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EPA
United States
Environmental Protection Agency
Office of Chemical Safety and
Pollution Prevention
Risk Evaluation for
Methylene Chloride
Systematic Review Supplemental File:
Data Extraction Tables for Human Health Hazard Studies
CASRN: 75-09-2
H
October 2019, DRAFT
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ntents
1	DATA EXTRACTION TABLE FOR EPIDEMIOLOGY STUDIES	4
2	DATA EXTRACTION TABLES FOR NON-CANCER ENDPOINTS FROM
ANIMAL TOXICITY STUDIES	24
21 Acute and Short-term Animal Toxicity Studies a	25
2.2	Subchronic and Chronic Animal Toxicity Studies a	30
2.3	Reproductive and Developmental Outcomes from Animal Toxicity Studies	36
3	DATA EXTRACTION TABLES FOR ANIMAL CANCER BIOASSAYS	39
3.1	Liver Tumor Data from Cancer Bioassays	39
3.2	Lung Tumor Data From Animal Cancer Bioassays	41
3.3	Mammary Gland Tumors from Animal Cancer Bioassays	42
3.1	Other Tumor Data From Animal Cancer Bioassays	44
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NOTE: Within each table, rows that are shaded are the new studies identified in the updated
literature search. Some of the studies from the updated literature search, although obtained
recently, were submitted several years ago under TSCA (e.g., section 8e, 8d, etc) and thus
have older dates. Rows that are not shaded are the key and supporting studies from the IRIS
Assessment (U.S. EPA. 2011). Studies that received unacceptable data quality ratings are not
included in the tables below.
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1 Data Extraction Table for Epidemiology Studies
Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Cancer
Non-Hodgkin lymphoma
(NHL)
518 women diagnosed with
NHL between 1996 and 2000
and 597 control women.
Job exposure matrix
(ever/never exposed to
DCM)
The risk of NHL was
increased with exposure to
DCM; OR (95% CI) = 1.69
(1.06,2.69). For the
diffuse large B-cell
lymphoma subtype, the
risk was also significantly
increased with exposure to
DCM; OR (95% CI) - 2.10
(1.15, 3.85).
Barry et al.
(2
High
Cancer
Breast cancer mortality
132,352 while women and
18,591 black women across
24 US states, 14.2 percent
and 24.7 percent of cases
were under 50 for white and
black women, respectively
50 percent of black cases
and 30 percent of white
cases were considered
exposed to DCM
Breast cancer mortality
risk was significantly
elevated for white and
black women in the highest
level of exposure. Risk of
breast cancer mortality was
significantly reduced in the
first level of exposure for
white women.
Cantor et
>5)
High
Cancer
Diagnosis of cancer in oral
cavity, oropharynx,
hypopharvnx. oral cavity, and
larynx (detailed list of codes in
text)
Casc-conlrol. women only.
296 cases. 775 controls,
diagnosed 2001-2007. general
population. 18-85 years,
subset of ICARE cohort
DCM. exposure qualitatively
stated as ever (job with
likely exposure > 1 month) or
never
Non-significant positive
association between DCM
and head/neck cancers in
ever/never and continuous
cumulative exposure
analysis: non-significant
negative association for
those exposed exclusively
to DCM (limited sample
size)

Medium
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Qinccr
Cancers of the bladder,
prostate, colon, stomach,
rectum, kidney, esophagus,
liver, and pancreas, as well as
melanoma and non-Hodgkin's
lymphoma.
3730 male. Canadian patients
aged 35 to 70 years diagnosed
1979-1985 in 18 largest
Montreal hospitals: 533
controls from electoral lists
in Quebec. A second control
group consisted of the
population controls together
with patients with cancers at
sites distal to the primary
cancer being assessed.
DCM exposure determined
from self-reported job
history categorized by
chemists and industrial
hygicnisls based on degree
of confidence, frequency,
and relative levels (not
quantitative)
Non-significant OR for all
cancer types

Medium
Cancer
Meningioma mortality
(1984-1992), United States,
649000 women (12980 cases,
51920 controls)
Methylene chloride based on
a job exposure matrix and
occupation code
Methylene chloride was
not significantly associated
with risk of meningioma
mortality.
Cocco et al.
(1999)
Medium
Cancer
Leukemia and chronic
lymphatic leukemia
355 cases of leukemia and
811 controls, and 103 cases
of chronic lymphatic
leukemia and 925 controls in
Italy, ages 20 to 74
DCM exposure based on
employment questionnaire
and expert rating,
A significant association
between exposure to DCM
and leukemia and chronic
lymphatic leukemia was
not observed at either
exposure level
Costantini
et al.
(2008)
Medium
Cancer
Renal cell carcinoma
White newly diagnosed cases
with age- and gender-
stratified random sample
white controls
JEM (developed by NCI)
No significant association
between DCM and RCC
for the total population nor
when separated by sex.
Dosemeci
et al.
(1999)
Medium
Cancer
Breast cancer incidence
Participants in the California
Teacher Study. 1995-2011.
(n=l 12.378 women)
National-Scale Air Toxics
Assessment modeled air
concentrations
No significant, association
between breast cancer
incidence and DCM
exposure.

High
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Cancer
Cause-specific mortality to
liver cancer, prostate cancer,
pancreatic cancer, and cervical
cancer
2187 men and 1024 women
working in Amcelle plant in
Cumberland, Maryland,
1970-1981
DCM, 38.2 and 14.3 percent
of men and women exposed
at the high exposure level
(350 to 700 ppm),
respectively
Prostate and cervical
cancer mortality were
elevated in both high and
low exposure groups, but
not significant. No
significant association
observed between
exposure to DCM and liver
or pancreatic cancer in
both men and women.
Gibbs et al.
£1996)
High
Cancer
Multiple myeloma
180 cases of multiple
myeloma (diagnosed between
January 1, 2000 and March
21, 2002; 35-74 years old)
and 481 controls (35-74 years
old)
Exposure to DCM estimated
with job exposure mat rix.
Individual cumulative
exposure scores were
calculated by multiplying the
midpoint of the intensity (in
ppm) by the midpoint of the
frequency (in hours/week)
by the number of years
worked in each exposed job.
When individuals with
reported exposure rated as
"low confidence" were
considered unexposed, a
significantly increased risk
of multiple myeloma was
observed in individuals
ever exposed to DCM; OR
(95% CI) = 2.0 (1.2 to 3.2).
A significant exposure-
related trend (p < 0.05)
was also observed for
duration of exposure. A
near-significant exposure-
related trend (p=0.06) was
observed for cumulative
exposure score with a 10-
year lag.
Gold et al.
(2.010)
High
Cancer
Liver and biliary cancer
Male employees in
photographic film support
manufacturing (n=l,311),
Eastman Kodak Company,
Rochester, NY, 1946-1970
Methylene chloride, area and
personal air samples
Occupational exposure to
methylene chloride was
not significantly associated
with death from liver or
biliary cancer.
Hearne and
Pifer
(1999)
High
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Cancer
Astrocytic brain cancer risk
Men in southern Louisiana,
United States, exposed from
1978 - 1980; in northern New
Jersey and Philadelphia,
Pennsylvania, United States,
exposed from 1979 - 1981
(n=620, 300 cases, 320
controls)
Methylene chloride, medium
exposure (2)
Chi trend for methylene
chloride= 2.08. Exposure
significantly associated
with astrocytic brain
cancer.
Heineman
et al.
(1994)
Medium
Cancer
Prostate cancer mortality
Employees of a cellulose
acetate/triacetate fibers plant
(n=3211; 2187 men. 1024
women), Cumberland. MD.
1970-1989
Methylene chloride, area and
personal air samples taken at
a similar plant owned by the
same company
High occupational
exposure to methylene
chloride was significantly
positively associated with
death from prostate cancer
in men with more than 20
years since first exposure.
There was also evidence of
a non-significant, positive
dose-response relationship
between methylene
chloride exposure and
prostate cancer mortality.
Gibbs et al.
(1996)
Medium
Cancer
Childhood acute lymphoblastic
leukemia
790 mothers interviewed
from both case and control
groups in Quebec Canada
between 1980 a€" 2000;
Children 0-14 yrs old. 848
cases, 916 controls
DCM exposure to mothers 2
years before pregnancy,
and up to birth.
Exposure level 0 (baseline):
No exposure
(none or
possible exposure); level 1.
Some exposure
(concentration x
frequency < 4);
level 2: Greater exposure
(concentration x
frequency > 4)
Maternal exposure to
DCM before or during
pregnancy resulted in
increased, but non-
significant risk of acute
lymphoblastic leukemia in
children
Infante-
Rivard et
al. (2005)
High
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Qinccr
Cholangiocarcinoma
95 proof-printing workers.
Osaka. Japan. 1987-2006
DCM. Mean cumulative
exposure (ppm-vcars). 591
Significant increase in
cholangiocarcinoma
incidence in this sample
compared to the general
population of Japan.
Incidence rate ratios arc
not significant.

Medium
Cancer
Cause-specific mortality
1271 textile workers, Rock
Hill, South Carolina, 1954-
1986
DCM, 8-hour TWA (ppm)
1700
Significant excess
mortality for accidents and
cancer of the biliary
passages & liver; all other
SMRs non-significant
Lanes et al.
(1990)
Medium
Cancer
All causes, malignant
neoplasms (total; buccal cavity;
biliary passages and liver;
melanoma; bronchus, trachea
and lung; breast; pancreas),
cerebrovascular disease,
ischemic heart disease, and
nonmalignant respiratory
disease
Cellulose fiber production
workers (n= 1271. Rock Hill.
South Carolina)
DCM in 1977 median of
140. 280. and 475 ppm in
three main areas
DCM was not significantly
associated with any
mortality, however, SMRs
were elevated for biliary
passages and liver
malignant neoplasms and
melanoma.
Lanes et al.
(1993)
Medium
Cancer
Lung cancer
Investigation of occupational
and environmental causes or
respiratory cancers (ICARE)
participants population-based
case-control study in France
2001-2007 (2274 men cases
and 2780 men controls)
Cumulative Exposure Index
(CEI) based on self-reported
job histories and probability,
intensity, and frequency of
exposure to DCM based on
jobs
DCM was not significantly
associated with lung
cancer in men.

Medium
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Cancer
All Non-Hodgkin lymphoma
and by Non-Hodgkin
lymphoma subtype (i.e,. small
lymphocytic, follicular, diffuse,
other),
All newly diagnosed cases of
Non-Hodgkin lymphomas,
chronic lymphocytic
leukemia (CLL) during 1991-
1993 among men and women
age 20 to 74 years in 11 areas
in Italy
DCM exposure based on
job-specific questionnaires
and industrial hygiene
experts for level of
probability (i.e,. low,
medium, high) and intensity
of exposure (i.e., very low,
low, medium, and high) with
durations of less than 15
years and 15 or more years.
DCM was not significantly
associated with non-
Hodgkin lymphoma either
based on intensity or
duration of exposure;
however, there was an
increase in the risk for
small lymphocytic non-
Hodgkin lymphoma
(borderline significance)
with medium/high
intensity.
Miligi et al.
(2.006)
High
Cancer
Mycosis fungoides (MF)
100 patients with Mycosis
Fungoides and 2846 controls.
35-69 years of age. from
Denmark. Sweden. France.
Germany. Italy, and Spain.
1995-1997
Occupational exposure to
DCM assessed with job
exposure matrix
A negative, non-significant
association was observed
between Mycosis
Fungoides and subjects
with exposure to DCM >=
median of control exposure
vs. unexposed subjects

High
Cancer
Brain cancer: glioma and
meningioma cases
489 glioma cases. 197
meningioma cases, and 799
controls from three USA
hospitals in Arizona.
Massachusetts and
Pennsylvania
Occupational exposure to
DCM via self-reported
occupational history and
industrial hvgicnist assigned
level of exposure
DCM was not associated
with glioma or
meningioma
Neta et al.
High
Cancer
Diagnosis of kidney cancer
General population case-
control study of kidney
cancer (1217 cases: 1235
controls). Detroit (2002 -
2007) and Chicago (2003).
Job exposure matrix was
used to determine years
exposed, average weekly
exposure and cumulative
hours exposed to DCM.
No significant associations
observed between
exposure to DCM and
kidney cancer.

High
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Cancer
Mortality from breast cancer
Aircraft maintenance workers
(n= 14,457; 10,730 men and
3725 women) at Hill Air
Force Base (Utah, USA), for
at least one year from 1952-
1956, and followed up
through 2000
Occupational exposure to
DCM (yes/no) based on job-
exposure matrix; no
quantitative assessment
available
Positive, non-statistically
significant association
between breast cancer
mortality in females and
occupational exposure to
DCM compared to no
exposure
Radican et
al. (2008)
Medium
Cancer
Glioma
Non-farm workers from the
Upper Midwest Health Study
(798 cases and 1141 controls
from Iowa. Michigan.
Minnesota, and Wisconsin
1995-1997)
DCM use (self-reported
occupational history through
1992. bibliographic database
of published exposure)
DCM was associated with
a significant decrease in
gliomas only when
including proxy-only
interviews and unexposed
participants or as an
ever/never exposure.

High
Cancer
Total lymphoma, HL, B-NHL,
T-NHL, B-NHL subentities
(DLBCL, FL, CLL, multiple
myeloma, marginal zone
lymphoma)
710 participating cases
(matched to 710 controls)
with malignant lymphoma
among men and women aged
18 to 80 years in 6 regions in
Germany
Cu mu la I ivc occupatio nal
exposure to DCM
[ppm*years] based on
intensity, the frequency, and
duration of DCM exposure
(0, >0 to <26.3, >26.3 to
<=175, >175 ppm*years)
DCM was not significantly
associated with malignant
lymphoma; however,
exposure to >175 ppm*yrs
was associated with an
increased (non-significant)
risk of malignant
lymphoma, B-cell non-
Hodgkin's lymphoma and
T-cell non-Hodgkin's
lymphoma.
Seidler et
al. (2007)
High
Cancer
Rectal cancer incidence
Greater Montreal
metropolitan area. Case-
control study of
occupalionally-exposed men
aged 35 to 70 years old (4263
cases. 533 population
controls: also hospital and
cancer controls).
Any or substantial exposure
The ORs for any and
substantial exposure to
DCM exposure and rectal
cancer were significantly
elevated at the p=0.1 level
(one-sided).

Medium
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Qinccr
Brain and other nervous system
cancer mortality
National Inst.it.ulc for
Occupational Safety and
Health (NIOSH) Cohort.
34494 workers at NY
microelectronics and business
machine facility. 2009. 52-
65yrs
Cumulative DCM exposure
score based on department-
exposure matrix
DCM was not significantly
associated with mortality
from brain or other
nervous system cancers.
(2014)
Medium
Qinccr
Acute myeloid lymphoma
Cases of acute myeloid
leukemia (n= 14.337)
diagnosed between 1961 and
2005. and controls
(n=71.027) matched by age.
sex. and country identified
from the Nordic Occupational
Cancer Study cohort
Cumulative DCM exposure
estimated using job exposure
matrix. Median (ppm-yr) 9.9
No significant increase in
acute myeloid leukemia
risk was observed with
low. moderate, or high
exposure to DCM.
compared to referent
group, when hazard ratios
were calculated using a 10-
year lag (p-valuc = 0.43).
Findings remained
statistically nonsignificant
when analysis was
stratified by sex or age

High
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Cancer
All malignant neoplasms
mortality
Male employees from
Branlham photographic film
base. United Kingdom
n= 1346 men (1034 exposed.
312 unexposed) exposed from
1960 - 1988
DCM. cumulative exposure,
median (1000 ppm-ycars)
36.0
DCM exposure was not
significantly associated
with all malignant
neoplasms mortality (p-
valuc = 0.60): Non-
significant excess of brain
cancer deaths in exposed
workers (p-valuc=0.9):
DCM exposure not
significantly associated
with ischemic heart disease
mortality (p-valuc=0.24):
DCM exposure not
significantly associated
with respiratory cancer
mortality (p-valuc=0.90):
DCM exposure was not
statistically associated with
all cancer mortality after
excluding respiratory
cancers (p-valuc=0.62): No
Cox regression coefficients
estimating relative risk
were statistically evaluated

Medium
Cancer
Lung cancer
Lung cancer cases and
randomly selected
population-based controls
frequency matched by sex
and age in Montreal Canada
DCM exposure (any or
substantial) was assessed by
a team of industrial chemists
and hygicnists based on self-
reported job histories.
No significant association
observed between any or
substantial exposure to
DCM and lung cancer in
the pooled analysis (or
either study individually)

Medium
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Qinccr
All malignant, neoplasms
mortality
Male employees. United
Slates. n=1346 men (1034
exposed. 312 unexposed)
exposed from I960 - 1988
Methylene chloride,
cumulative exposure (1000
ppm-ycars)
Exposure not significantly
associated with all
malignanl neoplasms, (p-
valuc=0.6). No Cox
regression coefficients
were statistically
evaluated.

Medium
Cancer
Non-Hodgkin Lymphoma
601 cases, 717 controls (all
women) in Connecticut,
1996-2000,21-84 years
Never, low, or medium-high
probability of exposure to
DCM
Non-Hodgkin Lymphoma
was associated with low
probability of exposure to
DCM, but not with
medium-high probability
of exposure to DCM
Wang et al.
(2009)
Medium
Cancer
Mortality due to prostate cancer
2187 men working in
Amcelle plant in
Cumberland, Maryland,
1970-1981
DCM: none (0 ppm): low
(50-100 ppm); high (350-
700 ppm)
Deaths from prostate
cancer were elevated in the
high and low groups, and
were statistically
significant in high exposed
workers with 20 years
since initial exposure were
included (SMR = 208.4,
p<0.05)
Gibbs et al.
(1996)
High
Cancer
All malignant neoplasms
mortality
Male employees, United
States, n=1346 men (1034
exposed, 312 unexposed)
exposed from 1960 - 1988
Methylene chloride,
cumulative exposure (1000
ppm-years)
Exposure not significantly
associated with all
malignant neoplasms, (p-
value=0.6). No Cox
regression coefficients
were statistically
evaluated.
Tom en son
(2
Medium
Cardiovascular
Birth defects
Offspring of 60.613 case-
mothers and 244.927 control-
molhcrs in United Stales
(Texas)
Exposed or non-exposed:
exposure risk estimates
based on proximity of
maternal residence to DCM
emissions
A weak negative
association was observed
between exposure to DCM
and septal heart defects

Medium
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Cardiovascular
Cause-specific mortality
1271 textile workers, Rock
Hill, South Carolina, 1954-
1986
DCM, 8-hour TWA (ppm)
1700
Significant excess
mortality for accidents and
cancer of the biliary
passages & liver; all other
SMRs non-significant
Lanes et al.
£1990)
Medium
Cardiovascular
All causes, malignant
neoplasms (total; buccal cavity;
biliary passages and liver;
melanoma; bronchus, trachea
and lung; breast; pancreas),
cerebrovascular disease,
ischemic heart disease, and
nonmalignant respiratory
disease
Cellulose fiber production
workers (n=1271, Rock Hill,
South Carolina)
DCM in 1977 median of
140, 280, and 475 ppm in
three main areas
DCM was not significantly
associated with any
mortality, however, SMRs
were elevated for biliary
passages and liver
malignant neoplasms and
melanoma.
Lanes et al.
(1993)
Medium
Cardiovascular
Chest discomfort with exercise
Adult employees of a
triacetate fibers plant
(n=150), 1984-1986, Rock
Hill, SC, and matched non-
exposed controls (n=260)
DCM. mean 475 ppm (8-
hour time weighted average),
for longer than 10 years
Occupational exposure to
methylene chloride for
more than 10 years did not
result in significant
differences in self-reported
cardiovascular symptoms
when comparing exposed
to unexposed workers
Soden
(1993)
Medium
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Cardiovascular
Ischemic heart disease
mortality
Male employees from
Branlham photographic film
base. United Kingdom
n= 1346 men (1034 exposed.
312 unexposed) exposed from
1960 - 1988
DCM. cumulative exposure,
median (1000 ppm-ycars)
36.0
DCM exposure was not
significantly associated
with all malignant
neoplasms mortality (p-
valuc = 0.60): Non-
significant excess of brain
cancer deaths in exposed
workers (p-valuc=0.9):
DCM exposure not
significantly associated
with ischemic heart disease
mortality (p-valuc=0.24):
DCM exposure not
significantly associated
with respiratory cancer
mortality (p-valuc=0.90):
DCM exposure was not
statistically associated with
all cancer mortality after
excluding respiratory
cancers (p-valuc=0.62): No
Cox regression coefficients
estimating relative risk
were statistically evaluated

Medium
Growth (early life)
and Development
Low birthweight
91,302 live births from 1976
to 1987 in Monroe County,
New York among residents
living near the Eastman
Kodak Company
Kodak Air Management
Program (KAMP) air
dispersion modeling system:
high (50 ug/m), moderate
(25 ug/m), low (10 ug/m),
and none
A significant association
between exposure to DCM
at all three levels and low
birthweight was not
observed
Bell et al.
High
Growth (early life)
and Development
Birth defects
Offspring of 60.613 case-
mothers and 244.927 conlrol-
molhcrs in United States
(Texas)
Exposed or non-exposed:
exposure risk estimates
based on proximity of
maternal residence to DCM
emissions
No significant association
was observed between
exposure to DCM and oral
clefts

Medium
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Growth (early life)
and Development
Spontaneous abortion
44 female pharmaceutical
factory workers in Finland
who had spontaneous
abortions while employed
(cases), 130 female
pharmaceutical factory
workers in Finland who had
normal births while employed
(controls)
DCM exposure based on a
questionnaire sent to factory
physicians or their nurses
A positive, borderline non-
significant association was
observed between
occupational exposure to
methylene chloride and
spontaneous abortion
Taskimem et
!6)
Medium
Hematological and
I mmunc
Primary Sjogren sy ndrome
Cases (11= 175) from three
University Hospitals and
matched controls (n=350)
(2010-2013)
Occupational DCM exposure
based on self-reported
occupational histories,
expert judgement of
industrial hygicnisls and
occupational practitioners, as
well as the French JEM
(used more for the
chlorinated solvents)
Significant increase in risk
for Sjogren's syndrome
with occupational DCM
exposure: OR was
increased with high final
cumulative exposure but
was not significant.

Medium
Hematological and
Immune
Total bilirubin, red cell count,
hemoglobin, hematocrit, mean
corpuscular volume, mean
corpuscular hemoglobin, mean
corpuscular hemoglobin
concentration,
carboxyhemoglobin, aspartate
aminotransferase, alanine
aminotransferase, lactate
dehydrogenase, alkaline
phosphatase, and
albumin.
266 exposed and 251
unexposed employees at two
fiber production plants in
North Carolina and Virginia
8-hour time-weighted
average dichloromethane
concentrations: unexposed,
60 and 140 ppm, 280 ppm,
and 475 ppm
There was a statistical
increase in aspartate
aminotransferase with
intensity of methylene
chloride exposure among
white women in the
exposed group, but not
among the white men, or
nonwhites of either sex.
Ott et al.
(1983)
Medium
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Hematological and
Immune
Hematocrit
Adult employees of a
triacetate fibers plant
(n=150), 1984-1986, Rock
Hill, SC, and matched non-
exposed controls (n=260)
DCM, mean 475 ppm (8-
hour time weighted average),
for longer than 10 years
Occupational exposure to
methylene chloride for
more than 10 years did not
result in a significant
difference in hematocrit
when comparing exposed
to unexposed workers
Soden
£1993)
Medium
Hematological and
Immune
Mortality due to
infectious and parasitic
diseases
Male employees in
photographic film support
manufacturing (n=l,311),
Eastman Kodak Company,
Rochester, NY, 1946-1970
Methylene chloride, area
and personal air samples
Occupational exposure to
methylene chloride was
significantly associated
with a decrease in
mortality from infectious
and parasitic diseases
Heame and
Pifer
(1999)
High
Hepatic
Scrum gamma glutamyl
transferase (GGT). scrum total
bilirubin, scrum aspartate
amino-trans(erase (AST),
scrum alanine aminotransferase
(ALT)
854 workers in a plastic
polymer facility in Indiana.
USA. i 985
DCM: non-exposed group
(>1.0 ppm). low-exposed
group (3.3 ppm). mcd-
cxposcd group (10.9 ppm).
high-exposed group (49.0
ppm)
Scrum gamma glutamyl
transferase (GGT). scrum
total bilirubin, scrum
aspartate amino-transferase
( AST), scrum alanine
aminotransferase (ALT)

Medium
Hepatic
Total bilirubin, red cell count,
hemoglobin, hematocrit, mean
corpuscular volume, mean
corpuscular hemoglobin, mean
corpuscular hemoglobin
concentration,
carboxyhemoglobin, aspartate
aminotransferase, alanine
aminotransferase, lactate
dehydrogenase, alkaline
phosphatase, and
albumin.
266 exposed and 251
unexposed employees at two
fiber production plants in
North Carolina and Virginia
8-hour time-weighted
average dichloromethane
concentrations: unexposed,
60 and 140 ppm, 280 ppm,
and 475 ppm
A consistent positively
significant association
between total bilirubin and
methylene chloride
exposure
was found in white men
and women, in non-white
women, but not in non-
white men.
Ott et al.
(1983)
Medium
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Hepatic
Mortality from cirrhosis and
other chronic liver disease
National Institute for
Occupational Safety and
Health (NIOSH) Cohort.
34494 workers at NY
microelectronics and business
machine facility. 2009. 52-
65yrs
Cumulative DCM exposure
score based on department-
exposure matrix
DCM exposure was not
significantly associated
with mortality from
diseases of the liver
(2014)
Medium
Hepatic
Total bilirubin
Adult employees of a
triacetate fibers plant
(n=150), 1984-1986, Rock
Hill, SC, and matched non-
exposed controls (n=260)
DCM, mean 475 ppm (8-
hour time weighted average),
for longer than 10 years
Occupational exposure to
methylene chloride for
more than 10 years did not
result in significant
differences in markers of
hepatic injury when
comparing exposed to
unexposed workers
Soden
(1993)
Medium
Mortality
Meningioma mortality
Women in United States. (n=
649000, 12980 cases. 51920
controls) exposed from 1984-
1992
Methylene chloride
Occupational hazard was
not significantly associated
with mortality from
meningioma.
Cocco et al.
(1999)
Medium
Mortality
Cause-specific mortality
1271 textile workers, Rock
Hill, South Carolina, 1954-
1986
DCM, 8-hour TWA (ppm)
1700
Significant excess
mortality for accidents and
cancer of the biliary
passages & liver; all other
SMRs non-significant
Lanes et al.
(1990)
Medium
Mortality
All causes, malignant
neoplasms (total; buccal cavity;
biliary passages and liver;
melanoma; bronchus, trachea
and lung; breast; pancreas),
cerebrovascular disease,
ischemic heart disease, and
nonmalignant respiratory
disease
Cellulose fiber production
workers (n=1271, Rock Hill,
South Carolina)
Methylene chloride; in 1977
median of 140, 280, and 475
ppm in three main areas
Methylene chloride was
not significantly associated
with any mortality,
however, SMRs were
elevated for biliary
passages and liver
malignant neoplasms and
melanoma.
Lanes et al.
(1993)
Medium
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Mortality
Mortality
Aircraft maintenance workers
(n= 14,457; 10,730 men and
3725 women) at Hill Air
Force Base (Utah, USA) for
at least one year from 1952-
1956 and followed up for
mortality through 2000
Exposure was assessed from
a JEM using data from
worker compensation files,
histories and telephone
books, organizational charts,
technical orders, position
descriptions, walk-through
surveys, interviews, and
limited measurement data..
For some analyses, exposure
was categorized by
cumulative exposure (using
inputs of continuous or
intermittent exposure, and
low or peak exposure, and
estimates of frequency and
intensity).
A significantly elevated
hazard ratio was observed
for methylene chloride
exposure and
nonmalignant respiratory
diseases in men.
Radican et
al. (2008)
Medium
Neurological/
Behavior
Birth defects
Offspring of 60.613 case-
mothers and 244.927 control-
mothers in United States
(Texas)
Exposed or non-exposed:
exposure risk estimates
based on proximity of
maternal residence to DCM
emissions
No significant association
was observed between
exposure to DCM and
neural tube defects

Medium
Neurological/
Behavior
Dizziness/vertigo
854 workers in a plastic
polymer facility in Indiana.
USA. i985
DCM: non-exposed group
(> 1.0 ppm). low-exposed
group (3.3 ppm). mcd-
cxposcd group (10.9 ppm).
high-exposed group (49.0
ppm).
There was significant trend
for increased
dizziness/vertigo in the
DCM exposed groups.

Medium
Neurological/
Behavior
Autism spectrum disorders
3.137 children in North
Carolina (1.931 total. 201
cases) and West Virginia
(1.246 total. 173 cases).
2000-2004. 8 years old
1996 modeled DCM in
ambient air. geometric mean
concentration: 539.8 (NC)
and 202..3 (WV) ng/mA3
A positive, non-significant
association between
ambient DCM (80th vs.
20th percentile) and autism
spectrum disorder

High
19

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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Neurological/
Behavior
Grip strength, motor speed,
reaction time, visual memory,
verbal memory, attention,
spatial ability
25 retired mechanics (mean
age 67.5 yrs) who had
worked between 1970 and
1984 for a single, unspecified
airline; location not clearly
specified but appears to be
California
Mean time-weighted
averages of DCM (in air)
ranged from 82 to 236 ppm
No statistically significant
differences in composite
scores between the
exposed and unexposed
groups
Lash et al.
Medium
Neurological/
Behavior
Autism Spectrum Disorder
Nurses' Health Study II
children (US: 325
cases/22101 controls).
DCM air concentrations at
mother's location at birth:
Mean: 0.4 ug/m.3
DCM exposure was not
significantly associated
with Autism Spectrum
Disorder. Although it was
close to significant (p=0.05
for Q1 compared to Q5.
there was no trend over
quintilcs (p for trend
=0.08). When separated by
sex. there was a significant
increase when comparing
Q5 to Q.1 (p=0.03) in boys,
but not girls.

High
Neurological/
Behavior
Diseases of the nervous system
mortality
National Institute for
Occupational Safetv and
Health (NIOSH) Cohort.
34494 workers at NY
microelectronics and business
machine facility. 2009. 52-
65yrs
Cumulative DCM exposure
score based on department-
exposure matrix
DCM exposure was not
significantly associated
with mortality from
diseases of the nervous
system.
(2014)
Medium
Neurological/
Behavior
Recurring severe headaches
Adult employees of a
triacetate fibers plant
(n=150), 1984-1986, Rock
Hill, SC, and matched non-
exposed controls (n=260)
DCM, mean 475 ppm (8-
hour time weighted average),
for longer than 10 years
Occupational exposure to
methylene chloride for
more than 10 years did not
result in significant
differences in self-reported
neurological symptoms
when comparing exposed
to unexposed workers
Soden
£1993)
Medium
20

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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Neurologic;) 1/
Behavior
Autism spectrum disorder
diagnosis with Social
Communication Questionnaire
score of 15+
217 cases. 224 interview
controls. 4856 birth
certificate controls, children
born from 2005-2009 in 6
counties of Pennsylvania
DCM exposure (239-273
ng/m3) during gestation
csl.iina.lcd with National Air
Toxics Assessment 2005
model from addresses at
birth
DCM positively associated
with Autism Spectrum
Disorder diagnosis relative
to birth certificate controls.
significant for fourth
quarlilc compared to first
quarlilc of exposure for
singleton births, non-
significant for all births
combined.

Medium
Neurological/
Behavior
Autism diagnosis
Children (n=641 cases) born
to mothers living within 5 km
of air pollutant monitoring
stations in Los Angeles
County during pregnancy.
1995-2006. monitored until
age 6
Maternal ambient DCM
exposure during entire
pregnancy
A positive, non-significant
association was observed
between autistic disorder
by age 6 years and
maternal ambient DCM
exposure

High
Neurological/
Behavior
Autism Spectrum Disorder
Children born 1994 followed
for 9 years. 284 cases and 657
birth month- and sex-matched
control births from the San
Francisco area
1996 EPA estimated annual
average concentrations of
DCM on the census tract
level, mean (SD) exposure
for cases: 0.68 (0.48 ug/m3)
Positive association
observed for 3rd
(significant) and 4th (not
significant) qua.rt.ilcs of
DCM exposure compared
to those exposed to the
median exposure level or
less.

Medium
Reproductive
Spontaneous abortion
Female pharmaceutical
factory workers in Finland.
44 cases, 130 controls, 1973-
1981
DCM exposure based on a
questionnaire sent to factory
physicians or their nurses
Borderline significant
positive association
between occupational
DCM exposure and
spontaneous abortion
Taskinen et
!6)
Low
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Respiratory
Cause-specific mortality
1271 textile workers, Rock
Hill, South Carolina, 1954-
1986
DCM, 8-hour TWA (ppm)
1700
Significant excess
mortality for accidents and
cancer of the biliary
passages & liver; all other
SMRs non-significant
Lanes et al.
£1990)
Medium
Respiratory
All causes, malignant
neoplasms (total; buccal cavity;
biliary passages and liver;
melanoma; bronchus, trachea
and lung; breast; pancreas),
cerebrovascular disease,
ischemic heart disease, and
nonmalignant respiratory
disease
Cellulose fiber production
workers (n=1271, Rock Hill,
South Carolina)
DCM in 1977 median of
140, 280, and 475 ppm in
three main areas
DCM was not significantly
associated with any
mortality, however, SMRs
were elevated for biliary
passages and liver
malignant neoplasms and
melanoma.
Lanes et al.
(1993)
Medium
Respiratory
Mortality from bronchitis
Aircraft maintenance workers
(n= 14,457; 10.730 men and
3725 women) at Hill Air
Force Base (Utah, U SA), for
at least one year from 1952-
1956, and followed up
through 2000
Occupational exposure to
DCM (yes/no) based on job-
exposure matrix; no
quantitative assessment
available
Positive, statistically
significant, association
between mortality from
bronchitis in males and
occupational exposure to
DCM compared to no
exposure
Radican et
al. (2008)
Medium
Respiratory
Mortality due to influenza and
pneumonia
Employees of a cellulose
acetate/triacetate fibers
plant (n=3211; 2187
men, 1024 women),
Cumberland, MD, 1970-
1989
Methylene chloride, area
and personal air samples
taken at a similar plant
owned by the same
company
High occupational
exposure to methylene
chloride had a non-
significant positive
association with death
from influenza and
pneumonia men with
more than 20 years since
first exposure
Gibbs
Medium
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Target Organ/
System
Outcome/ Endpoint
Study Population
Exposure
Results
Reference
Data Quality
Evaluation
Respiratory
Mortality due to respiratory
illness
Male employees in
photographic film support
manufacturing (n=l,311),
Eastman Kodak Company,
Rochester, NY, 1946-1970
Methylene chloride, area
and personal air samples
Occupational exposure to
methylene chloride was
not significantly
associated with mortality
from respiratory diseases
Heame and
Pifer
(1999)
High
aNot identified in U. S. EPA (2011); Identified through backwards searching from other sources or from TSCA submissions
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2 Data Extraction Tables for Non-Cancer Endpoints From Animal Toxicity Studies
Noncancer endpoints/studies are divided into separate tables: (1) acute and short-term studies; (2) subchronic and chronic studies; and (3)
reproductive and developmental studies (and related effects from repeat-dose studies). They are divided by endpoint. Within each endpoint, data
from the inhalation exposure route is presented before the oral exposure route. Oral data are included because they are considered for the weight
of the scientific evidence.
The LOAELs and NOAELs are presented for each endpoint and study that measured that endpoint to compare across toxicity studies. For studies
cited in previous assessments, the NOAELs/LOAELs cited within that assessment are presented in the tables in this appendix. For newly-
obtained studies, EPA reports any NOAELs and LOAELs chosen by the study authors (if available); if EPA disagreed with the NOAEL/LOAEL,
a separate value is also presented below. The NOAELs/LOAELS are presented from lowest to highest for each endpoint and exposure route.
24

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21 Acute and Short-term Animal Toxicity Studies a
25

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T;ir;ii'( Origin/
S\sU'iii
Siiulj Tjpe
Species/
Slr;iin/Se\
(Nil in hoi'/
uroii p)
Kxposmv
Route
Doses/
(onccnlnilions
Diii'iilion
NOAM./
1.OA l-'.l.
reported In
sluclj iiulhors
NOAII./
1.OA l-'.l.
(inii/inJ or
mii/kii-(l;i\)
l.lTcd
Reference'
Diilii Qu;ili(\
l-'.\iiliiiiiion
Body Weight
Short-term
Rat M/F
(5/scx?/group)
Oral
0, 100, 300, 600,
1200 mg/kg-
bw/day
7 days/week
for 14 days
Not Reported
LOAEL = 100
mg/kg-bw/day
i bodv weight
(M)
(%?)
General
Electric
(1976b)
Medium
(2.0)
Gastrointestinal
Short-term
Rat Other Both
(5)
Oral
0, 100, 300, 600,
1200 mg/kg-
bw/day
7 days/week
for 14 days
Not Reported
NOAEL = 300
mg/kg-bw/day
Blood/
congestion in
intestines and
stomach (plus
hemorrhage in
stomach) of
animals that
died
General
Electric
(1976b)
Medium
(2.0)
Hepatic
Acute/
Short-term
Rat.
Fischer 344
Inhalation,
vapor, whole
body
0, 1910,3910
ppm (1 day):
0. 1950.3870
ppm (10 day)
1 or 10 days:
6 hrs/day
Not Reported
LOAEL =
1950 ppm
(10 days)
1 day: no
effects
10 days: T#
eosinophils in
ccnlrilobular
cells
Shell Oil
(1986)
High (1.5)
Hepatic
Acute/
Shorl-lcrm
Mouse.
B6C3F1
Inhalation,
vapor, whole
body
0, 2010, 3710
ppm (1 day):
0, 1990, 3960
ppm (10 day)
1 or 10 days:
6 hrs/day
Not Reported
LOAEL =
1990 ppm
(10 days)
1 day: j liver wt
at 3710 ppm
10 days: t liver
wt at both
concentrations
Shell Oil
(1986)
High (1.5)
Immune
Acute/
Short-term
Mouse, CD-I
Inhalation
Acute:
0, 52, 95 ppm
Short-term:
0,51 ppm
Acute = 3 hrs
Short-term = 3
hrs/day for 5
days
Not Reported
NOAEL = 52
ppm
t mortality
(12.2%; p<
0.01) from S.
zooepidemicus;
i bactericidal
activity (by
12%; p< 0.001)
Aranyi et
al. (1986)
Medium (1.8)

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Immune
Short-term
Rat, Sprague-
Dawley
Inhalation
0, 5187 ppm
6 hrs/day, 5
days/wk for 28
days
Not Reported
NOAEL = 5187
ppm
No change in
IgM response
after injection
with sheep red
blood cells
[j spleen wts]
Warbrick
et al.
High (1.3)
Neurological
Shorl-lcrm
prc-tcsl
followed bv
acute lest
Rat. F344. M.
16 (pretest)
8/group (during
test)
Inhalation
Prc-tcsl: 2000
ppm
Test: 0. 2000
ppm
Prc-lcsl: 6
hrs/day: 3 days:
Test: 2.5-3.5
lvrs
Not reported
LOAEL = 2000
ppm
Changes in
somatosensory
evoked
potentials
(cerebellum/
sensory cortex):
reduced EEG
power
| measured in
aculc leslj
Dow
(1988)
High (1.5)
Neurological
Iclinical signs|
Acute/
Shorl-lcrm
Rat.
Fischer 344
Inhalation,
vapor, whole
body
0, 1910,3910
ppm (1 day):
0. 1950.3870
ppm (10 day)
1 or 10 days:
6 hrs/day
Not Reported
Not Determined
10 days:
subdued:
reduced
response to
noise stimulus
Shell Oil
(I9S6)
High (1.5)
Neurological
Iclinical signs|
Acute/
Shorl-lcrm
Mouse.
B6C3F1
Inhalation,
vapor, whole
body
0, 2010,3710
ppm (1 dav):
0, 1990, 3960
ppm (10 day)
1 or 10 days:
6 hrs/day
Not Reported
Not Determined
10 days:
subdued at 1990
ppm during last
hr of
exposure/day:
Hyperactive
first 3 hrs at
3960 ppm and
then subdued
later during
exposure
Shell Oil
(1986)
High (1.5)
Neurological
Acute
Rat, F344, F
(n=8/group)
Oral, gavage
0, 101, 337, 1012
or 1889 mg/kg
Single dose
(evaluated 4
and 24 hours
after dosing)

NOAEL= 337
(F)
Functional
observational
battery (FOB)
neuro-muscular
Moser et
al. (1995)
High (1.3)
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and
sensorimotor
parameters
significantly
different from
controls


Neurological
Short-term
Rat, F344, F
(n=8/group)
Oral, gavage
0, 34, 101, 337,
1012 or 1889
mg/kg-day
14 days

NOAEL= 101
(F)
Alterations in
FOB
parameters
(including
autonomic,
neuro-muscular
and
sensorimotor
and excitability
measures) from
day 4
Moser et
al. (1995)
High (1.3)
Neurological
Short-term
Rat Other Both
(5)
Oral
0, 100, 300, 600,
1200 mg/kg-
bw/day
7 days/ week
for 14 days
Not Reported
NOAEL = 100
mg/kg-bw/day
Decreased
general activity
General
Electric
(1976b)
Medium (2.0)
Respiratory
Short-term
Rat Other Both
(5)
Oral
0, 100, 300, 600,
1200
mg/kg-bw/day
7 days/ week
for 14 days
Not Reported
NOAEL = 300
mg/kg-bw/day
Gross
abnormalities in
the lungs
(pulmonary
congestion) of
animals that
died during the
study.
General
Electric
(1976b)
Medium (2.0)
Respiratory
Acute/
Short-term
Rat.
Fischer 344
Inhalation,
vapor, whole
body
0, 1910, 3910
ppm (1 day):
0. 1950.3870
ppm (10 day)
1 or 10 days:
6 hrs/day
Not Reported
NOAEL=
3870 ppm
(10 days)
No effects on
lung
Shell Oil
(1986)
High (1.5)
Respiratory
Acute/
Short-term
Mouse.
B6C3F1
Inhalation.
0, 2010, 3710
ppm (1 day):
1 or 10 days:
6 lvrs/day
Not Reported
Not Determined
1 day: Selective
va.cuolat.ion and
Shell Oil
(1986)
High (1.5)
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vapor, whole
body
0, 1990, 3960
ppin (10 day)



pyknosis of
Clara cells in
bronchiolar
epithelium
10 days: No
effects


Multiple organs
Shorl-lcrm
Dog M/F
(1/scx/dosc)
Oral (gavagc)
0, 25, 75, 150,
300 mg/kg-
bw/dav
7 days/week
for 14 days
Not reported
Not Determined
Congestion of
orga ns - no
clear dosc-
rcsponsc by
organ (lungs,
liver, lymph
nodes.
gastrointestinal
tracts, urethra)
Cyst in brain (at
lowest dose)
General
Electric
(1976a)
Low
(downgraded)
"Acute = < 1 day: Shorl-lcrm = > 1 day - days
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2.2 Subchronic and Chronic Animal Toxicity Studies a
TsiifiiM
Or»;m/
System
Slmlx
Tx pe
Species/
Str;iin/Sex
(Nil in hoi'/
{•roup)
I'.xposurc Route
Doses/
(onecnlnilions
Munition
NOAI I./I OAI.I.
reported In slntl>
illllllOI'S
NOAI'.I./
1.OA I.I. (iii^/iii3
or mii/k*i-cl;i>)
(Sex)
1". fleet
Reference
Diilii
Qii;ilil>
l.\;ilu;i(ion
Mortality
Chronic
Rat, Sprague
Dawley, M/F
(n~190/dose)
Inhalation, vapor,
whole body
0, 1755, 5264 or
12,283 mg/m3
(0, 500, 1500 or
3500 ppm)
6 hours/day,
5 days/week
for 2 years
NA
NOAEL = 5264
mg/m3
(F)
t mortality
Burek et
al. (1984)
High (1.5)
Mortality
Subchroni
c
Rat, F344,
M/F
(n=20/group)
Inhalation, vapor,
whole body
0, 1843, 3685,
7371, 14,742 or
29,483 mg/m3 (0,
525, 1050. 2100.
4200 or 8400
ppm)
6 hours/day,
5 days/week
for 13 weeks
NA
NOAEL= 14,742
mg/m3
1/10 (M) and
1/10 (F) died
NTP
(1986)
High (1.3)
Mortality
Subchroni
c
Mouse,
B6C3F1, M/F
(n=20/group)
Inhalation, vapor,
whole body
0, 1843, 3685,
7371, 14,742 or
29,483
mg/m3
(0, 525, 1050,
2100, 4200 or
8400 ppm)
6 hours/day,
5 days/week
for 13 weeks
NA
NOAEL= 14,742
mg/m3
4/10 (M) and
2/10 (F) died
NTP
(1986)
High (1.3)
Mortality
Chronic
Rat, Sprague
Dawley, M/F
(n=100/dose)
Oral, gavage
0, 100 or 500
mg/kg-day
4-5
days/week,
up to 64
weeks
NA
NOAEL = 100
mg/kg-bw/day
(M)
t mortality
(M/F) (M: stat.
signif.) led to
study
termination at
64 weeks
Maltoni et
al. (1988)
Medium
(1.9)
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TsiifiiM
()r»;in/
S\s(em
Slmlj
Tj pe
Species/
S(r;iin/Se\
(Nil in hoi'/
group)
Kxposure Roule
Doses/
Conccnlmlions
Dui'iilion
NOAI'.I./I.OAI'.I.
reported In slntl>
illllllOI'S
NOAI'.I./
1.OA 111. (iiiii/inJ
or mii/k*i-cl;i>)
(Sex)
r.lTeel
Reference
Diilii
Qii;ilil>
l-'\iiliiiil i«ui
Moi'lalils
Chronic
Mouse,
Swiss, M/F
(n=100/treate
d group; 120/
control
group)
Oral, ga\ age
oj |oo hi' 5(i()
mg/kg-bw/day
4-5 da\s
week, up to
64 weeks
\ \
\o\i:i. iuo
(M/F)
' Morialils
(M/F: stat.
signif.) led to
study
termination at
64 weeks
Mallom el
al. (1988)
Medium
(1.9)
Body weight
Subchroni
c
Rat, F344,
M/F
(n=20/group)
Inhalation, vapor,
whole body
0, 1843, 3685,
7371, 14,742 or
29,483 mg/m3 (0,
525, 1050, 2100,
4200 or 8400
ppm)
6 hours/day,
5 days/week
for 13 weeks
NA
NOAEL= 14,742
|Body weight
(M: 23%)
(F: 11%)
NTP
(1986)
High
(1.3)
Body
Weight
Subchroni
c
Dog/Beagle
(M/F)
(4/scx/group)
Oral
0. 12.5. 50. 200
mg/kg-bw/day
90 days
Not Reported
NOAEL = 200
mg/kg-bw/day
No changes in
body weight
General
Electric
(1976)
High
(1.5)
Body weight
Develop-
mental
Rat, F344, F
(n=17-
21/group)
Oral, gavage
0,337.5 or 450
mg/kg-bw/day
Gestation
days 6-19
NA
NOAEL= 337.5
(F)
^Maternal
weight gain
Narotsky
and
Kavlock
(1995)
High
(1.4)
Gastro-
intestinal
Chronic
Mouse,
B6C3F1, M/F
(n=100/group
)
Inhalation, vapor,
whole body
0, 7019 or
14,038 mg/m3 (0,
2000 or 4000
ppm)
6 hours/day,
5 days/week
for 2 years
NA
NOAEL=7019
(M/F)
Stomach
dilation (M/F)
NTP
0986)
High
(1.3)
Gaslroinlcsli
nal
Subchroni
c
Dog/Beagle
(M/F)
(4/scx/group)
Oral
0. 12.5. 50. 200
mg/kg-bw/day
90 days
Not Reported
NOAEL = 200
mg/kg-bw/day
No effects
General
Electric
(1976)
High
(1.5)
Immune
Chronic
Rat, F344,
M/F
(n=100/group
)
Inhalation, vapor,
whole body
0, 3510, 7019 or
14,038 mg/m3
(0, 1000, 2000 or
4000 ppm)
6 hours/day,
5 days/week
for 2 years
NA
NOAEL= 3510
(M)
Splenic
fibrosis
NTP
(1986)
High (1.3)
31

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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
TsiifiiM
()r»;in/
Sjslom
Siudj
1 \ |)0
Species/
S(r;iin/Sc\
(Nil in hoi'/
{•roup)
I'.xposurc Kouli*
Doses/
('niicciili'iilions
Dui'iilion
NOAI'.I./I.OAI'.I.
reported In slntl>
illllllOI'S
NOAI'.I./
1.OA I.I. (iii^/iii3
or mii/k*i-cl;i>)
(Sex)
r.lTecl
Reference
Diilii
Qii;ilil>
l-'\iiliiiil i«ui
1111111111IC
(lll'OIIIC
Mouse,
B6C3F1, M/F
(n=100/group
)
Inhalation, \apor,
whole body
(i, "ol'J ni"
14,038 mg/m3
(0, 2000 or 4000
ppm)
(> hours da\,
5 days/week
for 2 years
\ \
\o\i:i. "Hi';
(M)
Splenic
follicular
atrophy
YIP
( 6)
llighil i)
Hepatic
Chronic
Rat, F344,
M/F
(n=100/group
)
Inhalation, vapor,
whole body
0, 3510, 7019 or
14,038 mg/m3 (0,
1000, 2000 or
4000 ppm)
6 hours/day,
5 days/week
for 2 years
NA
LOAEL= 3510
(M/F)
Hepatocyte
vacuolation
and necrosis,
hemosiderosis
in liver (M/F);
hepatocyte-
megaly (F)
NTP
( 6)
High (1.3)
Hepatic
Chronic
Rat, Sprague-
Dawley, M/F
(n~190/group
)
Inhalation, vapor,
whole body
0, 1755. 5264 or
12,283 mg/m3 (0.
500, 1500 or
3500 ppm)
6 hours/day.
5 days/week
for 2 years
NA
LOAEL= 1755
(M/F)
Hepatocyte
vacuolation
(M/F);
multinucleated
hepatocytes
(F)
Burek
(1984)
High (1.5)
Hepatic
Chronic
Rat, Sprague
Dawley, M/F
(n=180/group
)
Inhalation, vapor,
whole body
0, 176, 702 or
1755 mg/m3 (0,
50, 200 or 500
ppm)
6 hours/day,
5 days/week
for 2 years
NA
NOAEL= 702
(F)
Hepatic lipid
vacuolation
and
multinucleated
hepatocytes
Nitschke
(1988)
High (1.3)
Hepatic
Chronic
Mouse,
B6C3F1, M/F
(n=100/group
)
Inhalation, vapor,
whole body
0, 7019 or
14,038 mg/m3
(0, 2000 or 4000
ppm)
6 hours/day,
5 days/week
for 2 years
NA
LOAEL = 7019
(F)
Hepatocyte
degeneration;
(t
hepatocellular
adenoma or
carcinoma)
NTP
(1986)
High (1.3)
32

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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
T;ir»e(
()r»;in/
S\s(em
Simlj
1 J \K-
Species/
S(r;iin/Sc\
(Nil in hoi'/
urou pi
Kxposurc Roulc
Doses/
(onccnlnilions
Diii'iilion
NOAI'.I./I.OAI'.I.
reported In slntl>
iiulhors
NOAI'.I./
1.OA I.I. (m^/mJ
or m*>/k*>-d:i>)
(Sex)
i.nw-i
Reference
Diilii
Qii;ilil>
r.\iilu;ilion
1 lcp;il it-
(hi'onic
Mouse,
B6C3F1, M/F
(n=20/group)
liihalalioii, \apor,
whole body
(), 1X4 % '(iS5,
7371, 14,742 or
29,483
mg/m3
(0, 525, 1050,
2100, 4200 or
8400 ppm)
(> hours da\,
5 days/week
for 13 weeks
\ \
\o\i:i. "^"i
(F); NOAEL =
14,742 (M)
1 lep;ilnc\ Ic
centrilobular
degeneration
YIP
( 6)
llighil l)
Hepatic
Chronic
Rat,
F344/DuCij
Inhalation, vapor,
whole body
0, 3510, 7019 or
14,038 mg/m3 (0,
1000, 2000 or
4000 ppm)
6 hours/day,
5 days/week
for 2 years
NA
LOAEL = 3510
mg/m3 (F)
Increased
basophilic foci
and increased
abs/rel liver wt
(p<0.01)
Aiso et al.
(2014)
High (1.1)
Hepatic
Chronic
Rat, F344,
M/F
(n=170/group
+ 270
controls)
Oral, drinking
water
0, 6, 52. 125 or
235 mg/kg-dav
(M);
0, 6, 58, 136 or
263 mg/kg-day
(F)
104 weeks
NA
NOAEL=6
(M/F)
t Non-
neoplastic
Foci/areas of
alteration
(M/F); t
incidence of
neoplastic
nodules; fatty
liver changes
(incidence
N/A)
Serota et
al.
(1986a)
High (1.3)
Hepatic
Subchroni
c
Rat, F344,
M/F
(n=30/group)
Oral, drinking
water
0, 166, 420 or
1200 mg/kg-day
(M);
0, 209, 607 or
1469 mg/kg-day
(F)
90 days
NA
LOAEL= 166
(M); LOAEL =
209 (F)
Hepatic
vacuolation
(generalized,
centrilobular,
or periportal)
Kirschma
n et al.
0986)
Low (2.5)
33

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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
TsiifiiM
()r»;in/
S\s(em
Siudj
1 J |)0
Species/
S(r;iin/Se\
(Nil in hoi'/
group)
Kxposure Roule
Doses/
(onccnlnilions
Dui'iilion
NOAI'.I./I.OAI'.I.
reported In slntl>
illllllOI'S
NOAI'.I./
1.OA 111. (iiig/mJ
or mii/k*i-cl;i>)
(Sex)
r.lTeel
Reference
Diilii
Qii;ilil>
r.\iilu;ilion
1 lepalic
Chrome
Mouse,
B6C3F1, M/F
(n=125, 200,
100, 100 and
125 [M];
n=100, 100,
50, 50 and 50
[F])
Ural, driiikiiig
water
u,<.|, 124, 1"
or 234 mg/kg-
day (M);
0, 59, 118, 172
or 238 mg/kg-
day (F)
1 < >4 weeks
\ \
\o\i:i. is5
(M/F)
Some e\ idenee
of fatty liver;
marginal
increase in the
Oil Red-O-
positive
material in the
liver
1 la/leloii
Labs
( 3)
Medium
(1.7)
Hepatic
Subchroni
c
Mouse,
B6C3F1, M/F
(n=30/group)
Oral, drinking
water
0, 226, 587 or
1911 mg/kg-day
(M);
0, 231,586 or
2030 mg/kg-dav
(F)
90 days
NA
NOAEL= 226
(M)
Hepatic
vacuolation
(increased
severity of
centrilobular
fatly change)
Kirschma
n(1986)
Low (2.5)
Hepatic
Subchroni
c
Dog/Beagle
(M/F)
(4/scx/ group)
Oral
0. 12.5. 50. 200
mg/kg-bw/day
90 days
Not Reported
NOAEL = 200
mg/kg-bw/day
No changes in
clinical
chemistry.
gross
pathology.
organ weight.
or
histopathologic
al lesions
General
Electric
(1976)
High
(1.5)
Neurological
Subchroni
c
Dog/Beagle
(M/F)
(4/sex/ group)
Oral
0. 12.5. 50. 200
mg/kg-bw/day
90 days
Not Reported
NOAEL = 200
mg/kg-bw/day
No changes in
clinical
chemistry.
gross
pathology.
organ weight.
or
histopathologic
al lesions
General
Electric
(1976)
High
(1-5)
34

-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
T;u»e(
()r»;in/
S\s(em
Siudx
Tx pe
Speeies/
S(r;iin/Sex
(Nil in hoi'/
uroii pi
Kxposure Roule
Doses/
(oneenlnilions
Diii'iilion
NOAI'.I./I.OAI'.I.
reported In slntl>
iiulhors
NOAI'.I./
1.OA I.I. (m^/mJ
or m«/k*i-cl;i>)
(Sex)
r.lTeel
Uel'erenee
Diilii
Qii;ilil>
l-'\iiliiiil i«ui
kciKll
Chronic
kal, 1-44,
M/F
(n=100/group
)
liihalalion, \apor,
whole body
ns "o In, "(i ll> or
14,038 mg/m3
(0, 1000, 2000 or
4000 ppm)
(> hours da\,
5 days/week
for 2 years
\ \
\<)\i:i. ' 5 111
(M); NOAEL =
7019 (F)
kcn;il luhular
degeneration
YIP
(1986)
Mennear
(1988)
llighil vi
Renal
Chronic
Mouse,
B6C3F1, M/F
(n=100/group
)
Inhalation, vapor,
whole body
0, 7019 or
14,038 mg/m3
(0, 2000 or 4000
ppm)
6 hours/day,
5 days/week
for 2 years
NA
LOAEL= 7019
(F); NOAEL =
7019(M)
Renal tubule
casts
NTP
(1986)
High (1.3)
Respiratory
Chronic
Rat, F344,
M/F
(n=100/group
)
Inhalation, vapor,
whole body
0, 3510, 7019 or
14,038 mg/m3
(0, 1000, 2000 or
4000 ppm)
6 hours/day,
5 days/week
for 2 years
NA
NOAEL= 7019
(F)
Nasal cavity
squamous
metaplasia
NTP
(1986)
High (1.3)
Respiratory
Subchroni
c
Rat, F344,
M/F
(n=20/group)
Inhalation, vapor,
whole body
0, 1843. 3685.
7371. 14.742 or
29,483 mg/m3
(0, 525, 1050,
2100, 4200 or
8400 ppm)
6 hours/day.
5 days/week
for 13 weeks
NA
NOAEL= 14,742
(M/F)
Foreign body
pneumonia
(focal
accumulation
of
mononuclear
and
multinucleated
inflammatory
cells)
NTP
(1986)
High (1.3)
Respiratory
Subchroni
c
Mouse,
B6C3F1, M/F
(n=20/group)
Inhalation, vapor,
whole body
0, 1843, 3685,
7371, 14,742 or
29,483 mg/m3
(0, 525, 1050,
2100, 4200 or
8400 ppm)
6 hours/day,
5 days/week
for 13 weeks
NA
NOAEL= 29,483
(M/F)
No
nonneoplastic
pulmonary
lesions
NTP
(1986)
High (1.3)
a Subchronic: > 30 - < 90 days; Chronic = > 90 days
35

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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
2.3 Reproductive and Developmental Outcomes from Animal Toxicity Studies
36

-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Tiiriiel Orjiiin/
Stsicni
Sluclj Tjpe
Spocios/
Sir;iin/Se\
(Nil in her/
until p)
r.xposurc
Rouk'
Doses/
( oiicon 1 r;i lions
Diii'iilioii
noaii./i.oa
111. (inii/inJ or
mg/kg-(l:i>)
(Sox)
I.ITcd
Reference
Diilii Qu;ili(\ l'\;iIn;i 1 ion
Body weight
Developmental
Rat, F344, F
(n=17-
21/group)
Oral, gavage
0,337.5 or 450
mg/kg-bw/day
Gestation days
6-19
NOAEL=
337.5
(F)
| Mater rial
weight gain
Narotsky
and
Kavlock
(1995)
High (1.4)
Developmental
Effects
Reproductive
Rat, Charles
River, M/F
(n=20/group)
Oral, gavage
0, 25,75 or 225
mg/kg-bw/day
90 days before
mating (10
days between
last exposure
and mating
period)
NOAEL= 225
No effects on
pup survival,
F1 body weight,
hematology, or
clinical
chemistry (up to
90 days of age),
or histology of
tissues fromFl
offspring
General
Electric
(1976)
High (1.5)
Developmental
Effects
Developmental
Rat, F344, F
(n=17-
21/group)
Oral, gavage
0,337.5 or 450
mg/kg-day
Gestation days
6-19
NOAEL= 450
No effect on
pup survival,
resorptions or
pup weight
Narotsky
and
Kavlock
(1995)
High (1.4)
Reproductive
Reproductive
Rat, Charles
River, M/F
(n=20/group)
Oral, gavage
0, 25,75 or 225
mg/kg
90 days before
mating (10
days between
last exposure
and mating
period); F1
offspring
received same
treatment as
parents for 90
days
NOAEL= 225
(M/F)
No effects on
fertility index or
number of pups
per litter
General
Electric
(1976)
High (1.5)
37

-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Tiiriiel Orjiiin/
Stsicni
Sluclj Tjpe
Spocios/
Sir;iin/Se\
(Nil in her/
until p)
r.xposuiT
Kouli'
Doses/
( oiicon 1 r;i lions
Diii'iilioii
noaii./i.oa
111. (inii/inJ or
mg/kg-(l:i>)
(Sox)
If led
Reference
Diilii Qu;ili(\ l'\;iIn;i 1 ion
Reproductive
Developmental
Rat, F344, F
(n=17-
21/group)
Oral, gavage
0,337.5 or 450
mg/kg-day
Gestation days
6-19
NOAEL= 450
(M/F)
No effect on
resorption rate,
number of live
litters, implants
or live pups
Narotsky
0995)
High (1.4)
Reproductive
Reproductive
Mouse, Swiss
Webster, M
Inhalation,
vapor, whole
body
0, 103, 144,212
ppm
2 hrs/day, 5
days/week for
6 weeks; males
then mated
with
unexposed
females
NOAEL = 103
ppm
I fertility (80%
vs. 95%)
(stat. sig. by one
test but not a
second; see U.S.
EPA ( )
Raje et al.
( 3)
Medium (2.0)
Reproductive
Chronic
Mouse,
B6C3F1, M/F
(n=100/group)
Inhalation,
vapor, whole
body
0, 7019 or
14,038 mg/m3
(0, 2000 or 4000
ppm)
6 hours/day,
5 days/week
for 2 years
NOAEL= 7019
(M)
Testicular
atrophy
NTP
0986)
High (1.3)
Reproductive
Chronic
Mouse,
B6C3F1, M/F
(n=100/group)
Inhalation,
vapor, whole
body
0, 7019 or
14,038 mg/m3
(0, 2000 or 4000
ppm)
6 hours/day,
5 days/week
for 2 years
LOAEL= 7019
(F)
Ovarian atrophy
NTP
0986)
High (1.3)
38

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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
3 Data Extraction Tables for Animal Cancer Bioassays
The following tables focus on liver, lung and mammary tumors and other statistically significantly increased tumor types observed in
animal cancer bioassays.
3.1 Liver Tumor Data from Cancer Bioassays
Reference
Sir;iin iind
Species
r.\|)ONIMY
mule
Sox
r.\|)ONIMY k'\C'ls
Tumor (\pi*
Si^niriciiiil
(losc-rclnlcd
(1011(1
Si^nirioiinl
p:iir\\ iso
comparison
r.xposuro lo\ol
w illi si^nirioiinl
inoroiiso
Diilii Qu;ili(\
l.\;ilu;Uion
NTP
(1986)
B6C3F1
mouse
Inhalation
M
0, 2000, 4000
ppm
Hepatocellular adenoma
or carcinoma
/
y
4000 ppm
High (1.3)
F
Hepatocellular adenoma
or carcinoma
/
y
> 2000 ppm
Aiso cl ;il.
(20141
BDFl
mouse
Inhalation
M
0, 1000, 2000,
4000 ppm
Hepatocellular adenoma
or carcinoma
y
y
> 2000 ppm
High (1.1)
Hepatic hemangioma
y
y
4000 ppm
Hepatic hemangioma or
hemangiosarcoma
~
-
-
F
H cpa 1 occ 11 u 1 a r adc no ma
or carcinoma
~
y
> 1000 ppm
Hepatic hemangioma
~
-
-
Hepatic hemangioma or
hemangiosarcoma
y
-
-
NTP
(1986)
F344 rat
Inhalation
M
0, 1000, 2000,
4000 ppm
Liver tumors
-
-
-
High (1.3)
F
Liver tumors
-
-
-

F344/DuCrj
Inhalation
M
0, 1000, 2000,
4000 ppm
H e pa tocc 11 ill a r adc no ma
or carcinoma
y
-
-
High (1.1)
39

-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Reference
Sir;iin iind
Species
l-lxposurc
route
Sex
l-lxposurc lc\cls
Tumor l\pc
Si^niriciinl
dose-reliiled
1 rend
Si^niriciinl
piiirwise
comparison
Mxposure lc\cl
\\ iili si^niriciinl
incrciise
Diilii Qu;ili(\
l-'.\;ilu ;i I ion
Aiso cl ;il.
(20141


F

Liver tumors
-
-
-

Burek et al.
(1984)
SD rat
Inhalation
M
0, 500, 1500,
3500 ppm
Liver tumors
-
-
-
High (1.5)
F
Liver tumors
-
-
-
Nitschke et
al. (1988)
SD rat
Inhalation
M
0, 50, 200, 500
ppm
Liver tumors
-
-
-
High (1.3)
F
Liver tumors
-
-
-
Maltoni et
al. (1988)
SD rat
Inhalation
F
0, 100 ppm
Liver tumors
-
-
-
Medium (2.0)
Burek et al.
(1984)
Syrian
golden
hamster
Inhalation
M
0, 500, 1500,
3500 ppm
Liver tumors
~
~
~
High (1.5)
Hazleton
Labs
( 3)
Serota et al.
(1986b)
B6C3F1
mouse
Oral (DW)
M
0, 61, 124, 177,
234 mg/kg-day
H e pal oce 11 ill ar adc no ma
or carcinoma
± (p=0.058)

>124 mg/kg-day
Medium (1.7)
F
0, 59, 118, 172,
238 mg/kg-day
Hepatocellular adenoma
or carcinoma



Serota et al.
( 6a)
F344 rat
Oral (DW)
M
0, 6, 52, 125, 235
mg/kg-day
Hepatic neoplastic
nodule or hepatocellular
carcinoma
~
~
~
High (1.3)
F
0, 6, 58, 136, 263
mg/kg-day
Hepatic neoplastic
nodule or hepatocellular
carcinoma


58 and 263
mg/kg-day
40

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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
3.2 Lung Tumor Data From Animal Cancer Bioassays
UiTitcikv
Sir;iin iind
Species
l'l\|)OMIIV
1(111(0
Sox
r.\|)ONIMV k'\C'ls
Tumor (\pi*
Si^niriciinl
(loso-rc'liik'd
(mid
Si^niriciinl
p:iir\\ iso
comp;i rison
Mxposmv Ic'M'l
w illi si^niriciinl
incroiiso
Diilii Qu;ili(\
l'.\iiliiiilion
NTP
(1986)
B6C3F1
mouse
Inhalation
M
0, 2000, 4000
ppm
Bronchoalveolar
adenoma or carcinoma
/
/
> 2000 ppm
High (1.3)
F
Bronchoalveolar
adenoma or carcinoma
/
/
> 2000 ppm
Aiso el al.
(2014)
BDF1
mouse
Inhalation
M
0, 1000, 2000,
4000 ppm
Bronchoalveolar
adenoma or carcinoma
/
/
> 1000 ppm
TBD(l.l)
F
Bronchoalveolar
adenoma or carcinoma
/
/
> 2000 ppm
NTP
(1986)
F344 rat
Inhalation
M
0, 1000, 2000,
4000 ppm
Lung tumors
-
-
-
High (1.3)
F
Lung tumors
-
-
-
Aiso cl al.
F344/DuCrj
Inhalation
M
0, 1000, 2000,
4000 ppm
Lung tumors
-
-
-
High (1.1)
F
Lung tumors
-
-
-
Burek et al.
( 4)
SD rat
Inhalation
M
0, 500, 1500,
3500 ppm
Lung tumors
-
-
-
High (1.5)
F
Lung tumors
-
-
-
Nitschke et
al. (1988)
SD rat
Inhalation
M
0, 50, 200, 500
ppm
Lung tumors
-
-
-
High (1.3)
F
Lung tumors
-
-
-
Maltoni et
al. (1988)
SD rat
Inhalation
F
0, 100 ppm
Lung tumors
-
-
-
Medium (2.0)
Burek et al.
(1984)
Syrian
golden
hamster
Inhalation
M
0, 500, 1500,
3500 ppm
Lung tumors
~
~
~
High (1.5)
41

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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
3.3 Mammary Gland Tumors from Animal Cancer Bioassays
UcTcrciKV
Si r;iin
iind
Species
l''.\|)osiiiv
mule
Sox
Doses «ir
Coiktii trillions
Tumor |\ pc
Si^nificiinl
dosc-ivliilcd
(rend
Si^nificiinl
pairw iso
comparison
Dose or
co neon li'ii lion
willi significant
incroiisi'
Diilii
Qualilv
l.\alua(inn
NTI'i i
1 i(.(-II
mouse
Inhalation
\1
0. 2i)()o. 4000 ppm
Mammars Illinois
-
-
-
1 huh < 1 '>

F
Mammary tumors
-
-
-
Aiso cl ;il.
(2014)
BDF1
mouse
Inhalation
M
0, 1000, 2000, 4000
ppm
Mammary tumors
-
-
-
High (1.1)
F
Mammary tumors
-
-
-
NTP (1986)
F344 rat
Inhalation
M
0, 1000, 2000, 4000
ppm
Mammary or subcutaneous tissue
adenoma, fibroadenoma, or fibroma
/
y
4000 ppm
High (1.3)
F
Mammary adenoma, fibroadenoma, or
adenocarcinoma
/
y
> 2000 ppm
Aiso cl ;il.
F344/Du
Crj
Inhalation
M
0, 1000, 2000, 4000
ppm
Mammary gland fibroadenoma
/
y
4000 ppm
High (1.1)
Mammary gland fibroadenoma or
adenoma
y

4000 ppm
Mammary gland fibroadenoma or
adenoma or adenocarcinoma
/
-

F
Mammary gland fibroadenoma
/
-

Mammary gland fibroadenoma or
adenoma
s/
-

Mammary gland fibroadenoma or
adenoma or adenocarcinoma

-

Burek et al.
( 4)
SD rat
Inhalation
M
0, 500, 1500, 3500
ppm
Mammary tumors
-
-
-
High (1.5)
F
Mammary tumors
- (dose-related t
no. tumors/
tumor-bearing
rat)


42

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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Reference
Si r;iin
illld
Species
I'ApOMII'O
ion (e
Sox
Doses or
( onci'ii trillions
Tumor i\ pe
Si^niriciinl
dose-rehi led
IivikI
Siu, 5()() ppm
Mammais lihioma, lihrosaieonia, or
undifferentiated sarcoma
-
-
-
llighil l)

F
Benign mammary tumors
- (dose-related t
no. tumors/
tumor-bearing
rat)


Maltoni et al.
(1988)
SD rat
Inhalation
F
0, 100 ppm
Mammary tumors
-
-
-
Medium
(2.0)
Burek et al.
(1984)
Syrian
golden
hamster
Inhalation
M
0, 500, 1500, 3500
ppm
Mammary tumors
~
~
~
High (1.5)
43

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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
3.1 Other Tumor Data From Animal Cancer Bioassays
Reference
Si r;iin
illld
Species
l'l\|)OMIIV
1(111(0
Sc\
Doses or
(oihtii trillions
Tumor (\po
Si<£iiiric;inl
dosc-rcl;Kcd
IivihI
Si^iiiric;inl
p:iir\\ isc
comparison
Dose or
concciilriilion
with siiiiiiliciiiK
incrciisc
Diilii
Qu;ili(\
l'.\iiliiiilion
NTP (1986)
B6C3F1
mouse
Inhalation
M
0, 2000, 4000 ppm
Hemangioma or hemangiosarcoma,
any site
-
y
4000 ppm
High (1.3)
F
Hemangioma or hemangiosarcoma,
any site
-
-
-
Aiso clal.
(2014)
BDF1
mouse
Inhalation
M
0, 1000, 2000, 4000
ppm
Adrenal gland phcochromocyloma

-
-
High (1.1)
F
Adrenal gland phcochromocyloma
-
-
-
NTP (1986)
F344 rat
Inhalation
M
0, 1000, 2000, 4000
ppm
Subcutaneous fibroma or
fibrosarcoma


4000 ppm
High (1.3)
Mesothelioma (all sites)

y
2000 ppm
F
Subcutaneous fibroma or
fibrosarcoma
-
-
-
Aiso el ;il.
(2014)
F344/
DuCrj nil
Inhalation
M
0, 1000, 2000, 4000
ppm
Subcutaneous fibroma
s/
s/
> 2000 ppm
High (1.1)
Subcutaneous fibroma or
fibrosarcoma
s/
s/
> 2000 ppm
Mesothelioma (peritoneal)

-
-
Mononuclear cell leukemia
-
-
-
F
Subcutaneous fibroma
-
-
-
Subcutaneous fibroma or
fibrosarcoma
-
-
-
Mesothelioma (peritoneal)
-
-
-
Mononuclear cell leukemia

(only at 2000
ppm)
-
44

-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Reference
Si min
illld
Species
l'l\pnslllV
ion (e
Sox
Doses or
( oiicciUr;i(ions
Tumor (\pe
Si<£iiiric;inl
dosc-rchKcd
(rend
Siiiiiil'iciiiH
p;iir\\ ise
comparison
Dose or
co neon initio n
with siiiiiiliciiiK
inciviiso
Diilii
Qn;ilil\
r.\iilu;ilion





Endometrial stromal polyp
~
-
-

Endometrial stromal sarcoma or
leiomyosarcoma
~
-
-
Burck el ;il.
(1984)
SD rat
Inhalation
M
0. 500. 1500. 3500
ppm
Salivary gland sarcomas
NR

-
High (1.5)
F
Salivary gland sarcomas
-
-
-
Hazleton
Labs (1983)
Serota et al.
( Si)
B6C3F1
mouse
Oral (DW)
M
0, 61, 124, 177, 234
mg/kg-day
Mammary tumors
-
-
-
Medium
(1.7)
F
0, 59, 118, 172, 238
mg/kg-day
Mammary tumors
-
-
-
Serota et al.
(1986a)
F344 rat
Oral (DW)
M
0, 6, 52, 125. or
235 mg/kg-day
Mammary tumors
-
-
-
High (1.3)
F
0, 6, 58, 136. or
263 mg/kg-day
Mammary tumors
-
-
-
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