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


Interagency Review Draft Document. Do Not Release or Distribute.
United States	Office of Chemical Safety and
bl	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
July 1, 2019, DRAFT
1

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Interagency Review Draft Document. Do Not Release or Distribute.
Table of Contents
1.	Acute Toxicity Studies	5
1.1.	Animal toxicity evaluation results of Garner et al 2007 for an acute inhalation
reproductive-sperm study on reproductive outcomes	5
1.2.	Animal toxicity evaluation results of Honma et al 2003 for an inhalation
neurotoxicity - traction time study on neurological/behavior outcomes	8
1.3.	Animal toxicity evaluation results of Ishidao et al 2002 for an acute, short-term
and subchronic inhalation studies study on hematological and immune, hepatic
outcomes	11
2.	Short - Term Toxicity Studies	14
2.1.	Animal toxicity evaluation results of Guo et al 2015 for a 12-day oral gavage
study on neurological/behavior outcomes	14
2.2.	Animal toxicity evaluation results of Liu et al 2009 for a 28-day inhalation-3
strains male mice, liver and repro study on hepatic, reproductive, body weight
outcomes	17
2.3.	Animal toxicity evaluation results of Mohideen et al 2013 for a 28-day
inhalation study on neurological/behavior outcomes	19
2.4.	Animal toxicity evaluation results of NTP 2011 for a 2-week inhalation dose
range finding study in rats and mice on mortality, nutrition and metabolic/adult
exposure body weight, neurological/behavior, respiratory, cardiovascular, renal,
hepatic, hematological and immune outcomes	22
2.5.	Animal toxicity evaluation results of Zhong et al 2013 for a 12-day oral gavage
neurotoxicity study in rats on nutrition and metabolic/adult exposure body weight,
neurological/behavior outcomes	28
2.6.	Animal toxicity evaluation results of Zong et al 2016 for a 28-day inhalation
study on neurological/behavior and hepatic outcomes	32
2.7.	Animal toxicity evaluation results of Zong et al 2016 for a 28-day inhalation
study on reproductive, hematological, immune, renal, and hepatic outcomes	35
3.	Subchronic Toxicity Studies	38
3.1.	Animal toxicity evaluation results of Anderson et al 2010 for a 4 and 10 week
inhalation immunotoxicity study in mice and rats on mortality, nutrition and
metabolic/adult exposure body weight, hematological and immune outcomes	38
3.2.	Animal toxicity evaluation results of Fueta et al 2007 for an inhalation
neurotoxicity-disinhibition and regional sensitivity study on neurological/behavior
outcomes	42
3.3.	Animal toxicity evaluation results of Honma et al 2003 for an inhalation
neurotoxicity study on neurological/behavior outcomes	45
3.4.	Animal toxicity evaluation results of Ichihara et al 2000 for a 12 week
inhalation reproductive tox study in male rats (hematol and immune) on
hematological and immune outcomes	48
3.5.	Animal toxicity evaluation results of Ichihara et al 2000 for a 12 week
inhalation reproductive tox study in male rats (renal, hepatic, endocrine) on renal,
hepatic, and endocrine outcomes	51
2

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3.6.	Animal toxicity evaluation results of Ichihara et al 2000 for a 12 week
inhalation reproductive tox study in male rats on nutrition and metabolic/adult
exposure body weight, and reproductive outcomes	54
3.7.	Animal toxicity evaluation results of Ishidao et al 2002 for an ADME -
metabolism after inhalation study on ADME/PBPK outcomes	57
3.8.	Animal toxicity evaluation results of NTP 2011 for a 3-month inhalation study
in rats and mice study on mortality, skin and connective tissue, ocular and sensory,
nutrition and metabolic/adult exposure body weight, respiratory, cardiovascular,
renal, hepatic, hematological and immune, clinical chemistry/biochemical, endocrine,
gastrointestinal, reproductive, thyroid outcomes	60
3.9.	Animal toxicity evaluation results of Yamada et al 2003 for an inhalation female
reproductive study on reproductive outcomes	63
3.10.	Animal toxicity evaluation results of Yu et al 2001 for a neurotoxicity-inhalation
study for 5 or 7 weeks on neurological outcomes	66
3.10. Animal toxicity evaluation results of Yu et al 2008 for an oral development-
dominant lethality, male reproductive study on growth (early life) and development,
reproductive outcomes	69
4. Chronic T oxicity Studies	72
4.1.	Animal toxicity evaluation results of Anonymous 1998 for a neurological study
on neurological/behavior outcomes	72
4.2.	Animal toxicity evaluation results of Brominated Solvents Consortium 2000 for
a summary of 2-gen study on growth (early life) and development outcomes	75
4.3.	Animal toxicity evaluation results of Bsoc 1998 for a summary of range-finding
repro/dev tox, full study in 4158101 study on growth (early life) and development
outcomes	78
4.4.	Animal toxicity evaluation results of Bsoc 1999 for a range-finding
developmental study on reproductive, growth (early life), and development outcomes
81
4.5.	Animal toxicity evaluation results of Bsoc 2001 for a summary of audited
results from 2-gen study on growth (early life) and development outcomes	84
4.6.	Animal toxicity evaluation results of ClinTrials 1997 for a 13 week inhalation
exposure study in rats on hematological and immune, neurological/behavior, renal,
hepatic, ocular and sensory, cardiovascular, clinical chemistry/biochemical,
endocrine, nutrition and metabolic/adult exposure body weight, respiratory, and
thyroid outcomes	87
4.7.	Animal toxicity evaluation results of ClinTrials 1997 for a 13-week inhalation
exposure in rats study on reproductive outcomes	92
4.8.	Animal toxicity evaluation results of Saito-Suzuki et al 1982 for a dominant
lethal mating experiment study on reproductive outcomes	96
4.9.	Animal toxicity evaluation results of WIL Research 2001 for a 2-generation
inhalation study - developmental study on growth (early life) and development
outcomes	99
4.10.	Animal toxicity evaluation results of WIL Research 2001 for a 2-generation
inhalation - kidney study on kidney outcomes	102
3

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4.10. Animal toxicity evaluation results of WIL Research 2001 for a 2-generation
inhalation - liver study on liver outcomes	105
4.10. Animal toxicity evaluation results of WIL Research 2001 for a 2-generation
inhalation - neurological study on neurological outcomes	108
4.10. Animal toxicity evaluation results of WIL Research 2001 for a 2-generation
inhalation - reproductive study on reproductive outcomes	Ill
5.	Cancer Studies	114
5.1. Animal toxicity evaluation results of NTP 2011 for a 2 year inhalation study in
rats and mice study on mortality, skin and connective tissue, ocular and sensory,
nutrition and metabolic/adult exposure body weight, respiratory, cardiovascular,
renal, hepatic, hematological and immune, endocrine, gastrointestinal, reproductive,
thyroid, cancer outcomes	114
6.	Genotoxicity Studies	117
6.1. Animal toxicity evaluation results of Young 2016	117
6.2	Animal toxicity evaluation results of Weinberg 2016 for a 4-week somatic
mutation gene inhalation study in transgenic mice study on hepatic and body weight
outcomes	122
6.3	Animal toxicity evaluation results of Saito-Suzuki et al 1982 for a dominant lethal
mating experiment study on reproductive outcomes	124
4

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1. Acute Toxicity Studies
1.1. Animal toxicity evaluation results of Garner et al 2007 for an acute inhalation
reproductive-sperm study on reproductive outcomes
Study reference:
Garner, C. E.,Sloan, C.,Sumner, S. C.,Burgess, J.,Davis, J.,Etheridge, A.,Parham, A.,Ghanayem, B. 1. (2007).
CYP2El-catalyzed oxidation contributes to the sperm toxicity of 1-bromopropane in mice Biology of
Reproduction, 76(3), 496-505
HERO ID: 1519112
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by name and form
(radiolabel and neat).
High
1
2
2
2. Test Substance
Source
The source was reported
and identify confirmed
by GCMS.
High
1
1
1
3. Test Substance
Purity
The reported purity was
such that effects likely
due to the test
substance.
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
Controls were used, but
not described. However,
the purpose of the study
was to determine the
contribution of CYP2E1
to the kinetics of
elimination via
comparison of Cyp2el
knockout and wild-type
mice. This limitation is
unlikely to have a major
impact on results.
Not Rated (NR)
NR
NR
NR
5. Positive Controls
Positive controls were
not required.
NR
NR
NR
NR
6. Randomized
Allocation
Allocation methods were
not reported.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
The method and
equipment used to
generate the test gas
were reported and
appropriate.
High
1
1
1
8. Consistency of
Exposure
Administration
Exposure administration
was consistent.
High
1
1
1
5

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Garner, C. E.,Sloan, C.,Sumner, S. C.,Burgess, J.,Davis, J.,Etheridge, A.,Parham, A.,Ghanayem, B. 1. (2007).
CYP2El-catalyzed oxidation contributes to the sperm toxicity of 1-bromopropane in mice Biology of
Reproduction, 76(3), 496-505
HERO ID: 1519112
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

9. Reporting of
Doses/Concentratio
ns
The initial concentration
was reported and
graphical depiction of
chamber concentrations
over time was provided.
The methods used to
measure chamber
concentrations were
reported, and based on
the graph, the initial
concentrations were
approximately 20%
above target. Because
both of the groups used
for comparison (wild
type and knockout)
received the same
exposure, this limitation
is unlikely to have a
substantial impact on
results.
Medium
2
2
4
10. Exposure
Frequency and
Duration
Duration was reported.
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
Only a single exposure
concentration was used.
Not Rated
NR
NR
NR
12. Exposure Route
and Method
It is unclear of the air
changes/hour in the
chamber.
Low
3
1
3
Test Organism
13. Test Animal
Characteristics
The source, strain, sex,
and age were reported.
Initial body weight and
health status were not
reported. Cyp2el mice
were included in the
study along with WT
mice.
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
All conditions except
room air changes were
reported.
Medium
2
1
2
6

15. Number per
Group
The number of animals
per group was
appropriate.
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Outcome assessment
methodology was
described and
appropriate.
High
1
2
2
17. Consistency of
Outcome
Assessment
Outcomes were assessed
consistently.
High
1
1
1
18. Sampling
Adequacy
Sampling was adequate.
High
1
1
1
19. Blinding of
Assessors
Blinding not required.
Not Rated
NR
NR
NR
20. Negative Control
Response
Negative control
responses were
appropriate.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No confounding
variables were reported,
but respiratory rate and
body temperature were
not measured or
reported.
Medium
2
2
4
22. Health
Outcomes Unrelated
to Exposure
No health outcomes
unrelated to exposure
were reported.
Medium
2
1
2
Data Presentation
and Analysis
23. Statistical
Methods
The methods were
reported and
appropriate.
High
1
1
1
24. Reporting of
Data
Data were adequately
reported.
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

26
38
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.4615
Overall Score:
Nearest *:
1.5
Overall Quality Level:
High
7

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1.2. Animal toxicity evaluation results of Honma et al 2003 for an inhalation
neurotoxicity - traction time study on neurological/behavior outcomes
Study reference:
Honma, T.,Suda, M.,Miyagawa, M. (2003). Inhalation of 1-bromopropane causes excitation in the central
nervous system of male F344 rats NeuroToxicology, 24(4-5), 563-575

HERO ID: 1519108

Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
Test substance identified
by name.
Medium
2
2
4
Test Substance
2. Test Substance
Source
Source identified.
Medium
2
1
2

3. Test Substance
Purity
Identified as GR grade.
Medium
2
1
2

4. Negative and
Vehicle Controls
Negative controls were
included.
High
1
2
2
Test Design
5. Positive Controls
Positive controls not
required.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Animals were allocated
so minimize mean body
weight differences
across groups.
Medium
2
1
2

7. Preparation and
Storage of Test
Substance
Inhalation exposure
information as described
in Sekiguchi et al., 2002
and Tsuga and Honma,
2000.
Medium
2
1
2
Exposure
Characterization
8. Consistency of
Exposure
Administration
Animals exposed during
the same time.
Inhalation exposure
information as described
in Sekiguchi et al., 2002
and Tsuga and Honma,
2000.
Medium
2
1
2
9. Reporting of
Doses/Concentratio
ns
Only target and
converted
concentrations were
reported.
Medium
2
2
4

10. Exposure
Frequency and
Duration
The frequency and
duration were reported;
however, the duration of
exposure did not span a
28-day period in the
repeated-dose inhalation
study
Medium
2
1
2
8

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Honma, T.,Suda, M.,Miyagawa, M. (2003). Inhalation of 1-bromopropane causes excitation in the central
nervous system of male F344 rats NeuroToxicology, 24(4-5), 563-575
HERO ID: 1519108
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
The number of groups
and spacing were
reported and the highest
concentration was based
on a previous study.
High
1
1
1
12. Exposure Route
and Method
Inhalation exposure
information as described
in Sekiguchi et al., 2002
and Tsuga and Honma,
2000.
Low
3
1
3
Test Organism
13. Test Animal
Characteristics
The source, species,
strain, age, sex, and
initial body weight were
reported. Health status
was not reported.
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
All conditions were
reported except for
room air changes.
Medium
2
1
2
15. Number per
Group
The number of animals
per experiment (n=4-5)
was adequate, but lower
than the typical number
used in studies of similar
type (N=10)
Medium
2
1
2
Outcome
Assessment
16. Outcome
Assessment
Methodology
Outcome assessment
methodology was
reported clearly (e.g., rat
forced to hang from
suspended bar; hang
time was recorded).
Standard motor/strength
test
High
1
2
2
17. Consistency of
Outcome
Assessment
Outcomes were assessed
consistently.
High
1
1
1
18. Sampling
Adequacy
Sampling was adequate
for the number of
evaluations per exposure
group.
High
1
1
1
9

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Honma, T.,Suda, M.,Miyagawa, M. (2003). Inhalation of 1-bromopropane causes excitation in the central
nervous system of male F344 rats NeuroToxicology, 24(4-5), 563-575
HERO ID: 1519108
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

19. Blinding of
Assessors
Blinding not required for
this endpoint (objective
measure of traction
time).
Not Rated
NR
NR
NR
20. Negative Control
Response
Negative control
responses were
appropriate.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rate was not
reported; however, body
temperature was
monitored and may
serve as a proxy for
respiration.
Medium
2
2
4
22. Health
Outcomes Unrelated
to Exposure
No health outcomes
unrelated to exposure
were reported.
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
reported and are
appropriate.
High
1
1
1
24. Reporting of
Data
Data were reported.
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

29
47
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.6207
Overall Score:
Nearest *:
1.6
Overall Quality Level:
High
10

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Interagency Review Draft Document. Do Not Release or Distribute.
1.3. Animal toxicity evaluation results of Ishidao et al 2002 for an acute, short-term
and subchronic inhalation studies study on hematological and immune, hepatic
outcomes
Study reference:
Ishidao, T.,Kunugita, N.,Fueta, Y.,Arashidani, K.,Hori, H. (2002). Effects of inhaled 1-bromopropane vapor on rat
metabolism Toxicology Letters, 134(1-3), 237-243
HERO ID: 1717491
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Identified by chemical
name.
High
1
2
2
2. Test Substance
Source
Manufacturer was
indicated without lot no.
Medium
2
1
2
3. Test Substance
Purity
Purity was not reported.
Low
3
1
3
Test Design
4. Negative and
Vehicle Controls
Air controls.
Not Rated
NR
NR
NR
5. Positive Controls
Positive controls were
not needed for repeat
dose studies.
Not Rated
NR
NR
NR
6. Randomized
Allocation
The study did not report
how animals were
allocated to study
groups.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Vapor generation
method and equipment
were reported.
High
1
1
1
8. Consistency of
Exposure
Administration
See footnote at end of
page.1
High
1
1
1
9. Reporting of
Doses/Concentratio
ns
Measured
concentrations were not
reported.
Low
3
2
6
10. Exposure
Frequency and
Duration
6h/day, 5 days/wk, 3, 4,
or 12 weeks (also single
day exposure).
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
High and low
concentrations were not
exposed for the same
durations (700 ppm for 4
and 12 weeks; 1500 ppm
for 3 weeks).
Low
3
1
3
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
11

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Ishidao, T.,Kunugita, N.,Fueta, Y.,Arashidani, K.,Hori, H. (2002). Effects of inhaled 1-bromopropane vapor on rat
metabolism Toxicology Letters, 134(1-3), 237-243
HERO ID: 1717491
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

12. Exposure Route
and Method
See footnote at end of
page.1
High
1
1
1
Test Organism
13. Test Animal
Characteristics
Commercial source
(species, strain, age
reported).
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Husbandry conditions
were not reported.
Low
3
1
3
15. Number per
Group
10/group
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Hematological
parameters were limited
to (RBC, WBC, Hb and
Hct). Serum ALT and AST
were the only hepatic
endpoints evaluated
(i.e., no liver wt. or
histopathology).
Unacceptable
4
2
8
17. Consistency of
Outcome
Assessment
See footnote at end of
page.1
High
1
1
1
18. Sampling
Adequacy
Data were not reported
for (4 week) 1500 ppm
exposure group.
Medium
2
1
2
19. Blinding of
Assessors
Blinding was not
reported; however,
outcomes were
objective.
Not rated
NR
NR
NR
20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rate was not
measured and 1-BP is
expected to be a
respiratory irritant.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
Data on attrition and/or
health outcomes
unrelated to exposure
were not reported.
Not Rated
NR
NR
NR
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
12

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Ishidao, T.,Kunugita, N.,Fueta, Y.,Arashidani, K.,Hori, H. (2002). Effects of inhaled 1-bromopropane vapor on rat
metabolism Toxicology Letters, 134(1-3), 237-243
HERO ID: 1717491
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Data Presentation
and Analysis
23. Statistical
Methods
See footnote at end of
page.1
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

26
50
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.9231
Overall Score:
Nearest *:
1.9
Overall Quality Level:
Medium


1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
13

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Interagency Review Draft Document. Do Not Release or Distribute.
2. Short - Term Toxicity Studies
2.1. Animal toxicity evaluation results of Guo et al 2015 for a 12-day oral gavage study
on neurological/behavior outcomes
Study reference:
Guo, Y.,Yuan, H.,Jiang, L.,Yang, J.,Zeng, T.,Xie, K.,Zhang, C.,Zhao, X. (2015). Involvement of decreased
neuroglobin protein level in cognitive dysfunction induced by 1-bromopropane in rats Brain Research, 1600, 1-
16
HERO ID: 2990971
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Identified by chemical
name
High
1
2
2
2. Test Substance
Source
Manufacturer was
reported without
lot/batch no.
Medium
2
1
2
3. Test Substance
Purity
See footnote at end of
page.1
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
See footnote at end of
page.1
High
1
2
2
5. Positive Controls
Positive controls are not
needed for neurotoxicity
studies.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Study did not report the
method used to allocate
animals to study groups.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
1-BP was dissolved in
corn oil; no further
details were reported.
Medium
2
1
2
8. Consistency of
Exposure
Administration
Gavage volume was not
reported.
Medium
2
1
2
9. Reporting of
Doses/Concentratio
ns
See footnote at end of
page.1
High
1
2
2
10. Exposure
Frequency and
Duration
Daily gavage
administration for 12
consecutive days differs
from typical
neurotoxicity study
designs.
Medium
2
1
2
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
14

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Guo, Y.,Yuan, H.,Jiang, L.,Yang, J.,Zeng, T.,Xie, K.,Zhang, C.,Zhao, X. (2015). Involvement of decreased
neuroglobin protein level in cognitive dysfunction induced by 1-bromopropane in rats Brain Research, 1600, 1-
16
HERO ID: 2990971
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
4 Treatment groups, plus
control. Dose levels and
spacing were not
justified, but a range of
responses was observed.
Medium
2
1
2
12. Exposure Route
and Method
Dosing volumes were
not reported.
Medium
2
1
2
Test Organism
13. Test Animal
Characteristics
Species, strain and
starting body weight
were reported; health
status and age were not.
(commercial source).
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Husbandry conditions
were reported and
appropriate.
High
1
1
1
15. Number per
Group
14/group
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Behavioral tests and
estimation of neuronal
loss.
High
1
2
2
17. Consistency of
Outcome
Assessment
See footnote at end of
page.1
High
1
1
1
18. Sampling
Adequacy
10/group for behavior;
4/group for
immunohistochemistry.
Medium
2
1
2
19. Blinding of
Assessors
Blinding was not
reported, but outcomes
were objective.
Not Rated
NR
NR
NR
20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No differences in initial
body weight
High
1
2
2
22. Health
Outcomes Unrelated
to Exposure
Data on attrition and/or
health outcomes
unrelated to exposure
were not reported
Not Rated
NR
NR
NR
15

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Guo, Y.,Yuan, H.,Jiang, L.,Yang, J.,Zeng, T.,Xie, K.,Zhang, C.,Zhao, X. (2015). Involvement of decreased
neuroglobin protein level in cognitive dysfunction induced by 1-bromopropane in rats Brain Research, 1600, 1-
16

HERO ID: 2990971





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Data Presentation
23. Statistical
Methods
See footnote at end of
page.1
High
1
1
1
and Analysis
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2


Sum of scores:

28
39
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.3929
Overall Score:
Nearest *:
1.4
Low: >=2.3 and <=3







Overall Quality Level:

High

16

-------
Interagency Review Draft Document. Do Not Release or Distribute.
2.2. Animal toxicity evaluation results of Liu et al 2009 for a 28-day inhalation-3 strains
male mice, liver and repro study on hepatic, reproductive, body weight outcomes
Study reference:
Liu, F., Ichihara, S., Mohideen, S. S., Sai, U., Kitoh, J., Ichihara, G. (2009). Comparative study on susceptibility to
1-bromopropane in three mice strains Toxicological Sciences, 112(1), 100-110
HERO ID: 1519113
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by name.
Medium
2
2
4
2. Test Substance
Source
Source identified.
Medium
2
1
2
3. Test Substance
Purity
The reported purity was
such that effects likely
due to test substance.
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
Concurrent negative
controls were included.
High
1
2
2
5. Positive Controls
Positive controls not
required.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Study did not report the
method used to
randomly allocate
animals to study groups.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Preparation of the test
material was reported;
storage was not.
Medium
2
1
2
8. Consistency of
Exposure
Administration
Exposures were
conducted during the
same time each day.
The inhalation exposure
system was as described
in Ichihara et al., 1997
and Takeuchi et al. 1989.
Not Rated
NR
NR
NR
9. Reporting of
Doses/Concentratio
ns
Target and mean
measured
concentrations were
reported
Medium
2
2
4
10. Exposure
Frequency and
Duration
Frequency and duration
were adequate.
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
The number of groups
and spacing were
reported and based on
preliminary experiments.
High
1
1
1
17

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Liu, F., Ichihara, S., Mohideen, S. S., Sai, U., Kitoh, J., Ichihara, G. (2009). Comparative study on susceptibility to
1-bromopropane in three mice strains Toxicological Sciences, 112(1), 100-110

HERO ID: 1519113

Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

12. Exposure Route
and Method
The inhalation exposure
system was as described
in Ichihara et al., 1997
and Takeuchi et al. 1989.
Not Rated
NR
NR
NR
Test Organism
13. Test Animal
Characteristics
The source, species,
strains, sex, and age
were reported. Initial
body weight and health
status were not
reported.
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
All conditions except
room air changes were
reported.
Medium
2
1
2

15. Number per
Group
The number of animals
per group is appropriate.
High
1
1
1

16. Outcome
Assessment
Methodology
Outcome assessment
methodology was
reported and
appropriate.
High
1
2
2

17. Consistency of
Outcome
Assessment
Outcomes were assessed
consistently.
High
1
1
1
Outcome
18. Sampling
Adequacy
Sampling was adequate.
High
1
1
1
Assessment
19. Blinding of
Assessors
Histopathological
examinations were
performed by
investigators blinded to
the strain and treatment
type.
High
1
1
1

20. Negative Control
Response
Negative control
responses responded
appropriately.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rate was not
reported or measured.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
See footnote at end of
page.1
High
1
1
1
18

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Liu, F., Ichihara, S., Mohideen, S. S., Sai, U., Kitoh, J., Ichihara, G. (2009). Comparative study on susceptibility to
1-bromopropane in three mice strains Toxicological Sciences, 112(1), 100-110
HERO ID: 1519113
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Data Presentation
and Analysis
23. Statistical
Methods
See footnote at end of
page.11
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

28
43
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.5357
Overall Score:
Nearest *:
1.5
Overall Quality Level:
High
2.3. Animal toxicity evaluation results of Mohideen et al 2013 for a 28-day inhalation
study on neurological/behavior outcomes
Study reference:
Mohideen, S. S., Ichihara, S., Subramanian, K., Huang, Z., Naito, H., Kitoh, J., Ichihara, G. (2013). Effects of
exposure to 1-bromopropane on astrocytes and oligodendrocytes in rat brain Journal of Occupational Health,
55(1), 29-38
HERO ID: 1717378
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
See footnote at end of
page.2
High
1
2
2
2. Test Substance
Source
See footnote at end of
page.1
High
1
1
1
3. Test Substance
Purity
See footnote at end of
page.1
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
See footnote at end of
page.1
High
1
2
2
1	Metric that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation
2	Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
19

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Mohideen, S. S., Ichihara, S., Subramanian, K., Huang, Z., Naito, H., Kitoh, J., Ichihara, G. (2013). Effects of
exposure to 1-bromopropane on astrocytes and oligodendrocytes in rat brain Journal of Occupational Health,
55(1), 29-38
HERO ID: 1717378
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

5. Positive Controls
Positive controls are not
needed for 28-day
inhalation study.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Method used to
randomly allocate
animals to study groups
was not reported.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Preparation of test
substance was reported;
storage was not.
Medium
2
1
2
8. Consistency of
Exposure
Administration
See footnote at end of
page.1
High
1
1
1
9. Reporting of
Doses/
Concentrations
See footnote at end of
page.1
High
1
2
2
10. Exposure
Frequency and
Duration
See footnote at end of
page.1
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
See footnote at end of
page.1
High
1
1
1
12. Exposure Route
and Method
The inhalation exposure
system was as described
in Ichihara et al.,2000.
Not Rated
NR
NR
NR
Test Organism
13. Test Animal
Characteristics
See footnote at end of
page.1
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
See footnote at end of
page.1
High
1
1
1
15. Number per
Group
3 rats/group for
histopathology (3 brain
sections. 9/group for
brain biochemistry.
Medium
2
1
2
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
20

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Mohideen, S. S., Ichihara, S., Subramanian, K., Huang, Z., Naito, H., Kitoh, J., Ichihara, G. (2013). Effects of
exposure to 1-bromopropane on astrocytes and oligodendrocytes in rat brain Journal of Occupational Health,
55(1), 29-38
HERO ID: 1717378
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Outcome
Assessment
16. Outcome
Assessment
Methodology
See footnote at end of
page.1
High
1
2
2
17. Consistency of
Outcome
Assessment
Assessments were
conducted consistently
across dose groups.
High
1
1
1
18. Sampling
Adequacy
See footnote at end of
page.1
High
1
1
1
19. Blinding of
Assessors
Blinding was not
reported, but outcomes
were objective.
Medium
2
1
2
20. Negative Control
Response
A negative control was
included and responded
appropriately.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rate was not
reported and 1-BP is
anticipated to be a
respiratory irritant'.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
See footnote at end of
page.1
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
See footnote at end of
page.1
High
1
1
1
24. Reporting of
Data
Some Western blot and
mRNA data were not
shown.
Medium
2
2
4
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

29
40
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.3793
Overall Score:
Nearest *:
1.4
Overall Quality Level:
High
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
21

-------
Interagency Review Draft Document. Do Not Release or Distribute.
2.4. Animal toxicity evaluation results of NTP 2011 for a 2-week inhalation dose range
finding study in rats and mice on mortality, nutrition and metabolic/adult
exposure body weight, neurological/behavior, respiratory, cardiovascular, renal,
hepatic, hematological and immune outcomes	
Study reference:
NTP, (2011). NTP technical report on the toxicology and carcinogenesis studies of 1-bromopropane (CAS No.
106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies), GRA and 1

HERO ID: 1737813





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
Chambers analyzed for
particles to ensure form
of 1-BP was vapor.
High
1
2
2
Test Substance
2. Test Substance
Source
See footnote at end of
page.1
High
1
1
1

3. Test Substance
Purity
See footnote at end of
page.1
High
1
1
1

4. Negative and
Vehicle Controls
See footnote at end of
page.1
High
1
2
2

5. Positive Controls
Positive controls not
typical for this study type
Not Rated
NR
NR
NR
Test Design
6. Randomized
Allocation
Random allocation into
groups with
approximately equal
initial mean body
weights
Medium
2
1
2

7. Preparation and
Storage of Test
Substance
See footnote at end of
page.1
High
1
1
1

8. Consistency of
Exposure
Administration
No inconsistencies in
administration were
reported.
High
1
1
1
Exposure
Characterization
9. Reporting of
Doses/Concentratio
ns
Analytical concentrations
were reported and
within 10% of nominal.
Chamber air analyzed by
GC every 20 min during
exposure
High
1
2
2

10. Exposure
Frequency and
Duration
See footnote at end of
page.1
High
1
1
1

11. Number of
Exposure Groups
and Dose Spacing
5 nonzero exposure
levels were used, ranging
16-fold and yielding
effects at the higher
concentrations.
High
1
1
1
22

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
NTP, (2011). NTP technical report on the toxicology and carcinogenesis studies of 1-bromopropane (CAS No.
106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies), GRA and 1
HERO ID: 1737813
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

12. Exposure Route
and Method
Study does not explicitly
state whether nose-only
or whole body, but it
appears to be dynamic
whole body chamber
with 15 air changes/hr.
Medium
2
1
2
Test Organism
13. Test Animal
Characteristics
See footnote at end of
page.1
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
See footnote at end of
page.1
High
1
1
1
15. Number per
Group
5/sex/group;
appropriate number for
study duration/purpose.
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Outcome assessment
described in detail;
appropriate methods
used.
High
1
2
2
17. Consistency of
Outcome
Assessment
No inconsistencies in
outcome assessment
were reported.
High
1
1
1
18. Sampling
Adequacy
Histopathology
examined on all control
and high exposure
animals, and to a no
effect level for organs
affected at the highest
exposure level.
High
1
1
1
19. Blinding of
Assessors
No subjective endpoints
evaluated apart from
clinical signs of toxicity.
Not Rated
NR
NR
NR
20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Body temperature and
were respiratory rates
not reported.
Low
3
2
6
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
23

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
NTP, (2011). NTP technical report on the toxicology and carcinogenesis studies of 1-bromopropane (CAS No.
106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies), GRA and 1
HERO ID: 1737813
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

22. Health
Outcomes Unrelated
to Exposure
See footnote at end of
page.1
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
See footnote at end of
page.1
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

29
35
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.2069
Overall Score:
Nearest *:
1.2
Overall Quality Level:
High
24

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Animal toxicity evaluation results of Zhang et al 2013 for 7-day and 4-week inhalation
studies on neurological/behavior, endocrine outcomes	
Study reference:
Zhang, L., Nagai, T., Yamada, K., Ibi, D., Ichihara, S., Subramanian, K., Huang, Z., Mohideen, S. S., Naito, H.,
Ichihara, G. (2013). Effects of sub-acute and sub-chronic inhalation of 1-bromopropane on neurogenesis in adult
rats Toxicology, 304(0), 76-82

HERO ID: 1717376





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
Identified by chemical
name.
High
1
2
2
Test Substance
2. Test Substance
Source
No details were provided
on the source of the test
substance.
Low
3
1
3

3. Test Substance
Purity
Purity was not reported.
Low
3
1
3

4. Negative and
Vehicle Controls
See footnote at end of
page.1
High
1
2
2
Test Design
5. Positive Controls
Positive controls were not
needed for this study
design.
Not Rated
NR
NR
NR

6. Randomized
Allocation
The study did not report
how animals were
allocated to study groups.
Low
3
1
3

7. Preparation and
Storage of Test
Substance
Method and equipment
was briefly described
(further details were
provided in another
paper (Ichihara et al,
2000)
Medium
2
1
2

8. Consistency of
Exposure
Administration
See footnote at end of
page.1
High
1
1
1
Exposure
Characterization
9. Reporting of
Doses/
Concentrations
Analytical concentrations
were not reported;
however, chamber
concentrations were
measured by GC every 10
seconds and
electronically controlled
to within +/- 5%.
Medium
2
2
4

10. Exposure
Frequency and
Duration
8h/day for 1 or 4 weeks.
Days per week was not
specified for the 4-week
studies.
Medium
2
1
2
25

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Zhang, L., Nagai, T., Yamada, K., Ibi, D., Ichihara, S., Subramanian, K., Huang, Z., Mohideen, S. S., Naito, H.,
Ichihara, G. (2013). Effects of sub-acute and sub-chronic inhalation of 1-bromopropane on neurogenesis in adult
rats Toxicology, 304(0), 76-82

HERO ID: 1717376





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
3 concentrations plus
control. Concentrations
were not justified, but a
range of responses was
observed.
High
1
1
1

12. Exposure Route
and Method
The inhalation exposure
system was as described
in Ichihara et al., 2000).
Dynamic whole-body
chamber.
Not Rated
NR
NR
NR

13. Test Animal
Characteristics
Species, strain, sex, age,
and starting body weight
were reported
(commercial source)
High
1
2
2
Test Organism
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Husbandry conditions
were reported and
appropriate.
High
1
1
1

15. Number per
Group
12/group (6 for
biochemistry; 6 for
histopathology)
High
1
1
1

16. Outcome
Assessment
Methodology
See footnote at end of
page.1
High
1
2
2

17. Consistency of
Outcome
Assessment
See footnote at end of
page.1
High
1
1
1
Outcome
Assessment
18. Sampling
Adequacy
6/group for biochemistry;
6/group for
histopathology
High
1
1
1

19. Blinding of
Assessors
Histopath. examiner was
blinded to exposure
group.
High
1
1
1

20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rate was not
measured and 1-BP is
expected to be a
respiratory irritant.
Low
3
2
6
26

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Zhang, L., Nagai, T., Yamada, K., Ibi, D., Ichihara, S., Subramanian, K., Huang, Z., Mohideen, S. S., Naito, H.,
Ichihara, G. (2013). Effects of sub-acute and sub-chronic inhalation of 1-bromopropane on neurogenesis in adult
rats Toxicology, 304(0), 76-82
HERO ID: 1717376
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

22. Health
Outcomes Unrelated
to Exposure
Data on attrition and/or
health outcomes
unrelated to exposure
were not reported.
Not Rated
NR
NR
NR
Data Presentation
and Analysis
23. Statistical
Methods
See footnote at end of
page.1
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

28
42
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.5000
Overall Score:
Nearest *:
1.5
Overall Quality Level:
High
27

-------
Interagency Review Draft Document. Do Not Release or Distribute.
2.5. Animal toxicity evaluation results of Zhong et al 2013 for a 12-day oral gavage
neurotoxicity study in rats on nutrition and metabolic/adult exposure body
weight, neurological/behavior outcomes	
Study reference:
Zhong, Z.,Zeng, T.,Xie, K.,Zhang, C.,Chen, J.,Bi, Y.,Zhao, X. (2013). Elevation of 4-hydroxynonenal and
malondialdehyde modified protein levels in cerebral cortex with cognitive dysfunction in rats exposed to 1-
bromopropane Toxicology, 306(0), 16-23
HERO ID: 1717375
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
See footnote at end of
page.1
High
1
2
2
2. Test Substance
Source
Test substance obtained
from manufacturer; lot
number not provided
and certificationof
authenticity not
reported.
Medium
2
1
2
3. Test Substance
Purity
See footnote at end of
page.1
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
See footnote at end of
page.1
High
1
2
2
5. Positive Controls
A strict requirement for
use of a positive control
in Morris water maze
testing was not
identified in guidance.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Method used for
allocation of animals in
test groups not reported.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
1-BP was dissolved in
corn oil; no further
details were reported.
Medium
2
1
2
8. Consistency of
Exposure
Administration
No inconsistencies in
exposure administration
were noted. Time of day
of gavage administration
was not reported.
Medium
2
1
2
9. Reporting of
Doses/Concentratio
ns
See footnote at end of
page.1
High
1
2
2
10. Exposure
Frequency and
Duration
Daily administration for
12 days; duration was
sufficient to elicit effect.
High
1
1
1
28

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Zhong, Z.,Zeng, T.,Xie, K.,Zhang, C.,Chen, J.,Bi, Y.,Zhao, X. (2013). Elevation of 4-hydroxynonenal and
malondialdehyde modified protein levels in cerebral cortex with cognitive dysfunction in rats exposed to 1-
bromopropane Toxicology, 306(0), 16-23
HERO ID: 1717375
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
3 nonzero dose groups
spanning a range of 4-
fold were used; effects
were seen at all doses,
so the low dose may not
have been low enough.
Dose selection was
based on preliminary
experiments.
Medium
2
1
2
12. Exposure Route
and Method
See footnote at end of
page.1
High
1
1
1
Test Organism
13. Test Animal
Characteristics
The test animal species,
strain, sex, lifestage, and
starting body weight
were reported, and the
test animal was obtained
from a commercial
source. Health status
and specific age were
not reported. Only male
rats were tested.
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Animal husbandry
conditions were
reported and adequate,
except number of
animals per cage.
Medium
2
1
2
15. Number per
Group
See footnote at end of
page.1
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
The only neurotoxicity
metric tested was the
Morris water maze. The
procedure was described
adequately.
Medium
2
2
4
17. Consistency of
Outcome
Assessment
Time of day of testing
was not reported, so the
consistency of outcome
assessment is uncertain.
Low
3
1
3
18. Sampling
Adequacy
All animals were
evaluated for all
endpoints.
High
1
1
1
29

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Zhong, Z.,Zeng, T.,Xie, K.,Zhang, C.,Chen, J.,Bi, Y.,Zhao, X. (2013). Elevation of 4-hydroxynonenal and
malondialdehyde modified protein levels in cerebral cortex with cognitive dysfunction in rats exposed to 1-
bromopropane Toxicology, 306(0), 16-23
HERO ID: 1717375
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

19. Blinding of
Assessors
Study did not report
blinding, but Morris
water maze test is
evaluated with largely
objective metrics
(escape latency, distance
traveled)
Medium
2
1
2
20. Negative Control
Response
Negative control
response was reported
and appeared to be
appropriate. Control
response in the MWM
was variable, but not so
variable that significant
differences were
masked.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No information on food
or water intake was
provided.
Medium
2
2
4
22. Health
Outcomes Unrelated
to Exposure
No health outcomes
unrelated to exposure
were noted. There was
no animal attrition.
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
Statistical analysis
methods were described
and appropriate.
High
1
1
1
24. Reporting of
Data
Data are presented
graphically with
overlapping SD bars that
preclude digitizing data
for independent analysis.
Medium
2
2
4

Sum of scores:

30
48
30

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Zhong, Z.,Zeng, T.,Xie, K.,Zhang, C.,Chen, J.,Bi, Y.,Zhao, X. (2013). Elevation of 4-hydroxynonenal and
malondialdehyde modified protein levels in cerebral cortex with cognitive dysfunction in rats exposed to 1-
bromopropane Toxicology, 306(0), 16-23

HERO ID: 1717375





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
High: >=1 and <1.7
Medium: >-1.7 and <2.3
Low: >=2.3 and <=3
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.6000
Overall Score:
Nearest *:
1.6
Overall Quality Level:
High


31

-------
Interagency Review Draft Document. Do Not Release or Distribute.
2.6. Animal toxicity evaluation results of Zong et al 2016 for a 28-day inhalation study
on neurological/behavior and hepatic outcomes
Study reference:
Zong, C.,Garner, C. E.,Huang, C.,Zhang, X.,Zhang, L.,Chang, J.,Toyokuni, S.,lto, H.,Kato, M.,Sakurai, T.,lchihara,
S.,lchihara, G. (2016). Preliminary characterization of a murine model for 1-bromopropane neurotoxicity: Role of
cytochrome P450 Toxicology Letters, 258, 249-258

HERO ID: 3539685





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
See footnote at end of
page.1
High
1
2
2
Test Substance
2. Test Substance
Source
See footnote at end of
page.1
High
1
1
1

3. Test Substance
Purity
See footnote at end of
page.1
High
1
1
1

4. Negative and
Vehicle Controls
See footnote at end of
page1
High
1
2
2
Test Design
5. Positive Controls
Positive controls are not
needed for repeat dose
inhalation studies.
Not Rated
NR
NR
NR

6. Randomized
Allocation
The study authors did
not report how animals
were allocated to study
groups.
Low
3
1
3

7. Preparation and
Storage of Test
Substance
Methods were briefly
described. Equipment
and methods used for
vapor generation are
reported in other
publications.
Not Rated
NR
NR
NR

8. Consistency of
Exposure
Administration
See footnote at end of
page1
High
1
1
1
Exposure
Characterization
9. Reporting of
Doses/Concentratio
ns
Measured
concentrations were not
reported; however,
concentrations were
measured every 5
seconds by GC and were
digitally controlled to be
within +/-5% of the
target.
Medium
2
2
4

10. Exposure
Frequency and
Duration

High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
32

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Zong, C.,Garner, C. E.,Huang, C.,Zhang, X.,Zhang, L.,Chang, J.,Toyokuni, S.,lto, H.,Kato, M.,Sakurai, T.,lchihara,
S.,lchihara, G. (2016). Preliminary characterization of a murine model for 1-bromopropane neurotoxicity: Role of
cytochrome P450 Toxicology Letters, 258, 249-258
HERO ID: 3539685
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
Concentrations were
justified by previous
data. 2 concentrations
plus control. A range of
responses was noted.
Medium
2
1
2
12. Exposure Route
and Method
See footnote at end of
page1
High
1
1
1
Test Organism
13. Test Animal
Characteristics
Species, strain, sex and
starting age was
reported; initial body
weight was not
(commercial source).
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Husbandry conditions
(except number of
animals per cage) were
reported
Medium
2
1
2
15. Number per
Group
5-6/group
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
See footnote at end of
page1
High
1
2
2
17. Consistency of
Outcome
Assessment
See footnote at end of
page1
High
1
1
1
18. Sampling
Adequacy
See footnote at end of
page1
High
1
1
1
19. Blinding of
Assessors
Blinding was not
reported for subjective
endpoints.
Low
3
1
3
20. Negative Control
Response
See footnote at end of
page1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rate was not
measured; 1-BP is
expected to cause
respiratory irritation.
Low
3
2
6
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
33

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Zong, C.,Garner, C. E.,Huang, C.,Zhang, X.,Zhang, L.,Chang, J.,Toyokuni, S.,lto, H.,Kato, M.,Sakurai, T.,lchihara,
S.,lchihara, G. (2016). Preliminary characterization of a murine model for 1-bromopropane neurotoxicity: Role of
cytochrome P450 Toxicology Letters, 258, 249-258
HERO ID: 3539685
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

22. Health
Outcomes Unrelated
to Exposure
Data on attrition and/or
health outcomes
unrelated to exposure
were not reported for
each study group.
Not Rated
NR
NR
NR
Data Presentation
and Analysis
23. Statistical
Methods
See footnote at end of
page1
High
1
1
1
24. Reporting of
Data
Incidence data were not
provided for
histopathology data.
Medium
2
2
4
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

28
44
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.5714
Overall Score:
Nearest *:
1.6
Overall Quality Level:
High
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
34

-------
Interagency Review Draft Document. Do Not Release or Distribute.
2.7. Animal toxicity evaluation results of Zong et al 2016 for a 28-day inhalation study
on reproductive, hematological, immune, renal, and hepatic outcomes
Study reference:
Zong, C., Zhang, X., Huang, C., Chang, J., Garner, C. E., Sakurai, T., Kato, M., Ichihara, S., Ichihara, G. (2016). Role
of cytochrome P450s in the male reproductive toxicity of 1-bromopropane Toxicology Research, 5(6), 1522-1529

HERO ID: 3554790





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
See footnote at end of
page.1
High
1
2
2
Test Substance
2. Test Substance
Source
See footnote at end of
page.1
High
1
1
1

3. Test Substance
Purity
99.81% pure
High
1
1
1

4. Negative and
Vehicle Controls
See footnote at end of
page.1
High
1
2
2
Test Design
5. Positive Controls
Positive controls are not
generally used for repeat
dose inhalation studies.
Not Rated
NR
NR
NR

6. Randomized
Allocation
Study authors did not
report how animals were
allocated to study
groups.
Low
3
1
3

7. Preparation and
Storage of Test
Substance
Details on equipment
were not reported
(provided in another
study;
Not Rated
NR
NR
NR

8. Consistency of
Exposure
Administration
See footnote at end of
page.1
High
1
1
1
Exposure
Characterization
9. Reporting of
Doses/Concentratio
ns
Measured
concentrations were not
reported; however,
chamber concentrations
were monitored every 5
seconds by GC. Values
ranged from +/-11 to
14%.
Medium
2
2
4

10. Exposure
Frequency and
Duration
8 h/day, 7 days/wk for 4
weeks
High
1
1
1

11. Number of
Exposure Groups
and Dose Spacing
2 concentrations plus
control. Concentrations
were not justified. Use of
3 test groups and a
control are generally
recommended.
Medium
2
1
2
35

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Zong, C., Zhang, X., Huang, C., Chang, J., Garner, C. E., Sakurai, T., Kato, M., Ichihara, S., Ichihara, G. (2016). Role
of cytochrome P450s in the male reproductive toxicity of 1-bromopropane Toxicology Research, 5(6), 1522-1529

HERO ID: 3554790





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

12. Exposure Route
and Method
The inhalation exposure
system was as described
in Ichihara et al., 2000.
(Whole body exposure.)
Analytical concentrations
showed significant
variability (std deviation
> 10%) in mean air
concentrations
Not Rated
NR
NR
NR

13. Test Animal
Characteristics
Species, strain, sex and
starting age were
reported, but not body
weight (commercial
source).
Medium
2
2
4
Test Organism
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Husbandry conditions
(except # animals per
cage) were reported.
Medium
2
1
2

15. Number per
Group
6/group
High
1
1
1

16. Outcome
Assessment
Methodology
See footnote at end of
page.1
High
1
2
2

17. Consistency of
Outcome
Assessment
See footnote at end of
page1
High
1
1
1
Outcome
Assessment
18. Sampling
Adequacy
See footnote at end of
page1
High
1
1
1

19. Blinding of
Assessors
Blinding was not
reported; some sperm
parameters may be
considered subjective.
Low
3
1
3

20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rate was not
reported and 1-BP is
expected to cause
respiratory irritation.
Low
3
2
6
36

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Zong, C., Zhang, X., Huang, C., Chang, J., Garner, C. E., Sakurai, T., Kato, M., Ichihara, S., Ichihara, G. (2016). Role
of cytochrome P450s in the male reproductive toxicity of 1-bromopropane Toxicology Research, 5(6), 1522-1529
HERO ID: 3554790
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

22. Health
Outcomes Unrelated
to Exposure
Data on attrition and/or
health outcomes
unrelated to exposure
were not reported for
each study group
Not Rated
NR
NR
NR
Data Presentation
and Analysis
23. Statistical
Methods
See footnote at end of
page1
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

27
41
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.5185
Overall Score:
Nearest *:
1.5
Overall Quality Level:
High
37

-------
Interagency Review Draft Document. Do Not Release or Distribute.
3. Subchronic Toxicity Studies
3.1. Animal toxicity evaluation results of Anderson et al 2010 for a 4 and 10 week
inhalation immunotoxicity study in mice and rats on mortality, nutrition and
metabolic/adult exposure body weight, hematological and immune outcomes
Study reference:
Anderson, S. E.,Munson, A. E.,Butterworth, L. F.,Germolec, D.,Morgan, D. L.,Roycroft, J. A.,Dill, J.,Meade, B. J.
(2010). Whole-body inhalation exposure to 1-bromopropane suppresses the IgM response to sheep red blood
cells in female B6C3F1 mice and Fisher 344/N rats Inhalation Toxicology, 22(2), 125-132
HERO ID: 1717420
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by name and CASRN
High
1
2
2
2. Test Substance
Source
Test substance obtained
from commercial source
without lot number and
analyzed for purity by GC
and elemental analysis.
Medium
2
1
2
3. Test Substance
Purity
Purity analyzed by
elemental analysis and
GC to be 99.5% or higher
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
Sham-treated negative
controls were exposed
to filtered conditioned
air.
High
1
2
2
5. Positive Controls
Positive controls are
recommended but not
mandatory for
immunotoxicity testing
Low
3
1
3
6. Randomized
Allocation
Paper reports animals
were randomized but
allocation method not
detailed.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Test substance
preparation and storage
reported and
appropriate; stability
during storage was
tested and no
degradation found.
High
1
1
1
38

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Anderson, S. E.,Munson, A. E.,Butterworth, L. F.,Germolec, D.,Morgan, D. L.,Roycroft, J. A.,Dill, J.,Meade, B. J.
(2010). Whole-body inhalation exposure to 1-bromopropane suppresses the IgM response to sheep red blood
cells in female B6C3F1 mice and Fisher 344/N rats Inhalation Toxicology, 22(2), 125-132
HERO ID: 1717420
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

8. Consistency of
Exposure
Administration
Details of the chamber
used for exposures, and
time of day of exposures,
were not reported.
However, concentrations
were monitored
continuously via on-line
GC-FID.
Medium
2
1
2
9. Reporting of
Doses/Concentratio
ns
Neither analytical
concentrations nor
variation of measured
values from nominal
concentrations were
reported.
Low
3
2
6
10. Exposure
Frequency and
Duration
See footnote at end of
page.1
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
3 nonzero
concentrations were
used, with 4-fold range.
Effects were seen at the
lowest exposure, so it is
not clear that it was low
enough.
Medium
2
1
2
12. Exposure Route
and Method
Animals were exposed
via whole-body
inhalation (15 air
changes per hour were
reported); The chamber
size was not reported.
Medium
2
1
2
Test Organism
13. Test Animal
Characteristics
The test animal species,
strain, sex, and age were
reported, and the test
animal was obtained
from a commercial
source. Only females
were tested. Starting
body weight was not
reported.
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Husbandry conditions
were reported,
appropriate, and
consistent across groups.
High
1
1
1
39

15. Number per
Group
8 females/group were
exposed. This is the
number recommended
by EPA for
immunotoxicity testing
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Thymus weights were
not measured; remaining
endpoints are sensitive
and appropriate
Medium
2
2
4
17. Consistency of
Outcome
Assessment
The only deviation from
the test plan was failure
to perform PFC assay on
rat spleens after 4 wks,
due to a shipping error.
Medium
2
1
2
18. Sampling
Adequacy
Experiment was
replicated, enabling
analysis of 8/group
immunized spleens for
IgM response to SRBC
and 8/group
unimmunized spleens to
splenocyte phenotyping
and NK cell activity.
High
1
1
1
19. Blinding of
Assessors
Blinding is
recommended for PFC
assay; study does not
report blinding.
Low
3
1
3
20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Authors note that PFC
and serum IgM response
peak on different days (4
or 5-6 days after
immunization) but
spleen and serum were
collected the same day
(3 days after
immunization).
Medium
2
2
4
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
40

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Anderson, S. E.,Munson, A. E.,Butterworth, L. F.,Germolec, D.,Morgan, D. L.,Roycroft, J. A.,Dill, J.,Meade, B. J.
(2010). Whole-body inhalation exposure to 1-bromopropane suppresses the IgM response to sheep red blood
cells in female B6C3F1 mice and Fisher 344/N rats Inhalation Toxicology, 22(2), 125-132
HERO ID: 1717420
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

22. Health
Outcomes Unrelated
to Exposure
Authors report that
there were 3 deaths
among mice exposed to
the highest
concentration during the
first week of the 4 week
exposure. It is unclear
why the number of
animals was reported to
be 5 for both the 4 week
and 10 week spleen
weight and PFC assays,
as these should have
been two separate
groups, unless there
were 3 additional deaths
in the group exposed for
10 weeks.
Low
3
1
3
Data Presentation
and Analysis
23. Statistical
Methods
Statistical analysis
methods were reported
and appropriate. Data
enabling independent
analysis were reported.
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

31
54
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.7419
Overall Score:
Nearest *:
1.7
Overall Quality Level:
Medium
41

-------
Interagency Review Draft Document. Do Not Release or Distribute.
3.2. Animal toxicity evaluation results of Fueta et al 2007 for an inhalation
neurotoxicity-disinhibition and regional sensitivity study on neurological/behavior
outcomes
Study reference:
Fueta, Y.,Ishidao, T.,Ueno, S.,Yoshida, Y.,Kunugita, N.,Hori, H. (2007). New approach to risk assessment of
central neurotoxicity induced by 1-bromopropane using animal models NeuroToxicology, 28(2), 270-273
HERO ID: 1519111
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by name.
Medium
2
2
4
2. Test Substance
Source
Source not identified.
Low
3
1
3
3. Test Substance
Purity
Purity and/or grade was
not reported.
Low
3
1
3
Test Design
4. Negative and
Vehicle Controls
See footnote at end of
page.1
High
1
2
2
5. Positive Controls
Positive controls not
required.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Allocation methods were
not reported.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Inhalation exposure
methods were as
described in Fueta et al.,
2004(1717472) which
referenced Ishidao et al.,
2002.
Not Rated
NR
NR
NR
8. Consistency of
Exposure
Administration
Inhalation exposure
methods were as
described in Fueta et al.,
2004(1717472) which
referenced Ishidao et al.,
2002.
Not Rated
NR
NR
NR
9. Reporting of
Doses/Concentratio
ns
Actual exposure
concentrations were not
reported.
Low
3
2
6
10. Exposure
Frequency and
Duration
See footnote at end of
page.1
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
See footnote at end of
page.1
High
1
1
1
42

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Fueta, YJshidao, T.,Ueno, S.,Yoshida, Y.,Kunugita, N.,Hori, H. (2007). New approach to risk assessment of
central neurotoxicity induced by 1-bromopropane using animal models NeuroToxicology, 28(2), 270-273
HERO ID: 1519111
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

12. Exposure Route
and Method
Inhalation exposure
methods were as
described in Fueta et al.,
2004(1717472) which
referenced Ishidao et al.,
2002.
Low
3
1
3
Test Organism
13. Test Animal
Characteristics
The source, species,
strain, sex, and age were
reported. Initial body
weight and health status
were not reported.
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Husbandry conditions
were not reported.
Low
3
1
3
15. Number per
Group
The number of animals
per group was reported
but not clearly stated for
all experiments.
Medium
2
1
2
Outcome
Assessment
16. Outcome
Assessment
Methodology
Outcome assessment
methodology was as
described in Fueta et al.,
2002 (1733939)and
2004(1717472).
Treatment of
hippocampal slices was
different in both studies.
Medium
2
2
4
17. Consistency of
Outcome
Assessment
Reporting of outcome
assessment and protocol
execution were
incomplete.
Medium
2
1
2
18. Sampling
Adequacy
Details regarding
sampling were not
reported.
Low
3
1
3
19. Blinding of
Assessors
Blinding not required.
Not Rated
NR
NR
NR
20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rate was not
reported or measured.
Low
3
2
6
43

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Fueta, YJshidao, T.,Ueno, S.,Yoshida, Y.,Kunugita, N.,Hori, H. (2007). New approach to risk assessment of
central neurotoxicity induced by 1-bromopropane using animal models NeuroToxicology, 28(2), 270-273
HERO ID: 1519111
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

22. Health
Outcomes Unrelated
to Exposure
Data on health outcomes
unrelated to exposure
were not reported.
Not Rated
NR
NR
NR
Data Presentation
and Analysis
23. Statistical
Methods
See footnote at end of
page.1
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

21
54
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
2.0400
Overall Score:
Nearest *:
2.0
Overall Quality Level:
Medium
44

-------
Interagency Review Draft Document. Do Not Release or Distribute.
3.3. Animal toxicity evaluation results of Honma et al 2003 for an inhalation
neurotoxicity study on neurological/behavior outcomes
Study reference:
Honma, T.,Suda, M.,Miyagawa, M. (2003). Inhalation of 1-bromopropane causes excitation in the central
nervous system of male F344 rats NeuroToxicology, 24(4-5), 563-575

HERO ID: 1519108

Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
Test substance identified
by name only.
Medium
2
2
4
Test Substance
2. Test Substance
Source
Source identified.
Medium
2
1
2

3. Test Substance
Purity
Identified as GR grade.
Medium
2
1
2

4. Negative and
Vehicle Controls
See footnote at end of
page.1
High
1
2
2

5. Positive Controls
Positive controls not
required.
Not Rated
NR
NR
NR
Test Design
6. Randomized
Allocation
Method used for
randomization not
reported; however,
animals were allocated
to minimize mean body
weight differences
across groups.
Medium
2
1
2

7. Preparation and
Storage of Test
Substance
Inhalation exposure
information as described
in Sekiguchi et al., 2002
and Tsuga and Honma,
2000.
Medium
2
1
2
Exposure
Characterization
8. Consistency of
Exposure
Administration
Animals exposed during
the same time as
described in Sekiguchi et
al., 2002 and Tsuga and
Honma, 2000.
Not Rated
NR
NR
NR
9. Reporting of
Doses/Concentratio
ns
Only target and
converted
concentrations were
reported.
Medium
2
2
4

10. Exposure
Frequency and
Duration
The frequency and
duration were reported;
however, the duration of
exposure did not span a
28-day period in the
repeated-dose inhalation
study
Medium
2
1
2
45

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Honma, T.,Suda, M.,Miyagawa, M. (2003). Inhalation of 1-bromopropane causes excitation in the central
nervous system of male F344 rats NeuroToxicology, 24(4-5), 563-575
HERO ID: 1519108
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
See footnote at end of
page.1
High
1
1
1
12. Exposure Route
and Method
Inhalation exposure
information as described
in Sekiguchi et al., 2002
and Tsuga and Honma,
2000.
Low
3
1
3
Test Organism
13. Test Animal
Characteristics
The source, species,
strain, age, sex, and
initial body weight were
reported. Health status
was not reported.
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
All conditions were
reported except for the
number of room air
changes.
Medium
2
1
2
15. Number per
Group
The number of animals
per dose group (n=4-5)
was lower than the
typical number used in
studies of similar type
(N=10)
Medium
2
1
2
Outcome
Assessment
16. Outcome
Assessment
Methodology
See footnote at end of
page.1
High
1
2
2
17. Consistency of
Outcome
Assessment
See footnote at end of
page.1
High
1
1
1
18. Sampling
Adequacy
See footnote at end of
page.1
High
1
1
1
19. Blinding of
Assessors
Blinding was not
reported for the
functional observation
experiments (e.g.,
passive avoidance, open
field behavior).
Unacceptable
4
1
4
20. Negative Control
Response
Negative control
responses were
appropriate.
High
1
1
1
46

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Honma, T.,Suda, M.,Miyagawa, M. (2003). Inhalation of 1-bromopropane causes excitation in the central
nervous system of male F344 rats NeuroToxicology, 24(4-5), 563-575
HERO ID: 1519108
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Although respiratory
rate was not measured;
body temperature was
monitored and may
serve as a proxy for
changes in respiration
rate.
Medium
2
2
4
22. Health
Outcomes Unrelated
to Exposure
No health outcomes
unrelated to exposure
were reported.
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
reported and are
appropriate.
High
1
1
1
24. Reporting of
Data
Data were reported.
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

29
49
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.6897
Overall Score:
Nearest *:
1.7
Overall Quality Level:
Unacceptable
Comment:
Blinding was not reported for the functional observation experiments (e.g., passive avoidance, open field behavior).
47

-------
Interagency Review Draft Document. Do Not Release or Distribute.
3.4. Animal toxicity evaluation results of Ichihara et al 2000 for a 12 week
inhalation reproductive tox study in male rats (hematol and immune) on
hematological and immune outcomes	
Study reference:
Ichihara, G.,Yu, X.,Kitoh, J.,Asaeda, N.,Kumazawa, T.,lwai, H.,Shibata, E.,Yamada, T.,Wang, H.,Xie, Z.,Maeda,
K.,Tsukamura, H.,Takeuchi, Y. (2000). Reproductive toxicity of 1-bromopropane, a newly introduced alternative
to ozone layer depleting solvents, in male rats Toxicological Sciences, 54(2), 416-423

HERO ID: 1309569





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
See footnote at end of
page.1
High
1
2
2
Test Substance
2. Test Substance
Source
Test substance source
reported but without
certification or analytical
verification of identity.
Medium
2
1
2

3. Test Substance
Purity
See footnote at end of
page.1
High
1
1
1

4. Negative and
Vehicle Controls
See footnote at end of
page.1
High
1
2
2
Test Design
5. Positive Controls
Positive controls not
typical for study type
Not Rated
NR
NR
NR
6. Randomized
Allocation
Authors report random
allocation; however,
randomization method
was not reported.
Low
3
1
3
Exposure
7. Preparation and
Storage of Test
Substance
Some information on the
method used to
generate the test
atmosphere was cited to
prior studies. There was
no description of the
exposure chamber;
however, chamber
concentrations were
measured every 10 sec
during exposure.
Low
3
1
3
Characterization
8. Consistency of
Exposure
Administration
No inconsistencies in
exposure administration
were noted.
High
1
1
1

9. Reporting of
Doses/Concentratio
ns
Analytical concentrations
reported; mean values
were within 10% of
nominal
High
1
2
2

10. Exposure
Frequency and
Duration
Frequency was reported
to be 8 hr/d for 12
weeks.
High
1
1
1
48

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Ichihara, G.,Yu, X.,Kitoh, J.,Asaeda, N.,Kumazawa, T.,lwai, H.,Shibata, E.,Yamada, T.,Wang, H.,Xie, Z.,Maeda,
K.,Tsukamura, H.,Takeuchi, Y. (2000). Reproductive toxicity of 1-bromopropane, a newly introduced alternative
to ozone layer depleting solvents, in male rats Toxicological Sciences, 54(2), 416-423
HERO ID: 1309569
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
3 nonzero exposure
groups ranging 4-fold
were used; max
concentration selected
based on prior study.
Effect seen at lowest
exposure level, so it may
not have been low
enough.
Medium
2
1
2
12. Exposure Route
and Method
Inhalation exposure
information as described
in Ichihara et al., 1997;
Takeuchi et al., 1989.
Exposure concentrations
were verified
analytically.
Medium
2
1
2
Test Organism
13. Test Animal
Characteristics
The test animal species,
strain, sex, health status,
and age, were reported
and appropriate, and the
test animal was obtained
from a commercial
source. Starting body
weight was not reported.
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Temp, humidity, and
photoperiod were
reported and
appropriate; cages,
housing, and diet were
not described.
Low
3
1
3
15. Number per
Group
9 males/group were
tested.
Medium
2
1
2
Outcome
Assessment
16. Outcome
Assessment
Methodology
Hematology endpoints
and spleen and thymus
weights evaluated; no
histopathology
Medium
2
2
4
17. Consistency of
Outcome
Assessment
No inconsistencies in
outcome assessment
were noted.
High
1
1
1
18. Sampling
Adequacy
All endpoints evaluated
in all animals
High
1
1
1
49

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Ichihara, G.,Yu, X.,Kitoh, J.,Asaeda, N.,Kumazawa, T.,lwai, H.,Shibata, E.,Yamada, T.,Wang, H.,Xie, Z.,Maeda,
K.,Tsukamura, H.,Takeuchi, Y. (2000). Reproductive toxicity of 1-bromopropane, a newly introduced alternative
to ozone layer depleting solvents, in male rats Toxicological Sciences, 54(2), 416-423
HERO ID: 1309569
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

19. Blinding of
Assessors
Endpoints were not
subjective
Not Rated
NR
NR
NR
20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rates, initial
body weights, and food
and water intake were
not reported.
Medium
2
2
4
22. Health
Outcomes Unrelated
to Exposure
One control rat was
excluded due to
splenoma
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
Statistical analysis
methods were reported
and appropriate.
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

29
45
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.5517
Overall Score:
Nearest *:
1.56
Overall Quality Level:
High
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
50

-------
Interagency Review Draft Document. Do Not Release or Distribute.
3.5. Animal toxicity evaluation results of Ichihara et al 2000 for a 12 week inhalation
reproductive tox study in male rats (renal, hepatic, endocrine) on renal, hepatic,
and endocrine outcomes
Study reference:
Ichihara, G.,Yu, X.,Kitoh, J.,Asaeda, N.,Kumazawa, T.,lwai, H.,Shibata, E.,Yamada, T.,Wang, H.,Xie, Z.,Maeda,
K.,Tsukamura, H.,Takeuchi, Y. (2000). Reproductive toxicity of 1-bromopropane, a newly introduced alternative
to ozone layer depleting solvents, in male rats Toxicological Sciences, 54(2), 416-423
HERO ID: 1309569
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by unambiguous name.
High
1
2
2
2. Test Substance
Source
Test substance source
reported (99.81%
purity); however, no
analytical verification or
lot number was
provided.
Medium
2
1
2
3. Test Substance
Purity
Purity reported to be
99.81%
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
Negative control group
was reported. Animals
were untreated (i.e.,
exposed to fresh air).
Medium
2
2
4
5. Positive Controls
Positive controls are not
typically used for this
study type.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Authors report random
allocation
High
1
1
1
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Some information on the
method used to
generate the test
atmosphere was cited to
prior studies. There was
no description of the
exposure chamber;
however, chamber
concentrations were
measured via gas
chromatography every
10 seconds during
exposure.
Low
3
1
3
8. Consistency of
Exposure
Administration
No inconsistencies in
exposure administration
were noted.
High
1
1
1
51

9. Reporting of
Doses/Concentratio
ns
Analytical concentrations
reported; mean values
were within 10% of
nominal
High
1
2
2
10. Exposure
Frequency and
Duration
Weekly frequency was
not reported. Frequency
was reported to be 8
hr/d for 12 weeks.
Low
3
1
3
11. Number of
Exposure Groups
and Dose Spacing
3 nonzero exposure
groups ranging 4-fold
were used; max
concentration selected
based on prior study.
Effect seen at lowest
exposure level, so it may
not have been low
enough.
Medium
2
1
2
12. Exposure Route
and Method
Inhalation exposure
information as described
in Ichihara et al., 1997;
Takeuchi et al., 1989.
Exposure concentrations
were verified
analytically.
Medium
2
1
2
Test Organism
13. Test Animal
Characteristics
The test animal species,
strain, sex, health status,
and age, were reported
and appropriate, and the
test animal was obtained
from a commercial
source. Starting body
weight was not reported.
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Temperature, humidity,
and photoperiod were
reported and
appropriate; the number
of animals per cage,,
and diet were not
described.
Medium
2
1
2
15. Number per
Group
9 males/group were
tested.
Medium
2
1
2
52

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Ichihara, G.,Yu, X.,Kitoh, J.,Asaeda, N.,Kumazawa, T.,lwai, H.,Shibata, E.,Yamada, T.,Wang, H.,Xie, Z.,Maeda,
K.,Tsukamura, H.,Takeuchi, Y. (2000). Reproductive toxicity of 1-bromopropane, a newly introduced alternative
to ozone layer depleting solvents, in male rats Toxicological Sciences, 54(2), 416-423

HERO ID: 1309569





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

16. Outcome
Assessment
Methodology
The only renal,
endocrine, and hepatic
endpoints evaluated
were organ weights (no
clinical chemistry or
histopathology)
Low
3
2
6
Outcome
Assessment
17. Consistency of
Outcome
Assessment
No inconsistencies in
outcome assessment
were noted.
High
1
1
1

18. Sampling
Adequacy
All endpoints evaluated
in all animals
High
1
1
1

19. Blinding of
Assessors
Endpoints were not
subjective
Not Rated
NR
NR
NR

20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rates, initial
body weights, and food
and water intake were
not reported.
Medium
2
2
4
22. Health
Outcomes Unrelated
to Exposure
One control rat was
excluded due to
splenoma
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
Statistical analysis
methods were reported
and appropriate.
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2


Sum of scores:

29
48
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.6552
Overall Score:
Nearest *:
1.7
Low: >=2.3 and <=3







Overall Quality Level:

High

1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
53

-------
Interagency Review Draft Document. Do Not Release or Distribute.
3.6. Animal toxicity evaluation results of Ichihara et al 2000 for a 12 week inhalation
reproductive tox study in male rats on nutrition and metabolic/adult exposure
body weight, and reproductive outcomes
Study reference:
Ichihara, G.,Yu, X.,Kitoh, J.,Asaeda, N.,Kumazawa, T.,lwai, H.,Shibata, E.,Yamada, T.,Wang, H.,Xie, Z.,Maeda,
K.,Tsukamura, H.,Takeuchi, Y. (2000). Reproductive toxicity of 1-bromopropane, a newly introduced alternative
to ozone layer depleting solvents, in male rats Toxicological Sciences, 54(2), 416-423
HERO ID: 1309569
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by unambiguous name.
High
1
2
2
2. Test Substance
Source
Test substance source
reported but without
certification or analytical
verification of identity.
Medium
2
1
2
3. Test Substance
Purity
Purity reported to be
99.81%
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
A concurrent negative
control group was
reported but it is unclear
whether the control was
sham-treated or
untreated.
Low
3
2
6
5. Positive Controls
Positive controls not
typical for study type
Not Rated
NR
NR
NR
6. Randomized
Allocation
Authors report random
allocation
High
1
1
1
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Some information on the
method used to
generate the test
atmosphere was cited to
prior studies. There was
no description of the
exposure chamber.
However, chamber
concentrations were
measured every 10 sec
during exposure.
Medium
2
1
2
8. Consistency of
Exposure
Administration
No inconsistencies in
exposure administration
were noted.
High
1
1
1
9. Reporting of
Doses/Concentratio
ns
analytical concentrations
reported; mean values
were within 10% of
nominal
High
1
2
2
54

10. Exposure
Frequency and
Duration
Weekly frequency was
not reported. Frequency
was reported to be 8
hr/d for 12 weeks.
Low
3
1
3
11. Number of
Exposure Groups
and Dose Spacing
3 nonzero exposure
groups ranging 4-fold
were used; max
concentration selected
based on prior study.
Effect seen at lowest
exposure level, so it may
not have been low
enough.
Medium
2
1
2
12. Exposure Route
and Method
Inhalation exposure
information as described
in Ichihara et al., 1997;
Takeuchi et al., 1989.
Exposure concentrations
were verified
analytically.
Medium
2
1
2
Test Organism
13. Test Animal
Characteristics
The test animal species,
strain, sex, health status,
and age, were reported
and appropriate, and the
test animal was obtained
from a commercial
source. Starting body
weight was not reported.
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Temp, humidity, and
photoperiod were
reported and
appropriate; cages,
housing, and diet were
not described.
Low
3
1
3
15. Number per
Group
9 males/group were
tested.
Medium
2
1
2
Outcome
Assessment
16. Outcome
Assessment
Methodology
Some methods were
cited to prior
publications.
Medium
2
2
4
17. Consistency of
Outcome
Assessment
No inconsistencies in
outcome assessment
were noted.
High
1
1
1
55

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Ichihara, G.,Yu, X.,Kitoh, J.,Asaeda, N.,Kumazawa, T.,lwai, H.,Shibata, E.,Yamada, T.,Wang, H.,Xie, Z.,Maeda,
K.,Tsukamura, H.,Takeuchi, Y. (2000). Reproductive toxicity of 1-bromopropane, a newly introduced alternative
to ozone layer depleting solvents, in male rats Toxicological Sciences, 54(2), 416-423
HERO ID: 1309569
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

18. Sampling
Adequacy
Study examined 12
seminiferous tubules per
rat, which is more than
the 10
recommended in prior
studies (according to
authors). All endpoints
evaluated in all animals
High
1
1
1
19. Blinding of
Assessors
Most endpoints were
not subjective
Medium
2
1
2
20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rates, initial
body weights, and food
and water intake were
not reported.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
One control rat was
excluded due to
splenoma
Medium
2
1
2
Data Presentation
and Analysis
23. Statistical
Methods
Statistical analysis
methods were reported
and appropriate.
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

30
53
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.7586
Overall Score:
Nearest *:
1.8
Overall Quality Level:
Medium


1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic
Review for TSCA Risk Evaluation.
56

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Interagency Review Draft Document. Do Not Release or Distribute.
3.7. Animal toxicity evaluation results of Ishidao et al 2002 for an ADME - metabolism
after inhalation study on ADME/PBPK outcomes
Study reference:
Ishidao, T.,Kunugita, N.,Fueta, Y.,Arashidani, K.,Hori, H. (2002). Effects of inhaled 1-bromopropane vapor on rat
metabolism Toxicology Letters, 134(1-3), 237-243
HERO ID: 1717491
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Identified by chemical
name.
High
1
2
2
2. Test Substance
Source
Manufacturer was
indicated without lot no.
Medium
2
1
2
3. Test Substance
Purity
Purity was not reported.
Low
3
1
3
Test Design
4. Negative and
Vehicle Controls
Negative controls were
not needed for
metabolism studies.
Not Rated
NR
NR
NR
5. Positive Controls
Positive controls were
not needed for
metabolism studies.
Not Rated
NR
NR
NR
6. Randomized
Allocation
The study did not report
how animals were
allocated to study
groups.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Vapor generation
method and equipment
were reported.
High
1
1
1
8. Consistency of
Exposure
Administration
See footnote at end of
page.1
High
1
1
1
9. Reporting of
Doses/Concentratio
ns
Nominal and analytical
concentrations were not
reported.
Low
3
2
6
10. Exposure
Frequency and
Duration
6h/day, 5 days/wk, 3, 4,
or 12 weeks (also single
day exposure).
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
Adequate for ADME;
however, high and low
concentration had
different exposure
durations ((700 ppm for
4 and 12 weeks; 1500
ppm for 3 weeks)..
High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
57

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Ishidao, T.,Kunugita, N.,Fueta, Y.,Arashidani, K.,Hori, H. (2002). Effects of inhaled 1-bromopropane vapor on rat
metabolism Toxicology Letters, 134(1-3), 237-243
HERO ID: 1717491
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

12. Exposure Route
and Method
The inhalation exposure
system was as described
in Hori et al., 1999.
Low
3
1
3
Test Organism
13. Test Animal
Characteristics
Commercial source
(species, strain, age
reported).
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Husbandry conditions
were not reported.
Low
3
1
3
15. Number per
Group
10/group
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
See footnote at end of
page.1
High
1
2
2
17. Consistency of
Outcome
Assessment
See footnote at end of
page.1
High
1
1
1
18. Sampling
Adequacy

Medium
2
1
2
19. Blinding of
Assessors
Blinding was not
reported; however,
outcomes were
objective.
Not Rated
NR
NR
NR
20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rate was not
measured and 1-BP is
expected to be a
respiratory irritant.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
Data on attrition and/or
health outcomes
unrelated to exposure
were not reported for
each study group.
Not Rated
NR
NR
NR
Data Presentation
and Analysis
23. Statistical
Methods
See footnote at end of
page.1
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2

Sum of scores:

26
44
58

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Ishidao, T.,Kunugita, N.,Fueta, Y.,Arashidani, K.,Hori, H. (2002). Effects of inhaled 1-bromopropane vapor on rat
metabolism Toxicology Letters, 134(1-3), 237-243
HERO ID: 1717491
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
High: >=1 and <1.7
Medium: >-1.7 and <2.3
Low: >=2.3 and <=3
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.6923
Overall Score:
Nearest *:
1.7
Overall Quality Level:
High
59

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Interagency Review Draft Document. Do Not Release or Distribute.
3.8. Animal toxicity evaluation results of NTP 2011 for a 3-month inhalation study in
rats and mice study on mortality, skin and connective tissue, ocular and sensory,
nutrition and metabolic/adult exposure body weight, respiratory, cardiovascular,
renal, hepatic, hematological and immune, clinical chemistry/biochemical,
endocrine, gastrointestinal, reproductive, thyroid outcomes
Study reference:
NTP, (2011). NTP technical report on the toxicology and carcinogenesis studies of 1-bromopropane (CAS No.
106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies), GRA and 1

HERO ID: 1737813





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
Chambers analyzed for
particles to ensure form
of 1-BP was vapor.
High
1
2
2
Test Substance
2. Test Substance
Source
See footnote at end of
page.1
High
1
1
1

3. Test Substance
Purity
See footnote at end of
page.1
High
1
1
1

4. Negative and
Vehicle Controls
See footnote at end of
page.1
High
1
2
2

5. Positive Controls
Positive controls not
typical for this study type
Not Rated
NR
NR
NR
Test Design
6. Randomized
Allocation
Random allocation into
groups with
approximately equal
initial mean body
weights
Medium
2
1
2

7. Preparation and
Storage of Test
Substance
See footnote at end of
page.1
High
1
1
1

8. Consistency of
Exposure
Administration
No inconsistencies in
administration were
reported.
High
1
1
1
Exposure
Characterization
9. Reporting of
Doses/Concentratio
ns
Analytical concentrations
were reported and
within 10% of nominal.
Chamber air analyzed by
GC every 20 min during
exposure
High
1
2
2

10. Exposure
Frequency and
Duration
See footnote at end of
page.1
High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
60

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
NTP, (2011). NTP technical report on the toxicology and carcinogenesis studies of 1-bromopropane (CAS No.
106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies), GRA and 1
HERO ID: 1737813
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
5 nonzero exposure
levels were used, ranging
16-fold and yielding
effects at the higher
concentrations.
High
1
1
1
12. Exposure Route
and Method
Study does not explicitly
state whether exposure
is nose-only or whole
body, but it appears to
be a dynamic whole
body chamber with 15
air changes/hr.
Medium
2
1
2
Test Organism
13. Test Animal
Characteristics
See footnote at end of
page.1
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
See footnote at end of
page.1
High
1
1
1
15. Number per
Group
10/sex/group;
appropriate number for
study duration/purpose.
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Outcome assessment
described in detail and
sensitive.
High
1
2
2
17. Consistency of
Outcome
Assessment
No inconsistencies in
outcome assessment
were reported.
High
1
1
1
18. Sampling
Adequacy
Histopathology
examined on all control
and high exposure
animals, and to a no
effect level for organs
affected at the highest
exposure levels.
High
1
1
1
19. Blinding of
Assessors
No subjective endpoints
evaluated apart from
clinical signs of toxicity.
Not Rated
NR
NR
NR
20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
61

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
NTP, (2011). NTP technical report on the toxicology and carcinogenesis studies of 1-bromopropane (CAS No.
106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies), GRA and 1
HERO ID: 1737813
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Body temperature and
respiratory rate were not
reported.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
See footnote at end of
page.1
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
See footnote at end of
page.1
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

29
35
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.2069
Overall Score:
Nearest *:
1.2
Overall Quality Level:
High
62

-------
Interagency Review Draft Document. Do Not Release or Distribute.
3.9. Animal toxicity evaluation results of Yamada et al 2003 for an inhalation female
reproductive study on reproductive outcomes
Study reference:
Yamada, T.,lchihara, G.,Wang, H.,Yu, X.,Maeda, K.,Tsukamura, H.,Kamijima, M.,Nakajima, T.,Takeuchi, Y. (2003).
Exposure to 1-bromopropane causes ovarian dysfunction in rats Toxicological Sciences, 71(1), 96-103
HERO ID: 1519107
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by name only.
Medium
2
2
4
2. Test Substance
Source
The source was
identified.
Medium
2
1
2
3. Test Substance
Purity
The reported purity (>
99.5%), analyzed by GC,
is such that effects likely
due to the test
substance.
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
Concurrent negative
controls were included;
however, limited details
were provided in the
study.
Medium
2
2
4
5. Positive Controls
Positive controls were
not required.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Allocation method was
not reported.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
The inhalation exposure
system was described in
Huang et al., 1989,1990,
and Takauchi et al.,
1989.
Not Rated
NR
NR
NR
8. Consistency of
Exposure
Administration
Animals were exposed
during the same time
daily. The inhalation
exposure system was
described in Huang et al.,
1989,1990, and
Takauchi et al., 1989.
Medium
2
1
2
9. Reporting of
Doses/Concentratio
ns
The target and actual
concentrations were
reported.
Medium
2
2
4
10. Exposure
Frequency and
Duration
Frequency and duration
were adequate.
High
1
1
1
63

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Yamada, T.,lchihara, G.,Wang, H.,Yu, X.,Maeda, K.,Tsukamura, H.,Kamijima, M.,Nakajima, T.,Takeuchi, Y. (2003).
Exposure to 1-bromopropane causes ovarian dysfunction in rats Toxicological Sciences, 71(1), 96-103
HERO ID: 1519107
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
The number of exposure
groups were reported
and were adequate to
show result; however,
rats of the 800 ppm
group were excluded
from analysis because
they became ill and were
euthanized before study
completion (8th week).
Medium
2
1
2
12. Exposure Route
and Method
The inhalation exposure
system was described in
Huang et al., 1989,1990,
and Takauchi et al.,
1989.
Low
3
1
3
Test Organism
13. Test Animal
Characteristics
Animal source, species,
strain, age and sex was
reported.
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
All husbandry conditions
except room air changes
were reported.
Medium
2
1
2
15. Number per
Group
The number of animals
per group was
appropriate.
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Outcome assessment
methodology was
described and
appropriate.
High
1
2
2
17. Consistency of
Outcome
Assessment
Outcomes were assessed
consistently; however,
rats of the 800 ppm
treatment group were
excluded from analysis
because they became ill
and were euthanized
before study completion
(8th week). .
Medium
2
1
2
18. Sampling
Adequacy
Sampling was adequate.
High
1
1
1
64

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Yamada, T.,lchihara, G.,Wang, H.,Yu, X.,Maeda, K.,Tsukamura, H.,Kamijima, M.,Nakajima, T.,Takeuchi, Y. (2003).
Exposure to 1-bromopropane causes ovarian dysfunction in rats Toxicological Sciences, 71(1), 96-103
HERO ID: 1519107
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

19. Blinding of
Assessors
Blinding was not
reported; however, no
subjective endpoints
were evaluated
Not Rated
NR
NR
NR
20. Negative Control
Response
Negative control
responses were
appropriate.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rate and
body temperature was
not reported.
Medium
2
2
4
22. Health
Outcomes Unrelated
to Exposure
No health outcomes
unrelated to exposure
were reported or
inferred.
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
reported and
appropriate.
High
1
1
1
24. Reporting of
Data
Data were reported.
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

28
45
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.6071
Overall Score:
Nearest *:
1.6
Overall Quality Level:
High
65

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Interagency Review Draft Document. Do Not Release or Distribute.
3.10. Animal toxicity evaluation results of Yu et al 2001 for a neurotoxicity-inhalation
study for 5 or 7 weeks on neurological outcomes
Study reference:
Yu, X.,Ichihara, G.,Kitoh, J.,Xie, Z.,Shibata, E.,Kamijima, M.,Takeuchi, Y. (2001). Neurotoxicity of 2-bromopropane
and 1-bromopropane, alternative solvents for chlorofluorocarbons Environmental Research, 85(1), 48-52
HERO ID: 1519105
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by name.
Medium
2
2
4
2. Test Substance
Source
Source identified.
Medium
2
1
2
3. Test Substance
Purity
Reported purity such
that effects likely due to
the test substance.
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
Negative control animals
were included.
High
1
2
2
5. Positive Controls
Positive controls not
required.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Allocation methods were
not reported.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
The inhalation exposure
system was described in
Takeuchi et al., 1989,
and Ichihara et al., 1997.
Not Rated
NR
NR
NR
8. Consistency of
Exposure
Administration
Exposure was
discontinued becaused
rats became emaciated
after 5-7 weeks of
exposure.
Low
3
1
3
9. Reporting of
Doses/Concentratio
ns
Target and measured
vapor concentrations
were reported.
Medium
2
2
4
10. Exposure
Frequency and
Duration
Exposure frequency and
duration were reported.
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
Only one concentration
group was exposed.
Low
3
1
1
12. Exposure Route
and Method
The exposure route and
method described in
Takeuchi et al., 1989,
and Ichihara et al., 1997.
Low
3
1
3
66

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Yu, XJchihara, G.,Kitoh, J.,Xie, Z.,Shibata, E.,Kamijima, M.,Takeuchi, Y. (2001). Neurotoxicity of 2-bromopropane
and 1-bromopropane, alternative solvents for chlorofluorocarbons Environmental Research, 85(1), 48-52

HERO ID: 1519105

Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

13. Test Animal
Characteristics
The source, species,
strain, age, sex, and
initial body weight were
reported. Health status
was not reported.
Medium
2
2
4
Test Organism
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
All conditions except
room air changes were
reported.
Medium
2
1
2

15. Number per
Group
The number of animals
per group was
appropriate.
High
1
1
1

16. Outcome
Assessment
Methodology
Outcome assessment
methodology was
reported.
High
1
2
2
Outcome
Assessment
17. Consistency of
Outcome
Assessment
Outcomes were assessed
consistently.
High
1
1
1
18. Sampling
Adequacy
Sampling was adequate.
High
1
1
1

19. Blinding of
Assessors
Blinding was not
required.
Not Rated
NR
NR
NR

20. Negative Control
Response
Negative control
responses were
appropriate.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No confounding
variables in test design
were reported.
High
1
2
2
22. Health
Outcomes Unrelated
to Exposure
No health outcomes
unrelated to treatment
were reported.
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
described and
appropriate.
High
1
1
1
24. Reporting of
Data
Data were reported.
High
1
2
2
High: >-1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

28
41
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
NA
Overall Score:
Nearest *:
NA
67

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Yu, XJchihara, G.,Kitoh, J.,Xie, Z.,Shibata, E.,Kamijima, M.,Takeuchi, Y. (2001). Neurotoxicity of 2-bromopropane
and 1-bromopropane, alternative solvents for chlorofluorocarbons Environmental Research, 85(1), 48-52
HERO ID: 1519105
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

Overall Quality Level:
Medium
Comment:
The reviewer downgraded this study's overall quality rating (high -> medium) because the study only evaluated
one concentration (1000 ppm). Note: The original calculated score for this study was 1.5. This value is not
presented above because the final rating was changed based on professional judgement.
68

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Interagency Review Draft Document. Do Not Release or Distribute.
3.10. Animal toxicity evaluation results of Yu et al 2008 for an oral development-
dominant lethality, male reproductive study on growth (early life) and
development, reproductive outcomes
Study reference:
Yu, W. J.,Kim, J. C.,Chung, M. K. (2008). Lack of dominant lethality in mice following 1-bromopropane treatment
Mutation Research: Genetic Toxicology and Environmental Mutagenesis, 652(1), 81-87
HERO ID: 1410098
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by name and CASRN.
High
1
2
2
2. Test Substance
Source
The source and Batch
number were reported.
High
1
1
1
3. Test Substance
Purity
The reported purity
(99%) was such that
effects likely due to the
test substance.
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
A vehicle control group
was included.
High
1
2
2
5. Positive Controls
An appropriate positive
control
(cyclophosphamide
monohydrate
40 mg/kg) was included.
High
1
1
1
6. Randomized
Allocation
Allocation method was
not reported.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Preparation of the test
substance was described
with limited details and
stability and
homogeneity of the
suspension was not
reported.
Medium
2
1
2
8. Consistency of
Exposure
Administration
Exposures were
administered
consistently.
High
1
1
1
9. Reporting of
Doses/Concentratio
ns
The doses were
reported.
High
1
2
2
10. Exposure
Frequency and
Duration
Frequency and duration
of dosing were reported.
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
The number of groups
were inadequate. OECD
478 recommends at least
three treated groups
should be analyzed.
Low
3
1
3
69

HERO ID: 1410098

Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

12. Exposure Route
and Method
Exposure route and
method were
appropriate.
High
1
1
1
Test Organism
13. Test Animal
Characteristics
The source, species,
strain, sex, age, and
health status were
reported; however,
initial body weight was
not reported. Although
OECD guideline test
recommends use of rats,
mice are acceptable.
Medium
2
2
2

14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Animal husbandry was
appropriate and
adequately reported.
High
1
1
1

15. Number per
Group
Number of animals per
group was adequate.
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Outcome assessment
methodology was
reported as mating mice
over a 6-week period;
however, the OECD 478
test guidelines
recommend weekly
mating over an 8-week
period to ensure that all
phases of male germ cell
maturation are
evaluated for dominant
lethal induction.
Unacceptable
4
2
8
17. Consistency of
Outcome
Assessment
Consistency of
assessment was
appropriate.
High
1
1
1

18. Sampling
Adequacy
Sampling was adequate.
High
1
1
1

19. Blinding of
Assessors
Assessors were not
blinded to treatment
group; however, no
subjective endpoints
were evaluated beyond
clinical signs.
Not Rated
NR
NR
NR
70

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Yu, W. J.,Kim, J. C.,Chung, M. K. (2008). Lack of dominant lethality in mice following 1-bromopropane treatment
Mutation Research: Genetic Toxicology and Environmental Mutagenesis, 652(1), 81-87
HERO ID: 1410098
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

20. Negative Control
Response
Negative control
response was
appropriate.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No confounding
variables were reported;
however, minor
inconsistencies and
uncertainties were noted
in data reporting.
Medium
2
2
4
22. Health
Outcomes Unrelated
to Exposure
No health outcomes
unrelated to exposure
were reported
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
described and
appropriate.
High
1
1
1
24. Reporting of
Data
Data for all outcomes
were reported.
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

28
44
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.571
Overall Score:
Nearest *:
1.61
Overall Quality Level:
Unacceptable1
Comment:
Footnote:
1 Consistent with the Application of Systematic Review in TSCA Risk Evaluations document, if a metric for a data
source receives a score of Unacceptable (score = 4), EPA will determine the study to be unacceptable. In this case,
one of the metrics were rated as unacceptable. As such, the study is considered unacceptable and the score is
presented solely to increase transparency.
71

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Interagency Review Draft Document. Do Not Release or Distribute.
4. Chronic Toxicity Studies
4.1. Animal toxicity evaluation results of Anonymous 1998 for a neurological study on
neurological/behavior outcomes
Study reference:
Anonymous, (1998). Follow-up submission: Neurotoxicity and effects of beta-amyloid protein translation
HERO ID: 4158104
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by name.
Medium
2
2
4
2. Test Substance
Source
Source not reported.
Low
3
1
3
3. Test Substance
Purity
Purity not reported.
Low
3
1
3
Test Design
4. Negative and
Vehicle Controls
Negative control group
was included.
High
1
2
2
5. Positive Controls
Positive controls not
required.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Method used for
randomization was not
reported.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
The method and
equipment used to
generate test
atmospheres were not
reported.
Unacceptable
4
1
4
8. Consistency of
Exposure
Administration
No details were
reported.
Unacceptable
4
1
4
9. Reporting of
Doses/Concentratio
ns
Target and actual
exposure levels were
reported, but no
analytical methods were
reported.
Medium
2
2
4
10. Exposure
Frequency and
Duration
Frequency and duration
data were reported.
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
The number of groups
and spacing were
reported but not
justified.
Medium
2
1
2
72

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Anonymous, (1998). Follow-up submission: Neurotoxicity and effects of beta-amyloid protein translation
HERO ID: 4158104
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

12. Exposure Route
and Method
Actual concentrations
were reported but no
information about the
inhalation chamber or
vapor generation
method was provided.
Low
3
1
3

13. Test Animal
Characteristics
The species, strain, and
sex were reported, but
source, and health status
were not reported.
Low
3
2
6
Test Organism
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
No information was
reported.
Low
3
1
3

15. Number per
Group

High
1
1
1

16. Outcome
Assessment
Methodology
Reporting was
incomplete, especially in
terms of assessing grip
strength and sperm
counts.
Low
3
2
6
Outcome
Assessment
17. Consistency of
Outcome
Assessment
Assessment details were
not fully reported.
Low
3
1
3
18. Sampling
Adequacy
Details were not
reported.
Low
3
1
3

19. Blinding of
Assessors
Blinding was not
reported for subjective
endpoints (e.g., of grip
strength).
Low
3
1
3

20. Negative Control
Response
Negative responses were
appropriate for the data
reported.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Initial body weight and
respiratory rate were not
reported.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
Data were not reported.
Low
3
1
3
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
described and
appropriate.
High
1
1
1
73

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Anonymous, (1998). Follow-up submission: Neurotoxicity and effects of beta-amyloid protein translation
HERO ID: 4158104
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

24. Reporting of
Data
Data were reported.
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

28
71
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
2.5357
Overall Score:
Nearest *:
2.51
Overall Quality Level:
Unacceptable1
Comment:
Footnote:
1 Consistent with our Application of A Systematic Review in TSCA Risk Evaluations document, if a metric for a data
source receives a score of Unacceptable (score = 4), EPA will determine the study to be unacceptable. In this case,
two of the metrics were rated as unacceptable. As such, the study is considered unacceptable and the score is
presented solely to increase transparency.
74

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Interagency Review Draft Document. Do Not Release or Distribute.
4.2. Animal toxicity evaluation results of Brominated Solvents Consortium 2000 for a
summary of 2-gen study on growth (early life) and development outcomes
Study reference:
Brominated Solvents, Consortium (2000). Initial submission: Letter from Brominated Solvents Consortium,
results from ongoing 2-generation reproductive inhalation toxicity study in rats w/l-bromopropane, dated
3/15/00
HERO ID: 4158094
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance was
identified by name and
CASRN.
High
1
2
2
2. Test Substance
Source
The source was not
reported.
Low
3
1
3
3. Test Substance
Purity
The purity was not
reported.
Low
3
1
3
Test Design
4. Negative and
Vehicle Controls
Concurrent negative
controls were found.
High
1
2
2
5. Positive Controls
Positive controls were
not required.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Allocation was not
reported in the
summary.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Information on
preparation and storage
was not reported.
Unacceptable
4
1
4
8. Consistency of
Exposure
Administration
Details were not
reported.
Unacceptable
4
1
4
9. Reporting of
Doses/Concentratio
ns
Nominal concentrations
reported.
Low
3
2
6
10. Exposure
Frequency and
Duration
Frequency and duration
were reported.
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
The number of groups
and spacing were
reported but not
justified.
Medium
2
1
2
12. Exposure Route
and Method
No details were
reported.
Unacceptable
4
1
4
Test Organism
13. Test Animal
Characteristics
The source, strain, initial
body weight, and health
status were not
reported.
Low
3
2
6
75

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Brominated Solvents, Consortium (2000). Initial submission: Letter from Brominated Solvents Consortium,
results from ongoing 2-generation reproductive inhalation toxicity study in rats w/l-bromopropane, dated
3/15/00
HERO ID: 4158094
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

14. Adequacy and
Consistency of
Animal Husbandry
Conditions
No details were
reported.
Low
3
1
3
15. Number per
Group
The number of animals
per group was
appropriate.
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
No details were
reported.
Unacceptable
4
2
8
17. Consistency of
Outcome
Assessment
No details were
reported.
Unacceptable
4
1
4
18. Sampling
Adequacy
No details were
reported.
Low
3
1
3
19. Blinding of
Assessors
Blinding not applicable.
Not Rated
NR
NR
NR
20. Negative Control
Response
Responses were not
sufficiently reported.
Unacceptable
4
1
4
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No details were
reported.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
No details were
reported.
Low
3
1
3
Data Presentation
and Analysis
23. Statistical
Methods
Data were not provided.
Unacceptable
4
1
4
24. Reporting of
Data
Data reported for
specific outcomes.
Low
3
2
6
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

21
78
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
3.7143
Overall Score:
Nearest *:
3.71
Overall Quality Level:
Unacceptable1
76

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Brominated Solvents, Consortium (2000). Initial submission: Letter from Brominated Solvents Consortium,
results from ongoing 2-generation reproductive inhalation toxicity study in rats w/l-bromopropane, dated
3/15/00
HERO ID: 4158094
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Comment:
Footnote:
1 Consistent with our Application of A Systematic Review in TSCA Risk Evaluations document, if a metric for a data
source receives a score of Unacceptable (score = 4), EPA will determine the study to be unacceptable. In this case,
seven of the metrics were rated as unacceptable. As such, the study is considered unacceptable and the score is
presented solely to increase transparency.
77

-------
Interagency Review Draft Document. Do Not Release or Distribute.
4.3. Animal toxicity evaluation results of Bsoc 1998 for a summary of range-finding
repro/dev tox, full study in 4158101 study on growth (early life) and development
outcomes
Study reference:
Bsoc, (1998). INITIAL SUBMISSION: LTR FR BROM'D SOLV COMM TO USEPA RE RANGE-FINDING DEVEL/REPROD
TOX STUDY IN RATS VIA WHOLE-BODY INHALATION EXPOS W/1-BROMOPROPANE, W/ATTCHMTS & DATED
12/23/98
HERO ID: 4158100
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by name and CASRN.
High
1
2
2
2. Test Substance
Source
Source not identified.
Low
3
1
3
3. Test Substance
Purity
Purity not reported.
Low
3
1
3
Test Design
4. Negative and
Vehicle Controls
Negative controls were
included.
High
1
2
2
5. Positive Controls
Positive controls were
not required.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Allocation method was
not reported.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
No details were
reported.
Unacceptable
4
1
4
8. Consistency of
Exposure
Administration
No details were
reported.
Unacceptable
4
1
4
9. Reporting of
Doses/Concentratio
ns
Concentrations reported,
but unclear if target,
nominal, or analytical.
Low
3
2
6
10. Exposure
Frequency and
Duration
Frequency and duration
were reported.
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
The number of groups
and spacing were
reported but not
justified.
Medium
2
1
2
12. Exposure Route
and Method
No details were
reported.
Unacceptable
4
1
4
Test Organism
13. Test Animal
Characteristics
The source, strain, age,
health status, and initial
body weight were not
reported.
Low
3
2
6
78

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Bsoc, (1998). INITIAL SUBMISSION: LTR FR BROM'D SOLV COMM TO USEPA RE RANGE-FINDING DEVEL/REPROD
TOX STUDY IN RATS VIA WHOLE-BODY INHALATION EXPOS W/1-BROMOPROPANE, W/ATTCHMTS & DATED
12/23/98
HERO ID: 4158100
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

14. Adequacy and
Consistency of
Animal Husbandry
Conditions
No details were
reported.
Low
3
1
3
15. Number per
Group
The number per group
was taken from
summary table.
Medium
2
1
2
Outcome
Assessment
16. Outcome
Assessment
Methodology
Incomplete reporting of
outcome assessment
methods. Endpoints not
sufficient to determine
developmental toxicity.
Low
3
2
6
17. Consistency of
Outcome
Assessment
No details were
reported.
Low
3
1
3
18. Sampling
Adequacy
Sampling for data
presented in tables was
appropriate, but not
sensitive for
developmental
outcomes.
Low
3
1
3
19. Blinding of
Assessors
Blinding not required.
Not Rated
NR
NR
NR
20. Negative Control
Response
Negative responses for
the reported data were
appropriate.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Parameters not reported
to have been measured.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
Data not reported.
Low
3
1
3
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
not described.
Low
3
1
3
24. Reporting of
Data
All data not reported,
but some summary
tables were included.
Low
3
2
6

Sum of scores:

26
64
79

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Bsoc, (1998). INITIAL SUBMISSION: LTR FR BROM'D SOLV COMM TO USEPA RE RANGE-FINDING DEVEL/REPROD
TOX STUDY IN RATS VIA WHOLE-BODY INHALATION EXPOS W/1-BROMOPROPANE, W/ATTCHMTS & DATED
12/23/98
HERO ID: 4158100
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
High: >=1 and <1.7
Medium: >-1.7 and <2.3
Low: >=2.3 and <=3
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
2.9231
Overall Score:
Nearest *:
2.91
Overall Quality Level:
Unacceptable1
Comment:
Footnote:
1 Consistent with the Application of Systematic Review in TSCA Risk Evaluations document, if a metric for a data
source receives a score of Unacceptable (score = 4), EPA will determine the study to be unacceptable. In this case,
three of the metrics were rated as unacceptable. As such, the study is considered unacceptable and the score is
presented solely to increase transparency.
80

-------
Interagency Review Draft Document. Do Not Release or Distribute.
4.4. Animal toxicity evaluation results of Bsoc 1999 for a range-finding developmental
study on reproductive, growth (early life), and development outcomes
Study reference:
Bsoc, (1999). SUPPORT: LETTER FROM BROMINATED SOLVENTS COMM TO USEPA REPORTING RESULTS FROM
AN UNAUDITED DRAFT REPORT FOR DEFINITIVE DEVELOPMENTAL STUDY IN RATS WITH 1-BROMOPROPANE,
DATED 030999
HERO ID: 4158101
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by name, certificate of
analysis, and purity
testing.
High
1
2
2
2. Test Substance
Source
Manufacturer, supplier,
lot number, and
certificate of analysis.
High
1
1
1
3. Test Substance
Purity
Purity (99.9%)
determined by purity
testing and was such
that effects likely due to
test substance.
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
Negative controls were
included.
High
1
2
2
5. Positive Controls
Positive controls were
not required.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Authors reported use of
randomization
procedure based on GD
0 body weights provided
by the sponsor. No
randomization
procedure for culling
pups was provided.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
No information was
provided other than
'stored at room
temperature'.
Medium
2
1
2
8. Consistency of
Exposure
Administration
The method and
equipment used to
generate the vapor were
reported; however, the
actual number of air
changes per hour is not
clear.
Low
3
1
3
9. Reporting of
Doses/Concentratio
ns
The nominal, target, and
analytical concentrations
were reported.
High
1
2
2
81

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Bsoc, (1999). SUPPORT: LETTER FROM BROMINATED SOLVENTS COMM TO USEPA REPORTING RESULTS FROM
AN UNAUDITED DRAFT REPORT FOR DEFINITIVE DEVELOPMENTAL STUDY IN RATS WITH 1-BROMOPROPANE,
DATED 030999
HERO ID: 4158101
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

10. Exposure
Frequency and
Duration
Frequency and duration
were reported and
justified.
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
The number of groups
and spacing were
determined by the
sponsor.
Medium
2
1
2
12. Exposure Route
and Method
Number of air
changes/hr not reported;
particle size of test
article is above the range
recommended for
pulmonary deposition in
OECD412 TG (< 2 jim)
Low
3
1
3
Test Organism
13. Test Animal
Characteristics
The source, species,
strain, sex, age, and
initial body weight were
reported. Health status
was not reported.
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
The housing, food,
water, lighting,
temperature, humidity,
and air changes were
reported.
High
1
1
1
15. Number per
Group
The number of animals
per group was
appropriate.
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Outcome assessment
methodology did not
include information on
body temperature or
respiration rate.
Medium
2
2
4
17. Consistency of
Outcome
Assessment
Outcomes were assessed
consistently.
High
1
1
1
18. Sampling
Adequacy
Limited information
provided; however
sampling was adequate.
Medium
2
1
2
19. Blinding of
Assessors
Blinding not required.
Not Rated
NR
NR
NR
82

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Bsoc, (1999). SUPPORT: LETTER FROM BROMINATED SOLVENTS COMM TO USEPA REPORTING RESULTS FROM
AN UNAUDITED DRAFT REPORT FOR DEFINITIVE DEVELOPMENTAL STUDY IN RATS WITH 1-BROMOPROPANE,
DATED 030999
HERO ID: 4158101
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

20. Negative Control
Response
Negative control
responses were
appropriate.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Respiratory rate was not
reported to have been
measured.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
Early delivery was
observed in two females
and one female had full
resorptions which
authors stated were not
related to exposure to
the test substance.
Low
3
1
3
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
clearly described and
appropriate.
High
1
1
1
24. Reporting of
Data
All data were reported.
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

29
48
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.6551
Overall Score:
Nearest *:
1.7
Overall Quality Level:
Medium


83

-------
Interagency Review Draft Document. Do Not Release or Distribute.
4.5. Animal toxicity evaluation results of Bsoc 2001 for a summary of audited results
from 2-gen study on growth (early life) and development outcomes
Study reference:
Bsoc, (2001). SUPPORT: LTR FROM BROMINATED SOLVENTS COMM TO USEPA, FOLLOW-UP SUBM FROM
AUDITED FINAL REPORT OF 2-GEN REPRODUCTIVE STUDY IN RATS OF INHALED 1-BROMOPROPANE EXPOSURE,
DATED 6/21/01
HERO ID: 4158095
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by name and CASRN.
High
1
2
2
2. Test Substance
Source
Source not identified.
Low
3
1
3
3. Test Substance
Purity
Purity not reported.
Low
3
1
3
Test Design
4. Negative and
Vehicle Controls
Negative controls were
included.
High
1
2
2
5. Positive Controls
Positive controls not
required.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Allocation method not
reported.
Low
3
1
3
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Information on
preparation and storage
not reported.
Unacceptable
4
1
4
8. Consistency of
Exposure
Administration
Details not reported.
Unacceptable
4
1
4
9. Reporting of
Doses/Concentratio
ns
Target concentrations
only were reported.
Unacceptable
4
2
8
10. Exposure
Frequency and
Duration
Frequency and duration
were reported.
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
The number of groups
and spacing were
reported but not
justified.
Medium
2
1
2
12. Exposure Route
and Method
No details were
reported.
Unacceptable
4
1
4
Test Organism
13. Test Animal
Characteristics
The source, strain, initial
body weight and health
status were not
reported.
Low
3
2
6
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
No details were
reported.
Low
3
1
3
84

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Bsoc, (2001). SUPPORT: LTR FROM BROMINATED SOLVENTS COMM TO USEPA, FOLLOW-UP SUBM FROM
AUDITED FINAL REPORT OF 2-GEN REPRODUCTIVE STUDY IN RATS OF INHALED 1-BROMOPROPANE EXPOSURE,
DATED 6/21/01
HERO ID: 4158095
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

15. Number per
Group
Number of F0 parental
animals not reported,
but number of F1
parental animals were
reported.
Low
3
1
3
Outcome
Assessment
16. Outcome
Assessment
Methodology
No details were
reported.
Unacceptable
4
2
8
17. Consistency of
Outcome
Assessment
No details were
reported.
Unacceptable
4
1
4
18. Sampling
Adequacy
Limited details were
reported.
Low
3
1
3
19. Blinding of
Assessors
Blinding not required.
Not Rated
4
NR
4
20. Negative Control
Response
Limited details on
negative control
responses were
provided, only in
comparison to treated
animals and only in text.
Low
3
1
3
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No details were
reported.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
No details were
reported.
Low
3
1
3
Data Presentation
and Analysis
23. Statistical
Methods
No numerical data
provided.
Unacceptable
4
1
4
24. Reporting of
Data
Results described only in
text.
Low
3
2
6
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

20
81
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
4.051
Overall Score:
Nearest *:
4.11
Overall Quality Level:
Unacceptable1
85

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Bsoc, (2001). SUPPORT: LTR FROM BROMINATED SOLVENTS COMM TO USEPA, FOLLOW-UP SUBM FROM
AUDITED FINAL REPORT OF 2-GEN REPRODUCTIVE STUDY IN RATS OF INHALED 1-BROMOPROPANE EXPOSURE,
DATED 6/21/01
HERO ID: 4158095
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Comment:
Footnote:
1 Consistent with the Application of Systematic Review in TSCA Risk Evaluations document, if a metric for a data
source receives a score of Unacceptable (score = 4), EPA will determine the study to be unacceptable. In this case,
seven of the metrics were rated as unacceptable. As such, the study is considered unacceptable and the score is
presented solely to increase transparency.
86

-------
Interagency Review Draft Document. Do Not Release or Distribute.
4.6. Animal toxicity evaluation results of ClinTrials 1997 for a 13 week inhalation
exposure study in rats on hematological and immune, neurological/behavior,
renal, hepatic, ocular and sensory, cardiovascular, clinical chemistry/biochemical,
endocrine, nutrition and metabolic/adult exposure body weight, respiratory, and
thyroid outcomes
87

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
ClinTrials, (1997). A 13-week inhalation toxicity study of a vapor formulation of ALBTA1 in the Albino Rat
HERO ID: 2991104
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by CASRN. and
tradename (ALBTA1)
Medium
2
2
4
2. Test Substance
Source
Test substance was
provided by study
sponsor. Batch number,
receipt date, and test
substance form as
received were reported.
Test substance
characterization was the
responsibility of the
sponsor; laboratory did
not verify identity and/or
composition, nor was
information from the
sponsor regarding
characterization
provided in the report.
Low
3
1
3
3. Test Substance
Purity
Test substance purity
was not reported.
Low
3
1
3
Test Design
4. Negative and
Vehicle Controls
A sham-treated control
group was exposed to
room air.
High
1
2
2
5. Positive Controls
Positive control not
typical for this study
type.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Animals assigned based
on randomization
procedure designed to
ensure homogeneity of
body weights.
Medium
2
1
2
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Test substance
preparation and storage
were fully reported and
adequate.
High
1
1
1
88

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
ClinTrials, (1997). A 13-week inhalation toxicity study of a vapor formulation of ALBTA1 in the Albino Rat
HERO ID: 2991104
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

8. Consistency of
Exposure
Administration
For 2 of the 3-month
exposure duration, an
incorrect T95 value (15
min vs correct value of
25 min) was used, which
reduced the animals'
exposures during that
time period; however
this is not expected to
significantly impact
outcome.
Medium
2
1
2
9. Reporting of
Doses/Concentratio
ns
Analytical concentrations
(measured by Miran
Infrared gas analyzer)
were reported and
within 10% of nominal.
High
1
2
2
10. Exposure
Frequency and
Duration
See footnote at end of
page.1
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
Four non-zero exposure
groups spanning a 6-fold
range were used. Effect
levels were identified by
the study authors
suggesting that the high
and low doses were
appropriate.
High
1
1
1
12. Exposure Route
and Method
Dynamic whole-body
exposure was used;
chamber air change rate
was 7.4/hr, below the
recommended 10-15/hr.
Low
3
1
3
Test Organism
13. Test Animal
Characteristics
The test animal species,
strain, sex, health status,
age, and starting body
weight were reported,
the test animal was
obtained from a
commercial source, and
the species and strain
were typical for the
study type.
High
1
2
2
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
89

14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Intermittent deviations
from the prescribed
humidity (n=13
occasions), temperature
(n=3), and photoperiod
(n=15) ranges were
noted, but not expected
to significantly influence
the results.
Medium
2
1
2
15. Number per
Group
15 rats/sex/group were
used; this number is
higher than
recommended by EPA
guidance
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Outcome assessment
methods and timing
were reported in detail.
Sensitive and thorough
outcome metrics were
evaluated.
High
1
2
2
17. Consistency of
Outcome
Assessment
No inconsistencies in
outcome assessment
were noted.
High
1
1
1
18. Sampling
Adequacy
FOB and motor activity
were assessed on first 10
animals/group.
Histopathology was
evaluated on
comprehensive organs
for control and high dose
only; in remaining
groups, respiratory
tissues, liver, and gross
lesions were examined
microscopically.
Medium
2
1
2
19. Blinding of
Assessors
Study reports that
technicians performing
FOB assessments were
blinded to treatment
group.
High
1
1
1
20. Negative Control
Response
Control response
reported and appeared
to be appropriate.
High
1
1
1
90

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
ClinTrials, (1997). A 13-week inhalation toxicity study of a vapor formulation of ALBTA1 in the Albino Rat
HERO ID: 2991104
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

21. Confounding
Variables in Test
Design and
Procedures
Body temperature, and
respiration rate were not
reported.
Low
3
2
6
Confounding /
Variable Control
22. Health
Outcomes Unrelated
to Exposure
Animal attrition was
limited to 4 animals that
apparently died as a
consequence of the
orbital bleeding
procedure or anesthesia.
These animals were
essentially evenly
distributed across
exposure groups.
Medium
2
1
2
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods and
results were reported
and appropriate to the
data, and data enabling
independent analysis
were also provided.
High
1
1
1

24. Reporting of
Data
Data were reported at
both group and
individual levels.
High
1
2
2


Sum of scores:

30
47
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.5666
Overall Score:
Nearest *:
1.6
Low: >=2.3 and <=3







Overall Quality Level:

High

91

-------
Interagency Review Draft Document. Do Not Release or Distribute.
4.7. Animal toxicity evaluation results of ClinTrials 1997 for a 13-week inhalation
exposure in rats study on reproductive outcomes
Study reference:
ClinTrials, (1997). A 13-week inhalation toxicity study of a vapor formulation of ALBTA1 in the Albino Rat
HERO ID: 2991104
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test substance identified
by CASRN. and
tradename (ALBTA1)
Medium
2
2
4
2. Test Substance
Source
Test substance was
provided by study
sponsor. Batch number,
receipt date, and test
substance form as
received were reported.
Test substance
characterization was the
responsibility of the
sponsor; laboratory did
not verify identity and/or
composition, nor was
information from the
sponsor regarding
characterization
provided in the report.
Low
3
1
3
3. Test Substance
Purity
Test substance purity
was not reported.
Low
3
1
3
Test Design
4. Negative and
Vehicle Controls
A sham-treated control
group was exposed to
room air.
High
1
2
2
5. Positive Controls
Positive control not
typical for this study
type.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Animals assigned based
on randomization
procedure designed to
ensure homogeneity of
body weights.
Medium
2
1
2
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Test substance
preparation and storage
were fully reported and
adequate.
High
1
1
1
92

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
ClinTrials, (1997). A 13-week inhalation toxicity study of a vapor formulation of ALBTA1 in the Albino Rat
HERO ID: 2991104
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

8. Consistency of
Exposure
Administration
For 2 of the 3-month
exposure duration, an
incorrect T95 value (15
min vs correct value of
25 min) was used, which
reduced the animals'
exposures during that
time period; however,
this is not expected to
significantly impact
outcome.
Medium
2
1
2
9. Reporting of
Doses/Concentratio
ns
Analytical concentrations
(measured by Miran
Infrared gas analyzer)
were reported and
within 10% of nominal.
High
1
2
2
10. Exposure
Frequency and
Duration
Exposure frequency and
duration were adequate.
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
Four non-zero exposure
groups spanning a 6-fold
range were used. Effect
levels were identified by
the study authors
suggesting that the high
and low doses were
appropriate.
High
1
1
1
12. Exposure Route
and Method
Dynamic whole-body
exposure was used;
chamber air change rate
was 7.4/hr, below the
recommended 10-15/hr.
Low
3
1
3
Test Organism
13. Test Animal
Characteristics
The test animal species,
strain, sex, health status,
age, and starting body
weight were reported,
the test animal was
obtained from a
commercial source, and
the species and strain
were typical for the
study type.
High
1
2
2
93

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
ClinTrials, (1997). A 13-week inhalation toxicity study of a vapor formulation of ALBTA1 in the Albino Rat
HERO ID: 2991104
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Intermittent deviations
from the prescribed
humidity (n=13
occasions), temperature
(n=3), and photoperiod
(n=15) ranges were
noted, but not expected
to significantly influence
the results.
Medium
2
1
2
15. Number per
Group
15 rats/sex/group were
used; this number is
higher than
recommended by EPA
guidance
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Outcome assessment
methods and timing
were reported in detail.
Reproductive endpoints
were limited to gonad,
prostate and uterine
weights and
histopathology.
High
1
2
2
17. Consistency of
Outcome
Assessment
No inconsistencies in
outcome assessment
were noted.
High
1
1
1
18. Sampling
Adequacy
Histopathology was
evaluated on
reproductive organs for
control and high dose
only.
Medium
2
1
2
19. Blinding of
Assessors
No subjective
reproductive outcomes
were evaluated.
Not Rated
NR
NR
NR
20. Negative Control
Response
Control response
reported and appeared
to be appropriate.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Body temperature and
respiration rate were not
reported.
Low
3
2
6
94

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
ClinTrials, (1997). A 13-week inhalation toxicity study of a vapor formulation of ALBTA1 in the Albino Rat
HERO ID: 2991104
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

22. Health
Outcomes Unrelated
to Exposure
Animal attrition was
limited to 4 animals that
apparently died as a
consequence of the
orbital bleeding
procedure or anesthesia.
These animals were
essentially evenly
distributed across
exposure groups.
Medium
2
1
2
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods and
results were reported
and appropriate to the
data, and data enabling
independent analysis
were also provided.
High
1
1
1
24. Reporting of
Data
Data were reported at
both group and
individual levels.
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

29
46
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.5862
Overall Score:
Nearest *:
1.6
Overall Quality Level:
High
95

-------
Interagency Review Draft Document. Do Not Release or Distribute.
4.8. Animal toxicity evaluation results of Saito-Suzuki et al 1982 for a dominant lethal
mating experiment study on reproductive outcomes
Study reference:
Saito-Suzuki, R.,Teramoto, S.,Shirasu, Y. (1982). Dominant lethal studies in rats with l,2-dibromo-3-
chloropropane and its structurally related compounds Mutation Research: Genetic Toxicology, 101(4), 321-327

HERO ID: 1737959

Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
Identity and structure of
test substance were
provided.
High
1
2
2
Test Substance
2. Test Substance
Source
Commercial source
indicated
High
1
1
1

3. Test Substance
Purity
>98%
High
1
1
1

4. Negative and
Vehicle Controls
Vehicle control
High
1
2
2
Test Design
5. Positive Controls
DBCP was used as a
positive control
High
1
1
1
6. Randomized
Allocation
The study did not report
how animals were
allocated into study
groups
Low
3
1
3

7. Preparation and
Storage of Test
Substance
Authors indicate test
substances were
dissolved in olive oil
prior to use.
High
1
1
1

8. Consistency of
Exposure
Administration
Groups appear to be
exposed in a consistent
manner
High
1
1
1
Exposure
Characterization
9. Reporting of
Doses/Concentratio
ns
A single dose is reported
with no indication of a
confirmation of the
actual dose.
Low
3
2
6

10. Exposure
Frequency and
Duration
Daily gavage for 5 -days
High
1
1
1

11. Number of
Exposure Groups
and Dose Spacing
A single dose was used
(10% of the LD50);
multiple doses (3) are
recommended
Low
3
1
3

12. Exposure Route
and Method
See footnote at end of
page.1
High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
96

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Saito-Suzuki, R.,Teramoto, S.,Shirasu, Y. (1982). Dominant lethal studies in rats with l,2-dibromo-3-
chloropropane and its structurally related compounds Mutation Research: Genetic Toxicology, 101(4), 321-327
HERO ID: 1737959
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Organism
13. Test Animal
Characteristics
See footnote at end of
page.1
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Animal husbandry was
not reported
Low
3
1
3
15. Number per
Group
The number of treated
animals/group was
appropriate (n = 15)
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
To determine if 1-BP
induces DL mutations
per se, the appropriate
method would include
exposures throughout
spermatogenesis (e.g.,
10 wks in the rat), w/ 5-7
treatments/wk) and one
pairing at the end.
Low
3
2
6
17. Consistency of
Outcome
Assessment
Consistent between
groups; however, OECD
478 TG recommends a
total of 10 weekly
matings post-treatment.
Low
3
1
3
18. Sampling
Adequacy
All pregnant mated
females were sampled
High
1
1
1
19. Blinding of
Assessors
Not necessary
Not Rated
NR
NR
NR
20. Negative Control
Response
Control measurements
were as expected;
positive control gave
expected positive results
High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
97

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Saito-Suzuki, R.,Teramoto, S.,Shirasu, Y. (1982). Dominant lethal studies in rats with l,2-dibromo-3-
chloropropane and its structurally related compounds Mutation Research: Genetic Toxicology, 101(4), 321-327
HERO ID: 1737959
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
It is unclear whether
the number of
pregnant females
was sufficient to
provide at least 400
implants as
indicated in the
OECD478 TG.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
No detailed information
of the animals (health,
initial body weights etc.)
were provided for
independent review
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
OECD guideline 478
suggests statistical
analysis should be done
considering the male as
the experimental unit,
including the male as a
test of variance.
Low
3
1
3
24. Reporting of
Data
Data was reported
clearly; however,
reporting of clinical signs
should be included
(OECD guideline 478)
Medium
2
2
4
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

30
54
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.8
Overall Score:
Nearest *:
1.8
Overall Quality Level:
Medium


98

-------
Interagency Review Draft Document. Do Not Release or Distribute.
4.9. Animal toxicity evaluation results of WIL Research 2001 for a 2-generation
inhalation study - developmental study on growth (early life) and development
outcomes
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
See footnote at end of
page.1
High
1
2
2
Test Substance
2. Test Substance
Source
Manufacturer and lot no.
provided.
High
1
1
1

3. Test Substance
Purity
Purity at least 99.8%.
High
1
1
1

4. Negative and
Vehicle Controls
negative controls
exposed to filtered air.
High
1
2
2
Test Design
5. Positive Controls
Positive controls not
used for 2-gen repro.
studies.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Animals were allocated
to study groups using a
computerized
randomization
procedure.
High
1
1
1

7. Preparation and
Storage of Test
Substance
Preparation and storage
conditions were
described and exposure
concentrations were
measured by GC every
35 minutes during
exposure.
High
1
1
1
Exposure
Characterization
8. Consistency of
Exposure
Administration
See footnote at end of
page.1
High
1
1
1
9. Reporting of
Doses/Concentratio
ns
Target and mean
analytical concentrations
were reported; no
information was
provided for variance
(CV).
Medium
2
2
4

10. Exposure
Frequency and
Duration
See footnote at end of
page.1
High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
99

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
3 treatment groups plus
negative control;
adequate spacing of
concentrations.
High
1
1
1

12. Exposure Route
and Method
Appropriate number of
air changes/hr. No
aerosol formation
detected in exposure
chambers.
High
1
1
1

13. Test Animal
Characteristics
See footnote at end of
page.1
High
1
2
2
Test Organism
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
See footnote at end of
page.1
High
1
1
1

15. Number per
Group
25/sex/group; litters
culled to 8/group.
High
1
1
1

16. Outcome
Assessment
Methodology
Methods were
appropriate and well
reported.
High
1
2
2

17. Consistency of
Outcome
Assessment
See footnote at end of
page.1
High
1
1
1
Outcome
18. Sampling
Adequacy
Litter considered as the
experimental unit.
High
1
1
1
Assessment
19. Blinding of
Assessors
Blinding not reported
but is not expected to
have a substantial
impact on results as
most endpoints are
objective.
Medium
2
1
2

20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No significant
differences between
study groups in Initial bw
and food consumption;
body temperature and
respiration rate were not
reported.
Low
3
2
6

22. Health
Outcomes Unrelated
to Exposure
See footnote at end of
page.1
High
1
1
1
100

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
well-reported and
appropriate.
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

30
37
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.2333
Overall Score:
Nearest *:
1.2
Overall Quality Level:
High
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
101

-------
Interagency Review Draft Document. Do Not Release or Distribute.
4.10. Animal toxicity evaluation results of WIL Research 2001 for a 2-generation
inhalation - kidney study on kidney outcomes
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
See footnote at end of
page1
High
1
2
2
Test Substance
2. Test Substance
Source
Commercial source,
manufacturer and lot
numbers provided.
High
1
1
1

3. Test Substance
Purity
At least 99.8% pure.
High
1
1
1

4. Negative and
Vehicle Controls
Negative control
exposed to filtered air.
High
1
2
2
Test Design
5. Positive Controls
Positive controls are not
used for 2-gen repro.
studies.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Animals were allocated
to study groups using a
computerized
randomization
procedure.
High
1
1
1

7. Preparation and
Storage of Test
Substance
Preparation and storage
conditions were
described and exposure
concentrations were
measured by GC every
35 minutes during
exposure.
High
1
1
1
Exposure
Characterization
8. Consistency of
Exposure
Administration
See footnote at end of
page1
High
1
1
1
9. Reporting of
Doses/Concentratio
ns
Target and mean
analytical concentrations
were reported; no
information was
provided for variance
(CV).
Medium
2
2
4

10. Exposure
Frequency and
Duration
See footnote at end of
page1
High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review
forTSCA Risk Evaluation.
102

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
3 treatment groups and
negative control; dose
spacing was adequate.
High
1
1
1
12. Exposure Route
and Method
Appropriate number of
air changes/hr. No
aerosol formation
detected in exposure
chambers.
High
1
1
1
Test Organism
13. Test Animal
Characteristics
See footnote at end of
page1
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
See footnote at end of
page1
High
1
1
1
15. Number per
Group
25/sex/group
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Methods were well-
described and
appropriate.
High
1
2
2
17. Consistency of
Outcome
Assessment
See footnote at end of
page1
High
1
1
1
18. Sampling
Adequacy
See footnote at end of
page1
High
1
1
1
19. Blinding of
Assessors
Blinding of assessors was
not reported; however,
substantial impacts are
not anticipated. Most
endpoints are objective.
Medium
2
1
2
20. Negative Control
Response
See footnote at end of
page1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No significant
differences in initial bw
and food consumption;
body temperature and
respiration rate were not
reported.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
See footnote at end of
page1
High
1
1
1
103

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
clearly described and
appropriate.
High
1
1
1
24. Reporting of
Data
See footnote at end of
page1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

30
37
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.2333
Overall Score:
Nearest *:
1.2
Overall Quality Level:
High
104

-------
Interagency Review Draft Document. Do Not Release or Distribute.
4.10. Animal toxicity evaluation results of WIL Research 2001 for a 2-generation
	inhalation - liver study on liver outcomes	
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
See footnote at end of
page1
High
1
2
2
Test Substance
2. Test Substance
Source
Commercial source,
manufacturer and lot
numbers provided.
High
1
1
1

3. Test Substance
Purity
At least 99.8% pure.
High
1
1
1

4. Negative and
Vehicle Controls
Negative control
exposed to filtered air.
High
1
2
2
Test Design
5. Positive Controls
Positive controls are not
used for 2-gen repro.
studies.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Animals were allocated
to study groups using a
computerized
randomization
procedure.
High
1
1
1

7. Preparation and
Storage of Test
Substance
Preparation and storage
conditions were
described; exposure
concentrations were
measured by GC every
35 minutes during
exposure.
High
1
1
1
Exposure
Characterization
8. Consistency of
Exposure
Administration
See footnote at end of
page1
High
1
1
1
9. Reporting of
Doses/Concentratio
ns
Target and mean
analytical concentrations
were reported; no
information was
provided for range or
variance.
Medium
2
2
4

10. Exposure
Frequency and
Duration
See footnote at end of
page1
High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
105

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
3 treatment groups and
negative control; dose
spacing was adequate.
High
1
1
1
12. Exposure Route
and Method
Appropriate number of
air changes/hr. No
aerosol formation
detected in exposure
chambers.
High
1
1
1
Test Organism
13. Test Animal
Characteristics
See footnote at end of
page1
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
See footnote at end of
page1
High
1
1
1
15. Number per
Group
25/sex/group
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Methods were well-
described and
appropriate.
High
1
2
2
17. Consistency of
Outcome
Assessment
See footnote at end of
page1
High
1
1
1
18. Sampling
Adequacy
See footnote at end of
page1
High
1
1
1
19. Blinding of
Assessors
Blinding of assessors was
not reported; however,
substantial impacts are
not anticipated as most
endpoints are objective.
Medium
2
1
2
20. Negative Control
Response
See footnote at end of
page1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No significant
differences in initial bw
and food consumption;
body temperature and
respiration rate were not
reported.
Low
3
2
6
106

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,
Low,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

22. Health
Outcomes Unrelated
to Exposure
See footnote at end of
page1
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
clearly described and
appropriate.
High
1
1
1
24. Reporting of
Data
See footnote at end of
page1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

30
37
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.2333
Overall Score:
Nearest *:
1.2
Overall Quality Level:
High
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic
Review for TSCA Risk Evaluation.
107

-------
Interagency Review Draft Document. Do Not Release or Distribute.
4.10. Animal toxicity evaluation results of WIL Research 2001 for a 2-generation
inhalation - neurological study on neurological outcomes
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
See footnote at end of
page1
High
1
2
2
2. Test Substance
Source
Commercial source,
manufacturer and lot
numbers provided.
High
1
1
1
3. Test Substance
Purity
At least 99.8% pure.
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
Negative control
exposed to filtered air.
High
1
2
2
5. Positive Controls
Positive controls are not
used for 2-gen repro.
studies.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Animals were allocated
to study groups using a
computerized
randomization
procedure.
High
1
1
1
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Preparation and storage
conditions were
described and exposure
concentrations were
measured by GC every
35 minutes during
exposure.
High
1
1
1
8. Consistency of
Exposure
Administration
See footnote at end of
page1
High
1
1
1
9. Reporting of
Doses/Concentratio
ns
Target and mean
analytical concentrations
were reported; no
information was
provided for variance.
Medium
2
2
4
10. Exposure
Frequency and
Duration
See footnote at end of
page1
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
3 treatment groups and
negative control; dose
spacing was adequate.
High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic
Review for TSCA Risk Evaluation.
108

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

12. Exposure Route
and Method
Appropriate number of
air changes/hr. No
aerosol formation
detected in exposure
chambers.
High
1
1
1
Test Organism
13. Test Animal
Characteristics
See footnote at end of
page1
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
See footnote at end of
page1
High
1
1
1
15. Number per
Group
25/sex/group
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Methods were well-
described and
appropriate.
High
1
2
2
17. Consistency of
Outcome
Assessment
See footnote at end of
page1
High
1
1
1
18. Sampling
Adequacy
See footnote at end of
page1
High
1
1
1
19. Blinding of
Assessors
Blinding of assessors was
not reported; however,
substantial impacts are
not anticipated as most
endpoints are objective.
Medium
2
1
2
20. Negative Control
Response
See footnote at end of
page1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No significant
differences between
study groups in initial bw
and food consumption;
body temperature and
respiration rate were not
reported.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
See footnote at end of
page1
High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
109

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
clearly described and
appropriate.
High
1
1
1
24. Reporting of
Data
See footnote at end of
page1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

30
37
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.2333
Overall Score:
Nearest *:
1.2
Overall Quality Level:
High
110

-------
Interagency Review Draft Document. Do Not Release or Distribute.
4.10. Animal toxicity evaluation results of WIL Research 2001 for a 2-generation
inhalation - reproductive study on reproductive outcomes
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
See footnote at end of
page.1
High
1
2
2
Test Substance
2. Test Substance
Source
Commercial source,
manufacturer and lot
numbers provided.
High
1
1
1

3. Test Substance
Purity
At least 99.8% pure.
High
1
1
1

4. Negative and
Vehicle Controls
Negative control
exposed to filtered air.
High
1
2
2
Test Design
5. Positive Controls
Positive controls are not
used for 2-gen repro.
studies.
Not Rated
NR
NR
NR
6. Randomized
Allocation
Animals were allocated
to study groups using a
computerized
randomization
procedure.
High
1
1
1

7. Preparation and
Storage of Test
Substance
Preparation and storage
conditions were
described and exposure
concentrations were
measured by GC every
35 minutes during
exposure.
High
1
1
1
Exposure
Characterization
8. Consistency of
Exposure
Administration
See footnote at end of
page.1
High
1
1
1
9. Reporting of
Doses/Concentratio
ns
Target and mean
analytical concentrations
were reported; no
information was
provided for range or
variance (CV).
Medium
2
2
4

10. Exposure
Frequency and
Duration
See footnote at end of
page.2
High
1
1
1
1	Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
2	Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
Ill

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
3 treatment groups and
negative control; dose
spacing was adequate.
High
1
1
1
12. Exposure Route
and Method
Appropriate number of
air changes/hr. No
aerosol formation
detected in exposure
chambers.
High
1
1
1
Test Organism
13. Test Animal
Characteristics
See footnote at end of
page.1
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
See footnote at end of
page.1
High
1
1
1
15. Number per
Group
25/sex/group
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
Methods were well-
described and
appropriate.
High
1
2
2
17. Consistency of
Outcome
Assessment
See footnote at end of
page.1
High
1
1
1
18. Sampling
Adequacy
See footnote at end of
page.1
High
1
1
1
19. Blinding of
Assessors
Blinding of assessors was
not reported; however,
substantial impacts are
not anticipated as most
endpoints are objective.
Medium
2
1
2
20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
No significant
differences between
study groups in initial bw
and food consumption;
body temperature and
respiration rate were not
reported.
Low
3
2
6
112

-------
Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
WIL Research (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in rats
HERO ID: 2990994
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

22. Health
Outcomes Unrelated
to Exposure
See footnote at end of
page.1
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods were
clearly described and
appropriate.
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

30
37
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.2333
Overall Score:
Nearest *:
1.2
Overall Quality Level:
High
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
113

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Interagency Review Draft Document. Do Not Release or Distribute.
5. Cancer Studies
5.1. Animal toxicity evaluation results of NTP 2011 for a 2 year inhalation study in rats
and mice study on mortality, skin and connective tissue, ocular and sensory,
nutrition and metabolic/adult exposure body weight, respiratory, cardiovascular,
renal, hepatic, hematological and immune, endocrine, gastrointestinal,
reproductive, thyroid, cancer outcomes	
Study reference:
NTP, (2011). NTP technical report on the toxicology and carcinogenesis studies of 1-bromopropane (CAS No.
106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies), GRA and 1

HERO ID: 1737813





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

1. Test Substance
Identity
Chambers analyzed for
particles to ensure form
of 1-BP was vapor.
High
1
2
2
Test Substance
2. Test Substance
Source
See footnote at end of
page.1
High
1
1
1

3. Test Substance
Purity
See footnote at end of
page.1
High
1
1
1

4. Negative and
Vehicle Controls
See footnote at end of
page.1
High
1
2
2

5. Positive Controls
Positive controls not
typical for this study type
Not Rated
NR
NR
NR
Test Design
6. Randomized
Allocation
Random allocation into
groups with
approximately equal
initial mean body
weights
Medium
2
1
2

7. Preparation and
Storage of Test
Substance
See footnote at end of
page.1
High
1
1
1

8. Consistency of
Exposure
Administration
No inconsistencies in
administration were
reported.
High
1
1
1
Exposure
Characterization
9. Reporting of
Doses/Concentratio
ns
Analytical concentrations
were reported and
within 10% of nominal.
Chamber air analyzed by
GC every 20 min during
exposure
High
1
2
2

10. Exposure
Frequency and
Duration
See footnote at end of
page.1
High
1
1
1
1 Metrics that received a "High" rating met the criteria as discussed in the Applications of Systematic Review for
TSCA Risk Evaluation.
114

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
NTP, (2011). NTP technical report on the toxicology and carcinogenesis studies of 1-bromopropane (CAS No.
106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies), GRA and 1

HERO ID: 1737813





Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

11. Number of
Exposure Groups
and Dose Spacing
3 nonzero exposure
levels were used, ranging
4-fold; effect levels were
identified.
High
1
1
1

12. Exposure Route
and Method
Study does not explicitly
state whether nose-only
or whole body; dynamic
whole-body chamber
with 15 air changes/hr.
Medium
2
1
2

13. Test Animal
Characteristics
See footnote at end of
page.1
High
1
2
2
Test Organism
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
See footnote at end of
page.1
High
1
1
1

15. Number per
Group
50/sex/group;
appropriate number for
study duration/purpose.
High
1
1
1

16. Outcome
Assessment
Methodology
Outcome assessment
was sensitive and
described in detail;
limited to BW and
histopath (no organ
weights, hematology, or
clinical chemistry).
High
1
2
2
Outcome
Assessment
17. Consistency of
Outcome
Assessment
No inconsistencies in
outcome assessment
were reported.
High
1
1
1

18. Sampling
Adequacy
All evaluations
performed on all animals
High
1
1
1

19. Blinding of
Assessors
No subjective endpoints
evaluated apart from
clinical signs of toxicity
Not Rated
NR
NR
NR

20. Negative Control
Response
See footnote at end of
page.1
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Body temperature and
respiratory rate were not
reported.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
See footnote at end of
page.1
High
1
1
1
115

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
NTP, (2011). NTP technical report on the toxicology and carcinogenesis studies of 1-bromopropane (CAS No.
106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies), GRA and 1
HERO ID: 1737813
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e., High, Medium, L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Data Presentation
and Analysis
23. Statistical
Methods
See footnote at end of
page.1
High
1
1
1
24. Reporting of
Data
See footnote at end of
page.1
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

29
35
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.2069
Overall Score:
Nearest *:
1.2
Overall Quality Level:
High
116

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Interagency Review Draft Document. Do Not Release or Distribute.
6. Genotoxicity Studies
6.1. Animal toxicity evaluation results of Young 2016
Study reference:
Young, R. R. (2016). In vivo mutation assay of n-propyl bromide at the ell locus in Big Blue® transgenic B6C3F1
mice exposed via whole-body inhalation. Provided by Julie Ownbey, ICL Industrial Products
HERO ID: 4140181
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
CAS number reported, in
Section 3.1. GLP
Compliance statement
on page 3 notes that the
characterization analyses
for the test substance
were not conducted
according to GLP
standards. The test
article was from a
commercial batch.
Medium
2
2
4
2. Test Substance
Source
The sponsor was
identified as the source
of the test substance
which was received by
WIL Research (now
Charles River Ashland).
[Section 3.1]
Low
3
1
3
3. Test Substance
Purity
Purity reported as 99.9%
(provided to study
authors by the Sponsor
and on file at Charles
River Ashland). [Section
3.1]
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
Vehicle controls were
exposed under the same
conditions to humidified
filtered air. [Sections 3.1
& 3.2]
High
1
2
2
5. Positive Controls
Positive controls
exposed to ethyl
nitrosourea (ENU, a
potent, direct acting
mutagen, with
mutagenicity observed in
target organs).
High
1
1
1
117

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Young, R. R. (2016). In vivo mutation assay of n-propyl bromide at the ell locus in Big Blue® transgenic B6C3F1
mice exposed via whole-body inhalation. Provided by Julie Ownbey, ICL Industrial Products
HERO ID: 4140181
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

6. Randomized
Allocation
Animals were assigned
to groups at random
based on body weight
stratification into a block
design using a computer
program [Appendix A],
Medium
2
1
2
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Study provides details on
the method and
equipment used to
generate vapors [Section
1.3 and Appendix C],
Test article storage also
reported [Appendix A
Study Protocol Section
7].
High
1
1
1
8. Consistency of
Exposure
Administration
Study includes details on
methods for generating
atmospheres for
inhalation exposures.
Positive control (not
characterized in the
certificate of analysis)
administered via the oral
route.
Medium
2
1
2
9. Reporting of
Doses/Concentratio
ns
Nominal concentrations
calculated daily.
Exposure concentrations
were analyzed at 45-
minute intervals using
GC. Mean nominal and
mean analyzed exposure
concentrations are
presented in the study
(text tables 2 & 3;
Section 9.5 Appendix A;
Appendix C).
High
1
2
2
10. Exposure
Frequency and
Duration
6 hours/day for 7
days/week for a 28-day
period; consistent with
OECDTG 488
(OECD, 2013)
High
1
1
1
118

11. Number of
Exposure Groups
and Dose Spacing
Maximum tolerated dose
was not achieved. OPPT
recommends use of dose
at least 1.5 times higher
than the highest dose
used in the NTP 2-year
cancer bioassay.
Low
3
1
3
12. Exposure Route
and Method
Whole-body inhalation
chamber; no mention of
condensation in the
exposure chamber.
Study authors report
variable distribution of
test article and < 15 air
changes per hour.
Low
3
1
3
Test Organism
13. Test Animal
Characteristics
The study includes
details regarding the
age, health status, and
starting body weights.
The study also provides
justification for selection
of the species and strain
used for this study.
High
1
2
2
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Same conditions for all
exposure groups. Mice
were housed in an
accredited facility and
received certified feed
and reverse osmosis-
treated drinking water.
High
1
1
1
15. Number per
Group
Six female
mice/exposure group.
The sample size is small,
but adequate for the
purposes of this study.
DNA analysis conducted
in five mice/group.
Tissues from one of the
mice were retained
frozen in reserve and not
processed further unless
needed.
Medium
2
1
2
119

HERO ID: 4140181

Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

16. Outcome
Assessment
Methodology
It is unclear how outliers
were verified as DNA
sequencing data was not
used to determine
whether 'jackpots' were
the cause of high inter-
individual variation.
Low
3
2
6

17. Consistency of
Outcome
Assessment
Mutant frequency in
negative controls
comparable to historical
controls; however,
because manifestation
time varies by tissue
type, the relevance of
the negative assay result
for lung tissue is
uncertain.
Low
3
1
3
Outcome
Assessment
18. Sampling
Adequacy
Evaluations were
conducted on all
exposure groups,
including the negative 1
and positive control
groups. The individual
animal was considered
the experimental unit.
High
1
1
1

19. Blinding of
Assessors
Plates were scored
visually for number of
plaques per plate.
Blinding not described in
study, but not required
for evaluation of an
objective endpoint. Not
expected to have a
substantial impact on
results.
Not Rated
NR
NR
NR

20. Negative Control
Response
Mutant frequency in
negative controls was
comparable to historical
controls.
High
1
1
1
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Body temperature and
respiration rate were not
reported.
Low
3
2
6
120

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Young, R. R. (2016). In vivo mutation assay of n-propyl bromide at the ell locus in Big Blue® transgenic B6C3F1
mice exposed via whole-body inhalation. Provided by Julie Ownbey, ICL Industrial Products
HERO ID: 4140181
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score

22. Health
Outcomes Unrelated
to Exposure
Body weight losses were
noted in all test
substance-treated
groups from Days 6 to 13
(relative
to Test Site Study Day 0);
however, the changes
were limited in
magnitude and did not
occur in a dose-related
manner; therefore, are
not considered
treatment related.
High
1
1
1
Data Presentation
and Analysis
23. Statistical
Methods
Statistical approaches for
evaluating results were
clearly described in the
study; however, analysis
for jackpot mutations
was not presented.
Medium
2
1
2
24. Reporting of
Data
Data presented in
summary tables, and raw
data included in
appendices.
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

29
52
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
1.7931
Overall Score:
Nearest *:
1.8
Overall Quality Level:
Medium
Comment:

121

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Interagency Review Draft Document. Do Not Release or Distribute.
6.2 Animal toxicity evaluation results of Weinberg 2016 for a 4-week somatic
mutation gene inhalation study in transgenic mice study on hepatic and body weight
outcomes
Study reference:
Weinberg, J. T. (2016). A 28-day somatic gene mutation study of 1-bromopropane in female Big Blue® B6C3F1
mice via whole-body inhalation
HERO ID: 4140180
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
Test subtsance identity
and CAS number clearly
stated
High
1
2
2
2. Test Substance
Source
Commercial source, lot#
provided
High
1
1
1
3. Test Substance
Purity
99.9%
High
1
1
1
Test Design
4. Negative and
Vehicle Controls
Filtered air control
High
1
2
2
5. Positive Controls
Positive control included
High
1
1
1
6. Randomized
Allocation
Computer randomized
High
1
1
1
Exposure
Characterization
7. Preparation and
Storage of Test
Substance
Comprehensive study
details were provided
High
1
1
1
8. Consistency of
Exposure
Administration
Study includes details on
methods used to
generate test
atmospheres for
inhalation exposures.
Variability (>20% CV)
observed in 62.5 ppm
treatment group.
Medium
2
1
2
9. Reporting of
Doses/Concentratio
ns
Analytical concentrations
provided
High
1
2
2
10. Exposure
Frequency and
Duration
6hrs/day 5 days/week
for 4 weeks
High
1
1
1
11. Number of
Exposure Groups
and Dose Spacing
Three exposure groups
and a control;
justification provided.
High
1
1
1
12. Exposure Route
and Method
Whole body inhalation
exposure; no aerosol
formation detected.
High
1
1
1
122

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Interagency Review Draft Document. Do Not Release or Distribute.
Study reference:
Weinberg, J. T. (2016). A 28-day somatic gene mutation study of 1-bromopropane in female Big Blue® B6C3F1
mice via whole-body inhalation
HERO ID: 4140180
Domain
Metric
Eval Comment
Qualitative
Determination
[i.e.,High,Medium,L
ow,Unacceptable,
or Not rated]
Metric
Score
Metric Weighting
Factor
Weighted
Score
Test Organism
13. Test Animal
Characteristics
Transgenic mice were
appropriate for the
purpose of the study (in
vivo genotoxicity; study
authors provide
justification for use of
females only
Medium
2
2
4
14. Adequacy and
Consistency of
Animal Husbandry
Conditions
Clearly reported and
acceptable.
High
1
1
1
15. Number per
Group
7 animals per group
High
1
1
1
Outcome
Assessment
16. Outcome
Assessment
Methodology
It is not clear how
outliers were verified.
DNA sequencing data
was not used to
determine whether
'jackpots' are the cause
of high inter-individual
variation, bioassay.
Low
3
2
6
17. Consistency of
Outcome
Assessment
Mutant frequency in
negative controls
comparable to historical
controls; however,
because manifestation
time varies by tissue
type, the relevance of a
negative assay result for
lung tissue is uncertain.
Low
3
1
3
18. Sampling
Adequacy
Liver/lung weights and
body weights reported
for all animals; samples
from the first 5 treated
or control from each
group were processed
for DNA isolation.
Tissues from the sixth
animal per group were
retained.
High
1
1
1
19. Blinding of
Assessors
Not necessary
Not Rated
NR
NR
NR
123

20. Negative Control
Response
Negative control
responses were
appropriate.
Low
3
1
3
Confounding /
Variable Control
21. Confounding
Variables in Test
Design and
Procedures
Body temperature and
respiration rate were not
reported.
Low
3
2
6
22. Health
Outcomes Unrelated
to Exposure
Data on attrition and/or
health outcomes
unrelated to exposure
were not reported for
each study group.
Not Rated
NR
NR
NR
Data Presentation
and Analysis
23. Statistical
Methods
Statistical methods
acceptable
High
1
1
1
24. Reporting of
Data
Raw data tables
provided
High
1
2
2
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Sum of scores:

29
42
Overall Score = Sum of Weighted Scores/Sum
of Metric Weighting Factors:
NA
Overall Score:
Nearest *:
NA
Overall Quality Level:
Medium
Comment:
The reviewer downgraded this study's overall quality rating (high -> medium). It is unclear whether the protocol
was adequate to identify the intended result, as the maximum tolerated dose was not evaluated (OPP
recommends testing at concentrations up to 1.5 times the maximum tolerated dose reported in the 2-year cancer
bioassay). The sensitivity of the transgenic test system is also influenced by the duration of the post-exposure
observation period. Note: The original calculated score for this study was 1.4. This value is not presented above
because the final rating was changed based on professional judgement.
6.3 Animal toxicity evaluation results of Saito-Suzuki et al 1982 for a dominant lethal
mating experiment study on reproductive outcomes
[See table in Section 4]
124

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