and the World Health Organization.; Other Non-Cancer Outcomes: These three stud-
ies, along with Rubino et al. 1979, HERO ID 000178, were evaluated for lung cancer as
part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk Evaluation (March
2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung cancer and laryngeal
cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020). In the Draft Asbestos
Part 1 Risk Evaluation, the cohort was rated as High for this Metric. In the Final As-
bestos Part 1 Risk Evaluation this metric was rated as Medium for laryngeal cancer
because "Cause specific mortalities were obtained from death certificates collected from
population registers, municipal registration offices, and local health authorities. Causes
of death were coded using ICD-9, however, the study authors did not report whether
cancer cases were histologically confirmed. It"s unclear if there may be any misclassi-
fication from obtaining vital status or cause of death from various sources."Evaluation
of all causes of death assessed in the cohort was based on death certificates and popula-
tion registers and coded according to the International Classification of Diseases (ICD).
Rubino et al., 1979, HERO ID 000178 coded causes of deaths according to ICD-7. Pi-
olatto et al. 1990, HERO ID 3082492 did not specify which version of the ICD was
used. Pira et al„ 2009, HERO ID 2592425 and Pira et al„ 2017, HERO ID 5060134 used
ICD-9 codes. Numbers of certified deaths for each cause for the general population were
obtained from the Italian National Institute of Statistics and the World Health Organiza-
tion.
Continued on next page ...
Page 496 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 3 of 3
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Hepatic/Liver: liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality,; Cancer/Carcinogenesis: oro-pharyngeal cancer mortality or
oral cavity/pharynx cancer mortality, esophageal cancer, liver cancer; Mortality: oro-pharyngeal cancer mortality or oral cavity/pharynx cancer mortality,
esophageal cancer, liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality, accidents and violence mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain
Metric
Rating
Comments
Metric 8: Reporting Bias
Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
This metric was rated as High in the Draft Asbestos Part 1 Risk Evaluation for lung
cancer and High in the Draft Asbestos Part 1 Risk Evaluation for lung cancer and la-
ryngeal cancer.However, results for some of the other outcomes assessed in the paper
were reported in less detail than the results for lung cancer, resulting in a lower rating for
this Metric for these other outcomes. For example, Table 4 in Pira et al., 2017, HERO
ID 5060134 reports mortality rate ratios (MRR) for lung cancer for selected indicators
of asbestos exposure, and does not include reporting of MRR for other outcomes. All
three papers reported SMRs for several outcomes, though there were some differences
between papers in terms of which specific outcomes were included. The most recent
follow-up (Pira et al., 2017, HERO ID 5060134) had the most complete reporting with
95% confidence intervals. Some of the results reported in Piolatto et al., 1990, HERO
ID 3082492 and Pira et al., 2009, HERO ID 2592425 did not include reporting of confi-
dence intervals.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10:
Covariate Characterization
Low SMRs were stratified by age and five-year categories of calendar year. Only males were
included. There is no mention of adjustment for race, but from 1981 onwards mortal-
ity ratios were standardized to male deaths from the Piedmont region where the mine
was located, which likely reduced the potential for confounding by race or SES. Prior
to 1981 mortality ratios were standardized to national mortality for Italy because re-
gional data were not available. The authors noted that potential confounding by smoking
and alcohol consumption were limitations. In particular, the authors note that potential
confounding by alcohol consumption is a concern for oral cancer, esophageal cancer,
liver cirrhosis, accidents and violence, which are known to be associated with alcohol
consumption.
High These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
This metric was rated High in the Draft and Medium in the Final Asbestos Part 1 Risk
Evaluation.As described in the Draft Asbestos Part 1 Risk Evaluation Systematic Re-
view Supplemental File, "Empirical data obtained from employment records. Smoking
information was obtained from medical records (when available)."
Continued on next page ...
Page 497 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 3 of 3
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Hepatic/Liver: liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality,; Cancer/Carcinogenesis: oro-pharyngeal cancer mortality or
oral cavity/pharynx cancer mortality, esophageal cancer, liver cancer; Mortality: oro-pharyngeal cancer mortality or oral cavity/pharynx cancer mortality,
esophageal cancer, liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality, accidents and violence mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain
Metric
Rating
Comments
Metric 11: Co-exposure Counfounding
Low No adjustments for potential co-exposures were described. The authors mentioned the
possibility of confounding by other occupational exposures. Samples of chrysotile from
the mine were examined in detail for contamination from other materials (Piolatto et al.,
1990 3082492) and fibrous amphiboles were not detected. Crocidolite was occasion-
ally present at the mine. Balangeroite accounted for 0.2-0.5% of total mass chrysotile
samples from the mine. Balangeroite is a fibrous silicate that is not considered a true
asbestos fiber and has similar dimensions to amphiboles (Piolatto et al., 1990 3082492,
Pira et al„ 2009 2592425, Pira et al„ 2017 5060134).
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the Balangero, Italy cohort in the Draft Asbestos Part 1 Risk
Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated for lung
cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec. 2020).
This Metric was rated as Medium in both the Draft and Final Risk Evaluations for As-
bestos Part l.As described in the Asbestos Part 1 Final Risk Evaluation Systematic
Review Supplemental File for laryngeal cancer, "SMRs were used to assess differences
in cause specific mortality rates between employees of an asbestos mine compared to
a reference population in the same region. This is an appropriate design for the study
question."
Medium The cohort size was generally adequate, although some outcomes, particularly some of
the cancer outcomes, had low numbers of observed causes of death.
Medium These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated
for lung cancer as part of the his Metric was rated as Medium in both the Draft and Final
Risk Evaluations for Asbestos Part 1.Balangero, Italy cohort in the Draft Asbestos Part
1 Risk Evaluation (March 2020). Pira et al. 2017, HERO ID 5060134 was evaluated
for lung cancer and laryngeal cancer in the Final Asbestos Part 1 Risk Evaluation (Dec.
2020). This metric was rated Medium in both the Draft and the Final Asbestos Part 1
Risk Evaluations.As described in the Final Asbestos Part 1 Risk Evaluation Systematic
Review Supplemental File, "The analysis was well-described and could be reproduced
with original data."
Medium The methods for calculating SMRs are transparent.
Continued on next page ...
Page 498 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3082492 Table: 3 of 3
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Piolatto, G., Negri, E., La Vecchia, C., Pira, E., Decarli, A., Peto, J. (1990). An update of cancer mortality among chrysotile asbestos miners in Balangero,
northern Italy. British lournal of Industrial Medicine 47(1990):810-814.
MISSING
Hepatic/Liver: liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality,; Cancer/Carcinogenesis: oro-pharyngeal cancer mortality or
oral cavity/pharynx cancer mortality, esophageal cancer, liver cancer; Mortality: oro-pharyngeal cancer mortality or oral cavity/pharynx cancer mortality,
esophageal cancer, liver cancer mortality, liver cirrhosis mortality or hepatic cirrhosis mortality, accidents and violence mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
3082492, 2592425, 5060134
3082492
Domain Metric Rating Comments
Additional Comments: These three studies, along with Rubino et al. 1979, HERO ID 000178, were evaluated for lung cancer as part of the Balangero, Italy cohort in the Draft
Asbestos Part 1 Risk Evaluation (March 2020), with an overall quality determination of High for lung cancer. Pira et al. 2017, HERO ID 5060134 was
evaluated for lung cancer and laryngeal cancer in the Final Risk Evaluation (Dec. 2020) with an overall quality determination of Medium for lung cancer
and Medium for laryngeal cancer. Potential confounding by alcohol consumption is a concern for the specific outcomes evaluated on this form.The main
fiber type was chrysotile. Crocidolite was occasionally present at the mine. Balangeroite, which is a fibrous silicate, accounted for 0.2-0.5% of total mass
chrysotile samples from the mine.This study assessed a cohort who worked in an open-air mine, and thus these outdoor exposures might be different than
exposures in other environments.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 499 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2964127 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Pira, E., Turbiglio, M., Maroni, M., Carrer, P., La Vecchia, C., Negri, E., Iachetta, R. (1999). Mortality among workers in the geothermal power plants at
Larderello, Italy. American lournal of Industrial Medicine 35(1999):536-539.
total mortality
Mortality: Total mortality, total cancer mortality
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
2964127
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM. Authors relay the use of an extensive job exposure
matrix that included quantitative exposure measures for asbestos, individual working
histories, and information on specific job activities and was applied by professionals in
toxicology, epidemiology, and occupational medicine. While the job exposure matrix is
robust and allows for presentation of results based on cumulative asbestos fiber levels,
there is no information provided on the analytical method used to measure asbestos fiber
levels, meriting a medium rating.
Medium In analyses with asbestos exposure, authors apply three exposure groupings (unexposed,
<= 5,000 fibers/L/year, >= 5,000 fibers/L/year) to the cohort. The range of exposure
appears appropriate to assess the impact of asbestos on the health effects of interest.
Additional Comments: This large occupational cohort study (n=3,946) examined mortality among Italian male workers in a geothermal plant. The approaches for participant
selection, exposure measurement, and outcome ascertainment were robust, but occupational co-exposures appear to have occurred. No adjustment for
these co-exposures was included in the calculation of SMRs for the total mortality among the cohort. Additionally, the comparison group used to assess the
SMR among this occupational population was the general population, which could have led to the healthy worker effect. Finally, recruitment and outcome
assessment occurred simultaneously, which prevents the ability to establish temporality of exposure and outcome.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 500 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081596 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Plato, N., Tornling, G., Hogstedt, C., Krantz, S. (1995). An index of past asbestos exposure as applied to car and bus mechanics. Annals of Occupational
Hygiene 39(1995):441-454.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Vital capacity (VC), Percent vital capacity (CV% ), Transfer factor (TLco), total lung capacity (TLC), Forced volume in 1 second
(FEV1)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3081596
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Medium The relationship between estimated mean cumulative exposure, and exposure as repre-
sented by years of employment, with outcomes of spirometry lung function parameters
of vital capacity (VC) forced volume in 1 second (FEV1), total lung capacity (TLC),
percent vital capacity (CV% ) and transfer factor (TLco) in Swedish car and bus me-
chanics (n=103) and a control group (n=83) of suburban bus drivers was investigated in
what appears to be a retrospective cohort study (dates of health outcome assessments
not detailed within text or main referenced study (Dahlqvist et al., 1992 (HERO ID
2248426)). The exposed study group was selected from local Swedish health records of
the Stockholm Local Vehicle Health Service and the local bus transportation company.
The criteria for selection included those workers of age greater than 40 years and with
greater than 20 years of employment as car or bus mechanics. Those with job histories
including spray painting, vehicle body repair activities, or asbestos exposure from other
sources were excluded. Both car mechanics (n=95) and bus mechanics (n=8) were in-
cluded for analyses. Dates of employment for selected sample of mechanics were not
specified, however the text (page 446) indicates mean asbestos exposures were esti-
mated for the period 1938-1986. The referenced study (Dahlqvist et al., 1992 (HERO
ID 2248426), utilized a total of 89 control bus drivers selected from 315 blue collar
workers and bus drivers within organizational and local Swedish traffic registries, with
exclusions made for those with occupational exposure to asbestos or other lung irritants
and other health disorders, and those dropping out. It is unclear if the number of car
and bus mechanics (n= 103) selected for study adequately represented the totality of the
exposure-outcome relationship for the reported approximately 25,000 Swedish car and
bus mechanics employed in the mid-1980"s.
High Characteristics, in terms of relevant variables of those possibly excluded due to miss-
ing outcome or exposure data, were not reported, however there was no indication that
missing data or subject drop-out was an issue within this study.
Continued on next page ...
Page 501 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3081596 Table: 1 of 1
... continued from previous page
Study Citation: Plato, N., Tornling, G., Hogstedt, C., Krantz, S. (1995). An index of past asbestos exposure as applied to car and bus mechanics. Annals of Occupational
Hygiene 39(1995):441-454.
Pulmonary Function/Spirometry Results
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 3081596
Lung/Respiratory: Vital capacity (VC), Percent vital capacity (CV% ), Transfer factor (TLco), total lung capacity (TLC), Forced volume in 1 second
(FEV1)
Asbestos - Chrysotile (serpentine): 12001-29-5
Domain
Metric
Rating
Comments
Metric 3:
Comparison Group
Medium A control group (n=83) of suburban bus drivers described as "without asbestos expo-
sure" was utilized for analyses. Comparison of baseline characteristics between car and
bus mechanics versus bus drivers was detailed, however text (page 445) lists smoking,
age and height were studied as potential confounding variables, and text (page 442)
indicates control bus drivers were investigated in the same way as mechanics. Text
(page 442) noted a similar percentage of non-smokers in bus drivers and mechanics. It
is unclear if consideration was given to the known potential for bus driver exposures
to asbestos fibers released from brakes, gaskets and clutch pads during bus driving
and spending time within bus garages. Uncertainty also exists regarding the potential
Healthy Worker Effects due to selection criteria and lack of information of completeness
of exposure and outcome data.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium Estimated mean cumulative exposure and exposure classified by years of employment
were the exposure variables utilized in analyses with lung function outcomes of interest
(Table 2). Text (page 449) noted asbestos was defined as airborne fibers released from
friction materials (brake shoes, pads, clutch linings) with length > 5 jUm and aspect
ratio >=3:1. Friction materials contained 30-70% chrysotile asbestos. Fiber counting
was performed utilizing phase-contrast optical microscopy (PCOM). Available histor-
ical measured individual exposures for available work history years and those from a
literature search were utilized within calculated asbestos index (AI; see Appendix of
main text for detail) in constructing estimated mean cumulative exposure. Calcula-
tions for modeled AI utilized considerations for eight exposure variables representing
job activity, technology level, workshop conditions and time. Models further utilized
a job-exposure matrix which accounted for type of vehicle, room ventilation, working
activity and working intensity. Job history and work activity data was obtained utiliz-
ing self-administered questionnaires and standardized personal interviews. Validation
models utilized in confirming adequate precision of AI exposure estimates. There is
uncertainty for exclusion of consideration of respiratory protection, however authors
indicated face masks were not utilized by workers. There is uncertainty in the use of
years of employment (Table 2) in terms of accurately representing the asbestos expo-
sure in analyses with lung function outcomes within this effort, however text (page 448)
notes employment time data from company records correlated closely to exposure time
from interviews or questionnaires. Additional uncertainty was revealed within text (page
448) as some mechanics had worked in non-asbestos exposed tasks, such as supervisors,
although their job title within company records was listed as "car mechanic".
Continued on next page ...
Page 502 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3081596 Table: 1 of 1
... continued from previous page
Study Citation: Plato, N., Tornling, G., Hogstedt, C., Krantz, S. (1995). An index of past asbestos exposure as applied to car and bus mechanics. Annals of Occupational
Hygiene 39(1995):441-454.
Pulmonary Function/Spirometry Results
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 3081596
Lung/Respiratory: Vital capacity (VC), Percent vital capacity (CV% ), Transfer factor (TLco), total lung capacity (TLC), Forced volume in 1 second
(FEV1)
Asbestos - Chrysotile (serpentine): 12001-29-5
Domain
Metric
Rating
Comments
Metric 5:
Metric 6:
Exposure Levels
Temporality
Medium
Medium
The estimated mean cumulative asbestos exposure was 2.6 f mL * year (0.1 -11.6 f mL
* year). The range and distribution of estimated exposure was adequate and exposure-
response model utilized a continuous measure of exposure.
The study group was restricted to mechanics with more than 20 years of employment as
car and/or bus mechanics. Due to the uncertain timing of lung function tests as dates of
testing were not detailed, there is uncertainty in terms of temporality between exposure
and outcome.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High
Medium
Pulmonary Function/Spirometry Results: Lung function testing was described as utiliz-
ing dynamic spirometry to measure parameters of vital capacity (VC) forced volume in
1 second (FEV1), total lung capacity (TLC), percent vital capacity (CV% ) and transfer
factor (TLco) utilizing standard methods according to guidelines within the American
Thoracic Society which were outlined within main text and within the referenced study
(Dahlqvist et al„ 1992 (HERO ID 2248426)).
There were no concerns for selective reporting as all outcomes which were outlined
within methods were also reported within the results. The effect estimates within Table
2 were reported only as slope, with detail on confidence intervals and standard errors
lacking.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium The final regression analyses results were reported as adjusted for smoking, age and
height, however justification for use of these confounders was lacking. The analysis was
restricted to males of age greater than 40 years and with more than 20 years of employ-
ment. A display table of the distribution of potential confounders between exposed and
non-exposed groups was lacking.
Medium While the methods utilized to obtain and validate data regarding potential con-
founders were described only as obtained through interview within the referenced study
(Dahlqvist et al., 1992 (HERO ID 2248426)), there is no indication that methods had
poor validity.
Medium Potential co-exposures, including brake dust, exhaust, welding fume, general dust and
silica dust, which might be associated with lung function outcomes of interest, were
discussed within this occupational study. There is some uncertainty regarding these
exposures as exposure levels for these contaminants were not obtained within this study.
Domain 5: Analysis
Continued on next page ...
Page 503 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3081596 Table: 1 of 1
... continued from previous page
Study Citation: Plato, N., Tornling, G., Hogstedt, C., Krantz, S. (1995). An index of past asbestos exposure as applied to car and bus mechanics. Annals of Occupational
Hygiene 39(1995):441-454.
Health Pulmonary Function/Spirometry Results
Outcome:
Target Lung/Respiratory: Vital capacity (VC), Percent vital capacity (CV% ), Transfer factor (TLco), total lung capacity (TLC), Forced volume in 1 second
Organ(s): (FEV1)
Asbestos Fiber Asbestos - Chrysotile (serpentine): 12001-29-5
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 3081596
Domain
Metric
Rating
Comments
Metric 12:
Study Design and Methods
Medium
Multivariate regression was utilized for analysis of the relationship between estimated
cumulative asbestos exposure and lung function outcomes of interest.
Metric 13:
Statistical Power
Medium
The number of subjects (n=103 car and bus mechanics, n=83 control bus drivers) was
adequate for this analysis.
Metric 14:
Reproducibility of Analyses
Medium
General statistical analysis methods were briefly reported, however details such as rules
for classification of smoking categories, consideration of outliers, transformation of
continuous variables and methods for dealing with missing data were not detailed.
Metric 15:
Statistical Analysis
Medium
The description of statistical analysis was very brief. However, details on some model
assumptions regarding morphologic fiber changes during heating were described.
Additional Comments:
This study estimated cumulative asbestos exposure within a sample (n=103) of Swedish car and bus mechanics utilizing a semi-quantitative Asbestos
Index (AI) constructed from historical and literature -based measured exposures along with exposure scenarios derived from employee self-administered
questionnaires and standardized personal work history interviews. The relationship between estimated mean cumulative asbestos exposure, and exposure as
represented by years of employment, with spirometry lung function parameters of vital capacity (VC) forced volume in 1 second (FEV1), total lung capacity
(TLC), percent vital capacity (CV% ) and transfer factor (TLco) was investigated. The transfer factor (TLco) was lower than expected in car mechanics
(Table 2), but no other lung function measures differed from those expected. Results (Table 1) also indicated a weak, non-significant relationship between
cumulative asbestos exposure and CV% .
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 504 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083628 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Polissar, L., Severson, R. K., Boatman, E. S. (1984). A case-control study of asbestos in drinking water and cancer risk. American Journal of Epidemiology
119(1984):456-471.
Lung Cancer; Laryngeal Cancer; buccal cavity and pharnyx, mouth, pharynx, digestive system, stomach, colon, rectum, pancreas, gallbladder, respiratory
system, bladder, kidney, all study sites cancer
Mouth: Buccal cavity and pharynx cancer, Mouth cancer, Pharyngeal cancer; Cancer/Carcinogenesis: Buccal cavity and pharynx cancer, Mouth cancer,
Pharyngeal cancer, Digestive system cancer, Stomach cancer, Colon cancer, Rectum cancer, Gallbladder cancer, Pancreatic cancer, Respiratory system
cancer, Laryngeal cancer, Lung cancer, Bladder cancer, Kidney cancer, All study sites cancer (buccal cavity, pharynx, digestive system, stomach, colon,
rectum gallbladder, pancreas, respiratory system, bladder, and kidney); Gastrointestinal: Digestive system cancer, Stomach cancer, Colon cancer, Rectum
cancer, Gallbladder cancer, Pancreatic cancer; Lung/Respiratory: Respiratory system cancer, Laryngeal cancer, Lung cancer; Renal/Kidney: Bladder
cancer, Kidney cancer
Asbestos - Chrysotile (serpentine): 12001-29-5
3083628, 3083701
3083628
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Continued on next page .
Page 505 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083628 Table: 1 of 1
... continued from previous page
Polissar, L., Severson, R. K., Boatman, E. S. (1984). A case-control study of asbestos in drinking water and cancer risk. American Journal of Epidemiology
119(1984):456-471.
Lung Cancer; Laryngeal Cancer; buccal cavity and pharnyx, mouth, pharynx, digestive system, stomach, colon, rectum, pancreas, gallbladder, respiratory
system, bladder, kidney, all study sites cancer
Mouth: Buccal cavity and pharynx cancer, Mouth cancer, Pharyngeal cancer; Cancer/Carcinogenesis: Buccal cavity and pharynx cancer, Mouth cancer,
Pharyngeal cancer, Digestive system cancer, Stomach cancer, Colon cancer, Rectum cancer, Gallbladder cancer, Pancreatic cancer, Respiratory system
cancer, Laryngeal cancer, Lung cancer, Bladder cancer, Kidney cancer, All study sites cancer (buccal cavity, pharynx, digestive system, stomach, colon,
rectum gallbladder, pancreas, respiratory system, bladder, and kidney); Gastrointestinal: Digestive system cancer, Stomach cancer, Colon cancer, Rectum
cancer, Gallbladder cancer, Pancreatic cancer; Lung/Respiratory: Respiratory system cancer, Laryngeal cancer, Lung cancer; Renal/Kidney: Bladder
cancer, Kidney cancer
Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
3083628, 3083701
3083628
Domain Metric Rating Comments
Metric 1: Participant Selection Medium These cancer case-control studies were designed around the Everett, Washington area
which uses the Sultan River as their primary source of drinking water. To address the
concern that some census tracts with large rates of migration could produce a popu-
lation with smaller than expected cumulative exposures, the study area was limited to
1970 census tracts that had lower than average migration rates. To determine migration
rates, the authors used the percent of the heads of households in a census tract resid-
ing continuously at the 1970 residence for at least 10 years, with the caveat that this is
biased towards including older persons as they are less likely to be migratory. The au-
thors report a "stability indicator" of 12 percent or greater (median 24 percent) for the 25
census tracts included in this study. Census tracts included the numbers 401-415, 418,
420, 501-504, 510, 512, 515, and 519, which represented 70% of the total population
who used the Sultan River as a drinking water source.Cases were identified through the
Cancer Surveillance System, which is a population-based tumor registry that covers 13
counties and nearly 3 million people in western Washington state. Cases who had in-
vasive or in situ cases of cancer of the buccal cavity (not the lip), pharynx, respiratory
system, digestive system, bladder, or kidney newly diagnosed between November 1977
and December 1980 were included. These cancers were chosen a priori based on pre-
ceding studies. Only participants who were between the ages of 40 and 79 years of age
who resided in the eligible census tracts at the time of diagnosis were included, and this
analysis included both living and deceased participants. The authors explain that qual-
ity control studies have demonstrated that this registry misses less than 2% of the total
cases eligible for inclusion, but this data is unpublished. In total, 445 cases were iden-
tified as eligible for this study, and after attrition the final analysis sample included 382
cases.Unmatched controls in the same age range and from the pooled group of tracts by
selecting 4 households at random from 88 geographic strata (n=669 households), then
contacted those that were not vacant for an interview (n=649). Authors obtained age-sex
data on residents, then tried to schedule an interview with each person of eligible age.
A control proxy (usually a spouse), were interviewed if the controls themselves was
unavailable. The final number of controls included in analyses was 462. It is unclear
what the "88 geographic strata" are. However, it would suggest these are portions of
the eligible census tracts from which cases were recruited, and would not be expected
to substantively bias results.The choice to exclude census tracts with high migration
rates may be considered an issue of external validity, as the authors aimed to examine a
highly-exposed population and those with high migration rate may have lower levels of
exposure. However, if understood as an issue of internal validity there is some limited
concern for selection bias as this choice is unlikely to be related to outcome status.
C°nt^ugepd«»e.
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083628 Table: 1 of 1
... continued from previous page
Polissar, L., Severson, R. K., Boatman, E. S. (1984). A case-control study of asbestos in drinking water and cancer risk. American Journal of Epidemiology
119(1984):456-471.
Lung Cancer; Laryngeal Cancer; buccal cavity and pharnyx, mouth, pharynx, digestive system, stomach, colon, rectum, pancreas, gallbladder, respiratory
system, bladder, kidney, all study sites cancer
Mouth: Buccal cavity and pharynx cancer, Mouth cancer, Pharyngeal cancer; Cancer/Carcinogenesis: Buccal cavity and pharynx cancer, Mouth cancer,
Pharyngeal cancer, Digestive system cancer, Stomach cancer, Colon cancer, Rectum cancer, Gallbladder cancer, Pancreatic cancer, Respiratory system
cancer, Laryngeal cancer, Lung cancer, Bladder cancer, Kidney cancer, All study sites cancer (buccal cavity, pharynx, digestive system, stomach, colon,
rectum gallbladder, pancreas, respiratory system, bladder, and kidney); Gastrointestinal: Digestive system cancer, Stomach cancer, Colon cancer, Rectum
cancer, Gallbladder cancer, Pancreatic cancer; Lung/Respiratory: Respiratory system cancer, Laryngeal cancer, Lung cancer; Renal/Kidney: Bladder
cancer, Kidney cancer
Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
3083628, 3083701
3083628
Domain
Metric
Rating
Comments
Metric 2:
Attrition
Medium
Of 445 eligible cases, 13.5% refused participation. Of 549 eligible controls, 11.7% re-
fused participation. Reasons for failure to interview cases were either refusal by the
primary physician (3.1% ), refusal by the patient (6.3% ), or "other reasons" (4.0% ). In
controls, failure to interview was either due to refusal by the patient (10.4% ) or "other
reasons" (1.3% ). Despite a lack of clarity as to what "other reasons" means, there is
little reason to suspect that attrition was related to the true outcome due to the case iden-
tification happening prior to interview. The attrition rates are also relatively low and are
not a cause for any specific concern. Due to there being only one non-white case, the
study was limited to whites and thus that one case, and 23 corresponding controls, were
excluded. Two cases were excluded as their interview data came from next-of-kin who
answered "virtually" all questions as "unknown." There is no discussion of missing data.
Metric 3:
Comparison Group
High
Controls were unmatched but were selected from the same age range (40-79) and from
the same census tracts as the cases. Since the authors report a final eligible sample of
549 for their control population, it may be assumed that 100 of the 649 households avail-
able for interview did not fall within the inclusion age range of 40-79. However, this
is not explicitly stated. After attrition, the final sample of controls was 462. Potential
differences between cases and controls were controlled for in statistical analyses, such
as age, alcohol consumption, sex, education, religion, race/ethnicity, family history,
asbestos-related occupations, and smoking.
Domain 2: Exposure Characterization
Continued on next page .
Page 507 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083628 Table: 1 of 1
... continued from previous page
Polissar, L., Severson, R. K., Boatman, E. S. (1984). A case-control study of asbestos in drinking water and cancer risk. American Journal of Epidemiology
119(1984):456-471.
Lung Cancer; Laryngeal Cancer; buccal cavity and pharnyx, mouth, pharynx, digestive system, stomach, colon, rectum, pancreas, gallbladder, respiratory
system, bladder, kidney, all study sites cancer
Mouth: Buccal cavity and pharynx cancer, Mouth cancer, Pharyngeal cancer; Cancer/Carcinogenesis: Buccal cavity and pharynx cancer, Mouth cancer,
Pharyngeal cancer, Digestive system cancer, Stomach cancer, Colon cancer, Rectum cancer, Gallbladder cancer, Pancreatic cancer, Respiratory system
cancer, Laryngeal cancer, Lung cancer, Bladder cancer, Kidney cancer, All study sites cancer (buccal cavity, pharynx, digestive system, stomach, colon,
rectum gallbladder, pancreas, respiratory system, bladder, and kidney); Gastrointestinal: Digestive system cancer, Stomach cancer, Colon cancer, Rectum
cancer, Gallbladder cancer, Pancreatic cancer; Lung/Respiratory: Respiratory system cancer, Laryngeal cancer, Lung cancer; Renal/Kidney: Bladder
cancer, Kidney cancer
Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
3083628, 3083701
3083628
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Both papers (Polissar et al., 1983a, HEROID 3083628; Polissar et al., 1983b, HEROID
3083701) reported that the authors met with representatives of water companies to de-
termine the source of tap water for given locations and dates. The authors provide a
conversion factor to convert asbestos concentrations from each water district into units
of Sultan River tap water asbestos concentration. The timing of water sampling for as-
bestos is unclear, so exposure might have been extrapolated for part of the study period.
The methods for analyzing the asbestos fibers for part of the study are in cited references
(Polissar et al. 1982, HERO ID 353) and (Millette et al. 1980, HERO ID 60455), which
describe using EPA methods for the identification and quantification of asbestos fibers,
including the use of transmission electron microscopy (TEM). Additional methods are in
a cited EPA report "Exposure to asbestos in drinking water in the United States," which
details the appropriate methods for analyzing asbestos in water samples. Tap water
exposure may be oral (via drinking water) or dermal (via bathing). Information on indi-
vidual water consumption levels was obtained via in-person interviews, which may be
subject to recall bias, especially for 47% of cases for whom interviews were conducted
with next-of-kin rather than the actual participant.
Medium In both papers, exposure was assessed as a continuous variable in logistic regression
models. Exposure levels are presented in "equivalent years of exposure." The authors
report a range of 0-30+ "equivalent years of exposure" and provide that 1 "unit" is equiv-
alent to 1 year x 207 million fibers/liter.
Medium Temporality is sufficiently established, as cases were required to reside in the relevant
census tracts for exposure at the time of their diagnosis. However, it is unclear whether
or not there is a sufficient consideration for latency. The authors do not report how far
back they estimate exposure history to obtain year-by-year estimates of exposure. How-
ever, two of the asbestos exposure variables included in their models ignore all exposure
history during a 10-year presumed latency period prior to diagnosis or interview, which
would consider at least 10 years of latency for cancer outcomes.
Domain 3: Outcome Assessment
Continued on next page .
Page 508 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083628 Table: 1 of 1
... continued from previous page
Polissar, L., Severson, R. K., Boatman, E. S. (1984). A case-control study of asbestos in drinking water and cancer risk. American Journal of Epidemiology
119(1984):456-471.
Lung Cancer; Laryngeal Cancer; buccal cavity and pharnyx, mouth, pharynx, digestive system, stomach, colon, rectum, pancreas, gallbladder, respiratory
system, bladder, kidney, all study sites cancer
Mouth: Buccal cavity and pharynx cancer, Mouth cancer, Pharyngeal cancer; Cancer/Carcinogenesis: Buccal cavity and pharynx cancer, Mouth cancer,
Pharyngeal cancer, Digestive system cancer, Stomach cancer, Colon cancer, Rectum cancer, Gallbladder cancer, Pancreatic cancer, Respiratory system
cancer, Laryngeal cancer, Lung cancer, Bladder cancer, Kidney cancer, All study sites cancer (buccal cavity, pharynx, digestive system, stomach, colon,
rectum gallbladder, pancreas, respiratory system, bladder, and kidney); Gastrointestinal: Digestive system cancer, Stomach cancer, Colon cancer, Rectum
cancer, Gallbladder cancer, Pancreatic cancer; Lung/Respiratory: Respiratory system cancer, Laryngeal cancer, Lung cancer; Renal/Kidney: Bladder
cancer, Kidney cancer
Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
3083628, 3083701
3083628
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
High Lung Cancer: Cancer cases were selected from the Cancer Surveillance System, a
population-based tumor registry with data on incident cancer cases. The registry is part
of the Surveillance, Epidemiology, and End Results (SEER) program at the National
Cancer Institute. The authors report ICD-O (ICD-Oncology) codes for each cancer
outcome.ICD-O codes 1620-1629 were used to define lung cancer.; Laryngeal Cancer:
Cancer cases were selected from the Cancer Surveillance System, a population-based
tumor registry with data on incident cancer cases. The registry is part of the Surveil-
lance, Epidemiology, and End Results (SEER) program at the National Cancer Insti-
tute. The authors report ICD-O (ICD-Oncology) codes for each cancer outcome.ICD-O
codes 1610-1619 were used to define laryngeal cancer.; Other Cancer(s): Cancer cases
were selected from the Cancer Surveillance System, a population-based tumor registry
with data on incident cancer cases. The registry is part of the Surveillance, Epidemi-
ology, and End Results (SEER) program at the National Cancer Institute. The authors
report ICD-O (ICD-Oncology) codes for each cancer outcome.ICD-O codes 1410-1499
were used to define buccal cavaity and pharyngeal cancer.ICD-O codes 1410-1459 and
1490-1499 were used to define mouth cancer.ICD-O codes 1460-1489 were used to de-
fine pharyngeal cancer.ICD-O codes 1500-1599 were used to define digestive system
cancer.ICD-O codes 1510-1519 were used to define stomach cancer.ICD-O coders 1530-
1539 were used to define colon cancer.ICD-O codes 1540-1549 were used to define rec-
tum cancer.ICD-O codes 1560-1569 were used to define gallblader cancer.ICD-O codes
1570-1579 were used to define pancreatic cancer.ICD-O codes 1610-639 and 1650-1659
were used to define respiratory system cancer.ICD-O codes 1880-1889 were used to
define bladder cancer.ICD-O codes 1890-1899 were used to define kidney cancer.
Medium All the study"s findings are reported in the abstract, results, or discussion. Effect esti-
mates are presented with standard errors. However, analyses of relative risk only present
the lower bound of 95% confidence intervals and are missing the upper bound. Statisti-
cal significance is indicated.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Medium Considered covariates included, age, smoking, alcohol consumption, sex, education,
religion, ethnicity, family history, and asbestos-related occupations. Results were also
sex-stratified. The authors state that these covariates were chosen as "well-established
risk factors."
Continued on next page ...
Page 509 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083628 Table: 1 of 1
... continued from previous page
Polissar, L., Severson, R. K., Boatman, E. S. (1984). A case-control study of asbestos in drinking water and cancer risk. American Journal of Epidemiology
119(1984):456-471.
Lung Cancer; Laryngeal Cancer; buccal cavity and pharnyx, mouth, pharynx, digestive system, stomach, colon, rectum, pancreas, gallbladder, respiratory
system, bladder, kidney, all study sites cancer
Mouth: Buccal cavity and pharynx cancer, Mouth cancer, Pharyngeal cancer; Cancer/Carcinogenesis: Buccal cavity and pharynx cancer, Mouth cancer,
Pharyngeal cancer, Digestive system cancer, Stomach cancer, Colon cancer, Rectum cancer, Gallbladder cancer, Pancreatic cancer, Respiratory system
cancer, Laryngeal cancer, Lung cancer, Bladder cancer, Kidney cancer, All study sites cancer (buccal cavity, pharynx, digestive system, stomach, colon,
rectum gallbladder, pancreas, respiratory system, bladder, and kidney); Gastrointestinal: Digestive system cancer, Stomach cancer, Colon cancer, Rectum
cancer, Gallbladder cancer, Pancreatic cancer; Lung/Respiratory: Respiratory system cancer, Laryngeal cancer, Lung cancer; Renal/Kidney: Bladder
cancer, Kidney cancer
Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
3083628, 3083701
3083628
Domain Metric Rating Comments
Metric 10: Covariate Characterization Medium Covariate information was collected via interview with cases and controls, except in cir-
cumstances in which that was not possible. In those cases, interviews were conducted
with next-of-kin. This impacted 7% of controls, and 47% of cases. It is uncertain how
reliable next-of-kin interviews may be, and the impact of this is differential between
cases and controls, leading to potential confounding bias. Quality control procedures on
interviews (by checking 85 questionnaires via callback) found that four of the five ques-
tions included in the validation check had >=93% agreement between the interviewer
and supervisor. A comparison of coding and independent recoding of answers found on
average one disagreement per 69 general questions and 7-10 questions on an average of
14 different past residences/workplaces. The authors also compared the results of some
subject interviews with the annual Everett City Directory address and occupational list-
ings and found a low level of disagreements between the interviews and the directory,
and indicate that this is not differential across different types of respondents. This may
not be sufficient to rule out recall bias for consumption related questions, such as alcohol
consumption, as it is unclear if next-of-kin interviews would know that information.
Metric 11: Co-exposure Counfounding Medium No relevant co-exposures are discussed or evaluated in this non-occupational population.
Domain 5: Analysis
Metric 12: Study Design and Methods Medium The authors use a logistic regression model to assess the relationship between asbestos
exposure and case/control status. Both regression coefficients and relative odds are
calculated. The authors present regression coefficients for asbestos exposure when es-
timated using workplace and residence data only. Relative odds are presented for three
other exposure variables, one of which was the same as the first exposure variable except
that it also multiplied the first variable by the self-reported total amount of water intake.
Two more were created that were similar to the first two, except that all residence and
work locations during a presumed 10-year latent period prior to diagnosis or interview
were ignored. This study design is appropriate for a case-control study and allows for
the comparison of different exposure assessment methods.
Continued on next page ...
Page 510 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083628 Table: 1 of 1
... continued from previous page
Polissar, L., Severson, R. K., Boatman, E. S. (1984). A case-control study of asbestos in drinking water and cancer risk. American Journal of Epidemiology
119(1984):456-471.
Lung Cancer; Laryngeal Cancer; buccal cavity and pharnyx, mouth, pharynx, digestive system, stomach, colon, rectum, pancreas, gallbladder, respiratory
system, bladder, kidney, all study sites cancer
Mouth: Buccal cavity and pharynx cancer, Mouth cancer, Pharyngeal cancer; Cancer/Carcinogenesis: Buccal cavity and pharynx cancer, Mouth cancer,
Pharyngeal cancer, Digestive system cancer, Stomach cancer, Colon cancer, Rectum cancer, Gallbladder cancer, Pancreatic cancer, Respiratory system
cancer, Laryngeal cancer, Lung cancer, Bladder cancer, Kidney cancer, All study sites cancer (buccal cavity, pharynx, digestive system, stomach, colon,
rectum gallbladder, pancreas, respiratory system, bladder, and kidney); Gastrointestinal: Digestive system cancer, Stomach cancer, Colon cancer, Rectum
cancer, Gallbladder cancer, Pancreatic cancer; Lung/Respiratory: Respiratory system cancer, Laryngeal cancer, Lung cancer; Renal/Kidney: Bladder
cancer, Kidney cancer
Asbestos - Chrysotile (serpentine): 12001-29-5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
3083628, 3083701
3083628
Domain
Metric
Rating
Comments
Metric 13:
Statistical Power
Medium
The final sample of 382 cases and 462 controls was sufficient to detect an effect, al-
though for some cancers the incidence is as low as 7 for both sexes and as low as 1 for
males. Statistical power was calculated for specified number of cases that could be de-
tected at the 5% one-sided level with 80% confidence. The authors report that for single-
sex analyses, "the minimum risk that could be detected"was under 2.0 for each for the
following sites or site groups: all study sites combined, digestive system, respiratory
system, colon and lung."
Metric 14:
Reproducibility of Analyses
Medium
Methods are sufficiently detailed so that, given access to the analytic data, the results
could be reproduced.
Metric 15:
Statistical Analysis
Medium
There are no significant assumptions in logistic regression models that would be ex-
pected to be violated in the present analysis.
Additional Comments:
These case-control studies are different publications of the same data. The authors examined Everett, Washington residents exposed to asbestos-
contaminated water from the Sultan River. They used a case-control design to assess asbestos exposure relative to cancer outcomes. There are some
uncertainties in this study, as the data on water consumption used in statistical analyses may be subject to recall bias differential by case status.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 511 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 353 Table: 1 of 1
Study Citation: Polissar, L., Severson, R. K., Boatman, E. S., Thomas, D. B. (1982). Cancer incidence in relation to asbestos in drinking water in the Puget Sound region.
American Journal of Epidemiology 116(1982):314-328.
Ovarian Cancer; Laryngeal Cancer; buccal cavity and pharynx cancer, esophagus cancer, stomach cancer, small intestine cancer, colon cancer, rectum
cancer, liver cancer, gallbladder cancer, pancreatic cancer, retroperitoneum cancer, respiratory system cancer, bones and joints cancer, soft tissue cancer,
melanoma, breast cancer, cervix cancer, corpus uteri cancer, uterine cancer, residual female genital cancer, prostate cancer, testis cancer, residual male
genital cancer, bladder cancer, kidney cancer, eye and orbit cancer, brain (CNS) cancer, thyroid cancer, Hodgkin's disease, Non-Hodgkin's lymphoma,
multiple myeloma, leukemia, cancer of other sites
Mortality: buccal cavity and pharynx cancer, esophagus cancer, stomach cancer, small intestine cancer, colon cancer, rectum cancer, liver cancer, gall-
bladder cancer, pancreatic cancer, retroperitoneum cancer, larynx cancer, respiratory system cancer, bones and joints cancer, soft tissue cancer, melanoma,
breast cancer, cervix cancer, corpus uteri cancer, uterine cancer, ovarian cancer, residual female genital cancer, prostate cancer, testis cancer, residual male
genital cancer, bladder cancer, kidney cancer, eye and orbit cancer, brain (CNS) cancer, thyroid cancer, Hodgkin's disease, Non-Hodgkin's lymphoma,
multiple myeloma, leukemia, cancer of other sites; Other sites: cancer of other sites; Immune/Hematological: Hodgkin's disease, Non-Hodgkin's lym-
phoma, multiple myeloma, leukemia; Thyroid: thyroid cancer; Neurological/Behavioral: brain (CNS) cancer; Reproductive/Developmental: breast cancer,
cervix cancer, corpus uteri cancer, uterine cancer, ovarian cancer, residual female genital cancer, prostate cancer, testis cancer, residual male genital cancer;
Ocular/Sensory: eye and orbit cancer; Skin/Connective Tissue: melanoma; Musculoskeletal: bones and joints cancer, soft tissue cancer; Lung/Respiratory:
larynx cancer, respiratory system cancer; Gastrointestinal: buccal cavity and pharynx cancer, esophagus cancer, stomach cancer, small intestine cancer,
colon cancer, rectum cancer, liver cancer, gallbladder cancer, pancreatic cancer, retroperitoneum cancer; Cancer/Carcinogenesis: buccal cavity and pharynx
cancer, esophagus cancer, stomach cancer, small intestine cancer, colon cancer, rectum cancer, liver cancer, gallbladder cancer, pancreatic cancer, retroperi-
toneum cancer, larynx cancer, respiratory system cancer, bones and joints cancer, soft tissue cancer, melanoma, breast cancer, cervix cancer, corpus uteri
cancer, uterine cancer, ovarian cancer, residual female genital cancer, prostate cancer, testis cancer, residual male genital cancer, bladder cancer, kidney
cancer, eye and orbit cancer, brain (CNS) cancer, thyroid cancer, Hodgkin's disease, Non-Hodgkin's lymphoma, multiple myeloma, leukemia, cancer of
other sites; Renal/Kidney: bladder cancer, kidney cancer
Asbestos Fiber Asbestos - Chrysotile (serpentine): 12001-29-5
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 353
Domain Metric Rating Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Uninformative PRIMARY EVALUATION STOPPED AFTER REVIEW OF METRIC 4 AND UN-
INFORMATIVE RATING DETERMINATIONThere is substantial risk of exposure
misclassification, as the study solely uses asbestos concentrations in drinking water with
no consideration of individual factors or measure of exposure on the individual level. As
such, exposure is anticipated to be subjected to substantial misclassification that would
significantly bias the results.
Metric 5: Exposure Levels Low Exposure levels are reported as high vs. low exposure based on the drinking water
source for the community, meriting a low rating for this domain. Different permutations
of high and low exposure are used in analyses including Sultan River (high exposure)
vs. all other areas (low exposure), Sultan River older districts (high exposure) vs. newer
districts (low exposure), Sultan River long term use (high exposure) vs. short term use
(low exposure).
Continued on next page ...
Health
Outcome:
Target
Organ(s):
Page 512 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 353 Table: 1 of 1
... continued from previous page
Study Citation: Polissar, L., Severson, R. K., Boatman, E. S., Thomas, D. B. (1982). Cancer incidence in relation to asbestos in drinking water in the Puget Sound region.
American Journal of Epidemiology 116(1982):314-328.
Ovarian Cancer; Laryngeal Cancer; buccal cavity and pharynx cancer, esophagus cancer, stomach cancer, small intestine cancer, colon cancer, rectum
cancer, liver cancer, gallbladder cancer, pancreatic cancer, retroperitoneum cancer, respiratory system cancer, bones and joints cancer, soft tissue cancer,
melanoma, breast cancer, cervix cancer, corpus uteri cancer, uterine cancer, residual female genital cancer, prostate cancer, testis cancer, residual male
genital cancer, bladder cancer, kidney cancer, eye and orbit cancer, brain (CNS) cancer, thyroid cancer, Hodgkin's disease, Non-Hodgkin's lymphoma,
multiple myeloma, leukemia, cancer of other sites
Mortality: buccal cavity and pharynx cancer, esophagus cancer, stomach cancer, small intestine cancer, colon cancer, rectum cancer, liver cancer, gall-
bladder cancer, pancreatic cancer, retroperitoneum cancer, larynx cancer, respiratory system cancer, bones and joints cancer, soft tissue cancer, melanoma,
breast cancer, cervix cancer, corpus uteri cancer, uterine cancer, ovarian cancer, residual female genital cancer, prostate cancer, testis cancer, residual male
genital cancer, bladder cancer, kidney cancer, eye and orbit cancer, brain (CNS) cancer, thyroid cancer, Hodgkin's disease, Non-Hodgkin's lymphoma,
multiple myeloma, leukemia, cancer of other sites; Other sites: cancer of other sites; Immune/Hematological: Hodgkin's disease, Non-Hodgkin's lym-
phoma, multiple myeloma, leukemia; Thyroid: thyroid cancer; Neurological/Behavioral: brain (CNS) cancer; Reproductive/Developmental: breast cancer,
cervix cancer, corpus uteri cancer, uterine cancer, ovarian cancer, residual female genital cancer, prostate cancer, testis cancer, residual male genital cancer;
Ocular/Sensory: eye and orbit cancer; Skin/Connective Tissue: melanoma; Musculoskeletal: bones and joints cancer, soft tissue cancer; Lung/Respiratory:
larynx cancer, respiratory system cancer; Gastrointestinal: buccal cavity and pharynx cancer, esophagus cancer, stomach cancer, small intestine cancer,
colon cancer, rectum cancer, liver cancer, gallbladder cancer, pancreatic cancer, retroperitoneum cancer; Cancer/Carcinogenesis: buccal cavity and pharynx
cancer, esophagus cancer, stomach cancer, small intestine cancer, colon cancer, rectum cancer, liver cancer, gallbladder cancer, pancreatic cancer, retroperi-
toneum cancer, larynx cancer, respiratory system cancer, bones and joints cancer, soft tissue cancer, melanoma, breast cancer, cervix cancer, corpus uteri
cancer, uterine cancer, ovarian cancer, residual female genital cancer, prostate cancer, testis cancer, residual male genital cancer, bladder cancer, kidney
cancer, eye and orbit cancer, brain (CNS) cancer, thyroid cancer, Hodgkin's disease, Non-Hodgkin's lymphoma, multiple myeloma, leukemia, cancer of
other sites; Renal/Kidney: bladder cancer, kidney cancer
Asbestos Fiber Asbestos - Chrysotile (serpentine): 12001-29-5
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 353
Domain Metric Rating Comments
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis. In addition (from metric 4): There is substantial risk of exposure misclassification, as the study solely uses asbestos concentrations in drinking
water with no consideration of individual factors or measure of exposure on the individual level. As such, exposure is anticipated to be subjected to
substantial misclassification that would significantly bias the results.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessment for the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Health
Outcome:
Target
Organ(s):
Page 513 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3081452 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Raffn, E., Villadsen, E., Engholm, G., Lynge, E. (1996). Lung cancer in asbestos cement workers in Denmark. Occupational and Environmental Medicine
53(1996):399-402.
Lung Cancer
Cancer/Carcinogenesis: Lung cancer, including adenocarcinomas, squamous cell carcinomas, and anaplastic carcinomas
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
No linked references.
3081452
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low
Low
Asbestos measurements were taken in 1948 and 1957, and were reported as 50-800
fibers/ml and 10-100 fibers/ml, respectively. 41% of measurements in 1973 were above
2 fibers/ml. However, not information is provided on the methods or type of equipment
used to generate this data.
Very limited information is provided pertaining to exposure levels for the individuals
working in the factory. They highlighted that measurements were taken during feeding
and unloading. In the discussion section, the authors mention that job titles were only re-
ported for individuals employed between 1928 and 1941, and not all of the roles within
the factory result in exposure to asbestos.
Additional Comments: As QC reviewer, I rate this study medium. This study investigated the relative and absolute risks of main types of lung cancer among asbestos cement
workers in Denmark.lt is important to note that while there were three types of asbestos mentioned by the authors, chrysolite comprised 90% of asbestos
used in the factory examined. Only three cases of lung cancer were found for the women included, so only results for men were reported.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 514 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3583594 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Raffn, E., Villadsen, E., Lynge, E. (1996). Colorectal cancer in asbestos cement workers in Denmark. American Journal of Industrial Medicine
30(1996):267-272.
Colorectal cancers
Cancer/Carcinogenesis: Colon cancer (all), Colorectal cancer (rectum), Colorectal cancer (NOS), Colon cancer (left side), Colon cancer (right side),
Colorectal cancer (all); Gastrointestinal: Colorectal cancer (rectum), Colorectal cancer (NOS), Colon cancer (left side), Colon cancer (right side), Colon
cancer (all), Colorectal cancer (all)
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4
ID(s): No linked references.
3583594
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low This metric is rated low because the study or any cited methods source does not ex-
plicitly mention the use of PCM or TEM. Atmospheric asbestos was measured in this
asbestos factory. These measurements were taken during the feeding of the mill and the
forming vessel, along with the unloading of containers. Measurements were taken in
1948 and 1957, and were recorded in particles per cubic centimeter. The Danish Na-
tional Institute of Occupational Health used these results to estimate the exposure levels
in 1948 and 1957.
Metric 5: Exposure Levels Medium There was a range of exposure levels included in this study, and they were sufficient
to develop an exposure-response estimate. The range of exposures reported indicate
that there was more than just exposed/unexposed in this cohort. For 1948, asbestos
concentrations ranged from 50 and 800 f/ml. For 1957, concentrations were estimated
between 10 and 100 f/ml. Some measurements were taken in 1973, and 41% of the
measurements were >2.0 f/ml.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 515 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2238696 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Richardson, D. B. (2009). Lung cancer in chrysotile asbestos workers: Analyses based on the two-stage clonal expansion model. Cancer Causes and
Control 20(2009):917-923.
Lung Cancer
Mortality: lung cancer mortality; Lung/Respiratory: lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
3081832, 66, 2238696, 6860087
2238696
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This occupational cohort study examines lung cancer mortality and its association with
asbestos exposure among a sub-cohort of white men (n= 1,256) employed at a South
Carolina asbestos textile plant. Men who had been employed for at least one month be-
tween 1940 and 1965. Follow-up to assess vital status continued through December 31,
2001. Authors note the cohort was restricted to male workers for simplicity of analyses,
but there is no comparison of the full eligible and participating study population.
High There is no evidence of subject loss for reasons other than death (the outcome of inter-
est), of subject exclusions from the analyses, or of substantial amounts of missing data
among the study population.
High All members of the study cohort were white males from a South Carolina asbestos tex-
tile plant who worked for at least one month in production during the 1940-1965 time
period. Sufficient information is provided to assert that individuals across exposure
ranges were similar.
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium Study authors reference Dement et al., 1983, 66 for discussion of the exposure mea-
surement approach including midget impinger and membrane filter sampling with data
obtained "from many sources including the company insurance carrier, the State Board
of Health, the U.S. Public Health Service, and the Company sampling program." The
reference also discusses conversion factors, but it appears that these were used to con-
vert midget impinger and membrane filter results to the comparable units. According to
a methods paper on United States Public Health Service/NIOSH membrane filter sam-
pling methods (Leidl et al., 1979, 237), PCM was used to analyze membrane filters and
quantify fiber levels. While the original text does not explicitly communicate the use of
PCM, the contextual information provided by these other citations and methods papers
provides sufficient information to merit a medium rating.
Medium The range and distribution of fiber levels based on cumulative exposure appears suf-
ficient to assess the association between the exposure and outcome. Authors present
continuous analyses with exposure increases per 10 fiber-years/mL and results from a
two-stage clonal expansion model by quartile of exposure (Ql: 0-1.7 fiber-years/mL;
Q2: 1.7-5.5 fiber-years/mL; Q3: 5.5-25.1 fiber-years/mL; Q4: 25.1-699.8 fiber-years/
mL).
Continued on next page ...
Page 516 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2238696 Table: 1 of 1
... continued from previous page
Richardson, D. B. (2009). Lung cancer in chrysotile asbestos workers: Analyses based on the two-stage clonal expansion model. Cancer Causes and
Control 20(2009):917-923.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: lung cancer mortality; Lung/Respiratory: lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
3081832, 66, 2238696, 6860087
2238696
Domain
Metric
Rating
Comments
Metric 6: Temporality
High The retrospective cohort study design enables establishment of temporality between ex-
posure and outcome. Exposure can be demonstrated to have occurred prior to outcome
ascertainment through the assessment of historical exposure records. Additionally, the
study includes a follow up period ranging from 36-61 years, an appropriate length to
assess lung cancer outcomes.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High Lung Cancer: Lung cancer data was collected from vital status records through Decem-
ber 31, 2001. Study authors identified cases using ICD codes at the time of death (from
revisions 5, 6, 7, 8, 9, and 10). The complete list of codes used for the study included
ICD-5 codes 047B-047F, ICD-6 codes 162 and 163, ICD-7 code 162.0, 162.1, 162.8,
163, ICD-8/-9 code 162, ICD-10 codes C33, C34.
Medium Results from two stage clonal expansion models and Cox proportional hazards regres-
sion models are reported as anticipated, including the effect estimates and confidence
intervals for all anticipated analyses. However, the number of participants in different
analytical groups is not reported, and many lower confidence limits are reported as not
determined.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Low Variations in race and sex were accounted for via the study design, as the population
was restricted to white male workers from the plant. Additionally, authors report the
development of age-specific two-stage clonal expansion models and report results from
Cox proportional hazard models by different age groupings. However, there is no indi-
cation that smoking status was measured and considered in analyses, which serves as a
key confounder for assessment of lung cancer. While authors note that confounding "by
lifestyle factors...will be small in occupational analyses", the lack of consideration of
this confounder merits a low rating.
High Due to the occupational nature of this study, it can be reasonably inferred that infor-
mation on covariates (including age, sex, and race) was collected from plant personnel
records.
Medium There is no direct evidence of a suspected co-exposure that was not accounted for in
the analyses. Authors report the cohort had "relatively pure exposures to chrysotile
asbestos" in the textile plant. While this may indicate some minor potential for co-
exposure, there is no direct evidence that would merit a low rating.
Domain 5: Analysis
Continued on next page ...
Page 517 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2238696 Table: 1 of 1
... continued from previous page
Study Citation:
Richardson, D. B. (2009). Lung cancer in chrysotile asbestos workers: Analyses based on the two-stage clonal expansion model. Cancer Causes and
Control 20(2009):917-923.
Lung Cancer
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): 3081832, 66, 2238696, 6860087
HERO ID: 2238696
Mortality: lung cancer mortality; Lung/Respiratory: lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
Domain
Metric
Rating
Comments
Metric 12:
Study Design and Methods
Medium
The retrospective cohort study design was appropriate to assess the exposure-outcome
relationship in the occupational setting, as was the use of the two-stage clonal expansion
model and the Cox proportional hazard model.
Metric 13:
Statistical Power
Medium
The sample size (n=l, 256) is sufficiently large to examine the outcome of interest,
which is further demonstrated by the number of observed cases (n=l 16 lung cancer
deaths).
Metric 14:
Reproducibility of Analyses
Medium
Authors provide extensive information on development of statistical models used for
analyses, including background information on the two-stage clonal expansion model
approach.
Metric 15:
Statistical Analysis
Medium
Authors appropriately employed the two-stage clonal expansion model to assess cancer
outcomes and the Cox proportional hazards model with discussion of the proportional
hazards assumption. The use of lags (assessed at 5, 10, and 15 years) in assessing the
exposure-outcome relationship is transparently reported.
Additional Comments:
This retrospective occupational cohort study examines lung cancer mortality and its association with cumulative asbestos exposure with an appropriate
follow-up period. The cohort was of sufficient size to assess the relationship, and the methods for exposure measurement, outcome ascertainment, and
statistical analyses were robust. A primary weakness in the study is the lack of consideration of smoking status as a potential confounder. While a clear
deficiency, authors note that the influence of smoking may not substantially impact results among occupational cohorts.The measurement exposure (M4)
and/or exposure levels (M5) metrics are rated as medium upon review by both set of reviewers. Note for M4: While the original text does not explicitly
communicate the use of PCM, the context information provided by other cited articles. Also, the overall quality determination (OQD) is rated medium.
Extraction has been completed and quality control reviewed.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 518 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083290 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Rodriguez-Roisin, R., Picado, C., Roca, J., Arrigo, S., Agusti-Vidal, A. (1986). Early lung function changes after short heavy exposure to chrysotile
asbestos in non-smoking women. Bulletin Europe"en de Physiopathologie Respiratoire 22(1986):225-229.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Forced vital capacity (FVC), Ratio of FEV1/FVC, Maximal expiratory flow at 75% of the forced vital capacity (MEF25% ), Maximal
expiratory flow at 50% of the forced vital capacity (MEF50% ), Peak expiratory flow (PEF), Forced expiratory volume in 1 second (FEV1)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3083290
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium 35 non-smoker female workers at a textile factory in Barcelona were subjects in this
occupational case-control study. The authors provide a reasonable amount of detail
about inclusion/exclusion criteria but details about recruitment circumstances (e.g.,
timeline, method of recruitment) were not discussed.
High There was no subject withdrawal, and a complete dataset was used for the analyses of
asbestos exposure with health outcomes.
Medium Controls were 35 non-smoking healthy females that were age- and height-matched and
selected from a sample of 870 non-smoking individuals living in the same geographical
area. They were randomly selected after stratification for sex, age, and height and "had
no known exposure to fibrogenic materials, no history of acute or chronic cardiorespira-
tory diseases, normal chest radiographs and absence of smoking habits." Thus, controls
were not recruited from the same population. The authors do not provide more informa-
tion on how the sample of controls was recruited or whether they were employed, but
concern for healthy worker effect is mitigated by the inclusion criteria.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
High Quantitative measures of asbestos were "sampled personally and randomly over a 13-
week sampling period" and an exposure index that was dependent on time exposed and
fiber concentration was calculated for each worker (according to recommendations of
the British Occupational Hygiene Society). Exposure was measured using PCM.
Medium The range and distribution of exposure is sufficient to develop an exposure-response
estimate, and the authors report 3 levels of exposure.
Low Temporality is established, but the latency period is short (1-7 yr according to Table 1).
It should be noted that the purpose of this study was to assess effects of high asbestos
exposure within a short period of time, though, and workers who were employed at the
factory for 10 years or more were excluded from the study.
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
High Pulmonary Function/Spirometry Results: Pulmonary function tests included standard-
ized spirometric measures such as FEV1, FVC, PEF, and MEF.
Continued on next page ...
Page 519 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083290 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Rodriguez-Roisin, R., Picado, C., Roca, J., Arrigo, S., Agusti-Vidal, A. (1986). Early lung function changes after short heavy exposure to chrysotile
asbestos in non-smoking women. Bulletin Europe"en de Physiopathologie Respiratoire 22(1986):225-229.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Forced vital capacity (FVC), Ratio of FEV1/FVC, Maximal expiratory flow at 75% of the forced vital capacity (MEF25% ), Maximal
expiratory flow at 50% of the forced vital capacity (MEF50% ), Peak expiratory flow (PEF), Forced expiratory volume in 1 second (FEV1)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3083290
Domain
Metric
Rating
Comments
Metric 8:
Reporting Bias
High
Results of the stepwise multiple regression, which analyzed associations of pulmonary
function test results with a continuous measure of exposure, are shown. Effect estimates
and standard errors are presented in the Results. Samples sizes are presumed (n=35 for
both exposed and controls), as there is no mention of missing data.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
High
Appropriate adjustments were made in the stepwise multiple regression analysis for
each lung function test. Age, height, weight, years of exposure, and cumulative exposure
index were treated as covariates. For each maximal flow rate analysis, FVC was also
included as a covariate. Smoking status was not included, because only non-smokers
were included in the study.
Metric 10:
Covariate Characterization
Medium
For this occupational study, it is presumed that personnel records were used to obtain
covariate data, since the authors did not specify otherwise.
Metric 11:
Co-exposure Counfounding
Low
The authors did not adjust for or measure potential co-exposures. Due to the lack of
safety regulations and protective equipment available to asbestos workers in the study, it
is quite possible that additional co-exposures in the factory were present. This could bias
the results away from the null.
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
This cross-sectional study uses an appropriate statistical method to address the research
question; specifically, the authors used stepwise multiple regression analysis for each
lung function test to analyze the correlation between lung function and duration and
cumulative index of asbestos exposure.
Metric 13:
Statistical Power
Medium
The number of cases and controls are adequate to detect an effect in the exposed pop-
ulation, and the authors report significantly lower FVC and FEV1 were found in the
exposed compared to the matched control population.
Metric 14:
Reproducibility of Analyses
Medium
The description of the analyses is clear and sufficient to understand how to conceptually
reproduce the analysis with access to the analytic data.
Metric 15:
Statistical Analysis
Low
Though it is explained why some covariates were included in the regression models, the
authors do not explicitly state that the regression model assumptions were met.
Additional Comments:
This occupational case-control study examined the association of severe asbestos exposure for a shorter duration with well-validated lung function tests.
It reported that shortly after heavy exposure, non-smokers showed significant reductions in lung function parameters compared to the matched control
population.
Continued on next page ...
Page 520 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3083290 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Rodriguez-Roisin, R., Picado, C., Roca, J., Arrigo, S., Agusti-Vidal, A. (1986). Early lung function changes after short heavy exposure to chrysotile
asbestos in non-smoking women. Bulletin Europe"en de Physiopathologie Respiratoire 22(1986):225-229.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Forced vital capacity (FVC), Ratio of FEV1/FVC, Maximal expiratory flow at 75% of the forced vital capacity (MEF25% ), Maximal
expiratory flow at 50% of the forced vital capacity (MEF50% ), Peak expiratory flow (PEF), Forced expiratory volume in 1 second (FEV1)
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3083290
Domain Metric
Rating
Comments
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 521 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3083350 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Roggli, V. L., Pratt, P. C., Brody, A. R. (1986). Asbestos content of lung tissue in asbestos associated diseases: a study of 110 cases. British Journal of
Industrial Medicine 43(1986):18-28.
Lung Cancer; Asbestosis; Pleural Plaques
Lung/Respiratory: Asbestosis, Parietal pleural plaques, lung cancer; Cancer/Carcinogenesis: lung cancer
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Anthophyllite: 17068-78-9; Asbestos - Tremolite:
14567-73-8; Asbestos - Actinolite: 12172-67-7; Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3083350
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Metric 5:
Measurement of Exposure
Exposure Levels
Low Asbestos bodies in lung tissue samples were quantified by LM and SEM, post-mortem.
Medium The range and distribution of exposure is sufficient to develop an exposure-response
estimate, which was done using a continuous measure of exposure.Median and range
asbestos bodies (AB) exposures measured via LM were as follows:. Asbestosis: 106,000
(range: 2,400 " 684,000) AB/g. Mesothelioma: 550 (range: 0.2 " 13,3000) AB/g. Lung
cancer: 102 (0.8 " 46,000) AB/g. Idiopathic pulmonary fibrosis: 9 (0.8 " 148) AB/g.
Normal lungs: 3 (0.2 " 22) AB/g.
Additional Comments: The overall rating for this study is low. This study investigated the asbestos content of lung tissue in groups of cases of asbestosis, malignant mesothelioma,
carcinoma of the lung, and parietal pleural plaques. Overall, this study was appropriately conducted, but not well powered (especially in terms of the
number of controls used). Asbestos bodies, which are indicative of asbestos exposure, were used as exposure to examine associations with lung disease.
When it came to findings, the authors reported statistically significant relationships between asbestos bodies asbestos fibers. While, this study had some
strengths, there were several limitations. For example, exposure misclassification during exposure assessment may have occurred. Additionally, the number
of controls used may be small to detect robust effect estimates.Overall, information on the measurement of exposure metric (M4) to assess exposure was
limited or rated low (authors used Asbestos bodies in lung tissue samples were quantified by LM and SEM, post-mortem). The exposure levels metric (M5)
information reported was adequate to determine exposure-response relationships.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 522 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709486 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Rohs, A., Lockey, J., Dunning, K., Shukla, R., Fan, H., Hilbert, T., Borton, E., Wiot, J., Meyer, C., Shipley, R., Lemasters, G., Kapil, V. (2008). Low-level
fiber-induced radiographic changes caused by Libby vermiculite: a 25-year follow-up study. American Journal of Respiratory and Critical Care Medicine
177(2008): 630-637.
Pleural Plaques
Lung/Respiratory: Pleural changes (localized and/or diffuse pleural thickening), Parenchymal changes
Asbestos - Tremolite: 14567-73-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos- Libby amphibole: 1318-09-8
ID(s): 709486,3014803
709486
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
High Rohs et al., 2008 (709486) and Lockey et al., 2012 3014803 analyze 25- and 3-year
follow-up data, respectively, on a 1980 cohort of 512 workers at a facility that processed
tremolite-contaminated Libby vermiculite (Lockey et al. 1984. 029685; 97% participa-
tion rate). At baseline, all employees exposed to vermiculite and a subset of unexposed
workers from the same plant were enrolled. The 25-year follow-up analyzed chest ra-
diographs for 280 workers taken in 2004-2005 (65% of 431 living; 55% of baseline).
The 30-year follow-up analyzed chest CT scans for 191 workers (44% of 431 living)
in their primary analyses (175 taken in 2010-11 for this study, 16 pre-existing). In ad-
dition, the longer follow-up used pre-existing x-rays taken from 2003-2011 to increase
their chest imaging sample size to 306 (71% of those still living). Risk of HWE bias is
limited given the lengthy follow-up and varied post-baseline duration of employment.
High In both Rohs et al., 2008 709486 and Lockey et al., 2012 3014803, potential attrition
bias was evaluated in sensitivity analyses that used baseline data to incorporate all living
subjects, assuming normal chest imaging in those who did not participate in follow-ups;
results did not change meaningfully. Survivorship bias was not assessed, but additionally
adding these 82 individuals to exposure categories would not eliminate associations of
the magnitude reported. Given the higher mean exposure in deceased workers, the study
may underestimate the prevalence of lung changes and the magnitude of associations.
High Rohs et al., 2008 RefID 709486 and Lockey et al., 2012 RefID 3014803 compared
health outcomes among workers in the cohort with higher vs. lower past exposure past
exposure. At baseline, the comparison group was selected to include workers whose
exposure to other substances was similar to the vermiculite-exposed group, with the
exception of limited or no vermiculite exposure.
Domain 2: Exposure Characterization
Continued on next page .
Page 523 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709486 Table: 1 of 1
... continued from previous page
Study Citation:
Rohs, A., Lockey, J., Dunning, K., Shukla, R., Fan, H., Hilbert, T., Borton, E., Wiot, J., Meyer, C., Shipley, R., Lemasters, G., Kapil, V. (2008). Low-level
fiber-induced radiographic changes caused by Libby vermiculite: a 25-year follow-up study. American Journal of Respiratory and Critical Care Medicine
177(2008): 630-637.
Pleural Plaques
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Pleural changes (localized and/or diffuse pleural thickening), Parenchymal changes
Asbestos - Tremolite: 14567-73-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos- Libby amphibole: 1318-09-8
ID(s): 709486,3014803
709486
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium MEDIUM. Rohs et al., 2008 RefID 709486 estimated retrospective cumulative fiber
exposure (CFE) using detailed job histories and available fiber counts that used PCM
and membrane filter samples (counting particles > 5jUm in length, <9 [im in diame-
ter, and aspect ratio of 3:1). Concerns: (i) Exposure monitoring was initiated in 1972;
extrapolations to earlier years may be underestimates. The area level measures taken
prior to 1976, when personal breathing zone sampling began, may also be less accurate
than later estimates, (ii) Information on extensive overtime worked was not available,
perhaps resulting in underestimates and/or misclassified exposure, (iii) Asbestos expo-
sure was estimated for 1963 to 1980; exposure before and after was assumed to be zero,
since Libby ore was not in use. However, ore used after 1980 was subsequently found to
contain about 1% asbestiform minerals. HIGH. In Lockey et al., 2012 RefID 3014803,
CFE estimates were refined using: (i) more detailed job information including improved
information on overtime; (ii) three times the original number of fiber measures (n=899);
and (iii) specific data on vermiculite sources both before and after Libby ore was used
(Borton et al 2012, PMID 22544162). Exposure after 1980 was estimated using updated
work histories collected in 2004 and/or 2010-11.
Medium CFE quartiles were used by Rohs et al., 2008 RefID 709486, defined as: 0.005-0.24,
0.25-0.74, 0.75-1.91 and 1.92-19.03 fiber/cc-years. Mean CFE was estimated at 2.48
fiber/cc-years among study participants. In Lockey et al., 2012 RefID 3014803, 5 expo-
sure categories were used (<0.15, 0.15-<0.45, 0.45-<1.35, 1.35-<10, and >=10 fiber-
years/cc). Mean CFE using the refined methods was 6.98 fibers/cc-years through 1980,
increasing to 7.5 fiber/cc-years through 2001 when vermiculite use was terminated.
High In Rohs et al., 2008 RefID 709486 exposure was assessed retrospectively. The mean
time since initial exposure was 36.8 and 32.1 years, respectively, for participants with
and without any pleural changes. Lockey et al., 2012 RefID 3014803 had 5 additional
years of follow-up.
Domain 3: Outcome Assessment
Continued on next page ...
Page 524 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709486 Table: 1 of 1
... continued from previous page
Study Citation:
Rohs, A., Lockey, J., Dunning, K., Shukla, R., Fan, H., Hilbert, T., Borton, E., Wiot, J., Meyer, C., Shipley, R., Lemasters, G., Kapil, V. (2008). Low-level
fiber-induced radiographic changes caused by Libby vermiculite: a 25-year follow-up study. American Journal of Respiratory and Critical Care Medicine
177(2008): 630-637.
Pleural Plaques
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Pleural changes (localized and/or diffuse pleural thickening), Parenchymal changes
Asbestos - Tremolite: 14567-73-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos- Libby amphibole: 1318-09-8
ID(s): 709486,3014803
709486
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
Metric 8:
Reporting Bias
High Pleural Plaques: Rohs et al., 2008 RefID 709486: Chest radiographs taken for the study
in 2004-2005 were evaluated by 2 board certified radiologists using 2000 ILO criteria;
a 3rd reader resolved disagreements. Radiographs had no identifiers; 10% normal radio-
graphs randomly interspersed were read correctly. Outcomes were defined as: localized
pleural plaques, diffuse pleural thickening, and interstitial changes. The prevalence of
pleural changes was 28.7% . Lockey et al., 2012 RefID 3014803 also used chest imag-
ing without identifiers evaluated by 2 or 3 independent readers. Primary measures used
high resolution CT (n=175) or CT (n=16 pre-existing) scans. Criteria used to evaluate
HRCT/CT scans were described in detail. The prevalence of lung changes increased to
>50% . HRCT/CT is generally more sensitive than X-rays; however, the authors noted
that minor underestimation could occur. Outcomes were defined as: localized and/or
diffuse pleural changes (52.9% ) and parenchymal changes (13.7% ). Pre-existing radio-
graphs that had been taken from 2003-2011 among participants who did not complete
HRCTs were also evaluated in a sensitivity analysis, increasing the imaging sample to
306.
High Both studies presented results for all aims and showed details such as numbers of cases
and non-cases by exposure category. Multivariable adjusted ORs were provided when
there was potential or apparent confounding. In Rohs et al RefID 709486 a few minor
aspects of multivariable models were not clear (treatment of missing BMI data in n=38
subjects with telephone interviews, inclusion or omission of non-participant baseline
data).
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Most associations were unadjusted, but confounding was assessed. Rohs et al., RefID
709486 showed adjustments for age and hire date which attenuated ORs. Rohs et al.,
RefID 709486 also showed that smoking was not associated with radiographic lung
change outcomes, so adjustment was not needed. In Lockey et al., RefID 3014803 mod-
els for parenchymal changes were adjusted for age and smoking a priori, and the authors
stated that there was no confounding by age, BMI or smoking in pleural change models
via results of backward elimination testing.
Medium Questionnaires and employment records were used in all studies. However, Rohs et al
RefID 709486 noted that "20 persons reported never smoking in the 1980 questionnaire
but subsequently reported a history of smoking in the 2004 questionnaire".
Medium Both Rohs et al RefID 709486 and Lockey et al RefID 3014803 evaluated co-exposure
to commercial asbestos by excluding individuals with any such exposure in sensitivity
analyses.
Continued on next page ...
Page 525 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709486 Table: 1 of 1
... continued from previous page
Study Citation:
Rohs, A., Lockey, J., Dunning, K., Shukla, R., Fan, H., Hilbert, T., Borton, E., Wiot, J., Meyer, C., Shipley, R., Lemasters, G., Kapil, V. (2008). Low-level
fiber-induced radiographic changes caused by Libby vermiculite: a 25-year follow-up study. American Journal of Respiratory and Critical Care Medicine
177(2008): 630-637.
Pleural Plaques
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Pleural changes (localized and/or diffuse pleural thickening), Parenchymal changes
Asbestos - Tremolite: 14567-73-8; Asbestos - Winchite: 12425-92-2; Asbestos- Richterite: 17068-76-7; Asbestos- Libby amphibole: 1318-09-8
ID(s): 709486,3014803
709486
Domain
Metric
Rating
Comments
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Medium
Medium
Medium
Appropriate analyses were used for all studies. Rohs et al RefID 709486 used logistic
regression to calculate ORs, and Lockey et al RefID 3014803 used log-binomial GEE
models to estimate RRs. Both follow-up studies evaluated the influence of including
living non-participants assuming normal chest imaging, and of limited the analysis to
workers hired after 1972 when exposure measures were based on monitoring data.
Both studies had adequate numbers of cases with radiographic lung changes for analysis
(n=80 in Rohs et al., RefID 709486, with additional cases in the subsequent follow-up).
The analyses presented are readily reproducible with sufficient detail provided.
The authors explained the rationale for their statistical methods used and covariates
examined (e.g. in Rohs et al., RefID 709486 BMI confounding was considered because
subpleural fat can mimic pleural thickening). The follow-up studies also evaluated fit
issues such as collinearity.
Additional Comments: Both of these studies had sufficient follow-up for asbestos-related lung changes to occur; the prevalence of radiographic pleural changes was 28.7% in
Rohs et al 709486 and 52.9% in Lockey et al 3014803, who used HRCT/CT after a longer follow-up. In the later study, fiber measures were improved
using updated information. Both authors conducted sensitivity analyses to evaluate bias due to attrition or non-participation; exposure measurement error;
and occupational exposure to commercial asbestos. Both studies observed pleural changes even among individuals in the lowest occupational exposure
categories, 0.005-0.24 fiber/cc-years in Rohs et al. 709486 and <0.15 fiber-years/cm3 in Lockey et al. 3014803. Lung changes were highly prevalent and
associations of high magnitude in the 2nd exposure category: 24.6% and crude OR of 4.02 for individuals with 0.29 to 0.85 fiber/cc-years in Rohs et al,
and 44.0% and crude RR of 5.0 for individuals with 0.15-<0.45 fiber-years/cm3 in Lockey et al. The Lockey et al 3014803 study also found associations
between fiber exposure and parenchymal abnormalities. Lockey et al reported no meaningful confounding. Rohs et al presented multivariable-adjusted
analyses which suggested some confounding by age and hire date but did not eliminate significance in the highest quartile. Lockey et al 3014803 also
conducted spirometry measures and reported associations between lung change outcomes and impaired lung function. These authors did not list actinolite
as a fiber.
Overall Quality Determination High
* No biomarkers were identified for this evaluation.
Page 526 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: m Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Rubino, G. F., Piolatto, G., Newhouse, M. L., Scansetti, G., Aresini, G. A., Murray, R. (1979). Mortality of chrysotile asbestos workers at the Balangero
Mine, northern Italy. Occupational and Environmental Medicine 36(1979): 187-194.
Laryngeal Cancer; gastrointestinal; lip, oral cavity and pharynx; stomach; colon and rectum, colon, rectum, peritoneum; respiratory organs; pleura;
bladder; nervous system; unspecified; Asbestosis; cirrhosis, cardiovascular disease, tuberculosis, influenza, pneumonia, and other respiratory diseases,
other pneumoconioses
Laryngeal: Laryngeal neoplasm mortality; Cancer/Carcinogenesis: Laryngeal neoplasm mortality, Gastrointestinal neoplasm mortality, Other sites neo-
plasms mortality, Lip, oral cavity, and pharynx malignant neoplasm mortality, Stomach malignant neoplasm mortality, Digestive organs and peritoneum
malignant neoplasm mortality, Respiratory organs neoplasm mortality, Pleura neoplasm mortality, Bladder neoplasm mortality, Nervous system neoplasm
mortality, small intestine, colon, and rectum neoplasm mortality, All malignant neoplasms mortality, Malignant neoplasm mortality, Colon and rectum
malignant neoplasm mortality, Colon malignant neoplasm mortality, Rectum malignant neoplasm mortality, Peritoneum malignant neoplasm mortality,
Unspecified malignant neoplasm mortality; Mortality: Laryngeal neoplasm mortality, Gastrointestinal neoplasm mortality, Other sites neoplasms mor-
tality, Influenza and pneumonia mortality, Asbestosis mortality, Tuberculosis of the lung mortality, Cardiovascular diseases mortality, Cirrhosis of the
liver mortality, Accidents mortality, All causes of mortality, Lip, oral cavity, and pharynx malignant neoplasm mortality, Stomach malignant neoplasm
mortality, Digestive organs and peritoneum malignant neoplasm mortality, Respiratory organs neoplasm mortality, Pleura neoplasm mortality, Bladder
neoplasm mortality, Nervous system neoplasm mortality, Psychiatric disorder mortality, Ischemic cardiopathy mortality, Other respiratory diseases mortal-
ity, Other pneumoconioses mortality, Other digestive diseases mortality, small intestine, colon, and rectum neoplasm mortality, All malignant neoplasms
mortality, Respiratory diseases (non-malignant) mortality, All other causes of mortality, Unknown cause of mortality, Malignant neoplasm mortality, Colon
and rectum malignant neoplasm mortality, Colon malignant neoplasm mortality, Rectum malignant neoplasm mortality, Peritoneum malignant neoplasm
mortality, Unspecified malignant neoplasm mortality, Digestive diseases mortality, Cirrhosis of the liver and other chronic liver dieseases mortality, Ex-
ternal causes mortality, Poorly defined cause of mortality; Gastrointestinal: Gastrointestinal neoplasm mortality, Stomach malignant neoplasm mortality,
Digestive organs and peritoneum malignant neoplasm mortality, Other digestive diseases mortality, small intestine, colon, and rectum neoplasm mortality,
Colon malignant neoplasm mortality, Colon and rectum malignant neoplasm mortality, Rectum malignant neoplasm mortality, Digestive diseases mortality;
Other sites: Other sites neoplasms mortality; Lung/Respiratory: Influenza and pneumonia mortality, Asbestosis mortality, Tuberculosis of the lung mortal-
ity, Respiratory organs neoplasm mortality, Pleura neoplasm mortality, Other respiratory diseases mortality, Other pneumoconioses mortality, Respiratory
diseases (non-malignant) mortality; Cardiovascular: Cardiovascular diseases mortality, Ischemic cardiopathy mortality; Hepatic/Liver: Cirrhosis of the
liver and other chronic liver dieseases mortality, Cirrhosis of the liver mortality; Head/mouth: Lip, oral cavity, and pharynx malignant neoplasm mortal-
ity; Renal/Kidney: Bladder neoplasm mortality; Neurological/Behavioral: Nervous system neoplasm mortality, Psychiatric disorder mortality; Abdomen:
Peritoneum malignant neoplasm mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
178, 6861719
178
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium From asbestos part 1: "Most complete report of exposure assessment is in initial co-
hort study ((Rubino et al., 1979) pg 189). Chrysotile fiber counts were first measured
in 1969 using membrane filter collection and phase contrast microscopy (frequency
not reported). To estimate exposure from 1946-1969, factory records on daily produc-
tion, equipment used, characteristics of the job and number of hours/day were used
(this method has considerable limitations due to basis on mean values for large job cat-
egories and no allowance for changes in weather). Simulated and measured data were
made comparable by using weighting factors (e.g., more dusty operation for 1-2 hr/d
compared with longer working hours in the past)."
Continued on next page ...
Page 527 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 178 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Rubino, G. F., Piolatto, G., Newhouse, M. L., Scansetti, G., Aresini, G. A., Murray, R. (1979). Mortality of chrysotile asbestos workers at the Balangero
Mine, northern Italy. Occupational and Environmental Medicine 36(1979): 187-194.
Laryngeal Cancer; gastrointestinal; lip, oral cavity and pharynx; stomach; colon and rectum, colon, rectum, peritoneum; respiratory organs; pleura;
bladder; nervous system; unspecified; Asbestosis; cirrhosis, cardiovascular disease, tuberculosis, influenza, pneumonia, and other respiratory diseases,
other pneumoconioses
Laryngeal: Laryngeal neoplasm mortality; Cancer/Carcinogenesis: Laryngeal neoplasm mortality, Gastrointestinal neoplasm mortality, Other sites neo-
plasms mortality, Lip, oral cavity, and pharynx malignant neoplasm mortality, Stomach malignant neoplasm mortality, Digestive organs and peritoneum
malignant neoplasm mortality, Respiratory organs neoplasm mortality, Pleura neoplasm mortality, Bladder neoplasm mortality, Nervous system neoplasm
mortality, small intestine, colon, and rectum neoplasm mortality, All malignant neoplasms mortality, Malignant neoplasm mortality, Colon and rectum
malignant neoplasm mortality, Colon malignant neoplasm mortality, Rectum malignant neoplasm mortality, Peritoneum malignant neoplasm mortality,
Unspecified malignant neoplasm mortality; Mortality: Laryngeal neoplasm mortality, Gastrointestinal neoplasm mortality, Other sites neoplasms mor-
tality, Influenza and pneumonia mortality, Asbestosis mortality, Tuberculosis of the lung mortality, Cardiovascular diseases mortality, Cirrhosis of the
liver mortality, Accidents mortality, All causes of mortality, Lip, oral cavity, and pharynx malignant neoplasm mortality, Stomach malignant neoplasm
mortality, Digestive organs and peritoneum malignant neoplasm mortality, Respiratory organs neoplasm mortality, Pleura neoplasm mortality, Bladder
neoplasm mortality, Nervous system neoplasm mortality, Psychiatric disorder mortality, Ischemic cardiopathy mortality, Other respiratory diseases mortal-
ity, Other pneumoconioses mortality, Other digestive diseases mortality, small intestine, colon, and rectum neoplasm mortality, All malignant neoplasms
mortality, Respiratory diseases (non-malignant) mortality, All other causes of mortality, Unknown cause of mortality, Malignant neoplasm mortality, Colon
and rectum malignant neoplasm mortality, Colon malignant neoplasm mortality, Rectum malignant neoplasm mortality, Peritoneum malignant neoplasm
mortality, Unspecified malignant neoplasm mortality, Digestive diseases mortality, Cirrhosis of the liver and other chronic liver dieseases mortality, Ex-
ternal causes mortality, Poorly defined cause of mortality; Gastrointestinal: Gastrointestinal neoplasm mortality, Stomach malignant neoplasm mortality,
Digestive organs and peritoneum malignant neoplasm mortality, Other digestive diseases mortality, small intestine, colon, and rectum neoplasm mortality,
Colon malignant neoplasm mortality, Colon and rectum malignant neoplasm mortality, Rectum malignant neoplasm mortality, Digestive diseases mortality;
Other sites: Other sites neoplasms mortality; Lung/Respiratory: Influenza and pneumonia mortality, Asbestosis mortality, Tuberculosis of the lung mortal-
ity, Respiratory organs neoplasm mortality, Pleura neoplasm mortality, Other respiratory diseases mortality, Other pneumoconioses mortality, Respiratory
diseases (non-malignant) mortality; Cardiovascular: Cardiovascular diseases mortality, Ischemic cardiopathy mortality; Hepatic/Liver: Cirrhosis of the
liver and other chronic liver dieseases mortality, Cirrhosis of the liver mortality; Head/mouth: Lip, oral cavity, and pharynx malignant neoplasm mortal-
ity; Renal/Kidney: Bladder neoplasm mortality; Neurological/Behavioral: Nervous system neoplasm mortality, Psychiatric disorder mortality; Abdomen:
Peritoneum malignant neoplasm mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): 178,6861719
178
Domain
Metric
Rating
Comments
Metric 5: Exposure Levels
Low Rubino et al., 1979, HEROID: 178 and Ferrante et al., 2020, HEROID: 6861719 analyze
these outcomes using dichotomous levels of exposure.
Additional Comments:
QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 528 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: m Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Rubino, G. F., Piolatto, G., Newhouse, M. L., Scansetti, G., Aresini, G. A., Murray, R. (1979). Mortality of chrysotile asbestos workers at the Balangero
Mine, northern Italy. Occupational and Environmental Medicine 36(1979):187-194.
Lung Cancer
Cancer/Carcinogenesis: Lung malignant neoplasm mortality; Lung/Respiratory: Lung malignant neoplasm mortality; Mortality: Lung malignant neoplasm
mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
178, 6861719
178
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
High The rating is based on asbestos part 1 evaluation description: "Subjects included men
from the Balangero mine worker cohort that were employed in an Italian asbestos mine.
The initial cohort ((Rubino et al., 1979, HEROID: 178), pg 188) consisted of 952 men
employed between 1/1/1930 and 12/31/1965, with at least 30 calendar days' employ-
ment during that period." and the description in the paper of interest (Ferrante et al.,
2020, HEROID: 6861719: "The cohort included 974 male workers employed for at least
6 months and active at the Balangero mine on 1st lanuary 1946 or hired subsequently
until the cessation of activity." While these accounts differ, it is likely meant to suggest
that only subjects with mortality, which began 1/1/46, are included in Ferrante et al.,
which extended mortality follow up to 5/31/2013.
High In Ferrante et al., 2020, HEROID: 6861719, only 21/974 (2% ) workers were lost by
follow up in 2013.
High As per asbestos part 1, this is rated high, however the paper in question Ferrante et al.,
2020, HEROID 6861719 does not explicitly address this metric. As per asbestos part
1: "The most complete data on comparison groups is available from the most recent
follow-up (Pira et al., 2017). General population mortality rates using the whole country
from 1955 until 1980 and specifically the Piedmont Region (where the mine is located)
from 1981 onwards (no regional rates available prior to 1981). The 1955-1959 rates
were applied to 1946-1954 period (no available data); this may have led to an underesti-
mate of expected deaths which may have showed and increased rate during this period.
Expected numbers of deaths (overall and selected cancers) were computed using age-
specific and calendar-year-specific (5-year categories) male death rates (Pira et al., 2017)
pg 559."
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium From asbestos part 1: "Most complete report of exposure assessment is in initial co-
hort study ((Rubino et al., 1979) pg 189). Chrysotile fiber counts were first measured
in 1969 using membrane filter collection and phase contrast microscopy (frequency
not reported). To estimate exposure from 1946-1969, factory records on daily produc-
tion, equipment used, characteristics of the job and number of hours/day were used
(this method has considerable limitations due to basis on mean values for large job cat-
egories and no allowance for changes in weather). Simulated and measured data were
made comparable by using weighting factors (e.g., more dusty operation for 1-2 hr/d
compared with longer working hours in the past)."
Continued on next page ...
Page 529 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 178 Table: 2 of 2
... continued from previous page
Rubino, G. F., Piolatto, G., Newhouse, M. L., Scansetti, G., Aresini, G. A., Murray, R. (1979). Mortality of chrysotile asbestos workers at the Balangero
Mine, northern Italy. Occupational and Environmental Medicine 36(1979):187-194.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Lung malignant neoplasm mortality; Lung/Respiratory: Lung malignant neoplasm mortality; Mortality: Lung malignant neoplasm
mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
178, 6861719
178
Domain
Metric
Rating
Comments
Metric 5:
Exposure Levels
Medium
The range and distribution of the cumulative exposure is sufficient to develop exposure-
response relations and the study reports 3 levels of exposure for analyses completed in
Ferrante et al„ 2020, HEROID: 6861719, table 4.
Metric 6:
Temporality
High
Ferrante et al., 2020, HEROID: 6861719 presents appropriate temporality between the
exposure to asbestos and the outcome of disease mortality, with follow up spanning into
2013.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High Lung Cancer: Ferrante et al., 2020, HEROID: 6861719 notes that: "Causes of death
were provided by the Death and Births Registry Office of the municipality of death and
were coded by us according to the International Classification of Diseases (ICD) classi-
fication (9th revision)." Authors do not explicitly state which code(s) were used in this
paper nor do they reference a methods paper. However, the asbestos part 1 evaluation
does state that certain ICD codes were referenced, and will use this rating as methods
are presumably the same across updates of analyses.
High Ferrante et al., 2020, HEROID: 6861719 reports Poisson regression outcomes with
relative risks and 95% CIs.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Ferrante et al., 2020, HEROID: 6861719 adjusted for age explicitly and sex and race
discretely based on the initial recruitment makeup of subjects, however there was no
adjustment for smoking.
High Ferrante et al., 2020, HEROID: 6861719 used occupational data from employers: "The
list of cohort members and their working periods and job assignments were extracted
from the factory rosters, stored after the mine bankruptcy in the Turin section of the
Italian State Archives, where we had access to them."
Low Ferrante et al., 2020, HEROID: 6861719 did not adjust for coexposures.
Domain 5: Analysis
Metric 12: Study Design and Methods Medium The study design (cohort with follow up and analyses of lung cancer mortality counts
by Poisson regression) was appropriate (Ferrante et al., 2020, HEROID: 6861719).
However it is unclear why authors did not complete a Cox survival model.
Metric 13: Statistical Power Medium The number of participants (n=953) are adequate to detect an effect in the exposed pop-
ulation (Ferrante et al., 2020, HEROID: 6861719).
Metric 14: Reproducibility of Analyses Medium The description of the analysis is sufficient to understand how to conceptually reproduce
the analysis with access to the analytic data (Ferrante et al., 2020, HEROID: 6861719).
Continued on next page ...
Page 530 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 178 Table: 2 of 2
... continued from previous page
Rubino, G. F., Piolatto, G., Newhouse, M. L., Scansetti, G., Aresini, G. A., Murray, R. (1979). Mortality of chrysotile asbestos workers at the Balangero
Mine, northern Italy. Occupational and Environmental Medicine 36(1979):187-194.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Cancer/Carcinogenesis: Lung malignant neoplasm mortality; Lung/Respiratory: Lung malignant neoplasm mortality; Mortality: Lung malignant neoplasm
mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
178, 6861719
178
Domain
Metric
Rating
Comments
Metric 15: Statistical Analysis
Low Relative risks were calculated for lung cancer mortality using Poisson regression, how-
ever model assumptions were not explicitly addressed (i.e., does outcome data fit the
Poisson distribution?). Authors state only: "95% CI were estimated assuming the Pois-
son distribution of observed cases." However, it is unclear if they mean all outcomes or a
specific one (potentially only mesothelioma).
Additional Comments:
This evaluation is solely for analyses done in Ferrante et al., 2020, HEROID: 6861719 for lung cancer mortality. All other analyses do not have a Medium
or higher rating for Metric 5 or are not SMR or regression analyses. Rubino et al., 1979, HEROID: 178 has no outcomes not already evaluated which have
a Medium or higher rating for Metric 5 or are not SMR or regression analyses and are thus not evaluated or extracted in any capacity here.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 531 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6866570 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Ryan, P. H., Rice, C. H., Lockey, J. E., Black, B., Burkle, J., Hilbert, T. J., Levin, L., Cole, B., Mckay, R., Wolfe, C., Lemasters, G. K. (2017). Childhood
exposure to Libby amphibole asbestos and respiratory health in young adults. Environmental Research 158470-479.
Pleuritic chest pain, Regular cough, shortness of breath, wheezing or whistling in the chest
Lung/Respiratory: Pleuritic chest pain, Regular cough, Shortness of breath, Wheezing or whistling in the chest
Asbestos- Libby amphibole: 1318-09-8
ID(s): No linked references.
6866570
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Low
Metric 2: Attrition
Metric 3: Comparison Group
High
Medium
Most key elements of study design are described (setting, inclusion criteria, partici-
pant recruitment) but details regarding participation rate at all steps of the study are not
provided. The is an analysis using subjects of the Childhood Health Investigation and
Exposure Follow-Up Study (CHIEFS). To be eligible, children must have been part of
2000-2001 ATSDR screening and have been 10-17 years old at that time. Children the
same age who did not participate but met ATSDR screening eligibility requirements
were also eligible. "Recruitment efforts included contact with the parents of the previ-
ous ATSDR participants, posts to social media, public outreach events including health
fairs, and advertisements in local and regional newspapers." A total of 312 subjects were
enrolled and completed at least one portion of the study. Of these, 234 (75% ) had pre-
viously participated in the ATSDR screening. 311 subjects had complete questionnaire
data and 304 had spirometry data. There is no cited information on the ATSDR screen-
ing eligibility requirements or the subjects themselves who were recruited. Because of
this, there is substantial potential for recruitment bias and no data to suggest differently.
Of the 312 participants, 304 had total spirometry data and 311 had complete question-
naire data. Explanations for why some data are missing or the characteristics of individ-
uals who did not provide some data were not discussed, but exposure and outcome data
were largely complete.
Based on what the authors present in the paper, there is some evidence that most partici-
pants are similar to each other (age, race/ethnicity). Statistical analyses adjusted for sex
and smoking history. However, analyses were not adjusted for BMI which was approx-
imately evenly distributed among the participants (normal - 39% ; overweight - 32%
; obese - 29% ). It is possible that BMI could have an effect on some spirometry data/
respiratory health outcomes.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium Exposure was estimated for 12 different activities, and a cumulative 12-activity metric
(fiber/cc - months) by combining previously completed exposure measurements using
PCM or PCM equivalent methods from different but comparable time periods and ac-
tivity frequency data from subject questionnaires. Exposure estimates and the rationale
for each were based on "literature values, available activity-based sampling results, and
the US EPA Contaminant Screening Survey results." While this method does use 'expert
judgement', it is no different that the creation of JEM, except for a community setting.
Continued on next page ...
Page 532 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6866570 Table: 1 of 2
... continued from previous page
Ryan, P. H., Rice, C. H., Lockey, J. E., Black, B., Burkle, J., Hilbert, T. J., Levin, L., Cole, B., Mckay, R., Wolfe, C., Lemasters, G. K. (2017). Childhood
exposure to Libby amphibole asbestos and respiratory health in young adults. Environmental Research 158470-479.
Pleuritic chest pain, Regular cough, shortness of breath, wheezing or whistling in the chest
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Lung/Respiratory: Pleuritic chest pain, Regular cough, Shortness of breath, Wheezing or whistling in the chest
Asbestos- Libby amphibole: 1318-09-8
No linked references.
6866570
Domain
Metric
Rating
Comments
Metric 5:
Metric 6:
Exposure Levels
Temporality
Medium
Low
Only analyses contributing to the creation of figure 2 present results using continuous
(i.e., non-dichotomous) exposures. While distributions are highly skewed, it is feasible
that these can be used in dose response analysis. The 12-activities cumulative exposure
median was 4.99 f/cc - months, ranging from 0.01 - 114.3 f/cc - months.
Temporality is established, but it is not certain whether there was adequate follow-up in
consideration of latency. However, the study's focus was to assess associations of esti-
mated LAA exposure during childhood (<= 18 years of age) with adverse respiratory
health effects and most participants were evaluated as young adults in their mid-20s,
and 98% of subjects were born prior to the mine closing in 1990. The authors make the
case that additional follow-up studies in this cohort should be done, and that the data
presented in this paper should be thought of as "baseline" data "upon which future health
outcomes can be compared."
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Uninformative
High
Other Non-Cancer Outcomes: Only self-reported health outcomes were used without
validation. There is little detail on how the survey was conducted (i.e., by a trained
surveyor or nurse), that might increase confidence in the outcome measure.
The findings are clearly presented with adjusted odds ratios and 95% CI's as a log base 2
transformation (i.e., a 2-folder increase in exposure).
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Low
High
Low
Final analyses were adjusted for sex and smoking history but not BMI or other potential
important confounders, such as asthma. The authors do not provide reasoning or their
methodology for selecting those particular covariates to be used in the analyses.
Covariate data were assessed using valid and reliable methodology. A questionnaire
adapted from the ATSDR medical screening survey was used to collect demographic
information, residential and occupational history, and respiratory health history.
There is no discussion of other exposures (i.e., other activities or jobs) might have im-
pacted the subjects.
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
The study design was appropriate for the research question, and the study used an ap-
propriate statistical method to assess associations between estimated asbestos exposure
during childhood with the health outcomes of interest in young adults (logistic regres-
sion analyses).
Continued on next page ...
Page 533 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 6866570 Table: 1 of 2
... continued from previous page
Ryan, P. H., Rice, C. H., Lockey, J. E., Black, B., Burkle, J., Hilbert, T. J., Levin, L., Cole, B., Mckay, R., Wolfe, C., Lemasters, G. K. (2017). Childhood
exposure to Libby amphibole asbestos and respiratory health in young adults. Environmental Research 158470-479.
Pleuritic chest pain, Regular cough, shortness of breath, wheezing or whistling in the chest
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Pleuritic chest pain, Regular cough, Shortness of breath, Wheezing or whistling in the chest
Asbestos- Libby amphibole: 1318-09-8
ID(s): No linked references.
6866570
Domain
Metric
Rating
Comments
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The number of participants (n=311) was adequate to detect an effect in subgroups of the
sample, specifically those subjects who reported being involved with certain activities
related to increased asbestos exposure during childhood.
Medium If given access to the analytic data, one would be able to reproduce the analyses based
on the description of the statistical methodology.
Low Though the statistical model building process was appropriate, the authors do not explic-
itly state that model assumptions were met.
Additional Comments: Note that only analyses in figure 2 meet the "medium or high" rating for metric 5, and thus are the focus of this evaluation. QC was not completed for
extraction, as the overall quality determination was uninformative. This cohort study retrospectively estimated childhood exposure to Libby amphibole
asbestos (LAA) in young adults who grew up in Libby, MT; of this sample 98% were born prior to the mine closure in 1990. Exposure estimates depended
on participant report of the frequency of engaging certain activities related to LAA exposure during childhood, and they found that heating vermiculite,
fishing on the Kootenai River, and engaging in activities along or near Rainy Creek Road were associated with respiratory symptoms (not spirometry
outcomes) in young adulthood. One notable limitation not addressed in the metrics under consideration is that of possible recall bias among participants,
which may impact exposure estimates. Another is that health outcomes are based solely on self-report without confirmation or validation.
Overall Quality Determination Uninformative
* No biomarkers were identified for this evaluation.
Page 534 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6866570 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Ryan, P. H., Rice, C. H., Lockey, J. E., Black, B., Burkle, J., Hilbert, T. J., Levin, L., Cole, B., Mckay, R., Wolfe, C., Lemasters, G. K. (2017). Childhood
exposure to Libby amphibole asbestos and respiratory health in young adults. Environmental Research 158470-479.
Pulmonary Function/Spirometry Results; Pleural and interstitial changes
Lung/Respiratory: Forced expiratory volume in 1 second (FEV1) % predicted, Forced vital capacity (FVC) % predicted, FEV1/FVC % predicted, Pleural
Changes, Interstitial Changes
Asbestos- Libby amphibole: 1318-09-8
ID(s): No linked references.
6866570
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium Exposure was estimated for 12 different activities, and a cumulative 12-activity metric
(fiber/cc - months) by combining previously completed exposure measurements using
PCM or PCM equivalent methods from different but comparable time periods and ac-
tivity frequency data from subject questionnaires. Exposure estimates and the rationale
for each were based on "literature values, available activity-based sampling results, and
the US EPA Contaminant Screening Survey results." While this method does use 'expert
judgement', it is no different that the creation of JEM, except for a community setting.
Metric 5: Exposure Levels Low Analyses are only completed for these outcomes using dichotomous exposure variables.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 for these outcomes because the analysis does not have sufficient exposure information to be
useful for dose-response analysis.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 535 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 517889 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Santibanez, M., Vioque, J., Alguacil, J., Barber, X., de la Hera, G., Kauppinen, T. (2008). Occupational exposures and risk of oesophageal cancer by
histological type: a case-control study in eastern Spain. Occupational and Environmental Medicine 65(2008):774-781.
Oesophageal cancer
Gastrointestinal: Oesophageal cancer; Cancer/Carcinogenesis: Oesophageal cancer
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
517889
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low There was an interview conducted to ascertain information about occupational history
and resulting potential exposures. Asbestos exposure was classified as low (<0.26 fi-
bres/err^ 3) and high (>0.26 fibres/cmA 3). These concentrations were "based on the
product of the probability and the intensity of exposure to each agent for at least 1 year"
(Santibanez et al., 2008).The study or any cited methods source does not explicitly men-
tion the use of PCM or TEM.
Low In Table 2, asbestos exposure levels were only reported as high or low, although the
authors do note that there is an unexposed category. However, the range of exposure in
the population is limited and is based on responses to interview questions.
Additional Comments: Based on the auto-calculated score, this paper was rated as a medium. However, there were some shortcomings in the paper that should be mentioned. The
authors highlight that the case-control design of this study may not be the best option for occupational exposures. There also may have been a low number
of individuals present in each job classification. They also noted that the FINJEM job exposure matrix may have resulted in overestimation of asbestos
exposure, as there were no asbestos mines in Spain.NOTE: Based on the current guidelines, this study would not have undergone further evaluation after
metric 4 and 5. Metric 4 was rated as low because there was no mention in the study or cited sources about the use of PCM or TEM.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 536 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2569533 Table: 1 of 1
Study Citation: Santibaf
n}ez, M., Alguacil, J., de La Hera, M. G., Navarrete-Mu{
n}oz, E. M., Llorca, J., Aragonfe, N., Kauppinen, T., Vioque, J., PANESOES Study Group (2012). Occupational exposures and risk of stomach cancer by
histological type. Occupational and Environmental Medicine 69(2012):268-275.
stomach cancer-all histological subtypes, intestinal adenocarcinoma, diffuse adenocarcinoma, lymphoma
Gastrointestinal: Stomach cancer-lymphoma, Stomach cancer-diffuse adenocarcinoma, Stomach cancer-intestinal adenocarcinoma, Stomach cancer-all
histological subtypes
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
2569533
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The FINJEM job exposure matrix was utilized to explore occupational exposure to
various chemical, physical, ergonomic and psychosocial factors, including asbestos.
Further information on the FINJEM was noted within referenced details of Kauppinen
et al., 1998 (full text found but HERO ID not available) which describes the JEM as
utilizing detailed quantitative industrial hygiene sampling results over time ascribed to
occupational job titles and overviewed by industry experts. Details regarding utilization
of PCM or TEM for asbestos analysis are not provided. It is unclear if the time periods
with quantitative measures within the JEM corresponded to the time periods of interest.
Low Outcome odds ratios in Tables 3 and 4 were presented across only two asbestos expo-
sure categories of Low (<=0.26 fibers/cmA 3) and High (>0.26 fibers/cmA 3), with the
reference category for each odds ratio including all remaining exposed groups.
Additional Comments: HERO ID 2569533 Santibanez (2012) was not evaluated for any metrics except Metrics 4 and 5 and had no data extracted because it did not have sufficient
exposure information to be useful for dose-response analysis.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 537 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6868480 Table: 1 of 2
Study Citation: Satta, G., Serra, T., Meloni, F., Lazzarato, A., Argiolas, A., Bosu, E., Coratza, A., Frau, N., Lai, M., Lecca, L. I., Mascia, N., Pilia, I., Piras, V., Sferlazzo,
G., Campagna, M., Cocco, P. (2019). Pulmonary Function and CT Scan Imaging at Low-Level Occupational Exposureto Asbestos. International Journal
of Environmental Research and Public Health 17(2019):50.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Vital capacity (VC), Forced expiratory volume in 1 second (FEV1), Residual volume (RV), Diffusion lung capacity test with carbon
monoxide (DLCO)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
6868480
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This study determined exposure estimates using a retrospective assessment approach
that included referring to the Datamyant database and abstract the time-weighted aver-
age concentration of asbestos fibers for each job task. To estimate indirect exposure re-
sulting from the contamination of the work environment, they based calculations on the
Ev@lutil database. Overall they relied upon professional judgment and were not able to
collect direct exposure samples. The methods of quantifying fiber was not specified.
Medium Subjects were divided into exposure quartiles, indicating there were 4 exposure groups.
The range of exposure is likely sufficient to detect a relationship, based on the exposure
information in Table 1 and frequency distribution of exposures in Figure 1.
Additional Comments: This cross-sectional occupational study examined associations of retrospective estimates of low-level asbestos exposure with respiratory function tests and
HRCT reports ((Gamsu grades for pleuro-parenchymal alterations). There were no associations of asbestos with pulmonary function, but the study reported
increased odds of developing lung fibrosis: risk in the top quartile of cumulative exposure was increased 8-fold, and for cumulative exposures above 10
fibers/mL-years risk was increased 11 -fold.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 538 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6868480 Table: 2 of 2
Study Citation: Satta, G., Serra, T., Meloni, F., Lazzarato, A., Argiolas, A., Bosu, E., Coratza, A., Frau, N., Lai, M., Lecca, L. I., Mascia, N., Pilia, I., Piras, V., Sferlazzo,
G., Campagna, M., Cocco, P. (2019). Pulmonary Function and CT Scan Imaging at Low-Level Occupational Exposureto Asbestos. International Journal
of Environmental Research and Public Health 17(2019):50.
Pleural Plaques
Lung/Respiratory: Interstitial fibrosis of lung parenchyma based on result of high-resolution computerized tomography (HRCT) scan
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
6868480
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This study determined exposure estimates using a retrospective assessment approach
that included referring to the Datamyant database and abstract the time-weighted aver-
age concentration of asbestos fibers for each job task. To estimate indirect exposure re-
sulting from the contamination of the work environment, they based calculations on the
Ev@lutil database. Overall they relied upon professional judgment and were not able to
collect direct exposure samples. The methods of quantifying fiber was not specified.
Medium Subjects were divided into exposure quartiles, indicating there were 4 exposure groups.
The range of exposure is likely sufficient to detect a relationship, based on the exposure
information in Table 1 and frequency distribution of exposures in Figure 1.
Additional Comments: This cross-sectional occupational study examined associations of retrospective estimates of low-level asbestos exposure with respiratory function tests and
HRCT reports ((Gamsu grades for pleuro-parenchymal alterations). There were no associations of asbestos with pulmonary function, but the study reported
increased odds of developing lung fibrosis: risk in the top quartile of cumulative exposure was increased 8-fold, and for cumulative exposures above 10
fibers/mL-years risk was increased 11 -fold.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 539 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3864418 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Schikowsky, C., Felten, M. K., Eisenhawer, C., Das, M., Kraus, T. (2017). Lung function not affected by asbestos exposure in workers with normal
Computed Tomography scan. American Journal of Industrial Medicine 60(2017):422-431.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Airway resistance, Carbon monoxide diffusing capacity adjusted for alveolar volume (DLCO/VA), Forced expiratory volume in 1
second, Forced vital capacity (FVC)
Asbestos - Not specified: 1332-21-4
No linked references.
3864418
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low For this study, the cumulative exposure to asbestos was estimated for each participant.
These values were determined based on job titles, main occupational tasks, and self-
reported periods of exposure. The authors indicated that a computer program was used
to determine these concentrations based on ambient monitoring data at defined work-
places. Cumulative exposure "was expressed as the product of the total exposure dura-
tion and the 8-h time weighted average fiber concentration" in fiber-years (Schikowsky
et al., 2017). This metric is rated low because the study or any cited methods source
does not mention the use of PCM or TEM.
Medium The range of exposure present in this study is adequate for examining an exposure-
response relationship. The average cumulative asbestos exposure for the participants
was 49.0 fiber years, with a range of 0.1-844.9 fiber years.
Additional Comments: This study had a number of strengths and limitations. One of the biggest limitations is a lack of direct asbestos measurements. Cumulative asbestos exposure
was estimated based on job titles, occupational tasks, and self-reported periods of exposure. This limits the potential for a dose-response relationship. The
authors also reported that there was no statistically significant differences between lung function and asbestos exposure. Strengths of this study included
using regression analyses to be able to perform intra-group comparisons, such as based on smoking status. It is important to note that metric 4 was rated as
low because there was no mention of PCM or TEM in the methods or any cited source.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 540 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2558775 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Schnatter, A. R., Nicolich, M. J., Lewis, R. J., Thompson, F. L., Dineen, H. K., Drummond, I., Dahlman, D., Katz, A. M., Th&iault, G. (2012). Lung
cancer incidence in Canadian petroleum workers. Occupational and Environmental Medicine 69(2012):877-882.
Lung Cancer
Cancer/Carcinogenesis: Lung cancer; Lung/Respiratory: Lung cancer
Asbestos - Not specified: 1332-21-4
No linked references.
2558775
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low Quantitative asbestos exposure levels were reported and the source of exposure data
was provided. Employment history for study subjects were obtained and largely com-
plete. The study didn't mention exposure measurement methods, and the concentration
were from industrial hygiene surveys and frequency scores. There is no direct evidence
indicates exposure measurement were biased.
Low Asbestos exposure in tertiles and continuous level were reported, but the range of ex-
posure is not sufficient and lack of exposure contrast to develop an exposure-response
estimate.
Additional Comments: The primary concern of this study is lack of sufficient exposure range to detect an effect. There are no other concerns of bias or study design deficiency.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 541 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3531424 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Seidler, A., Becker, N., Nieters, A., Arhelger, R., Mester, B., Rossnagel, K., Deeg, E., Eisner, G., Melis, M., Sesler, S., Avataneo, G., Meloni, M., Cocco, P.
(2010). Asbestos exposure and malignant lymphoma: a multicenter case-control study in Germany and Italy. International Archives of Occupational and
Environmental Health 83(2010):563-570.
Lymphoma
Cancer/Carcinogenesis: B-cell non-Hodgkin"s lymphoma (B-NHL), Hodgkin"s lymphoma (HL), T-cell non-Hodgkin"s lymphoma (T-NHL)
Asbestos - Not specified: 1332-21-4
ID(s): No linked references.
3531424
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Low
Exposure was estimates solely using professional judgement, no evidence of measure-
ments was provided.
Metric 5:
Exposure Levels
Medium
The authors reported four levels (in fiber-years) of exposure for regression analysis.
Additional Comments: None
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 542 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 257 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Lung Cancer; Laryngeal Cancer; All cancer mortality; Non-respiratory infectious disease mortality
Mortality: All cause mortality, Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and colon-rectum) mor-
tality, Non-infectious respiratory diseases (including asbestosis) mortality, All "asbestos" diseases (lung cancer, gastrointestinal cancer, mesothelioma,
cancers of buccal cavity, pharynx, larynx, and kidney and non-infectious respiratory diseases) mortality, All cancer mortality, Larynx, buccal, pharynx
cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality, Other and unspecified cancer mortality, Cardiovas-
cular diseases mortality; Lung/Respiratory: Lung cancer mortality, Non-infectious respiratory diseases (including asbestosis) mortality, Larynx, buccal,
pharynx cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, All cancer mortality, Larynx, buccal, pharynx cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pan-
creas cancer mortality, Other and unspecified cancer; Gastrointestinal: Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality; Cardiovascular: Cardiovascular diseases
mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
257
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
High In this retrospective cohort study, Seidel et al 1984 (HEROID 257) examined cause-
specific mortality in a cohort of male workers at an amosite asbestos factory in Paterson,
NJ that operated from June 1941 to November 1954. The cohort was described as al-
most entirely white (mentioned in Seidman et al., 1979 HEROID 94625). This study
excluded deaths in the first five years, analyzing mortality occurring 5-40 years after
employment. Of all 933 men recruited to work from June 1941 to December 1945, this
study excluded 113: 35 who worked with asbestos elsewhere (21 before starting and 14
afterwards); 40 who died within 5 years; and 38 lost to follow-up shortly after leaving
the plant. The remaining 820 participants had worked at the facility for as little as one
month up to several years. The mean age at employment was 41.9 years (50.8% aged
>40 years). Three aspects of participant selection helped to limit bias. First, the study
avoided healthy worker selection bias because all workers were eligible for inclusion
regardless of date of initial employment, and regardless of duration of employment. In
addition, the study used an exposure lag to reduce potential bias by taking disease la-
tency into account: asbestos exposure at this plant may not have been causally related
to disease outcomes with latency periods of >5 years. Finally, participants exposed to
asbestos in other work settings were excluded.
High Only a few eligible workers (n=38) had been lost to follow-up at the start of this study.
There was little additional attrition of the 820 participants in this follow-up through
1982, which included: 4 additional men lost to follow-up, and 5 who contributed person-
time until starting asbestos work elsewhere (i.e., became ineligible; see p. 3). Of the 811
remaining men, 593 had died and 218 were still alive, accounting for the complete co-
hort. A later publication (Seidman et al., 1986, HEROID 290) reported similar numbers
(5 lost to follow-up, 6 who began asbestos work elsewhere, 216 alive). Table 1 shows,
for each 5-year period of follow-up, the number of workers at risk, the mean age of
those workers, and the number of deaths that occurred, along with the small number lost
to follow-up.
Continued on next page ...
Page 543 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 257 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Lung Cancer; Laryngeal Cancer; All cancer mortality; Non-respiratory infectious disease mortality
Mortality: All cause mortality, Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and colon-rectum) mor-
tality, Non-infectious respiratory diseases (including asbestosis) mortality, All "asbestos" diseases (lung cancer, gastrointestinal cancer, mesothelioma,
cancers of buccal cavity, pharynx, larynx, and kidney and non-infectious respiratory diseases) mortality, All cancer mortality, Larynx, buccal, pharynx
cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality, Other and unspecified cancer mortality, Cardiovas-
cular diseases mortality; Lung/Respiratory: Lung cancer mortality, Non-infectious respiratory diseases (including asbestosis) mortality, Larynx, buccal,
pharynx cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, All cancer mortality, Larynx, buccal, pharynx cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pan-
creas cancer mortality, Other and unspecified cancer; Gastrointestinal: Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality; Cardiovascular: Cardiovascular diseases
mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
257
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Domain
Metric
Rating
Comments
Metric 3:
Comparison Group
High Standardized mortality ratios were calculated comparing all eligible workers in the co-
hort to white male residents of New Jersey in the same 5-year age groups during the
same calendar periods. The authors reported elsewhere (Seidman et al., 1979 HEROID
94625) that death rates from cancer in New Jersey were "among the highest in the
United States". The choice of the state referent helped to account for the regional back-
ground rates of cancer mortality.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low No fiber or dust count measures were available for this facility. Estimates were based
on measures taken in 1967, 1970 and 1971 at two other plants run by the same company
(in Tyler, TX; Port Allegany, PA) making the same products with the same machinery.
Details on sampling equipment and procedures, or references to obtain that informa-
tion, were not provided. Dr. William Nicholson helped to "assign plausible estimates" to
"particular jobs" (i.e., estimates were extrapolated from later measures at other facilities
using professional judgment). There were no details on how data were used, no discus-
sion of comparable ventilation/dust extraction, and no references cited. It is not possible
to ascertain the likely validity of fiber count estimates. Fiber-years/cc for each worker
was calculated by multiplying estimated fiber counts for each job duty by the duration
of work in that post. The median count of fibers > 5[i per cc across jobs was 50; counts
for a list of job titles were shown in Table 5 (e.g., 5 for office workers, 15 for inspectors
and foremen, 50 for production supervisors, 100 for pulverizers). Potential sources of
error noted by the authors included: (i) the tendency for industrial hygienists to over-
sample dustier areas (counts too high, underestimate dose-response); (ii) the possibility
that short-term workers "may have experienced an apprenticeship period in which they
did some of the dirtier work in their department" (counts too low, over-estimate effect of
short-term exposure); and (iii) lack of information on use of respirators (measurement
error, uncertain if a source of bias). The study reports that there was a "concerted ef-
fort to have the Paterson plant workers use respirator protectors" although no details on
compliance are provided.
Continued on next page ...
Page 544 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 257 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Lung Cancer; Laryngeal Cancer; All cancer mortality; Non-respiratory infectious disease mortality
Mortality: All cause mortality, Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and colon-rectum) mor-
tality, Non-infectious respiratory diseases (including asbestosis) mortality, All "asbestos" diseases (lung cancer, gastrointestinal cancer, mesothelioma,
cancers of buccal cavity, pharynx, larynx, and kidney and non-infectious respiratory diseases) mortality, All cancer mortality, Larynx, buccal, pharynx
cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality, Other and unspecified cancer mortality, Cardiovas-
cular diseases mortality; Lung/Respiratory: Lung cancer mortality, Non-infectious respiratory diseases (including asbestosis) mortality, Larynx, buccal,
pharynx cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, All cancer mortality, Larynx, buccal, pharynx cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pan-
creas cancer mortality, Other and unspecified cancer; Gastrointestinal: Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality; Cardiovascular: Cardiovascular diseases
mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
257
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Domain
Metric
Rating
Comments
Metric 5:
Exposure Levels
Medium
Exposure was analyzed using categories of fiber-years/cc and work duration. Data were
presented using 8 categories of fiber-years/cc (<6, 6-11.9, 12-24.9, 25-49.9, 50-99.9,
100-149.9, 150-249.9, 250+ fiber-years/cc), as well as dichotomized (<25 vs 25+
fiber-years/cc). Exposure duration was classified in 7 categories (<1 month, 1 month,
2 months, 3-5 months, 6-11 months, 1 year, 2+ years); boundaries for these periods
were not provided. In addition, some analyses calculated SMRs classified by depart-
ment of work (e.g., Table 11 in HEROID 257; see also Table XIII in Seidman et al, 1986
HEROID 290).
Metric 6:
Temporality
High
Temporality and duration of follow-up was appropriate for the outcomes evaluated (mul-
tiple cancers, mesothelioma, and asbestosis). Follow-up ranged from a minimum of 5 to
a maximum of 40 years.
Domain 3: Outcome Assessment
Continued on next page .
Page 545 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 257 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Lung Cancer; Laryngeal Cancer; All cancer mortality; Non-respiratory infectious disease mortality
Mortality: All cause mortality, Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and colon-rectum) mor-
tality, Non-infectious respiratory diseases (including asbestosis) mortality, All "asbestos" diseases (lung cancer, gastrointestinal cancer, mesothelioma,
cancers of buccal cavity, pharynx, larynx, and kidney and non-infectious respiratory diseases) mortality, All cancer mortality, Larynx, buccal, pharynx
cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality, Other and unspecified cancer mortality, Cardiovas-
cular diseases mortality; Lung/Respiratory: Lung cancer mortality, Non-infectious respiratory diseases (including asbestosis) mortality, Larynx, buccal,
pharynx cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, All cancer mortality, Larynx, buccal, pharynx cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pan-
creas cancer mortality, Other and unspecified cancer; Gastrointestinal: Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality; Cardiovascular: Cardiovascular diseases
mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
257
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Domain Metric Rating Comments
Metric 7: Outcome Measurement or Medium Lung Cancer: The authors reported analyzing causes of death derived principally using
Characterization the "best evidence" available to classify cause of death, as well as analyses using only
death certificate (DC) information. Best evidence (BE) classification incorporated ad-
ditional information from autopsy, surgical specimens, x-ray films and clinical findings
(Seidman et al., 1979 HEROID 94625). Tables indicate when BE or DC coding was
used, and comparisons of counts based on each method are shown (e.g., Table 6A). The
authors did not describe best evidence sources or methods used to link participants to
these sources or death certificates, did not provide ICD codes, and did not discuss in-
volving a nosologist. Insights on BE sources can be inferred from acknowledgements
(e.g., see Seidman et al, 1986 HEROID 290), which mention receiving generous help
from medical facilities including hospitals, pathologists, and state health departments,
with several facilities and clinicians listed by name.; Laryngeal Cancer: The authors
reported analyzing causes of death derived principally using the "best evidence" avail-
able to classify cause of death, as well as analyses using only death certificate (DC)
information. Best evidence (BE) classification incorporated additional information from
autopsy, surgical specimens, x-ray films and clinical findings (Seidman et al., 1979
HEROID 94625). Tables indicate when BE or DC coding was used, and comparisons of
counts based on each method are shown (e.g., Table 6A). The authors did not describe
best evidence sources or methods used to link participants to these sources or death cer-
tificates, did not provide ICD codes, and did not discuss involving a nosologist. Insights
on BE sources can be inferred from acknowledgements (e.g., see Seidman et al, 1986
HEROID 290), which mention receiving generous help from medical facilities including
hospitals, pathologists, and state health departments, with several facilities and clini-
cians listed by name. There were limited details on how outcomes were defined. In this
study, cancers of the larynx, buccal and pharynx were combined.; Other Cancer(s): The
authors reported analyzing causes of death derived principally using the "best evidence"
available to classify cause of death, as well as analyses using only death certificate (DC)
information. Best evidence (BE) classification incorporated additional information from
autopsy, surgical specimens, x-ray films and clinical findings (Seidman et al., 1979
HEROID 94625). Tables indicate when BE or DC coding was used, and comparisons of
counts based on each method are shown (e.g., Table 6A). The authors did not describe
best evidence sources or methods used to link participants to these sources or death cer-
tificates, did not provide ICD codes, and did not discuss involving a nosologist. Insights
r> sa/: t on BE sources can be inferred from acknowledgements (e.g., see Seidman et al, 1986
rdge 310 01 OUO HEROID 290), which mention receiving generous help from medical facilities including
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 257 Table: 1 of 1
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Lung Cancer; Laryngeal Cancer; All cancer mortality; Non-respiratory infectious disease mortality
Mortality: All cause mortality, Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and colon-rectum) mor-
tality, Non-infectious respiratory diseases (including asbestosis) mortality, All "asbestos" diseases (lung cancer, gastrointestinal cancer, mesothelioma,
cancers of buccal cavity, pharynx, larynx, and kidney and non-infectious respiratory diseases) mortality, All cancer mortality, Larynx, buccal, pharynx
cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality, Other and unspecified cancer mortality, Cardiovas-
cular diseases mortality; Lung/Respiratory: Lung cancer mortality, Non-infectious respiratory diseases (including asbestosis) mortality, Larynx, buccal,
pharynx cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, All cancer mortality, Larynx, buccal, pharynx cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pan-
creas cancer mortality, Other and unspecified cancer; Gastrointestinal: Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality; Cardiovascular: Cardiovascular diseases
mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
257
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Domain
Metric
Rating
Comments
Metric 8:
Reporting Bias
High
Information is presented for all outcomes described. The authors present details on the
observed and expected numbers of deaths stratified by categories of exposure or time
period, along with the resulting SMRs; statistical significance is indicated. There is no
evidence of selective reporting.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High
Medium
Low
SMR calculations accounted for expected cases based on 5-year age groups and calendar
period of death. The participants were male and described as almost exclusively white,
so sex and race adjustments were not needed. No other covariates were considered (e.g.,
smoking, alcohol), as is habitual in SMR studies.
Information on age and calendar period of death were likely obtained from plant
records, death certificates and other medical record sources.
In this occupational setting, potential co-exposures are not discussed. There is no in-
formation to suggest the presence of other important co-exposures in this setting. The
factory supplied the US. Navy with asbestos insulation for the pipes, boilers, and tur-
bines of its ships. The procedures in the factory were described on p. 5 (Seidman et al.,
1984, HEROID 257).
Domain 5: Analysis
Metric 12:
Metric 13:
Metric 14:
Study Design and Methods
Statistical Power
Reproducibility of Analyses
Medium
Medium
Medium
The retrospective cohort design was appropriate. The study used appropriate methods to
calculate SMRs. Poisson distribution assumptions were used to calculate two-sided tests
of significance. This study calculated SMRs for increasing cumulative follow-up, adding
5-year increments of elapsed time since first employment (e.g., 5-10y, 5-15y).
Sample size was adequate (n=820) and mortality was high (>50% ). Cancer types were
pooled when data were sparse (e.g., gastrointestinal). The authors noted, however, that
the number of man-years included in the analyses was short due to the high death rates.
The descriptions of analyses are brief but adequate. Tables included detailed counts of
observed and expected deaths.
Continued on next page ...
Page 547 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 257 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
... continued from previous page
Seidman, H. (1984). Short-term asbestos work exposure and long-term observation.
Lung Cancer; Laryngeal Cancer; All cancer mortality; Non-respiratory infectious disease mortality
Mortality: All cause mortality, Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and colon-rectum) mor-
tality, Non-infectious respiratory diseases (including asbestosis) mortality, All "asbestos" diseases (lung cancer, gastrointestinal cancer, mesothelioma,
cancers of buccal cavity, pharynx, larynx, and kidney and non-infectious respiratory diseases) mortality, All cancer mortality, Larynx, buccal, pharynx
cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality, Other and unspecified cancer mortality, Cardiovas-
cular diseases mortality; Lung/Respiratory: Lung cancer mortality, Non-infectious respiratory diseases (including asbestosis) mortality, Larynx, buccal,
pharynx cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality, Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, All cancer mortality, Larynx, buccal, pharynx cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pan-
creas cancer mortality, Other and unspecified cancer; Gastrointestinal: Gastro-intestinal cancer (grouped together cancer of esophagus, stomach, and
colon-rectum) mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality; Cardiovascular: Cardiovascular diseases
mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
257
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Domain
Metric
Rating
Comments
Metric 15: Statistical Analysis
Medium
The SMR methods used were appropriate.
Additional Comments: This retrospective cohort study evaluated mortality in 820 workers at an amosite factory in New Jersey that operated between 1941 and 1954. Workers
were almost exclusively white males. Results are presented as SMRs using the New Jersey population as the referent. The cohort had important strengths.
First, analyses included deaths that occurred from 5 to 40 years after employment, incorporating a lag to accommodate disease latency and reducing
potential attribution bias. Second, the study reduced the likelihood of healthy worker selection bias by including all workers who were not exposed to
asbestos elsewhere regardless of date of initial employment, and regardless of duration of employment. Third, employment patterns facilitated the analysis
of mortality in workers with as little as one month of employment, and included multiple time windows of less than one year duration of employment.
The authors noted that this cohort offered a unique opportunity to study "men with a very limited duration of intense work exposure to amosite asbestos,
followed by long observation". Fourth, with a mean age at employment of more than 40 years (due to the ongoing war "siphoning off" younger men),
mortality was high, with deaths accumulating after a relatively short period. 52 deaths occurred within 5-10 years of employment, and cumulative mortality
through 40 years of follow-up was high (n=593). Finally, the authors were able to access medical records that appear to have improved the characterization
of outcomes such as mesotheliomas. Details on the methods used were not included in this manuscript, but are discussed elsewhere (e.g., Selikoff et al.,
1992 HEROID 709720). The study"s major limitation is that fiber count data were not available for this facility. Estimates were extrapolated based on
measures taken at later dates at other locations operated by the same company, based on professional judgment. Validity of these estimates cannot be
ascertained.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 548 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 290 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Seidman, H., Selikoff, I. J., Gelb, S. K. (1986). Mortality experience of amosite asbestos factory workers: Dose-response relationships 5 to 40 years after
onset of short-term work exposure. American Journal of Industrial Medicine 10(1986):479-514.
Lung Cancer; Laryngeal Cancer; GI cancers, Renal/kidney cancers,; Asbestosis; non-infectious pulmonary diseases
Cancer/Carcinogenesis: All cancer, lung cancer, pleural mesothelioma, peritoneal mesothelioma, mesothelioma non-specified, larynx buccal and pharynx
cancer, esophagus cancer, stomach cancer, colon-rectum cancer, kidney cancer, bladder cancer, pancreas cancer, other and unspecified cancer mortality;
Lung/Respiratory: Lung cancer mortality, Non-infectious pulmonary diseases mortality, Asbestosis mortality; Gastrointestinal: Esophagus cancer mortal-
ity, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality; Renal/Kidney: Kidney cancer mortality, bladder cancer mortality;
Cardiovascular: Cardiovascular diseases mortality; Mortality: Lung cancer mortality, Non-infectious pulmonary diseases mortality, Asbestosis mortality,
Esophagus cancer mortality, Stomach cancer mortality, Colon-rectum cancer mortality, Pancreas cancer mortality, Kidney cancer mortality, Bladder cancer
mortality, Cardiovascular diseases mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
290
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because the study or any cited methods source does not explic-
itly mention the use of PCM or TEM.Authors state that there was "no direct observa-
tions of fiber counts in this factory". Instead, fiber counts from other Paterson factories
were used in this study. There is more information of the earlier version of this study,
which reports that that Paterson factory used the same fibers and followed the same
production process. Samples were made in October 1971 and followed "5u + fibers av-
eraged as high as 23 fibers/ml (Seidman et al., 1979). There is no defining of what tools
were used to measure fibers in either study.
Medium Range of exposure is appropriate, as it ranges in elapsed number of years since onset of
work as 5-9 years, 5-14 years, 5-19 years, 5-24 years, 5-29 years, 5-34 years, and 5-39
years. However, the exposure dose is not based on fiber concentration but on exposure
time.
Additional Comments: Please note that this study would not be fully evaluated under the current guidelines. This is due to the low rating for metric 4, as no PCM or TEM was
mentioned in the study or a cited sourceThis study is a follow-up to RefID 94625 by the same authors. Comments referencing this study will be cited as
(Seidman et al., 1979).Overall, this study provides an analysis of workers from the Paterson factory to that of the general New lersey population. There is
some discrepancy when it comes to the race of the cohort and the comparison groups, and age is not provided in the study. Confidence intervals are also
not provided in the study results of SMRs and SIRs, but significant is noted when appropriate. Smoking is not a part of the analysis as a confounder, which
may have introduced bias to both the workers and comparison group.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 549 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 94625 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Seidman, H., Selikoff, I. J., Hammond, E. C. (1979). Short-term asbestos work exposure and long-term observation. Annals of the New York Academy of
Sciences 33061-89.
Lung Cancer
Mortality: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality; Lung/Respiratory: Lung cancer mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
94625
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3: Comparison Group
Medium Key elements of the study design were reported within this retrospective cohort study
of an initial group of n=933 males recruited to work at an amosite asbestos factory in
Paterson, New Jersey from June, 1941 through December, 1945 who were followed
up for mortality outcomes from five through 35 years after onset of work. The authors
aimed to study a population of men with a limited duration of intense work exposure to
amosite asbestos with a long observation period. Authors described the population in
the initial years as almost entirely white. Authors noted that n=113 men were excluded
from analysis including n=20 with prior asbestos work. Additional men with less than
five years of employment were excluded due to leaving work to take up asbestos work
elsewhere (n=14), death in the first five years of employment (n=41), and loss to follow-
up after leaving work in the first five years of employment (n=38). A total of n=820
male workers were left for the current analysis. The distributions of these exclusions
with respect to exposure and outcomes were not reported.
Medium Cause of death information was available for all n=528 deaths occurring after 5 years
from onset of asbestos work among the n=820 workers in the cohort for study. The
authors described a number of workers withdrawn alive at some time between 5 and
35 years of work to include n=5 men lost to follow-up, n=5 men who left the study site
work to work elsewhere, and n=155 men who had begun work 1943-1945 but who had
not yet attained their 35th year of observation by December 31, 1977. Exposure data for
participants and those lost follow-up were not obtained as the study authors noted use
of length of time worked in the amosite asbestos factory as the measure of asbestos dose
with no measured exposure estimates given for categories of years worked.
Medium The choice of a reference population is reported as the age- and year-specific white
male general New Jersey population for the SMR analyses results. There is potential
for healthy worker effect in terms of possible left truncation bias, as the cohort for the
current study was restricted to workers with at least five years of employment, such that
all workers had to survive for at least five years to be included.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Method of quantifying/counting fibers was not specified.
Metric 5: Exposure Levels Medium Medium based on use of US PHS NIOSH data (collected via PCM) for asbestos esti-
mates extrapolated from PA and TX plant. Some professional judgement exercised in
deriving estimates based on job function but estimates not solely based on judgement.
Continued on next page ...
Page 550 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 94625 Table: 1 of 2
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Seidman, H., Selikoff, I. J., Hammond, E. C. (1979). Short-term asbestos work exposure and long-term observation. Annals of the New York Academy of
Sciences 33061-89.
Lung Cancer
Mortality: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality; Lung/Respiratory: Lung cancer mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
94625
Domain
Metric
Rating
Comments
Metric 6:
Temporality
Medium
The study presents an appropriate temporality and the interval between exposure and
outcome is appropriate considering the latency of disease. The range of elapsed years
since onset of work ranged from 5-10 to 30-35 years.
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Metric 8: Reporting Bias
Medium Lung Cancer: Lung cancer mortality data for the worker population was described as
obtained through death certificate information only for some analyses, as well as accord-
ing to "best evidence" established from additional information obtained from autopsy,
surgical specimens, x-ray films and clinical findings for other analyses. ICD codes were
not detailed, however authors noted that coding for the cause of death was that of the
VI through VIII revisions of the International List in use in the U.S. from 1949 onward.
Data for the number of deaths by cause of death in the New Jersey general white male
population through 1975 was described as available through the annual vital statistics
publications, with additional data for 1976 obtained from the National Center for Health
Statistics. As mortality data for 1977 was not yet available, the study authors extrap-
olated for 1977 the data from 1970-1976. Authors described additional extrapolations
necessary to account for the V to VI revision of the International List, as well as as-
sumptions made in calculations of the comparison population rates for lung cancer, as
the numbers of deaths by age were described as available for total cancer of the respira-
tory system but not for lung cancer specifically for New Jersey white males.
Medium There were no concerns for selective reporting. SMRs in Table 2 and mortality rates
across age and time since first exposure groups per man years in production workers
in Table 3 were reported as single values, with no measures of variation or confidence
intervals.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Medium Other than stratification for years since first exposure and age in SMR results, no ad-
ditional adjustments or consideration for differences between exposed and comparison
groups regarding distributions of relevant covariates (such as smoking status) were de-
tailed. The cohort for study and the comparison population for SMR analyses was re-
stricted to males. The study also notes that the initial group was "almost entirely white.
Metric 10: Covariate Characterization Medium Although not specified within this occupational study, it is assumed that personnel files
were utilized to obtain age and time since first employed/exposed data.
Continued on next page ...
Page 551 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 94625 Table: 1 of 2
... continued from previous page
Study Citation: Seidman, H., Selikoff, I. J., Hammond, E. C. (1979). Short-term asbestos work exposure and long-term observation. Annals of the New York Academy of
Sciences 33061-89.
Health Lung Cancer
Outcome:
Target Mortality: Lung cancer mortality; Cancer/Carcinogenesis: Lung cancer mortality; Lung/Respiratory: Lung cancer mortality
Organ(s):
Asbestos Fiber Asbestos - Amosite (grunerite): 12172-73-5
Type(s):
Linked HERO ID(s): No linked references.
HERO ID: 94625
Domain
Metric
Rating
Comments
Metric 11: Co-exposure Counfounding
Low Potential co-exposures were not detailed. The members of the cohort were described
only as males recruited to work at an amosite asbestos factory in Paterson, New Jersey
from June, 1941 through December, 1945 and followed up for mortality outcomes from
five through 35 years after onset of work. Considerations for workers who might have
initially left and worked elsewhere with additional exposures but eventually returned
to asbestos work were not detailed. However, there was no evidence that there was an
unbalanced provision of co-exposures among exposure groups. There is no mention of
co-exposure , so Low is appropriate based on that.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design was appropriate as an early study to address the research aims, how-
ever no quantitative measures of exposure were described for the groups utilized within
the SMR analyses presented.
Medium The number of participants (n=820) was adequate, however formal statistical compar-
isons between exposed and non-exposed workers, or across elapsed years since onset of
work groups were not detailed.
Medium The description of SMR analyses and formation of rates for the comparison population
was presented in detail and generally sufficient to understand.
N/A Model building was not presented, but the study's approach of calculating SMRs is
appropriate.
Additional Comments: This study extended the follow-up of a previous report on the mortality experience of a group of Paterson, New Jersey amosite asbestos factory workers
followed from the onset of work, 1941-1945, through 30 years of observation. The current study extended the observation period to 35 years after onset of
work and noted that several men previously lost to follow up were located and included in this study reporting mortality experience for workers 5 through
35 years after onset of work. There were no direct asbestos or asbestos dust counts available for this facility. Although authors noted a single average fiber
count from 1971 within a similar factory, no other quantitative estimates of exposures were included within the analysis of this population, which reported
SMR"s across elapsed years since onset of work. Authors noted use of length of time worked in the amosite asbestos factory as a measure of asbestos
dosage.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 552 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 94625 Table: 2 of 2
Seidman, H., Selikoff, I. J., Hammond, E. C. (1979). Short-term asbestos work exposure and long-term observation. Annals of the New York Academy of
Sciences 33061-89.
all cancers mortality; all cause mortality, all asbestos diseases mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: All cause mortality, All asbestos diseases mortality (asbestosis, other noninfectious pulmonary diseases, lung cancer, mesotheliomas, esophagus
cancer, stomach cancer, colon-rectum cancel, laryngeal cancer), All cancers mortality; Cancer/Carcinogenesis: All cancers mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
94625
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium Key elements of the study design were reported within this retrospective cohort study of
an initial group of n=933 males recruited to work at an amosite asbestos factory in Pa-
terson, New Jersey from June, 1941 through December, 1945 who were followed up for
mortality outcomes from five through 35 years after onset of work. Authors described
the population in the initial years as almost entirely white. Authors noted that n=l 13
men were excluded from analysis including n=20 with prior asbestos work. Additional
men with less than five years of employment were excluded due to leaving work to take
up asbestos work elsewhere (n=14), death in the first five years of employment (n=41),
and loss to follow-up after leaving work in the first five years of employment (n=38). A
total of n=820 male workers were left for the current analysis. The distributions of these
exclusions with respect to exposure and outcomes were not reported.
Medium Cause of death information was available for all n=528 deaths occurring after 5 years
from onset of asbestos work among the n=820 workers in the cohort for study. The
authors described a number of workers withdrawn alive at some time between 5 and
35 years of work to include n=5 men lost to follow-up, n=5 men who left the study site
work to work elsewhere, and n=155 men who had begun work 1943-1945 but who had
not yet attained their 35th year of observation by December 31, 1977. Exposure data for
participants was not obtained as the study authors noted use of length of time worked in
the amosite asbestos factory as the measure of asbestos dose with no measured exposure
estimates given for categories of years worked.
Medium The choice of a reference population is reported as the age- and year-specific white
male general New Jersey population for the SMR analyses results. There is potential
for healthy worker effect in terms of possible left truncation bias, as the cohort for the
current study was restricted to workers with at least five years of employment, such that
all workers had to survive for at least five years to be included.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Method of quantifying/counting fibers was not specified.
Metric 5: Exposure Levels Medium Medium based on use of US PHS NIOSH data (collected via PCM) for asbestos esti-
mates extrapolated from PA and TX plant. Some professional judgement exercised in
deriving estimates based on job function but estimates not solely based on judgement.
Metric 6: Temporality Medium The study presents an appropriate temporality and the interval between exposure and
outcome is appropriate considering the latency of disease.
Domain 3: Outcome Assessment
Continued on next page ...
Page 553 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 94625 Table: 2 of 2
... continued from previous page
Seidman, H., Selikoff, I. J., Hammond, E. C. (1979). Short-term asbestos work exposure and long-term observation. Annals of the New York Academy of
Sciences 33061-89.
all cancers mortality; all cause mortality, all asbestos diseases mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: All cause mortality, All asbestos diseases mortality (asbestosis, other noninfectious pulmonary diseases, lung cancer, mesotheliomas, esophagus
cancer, stomach cancer, colon-rectum cancel, laryngeal cancer), All cancers mortality; Cancer/Carcinogenesis: All cancers mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
94625
Domain
Metric
Rating
Comments
Metric 7: Outcome Measurement or
Characterization
Medium Other Cancer(s): SMR results were reported for cumulative probabilities of death from
all causes, all asbestos diseases, all cancers, and lung cancer. Additional mortality count
data was reported for detailed cancer sites within Tables 3A and 3B, however SMR
analyses were not conducted for such detail. Authors noted the "all asbestos diseases"
category included asbestosis and other noninfectious pulmonary diseases, lung cancer,
mesotheliomas, cancers of the esophagus, stomach and colon-rectum, cancers of the
larynx, buccal cavity, pharynx and kidney. Mortality data for the worker population was
described as obtained through death certificate information only for some analyses, as
well as according to "best evidence" established from additional information obtained
from autopsy, surgical specimens, x-ray films and clinical findings for other analyses.
ICD codes were not detailed, however authors noted that coding for the cause of death
was that of the VI through VIII revisions of the International List in use in the U.S. from
1949 onward. Data for the number of deaths by cause of death in the New Jersey general
white male population through 1975 was described as available through the annual
vital statistics publications, with additional data for 1976 obtained from the National
Center for Health Statistics. As mortality data for 1977 was not yet available, the study
authors extrapolated for 1977 the data from 1970-1976. Authors described additional
extrapolations necessary to account for the V to VI revision of the International List, as
well as assumptions made in calculations of the comparison population rates for lung
cancer, as the numbers of deaths by age were described as available for total cancer of
the respiratory system but not for lung cancer specifically for New Jersey white males.;
Other Non-Cancer Outcomes: SMR results were reported for cumulative probabilities of
death from all causes, all asbestos diseases, and all cancers. Additional mortality count
data was reported for detailed cancer sites within Tables 3A and 3B, however SMR
analyses were not conducted for such detail. Authors noted the "all asbestos diseases"
category included asbestosis and other noninfectious pulmonary diseases, lung cancer,
mesotheliomas, cancers of the esophagus, stomach and colon-rectum, cancers of the
larynx, buccal cavity, pharynx and kidney. Mortality data for the worker population was
described as obtained through death certificate information only for some analyses, as
well as according to "best evidence" established from additional information obtained
from autopsy, surgical specimens, x-ray films and clinical findings for other analyses.
ICD codes were not detailed, however authors noted that coding for the cause of death
was that of the VI through VIII revisions of the International List in use in the U.S. from
1949 onward. Data for the number of deaths by cause of death in the New Jersey general
white male population through 1975 was described as available through the annual
vital statistics publications, with additional data for 1976 obtained from the National
Center for Health Statistics. As mortality data for 1977 was not yet available, the study
authors extrapolated for 1977 the data from 1970-1976. Authors described additional
extrapolations necessary to account for the V to VI revision of the International List.
Continued on next page ...
Page 554 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 94625 Table: 2 of 2
... continued from previous page
Seidman, H., Selikoff, I. J., Hammond, E. C. (1979). Short-term asbestos work exposure and long-term observation. Annals of the New York Academy of
Sciences 33061-89.
all cancers mortality; all cause mortality, all asbestos diseases mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: All cause mortality, All asbestos diseases mortality (asbestosis, other noninfectious pulmonary diseases, lung cancer, mesotheliomas, esophagus
cancer, stomach cancer, colon-rectum cancel, laryngeal cancer), All cancers mortality; Cancer/Carcinogenesis: All cancers mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
94625
Domain
Metric
Rating
Comments
Metric 8:
Reporting Bias
Medium
There were no concerns for selective reporting. SMR"s in Table 2 and mortality rates
across age and time since first exposure groups per man years in production workers
in Table 3 were reported as single values, with no measures of variation or confidence
intervals.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
Medium
Other than stratification for years since first exposure and age in SMR results, no addi-
tional adjustments or consideration for differences between exposed and comparison
groups regarding distributions of relevant covariates (such as smoking status) were
detailed. The cohort for study and the comparison population for SMR analyses was
restricted to males.
Metric 10:
Covariate Characterization
Medium
Although not specified within this occupational study, it is assumed that personnel files
were utilized to obtain age and time since first employed/exposed data.
Metric 11:
Co-exposure Counfounding
Low
Potential co-exposures were not detailed. The members of the cohort were described
only as males recruited to work at an amosite asbestos factory in Paterson, New Jersey
from June, 1941 through December, 1945 and followed up for mortality outcomes from
five through 35 years after onset of work. Considerations for workers who might have
initially left and worked elsewhere with additional exposures but eventually returned
to asbestos work were not detailed. However, there was no evidence that there was an
unbalanced provision of co-exposures among exposure groups. There is no mention of
co-exposure, so Low is appropriate based on that.
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
The study design was appropriate as an early study to address the research aims, how-
ever no quantitative measures of exposure were described for the groups utilized within
the SMR analyses presented.
Metric 13:
Statistical Power
Medium
The number of participants (n=820) was adequate, however formal statistical compar-
isons between exposed and non-exposed workers, or across elapsed years since onset of
work groups were not detailed.
Metric 14:
Reproducibility of Analyses
Medium
There was no presentation of analyses presenting results associated with exposures
or estimated exposures and no formal statistical analysis was conducted to examine
differences between exposure groups as represented by length of time worked. The
description of SMR analyses and formation of rates for the comparison population was
presented in detail and generally sufficient to understand.
Metric 15:
Statistical Analysis
Medium
Model building was not presented.
Continued on next page ...
Page 555 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 94625 Table: 2 of 2
... continued from previous page
Seidman, H., Selikoff, I. J., Hammond, E. C. (1979). Short-term asbestos work exposure and long-term observation. Annals of the New York Academy of
Sciences 33061-89.
all cancers mortality; all cause mortality, all asbestos diseases mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: All cause mortality, All asbestos diseases mortality (asbestosis, other noninfectious pulmonary diseases, lung cancer, mesotheliomas, esophagus
cancer, stomach cancer, colon-rectum cancel, laryngeal cancer), All cancers mortality; Cancer/Carcinogenesis: All cancers mortality
Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
94625
Domain
Metric
Rating
Comments
Additional Comments:
This study extended the follow-up of a previous report on the mortality experience of a group of Paterson, New Jersey amosite asbestos factory workers
followed from the onset of work, 1941-1945, through 30 years of observation. The current study extended the observation period to 35 years after onset of
work and noted that several men previously lost to follow up were located and included in this study reporting mortality experience for workers 5 through
35 years after onset of work. There were no direct asbestos or asbestos dust counts available for this facility. Although authors noted a single average fiber
count from 1971 within a similar factory, no other quantitative estimates of exposures were included within the analysis of this population, which reported
SMR"s across elapsed years since onset of work. Authors noted use of length of time worked in the amosite asbestos factory as a measure of asbestos
dosage.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 556 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2079021 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Seld&i, A. I., Berg, N. P., Lundgren, E. A., Hillerdal, G., Wik, N. G., Ohlson, C. G., Bodin, L. S. (2001). Exposure to tremolite asbestos and respiratory
health in Swedish dolomite workers. Occupational and Environmental Medicine 58(2001):670-677.
Pulmonary Function/Spirometry Results
Lung/Respiratory: Vital capacity (VC), Forced expiratory volume in 1 second (FEV1)
Asbestos - Tremolite: 14567-73-8
ID(s): No linked references.
2079021
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection Medium All participants were invited to participate, and 95% participated. Available information
indicates a low risk of selection bias.
Metric 2: Attrition High Most data was available, however several participants declined to participate in the ra-
diographical portion of the study (n=3), and one participants film could not be retrieved.
These participants were excluded from the analysis of pleural plaques.
Metric 3: Comparison Group High The study population consisted of workers from two different facilities. Based on demo-
graphic data from table 3, it appears that these two populations are similar enough to be
comparable.
Domain 2: Exposure Characterization
Metric 4:
Metric 5:
Metric 6:
Measurement of Exposure
Exposure Levels
Temporality
Medium Fiber counting was conducted using microscopy, and the methodology is well described.
Personal air monitoring of total dust and tremolite asbestos was also conducted, but
there is no mention of midget impingers; however, the study did specify that "The dust
sampling method conformed to the corresponding United States standard and had been
used since the 1960s". Overall mean exposure to dust was based on a JEM, but informa-
tion on how the JEM was derived is not provided.
Medium Exposure was adequately measured, able to develop an exposure response estimate.
Low Temporality cannot be established in cross-sectional studies.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High Pulmonary Function/Spirometry Results: FEV1 and FVC measured using a dry wedge
spirometer according to the standards of the American Thoracic Society.
High All results are reported, no concerns for reporting bias.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment High Appropriate adjustments were made. Models were adjusted for age, sex, smoking habits,
BMI, and duration of employment.
Metric 10: Covariate Characterization Medium Covariate data was self-reported on questionnaires.
Metric 11: Co-exposure Counfounding Low potential co-exposures were not assessed or discussed.
Domain 5: Analysis
Continued on next page ...
Page 557 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2079021 Table: 1 of 1
... continued from previous page
Seld&i, A. I., Berg, N. P., Lundgren, E. A., Hillerdal, G., Wik, N. G., Ohlson, C. G., Bodin, L. S. (2001). Exposure to tremolite asbestos and respiratory
health in Swedish dolomite workers. Occupational and Environmental Medicine 58(2001):670-677.
Pulmonary Function/Spirometry Results
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Lung/Respiratory: Vital capacity (VC), Forced expiratory volume in 1 second (FEV1)
Asbestos - Tremolite: 14567-73-8
ID(s): No linked references.
2079021
Domain
Metric
Rating
Comments
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium
Medium
Medium
Low
Multiple logistic regression was used to determine the association between dust ex-
posure and respiratory symptoms. Lung function was assessed with linear regression
models.
The final sample size was 137, which may be adequate to detect an overall robust effect.
The description of the analysis is adequate to be reproducible.
Statistical model building is not discussed. Evaluation of covariates is not discussed,
handling of missing data is not discussed, regression model assumptions and linearity
are not discussed.
Additional Comments: As QC reviewer, I rate this study medium. The authors investigated exposure to tremolite asbestos and respiratory health among Swedish dolomite
workers. While they did not find strong relationships between exposure to tremolite asbestos and respiratory outcomes, they had developed a robust
exposure assessment associated the workers. The authors were also able account for potential confounders in their statistical models when assessing the
potential impact of exposures on respiratory health outcomes.The measurement exposure (M4) and/or exposure levels (M5) metrics are rated as medium
upon review by both set of reviewers. Also, the overall quality determination (OQD) is rated medium. Extraction has been completed and quality control
reviewed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 558 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3079343 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Sichletidis, L., Chloros, D., Spyratos, D., Haidich, A. B., Fourkiotou, I., Kakoura, M., Patakas, D. (2009). Mortality from occupational exposure to
relatively pure chrysotile: A 39-year study. Respiration 78(2009):63-68.
Lung Cancer; Cardiovascular mortality
Mortality: All-cause mortality; Lung/Respiratory: Lung neoplasms mortality; Cancer/Carcinogenesis: Malignant neoplasms mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3079343
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The paper reported that the plant used chrysotile asbestos with low amphibole con-
tamination, and that exposure was assessed in 32 areas 4 times/year over a mean of 8h
(Casella air pump, Millipore AA filters). Fibers were "counted in 100 different optical
fields of filter surface" by "contrast phase microscope (x450)", limited to "fibers with
length >5 jUm, diameter <3jUm and length/diameter ratio > 3/1" per EEC directive.
These data were used to calculate cumulative years and fiber-years of exposure for each
participant. The manuscript does not describe the use of detailed employment records to
estimate individual exposure.
Medium Airborne asbestos fiber concentration was measured at 32 different points 4 times an-
nually. Exposure was highly variable. Median (IQR) fibers/cm3 x years were 44.5
(15.6"66.6) and 54.7 (37.4"71.9) among living and deceased participants, respectively.
Exposure was treated continuously.
Additional Comments: This study analyzed mortality among 317 cement workers at a factory in Greece with low-level exposure to chrysotile asbestos. 52 deaths (16 lung cancer)
occurred between 1968 and 2006. SMRs vs the general population indicated decreased overall mortality, suggesting risk of a healthy worker effect (HWE)
bias. HRs showed no increase in mortality associated with fiber-years of exposure, and reduced mortality associated with greater years of exposure,
while smoking was associated with mortality. These findings led the researchers to postulate that the SMR of 1.7 for lung cancer was largely attributable to
smoking. However, failure to account for differential duration of employment - the tendency for earlier "selection of unhealthy people out of the workforce"
- recommended to reduce HWE bias, might also contribute to the absence of an association.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 559 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082687 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Sluis-Cremer, G. K., Hnizdo, E. (1989). Progression of irregular opacities in asbestos miners. British Journal of Industrial Medicine 46(1989):846-852.
Irregular lung opacities (suggestive of asbestosis)
Lung/Respiratory: Progression of irregular lung opacities suggestive of asbestosis
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
No linked references.
3082687
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low The study or any cited methods source does not explicitly mention the use of PCM or
TEM.Sluis-Cremer et al. 1989 RefID 3082687: The study used available and ongo-
ing fiber concentration measures (since 1945) at asbestos mines (p. 847). Duration of
exposure was estimated based on numbers of shifts worked (280 shifts = 1 year), with
fiber-years calculated as duration X concentration. No details on methods used were
provided, but the precision and validity of pre-1975 measures are uncertain. (Sluis-
Cremer et al. 1990 RefID 3082523 indicates that konimeters and thermal precipitators
were used through 1975 when membrane filter methods were initiated). Fiber years be-
fore 1970 were estimated based on self-reported work histories; subsequent exposure
was continuously computed and updated every 6 months. One concern is the statement
that "In the earlier period if the total exposure of the man who left the mine amounted
to less than 500 fibre-shifts the exposure was recorded as zero." It is not known if this
assumption was applied to any study participants, and if so to how many.
Metric 5: Exposure Levels Medium Sluis-Cremer et al. 1989 RefID 3082687: The exposure-outcome gradient was assessed
using continuous exposure measures that included: years of exposure prior to baseline,
years of exposure and fiber-years of exposure among those exposed after baseline (see
Table 4). Analyses were also stratified by any vs no exposure after baseline.
Additional Comments: This large prospective study examined whether asbestos exposure was associated with progression of irregular lung opacities in 1454 asbestos mine
workers (67% of participants in an earlier cross-sectional study). Participants had an x-ray taken as part of the baseline study and were identified as having
a subsequent x-ray a mean of 8-9 years later. Asbestos exposure before the baseline x-ray was associated with progression among workers regardless of
whether exposure was discontinued after that time. Exposure after the 1st x-ray was also associated with progression in the group with such exposure.
Indications for the 2nd x-ray, which was not conducted as part of this study, were not discussed. Given the long latency for asbestosis, is a potential concern
that in the follow-up time available, the analysis sample of men who had an indication for a follow-up x-ray may not be equally representative of lung
changes progressing relatively slowly vs relatively quickly.2/8/2023 UPDATE: DUE TO CHANGES IN THE GUIDANCE FOR SQE, ALL METRICS
RATINGS EXCEPT FOR 4 AND 5 SHOULD BE IGNORED BECAUSE METRIC 4 WAS RATED "LOW".
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 560 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3082523 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Sluis-Cremer, G. K., Hnizdo, E., u Toit, R. S. J. (1990). Evidence for an amphibole asbestos threshold exposure for asbestosis assessed by autopsy in South
African asbestos miners. Annals of Occupational Hygiene 34(1990):443-451.
Asbestosis
Lung/Respiratory: Asbestosis (lung autopsy, histological)
Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Tremolite: 14567-73-8; Asbestos - Anthophyllite:
17068-78-9
No linked references.
3082523
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low The study or any cited methods source does not explicitly mention the use of PCM or
TEM.Exposure was quantified using available fiber measures and the duration of work
at each mine (primarily from annual worker interviews). Chronological exposures were
summed; average fiber-years were obtained dividing this sum by years of exposure.
Several sources of error are of concern. First, as measurement methods at the mines
changed over time, comparability and validity are uncertain, particularly before 1975
when membrane filter measures were initiated. Also, measurement intervals were gen-
erally 5-10 years prior to 1965, and subsequently 1-2 years. Second, for workers who
stopped mining prior to the start of annual interviewing in 1954, family members pro-
vided less reliable work histories. Finally, for smaller mines with limited data, industry
mean exposures were used. Details on temporal changes in fiber measurement methods
included: (i) 1940-1965 konimeter measures of particles < 5jUm and aspect ratio >2;
(ii) thermal precipitator (reported to undercount) measures from 1965-1970 of particles
>5 jUm and aspect ratio >3, then 1970-1975 of particles >3jUm and maximum length
lOOjUm; and (iii) the International Membrane Filter method from 1975 on (i.e. >5 jUm).
Unspecified conversion factors were used to improve comparability.
Metric 5: Exposure Levels Medium The exposure-outcome gradient was assessed using continuous exposure measures that
included: age at first exposure, years of exposure, residence time in mining areas, av-
erage fiber concentration, and cumulative fiber-years of exposure. Fiber-years, average
fiber concentrations, and mining area residence time were also categorized for descrip-
tive analyses (Tables 4-6).
Additional Comments: This study analyzed associations between multiple measures of asbestos exposure and the probability of asbestosis identified post-mortem in lung tissue
among 807 S. African asbestos miners. The aim was to evaluate whether there appears to be a threshold dose below which asbestosis may not occur. The
authors found cases of asbestosis among miners exposed to concentrations as low as <=2 fibers/mL (Table 5), and among subjects with >2-5 fiber-years
of cumulative exposure (Table 4). Dose-response estimates used continuous exposure variables; however, use of a stepwise algorithm to fit those models
is a limitation.2/7/2023 UPDATE: DUE TO CHANGES IN THE GUIDANCE FOR SQE, ALL METRICS RATINGS EXCEPT FOR 4 AND 5 SHOULD
BE IGNORED BECAUSE METRIC 4 WAS RATED "LOW".
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 561 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3080235 Table: 1 of 1
Smailyte, G., Kurtinaitis, J., Andersen, A. (2004). Cancer mortality and morbidity among Lithuanian asbestos-cement producing workers. Scandinavian
Journal of Work, Environment and Health 30(2004):64-70.
Lung Cancer; Laryngeal Cancer; Stomach, colon, rectal, laryngeal
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: All cause, Infectious disease, Malignant neoplasms, Circulatory diseases, Respiratory diseases, Diseases of the digestive system, Cirrhosis of the
liver, Diseases of the genitourinary system; Cancer/Carcinogenesis: Malignant neoplasms, Stomach cancer, Colon and rectum cancer, Lung cancer, Pleura
cancer (mesothelioma), Breast cancer, Female genital organs mortality, Alcohol-related cancers, Other types of cancer, Laryngeal cancer; Cardiovascular:
Circulatory diseases; Gastrointestinal: Diseases of the digestive system, Stomach cancer, Colon and rectum cancer; Lung/Respiratory: Respiratory disease
mortality, Lung cancer, Pleura cancer (mesothelioma), Laryngeal cancer; Reproductive/Developmental: Breast cancer, Female genital organs cancer
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
3080235
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The authors highlight that the exposure data for both facilities is limited. No measure-
ments were taken at factory A, so no data is available. Factory B had annual dust mass
measurements from 1975-1993, and fibers per milliliter were available for 1996-1998.
There was no discussion of the tools used to ascertain these measurements. There is a
discussion that preparation and handling of the asbestos products remained largely the
same over time, but there were improvements in ventilation.This metric is rated low be-
cause the study or any cited methods source does not explicitly mention the use of PCM
or TEM.
Low There was no information available for exposure levels in factory A. The authors report
the dust concentrations of asbestos in factory B varied from 1.9-4.0 mg/mA 3 for 1975-
89, and was 1.2-2.2 mg/mA 3 from 1990-1993. In 1996-1998, the fiber concentration
showed the highest levels for workers who fed the mill with asbestos from sacks and for
those involved in sawing the end products. The exposure level for these two groups was
0.5-1.0 f/ml.
Additional Comments:
There were several concerns with this paper. One that stood out was a lack of exposure measurements for one of the factories included in the study.
Another shortcoming was a lack of in-depth description of the analyses that they conducted. There was also a lack of discussion about potential co-
exposures participants may have faced. All of these issues contributed to a low confidence rating.NOTE: Under the new guidance, this study would not
have undergone further evaluation because metric 4 was rated as low due to no explicit mention of PCM or TEM in this study or cited methods sources.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 562 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3079871 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Soldan, K., Pooley, F. D., Hansen, J., Andersen, A., Chang-Claude, J., Ferro, G., Ohgaki, H., Skov, B. G., Cherrie, J. W., Saracci, R., Boffetta, P. (2006).
Lung fibre burden in lung cancer cases employed in the rock and slag wool industry. Annals of Occupational Hygiene 50(2006):241-248.
Lung Cancer
Cancer/Carcinogenesis: Lung cancer; Mortality: Lung cancer
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos -
Tremolite: 14567-73-8
No linked references.
3079871
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
High
Metric 2: Attrition
Metric 3: Comparison Group
High
Medium
This is a retrospective case-control study of male rock and slag workers from seven
different factories who died of primary lung cancer between 1971 and 1994 (up to 1996
in Denmark). This study population makes up the European cohort of rock and slag
workers from Denmark, Germany, Norway and Sweden. Lung samples were taken from
30 lung cancer cases from the cohort. More details are reported in a previous paper
(Kj"rheim et al., 2002, HEROID: 6874042), where the original cohort size consisted of
9,174 men.
Of the original 9,174 eligible workers in the cohort, this study only utilized 30 lung
samples from cases. Of those 30, 13 cases were deemed to be abnormal lung tissue and
were not sent for further pathology/fibre analysis, adequately describing the reason why
those cases were excluded.
This study did not describe the controls, but referenced a previous study (Kj"rheim et
al., 2002, HEROID: 6874042) where two control series were created and then combined
into one control group. Control series 1 consisted of male workers from the same fac-
tories who were alive and eligible in the cohort but had died before interviews. Control
series 2 consisted of incidence density-sampled controls matched to cases on plant and
date of birth.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Authors report that dust was extracted from lung tissue samples of cases using a F.E.I.
Technai 12 analytical transmission electron microscope (TEM). This was completed
only once/for one time period.
Medium Authors used tertiles for duration of exposure (Tl, T2, T3) and for cumulative exposure
(Tl, T2, T3) for combined amosite and crocidolite concentration (per gram lung tissue *
10A 6).
High Study consisted of male workers employed from start of production (between 1937 and
1950) until the end of 1976. Follow up occurred from 1971-1996 (1995 for Denmark),
presenting appropriate temporality between exposure and outcome.
Domain 3: Outcome Assessment
Metric 7:
Outcome Measurement or
Characterization
Medium Lung Cancer: Lung cancer cases were confirmed by International Classification of Dis-
eases, 9th revision [ICD-9], codes (Kj"rheim et al., 2002, HEROID: 6874042). The
exact codes were not provided.
Continued on next page ...
Page 563 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3079871 Table: 1 of 1
... continued from previous page
Soldan, K., Pooley, F. D., Hansen, J., Andersen, A., Chang-Claude, J., Ferro, G., Ohgaki, H., Skov, B. G., Cherrie, J. W., Saracci, R., Boffetta, P. (2006).
Lung fibre burden in lung cancer cases employed in the rock and slag wool industry. Annals of Occupational Hygiene 50(2006):241-248.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Cancer/Carcinogenesis: Lung cancer; Mortality: Lung cancer
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos
Tremolite: 14567-73-8
ID(s): No linked references.
3079871
Domain
Metric
Rating
Comments
Metric 8:
Reporting Bias
Medium
Findings are reported consistently throughout the paper and are extractable, but they
were not complete; Chrysotile and Tremolite concentrations per gram dry lung tissue X
10A 6 were reported per sample but were not part of the odds ratios' analyses.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High
High
Medium
Age, cigarette consumption, and time between end of exposure and lung sampling
(clearance time) were adjusted for in all models.
Authors collected questionnaire responses from relatives of cases and controls with
questions regarding demographic variables, residential history, general occupational
history, occupational history within the rock, slag and wool (RSW) companies, tobacco
smoking and alcohol drinking.
Man-made vitreous fibres (MMVF) are observed and analyzed in this paper alongside
asbestos. Authors address these fibres separately and are adjusted for in their respective
models.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium This study uses an appropriate statistical method to address the relationship between the
lung asbestos fibres and the variables of estimated exposure, with and without additional
variables that may affect fibre retention in lung cancer cases (odds ratio).
Uninformative This case control study consisted of only 13 cases and controls. Authors mention in the
discussion section that this weakness resulted in low statistical power and highlighted
that a large pathology department had incinerated many of the eligible samples.
Medium The description of the analysis is sufficient to understand how to conceptually reproduce
the analysis with access to the analytic data.
Medium The models for calculating the odds ratios are transparent and authors described which
variables were included (except for the exclusion of Chrysotile and Tremolite).
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric 16: Use of Biomarker of Exposure Medium
Metric 17:
Effect Biomarker
Metric 18: Method Sensitivity
Medium
Medium
The biomarker is derived from multiple parent chemicals (MMVF, amosite, crocidolite,
chrysotile and tremolite)
Thirteen lung tissue samples were used for fibre analysis and fibre burden with validated
methods, but an AOP is not clear.
Authors report that "examination of the extracted dust preparationsdetermined fibre type,
fibre dimension and numbers of fibres per gram of dry lung tissue. All fibres detected
were included, irrespective of size. The limit of detection in all cases was 0.03 million
fibres gA -1 of dried tissue"
Continued on next page ...
Page 564 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3079871 Table: 1 of 1
... continued from previous page
Soldan, K., Pooley, F. D., Hansen, J., Andersen, A., Chang-Claude, J., Ferro, G., Ohgaki, H., Skov, B. G., Cherrie, J. W., Saracci, R., Boffetta, P. (2006).
Lung fibre burden in lung cancer cases employed in the rock and slag wool industry. Annals of Occupational Hygiene 50(2006):241-248.
Lung Cancer
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Cancer/Carcinogenesis: Lung cancer; Mortality: Lung cancer
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos
Tremolite: 14567-73-8
ID(s): No linked references.
3079871
Domain
Metric
Rating
Comments
Metric 19:
Biomarker Stability
High
Storage history was known and investigated via death certificates and medical files.
When confirmed, a pathologist was contacted to arrange and prepare the samples.
Metric 20:
Sample Contamination
Medium
There is no information included about contamination.
Metric 21:
Method Requirements
Low
Authors only discuss using "a F.E.I. Technai 12 analytical transmission electron mi-
croscope (TEM), giving a magnification of 20 000"30 000" for the dust extracted from
tissue samples.
Metric 22:
Matrix Adjustment
Low
No established matrix adjustment was conducted.
Additional Comments:
Overall, this study was well done but had a major issue in its sampling. This study has a low sample size which weakens the statistical power and potentially
skews the results (deeming the study uninformative). As a result, data were not extracted.
Overall Quality Determination
Uninformative
Page 565 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709497 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environmental
Health Perspectives 115(2007):579-585.
Lung Cancer; Asbestosis
Mortality: All causes mortality, Lung cancer mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Lung/Respiratory: Lung cancer
mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Cancer/Carcinogenesis: Lung cancer mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos - Tremolite: 14567-73-8
709497, 709457, 711560, 2238712
709497
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Medium Subjects were vermiculite miners, millers, and processors from a mine operating in
Libby, Montana. The authors specify that some subjects may have been "assigned jobs
in the screening plant, railroad loading dock, expansion plants, or an office located in
the town of Libby (several miles from the mine)." The cohort was designed to include
all white males hired at Libby from September 1935 to December 1981, and the to-
tal cohort was identified in May 1982 and subjects were followed through December
2001. It is not clear exactly how subjects were recruited or identified, though it is im-
plied that the authors used data from an existing NIOSH database. Demographic data
was collected from a NIOSH database and then validated against microfilm company
records. One person originally identified (presumably from the NIOSH database) was
removed due to company records stating that the employee never actually worked. After
excluding 9 participants for missing demographic data, there were 1,871 study subjects.
However, after additional exclusions based on missing outcome data and to limit the
analysis sample to only white men, the final analytic sample consisted of 1,672 workers
(Sullivan et al. 2007 HERO ID: 709497).Moolgavkar et al. 2010 (HERO ID: 709457)
used the same cohort as Sullivan et al. 2007 (HERO ID: 709497) but they also excluded
10 individuals who were missing vital status and thus resulted in a final analytic sample
of 1,662. Bateson et al. 2010 (HERO ID: 2238712) used the same cohort data as Sulli-
van et al. 2007 (HERO ID: 709497), but do not appear to have made any exclusions for
missing data and do not appear to have limited their sample to only white men, resulting
in a final sample of 1,871 subjects. However, they also analyzed a sub-cohort of workers
only hired after 12/31/1959 (n=880) to control for missing employment data in workers
hired earlier. The authors also followed up their participants through 12/31/2006, five
years longer than the other studies in this cohort.There is no evidence that the exposure-
outcome distribution of those included in these studies is different from those excluded.
High In Sullivan et al. 2007 (HERO ID: 709497), after 1,871 subjects were identified for
inclusion, 104 were excluded due to not being white males, and 95 were excluded due
to dying or being lost to follow-up before 1960. Prior to 1960 comparison rates for
asbestosis in NIOSH Life Table Analysis system were not available, requiring exclusion
from the analysis sample. In Moolgavkar et al. 2010 (HERO ID: 709457) an additional
10 participants were excluded due to missing vital status, although it is not clear how
these cases were handled in the original study. Bateson et al. 2014 (HERO ID: 2238712)
does not appear to have made any exclusions. There is overall a low rate of attrition and
it is unlikely to be influenced by both exposure and outcome.
Continued on next page ...
Page 566 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709497 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environmental
Health Perspectives 115(2007):579-585.
Lung Cancer; Asbestosis
Mortality: All causes mortality, Lung cancer mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Lung/Respiratory: Lung cancer
mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Cancer/Carcinogenesis: Lung cancer mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos - Tremolite: 14567-73-8
ID(s): 709497, 709457, 711560, 2238712
709497
Domain Metric Rating Comments
Metric 3: Comparison Group Medium In Sullivan et al. 2007 (HERO ID: 709497) and Moolgavkar et al. 2010 (HERO ID:
709457) SMRs were calculated as the primary statistical analysis. Reference mortal-
ity rates were pulled from the NIOSH Life Table Analysis system. It is not specified
whether this reference population was the general US population or an occupational-
only population. Since the analysis samples only contained white males, there was
no need to adjust by race or sex. However, SMRs were adjusted for age at risk and
calendar-year of follow-up in Sullivan et al. 2007 (HERO ID: 709497). There is no dis-
cussion of other SMR adjustments in Moolgavkar et al. 2010 (HERO ID: 709457), but it
is possible that they used the same adjustment factors as Sullivan et al. 2007 (HERO ID:
709497), since the authors pulled the majority of their data from that study.Moolgavkar
et al. 2010 (HERO ID: 709457) also performed two regression analyses, one of which
was only reported to control for year of birth, and another for mesothelioma that did
not report any adjustments.Bateson et al. 2014 (HERO ID: 2238712) also conducted
a regression analysis and thus participants were compared to each other in statistical
analyses. Statistical analysis controlled for age, gender, race, and date of birth to ensure
comparisons were appropriate.
Domain 2: Exposure Characterization
Continued on next page ...
Page 567 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709497 Table: 1 of 2
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environmental
Health Perspectives 115(2007):579-585.
Lung Cancer; Asbestosis
Mortality: All causes mortality, Lung cancer mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Lung/Respiratory: Lung cancer
mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Cancer/Carcinogenesis: Lung cancer mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos - Tremolite: 14567-73-8
ID(s): 709497, 709457, 711560, 2238712
709497
Domain
Metric
Rating
Comments
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium In this cohort, all studies used the exact same method of assessing exposure through
quantification using PCM and assignment to participants via a job-exposure matrix,
based on one used in an earlier NIOSH study (Amandus and Wheeler, 1987 HERO
ID: 29839). In Sullivan et al. 2007 (HERO ID: 709497) and Moolgavkar et al. 2010
(HERO ID: 709457) adjustments to the JEM were made, most notably to assign workers
with the "common laborer" job assignments or unknown job assignments the average
estimated exposure intensity for all unskilled jobs, as opposed to using the relatively
low exposure estimate for the mill yard in Libby. Thus, estimates of cumulative expo-
sure were higher in this cohort study than other studies using the same JEM. Obtaining
work histories for these studies resulted in additional jobs that were not detailed in the
original NIOSH JEM. Exposure estimates for these jobs and corresponding calendar
periods were extrapolated based on review of exposure records from other studies of
Libby workers and professional judgment. Work history to assign exposure was gath-
ered from a NIOSH database created in the 1980"s and was validated against microfilm
company records. The authors do not specify how many samples were analyzed for use
in the JEM. In statistical analysis results were presented in terms of cumulative exposure
(fiber/cc-years).The authors in Bateson et al. 2014 (HERO ID: 2238712) used the same
exposure data as the other studies in this cohort, but they were concerned about poten-
tial exposure misclassification due to the missing job data indicated in the Sullivan et
al. 2007 (HERO ID: 709497) study, which was originally compensated for by assign-
ing them the average level of exposure. The authors in Bateson et al. 2014 (HERO ID:
2238712) noted that most workers missing job data were hired before 1960, and thus
analyzed both the full cohort and only those hired after 12/31/1959 to address this issue.
The authors also reported residence-time-weighted exposure, which is a metric that pro-
vides additional weight to earlier exposure. In statistical analysis results were presented
in terms of cumulative exposure (fiber/cc-years).
Medium All studies in the cohort have an adequate distribution of exposure to detect an effect.
All studies report at least three levels of exposure or use a continuous model of exposure
in their SMR analyses.
High In all studies there was a minimum of 20 years of follow-up since a participant"s first
exposure, and the workers hired earliest had >65 years of prior exposure data since the
study was designed to capture those employed between 1935 and 1981.
Domain 3: Outcome Assessment
Continued on next page .
Page 568 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709497 Table: 1 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environmental
Health Perspectives 115(2007):579-585.
Lung Cancer; Asbestosis
Mortality: All causes mortality, Lung cancer mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Lung/Respiratory: Lung cancer
mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Cancer/Carcinogenesis: Lung cancer mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos - Tremolite: 14567-73-8
ID(s): 709497, 709457, 711560, 2238712
709497
Domain Metric Rating Comments
Metric 7: Outcome Measurement or Medium Lung Cancer: Vital status was determined through 2001 by the National Death Index
Characterization resources, the Social Security Administration resources, the internet (Ancestry.com;
RootsWeb.com, and electronic links to state death records). And a tracking service.
Workers found to be alive on or after 1/1/1979, when the National Death Index tracking
began, but not found in the Index, were assumed to be alive as of 12/31/2001. Vital sta-
tus follow-up was successful for 97.8% of the cohort. While some of the resources have
a high degree of certainty, others such as the internet-based resources are of questionable
quality. There is no explanation of what percentage each resource was used to ascertain
vital status, but the more reliable method such as National Death Index are likely to be
more informative and thus used more often. Thus, while there is some uncertainty that
the vital status ascertainment was fully accurate, it is unlikely that a significant num-
ber of participants would have their vital status changed or that this would be related to
their exposure status. Additionally, Bateson et al. 2014 (HERO ID: 2238712) report that
all outcome data was retrieved from the National Death Index.For 97% of the partici-
pants known to be deceased, exact cause of death was pulled from death certificates and
coded using the ICD codes relevant at the time of death, ranging from ICD-8 to ICD-
10. Deaths prior to 1979 were coded by a single National Center for Health Statistics-
trained nosologist; after 1979 ICD codes were obtained from the National Death Index.
Final results present ICD-9 codes, so it can be assumed that all codes were converted to
that system, although their methodology is not explained.ICD-9 code 162 was reported
for lung cancer.; Asbestosis: Vital status was determined through 2001 by the National
Death Index resources, the Social Security Administration resources, the internet (An-
cestry.com; RootsWeb.com, and electronic links to state death records). And a tracking
service. Workers found to be alive on or after 1/1/1979, when the National Death In-
dex tracking began, but not found in the Index, were assumed to be alive as of 12/31/
2001. Vital status follow-up was successful for 97.8% of the cohort. While some of the
resources have a high degree of certainty, others such as the internet-based resources
are of questionable quality. There is no explanation of what percentage each resource
was used to ascertain vital status, but the more reliable method such as National Death
Index are likely to be more informative and thus used more often. Thus, while there is
some uncertainty that the vital status ascertainment was fully accurate, it is unlikely that
a significant number of participants would have their vital status changed or that this
would be related to their exposure status. Additionally, Bateson et al. 2014 (HERO ID:
2238712) report that all outcome data was retrieved from the National Death Index.For
97% of the participants known to be deceased, exact cause of death was pulled from
death certificates and coded using the ICD codes relevant at the time of death, ranging
from ICD-8 to ICD-10. Deaths prior to 1979 were coded by a single National Center
for Health Statistics-trained nosologist; after 1979 ICD codes were obtained from the
National Death Index. Final results present ICD-9 codes, so it can be assumed that all
codes were converted to that system, although their methodology is not explained.ICD-9
code 151 was reported for asbestosis.; Other Non-Cancer Outcomes: Vital status was
determined through 2001 by the National Death Index resources, the Social Security Ad-
Page 569 Of 606 ministration resources, the internet (Ancestry.com; RootsWeb.com, and electronic links
. I,.. I L 1,1 A . I .. ! I-: U,' ..I- I I U, .. K... , 1 /
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709497 Table: 1 of 2
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environmental
Health Perspectives 115(2007):579-585.
Lung Cancer; Asbestosis
Mortality: All causes mortality, Lung cancer mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Lung/Respiratory: Lung cancer
mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Cancer/Carcinogenesis: Lung cancer mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos - Tremolite: 14567-73-8
709497, 709457, 711560, 2238712
709497
Domain
Metric
Rating
Comments
Metric 8:
Reporting Bias
High
All stated outcomes are reported in the results.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium In both Sullivan et al. 2007 (HERO ID: 709497) and Moolgavkar et al. 2010 (HERO ID:
709457) SMRs were calculated and the sample only included white males, so there was
no need to adjust for race and gender. While Sullivan et al. 2007 (HERO ID: 709497)
state that they also adjusted for age at risk and calendar year of follow-up, there is no
discussion of other SMR adjustments in Moolgavkar et al. 2010 (HERO ID: 709457). It
is unlikely that they did not adjust for age, but this cannot be assumed. Moolgavkar et al.
2010 (HERO ID: 709457) also performed a Cox proportional hazards model analysis
in which they adjusted for year of birth. They state that they used year of birth as a
"rough surrogate" for smoking habits as well, which is not a sufficient consideration for
smoking. Bateson et al. 2014 (HERO ID: 2238712) also performed a Cox proportional
hazards model, and adjustments were made for gender, race, date of birth, and age. This
metric would be rated as "Low" for lung cancer-related outcomes if the only analyses
were regression analyses due to the lack of formal adjustment for smoking habits.
Medium All covariate information was obtained from the NIOSH database and cross-checked
against microfilmed company records.
Low In this occupational setting, no co-exposures are adjusted for. Sullivan et al. 2007
(HERO ID: 709497) notes that there was insufficient data to estimate exposure to other
contaminants such as diesel particulate generated by mine machinery, or exposure to
silica.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Medium The use of SMRs and regression analyses to understand the long-term impact of as-
bestos exposure on mortality is appropriate. The use of a cohort design is also appropri-
ate to assess outcomes with a long latency such as lung cancer.
Medium The number of participants used in the analysis sample varies by study, but is always
sufficiently large to detect an effect. Sullivan et al. 2007 (HERO ID: 709497) had a final
analysis sample of 1,672; Moolgavkar et al. 2010 (HERO ID: 709457) had a final anal-
ysis sample of 1,662; and Bateson et al. 2014 (HERO ID: 2238712) had a final analysis
sample of 1,871 and sub-cohort samples of 991 and 890. There is not a significant dis-
cussion of power, but Sullivan et al. 2007 (HERO ID: 709497) states that the study has
low power for lung cancer outcomes at lower exposure levels.
Continued on next page ...
Page 570 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 709497 Table: 1 of 2
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environmental
Health Perspectives 115(2007):579-585.
Lung Cancer; Asbestosis
Mortality: All causes mortality, Lung cancer mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Lung/Respiratory: Lung cancer
mortality, Nonmalignant respiratory disease mortality, Asbestosis mortality; Cancer/Carcinogenesis: Lung cancer mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos - Tremolite: 14567-73-8
ID(s): 709497, 709457, 711560, 2238712
709497
Domain
Metric
Rating
Comments
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium While several details are not explained in detail, such as how the ICD-8 through ICD-10
codes were converted to ICD-9 codes, overall the descriptions of methods across the
cohort are detailed enough that it would be possible to reproduce the results given access
to the analytic data.
Medium While there is no formal discussion of assumptions in statistical models in both Sullivan
et al. 2007 (HERO ID: 709497) and Bateson et al. 2014 (HERO ID: 2238712, there
are no assumptions in SMR or Cox proportional hazards model that would reasonably
expect to be unmet. Moolgavkar et al. 2010 (HERO ID: 709457) contains those same
analyses without a formal discussion of assumptions, but also analyses mesothelioma
using a maximum likelihood equation in which they assume a Poisson distribution.
Additional Comments: In these cohort studies of Libby, Montana employees exposure was measured via PCM and assigned using a JEM. Participants were followed up for a
minimum of 20 years from first exposure, and mortality outcomes were examined in relation to asbestos exposure through SMR and regression analysis.
While there is some potential for outcome and exposure misclassification, the impact of potential misclassification is unlikely to significantly bias the
results of the cohort. Significant effects were found for most outcomes, in particular asbestosis and lung cancer.The measurement exposure (M4) and/or
exposure levels (M5) metrics are rated as medium upon review by both set of reviewers. Also, the overall quality determination (OQD) is rated medium.
Extraction has been completed and quality control reviewed.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 571 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 709497 Table: 2 of 2
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Sullivan, P. A. (2007). Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environmental
Health Perspectives 115(2007):579-585.
Asbestosis
Mortality: All cancer mortality, Cancer of the pleura mortality, Cancer of unspecified sites mortality, Connective tissue cancer mortality, Chronic obstructive
pulmonary disease mortality, Other nonmalignant respiratory disease mortality (non-asbestosis, non-COPD); Cancer/Carcinogenesis: All cancer mortality,
Cancer of the pleura mortality, Cancer of unspecified sites mortality, Connective tissue cancer mortality; Lung/Respiratory: Cancer of the pleura mortality,
Chronic obstructive pulmonary disease mortality, Other nonmalignant respiratory disease mortality (non-asbestosis, non-COPD); Skin/Connective Tissue:
Connective tissue cancer mortality
Asbestos- Libby amphibole: 1318-09-8; Asbestos- Richterite: 17068-76-7; Asbestos - Winchite: 12425-92-2; Asbestos - Tremolite: 14567-73-8
709497, 709457, 711560, 2238712
709497
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Medium In this cohort, all studies used the exact same method of assessing exposure through
quantification using PCM and assignment to participants via a job-exposure matrix,
based on one used in an earlier NIOSH study (Amandus and Wheeler, 1987 HERO ID:
29839). In Sullivan et al. 2007 (HERO ID: 709497) and Moolgavkar et al. 2010 (HERO
ID: 709457) adjustments to the JEM were made, most notably to assign workers with
the "common laborer" job assignments or unknown job assignments the average esti-
mated exposure intensity for all unskilled jobs, as opposed to using the relatively low
exposure estimate for the mill yard in Libby. Thus, estimates of cumulative exposure
were higher in this cohort study than other studies using the same JEM. Additionally,
obtaining work histories for these studies resulted in additional jobs that were not de-
tailed in the original NIOSH JEM. Exposure estimates for these jobs and corresponding
calendar periods were extrapolated based on review of exposure records from other stud-
ies of Libby workers and professional judgment. Work history to assign exposure was
gathered from a NIOSH database created in the 1980"s and was validated against mi-
crofilm company records. The authors do not specify how many samples were analyzed
for use in the JEM. In statistical analysis results were presented in terms of cumula-
tive exposure (fiber/cc-years).The authors in Bateson et al. 2014 (HERO ID: 2238712)
were concerned about potential exposure misclassification due to the missing job data
indicated in the Sullivan et al. 2007 study, which was originally compensated for by as-
signing them the average level of exposure. The authors in Bateson et al. 2014 (HERO
ID: 2238712) noted that most workers missing job data were hired before 1960, and thus
analyzed both the full cohort and only those hired after 12/31/1959 to address this issue.
The authors also reported residence-time-weighted exposure, which is a metric that pro-
vides additional weight to earlier exposure. In statistical analysis results were presented
in terms of cumulative exposure (fiber/cc-years).
Metric 5: Exposure Levels Low All outcome evaluated in this form were only analyzed as "unexposed vs, exposed", thus
limting their usefulness in dose-response analysis.
Additional Comments: The outcomes in this evaluation did not meet the criteria for dose-response analysis due to a "Low" rating for Metric 5.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 572 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6868329 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
ID(s):
Suraya, A., Nowak, D., Sulistomo, A. W., Ghanie Icksan, A., Syahruddin, E., Berger, U., Bose-O'Reilly, S. (2020). Asbestos-Related Lung Cancer: A
Hospital-Based Case-Control Study in Indonesia. International Journal of Environmental Research and Public Health 17(2020):591-591.
Lung Cancer
Lung/Respiratory: Lung cancer; Cancer/Carcinogenesis: Lung cancer
Asbestos - Not specified: 1332-21-4
No linked references.
6868329
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The cumulative occupational asbestos exposure was expressed in fiber-years, which was
fiber concentration in weighted arithmetic mean (WAM), expressed in fiber/milliliter
(f/mL) of air multiplied by the total duration of exposure in years. It was not mentioned
that TEM and PCM were used.
Medium Range of exposure sufficient to develop exposure-response estimate (Table 5). Exposed
>=10 fiber-years, exposed <10 fiber-years, not exposed referent groups.
Additional Comments: "Five subjects were suspected mesothelioma cases, three subjects were suspected asbestosis, and two subjects were suspected of interstitial lung diseases,"
however not analyzed for or confirmed so did not include as outcomes. Metric 4 low, so stopped evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 573 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3080436 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Szeszenia-D^browska, N., Wilczyhska, U., Szymczak, W., Strzelecka, A. (2002). Mortality study of workers compensated for asbestosis in Poland,
1970-1997. International Journal of Occupational Medicine and Environmental Health 15(2002):267-278.
Lung Cancer; Ovarian Cancer; Laryngeal Cancer; Rectum and anus, liver, stomach, gallbladder, pancreas, prostate, bladder, kidney, brain, thyroid, bone,
skin, breast; Asbestosis; Circulatory system diseases, respiratory system diseases, digestive system diseases, genitourinary system diseases, musculoskeletal
system diseases, ill-defined conditions
Lung/Respiratory: Respiratory diseasesMalignant neoplasms; Mortality: Malignant neoplasmsPancreas cancer
Asbestos - Not specified: 1332-21-4
No linked references.
3080436
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The authors do not describe the process used to determine asbestos exposure concen-
trations. It is mentioned that "weighted asbestos concentrations, expressed in mg/mA 3
of air were usually the basis for assessing the exposure" (Szeszenia-D"browska et al.,
2002).
Medium The authors provide information on the estimated exposure that workers in various
settings experienced during their tenure.
Additional Comments: This study assessed the risk of asbestos-related malignancies among individuals with diagnosed asbestosis. This study provided a lot of information on
SMR for individuals diagnosed with asbestosis in Poland, using the general population as the comparison group. When it comes exposure of interest,
the authors used weighted asbestos concentrations to assessing exposures; they did not provide details about the methods and equipment used to generate
these values. On the other hand, they used ICD-9 codes to ascertain health and mortality outcomes.While information on the measurement of exposure
metric (M4) to assess exposure was limited or rated low. The exposure levels metric (M5) information reported was adequate or rated medium to determine
exposure-response relationships. The overall rating for this outcome/study is medium.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 574 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 6861363 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Tamura, M., Okamoto, Y., Tokuyama, T., Yoneda, T., Kasuga, H., Miyazaki, R., Narita, N. (1998). Correlation of total amount of exposure and dust
concentration at first exposure to chest X-P course findings in asbestos plant employees. International Congress Series, vol. 1153 653-657.
Asbestosis
Lung/Respiratory: Asbestosis
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
6861363
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Metric 5:
Measurement of Exposure
Exposure Levels
Low
Low
The method of quantifying/counting fibers was not specified by the authors.
The authors only reported yearly fiber concentrations from 1945-1966.
Additional Comments: None
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 575 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3077807 Table: 1 of 1
Study Citation: Terra-Filho, M., Bagatin, E., Nery, L. E., Ndpolis, L. M., Neder, J. A., de Souza Portes Meirelles, G., Silva, C. I., Muller, N. L. (2015). Screening
of miners and millers at decreasing levels of asbestos exposure: comparison of chest radiography and thin-section computed tomography. PLoS ONE
10(2015):e0118585.
Asbestosis; Pulmonary Function/Spirometry Results; Pleural Plaques; interstitial abnormalities
Lung/Respiratory: lung function (FVC, FEV1, FVC/FEV1, FEF25-75% ), Asbestosis, pleural abnormalities, interstitial abnormalities
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Tremolite: 14567-73-8
ID(s): No linked references.
3077807
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium Some key elements of the study design were not present but available information indi-
cates a low risk of selection bias. All workers were employed at an asbestos mining and
milling company based in Brazil. Participants had worked at the company for at least
a year (Bagatin et al., 2005 RefID 2078960). To capture the development of asbestos
mining and milling in the country, four groups were created from different time peri-
ods: Group 1 taking place in 1940-1966, Group 2 in 1967-1976, Group 3 in 1977-1980,
and Group 4 taking place after 1981. All groups were exposed to chrysotile and Group
1 was also exposed to tremolite. Characteristics such as gender, age, time of exposure,
smoking, and mean spirometry measures are provided in Table 1. Exclusion criteria are
not known. While recruitment methods aren"t clear, Bagatin et al., 2005 RefID 2078960
stated a four-year "multi-institutional effort, which included local municipalities and
union workers, was responsible for recruiting the subjects who participated in the study."
High This study reports cross-sectional retrospective data and thus subject withdrawal from
the study is not of concern. Outcome and exposure data appear to be complete.
Medium Differences in SES or race/ethnicity are plausible given that the groups represent two
different regions of Brazil (Bahia and Goias) but not provided in the study. Nonethe-
less, all subjects appear to be recruited from the same eligible population and appear
to be similar. Healthy worker effect may be of concern due to spirometric values being
compared to predicted values of the adult Brazilian population.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
High For Groups 3 and 4 (after 1976), airborne samples from occupational settings were
routinely collected via a constant-flow sampler, followed by a membrane filter to collect
fibers and PCM to count fibers.
Medium The range and distribution of exposure was sufficient to develop and exposure-response
estimate. Mean cumulative exposure for groups were: "Group I: 110.9 ± 140.3 fibres-
cc-years; Group II: 44.1 ± 49.4 fibres-cc-years; Group III: 7.6 ± 5.4 fibres-cc-years;
Group IV: 3.6 ± 4.4 fibres-cc-years"
Continued on next page ...
Page 576 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077807 Table: 1 of 1
... continued from previous page
Study Citation: Terra-Filho, M., Bagatin, E., Nery, L. E., Ndpolis, L. M., Neder, J. A., de Souza Portes Meirelles, G., Silva, C. I., Muller, N. L. (2015). Screening
of miners and millers at decreasing levels of asbestos exposure: comparison of chest radiography and thin-section computed tomography. PLoS ONE
10(2015):e0118585.
Asbestosis; Pulmonary Function/Spirometry Results; Pleural Plaques; interstitial abnormalities
Lung/Respiratory: lung function (FVC, FEV1, FVC/FEV1, FEF25-75% ), Asbestosis, pleural abnormalities, interstitial abnormalities
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Tremolite: 14567-73-8
ID(s): No linked references.
3077807
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Domain
Metric
Rating
Comments
Metric 6: Temporality
Medium The longitudinal analysis conducted in the study established temporality but adequate
follow-up is unclear. 301 subjects who were free of any asbestos-related abnormalities
were first evaluated in 1997-2000 and then reevaluated in 2007-2010 which seems to
imply a 10-year latency period, though it"s not clear if a subject evaluated in 2000 and
would"ve been reevaluated in 2007 (i.e. 7-year latency which is grounds for "Low"). For
the cross-sectional data, temporality is unclear. Although exposure measurements are
retrospective, it is unclear, if signs of adverse health outcomes preceded exposure as the
health history of these workers at the beginning of employment is not available.
Domain 3: Outcome Assessment
Metric 7: Outcome Measurement or
Characterization
Metric 8: Reporting Bias
High Asbestosis: Determined by two independent thoracic radiologists who knew about sub-
jects" exposure to asbestos but were blinded to other demographic and lung function
characteristics. Readers assessed different kinds of pulmonary abnormalities via Thin-
section computed tomography (CT) images to determine if they were or not "definitely-
indicative" of lung fibrosis compatible with asbestosis.; Pulmonary Function/Spirometry
Results: FVC, FEV1, FEV1/FVC ratio, and forced expiratory flow between 25% and
75% of FVC (FEF25-75% ) were measured using a calibrated pneumotachograph in
Multispiro System.; Pleural Plaques: Through chest radiography (CXR), pleural plaques
were determined by three blinded radiologists who followed ILO standards for classi-
fication. Through Thin-section CT scans (via X-vision scanner), pleural plaques were
assessed by two independent thoracic radiologists who knew about subjects" exposure
to asbestos but were blinded to other demographic and lung function characteristics.
Presence of pleural plaques was determined if the follow pleural abnormality was found:
"circumscribedquadrangular pleural elevation with sharp borders and soft tissue density,
possibly calcified, in typical posterolateral and anterolateral location."; Other Non-
Cancer Outcomes: Through chest radiography (CXR), interstitial abnormalities were
determined by three blinded radiologists who followed ILO standards for classification.
Through Thin-section CT scans (via X-vision scanner), interstitial abnormalities were
assessed by two independent thoracic radiologists who knew about subjects" exposure to
asbestos but were blinded to other demographic and lung function characteristics.
High All results seem to be reported in all aspects of the report, including p-values sample
sizes, confidence intervals, and standard deviations. Footnotes are provided for addi-
tional clarification on analyses.
Domain 4: Potential Confounding / Variability Control
Continued on next page ...
Page 577 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3077807 Table: 1 of 1
... continued from previous page
Study Citation: Terra-Filho, M., Bagatin, E., Nery, L. E., Ndpolis, L. M., Neder, J. A., de Souza Portes Meirelles, G., Silva, C. I., Muller, N. L. (2015). Screening
of miners and millers at decreasing levels of asbestos exposure: comparison of chest radiography and thin-section computed tomography. PLoS ONE
10(2015):e0118585.
Asbestosis; Pulmonary Function/Spirometry Results; Pleural Plaques; interstitial abnormalities
Lung/Respiratory: lung function (FVC, FEV1, FVC/FEV1, FEF25-75% ), Asbestosis, pleural abnormalities, interstitial abnormalities
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Tremolite: 14567-73-8
ID(s): No linked references.
3077807
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Domain
Metric
Rating
Comments
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
Medium Authors mentioned that confounders were controlled for in logistic regression analyses,
but the exact variables considered as confounding are not specified. Knowing the exact
confounding variables is critical given that the groups represent different regions of
Brazil, which is known to be a culturally-diverse country. Table 4 presents smoking
adjusted estimates for lung function are provided.
Medium As an occupational study, it can be assumed that covariate data were collected from
personnel records. Information on gender, age, time of exposure, smoking history, and
mean spirometric test values are provided in Table 1.
Low Co-exposures were not explicitly assessed. Although subjects came from an asbestos
mining and milling company, co-exposures may be likely for workers present prior
to 1976 where no formal fiber counting method was established yet. In the cases of
asbestosis, the etiology of asbestosis rules out other potential co-exposures.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium The study design was appropriate to address the research question. Kolmogorov-
Smirnov test was used to test for normality. "Categorical variables were tested using
the chi-squared or Fisher exact tests. Continuous variables were compared with analysis
of variance (ANOVA) or Kruskal-Wallis test, with Bonferroni correction for multiple
comparisons." Additionally, Poisson regression models were used for the longitudinal
analyses.
Medium The number of participants (n = 1418) seemed adequate to detect an effect in all groups
(n= 123, 600, 479, 216). The case-control study had small sample sizes (cases = 73;
controls = 21).
Medium The description of the analyses is sufficient to understand how to conceptually reproduce
the analysis with access to the analytic data.
Low Description of assumptions made in the models are not provided.
Additional Comments: Prior to 1976, no formal fiber measurement was used. As a result, a subjective, logarithmic scale was used to estimate levels in groups 1 and 2. Exposure
estimates in Groups 1 and 2 may not be reliable due to the lack of a formal fiber counting method during the time frames of each group.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 578 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 783706 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
van Cleemput, J., de Raeve, H., Verschakelen, J. A., Rombouts, J., Lacquet, L. M., Nemery, B. (2001). Surface of localized pleural plaques quantitated
by computed tomography scanning: No relation with cumulative asbestos exposure and no effect on lung function. American Journal of Respiratory and
Critical Care Medicine 163(2001):705-710.
Pulmonary Function/Spirometry Results; Pleural Plaques
Lung/Respiratory: Size of pleural plaques, Pulmonary function: FEV1, FVC, and transfer factor for carbon monoxide
Asbestos - Amosite (grunerite): 12172-73-5; Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
783706
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low The authors did not specify the method for quantifying fibers so it is unknown whether
PCM, TEM, or another microscopy method was used, but exposure was quantified in
fiber-years/ml. Fiber measurements from 1970-1985 were obtained by static sampling
during peak installation activities, which the authors noted may have contributed to
overestimations. Measurements after 1985 were obtained by personal monitoring that
measured 8-h time-weighted personal exposures, which likely better captured true expo-
sures.
Medium There was a sufficiently wide range and distribution of exposure. The study used a con-
tinuous measurement of cumulative asbestos exposure with estimates ranging from 16.4
to 98.7 fiber-years/ml with a mean of 26.3 +/- 12.6 fiber-years/ml. However, there was
no statistically significant association between cumulative asbestos exposure and pleural
plaque surface area.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis. Metric 4 was rated Low because the method for quantifying fibers was not specified. The authors did not specify the method for quantifying fibers
so it is unknown whether PCM, TEM, or another microscopy method was used, but exposure was quantified in fiber-years/ml, which could potentially be
useful. However, the study assessed the association between past asbestos exposure and the size (rather than the prevalence) of pleural plaques, and found
no statistically significant association. The study also assessed the association between pleural plaque size (rather than asbestos exposure) and pulmonary
function. Thus, the study does not have sufficient information for dose-response quantification for the association between asbestos exposure and the
prevalence of pleural plaques or pulmonary function levels.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 579 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 1093622 Table: 1 of 1
Study Citation: Vathesatogkit, P., Harkin, T. J., Addrizzo-Harris, D. J., Bodkin, M., Crane, M., Rom, W. N. (2004). Clinical correlation of asbestos bodies in BAL fluid.
Chest 126(2004):966-971.
Pleural Plaques; Chronic cough, sputum production, dyspnea, wheeze, total macrophages, total lymphocytes, total neutrophils, total eosinophils, diffuse
pleural thickening, sublpleural reticular changes, subpleural lines, fibrosis, bronchiectesis, emphysema, rounded atelectesis
Lung/Respiratory: Asbestos bodies
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Asbestos - Not specified: 1332-21-4
HERO ID:
1093622
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Uninformative
Uninformative
Subjects were categorized as exposed or unexposed. Subjects who worked at the electric
utility company. For exposed subjects, no information about timing, length, frequency,
or nature of exposure is reported.BAL fluid was inspected for asbestos bodies as a form
of biomonitoring in asbestos-exposed subjects only.
Exposure was dichotomized: exposed or unexposed. For exposed subjects, no informa-
tion about timing, length, frequency, or nature of exposure is reported.BAL fluid was
inspected for asbestos bodies as a form of biomonitoring in asbestos-exposed subjects
only.
Additional Comments: None
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessment for the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 580 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3656846 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
W. R. Grace & Co., (1988). Health of vermiculite miners exposed to trace amounts of fibrous tremolite with cover letter dated 022988.
Lung Cancer; Abdominal, Other Malignant Neoplasms; All cause mortality, respiratory, circulatory disease, all other causes
Mortality: Other cause of mortality, Respiratory, Circulatory disease; Cancer/Carcinogenesis: Respiratory, Abdominal, Other malignant neoplasms; Lung/
Respiratory: Respiratory malignant neoplasms; Gastrointestinal: Abdominal malignant neoplasms; Other malignant neoplasms: Other malignant neo-
plasms
Asbestos - Tremolite: 14567-73-8; Asbestos- Exposure reported as PCM or TEM (including conversion factors for dust)
No linked references.
3656846
Domain Metric Rating Comments
Domain 1: Study Participation
Metric 1: Participant Selection High The cohort included 194 men in the mining and milling of vermiculite in South Carolina
Metric 2: Attrition High There was no subject loss to follow up during the study (or exclusion from the analysis
sample) and outcome and exposure data were largely complete.
Metric 3: Comparison Group Medium Mortality of cohort was compared with white and black men in USA. "The age distri-
bution of the non-exposed group was unknown." The authors did not provide detailed
information about the control group.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure High Air samples were collected using membrane filters, and fibers were measured through
PCM and 'analytical electron microscopy'.
Metric 5: Exposure Levels Medium The authors reported cumulative exposure of 3 groups (units: f/ml.y): <1, n=103; 1 -
<10, n=83; >= 10, n=8.
Metric 6: Temporality Medium Temporality is established between exposure and outcome - 15 years or more from 1st
employment that lasted 6 months or more (minimum latency of 15 years).
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Medium Lung Cancer: Death certificates were obtained, registered causes of death were coded by
a qualified nosologist, including ICD codes but without being specific (reported ranges
of ICD codes).; Other Cancer(s): The authors state that they identified a specific health
outcome, but less-established methods were used and they did not conduct method vali-
dation (Histology/pathology not specified).; Other Non-Cancer Outcomes: The authors
state that they identified a specific health outcome including ranges of ICD codes per
mortality cause category, but validation methods were not reported (Histology/pathology
not specified).
High All the study findings were reported throughout the manuscript, including the number of
cases/controls by race, and cumulative exposure for the combined study population.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment Low The authors reported mortality data by race but SMRs were estimated for the totals,
only. Smoking was not considered as a potential confounder.
Metric 10: Covariate Characterization Medium Age, latency period, exposure level, race, and biomarkers were assessed but detailed
methods were not reported.
Continued on next page ...
Page 581 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3656846 Table: 1 of 1
... continued from previous page
W. R. Grace & Co., (1988). Health of vermiculite miners exposed to trace amounts of fibrous tremolite with cover letter dated 022988.
Lung Cancer; Abdominal, Other Malignant Neoplasms; All cause mortality, respiratory, circulatory disease, all other causes
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Other cause of mortality, Respiratory, Circulatory disease; Cancer/Carcinogenesis: Respiratory, Abdominal, Other malignant neoplasms; Lung/
Respiratory: Respiratory malignant neoplasms; Gastrointestinal: Abdominal malignant neoplasms; Other malignant neoplasms: Other malignant neo-
plasms
Asbestos - Tremolite: 14567-73-8; Asbestos- Exposure reported as PCM or TEM (including conversion factors for dust)
No linked references.
3656846
Domain
Metric
Rating
Comments
Metric 11:
Co-exposure Counfounding
Low
Co-exposures were not discussed; however, sputum specimen biomarkers were detected
through light microscopy.
Domain 5: Analysis
Metric 12:
Metric 13:
Metric 14:
Metric 15:
Study Design and Methods
Statistical Power
Reproducibility of Analyses
Statistical Analysis
Medium
Medium
Medium
Medium
The cohort study design was appropriate to evaluate the impact of exposure to tremolite
and mortality outcomes.
Mortality of cohort was compared with white and black men in USA using "person-
years at risk method" to compute expected number of deaths and SMRs using monson"s
computer program.
The description of the analysis is sufficient to understand how to conceptually reproduce
the analysis with access to the analytic data.
The calculation of SMRs was transparent.
Domain 6: Other (if applicable) Considerations for Biomarker Selection and Measurement (Lakind et al. 2014)
Metric 16: Use of Biomarker of Exposure
Metric 17: Effect Biomarker
Metric 18: Method Sensitivity
Metric 19: Biomarker Stability
Metric 20: Sample Contamination
Metric 21: Method Requirements
Metric 22: Matrix Adjustment
Low
N/A
Low
Low
Low
Medium
Low
7 of 76 saliva specimens were not analyzed because of technical difficulties, therefore
69 samples were analyzed. 9 of 69 had atypical ferruginous bodies not exceeding 4 per
pellet. 2 of 69 had typical ferruginous bodies (1 and 5 per pellet). No details of accuracy
and precision were included.
Effect biomarkers were not sampled, only exposure biomarkers.
LOD/LOQ were not reported.
The authors did not report a specified storage history of the sputum samples.
Contamination or lack thereof of samples was not reported. There is no use or docu-
mentation of the steps taken to provide the necessary assurance that the study data is
reliable.
Samples were "digested and then filtered to count the typical and atypical ferruginous
bodies by light microscopy EH 300 x magnification." It is unclear if the method has
known interferants.
No established method for matrix adjustment was conducted for sputum samples.
Additional Comments: Did not extract data related to malignant neoplasm deaths as we aren"t extracting data on cancer. Analyzed outcomes of radiology and mortality in separate
forms, as the methodology was different for the radiology vs. mortality outcomes. Study analyzes deaths by race (black and white). Radiology groups
involved 68 employees who were filmed (total of 83 films across participants), 25 films taken from employees in another division of the company who were
"not believed to have been exposed to dust", and 25 films from Montana mine selected at random from men with and without parenchymal small opacities.
Did not select libby amphibole since South Carolina would likely not be considered close to Libby MT. Did not extract any data on cancer (including for
mortality results) but did mark them since they were addressed in the paper in the extraction form.
Continued on next page ...
Page 582 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 3656846 Table: 1 of 1
... continued from previous page
W. R. Grace & Co., (1988). Health of vermiculite miners exposed to trace amounts of fibrous tremolite with cover letter dated 022988.
Lung Cancer; Abdominal, Other Malignant Neoplasms; All cause mortality, respiratory, circulatory disease, all other causes
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Mortality: Other cause of mortality, Respiratory, Circulatory disease; Cancer/Carcinogenesis: Respiratory, Abdominal, Other malignant neoplasms; Lung/
Respiratory: Respiratory malignant neoplasms; Gastrointestinal: Abdominal malignant neoplasms; Other malignant neoplasms: Other malignant neo-
plasms
Asbestos - Tremolite: 14567-73-8; Asbestos- Exposure reported as PCM or TEM (including conversion factors for dust)
No linked references.
3656846
Domain Metric
Rating
Comments
Overall Quality Determination
Medium
Page 583 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2638749 Table: 1 of 5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
Lung Cancer; Asbestosis
Cancer/Carcinogenesis: All cancer mortality, lung cancer mortality, gastrointestinal cancer mortality.; Lung/Respiratory: lung cancer mortality, nonmalig-
nant respiratory disease mortality, asbestosis mortality, mesothelioma mortality; Mortality: all cause mortality, all cancer mortality, lung cancer mortality,
gastrointestinal cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
2638749
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This prospective occupational study examined the health effects of asbestos exposure
among a group of workers from an asbestos textile factory in China. Male workers were
included in the study if they were registered workers in the factory on January 1972 and
did not have signs of malignant tumors. Follow up continued through 2008. 586 workers
were recruited for the original cohort, and 577 workers remained through the follow
up period (98.5% participation rate at final follow up). While the study authors boast a
high participation rate, it is unclear what percentage of the total eligible workers were
initially recruited in 1972..
High This study had a participation rate of 98.5% at the final follow up, a high rate that mini-
mizes concerns about bias introduced via subject attrition. Analyses were limited to the
577 subjects that had complete follow up information. Outcome and exposure data were
complete for study subjects.
High Authors provide a description of comparisons between the three exposure groups and
noted differences in age, exposure duration, and smoking in the three groups. These
variables were included as cofounders in Cox proportional hazard models, thus effec-
tively controlling for the differences between the groups.
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium Asbestos levels in the factory were quantitatively measured via TEM in 1982 and 2006,
with an assertion that levels remained over 2 mg/mA 3 during the study period. Personal
sampling was conducted to assess the levels in different areas of the factory, which
was ultimately used to construct three exposure groups (high, medium, low). Authors
note that 70% of the workers had stable positions in the factory for the duration of the
study. These positions were used to place workers into exposure categories. While these
exposure estimates were based on quantitative measures and the role in the factory,
there is still potential for nondifferential misclassification of exposure due to the limited
quantitative measuring and the lack of specificity about those who did have varying roles
during their employment.
Medium Exposure categories were high, medium, and low, based on the job description of work-
ers and sampling results from the factory. The low category was used as a reference
group for comparison purposes.
Continued on next page ...
Page 584 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 1 of 5
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
Lung Cancer; Asbestosis
Cancer/Carcinogenesis: All cancer mortality, lung cancer mortality, gastrointestinal cancer mortality.; Lung/Respiratory: lung cancer mortality, nonmalig-
nant respiratory disease mortality, asbestosis mortality, mesothelioma mortality; Mortality: all cause mortality, all cancer mortality, lung cancer mortality,
gastrointestinal cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain
Metric
Rating
Comments
Metric 6:
Temporality
High
This study has over 30 years of follow-up, and subjects did not have signs of malignan-
cies during recruitment. This is an appropriate timeframe to assess lung cancer or other
outcomes of interest.
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Medium
High
Lung Cancer: Lung cancer deaths were identified through personnel records from the
factory. There is no indication that ICD codes were used to identify cases. Authors note
that half of the cases were confirmed pathologically, though because half of the cases
were not confirmed, this domain was rated medium.; Asbestosis: Asbestosis deaths were
also ascertained through personnel records from the factory. There is no indication that
ICD codes or lung tissue scarring were used to identify cases.
Hazard ratios and 95% confidence intervals (CI) were reported for lung cancer and
asbestosis mortality. Cases for each exposure category were reported in a separate table.
While these numbers were not reported directly in the results table, there is enough
information to merit a high rating.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High
Medium
Medium
The study authors appropriately adjusted for variables that vary among the three expo-
sure groups. Age, duration of exposure, and smoking were included as covariates in Cox
proportional hazard models.
Data on covariates was collected from factory records. Additionally, smoking informa-
tion was collected from individuals via interview or from family members via interview.
There was no indication of validation of factory records, though the records can be as-
sumed to be fairly accurate.
This study took place in an asbestos textile factory. There is no indication that co-
exposures were present in the occupational setting.
Domain 5: Analysis
Metric 12:
Metric 13:
Study Design and Methods
Statistical Power
Medium
Medium
This study used a prospective cohort design to assess lung cancer mortality, which has a
long latency period. This is an appropriate design for this health outcome. Additionally,
Cox proportional hazard models were used to compare the medium and high exposure
groups to the low exposure group (referent).
While the overall cohort numbers are appropriate, there are concerns about the statistical
power of the model to assess lung cancer and asbestosis. While some the low exposure
group had less than 10 subjects, the effect estimates presented appear to be robust for
these two outcomes.
Continued on next page ...
Page 585 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 1 of 5
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
Lung Cancer; Asbestosis
Cancer/Carcinogenesis: All cancer mortality, lung cancer mortality, gastrointestinal cancer mortality.; Lung/Respiratory: lung cancer mortality, nonmalig-
nant respiratory disease mortality, asbestosis mortality, mesothelioma mortality; Mortality: all cause mortality, all cancer mortality, lung cancer mortality,
gastrointestinal cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain
Metric
Rating
Comments
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium Adequate information is provided to conceptually reproduce the analyses reported in the
study.
Low While the model to assess the hazard of lung cancer and asbestosis mortality is clear,
it is unclear if Cox proportional hazard model assumptions were met. Authors do not
discuss any tests to assess the appropriateness of the statistical model.
Additional Comments: For the lung cancer and asbestosis assessments, there are a limited number of cases across the exposure categories. For the low exposure category, <10
cases were present, which limits the statistical power of the analysis and brings into question the ability of the study to detect an effect. Otherwise, the
study presents appropriate approaches to participant selection, exposure assessment, and control for potential confounders.The measurement exposure
(M4) and/or exposure levels (M5) metrics are rated medium upon review by both set of reviewers. However, the overall quality determination (OQD) is
rated uninformative, upgraded to medium.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 586 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 2 of 5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
gastrointestinal cancer
Cancer/Carcinogenesis: All cancer mortality, lung cancer mortality, gastrointestinal cancer mortality.; Gastrointestinal: gastrointestinal cancer mortality;
Mortality: all cause mortality, all cancer mortality, lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality,
asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
2638749
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This prospective occupational study examined the health effects of asbestos exposure
among a group of workers from an asbestos textile factory in China. Male workers were
included in the study if they were registered workers in the factory on January 1972
and did not have signs of malignant tumors. Follow up continued through 2008. 586
workers were recruited for the original cohort, and 577 workers remained through the
follow up period (98.5% participation rate at final follow up). While the study boasts a
high participation rate, it is unclear what percentage of the total eligible workers were
initially recruited in 1972, preventing a high rating in this domain.
High This study had a participation rate of 98.5% at the final follow up, a high rate that mini-
mizes concerns about bias introduced via subject attrition. Analyses were limited to the
577 subjects that had complete follow up information. Outcome and exposure data are
complete for study subjects.
High Authors provide a description of comparisons between the three exposure groups and
noted differences in age, exposure duration, and smoking in the three groups. These
variables were included as cofounders in Cox proportional hazard models, thus effec-
tively controlling for the differences between the groups.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Asbestos levels in the factory were quantitatively measured via TEM in 1982 and 2006,
with an assertion that levels remained over 2 mg/mA 3 during the study period. Personal
sampling was conducted to assess the levels in different areas of the factory, which
was ultimately used to construct three exposure groups (high, medium, low). Authors
note that 70% of the workers had stable positions in the factory for the duration of the
study. These positions were used to place workers into exposure categories. While these
exposure estimates were based on quantitative measures and the role in the factory,
there is still potential for nondifferential misclassification of exposure due to the limited
quantitative measuring and the lack of specificity about those who did have varying roles
during their employment.
Medium Exposure categories were high, medium, and low, based on the job description of work-
ers and sampling results from the factory.
High This study has over 30 years of follow-up, and subjects did not have signs of malignan-
cies during recruitment. This is an appropriate timeframe to assess malignancies.
Domain 3: Outcome Assessment
Continued on next page ...
Page 587 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 2 of 5
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
gastrointestinal cancer
Cancer/Carcinogenesis: All cancer mortality, lung cancer mortality, gastrointestinal cancer mortality.; Gastrointestinal: gastrointestinal cancer mortality;
Mortality: all cause mortality, all cancer mortality, lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality,
asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
2638749
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
Medium
Other Cancer(s): Gastrointestinal cancer deaths were identified through personnel
records from the factory. There is no indication that ICD codes were used to identify
cases. Authors note that half of the cases were confirmed pathologically, though because
half of the cases were not confirmed, this domain was rated medium.
Metric 8:
Reporting Bias
High
Hazard ratios and 95% CI are reported for gastrointestinal cancer mortality. Cases for
each exposure category are reported in a separate table. While these numbers are not
reported directly in the results table, there is enough information to merit a high rating.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
High
The authors appropriately adjust for variables that vary among the three exposure
groups. Age, duration of exposure, and smoking were included as covariates in Cox
proportional hazard models.
Metric 10:
Covariate Characterization
Medium
Data on covariates was collected from factory records. Additionally, smoking informa-
tion was collected from individuals via interview or from family members via interview.
There was no indication of validation of factory records, though the records can be as-
sumed to be fairly accurate, thus meriting a medium rating.
Metric 11:
Co-exposure Counfounding
Medium
This study took place in an asbestos textile factory. There is no indication that co-
exposures were present in the occupational setting.
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
This study used a prospective cohort design to assess gastrointestinal cancer mortality,
which has a long latency period. This is an appropriate design for this health outcome.
Additionally a Cox proportional hazard model was used to compare the medium and
high exposure groups to the low exposure group (referent).
Metric 13:
Statistical Power
Medium
While the overall cohort numbers are appropriate, there are concerns about the statistical
power of the model to assess gastrointestinal cancer. Two exposure categories (low and
high) have less than 10 subjects, which could limit the ability to detect robust effect
estimates.
Metric 14:
Reproducibility of Analyses
Medium
Overall, adequate information was provided to conceptually reproduce the analyses
reported in the study.
Metric 15:
Statistical Analysis
Low
While the model to assess the hazard of gastrointestinal cancer mortality is clear, it
is unclear if Cox proportional hazard model assumptions were met. Authors did not
discuss any tests to assess the appropriateness of the statistical model.
Continued on next page ...
Page 588 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 2 of 5
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
gastrointestinal cancer
Cancer/Carcinogenesis: All cancer mortality, lung cancer mortality, gastrointestinal cancer mortality.; Gastrointestinal: gastrointestinal cancer mortality;
Mortality: all cause mortality, all cancer mortality, lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality,
asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
ID(s): No linked references.
2638749
Domain
Metric
Rating
Comments
Additional Comments:
For the gastrointestinal cancer assessment, there were a limited number of cases across the exposure categories. Two exposure categories (low and high)
have less than 10 subjects, which could limit the ability to detect robust effect estimates. Otherwise, the study presents appropriate approaches to participant
selection, exposure assessment, and control for potential confounders (including smoking).The measurement exposure (M4) and/or exposure levels (M5)
metrics are rated medium upon review by both set of reviewers. However, the overall quality determination (OQD) was initially rated uninformative, but
upgraded to medium.
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 589 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 3 of 5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
non malignant respiratory disease mortality
Lung/Respiratory: lung cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality, mesothelioma mortality; Mortality: all cause
mortality, all cancer mortality, lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This prospective occupational study examined the health effects of asbestos exposure
among a group of workers from an asbestos textile factory in China. Male workers were
included in the study if they were registered workers in the factory on January 1972
and did not have signs of malignant tumors. Follow up continued through 2008. 586
workers were recruited for the original cohort, and 577 workers remained through the
follow up period (98.5% participation rate at final follow up). While the study boasts a
high participation rate, it is unclear what percentage of the total eligible workers were
initially recruited in 1972, preventing a high rating in this domain.
High This study had a participation rate of 98.5% at the final follow up, a high rate that mini-
mizes concerns about bias introduced via subject attrition. Analyses were limited to the
577 subjects that had complete follow up information. Outcome and exposure data are
complete for study subjects.
High Authors provide a description of comparisons between the three exposure groups and
noted differences in age, exposure duration, and smoking in the three groups. These
variables were included as cofounders in Cox proportional hazard models, thus effec-
tively controlling for the differences between the groups.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Asbestos levels in the factory were quantitatively measured via TEM in 1982 and 2006,
with an assertion that levels remained over 2 mg/mA 3 during the study period. Personal
sampling was conducted to assess the levels in different areas of the factory, which
was ultimately used to construct three exposure groups (high, medium, low). Authors
note that 70% of the workers had stable positions in the factory for the duration of the
study. These positions were used to place workers into exposure categories. While these
exposure estimates were based on quantitative measures and the role in the factory,
there is still potential for nondifferential misclassification of exposure due to the limited
quantitative measuring and the lack of specificity about those who did have varying roles
during their employment.
Medium Exposure categories were high, medium, and low, based on the job description of work-
ers and sampling results from the factory.
High This study has over 30 years of follow-up, and subjects did not have signs of malig-
nancies during recruitment. This is an appropriate timeframe to assess nonmalignant
respiratory disease and sufficiently accounts for temporality.
Domain 3: Outcome Assessment
Continued on next page ...
Page 590 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 3 of 5
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
non malignant respiratory disease mortality
Lung/Respiratory: lung cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality, mesothelioma mortality; Mortality: all cause
mortality, all cancer mortality, lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain
Metric
Rating
Comments
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
Medium Other Non-Cancer Outcomes: Non-malignant respiratory disease deaths were ascer-
tained through personnel records from the factory. There is no indication that ICD codes
were used to identify cases or that all death certificate fields were searched to identify
cases.
High Hazard ratios and 95% CI are reported for nonmalignant respiratory mortality. Cases
for each exposure category are reported in a separate table. While these numbers are not
reported directly in the results table, there is enough information to merit a high rating.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High The authors appropriately adjust for variables that vary among the three exposure
groups. Age, duration of exposure, and smoking were included as covariates in Cox
proportional hazard models.
Medium Data on covariates was collected from factory records. Additionally, smoking informa-
tion was collected from individuals via interview or from family members via interview.
There was no indication of validation of factory records, though the records can be as-
sumed to be fairly accurate, thus meriting a medium rating.
Medium This study took place in an asbestos textile factory. There is no indication that co-
exposures were present in the occupational setting.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium This study used a prospective cohort design to assess nonmalignant respiratory mortal-
ity. This is an appropriate design for this health outcome. Additionally a Cox propor-
tional hazard models were used to compare the medium and high exposure groups to the
low exposure group (referent).
Medium The number of participants in each exposure group appears adequate to detect robust
effect estimates when assessing exposures and nonmalignant respiratory disease.
Medium Adequate information is provided to conceptually reproduce the analyses reported in the
study.
Low While the model to assess the hazard of non-malignant respiratory mortality is clear, it is
unclear if Cox proportional hazard model assumptions were met. Authors do not discuss
any tests to assess the appropriateness of the statistical model.
Continued on next page ...
Page 591 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 3 of 5
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
non malignant respiratory disease mortality
Lung/Respiratory: lung cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality, mesothelioma mortality; Mortality: all cause
mortality, all cancer mortality, lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain Metric Rating Comments
Additional Comments: For the nonmalignant respiratory disease assessment, there are a limited number of cases across the exposure categories. For some exposure categories,
<50 cases were present, which limits the statistical power of the analysis and brings into question the ability of the study to detect an effect. Otherwise,
the study presents appropriate approaches to participant selection, exposure assessment, and control for potential confounders.The measurement exposure
(M4) and/or exposure levels (M5) metrics are rated medium upon review by both set of reviewers. However, the overall quality determination (OQD) was
rated uninformative, but then upgraded to medium.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 592 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 4 of 5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
all cause mortality
Mortality: all cause mortality, all cancer mortality, lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality,
asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This prospective occupational study examined the health effects of asbestos exposure
among a group of workers from an asbestos textile factory in China. Male workers were
included in the study if they were registered workers in the factory on January 1972
and did not have signs of malignant tumors. Follow up continued through 2008. 586
workers were recruited for the original cohort, and 577 workers remained through the
follow up period (98.5% participation rate at final follow up). While the study boasts a
high participation rate, it is unclear what percentage of the total eligible workers were
initially recruited in 1972, preventing a high rating in this domain.
High This study had a participation rate of 98.5% at the final follow up, a high rate that mini-
mizes concerns about bias introduced via subject attrition. Analyses were limited to the
577 subjects that had complete follow up information. Outcome and exposure data are
complete for study subjects.
High Authors provide a description of comparisons between the three exposure groups and
noted differences in age, exposure duration, and smoking in the three groups. These
variables were included as cofounders in Cox proportional hazard models, thus effec-
tively controlling for the differences between the groups.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Asbestos levels in the factory were quantitatively measured via TEM in 1982 and 2006,
with an assertion that levels remained over 2 mg/mA 3 during the study period. Personal
sampling was conducted to assess the levels in different areas of the factory, which
was ultimately used to construct three exposure groups (high, medium, low). Authors
note that 70% of the workers had stable positions in the factory for the duration of the
study. These positions were used to place workers into exposure categories. While these
exposure estimates were based on quantitative measures and the role in the factory,
there is still potential for nondifferential misclassification of exposure due to the limited
quantitative measuring and the lack of specificity about those who did have varying roles
during their employment.
Medium Exposure categories were high, medium, and low, based on the job description of work-
ers and sampling results from the factory.
High This study has over 30 years of follow-up, and subjects did not have signs of malignan-
cies during recruitment. This is an appropriate timeframe to assess all cause mortality
and sufficiently accounts for temporality.
Domain 3: Outcome Assessment
Continued on next page ...
Page 593 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 4 of 5
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
all cause mortality
Mortality: all cause mortality, all cancer mortality, lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality,
asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain Metric Rating Comments
Metric 7: Outcome Measurement or High Other Non-Cancer Outcomes: Deaths were identified through personnel records from
Characterization the factory and from death registries, which is a valid approach to capture mortality data.
Metric 8: Reporting Bias High Hazard ratios and 95% CI are reported for nonmalignant respiratory mortality. Cases
for each exposure category are reported in a separate table. While these numbers are not
reported directly in the results table, there is enough information to merit a high rating.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High The authors appropriately adjust for variables that vary among the three exposure
groups. Age, duration of exposure, and smoking were included as covariates in Cox
proportional hazard models.
Medium Data on covariates was collected from factory records. Additionally, smoking informa-
tion was collected from individuals via interview or from family members via interview.
There was no indication of validation of factory records, though the records can be as-
sumed to be fairly accurate, thus meriting a medium rating.
Medium This study took place in an asbestos textile factory. There is no indication that co-
exposures were present in the occupational setting.
Domain 5: Analysis
Metric 12: Study Design and Methods
Metric 13: Statistical Power
Metric 14: Reproducibility of Analyses
Metric 15: Statistical Analysis
Medium This study used a prospective cohort design to assess all cause mortality. This is an
appropriate design for this health outcome. Additionally a Cox proportional hazard
model was used to compare the medium and high exposure groups to the low exposure
group (referent).
Medium The sample size was appropriate to generate adequate statistical power to assess the
hazard of all cause mortality in the study cohort.
Medium Adequate information is provided to conceptually reproduce the analyses reported in the
study.
Low While the model to assess the hazard of all cause mortality is clear, it is unclear if Cox
proportional hazard model assumptions were met. Authors do not discuss any tests to
assess the appropriateness of the statistical model.
Additional Comments: Medium. This prospective cohort study examined the hazard of all cause mortality among an occupational population of male asbestos textile workers in
China. The paper presents appropriate approaches to participant selection, exposure assessment, and control for potential confounders. Additionally, the
sample sizes of the cohort and subgroups were adequate to detect robust effect estimates.The measurement exposure (M4) and/or exposure levels (M5)
metrics are rated as medium upon review by both set of reviewers. Also, the overall quality determination (OQD) for this outcome is rated medium.
Extraction has been completed and quality control reviewed.
Continued on next page ...
Page 594 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 4 of 5
... continued from previous page
Study Citation: Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
all cause mortality
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
Mortality: all cause mortality, all cancer mortality, lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality,
asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
HERO ID:
2638749
Domain Metric
Rating
Comments
Overall Quality Determination
Medium
* No biomarkers were identified for this evaluation.
Page 595 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 5 of 5
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
all cancer mortality
Cancer/Carcinogenesis: All cancer mortality, lung cancer mortality, gastrointestinal cancer mortality.; Mortality: all cause mortality, all cancer mortality,
lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1: Participant Selection
Metric 2: Attrition
Metric 3: Comparison Group
Medium This prospective occupational study examined the health effects of asbestos exposure
among a group of workers from an asbestos textile factory in China. Male workers were
included in the study if they were registered workers in the factory on January 1972
and did not have signs of malignant tumors. Follow up continued through 2008. 586
workers were recruited for the original cohort, and 577 workers remained through the
follow up period (98.5% participation rate at final follow up). While the study boasts a
high participation rate, it is unclear what percentage of the total eligible workers were
initially recruited in 1972, preventing a high rating in this domain.
High This study had a participation rate of 98.5% at the final follow up, a high rate that mini-
mizes concerns about bias introduced via subject attrition. Analyses were limited to the
577 subjects that had complete follow up information. Outcome and exposure data are
complete for study subjects.
High Authors provide a description of comparisons between the three exposure groups and
noted differences in age, exposure duration, and smoking in the three groups. These
variables were included as cofounders in Cox proportional hazard models, thus effec-
tively controlling for the differences between the groups.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
Medium Asbestos levels in the factory were quantitatively measured via TEM in 1982 and 2006,
with an assertion that levels remained over 2 mg/mA 3 during the study period. Personal
sampling was conducted to assess the levels in different areas of the factory, which
was ultimately used to construct three exposure groups (high, medium, low). Authors
note that 70% of the workers had stable positions in the factory for the duration of the
study. These positions were used to place workers into exposure categories. While these
exposure estimates were based on quantitative measures and the role in the factory,
there is still potential for nondifferential misclassification of exposure due to the limited
quantitative measuring and the lack of specificity about those who did have varying roles
during their employment.
Medium Exposure categories were high, medium, and low, based on the job description of work-
ers and sampling results from the factory.
High This study has over 30 years of follow-up, and subjects did not have signs of malignan-
cies during recruitment. This is an appropriate timeframe to assess cancer mortality,
which has a long latency period, and sufficiently accounts for temporality.
Domain 3: Outcome Assessment
Continued on next page ...
Page 596 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 5 of 5
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
all cancer mortality
Cancer/Carcinogenesis: All cancer mortality, lung cancer mortality, gastrointestinal cancer mortality.; Mortality: all cause mortality, all cancer mortality,
lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain
Metric
Rating
Comments
Metric 7:
Outcome Measurement or
Characterization
Medium
Other Cancer(s): Cancer deaths were identified through personnel records from the
factory. There is no indication that ICD codes were used to identify cases. Authors note
that half of the cases were confirmed pathologically, though because half of the cases
were not confirmed, this domain was rated medium.
Metric 8:
Reporting Bias
High
Hazard ratios and 95% CI are reported for all cancer mortality. Cases for each exposure
category are reported in a separate table. While these numbers are not reported directly
in the results table, there is enough information to merit a high rating.
Domain 4: Potential Confounding / Variability Control
Metric 9:
Covariate Adjustment
High
The authors appropriately adjust for variables that vary among the three exposure
groups. Age, duration of exposure, and smoking were included as covariates in Cox
proportional hazard models.
Metric 10:
Covariate Characterization
Medium
Data on covariates was collected from factory records. Additionally, smoking informa-
tion was collected from individuals via interview or from family members via interview.
There was no indication of validation of factory records, though the records can be as-
sumed to be fairly accurate, thus meriting a medium rating.
Metric 11:
Co-exposure Counfounding
Medium
This study took place in an asbestos textile factory. There is no indication that co-
exposures were present in the occupational setting.
Domain 5: Analysis
Metric 12:
Study Design and Methods
Medium
This study used a prospective cohort design to assess all cancer mortality. This is an
appropriate design for this health outcome. Additionally a Cox proportional hazard
model was used to compare the medium and high exposure groups to the low exposure
group (referent).
Metric 13:
Statistical Power
Medium
While the overall cohort numbers are appropriate, there are concerns about the statistical
power of the model to assess nonmalignant respiratory disease. The lowest exposure
group had 15 cases while the other exposure groups had fewer than 50, which may limit
the ability to detect an effect.
Metric 14:
Reproducibility of Analyses
Medium
Adequate information is provided to conceptually reproduce the analyses reported in the
study.
Metric 15:
Statistical Analysis
Low
While the model to assess the hazard of all cancer mortality is clear, it is unclear if Cox
proportional hazard model assumptions were met. Authors do not discuss any tests to
assess the appropriateness of the statistical model.
Continued on next page ...
Page 597 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 2638749 Table: 5 of 5
... continued from previous page
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X. R., Yu, I. T. S., Qiu, H., Wang, M. Z., Lan, Y. J., Tse, L. Y., Yano, E., Christiani, D. C. (2012). Cancer mortality among Chinese chrysotile
asbestos textile workers. Lung Cancer 75(2012):151-155.
all cancer mortality
Cancer/Carcinogenesis: All cancer mortality, lung cancer mortality, gastrointestinal cancer mortality.; Mortality: all cause mortality, all cancer mortality,
lung cancer mortality, gastrointestinal cancer mortality, nonmalignant respiratory disease mortality, asbestosis mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2638749
Domain Metric Rating Comments
Additional Comments: For the all cancer mortality assessment, there are a limited number of cases across the exposure categories. For the low exposure category, fewer than
20 cases were reported, and for the other exposure categories, <50 cases were present, which limits the statistical power of the analysis and brings into
question the ability of the study to detect an effect. Otherwise, this prospective cohort study examined all cancer mortality among a group of male asbestos
textile workers and presents appropriate approaches to participant selection, exposure assessment, and control for potential confounders.The measurement
exposure (M4) and/or exposure levels (M5) metrics are rated as medium upon review by both set of reviewers. However, the overall quality determination
(OQD) for this outcome was initially rated uninformative, but upgraded to medium.
Overall Quality Determination Medium
* No biomarkers were identified for this evaluation.
Page 598 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 2572504 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wang, X., Lin, S., Yano, E., Qiu, H., Yu, I. T., Tse, L., Lan, Y., Wang, M. (2012). Mortality in a Chinese chrysotile miner cohort. International Archives of
Occupational and Environmental Health 85(2012):405-412.
GI cancer, all cancer; All cause mortality, non-malignant respiratory disease mortality
Mortality: All cause mortality, All cancer mortality, GI cancer mortality, Non-malignant respiratory disease mortality; Gastrointestinal: GI cancer mortality;
Lung/Respiratory: Non-malignant respiratory disease mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
No linked references.
2572504
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Medium Asbestos dust concentrations in the mine were described as measured periodically for
total dust with available data up to 1995 briefly summarized in the text. Additional fix-
ing point sampling in various workshops in 2006 with 28 breathing-zone samples in
eight workshops collected and analyzed in accordance with HSE Methods (HSE 2000)
was also briefly summarized. Conversion factors were applied to the dust measurements
in 2006 with resulting average 2006 fiber concentration in the mine reported as 29.0
f/mL (range: 2.9 to 63.8 f/mL). However, side-by-side sampling and analysis were not
noted.
Low The data to develop adquate exposure-response relationships is limited.
Additional Comments: This retrospective cohort study examined the association between asbestos exposure and cause-specific mortality in a cohort of chrysotile asbestos miners
in China 1981-2006. A total of n=l,539 male mine workers, with n=l,080 mining ("miner and miller group" composed of those directly engaged in
asbestos mining and milling, mechanical maintenance and transportation) workers and n=459 controls (administrative management, office work, cooks)
were included for study. Authors noted workers were followed up 1981 through 2006 "irrespective of retirement status", however it was unclear if workers
were followed who might have left the mine prior to the retirement. Average dust and flber/mL exposure was briefly detailed within text for the overall
population, but not specific populations within results or utilized within SMR or Cox regression results. However Cox regression utilized length of
follow-up as the time dimension, while taking into account employment years. Authors noted that control workers were exposed to asbestos, and control
worker SMR of nonmalignant respiratory disease was 85% greater than expected, although had mortality rates similar to national rates for other causes.
All mortality rates of selected causes were substantially higher in the miner group than in the controls. The authors reported SMR"s of nonmalignant
respiratory diseases in the miners as 3.53 (2.78, 4.48), and noted that asbestos exposure was related to over a threefold risk for respiratory diseases and all
cancers, while adjusting for smoking and age.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 599 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 730085 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Weiderpass, E., Pukkala, E., Kauppinen, T., Mutanen, P., Paakkulainen, H., Vasama-Neuvonen, K., Boffetta, P., Partanen, T. (1999). Breast cancer and
occupational exposures in women in Finland. American Journal of Industrial Medicine 36(1999):48-53.
breast cancer
Cancer/Carcinogenesis: Breast cancer; Reproductive/Developmental: Breast cancer
Asbestos - Not specified: 1332-21-4
No linked references.
730085
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure Low Asbestos analytic method for data within the FINJEM was not specified. Methods used
to quantify the exposure were not well defined, and sources of data and detailed methods
of exposure assessment were not reported. Asbestos exposure was defined in models as
the product of probability and exposure level obtained from data from the Finnish na-
tional job exposure matrix (FINJEM) developed at the Finnish Institute of Occupational
Health, which included data described as estimates based on professional judgment and
derived from industrial hygiene measurements when available 1960-1984. Details of
analytical method (PCM/TEM) for asbestos samples were not provided within the main
text or the referenced article by Kauppinen et al., 1998 (HERO ID not available). Ad-
ditional searches regarding FINJEM data analytical methods located Kauppinen et al.,
2013 (HERO ID 2634525), which noted levels of chemical exposures in FINJEM were
determined by experienced IH's using "...data from the Database of Occupational Ex-
posure Measurements (DOEM) (Kauppinen, 2001; Heikkil" et al., 2005; Saalo et al.,
2010), the Register of Employees Exposed to Carcinogens (ASA) (Kauppinen et al.,
2007; Saalo et al., 2011), and the Finnish Work and Health Surveys (Perki"-M"kel" et
al., 2010)". Checking for information on the DOEM, Kauppinen et al., 2014 (HERO ID
6735112) "Use of the Finnish Information System on Occupational Exposure (FINJEM)
in epidemiologic, surveillance, and other applications" was found which also did not
detail asbestos sampling and analytic methods.
Metric 5: Exposure Levels Low The range and distribution of exposure was described only as subdivided into three
factored categories for each agent: zero; low (roughly below median among job titles
with exposure probability .0); and medium/high. Measured levels were not summarized.
Additional Comments: Weiderpass et al., 1999 (HERO ID 730085) was not evaluated for any metrics except Metric 4 and 5 as it did not have sufficient exposure information to
be useful for dose-response analysis.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 600 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 263 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Weill, H., Hughes, J., Waggenspack, C. (1979). Influence of dose and fiber type on respiratory malignancy risk in asbestos cement manufacturing. American
Review of Respiratory Disease 120(1979):345-354.
Lung Cancer; Digestive system, other (residual) cancers; Cardiovascular diseases, all other causes mortality
Gastrointestinal: Digestive system neoplasm mortality; Mortality: Digestive system neoplasm mortality, Respiratory system neoplasm mortality, Other
neoplasm mortality, Major cardiovascular diseases mortality, Total neoplasm mortality, All other causes mortality; Cancer/Carcinogenesis: Digestive
system neoplasm mortality, Respiratory system neoplasm mortality, Other neoplasm mortality, Total neoplasm mortality; Lung/Respiratory: Respiratory
system neoplasm mortality; other neoplasms, unspecified: Other neoplasm mortality; Cardiovascular: Major cardiovascular diseases mortality; Total
neoplasm mortality: Total neoplasm mortality; other, unspecified: All other causes mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
ID(s): No linked references.
263
Domain
Metric
Rating
Comments
Domain 1: Study Participation
Metric 1:
Participant Selection
Metric 2:
Attrition
Metric 3:
Comparison Group
Medium This study focuses on a cohort of 5645 men across two asbestos cement building ma-
terials plants New Orleans, LA who had at least 20 years of follow-up available. 35%
worked at the first plant (roofing products), 64% worked at the second plant (roofing,
piping, and flooring products), and 1% worked at both plants with a similar distribution
of lengths of employment in both plants however a greater proportion of workers in the
second plant were employed for more than 20 years. No recruitment methods were or
other inclusion or exclusion criteria were described.
Medium The study authors were able to confirm that 11% of the cohort were known to have died
and that approximately 64% were known to be alive in 1974 however for the remaining
25% were unable to be traced and the authors stated analysis adjustments were not pos-
sible for this group. These primarily would have been subjects between 45 an 64 years
of age in 1974. Based on subsequent discussion and review of additional information,
the rating was adjusted based on adequately addressed is from either imputation or if
there aren"t differences between groups in terms of reasons for loss.
Medium The subjects were categorized into 5 exposure categories and mean follow-up and mean
age at initial exposure were similar across the groups however no statement was pro-
vided about the distribution of age across the exposure groups. SMR analysis was con-
ducted on the basis of race-age-cause specific rates for both the U.S. and for Louisiana
male populations for 1950, 1960, and 1970.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Metric 6: Temporality
High Hammad et al. 1979 details the sampling data collected and the determination of as-
bestos fiber measurements in the samples. Impinger filter pairs were collected from
personal samples. Asbestos fibers were counted on filter samples using PCM. Paired
samples were collected for various job functions or "zones".
Medium Table 1 and 2 in the publication present 5 different exposure levels, including SMRs in
Table 2. Table 3-25 in the 1986 assessment presents SMRs and RRs for the 5 exposure
groups.
High The study presents appropriate temporality between exposure and outcome, with all
workers having >=20 years of follow up.
Continued on next page ...
Page 601 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 263 Table: 1 of 1
... continued from previous page
Weill, H., Hughes, J., Waggenspack, C. (1979). Influence of dose and fiber type on respiratory malignancy risk in asbestos cement manufacturing. American
Review of Respiratory Disease 120(1979):345-354.
Lung Cancer; Digestive system, other (residual) cancers; Cardiovascular diseases, all other causes mortality
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
Gastrointestinal: Digestive system neoplasm mortality; Mortality: Digestive system neoplasm mortality, Respiratory system neoplasm mortality, Other
neoplasm mortality, Major cardiovascular diseases mortality, Total neoplasm mortality, All other causes mortality; Cancer/Carcinogenesis: Digestive
system neoplasm mortality, Respiratory system neoplasm mortality, Other neoplasm mortality, Total neoplasm mortality; Lung/Respiratory: Respiratory
system neoplasm mortality; other neoplasms, unspecified: Other neoplasm mortality; Cardiovascular: Major cardiovascular diseases mortality; Total
neoplasm mortality: Total neoplasm mortality; other, unspecified: All other causes mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
ID(s): No linked references.
263
Domain
Metric
Rating
Comments
Domain 3: Outcome Assessment
Metric 7:
Metric 8:
Outcome Measurement or
Characterization
Reporting Bias
High
High
Lung Cancer: High - Death certificates were coded by a nosologist with the U.S. Public
Heatlh Service according to ICD-8 codes (160-163).; Other Cancer(s): High - Death
certificates were coded by a nosologist with the U.S. Public Heatlh Service accord-
ing to ICD-8 codes ( all malignant neoplasms: 140-209; digestive system neoplasms:
150-159).; Other Non-Cancer Outcomes: High - Death certificates were coded by a
nosologist with the U.S. Public Heatlh Service according to ICD-8 codes (cardiovascular
diseases: 390-448).
Findings of SMR and OR analyses are reported with case numbers.
Domain 4: Potential Confounding / Variability Control
Metric 9: Covariate Adjustment
Metric 10: Covariate Characterization
Metric 11: Co-exposure Counfounding
High
High
Medium
SMR analysis was conducted on the basis of race-age-cause specific rates for both the
U.S. and for Louisiana male populations for 1950, 1960, and 1970.
The study assessed age and sex and these are assumed to have been obtained from per-
sonnel records. Assessment of SES was not described however this is unlikely to intro-
duce bias as the exposure was based on job history and it is assumed that the workers in
the asbestos cement building materials plants have similar SES.
Co-exposures are not discussed in detail, but authors note the use of silica in plants and
there is no direct evidence for an unbalanced provision of additional co-exposure across
study groups.
Domain 5: Analysis
Metric 12:
Metric 13:
Study Design and Methods
Statistical Power
Medium
Medium
The cohort study design is appropriate for the analysis of SMR by asbestos dust expo-
sure categories. Further analysis utilized a matched case-control design for lung cancer
cases that were assigned 4 controls matched on same birth year, race, survived into the
same year as the case, and did not subsequently die to a malignancy.
There is adequate power to detect an association in this study, which utilized 5645 male
subjects with at least 20 years of follow-up. Of these subjects, 11% were known to have
died.
The description of the analysis is sufficient to understand how to conceptually reproduce
the analysis with access to the data and the U.S. and Louisiana race-age-cause-specific
mortality rates.
Metric 14:
Reproducibility of Analyses
Medium
Continued on next page ...
Page 602 of 606
-------
Asbestos
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Human Health Hazard Epidemology Evaluation
HERO ID: 263 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO
HERO ID:
... continued from previous page
Weill, H., Hughes, J., Waggenspack, C. (1979). Influence of dose and fiber type on respiratory malignancy risk in asbestos cement manufacturing. American
Review of Respiratory Disease 120(1979):345-354.
Lung Cancer; Digestive system, other (residual) cancers; Cardiovascular diseases, all other causes mortality
Gastrointestinal: Digestive system neoplasm mortality; Mortality: Digestive system neoplasm mortality, Respiratory system neoplasm mortality, Other
neoplasm mortality, Major cardiovascular diseases mortality, Total neoplasm mortality, All other causes mortality; Cancer/Carcinogenesis: Digestive
system neoplasm mortality, Respiratory system neoplasm mortality, Other neoplasm mortality, Total neoplasm mortality; Lung/Respiratory: Respiratory
system neoplasm mortality; other neoplasms, unspecified: Other neoplasm mortality; Cardiovascular: Major cardiovascular diseases mortality; Total
neoplasm mortality: Total neoplasm mortality; other, unspecified: All other causes mortality
Asbestos - Chrysotile (serpentine): 12001-29-5; Asbestos - Crocidolite (riebeckite): 12001-28-4; Asbestos - Amosite (grunerite): 12172-73-5
ID(s): No linked references.
263
Domain
Metric
Rating
Comments
Metric 15: Statistical Analysis
Medium The method for calculating the SMR is transparently reported as in the study. Further
analysis utilized a matched case-control design for lung cancer cases that were assigned
4 controls matched on same birth year, race, survived into the same year as the case, and
did not subsequently die to a malignancy. There are no explicit modeling assumptions to
meet.
Additional Comments:
Occupational cohort study of 5645 workers in two asbestos cement building materials plants in New Orleans, LA. Subjects were exposed primarily to
chrysotile dust however crocidolite was mentioned as another form of asbestos used in the plants and the study referenced workers exposed to amosite in
one factory. Exposures were only in particle units, with no fiber conversion factors.
Overall Quality Determination
High
* No biomarkers were identified for this evaluation.
Page 603 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 677716 Table: 1 of 1
Study Citation: Wigle, D. T., Mao, Y., Semenciw, R., Smith, M. H., Toft, P. (1986). Contaminants in drinking water and cancer risks in Canadian cities. Canadian Journal
of Public Health 77(1986):335-342.
Tongue, pharynx, esophagus, stomach, large intestine including rectum, pancreas, gastrointestinal, breast, ovary, prostate, kidney, bladder; coronary heart
disease
Cancer/Carcinogenesis: breast, bladder, kidney, prostate, ovary, large intestine including rectum, stomach, esophagus, Tongue, mouth and pharynx, Gas-
trointestinal (ICDA 150-159), pancreas; Cardiovascular: coronary heart disease
Asbestos - Chrysotile (serpentine): 12001-29-5
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s): No linked references.
HERO ID:
677716
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
Metric 5: Exposure Levels
Low The method of quantifying/counting asbestos fibers was not specified. The authors only
cited the sources of the monitoring data. There was no clear description of how exposure
was measured.
Low The range of fibers/L for the different localities was wide. Table III presents two level of
asbestos concentration of localities associated with age-standardized mortality rates of
multiple cancer sites. Even though Table VII presented beta coefficients in the multiple
regression analysis, the asbestos exposure levels were not presented.
Additional Comments: None
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 604 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 626626 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Wortley, P., Vaughan, T. L., Davis, S., Morgan, M. S., Thomas, D. B. (1992). A case-control study of occupational risk factors for laryngeal cancer. British
Journal of Industrial Medicine 49(1992):837-844.
Laryngeal Cancer
Cancer/Carcinogenesis: Laryngeal cancer; Lung/Respiratory: Laryngeal cancer
Asbestos - Not specified: 1332-21-4
No linked references.
626626
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Uninformative Exposure in this study was estimated solely by professional judgment. Job titles and
industry were coded according to the 1980 United States census codes. 505 individual
occupation codes were consolidated into 62 broader categories. A panel of four indus-
trial hygienists from the University of Washington developed the job exposure matrix for
participants. They had created JEMs previously. They classified the exposures examined
into four levels based on likelihood and degree of exposure. There were no quantitative
measures of exposure mentioned in this study.
Medium Four levels of exposure were generated for each individual participating in the study.
These were classified as no, low, medium, and high levels of exposure. These levels
were determined for participants based on the number of years employed in their jobs.
Additional Comments: While the authors were extremely thorough in their description of the steps taken for this study, there were some limitations in terms of being useful for
asbestos studies. There was a lack of power to detect an increase in risk. There were some positives for this study, such as adjusting for smoking and
drinking in their models, which has not been often in some other studies.Overall, information on the measurement of exposure metric (M4) to assess
exposure was limited. Therefore, the overall quality determination (OQD) is rated uninformative.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessment for the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 605 of 606
-------
PUBLIC RELEASE DRAFT - DO NOT CITE OR QUOTE
April 2024
Asbestos Human Health Hazard Epidemology Evaluation hero id: 3080569 Table: 1 of 1
Study Citation:
Health
Outcome:
Target
Organ(s):
Asbestos Fiber
Type(s):
Linked HERO ID(s):
HERO ID:
Yano, E., Wang, Z. M., Wang, X. R., Wang, M. Z., Lan, Y. J. (2001). Cancer mortality among workers exposed to amphibole-free chrysotile asbestos.
American Journal of Epidemiology 154(2001):538-543.
Lung Cancer; All cancers mortality; All cause mortality
Mortality: Lung cancer mortality, All cancers mortality, All cause mortality; Lung/Respiratory: Lung cancer mortality; Cancer/Carcinogenesis: All cancers
mortality, Lung cancer mortality
Asbestos - Chrysotile (serpentine): 12001-29-5
2538846, 3080569
3080569
Domain
Metric
Rating
Comments
Domain 2: Exposure Characterization
Metric 4:
Measurement of Exposure
Metric 5: Exposure Levels
Low This metric is rated Low because authors in this paper do not explicitly cite use of PCM
or TEM for use with the samples used in this analysis. While they mention use of TEM,
they appear to reference chrysotile in general: "The amphibole contamination in com-
mercial chrysotile has been assessed by N. Kohyama (National Institute for Industrial
Health, Kawasaki, Japan, personal communication, 2000). He used the x-ray diffrac-
tion analysis and analytical transmission electron microscopy method, which can detect
amphibole contamination of 0.001 percent or more." The actual measurements used in
analysis are reported to be from "personal samplers that workers wore for 3 days in June
1999." The quantification method is not specified. The authors also mention collecting
dust measurements, but no conversion factors are reported.
Medium The authors reported summary statistics for multiple levels of exposure.
Additional Comments: QC was not completed for metrics other than Metrics 4 and 5 because the study does not have sufficient exposure information to be useful for dose-response
analysis.
* No biomarkers were identified for this evaluation.
** As described in Section Appendix Section A.2. of the Quantitative Approach to the Human Health Assessmentfor the Risk Evaluation for Asbestos Part 2: Supplemental Evaluation
Including Legacy Uses and Associated Disposals of Asbestos, to be considered as being informative for dose-response analysis, metrics 4 and 5 would need metric ratings of Medium
or High. This reference did not satisfy this requirement; therefore a full data quality evaluation was not conducted.
Page 606 of 606
------- |