Risk Evaluation for 1-Bromopropane (n-Propyl Bromide) CASRN: 106-94-5 Systematic Review Supplemental File: Data Quality Evaluation of Human Health Hazard Studies Epidemiologic Studies


Interagency Review Draft Document. Do Not Release or Distribute.
xvEPA
United States	Office of Chemical Safety and
Environmental Protection Agency	Pollution Prevention
Risk Evaluation for
1-Bromopropane
(w-Propyl Bromide)
CASRN: 106-94-5
Systematic Review Supplemental File:
Data Quality Evaluation of Human Health Hazard Studies -
Epidemiologic Studies
My 2019, DRAFT

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Interagency Review Draft Document. Do Not Release or Distribute.
Table of Contents
1.1.	Epidemiologic evaluation results of Ichihara et al. (2004); l-BP_control workers_distal
latency-Neurological/Behavior; HERO ID: 1519100	1
1.2.	Epidemiologic evaluation results of Li et al. (2010); 1-BP Factories in China_cumulative
exposure_neurobehavioral test-Neurological/Behavior; HERO ID: 1519103	5
1.3.	Epidemiologic evaluation results of Toraason et al. (2006); Cross-
sectional_Occupational_NC_NIOSH_cohort_l-BP_DNAdamage; HERO ID: 3974874	 11

-------
Study Citation:
Data Type:
HERO ID:
G. Ichihara, W. Li, E. Shibata, X. Ding, H. Wang, Y. Liang, S. Peng, S. Itohara, M. Kamijima, Q. Fan, Y. Zhang, E. Zhong, X.
Wu, W. M. Valentine, Y. Takeuchi (2004). Neurologic abnormalities in workers of a 1-bromopropane factory Environmental Health
Perspectives, 112(13,13), 1319-1325
Jiangsu 1 -BP control workers distal latency-Neurological/Behavior
1519100
Domain
Metric
Rating^ MWF* Score
('aminciil sTT
Domain 1: Study Participation
Metric 1: Participant selection
Metric 2: Attrition
Metric 3: Comparison Group
High x 0.4 0.4
High x 0.4 0.4
High x 0.2 0.2
Participants were female workers in 1-bromopropane
(1-BP) production facilities in the Jiangsu Province
of China. The 1-BP production process and inclu-
sion/exclusion criteria were described in detail. Sur-
vey was conducted in 2001.
There was minimal attrition in the analysis sample.
Four workers were excluded from some analyses due
to inability to find age-matched controls.
Unexposed controls were age-matched and selected
randomly from a cohort of female workers in a beer
factory in the same city, with participants living in
the same area. These workers were recruited dur-
ing the same time frame. For neurobehavioral test-
ing outcome analysis, both age and education were
matched for controls.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
High x 0.4
Metric 5: Exposure levels
Metric 6: Temporality
Medium x 0.2
Medium x 0.4
0.4 Exposure to 1-BP was measured during an 8-hour
work shift with a passive sampler (Sibata Scientific
Technology Ltd., Tokyo, Japan) attached to each
worker. The sampler was stored at 4 degrees C, and
then analyzed using GC-MS (GCD system G1800A,
Hewlett Packard). This represents a well-established
method using a direct measurement of exposure.
0.4 The study evaluated both exposed workers at a 1-
BP production facility and unexposed workers at a
nearby facility. In addition, they also looked at lev-
els of exposure and length of employment within the
1-BP factory workers. Exposure estimates for TWA
for 8-hr shifts ranged from 0-49.19 ppm.
0.8 In this cross sectional study, the electrophysiological
and neurobehavioral outcomes were assessed at the
same time as sampling. Exposed workers had been
at the factory for 27 +/- 31 months. Unclear if that
temporality of outcome and exposure is appropriate.
Domain 3: Outcome Assessment
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Study Citation:
Data Type:
HERO ID:
G. Ichihara, W. Li, E. Shibata, X. Ding, H. Wang, Y. Liang, S. Peng, S. Itohara, M. Kamijima, Q. Fan, Y. Zhang, E. Zhong, X.
Wu, W. M. Valentine, Y. Takeuchi (2004). Neurologic abnormalities in workers of a 1-bromopropane factory Environmental Health
Perspectives, 112(13,13), 1319-1325
Jiangsu 1 -BP control workers distal latency-Neurological/Behavior
1519100
Domain
Metric
Rating^ MWF* Score
Comments^
Metric 7: Outcome measurement or characterization
Medium x 0.667 1.33
Metric 8: Reporting Bias
Low
x 0.333
1.0
Vibration sensation examinations were conducted by
one trained neurologist. Electrophysiological out-
comes included distal latency and nerve conduction
velocity. These measurements were recorded using
a Neuropack evoked potential/electromyogram mea-
surement system (model MEB5508; Nihon Kohden,
Co., Tokyo, Japan). For neurobehavioral testing,
the WHO sponsored Neurobehavioral Core Test Bat-
tery was used as well as the Profile of Mood States
(POMS) questionnaire. A Gravicorder GS-30 sta-
bilometer (Anima Co., Tokyo, Japan) was used to
measure postural balance and sway. Blinding is not
discussed for both the vibration sensation assess-
ments and the neurobehavioral testing, which may
introduce bias into some results.
Some of the clinical chemistry results are discussed,
but not reported in a fashion that could be included
in meta-analyses. Other results include full tabula-
tion, including the number of pairs in the compari-
son.
Domain 4: Potential Counfounding/Variable Control
Metric 9: Covariate Adjustment
Medium x 0.5
Metric 10: Covariate Characterization
Medium x 0.25
0.5
Control workers were age-matched, and in the
neurobehavioral analyses workers were age- and
education-matched. The study authors state that
only one worker from each group was an alcohol
drinker, and none of the workers were smokers or had
diabetes. All workers were female. Length of em-
ployment differed strongly between the exposed (27
+ /- 31 months) and unexposed (168 +/- 67 month),
but was not adjusted for in the analysis..
There was no discussion of covariate collection, but
it is assumed that this was conducted during the
medical examination. There is no evidence to sug-
gest this is an invalid method.
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Study Citation: G. Ichihara, W. Li, E. Shibata, X. Ding, H. Wang, Y. Liang, S. Peng, S. Itohara, M. Kamijima, Q. Fan, Y. Zhang, E. Zhong, X.
Wu, W. M. Valentine, Y. Takeuchi (2004). Neurologic abnormalities in workers of a 1-bromopropane factory Environmental Health
Perspectives, 112(13,13), 1319-1325
Data Type: Jiangsu 1-BP control workers distal latency-Neurological/Behavior
HERO ID: 1519100
Domain Metric Rating^ MWF* Score Comments^
Metric 11: Co-exposure Confounding Medium x 0.25 0.5 The study authors state that 1-BP was the only
substance produced at the factory at the time of
the survey. The factory produced exclusively 2-BP
prior to 1996, when 1-BP production started there.
In 1999, the facility stopped all 2-BP production.
Some workers may have been exposed to both, but
this was addressed with a subsample of workers that
were hired after the switch was made (1999). Four
control workers reported prior exposure to other sub-
stances including ammonia and formalin. This is not
expected to appreciably bias the results.
Domain 5: Analysis
Metric 12
Study Design and Methods
Medium
x 0.4
0.8
This study looks cross-sectionally at the prevalence
of neurobehavioral deficits in two populations of
workers (exposed/unexposed).
Metric 13
Statistical power
Medium
x 0.2
0.4
There were sufficient number of pairs to detect an
effect of 1-BP in the exposed population.
Metric 14
Reproducibility of analyses
Medium
x 0.2
0.4
Outpoints for length of employment and exposure
level were described. Other details on the analysis
were described in so that it could be reproduced.
Metric 15
Statistical models
Medium
x 0.2
0.4
The choice of statistical tests to compare means was
transparent. A t-test was applied for continuous
variables, while the Wilcoxon and Fisher's test were
used for menstruation outcome comparisons.
Domain 6: Other Considerations for Biomarker Selection and Measurement

Metric 16
Use of Biomarker of Exposure

NA
NA

Metric 17
Effect biomarker

NA
NA

Metric 18
Method Sensitivity

NA
NA

Metric 19
Biomarker stability

NA
NA

Metric 20
Sample contamination

NA
NA

Metric 21
Method requirements

NA
NA

Metric 22
Matrix adjustment

NA
NA

Overall Quality Determination1"
Medium

1.8

Extracted Yes
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Study Citation: G. Ichihara, W. Li, E. Shibata, X. Ding, H. Wang, Y. Liang, S. Peng, S. Itohara, M. Kamijima, Q. Fan, Y. Zhang, E. Zhong, X.
Wu, W. M. Valentine, Y. Takeuchi (2004). Neurologic abnormalities in workers of a 1-bromopropane factory Environmental Health
Perspectives, 112(13,13), 1319-1325
Data Type:	Jiangsu_l-BP_control workers_distal latency-Neurological/Behavior
HERO ID:	1519100
Domain	Metric	Rating^ MWF* Score	Comments^
MWF = Metric Weighting Factor
High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.
The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.
4	if any metric is Unacceptable
Overall rating =
J]. (Metric Score; x MWF;) / ]T\ MWF3
(round to the nearest tenth) otherwise
where High => 1 to < 1.7; Medium => 1.7 to < 2.3; Low => 2.3 to < 3.0. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed out and
an arrow points to the new rating,
ft This metric met the criteria for high confidence as expected for this type of study

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Study Citation:
Data Type:
HERO ID:
Li, W.,Shibata, E.,Zhou, Z.,Ichihara, S.,Wang, H.,Wang, Q.,Li, J.,Zhang, L.,Wakai, K.,Takeuchi, Y.,Ding, X.,Ichihara, G. (2010). Dose-
dependent neurologic abnormalities in workers exposed to 1-bromopropane Journal of Occupational and Environmental Medicine, 52(8),
769-777
1-BP Factories in China_cumulative exposure_neurobehavioral test-Neurological/Behavior
1519103
Domain
Metric
Rating^ MWF* Score
Comments^
Domain 1: Study Participation
Metric 1: Participant selection
Low
x 0.4
Metric 2:
Attrition
Medium x 0.4
1.2 Authors report that 87 female and 29 male workers
at 3 1-BP factories (in Yixing city, Jiangsu Province
in 2001 and 2004; in Yancheng city, Jiangsu Province
in 2003; and in Weifang city, Shandong Province in
2005) were included in this study. It is not reported
why these provinces or factories were selected, or if
they are the only three factories of their kind. Sex-
, age- (within 3 years), and region-matched control
workers were randomly recruited from a beer fac-
tory in 2001, a refrigeration equipment factory in
2003, a knitting workshop in 2004, and a steel opera-
tion factory in 2005, but the authors do not describe
why these specific locations were selected. The au-
thors did not describe the recruitment process, and
it is not clear whether the same workers included in
the Ichihara et al 2004 study were recruited for this
study.
0.8 The study explained that only the data of 60 female
and 26 male exposed workers (out of 87 female work-
ers and 29 male workers) could be used in the anal-
ysis because: data of 6 other females examined in
2001 could not be used because the period of expo-
sure was <1 month; data of other females examined
in 2001 and one male worker in Yancheng in 2003
could not be used because the period of exposure or
exposure level was unknown; and age-matched con-
trols could not be recruited for one male worker in
Yixing in 2003, one female worker in Yixing in 2004,
and 4 females and 1 male in Weifang in 2005.
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Study Citation:
Data Type:
HERO ID:
Li, W.,Shibata, E.,Zhou, Z.,Ichihara, S.,Wang, H.,Wang, Q.,Li, J.,Zhang, L.,Wakai, K.,Takeuchi, Y.,Ding, X.,Ichihara, G. (2010). Dose-
dependent neurologic abnormalities in workers exposed to 1-bromopropane Journal of Occupational and Environmental Medicine, 52(8),
769-777
1-BP Factories in China_cumulative exposure_neurobehavioral test-Neurological/Behavior
1519103
Domain
Metric
Rating^ MWF* Score
Comments^
Metric 3: Comparison Group
Low X 0.2 0.6 Control workers were randomly selected from a beer
factory in 2001, a refrigeration equipment factory in
2003, a knitting workshop in 2004, and a steel op-
eration factory in 2005. The controls were matched
based on sex, age (within 3 years), and region. Fur-
ther differences were considered in the statistical
analysis including alcohol consumption and height
and body weight. However, minimal details were
provided on selection methods for the participants
or why different factories were used for the different
years. A table of characteristics was provided, but
only included a few parameters. Therefore, there is
only indirect evidence that the groups were similar.
. Ambient exposure levels varied by job and by plant
and were collected in different years for each plant.
For example, the ambient concentrations of a€ceraw
product collectiona€ were more than 3 times higher
at the Yancheng plant (analyzed in 2003) than at
the Yixing plant. Exposure was measured only once
for some of the female employees over 8- or 12-hour
work shifts but TWA exposure concentrations to 1-
BP were reported. TWAs were used to assign expo-
sure groups, based on either 1 or 2 samples only. The
median exposure level of the high exposure groups
for females was 22.58 ppm but the range was 15.28-
106.4 ppm, indicating that some of the workers were
exposed to levels much higher than the lowest ex-
posed workers in that group.
Domain 2: Exposure Characterization
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Study Citation:
Data Type:
HERO ID:
Li, W.,Shibata, E.,Zhou, Z.,Ichihara, S.,Wang, H.,Wang, Q.,Li, J.,Zhang, L.,Wakai, K.,Takeuchi, Y.,Ding, X.,Ichihara, G. (2010). Dose-
dependent neurologic abnormalities in workers exposed to 1-bromopropane Journal of Occupational and Environmental Medicine, 52(8),
769-777
1-BP Factories in China cumulative exposure neurobehavioral test-Neurological/Behavior
1519103
Domain
Metric
Rating^ MWF* Score
Comments^
Metric 4: Measurement of Exposure
Medium x 0.4
Metric 5: Exposure levels
Metric 6: Temporality
Low x 0.2
Low x 0.4
0.8 Individual exposure during a work shift was assessed
using a passive sampler that was attached to each
worker during one 8- or 12-hour shift. Analysis was
carried out using gas chromatography-mass spec-
trometry Assessment of individual exposure was
conducted twice for 2 shifts, except that it was con-
ducted only once for each 5 female workers in Yixing
in 2001 and 2 female workers in Yancheng in 2003
and 3 times for one female worker in Yancheng in
2003. Cumulative exposure was the product of ex-
posure level (based on the individual TWA concen-
tration) and period of exposure (in months). The
cumulative exposure measures were based on only
1-3- day measurements of individual exposure lev-
els.
0.6 The range and distribution of exposure is adequate
to develop an exposure-response relationship. The
study used a continuous measure of exposure based
on cumulative exposure (time-weighted-average x
months of exposure) in the analysis.
1.2 Exposed factory workers were exposed for approxi-
mately 3-4 years, on average, before outcome assess-
ment so temporality is established. However, it is
unclear if the exposure fell within the relevant win-
dows for all outcomes. Controls were recruited in
different years from different plants.
Domain 3: Outcome Assessment
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Study Citation:
Data Type:
HERO ID:
Li, W.,Shibata, E.,Zhou, Z.,Ichihara, S.,Wang, H.,Wang, Q.,Li, J.,Zhang, L.,Wakai, K.,Takeuchi, Y.,Ding, X.,Ichihara, G. (2010). Dose-
dependent neurologic abnormalities in workers exposed to 1-bromopropane Journal of Occupational and Environmental Medicine, 52(8),
769-777
1-BP Factories in China cumulative exposure neurobehavioral test-Neurological/Behavior
1519103
Domain
Metric
Rating^ MWF* Score
Comments^
Metric 7: Outcome measurement or characterization
Low
x 0.667
Metric 8: Reporting Bias
Medium x 0.333 0.67
The neurobehavioral tests were conducted on the
basis of the Chinese edition of the WHO Neurobe-
havioral Core Test Battery by trained Chinese re-
searchers. The electrophysiological tests , including
nerve conduction velocity, DL, F-wave conduction
velocity sensory nerve conduction velocity, and F-
wave studies were conducted using standard tech-
niques. Description was provided in detail. Indi-
vidual skin temperatures should have been taken at
the site of the test (on the foot) based on standard
methods (results are affected by body temperature
on the foot). As acknowledged in the report by the
study authors, vibration sense is inherently impre-
cise (based on the sensitivity of the subject relative
to the examiner). Evidence of a high degree of vari-
ability was shown in the large standard deviations
reported for vibration sense in females.
The authors only presented the results with signifi-
cant trend with exposure in the tables. The authors
state that the other results are not significant but
they do not present the non-significant results. Vi-
bration sense can be influenced by BMI, but it was
not reported or controlled in the study.
Domain 4: Potential Counfounding/Variable Control
Metric 9: Covariate Adjustment
Medium x 0.5
Metric 10: Covariate Characterization
Medium x 0.25
0.5
The controls were matched based on sex, age (within
3 years), and region. Further differences were ad-
justed for in the statistical analysis. Since all the
subjects were factory workers, it can be assumed
that they had similar socioeconomic status. Vibra-
tion sense can be influenced by BMI, but it was not
reported or controlled in the study.
Potential confounders were assessed using a ques-
tionnaire that was filled out by investigators from
the local CDC who could communicate with the
workers in their own dialect. However, the authors
don't report that the questionnaire was validated.
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.. . continued from previous page
Study Citation: Li, W.,Shibata, E.,Zhou, Z.,Ichihara, S.,Wang, H.,Wang, Q.,Li, J.,Zhang, L.,Wakai, K.,Takeuchi, Y.,Ding, X.,Ichihara, G. (2010). Dose-
dependent neurologic abnormalities in workers exposed to 1-bromopropane Journal of Occupational and Environmental Medicine, 52(8),
769-777
Data Type: 1-BP Factories in China cumulative exposure neurobehavioral test-Neurological/Behavior
HERO ID: 1519103
Domain Metric Rating^ MWF* Score Comments^
Metric 11: Co-exposure Confounding Medium X 0.25 0.5 There were data presented on one female worker who
reported handling 2-BP and several male controls
and male workers who reported using other chem-
icals. The exposure period for these workers was
adjusted for these workers. Controls all came from
different factories. It is unlikely there was differen-
tial co-exposure across groups that would have bi-
ased the results.
Domain 5: Analysis

Metric 12
Study Design and Methods
Medium
x 0.4
0.8
The study design (cross-sectional) was appropriate
to assess the effects of f-BP exposure on various
health effects and the statistical method (regression
analysis) was appropriate. Although the study was
cross-sectional in nature, cumulative exposures were
assessed.
Metric 13
Statistical power
Medium
x 0.2
0.4
The number of participants (60 female and 26 male

workers and same number of controls) was sufficient
to detect an effect.
Metric 14
Reproducibility of analyses
Medium
x 0.2
0.4
The description of the statistical methods is suffi-
cient to reproduce the ANCOVA regression models
and the adjustment factors were included in the foot-
notes to Table 7.
Metric 15
Statistical models
Medium
x 0.2
0.4
The adjustment factors included in the ANCOVA
model were determined by ANOVA models and
model assumptions were met.
Domain 6: Other Considerations for Biomarker Selection and Measurement

Metric 16
Use of Biomarker of Exposure

NA
NA

Metric 17
Effect biomarker

NA
NA

Metric 18
Method Sensitivity

NA
NA

Metric 19
Biomarker stability

NA
NA

Metric 20
Sample contamination

NA
NA

Metric 21
Method requirements

NA
NA

Metric 22
Matrix adjustment

NA
NA

Overall Quality Determination+
Low

2.4

Extracted Yes
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. continued from previous page
Study Citation: Li, W.,Shibata, E.,Zhou, Z.,Ichihara, S.,Wang, H.,Wang, Q.,Li, J.,Zhang, L.,Wakai, K.,Takeuchi, Y.,Ding, X.,Ichihara, G. (2010). Dose-
dependent neurologic abnormalities in workers exposed to 1-bromopropane Journal of Occupational and Environmental Medicine, 52(8),
769-777
Data Type:	1-BP Factories in China_cumulative exposure_neurobehavioral test-Neurological/Behavior
HERO ID:	1519103
Domain	Metric	Rating^ MWF* Score	Comments^
MWF = Metric Weighting Factor
High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.
The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.
4	if any metric is Unacceptable
Overall rating =
J]. (Metric Score; x MWF;) / ]T\ MWF3
(round to the nearest tenth) otherwise
where High => 1 to < 1.7; Medium => 1.7 to < 2.3; Low => 2.3 to < 3.0. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed out and
an arrow points to the new rating,
ft This metric met the criteria for high confidence as expected for this type of study

-------
Study Citation: M. Toraason, D. W. Lynch, D. G. DeBord, N. Singh, E. Kreig, M. A. Butler, C. A. Toennis, J. Nemhauser (2006). DNA damage in
leukocytes of workers occupationally exposed to 1-bromopropane 1 01-014
Data Type: Cross-sectional_Occupational_NC_NIOSH_cohort_l-BP_DNAdamage_air_quartiles-Other (please specify below)
HERO ID: 3974874
Domain
Metric
Rating^ MWF* Score
Comments^
Domain 1: Study Participation
Metric 1: Participant selection
Medium x 0.4
Metric 2:
Attrition
Low
x 0.4
Metric 3: Comparison Group
Low
x 0.2
0.8 A subset of 64 occupationally exposed workers (18
males, 46 females) originally evaluated in a NIOS
Health Hazard Evaluation were used for this study.
Workers were assessed in 2001 and worked at 2
facilities where 1-bromopropane (1-BP) was a sol-
vent vehicle for spray adhesives: Marx Industries
Inc., Sawmills, NC and STN Cushion Company,
Thomasville, NC. It is unclear what fraction of the
original NIOSH study participants chose to join this
more in depth study and if any bias was introduced
with that selection process.
1.2 No attrition is discussed. Study participants are a
subset of the NIOSH study who were interested in
participating. Not all subjects participated in the
personal air monitoring (50/64) and results in Ta-
ble 5 are reported for 48-60 participants.. In cases
of missing exposure data, subjects were assigned to
quartiles based on the single measurements avail-
able.
0.6 Rather than using population controls, workers at
the same factories were considered exposed or unex-
posed based on job title. The NIOSH assessment
found that sprayers had high 1-BP exposure (ex-
posed) and non-sprayers had relatively low 1-BP ex-
posure. Thus, 19 sprayers served as the exposed
population and 45 non-sprayers served as controls.
Sprayers at Facility A had exposures an order of
magnitude higher than sprayers at Facility B and
the 6 sprayers at Facility B were all female.
Domain 2: Exposure Characterization
Metric 4: Measurement of Exposure
High X 0.4 0.4 Personal air monitoring collected samples from the
breathing zone of 50 participants for 1-3 days. Sam-
ples were analyzed with GC-FID. An 8-hr time
weighted average concentration was used for these
assessments. In addition, a biomarker of exposure
(Br) was assessed in blood and urine at the start
and end of the work week. Estimated exposure from
these methods was highly correlated, increasing con-
fidence in the measurements.
Continued on next page

Metric 7: Outcome measurement or characterization
Medium
X
0.667
1.33
DNA damage in leukocytes was the only outcome
assessed in this study. Blood samples were collected
at the beginning and end of work week. A comet
assay was used to determine average number of DNA
breaks in 100 leukocytes per sample.
Metric 8: Reporting Bias
Medium
X
0.333
0.67
Study fully reports exposures by job title/facility,
biomarkers for start and end of week, comet analysis
results, correlations between exposure and the de-
termined associations. Covariates are clearly stated
for each analysis. Confidence intervals or standard
deviation not included with analysis, but p values
were.
Domain 4: Potential Counfounding/Variable Control

Metric 9: Covariate Adjustment
Low
X
0.5
1.5
Models were adjusted for gender, age, smoking sta-
tus, facility and glutathione S-transferase (GST)
polymorphisms. No adjustments were made for SES,
which may vary with job description (and associated
exposure).
Metric 10: Covariate Characterization
Low
X
0.25
0.75
GST polymorphisms were assessed from blood sam-
ples. Source of other covariate information not
stated.
Metric 11: Co-exposure Confounding
Medium
X
0.25
0.5
No indication of other co-exposures of concern.
Domain 5: Analysis
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Study Citation: M. Toraason, D. W. Lynch, D. G. DeBord, N. Singh, E. Kreig, M. A. Butler, C. A. Toennis, J. Nemhauser (2006). DNA damage in
leukocytes of workers occupationally exposed to 1-bromopropane 1 01-014
Data Type: Cross-sectional Occupational NC NIOSH cohort 1-BP DNAdamage air quartiles-Other (please specify below)
HERO ID: 3974874
Domain
Metric
Rating^ MWF* Score
('aminciil sTT
Metric 12: Study Design and Methods
Metric 13: Statistical power
Metric 14: Reproducibility of analyses
Metric 15: Statistical models
Medium x 0.4 0.8
Medium
Medium
x 0.2 0.4
x 0.2 0.4
Medium x 0.2 0.4
In this cross sectional study, participants working at
facilities using 1-BP were assessed for DNA damage
in leukocytes. Paired analyses and linear regression
models were used to determine the relationships be-
tween biomarkers of 1-BP exposure and DNA dam-
age.
There was sufficient participation (64 subjects) to
determine a significant effect.
Details on the multiple linear regression models used
in the analysis of 1-BP and DNA damage are lim-
ited but include variables used, including covariates
in adjusted models, transformations of continuous
variables, use of quartiles of exposure and how miss-
ing values were dealt with.
Multiple linear regression models were used to deter-
mine relationship between 1-BP exposure markers
(air, urine, blood) and DNA damage assessed using
comet assay. Exposure divided by quartile, as well
as continuous (log base 10 transformed).
Domain 6: Other Considerations for Biomarker Selection and Measurement
Metric 16: Use of Biomarker of Exposure
Metric 17: Effect biomarker
Metric 18: Method Sensitivity
Metric 19: Biomarker stability
High X 0.143 0.14 Levels of Br in serum and urine were used as a
biomarker for exposure. Samples were obtained at
the start and end of the work week (Monday morn-
ing and Thursday afternoon). Authors report that
Br is a metabolite of 1-BP with a low excretion
rate, which makes it an ideal biomarker for expo-
sure. Estimated exposure from these biomarkers was
highly correlated to personal air monitoring, increas-
ing confidence in the measurements.
High X 0.143 0.14 DNA breaks in leukocytes served as a metric for
DNA damage. This was evaluated using the comet
assay, a well-established method.
Medium X 0.143 0.29 Limits of detection were not presented, but only 14
individuals were missing exposure biomarkers, indi-
cating sufficient sensitivity.
Medium X 0.143 0.29 Storage history for samples described in detail, indi-
cates that samples were shipped to lab on ice imme-
diately and subsequently frozen. Exposure biomark-
ers not expected to degrade, but no stability assess-
ment reported.
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Study Citation: M. Toraason, D. W. Lynch, D. G. DeBord, N. Singh, E. Kreig, M. A. Butler, C. A. Toennis, J. Nemhauser (2006). DNA damage in
leukocytes of workers occupationally exposed to 1-bromopropane 1 01-014
Data Type:	Cross-sectional_Occupational_NC_NIOSH_cohort_l-BP_DNAdamage_air_quartiles-Other (please specify below)
HERO ID:	3974874
Domain Metric
Rating^
MWF*
Score
('ammoiilsTT
Metric 20: Sample contamination
Medium
x 0.143
0.29
No indication that contamination occurred, but no
description of ways to the authors took steps to
avoid contamination.
Metric 21: Method requirements
Low
x 0.143
0.43
Details on exposure biomarker methods are not de-
scribed in this study. Citation with details (Vaise-
man et al 1986) was not freely available to review.
Metric 22: Matrix adjustment
Low
x 0.143
0.43
Details on exposure biomarker methods are not de-
scribed in this study. Citation with details (Vaise-
man et al 1986) was not freely available to review.
Adjustments for creatine would be important for this
study.
Overall Quality Determination1"
Medium

2.1

Extracted
Yes




MWF = Metric Weighting Factor
High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.
The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.
Overall rating =
J]. (Metric Score; x MWF;) / J] . MWFj
if any metric is Unacceptable
(round to the nearest tenth) otherwise
where High => 1 to < 1.7; Medium => 1.7 to < 2.3; Low => 2.3 to < 3.0. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed out and
an arrow points to the new rating.
t This metric met the criteria for high confidence as expected for this type of study

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