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www.epa.gov/iris
f/EPA
ANNOTATED REFERENCE OUTLINE
FOR THE TOXICOLOGICAL REVIEW
OF
Hexavalent Chromium
(Chromium IV)
(CAS No. 18540-29-9)
In Support of Summary Information on the
Integrated Risk Information System (IRIS)
12/15/08
[author: insert current date for this draft or Agency completion date (month and year) iffinal]
NOTICE
This document is a [author: insert Agency Review or external review] draft. It has not been
formally released by the U.S. Environmental Protection Agency and should not at this stage be
construed to represent Agency position on this chemical. It is being circulated for review of its
technical accuracy and science policy implications.
U.S. Environmental Protection Agency
Washington, DC

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This document contains citations of references, listed in chapters/sections in which the
references may be cited in an update of the August 1998 Toxicological Review of Hexavalent
Chromium (CAS No. 15840-29-9). The following search strategy was employed to identify the
listed citations.
(1)	Literature searches (PubMed, Toxcenter, Toxline NTIS, TSCATS, and TSACATS 2)
conducted and screened for update of the 2008 Draft ATSDR Toxicological Profile for
Chromium (prepared by SRC in October 2008) were reviewed for relevant literature.
Searches were conducted for the period from 1999 through February 2008.
(2)	Updated literature searches [PubMed, Toxline (with NTIS), DART, CCRIS, HSDB,
GENTOX, RTECS, TSCATS, ToxCenter (STN Biosis & Chem Abs)] were conducted
for the period of January 2008 to November 7, 2008 to identify new literature published
after February 2008. Searches were conducted for the following CASRNs: 1333-82-0,
7758-97-6, 7775-11-3, 7778-50-9, 7788-98-9, 7789-00-6, 7789-06-2, 7789-09-5, 7789-
12-0, 13530-65-9, 13765-19-0, and 18540-29-9.
(3)	Bibliographies of the 1998 IRIS Toxicological Review of Hexavalent Chromium and
the 2008 ATSDR Draft Toxicological Profile for Chromium were reviewed to identify
literature published prior to 1999.
The reference file that accompanies this document is in "Endnote" format per agreement
with EPA (December 2, 2008 teleconference with Ted Burner of EPA and Peter McClure and
Julie Klotzbach of SRC). The Endnote file contains all citations (with linked pdf files) listed in
the following annotated outline.
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REVIEWS
ACGIH (American Conference of Governmental Industrial Hygienists) (2007) Chromium. In:
Threshold limit values for chemical substances and physical agents and biological exposure
indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists; pp. 20.
Baetjer, AM. (1950) Pulmonary carcinoma in chromate workers. I. A review of the literature and
report of cases. Arch Ind Hyg Occup Med 2(5):487-504.
Bagdon, RE; Hazen, RE. (1991) Skin permeation and cutaneous hypersensitivity as a basis for
making risk assessments of chromium as a soil contaminant. Environ Health Perspect 92:111-
119.
Barceloux, DG. (1999) Chromium. J Toxicol Clin Toxicol 37(2): 173-194.
Chen, F; Shi, X. (2002) Intracellular signal transduction of cells in response to carcinogenic
metals. Crit Rev Oncol Hematol 42(1): 105-121.
Chiu, A; Katz, AJ; Beaubier, J; et al. (2004) Genetic and cellular mechanisms in chromium and
nickel carcinogenesis considering epidemiologic findings. Mol Cell Biochem 255(1-2): 181-194.
Codd, R; Dillon, CT; Levina, A; et al. (2001) Studies on the genotoxicity of chromium: From the
test tube to the cell. Coord Chem Rev 216-217:537-582.
Cohen, MD; Kargacin, B; Klein, CB; et al. (1993) Mechanisms of chromium carcinogenicity and
toxicity. Crit Rev Toxicol 23(3):255-281.
Costa, M. (1997) Toxicity and carcinogenicity of Cr(VI) in animal models and humans. Crit Rev
Toxicol 27(5):431-442.
Costa, M. (1998) Carcinogenic metals. Sci Prog 81 (Pt 4):329-339.
Costa, M. (2003) Potential hazards of hexavalent chromate in our drinking water. Toxicol Appl
Pharmacol 188(1): 1-5.
Costa, M; Klein, CB. (2006) Toxicity and carcinogenicity of chromium compounds in humans.
Crit Rev Toxicol 36(2): 155-163.
De Flora, S. (2000) Threshold mechanisms and site specificity in chromium(VI) carcinogenesis.
Carcinogenesis 21(4):533-541.
De Flora, S; Bagnasco, M; Serra, D; et al. (1990) Genotoxicity of chromium compounds. A
review. MutatRes 238(2):99-172.
Desoize, B. (2002) Cancer and metals and metal compounds: Part I-carcinogenesis. Crit Rev
Oncol Hematol 42(1): 1-3.
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Goldbohm, RA; Tielemans, EL; Heederik, D; et al. (2006) Risk estimation for carcinogens based
on epidemiological data: a structured approach, illustrated by an example on chromium. Regul
Toxicol Pharmacol 44(3):294-310.
IARC (International Agency for Research on Cancer). (2008) Agents reviewed by the IARC
monographs: Volumes 1-99. Lyon, France: International Agency for Research on Cancer.
http://monographs.iarc.fr/ENG/Classification/index.php.
Langard, S. (1988) Chromium carcinogenicity; a review of experimental animal data. Sci Total
Environ 71(3):341-350.
Langard, S. (1990) One hundred years of chromium and cancer: a review of epidemiological
evidence and selected case reports. Am J Ind Med 17(2):189-215.
Leonard, A; Lauwerys, RR. (1980) Carcinogenicity and mutagenicity of chromium. Mutat Res
76(3):227-239.
Levina, A; Lay, PA. (2005) Mechanistic studies of relevance to the biological activities of
chromium. Coord Chem Rev 249(3-4):281-298.
NIOSH (National Institute of Occupational Safety and Health). (1994) Elements in blood or
tissue. Method: 8005. In: NIOSH manual of analytical methods. 4th ed. Cincinnati, OH:
Department of Health and Human Services, National Institute of Occupational Safety and
Health. DHHS publication no. 94-113.
NIOSH (National Institute of Occupational Safety and Health). (1994) Metals in urine. Method:
8310. In: NIOSH manual of analytical methods. 4th ed. Cincinnati, OH: Department of Health
and Human Services, National Institute of Occupational Safety and Health. DHHS publication
no. 94-113.
NIOSH (National Institute of Occupational Safety and Health). (1994) Chromium and chromium
compounds, as Cr. Method: 7024. In: NIOSH manual of analytical methods. 4th ed.
Cincinnati, OH: Department of Health and Human Services, National Institute of Occupational
Safety and Health. DHHS publication no. 94-113.
NIOSH (National Institute of Occupational Safety and Health). (1994) Elements by ICP.
Method: 7300. In: Niosh manual of analytical methods. 4th ed. Cincinnati, OH: Department
of Health and Human Services, National Institute of Occupational Safety and Health. DHHS
publication no. 94-113.
NIOSH (National Institute of Occupational Safety and Health). (1994) Chromium, hexavalent.
Method: 7600. In: Niosh manual of analytical methods. 4th ed. Cincinnati, OH: Department
of Health and Human Services, National Institute of Occupational Safety and Health. DHHS
publication no. 94-113Health.
NIOSH (National Institute of Occupational Safety and Health). (1994) Chromium, hexavalent.
Method: 7604. In: NIOSH manual of analytical methods. 4th ed. Cincinnati, OH: Department
of Health and Human Services, National Institute of Occupational Safety and Health. DHHS
publication no. 94-113.
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NIOSH (National Institute of Occupational Safety and Health). (2005) Chromium. In: NIOSH
pocket guide to chemical hazards. Atlanta, GA: National Institute for Occupational Safety and
Health, Centers for Disease Control and Prevention.
NIOSH (National Institute of Occupational Safety and Health). (2008) International chemical
safety cards. U.S. National Version. National Institute for Occupational Safety and Health.
Norseth, T. (1981) The carcinogenicity of chromium. Environ Health Perspect 40:121-130.
NTP (National Toxicology Program). (2005) Report on carcinogens. 11th edition. Research
Triangle Park, NC: U.S. Department of Health and Human Services, Public Health Service,
http ://ntp-server. niehs. nih. gov/ntp/roc/toc 11. html.
O'Brien, TJ; Ceryak, S; Patierno, SR. (2003) Complexities of chromium carcinogenesis: role of
cellular response, repair and recovery mechanisms. Mutat Res 533(l-2):3-36.
OSHA (Occupational Safety and Health Administration). (1998) Air contaminants; final rule.
U.S. Department of labor. Occupational safety and health administration. Fed Regist 54:2930.
OSHA (Occupational Safety and Health Administration). (2007) Chromium (VI). Occupational
Safety and Health Administration. Code of Federal Regulations 29 CFR 1910.26.
OSHA (Occupational Safety and Health Administration). (2007) Chromium (VI). Code of
Federal Regulations. Occupational Safety and Health Administration 29 CFR 1915.1026.
OSHA (Occupational Safety and Health Administration). (2007) Safety and health regulations
for construction. Chromium (VI). Occupational Safety and Health Administration. Code of
Federal Regulations 29 CFR 1926.1126.
Paustenbach, DJ; Sheehan, PJ; Paull, JM; et al. (1992) Review of the allergic contact dermatitis
hazard posed by chromium-contaminated soil: identifying a "safe" concentration. J Toxicol
Environ Health 37(1): 177-207.
Paustenbach, DJ; Finley, BL; Mowat, FS; et al. (2003) Human health risk and exposure
assessment of chromium (VI) in tap water. J Toxicol Environ Health A 66(14): 1295-1339.
Pellerin, C; Booker, SM. (2000) Reflections on hexavalent chromium: health hazards of an
industrial heavyweight. Environ Health Perspect 108(9):A402-407.
Polak, L. (1983) Immunology of chromium. In: Chromium: metabolism and toxicity. Burrows,
D, ed. Boca Raton, FL: CRC Press, pp. 51-135.
Post, GB; Stern, AH. (2006) Comments on article "Toxicity and carcinogenicity of chromium
compounds in humans" by Costa and Klein. Crit Rev Toxicol 36(9):777-778; discussion 779.
Proctor, DM; Otani, JM; Finley, BL; et al. (2002) Is hexavalent chromium carcinogenic via
ingestion? A weight-of-evidence review. J Toxicol Environ Health A 65(10):701-746.
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Pulido, MD; Parrish, AR. (2003) Metal-induced apoptosis: mechanisms. Mutat Res 533(1-
2):227-241.
Salnikow, K; Zhitkovich, A. (2008) Genetic and epigenetic mechanisms in metal carcinogenesis
and cocarcinogenesis: nickel, arsenic, and chromium. Chem Res Toxicol 21(l):28-44.
Sedman, RM; Beaumont, J; McDonald, T; et al. (2006) Review of the evidence regarding the
carcinogenicity of hexavalent chromium in drinking water. J Environ Sci Health Part C Environ
Carcinogen Rev 24(1): 155-182.
Shrivastava, R; Upreti, RK; Seth, PK; et al. (2002) Effects of chromium on the immune system.
FEMS Immunol Med Microbiol 34(1): 1-7.
Singh, J; Carlisle, DL; Pritchard, DE; et al. (1998) Chromium-induced genotoxicity and
apoptosis: relationship to chromium carcinogenesis (review). Oncol Rep 5(6): 1307-1318.
Smith, AH. (2008) Hexavalent chromium, yellow water, and cancer: a convoluted saga.
Epidemiology 19(l):24-26.
Sunderman, JW, Jr. (1976) A review of the carcinogenicities of nickel, chromium and arsenic
compounds in man and animals. Prev Med 5(2):279-294.
Watanabe, M; Takayama, Y; Koike, M; et al. (1985) In vivo clastogenicity of lead chromate in
mice. Tohoku J Exp Med 146(3):373-374.
WHO (World Health Organization). (1988) Chromium. Environmental health criteria 61.
Geneva: United Nations Environment Programme. International Labour Organisation. World
Health Organization, http://www.inchem.org/documents/ehc/ehc/ehc61 .htm.
Wise, SS; Holmes, AL; Wise, JP, Sr. (2008) Hexavalent chromium-induced DNA damage and
repair mechanisms. Rev Environ Health 23(l):39-57.
Yao, H; Guo, L; Jiang, BH; et al. (2008) Oxidative stress and chromium(VI) carcinogenesis. J
Environ Pathol Toxicol Oncol 27(2):77-88.
Zhitkovich, A. (2005) Importance of chromium-DNA adducts in mutagenicity and toxicity of
chromium(VI). Chem Res Toxicol 18(1):3-11.
2. CHEMICAL AND PHYSICAL INFORMATION
Alimonti, A; Petrucci, F; Krachler, M; et al. (2000) Reference values for chromium, nickel and
vanadium in urine of yougsters from the urban area of Rome. J Environ Mo nit 2(4):351-354.
Ashley, K; Howe, AM; Demange, M; et al. (2003) Sampling and analysis considerations for the
determination of hexavalent chromium in workplace air. J Environ Monit 5(5):707-716.
Barceloux, DG. (1999) Chromium. Clin Toxicol 37(2): 173-194.
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Blade, LM; Yencken, MS; Wallace, ME; et al. (2007) Hexavalent chromium exposures and
exposure control technologies in American enterpise: results of NIOSH field research study. J
Occup Environ Hyg 4(8):596-618.
Hartford, WH. (1979). Chromium compounds. In: Grayson M, ed. Kirk-Othmer encyclopedia of
chemical technology. 3rd ed. Vol. 6. New York, NY: John Wiley and Sons; pp. 82-120.
Hemminki, K; Vainio, H. (1984) Human exposure to potentially carcinogenic compounds. IARC
Scientific Publ No. 59:37-45.
Johnson, J; Schewel, L; Graedel, TE. (2006) The contemporary anthropogenic chromium cycle.
Environ Sci Technol 40:7060-7069.
Kumpulainen, JT; Wolf, WR; Veillon, C; et al. (1979). Determination of chromium in selected
United States diets. J Agric Food Chem 27(3):490-494.
Lide DR. (1998) Chromium. In: Lide DR, ed. CRC handbook of chemistry and physics. 79th ed.
Boca Raton, FL: CRC Press; pp. 4-8.
Loyaux-Lawniczak, S; Lecomte, P; Ehrhardt, J. (2001). Behavior of hexavalent chromium in a
polluted groundwater: redox processes and immobilization in soils. Environ Sci Technol
35:1350-1357.
O'Neil, MJ; Heckelman, PE; Koch, CB; et al. eds. (2006) The Merck index. 14th ed. Whitehouse
Station, NJ: Merck & Co., Inc.; pp. 370, 372.
Papp JF, Lipin BR. (2001) Chromium and chromium alloys. In: Kirk-Othmer encyclopedia of
chemical technology. John Wiley & Sons, Inc; pp. 468-526.
http://mrw.interscience.wiley.com/emrw/9780471238966/kirk/article/chrowest.a01/current/pdf.
(accessed May 21, 2008).
Pellerin C, Booker SM. (2000) Reflections on hexavalent chrom. Health hazards of an industrial
heavyweight. Environ Health Perspect 108(9): A403-A407.
Shanker, AK; Cervantes, C; Loza-Tavera, H; et al. (2005) Chromium toxicity in plants. Environ
Int 31: 739-753.
U.S. EPA (Environmental Protection Agency). (1984). Health assessment document for
chromium. Research Triangle Park, NC: Environmental Assessment and Criteria Office, U.S.
Environmental Protection Agency. EPA600883014F.
Westbrook, JH. (1979) Chromium and chromium alloys. In: Grayson M, ed. Kirk-Othmer
encyclopedia of chemical technology, Vol. 6, 3rd ed. New York, NY: John Wiley and Sons; pp.
54-82
WHO (World Health Organization). (2003) Chromium in drinking water. Background document
for development of WHO guidelines for drinking water quality. Geneva: World Health
Organization.
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3. TOXICOKINETICS
3.1. ABSORPTION
Baetjer, AM; Damron, C; Budacz, V. (1959) The distribution and retention of chromium in men
and animals. AMA Arch Ind Health 20:136-150.
Bagdon, RE; Hazen, RE. (1991) Skin permeation and cutaneous hypersensitivity as a basis for
making risk assessments of chromium as a soil contaminant. Environ Health Perspect 92:111-
119.
Baranowska-Dutkiewicz, B. (1981) Absorption of hexavalent chromium by skin in man. Arch
Toxicol 47(l):47-50.
Bragt, PC; van Dura, EA. (1983) Toxicokinetics of hexavalent chromium in the rat after
intratracheal administration of chromates of different solubilities. Ann Occup Hyg 27(3):315-
322.
Cavalleri, A; Minoia, C. (1985) [Serum and erythrocyte chromium distribution and urinary
elimination in persons occupationally exposed to chromium (VI) and chromium (III)]. G Ital
Med Lav 7(l):35-38.
Chen, NS; Tsai, A; Dyer, IA. (1973) Effect of chelating agents on chromium absorption in rats.
JNutr 103(8): 1182-1186.
Clapp, TC; Umbreit, TH; Meeker, RJ; et al. (1991) Bioavailability of lead and chromium from
encapsulated pigment materials. Bull Environ Contam Toxicol 46(2):271-275.
Cohen, MD; Sisco, M; Baker, K; et al. (2003) Impact of coexposure to ozone on the carcinogenic
potential of inhaled chromium. 1. effects on retention and on extra- and intracellular distribution.
J Toxicol Environ Health A 66(l):39-55.
Corbett, GE; Finley, BL; Paustenbach, DJ; et al. (1997) Systemic uptake of chromium in human
volunteers following dermal contact with hexavalent chromium (22 mg/L). J Expo Anal Environ
Epidemiol 7(2): 179-189.
De Flora, S; Badolati, GS; Serra, D; et al. (1987) Circadian reduction of chromium in the gastric
environment. MutatRes 192(3): 169-174.
Donaldson, RM, Jr.; Barreras, RF. (1966) Intestinal absorption of trace quantities of chromium.
J Lab Clin Med 68(3):484-493.
Edel, J; Sabbioni, E. (1985) Pathways of Cr (III) and Cr (VI) in the rat after intratracheal
administration. Hum Toxicol 4(4):409-416.
Febel, H; Szegedi, B; Huszar, S. (2001) Absorption of inorganic, trivalent and hexavalent
chromium following oral and intrajejunal doses in rats. Acta Vet Hung 49(2):203-209.
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Finley, BL; Kerger, BD; Katona, MW; et al. (1997) Human ingestion of chromium (VI) in
drinking water: pharmacokinetics following repeated exposure. Toxicol Appl Pharmacol
142(1): 151-159.
Finley, BL; Scott, PK; Norton, RL; et al. (1996) Urinary chromium concentrations in humans
following ingestion of safe doses of hexavalent and trivalent chromium: implications for
biomonitoring. J Toxicol Environ Health 48(5):479-499.
Garcia, E; Cabrera, C; Lorenzo, ML; et al. (2001) Estimation of chromium bioavailability from
the diet by an in vitro method. Food Addit Contam 18(7):601-606.
Henderson, RF; Rebar, AH; Pickrell, JA; et al. (1979) Early damage indicators in the lung. III.
Biochemical and cytological response of the lung to inhaled metals salts. Toxicol Appl
Pharmacol 50(1): 123-136.
Kalliomaki, PL; Aitio, A; Hyvarinen, HK; et al. (1986) Lung clearance, transportation, and
excretion of metals in rats after intratracheal instillation of activated welding fumes. In: Stern,
RM; ed. International conference on health hazards and biological effects of welding fumes and
gases, International Congress Series Vol. 676. New York, NY: Excepta Medica, Elsevier
Science Publ Co.; pp. 345-348.
Kargacin, B; Squibb, KS; Cosentino, S; et al. (1993) Comparison of the uptake and distribution
of chromate in rats and mice. Biol Trace Elem Res 36:307-318.
Kerger, BD; Finley, BL; Corbett, GE; et al. (1997) Ingestion of chromium(VI) in drinking water
by human volunteers: absorption, distribution, and excretion of single and repeated doses. J
Toxicol Environ Health 50(l):67-95.
Kerger, BD; Paustenbach, DJ; Corbett, GE; et al. (1996) Absorption and elimination of trivalent
and hexavalent chromium in humans following ingestion of a bolus dose in drinking water.
Toxicol Appl Pharmacol 141(1):145-158.
Langard, S; Gundersen, N; Tsalev, DL; et al. (1978) Whole blood chromium level and chromium
excretion in the rat after zinc chromate inhalation. Acta Pharmacol Toxicol (Copenh) 42(2): 142-
149.
Liden, S; Lundberg, E. (1979) Penetration of chromium in intact human skin in vivo. J Invest
Dermatol 72(l):42-45.
MacKenzie, RD; Anwar, RA; Byerrum, RU; et al. (1959) Absorption and distribution of Cr51 in
the albino rat. Arch Biochem Biophys 79:200-250.
Minoia, C; Cavalleri, A. (1988) Chromium in urine, serum and red blood cells in the biological
monitoring of workers exposed to different chromium valency states. Sci Total Environ
71(3):323-327.
Paustenbach, DJ; Hays, SM; Brien, BA; et al. (1996) Observation of steady state in blood and
urine following human ingestion of hexavalent chromium in drinking water. J Toxicol Environ
Health 49(5):453-461.
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Perrault, G; Dufresne, A; Strati, G; et al. (1995) Physico-chemical fate of chromium compounds
in the sheep lung model. J Toxicol Environ Health 44(2):247-262.
Sayato, Y; Nakamuro, K; Matsui, S; et al. (1980) Metabolic fate of chromium compounds. I.
Comparative behavior of chromium in rat administered with Na251CrC>4 and 51CrCl3. J
Pharmacobiodyn 3(1): 17-23.
Spruit, D; vanNeer, FCJ. (1966) Penetration rate of Cr(III) and Cr(VI). Dermatologica 132:179-
182.
Suzuki, Y; Homma, K; Minami, M; et al. (1984) Distribution of chromium in rats exposed to
hexavalent chromium and trivalent chromium aerosols. Ind Health 22(4):261-277.
Tossavainen, A; Nurminen, M; Mutanen, P; et al. (1980) Application of mathematical modelling
for assessing the biological half-times of chromium and nickel in field studies. Br J Ind Med
37(3):285-291.
Wiegand, HJ; Ottenwalder, H; Bolt, HM. (1987) Bioavailability and metabolism of hexavalent
chromium compounds. Toxicol Environ Chem 14:263-275.
Witmer, CM; Harris, R; Shupack, SI. (1991) Oral bioavailability of chromium from a specific
site. Environ Health Perspect 92:105-110.
Witmer, CM; Park, HS; Shupack, SI. (1989) Mutagenicity and disposition of chromium. Sci
Total Environ 86(1-2): 131-148.
Yamaguchi, S; Sano, K; Shimojo, N. (1983) On the biological half-time of hexavalent chromium
in rats. Ind Health 21(l):25-34.
3.2. DISTRIBUTION
Aaseth, J; Alexander, J; Norseth, T. (1982) Uptake of 51Cr-chromate by human erythrocytes-a
role of glutathione. Acta Pharmacol Toxicol (Copenh) 50(4):310-315.
Baetjer, AM; Damron, C; Budacz, V. (1959) The distribution and retention of chromium in men
and animals. AMA Arch Ind Health 20:136-150.
Baranowski, J; Norska-Borowka, I; Baranowska, I. (2002) Determination of heavy metals in the
bones and livers of deceased neonatal humans. Bull Environ Contam Toxicol 69(1): 1-7.
Behari, JR; Tandon, SK. (1980) Chelation in metal intoxication. VIII. Removal of chromium
from organs of potassium chromate administered rats. Clin Toxicol 16(l):33-40.
Berndt, WO. (1976) Renal chromium accumulation and its relationship to chromium-induced
nephrotoxicity. J Toxicol Environ Health l(3):449-459.
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Bragt, PC; van Dura, EA. (1983) Toxicokinetics of hexavalent chromium in the rat after
intratracheal administration of chromates of different solubilities. Ann Occup Hyg 27(3):315-
322.
Bryson, WG; Goodall, CM. (1983) Differential toxicity and clearance kinetics of chromium(III)
or (VI) in mice. Carcinogenesis 4(12): 1535-1539.
Cavalleri, A; Minoia, C. (1985) [Serum and erythrocyte chromium distribution and urinary
elimination in persons occupationally exposed to chromium (VI) and chromium (III)]. G Ital
Med Lav 7(l):35-38.
Cikrt, M; Bencko, V. (1979) Biliary excretion and distribution of 51Cr(III) and 51Cr(VI) in rats.
J Hyg Epidemiol Microbiol Immunol 23:241-246.
Cohen, MD; Sisco, M; Baker, K; et al. (2003) Impact of coexposure to ozone on the carcinogenic
potential of inhaled chromium. 1. effects on retention and on extra- and intracellular distribution.
J Toxicol Environ Health A 66(l):39-55.
Coogan, TP; Motz, J; Snyder, CA; et al. (1991) Differential DNA-protein crosslinking in
lymphocytes and liver following chronic drinking water exposure of rats to potassium chromate.
Toxicol Appl Pharmacol 109(l):60-72.
Coogan, TP; Squibb, KS; Motz, J; et al. (1991) Distribution of chromium within cells of the
blood. Toxicol Appl Pharmacol 108( 1): 157-166.
Danielsson, BRG; Hassoun, E; Dencker, L. (1982) Embryotoxicity of chromium: distribution in
pregnant mice and effects on embryonic cells in vitro. Arch Toxicol 51:233-245.
Edel, J; Sabbioni, E. (1985) Pathways of Cr (III) and Cr (VI) in the rat after intratracheal
administration. Hum Toxicol 4(4):409-416.
Febel, H; Szegedi, B; Huszar, S. (2001) Absorption of inorganic, trivalent and hexavalent
chromium following oral and intrajejunal doses in rats. Acta Vet Hung 49(2):203-209.
Finley, BL; Kerger, BD; Katona, MW; et al. (1997) Human ingestion of chromium (VI) in
drinking water: pharmacokinetics following repeated exposure. Toxicol Appl Pharmacol
142(1): 151-159.
Gao, M; Levy, LS; Braithwaite, RA; et al. (1993) Monitoring of total chromium in rat fluids and
lymphocytes following intratracheal administration of soluble trivalent or hexavalent chromium
compounds. Hum Exp Toxicol 12(5):377-382.
Gray, SJ; Sterling, K. (1950) The tagging of red cells and plasma proteins with radioactive
chromium. J Clin Invest 29(12): 1604-1613.
Gregus, Z; Klaassen, CD. (1986) Disposition of metals in rats: a comparative study of fecal,
urinary, and biliary excretion and tissue distribution of eighteen metals. Toxicol Appl Pharmacol
85(l):24-38.
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Iijima, S; Matsumoto, N; Lu, CC. (1983) Transfer of chromic chloride to embryonic mice and
changes in the embryonic mouse neuroepithelium. Toxicology 26(3-4):257-265.
Iyengar, V; Woittiez, J. (1988) Trace elements in human clinical specimens: evaluation of
literature data to identify reference values. Clin Chem 34(3):474-481.
Kitagawa, S; Seki, H; Kametani, F; et al. (1982) Uptake of hexavalent chromium by bovine
erythrocytes and its interaction with cytoplasmic components; the role of glutathione. Chem
Biol Interact 40(3):265-274.
Langard, S; Gundersen, N; Tsalev, DL; et al. (1978) Whole blood chromium level and chromium
excretion in the rat after zinc chromate inhalation. Acta Pharmacol Toxicol (Copenh) 42(2): 142-
149.
Lukanova, A; Toniolo, P; Zhitkovich, A; et al. (1996) Occupational exposure to Cr(VI):
comparison between chromium levels in lymphocytes, erythrocytes, and urine. Int Arch Occup
Environ Health 69(l):39-44.
MacKenzie, RD; Anwar, RA; Byerrum, RU; et al. (1959) Absorption and distribution of Cr51 in
the albino rat. Arch Biochem Biophys 79:200-250.
Matsumoto, N; Iijima, S; Katsunuma, H. (1976) Placental transfer of chromic chloride and its
teratogenic potential in embryonic mice. J Toxicol Sci 2:1-13.
Minoia, C; Cavalleri, A. (1988) Chromium in urine, serum and red blood cells in the biological
monitoring of workers exposed to different chromium valency states. Sci Total Environ
71(3):323-327.
Mutti, A; Cavatorta, A; Borghi, L; et al. (1979) Distribution and urinary excretion of chromium.
Studies on rats after administration of single and repeated doses of potassium dichromate. Med
Lav 70(3):171-179.
NTP (National Toxicology Program). (2007) NTP technical report on the toxicity studies of
sodium dichromate dihydrate (CAS No. 7789-12-0) administered in drinking water to male and
female F344/N rats and B6C3F1 mice and male BALB/c and a/w3-C57BL/6 mice. Washington,
DC: National Toxicology Program. Toxicity Report Series Number 72.
http://ntp.niehs.nih.gov/ntp/htdocs/ST_rpts/TOX72.pdf.
NTP (National Toxicology Program). (2008) NTP technical report on the toxicology and
carcinogenesis studies of sodium dichromate dihydrate (CAS No. 7789-12-0) in F344/N rats and
B6C3F1 mice (drinking water studies). Washington, DC: National Toxicology Program; NTP
TR 546. http://ntp.niehs.nih.gov/files/546_web_FINAL.pdf.
Paustenbach, DJ; Hays, SM; Brien, BA; et al. (1996) Observation of steady state in blood and
urine following human ingestion of hexavalent chromium in drinking water. J Toxicol Environ
Health 49(5):453-461.
Richelmi, P; Baldi, C; Minoia, C. (1984) Blood levels of hexavalent chromium in rats. "In vitro"
and "in vivo" experiments. Int J Environ Anal Chem 17(3 -4): 181 -186.
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Saner, G; Yuzbasiyan, V; Cigdem, S. (1984) Hair chromium concentration and chromium
excretion in tannery workers. Br J Ind Med 41(2):263-266.
Saxena, DK; Murthy, RC; Jain, VK; et al. (1990) Fetoplacental-maternal uptake of hexavalent
chromium administered orally in rats and mice. Bull Environ Contam Toxicol 45(3):430-435.
Sayato, Y; Nakamuro, K; Matsui, S; et al. (1980) Metabolic fate of chromium compounds. I.
Comparative behavior of chromium in rat administered with Na251CrC>4 and 51CrCl3. J
Pharmacobiodyn 3(1): 17-23.
Suzuki, Y; Homma, K; Minami, M; et al. (1984) Distribution of chromium in rats exposed to
hexavalent chromium and trivalent chromium aerosols. Ind Health 22(4):261-277.
Tandon, SK; Behari, JR; Kachru, DN. (1979) Distribution of chromium in poisoned rats.
Toxicology 13(l):29-34.
Weber, H. (1983) Long-term study of the distribution of soluble chromate-51 in the rat after a
single intratracheal administration. J Toxicol Environ Health 11(4-6):749-764.
Wiegand, HJ; Ottenwalder, H; Bolt, HM. (1985) Fast uptake kinetics in vitro of 5 lCr (VI) by red
blood cells of man and rat. Arch Toxicol 57(1):31-34.
Wiegand, HJ; Ottenwalder, H; Bolt, HM. (1987) Bioavailability and metabolism of hexavalent
chromium compounds. Toxicol Environ Chem 14:263-275.
Witmer, CM; Harris, R. (1991) Chromium content of bone after oral and intraperitoneal (IP)
administration of chromium (VI) to rats (Abstract). Toxicologist 11:41.
Witmer, CM; Harris, R; Shupack, SI. (1991) Oral bioavailability of chromium from a specific
site. Environ Health Perspect 92:105-110.
Witmer, CM; Park, HS; Shupack, SI. (1989) Mutagenicity and disposition of chromium. Sci
Total Environ 86(1-2): 131-148.
Yamaguchi, S; Sano, K; Shimojo, N. (1983) On the biological half-time of hexavalent chromium
in rats. Ind Health 21(l):25-34.
3.3. METABOLISM
Aaseth, J; Alexander, J; Norseth, T. (1982) Uptake of 51Cr-chromate by human erythrocytes-a
role of glutathione. Acta Pharmacol Toxicol (Copenh) 50(4):310-315.
Aiyar, J; Berkovits, HJ; Floyd, RA; et al. (1991) Reaction of chromium(VI) with glutathione or
with hydrogen peroxide: identification of reactive intermediates and their role in chromium(VI)-
induced DNA damage. Environ Health Perspect 92:53-62.
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Aiyar, J; Borges, K; Floyd, RA; et al. (1989) Role of chromium(V), glutathione thiyl radical and
hydroxyl radical intermediates in chromium(VI)-induced DNA damage. Toxicol Environ Chem
22:135-148.
Borthiry, GR; Antholine, WE; Myers, JM; et al. (2008) Reductive activation of hexavalent
chromium by human lung epithelial cells: generation of Cr(V) and Cr(V)-thiol species. J Inorg
Biochem 102(7): 1449-1462.
Bragt, PC; van Dura, EA. (1983) Toxicokinetics of hexavalent chromium in the rat after
intratracheal administration of chromates of different solubilities. Ann Occup Hyg 27(3):315-
322.
Chen, F; Ye, J; Zhang, X; et al. (1997) One-electron reduction of chromium(VI) by a-lipoic acid
and related hydroxyl radical generation, dG hydroxylation and nuclear transcription factor-icB
activation. Arch Biochem Biophys 338(2): 165-172.
Corbett, GE; Dodge, DG; O'Flaherty, E; et al. (1998) In vitro reduction kinetics of hexavalent
chromium in human blood. EnvironRes 78(1):7-11.
De Flora, S; Badolati, GS; Serra, D; et al. (1987) Circadian reduction of chromium in the gastric
environment. MutatRes 192(3): 169-174.
De Flora, S; Bennicelli, C; Zanacchi, P; et al. (1984) Metabolic activation and deactivation of
mutagens by preparations of human lung parenchyma and bronchial tree. Mutat Res 139(1):9-
14.
De Flora, S; Camoirano, A; Bagnasco, M; et al. (1997) Estimates of the chromium(VI) reducing
capacity in human body compartments as a mechanism for attenuating its potential toxicity and
carcinogenicity. Carcinogenesis 18(3):531-537.
Edel, J; Sabbioni, E. (1985) Pathways of Cr (III) and Cr (VI) in the rat after intratracheal
administration. Hum Toxicol 4(4):409-416.
Gruber, JE; Jennette, KW. (1978) Metabolism of the carcinogen chromate by rat liver
microsomes. Biochem Biophys Res Commun 82(2):700-706.
Jannetto, PJ; Antholine, WE; Myers, CR. (2001) Cytochrome b(5) plays a key role in human
microsomal chromium(VI) reduction. Toxicology 159(3):119-133.
Jennette, KW. (1982) Microsomal reduction of the carcinogen chromate produces chromium(V).
J Am Chem Soc 104:874-875.
Kortenkamp, A; Casadevall, M; Da Cruz Fresco, P. (1996) The reductive conversion of the
carcinogen chromium (VI) and its role in the formation of DNA lesions. Ann Clin Lab Sci
26(2): 160-175.
Liu, KJ; Mader, K; Shi, X; et al. (1997) Reduction of carcinogenic chromium(VI) on the skin of
living rats. Magn Reson Med 38(4):524-526.
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Myers, CR; Myers, JM. (1998) Iron stimulates the rate of reduction of hexavalent chromium by
human microsomes. Carcinogenesis 19(6): 1029-1038.
Ning, J; Grant, MH. (2000) The role of reduced glutathione and glutathione reductase in the
cytotoxicity of chromium (VI) in osteoblasts. Toxicol In Vitro 14(4):329-335.
Petiilli, FL; DeFlora, S. (1978) Metabolic deactivation of hexavalent chromium mutagenicity.
MutatRes 54:139-147.
Petiilli, FL; Romano, M; Bennicelli, C; et al. (1986) Metabolic reduction and detoxification of
hexavalent chromium. In: Serrone, DM; ed. Chromium symposium 1986: an update.
Pittsburgh, PA: Industrial Health Foundation Inc.; pp. 112-130.
Petiilli, FL; Rossi, GA; Camoirano, A; et al. (1986) Metabolic reduction of chromium by
alveolar macrophages and its relationships to cigarette smoke. J Clin Invest 77(6): 1917-1924.
Pratt, PF; Myers, CR. (1993) Enzymatic reduction of chromium(VI) by human hepatic
microsomes. Carcinogenesis 14(10):2051-2057.
Sayato, Y; Nakamuro, K; Matsui, S; et al. (1980) Metabolic fate of chromium compounds. I.
Comparative behavior of chromium in rat administered with Na251CrC>4 and 51CrCl3. J
Pharmacobiodyn 3(1): 17-23.
Suzuki, Y; Fukuda, K. (1990) Reduction of hexavalent chromium by ascorbic acid and
glutathione with special reference to the rat lung. Arch Toxicol 64(3): 169-176.
Visek, WJ; Whitney, IB; Kuhn, USG, III; et al. (1953) Metabolism of CR-51 by animals as
influenced by chemical state. Proc Soc Exp Biol Med 84:610-615.
Wiegand, HJ; Ottenwalder, H; Bolt, HM. (1984) The reduction of chromium (VI) to chromium
(III) by glutathione: an intracellular redox pathway in the metabolism of the carcinogen
chromate. Toxicology 33(3-4):341-348.
3.4. ELIMINATION
Baetjer, AM; Damron, C; Budacz, V. (1959) The distribution and retention of chromium in men
and animals. AMA Arch Ind Health 20:136-150.
Bragt, PC; van Dura, EA. (1983) Toxicokinetics of hexavalent chromium in the rat after
intratracheal administration of chromates of different solubilities. Ann Occup Hyg 27(3):315-
322.
Bryson, WG; Goodall, CM. (1983) Differential toxicity and clearance kinetics of chromium(III)
or (VI) in mice. Carcinogenesis 4(12): 1535-1539.
Casey, CE; Hambidge, KM. (1984) Chromium in human milk from American mothers. Br J
Nutr 52(l):73-77.
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Cavalleri, A; Minoia, C. (1985) [Serum and erythrocyte chromium distribution and urinary
elimination in persons occupationally exposed to chromium (VI) and chromium (III)]. G Ital
Med Lav 7(l):35-38.
Cavalleri, A; Minoia, C; Richelmi, P; et al. (1985) Determination of total and hexavalent
chromium in bile after intravenous administration of potassium dichromate in rats. Environ Res
37(2):490-496.
Cikrt, M; Bencko, V. (1979) Biliary excretion and distribution of 51Cr(III) and 51Cr(VI) in rats.
J Hyg Epidemiol Microbiol Immunol 23:241-246.
Donaldson, RM, Jr.; Barreras, RF. (1966) Intestinal absorption of trace quantities of chromium.
J Lab Clin Med 68(3):484-493.
Edel, J; Sabbioni, E. (1985) Pathways of Cr (III) and Cr (VI) in the rat after intratracheal
administration. Hum Toxicol 4(4):409-416.
Febel, H; Szegedi, B; Huszar, S. (2001) Absorption of inorganic, trivalent and hexavalent
chromium following oral and intrajejunal doses in rats. Acta Vet Hung 49(2):203-209.
Finley, BL; Kerger, BD; Katona, MW; et al. (1997) Human ingestion of chromium (VI) in
drinking water: pharmacokinetics following repeated exposure. Toxicol Appl Pharmacol
142(1): 151-159.
Finley, BL; Scott, PK; Norton, RL; et al. (1996) Urinary chromium concentrations in humans
following ingestion of safe doses of hexavalent and trivalent chromium: implications for
biomonitoring. J Toxicol Environ Health 48(5):479-499.
Langard, S; Gundersen, N; Tsalev, DL; et al. (1978) Whole blood chromium level and chromium
excretion in the rat after zinc chromate inhalation. Acta Pharmacol Toxicol (Copenh) 42(2): 142-
149.
Manzo, L; Di Nucci, A; Edel, J; et al. (1983) Biliary and gastrointestinal excretion of chromium
after administration of Cr-III and Cr-VI in rats. Res Commun Chem Pathol Pharmacol
42(1): 113-125.
Minoia, C; Cavalleri, A. (1988) Chromium in urine, serum and red blood cells in the biological
monitoring of workers exposed to different chromium valency states. Sci Total Environ
71(3):323-327.
Mutti, A; Cavatorta, A; Borghi, L; et al. (1979) Distribution and urinary excretion of chromium.
Studies on rats after administration of single and repeated doses of potassium dichromate. Med
Lav 70(3): 171-179.
Norseth, T; Alexander, J; Aaseth, J; et al. (1982) Biliary excretion of chromium in the rat: a role
of glutathione. Acta Pharmacol Toxicol (Copenh) 51(5):450-455.
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Paustenbach, DJ; Hays, SM; Brien, BA; et al. (1996) Observation of steady state in blood and
urine following human ingestion of hexavalent chromium in drinking water. J Toxicol Environ
Health 49(5):453-461.
Petersen, R; Thomsen, JF; Jorgensen, NK; et al. (2000) Half life of chromium in serum and urine
in a former plasma cutter of stainless steel. Occup Environ Med 57(2): 140-142.
Saner, G; Yuzbasiyan, V; Cigdem, S. (1984) Hair chromium concentration and chromium
excretion in tannery workers. Br J Ind Med 41(2):263-266.
Sayato, Y; Nakamuro, K; Matsui, S; et al. (1980) Metabolic fate of chromium compounds. I.
Comparative behavior of chromium in rat administered with Na251CrC>4 and 51CrCl3. J
Pharmacobiodyn 3(1): 17-23.
Wiegand, HJ; Ottenwalder, H; Bolt, HM. (1987) Bioavailability and metabolism of hexavalent
chromium compounds. Toxicol Environ Chem 14:263-275.
Witmer, CM; Harris, R; Shupack, SI. (1991) Oral bioavailability of chromium from a specific
site. Environ Health Perspect 92:105-110.
Witmer, CM; Park, HS; Shupack, SI. (1989) Mutagenicity and disposition of chromium. Sci
Total Environ 86(1-2): 131-148.
Yamaguchi, S; Sano, K; Shimojo, N. (1983) On the biological half-time of hexavalent chromium
in rats. Ind Health 21(l):25-34.
3.5. PHYSIOLOGICALLY BASED TOXICOKINETIC MODELS
O'Flaherty, EJ. (1993) A pharmacokinetic model for chromium. Toxicol Lett 68(1-2): 145-158.
O'Flaherty, EJ. (1993) Physiologically based models for bone-seeking elements. IV. Kinetics of
lead disposition in humans. Toxicol Appl Pharmacol 118(1): 16-29.
O'Flaherty, EJ. (1993) Chromium as an essential and toxic metal. Scand J Work Environ Health
19 Suppl 1:124-125.
OFlaherty, EJ. (1995) Physiologically based models for bone-seeking elements. V. Lead
absorption and disposition in childhood. Toxicol Appl Pharmacol 131(2):297-308.
O'Flaherty, EJ. (1996) A physiologically-based model of chromium kinetics in the rat. Toxicol
Appl Pharmacol 138:54-64.
OFlaherty, EJ. (1998) Physiologically based models of metal kinetics. Crit Rev Toxicol
28(3):271-317.
O'Flaherty, EJ; Radike, MJ (1991) Pharmacokinetic modeling of trivalent and hexavalent
chromium based on ingestion and inhalation of soluble chromium compounds. Cincinnati, OH:
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Armstrong Laboratory. Air Force Systems Command. Wright-Patterson Air Force BaseADA256
238/7.
O'Flaherty, EJ; Kerger, BD; Hays, SM; et al. (2001) A physiologically based model for the
ingestion of chromium(III) and chromium(VI) by humans. Toxicol Sci 60(2): 196-213.
4. HAZARD IDENTIFICATION
|4.1. STUDIES IN HUMANS—EPIDEMIOLOGY, CASE REPORTS, CLINICAL
CONTROLS
Anderson RA. 1998. Chromium, glucose intolerance and diabetes. J Am Coll Nutr 17(6):548-
555.
Anderson RA. 2003. Chromium and insulin resistance. Nutr Res Rev 16(2):267-275.
IOM. 2001. Chromium. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron,
chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc
(2000). A Report of the Panel on Micronutrients, subcommittees on upper reference levels of
nutrients and of interpretation and uses of dietary reference intakes, and the standing committee
on the scientific evaluation of dietary reference intakes. Washington, DC: Food and Nutrition
Board. Institute of Medicine. National Academy Press, 197-223.
Jacquamet L, Sun Y, Hatfield J, et al. 2003. Characterization of chromodulin by x-ray
absorption and electron paramagnetic resonance spectroscopies and magnetic susceptibility
measurements. J Am Chem Soc 125:774-780.
Stearns DM. 2000. Is chromium a trace essential metal? Biofactors 11(3): 149-162.
Comment [SU1]: .Nolo 10 liPA: The
introduction to this section will include a
brief discussion of the essentiality of
chromium.
4.1.1. Human Oral
[4.1.1.1 Acute Exposurc[	
Clochesy, JM. (1984) Chromium ingestion: a case report. J Emerg Nurs 10(6):281-282.
Fristedt, B; Lindqvist, B; Schuetz, A; et al. (1965) Survival in a case of acute oral chromic acid
poisoning with acute renal failure treated by haemodialysis. Acta Med Scand 177:153-159.
Goldman, M; Karotkin, RH. (1935) Acute potassium bichromate poisoning. Am J Med Sci
189:400-403.
Hantson, P; Van Caenegem, O; Decordier, I; et al. (2005) Hexavalent chromium ingestion:
biological markers of nephrotoxicity and genotoxicity. Clin Toxicol (Phila) 43(2): 111-112.
Hasan, A. (2007) A case report: ammonium dichromate poisoning. Biomedical Research
18(l):35-37.
Comment [SU2]: Note to EPA: This
section includes studies of accidental or
intentional ingestion. SRC proposes that
this section provide an overall description
of effects of acute oral exposure, but will
not include study summaries.
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Iserson, KV; Banner, W; Froede, RC; et al. (1983) Failure of dialysis therapy in potassium
dichromate poisoning. J Emerg Med 1(2): 143-149.
Kaufman, DB; DiNicola, W; Mcintosh, R. (1970) Acute potassium dichromate poisoning.
Treated by peritoneal dialysis. Am J Dis Child 119(4):374-376.
Loubieres, Y; de Lassence, A; Bernier, M; et al. (1999) Acute, fatal, oral chromic acid poisoning.
J Toxicol Clin Toxicol 37(3):333-336.
Partington, CN. (1950) Acute poisoning with potassium bichromate. Br Med J 2(4688): 1097-
1098.
Reichelderfer, TE. (1968) Accidental death of an infant caused by ingestion of ammonium
dichromate. SouthMedJ61:96-97.
Saryan, LA; Reedy, M. (1988) Chromium determinations in a case of chromic acid ingestion. J
Anal Toxicol 12(3):162-164.
Sharma, BK; Singhal, PC; Chugh, KS. (1978) Intravascular haemolysis and acute renal failure
following potassium dichromate poisoning. Postgrad Med J 54(632):414-415.
(4.1.1.2 Environmental Exposure^	
Beaumont, JJ; Sedman, RM; Reynolds, SD; et al. (2008) Cancer mortality in a Chinese
population exposed to hexavalent chromium in drinking water. Epidemiology 19(1): 12-23.
Bick, RL; Girardi, TV; Lack, WJ; et al. (1996) Hodgkin's disease in association with hexavalent
chromium exposure. Int J Hematol 64(3-4):257-262.
Brandt-Rauf, P. (2006) Editorial retraction. Cancer mortality in a Chinese population exposed to
hexavalent chromium in water. J Occup Environ Med 48(7):749.
Eizaguirre-Garcia, D; Rodriguez-Andres, C; Watt, GC. (2000) Congenital anomalies in Glasgow
between 1982 and 1989 and chromium waste. J Public Health Med 22(l):54-58.
Eizaguirre-Garcia, D; Rodriguez-Andres, C; Watt, GC; et al. (1999) A study of leukaemia in
Glasgow in connection with chromium-contaminated land. J Public Health Med 21(4):435-438.
Merler, E. (2008) [Carcinogenicity of hexavalent chromium in animals and humans when
adsorbed from the gastrointestinal tract]. Epidemiol Prev 32(2):74-75.
Smith, AH. (2008) Hexavalent chromium, yellow water, and cancer: a convoluted saga.
Epidemiology 19(l):24-26.
Zhang, JD; Li, S. (1997) Cancer mortality in a Chinese population exposed to hexavalent
chromium in water. J Occup Environ Med 39(4):315-319.
Comment [SU3]: Note to EPA: These
studies are environmental exposure
studies. Study descriptions will be
developed for studies included in this
section.
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Zhang, JD; Li, XL. (1987) [Chromium pollution of soil and water in Jinzhou]. Zhonghua Yu
Fang Yi Xue Za Zhi 21(5):262-264.
4.1.2. Human Inhalation
|*. 1.2.1 Chronic Workers	
Alderson, MR; Rattan, NS; Bidstrup, L. (1981) Health of workmen in the chromate-producing
industry in Britain. Br J Ind Med 38(2): 117-124.
Alexander, BH; Checkoway, H; Wechsler, MS; et al. (1996) Lung cancer in chromate-exposed
aerospace workers. J Occup Environ Med 38(12): 1253-1258.
Axelsson, G; Rylander, R; Schmidt, A. (1980) Mortality and incidence of tumours among
ferrochromium workers. Br J Ind Med 37(2): 121-127.
Baetjer, AM. (1950) Pulmonary carcinoma in chromate workers. II. Incidence on basis of
hospital records. Arch Ind Hyg Occup Med 2:505-516.
Baetjer, AM. (1950) Pulmonary carcinoma in chromate workers. I. A review of the literature and
report of cases. Arch Ind Hyg Occup Med 2(5):487-504.
Bidstrup, PL. (1951) Carcinoma of the lung in chromate workers. Br J Ind Med 8(4):302-305.
Bidstrup, PL; Case, RA. (1956) Carcinoma of the lung in workmen in the bichromates-producing
industry in Great Britain. Br J Ind Med 13(4):260-264.
Blair, J. (1928) Chrome ulcers. Report of twelve cases. J Am Med Assoc 90:1927-1928.
Bloomfield, JJ; Blum, W. (1928) Health hazards in chromium plating. Public Health Rep
43:2330-2351.
Bourne, HG, Jr.; Yee, HT. (1950) Occupational cancer in a chromate plant - an environmental
appraisal. Ind Med Surg 19(12):563-567.
Bovet, P; Lob, M; Grandjean, M. (1977) Spirometric alterations in workers in the chromium
electroplating industry. Int Arch Occup Environ Health 40(l):25-32.
Braver, ER; Infante, P; Chu, K. (1985) An analysis of lung cancer risk from exposure to
hexavalent chromium. Teratog Carcinog Mutagen 5(5):365-378.
Brinton, HP; Rasier, ES; Koven, AL. (1952) Morbidity and mortality experience among
chromate workers. Public Health Rep 67:835-887.
Carter, WW. (1929) The effect of chromium poisoning on the nose and throat. Medical journal
and record 130:125-127.
- - Comment [SU4]: Note to EPA: This
section will include studies on noncancer
and cancer effects in chrome platers,
chrome electroplaters, chromate and
dichromate production workers, chromate
pigment production workers,
ferrochromium alloy production workers,
and stainless steel production workers.
Detailed study descriptions will be
developed for all suitable studies.
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Cohen, SR; David, DM; Kramkowski, RS. (1974) Clinical manifestations of chromic acid
toxicity: Nasal lesions in electroplate workers. Cutis 13:558-568.
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meta-analyses. Regul Toxicol Pharmacol 43(3):225-231.
Crump, C; Crump, K; Hack, E; et al. (2003) Dose-response and risk assessment of airborne
hexavalent chromium and lung cancer mortality. Risk Anal 23(6): 1147-1163.
Dacosta, JC; Jones, JF. (1916) Tanners' ulcer: chrome sores-chrome holes-acid bites. Ann Surg
63(2):155-166.
Dalager, NA; Mason, TJ; Fraumeni, JF, Jr.; et al. (1980) Cancer mortality among workers
exposed to zinc chromate paints. J Occup Med 22(l):25-29.
Davies, JM. (1978) Lung-cancer mortality of workers making chrome pigments. Lancet 1:384.
Davies, JM. (1979) Lung cancer mortality of workers in chromate pigment manufacture: An
epidemiological survey. J Oil Colour Chem Assoc 62:157-163.
Davies, JM. (1984) Lung cancer mortality among workers making lead chromate and zinc
chromate pigments at three English factories. Br J Ind Med 41(2): 158-169.
Davies, JM; Easton, DF; Bidstrup, PL. (1991) Mortality from respiratory cancer and other causes
in United Kingdom chromate production workers. Br J Ind Med 48(5):299-313.
Edmundson, WF. (1951) Chrome ulcers of the skin and nasal septum and their relation to patch
testing. J Invest Dermatol 17(1): 17-19.
EEH (1976) An epidemiological study of lead chromate plants: final report. Berkeley, CA:
Equitable Environmental Health, Inc.
EEH (1983) Mortality in employees of three plants which produced chromate pigments.
Berkeley, CA: Equitable Environmental Health, Inc. .
Enterline, PE. (1974) Respiratory cancer among chromate workers. J Occup Med 16(8):523-
526.
Franchini, I; Magnani, F; Mutti, A. (1983) Mortality experience among chromeplating workers.
Initial findings. Scand J Work Environ Health 9(3):247-252.
Franchini, I; Mutti, A. (1988) Selected toxicological aspects of chromium(VI) compounds. Sci
Total Environ 71(3):379-387.
Frentzel-Beyme, R. (1983) Lung cancer mortality of workers employed in chromate pigment
factories. A multicentric European epidemiological study. J Cancer Res Clin Oncol 105(2): 183-
188.
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Gibb, HJ; Lees, PS; Pinsky, PF; et al. (2000) Clinical findings of irritation among chromium
chemical production workers. Am J Ind Med 38(2): 127-131.
Gibb, HJ; Lees, PS; Pinsky, PF; et al. (2000) Lung cancer among workers in chromium chemical
production. Am J Ind Med 38(2): 115-126.
Gomes, ER. (1972) Incidence of chromium-induced lesions among electroplating workers in
Brazil. IMS Ind Med Surg 41(12):21-25.
Haguenoer, JM; Dubois, G; Frimat, P; et al. (1981) [Mortality due to bronch-pulmonary cancer
in a factory producing pigments based on lead and zinc chromates]. In: Prevention of
occupational cancer - International Symposium, Occupational Safety and Health Series 46.
Geneva, Switzerland: International Labour Office; pp. 168-176.
Halasova, E; Baska, T; Kukura, F; et al. (2005) Lung cancer in relation to occupational and
environmental chromium exposure and smoking. Neoplasma 52(4):287-291.
Hamilton, A; Hardy, HLE. (1974) Chromium. In: Industrial toxicology. Acton, MA: Publishing
Sciences Group, pp. 71-76.
Hanslian, L; Nauratli, J; Jurak, J; et al. (1967) Upper respiratory tract lesions from chromic acid
aerosols. Pracovni Lekar (Czech., English abstr.). 19:294-298.
Hanslian, L; Navratil, J; Jurak, J; et al. (1967) Damage to the upper respiratory tract by a
chromic acid aerosol. Pracovni Lekarstvi 19:294-298.
Hayes, RB; Lilienfeld, AM; Snell, LM. (1979) Mortality in chromium chemical production
workers: a prospective study. Int J Epidemiol 8(4):365-374.
Hayes, RB; Sheffet, A; Spirtas, R. (1989) Cancer mortality among a cohort of chromium
pigment workers. Am J Ind Med 16(2): 127-133.
Hill, WJ; Ferguson, WS. (1979) Statistical analysis of epidemiological data from a chromium
chemical manufacturing plant. J Occup Med 21(2): 103-106.
Huang, YL; Chen, CY; Sheu, JY; et al. (1999) Lipid peroxidation in workers exposed to
hexavalent chromium. J Toxicol Environ Health A 56(4):235-247.
Huvinen, M; Makitie, A; Jarventaus, H; et al. (2002) Nasal cell micronuclei, cytology and
clinical symptoms in stainless steel production workers exposed to chromium. Mutagenesis
17(5):425-429.
Huvinen, M; Uitti, J; Oksa, P; et al. (2002) Respiratory health effects of long-term exposure to
different chromium species in stainless steel production. Occup Med (Lond) 52(4):203-212.
Huvinen, M; Uitti, J; Zitting, A; et al. (1996) Respiratory health of workers exposed to low levels
of chromium in stainless steel production. Occup Environ Med 53(11):741-747.
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Ishikawa, Y; Nakagawa, K; Satoh, Y; et al. (1994) Characteristics of chromate workers' cancers,
chromium lung deposition and precancerous bronchial lesions: an autopsy study. Br J Cancer
70(1): 160-166.
Ishikawa, Y; Nakagawa, K; Satoh, Y; et al. (1994) "Hot spots" of chromium accumulation at
bifurcations of chromate workers' bronchi. Cancer Res 54(9):2342-2346.
Itoh, T; Takahashi, K; Okubo, T. (1996) Mortality of chromium plating workers in Japan. A 16-
year follow-up study. Sangyo Ika Daigaku Zasshi 18:7-18.
Kalahasthi, R; Rao, RHR; Krishna murthy, RB; et al. (2007) Effect of chromium (VI) exposure
on serum amylase activity in chromium plating workers. Environ Sci Indian J 2(1): 1-6.
Kalahasthi, RB; Rao, RH; Murthy, RB; et al. (2006) Effect of chromium(VI) on the status of
plasma lipid peroxidation and erythrocyte antioxidant enzymes in chromium plating workers.
ChemBiol Interact 164(3): 192-199.
Kitamura, F; Yokoyama, K; Araki, S; et al. (2003) Increase of olfactory threshold in plating
factory workers exposed to chromium in Korea. Ind Health 41(3):279-285.
Kleiner, AM; Stolbun, BM; Likhacheva, EI; et al. (1970) [Certain indices of the functional status
of the myocardium and hemodynamics in chronic occupational poisoning by chromium
compounds]. Gig TrProfZabol 14(12):7-10.
Kleinfeld, M; Rosso, A. (1965) Ulcerations of the nasal septum due to inhalation of chromic acid
mist. Ind Med Surg 34:242-243.
Korallus, V; Lange, H; Ness, A; et al. (1982) Relationships between precautionary measures and
bronchial carcinoma mortality in the chromate-producing industry. Arbeitsmedizin, Social
Medizin Preventivmedizin 17(7):159-167.
Kumar, S; Sathwara, NG; Gautam, AK; et al. (2005) Semen quality of industrial workers
occupationally exposed to chromium. J Occup Health 47(5):424-430.
Kuo, HW; Lai, JS; Lin, TI. (1997) Nasal septum lesions and lung function in workers exposed to
chromic acid in electroplating factories. Int Arch Occup Environ Health 70(4):272-276.
Langard, S. (1980) A survey of respiratory symptoms and lung function in ferrochromium and
ferrosilicon workers. Int Arch Occup Environ Health 46(1): 1-9.
Langard, S. (1990) One hundred years of chromium and cancer: a review of epidemiological
evidence and selected case reports. Am J Ind Med 17(2):189-215.
Langard, S. (1993) Role of chemical species and exposure characteristics in cancer among
persons occupationally exposed to chromium compounds. Scand J Work Environ Health 19
Suppl 1:81-89.
Langard, S; Andersen, A; Gylseth, B. (1980) Incidence of cancer among ferrochromium and
ferrosilicon workers. Br J Ind Med 37(2): 114-120.
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Langard, S; Andersen, A; Ravnestad, J. (1990) Incidence of cancer among ferrochromium and
ferrosilicon workers: an extended observation period. Br J Ind Med 47(1): 14-19.
Langard, S; Vigander, T. (1983) Occurrence of lung cancer in workers producing chromium
pigments. Br JIndMed40(l):71-74.
Li, H; Chen, Q; Li, S; et al. (2001) Effect of Cr(VI) exposure on sperm quality: human and
animal studies. Ann Occup Hyg 45(7):505-511.
Lieberman, H. (1941) Chrome ulcerations of the nose and throat. New Engl J Med 225:132-133.
Lindberg, E; Hedenstierna, G. (1983) Chrome plating: symptoms, findings in the upper airways,
and effects on lung function. Arch Environ Health 38(6):367-374.
Lindberg, E; Vesterberg, O. (1983) Monitoring exposure to chromic acid in chromeplating by
measuring chromium in urine. Scand J Work Environ Health 9(4):333-340.
Lindberg, E; Vesterberg, O. (1983) Urinary excretion of proteins in chromeplaters,
exchromeplaters and referents. Scand J Work Environ Health 9(6):505-510.
Liu, CS; Kuo, HW; Lai, JS; et al. (1998) Urinary N-acetyl-beta-glucosaminidase as an indicator
of renal dysfunction in electroplating workers. Int Arch Occup Environ Health 71(5):348-352.
Luippold, RS; Mundt, KA; Austin, RP; et al. (2003) Lung cancer mortality among chromate
production workers. Occup Environ Med 60(6):451-457.
Machle, W; Gregorius, F. (1948) Cancer of the respiratory system in the United States chromate
producing industry. Public Health Rep 63(35): 1114-1127.
Mancuso, RF. (1951) Occupational cancer and other health hazards in a chromate plant: a
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Mancuso, TF. (1997) Chromium as an industrial carcinogen: Part II. Chromium in human
tissues. Am J Ind Med 31(2): 140-147.
Mancuso, TF. (1997) Chromium as an industrial carcinogen: Part I. Am J Ind Med 31(2): 129-
139.
Mancuso, TF; Hueper, WC. (1951) Occupational cancer and other health hazards in a chromate
plant: a medical appraisal. I. Lung cancers in chromate workers. Ind Med Surg 20(8):358-363.
Meyers, JB. (1950) Acute pulmonary complications following inhalation of chromic acid mist;
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4.1.2.x Welders
Angerer, J; Amin, W; Heinrich-Ramm, R; et al. (1987) Occupational chronic exposure to metals.
I. Chromium exposure of stainless steel welders-biological monitoring. Int Arch Occup Environ
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malignancy with reference to paternal welding exposure. Scand J Work Environ Health 18:169-
177.
Comment [SU5]: Nolo 10 liPA:
Welding fumes includes exposure to
mixture of chemicals, including
chromium, nickely and ozone. SRC
proposes to provide a brief overview of
this literature, but not include study
summaries.
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Bradshaw, LM; Fishwick, D; Slater, T; et al. (1998) Chronic bronchitis, work related respiratory
symptoms, and pulmonary function in welders in New Zealand. Occup Environ Med 55(3): 150-
154.
Danadevi, K; Rozati, R; Reddy, PP; et al. (2003) Semen quality of Indian welders occupationally
exposed to nickel and chromium. Reprod Toxicol 17(4):451-456.
Elis, A; Froom, P; Ninio, A; et al. (2001) Employee exposure to chromium and plasma lipid
oxidation. Int J Occup Environ Health 7(3):206-208.
Hjollund, NH. (1995) Male-mediated risk of spontaneous abortion with reference to stainless
steel welding. Scand J Work Environ Health 21:272-276.
Hjollund, NH; Bonde, JP; Ernst, E; et al. (2005) Spontaneous abortion in IVF couples~a role of
male welding exposure. Hum Reprod 20(7): 1793-1797.
Hjollund, NH; Bonde, JP; Jensen, TK; et al. (2000) Male-mediated spontaneous abortion among
spouses of stainless steel welders. Scand J Work Environ Health 26(3): 187-192.
Hjollund, NH; Bonde, JP; Jensen, TK; et al. (1998) Semen quality and sex hormones with
reference to metal welding. Reprod Toxicol 12(2):91-95.
Kilburn, KH; Warshaw, R; Boylen, CT; et al. (1990) Cross-shift and chronic effects of stainless-
steel welding related to internal dosimetry of chromium and nickel. Am J Ind Med 17(5):607-
615.
Lee, CR; Yoo, CI; Lee, J; et al. (2002) Nasal septum perforation of welders. Ind Health
40(3):286-289.
Littorin, M; Welinder, H; Hultberg, B. (1984) Kidney function in stainless steel welders. Int
Arch Occup Environ Health 53(3):279-282.
Marini, F; Ferre, MP; Gross, H; et al. (1995) Does welding stainless steel cause cancer? Scand J
Work Environ Health 21(l):65-68.
Sjogren, B. (1980) A retrospective cohort study of mortality among stainless steel welders.
Scand J Work Environ Health 6(3): 197-200.
Sjogren, B; Gustavsson, A; Hedstrom, L. (1987) Mortality in two cohorts of welders exposed to
high- and low-levels of hexavalent chromium. Scand J Work Environ Health 13(3):247-251.
Sjogren, B; Hedstrom, L; UlfVarson, U. (1983) Urine chromium as an estimator of air exposure
to stainless steel welding fumes. Int Arch Occup Environ Health 51(4):347-354.
Verschoor, MA; Bragt, PC; Herber, RF; et al. (1988) Renal function of chrome-plating workers
and welders. Int Arch Occup Environ Health 60(l):67-70.
[4.1.2.y Cement Workcrs[	
Comment [SU6]: Nolo 10 liPA:
Occupational exposure of cement
workers includes exposure to chromium,
in addition to other chemicals. SRC
proposes to provide a brief overview of
this literature, but not include study
summaries.
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Rafnsson, V; Gunnarsdottir, H; Kiilunen, M. (1997) Risk of lung cancer among masons in
Iceland. Occup Environ Med 54(3): 184-188.
Rafnsson, V; Johannesdottir, SG. (1986) Mortality among masons in Iceland. Br J Ind Med
43(8):522-525.
Smailyte, G; Kurtinaitis, J; Andersen, A. (2004) Mortality and cancer incidence among
Lithuanian cement producing workers. Occup Environ Med 61(6):529-534.
4.I.2.Z. Environmental Exposure
Axelsson, G; Rylander, R. (1980) Environmental chromium dust and lung cancer mortality.
Environ Res 23(2):469-476.
Fryzek, JP; Mumma, MT; McLaughlin, JK; et al. (2001) Cancer mortality in relation to
environmental chromium exposure. J Occup Environ Med 43(7):635-640.
Halasova, E; Baska, T; Kukura, F; et al. (2005) Lung cancer in relation to occupational and
environmental chromium exposure and smoking. Neoplasma 52(4):287-291.
Snyder, CA; Udasin, I; Waterman, SJ; et al. (1996) Reduced IL-6 levels among individuals in
Hudson County, New Jersey, an area contaminated with chromium. Arch Environ Health
51(l):26-28.
4.2. LESS-THAN-LIFETIME AND CHRONIC STUDIES AND CANCER BIOASSAYS
IN ANIMALS—ORAL AND INHALATION
4.2.1. Oral
Acharya, S; Mehta, K; Krishnan, S; et al. (2001) A subtoxic interactive toxicity study of ethanol
and chromium in male Wistar rats. Alcohol 23(2):99-108.
Acosta, M; Borras, M; de Lapuente, J; et al. (2004) Differential histopathological response to
oral administration of potassium dichromate (K2Cr207)between the wood mouse (Apodemus
sylvaticus) and the laboratory mouse (Mus musculus). Toxicol Appl Pharmacol 197:371.
Anand, SS. (2005) Protective effect of vitamin B6 in chromium-induced oxidative stress in liver.
J Appl Toxicol 25(5):440-443.
Anwar, RA; Langham, CF; Hoppert, CA; et al. (1961) Chronic toxicity studies. III. Chronic
toxicity of cadmium and chromium in dogs. Arch Environ 3:456-460.
Asmatullah; Noreen, MA. (1999) Effect of oral administration of hexavalent chromium on total
body weight, chromium uptake and histological structure of mouse liver. Punjab University
Journal of Zoology 14:53-63.
Bagchi, D; Hassoun, EA; Bagchi, M; et al. (1995) Oxidative stress induced by chronic
administration of sodium dichromate [Cr(VI)] to rats. Comp Biochem Physiol C Pharmacol
Toxicol Endocrinol 110(3):281-287.
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Borneff, I; Engelhardt, K; Griem, W; et al. (1968) Mouse drinking study with 3,4-benzpyrene
and potassium chromate. Archiv fuer Hygiene und Bakteriologie 152:45-53.
Cole, DC; Rodu, B. (2003) Chrome exposure and lung cancer, stomach cancer and other causes
of death: An epidemiologic meta-analysis. Toxicologist 72(S-1):58.
Diaz-Mayans, J; Laborda, R; Nunez, A. (1986) Hexavalent chromium effects on motor activity
and some metabolic aspects of Wistar albino rats. Comp Biochem Physiol C 83(1): 191-195.
Geetha, S; Sai Ram, M; Mongia, SS; et al. (2003) Evaluation of antioxidant activity of leaf
extract of Seabuckthorn (Hippophae rhamnoides L.) on chromium(VI) induced oxidative stress
in albino rats. J Ethnopharmacol 87(2-3):247-251.
Indus Bio-Test Labs Inc. (1992) Initial submission: letter from Ciba-Geigy Corp to USEPA Re:
90-day subacute oral toxicity study with medium chrome yellow in beagle dogs with attachments
and cover letter dated 101992. Submitted under TSCA Section 8ECP; NTIS No. OTS0571473.
Industrial Health Foundation. (1987) Final report regarding testing sodium dichromate and
soluble calcium chromate for carcinogenicity in rats with cover letter dated 042287. Submitted
under TSCA Section 8E; NTIS No. OTS0503685-2.
Kumar, A; Rana, SV. (1982) Lipid accumulation in chromium poisoned rats. Int J Tissue React
4(4):291-295.
Kumar, A; Rana, SV. (1984) Enzymological effects of hexavalent chromium in the rat kidney.
Int J Tissue React 6(2): 135-139.
Kumar, A; Rana, SV; Prakash, R. (1985) Dysenzymia induced by hexavalent chromium in rat
liver. Int J Tissue React 7(4):333-338.
Mackenzie, RD; Byerrum, RU; Decker, CF; et al. (1958) Chronic toxicity studies. II. Hexavalent
and trivalent chromium administered in drinking water to rats. AMA Arch Ind Health
18(3):232-234.
Maruyama, Y. (1982) The health effect of mice given oral administration of trivalent and
hexavalent chromium over a long-term. Acta Scholae Medicinalis Universitatis in Gifu 31:25-
46.
Maruyama, Y. (1983) Gifu Daigaku Igakubu Kiyo 3 l(l):25-46.
Merkur'eva, RV; Krasovskii, GN; Litvinov, NN; et al. (1984) [Comparative characteristics of the
changes in the microsomal enzyme system under the biological action of chromium and
chloroprene]. Gig Sanit (5): 10-11.
Merler, E. (2008) [Carcinogenicity of hexavalent chromium in animals and humans when
adsorbed from the gastrointestinal tract]. Epidemiol Prev 32(2):74-75.
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NTP (National Toxicology Program). (2007) NTP technical report on the toxicity studies of
sodium dichromate dihydrate (CAS No. 7789-12-0) administered in drinking water to male and
female F344/N rats and B6C3F1 mice and male BALB/c and c:w/3-C57BL/6 mice. Washington,
DC: National Toxicology Program. Toxicity Report Series Number 72.
http://ntp.niehs.nih.gov/ntp/htdocs/ST_rpts/TOX72.pdf.
NTP (National Toxicology Program). (2008) NTP technical report on the toxicology and
carcinogenesis studies of sodium dichromate dihydrate (CAS No. 7789-12-0) in F344/N rats and
B6C3F1 mice (drinking water studies). Washington, DC: National Toxicology Program; NTP
TR 546. http://ntp.niehs.nih.gov/files/546_web_FINAL.pdf.
Omotoso, OT; Sanya, BT. (2007) Growth performance and haematology of the laboratory rat,
Rattus norvegicus fed on protein supplements and heavy metals. Pakistan Journal of Scientific
and Industrial Research 50(4):254-260.
Quinteros, FA; Poliandri, AH; Machiavelli, LI; et al. (2007) In vivo and in vitro effects of
chromium VI on anterior pituitary hormone release and cell viability. Toxicol Appl Pharmacol
218(l):79-87.
Rafael, AI. (2006) An in vivo study on the effects of hexavalent chromium contaminated
drinking water on rat livers. Metal Ions Biol Med 9:315-318.
Rafael, AI; Almeida, A; Santos, P; et al. (2007) A role for transforming growth factor-beta
apoptotic signaling pathway in liver injury induced by ingestion of water contaminated with high
levels of Cr(VI). Toxicol Appl Pharmacol 224(2): 163-173.
Stohs, SJ; Bagchi, D; Hassoun, E; et al. (2000) Oxidative mechanisms in the toxicity of
chromium and cadmium ions. J Environ Pathol Toxicol Oncol 19(3):201-213.
Stohs, SJ; Bagchi, D; Hassoun, E; et al. (2001) Oxidative mechanisms in the toxicity of
chromium and cadmium ions. J Environ Pathol Toxicol Oncol 20(2):77-88.
U.S. EPA (Environmental Protection Agency). (1992) Initial submission: letter from Ciba-Geigy
Corp to USEPA regarding subacute oral toxicity studies of medium chrome yellow in rats with
attachments and cover letter dated 101992. Submitted under TSCA Section 8ECP; NTIS No.
OTS0571260.
Vyskocil, A; Viau, C; Cizkova, M; et al. (1993) Kidney function in male and female rats
chronically exposed to potassium dichromate. J Appl Toxicol 13(5):375-376.
Zabulyte, D; Uleckiene, S; Kalibatas, J; et al. (2006) Investigation of combined effect of
chromium (VI) and nitrate in experiments on rats. Trace Elem Electrolytes 23(4):287-291.
4.2.2. Inhalation
Adachi, S. (1987) Effect of chromium compounds on the respiratory system. Part 5. Long term
inhalation of chromic acid mist in electroplating by C57BL female mice and recapitulation on
our experimental studies. Jpn J Ind Health 29:17-33.
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Adachi, S. (1987) [Effects of chromium compounds on the respiratory system. 5. Long term
inhalation of chromic acid mist in electroplating by C57BL female mice and recapitulation of our
experimental studies]. Sangyo Igaku 29(1): 17-33.
Adachi, S; Yoshimura, H; Katayama, H; et al. (1986) [Effects of chromium compounds on the
respiratory system. Part 4. Long-term inhalation of chromic acid mist in electroplating to ICR
female mice]. Sangyo Igaku 28(4):283-287.
Adachi, S; Yoshimura, H; Miyayama, R; et al. (1981) [Effects of chromium compounds to the
respiratory system. Part 1. An experimental study of inhalation of chromic acid mist in
electroplating (author's transl)]. Sangyo Igaku 23(3):294-299.
Baetjer, AM; Lowney, JF; Steffee, H; et al. (1959) Effect of chromium on incidence of lung
tumors in mice and rats. AMA Arch Ind Health 20:124-135.
Bayer, AG. (1982) Testing sodium dichromate and soluble calcium chromate for carcinogenicity
in rats with cover letter dated 101982 and EPA Response dated 121382. EPA Document No. 88-
8300442; Submitted under TSCA Section 8; NTIS No. OTS0503685.
Glaser, U; Hochrainer, D; Kloppel, H; et al. (1985) Low level chromium (VI) inhalation effects
on alveolar macrophages and immune functions in Wistar rats. Arch Toxicol 57(4):250-256.
Glaser, U; Hochrainer, D; Kloppel, H; et al. (1986) Carcinogenicity of sodium dichromate and
chromium (Will) oxide aerosols inhaled by male Wistar rats. Toxicology 42(2-3):219-232.
Glaser, U; Hochrainer, D; Oldiges, H. (1988) Investigations of the lung carcinogenic potentials
of sodium dichromate and CrWIII oxide aerosols in Wistar rats. Environ Hyg 1:111-116.
Glaser, U; Hochrainer, D; Steinhoff, D. (1990) Investigation of irritating properties of inhaled
CrVI with possible influence on its carcinogenic action. Environ Hyg (2):235-245.
Industrial Health Foundation. (1989) Report on the subchronic inhalation toxicity of sodium
dichromate in rats with attachment and cover letter dated 112089. Submitted under TSCA
Section FYI; NTIS No. OTS0000729.
Johansson, A; Lundborg, M; Hellstrom, P; et al. (1980) Effect of iron, cobalt, and chromium dust
on rabbit alveolar macrophages: a comparison with the effects of nickel dust. Environmental
Research 21:165-176.
Johansson, A; Robertson, B; Curstedt, T; et al. (1986) Rabbit lung after inhalation of hexa- and
trivalent chromium. Environ Res 41(1): 110-119.
Johansson, A; Wiernik, A; Jarstrand, C; et al. (1986) Rabbit alveolar macrophages after
inhalation of hexa- and trivalent chromium. Environ Res 39(2):372-385.
Kim, HY; Lee, SB; Jang, BS. (2004) Subchronic inhalation toxicity of soluble hexavalent
chromium trioxide in rats. Arch Toxicol 78(7):363-368.
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Laskin, S. (1972) Research in environmental sciences. Washington, DC: Institute of
Environmental Medicine, pp. 92-97.
Lee, KP; Ulrich, CE; Geil, RG; et al. (1988) Effects of inhaled chromium dioxide dust on rats
exposed for two years. Fundam Appl Toxicol 10:125-145.
Lee, KP; Ulrich, CE; Geil, RG; et al. (1989) Inhalation toxicity of chromium dioxide dust to rats
after two years exposure. Sci Total Environ 86(l-2):83-108.
Nettesheim, P; Hanna, MG, Jr.; Doherty, DG; et al. (1971) Effect of calcium chromate dust,
influenza virus, and 100 R wholebody X-radiation on lung tumor incidence in mice. J Nat
Cancer Inst 47:1129-1144.
Pokrovskaya, LV; Shabynina, NK. (1973) On carcinogenic hazard in production of chromium
ferroalloys. Gig Tr ProfZabol 10:23-26.
U.S. EPA (Environmental Protection Agency). (1979) Letter from CIBA-GEIGY corporation to
USEPA submitting preliminary test results on strontium chromate with attachments. Submitted
under TSCA Section 8E; NTIS No. OTS0200607.
Zeidler-Erdely, PC; Kashon, ML; Battelli, LA; et al. (2008) Pulmonary inflammation and tumor
induction in lung tumor susceptible A/J and resistant C57BL/6J mice exposed to welding fume.
Part Fibre Toxicol 5:12.
4.3. REPRODUCTIVE/DEVELOPMENTAL STUDIES—ORAL AND INHALATION
4.3.1. Reproductive/Developmental Studies Oral
Al-Hamood, MH; Elbetieha, A; Bataineh, H. (1998) Sexual maturation and fertility of male and
female mice exposed prenatally and postnatally tp trivalent and hexavalent chromium
compounds. Reproduction Fertility and Development 10(2): 179-183.
Aruldhas, MM; Subramanian, S; Sekar, P; et al. (2005) Chronic chromium exposure-induced
changes in testicular histoarchitecture are associated with oxidative stress: study in a non-human
primate (Macaca radiata Geoffroy). Hum Reprod 20(10):2801-2813.
Aruldhas, MM; Subramanian, S; Sekhar, P; et al. (2004) Microcanalization in the epididymis to
overcome ductal obstruction caused by chronic exposure to chromium - a study in the mature
bonnet monkey (Macaca radiata Geoffroy). Reproduction 128(1): 127-137.
Aruldhas, MM; Subramanian, S; Sekhar, P; et al. (2006) In vivo spermatotoxic effect of
chromium as reflected in the epididymal epithelial principal cells, basal cells, and intraepithelial
macrophages of a nonhuman primate (Macaca radiata Geoffroy). Fertil Steril 86(4 Suppl): 1097-
1105.
Banu, SK; Samuel, JB; Arosh, JA; et al. (2008) Lactational exposure to hexavalent chromium
delays puberty by impairing ovarian development, steroidogenesis and pituitary hormone
synthesis in developing Wistar rats. Toxicol Appl Pharmacol 232(2): 180-189.
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Bataineh, H; al-Hamood, MH; Elbetieha, A; et al. (1997) Effect of long-term ingestion of
chromium compounds on aggression, sex behavior and fertility in adult male rat. Drug Chem
Toxicol 20(3): 133-149.
Bataineh, HN; Bataineh, Z; Daradka, H. (2007) Short-term exposure of female rats to industrial
metal salts: Effect on implantation and pregnancy. Reproductive medicine and biology 6(3): 179-
183.
Chowdhury, AR; Mitra, C. (1995) Spermatogenic and steroidogenic impairment after chromium
treatment in rats. Indian J Exp Biol 33(7):480-484.
Elbetieha, A; Al-Hamood, MH. (1997) Long-term exposure of male and female mice to trivalent
and hexavalent chromium compounds: effect on fertility. Toxicology 116(l-3):39-47.
Elsaieed, EM; Nada, SA. (2002) Teratogenicity of hexavalent chromium in rats and the
beneficial role of ginseng. Bull Environ Contam Toxicol 68(3):361-368.
Fadhel, ZA; Al-Hamood, MH. (2000) Chromium-induced lipid peroxidation in nursing mice and
their offspring. Res Commun Pharmacol Toxicol 5:167-175.
Finley, BL; Johnson, EM; Holson, JF. (1993) Comment on "Comparative effects of trivalent and
hexavalent chromium on spermatogenesis of the mouse.". Toxicol Environ Chem 39:133-137.
Junaid, M; Murthy, RC; Saxena, DK. (1995) Chromium fetotoxicity in mice during late
pregnancy. Vet Hum Toxicol 37(4):320-323.
Junaid, M; Murthy, RC; Saxena, DK. (1996) Embryotoxicity of orally administered chromium in
mice: exposure during the period of organogenesis. Toxicol Lett 84(3): 143-148.
Junaid, M; Murthy, RC; Saxena, DK. (1996) Embryo- and fetotoxicity of chromium in
pregestationally exposed mice. Bull Environ Contam Toxicol 57(2):327-334.
Kanojia, RK; Junaid, M; Murthy, RC. (1996) Chromium induced teratogenicity in female rat.
Toxicol Lett 89(3):207-213.
Kanojia, RK; Junaid, M; Murthy, RC. (1998) Embryo and fetotoxicity of hexavalent chromium:
a long-term study. Toxicol Lett 95(3): 165-172.
Li, H; Chen, Q; Li, S; et al. (2001) Effect of Cr(VI) exposure on sperm quality: human and
animal studies. Ann Occup Hyg 45(7):505-511.
Murthy, RC; Junaid, M; Saxena, DK. (1996) Ovarian dysfunction in mice following chromium
(VI) exposure. Toxicol Lett 89(2): 147-154.
NTP (National Toxicology Program). (1996) Final report on the reproductive toxicity of
potassium dichromate (hexavalent) (CAS No. 7778-50-9) administered in diet to SD rats.
National Institute of Environmental Health Sciences, National Toxicology Program.
PB97125355.
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NTP (National Toxicology Program). (1996) Final report on the reproductive toxicity of
potassium dichromate (hexavalent) (CAS No. 7778-50-9) administered in diet to BALB/c mice.
National Institute of Environmental Health Sciences, National Toxicology Program.
PB97125363.
NTP (National Toxicology Program). (1997) Final report on the reproductive toxicity of
potassium dichromate (CAS No. 7778-50-9) administered in diet to BALB/c mice. National
Institute of Environmental Health Sciences, National Toxicology Program. PB97144919.
Subramanian, S; Rajendiran, G; Sekhar, P; et al. (2006) Reproductive toxicity of chromium in
adult bonnet monkeys (Macaca radiata Geoffrey). Reversible oxidative stress in the semen.
Toxicol Appl Pharmacol 215(3):237-249.
Trivedi, B; Saxena, DK; Murthy, RC; et al. (1989) Embryotoxicity and fetotoxicity of orally
administered hexavalent chromium in mice. Reprod Toxicol 3(4):275-278.
Yousef, MI; El-Demerdash, FM; Kamil, KI; et al. (2006) Ameliorating effect of folic acid on
chromium(VI)-induced changes in reproductive performance and seminal plasma biochemistry
in male rabbits. Reprod Toxicol 21(3):322-328.
Zahid, ZR; Al-Hakkak, ZS; Kadhim, AHH; et al. (1990) Comparative effects of trivalent and
hexavalent chromium on spermatogenesis of the mouse. Toxicol Environ Chem 25:131-136.
4.3.2. Reproductive/Developmental Studies Inhalation
4.4. OTHER ENDPOINT-SPECIFIC STUDIES
4.4.1. SENSITIZATION (Human and Animal Studies)
Adams, RM. (1990) In: Occupational skin disease, 2nd ed., Adams, RM, ed. Philadelphia: W.B.
Saunders, pp. 26-31.
Allenby, CF; Goodwin, BF. (1983) Influence of detergent washing powders on minimal eliciting
patch test concentrations of nickel and chromium. Contact Dermatitis 9(6):491-499.
Aoyama, K; Baohui, X. (2007) Contact sensitizer potassium dichromate alters lymphocyte
populations in draining lymph nodes and blood in mice. Toxicology mechanisms and methods
17(8):475-481.
Athavale, P; Shum, KW; Chen, Y; et al. (2007) Occupational dermatitis related to chromium and
cobalt: experience of dermatologists (EPIDERM) and occupational physicians (OPRA) in the
U.K. over an 11-year period (1993-2004). Br J Dermatol 157(3):518-522.
Bagdon, RE; Hazen, RE. (1991) Skin permeation and cutaneous hypersensitivity as a basis for
making risk assessments of chromium as a soil contaminant. Environ Health Perspect 92:111-
119.
Balasubramaniam, P; Gawkrodger, DJ. (2003) Chromate: still an important occupational allergen
for men in the UK. Contact Dermatitis 49(3): 162-163.
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Balato, A; Balato, N; Di Costanzo, L; et al. (2008) Contact sensitization of older patients in an
academic department in Naples, Italy. Dermatitis 19(4):209-212.
Basketter, D; Horev, L; Slodovnik, D; et al. (2001) Investigation of the threshold for allergic
reactivity to chromium. Contact Dermatitis 44(2):70-74.
Basketter, DA; Briatico-Vangosa, G; Kaestner, W; et al. (1993) Nickel, cobalt and chromium in
consumer products: a role in allergic contact dermatitis? Contact Dermatitis 28(1): 15-25.
Bock, M; Schmidt, A; Bruckner, T; et al. (2003) Occupational skin disease in the construction
industry. Br J Dermatol 149(6): 1165-1171.
Bright, P; Burge, PS; O'Hickey, SP; et al. (1997) Occupational asthma due to chrome and nickel
electroplating. Thorax 52(l):28-32.
Bruynzeel, DP; Hennipman, G; van Ketel, WG. (1988) Irritant contact dermatitis and chromium
passivated metal. Contact Derm 19:175-179.
Burrows, D (1983) Adverse chromate reactions on the skin. In: Burrows, D; ed. Chromium:
metabolism and toxicity. Boca Raton, FL: CRC Press, Inc.; pp. 137-163.
Burrows, D; Adams, RM. (1990) In: Occupational skin disease, 2nd ed., Adams, RM, ed.
Philadelphia: W.B. Saunders, pp. 349-386.
Castanedo-Tardan, MP; Jacob, SE. (2008) Potassium dichromate. Dermatitis 19(4):E24-25.
Chen, CJ; Shih, TS; Chang, HY; et al. (2008) The total body burden of chromium associated
with skin disease and smoking among cement workers. Sci Total Environ 391(1):76-81.
Christensen, OB; Christensen, MB; Maibach, HI. (1984) Flare-up reactions and desensitization
from oral dosing in chromate-sensitive guinea pigs. Contact Dermatitis 10(5):277-279.
Cruz, MJ; Costa, R; Marquilles, E; et al. (2006) [Occupational asthma caused by chromium and
nickel]. ArchBronconeumol 42(6):302-306.
Edmundson, WF. (1951) Chrome ulcers of the skin and nasal septum and their relation to patch
testing. J Invest Dermatol 17(1): 17-19.
Engel, HO; Calnan, CD. (1963) Chromate dermatitis from paint. Br J Ind Med 20:192-198.
Eun, HC; Marks, R. (1990) Dose-response relationships for topically applied antigens. Br J
Dermatol 122(4):491-499.
Fernandez-Nieto, M; Quirce, S; Carnes, J; et al. (2006) Occupational asthma due to chromium
and nickel salts. Int Arch Occup Environ Health 79(6):483-486.
Fernandez-Nieto, M; Quirce, S; Cuesta, J; et al. (2003) Occupational asthma due to chrome and
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Finley, BL; Paustenbach, DJ. (1997) Using applied research to reduce uncertainty in health risk
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Flint, GN; Carter, SV; Fairman, B. (1998) Skin allergy from exposure to alloys of chromium.
Contact Dermatitis 39(6):315-316.
Fowler, J. (1990) Allergic contact dermatitis to metals. Am J Contact Derm l(4):212-223.
Fowler, JF, Jr.; Kauffman, CL; Marks, JG, Jr.; et al. (1999) An environmental hazard assessment
of low-level dermal exposure to hexavalent chromium in solution among chromium-sensitized
volunteers. J Occup Environ Med 41(3): 150-160.
Fregert, S. (1981) Chromium valencies and cement dermatitis. Br J Dermatol 105(suppl. 21):7-
9.
Gass, JK; Todd, PM. (2007) Multiple manifestations of chromate contact allergy. Contact
Dermatitis 56(5):290-291.
Goitre, M; Bedello, PG; Cane, D. (1982) Chromium dermatitis and oral administration of the
metal. Contact Dermatitis 8(3):208-209.
Gross, PR; Katz, SA; Samitz, MH. (1968) Sensitization of guinea pigs to chromium salts. J
Invest Dermatol 50(5):424-427.
Hansen, MB; Johansen, JD; Menne, T. (2003) Chromium allergy: significance of both Cr(III)
and Cr(VI). Contact Dermatitis 49(4):206-212.
Hansen, MB; Menne, T; Johansen, JD. (2006) Cr(III) and Cr(VI) in leather and elicitation of
eczema. Contact Dermatitis 54(5):278-282.
Hansen, MB; Menne, T; Johansen, JD. (2006) Cr(III) reactivity and foot dermatitis in Cr(VI)
positive patients. Contact Dermatitis 54(3): 140-144.
Ikarashi, Y; Tsuchiya, T; Nakamura, A. (1992) Detection of contact sensitivity of metal salts
using the murine local lymph node assay. Toxicol Lett 62(1):53-61.
Ingber, A; Gammelgaard, B; David, M. (1998) Detergents and bleaches are sources of chromium
contact dermatitis in Israel. Contact Dermatitis 38(2): 101-104.
Iyer, VJ; Baneijee, G; Govindram, CB; et al. (2002) Role of different valence states of chromium
in the elicitation of allergic contact dermatitis. Contact Dermatitis 47(6):357-360.
Jansen, LH; Berrens, L. (1968) Sensitization and partial desensitization of guinea-pigs to
trivalent and hexavalent chromium. Dermatologica 137(2):65-73.
Kaaber, K; Veien, NK. (1977) The significance of chromate ingestion in patients allergic to
chromate. Acta Derm Venereol 57(4):321-323.
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Katsarou, A; Baxevanis, C; Armenaka, M; et al. (1997) Study of persistence and loss of patch
test reactions to dichromate and cobalt. Contact Dermatitis 36(2):87-90.
Keskinen, H; Kalliomaki, PL; Alanko, K. (1980) Occupational asthma due to stainless steel
welding fumes. Clin Allergy 10(2): 151-159.
Lee, HS; Goh, CL. (1988) Occupational dermatosis among chrome platers. Contact Dermatitis
18(2):89-93.
Leroyer, C; Dewitte, JD; Bassanets, A; et al. (1998) Occupational asthma due to chromium.
Respiration 65(5):403-405.
Lindemann, M; Rietschel, F; Zabel, M; et al. (2008) Detection of chromium allergy by cellular in
vitro methods. Clin Exp Allergy 38(9): 1468-1475.
Mali, JW; Malten, K; van Neer, FC. (1966) Allergy to chromium. Arch Dermatol 93(l):41-44.
Mali, JW; Van, K; Van, N. (1963) Some aspects of the behavior of chromium compounds in the
skin. JInvestDermatol41:lll-122.
Moller, DR; Brooks, SM; Bernstein, DI; et al. (1986) Delayed anaphylactoid reaction in a worker
exposed to chromium. J Allergy Clin Immunol 77(3):451-456.
Mor, S; Ben-Efraim, S; Leibovici, J; et al. (1988) Successful contact sensitization to chromate in
mice. Int Arch Allergy Appl Immunol 85(4):452-457.
Nethercott, J; Paustenbach, D; Adams, R; et al. (1994) A study of chromium induced allergic
contact dermatitis with 54 volunteers: implications for environmental risk assessment. Occup
Environ Med 51(6):371-380.
Newhouse, ML. (1963) A cause of chromate dermatitis among assemblers in an automobile
factory. Br J Ind Med 20:199-203.
Novey, HS; Habib, M; Wells, ID. (1983) Asthma and IgE antibodies induced by chromium and
nickel salts. J Allergy Clin Immunol 72(4):407-412.
Olaguibel, JM; Basomba, A. (1989) Occupational asthma induced by chromium salts. Allergol
Immunopathol (Madr) 17(3): 133-136.
Peltonen, L; Fraki, J. (1983) Prevalence of dichromate sensitivity. Contact Dermatitis 9(3): 190-
194.
Piela, Z; Kiec-Swierczynska, M. (1998) [Skin reactivity in subjects sensitive to different
concentrations of nickel, chromium and cobalt]. Med Pr 49(5):457-463.
Polak, L. (1983) Immunology of chromium. In: Chromium: metabolism and toxicity. Burrows,
D, ed. Boca Raton, FL: CRC Press, pp. 51-135.
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Polak, L; Turk, JL; Frey, FR. (1973) Studies on contact hypersensitivity to chromium
compounds. Progr Allergy 17:145-219.
Proctor, DM; Fredrick, MM; Scott, PK; et al. (1998) The prevalence of chromium allergy in the
United States and its implications for setting soil cleanup: a cost-effectiveness case study. Regul
Toxicol Pharmacol 28(l):27-37.
Roto, P; Sainio, H; Reunala, T; et al. (1996) Addition of ferrous sulfate to cement and risk of
chromium dermatitis among construction workers. Contact Dermatitis 34(l):43-50.
Samitz, MH; Shrager, J. (1966) Patch test reactions to hexavalent and trivalent chromium
compounds. Arch Dermatol 94(3):304-306.
Sastre, J; Fernandez-Nieto, M; Maranon, F; et al. (2001) Allergenic cross-reactivity between
nickel and chromium salts in electroplating-induced asthma. J Allergy Clin Immunol
108(4):650-651.
Scott, PK; Proctor, DM. (1997) Evaluation of 10% minimum elicitation threshold for Cr(VI)-
induced allergic contact dermititis using benchmark dose methods. J Soil Contam 6(6):707-731.
Shah, M; Palmer, IR. (2002) An ultrastructural study of chronic chromate hand dermatitis. Acta
Derm Venereol 82(4):254-259.
Shelnutt, SR; Goad, P; Belsito, DV. (2007) Dermatological toxicity of hexavalent chromium.
Crit Rev Toxicol 37(5):375-387.
Stern, AH; Bagdon, RE; Hazen, RE; et al. (1993) Risk assessment of the allergic dermatitis
potential of environmental exposure to hexavalent chromium. J Toxicol Environ Health
40(4):613-641.
Thompson, TR; Belsito, DV. (2002) Regional variation in prevalence and etiology of allergic
contact dermatitis. Am J Contact Dermat 13(4): 177-182.
Venugopal, B; Luckey, TD (1978) Metal toxicity in mammals, 2. In: New York: Plenum
Press; p. 74.
Wong, SS; Chan, MT; Gan, SL; et al. (1998) Occupational chromate allergy in Singapore: a
study of 87 patients and a review from 1983 to 1995. Am J Contact Dermat 9(1): 1-5.
4.4.2. IMMUNOLOGICAL EFFECTS (Human and Animal Studies)
Antonini, JM; Roberts, JR. (2007) Chromium in stainless steel welding fume suppresses lung
defense responses against bacterial infection in rats. J Immunotoxicol 4(2): 117-127.
Aoyama, K; Baohui, X. (2007) Contact sensitizer potassium dichromate alters lymphocyte
populations in draining lymph nodes and blood in mice. Toxicology mechanisms and methods
17(8):475-481.
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Boscolo, P; Di Gioacchino, M; Bavazzano, P; et al. (1997) Effects of chromium on lymphocyte
subsets and immunoglobulins from normal population and exposed workers. Life Sci
60(16): 1319-1325.
Cohen, MD; Prophete, C; Sisco, M; et al. (2006) Pulmonary immunotoxic potentials of metals
are governed by select physicochemical properties: chromium agents. J Immunotoxicol 3(2):69-
81.
Cohen, MD; Zelikoff, JT; Chen, LC; et al. (1998) Immunotoxicologic effects of inhaled
chromium: role of particle solubility and co-exposure to ozone. Toxicol Appl Pharmacol
152(l):30-40.
Descotes, J. (1988) Identification of contact allergens: the mouse ear sensitization assay. J
Toxicol Cutan Ocular Toxicol 7(4):263-272.
Ikarashi, Y; Ohno, K; Tsuchiya, T; et al. (1992) Differences of draining lymph node cell
proliferation among mice, rats and guinea pigs following exposure to metal allergens.
Toxicology 76(3):283-292.
Ikarashi, Y; Tsuchiya, T; Nakamura, A. (1992) Detection of contact sensitivity of metal salts
using the murine local lymph node assay. Toxicol Lett 62(1):53-61.
Kucharz, EJ; Sierakowski, SJ. (1987) Immunotoxicity of chromium compounds: effect of
sodium dichromate on the T cell activation in vitro. Arh Hig Rada Toksikol 38(3):239-243.
Kuo, HW; Wu, ML. (2002) Effects of chromic acid exposure on immunological parameters
among electroplating workers. Int Arch Occup Environ Health 75(3): 186-190
Mignini, F; Streccioni, V; Baldo, M; et al. (2004) Individual susceptibility to hexavalent
chromium of workers of shoe, hide, and leather industries. Immunological pattern of HLA-B8,
DR3-positive subjects. Prev Med 39(4):767-775.
Polak, L. (1983) Immunology of chromium. In: Chromium: metabolism and toxicity. Burrows,
D, ed. Boca Raton, FL: CRC Press, pp. 51-135.
Snyder, CA; Valle, CD. (1991) Immune function assays as indicators of chromate exposure.
Environ Health Perspect 92:83-86.
Wang, JY; Tsukayama, DT; Wicklund, BH; et al. (1996) Inhibition of T and B cell proliferation
by titanium, cobalt, and chromium: role of IL-2 and IL-6. J Biomed Mater Res 32(4):655-661.
4.4.3. Carcinogenicity Studies - Parenteral Exposure (Animal Studies)
Baetjer, AM; Lowney, JF; Steffee, H; et al. (1959) Effect of chromium on incidence of lung
tumors in mice and rats. AMA Arch Ind Health 20:124-135.
Hueper, WC. (1961) Environmental carcinogenesis and cancers. Cancer Res 21:842-857.
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Hueper, WC; Payne, WW. (1959) Experimental cancers in rats produced by chromium
compounds and their significance to industry and public health. Am Ind Hyg Assoc J 20(4):274-
280.
Hueper, WC; Payne, WW. (1962) Experimental studies in metal carcinogenesis. Chromium,
nickel, iron, arsenic. Arch Environ Health 5:445-462.
Hueper, WC. (1955) Experimental studies in metal cancerigenesis. VII. Tissue reactions to
parenterally introduced powdered metallic chromium and chromite ore. J Natl Cancer Inst
16(2):447-470.
Hueper, WC. (1958) Experimental studies in metal cancerogenesis. X. Cancerogenic effects of
chromite ore roast deposited in muscle tissue and pleural cavity of rats. Am Med Assoc Arch
Ind Health 18:284-291.
Levy, LS; Martin, PA. (1983) The effects of a range of chromium containing materials on rat
lung. Dye Color Manufacturers Assoc.
Levy, LS; Venitt, S. (1975) Proceedings: carcinogenic and mutagenic activity of chromium
containing materials. Br J Cancer 32(2):254-255.
Levy, LS; Venitt, S. (1986) Carcinogenicity and mutagenicity of chromium compounds: the
association between bronchial metaplasia and neoplasia. Carcinogenesis 7(5):831-835.
Payne, WW. (1960) Production of cancers in mice and rats by chromium compounds. AMA
Arch Ind Health 21:530-535.
Roe, FJ; Carter, RL. (1969) Chromium carcinogenesis: calcium chromate as a potent carcinogen
for the subcutaneous tissues of the rat. Br J Cancer 23(1): 172-176.
Steffee, CH; Baetjer, AM. (1965) Histopathological effects of chromate chemicals. Report of
studies in rabbits, guinea pigs, rats and mice. Arch Environ Health 11:66.
Steinhoff, D. (1986) Carcinogenicity study with sodium dichromate in rats. Experimental
Pathology 80:129-141.
Steinhoff, S; Gad, SC; Hatfield, GK; et al. (1983) Listing sodium dichromate and soluble
calcium chromate for carcinogenicity in rats. Bayer AG Institute of Toxicology (Sept.,
unpublished).
Steinhoff, S; Gad, SC; Hatfield, GK; et al. (1986) Carcinogenecity study with sodium
dichromate in rats. Exp Pathol 30:129-141.
Yu, W; Sipowicz, MA; Diwan, BA; et al. (1998) Preconception exposure of male mice to
urethane or chromium: Increased tumors in multiple organs of offspring. Proc Am Assoc Cancer
Res 39:21.
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4.4.4. Parenteral Reproductive Toxicity - Testicular Effects (Animal Studies)
Acharya, UR; Mishra, M; Tripathy, RR; et al. (2006) Testicular dysfunction and antioxidative
defense system of Swiss mice after chromic acid exposure. Reprod Toxicol 22(1):87-91.
Behari, J; Chandra, SV; Tandon, SK. (1978) Comparative toxicity of trivalent and hexavalent
chromium to rabbits. III. Biochemical and histological changes in testicular tissue. Acta Biol
Med Ger 37(3):463-468.
Chandra, AK; Chatteijee, A; Ghosh, R; et al. (2007) Effect of curcumin on chromium-induced
oxidative damage in male reproductive system. Environ Toxicol Pharmacol 24(2): 160-166.
Chandra, AK; Chatteijee, A; Ghosh, R; et al. (2007) Chromium induced testicular impairment in
relation to adrenocortical activities in adult albino rats. Reprod Toxicol 24(3-4):388-396.
Murthy, RC; Saxena, DK; Gupta, SK; et al. (1991) Ultrastructural observations in testicular
tissue of chromium-treated rats. Reprod Toxicol 5(5):443-447.
4.5. MECHANISTIC DATA AND OTHER STUDIES IN SUPPORT OF THE MODE OF
ACTION
4.5.1. Genotoxicity
4.5.1.1 In Vitro Genotoxicity
Adams, SP; Laws, GM; Storer, RD; et al. (1996) Detection of DNA damage induced by human
carcinogens in acellular assays: potential application for determining genotoxic mechanisms.
MutatRes 368(3-4):235-248.
Arlauskas, A; Baker, RS; Bonin, AM; et al. (1985) Mutagenicity of metal ions in bacteria.
Environ Res 36(2):379-388.
Bennicelli, C; Camoirano, A; Petruzzelli, S; et al. (1983) High sensitivity of Salmonella TA102
in detecting hexavalent chromium mutagenicity and its reversal by liver and lung preparations.
MutatRes 122(l):l-5.
Bianchi, V; Celotti, L; Lanfranchi, G; et al. (1983) Genetic effects of chromium compounds.
MutatRes 117(3-4):279-300.
Bianchi, V; Dal Toso, R; Debetto, P; et al. (1980) Mechanisms of chromium toxicity in
mammalian cell cultures. Toxicology 17(2):219-224.
Biedermann, KA; Landolph, JR. (1987) Induction of anchorage independence in human diploid
foreskin fibroblasts by carcinogenic metal salts. Cancer Res 47(14):3815-3823.
Blankenship, LJ; Carlisle, DL; Wise, JP; et al. (1997) Induction of apoptotic cell death by
particulate lead chromate: differential effects of vitamins C and E on genotoxicity and survival.
Toxicol Appl Pharmacol 146(2):270-280.
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Blasiak, J; Trzeciak, A; Malecka-Panas, E; et al. (1999) DNA damage and repair in human
lymphocytes and gastric mucuosa cells exposed to chromium and curcumin. Teratog Carcinog
Mutagen 19:19-31.
Blasiak, J; Kowalik, J. (2000) A comparison of the in vitro genotoxicity of tii- and hexavalent
chromium. Mutat Res 469(1): 135-145.
Bonatti, S; Meini, M; Abbondandolo, A. (1976) Genetic effects of potassium dichromate in
Schizosaccharomyces pombe. Mutat Res 38(2): 147-150.
Brams, A; Buchet, JP; Crutzen-Fayt, MC; et al. (1987) A comparative study, with 40 chemicals,
of the efficiency of the Salmonella assay and the SOS chromotest (kit procedure). Toxicol Lett
38(1-2): 123-133.
Bridgewater, LC; Manning, FC; Patierno, SR. (1994) Base-specific arrest of in vitro DNA
replication by carcinogenic chromium: relationship to DNA interstrand crosslinking.
Carcinogenesis 15(ll):2421-2427.
Bridgewater, LC; Manning, FC; Patierno, SR. (1998) Arrest of replication by mammalian DNA
polymerases alpha and beta caused by chromium-DNA lesions. Mol Carcinog 23(4):201-206.
Briggs, JA; Briggs, RC. (1988) Characterization of chromium effects on a rat liver epithelial cell
line and their relevance to in vitro transformation. Cancer Res 48(22):6484-6490.
Bronzetti, GL; Galli, A. (1989) Influence of nta on the chromium genotoxicity. Toxicol Environ
Chem 23:101-104.
Bronzetti, G; Galli, A; Boccardo, P; et al. (1986) Genotoxicity of chromium in vitro on yeast:
Interaction with DNA. Toxicol Environ Chem 13:103-111.
Brusick, DJ; Simmon, VF; Rosenkranz, HS; et al. (1980) An evaluation of the Escherichia coli
WP2 and WP2 uvrA reverse mutation assay. Mutat Res 76(2): 169-190.
Camyre, E; Wise, SS; Milligan, P; et al. (2007) Ku80 deficiency does not affect particulate
chromate-induced chromosome damage and cytotoxicity in Chinese hamster ovary cells.
Toxicol Sci 97(2):348-354.
Capellmann, M; Mikalsen, A; Hindrum, M; et al. (1995) Influence of reducing compounds on
the formation of DNA-protein cross-links in HL-60 cells induced by hexavalent chromium.
Carcinogenesis 16(5): 1135-1139.
Casto, BC; Meyers, J; DiPaolo, JA. (1979) Enhancement of viral transformation for evaluation
of the carcinogenic or mutagenic potential of inorganic metal salts. Cancer Res 39(1): 193-198.
Celotti, L; Furlan, D; Seccati, L; et al. (1987) Interactions of nitrilotriacetic acid (NTA) with
Cr(VI) compounds in the induction of gene mutations in cultured mammalian cells. Mutat Res
190(l):35-39.
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Cemeli, E; Carder, J; Anderson, D; et al. (2003) Antigenotoxic properties of selenium
compounds on potassium dichromate and hydrogen peroxide. Teratog Carcinog Mutagen
23(Suppl 2):53-67.
Codina, JC; Perez-Torrente, C; Perez-Garcia, A; et al. (1995) Comparison of microbial tests for
the detection of heavy metal genotoxicity. Arch Environ Contam Toxicol 29(2):260-265.
Costa, M; Zhitkovich, A; Harris, M; et al. (1997) DNA-protein cross-links produced by various
chemicals in cultured human lymphoma cells. J Toxicol Environ Health 50(5):433-449.
De Flora, S. (1978) Metabolic deactivation of mutagens in the Salmonella-microsome test.
Nature 271(5644):455-456.
De Flora, S. (1981) Study of 106 organic and inorganic compounds in the Salmonella/microsome
test. Carcinogenesis 2(4):283-298.
De Flora, S; Bennicelli, C; Camoirano, A; et al. (1988) Influence of DT diaphorase on the
mutagenicity of organic and inorganic compounds. Carcinogenesis 9(4):611-617.
De Flora, S; Bennicelli, C; Zanacchi, P; et al. (1984) In vitro effects of N-acetylcysteine on the
mutagenicity of direct-acting compounds and procarcinogens. Carcinogenesis 5(4):505-510.
De Flora, S; Bennicelli, C; Zanacchi, P; et al. (1984) Metabolic activation and deactivation of
mutagens by preparations of human lung parenchyma and bronchial tree. Mutat Res 139(1):9-
14.
De Flora, S; Zanacchi, P; Camoirano, A; et al. (1984) Genotoxic activity and potency of 135
compounds in the Ames reversion test and in a bacterial DNA-repair test. Mutat Res
133(3):161-198.
Depault, F; Cojocaru, M; Fortin, F; et al. (2006) Genotoxic effects of chromium(VI) and
cadmium(II) in human blood lymphocytes using the electron microscopy in situ end-labeling
(EM-ISEL) assay. Toxicol In Vitro 20(4):513-518.
DiPaolo, JA; Casto, BC. (1979) Quantitative studies of in vitro morphological transformation of
Syrian hamster cells by inorganic metal salts. Cancer Res 39(3): 1008-1013.
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Ning, J; Grant, MH. (2000) The role of reduced glutathione and glutathione reductase in the
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2	Xie, H; Wise, SS; Wise, JP, Sr. (2008) Deficient repair of particulate hexavalent chromium-
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9	Zhitkovich, A; Voitkun, V; Costa, M. (1996) Formation of the amino acid-DNA complexes by
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14	4.6. SYNTHESIS OF MAJOR NONCANCER EFFECTS
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16	4.6.1. Oral
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18	4.6.2. Inhalation
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20	4.6.3. Mode of Action Information
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22	4.7. EVALUATION OF CARCINOGENICITY
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24	4.7.1. Summary of Overall Weight-of-Evidence
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26	4.7.2. Synthesis of Human, Animal, and Other Supporting Evidence
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28	4.7.3. Mode of Action Information
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30	4.7.2.1. Hypothesized Mode of Action
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32	4.7.2.2. Experimental Support for the Hypothesized Mode ofAction
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34	4.7.2.3. Other Possible Modes of Action
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36	4.7.2.4. Conclusions About the Hypothesized Mode of Action
37
38	Support for the hypothesized mode of action in test animals
39	Relevance of the hypothesized mode of action to humans
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Populations or lifestages particularly susceptible to the hypothesized mode of action
4.8. SUSCEPTIBLE POPULATIONS AND LIFE STAGES
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toxicity: bronchoalveolar lavage fluid analysis. Fundam Appl Toxicol 5:451-458.
Henderson, RF; Rebar, AH; Pickrell, JA; et al. (1979) Early damage indicators in the lung. III.
Biochemical and cytological response of the lung to inhaled metals salts. Toxicol Appl
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Malsch, PA; Proctor, DM; Finley, BL. (1994) Estimation of a chromium reference concentration
using the benchmark dose method: a case study. Regl Toxicol Pharmacol 20:58-82.
Malsch, PA; Proctor, DM; Finley, BL. (1994) Estimation of a chromium inhalation reference
concentration using the benchmark dose method: a case study. Regul Toxicol Pharmacol 20(1 Pt
l):58-82.
Venet, A; Clavel, F; Israel-Biet, D; et al. (1985) Lung in acquired immune deficiency syndrome:
infectious and immunological status assessed by bronchoalveolar lavage. Bull Eur Physiopathol
Respir 21:535-543.
5.1.	ORAL REFERENCE DOSE (RfD)
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5.1.1.	Choice of Principal Study and Critical Effect—with Rationale and Justification
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5.1.2.	Methods of Analysis—Including Models (PBPK, BMD, etc.)
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5.1.3.	RfD Derivation—Including Application of Uncertainty Factors (UFs)
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5.1.4.	Previous RfD Assessment (if any)]
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5.2.	INHALATION REFERENCE CONCENTRATION (RfC)
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5.2.1.	Choice of Principal Study and Critical Effect—with Rationale and Justification
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5.2.2.	Methods of Analysis—Including Models (PBPK, BMD, etc.)
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5.2.3.	RfC Derivation—Including Application of Uncertainty Factors (UFs)
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5.2.4.	Previous RfC Assessment (if any)]
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5.3. CANCER ASSESSMENT
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5.3.1.	Choice of Study/Data—with Rationale and Justification
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5.3.2.	Dose-response Data
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5.3.3.	Dose Conversion
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5.3.4.	Extrapolation Method(s)
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information on quantitation] Text starts here...
5.3.5.	Oral Slope Factor and Inhalation Unit Risk
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6. MAJOR CONCLUSIONS IN THE CHARACTERIZATION OF HAZARD AND DOSE
RESPONSE
6.1. HUMAN HAZARD POTENTIAL
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6.2. DOSE RESPONSE
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