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)

Scheduled Peer Review Date: November 19, 2009

NOTICE

This DRAFT Technical Report is distributed solely for the purpose of predissemination peer review under the applicable information 

quality guidelines. It has not been formally disseminated by the NTP. It does not represent and should not be construed to represent 

NTP determination or policy.

NTP TR 564

NIH Publication No. 10-5906

National Toxicology Program

National Institutes of Health

Public Health Service

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOREWORD

The National Toxicology Program (NTP) is an interagency program within the Public Health Service (PHS) of the 

Department of Health and Human Services (HHS) and is headquartered at the National Institute of Environmental 

Health Sciences of the National Institutes of Health (NIEHS/NIH). Three agencies contribute resources to the 

program: NIEHS/NIH, the National Institute for Occupational Safety and Health of the Centers for Disease Control 

and Prevention (NIOSH/CDC), and the National Center for Toxicological Research of the Food and Drug 

Administration (NCTR/FDA). Established in 1978, the NTP is charged with coordinating toxicological testing 

activities, strengthening the science base in toxicology, developing and validating improved testing methods, and 

providing information about potentially toxic substances to health regulatory and research agencies, scientific and 

medical communities, and the public.

The Technical Report series began in 1976 with carcinogenesis studies conducted by the National Cancer Institute. 

In 1981, this bioassay program was transferred to the NTP. The studies described in the Technical Report series are 

designed and conducted to characterize and evaluate the toxicologic potential, including carcinogenic activity, of 

selected substances in laboratory animals (usually two species, rats and mice). Substances selected for NTP toxicity 

and carcinogenicity studies are chosen primarily on the basis of human exposure, level of production, and chemical 

structure. The interpretive conclusions presented in NTP Technical Reports are based only on the results of these 

NTP studies. Extrapolation of these results to other species, including characterization of hazards and risks to 

humans, requires analyses beyond the intent of these reports. Selection per se is not an indicator of a substance’s 

carcinogenic potential.

The NTP conducts its studies in compliance with its laboratory health and safety guidelines and FDA Good 

Laboratory Regulations and must meet or exceed all applicable federal, state, and local health and safety regulations. 

Animal care and use are in accordance with the Public Health Service Policy on Humane Care and Use of Animals. 

Studies are subjected to retrospective quality assurance audits before being presented for public review.

NTP Technical Reports are indexed in the NIH/NLM PubMed database and are available free of charge 

electronically on the NTP website (http://ntp.niehs.nih.gov) or in hardcopy upon request from the NTP Central Data 

Management group at cdm@niehs.nih.gov or (919) 541-3419.
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)

Scheduled Peer Review Date: November 19, 2009 

NOTICE

This DRAFT Technical Report is distributed solely for the purpose of predissemination peer review under the applicable information 

quality guidelines. It has not been formally disseminated by the NTP. It does not represent and should not be construed to represent 

NTP determination or policy.

NTP TR 564 

NIH Publication No. 10-5906

National Toxicology Program 

National Institutes of Health

Public Health Service

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
2

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

CONTRIBUTORS

National Toxicology Program 

Evaluated and interpreted results and reported findings

D.L. Morgan, Ph.D., Study Scientist

M.F. Cesta, D.V.M., Study Pathologist

J.B. Bishop, Ph.D.

J.R. Bucher, Ph.D.

R.S. Chhabra, Ph.D.

P.M. Foster, Ph.D.

D. Germolec, Ph.D.

R.A. Herbert, D.V.M., Ph.D.

M.J. Hooth, Ph.D.

A.P. King-Herbert, D.V.M.

G.E. Kissling, Ph.D.

D.E. Malarkey, D.V.M., Ph.D.

J.H. Roycroft, Ph.D.

C.S. Smith, Ph.D.

G.S. Travlos, D.V.M.

S. Waidyanatha, Ph.D.

N.J. Walker, Ph.D.

K.L. Witt, M.S.

Battelle Toxicology Northwest 

Conducted studies and evaluated pathology findings

J.A. Dill, Ph.D., Principal Investigator

S.L. Grumbein, D.V.M., Ph.D.

S.J. Harbo, D.V.M.

B.K. Hayden

R.A. Renne, D.V.M.

Experimental Pathology Laboratories, Inc.

Provided pathology review

M.H. Hamlin, II, D.V.M., Principal Investigator

E.T. Adams, D.V.M., Ph.D.

R.A. Miller, D.V.M., Ph.D.

J.C. Peckham, D.V.M., M.S., Ph.D.

C.C. Shackelford, D.V.M., M.S., Ph.D.

TherImmune Research Corporation

Provided SMVCE analysis

G.W. Wolfe, Ph.D., Principal Investigator

Y. Wang, M.S.

Dynamac Corporation 

Prepared quality assessment audits

S. Brecher, Ph.D., Principal Investigator

S. Iyer, B.S.

V.S. Tharakan, D.V.M.

NTP Pathology Working Group 

Evaluated slides and contributed to pathology report on 

2-year rats (December 11, 2007) 

G.D. Hill, D.V.M., Ph.D., Coordinator

ILS, Inc.

E.T. Adams, D.V.M., Ph.D.

Experimental Pathology Laboratories, Inc.

M.F. Cesta, D.V.M. National Toxicology Program

S.A. Elmore, D.V.M., M.S.

National Toxicology Program

P.M. Foster, Ph.D., Observer

National Toxicology Program

B. Hamilton, D.V.M., Ph.D.

GlaxoSmithKline

R.A. Herbert, D.V.M., Ph.D.

National Toxicology Program

R.R. Maronpot, D.V.M. Consultant

R.A. Miller, D.V.M., Ph.D.

Experimental Pathology Laboratories, Inc.

D.L. Morgan, Ph.D., Observer

National Toxicology Program

S. Newbigging, M.Sc., D.V.M., D.V.Sc., Observer

ILS, Inc.

A. Nyska, D.V.M. National Toxicology Program

R.E. Sills, D.V.M., Ph.D., Observer

National Toxicology Program

B.P. Singh, B.V.Sc., M.S.

National Toxicology Program
1-Bromopropane, NTP TR 564 3

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NTP Pathology Working Group

Evaluated slides and contributed to pathology report on 

2-year mice (February 5, 2008) 

K.R. Hobbie, D.V.M., Coordinator

ILS, Inc.

M.F. Cesta, D.V.M.

National Toxicology Program

S.A. Elmore, D.V.M., M.S.

National Toxicology Program

P.M. Foster, Ph.D., Observer

National Toxicology Program

S.L. Grumbein, D.V.M., Ph.D.

Battelle Toxicology Northwest

B. Hamilton, D.V.M., Ph.D.

GlaxoSmithKline

T. Kojitani, D.V.M., Ph.D., Observer

National Toxicology Program

D.E. Malarkey, D.V.M., Ph.D.

National Toxicology Program

R.R. Maronpot, D.V.M.

Consultant

R.A. Miller, D.V.M., Ph.D.

Experimental Pathology Laboratories, Inc.

D.L. Morgan, Ph.D., Observer

National Toxicology Program

J.C. Peckham, D.V.M., M.S., Ph.D.

Experimental Pathology Laboratories, Inc.

C.C. Shackelford, D.V.M., M.S., Ph.D.

Experimental Pathology Laboratories, Inc.

SRA International, Inc.

Provided statistical analyses

P.W. Crockett, Ph.D., Principal Investigator

L.J. Betz, M.S.

K.P. McGowan, M.B.A.

Biotechnical Services, Inc.

Prepared Technical Report

S.R. Gunnels, M.A., Principal Investigator

L.M. Harper, B.S.

P.C. Rathman, B.S.E.

D.C. Serbus, Ph.D.
4 1-Bromopropane, NTP TR 564

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5 

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CONTENTS

ABSTRACT ................................................................................................................................................................. 7 

EXPLANATION OF LEVELS OF EVIDENCE OF CARCINOGENIC ACTIVITY........................................14 

TECHNICAL REPORTS REVIEW SUBCOMMITTEE .....................................................................................15 

SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS................................16 

INTRODUCTION .....................................................................................................................................................17

MATERIALS AND METHODS..............................................................................................................................31

RESULTS...................................................................................................................................................................51

DISCUSSION AND CONCLUSIONS.....................................................................................................................97

REFERENCES ........................................................................................................................................................105 

APPENDIX A Summary of Lesions in Male Rats in the 2-Year Inhalation Study 

of 1-Bromopropane .....................................................................................................................A-1 

APPENDIX B Summary of Lesions in Female Rats in the 2-Year Inhalation Study 

of 1-Bromopropane ....................................................................................................................B-1 

APPENDIX C Summary of Lesions in Male Mice in the 2-Year Inhalation Study 

of 1-Bromopropane ....................................................................................................................C-1 

APPENDIX D Summary of Lesions in Female Mice in the 2-Year Inhalation Study 

of 1-Bromopropane ....................................................................................................................D-1 

APPENDIX E Genetic Toxicology......................................................................................................................E-1 

APPENDIX F Clinical Pathology Results..........................................................................................................F-1 

APPENDIX G Organ Weights and Organ-Weight-to-Body-Weight Ratios.................................................. G-1 

APPENDIX H Reproductive Tissue Evaluations and Estrous Cycle Characterization................................ H-1 
6 1-Bromopropane, NTP TR 564

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APPENDIX I Chemical Characterization and 

Generation of Chamber Concentrations....................................................................................I-1 

APPENDIX J Ingredients, Nutrient Composition, and Contaminant Levels

in NTP-2000 Rat and Mouse Ration...........................................................................................J-1 

APPENDIX K Sentinel Animal Program.......................................................................................................... K-1 
7 

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ABSTRACT

1-BROMOPROPANE

CAS No. 106-94-5 

Chemical Formula: C3H7Br Molecular Weight: 122.99

Synonyms: 1-BP; propyl bromide; n-BP; N-propyl bromide

In the early to mid 1990s, 1-bromopropane was used primarily as an intermediate in the production of pesticides, 

quaternary ammonium compounds, flavors and fragrances, pharmaceuticals, and other chemicals in well-controlled, 

closed processes. In the mid to late 1990s, it was introduced as a less toxic replacement for methylene chloride in 

emissive applications such as vapor and immersion degreasing operations and critical cleaning of electronics and 

metals. 1-Bromopropane was also introduced as a nonflammable, nontoxic, fast-drying, and inexpensive solvent for 

adhesive resins, and has been marketed as a replacement for ozone depleting refrigerants. 1-Bromopropane was 

nominated for study by the Occupational Safety and Health Administration based on the potential for widespread 

occupational and environmental exposure and a lack of toxicity and carcinogenicity data. Male and female F344/N 

rats and B6C3F1 mice were exposed to 1-bromopropane (99% or greater pure) by inhalation for 2 weeks, 3 months, 

or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli and mouse 

peripheral blood.
8 1-Bromopropane, NTP TR 564

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2-WEEK STUDY IN RATS

Groups of five male and five female rats were exposed to 1-bromopropane vapor at concentrations of 0, 125, 250, 

500, 1,000, or 2,000 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 16 days. All rats survived to 

the end of the study except one 500 ppm male. Mean body weights of 2,000 ppm rats were significantly less than 

those of the chamber controls. The absolute kidney weight of 1,000 ppm males, relative kidney weights of all 

exposed groups of males, and absolute and relative kidney weights of all exposed groups of females were 

significantly increased. The absolute and relative liver weights of 1,000 ppm males, relative liver weights of 500 

and 2,000 ppm males, and absolute and relative liver weights of 500 ppm or greater females were significantly 

increased. Nasal lesions included suppurative inflammation in males exposed to 500 ppm or greater, respiratory 

epithelial necrosis in 1,000 and 2,000 ppm males, and respiratory epithelial regeneration in 1,000 and 2,000 ppm 

females.

2-WEEK STUDY IN MICE

Groups of five male and five female mice were exposed to 1-bromopropane vapor at concentrations of 0, 125, 250, 

500, 1,000, or 2,000 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 17 days. All 2,000 ppm males, 

two 2,000 ppm females, four 500 ppm males, one 1,000 ppm male, and one 1,000 ppm female died early. The mean 

body weight gain of 1,000 ppm males was significantly less than that of the chamber controls. Abnormal breathing, 

lethargy, and eye discharge were observed primarily during week 1 in groups exposed to 500 ppm or greater. Liver 

weights of 1,000 ppm males and of females exposed to 500 ppm or greater were significantly increased. Kidney 

weights of 1,000 and 2,000 ppm females were significantly increased. Microscopic lesions related to 

1-bromopropane exposure occurred in the lung, liver, and nose of males and females and were primarily seen in 

mice exposed to 500 ppm or greater. 

3-MONTH STUDY IN RATS

Groups of 10 male and 10 female rats were exposed to 1-bromopropane vapor at concentrations of 0, 62.5, 125, 250, 

500, or 1,000 ppm, 6 hours plus T90 (10 minutes) per day, 5 days per week for 14 weeks. Additional clinical 

pathology groups of 10 male and 10 female rats were exposed to the same concentrations for 23 days. All rats 
1-Bromopropane, NTP TR 564 9 

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survived to the end of the study. Mean body weights of 1,000 ppm males were significantly less than those of the 

chamber controls. The increases in sorbitol dehydrogenase activities in 500 ppm males and 1,000 ppm males and 

females were consistent with the histopathologic evidence of mild hepatotoxicity caused by 1-bromopropane. Liver 

weights of males exposed to 250 ppm or greater and of females exposed to 125 ppm or greater were significantly 

increased. Spleen and kidney weights of 1,000 ppm females were significantly increased. Results of sperm count 

and vaginal cytology evaluations showed exposure concentration-related decreases in sperm motility and counts in 

male rats, reaching 28% and 37%, respectively, in the 1,000 ppm group. Female rats in all three exposure groups 

evaluated exhibited altered estrous cycles, spending significantly more time in extended estrus and less time in 

extended diestrus. The incidences of cytoplasmic vacuolization of the liver were significantly increased in males 

exposed to 250 ppm or greater and in females exposed to 500 ppm or greater. Hepatocyte degeneration was also 

observed in 1,000 ppm females.

3-MONTH STUDY IN MICE

Groups of 10 male and 10 female mice were exposed to 1-bromopropane vapor at concentrations of 0, 62.5, 125, 

250, or 500 ppm, 6 hours plus T90 (10 minutes) per day, 5 days per week for 14 weeks. One 250 ppm male and four 

males and five females in the 500 ppm groups died early. Mean body weights of exposed groups were similar to 

those of the chamber controls. Lethargy was observed in males and females exposed to 500 ppm, and abnormal 

breathing was observed in moribund mice. The kidney, liver, and lung weights of 500 ppm females were 

significantly greater than those of the chamber controls. The kidney weights of 500 ppm males were significantly 

decreased. Male mice in the 500 ppm group had decreased sperm counts that were 28% less than that in the 

chamber controls. Female mice exhibited altered estrous cycles, with females in the 500 ppm group spending 

significantly more time in extended diestrus and those in the 250 ppm group spending significantly more time in 

extended estrus compared to the chamber controls. Nonneoplastic lesions were observed in the nose, larynx, 

trachea, lung, and liver of 500 ppm males and females and in the adrenal cortex of 500 ppm females.
10 1-Bromopropane, NTP TR 564

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2-YEAR STUDY IN RATS

Groups of 50 male and 50 female rats were exposed to 1-bromopropane vapor at concentrations of 0, 125, 250, or 

500 ppm, 6 hours plus T90 (10 minutes) per day, 5 days per week for 105 weeks. Survival of 500 ppm males was 

significantly less than that of the chamber control group. Mean body weights of exposed groups were similar to 

those of the chamber controls.

Increased incidences of macroscopic, soft, pale-yellow to green, variably sized nodules were seen predominantly in 

the nose and skin of exposed rats. The number of animals with multiple masses was increased in the 500 ppm 

groups. In most cases, these lesions were microscopically shown to be suppurative inflammation, many with 

Splendore-Hoeppli material.

The incidence of adenoma of the large intestine (colon or rectum) in 500 ppm females was significantly greater than 

that in the chamber control group. The incidence of adenoma of the large intestine in 250 ppm males exceeded the 

historical control ranges for inhalation studies and all routes.

The incidences of keratoacanthoma, basal cell adenoma, basal cell carcinoma, or squamous cell carcinoma 

(combined) in all exposed groups of males were significantly greater than that in the chamber control group and 

exceeded the historical control range for inhalation studies. The incidences of keratoacanthoma and of 

keratoacanthoma or squamous cell carcinoma (combined) in 250 and 500 ppm males were also significantly 

increased and exceeded the historical control ranges for inhalation studies. In 500 ppm females, the incidence of 

squamous cell papilloma, keratoacanthoma, basal cell adenoma, or basal cell carcinoma (combined) exceeded the 

historical control range for inhalation studies.

The incidence of malignant mesothelioma in 500 ppm males was significantly greater than that in the chamber 

control group.

The incidences of pancreatic islet adenoma in all exposed groups of males and of pancreatic islet adenoma or 

carcinoma (combined) in 125 and 250 ppm males were significantly increased.
1-Bromopropane, NTP TR 564 11

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Treatment-related nonneoplastic lesions were observed in the respiratory system of exposed male and female rats. 

In the nose, the incidences of suppurative chronic inflammation, chronic active inflammation, glandular hyperplasia, 

respiratory epithelial hyperplasia (females), and respiratory metaplasia of the olfactory epithelium (females) were 

increased in all exposed groups. In the larynx, the incidences of chronic active inflammation and squamous 

metaplasia (except 125 ppm females) were increased in all exposed groups, and the incidences of suppurative 

chronic inflammation were increased in the 500 ppm groups. In the trachea, there were increased incidences of 

chronic active inflammation in all exposed groups of females and 500 ppm males, and the incidence of epithelial 

hyperplasia was increased in 500 ppm females. 

2-YEAR STUDY IN MICE

Groups of 50 male and 50 female mice were exposed to 1-bromopropane vapor at concentrations of 0, 62.5, 125, or 

250 ppm, 6 hours plus T90 (10 minutes) per day, 5 days per week for 105 weeks. Survival of exposed groups was 

similar to that of the chamber controls. Mean body weights of all exposed groups were similar to those of the 

chamber controls throughout the study.

In the females, there were increased incidences of alveolar/bronchiolar adenoma, alveolar/bronchiolar carcinoma, 

and alveolar/bronchiolar adenoma or carcinoma (combined); the incidences of alveolar/bronchiolar adenoma or 

carcinoma (combined) were significantly increased in all exposed groups of females. There were significantly 

increased incidences of cytoplasmic vacuolization of the bronchiolar epithelium in all exposed male groups and 

regeneration of the bronchiolar epithelium in all exposed groups of males and females. 

In the nose, there were significantly increased incidences of cytoplasmic vacuolization of the respiratory epithelium 

in all exposed groups of males and in 125 and 250 ppm females. There were significantly increased incidences of 

respiratory epithelial hyperplasia in all exposed female groups and in 62.5 and 250 ppm males. There were 

significantly increased incidences of respiratory metaplasia of olfactory epithelium in 62.5 and 125 ppm males and 

125 and 250 ppm females.
12 1-Bromopropane, NTP TR 564

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There were significantly increased incidences of cytoplasmic vacuolization of respiratory epithelium in the larynx 

and trachea of all exposed male groups and in the trachea of 62.5 and 125 ppm females.

GENETIC TOXICOLOGY

1-Bromopropane was not mutagenic in either of two independent bacterial mutagenicity assays, each conducted with 

and without induced rat liver activation enzymes. Bacterial strains tested included S. typhimurium strains TA97,

TA98, TA100, and TA1535, as well as E. coli strain WP2 uvrA/pKM101. In addition, no increases in the 

frequencies of micronucleated normochromatic erythrocytes were seen in male or female B6C3F1 mice exposed for 

3 months to 62.5 to 500 ppm 1-bromopropane via inhalation.

CONCLUSIONS

Under the conditions of these 2-year inhalation studies, there was some evidence of carcinogenic activity* of 

1-bromopropane in male F344/N rats based on the occurrence of rare adenomas of the large intestine and increased 

incidences of neoplasms of the skin. Increased incidences of malignant mesothelioma and pancreatic islet adenoma 

may also have been related to 1-bromopropane exposure. There was clear evidence of carcinogenic activity of 

1-bromopropane in female F344/N rats based on increased incidences of adenoma of the large intestine. Increased 

incidences of neoplasms of the skin may also have been related to 1-bromopropane exposure. There was no 

evidence of carcinogenic activity of 1-bromopropane in male B6C3F1 mice exposed to concentrations of 62.5, 125, 

or 250 ppm 1-bromopropane. There was clear evidence of carcinogenic activity of 1-bromopropane in female 

B6C3F1 mice based on increased incidences of alveolar/bronchiolar neoplasms. 

Exposure to 1-bromopropane resulted in increased incidences of nonneoplastic lesions in the nose of rats and mice, 

the larynx of rats and male mice, the trachea of female rats and male and female mice, and the lung of mice. 

Suppurative inflammatory lesions with Splendore-Hoeppli material were present primarily in the nose and skin of 

male and female rats exposed to 1-bromopropane.

* Explanation of Levels of Evidence of Carcinogenic Activity is on page 14.
1-Bromopropane, NTP TR 564 13

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Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies of 1-Bromopropane

Male

F344/N Rats

Female

F344/N Rats

Male

B6C3F1 Mice

Female

B6C3F1 Mice

Concentrations in air 0, 125, 250, or 500 ppm 0, 125, 250, or 500 ppm 0, 62.5, 125, or 250 ppm 0, 62.5, 125, or 250 ppm

Body weights Exposed groups similar to 

the chamber control group

Exposed groups similar to 

the chamber control group

Exposed groups similar to 

the chamber control group

Exposed groups similar to 

the chamber control group

Survival rates 23/50, 26/50, 18/50, 13/50 34/50, 33/50, 30/50, 24/50 37/50, 33/50, 32/50, 36/50 36/50, 40/50, 37/50, 42/50

Nonneoplastic effects Nose: inflammation, 

suppurative, chronic

(0/50, 1/48, 2/48, 7/50); 

inflammation, chronic 

active (29/50, 33/48, 

34/48, 35/50); glands, 

hyperplasia (5/50, 14/48, 

14/48, 15/50)

Larynx: inflammation, 

chronic active (21/50, 

28/50, 31/50, 26/50)

Nose: inflammation, 

suppurative, chronic 

(0/50, 1/50, 3/49, 7/50); 

inflammation, chronic 

active (24/50, 37/50, 

37/49, 36/50); glands, 

hyperplasia (6/50, 23/50, 

28/49, 30/50); respiratory 

epithelium, hyperplasia 

(5/50, 13/50, 9/49, 18/50); 

olfactory epithelium, 

metaplasia, respiratory 

(3/50, 4/50, 6/49, 9/50)

Larynx: inflammation, 

chronic active (18/50, 

25/50, 30/50, 32/50); 

metaplasia, squamous 

(3/50, 2/50, 6/50, 21/50)

Trachea: inflammation, 

chronic active (0/50, 4/50, 

1/50, 6/50); epithelium, 

hyperplasia (0/50, 0/50, 

0/50, 4/50)

Lung: bronchiole, 

vacuolization cytoplasmic

(0/50, 18/50, 19/49, 

17/49); bronchiole, 

regeneration (1/50, 44/50, 

38/49, 47/49)

Nose: respiratory 

epithelium, vacuolization 

cytoplasmic (0/50, 12/50, 

19/50, 20/50); respiratory 

epithelium, hyperplasia 

(16/50, 29/50, 23/50, 

26/50); olfactory 

epithelium, metaplasia, 

respiratory (0/50, 7/50, 

6/50, 3/50)

Larynx: vacuolization 

cytoplasmic (0/48, 5/50, 

10/48, 11/50)

Trachea: vacuolization 

cytoplasmic (0/49, 15/50, 

24/47, 24/50)

Lung: bronchiole, 

regeneration (0/50, 45/50, 

43/50, 49/50)

Nose: respiratory 

epithelium, vacuolization 

cytoplasmic (0/50, 3/50, 

5/50, 8/50); respiratory 

epithelium, hyperplasia 

(11/50, 25/50, 28/50, 

27/50); olfactory 

epithelium, metaplasia, 

respiratory (0/50, 4/50, 

5/50, 14/50)

Trachea: vacuolization 

cytoplasmic (0/50, 8/49, 

7/50, 4/50)

Neoplastic effects Large intestine: adenoma

(0/50, 0/50, 2/50, 1/50)

Skin: keratoacanthoma

(0/50, 3/50, 6/50, 6/50); 

keratoacanthoma or 

squamous cell carcinoma 

(1/50, 4/50, 6/50, 8/50); 

keratoacanthoma, basal 

cell adenoma, basal cell 

carcinoma, or squamous 

cell carcinoma (1/50, 

7/50, 9/50, 10/50)

Large intestine: adenoma 

(0/50, 1/50, 2/50, 5/50)

None Lung: 

alveolar/bronchiolar 

adenoma (1/50, 6/50, 

4/50, 10/50); 

alveolar/bronchiolar 

carcinoma (0/50, 7/50, 

5/50, 4/50); 

alveolar/bronchiolar 

adenoma or carcinoma 

(1/50, 9/50, 8/50, 14/50)

Equivocal findings Malignant mesothelioma: 

(0/50, 2/50, 2/50, 4/50)

Pancreatic islets: 

adenoma (0/50, 5/50, 

4/50, 5/50)

Skin: squamous cell 

papilloma, 

keratoacanthoma, basal 

cell adenoma, or basal 

cell carcinoma (1/50, 

1/50, 1/50, 4/50)

None None

Level of evidence of 

carcinogenic activity Some evidence Clear evidence No evidence Clear evidence

Genetic toxicology

Bacterial gene mutations: Negative in Salmonella typhimurium strains TA97, TA98, TA100, and TA1535 with 

and without S9; and in Escherichia coli WP2 uvrA/pKM101 with and without S9

Micronucleated erythrocytes

Mouse peripheral blood in vivo: Negative
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EXPLANATION OF LEVELS OF EVIDENCE OF CARCINOGENIC ACTIVITY

The National Toxicology Program describes the results of individual experiments on a chemical agent and notes the strength of the evidence for 

conclusions regarding each study. Negative results, in which the study animals do not have a greater incidence of neoplasia than control animals, 

do not necessarily mean that a chemical is not a carcinogen, inasmuch as the experiments are conducted under a limited set of conditions. 

Positive results demonstrate that a chemical is carcinogenic for laboratory animals under the conditions of the study and indicate that exposure to 

the chemical has the potential for hazard to humans. Other organizations, such as the International Agency for Research on Cancer, assign a 

strength of evidence for conclusions based on an examination of all available evidence, including animal studies such as those conducted by the 

NTP, epidemiologic studies, and estimates of exposure. Thus, the actual determination of risk to humans from chemicals found to be 

carcinogenic in laboratory animals requires a wider analysis that extends beyond the purview of these studies.

Five categories of evidence of carcinogenic activity are used in the Technical Report series to summarize the strength of evidence observed in 

each experiment: two categories for positive results (clear evidence and some evidence); one category for uncertain findings (equivocal 

evidence); one category for no observable effects (no evidence); and one category for experiments that cannot be evaluated because of major 

flaws (inadequate study). These categories of interpretative conclusions were first adopted in June 1983 and then revised on March 1986 for use 

in the Technical Report series to incorporate more specifically the concept of actual weight of evidence of carcinogenic activity. For each 

separate experiment (male rats, female rats, male mice, female mice), one of the following five categories is selected to describe the findings. 

These categories refer to the strength of the experimental evidence and not to potency or mechanism.

• Clear evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing a dose-related (i) increase of 

malignant neoplasms, (ii) increase of a combination of malignant and benign neoplasms, or (iii) marked increase of benign neoplasms 

if there is an indication from this or other studies of the ability of such tumors to progress to malignancy.

• Some evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing a chemical-related increased 

incidence of neoplasms (malignant, benign, or combined) in which the strength of the response is less than that required for clear 

evidence.

• Equivocal evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing a marginal increase of 

neoplasms that may be chemical related.

• No evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing no chemical-related increases in 

malignant or benign neoplasms

• Inadequate study of carcinogenic activity is demonstrated by studies that, because of major qualitative or quantitative limitations, 

cannot be interpreted as valid for showing either the presence or absence of carcinogenic activity.

For studies showing multiple chemical-related neoplastic effects that if considered individually would be assigned to different levels of evidence 

categories, the following convention has been adopted to convey completely the study results. In a study with clear evidence of carcinogenic 

activity at some tissue sites, other responses that alone might be deemed some evidence are indicated as “were also related” to chemical exposure. 

In studies with clear or some evidence of carcinogenic activity, other responses that alone might be termed equivocal evidence are indicated as 

“may have been” related to chemical exposure.

When a conclusion statement for a particular experiment is selected, consideration must be given to key factors that would extend the actual 

boundary of an individual category of evidence. Such consideration should allow for incorporation of scientific experience and current 

understanding of long-term carcinogenesis studies in laboratory animals, especially for those evaluations that may be on the borderline between 

two adjacent levels. These considerations should include:

• adequacy of the experimental design and conduct;

• occurrence of common versus uncommon neoplasia;

• progression (or lack thereof) from benign to malignant neoplasia as well as from preneoplastic to neoplastic lesions;

• some benign neoplasms have the capacity to regress but others (of the same morphologic type) progress. At present, it is impossible 

to identify the difference. Therefore, where progression is known to be a possibility, the most prudent course is to assume that benign 

neoplasms of those types have the potential to become malignant;

• combining benign and malignant tumor incidence known or thought to represent stages of progression in the same organ or tissue;

• latency in tumor induction;

• multiplicity in site-specific neoplasia;

• metastases;

• supporting information from proliferative lesions (hyperplasia) in the same site of neoplasia or other experiments (same lesion in 

another sex or species);

• presence or absence of dose relationships;

• statistical significance of the observed tumor increase;

• concurrent control tumor incidence as well as the historical control rate and variability for a specific neoplasm;

• survival-adjusted analyses and false positive or false negative concerns;

• structure-activity correlations; and

• in some cases, genetic toxicology. 
1-Bromopropane, NTP TR 564 15

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NATIONAL TOXICOLOGY PROGRAM BOARD OF SCIENTIFIC COUNSELORS

TECHNICAL REPORTS REVIEW SUBCOMMITTEE

The members of the Technical Reports Review Subcommittee who evaluated the draft NTP Technical Report on 1-bromopropane on 

November 19, 2009, are listed below. Subcommittee members serve as independent scientists, not as representatives of any institution, company, 

or governmental agency. In this capacity, subcommittee members have five major responsibilities in reviewing the NTP studies:

• to ascertain that all relevant literature data have been adequately cited and interpreted,

• to determine if the design and conditions of the NTP studies were appropriate,

• to ensure that the Technical Report presents the experimental results and conclusions fully and clearly,

• to judge the significance of the experimental results by scientific criteria, and

• to assess the evaluation of the evidence of carcinogenic activity and other observed toxic responses.

Raymond F. Novak, Ph.D., Chairperson

Children’s Hospital of Michigan

Wayne State University School of Medicine

Detroit, MI 

Tracie E. Bunton, D.V.M., Ph.D.

Toxicology Consultant

Eicarte LLC

Gettysburg, PA

Russell C. Cattley, V.M.D., Ph.D.

Amgen

Thousand Oaks, CA

David A. Eastmond, Ph.D.

Department of Cell Biology and Neuroscience

University of California

Riverside, CA

Stephen W. Looney, Ph.D.

Department of Biostatistics

Medical College of Georgia

Augusta, GA

Mitzi Nagarkatti, Ph.D.

Department of Pathology, Microbiology, and Immunology

University of South Carolina School of Medicine

Columbia, SC

Michael V. Pino, D.V.M., Ph.D.

Drug Safety Evaluation

Sanofi-aventis

Alfortville, France

Kenneth M. Portier, Ph.D.

American Cancer Society

Atlanta, GA

Jim E. Riviere, D.V.M., Ph.D.

College of Veterinary Medicine

North Carolina State University

Raleigh, NC

James L. Sherley, M.D., Ph.D.

Programs in Regenerative Biology and Cancer

Boston Biomedical Research Institute

Watertown, MA

Justin G. Teeguarden, Ph.D.

Pacific Northwest National Laboratory

Richland, WA
16 1-Bromopropane, NTP TR 564

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SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS

NOTE: A summary of the Technical Reports Review Subcommittee’s remarks will appear in a future draft of this 

report.
17

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INTRODUCTION

1-BROMOPROPANE

CAS No. 106-94-5 

Chemical Formula: C3H7Br Molecular Weight: 122.99

Synonyms: 1-BP; propyl bromide; n-BP; N-propyl bromide

CHEMICAL AND PHYSICAL PROPERTIES

1-Bromopropane is a colorless to pale yellow liquid with a strong, characteristic odor. The boiling point is 71° C 

and the vapor pressure is 110.8 mm Hg at 20° C (UNEP, 2001; Merck, 2006). 1-Bromopropane is less flammable 

than many other halogenated alkanes at room temperature. Thermal decomposition of 1-bromopropane produces 

hydrogen bromide. 1-Bromopropane reacts with oxidizing agents to produce hazardous flammable compounds and 

can react with water to form acids. The 1-bromopropane used for industrial applications and in most commercial 

products is stabilized to inhibit hydrolysis, and formulated to improve performance and enhance the useable life of 

the product (UNEP, 2001; HSDB, 2009). 
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PRODUCTION, USE, AND HUMAN EXPOSURE

Industrial production of 1-bromopropane generally involves reacting propanol with an excess of hydrogen bromide 

gas. The principal product is 1-bromopropane with small amounts of 2-bromopropane (isopropyl bromide) and 

other by-products. Various modifications of the synthetic method are used to increase the purity of the 

1-bromopropane, and distillation procedures are often used to remove most of the by-products (UNEP, 2001). 

In 2006, worldwide annual production capacity of 1-bromopropane was estimated at greater than 20,000 metric tons 

(44 million pounds/year), of which 5,000 metric tons were thought to be used as a pharmaceutical intermediate or 

process agent. United States production was estimated at approximately 5,000 metric tons (11 million pounds/year) 

and growing at a rate of 15% to 20% per year (UNEP, 2006). 

In the early to mid 1990s, 1-bromopropane was used primarily as an intermediate in the production of pesticides, 

quaternary ammonium compounds, flavors and fragrances, pharmaceuticals, and other chemicals in well-controlled, 

closed processes (Hanley et al., 2006). In the mid to late 1990s, 1-bromopropane was introduced as a less toxic 

replacement for methylene chloride in emissive applications such as vapor and immersion degreasing operations and 

critical cleaning of electronics and metals. 1-Bromopropane has a relatively high vapor pressure and is well-suited 

for use in cleaning equipment where it is repeatedly vaporized. Because it is relatively nonflammable, 

1-bromopropane can be used safely in metal cleaning processes where heating is required. 1-Bromopropane was 

also introduced as a nonflammable, nontoxic, fast-drying, and inexpensive solvent for adhesive resins. Aerosolapplied adhesives containing 1-bromopropane were used extensively by foam fabricating companies (Hanley et al., 

2006). Because 1-bromopropane has a relatively short atmospheric half-life (16 days), it is considered to have a 

relatively low ozone depletion potential and has been marketed as a replacement for ozone depleting refrigerants 

(e.g., chlorofluorohydrocarbons and hydrochlorofluorocarbons) (Fed. Regist., 2000). 

Emissive use of 1-bromopropane leads to substantial dermal and inhalation exposure of workers. Currently, there 

are no data available for dermal exposure to 1-bromopropane. The National Institute for Occupational Safety and 

Health (NIOSH) obtained personal breathing zone exposure data for workers at three foam fabrication plants that 

used spray adhesives containing 1-bromopropane. In these three plants, 8-hour time-weighted average (TWA) 
1-Bromopropane, NTP TR 564 19

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exposures ranged from 18 to 381 ppm (mean = 142 ppm) (NIOSH, 2002, 2003). In two of these plants the 8-hour 

TWA exposure concentrations of 1-bromopropane were significantly lowered (1.2 to 58 ppm; mean = 19 ppm) after 

improvements were made in ventilation (NIOSH, 2002). 

ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Experimental Animals 

Rats (strain not specified) dosed with [14C]-1-bromopropane exhaled unchanged 1-bromopropane and [14C]-carbon 

dioxide (Jones and Walsh, 1979). The metabolites, N-acetyl-S-(2-hydroxypropyl)cysteine, N-acetylS-propylcysteine, and the corresponding S-oxide [N-acetyl-3-(propylsulfinyl)alanine] were identified in the urine

(Barnsley et al., 1964, 1966; Barnsley, 1966; Jones and Walsh, 1979). Lee et al. (2007a) observed S-propyl 

glutathione in livers of BALB/c mice following a single oral dose of 1,000 mg/kg 1-bromopropane, with maximum 

levels of S-propyl glutathione detected 6 hours after administration. Exposure to 1-bromopropane has been shown

to deplete glutathione in rat brain in a dose-dependent manner, independent of duration of exposure (Wang et al., 

2003). In male Wistar rats exposed to 700 or 1,500 ppm 1-bromopropane vapor, 6 hours a day, 5 days a week, for 3 

or more weeks, 1-bromopropane in blood decreased rapidly to the detection limit within 0.7 hours when exposure 

ceased. On the other hand, bromide ions persisted longer in both blood and urine; the biological half-life of bromide 

ion was 4.7 to 15.0 days in blood and 5.0 to 7.5 days in urine (Ishidao et al., 2002). 

The disposition and metabolism of 1-bromopropane and the factors influencing them were extensively examined by 

the National Toxicology Program (NTP) in male F344/N rats and B6C3F1 mice following inhalation exposure 

(800 ppm) or intravenous administration (5, 20, or 100 mg/kg) (Garner et al., 2006). [13C3]-1-bromopropane and 

[

14C]-1-bromopropane were co-administered to enable characterization of urinary metabolites using nuclear 

magnetic resonance spectroscopy and liquid chromatography coupled with either tandem mass spectrometry or 

radiochromatography. By 4 hours following intravenous administration, rats and mice exhaled a majority of the 

administered [14C]-1-bromopropane dose as either volatile organic compounds (rats, 50% to 71% ; mice, 39% to 

48%) or carbon dioxide (rats, 10% to 30%; mice, 19% to 26%). The radioactivity was also excreted in urine (rats, 

13% to 19%; mice, 13% to 23%) and feces (rats, < 2 %; mice, 4%) or retained in tissues and carcass (rats, ≤ 6%; 

mice, < 4%). The urinary metabolites characterized in rats and mice following both inhalation exposure and 
20 1-Bromopropane, NTP TR 564

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intravenous administration were N-acetyl-S-propylcysteine, N-acetyl-S-(2-hydroxypropyl)cysteine, N-acetyl3-(propylsulfinyl)alanine, 1-bromo-2-hydroxypropane-O-glucuronide, N-acetyl-S-(2-oxopropyl)cysteine, and 

N-acetyl-3-[(2-oxopropyl)sulfinyl]alanine. 

In rats, but not in mice, the route of elimination and the metabolite distribution changed significantly as the dose 

increased, with the percentage of dose excreted as volatile organic compounds increasing significantly between the 

mid- and high-dose groups (Garner et al., 2006). Concomitantly, the percentage of the dose exhaled as carbon 

dioxide decreased. An investigation of the molar ratio of exhaled carbon dioxide to the total released bromide 

showed that the proportion of 1-bromopropane metabolized via oxidation to pathways dependent on glutathione 

conjugation with bromine replacement decreased with increasing dose in rats. As the dose increased, the relative 

proportion of N-acetyl-S-propylcysteine and N-acetyl-S-(2-hydroxypropyl)cysteine shifted such that the N-acetylS-propylcysteine peak predominated at 100 mg/kg accounting for more than 80% of the urinary radioactivity and 

indicating saturation of oxidation pathways. Rats pretreated with 1-aminobenzotriazole, a potent inhibitor of 

cytochrome P450, had decreased total radioactivity excreted in urine, exhaled as carbon dioxide, or retained in liver 

with a concomitant increase in radioactivity in expired volatile organic compounds. The number of urinary 

metabolites was reduced from 10 to one with N-acetyl-S-propylcysteine accounting for more than 90% of the total 

urinary radioactivity in the pretreated rats. These data demonstrate a role for P450 and glutathione in the 

dose-dependent metabolism and disposition of 1-bromopropane in the rat. 

Garner et al. (2007) also investigated the contribution of cytochrome P450 2E1 (CYP2E1) to 1-bromopropane

metabolism using CYP2E1 knockout and wild type mice. The mercapturic acid of 1-bromo-2-hydroxypropane, 

N-acetyl-S-(2-hydroxypropyl)cysteine, was observed as the major urinary metabolite in wild type mice; the products 

of direct conjugation of 1-bromopropane with glutathione were reportedly insignificant. The ratio of glutathione 

conjugation to 2-hydroxylation was increased fivefold in the CYP2E1 knockout mice relative to wild type mice. In 

Sprague-Dawley rats exposed to up to 1,800 ppm 1-bromopropane/kg (6 hours a day, 5 days a week, for 8 weeks), 

Kim et al. (1999) showed that 1-bromopropane primarily induced CYP2E1 as the major form of CYP and that 

glutathione S-transferase (GST) enzymes played important roles in the metabolism. Sex dependence in the 

metabolic mechanism in the rat liver was also proposed (Kim et al., 1999). These results suggest that CYP2E1 is a 
1-Bromopropane, NTP TR 564 21

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major metabolic enzyme of 1-bromopropane although other P450s may be involved. Based on these findings, 

Garner et al. (2006) proposed a scheme for the metabolism of 1-bromopropane in rodents (Figure 1).

Humans

N-acetyl-S-propylcysteine was detected in the urine of occupationally exposed workers (Ichihara et al., 2004a). In 

another study, workers exposed to 1-bromopropane at two facilities using 1-bromopropane adhesives showed a 

significant association of 48-hour urinary bromide ion concentration with 1-bromopropane exposure measured in the 

breathing zone (Hanley et al., 2006). These data demonstrate that urinary elimination is an important excretion 

pathway of 1-bromopropane in humans.

GENERAL TOXICITY

Experimental Animals 

The acute toxicity of 1-bromopropane has been investigated in rats by several routes of administration. The 

inhalation LC50 for 1-bromopropane was reported as 7,000 ppm for 4 hours in Wistar rats (ACGIH, 2005). For 

non-inhalation routes, the LD50 was reported as 2.9 g/kg in rats and 2.5 g/kg in mice by intraperitoneal injection 

(Patty’s, 2001). The LD50 for oral and dermal routes of administration in rats is greater than 2,000 mg/kg (ACGIH, 

2005).

The LC50 for 2-bromopropane, a structurally related brominated alkane is reported as 31,171 ppm for a 4-hour 

inhalation exposure in mice (ACGIH, 2005). The LD50 for intraperitoneal injection of 2-bromopropane in mice is 

4.8 g/kg (Lewis, 1996). In rats, the LD50 for oral administration of 2-bromopropane is greater than 2,000 mg/kg 

(ACGIH, 2005).
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FIGURE 1 

Proposed Metabolism of 1-Bromopropane in Rodents 

Metabolites shown in bold font were characterized in urine 

from rodents exposed to 1-bromopropane (Garner et al., 2006)
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REPRODUCTIVE AND DEVELOPMENTAL TOXICITY

Experimental Animals

1-Bromopropane was shown to cause developmental toxicity in rat pups whose dams were exposed during the 

period of in utero development (Huntingdon Life Sciences, 2001). Decreased fetal weights and increased incidences 

of skeletal variations were observed in pups of dams exposed to 1-bromopropane at 500 ppm or greater for 

6 hours/day during gestation days 6 through 19.

A two-generation reproductive toxicity study (WIL Research Laboratories, 2001) showed exposure of rats to 

250 ppm or greater altered numerous reproductive endpoints in both females and males. These included decreased 

sperm motility and percent normal sperm in males and decreased litter size, decreased numbers of implantation sites, 

increased ovarian follicular cysts, and increased estrous cycle length in females. Another study in Wistar rats 

(Ichihara et al., 2000a) comparing reproductive toxicities of 1- and 2-bromopropane demonstrated that exposure to 

400 or 800 ppm 1-bromopropane for 12 weeks (8 hours/day, 7 days/week) inhibited sperm count and sperm 

motility; it was less toxic than 2-bromopropane. Yamada et al. (2003) reported that female Wistar rats exposed to 

400 ppm 1-bromopropane 8 hours/day for 12 weeks had a significant increase in the number of irregular estrous 

cycles with extended diestrus. Histological examination of the ovary showed a significant reduction in the number 

of normal antral follicles, and a decrease in the number of normal growing follicles in the 400 ppm group.

Humans

The NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) evaluated the potential for 

1-bromopropane to produce adverse reproductive and developmental effects in humans (NTP, 2003). CERHR 

concluded that there was convincing evidence for reproductive and developmental toxicity in experimental animals. 

Evidence in humans was limited, but in the monograph, note was made of a new case that was not available to the 

expert panel indicating positive findings in women (altered menstruation) occupationally exposed to 

1-bromopropane. The overall NTP conclusion was that “there is serious concern for reproductive and 

developmental effects of 1-bromopropane at the upper end of the human occupational exposure range (18 to 
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381 ppm).” “Serious concern” is the highest level of NTP conclusion regarding the possibilities that human 

development and reproduction might be adversely affected.

NEUROTOXICITY

Experimental Animals 

In an animal study designed to evaluate the neurotoxic effects of 2-bromopropane on rat tail nerve, 1-bromopropane 

was used as a negative control (Yu et al., 1998). Wistar rats were exposed to air, 100, or 1,000 ppm 

2-bromopropane or 1,000 ppm 1-bromopropane 8 hours/day, 7 days per week for up to 7 weeks. Unexpectedly, 

1-bromopropane was found to be more neurotoxic than 2-bromopropane. Electrophysiological changes (decreased 

maximum motor nerve conduction velocity and increased distal latency) and histopathologic changes in peripheral 

nerves were detected in rats exposed to 1,000 ppm 1-bromopropane for 4 weeks. The exposures were discontinued 

after 5 weeks because of hindlimb paralysis in exposed rats. No changes were observed in rats exposed to the same 

concentration of 2-bromopropane. Histopathologic changes were also observed in axons in the gracile nucleus and 

in Purkinje cells in the cerebellum, suggesting that 1-bromopropane may also be toxic to the CNS. Ohnishi et al. 

(1999) also reported that exposure to 1,500 ppm 1-bromopropane 6 hours/day, 5 days per week for 4 weeks resulted 

in degeneration of Purkinje cells in the rat cerebellum. In a subsequent inhalation study, male Wistar rats exposed to 

800 ppm 1-bromopropane showed myelin degeneration in the peripheral nerves, pre-terminal axon swelling in the 

gracile nucleus in the medulla oblongata, weight loss in the cerebrum, limb muscle weakness, distal latency 

prolongation, and decrease of motor nerve conduction velocity (Ichihara et al., 2000b). 

Humans

The first case of 1-bromopropane toxicity in humans was reported by Sclar (1999). A worker developed weakness 

in the proximal extremities and right hand after using an industrial metal cleaning and degreasing solvent that 

contained 1-bromopropane (95.5% by weight) to strip metal for about 2 months. Nerve conduction studies indicated 

a primary symmetric demyelinating polyneuropathy, and magnetic resonance imaging scans revealed evidence of 

central nervous system (CNS) involvement. Subsequently, neurological signs of toxicity were reported in three 

workers at a foam fabrication factory where they used a spray adhesive containing 1-bromopropane (Ichihara et al., 
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2004b). The workers complained of numbness in the feet, thighs, and buttocks, and reduced sensations of vibration 

in the feet suggesting peripheral neuropathy. Other symptoms such as headache, dizziness, and memory loss 

suggested adverse effects on the CNS. NIOSH reported that four additional workers in a different cushion 

manufacturing company were hospitalized about a year earlier with similar neurological symptoms (NIOSH, 2002). 

All four workers had elevated serum bromide levels; however, exposure-related effects on blood cell counts, male 

reproductive functions, or nerve conduction velocity were not detected. NIOSH conducted health hazard 

evaluations at another foam cushion manufacturing plant where 1-bromopropane was used in the spray adhesive 

(NIOSH, 2003). Workers complained of headaches, painful tingling in the hands or feet, tremor, and feeling drunk 

when not drinking, indicating possible CNS and peripheral neurotoxicity.

In 1995, a new cleaning solvent containing about 97% 2-bromopropane (isopropyl bromide) was introduced in a 

Korean electronics manufacturing company to replace Freon (CFC-113). Workers exposed to 2-bromopropane 

presented with symptoms such as hand numbness, suggesting that 2-bromopropane exposure caused polyneuropathy 

(Kim et al., 1996; Park et al., 1997). 

IMMUNOTOXICITY

1-Bromopropane was demonstrated to cause immunosuppression after oral administration to mice. A single 

treatment of female BALB/c mice with 1-bromopropane by gavage significantly suppressed the antibody response 

to T-cell dependent antigen and the production of splenic intracellular IL-2 in response to conconavalin A (Lee 

et al., 2007a). Similarly, oral treatment with 1,3-dibromopropane significantly suppressed the antibody response to 

T-dependent antigen in a dose-dependent manner. Mice treated with 1,3-dibromopropane for 7 consecutive days 

suppressed the antibody response to T-dependent antigen sheep red blood cells (SRBC) (Lee et al., 2007b). The 

structurally related chemical 2-bromopropane was first indicated to be immunotoxic in a study designed to evaluate 

reproductive toxicity in male rats. In this study, leukocyte numbers were significantly decreased in rats treated with 

2-bromopropane concentrations that caused reproductive toxicity (Yu et al., 1997). In a subsequent study (Jeong 

et al., 2002), 2-bromopropane was shown to cause immunosuppression in rats following oral exposure to 

1,000 mg/kg of 2-bromopropane for 28 consecutive days. 2-Bromopropane treatment significantly reduced numbers 

of leukocytes, spleen cells, and thymic cells and suppressed the antibody response to SRBCs. 
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As part of the inhalation studies reported in this Technical Report, the potential immunotoxicity of 1-bromopropane 

was investigated because of the earlier reports of immunosuppression following oral exposure to 1-bromopropane

(Lee et al., 2007a) and the immunotoxicity of structurally related chemicals. In an NTP study, 1-bromopropane was 

found to cause some evidence of immunosuppression in F344/N rats and B6C3F1 mice after inhalation exposure for 

4 and 10 weeks (Anderson et al., 2009). Significant decreases in total spleen cells and T-cells were detected after 

exposure for 4 weeks to 1-bromopropane concentrations ranging from 125 to 1,000 ppm. In addition, significant 

decreases in the IgM response to SRBCs were observed in both species after exposure to 1-bromopropane.

CARCINOGENICITY

There have been no carcinogenicity studies of 1-bromopropane in experimental animals or epidemiology studies in 

humans. However, NTP studies in rodents have demonstrated that several structurally related brominated 

hydrocarbons are potent multisite carcinogens. Inhalation exposure of F344/N rats to 1,2-dibromoethane (ethylene 

dibromide) caused carcinomas and adenocarcinomas of the nasal cavity and hemangiosarcomas of the circulatory 

system in males and females, mesotheliomas of the tunica vaginalis and adenomatous polyps of the nasal cavity in 

males, and fibroadenomas of the mammary gland and alveolar/bronchiolar adenomas and carcinomas in females 

(NTP, 1982a). 1,2-Dibromoethane was also carcinogenic in B6C3F1 mice, causing alveolar/bronchiolar adenomas 

and carcinomas in males and females; and hemangiosarcomas of the circulatory system, fibrosarcomas in 

subcutaneous tissue, carcinomas of the nasal cavity, and adenocarcinomas of the mammary gland in females. 

Inhalation exposure to 1,2-dibromo-3-chloropropane caused carcinomas, squamous-cell carcinomas, and 

adenocarcinomas of the nasal cavity and squamous cell papillomas of the tongue in male and female F344/N rats 

(NTP, 1982b). In B6C3F1 mice, 1,2-dibromo-3-chloropropane caused adenocarcinomas of the nasal cavity and 

papillary carcinomas in females and squamous cell carcinomas of the nasal cavity and alveolar/bronchiolar 

adenomas and carcinomas in males and females. Dermal application of 2,3-dibromo-1-propanol caused tumors at 

multiple sites in F344/N rats and B6C3F1 mice (NTP, 1993). 
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GENETIC TOXICITY

Published data on the genotoxicity of 1-bromopropane suggest that, when tested appropriately to control for 

volatility, the compound demonstrates direct-acting mutagenicity in bacteria, and it has a weak potential for 

induction of chromosomal damage in vitro and in vivo in some mammalian test systems. Barber et al. (1981) 

reported that 1-bromopropane, tested over a concentration range of 1.1 to 20.3 μM, was mutagenic in Salmonella 

typhimurium strains TA100 and TA1535, with or without induced rat liver S9 activation enzymes; the lowest 

effective concentration was 4.9 μM, and potency of response, which directly correlated with concentration, was 

unaffected by the addition of S9, thus indicating that 1-bromopropane is a direct-acting mutagen in Salmonella. 

Barber et al. (1981) used a closed system to control for the volatility of 1-bromopropane. Yu et al. (2008) 

conducted a dominant lethal assay in male ICR mice administered 1-bromopropane (300 or 600 mg/kg per day) by 

gavage for 10 days and mated once weekly for 6 weeks to undosed female mice. Females were sacrificed and 

uterine contents were examined on gestation days 15 through 17. No significant treatment-related increases in preor post-implantation losses, resorptions, nonviable fetuses, or other fertility endpoints were seen at either dose at any 

mating time point. The authors concluded that under these experimental conditions, 1-bromopropane did not induce 

dominant lethal mutations in germ cells of male mice. Negative results were also reported from an earlier dominant 

lethal study conducted in male Sprague-Dawley rats treated with 400 mg/kg per day 1-bromopropane by gavage for 

5 consecutive days and mated to undosed females once weekly for 8 successive weeks (Saito-Suzuki et al., 1982); 

females were sacrificed 13 to 14 days after mating and uterine contents showed no significant treatment-related 

changes in most indicators of fertility or embryonic deaths compared with the vehicle controls. The one exception 

was a marginally elevated frequency of dead implants observed at mating week 8, in the absence of a significant 

dominant lethal mutation index. In a parallel investigation at the same laboratory, male Sprague-Dawley rats were 

treated with 200 mg/kg per day 1,2-dibromopropane for 5 days and mated to undosed females for 8 weeks 

(Saito-Suzuki et al., 1982). Examination of uterine contents at gestation day 13 or 14 revealed small increases in 

dead implants and in the dominant lethal mutation index in the week-1 mating group, but no other indications of 

adverse effects were observed for 1,2-dibromopropane. In contrast, 1,2,3-tribromopropane (50 mg/kg per day for 

5 days) induced a significant increase in dominant lethal mutations in male Sprague-Dawley rats in post-meiotic 

sperm (primarily early spermatids, mating weeks 5 and 6) (Saito-Suzuki et al., 1982).
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NIOSH assessed DNA-damage levels, measured by the alkaline single cell gel electrophoresis (Comet) assay in 

peripheral leukocytes of 64 workers from two facilities where spray adhesives containing 1-bromopropane were

used (Toraason et al., 2006). Workers were divided into two groups based on 1-bromopropane exposure level (high 

or low); bromide levels in blood were used as an internal confirmation of exposure, along with personal breathing 

zone air samples that were used to calculate TWAs of 1-bromopropane concentrations. Although the high exposure 

group showed significantly increased levels of urine and serum bromide compared with the low exposure group, no 

significant differences were seen in the levels of DNA damage between the two exposure groups. Overall DNA 

damage measurements made at the end of the work week in one facility showed a small but not statistically 

significant increase, the result of a significant (P<0.05) increase in the lowest exposure group only, while 

end-of-week DNA damage measures at the second facility were actually lower in both exposure groups than at the 

beginning of the work week. Polymorphisms in GST genes GSTM1 and GSTT1 were considered in the data 

analysis process along with other factors associated with DNA damage induction such as smoking, age, and gender. 

In addition to the in vivo assessments of DNA damage in exposed workers, whole blood cultures from an unexposed 

individual were treated in vitro with either 1-bromopropane or 2-bromopropane, and evaluated for DNA damage 

using the Comet assay (Toraason et al., 2006). Both 1-bromopropane and 2-bromopropane induced significant 

increases in DNA damage at the highest concentration tested, 1 mM; in addition, both compounds increased the 

number of apoptotic cells (cells with diffuse DNA) at 0.1 mM, a 10-fold lower concentration than required to induce 

significant levels of DNA damage.

REGULATORY STANDARDS

The ozone-depleting solvents methyl chloroform and CFC-113 were phased out of production in the United States 

beginning in 1996 under the United States Environmental Protection Agency (USEPA) regulations and under the 

Montreal Protocol on Substances that Deplete the Ozone Layer. In the late 1990s, 1-bromopropane was introduced 

as a replacement for methyl chloroform and CFC-113 for cleaning metal parts and electronics and as a nontoxic 

replacement for methylene chloride and methyl chloroform adhesives. As the United States Occupational Safety 

and Health Administration (OSHA) began phasing in a more restrictive exposure standard for methylene chloride, 

the use of 1-bromopropane in adhesives increased. In April 2000, OSHA’s final phase for instituting a workplace 

exposure standard for methylene chloride took full effect, leading companies to switch to 1-bromopropane rather 
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than install ventilation or other controls needed to reduce employee methylene chloride exposures to the requisite 

25 ppm level. The increased production and use of 1-bromopropane was a concern because it was not regulated to 

protect workers, consumers, or the environment.

Several companies petitioned the USEPA’s Significant New Alternatives Policy (SNAP) program to accept the use 

of 1-bromopropane as an alternative to ozone-depleting solvents (Fed. Regist., 1999). In 2007, the USEPA issued a 

final ruling, finding 1-bromopropane acceptable as a substitute for methyl chloroform and for CFC-113 in metals, 

electronics and precision cleaning (Fed. Regist., 2007a). This rule did not address the use of 1-bromopropane as an 

aerosol solvent or as a carrier solvent in adhesives or coatings. The USEPA proposed a new rule to prohibit the use 

of 1-bromopropane as a carrier solvent in adhesives and as a solvent in aerosol cans, and restrict the use of 

1-bromopropane to that of a carrier solvent in coatings (Fed. Regist., 2007b). The American Conference of 

Governmental Industrial Hygienists (2009) has recommended a threshold limit value 8-hour time-weighted average 

for 1-bromopropane of 10 ppm.

STUDY RATIONALE

1-Bromopropane was nominated by OSHA for evaluation of toxicokinetics, genetic toxicity, reproductive and 

developmental toxicity, neurotoxicity, and carcinogenicity. The nomination was based on the potential for 

widespread occupational and environmental exposure to 1-bromopropane and a lack of toxicity and carcinogenicity 

data. Because previous short-term studies demonstrated that 1-bromopropane is a neurotoxicant and a reproductive 

toxicant in animals (Yu et al., 1998; Ichihara et al, 2000a), the main focus of the current studies was to evaluate the 

chronic toxicity and carcinogenicity of 1-bromopropane. 

The 2-week, 3-month, and 2-year studies were conducted in male and female F344/N rats and B6C3F1 mice to 

evaluate the toxicity and carcinogenicity of 1-bromopropane in association with inhalation exposure. Additional 

studies were conducted to evaluate the absorption, distribution, metabolism, and excretion of 1-bromopropane and 

its potential immunotoxicity (Garner et al., 2006; Anderson et al., 2009). 
30 1-Bromopropane, NTP TR 564

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31

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MATERIALS AND METHODS 

PROCUREMENT AND CHARACTERIZATION OF 1-BROMOPROPANE

1-Bromopropane was obtained in 55-gallon metal drums from Diaz Chemical Corporation (Holley, NY) in one lot 

(106-015) and from Albemarle PCC (Thann, France) in one lot (1581313004). Lot 106-015 was used in the 2-week 

and 3-month studies, and lot 1581313004 was used during the 2-year studies. Identity and purity analyses were 

conducted by the study laboratory at Battelle Toxicology Northwest (Richland, WA), and by Chemir/Polytech 

Laboratories, Inc. (Maryland Heights, MO) (Appendix I). Reports on analyses performed in support of the 

1-bromopropane studies are on file at the National Institute of Environmental Health Sciences. 

Both lots of the chemical, a colorless to pale yellow liquid with a strong, characteristic odor, were identified as 

1-bromopropane by Chemir/Polytech Laboratories, Inc., by infrared and 1H-nuclear magnetic resonance 

spectroscopy. 

For lot 106-015, Karl Fischer titration indicated a water content of 39 ppm. Elemental analyses for carbon, 

hydrogen, nitrogen, and sulfur were in agreement with the theoretical values for 1-bromopropane; residual HBr was 

determined to be 1.3 ppm. Gas chromatography (GC) indicated one major peak and three impurities with areas 

exceeding 0.1% of the total peak area. Using prepared standards, the impurities were identified as 1-propanol 

(0.14%), 2-bromopropane (0.11%), and di-n-propyl ether (0.74%). Measured purity of the bulk chemical was 

consistent throughout the sampled metal drum, and the overall purity of lot 106-015 was determined to be 

approximately 99%.

For lot 1581313004, Karl Fischer titration indicated a water content of 119 ppm. Elemental analyses for carbon, 

hydrogen, nitrogen, and sulfur were in agreement with the theoretical values for 1-bromopropane; residual HBr was 
32 1-Bromopropane, NTP TR 564

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determined to be 61.6 ppm. GC detected one major peak and no impurities with areas greater than 0.1% of the total 

peak area. Three impurities identified with prepared standards were 1-propanol (0.03%), 2-bromopropane (0.02%), 

and di-n-propyl ether (0.02%). Measured purity of the bulk chemical was consistent throughout the sampled metal 

drums, and the overall purity of lot 1581313004 was determined to 99.9% or greater. 

To ensure stability, the bulk chemical was stored at controlled room temperature in the original shipping containers 

(55-gallon metal drums). Periodic reanalyses of the bulk chemical were performed during the 2-week, 3-month, and 

2-year studies by the study laboratory using GC, and no degradation of the bulk chemical was detected.

VAPOR GENERATION AND EXPOSURE SYSTEM

A preheater was necessary for the 2-week and 3-month studies. 1-Bromopropane was pumped through a preheater 

and into a heated glass column filled with glass beads that increased the surface area for vaporization. Heated 

nitrogen entered the column from below and assisted in vaporizing the chemical while conveying it into a short 

distribution manifold. Concentration in the manifold was determined by the chemical pump rate and nitrogen flow 

rate. The pressure in the distribution manifold was kept fixed to ensure constant flow through the manifold and into 

all chambers as the flow of vapor to each chamber was adjusted.

Metering valves at the manifold controlled flow to each chamber through individual Teflon® delivery lines that 

carried the vapor from the manifold to three-way exposure valves at the chamber inlets. The exposure valves 

diverted vapor delivery to exposure chamber exhaust until the generation system was stable and exposures were 

ready to proceed. To initiate exposure, the chamber exposure valves were rotated to allow the 1-bromopropane 

vapor to flow to each exposure chamber inlet duct where it was further diluted with filtered, conditioned air to 

achieve the desired exposure concentration.

The study laboratory designed the inhalation exposure chamber (Harford Systems Division of Lab Products, Inc., 

Aberdeen, MD) so that uniform vapor concentrations could be maintained throughout the chamber with the catch 

pans in place. The total active mixing volume of each chamber was 1.7 m3

. A small particle detector was used with 
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and without animals in the exposure chambers to ensure that 1-bromopropane vapor, and not aerosol, was produced. 

No particle counts above the minimum resolvable level (approximately 200 particles/cm3

) were detected. 

VAPOR CONCENTRATION MONITORING

Chamber and room concentrations of 1-bromopropane were monitored by an on-line gas chromatograph. Samples 

were drawn from each exposure chamber approximately every 20 (2-week and 3-month studies) or 30 (2-year 

studies) minutes during each 6-hour exposure period using Hastelloy®-C stream-select and gas-sampling valves in a 

separate, heated valve oven. The sample lines composing each sample loop were made from Teflon® tubing and 

were connected to the exposure chamber relative humidity sampling lines at a location close to the gas 

chromatograph. A vacuum regulator maintained a constant vacuum in the sample loop to compensate for variations 

in sample line pressure. An in-line flow meter between the vacuum regulator and the gas chromatograph allowed 

digital measurement of sample flow. Summaries of the chamber vapor concentrations are given in Tables I2 

through I4.

The on-line gas chromatograph was checked throughout the day for instrument drift against an on-line standard 

vapor of 1-bromopropane in nitrogen supplied by a standard generator. The on-line gas chromatograph was 

recalibrated as required to meet acceptance criteria. Calibration was performed by comparing chamber 

concentration data to data from grab samples that were collected with activated coconut charcoal gas sampling 

tubes, extracted with methylene chloride containing 1-bromobutane as an internal standard, and analyzed using an 

off-line gas chromatograph. Known volumes of chamber atmosphere were sampled at a constant flow rate ensured 

by a calibrated critical orifice. The off-line gas chromatograph was calibrated with gravimetrically prepared 

standards of 1-bromopropane containing 1-bromobutane as an internal standard in methylene chloride.

CHAMBER ATMOSPHERE CHARACTERIZATION

Buildup and decay rates for chamber vapor concentrations were determined with and without animals present in the 

chambers. At a chamber airflow rate of 15 air changes per hour, the theoretical value for the time to achieve 90% of 

the target concentration after the beginning of vapor generation (T90) and the time for the chamber concentration to 
34 1-Bromopropane, NTP TR 564

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decay to 10% of the target concentration after vapor generation was terminated (T10) was approximately 

12.5 minutes. A T90 value of 12 minutes was selected for the 2-week studies, and a T90 value of 10 minutes was 

selected for the 3-month and 2-year studies.

Evaluations of chamber uniformity and persistence and monitoring for 1-bromopropane degradation impurities were 

conducted periodically throughout the studies by GC. Chamber uniformity was maintained and no degradation was 

detected.

2-WEEK STUDIES

Male and female F344/N rats and B6C3F1 mice were obtained from Taconic Farms, Inc. (Germantown, NY). On 

receipt, the rats and mice were approximately 4 weeks old. Animals were quarantined for 13 days and were 

approximately 6 weeks old on the first day of the studies. Before the studies began, 10 female rats and five male 

and five female mice were randomly selected for parasite evaluation and gross observation for evidence of disease. 

At terminal sacrifice, serologic analyses were performed on five male and five female chamber control rats and mice 

using the protocols of the NTP Sentinel Animal Program (Appendix K).

Groups of five male and five female rats and mice were exposed to 1-bromopropane vapor at concentrations of 0, 

125, 250, 500, 1,000, or 2,000 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 16 (rats) or 17 (mice) 

days. Feed was available ad libitum except during exposure periods; water was available ad libitum. Rats and mice 

were housed individually. Clinical findings were recorded twice daily on exposure days for rats and mice. The 

animals were weighed initially, on days 6 and 13, and at the end of the studies. Details of the study design and 

animal maintenance are summarized in Table 1.

Necropsies were performed on all animals. The heart, right kidney, liver, lung, right testis, and thymus were 

weighed. Tissues for microscopic examination were fixed and preserved in 10% neutral buffered formalin (except 

eyes were first fixed in Davidson’s solution), processed and trimmed, embedded in paraffin, sectioned to a thickness 

of 4 to 6 μm, and stained with hematoxylin and eosin. Histopathologic examinations were performed on all 

chamber control and 2,000 ppm animals. The lung and nose of rats and mice; the mediastinal lymph node, sciatic 
1-Bromopropane, NTP TR 564 35

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nerve, and spinal cord of rats; and the liver of mice were examined to a no-effect level. Table 1 lists the tissues and 

organs examined.

3-MONTH STUDIES

The 3-month studies were conducted to evaluate the cumulative toxic effects of repeated exposure to 

1-bromopropane and to determine the appropriate exposure concentrations to be used in the 2-year studies.

Male and female F344/N rats and B6C3F1 mice were obtained from Taconic Farms, Inc. (Germantown, NY). On 

receipt, the rats and mice were approximately 3 to 4 weeks old. Animals were quarantined for 12 (female rats and 

male and female mice) or 13 (male rats) days and were approximately 5 to 6 weeks old on the first day of the 

studies. Before the studies began, five male and five female rats and mice were randomly selected for parasite 

evaluation and gross observation for evidence of disease. Serological analyses were performed on five male and 

five female sentinel rats and mice during week 1 and five male and five female chamber control rats and mice at the 

end of the studies using the protocols of the NTP Sentinel Animal Program (Appendix K).

Groups of 10 male and 10 female rats and mice were exposed to 1-bromopropane vapor at concentrations of 0, 62.5, 

125, 250, 500, or 1,000 ppm (rats only), 6 hours plus T90 (10 minutes) per day, 5 days per week for 14 weeks. 

Additional clinical pathology groups of 10 male and 10 female rats were exposed to the same concentrations for 

23 days. One additional exposure day was scheduled during the last exposure week to give the rats at least 

2 consecutive days of exposure before terminal sacrifice. Feed was available ad libitum except during exposure 

periods; water was available ad libitum. Rats and mice were housed individually. Clinical findings were recorded

on day 9 (male rats) or 10 and then weekly. Core study animals were weighed initially, on day 9 (male rats) or 10,

weekly thereafter, and at the end of the studies. Details of the study design and animal maintenance are summarized 

in Table 1.

Animals were anesthetized with carbon dioxide, and blood was collected from the retroorbital sinus of clinical 

pathology rats on days 3 and 23 and from core study rats at the end of the study for hematology and clinical 

chemistry analyses; blood was collected from the retroorbital sinus of mice at the end of the study for hematology 
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analyses. Blood samples for hematology analyses were placed in tubes containing potassium EDTA. Erythrocyte, 

leukocyte, and platelet counts; hemoglobin; packed red cell volume; mean cell volume; mean cell hemoglobin; and 

mean cell hemoglobin concentration were determined using an Abbott Cell-Dyn 3700 hematology analyzer (Abbott 

Diagnostic Systems, Abbott Park, IL). Manual hematocrit values were determined using a microcentrifuge (Heraeus 

Haemofuge, Germany) and a Damon/IEC capillary reader (International Equipment Company, Needham Heights, 

MA) for comparison to Cell-Dyn values for packed cell volume. Blood smears for rats and mice were stained with 

Romanowsky-type aqueous stain in a Wescor 7100 Aerospray Slide Stainer (Wescor, Inc., Logan, UT). Leukocyte 

differential counts for rats and mice were based on classifying a minimum of 100 white cells. Reticulocytes were 

stained with New Methylene Blue and enumerated as a reticulocyte:erythrocyte ratio using the Miller disc method 

(Brecher and Schneiderman, 1950). Blood samples for clinical chemistry analyses were placed in tubes containing 

separator gel and allowed to clot. After clot retraction occurred, the samples were centrifuged, and the serum was 

aliquoted for assay of serum chemistry analytes using a Roche Hitachi 912 (Roche Diagnostic Corporation, 

Indianapolis, IN). Table 1 lists the parameters measured.

At the end of the 3-month studies, samples were collected for sperm motility and vaginal cytology evaluations on 

rats and mice exposed to 0, 125 (mice), 250, 500, or 1,000 (rats) ppm. The parameters evaluated are listed in 

Table 1. For 12 consecutive days prior to scheduled terminal sacrifice, the vaginal vaults of the females were 

moistened with saline, if necessary, and samples of vaginal fluid and cells were stained. Relative numbers of 

leukocytes, nucleated epithelial cells, and large squamous epithelial cells were determined and used to ascertain 

estrous cycle stage (i.e., diestrus, proestrus, estrus, and metestrus). Male animals were evaluated for sperm count 

and motility. The left testis and left epididymis were isolated and weighed. The tail of the epididymis (cauda 

epididymis) was then removed from the epididymal body (corpus epididymis) and weighed. Test yolk (rats) or 

modified Tyrode’s buffer (mice) was applied to slides and a small incision was made at the distal border of the 

cauda epididymis. The sperm effluxing from the incision were dispersed in the buffer on the slides, and the numbers 

of motile and nonmotile spermatozoa were counted for five fields per slide by two observers. Following completion 

of sperm motility estimates, each left cauda epididymis was placed in buffered saline solution. Caudae were finely 

minced, and the tissue was incubated in the saline solution and then heat fixed at 65° C. Sperm density was then 

determined microscopically with the aid of a hemacytometer. To quantify spermatogenesis, the testicular spermatid 
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head count was determined by removing the tunica albuginea and homogenizing the left testis in phosphate-buffered 

saline containing 10% dimethyl sulfoxide. Homogenization-resistant spermatid nuclei were counted with a 

hemacytometer. 

Necropsies were performed on all core study animals. The heart, right kidney, liver, lung, spleen, right testis, and 

thymus were weighed. Tissues for microscopic examination were fixed and preserved in 10% neutral buffered 

formalin (eyes were fixed in Davidson’s solution for up to 3 days and then transferred to 10% neutral buffered 

formalin), processed and trimmed, embedded in paraffin, sectioned to a thickness of 4 to 6 μm, and stained with 

hematoxylin and eosin. Complete histopathologic examinations were performed on all chamber control, 250 and 

500 ppm mice, and 1,000 ppm rats. The larynx, liver, lung, and nose of rats and mice, the prostate gland of male 

rats, the trachea of mice, and the adrenal gland and kidney of female mice were examined in all groups; the 

remaining tissues were examined to a no-effect level in the remaining exposure groups. Table 1 lists the tissues and 

organs routinely examined.

After a review of the laboratory reports and selected histopathology slides by a quality assessment pathologist, the 

findings and reviewed slides were submitted to a NTP Pathology Working Group (PWG) coordinator for a second 

independent review. Any inconsistencies in the diagnoses made by the laboratory and quality assessment 

pathologists were resolved. Final diagnoses for reviewed lesions represent a consensus between the laboratory 

pathologist, NTP pathologist, reviewing pathologist(s), if any, and the PWG coordinator. Details of these review 

procedures have been described, in part, by Maronpot and Boorman (1982) and Boorman et al. (1985).

2-YEAR STUDIES

Study Design

Groups of 50 male and 50 female rats and mice were exposed to 1-bromopropane vapor at concentrations of 0, 62.5 

(mice only), 125, 250, or 500 (rats only) ppm, 6 hours plus T90 (10 minutes) per day, 5 days per week for up to 

105 weeks. 
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Source and Specification of Animals

Male and female F344/N rats and B6C3F1 mice were obtained from Taconic Farms, Inc. (Germantown, NY), for 

use in the 2-year studies. Rats were quarantined for 13 days and mice were quarantined for 11 days before the 

beginning of the studies. Five male and five female rats and 10 male mice were randomly selected for parasite 

evaluation and gross observation of disease. Rats and mice were approximately 5 to 6 weeks old at the beginning of 

the studies. The health of the animals was monitored during the studies according to the protocols of the NTP 

Sentinel Animal Program (Appendix K).

Animal Maintenance

Rats and mice were housed individually. Feed was available ad libitum except during exposure periods; water was

available ad libitum. Cages, racks, and chambers were changed weekly. Cages were rotated weekly in chambers. 

Further details of animal maintenance are given in Table 1. Information on feed composition and contaminants is 

provided in Appendix J. 

Clinical Examinations and Pathology 

All animals were observed twice daily. Clinical findings were recorded for all animals every 4 weeks through 

week 93, every 2 weeks thereafter, and at the end of the studies. Rats and mice were weighed initially, weekly for 

the first 13 weeks, then every 4 weeks through week 93, every 2 weeks thereafter, and at the end of the studies. 

Complete necropsies and microscopic examinations were performed on all rats and mice. At necropsy, all organs 

and tissues were examined for grossly visible lesions, and all major tissues were fixed and preserved in 10% neutral 

buffered formalin (eyes were fixed in Davidson’s solution for up to 72 hours and then transferred to 10% neutral 

buffered formalin), processed and trimmed, embedded in paraffin, sectioned to a thickness of 4 to 6 μm, and stained 

with hematoxylin and eosin for microscopic examination. For all paired organs (e.g., adrenal gland, kidney, ovary), 

samples from each organ were examined. Tissues examined microscopically are listed in Table 1.

Microscopic evaluations were completed by the study laboratory pathologist, and the pathology data were entered 

into the Toxicology Data Management System. The slides, paraffin blocks, and residual wet tissues were sent to the 
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NTP Archives for inventory, slide/block match, and wet tissue audit. The slides, individual animal data records, and 

pathology tables were evaluated by an independent quality assessment laboratory. The individual animal records 

and tables were compared for accuracy, the slide and tissue counts were verified, and the histotechnique was 

evaluated. For the 2-year studies, a quality assessment pathologist evaluated slides from all tumors and all potential 

target organs, which included the larynx, nose, and trachea of rats and mice and the lung of mice. 

The quality assessment report and the reviewed slides were submitted to the NTP PWG coordinator, who reviewed 

the selected tissues and addressed any inconsistencies in the diagnoses made by the laboratory and quality 

assessment pathologists. Representative histopathology slides containing examples of lesions related to chemical 

administration, examples of disagreements in diagnoses between the laboratory and quality assessment pathologists, 

or lesions of general interest were presented by the coordinator to the PWG for review. The PWG consisted of the 

quality assessment pathologist and other pathologists experienced in rodent toxicologic pathology. This group 

examined the tissues without any knowledge of dose groups or previously rendered diagnoses. When the PWG 

consensus differed from the opinion of the laboratory pathologist, the diagnosis was changed. Final diagnoses for 

reviewed lesions represent a consensus between the laboratory pathologist, reviewing pathologist(s), and the PWG. 

Details of these review procedures have been described, in part, by Maronpot and Boorman (1982) and Boorman 

et al. (1985). For subsequent analyses of the pathology data, the decision of whether to evaluate the diagnosed 

lesions for each tissue type separately or combined was generally based on the guidelines of McConnell et al.

(1986).

Three standard sections are taken through the nose in NTP studies, and these are referred to as Levels I, II, and III. 

Proceeding from anterior to posterior, Level I is taken immediately posterior to the upper incisor teeth; Level II is 

taken through the level of the incisive papilla anterior to the first palatal ridge; and Level III is taken through the 

middle of the second molar teeth (Figure 2). The mucosa of the nasal passages in Levels I and II is lined by 

respiratory and transitional epithelium, except for the ventral meatus of Levels I and II (squamous epithelium) and 

the dorsal meatus of Level II (olfactory epithelium). Level III is lined almost entirely by olfactory epithelium, 

except for the ventral meatus, which is lined by respiratory epithelium.
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FIGURE 2 

Rodent Nasal Cavity Diagram Illustrating the Levels of Sections

Level I: Immediately posterior to incisor teeth

Level II: At incisive papilla anterior to first palatal ridge

Level III: Section taken through the second molar

MT=maxilloturbinate; NT=nasoturbinate; ET=ethmoid turbinates
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TABLE 1 

Experimental Design and Materials and Methods in the Inhalation Studies of 1-Bromopropane

2-Week Studies 3-Month Studies 2-Year Studies

Study Laboratory

Battelle Toxicology Northwest 

(Richland, WA)

Battelle Toxicology Northwest 

(Richland, WA)

Battelle Toxicology Northwest 

(Richland, WA)

Strain and Species

F344/N rats F344/N rats F344/N rats

B6C3F1 mice B6C3F1 mice B6C3F1 mice

Animal Source

Taconic Farms, Inc. (Germantown, NY) Taconic Farms, Inc. (Germantown, NY) Taconic Farms, Inc. (Germantown, NY)

Time Held Before Studies

13 days Rats: 12 (females) or 13 (males) days Rats: 13 days

Mice: 12 days Mice: 11 days

Average Age When Studies Began

6 weeks 5 to 6 weeks 5 to 6 weeks

Date of First Exposure

July 15, 2002 Rats: November 11 (females) or 12 (males), 

2002

Mice: November 11, 2002

Rats: July 14, 2003

Mice: July 21, 2003

Duration of Exposure

6 hours plus T90 (12 minutes) per day, 5 days 

per week, for 16 (rats) or 17 (mice) days

6 hours plus T90 (10 minutes) per day, 5 days 

per week, for 14 weeks

6 hours plus T90 (10 minutes) per day, 5 days 

per week, for 105 weeks

Date of Last Exposure

Rats: July 30, 2002

Mice: July 31, 2002

Rats: February 10 (females) or 11 (males), 

2003

Mice: February 12 (males) or 13 (females), 

2003

Rats: July 13, 2005

Mice: July 21, 2005

Necropsy Dates

Rats: July 31, 2002

Mice: August 1, 2002

Rats: February 11 (females) or 12 (males), 

2003

Mice: February 13 (males) or 14 (females),

2003

Rats: July 11-14, 2005

Mice: July 18-22, 2005

Average Age at Necropsy

8 weeks 18 to 19 weeks Rats: 110 weeks

Mice: 109 to 111 weeks

Size of Study Groups

5 males and 5 females Rats: 10 males and 10 females 

Mice: 10 males and 10 females

50 males and 50 females

Method of Distribution

Animals were distributed randomly into 

groups of approximately equal initial mean 

body weights.

Same as 2-week studies Same as 2-week studies

Animals per Cage

1 1 1

Method of Animal Identification

Tail tattoo Tail tattoo Tail tattoo
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TABLE 1 

Experimental Design and Materials and Methods in the Inhalation Studies of 1-Bromopropane

2-Week Studies 3-Month Studies 2-Year Studies

Diet

NTP-2000 irradiated pelleted diet (Zeigler 

Brothers, Inc., Gardners, PA); available 

ad libitum, except during exposure periods; 

changed weekly

Same as 2-week studies Same as 2-week studies

Water

Tap water (Richland, WA, municipal supply) 

via automatic watering system (Edstrom 

Industries, Waterford, WI); available 

ad libitum

Same as 2-week studies Same as 2-week studies

Cages

Stainless steel, wire bottom (Lab Products, 

Inc., Seaford, DE); changed weekly, rotated 

daily

Same as 2-week studies, except rotated 

weekly

Same as 3-month studies

Cageboard

Untreated paper cage pan liner (Sheperd 

Specialty Papers, Kalamazoo, MI); changed 

daily

Same as 2-week studies Same as 2-week studies

Chamber Air Supply Filters

Single HEPA (open stock), charcoal (RSE, 

Inc., New Baltimore, MI), Purafil 

(Environmental Systems, Lynnwood, WA), 

all new at study start

Same as 2-week studies, except not changed 

after 2-week studies

Same as 2-week studies, except single HEPA 

changed annually

Chambers

Stainless steel, excreta pan at each of six 

levels (Lab Products, Inc., Seaford, DE); 

chambers changed weekly; excreta pans 

changed daily

Same as 2-week studies Same as 2-week studies

Chamber Environment

Temperature: 72° ± 3° F Temperature: 72° ± 3° F Temperature: 72° ± 3° F

Relative humidity: 50% ± 15% Relative humidity: 50% ± 15% Relative humidity: 50% ± 15%

Room fluorescent light: 12 hours/day Room fluorescent light: 12 hours/day Room fluorescent light: 12 hours/day

Chamber air changes: 15 ± 2/hour Chamber air changes: 15 ± 2/hour Chamber air changes: 15 ± 2/hour

Exposure Concentrations

0, 125, 250, 500, 1,000, or 2,000 ppm Rats: 0, 62.5, 125, 250, 500, or 1,000 ppm

Mice: 0, 62.5, 125, 250, or 500 ppm

Rats: 0, 125, 250, or 500 ppm

Mice: 0, 62.5, 125, or 250 ppm

Type and Frequency of Observation

Observed twice daily; animals were weighed 

initially, on days 6 and 13, and at the end of 

the studies; clinical findings were recorded 

twice daily on exposure days.

Observed twice daily; core study animals 

were weighed initially, on days 9 (male rats) 

or 10, weekly thereafter, and at the end of the 

studies. Clinical findings were recorded on 

day 9 (male rats) or 10 and then weekly.

Observed twice daily; animals were weighed 

initially, weekly for 13 weeks, every 4 weeks

through week 93, every 2 weeks thereafter, 

and at the end of the studies; clinical findings 

were recorded every 4 weeks through 

week 93, every 2 weeks thereafter, and at the 

end of the studies.
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TABLE 1 

Experimental Design and Materials and Methods in the Inhalation Studies of 1-Bromopropane

2-Week Studies 3-Month Studies 2-Year Studies

Method of Sacrifice

Carbon dioxide asphyxiation Same as 2-week studies Same as 2-week studies

Necropsy

Necropsies were performed on all animals. 

Organs weighed were heart, right kidney, 

liver, lung, right testis, and thymus.

Necropsies were performed on core study 

animals. Organs weighed were heart, right 

kidney, liver, lung, spleen, right testis, and 

thymus. 

Necropsies were performed on all animals.

Clinical Pathology

None Blood was collected from the retroorbital 

sinus of clinical pathology rats on days 3 and 

23 and from core study rats at the end of the 

studies for hematology and clinical chemistry. 

Blood was collected from the retroorbital 

sinus of mice at the end of the study for 

hematology.

None

Hematology: hematocrit; packed red cell 

volume; hemoglobin; erythrocyte, nucleated 

erythrocyte, reticulocyte, and platelet counts; 

mean cell volume; mean cell hemoglobin; 

mean cell hemoglobin concentration; and 

leukocyte count and differentials

Clinical chemistry: urea nitrogen, creatinine, 

total protein, albumin, globulin, alanine 

aminotransferase, alkaline phosphatase, 

creatine kinase, sorbitol dehydrogenase, and 

bile acids

Histopathology

Histopathology was performed on 0 and 

2,000 ppm rats and mice. In addition to gross 

lesions and tissue masses, the following 

tissues were examined: lung, mediastinal 

lymph node, nose, sciatic nerve, and spinal 

cord of rats and liver, lung, and nose of mice. 

These tissues were examined to a no-effect 

level in the remaining exposure groups.

Complete histopathology was performed on 0 

and 1,000 ppm core study rats and 0, 250, and 

500 ppm mice. In addition to gross lesions 

and tissue masses, the following tissues were 

examined to a no-effect level: adrenal gland, 

bone with marrow, brain, clitoral gland, 

esophagus, eyes, gallbladder (mice), 

Harderian gland, heart and aorta, large 

intestine (cecum, colon, rectum), small 

intestine (duodenum, jejunum, ileum), kidney, 

larynx, liver, lung, lymph nodes (mandibular, 

mesenteric, bronchial, mediastinal), 

mammary gland, nose, ovary, pancreas, 

parathyroid gland, pituitary gland, preputial 

gland, prostate gland, salivary gland, skin, 

spleen, stomach (forestomach and glandular), 

testis with epididymis and seminal vesicle, 

thymus, thyroid gland, trachea, urinary 

bladder, and uterus. In addition, the liver, 

larynx, lung, and nose of rats and mice; the 

trachea of mice; the prostate gland of male 

rats; and the adrenal gland and kidney of 

female mice were examined in the remaining 

groups.

Complete histopathology was performed on 

all rats and mice. In addition to gross lesions 

and tissue masses, the following tissues were 

examined: adrenal gland, bone with marrow, 

brain, clitoral gland, esophagus, eye, 

gallbladder (mice only), Harderian gland, 

heart with aorta, large intestine (cecum, colon, 

rectum), small intestine (duodenum, jejunum, 

ileum), kidney, larynx, liver, lung, lymph 

nodes (mandibular, mesenteric, bronchial, 

mediastinal), mammary gland, nose, ovary, 

pancreas, pancreatic islets, parathyroid gland, 

pituitary gland, preputial gland, prostate 

gland, salivary gland, skin, spleen, stomach 

(forestomach and glandular), testis with 

epididymis and seminal vesicle, thymus, 

thyroid gland, trachea, urinary bladder, and 

uterus.
44 1-Bromopropane, NTP TR 564

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TABLE 1 

Experimental Design and Materials and Methods in the Inhalation Studies of 1-Bromopropane

2-Week Studies 3-Month Studies 2-Year Studies

Sperm Motility

and Vaginal Cytology

None At the end of the studies, sperm samples were 

collected from male animals in the 0, 125 

(mice), 250, 500, and 1,000 (rats) ppm groups 

for sperm motility evaluations. The following 

parameters were evaluated: spermatid heads 

per testis and per gram testis, spermatid 

counts, and epididymal spermatozoal motility 

and concentration. The left cauda, left 

epididymis, and left testis were weighed. 

Vaginal samples were collected for up to 

12 consecutive days prior to the end of the 

studies from females exposed to 0, 125 

(mice), 250, 500, or 1,000 (rats) ppm for 

vaginal cytology evaluations. The percentage 

of time spent in the various estrous cycle 

stages and estrous cycle length were 

evaluated.

None

STATISTICAL METHODS

Survival Analyses 

The probability of survival was estimated by the product-limit procedure of Kaplan and Meier (1958) and is 

presented in the form of graphs. Animals found dead of other than natural causes were censored; animals dying 

from natural causes were not censored. Statistical analyses for possible dose-related effects on survival used Cox’s 

(1972) method for testing two groups for equality and Tarone’s (1975) life table test to identify dose-related trends. 

All reported P values for the survival analyses are two sided.

Calculation of Incidence

The incidences of neoplasms or nonneoplastic lesions are presented in Tables A1, A4, B1, B4, C1, C3, D1, and D4

as the numbers of animals bearing such lesions at a specific anatomic site and the numbers of animals with that site 

examined microscopically. For calculation of statistical significance, the incidences of most neoplasms (Tables A2, 

B2, C2, and D2) and all nonneoplastic lesions are given as the numbers of animals affected at each site examined 

microscopically. However, when macroscopic examination was required to detect neoplasms in certain tissues (e.g., 

mesentery, pleura, peripheral nerve, skeletal muscle, tongue, tooth, and Zymbal’s gland) before microscopic 
1-Bromopropane, NTP TR 564 45

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evaluation, the denominators consist of the number of animals that had a gross abnormality. When neoplasms had 

multiple potential sites of occurrence (e.g., leukemia or lymphoma), the denominators consist of the number of 

animals on which a necropsy was performed. Tables A2, B2, C2, and D2 also give the survival-adjusted neoplasm 

rate for each group and each site-specific neoplasm. This survival-adjusted rate (based on the Poly-3 method 

described below) accounts for differential mortality by assigning a reduced risk of neoplasm, proportional to the 

third power of the fraction of time on study, only to site-specific, lesion-free animals that do not reach terminal 

sacrifice.

Analysis of Neoplasm and Nonneoplastic Lesion Incidences

The Poly-k test (Bailer and Portier, 1988; Portier and Bailer, 1989; Piegorsch and Bailer, 1997) was used to assess 

neoplasm and nonneoplastic lesion prevalence. This test is a survival-adjusted quantal-response procedure that 

modifies the Cochran-Armitage linear trend test to take survival differences into account. More specifically, this 

method modifies the denominator in the quantal estimate of lesion incidence to approximate more closely the total 

number of animal years at risk. For analysis of a given site, each animal is assigned a risk weight. This value is one 

if the animal had a lesion at that site or if it survived until terminal sacrifice; if the animal died prior to terminal 

sacrifice and did not have a lesion at that site, its risk weight is the fraction of the entire study time that it survived, 

raised to the kth power.

This method yields a lesion prevalence rate that depends only upon the choice of a shape parameter for a Weibull 

hazard function describing cumulative lesion incidence over time (Bailer and Portier, 1988). Unless otherwise 

specified, a value of k=3 was used in the analysis of site-specific lesions. This value was recommended by Bailer 

and Portier (1988) following an evaluation of neoplasm onset time distributions for a variety of site-specific 

neoplasms in control F344 rats and B6C3F1 mice (Portier et al., 1986). Bailer and Portier (1988) showed that the 

Poly-3 test gave valid results if the true value of k was anywhere in the range from 1 to 5. A further advantage of 

the Poly-3 method is that it does not require lesion lethality assumptions. Variation introduced by the use of risk 

weights, which reflect differential mortality, was accommodated by adjusting the variance of the Poly-3 statistic as 

recommended by Bieler and Williams (1993).
46 1-Bromopropane, NTP TR 564

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Tests of significance included pairwise comparisons of each exposed group with controls and a test for an overall 

exposure-related trend. Continuity-corrected Poly-3 tests were used in the analysis of lesion incidence, and reported 

P values are one sided. The significance of lower incidences or decreasing trends in lesions is represented as 1–P 

with the letter N added (e.g., P=0.99 is presented as P=0.01N).

Analysis of Continuous Variables

Two approaches were employed to assess the significance of pairwise comparisons between exposed and control 

groups in the analysis of continuous variables. Organ and body weight data, which historically have approximately 

normal distributions, were analyzed with the parametric multiple comparison procedures of Dunnett (1955) and 

Williams (1971, 1972). Hematology, clinical chemistry, spermatid, and epididymal spermatozoal data, which have 

typically skewed distributions, were analyzed using the nonparametric multiple comparison methods of Shirley 

(1977) (as modified by Williams, 1986) and Dunn (1964). Jonckheere’s test (Jonckheere, 1954) was used to assess 

the significance of the dose-related trends and to determine whether a trend-sensitive test (Williams’ or Shirley’s 

test) was more appropriate for pairwise comparisons than a test that does not assume a monotonic dose-related trend 

(Dunnett’s or Dunn’s test). Prior to statistical analysis, extreme values identified by the outlier test of Dixon and 

Massey (1957) were examined by NTP personnel, and implausible values were eliminated from the analysis. 

Because vaginal cytology data are proportions (the proportion of the observation period that an animal was in a 

given estrous stage), an arcsine transformation was used to bring the data into closer conformance with a normality 

assumption. Treatment effects were investigated by applying a multivariate analysis of variance (Morrison, 1976) to 

the transformed data to test for simultaneous equality of measurements across exposure concentrations. Proportions 

of regular cycling females in each exposed group were compared to the control group using the Fisher exact test 

(Gart et al., 1979). Tests for extended periods of estrus and diestrus were constructed based on a Markov chain 

model proposed by Girard and Sager (1987). For each exposure group, a transition probability matrix was estimated 

for transitions among the proestrus, estrus, metestrus, and diestrus stages, with provision for extended stays within 

estrus and diestrus. Equality of transition matrices among exposure groups and between the control group and each 

exposed group was tested using chi-square statistics.
1-Bromopropane, NTP TR 564 47

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Historical Control Data 

The concurrent control group represents the most valid comparison to the treated groups and is the only control 

group analyzed statistically in NTP bioassays. However, historical control data are often helpful in interpreting 

potential treatment-related effects, particularly for uncommon or rare neoplasm types. For meaningful comparisons, 

the conditions for studies in the historical database must be generally similar. One significant factor affecting the 

background incidence of neoplasms at a variety of sites is diet. In 1995, the NTP incorporated a new diet 

(NTP-2000) that contains less protein and more fiber and fat than the NIH-07 diet previously used in toxicity and 

carcinogenicity studies (Rao, 1996, 1997). The NTP historical database contains all studies that use the NTP-2000 

diet with histopathology findings completed within the most recent 5-year period. A second potential source of 

variability is route of administration. In general, the historical database for a given study will include studies using 

the same route of administration, and the overall incidences of neoplasms for all routes of administration are 

included for comparison, including the present study.

QUALITY ASSURANCE METHODS

The 3-month and 2-year studies were conducted in compliance with Food and Drug Administration Good 

Laboratory Practice Regulations (21 CFR, Part 58). In addition, as records from the 2-year studies were submitted 

to the NTP Archives, these studies were audited retrospectively by an independent quality assurance contractor. 

Separate audits covered completeness and accuracy of the pathology data, pathology specimens, final pathology 

tables, and a draft of this NTP Technical Report. Audit procedures and findings are presented in the reports and are 

on file at NIEHS. The audit findings were reviewed and assessed by NTP staff, and all comments were resolved or 

otherwise addressed during the preparation of this Technical Report.

GENETIC TOXICOLOGY

The genetic toxicity of 1-bromopropane was assessed by testing the ability of the chemical to induce mutations in 

various strains of Salmonella typhimurium and Escherichia coli and increases in the frequency of micronucleated 

erythrocytes in mouse peripheral blood. Micronuclei (literally “small nuclei” or Howell-Jolly bodies) are 

biomarkers of induced structural or numerical chromosomal alterations and are formed when acentric fragments or 
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whole chromosomes fail to incorporate into either of two daughter nuclei during cell division (Schmid, 1975; 

Heddle et al., 1983). The protocols for these studies and the results are given in Appendix E.

The genetic toxicity studies have evolved from an earlier effort by the NTP to develop a comprehensive database 

permitting a critical anticipation of a chemical’s carcinogenicity in experimental animals based on numerous 

considerations, including the molecular structure of the chemical and its observed effects in short-term in vitro and 

in vivo genetic toxicity tests (structure-activity relationships). The short-term tests were originally developed to 

clarify proposed mechanisms of chemical-induced DNA damage based on the relationship between electrophilicity 

and mutagenicity (Miller and Miller, 1977) and the somatic mutation theory of cancer (Straus, 1981; Crawford, 

1985). However, it should be noted that not all cancers arise through genotoxic mechanisms.

DNA reactivity combined with Salmonella mutagenicity is highly correlated with induction of carcinogenicity in 

multiple species/sexes of rodents and at multiple tissue sites (Ashby and Tennant, 1991). A positive response in the 

Salmonella test was shown to be the most predictive in vitro indicator for rodent carcinogenicity (89% of the 

Salmonella mutagens are rodent carcinogens) (Tennant et al., 1987; Zeiger et al., 1990). Additionally, no battery of 

tests that included the Salmonella test improved the predictivity of the Salmonella test alone. However, these other 

tests can provide useful information on the types of DNA and chromosomal damage induced by the chemical under 

investigation. 

The predictivity for carcinogenicity of a positive response in acute in vivo bone marrow chromosome aberration or 

micronucleus tests appears to be less than that in the Salmonella test (Shelby et al., 1993; Shelby and Witt, 1995). 

However, clearly positive results in long-term peripheral blood micronucleus tests have high predictivity for rodent 

carcinogenicity; a weak response in one sex only or negative results in both sexes in this assay do not correlate well 

with either negative or positive results in rodent carcinogenicity studies (Witt et al., 2000). Because of the 

theoretical and observed associations between induced genetic damage and adverse effects in somatic and germ 

cells, the determination of in vivo genetic effects is important to the overall understanding of the risks associated 

with exposure to a particular chemical. Most organic chemicals that are identified by the International Agency for 

Research on Cancer as human carcinogens, other than hormones, are genotoxic. The vast majority of these are 
1-Bromopropane, NTP TR 564 49

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detected by both the Salmonella assay and rodent bone marrow cytogenetics tests (Shelby, 1988; Shelby and Zeiger, 

1990). 
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51

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RESULTS

RATS

2-WEEK STUDY

Except for one 500 ppm male that died on day 14, all rats survived to the end of the study (Table 2). Final mean 

body weights and body weight gains of 2,000 ppm rats were significantly less than those of the chamber controls, as 

was the body weight gain of 1,000 ppm males. The neurological sign of hind limb splaying was observed in some 

2,000 ppm rats after 1 week of exposure to 1-bromopropane. This was a transient change and the animals showed 

marked improvement after 1 day.

TABLE 2 

Survival and Body Weights of Rats in the 2-Week Inhalation Study of 1-Bromopropane

Final Weight Concentration a Mean Body Weightb (g) Survival Relative to Controls (ppm) Initial Final Change (%)

Male

0 5/5 99 ± 4 169 ± 4 69 ± 3 

125 5/5 99 ± 4 167 ± 4 68 ± 1 99

250 5/5 98 ± 4 169 ± 5 70 ± 3 100

500 4/5c 98 ± 4 166 ± 6 69 ± 1 98 

1,000 5/5 102 ± 4 164 ± 5 63 ± 2* 97

2,000 5/5 98 ± 4 123 ± 4** 25 ± 2** 73

Female

0 5/5 87 ± 3 120 ± 2 33 ± 1

125 5/5 88 ± 2 124 ± 3 37 ± 2 104

250 5/5 86 ± 3 120 ± 4 34 ± 3 100 

500 5/5 89 ± 3 124 ± 5 35 ± 3 104

1,000 5/5 88 ± 2 119 ± 2 31 ± 1 99 

2,000 5/5 89 ± 2 107 ± 2* 18 ± 1** 89

* Significantly different (P≤0.05) from the chamber control group by Williams’ or Dunnett’s test

** P≤0.01

a Number of animals surviving at 2 weeks/number initially in group

b Weights and weight changes are given as mean ± standard error. Subsequent calculations are based on animals surviving to the end of the 

study.

c Day of death: 14
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The absolute right kidney weights of 1,000 ppm males and all exposed groups of females were significantly greater 

than those of the chamber controls (Table G1). The relative right kidney weights were significantly increased in all 

exposed groups of both sexes. Absolute liver weights were significantly increased in 1,000 ppm males and 500 ppm

or greater females. Relative liver weights were significantly increased in 500 ppm or greater males and all exposed 

groups of females.

Microscopic lesions related to 1-bromopropane exposure occurred in the nose. Incidences of minimal to mild 

suppurative inflammation occurred in males exposed to 500 ppm or greater, incidences of minimal respiratory 

epithelium necrosis occurred in 1,000 and 2,000 ppm males, and incidences of minimal respiratory epithelium 

regeneration occurred in 1,000 and 2,000 ppm females (Table 3).

Sciatic nerve and spinal cord were examined microscopically, but no lesions were identified.

Exposure Concentration Selection Rationale: Based on decreased body weights and indications of neurotoxicity at 

2,000 ppm in the 2-week study, 1-bromopropane exposure concentrations selected for the 3-month inhalation study 

in rats were 62.5, 125, 250, 500, and 1,000 ppm.

TABLE 3 

Incidences of Nonneoplastic Lesions in the Nose of Rats in the 2-Week Inhalation Study of 1-Bromopropane

Chamber

Control 125 ppm 250 ppm 500 ppm 1,000 ppm 2,000 ppm

Male

Number Examined Microscopically 5 0 5 5 5 5

Respiratory Epithelium, 

Necrosisa 0 0 0 2 (1.0)b 1 (1.0) 

Suppurative Inflammation 0 0 1 (1.0) 2 (1.5) 2 (1.5)

Female

Number Examined Microscopically 5 0 0 5 5 5

Respiratory Epithelium,

Regeneration 0 0 1 (1.0) 1 (1.0)

a Number of animals with lesion

b Average severity grade of lesions in affected animals: 1=minimal, 2=mild, 3=moderate, 4=marked
1-Bromopropane, NTP TR 564 53

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3-MONTH STUDY

All rats survived to the end of the study (Table 4). The final mean body weight and mean body weight gain of 

1,000 ppm males were significantly less than those of the chamber controls (Table 4 and Figure 3). Mean body 

weights of exposed females were similar to those of the chamber controls.

TABLE 4 

Survival and Body Weights of Rats in the 3-Month Inhalation Study of 1-Bromopropane

Final Weight Concentration a Mean Body Weightb (g) Survival Relative to Controls (ppm) Initial Final Change (%)

Male

0 10/10 99 ± 2 345 ± 7 246 ± 6 

62.5 10/10 102 ± 2 346 ± 5 244 ± 5 100 

125 10/10 100 ± 2 348 ± 6 248 ± 5 101

250 10/10 101 ± 3 350 ± 7 250 ± 6 101 

500 10/10 99 ± 2 344 ± 10 245 ± 10 100

1,000 10/10 100 ± 2 305 ± 6** 205 ± 4** 88 

Female

0 10/10 88 ± 1 202 ± 3 114 ± 3 

62.5 10/10 92 ± 3 203 ± 5 111 ± 3 101

125 10/10 88 ± 2 207 ± 4 120 ± 4 103 

250 10/10 91 ± 2 209 ± 2 119 ± 3 104 

500 10/10 86 ± 2 205 ± 3 119 ± 3 102 

1,000 10/10 88 ± 2 190 ± 4 102 ± 3 95 

** Significantly different (P≤0.01) from the chamber control group by Dunnett’s or Williams’ test

a Number of animals surviving at 3 months/number initially in group

b Weights and weight changes are given as mean ± standard error.
54 1-Bromopropane, NTP TR 564

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FIGURE 3 

Growth Curves for Rats Exposed to 1-Bromopropane

by Inhalation for 3 Months 
1-Bromopropane, NTP TR 564 55

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There were no changes in hematology endpoints that were considered related 1-bromopropane exposure (Table F1). 

There were early, transient decreases in albumin and total protein concentrations and alanine aminotransferase 

activities in most exposed groups of male and female rats. These transient decreases may have been associated with 

effects of 1-bromopropane on hepatic protein metabolism. Additionally, sorbitol dehydrogenase (SDH) activity was

increased at day 23 and at the end of the study in females exposed to 1,000 ppm and at the end of the study in males 

exposed to 500 or 1,000 ppm. Increased SDH activity would be consistent with mild hepatotoxicity caused by

1-bromopropane.

The absolute and relative liver weights of males exposed to 250 ppm or greater and females exposed to 125 ppm or 

greater were significantly increased (Table G2). The absolute spleen weights of females exposed to 125 ppm or 

greater and the relative spleen weight of 1,000 ppm females were greater than those of the chamber controls. In 

addition, the absolute and relative right kidney weights of 1,000 ppm females were greater than those of the chamber 

controls.

There were significant exposure concentration-related decreases in sperm motility in male rats exposed to 250 ppm 

or greater (6.7%, 10.1%, and 27.7% in the 250, 500, and 1,000 ppm groups, respectively), and there were significant 

decreases in the number of sperm per gram cauda and the total sperm per cauda (25.2% and 36.8%, respectively), as 

well as significant decreases in the absolute weights of the cauda (14%) and left epididymis (19%) of 1,000 ppm 

male rats (Table H1). Female rats in each of the exposure groups evaluated differed significantly from the chamber 

controls in the relative amount of time spent in the various estrous cycle stages, with each exposed group spending 

significantly more time in extended estrus and significantly less time in extended diestrus (Table H2).

Treatment-related lesions occurred in the liver. There were significantly increased incidences of hepatocellular 

cytoplasmic vacuolization in males exposed to 250 ppm or greater and in females exposed to 500 or 1,000 ppm 

(Table 5). The incidence of hepatocellular vacuolar degeneration was significantly increased in 1,000 ppm females. 

Hepatocellular cytoplasmic vacuolization consisted of swollen hepatocytes with centrally located nuclei and one to 

three variably sized vacuoles displacing the cytoplasm. Hepatocellular vacuolar degeneration consisted of a distinct 
56 1-Bromopropane, NTP TR 564

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TABLE 5

Incidences of Nonneoplastic Lesions of the Liver in Rats in the 3-Month Inhalation Study of 1-Bromopropane

Chamber 

Control 62.5 ppm 125 ppm 250 ppm 500 ppm 1,000 ppm

Male

Number Examined Microscopically 10 10 10 10 10 10

Vacuolization Cytoplasmica 0 0 0 5* (1.0)b 10**(2.2) 10**(2.8)

Female

Number Examined Microscopically 10 10 10 10 10 10

Vacuolization Cytoplasmic 0 0 0 0 10**(1.1) 10**(2.6)

Hepatocyte, Degeneration 0 0 0 0 0 7**(1.9)

* Significantly different (P≤0.05) from the chamber control group by the Fisher exact test

** P≤0.01

a Number of animals with lesion

b Average severity grade of lesions in affected animals: 1=minimal, 2=mild, 3=moderate, 4=marked

population of enlarged, pale-staining, degenerative, “balloon-like” cells admixed with low numbers of necrotic 

hepatocytes. The lesion involved hepatocytes surrounding the central vein, but in the most severe cases, the 

vacuolated hepatocytes extended into the midzonal region.

The incidence of minimal, suppurative, prostatic inflammation in 1,000 ppm males was increased, but the increase 

was not statistically significant (data not shown). The increasing trend of this lesion, however, was significant. 

Because this lesion is a common background finding in F344/N rats, the biological significance of the increased 

incidence in the 1,000 ppm males is unclear (Boorman et al., 1990).

Exposure Concentration Selection Rationale: Based on decreased body weights and increased incidences of liver

lesions in the 3-month study, 1-bromopropane exposure concentrations selected for the 2-year inhalation study in 

rats were 125, 250, and 500 ppm. Although 500 ppm caused vacuolization in liver, this lesion was not considered 

life-threatening and the use of this concentration was not expected to compromise the 2-year study.
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2-YEAR STUDY

Survival

Estimates of 2-year survival probabilities for male and female rats are shown in Table 6 and in the Kaplan-Meier 

survival curves (Figure 4). Survival of 500 ppm males was significantly less than that of the chamber control group. 

The majority of the early deaths in the 500 ppm males were attributed to various types of neoplasia, none of which 

were treatment related. However, in nine of these males, the cause of death was attributed to inflammation in 

various organs, all of which contained Splendore-Hoeppli material. Survival of exposed groups of females 

decreased with increasing exposure concentration, but survival in each exposed group was not significantly different 

from that of chamber control group.

TABLE 6

Survival of Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber 

Control 125 ppm 250 ppm 500 ppm

Male

Animals initially in study 50 50 50 50

Moribund 24 20 28 35

Natural deaths 3 4 4 2

Animals surviving to study termination 23 26 18 13

Percent probability of survival at end of studya 46 52 36 26

Mean survival (days)b 679 671 654 639

Survival analysisc P=0.009 P=0.844N P=0.262 P=0.033

Female

Animals initially in study 50 50 50 50

Accidental deathsd 0 0 0 2

Moribund 13 17 17 23

Natural deaths 3 0 3 1

Animals surviving to study termination 34 33 30 24

Percent probability of survival at end of study 68 66 60 50

Mean survival (days) 702 692 683 637

Survival analysis P=0.028 P=0.858 P=0.419 P=0.054

a Kaplan-Meier determinations

b Mean of all deaths (uncensored, censored, and terminal sacrifice)

c The result of the life table trend test (Tarone, 1975) is in the chamber control column, and the results of the life table pairwise comparisons 

(Cox, 1972) with the chamber controls are in the exposed group columns. A lower mortality in an exposed group is indicated by N.

d Censored from survival analyses
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FIGURE 4 

Kaplan-Meier Survival Curves for Rats 

Exposed to 1-Bromopropane by Inhalation for 2 Years
1-Bromopropane, NTP TR 564 59

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Body Weights and Clinical and Macroscopic Findings

Mean body weights of exposed groups of male and female rats were similar to those of the chamber controls 

throughout the study (Tables 7 and 8; Figure 5). In males, clinical findings that appeared to be related to 

1-bromopropane exposure included head mass (0 ppm, 1/50; 125 ppm, 2/50; 250 ppm, 5/50, 500 ppm, 9/50) and 

torso/ventral ulcer/abscess (2/50, 7/50, 6/50, 20/50). No clinical findings related to exposure to 1-bromopropane 

were observed in females. In male and female rats exposed to 1-bromopropane, there was an exposure-related 

increased incidence of soft, pale-yellow to green, variably sized nodules. These lesions were predominantly located 

in the nose and/or skin, but other sites included bone, ear, Harderian gland, larynx, lung, muscle, peritoneum, 

preputial gland, and prostate gland. The incidences of these lesions were greater in males (2, 3, 6, 15) than in 

females (1, 2, 0, 7). In addition, the number of animals with multiple masses was increased in the 500 ppm groups. 

In most cases, these lesions were microscopically shown to be suppurative inflammation, many with SplendoreHoeppli material.
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TABLE 7 

Mean Body Weights and Survival of Male Rats in the 2-Year Inhalation Study of 1-Bromopropane

Days Chamber Control 125 ppm 250 ppm 500 ppm

on Av. Wt. No. of Av. Wt. Wt. (% of No. of Av. Wt. Wt. (% of No. of Av. Wt. Wt. (% of No. of 

Study (g) Survivors (g) controls) Survivors (g) controls) Survivors (g) controls) Survivors

 

1 104 50 103 99 50 103 99 50 104 100 50

9 137 50 136 99 50 138 100 50 138 100 50

16 162 50 163 101 50 165 102 50 166 103 50

23 187 50 191 102 50 194 104 50 194 104 50

30 206 50 213 104 50 217 106 50 218 106 50

37 223 50 232 104 50 238 107 50 242 109 50

44 239 50 251 105 50 257 108 50 260 109 50

51 253 50 268 106 50 273 108 50 275 108 50

58 267 50 283 106 50 287 107 50 290 109 50

65 279 50 297 106 50 301 108 50 304 109 50

72 291 50 309 106 50 314 108 50 318 109 50

79 300 50 320 107 50 323 108 50 328 109 50

86 310 50 330 107 50 331 107 50 337 109 50

114 346 50 366 106 50 366 106 50 370 107 50

142 373 50 390 105 50 391 105 50 394 106 50

170 393 50 413 105 50 411 104 50 410 104 50

198 413 50 432 105 50 428 104 50 426 103 50

226 428 50 448 105 50 446 104 50 438 102 50

254 443 50 462 104 50 459 104 50 448 101 50

282 453 50 473 105 50 467 103 50 454 100 50

310 463 50 485 105 50 479 103 50 462 100 50

338 470 50 493 105 49 484 103 50 467 100 50

366 478 50 508 106 49 498 104 50 474 99 50

394 489 50 517 106 49 507 104 50 483 99 49

422 495 50 523 106 49 517 104 49 486 98 48

450 502 49 530 106 49 525 104 49 493 98 46

478 508 49 540 106 49 532 105 49 503 99 45

506 510 48 546 107 48 536 105 48 505 99 43

534 520 47 551 106 47 545 105 44 513 99 42

562 520 47 551 106 44 552 106 41 517 100 40

590 519 45 555 107 41 550 106 38 522 101 36

618 527 41 557 106 37 557 106 31 521 99 35

646 523 38 564 108 35 556 106 30 517 99 30

660 527 32 568 108 33 556 106 29 520 99 25

674 520 30 565 109 31 550 106 27 520 100 22

688 527 27 566 107 30 546 104 25 514 98 19

702 517 27 557 108 29 544 105 20 512 99 16

716 517 24 551 107 27 541 105 19 503 97 14

 

 

Mean for weeks 

1-13 228 238 104 242 106 244 106

14-52 420 440 105 437 104 430 103

53-103 512 547 107 538 105 506 99 

 

 
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TABLE 8 

Mean Body Weights and Survival of Female Rats in the 2-Year Inhalation Study of 1-Bromopropane

Days Chamber Control 125 ppm 250 ppm 500 ppm

on Av. Wt. No. of Av. Wt. Wt. (% of No. of Av. Wt. Wt. (% of No. of Av. Wt. Wt. (% of No. of 

Study (g) Survivors (g) controls) Survivors (g) controls) Survivors (g) controls) Survivors

 

1 88 50 87 99 50 88 100 50 88 99 50

9 108 50 108 100 50 109 101 50 106 98 50

16 122 50 122 100 50 125 102 50 121 99 50

23 137 50 137 100 50 140 102 50 135 99 50

30 146 50 147 100 50 151 103 50 147 100 50

37 155 50 157 102 50 161 104 50 157 101 50

44 163 50 166 101 50 170 104 50 166 102 49

51 170 50 172 101 50 177 104 50 170 100 49

58 175 50 177 102 50 183 105 50 176 101 49

65 180 50 183 101 50 188 105 50 183 102 49

72 185 50 187 102 50 194 105 50 188 102 49

79 189 50 192 102 50 198 105 50 194 103 49

86 191 50 196 103 50 202 106 50 198 104 49

114 203 50 210 103 50 217 107 50 214 105 49

142 215 50 220 102 50 227 106 50 224 104 48

170 226 50 229 102 50 237 105 50 232 103 48

198 233 50 238 102 50 246 106 50 241 104 48

226 243 50 248 102 50 256 105 50 247 102 48

254 254 50 258 102 50 266 105 50 257 101 48

282 262 50 265 101 50 272 104 50 263 101 48

310 270 50 274 101 50 281 104 50 271 100 48

338 281 50 283 101 50 290 103 50 279 99 48

366 293 50 297 101 50 300 102 50 289 98 48

394 306 50 309 101 50 313 102 50 301 98 47

422 318 50 318 100 50 321 101 49 304 96 47

450 328 49 326 99 49 333 102 49 320 98 45

478 337 49 334 99 49 343 102 48 328 97 44

506 348 48 344 99 48 352 101 48 333 96 42

534 357 48 351 98 47 357 100 47 340 95 41

562 360 48 353 98 47 362 101 44 346 96 41

590 369 48 362 98 44 370 100 44 354 96 37

618 370 47 361 98 42 370 100 40 350 95 34

646 376 43 363 97 39 376 100 38 353 94 31

660 382 41 366 96 38 375 98 38 355 93 30

674 380 41 367 97 38 376 99 38 356 94 30

688 384 38 371 97 37 379 99 32 362 94 27

702 382 36 371 97 36 374 98 31 358 94 27

716 387 35 373 97 34 374 97 31 357 92 26

 

 

Mean for weeks 

1-13 155 156 101 160 104 156 101

14-52 243 247 102 255 105 248 102

53-103 355 348 98 355 100 338 95

 
62 1-Bromopropane, NTP TR 564

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FIGURE 5 

Growth Curves for Rats Exposed to 1-Bromopropane

by Inhalation for 2 Years
1-Bromopropane, NTP TR 564 63

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Pathology and Statistical Analyses

This section describes the statistically significant or biologically noteworthy changes in the incidences of malignant 

mesothelioma and neoplasms or nonneoplastic lesions of the large intestine, skin, pancreatic islets, nose, larynx, 

trachea, and lung. Summaries of the incidences of neoplasms and nonneoplastic lesions, statistical analyses of 

primary neoplasms that occurred with an incidence of at least 5% in at least one animal group, and historical 

incidences for the neoplasms mentioned in this section are presented in Appendix A for male rats and Appendix B 

for female rats.

Large Intestine: The incidence of adenoma of the large intestine (colon or rectum) in 500 ppm females was 

significantly greater than that in the chamber controls (Tables 9, B1, and B2). The incidences in the 250 and 

500 ppm groups of females exceeded the historical ranges for controls in inhalation studies and all routes of 

administration (Tables 9 and B3a). In 250 and 500 ppm males, the incidences of adenoma of the large intestine

were slightly increased compared to that in the chamber controls; although the increases were not statistically 

significant, the incidence in the 250 ppm group exceeded the historical control ranges for inhalation studies and all 

routes (Tables 9 and A3a). 

Large intestine adenomas were polypoid masses that protruded into the intestinal lumen (Plates 1 and 2). The 

epithelium lining the glands had fewer goblet cells than the epithelium from normal glands and was occasionally 

thickened by multiple layers of slightly enlarged neoplastic epithelial cells with basophilic cytoplasm and enlarged 

nuclei. There were variable numbers of mixed inflammatory cells in the stroma around the glands and in the stalk. 

No invasion of the submucosa layer of the large intestine was observed.
64 1-Bromopropane, NTP TR 564

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TABLE 9

Incidences of Adenoma of the Large Intestine in Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber 

Control 125 ppm 250 ppm 500 ppm

Male

Colona 50 50 50 50

Adenomab 0 0 0 1

Rectum 50 50 50 50

Adenoma 0 0 2 0

Colon or Rectum: Adenomac

Overall rated 0/50 (0%) 0/50 (0%) 2/50 (4%) 1/50 (2%)

Adjusted ratee 0.0% 0.0% 5.3% 2.8%

Terminal ratef 0/23 (0%) 0/26 (0%) 2/18 (11%) 0/13 (0%)

First incidence (days) —h — 729 (T) 682

Poly-3 testg P=0.197 —i P=0.216 P=0.472

Female

Colon 50 50 50 50

Adenoma 0 1 1 1 

Rectum 50 50 50 50

Adenoma 0 0 1 4 

Colon or Rectum: Adenomaj

Overall rate 0/50 (0%) 1/50 (2%) 2/50 (4%) 5/50 (10%)

Adjusted rate 0.0% 2.3% 4.7% 13.3%

Terminal rate 0/34 (0%) 1/33 (3%) 1/30 (3%) 4/24 (17%)

First incidence (days) — 730 (T) 607 719

Poly-3 test P=0.004 P=0.493 P=0.225 P=0.018

(T)Terminal sacrifice

a Number necropsied

b Number of animals with neoplasm

c Historical incidence for 2-year inhalation studies with chamber controls (mean ± standard deviation): 

 0/349; all routes: 2/1,398 (0.1% ± 0.5%), range 0%-2% 

d Number of animals with neoplasm per number of animals necropsied

e Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality

f Observed incidence at terminal kill

g Beneath the chamber control incidence are the P values associated with the trend test. Beneath the exposed group incidence are the P values 

corresponding to pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for differential 

mortality in animals that do not reach terminal sacrifice.

h Not applicable; no neoplasm in animal group

i Value of statistic cannot be computed.

j Historical incidence for inhalation studies: 0/350; all routes 3/1,350 (0.2% ± 0.6%), range 0%-2% 
1-Bromopropane, NTP TR 564 65

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Skin: In male rats, there were exposure concentration-related increased incidences of keratoacanthoma; 

keratoacanthoma or squamous cell carcinoma (combined); and keratoacanthoma, basal cell adenoma, basal cell 

carcinoma, or squamous cell carcinoma (combined) (Tables 10, A1, and A2). The incidences of keratoacanthoma 

and of keratoacanthoma or squamous cell carcinoma (combined) in 250 and 500 ppm males were significantly 

increased and exceeded the historical control ranges for inhalation studies (Tables 10 and A3b). The incidences of 

keratoacanthoma, basal cell adenoma, basal cell carcinoma, or squamous cell carcinoma (combined) were 

significantly increased in all exposed groups of males and exceeded the historical control range for inhalation 

studies. The incidences of basal cell adenoma in 250 ppm males and of squamous cell carcinoma in 500 ppm males 

were not significantly increased, but they exceeded the respective historical control ranges for inhalation studies 

(Tables 10, A1, and A3b). 

In female rats, there were increased incidences of squamous cell papilloma, keratoacanthoma, basal cell adenoma, or 

basal cell carcinoma (combined) in the 500 ppm group (Tables 10, B1, and B2). Although the increased incidences 

were not significant, they exceeded the respective historical control ranges for inhalation studies (Tables 10 and 

B3b).

Keratoacanthomas were well-demarcated, variably sized, crateriform masses in the dermis composed of squamous 

epithelium that formed thick folds. The center of the mass was filled with abundant keratin. Squamous cell 

carcinomas were characterized as masses composed of cords of pleomorphic squamous cells infiltrating the dermis 

and/or subcutis. There were varying amounts of keratin and fibrous connective tissue, which separated the cords of 

squamous cells within the neoplasms. Basal cell adenomas were well-demarcated masses composed of cords and 

lobules of basal cells with areas of sebaceous or squamous differentiation. Basal cell carcinomas had a similar 

appearance, but the cells in the carcinomas were more pleomorphic. The carcinomas were locally invasive and often 

contained areas of necrosis.
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TABLE 10

Incidences of Neoplasms of the Skin in Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber 

Control 125 ppm 250 ppm 500 ppm

Male

Number Necropsied 50 50 50 50

Basal Cell Adenomaa,b 0 1 2 1

Keratoacanthomac

Overall rated 0/50 (0%) 3/50 (6%) 6/50 (12%) 6/50 (12%)

Adjusted ratee 0.0% 7.4% 15.4% 16.2% 

Terminal ratef 0/23 (0%) 3/26 (12%) 2/18 (11%) 2/13 (15%)

First incidence (days) —h 729 (T) 488 562

Poly-3 testg P=0.008 P=0.115 P=0.012 P=0.010

Squamous Cell Carcinomai 1 1 0 2

Keratoacanthoma or Squamous Cell Carcinomaj

Overall rate 1/50 (2%) 4/50 (8%) 6/50 (12%) 8/50 (16%)

Adjusted rate 2.4% 9.8% 15.4% 21.4% 

Terminal rate 0/23 (0%) 3/26 (12%) 2/18 (11%) 3/13 (23%)

First incidence (days) 669 711 488 562

Poly-3 test P=0.006 P=0.171 P=0.044 P=0.009

Keratoacanthoma, Basal Cell Adenoma, Basal Cell Carcinoma, or Squamous Cell Carcinomak

Overall rate 1/50 (2%) 7/50 (14%) 9/50 (18%) 10/50 (20%)

Adjusted rate 2.4% 17.0% 22.6% 26.7%

Terminal rate 0/23 (0%) 5/26 (19%) 2/18 (11%) 4/13 (31%)

First incidence (days) 669 585 488 562

Poly-3 test P=0.003 P=0.028 P=0.006 P=0.002

Female

Squamous Cell Papilloma, Keratoacanthoma, Basal Cell Adenoma, or Basal Cell Carcinomal

Overall rate 1/50 (2%) 1/50 (2%) 1/50 (2%) 4/50 (8%)

Adjusted rate 2.2% 2.3% 2.4% 10.6%

Terminal rate 1/34 (3%) 1/33 (3%) 1/30 (3%) 4/24 (17%)

First incidence (days) 730 (T) 730 (T) 730 (T) 730 (T)

Poly-3 test P=0.050 P=0.753 P=0.746 P=0.128

(T)Terminal sacrifice

a Number of animals with neoplasm

b Historical incidence for 2-year inhalation studies with chamber controls (mean ± standard deviation): 4/349 (1.2% ± 1.1%), range 0%-2%; 

all routes: 15/1,398 (1.1% ± 1.4%), range 0%-4% 

c Historical incidence for inhalation studies: 10/349 (2.9% ± 3.7%), range 0%-8%; all routes: 66/1,398 (4.7% ± 4.2%), range 0%-16% 

d Number of animals with neoplasm per number of animals necropsied

e Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality

f Observed incidence at terminal kill

g Beneath the chamber control incidence are the P values associated with the trend test. Beneath the exposed group incidence are the P values 

corresponding to pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for differential 

mortality in animals that do not reach terminal sacrifice. 

h Not applicable; no neoplasm in animal group

i Historical incidence for inhalation studies: 1/349 (0.3% ± 0.8%), range 0%-2%; all routes: 8/1,398 (0.6% ± 0.9%), range 0%-2% 

j Historical incidence for inhalation studies: 11/349 (3.2% ± 3.5%), range 0%-8%; all routes: 74/1,398 (5.3% ± 4.1%), range 0%-16% 

k Historical incidence for inhalation studies: 19/349 (5.5% ± 4.5%), range 0%-10%; all routes: 97/1,398 (6.9% ± 4.9%), range 0%-20% 

l Historical incidence for inhalation studies: 2/350 (0.6% ± 1.0%), range 0%-2%; all routes: 16/1,350 (1.2% ± 1.8%), range 0%-6% 
1-Bromopropane, NTP TR 564 67

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Malignant Mesothelioma: The incidence of malignant mesothelioma in 500 ppm male rats was significantly greater 

than that in the chamber controls (Tables 11, A1, and A2). The incidence in the 500 ppm group exceeded the 

historical ranges for controls in inhalation studies and all routes (Tables 11 and A3c).

This neoplasm was found in the epididymis in all affected animals with other tissues variably affected, particularly 

the testis, which was affected in all but one animal. This suggests that the tunica vaginalis, the most common site of 

origin for mesotheliomas in F344/N rats (Hall, 1990), was the site of origin for all mesotheliomas in this study. 

These mesotheliomas were characterized by numerous, complex, papillary structures composed of pedunculated, 

fibrovascular stalks covered by one to several layers of cuboidal to flattened mesothelial cells (Plates 3 and 4). The 

stroma was prominent and often contained clusters of pleomorphic mesothelial cells that sometimes formed 

disorganized tubular structures. There was often extensive invasion of skeletal muscle and adipose tissue, but 

minimal invasion of underlying tissues at other sites.

TABLE 11

Incidences of Malignant Mesothelioma in Male Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber 

Control 125 ppm 250 ppm 500 ppm

Malignant Mesotheliomaa

Overall rateb 0/50 (0%) 2/50 (4%) 2/50 (4%) 4/50 (8%)

Adjusted ratec 0.0% 4.9% 5.2% 10.8%

Terminal rated 0/23 (0%) 2/26 (8%) 0/18 (0%) 1/13 (8%)

First incidence (days) —f 729 (T) 536 394

Poly-3 teste P=0.031 P=0.233 P=0.220 P=0.046

(T)Terminal sacrifice

a Historical incidence for 2-year inhalation studies with chamber controls (mean ± standard deviation): 5/349 (1.4% ± 2.2%), range 0%-6%; 

all routes: 35/1,398 (2.5% ± 2.3%), range 0%-6% 

b Number of animals with neoplasm per number of animals necropsied

c Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality

d Observed incidence at terminal kill

e Beneath the chamber control incidence are the P values associated with the trend test. Beneath the exposed group incidence are the P values 

corresponding to pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for differential 

mortality in animals that do not reach terminal sacrifice. 

f Not applicable; no neoplasm in animal group
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Pancreatic Islets: In male rats, the incidences of pancreatic islet adenoma were significantly increased in all 

exposed groups compared to the chamber controls (Tables 12, A1, and A2). However, the incidences were within 

the historical control ranges for inhalation studies and for all routes (Tables 12 and A3d). The incidences of 

pancreatic islet carcinoma were increased in the 125 and 250 ppm groups, but these increases were not statistically

significant. However, the incidence in the 125 ppm group exceeded the historical control ranges for inhalation 

studies and for all routes. The incidences of pancreatic islet adenoma or carcinoma (combined) were significantly 

increased in the 125 and 250 ppm groups, and the incidence in the 125 ppm group exceeded the historical control 

ranges for inhalation studies and for all routes of administration.

TABLE 12

Incidences of Pancreatic Islet Neoplasms in Male Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber 

Control 125 ppm 250 ppm 500 ppm

Adenomaa

Overall rateb 0/50 (0%) 5/50 (10%) 4/50 (8%) 5/50 (10%)

Adjusted ratec 0.0% 12.2% 10.4% 13.9%

Terminal rated 0/23 (0%) 4/26 (15%) 1/18 (6%) 4/13 (31%)

First incidence (days) —f 666 608 697

Poly-3 teste P=0.043 P=0.029 P=0.050 P=0.019

Carcinomag

Overall rate 3/50 (6%) 7/50 (14%) 5/50 (10%) 3/50 (6%)

Adjusted rate 7.2% 17.0% 13.0% 8.3% 

Terminal rate 2/23 (9%) 3/26 (12%) 3/18 (17%) 2/13 (15%)

First incidence (days) 686 687 578 687

Poly-3 test P=0.0516N P=0.149 P=0.312 P=0.594

Adenoma or Carcinomah

Overall rate 3/50 (6%) 10/50 (20%) 9/50 (18%) 8/50 (16%)

Adjusted rate 7.2% 24.2% 23.1% 22.2% 

Terminal rate 2/23 (9%) 5/26 (19%) 4/18 (22%) 6/13 (46%)

First incidence (days) 686 666 578 687

Poly-3 test P=0.093 P=0.031 P=0.043 P=0.057

a Historical incidence for 2-year inhalation studies with chamber controls (mean ± standard deviation): 20/349 (5.7% ± 3.9%), range 0%-12%; 

all routes: 90/1,394 (6.5% ± 3.6%), range 0%-14% 

b Number of animals with neoplasm per number of animals with pancreatic islets examined microscopically

c Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality

d Observed incidence at terminal kill

e Beneath the chamber control incidence are the P values associated with the trend test. Beneath the exposed group incidence are the P values 

corresponding to pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for differential 

mortality in animals that do not reach terminal sacrifice. A negative trend is indicated by N. 

f Not applicable; no neoplasm in animal group

g Historical incidence for inhalation studies: 17/349 (4.9% ± 3.3%), range 2%-10%; all routes: 29/1,394 (2.1% ± 2.6%), range 0%-10% 

h Historical incidence for inhalation studies: 37/349 (10.6% ± 4.8%), range 6%-18%; all routes: 119/1,394 (8.6% ± 4.0%), range 0%-18%
1-Bromopropane, NTP TR 564 69

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Adenomas were usually discrete, well-circumscribed masses of islet cells that were 1 mm in diameter or larger and 

compressed the surrounding acinar tissue. Occasionally, adenomas were encapsulated by a thin band of fibrous 

connective tissue. In some adenomas, groups of exocrine pancreatic acini were present within the adenomas at their 

periphery. Carcinomas, which tended to be larger than adenomas, were characterized by varying degrees of atypia 

and pleomorphism of the neoplastic cells, and they typically invaded the surrounding fibrous capsule or pancreatic 

tissue.

Nose: Incidences of suppurative chronic inflammation in 500 ppm males and females were significantly greater 

than those in the chamber controls (Tables 13, A4, and B4). Suppurative chronic inflammation was characterized by 

marked numbers of neutrophils with intralesional Splendore-Hoeppli material within the nasal cavity lumen, located 

primarily in Levels II and III of the nasal sections only (Plates 5 and 6). The designation of chronic was used to 

differentiate suppurative inflammation with Splendore-Hoeppli material from suppurative inflammation without 

Splendore-Hoeppli material, which was observed in other organs. Occasionally, neutrophils in the affected area 

would invade the subjacent lamina propria. Application of special staining for bacteria indicated the presence of 

Giemsa-positive and Gram-negative bacteria associated with the Splendore-Hoeppli material.

Chronic active inflammation was diagnosed in many animals of both sexes, including the chamber controls

(Tables 13, A4, and B4). The incidences in all exposed groups of females were significantly increased compared to 

that in the chamber controls. Chronic active inflammation was most commonly observed in Level II of nasal 

sections, and was characterized by the presence of lymphocytes and macrophages, with fewer neutrophils within or 

around the nasolacrimal duct, or within the lumina of submucosal glands or the lamina propria of the septum and 

turbinates.

The severity of epithelial hyaline droplet accumulation was increased in all exposed groups of females compared to 

that in the chamber controls (Table 13). Hyaline droplet accumulation was characterized by the presence of 

intracytoplasmic, eosinophilic globules primarily within the olfactory epithelium and to a lesser extent the 
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TABLE 13 

Incidences of Selected Nonneoplastic Lesions of the Respiratory System in Rats

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber 

Control 125 ppm 250 ppm 500 ppm

Male

Nosea 50 48 48 50

Inflammation, Suppurative, Chronicb 0 1 (4.0)c 2 (4.0) 7** (4.0)

Inflammation, Chronic Active 29 (1.6) 33 (1.4) 34 (1.5) 35 (1.5)

Epithelium, Accumulation, 

Hyaline Droplet 44 (1.0) 39 (1.5) 36 (1.3) 44 (1.3)

Glands, Hyperplasia 5 (2.0) 14* (2.0) 14** (2.0) 15** (2.0)

Larynx 50 50 50 50

Inflammation, Suppurative, Chronic 0 0 0 1 (4.0)

Inflammation, Chronic Active 21 (1.4) 28 (1.3) 31* (1.4) 26 (1.3)

Metaplasia, Squamous 4 (1.0) 6 (1.0) 8 (1.1) 5 (1.2)

Trachea 50 50 50 50

Inflammation, Chronic Active 1 (2.0) 1 (1.0) 1 (1.0) 4 (1.5)

Epithelium, Hyperplasia 1 (2.0) 0 0 1 (2.0)

Lung 50 50 50 50

Inflammation, Suppurative, Chronic 0 0 1 (4.0) 3 (4.0)

Female

Nose 50 50 49 50

Inflammation, Suppurative, Chronic 0 1 (4.0) 3 (4.0) 7** (4.0)

Inflammation, Chronic Active 24 (1.3) 37** (1.5) 37** (1.5) 36** (1.3)

Epithelium, Accumulation, 

Hyaline Droplet 48 (1.1) 48 (1.8) 48 (1.7) 47 (1.9)

Glands, Hyperplasia 6 (2.0) 23** (2.0) 28** (2.0) 30** (2.0)

Respiratory Epithelium, Hyperplasia 5 (1.2) 13* (1.3) 9 (1.7) 18** (1.5)

Olfactory Epithelium, Metaplasia,

Respiratory 3 (1.7) 4 (1.8) 6 (1.8) 9* (2.2)

Larynx 50 50 50 50

Inflammation, Suppurative, Chronic 0 0 0 3 (4.0)

Inflammation, Chronic Active 18 (1.1) 25 (1.5) 30** (1.4) 32** (1.5)

Metaplasia, Squamous 3 (1.3) 2 (1.5) 6 (1.3) 21** (1.7)

Trachea 50 50 50 50

Inflammation, Chronic Active 0 4 (1.0) 1 (1.0) 6** (1.7)

Epithelium, Hyperplasia 0 0 0 4* (1.8)

Lung 50 50 50 50

Inflammation, Suppurative, Chronic 0 0 0 4* (4.0)

* Significantly different (P≤0.05) from the chamber control group by the Poly-3 test

** P≤0.01

a Number of animals with tissue examined microscopically

b Number of animals with lesion

c Average severity grade of lesions in affected animals: 1=minimal, 2=mild, 3=moderate, 4=marked
1-Bromopropane, NTP TR 564 71

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respiratory epithelium. In general, this lesion was seen in many animals in the chamber control and exposed groups 

and it occurred most often in Levels II and III.

The incidences of glandular hyperplasia were significantly increased in all exposed groups of males and females 

(Tables 13, A4, and B4). Glandular hyperplasia occurred most often in Level II of the nasal section, and was at 

times associated with inflammation. This lesion consisted of mild to moderate proliferation of submucosal glands. 

The incidences of respiratory epithelial hyperplasia were significantly increased in 125 and 500 ppm females 

(Tables 13 and B4). Respiratory epithelial hyperplasia was located most often along the septum in Level II and 

occasionally the ethmoid turbinates in Level III of the nasal sections. This lesion consisted of thickening of the 

respiratory epithelium by increased numbers of tall, columnar, respiratory epithelial cells.

The incidence of respiratory metaplasia of the olfactory epithelium was significantly increased in 500 ppm females 

(Tables 13 and B4). This lesion was primarily located in Level II at the dorsal meatus and septum but occasionally 

in Level III of the nasal sections. In the affected areas, the olfactory epithelium had been replaced by ciliated 

respiratory epithelium. 

Larynx: Suppurative chronic inflammation was present in only one male and three females exposed to 500 ppm 

(Tables 13 and B4). This lesion was not seen in the chamber controls of either sex. Suppurative, chronic 

inflammation of the larynx was characterized by marked numbers of neutrophils, often degenerate, within the glands 

and lamina propria with intraglandular Splendore-Hoeppli material (Plate 7). 

The incidences of chronic active inflammation in 250 ppm males and females and 500 ppm females were 

significantly increased (Tables 13, A4, and B4). This lesion consisted of minimal to moderate numbers of 

lymphocytes, macrophages, and neutrophils within the lamina propria and glandular lumens.
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In females, the incidence of squamous metaplasia in the 500 ppm group was significantly greater than that in the 

chamber controls (Tables 13 and B4). Squamous metaplasia was characterized by the replacement of normal 

respiratory epithelium by squamous epithelial cells.

Trachea: In females, the incidences of chronic active inflammation and epithelial hyperplasia were significantly 

increased in the 500 ppm group (Tables 13 and B4). Both lesions also occurred in males, but the incidences were 

not significantly increased. Chronic active inflammation was characterized by the presence of minimal to moderate 

infiltrates of lymphocytes and macrophages, with fewer neutrophils in the lamina propria. Hyperplasia of the 

epithelium consisted of increased numbers of respiratory epithelial cells with densely packed nuclei.

Lung: Suppurative chronic inflammation occurred in a few 500 ppm males and females and in one 250 ppm male

(Tables 13, A4, and B4). The lesion was morphologically similar to that seen in other organs.

Other Findings: Suppurative chronic inflammation with Splendore-Hoeppli material was sporadically observed in 

several other organs of exposed animals, including skin [all exposed groups of males (with an exposure 

concentration-related increase in incidences), and 125 and 500 ppm females], prostate gland (500 ppm males), 

preputial gland (125 ppm males), Harderian gland (500 ppm males and females), skeletal muscle (500 ppm males), 

bone (500 ppm males and females), ear (500 ppm females), and peritoneum (500 ppm males) (Tables A4 and B4). 

The designation of chronic was given to all diagnoses in which Splendore-Hoeppli material was present to 

distinguish it from suppurative inflammation without Splendore-Hoeppli material.
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MICE

2-WEEK STUDY

All early deaths occurred during the first week of exposure; all 2,000 ppm males and two 2,000 ppm females, four 

500 ppm males, one 1,000 ppm male, and one 1,000 ppm female died early (Table 14). Final mean body weights of 

exposed groups were similar to those of the chamber controls; the mean body weight gain of 1,000 ppm males was 

significantly decreased. Abnormal breathing, lethargy, and eye discharge were observed primarily during week 1 

and occurred only in groups exposed to 500 ppm or greater.

TABLE 14

Survival and Body Weights of Mice in the 2-Week Inhalation Study of 1-Bromopropane

Final Weight Concentration a Mean Body Weightb (g) Survival Relative to Controls (ppm) Initial Final Change (%)

Male

0 5/5 23.9 ± 0.2 28.0 ± 0.4 4.1 ± 0.3 

125 5/5 24.2 ± 0.1 28.9 ± 0.5 4.7 ± 0.5 103

250 5/5 23.7 ± 0.3 27.0 ± 0.4 3.3 ± 0.2 96

500 1/5c 24.0 ± 0.4 25.8 2.1 92 

1,000 4/5d 23.9 ± 0.2 26.6 ± 0.5 2.6 ± 0.8* 95 

2,000 0/5e 24.1 ± 0.2 — — 

Female

0 5/5 20.0 ± 0.5 22.9 ± 0.2 3.0 ± 0.3

125 5/5 19.4 ± 0.4 22.2 ± 0.5 2.8 ± 0.5 97

250 5/5 20.4 ± 0.2 22.8 ± 0.2 2.5 ± 0.2 100

500 5/5 19.8 ± 0.2 23.4 ± 0.6 3.6 ± 0.5 102 

1,000 4/5f 19.8 ± 0.3 22.8 ± 0.5 3.3 ± 0.6 99

2,000 3/5d 19.8 ± 0.2 22.7 ± 0.3 3.2 ± 0.2 99 

* Significantly different (P≤0.05) from the chamber control group by Williams’ test

a Number of animals surviving at 2 weeks/number initially in group

b Weights and weight changes are given as mean ± standard error. Subsequent calculations are based on animals surviving to the end of the 

study.

c Days of death: 4, 4, 4, 5

d Day of deaths: 3 

e Days of death: 2, 2, 2, 2, 3

f Day of death: 5 
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In 1,000 ppm males, the absolute and relative heart weights were significantly less than those of the chamber 

controls while the absolute and relative liver weights were significantly greater than those of the chamber controls 

(Table G3). Absolute right kidney weights were significantly increased in 250 ppm or greater females, and the 

relative right kidney weights were significantly increased in 1,000 and 2,000 ppm females. Absolute and relative 

liver weights of 500 ppm or greater females were significantly greater than those of the chamber controls. The 

absolute and relative thymus weights of 1,000 and 2,000 ppm females were significantly decreased. 

Microscopic lesions related to 1-bromopropane exposure occurred in the lung, liver, and nose of males and females 

and were primarily seen in mice exposed to 500 ppm or greater (Table 15). Bronchiole necrosis occurred in the 

lungs of all exposed male and female mice and the severity of this lesion was increased in the 2,000 ppm groups. 

The lungs of exposed mice also had sporadic incidences of regeneration, cytoplasmic vacuolization, and acute 

inflammation involving bronchiolar epithelium. Incidences of centrilobular necrosis occurred in the liver of most 

males and females exposed to 500 ppm or greater. In addition, the incidences of centrilobular chronic inflammation 

and cytoplasmic vacuolization were significantly increased in 1,000 ppm males and females. Sporadic incidences of 

nasal lesions occurred in exposed groups of mice; the no-effect level for nose lesions was 250 ppm in males and 500 

ppm in females.

Exposure Concentration Selection Rationale: Based on decreased survival and increased liver and kidney weights

in the 2-week study, 1-bromopropane exposure concentrations selected for the 3-month inhalation study in mice

were 62.5, 125, 250, and 500 ppm. 
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TABLE 15

Incidences of Selected Nonneoplastic Lesions in Mice in the 2-Week Inhalation Study of 1-Bromopropane

Chamber 

Control 125 ppm 250 ppm 500 ppm 1,000 ppm 2,000 ppm

Male

Lunga 5 5 5 5 5 5

Bronchiole, Necrosisb 0 5** (1.0) c 5** (1.0) 5** (2.0) 5** (1.4) 5** (3.4)

Bronchiole, Regeneration 0 5** (1.0) 5** (1.0) 2 (2.0) 4* (1.5) 0

Bronchiole, Vacuolization,

Cytoplasmic 0 0 0 4* (3.0) 1 (3.0) 0 

Perivascular, Inflammation, Acute 0 0 0 3 (2.0) 0 5** (1.4)

Liver 5 0 5 5 5 5 

Centrilobular, Necrosis 0 0 5** (3.8) 5** (3.2) 5** (2.4)

Centrilobular, Inflammation, 

Chronic 0 0 1 (2.0) 4* (3.3) 0 

Centrilobular, Vacuolization,

Cytoplasmic 0 0 3 (1.7) 4* (2.0) 0

Nose 5 0 5 5 5 5

Glands, Necrosis 0 0 4* (2.8) 3 (1.7) 5** (2.6)

Inflammation, Suppurative 0 0 0 3 (1.7) 0 

Olfactory Epithelium, Atrophy 0 0 0 4* (1.8) 0 

Olfactory Epithelium, Necrosis 0 0 4* (2.0) 2 (2.0) 5** (3.8)

Olfactory Epithelium, 

Regeneration 0 0 1 (1.0) 4* (2.3) 0 

Respiratory Epithelium, Necrosis 0 0 0 1 (3.0) 5** (2.8)

Respiratory Epithelium, 

Vacuolization, Cytoplasmic 0 0 4* (3.0) 1 (3.0) 0 
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TABLE 15

Incidences of Selected Nonneoplastic Lesions in Mice in the 2-Week Inhalation Study of 1-Bromopropane

Chamber 

Control 125 ppm 250 ppm 500 ppm 1,000 ppm 2,000 ppm

Female

Lung 5 5 5 5 5 5

Bronchiole, Necrosis 0 5** (1.2) 5** (1.0) 5** (1.0) 5** (1.4) 5** (2.2)

Bronchiole, Regeneration 0 5** (1.2) 5** (1.0) 5** (2.0) 4* (1.8) 3 (2.3)

Bronchiole, Vacuolization,

Cytoplasmic 0 0 0 0 1 (3.0) 0

Perivascular, Inflammation, Acute 0 0 0 0 1 (1.0) 2 (4.0)

Liver 5 0 5 5 5 5 

Centrilobular, Necrosis 0 0 3 (1.3) 5** (2.8) 5** (1.8)

Centrilobular, Inflammation, 

Chronic 0 0 3 (1.3) 4* (3.0) 3 (1.3)

Centrilobular, Vacuolization,

Cytoplasmic 0 0 3 (1.7) 5** (1.4) 3 (2.0)

Nose 5 0 0 5 5 5 

Glands, Necrosis 0 0 1 (3.0) 2 (3.0)

Inflammation, Suppurative 0 0 0 1 (1.0)

Olfactory Epithelium, Atrophy 0 0 4* (1.0) 3 (1.7)

Olfactory Epithelium, Necrosis 0 0 1 (3.0) 2 (4.0)

Olfactory Epithelium, 

Regeneration 0 0 4* (1.5) 3 (2.3)

Respiratory Epithelium, Necrosis 0 0 1 (2.0) 2 (2.5)

Respiratory Epithelium, 

Vacuolization, Cytoplasmic 0 0 1 (4.0) 0 

* Significantly different (P≤0.05) from the chamber control group by the Fisher exact test

** P≤0.01

a Number of animals with tissue examined microscopically

b Number of animals with lesion

c Average severity grade of lesions in affected animals: 1=minimal, 2=mild, 3=moderate, 4=marked
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3-MONTH STUDY

One 250 ppm male and four males and five females in the 500 ppm groups died early (Table 16). Final mean body 

weights and body weight gains of all exposed groups were similar to those of the chamber control groups (Table 16 

and Figure 6). By day 3, lethargy was observed in males and females exposed to 500 ppm, and abnormal breathing 

was observed in moribund mice during week 1. 

There were no changes in hematology endpoints that were considered to be related to 1-bromopropane exposure

(Table F2).

Absolute right kidney weights of 250 and 500 ppm males, and the relative right kidney weight of 500 ppm males were 

significantly less than those of the chamber controls (Table G4). Relative liver weights of 250 and 500 ppm males 

were significantly increased. The absolute and relative right kidney, liver, and lung weights of 500 ppm females and 

the relative liver weight of 250 ppm females were significantly greater than those of the chamber controls. 

TABLE 16

Survival and Body Weights of Mice in the 3-Month Inhalation Study of 1-Bromopropane

Concentration Mean Body Weightb (g) Survivala Relative to Controls (ppm) Initial Final Change (%)

Male

0 10/10 23.6 ± 0.3 39.6 ± 0.8 16.0 ± 0.7

62.5 10/10 23.7 ± 0.2 39.0 ± 0.9 15.3 ± 0.8 98

125 10/10 23.6 ± 0.1 39.6 ± 0.6 15.9 ± 0.6 100 

250 9/10c 23.6 ± 0.3 37.9 ± 0.7 14.4 ± 0.6 96

500 6/10d 23.4 ± 0.3 37.4 ± 1.4 14.2 ± 1.2 95 

Female

0 10/10 19.9 ± 0.2 30.9 ± 0.7 11.0 ± 0.5

62.5 10/10 20.3 ± 0.3 33.0 ± 1.3 12.7 ± 1.1 107 

125 10/10 20.4 ± 0.3 31.9 ± 0.8 11.5 ± 0.6 103 

250 10/10 19.7 ± 0.3 30.2 ± 0.9 10.4 ± 0.9 98

500 5/10e 20.2 ± 0.1 31.3 ± 1.4 11.0 ± 1.5 101 

Final Weight

a Number of animals surviving at 3 months/number initially in group

b Weights and weight changes are given as mean ± standard error. Differences from the chamber control group are not significant by Dunnett’s 

test. Subsequent calculations are based on animals surviving to the end of the study.

c Week of death: 4 

d Weeks of death: 1, 1, 1, 2

e Week of deaths: 1
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FIGURE 6 

Growth Curves for Mice Exposed to 1-Bromopropane

by Inhalation for 3 Months 
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There were slight increases in the cauda epididymis weights (9.1% and 17.1%) and significant decreases in sperm 

motility (4.1% and 3.8%) in 250 and 500 ppm male mice, respectively (Table H3). There was also a significant 

decrease in the sperm per gram cauda (28%) in 500 ppm males. Exposed groups of female mice differed 

significantly from the chamber controls in the relative amount of time spent in the various stages of estrous 

(Table H4). Female mice in the 500 ppm group spent significantly more time in extended diestrus than the chamber 

controls; 250 ppm females spent significantly more time in extended estrus than the chamber controls. The length of 

the estrous cycle of 500 ppm females was increased slightly (one half day).

Treatment-related nasal lesions were seen only in mice that died early. Incidences of cytoplasmic vacuolization of 

the respiratory epithelium were significantly increased in 500 ppm males and females, and the incidence of necrosis 

of the respiratory epithelium was significantly increased in 500 ppm females (Table 17). Olfactory epithelium 

necrosis and necrosis of the lateral nasal glands occurred in a few 500 ppm males. A single incidence of 

cytoplasmic vacuolization of the respiratory epithelium occurred in a male exposed to 250 ppm. Respiratory 

epithelial lesions were located in the lateral walls and turbinates of Level I. The olfactory necrosis was located in 

the dorsal meatus of Level II and in the dorsal meatus, septum, and turbinates of Level III. Vacuolation consisted of 

a single, large, clear vacuole displacing the cytoplasm. Necrosis was characterized by cells with increased 

cytoplasmic eosinophilia with loss of cellular detail and/or pyknotic or fragmented nuclei. Necrotic cells were 

frequently sloughed into the airways or missing.

Incidences of cytoplasmic vacuolization and necrosis of the respiratory epithelium lining the larynx and trachea 

occurred in male and female mice exposed to 500 ppm that died early and in the one early death male exposed to

250 ppm; the incidences of tracheal cytoplasmic vacuolization were significantly increased in 500 ppm males and 

females (Table 17). Vacuolation of the laryngeal lining epithelium also occurred in one 62.5 ppm female that 

survived to the end of the study. Vacuolation was characterized by cells with a large expansile clear space 

occupying the majority of the cytoplasm. These cells often had a pyknotic nucleus at the center, suggesting that 

vacuolation progressed to necrosis. These cells had often lost their cilia. Hyperplasia of the tracheal epithelium

occurred in two 500 ppm males (one an early death and the other a terminal animal). Hyperplasia was characterized 

by increased cell numbers with loss of the normal organization of the epithelium.
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TABLE 17

Incidences of Selected Nonneoplastic Lesions in Mice in the 3-Month Inhalation Study of 1-Bromopropane

Chamber 

Control 62.5 ppm 125 ppm 250 ppm 500 ppm

Male

Nosea 10 10 10 10 10

Respiratory Epithelium, Vacuolization 

Cytoplasmicb 0 0 0 1 (3.0)c 4* (3.0)

Respiratory Epithelium, Necrosis 0 0 0 0 2 (1.5)

Olfactory Epithelium, Necrosis 0 0 0 0 2 (2.5)

Glands, Necrosis 0 0 0 0 1 (2.0)

Larynx 10 10 10 10 9

Vacuolization Cytoplasmic 0 0 0 1 (1.0) 3 (1.7)

Necrosis 0 0 0 0 2 (1.5)

Trachea 10 10 10 10 10

Vacuolization, Cytoplasmic 0 0 0 1 (3.0) 4* (1.0)

Necrosis 0 0 0 1 (2.0) 0

Hyperplasia 0 0 0 0 2 (1.0)

Lung 10 10 10 10 10

Bronchiole, Vacuolization Cytoplasmic 0 0 0 1 (3.0) 4* (2.5)

Bronchiole, Necrosis 0 0 0 1 (2.0) 3 (2.0)

Bronchiole, Regeneration 3 (1.0) 3 (1.0) 4 (1.0) 7 (1.0) 5 (1.0)

Liver 10 10 10 10 10

Necrosis 0 0 0 0 4* (4.0)

Hepatocyte, Degeneration 0 0 0 0 4* (2.5)

Vacuolization Cytoplasmic 0 0 0 0 1 (1.0)

Inflammation, Chronic 0 0 0 1 (1.0) 6** (1.3)

Mineralization 0 0 0 0 5* (1.8)
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TABLE 17

Incidences of Selected Nonneoplastic Lesions in Mice in the 3-Month Inhalation Study of 1-Bromopropane

Chamber 

Control 62.5 ppm 125 ppm 250 ppm 500 ppm

Female

Nose 10 10 10 10 10

Respiratory Epithelium, Vacuolization 

Cytoplasmic 0 0 0 0 5* (3.0)

Respiratory Epithelium, Necrosis 0 0 0 0 5* (1.4)

Larynx 10 10 10 10 10

Vacuolization Cytoplasmic 0 1 (1.0) 0 0 1 (1.0)

Necrosis 0 0 0 0 1 (1.0)

Trachea 10 10 10 9 10

Vacuolization Cytoplasmic 0 0 0 0 4* (2.0)

Necrosis 0 0 0 0 2 (2.5)

Lung 10 10 10 10 10

Bronchiole, Vacuolization Cytoplasmic 0 0 0 0 5* (3.2)

Bronchiole, Necrosis 0 0 0 0 5* (2.0)

Bronchiole, Regeneration 1 (1.0) 4 (1.0) 5 (1.0) 5 (1.0) 3 (1.0)

Liver 10 10 10 10 10

Necrosis 0 0 0 0 5* (3.6)

Hepatocyte, Degeneration 0 0 0 0 5* (2.2)

Inflammation, Chronic 0 0 0 0 5* (1.8)

Mineralization 0 0 0 0 4* (1.5)

Adrenal Cortex 10 10 10 10 10

Necrosis 0 0 0 0 5* (3.4)

Inflammation, Chronic 0 0 0 0 2 (2.0)

* Significantly different (P≤0.05) from the chamber control group by the Fisher exact test

** P≤0.01

a Number of animals with tissue examined microscopically

b Number of animals with lesion

c Average severity grade of lesions in affected animals: 1=minimal, 2=mild, 3=moderate, 4=marked
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In the lung, incidences of cytoplasmic vacuolization of the bronchiolar epithelium were significantly increased in 

500 ppm males and females (Table 17). This lesion also occurred in the 250 ppm male that died early. The 

incidence of necrosis of the bronchiolar epithelium was significantly increased in 500 ppm females; this lesion also 

occurred in 500 ppm males and the 250 ppm male that died early. Necrosis consisted of epithelial cells with 

pyknotic nuclei, sloughed epithelial cells, and areas of bronchial mucosa devoid of epithelial cells or lined by 

attenuated epithelial cells. Cells remaining often contained colorless vacuoles displacing the cytoplasm. 

Regeneration of bronchiolar epithelium occurred in all groups of mice and was not treatment related. Regeneration 

was described as flattened and disorganized epithelium with variation in nuclear size and location. Nuclei tended to 

be apical rather than basilar. This lesion was graded as minimal in all cases.

In the liver, incidences of hepatocellular necrosis and hepatocellular degeneration were significantly increased in 

500 ppm males and females; a single incidence of cytoplasmic vacuolization occurred in a 500 ppm male (Table 17). 

These lesions were also seen in the early death animals in the 500 ppm groups. Necrosis often extended beyond the 

centrilobular zone and was massive in some animals; it was characterized by uniform eosinophilic staining of 

hepatocytes and loss of cellular detail. Cytoplasmic degeneration and/or vacuolation, which were often seen 

peripheral to the necrosis, consisted of swollen and foamy hepatocytes with one large or many tiny clear vacuoles 

displacing the cytoplasm and with centrally located nuclei with condensed chromatin. Chronic inflammation 

occurred in 500 ppm terminal sacrifice animals of both sexes and in one male exposed to 250 ppm, and the 

incidences of this lesion were significantly increased in the 500 ppm groups. The inflammation consisted of 

lymphocytes, macrophages, large pigment-laden macrophages, and occasional multinucleated giant cells. 

Mineralization occurred in 500 ppm mice of both sexes that survived to the end of the study, and the incidences of 

this lesion were significantly increased in these groups. 

Necrosis of the adrenal cortex (the zona fasciculata being most affected with extension into the zona glomerulosa to 

a lesser degree) occurred in 500 ppm female mice that died early, and the incidence of this lesion was significantly 

increased in this group (Table 17). Chronic inflammation was noted at the corticomedullary junction in the adrenal 

cortex of two 500 ppm females that survived to the end of the study.
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Exposure Concentration Selection Rationale: Based on mortality at the highest exposure concentration, changes in 

organ weights, and the incidences of various nonneoplastic lesions in the 3-month study, 1-bromopropane exposure 

concentrations selected for the 2-year inhalation study in mice were 62.5, 125, and 250 ppm. 
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2-YEAR STUDY

Survival

Estimates of 2-year survival probabilities for male and female mice are shown in Table 18 and in the Kaplan-Meier 

survival curves (Figure 7). Survival of exposed groups of mice was similar to that of the chamber control groups.

TABLE 18

Survival of Mice in the 2-Year Inhalation Study of 1-Bromopropane

62.5 ppm 125 ppm 250 ppm Control

Male

Animals initially in study 50 50 50 50

Moribund 6 13 9 9 

Natural deaths 7 4 9 5 

Animals surviving to study termination 37 33 32 36

Percent probability of survival at end of studya 74 66 64 72

Mean survival (days)b 689 686 703 658

Survival analysisc P=0.934 P=0.526 P=0.486 P=0.888

Female

Animals initially in study 50 50 50 50

Moribund 10 7 8 8 

Natural deaths 4 3 5 0 

Animals surviving to study termination 36d 40 37 42d

Percent probability of survival at end of study 72 80 74 82

Mean survival (days) 698 713 699 714

Survival analysis P=0.363N P=0.413N P=0.967N P=0.298N

Chamber 

a Kaplan-Meier determinations

b Mean of all deaths (uncensored, censored, and terminal sacrifice)

c The result of the life table trend test (Tarone, 1975) is in the chamber control column, and the results of the life table pairwise comparisons 

(Cox, 1972) with the chamber controls are in the exposed group columns. A negative trend or lower mortality in an exposure group is 

indicated by N. 

d Includes one animal that died during the last week of the study
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FIGURE 7 

Kaplan-Meier Survival Curves for Mice 

Exposed to 1-Bromopropane by Inhalation for 2 Years 
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Body Weights and Clinical Findings

Mean body weights of exposed groups of male and female mice were similar to those of the chamber controls 

throughout the study (Figure 8; Tables 19 and 20). No clinical findings related to exposure to 1-bromopropane were 

observed.
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FIGURE 8 

Growth Curves for Mice Exposed to 1-Bromopropane

by Inhalation for 2 Years
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TABLE 19

Mean Body Weights and Survival of Male Mice in the 2-Year Inhalation Study of 1-Bromopropane

Days Chamber Control 62.5 ppm 125 ppm 250 ppm

on Av. Wt. No. of Av. Wt. Wt. (% of No. of Av. Wt. Wt. (% of No. of Av. Wt. Wt. (% of No. of 

Study (g) Survivors (g) controls) Survivors (g) controls) Survivors (g) controls) Survivors

 

1 23.2 50 23.2 100 50 23.1 100 50 22.8 98 50

12 25.7 50 26.0 101 50 26.0 101 50 25.6 99 50

19 26.8 50 27.2 101 50 27.0 101 50 26.7 100 50

26 27.9 50 28.3 101 50 28.1 101 50 27.6 99 50

33 29.2 50 29.3 100 50 29.0 100 50 28.5 98 50

40 30.2 50 30.0 99 50 29.7 99 50 29.3 97 50

47 31.3 50 31.1 99 50 31.0 99 50 30.1 96 48

54 32.2 50 32.2 100 50 31.6 98 50 31.0 96 48

61 33.3 50 33.3 100 50 32.5 98 50 32.0 96 48

68 34.6 50 34.4 99 50 33.8 98 50 32.9 95 48

75 34.8 50 34.8 100 50 34.3 99 50 33.3 96 48

82 35.2 50 35.5 101 50 34.7 98 50 34.0 96 48

89 36.2 50 36.4 100 50 35.6 98 50 34.7 96 48

117 39.5 50 39.7 100 50 39.0 99 50 38.6 98 48

145 42.1 50 42.1 100 50 40.2 96 50 40.9 97 48

173 44.1 50 44.6 101 50 42.9 97 50 43.1 98 48

201 45.6 50 46.3 102 50 44.6 98 50 44.9 98 48

229 48.4 50 48.6 101 50 47.0 97 50 46.7 97 48

257 49.3 50 49.7 101 50 48.2 98 50 47.9 97 48

285 50.3 50 50.8 101 50 49.5 98 50 49.4 98 48

313 50.6 50 51.1 101 50 49.9 99 50 49.7 98 48

341 51.4 49 51.8 101 50 50.7 99 50 50.5 98 48

369 52.3 49 52.5 101 50 51.4 98 50 51.4 98 47

397 52.0 49 51.9 100 50 51.3 99 50 51.2 99 46

425 52.5 48 52.4 100 48 51.8 99 50 51.7 99 45

453 52.6 48 52.6 100 47 52.2 99 50 52.5 100 45

481 53.0 47 52.3 99 47 51.9 98 50 52.5 99 43

509 53.3 47 52.8 99 47 52.3 98 50 53.2 100 43

537 53.4 47 52.9 99 46 52.2 98 49 53.2 100 43

565 52.8 45 52.6 100 45 51.9 98 49 53.3 101 42

593 53.2 43 53.1 100 43 51.7 97 49 53.5 101 41

621 53.4 41 51.7 97 43 52.2 98 45 53.5 100 40

649 52.6 41 51.0 97 41 51.5 98 42 53.0 101 39

663 52.1 41 51.0 98 38 50.6 97 41 52.6 101 39

677 51.8 41 50.9 98 38 50.8 98 39 52.6 102 39

691 51.3 39 50.4 98 36 50.0 98 37 51.8 101 38

705 50.9 39 50.4 99 35 49.8 98 35 51.3 101 37

719 50.9 37 50.5 99 33 50.4 99 32 51.7 102 36

 

 

Mean for weeks 

1-13 30.8 30.9 100 30.5 99 29.9 97

14-52 46.8 47.2 101 45.8 98 45.7 98

53-103 52.4 51.8 99 51.4 98 52.4 100

 

 
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TABLE 20

Mean Body Weights and Survival of Female Mice in the 2-Year Inhalation Study of 1-Bromopropane

Days Chamber Control 62.5 ppm 125 ppm 250 ppm

on Av. Wt. No. of Av. Wt. Wt. (% of No. of Av. Wt. Wt. (% of No. of Av. Wt. Wt. (% of No. of 

Study (g) Survivors (g) controls) Survivors (g) controls) Survivors (g) controls) Survivors

 

1 19.4 50 19.4 100 50 19.2 99 50 19.1 98 50

12 21.2 50 21.1 100 50 21.3 101 50 21.1 100 50

19 22.3 50 22.3 100 50 22.1 99 50 22.1 99 50

26 23.4 50 23.2 99 50 23.2 99 50 23.3 100 50

33 24.3 50 24.2 99 50 24.2 100 50 24.3 100 50

40 24.8 50 24.7 99 50 25.0 101 50 25.0 101 50

47 26.2 50 25.7 98 50 26.2 100 50 25.8 99 50

54 26.9 50 26.5 99 50 26.4 98 50 26.5 99 50

61 27.3 50 27.0 99 50 27.4 100 50 26.8 98 50

68 27.5 50 27.0 98 50 27.6 100 50 27.2 99 50

75 28.0 50 27.7 99 50 28.2 100 50 27.6 98 50

82 28.7 50 28.4 99 50 28.8 100 50 28.4 99 50

89 29.5 50 28.4 96 50 29.3 100 50 28.5 97 50

117 32.1 50 31.6 99 50 32.6 102 50 31.0 97 50

145 34.6 50 34.3 99 50 34.8 101 50 33.0 95 50

173 37.4 50 37.0 99 50 37.9 101 50 34.8 93 50

201 38.8 50 39.0 100 50 39.9 103 50 36.4 94 50

229 42.1 50 42.1 100 50 43.2 103 50 39.1 93 50

257 44.4 50 44.5 100 50 45.2 102 50 41.0 92 50

285 46.8 50 46.9 100 50 47.5 101 50 43.8 94 50

313 48.2 50 48.1 100 50 48.7 101 50 45.4 94 50

341 49.3 50 49.8 101 50 50.4 102 50 46.6 95 50

369 52.8 50 52.1 99 50 53.2 101 49 49.8 94 50

397 53.6 50 53.6 100 50 54.0 101 49 50.8 95 50

425 55.8 50 55.4 99 50 55.2 99 49 52.7 94 50

453 57.2 50 57.3 100 50 57.8 101 49 55.0 96 50

481 58.6 49 58.5 100 50 58.8 100 49 55.6 95 49

509 60.2 49 59.9 100 49 59.6 99 49 56.9 95 49

537 60.9 49 60.8 100 49 60.3 99 47 58.2 96 49

565 60.4 46 61.3 102 48 60.7 101 47 59.2 98 48

593 61.2 45 62.1 101 47 61.3 100 45 60.1 98 47

621 59.3 43 61.5 104 47 61.0 103 43 60.0 101 47

649 58.2 40 61.6 106 46 59.9 103 42 59.7 103 46

663 56.6 40 60.6 107 45 59.8 106 41 58.8 104 44

677 56.2 38 60.4 107 44 59.5 106 41 58.8 105 44

691 55.8 37 59.5 107 42 58.6 105 40 57.2 103 44

705 55.3 37 59.4 108 42 57.9 105 39 56.5 102 43

719 55.9 36 60.1 108 41 58.0 104 37 55.7 100 42

 

 

Mean for weeks 

1-13 25.3 25.0 99 25.3 100 25.1 99

14-52 41.5 41.5 100 42.2 102 39.0 94

53-103 57.4 59.0 103 58.5 102 56.6 99

 
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Pathology and Statistical Analyses 

This section describes the statistically significant or biologically noteworthy changes in the incidences of neoplasms 

and/or nonneoplastic lesions of the lung, nose, larynx, and trachea. Summaries of the incidences of neoplasms and 

nonneoplastic lesions, statistical analyses of primary neoplasms that occurred with an incidence of at least 5% in at 

least one animal group, and historical incidences for the neoplasms mentioned in this section are presented in 

Appendix C for male mice and Appendix D for female mice. 

Lung: In the females, there were treatment-related increased incidences of alveolar/bronchiolar adenoma, 

alveolar/bronchiolar carcinoma, and alveolar/bronchiolar adenoma or carcinoma (combined). The incidences of 

alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in all exposed groups

(Tables 21, D1, and D2). The incidence of alveolar/bronchiolar adenoma in 250 ppm females and the incidences of 

alveolar/bronchiolar carcinoma in 62.5 and 125 ppm females were significantly increased. The incidences of 

alveolar/bronchiolar adenoma in the 250 ppm group and of alveolar/bronchiolar carcinoma and alveolar/bronchiolar

adenoma or carcinoma (combined) in all exposed female groups exceeded the respective historical control ranges for 

inhalation studies (Tables 21 and D3). 

Alveolar/bronchiolar carcinomas varied from moderately-differentiated, circumscribed lesions to anaplastic, poorly 

circumscribed, infiltrative lesions. They were variable in size and shape and their growth patterns were papillary or 

solid with regions of squamous metaplasia, spindle cell differentiation, and necrosis. Alveolar/bronchiolar

adenomas were usually smaller, well-differentiated, circumscribed lesions that often compressed the adjacent 

parenchyma; and most were papillary. 

Cytoplasmic vacuolization of bronchiolar epithelium occurred in all exposed groups of male and female mice, and 

the incidences in all exposed groups of male mice were significantly increased (Tables 21, C3, and D4). This lesion 

did not occur in chamber control mice. Histologically, this lesion was characterized by large, solitary, clear 

vacuoles, expanding the cytoplasm of bronchiolar epithelial cells (Plates 8 through 10). Affected epithelial cells 

often lacked cilia. This lesion is similar to that described in the 3-month inhalation study of 1-bromopropane in 

mice. 
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TABLE 21

Incidences of Neoplasms and Nonneoplastic Lesions of the Respiratory System in Mice

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber 

Control 62.5 ppm 125 ppm 250 ppm

Male

Lunga 50 50 49 49

Bronchiole, Vacuolization Cytoplasmicb 0 18** (1.7) c 19** (1.7) 17** (1.8)

Bronchiole, Regeneration 1 (1.0) 44** (1.0) 38** (1.3) 47** (1.6)

Bronchiole, Necrosis 0 0 0 1 (3.0)

Nose 50 50 50 50

Respiratory Epithelium,

Vacuolization Cytoplasmic 0 12** (1.8) 19** (1.9) 20** (2.2)

Respiratory Epithelium, Hyperplasia 16 (1.3) 29** (2.0) 23 (2.0) 26* (2.7)

Olfactory Epithelium, Metaplasia,

Respiratory 0 7** (1.6) 6* (1.3) 3 (1.3)

Olfactory Epithelium, Atrophy 2 (2.0) 4 (2.3) 7 (2.3) 4 (1.8)

Larynx 48 50 48 50

Vacuolization Cytoplasmic 0 5* (1.4) 10** (1.1) 11** (1.6)

Trachea 49 50 47 50

Vacuolization Cytoplasmic 0 15** (1.5) 24** (1.8) 24** (2.3)

Female

Lung 50 50 50 50

Bronchiole, Vacuolization Cytoplasmic 0 3 (1.7) 4 (1.5) 3 (1.3)

Bronchiole, Regeneration 0 45** (1.2) 43** (1.3) 49** (1.6)

Bronchiole Necrosis 0 0 1 (3.0) 0

Alveolar/bronchiolar Adenoma, Multiple 0 0 0 2

Alveolar/bronchiolar Adenoma (includes multiple)d

Overall ratee 1/50 (2%) 6/50 (12%) 4/50 (8%) 10/50 (20%)

Adjusted ratef 2.2% 12.8% 8.9% 20.8%

Terminal rateg 1/36 (3%) 6/40 (15%) 4/37 (11%) 7/41 (17%)

First incidence (days) 731 (T) 731 (T) 731 (T) 649

Poly-3 testh P=0.007 P=0.064 P=0.181 P=0.006

Alveolar/bronchiolar Carcinoma, Multiple 0 2 1 1

Alveolar/bronchiolar Carcinoma (includes multiple)i

Overall rate 0/50 (0%) 7/50 (14%) 5/50 (10%) 4/50 (8%)

Adjusted rate 0.0% 14.9% 11.1% 8.5%

Terminal rate 0/36 (0%) 6/40 (15%) 5/37 (14%) 4/41 (10%)

First incidence (days) —j 709 731 (T) 731 (T)

Poly-3 test P=0.277 P=0.009 P=0.031 P=0.068

Alveolar/bronchiolar Adenoma or Carcinomak

Overall rate 1/50 (2%) 9/50 (18%) 8/50 (16%) 14/50 (28%)

Adjusted rate 2.2% 19.2% 17.8% 29.2%

Terminal rate 1/36 (3%) 8/40 (20%) 8/37 (22%) 11/41 (27%)

First incidence (days) 731 (T) 709 731 (T) 649

Poly-3 test P<0.001 P=0.010 P=0.016 P<0.001
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TABLE 21

Incidences of Neoplasms and Nonneoplastic Lesions of the Respiratory System in Mice

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber 

Control 62.5 ppm 125 ppm 250 ppm

Female (continued)

Nose 50 50 50 50

Respiratory Epithelium,

Vacuolization Cytoplasmic 0 3 (1.3) 5* (1.6) 8** (1.6)

Respiratory Epithelium, Hyperplasia 11 (1.1) 25** (1.4) 28** (1.5) 27** (1.7)

Olfactory Epithelium, Metaplasia,

Respiratory 0 4 (1.0) 5* (1.0) 14** (1.1)

Olfactory Epithelium, Atrophy 0 0 0 6* (1.3)

Larynx 50 50 50 50

Vacuolization Cytoplasmic 0 3 (1.3) 2 (2.0) 2 (2.5)

Trachea 50 49 50 50

Vacuolization Cytoplasmic 0 8** (1.5) 7** (1.9) 4 (2.0)

* Significantly different (P≤0.05) from the chamber control group by the Poly-3 test

** P≤0.01

(T)Terminal sacrifice

a Number of animals with tissue examined microscopically

b Number of animals with lesion

c Average severity grade of lesions in affected animals: 1=minimal, 2=mild, 3=moderate, 4=marked

d Historical incidence for 2-year inhalation studies with chamber controls (mean ± standard deviation): 18/350 (5.1% ± 3.8%), range 2%-12%; 

all routes: 73/1,496 (4.9% ± 3.4%), range 0%-12%

e Number of animals with neoplasm per number of animals with lung examined microscopically

f Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality

g Observed incidence at terminal kill

h Beneath the chamber control incidence is the P value associated with the trend test. Beneath the exposed group incidence is the P value 

corresponding to pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for differential 

mortality in animals that do not reach terminal sacrifice.

i Historical incidence for inhalation studies: 9/350 (2.6% ± 2.8%), range 0%-6%; all routes: 59/1,496 (3.9% ± 3.4%), range 0%-12% 

j Not applicable; no neoplasms in animal group

k Historical incidence for inhalation studies: 27/350 (7.7% ± 3.6%), range 2%-12%; all routes: 128/1,496 (8.6% ± 3.7%), range 2%-18% 

Cytoplasmic vacuolization of bronchiolar epithelium often accompanied bronchiolar regeneration and was 

accompanied by bronchiole necrosis in one 250 ppm male and one 125 ppm female (Tables 21, C3, and D4). 

Bronchiolar regeneration occurred in most exposed male and female mice, but not in chamber controls (except for a

single chamber control male with minimal regeneration). The incidences were similar among exposed groups, 

although slight exposure concentration-related increases in severities were noted. Histologically, bronchiolar 

regeneration was characterized by disorganized, elongated, and flattened epithelial cells lining terminal bronchioles

(Plates 8 through 10). Regenerative epithelial cells often had increased basophilia, lacked cilia, had variable 

amounts of cytoplasm, and had increased nuclear to cytoplasmic ratios. Nuclei of regenerative cells tended to be 
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apical rather than basilar, and often varied in size and shape. In the affected bronchioles there was evidence of cell 

loss. Many of the affected bronchioles contained sloughed epithelial cells and occasional necrotic epithelial cells 

characterized by small, pyknotic nuclei and homogenous, hypereosinophilic cytoplasm.

Nose: There were exposure concentration-related increased incidences of cytoplasmic vacuolization of respiratory 

epithelium in male and female mice; the incidences in all exposed groups of males and in 125 and 250 ppm females 

were significantly increased (Tables 21, C3, and D4). This lesion did not occur in chamber control mice. 

Cytoplasmic vacuolization involved the respiratory epithelium on the lateral surfaces of nasoturbinates in Levels I 

and II (Plate 11). Histologically, this lesion was characterized by large, solitary, clear vacuoles expanding the 

cytoplasm of respiratory epithelial cells. Oftentimes, affected epithelial cells lacked cilia. Occasionally, nuclei of 

affected epithelial cells were pyknotic. This lesion is similar to that described in the 3-month inhalation study of 

1-bromopropane in mice.

There were treatment-related increased incidences of respiratory epithelial hyperplasia in the dorsal meatus(es) in

Level I in mice of both sexes (Tables 21, C3, and D4); the incidences in all exposed female groups and in 62.5 and 

250 ppm males were significantly increased. Although present in chamber controls, the incidence and severity of 

respiratory epithelial hyperplasia increased with increasing exposure concentration, and male mice were more 

severely affected than female mice. Histological criteria for respiratory epithelial hyperplasia included thickened 

epithelium due to increased cellularity, submucosal epithelial invaginations with intraepithelial crypt-like structures 

(pseudoglands), and/or finger-like projections of epithelium that extended into the nasal cavity. Lesions were 

graded minimal, mild, moderate, or marked (i.e., grades 1, 2, 3, or 4) depending upon the degree of involvement of 

one or both meatus(es). Grade 0 was normal. Grade 1 (minimal) respiratory epithelial hyperplasia was diagnosed 

when the respiratory epithelium displayed focal or regional mucosal thickening with submucosal epithelial 

invaginations in one or both dorsal meatus(es). Grade 2 (mild) respiratory epithelial hyperplasia was diagnosed 

when at least 2/3 of one or both dorsal meatus(es) displayed respiratory epithelium with submucosal epithelial 

invaginations and/or epithelial papillary projections that together involved < 25% into the dorsal meatus(es). 

Grade 3 (moderate) respiratory epithelial hyperplasia was diagnosed when two thirds to all of both dorsal 

meatus(es) displayed respiratory epithelium with submucosal epithelial invaginations forming intraepithelial 
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crypt-like structures (pseudoglands) and finger-like papillary projections of epithelium that together involved 25% to 

50% into the dorsal meatus(es). Grade 4 (marked) respiratory epithelial hyperplasia was diagnosed when 

approximately all of both dorsal meatuses had hyperplastic respiratory epithelium with tortuous, submucosal 

invaginations forming intraepithelial crypt-like structures (pseudoglands) and finger-like papillary projections of 

epithelium that together involved 50% to 75% into the dorsal meatuses.

There were treatment-related increased incidences of respiratory metaplasia of olfactory epithelium in male mice 

and exposure concentration-related increases in female mice; incidences of this lesion were significantly increased 

in 62.5 and 125 ppm males and 125 and 250 ppm females (Tables 21, C3, and D4). This lesion was not observed in 

chamber control mice. Located at Levels II and/or III of the nasal sections, the lesion was characterized as 

segmental replacement of olfactory epithelium by ciliated, pseudostratified epithelium resembling respiratory 

epithelium of the anterior nasal cavity; this lesion was often associated with submucosal inflammation and/or 

glandular hyperplasia. The severity of the lesions was graded minimal to mild based on the degree of involvement 

of the dorsal meatuses and/or turbinates.

The incidence of olfactory epithelial atrophy was significantly increased in 250 ppm females (Tables 21 and D4). 

The incidences of this lesion were slightly increased in all exposed groups of males, but the increases were not 

statistically significant (Tables 21 and C3). This lesion consisted of segmental thinning of the olfactory epithelium 

at Level II and/or III of the nasal cavity due to loss of neuronal cells with primarily sustentacular and basal cells 

remaining. It was often associated with submucosal inflammation and/or glandular hyperplasia, and usually was 

present within the dorsal meatuses.

Larynx and Trachea: There were increased incidences of cytoplasmic vacuolization of respiratory epithelium in the 

larynx and the trachea of exposed males and females; the incidences were significantly increased in both tissues in 

all exposed groups of males, and in the trachea of 62.5 and 125 ppm females (Tables 21, C3, and D4). This lesion 

did not occur in chamber control mice. Histologically, this lesion was characterized by large, solitary, clear 

vacuoles expanding the cytoplasm of respiratory epithelial cells (Plate 12). Affected epithelial cells often lacked 
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cilia. Occasionally, nuclei of affected epithelial cells were pyknotic. This lesion is similar to that described in the 

3-month inhalation study of 1-bromopropane in mice.

GENETIC TOXICOLOGY

1-Bromopropane (doses up to 10,000 μg/plate) was not mutagenic in either of two independent bacterial 

mutagenicity assays, with or without exogenous metabolic activation (Table E1). Bacterial strains tested included

Salmonella typhimurium strains TA97, TA98, TA100, and TA1535, as well as Escherichia coli strain 

WP2 uvrA/pKM101. In addition to the negative results in the two bacterial tests, no increases in the frequencies of 

micronucleated normochromatic erythrocytes were seen in peripheral blood of male or female B6C3F1 mice 

exposed for 3 months to 62.5 to 500 ppm 1-bromopropane via inhalation (Table E2). The percentage of 

reticulocytes (polychromatic erythrocytes) in the peripheral blood of male and female mice was unaltered by 

1-bromopropane exposure, suggesting a lack of chemical-associated bone marrow toxicity.
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PLATE 1 

Polypoid adenoma in the large intestine (rectum) of a female F344/N rat 

exposed to 500 ppm 1-bromopropane by inhalation for 2 years. The adenoma 

occupies the majority of the intestinal lumen. H&E

PLATE 2 

Higher magnification of Plate 1. Note the multiple layers of basophilic 

neoplastic epithelial cells lining the glands. H&E

PLATE 4 

Higher magnification of Plate 3. Note the cuboidal to flattened neoplastic 

mesothelial cells lining the papillary structures and the prominent stroma 

containing clusters of neoplastic mesothelial cells. H&E

PLATE 3 

Malignant mesothelioma on the parietal surface of the peritoneal cavity of a 

male F344/N rat exposed to 500 ppm 1-bromopropane by inhalation for 

2 years. Note the complex papillary structures. H&E
PLATE 5 

Suppurative chronic inflammation (arrows) in Level II of the nasal cavity of a 

male F344/N rat exposed to 500 ppm 1-bromopropane by inhalation for 

2 years. H&E

PLATE 6 

Higher magnification of Plate 5. The suppurative chronic inflammation is 

composed of abundant eosinophilic necrotic cellular debris, fibrin, and 

neutrophils, and contains Splendore-Hoeppli material (arrow). These lesions 

were often bordered by a dense, fibrous capsule. H&E

PLATE 7 

Larynx of a male F344/N rat exposed to 500 ppm 1-bromopropane by 

inhalation for 2 years. Note the squamous metaplasia of the lining 

epithelium (arrowheads) associated with chronic active inflammation within 

the submucosa and suppurative chronic inflammation within the lumen of the 

glands (arrows). H&E

PLATE 8 

Bronchiolar epithelial regeneration and vacuolization in the lung of a male 

B6C3F1 mouse exposed to 250 ppm 1-bromopropane by inhalation for 

2 years. There are sloughed epithelial cells in the lumen of the bronchiole 

(arrows) indicative of epithelial cell loss. H&E
PLATE 9 

Higher magnification of Plate 8. The regenerated epithelium has prominent, 

polyhedral cells and is disorganized with loss of cilia (arrows). There is also 

vacuolization of the bronchiolar epithelium. H&E

PLATE 10

Bronchiolar epithelial necrosis and cytoplasmic vacuolization in the lung of a 

male B6C3F1 mouse exposed to 250 ppm 1-bromopropane by inhalation for 

2 years. Note the abundant necrotic cells sloughing into the bronchiolar lumen 

(arrows). H&E

PLATE 11

Cytoplasmic vacuolization of the respiratory epithelium lining the 

nasoturbinates (arrows) in Level I of the nasal cavity of a male B6C3F1 mouse 

exposed to 250 ppm 1-bromopropane by inhalation for 2 years. H&E

PLATE 12

Vacuolization of the respiratory epithelium (arrows) in the trachea of a male 

B6C3F1 mouse exposed to 250 ppm 1-bromopropane by inhalation for 

2 years. H&E
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DISCUSSION AND CONCLUSIONS

Occupational exposure to 1-bromopropane is expected to increase significantly because of its increasing use as a 

presumably less toxic and less flammable replacement for several high-production volume chemicals used in 

emissive applications such as vapor and immersion degreasing operations and critical cleaning of electronics and 

metals. 1-Bromopropane has also been proposed as a replacement for ozone depleting refrigerants (Fed. Regist., 

2000). 1-Bromopropane was nominated for study based on the potential for widespread exposure to this chemical

and a lack of chronic toxicity and carcinogenicity data. Because previous short-term studies demonstrated that 

1-bromopropane is a neurotoxicant and a reproductive toxicant in laboratory animals (Yu et al., 1998; Ichihara et al., 

2000a), the main focus of the current studies was to evaluate the chronic toxicity and carcinogenicity of 

1-bromopropane. 

Exposure to 1-bromopropane concentrations of 500 ppm or greater in the 2-week and 3-month studies resulted in 

early deaths of mice. The liver was identified as the primary target site in these mice, and severe centrilobular 

necrosis was likely the cause of death. In the 2-week study, moderate to marked centrilobular necrosis was present 

in all males and most females exposed to 500 ppm or greater. In the 3-month study, extensive hepatic centrilobular 

necrosis was present only in 500 ppm mice that died early. Centrilobular chronic inflammation was present in livers 

of surviving 500 ppm mice, and no hepatocellular lesions were observed in mice exposed to lower concentrations

except in one 250 ppm male. The centrilobular location of the lesions in the region of the liver that contains the 

highest levels of P450 activity suggests that the hepatotoxicity may be due to a reactive metabolite of 

1-bromopropane. In mice, 1-bromopropane is oxidatively metabolized in the liver by cytochrome P450 2E1 

(CYP2E1) to reactive metabolites that may be responsible for the toxicity of 1-bromopropane (Garner et al., 2007; 

Liu et al., 2009). 2-Oxo-1-bromopropane, a highly reactive oxidative metabolite of 1-bromopropane (Robinson 

et al., 1989), has been shown to alkylate proteins and inactivate enzymes (Beeley and Neurath, 1968; Cohen et al., 

1982; Mitchell et al., 1998). Detoxification of 1-bromopropane metabolites occurs primarily via
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glutathione-S-transferase (GST) -mediated conjugation with glutathione (Liu et al., 2009). Glutathione is important 

in protecting tissues from alkylating metabolites. Marked reduction or depletion of liver glutathione results in 

enhanced toxicity (Ketterer et al., 1983). In the current studies, mice exposed to concentrations greater than 

250 ppm may have produced levels of metabolites that exceeded the amount of glutathione available for 

conjugation. Oxidative metabolites of 1-bromopropane may also deplete glutathione by inhibiting enzymes required 

for glutathione synthesis. Alternatively, 1-bromopropane metabolites may inhibit hepatocellular GST thereby 

preventing glutathione conjugation. These mechanisms are supported by recent studies comparing the susceptibility

of three strains of male inbred mice (BALB/cA, C57BL/6, DBA/2J) to 1-bromopropane-mediated hepatotoxicity 

(Liu et al., 2009). BALB/cA mice were the most susceptible to 1-bromopropane hepatotoxicity and also had the 

highest CYP2E1 activity, the lowest glutathione levels, and the lowest GST activity. 

Rats were less sensitive than mice to 1-bromopropane toxicity in the 2-week and 3-month studies. In the 2-week rat 

study, there were no treatment-related deaths and significantly lower body weights occurred only in the 1,000 and 

2,000 ppm groups. Liver weights were increased in most groups of exposed rats; however, there was no 

histopathologic evidence of toxicity. In the 3-month study, a mild cytoplasmic vacuolization was present in the liver

of all 500 and 1,000 ppm rats, and in half of the 250 ppm male rats. Other indications of mild hepatotoxicity in 

exposed rats were increased liver weights and increases in serum sorbitol dehydrogenase levels. Qualitatively, rats 

and mice produce the same oxidative metabolites of 1-bromopropane (Garner et al., 2007); however, mice were 

reported to have a greater capacity to oxidatively metabolize 1-bromopropane than rats (Garner et al., 2006). This 

species difference in metabolic capacity may partially explain why extensive hepatotoxicity and early deaths 

occurred in exposed mice and not in rats. 

1-Bromopropane also caused lesions in the respiratory tract of mice, although these lesions were not considered as 

severe as those in the liver. In the 2-week study, respiratory tract lesions were most severe in mice that died early 

after exposure to 500 ppm or greater. Necrosis and vacuolization of the nasal respiratory and olfactory epithelium 

and prominent necrosis of the bronchiolar epithelium were present only in early death mice. In survivors exposed to 

500 ppm or greater, lesions consisted primarily of regeneration of the olfactory epithelium and the bronchiolar 

epithelium. In the 3-month study, mild necrosis of the nasal respiratory and olfactory epithelium and minimal 
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necrosis of the epithelium lining the larynx and trachea were observed primarily in 500 ppm mice that died early. 

Minimal regeneration of the bronchiolar epithelium was observed in the majority of 250 and 500 ppm mice that 

survived to the end of the study. Although the upper respiratory tract lesions in exposed mice may be due to a direct 

irritant effect, metabolism of 1-bromopropane to a toxic metabolite by the nasal epithelium cannot be ruled out. 

In the 2-week and 3-month studies, rats were less susceptible than mice to 1-bromopropane-related lesions in the 

nasal cavity. In the 2-week study, foci of minimal necrosis of the respiratory epithelium and minimal to mild 

suppurative inflammation were present in a few 1,000 and 2,000 ppm male rats. There were no exposure-related 

nasal lesions in rats exposed for 3 months. Although the mechanism of this species difference is unclear, it may be 

associated with differences in metabolic capability in the nasal epithelium. 

The potential immunotoxicity of 1-bromopropane was investigated because of earlier reports of immunosuppression 

following oral exposure to 1-bromopropane (Lee et al., 2007a), and the structurally related chemicals 

2-bromopropane (Jeong et al., 2002), and 1,3-dibromopropane (Lee et al., 2007b). 1-Bromopropane caused some 

evidence of immunosuppression in F344/N rats and B6C3F1 mice after inhalation exposure for 4 and 10 weeks

(Anderson et al., 2009). Significant decreases in the IgM response to sheep red blood cells (SRBCs) were observed 

in both species after exposure to 1-bromopropane (Anderson et al., 2009). In addition, significant decreases in the 

total number of spleen cells and T-cells were observed in mice after 4 weeks of exposure to 1-bromopropane 

concentrations ranging from 125 to 1,000 ppm. Lee et al. (2007a,b) suggested that the immunotoxicity of 

1-bromopropane and 1,3-dibromopropane may result from depletion of glutathione. Immunosuppression caused by 

these two chemicals was correlated with chemical-induced hepatotoxicity and decreases in liver and spleen 

glutathione. Partial depletion of glutathione has been shown to affect immune function (effector phase of cytotoxic 

T-cell responses and IL-2 dependent functions) (Dröge et al., 1994). Although glutathione levels were not measured 

in the current studies, it is possible that the hepatotoxicity and immunotoxicity observed in mice and rats after 

inhalation of 1-bromopropane may be due to reduced levels of glutathione. 

In the 2-year study of 1-bromopropane in mice, there was no reduction in survival and no effect on body weights of 

males or females. Chronic inhalation of 1-bromopropane resulted in neoplasms in female mice but not in male
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mice. There was clear evidence that 1-bromopropane exposure caused increased incidences of alveolar/bronchiolar 

adenoma or carcinoma (combined) in female mice. Because alveolar/bronchiolar adenomas are known to progress 

to carcinomas (Boorman and Eustis, 1990), the NTP combines the incidences of these neoplasms. The incidences of 

alveolar/bronchiolar adenoma or carcinoma (combined) in female mice increased in an exposure concentrationrelated manner, were significantly greater than that in the chamber controls at all exposure concentrations, and 

exceeded the range in historical controls for inhalation studies. The incidence of alveolar/bronchiolar adenoma in 

female mice exposed to 250 ppm was significantly increased compared to that in the chamber controls and exceeded 

the range in historical controls for inhalation studies and for all routes. The incidences of alveolar/bronchiolar 

carcinoma in 62.5 and 125 ppm female mice were significantly increased compared to the chamber controls; 

although not statistically increased, alveolar/bronchiolar carcinoma occurred in 8% of the 250 ppm females. The 

incidences in all exposed groups of female mice exceeded the historical control range for inhalation studies and the 

incidence in the 62.5 ppm females exceeded the historical control range from all routes. Alveolar/bronchiolar 

carcinoma was not observed in chamber control female mice. Chronic exposure to the structurally related 

1,2-dibromoethane also caused alveolar/bronchiolar adenomas and carcinomas in male and female mice and female 

rats (NTP, 1982a).

In the 2-year study in rats, survival of 500 ppm males was reduced; however, there were no chemical-related effects 

on body weights. Exposure to 1-bromopropane for 2 years resulted in neoplasms in rats at various sites. There was 

clear evidence that increased incidences of adenoma of the large intestine (colon and rectum) were treatment related 

in female rats. The increased incidences of adenoma were exposure concentration related, and the incidence in the

500 ppm group was significantly greater than that in the chamber controls. There was some evidence that adenomas 

of the large intestine in male rats were treatment related. Adenomas were found in the large intestine of two 

250 ppm male rats (4%) and in one 500 ppm male rat (2%). Although the increased incidences in males were not 

statistically significant, the presence of these neoplasms in females and the low historical occurrence of these

neoplasms suggest that they were treatment related. Adenomas of the large intestine are rare in control male and 

female rats, occurring at a rate of less than 0.2%. Although no large intestine carcinomas were observed in male or 

female rats in the current study, adenomas of the large intestine can progress to carcinomas (Deschner, 1983; Chang, 

1984; Nigro, 1985). Oral treatment of rats with two brominated methanes (bromodichloromethane and 
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tribromomethane) also resulted in significantly increased incidences of adenocarcinoma of the large intestine in both 

male and female rats (NTP, 1987, 1989).

There was some evidence that chronic exposure to 1-bromopropane caused an increase in the incidences of

neoplasms of the skin in male rats, and skin neoplasms in female rats may have been related to exposure. In males, 

the combined incidences of all neoplasms of epithelial origin increased in a significant exposure concentrationdependent manner. The incidences were significantly increased in all exposed groups of males relative to chamber

controls and exceeded the range in historical controls from inhalation studies. The most numerous neoplasms were 

identified as keratoacanthoma, a benign neoplasm that morphologically resembles squamous cell carcinoma. In 

males, the incidences of keratoacanthoma increased with a positive trend; the incidences in the 250 and 500 ppm 

groups were significantly increased compared to chamber controls, and exceeded the historical control range for 

inhalation studies. The increased incidence of keratoacanthoma is a concern because there is evidence that it can 

progress to squamous cell carcinoma, a highly malignant tumor (Elwell et al., 1990). Squamous cell carcinoma is a 

rare neoplasm occurring in only 0.6% of historical controls from all studies. Although not statistically significant, 

the incidence of squamous cell carcinoma in 500 ppm male rats was greater than that in the chamber controls and 

exceeded the historical control ranges for inhalation studies and for all routes. In females, the incidence of 

squamous cell papilloma, keratoacanthoma, basal cell adenoma, or basal cell carcinoma (combined) in the 500 ppm 

group exceeded the historical control range for inhalation studies. Keratoacanthomas occurred in females, but 

unlike in the males, the incidences were not increased compared to the concurrent chamber controls or historical 

controls. No squamous cell carcinomas were seen in female rats.

The evidence that 1-bromopropane exposure was associated with an increased incidence of pancreatic islet adenoma 

in male rats was equivocal. Although the increased incidences of pancreatic islet adenoma were statistically 

significant at all exposure concentrations, the incidence in the chamber controls (0/50) was less than the mean in 

historical controls from inhalation studies (6%), and the incidences in exposed groups did not exceed the historical 

control ranges of inhalation studies or all routes. 
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The evidence for malignant mesothelioma in all organs was equivocal in male rats. The incidences of malignant 

mesothelioma occurred with a positive trend, but only the incidence in the 500 ppm group was significantly 

increased. The overall strength of this evidence was considered equivocal because of the common occurrence of 

malignant mesothelioma in male rats in 2-year NTP studies. The historical control range for malignant 

mesothelioma in male rats for inhalation studies and by all routes is 0% to 6%. Although the incidence in the 

500 ppm group was significantly increased, it only exceeded the historical control range by one incidence. 

An unusual nonneoplastic finding in rats exposed to 1-bromopropane for 2 years was the presence of SplendoreHoeppli reaction material associated with suppurative inflammation. Lesions with Splendore-Hoeppli material were 

present primarily in the nose and skin of exposed male and female rats, although other sites were affected. The 

exact composition and mechanism of formation of Splendore-Hoeppli material is unknown, but it is thought to 

represent deposition of antigen-antibody complexes and debris from host inflammatory cells (Hussein, 2008). 

Alternatively, it may represent glycoproteins, lipid, and calcium derived from host leukocytes (Bhagavan et al., 

1982). Histologically, Splendore-Hoeppli material appears as strongly eosinophilic, amorphous material 

surrounding or adjacent to the causative agent, typically fungi, helminthes or bacteria (Hussein, 2008). The 

Splendore-Hoeppli bodies appear microscopically as distinct radiating, star-like, or club-shaped configurations. In 

the United States, Splendore-Hoeppli bodies are often seen in association with botryomycotic infections caused by 

Proteus, Escherichia coli or Pseudomonas aeruginosa (Wenig et al., 1996). In this study, cultures from four of five 

1-bromopropane-exposed rats with this lesion were positive for P. aeruginosa. It is not clear why lesions with 

Splendore-Hoeppli bodies were only present in rats, since both rats and mice were equally immunosuppressed after 

1-bromopropane exposure. Species differences in the presence of opportunistic bacteria, or differences in innate 

resistance to infection, may have played a role in this difference.

The presence of lesions with Splendore-Hoeppli bodies in rats was considered to be treatment related. The 

incidence of lesions with Splendore-Hoeppli bodies increased with 1-bromopropane exposure concentration, and 

was considerably higher in males (34%) and females (28%) exposed to 500 ppm. Lesions with Splendore-Hoeppli 

bodies were not present in chamber control rats. Although the mechanism is not clear, immunosuppression in 

1-bromopropane-exposed rats may have contributed to the development of Splendore-Hoeppli bodies. The 
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development of botryomycosis and formation of Splendore-Hoeppli bodies in humans may be facilitated by 

immunosuppression as it has been associated with diabetes, immunoglobulin deficiency, cutaneous anergy, 

corticosteroid treatment, and AIDS (Schlossberg et al., 1980; Brunken et al., 1983; Patterson et al., 1987).

Because adequate data were available demonstrating the developmental and reproductive toxicity of 

1-bromopropane, only sperm motility and vaginal cytology were evaluated in the current studies. Based upon the 

effects on sperm count and motility and estrous cyclicity seen in the 3-month studies, we conclude that 

1-bromopropane has the potential to produce adverse effects on fertility and reproductive performance in rodent 

studies involving similar exposures. The NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) 

conducted an extensive evaluation on the potential effects of 1-bromopropane on human reproduction and 

development (NTP, 2003). The CERHR concluded that based upon the available data, inhaled 1-bromopropane 

causes prenatal developmental toxicity and reproductive toxicity in male and female rats; however, available human 

data were insufficient to draw conclusions on the potential for reproductive or developmental toxicity. The overall 

NTP conclusion was that “there is serious concern for reproductive and developmental effects of 1-bromopropane at 

the upper end of the human occupational exposure range (18 to 381 ppm).” “Serious concern” is the highest level of 

NTP conclusion regarding the possibilities that human development and reproduction might be adversely affected.

CONCLUSIONS

Under the conditions of these 2-year inhalation studies, there was some evidence of carcinogenic activity* of 

1-bromopropane in male F344/N rats based on the occurrence of rare adenomas of the large intestine and increased 

incidences of neoplasms of the skin. Increased incidences of malignant mesothelioma and pancreatic islet adenoma 

may also have been related to 1-bromopropane exposure. There was clear evidence of carcinogenic activity of 

1-bromopropane in female F344/N rats based on increased incidences of adenoma of the large intestine. Increased 

incidences of neoplasms of the skin may also have been related to 1-bromopropane exposure. There was no 

evidence of carcinogenic activity of 1-bromopropane in male B6C3F1 mice exposed to concentrations of 62.5, 125, 

or 250 ppm 1-bromopropane. There was clear evidence of carcinogenic activity of 1-bromopropane in female 

B6C3F1 mice based on increased incidences of alveolar/bronchiolar neoplasms.
104 1-Bromopropane, NTP TR 564

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Exposure to 1-bromopropane resulted in increased incidences of nonneoplastic lesions in the nose of rats and mice, 

the larynx of rats and male mice, the trachea of female rats and male and female mice, and the lung of mice. 

Suppurative inflammatory lesions with Splendore-Hoeppli material were present primarily in the nose and skin of 

male and female rats exposed to 1-bromopropane.

* Explanation of Levels of Evidence of Carcinogenic Activity is on page 14. 
105

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REFERENCES

The Aldrich Library of 13C and 1H FT-NMR Spectra (1993). Vol. 1, 1st ed., p. 82(C). Aldrich Chemical Co., Inc., 

Milwaukee, WI.

The Aldrich Library of FT-IR Spectra (1997). Vol. 1, 2nd ed., p. 84(B). Aldrich Chemical Co., Inc., Milwaukee, 

WI.

American Conference of Governmental Industrial Hygienists (ACGIH) (2005). Documentation of the TLV’s and 

BEI’s with Other World Wide Occupational Exposure Values. CD-ROM. ACGIH, Cincinnati, OH.

American Conference of Governmental Industrial Hygienists (ACGIH) (2009). 2009 TLVs® and BEIs® Threshold 

Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. ACGIH, Cincinnati, 

OH.

Anderson, S.E., Munson, A.E., Butterworth, L.F., Germolec, D., Morgan, D.L., Roycroft, J.R., Dill, J., and 

Mead, B.J. (2009). Whole body inhalation exposure to 1-bromopropane suppresses the IgM response to sheep red 

blood cells in female B6C3F1 mice and Fischer 344 rats. Inhal. Tox. (in press). 

Ashby, J., and Tennant, R.W. (1991). Definitive relationships among chemical structure, carcinogenicity and 

mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat. Res. 257, 229-306.

Bailer, A.J., and Portier, C.J. (1988). Effects of treatment-induced mortality and tumor-induced mortality on tests 

for carcinogenicity in small samples. Biometrics 44, 417-431.

Barber, E.D., Donish, W.H., and Mueller, K.R. (1981). A procedure for the quantitative measurement of the 

mutagenicity of volatile liquids in the Ames Salmonella/microsome assay. Mutat. Res. 90, 31-48.

Barnsley, E.A. (1966). The formation of 2-hydroxypropylmercapturic acid from 1-halogenopropanes in the rat. 

Biochem. J. 100, 362-372.

Barnsley, E.A., Thomson, A.E.R., and Young, L. (1964). Biochemical studies of toxic agents. 15. The 

biosynthesis of ethylmercapturic acid sulphoxide. Biochem. J. 90, 588-596.

Barnsley, E.A., Grenby, T.H., and Young, L. (1966). The metabolism of 1- and 2-bromopropane in rats. Biochem. 

J. 100, 282-288.

Beeley, J.G., and Neurath, H. (1968). The reaction of trypsin with bromoacetone. Biochemistry 7, 1239-1251.

Bhagavan, B.S., Ruffier, J., and Shinn, B. (1982). Pseudoactinomycotic radiate granules in the lower female genital 

tract: Relationship to the Splendore-Hoeppli phenomenon. Hum. Pathol. 13, 898-904.

Bieler, G.S., and Williams, R.L. (1993). Ratio estimates, the delta method, and quantal response tests for increased 

carcinogenicity. Biometrics 49, 793-801.

Boorman, G.A., and Eustis, S.L. (1990). Lung. In Pathology of the Fischer Rat. Reference and Atlas (G.A. 

Boorman, S.L. Eustis, M.R. Elwell, C.A. Montgomery, Jr., and W.F. MacKenzie, Eds.), pp. 339-368. Academic 

Press, Inc., San Diego.
106 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

Boorman, G.A., Montgomery, C.A., Jr., Eustis, S.L., Wolfe, M.J., McConnell, E.E., and Hardisty, J.F. (1985). 

Quality assurance in pathology for rodent carcinogenicity studies. In Handbook of Carcinogen Testing (H.A. 

Milman and E.K. Weisburger, Eds.), pp. 345-357. Noyes Publications, Park Ridge, NJ.

Boorman, G.A., Elwell, M.R., and Mitsumori, K. (1990). Male accessory sex glands, penis, and scrotum. In 

Pathology of the Fischer Rat. Reference and Atlas (G.A. Boorman, S.L. Eustis, M.R. Elwell, C.A. Montgomery, Jr., 

and W.F. MacKenzie, Eds.), pp. 419-428. Academic Press, Inc., San Diego.

Brecher, G., and Schneiderman, M. (1950). A time-saving device for the counting of reticulocytes. Am. J. Clin. 

Pathol. 20, 1079-1083.

Brunken, R.C., Lichon-Chao, N., and van der Broek, H. (1983). Immunologic abnormalities in botryomycosis. A 

case report with review of the literature. J. Am. Acad. Dermatol. 9, 428-434.

Chang, W.W. (1984). Histogenesis of colon cancer in experimental animals. Scand. J. Gastroenterol. Suppl. 104, 

27-43.

Code of Federal Regulations (CFR) 21, Part 58.

Cohen, S.G., Lieberman, D.L., and Hasan, F.B. (1982). 1-Bromopinacolone, an active site-directed covalent 

inhibitor for acetylcholinesterase. J. Biol. Chem. 257, 14,087-14,092.

Cox, D.R. (1972). Regression models and life-tables. J. R. Stat. Soc. B34, 187-220. 

Crawford, B.D. (1985). Perspectives on the somatic mutation model of carcinogenesis. In Advances in Modern 

Environmental Toxicology. Mechanisms and Toxicity of Chemical Carcinogens and Mutagens (M.A. Mehlman, 

W.G. Flamm, and R.J. Lorentzen, Eds.), pp. 13-59. Princeton Scientific Publishing Co., Inc., Princeton, NJ.

Deschner, E.E. (1983). Adenomas: Preneoplastic events, growth and development in man and experimental 

systems. Pathol. Annu. 18, 205-219.

Dixon, W.J., and Massey, F.J., Jr. (1957). Introduction to Statistical Analysis, 2nd ed., pp. 276-278, 412. 

McGraw-Hill Book Company, Inc., New York.

Dröge, W., Eck, H.P., Mihm, S., Roth, S., Kinscherf, R., and Fischbach, T. (1994). The role of a cysteine and 

glutathione deficiency in the immunopathology of HIV infection. Acta Microbiol. Immunol. Hung. 41, 17-20.

Dunn, O.J. (1964). Multiple comparisons using rank sums. Technometrics 6, 241-252.

Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Am. 

Stat. Assoc. 50, 1096-1121.

Elwell, M.R., Stedham, M.A., and Kovatch, R.M. (1990). Skin and subcutis. In Pathology of the Fischer Rat. 

Reference and Atlas (G.A. Boorman, S.L. Eustis, M.R. Elwell, C.A. Montgomery, Jr., and W.F. MacKenzie, Eds.), 

pp. 261-277. Academic Press, Inc., San Diego.

Federal Register (1999). Protection of stratospheric ozone: Listing of substitutes for ozone-depleting substances 

(40 CFR Part 82), Vol. 64, No. 32, pp. 8043-8048. U.S. Environmental Protection Agency, Washington, DC.

Federal Register (2000). Protection of stratospheric ozone: Notice 14 for significant new alternatives policy 

program (40 CFR Part 82), Vol. 65, No. 243, pp. 78,977-78,989. U.S. Environmental Protection Agency, 

Washington, DC.

Federal Register (2007a). Protection of stratospheric ozone: Listing of substitutes for ozone-depleting substances –

n-propyl bromide in solvent cleaning (40 CFR Part 82), Vol. 72, No. 103, pp. 30,142-30,167. U.S. Environmental 

Protection Agency, Washington, DC.
1-Bromopropane, NTP TR 564 107

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

Federal Register (2007b). Protection of stratospheric ozone: Listing of substitutes for ozone-depleting substances –

n-propyl bromide in adhesives, coatings, and aerosols (40 CFR Part 82), Vol. 72, No. 103, pp. 30,168-30,207. U.S. 

Environmental Protection Agency, Washington, DC.

Garner, C.E., Sumner, S.C.J., Davis, J.G., Burgess, J.P., Yueh, Y., Demeter, J., Zhan, Q., Valentine, J., 

Jeffcoat, A.R., Burka, L.T., and Mathews, J.M. (2006). Metabolism and disposition of 1-bromopropane in rats and 

mice following inhalation or intravenous administration. Toxicol. Appl. Pharmacol. 215, 23-36.

Garner, C.E., Sloan, C., Sumner, S.C.J., Burgess, J., Davis, J., Etheridge, A., Parham, A., and Ghanayem, B.I. 

(2007). CYP2E1-catalyzed oxidation contributes to the sperm toxicity of 1-bromopropane in mice. Biol. Reprod.

76, 496-505.

Gart, J.J., Chu, K.C., and Tarone, R.E. (1979). Statistical issues in interpretation of chronic bioassay tests for 

carcinogenicity. JNCI 62, 957-974.

Girard, D.M., and Sager, D.B. (1987). The use of Markov chains to detect subtle variation in reproductive cycling. 

Biometrics 43, 225-234.

Hall, W.C. (1990). Peritoneum, retroperitoneum, mesentery, and abdominal cavity. In Pathology of the Fischer 

Rat. Reference and Atlas (G.A. Boorman, S.L. Eustis, M.R. Elwell, C.A. Montgomery, Jr., and W.F. MacKenzie, 

Eds.), pp. 63-69. Academic Press, Inc., San Diego.

Hanley, K.W., Petersen, M., Curwin, B.D., and Sanderson, W.T. (2006). Urinary bromide and breathing zone 

concentrations of 1-bromopropane from workers exposed to flexible foam spray adhesives. Ann. Occup. Hyg. 50, 

599-607.

Hazardous Substances Data Bank (HSDB) (2009). TOXNET: Toxicology Data Network. National Library of 

Medicine. <http://toxnet.nlm.nih.gov>

Heddle, J.A., Hite, M., Kirkhart, B., Mavournin, K., MacGregor, J.T., Newell, G.W., and Salamone, M.F. (1983). 

The induction of micronuclei as a measure of genotoxicity. A report of the U.S. Environmental Protection Agency 

Gene-Tox Program. Mutat. Res. 123, 61-118.

Huntingdon Life Sciences (2001). A developmental toxicity study in rat via whole body inhalation exposure. Study 

No. 98-4141. East Millstone, NJ. Study sponsored by Brominated Solvents Committee (BSC).

Hussein, M.R. (2008). Mucocutaneous Splendore-Hoeppli phenomenon. J. Cutan. Pathol. 35, 979-988.

Ichihara, G., Yu, X., Kitoh, J., Asaeda, N., Kumazawa, T., Iwai, H., Shibata, E., Yamada, T., Wang, H., Xie, Z., 

Maeda, K., Tsukamura, H., and Takeuchi, Y. (2000a). Reproductive toxicity of 1-bromopropane, a newly 

introduced alternative to ozone layer depleting solvents, in male rats. Toxicol. Sci. 54, 416-423.

Ichihara, G., Kitoh, J., Yu, X., Asaeda, N., Iwai, H., Kumazawa, T., Shibata, E., Yamada, T., Wang, H., Xie, Z., and 

Takeuchi, Y. (2000b). 1-Bromopropane, an alternative to ozone layer depleting solvents, is dose-dependently 

neurotoxic to rats in long-term inhalation exposure. Toxicol. Sci. 55, 116-123.

Ichihara, G., Li, W., Ding, X., Peng, S., Yu, X., Shibata, E., Yamada, T., Wang, H., Itohara, S., Kanno, S., Sakai, K., 

Ito, H., Kanefusa, K., and Takeuchi, Y. (2004a). A survey on exposure level, health status, and biomarkers in 

workers exposed to 1-bromopropane. Am. J. Ind. Med. 45, 63-75.

Ichihara, G., Li, W., Shibata, E., Ding, X., Wang, H., Liang, Y., Peng, S., Itohara, S., Kamijima, M., Fan, Q., 

Zhang, Y., Zhong, E., Wu, X., Valentine, W.M., and Takeuchi, Y. (2004b). Neurologic abnormalities in workers of 

a 1-bromopropane factory. Environ. Health Perspect. 112, 1319-1325.

Ishidao, T., Kunugita, N., Fueta, Y., Arashidani, K., and Hori, H. (2002). Effects of inhaled 1-bromopropane vapor 

on rat metabolism. Toxicol. Lett. 134, 237-243.
108 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

Jeong, T.C., Lee, E.S., Chae, W., Koh, W.S., Kang, B.H., and Han, S.S. (2002). Immunotoxic effects of 

2-bromopropane in male Sprague-Dawley rats: A 28-day exposure study. J. Toxicol. Environ. Health A. 65, 

383-394.

Jonckheere, A.R. (1954). A distribution-free k-sample test against ordered alternatives. Biometrika 41, 133-145.

Jones, A.R., and Walsh, D.A. (1979). The oxidative metabolism of 1-bromopropane in the rat. Xenobiotica 9, 

763-772.

Kaplan, E.L., and Meier, P. (1958). Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc.

53, 457-481.

Ketterer, B., Coles, B., and Meyer, D.J. (1983). The role of glutathione in detoxication. Environ. Health Perspect.

49, 59-69.

Kim, K.W., Kim, H.Y., Park, S.S., Jeong, H.S., Park, S.H., Lee, J.Y., Jeong, J.H., and Moon, Y.H. (1999). Gender 

differences in activity and induction of hepatic microsomal cytochrome P-450 by 1-bromopropane in SpragueDawley rats. Biochem. Mol. Biol. Rep. 32, 232-238.

Kim, Y., Jung, K., Hwang, T., Jung, G., Kim, H., Park, J., Kim, J., Park, J., Park, D., Park, S., Choi, K., and 

Moon, K. (1996). Hematopoietic and reproductive hazards of Korean electronic workers exposed to solvents 

containing 2-bromopropane. Scand. J. Work Environ. Health 22, 387-391.

Lee, S.K., Jeon, T.W., Kim, Y.B., Lee, E.S., Jeong, H.G., and Jeong, T.C. (2007a). Role of glutathione conjugation 

in the hepatotoxicity and immunotoxicity induced by 1-bromopropane in female BALB/c mice. J. Appl. Toxicol. 27, 

358-367.

Lee, S.K., Lee, D.J., Jeong, H., Bista, S.R., Kang, M.J., Lee, E.S., Son, J.K., Nam, D.H., Chang, H.W., Lee, S.H., 

Jahng, Y., and Jeong, T.C. (2007b). Hepatotoxic and immunotoxic effects produced by 1,3-dibromopropane and its 

conjugation with glutathione in female BALB/c mice. J. Toxicol. Environ. Health A. 70, 1381-1390.

Lewis, R.J., Sr. (1996). Sax’s Dangerous Properties of Industrial Materials, 9th ed., Volumes 1-3, p. 528. 

Van Nostrand Reinhold, New York.

Liu, F., Ichihara, S., Mohideen, S.S., Sai, U., Kitoh, J., and Ichihara, G. (2009). Comparative study on susceptibility 

to 1-bromopropane in three mice strains. Toxicol. Sci. July (e-publication ahead of print).

McConnell, E.E., Solleveld, H.A., Swenberg, J.A., and Boorman, G.A. (1986). Guidelines for combining 

neoplasms for evaluation of rodent carcinogenesis studies. JNCI 76, 283-289.

MacGregor, J.T., Wehr, C.M., Henika, P.R., and Shelby, M.D. (1990). The in vivo erythrocyte micronucleus test: 

Measurement at steady state increases assay efficiency and permits integration with toxicity studies. Fundam. Appl. 

Toxicol. 14, 513-522.

Maronpot, R.R., and Boorman, G.A. (1982). Interpretation of rodent hepatocellular proliferative alterations and 

hepatocellular tumors in chemical safety assessment. Toxicol. Pathol. 10, 71-80.

The Merck Index (2006). 14th ed. (M.J. O’Neil, Ed.), p.1349. Merck and Company, Inc., Whitehouse Station, NJ. 

Miller, J.A., and Miller, E.C. (1977). Ultimate chemical carcinogens as reactive mutagenic electrophiles. In Origins 

of Human Cancer (H.H. Hiatt, J.D. Watson, and J.A. Winsten, Eds.), pp. 605-627. Cold Spring Harbor Laboratory, 

Cold Spring Harbor, NY.

Mitchell, A.E., Zheng, J., Hammock, B.D., Lo Bello, M., and Jones, A.D. (1998). Structural and functional 

consequences of haloenol lactone inactivation of murine and human glutathione S-transferase. Biochemistry 37, 

6752-6759.
1-Bromopropane, NTP TR 564 109

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

Morrison, D.F. (1976). Multivariate Statistical Methods, 2nd ed., pp. 170-179. McGraw-Hill Book Company, 

New York.

National Institute for Occupational Safety and Health (NIOSH) (2002). Health Hazard Evaluation Report: STN 

Cushion Company, Thomasville, North Carolina. Report No. 2000-0410-2891. Department of Health and Human 

Services, Centers for Disease Control and Prevention, Washington, DC.

National Institute for Occupational Safety and Health (NIOSH) (2003). Health Hazard Evaluation Report: Marx 

Industries, Inc., Sawmills, North Carolina. Report No. 99-0260-2906. Department of Health and Human Services, 

Centers for Disease Control and Prevention, Washington, DC.

National Toxicology Program (NTP) (1982a). Carcinogenesis Bioassay of 1,2-Dibromoethane (CAS No. 106-93-4) 

in F344 Rats and B6C3F1 Mice (Inhalation Study). Technical Report Series No. 210. NIH Publication 

No. 82-1766. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, 

Research Triangle Park, NC, and Bethesda, MD.

National Toxicology Program (NTP) (1982b). Carcinogenesis Bioassay of 1,2-Dibromo-3-chloropropane 

(CAS No. 96-12-8) in F344 Rats and B6C3F1 Mice (Inhalation Study). Technical Report Series No. 206. NIH 

Publication No. 82-1762. U.S. Department of Health and Human Services, Public Health Service, National 

Institutes of Health, Research Triangle Park, NC, and Bethesda, MD.

National Toxicology Program (NTP) (1987). Toxicology and Carcinogenesis Studies of Bromodichloromethane 

(CAS No. 75-27-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies). Technical Report Series No. 321. NIH 

Publication No. 88-2537. U.S. Department of Health and Human Services, Public Health Service, National 

Institutes of Health, Research Triangle Park, NC.

National Toxicology Program (NTP) (1989). Toxicology and Carcinogenesis Studies of Tribromomethane 

(Bromoform) (CAS No. 75-25-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies). Technical Report Series 

No. 350. NIH Publication No. 89-2805. U.S. Department of Health and Human Services, Public Health Service, 

National Institutes of Health, Research Triangle Park, NC.

National Toxicology Program (NTP) (1993). Toxicology and Carcinogenesis Studies of 2,3-Dibromo-1-propanol 

(CAS No. 96-13-9) in F344/N Rats and B6C3F1 Mice (Dermal Studies). Technical Report Series No. 400. NIH 

Publication No. 94-2855. U.S. Department of Health and Human Services, Public Health Service, National 

Institutes of Health, Research Triangle Park, NC.

National Toxicology Program (NTP) (2003). NTP-CERHR Monograph on the Potential Human Reproductive and 

Developmental Effects of 1-Bromopropane. NIH Publication No. 04-4479. U.S. Department of Health and Human 

Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.

Nigro, N.D. (1985). Animal model for colorectal cancer. Prog. Clin. Biol. Res. 186, 161-173.

Ohnishi, A., Ishidao, T., Kasai, T., Arashidani, K., and Hori, H. (1999). Neurotoxicity of 1-bromopropane in rats. 

J. UOEH 21, 23-28.

Park, J.-S., Kim, Y., Park, D.W., Choi, K.S., Park, S.-H., and Moon, Y.-H. (1997). An outbreak of hematopoietic 

and reproductive disorders due to solvents containing 2-bromopropane in an electronic factory, South Korea: 

Epidemiological survey. J. Occup. Health 39, 138-143.

Patterson, J.W., Kitces, E.N., and Neafie, R.C. (1987). Cutaneous botryomycosis in a patient with acquired 

immunodeficiency syndrome. J. Am. Acad. Dermatol. 16, 238-242.

Patty’s Industrial Hygiene and Toxicology (2001). 5th ed. (E. Bingham, B., Cohrssen, and C.H. Powell, Eds.). 

John Wiley & Sons, Inc., New York.
110 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

Piegorsch, W.W., and Bailer, A.J. (1997). Statistics for Environmental Biology and Toxicology, Section 6.3.2. 

Chapman and Hall, London.

Portier, C.J., and Bailer, A.J. (1989). Testing for increased carcinogenicity using a survival-adjusted quantal 

response test. Fundam. Appl. Toxicol. 12, 731-737.

Portier, C.J., Hedges, J.C., and Hoel, D.G. (1986). Age-specific models of mortality and tumor onset for historical 

control animals in the National Toxicology Program’s carcinogenicity experiments. Cancer Res. 46, 4372-4378.

Rao, G.N. (1996). New diet (NTP-2000) for rats in the National Toxicology Program toxicity and carcinogenicity 

studies. Fundam. Appl. Toxicol. 32, 102-108.

Rao, G.N. (1997). New nonpurified diet (NTP-2000) for rodents in the National Toxicology Program’s toxicology 

and carcinogenesis studies. J. Nutr. 127, 842s-846s.

Robinson, M., Bull, R.J., Olson, G.R., and Stober, J. (1989). Carcinogenic activity associated with halogenated 

acetones and acroleins in the mouse skin assay. Cancer Lett. 48, 197-203.

Saito-Suzuki, R., Teramoto, S., and Shirasu, Y. (1982). Dominant lethal studies in rats with 1,2-dibromo3-chloropropane and its structurally related compounds. Mutat. Res. 101, 321-327.

Schlossberg, D., Keeney, G.E., Lifton, L.J., and Azizhkan, R.G. (1980). Anaerobic botryomycosis. J. Clin. 

Microbiol. 11, 184-185.

Schmid, W. (1975). The micronucleus test. Mutat. Res. 31, 9-15.

Sclar, G. (1999). Encephalomyeloradiculoneuropathy following exposure to an industrial solvent. Clin. Neurol. 

Neurosurg. 101, 199-202.

Shelby, M.D. (1988). The genetic toxicity of human carcinogens and its implications. Mutat. Res. 204, 3-15.

Shelby, M.D., and Witt, K.L. (1995). Comparison of results from mouse bone marrow chromosome aberration and 

micronucleus tests. Environ. Mol. Mutagen. 25, 302-313.

Shelby, M.D., and Zeiger, E. (1990). Activity of human carcinogens in the Salmonella and rodent bone-marrow 

cytogenetics tests. Mutat. Res. 234, 257-261.

Shelby, M.D., Erexson, G.L., Hook, G.J., and Tice, R.R. (1993). Evaluation of a three-exposure mouse bone 

marrow micronucleus protocol: Results with 49 chemicals. Environ. Mol. Mutagen. 21, 160-179.

Shirley, E. (1977). A non-parametric equivalent of Williams’ test for contrasting increasing dose levels of a 

treatment. Biometrics 33, 386-389.

Straus, D.S. (1981). Somatic mutation, cellular differentiation, and cancer causation. JNCI 67, 233-241.

Tarone, R.E. (1975). Tests for trend in life table analysis. Biometrika 62, 679-682.

Tennant, R.W., Margolin, B.H., Shelby, M.D., Zeiger, E., Haseman, J.K., Spalding, J., Caspary, W., Resnick, M., 

Stasiewicz, S., Anderson, B., and Minor, R. (1987). Prediction of chemical carcinogenicity in rodents from in vitro 

genetic toxicity assays. Science 236, 933-941.

Toraason, M., Lynch, D.W., DeBord, D.G., Singh, N., Krieg, E., Butler, M.A., Toennis, C.A., and Nemhauser, J.B. 

(2006). DNA damage in leukocytes of workers occupationally exposed to 1-bromopropane. Mutat. Res. 603, 1-14.
1-Bromopropane, NTP TR 564 111

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

United Nations Environment Programme (UNEP) (2001). Montreal Protocol on Substances that Deplete the Ozone 

Layer. Report on the Geographical Market Potential and Estimated Emissions of n-Propyl Bromide. Report of the 

Technology and Economic Assessment Panel. Nairobi, Kenya. <http://www.teap.org>

United Nations Environment Programme (UNEP) (2006). Montreal Protocol on Substances that Deplete the Ozone 

Layer. 2006 Report of the Chemicals Technical Options Committee. Nairobi, Kenya. 

<http://ozone.unep.org/Assessment_Panels/TEAP/Reports/CTOC/>

Wang, H., Ichihara, G., Ito, H., Kato, K., Kitoh, J., Yamada, T., Yu, X., Tsuboi, S., Moriyama, Y., and Takeuchi, Y. 

(2003). Dose-dependent biochemical changes in rat central nervous system after 12-week exposure to 

1-bromopropane. Neurotoxicology 24, 199-206.

Wenig, B.M., Smirniotopoulos, J.G., and Heffner, D.K. (1996). Botryomycosis (‘bacterial ball’) of the sinonasal 

tract caused by Pseudomonas aeruginosa. Arch. Pathol. Lab. Med. 120, 1123-1128.

WIL Research Laboratories (2001). An inhalation two-generation reproductive toxicity study of 1-bromopropane in 

rats. Study No. WIL-380001. Ashland, OH. Study sponsored by Brominated Solvents Committee (BSC).

Williams, D.A. (1971). A test for differences between treatment means when several dose levels are compared with 

a zero dose control. Biometrics 27, 103-117.

Williams, D.A. (1972). The comparison of several dose levels with a zero dose control. Biometrics 28, 519-531.

Williams, D.A. (1986). A note on Shirley’s nonparametric test for comparing several dose levels with a zero-dose 

control. Biometrics 42, 183-186.

Witt, K.L., Knapton, A., Wehr, C.M., Hook, G.J., Mirsalis, J., Shelby, M.D., and MacGregor, J.T. (2000). 

Micronucleated erythrocyte frequency in peripheral blood of B6C3F1 mice from short-term, prechronic, and chronic 

studies of the NTP Carcinogenesis Bioassay Program. Environ. Mol. Mutagen. 36, 163-194.

Yamada, T., Ichihara, G., Wang, H., Yu, X., Maeda, K., Tsukamura, H., Kamijima, M., Nakajima, T., and 

Takeuchi, Y. (2003). Exposure to 1-bromopropane causes ovarian dysfunction in rats. Toxicol. Sci. 71, 96-103.

Yu, I.J., Chung, Y.H., Lim, C.H., Maeng, S.H., Lee, J.Y., Kim, H.Y., Lee, S.J., Kim, C.H., Kim, T.G., Lim, C.H., 

Park, J.S., and Moon, Y.H. (1997). Reproductive toxicity of 2-bromopropane in Sprague Dawley rats. Scand. J. 

Work. Environ. Health 23, 281-288.

Yu, W.J., Kim, J.C., and Chung, M.K. (2008). Lack of dominant lethality in mice following 1-bromopropane 

treatment. Mutat. Res. 652, 81-87.

Yu, X., Ichihara, G., Kitoh, J., Xie, Z., Shibata, E., Kamijima, M., Asaeda, N., and Takeuchi, Y. (1998). 

Preliminary report on the neurotoxicity of 1-bromopropane, an alternative solvent for chlorofluorocarbons. 

J. Occup. Health 40, 234-235.

Zeiger, E., Haseman, J.K., Shelby, M.D., Margolin, B.H., and Tennant, R.W. (1990). Evaluation of four in vitro 

genetic toxicity tests for predicting rodent carcinogenicity: Confirmation of earlier results with 41 additional 

chemicals. Environ. Mol. Mutagen. 16 (Suppl. 18), 1-14.

Zeiger, E., Anderson, B., Haworth, S., Lawlor, T., and Mortelmans, K. (1992). Salmonella mutagenicity tests: 

V. Results from the testing of 311 chemicals. Environ. Mol. Mutagen. 19 (Suppl. 21), 2-141.
112 1-Bromopropane, NTP TR 564

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A-1

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APPENDIX A

SUMMARY OF LESIONS IN MALE RATS

IN THE 2-YEAR INHALATION STUDY

OF 1-BROMOPROPANE

TABLE A1 Summary of the Incidence of Neoplasms in Male Rats

in the 2-Year Inhalation Study of 1-Bromopropane .......................................................................A-2

TABLE A2 Statistical Analysis of Primary Neoplasms in Male Rats

in the 2-Year Inhalation Study of 1-Bromopropane ......................................................................A-6

TABLE A3a Historical Incidence of Large Intestine (Colon or Rectum) Neoplasms 

in Control Male F344/N Rats ..........................................................................................................A-10

TABLE A3b Historical Incidence of Skin Neoplasms in Control Male F344/N Rats.......................................A-11

TABLE A3c Historical Incidence of Malignant Mesothelioma in Control Male F344/N Rats........................A-12

TABLE A3d Historical Incidence of Pancreatic Islet Neoplasms in Control Male F344/N Rats ....................A-12

TABLE A4 Summary of the Incidence of Nonneoplastic Lesions in Male Rats

in the 2-Year Inhalation Study of 1-Bromopropane ....................................................................A-13
A-2 1-Bromopropane, NTP TR 564

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TABLE A1

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Inhalation Study of 1-Bromopropanea

Chamber Control 125 ppm 250 ppm 500 ppm

Disposition Summary

Animals initially in study 50 50 50 50

Early deaths

Moribund 24 20 28 35

Natural deaths 3 4 4 2

Survivors

Terminal sacrifice 23 26 18 13

Animals examined microscopically 50 50 50 50

Alimentary System

Esophagus (50) (50) (50) (50)

Intestine large, cecum (47) (47) (47) (48)

Intestine large, colon (48) (48) (48) (48)

Adenoma 1 (2%)

Intestine large, rectum (48) (48) (48) (49)

Adenoma 2 (4%)

Carcinoid tumor malignant 1 (2%)

Polyp adenomatous 1 (2%)

Intestine small, duodenum (48) (48) (48) (48)

Intestine small, ileum (47) (47) (46) (48)

Intestine small, jejunum (47) (47) (46) (48)

Adenoma 1 (2%)

Liver (50) (50) (50) (50)

Hepatocellular carcinoma 2 (4%) 1 (2%)

Mesentery (13) (13) (8) (19)

Sarcoma 1 (13%)

Oral mucosa (3) (0) (2) (4)

Squamous cell carcinoma 1 (33%) 1 (50%) 2 (50%)

Pancreas (50) (50) (50) (50)

Salivary glands (50) (50) (50) (50)

Stomach, forestomach (50) (50) (50) (50)

Stomach, glandular (50) (50) (50) (50)

Tongue (0) (0) (1) (1)

Cardiovascular System

Heart (50) (50) (50) (50)

Endocrine System

Adrenal cortex (50) (50) (50) (50)

Adenoma 1 (2%) 1 (2%)

Adrenal medulla (50) (50) (50) (50)

Pheochromocytoma benign 8 (16%) 8 (16%) 5 (10%) 7 (14%)

Pheochromocytoma complex 1 (2%) 1 (2%)

Pheochromocytoma malignant 1 (2%) 1 (2%) 1 (2%)

Bilateral, pheochromocytoma benign 2 (4%) 1 (2%) 2 (4%) 1 (2%)

Islets, pancreatic (50) (50) (50) (50)

Adenoma 5 (10%) 4 (8%) 5 (10%)

Carcinoma 3 (6%) 7 (14%) 5 (10%) 3 (6%)

Parathyroid gland (46) (48) (47) (46)

Pituitary gland (50) (50) (50) (49)

Pars distalis, adenoma 37 (74%) 36 (72%) 33 (66%) 31 (63%)
1-Bromopropane, NTP TR 564 A-3

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TABLE A1

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Endocrine System (continued)

Thyroid gland (50) (50) (50) (49)

C-cell, adenoma 5 (10%) 4 (8%) 3 (6%) 3 (6%)

C-cell, carcinoma 4 (8%) 3 (6%) 2 (4%)

Follicular cell, adenoma 2 (4%)

Follicular cell, carcinoma 2 (4%) 2 (4%) 1 (2%)

General Body System

Peritoneum (0) (0) (0) (2)

Genital System

Coagulating gland (3) (0) (1) (2)

Epididymis (50) (50) (50) (50)

Penis (0) (3) (1) (1)

Preputial gland (50) (50) (49) (50)

Adenoma 4 (8%) 1 (2%) 1 (2%) 1 (2%)

Carcinoma 2 (4%) 2 (4%) 3 (6%)

Prostate (50) (50) (50) (50)

Adenoma 1 (2%)

Seminal vesicle (50) (49) (49) (50)

Testes (50) (50) (50) (50)

Bilateral, interstitial cell, adenoma 22 (44%) 20 (40%) 16 (32%) 17 (34%)

Interstitial cell, adenoma 12 (24%) 18 (36%) 16 (32%) 12 (24%)

Hematopoietic System

Bone marrow (50) (50) (50) (50)

Lymph node (5) (5) (5) (4)

Deep cervical, carcinoma, metastatic,

thyroid gland 1 (20%)

Lymph node, bronchial (3) (6) (5) (8)

Lymph node, mandibular (3) (1) (0) (6)

Lymph node, mediastinal (30) (25) (23) (32)

Carcinoma, metastatic, thyroid gland 1 (3%)

Lymph node, mesenteric (50) (50) (50) (50)

Spleen (50) (50) (49) (50)

Thymus (43) (41) (47) (46)

Integumentary System

Mammary gland (40) (36) (39) (36)

Fibroadenoma 2 (5%) 2 (6%) 1 (3%) 1 (3%)

Skin (50) (50) (50) (50)

Basal cell adenoma 1 (2%) 2 (4%) 1 (2%)

Basal cell carcinoma 2 (4%) 1 (2%) 2 (4%)

Fibrous histiocytoma 1 (2%)

Hemangiosarcoma 1 (2%)

Keratoacanthoma 3 (6%) 4 (8%) 5 (10%)

Keratoacanthoma, multiple 2 (4%) 1 (2%)

Squamous cell carcinoma 1 (2%) 1 (2%) 2 (4%)

Pinna, neural crest tumor 1 (2%)

Sebaceous gland, adenoma 2 (4%) 1 (2%)

Sebaceous gland, carcinoma 1 (2%)

Subcutaneous tissue, fibroma 3 (6%) 5 (10%) 1 (2%)

Subcutaneous tissue, lipoma 2 (4%) 1 (2%) 1 (2%)
A-4 1-Bromopropane, NTP TR 564

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TABLE A1

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Musculoskeletal System

Bone (50) (50) (50) (50)

Chordoma 1 (2%)

Osteosarcoma 1 (2%)

Skeletal muscle (1) (1) (3) (3)

Chordoma, metastatic, bone 1 (100%)

Nervous System

Brain (50) (50) (50) (50)

Oligodendroglioma malignant 1 (2%)

Osteosarcoma 1 (2%)

Spinal cord (1) (1) (2) (1)

Respiratory System

Larynx (50) (50) (50) (50)

Carcinoma, metastatic, thyroid gland 1 (2%)

Lung (50) (50) (50) (50)

Alveolar/bronchiolar adenoma 2 (4%) 3 (6%) 1 (2%) 5 (10%)

Alveolar/bronchiolar adenoma, multiple 1 (2%)

Alveolar/bronchiolar carcinoma 1 (2%) 1 (2%) 2 (4%) 1 (2%)

Carcinoma, metastatic, preputial gland 1 (2%)

Carcinoma, metastatic, thyroid gland 1 (2%)

Chordoma, metastatic, bone 1 (2%)

Nose (50) (48) (48) (50)

Trachea (50) (50) (50) (50)

Carcinoma, metastatic, thyroid gland 1 (2%)

Special Senses System

Eye (49) (49) (50) (50)

Melanoma malignant 1 (2%)

Harderian gland (50) (50) (50) (50)

Lacrimal gland (1) (0) (0) (0)

Zymbal’s gland (0) (1) (2) (2)

Adenoma 1 (50%)

Carcinoma 1 (100%) 2 (100%) 1 (50%)

Urinary System

Kidney (50) (50) (50) (49)

Liposarcoma 1 (2%)

Stromal nephroma 1 (2%)

Cortex, renal tubule, adenoma 1 (2%)

Pelvis, papilloma 1 (2%)

Urinary bladder (50) (50) (50) (50)

Transitional epithelium, carcinoma 1 (2%)

Systemic Lesions

Multiple organsb (50) (50) (50) (50)

Histiocytic sarcoma 1 (2%) 2 (4%)

Leukemia mononuclear 29 (58%) 22 (44%) 16 (32%) 24 (48%)

Lymphoma malignant 1 (2%)

Mesothelioma malignant 2 (4%) 2 (4%) 4 (8%)
1-Bromopropane, NTP TR 564 A-5

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TABLE A1

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Neoplasm Summary

Total animals with primary neoplasmsc 50 50 48 49

Total primary neoplasms 150 160 139 143

Total animals with benign neoplasms 48 49 47 48

Total benign neoplasms 102 110 98 96

Total animals with malignant neoplasms 38 33 32 32

Total malignant neoplasms 47 50 41 47

Total animals with metastatic neoplasms 3 1

Total metastatic neoplasms 4 4

Total animals with uncertain neoplasmsbenign or malignant 1

Total uncertain neoplasms 1

a Number of animals examined microscopically at the site and the number of animals with neoplasm

b Number of animals with any tissue examined microscopically

c Primary neoplasms: all neoplasms except metastatic neoplasms
A-6 1-Bromopropane, NTP TR 564

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TABLE A2

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Adrenal Medulla: Benign Pheochromocytoma

Overall ratea 10/50 (20%) 9/50 (18%) 7/50 (14%) 8/50 (16%)

Adjusted rateb 23.9% 21.7% 18.1% 21.6%

Terminal ratec 8/23 (35%) 7/26 (27%) 3/18 (17%) 3/13 (23%)

First incidence (days) 660 585 618 453

Poly-3 testd P=0.432N P=0.506N P=0.354N P=0.509N

Adrenal Medulla: Benign, Malignant, or Complex Pheochromocytoma

Overall rate 11/50 (22%) 10/50 (20%) 8/50 (16%) 10/50 (20%)

Adjusted rate 25.8% 24.1% 20.6% 26.7%

Terminal rate 8/23 (35%) 8/26 (31%) 4/18 (22%) 4/13 (31%)

First incidence (days) 429 585 618 453

Poly-3 test P=0.525 P=0.526N P=0.385N P=0.566

Lung: Alveolar/bronchiolar Adenoma

Overall rate 2/50 (4%) 4/50 (8%) 1/50 (2%) 5/50 (10%)

Adjusted rate 4.8% 9.8% 2.7% 13.7%

Terminal rate 2/23 (9%) 3/26 (12%) 1/18 (6%) 3/13 (23%)

First incidence (days) 729 (T) 648 729 (T) 575

Poly-3 test P=0.162 P=0.331 P=0.533N P=0.165

Lung: Alveolar/bronchiolar Adenoma or Carcinoma

Overall rate 3/50 (6%) 5/50 (10%) 3/50 (6%) 6/50 (12%)

Adjusted rate 7.2% 12.2% 8.0% 16.4%

Terminal rate 3/23 (13%) 4/26 (15%) 2/18 (11%) 3/13 (23%)

First incidence (days) 729 (T) 648 725 575

Poly-3 test P=0.169 P=0.349 P=0.620 P=0.181

Pancreatic Islets: Adenoma

Overall rate 0/50 (0%) 5/50 (10%) 4/50 (8%) 5/50 (10%)

Adjusted rate 0.0% 12.2% 10.4% 13.9%

Terminal rate 0/23 (0%) 4/26 (15%) 1/18 (6%) 4/13 (31%)

First incidence (days) —e 666 608 697

Poly-3 test P=0.043 P=0.029 P=0.050 P=0.019

Pancreatic Islets: Carcinoma

Overall rate 3/50 (6%) 7/50 (14%) 5/50 (10%) 3/50 (6%)

Adjusted rate 7.2% 17.0% 13.0% 8.3%

Terminal rate 2/23 (9%) 3/26 (12%) 3/18 (17%) 2/13 (15%)

First incidence (days) 686 687 578 687

Poly-3 test P=0.516N P=0.149 P=0.312 P=0.594

Pancreatic Islets: Adenoma or Carcinoma

Overall rate 3/50 (6%) 10/50 (20%) 9/50 (18%) 8/50 (16%)

Adjusted rate 7.2% 24.2% 23.1% 22.2%

Terminal rate 2/23 (9%) 5/26 (19%) 4/18 (22%) 6/13 (46%)

First incidence (days) 686 666 578 687

Poly-3 test P=0.093 P=0.031 P=0.043 P=0.057

Pituitary Gland (Pars Distalis): Adenoma

Overall rate 37/50 (74%) 36/50 (72%) 33/50 (66%) 31/49 (63%)

Adjusted rate 79.8% 76.0% 73.4% 71.3%

Terminal rate 19/23 (83%) 20/26 (77%) 12/18 (67%) 9/13 (69%)

First incidence (days) 534 505 514 394

Poly-3 test P=0.189N P=0.421N P=0.307N P=0.226N
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TABLE A2

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Preputial Gland: Adenoma

Overall rate 4/50 (8%) 1/50 (2%) 1/49 (2%) 1/50 (2%)

Adjusted rate 9.6% 2.5% 2.7% 2.8%

Terminal rate 3/23 (13%) 0/26 (0%) 0/18 (0%) 0/13 (0%)

First incidence (days) 669 711 688 642

Poly-3 test P=0.152N P=0.184N P=0.212N P=0.224N

Preputial Gland: Carcinoma

Overall rate 2/50 (4%) 2/50 (4%) 3/49 (6%) 0/50 (0%)

Adjusted rate 4.8% 4.9% 7.9% 0.0%

Terminal rate 1/23 (4%) 1/26 (4%) 1/18 (6%) 0/13 (0%)

First incidence (days) 660 660 575 —

Poly-3 test P=0.257N P=0.688 P=0.458 P=0.272N

Preputial Gland: Adenoma or Carcinoma

Overall rate 6/50 (12%) 3/50 (6%) 4/49 (8%) 1/50 (2%)

Adjusted rate 14.3% 7.3% 10.5% 2.8%

Terminal rate 4/23 (17%) 1/26 (4%) 1/18 (6%) 0/13 (0%)

First incidence (days) 660 660 575 642

Poly-3 test P=0.080N P=0.251N P=0.428N P=0.082N

Skin: Keratoacanthoma

Overall rate 0/50 (0%) 3/50 (6%) 6/50 (12%) 6/50 (12%)

Adjusted rate 0.0% 7.4% 15.4% 16.2%

Terminal rate 0/23 (0%) 3/26 (12%) 2/18 (11%) 2/13 (15%)

First incidence (days) — 729 (T) 488 562

Poly-3 test P=0.008 P=0.115 P=0.012 P=0.010

Skin: Basal Cell Adenoma or Basal Cell Carcinoma

Overall rate 0/50 (0%) 3/50 (6%) 3/50 (6%) 3/50 (6%)

Adjusted rate 0.0% 7.3% 7.8% 8.3%

Terminal rate 0/23 (0%) 2/26 (8%) 0/18 (0%) 2/13 (15%)

First incidence (days) — 585 618 687

Poly-3 test P=0.111 P=0.117 P=0.105 P=0.094

Skin: Keratoacanthoma or Squamous Cell Carcinoma

Overall rate 1/50 (2%) 4/50 (8%) 6/50 (12%) 8/50 (16%)

Adjusted rate 2.4% 9.8% 15.4% 21.4%

Terminal rate 0/23 (0%) 3/26 (12%) 2/18 (11%) 3/13 (23%)

First incidence (days) 669 711 488 562

Poly-3 test P=0.006 P=0.171 P=0.044 P=0.009

Skin: Basal Cell Carcinoma or Squamous Cell Carcinoma

Overall rate 1/50 (2%) 3/50 (6%) 1/50 (2%) 4/50 (8%)

Adjusted rate 2.4% 7.4% 2.6% 11.0%

Terminal rate 0/23 (0%) 2/26 (8%) 0/18 (0%) 2/13 (15%)

First incidence (days) 669 711 697 659

Poly-3 test P=0.124 P=0.297 P=0.739 P=0.138

Skin: Keratoacanthoma, Basal Cell Adenoma, Basal Cell Carcinoma, or Squamous Cell Carcinoma

Overall rate 1/50 (2%) 7/50 (14%) 9/50 (18%) 10/50 (20%)

Adjusted rate 2.4% 17.0% 22.6% 26.7%

Terminal rate 0/23 (0%) 5/26 (19%) 2/18 (11%) 4/13 (31%)

First incidence (days) 669 585 488 562

Poly-3 test P=0.003 P=0.028 P=0.006 P=0.002
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TABLE A2

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Skin (Subcutaneous Tissue): Fibroma

Overall rate 3/50 (6%) 5/50 (10%) 1/50 (2%) 0/50 (0%)

Adjusted rate 7.1% 12.0% 2.6% 0.0%

Terminal rate 1/23 (4%) 2/26 (8%) 0/18 (0%) 0/13 (0%)

First incidence (days) 646 560 690 —

Poly-3 test P=0.053N P=0.349 P=0.342N P=0.149N

Skin: Fibroma or Fibrous Histiocytoma

Overall rate 3/50 (6%) 5/50 (10%) 2/50 (4%) 0/50 (0%)

Adjusted rate 7.1% 12.0% 5.2% 0.0%

Terminal rate 1/23 (4%) 2/26 (8%) 0/18 (0%) 0/13 (0%)

First incidence (days) 646 560 614 —

Poly-3 test P=0.075N P=0.349 P=0.542N P=0.149N

Testes: Adenoma

Overall rate 34/50 (68%) 38/50 (76%) 32/50 (64%) 29/50 (58%)

Adjusted rate 73.9% 82.7% 75.9% 68.7%

Terminal rate 17/23 (74%) 22/26 (85%) 18/18 (100%) 8/13 (62%)

First incidence (days) 501 528 520 500

Poly-3 test P=0.198N P=0.204 P=0.516 P=0.371N

Thyroid Gland (C-Cell): Adenoma

Overall rate 5/50 (10%) 4/50 (8%) 3/50 (6%) 3/49 (6%)

Adjusted rate 11.9% 9.7% 7.7% 8.5%

Terminal rate 2/23 (9%) 3/26 (12%) 1/18 (6%) 2/13 (15%)

First incidence (days) 660 505 488 710

Poly-3 test P=0.356N P=0.510N P=0.397N P=0.451N

Thyroid Gland (C-Cell): Carcinoma

Overall rate 4/50 (8%) 3/50 (6%) 2/50 (4%) 0/49 (0%)

Adjusted rate 9.7% 7.3% 5.2% 0.0%

Terminal rate 4/23 (17%) 2/26 (8%) 1/18 (6%) 0/13 (0%)

First incidence (days) 729 (T) 687 554 —

Poly-3 test P=0.051N P=0.508N P=0.373N P=0.082N

Thyroid Gland (C-Cell): Adenoma or Carcinoma

Overall rate 9/50 (18%) 7/50 (14%) 5/50 (10%) 3/49 (6%)

Adjusted rate 21.4% 16.9% 12.6% 8.5%

Terminal rate 6/23 (26%) 5/26 (19%) 2/18 (11%) 2/13 (15%)

First incidence (days) 660 505 488 710

Poly-3 test P=0.066N P=0.400N P=0.223N P=0.102N

Thyroid Gland (Follicular Cell): Adenoma or Carcinoma

Overall rate 0/50 (0%) 2/50 (4%) 2/50 (4%) 3/49 (6%)

Adjusted rate 0.0% 4.9% 5.2% 8.4%

Terminal rate 0/23 (0%) 2/26 (8%) 1/18 (6%) 2/13 (15%)

First incidence (days) — 729 (T) 590 687

Poly-3 test P=0.075 P=0.233 P=0.219 P=0.093

All Organs: Malignant Mesothelioma

Overall rate 0/50 (0%) 2/50 (4%) 2/50 (4%) 4/50 (8%)

Adjusted rate 0.0% 4.9% 5.2% 10.8%

Terminal rate 0/23 (0%) 2/26 (8%) 0/18 (0%) 1/13 (8%)

First incidence (days) — 729 (T) 536 394

Poly-3 test P=0.031 P=0.233 P=0.220 P=0.046
1-Bromopropane, NTP TR 564 A-9

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TABLE A2

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

All Organs: Mononuclear Cell Leukemia

Overall rate 29/50 (58%) 22/50 (44%) 16/50 (32%) 24/50 (48%)

Adjusted rate 62.7% 49.8% 40.1% 59.9%

Terminal rate 13/23 (57%) 10/26 (39%) 8/18 (44%) 9/13 (69%)

First incidence (days) 501 540 578 527

Poly-3 test P=0.429N P=0.147N P=0.024N P=0.483N

All Organs: Benign Neoplasms

Overall rate 48/50 (96%) 49/50 (98%) 47/50 (94%) 48/50 (96%)

Adjusted rate 97.6% 99.8% 97.8% 97.9%

Terminal rate 23/23 (100%) 26/26 (100%) 18/18 (100%) 13/13 (100%)

First incidence (days) 429 505 488 394

Poly-3 test P=0.611N P=0.444 P=0.794 P=0.760

All Organs: Malignant Neoplasms

Overall rate 38/50 (76%) 33/50 (66%) 32/50 (64%) 32/50 (64%)

Adjusted rate 79.4% 72.5% 73.5% 74.5%

Terminal rate 18/23 (78%) 19/26 (73%) 15/18 (83%) 11/13 (85%)

First incidence (days) 429 316 488 394

Poly-3 test P=0.366N P=0.287N P=0.328N P=0.373N

All Organs: Benign or Malignant Neoplasms

Overall rate 50/50 (100%) 50/50 (100%) 48/50 (96%) 49/50 (98%)

Adjusted rate 100.0% 100.0% 98.8% 99.4%

Terminal rate 23/23 (100%) 26/26 (100%) 18/18 (100%) 13/13 (100%)

First incidence (days) 429 316 488 394

Poly-3 test P=0.592N —f P=0.826N P=0.992N

(T)Terminal sacrifice

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for adrenal 

medulla, lung, pancreatic islets, pituitary gland, preputial gland, testes, and thyroid gland; for other tissues, denominator is number of animals 

necropsied.

b Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality

c Observed incidence at terminal kill

d Beneath the chamber control incidence is the P value associated with the trend test. Beneath the exposed group incidence are the P values 

corresponding to pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for the differential 

mortality in animals that do not reach terminal sacrifice. A negative trend or a lower incidence in an exposure group is indicated by N.

e Not applicable; no neoplasms in animal group

f Value of statistic cannot be computed.
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TABLE A3a

Historical Incidence of Large Intestine (Colon or Rectum) Neoplasms in Control Male F344/N Ratsa

Study (Study Start) Incidence in Controls

Adenoma Carcinoma Adenoma or Carcinoma

Historical Incidence: Inhalation Studies 

1-Bromopropane (July, 2003) 0/50 0/50 0/50

Cumene (June, 2001) 0/50 0/50 0/50

Diethylamine (August, 2003) 0/50 0/50 0/50

Methyl isobutyl ketone (May, 2000) 0/50 0/50 0/50

α-Methylstyrene (August, 2001) 0/50 0/50 0/50

Propargyl alcohol (October, 2001) 0/49 0/49 0/49

Tetralin (June, 2003) 0/50 0/50 0/50

Total (%) 0/349 0/349 0/349

Overall Historical Incidence: All Routes

Total (%) 2/1,398 (0.1%) 1/1,398 (0.1%) 3/1,398 (0.2%)

Mean ± standard deviation 0.1% ± 0.5% 0.1% ± 0.4% 0.2% ± 0.6%

Range 0%-2% 0%-2% 0%-2%

a Data as of April 29, 2009
1-Bromopropane, NTP TR 564 A-11

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TABLE A3b

Historical Incidence of Skin Neoplasms in Control Male F344/N Ratsa

Study (Study Start) Incidence in Controls

Keratoacanthoma Basal Cell Adenoma Squamous Cell Carcinoma

Historical Incidence: Inhalation Studies 

1-Bromopropane (July, 2003) 0/50 0/50 1/50

Cumene (June, 2001) 4/50 1/50 0/50

Diethylamine (August, 2003) 0/50 0/50 0/50

Methyl isobutyl ketone (May, 2000) 0/50 0/50 0/50

α-Methylstyrene (August, 2001) 1/50 1/50 0/50

Propargyl alcohol (October, 2001) 4/49 1/49 0/49

Tetralin (June, 2003) 1/50 1/50 0/50

Total (%) 10/349 (2.9%) 4/349 (1.2%) 1/349 (0.3%)

Mean ± standard deviation 2.9% ± 3.7% 1.2.% ± 1.1% 0.3% ± 0.8%

Range 0%-8% 0%-2% 0%-2%

Overall Historical Incidence: All Routes

Total (%) 66/1,398 (4.7%) 15/1,398 (1.1%) 8/1,398 (0.6%)

Mean ± standard deviation 4.7% ± 4.2% 1.1% ± 1.4% 0.6% ± 0.9%

Range 0%-16% 0%-4% 0%-2%

Keratoacanthoma or

Squamous Cell Carcinoma

Keratoacanthoma, Basal Cell Adenoma, 

Basal Cell Carcinoma, or

Squamous Cell Carcinoma

Historical Incidence: Inhalation Studies 

1-Bromopropane (July, 2003) 1/50 1/50

Cumene (June, 2001) 4/50 5/50

Diethylamine (August, 2003) 0/50 1/50

Methyl isobutyl ketone (May, 2000) 0/50 0/50

α-Methylstyrene (August, 2001) 1/50 2/50

Propargyl alcohol (October, 2001) 4/49 5/49

Tetralin (June, 2003) 1/50 5/50

Total (%) 11/349 (3.2%) 19/349 (5.4%)

Mean ± standard deviation 3.2% ± 3.5% 5.5% ± 4.5%

Range 0%-8% 0%-10%

Overall Historical Incidence: All Routes

Total (%) 74/1,398 (5.3%) 97/1,398 (6.9%)

Mean ± standard deviation 5.3% ± 4.1% 6.9% ± 4.9%

Range 0%-16% 0%-20%

a Data as of April 29, 2009
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TABLE A3c

Historical Incidence of Malignant Mesothelioma in Control Male F344/N Ratsa

Study (Study Start) Incidence in Controls

Historical Incidence: Inhalation Studies 

1-Bromopropane (July, 2003) 0/50

Cumene (June, 2001) 3/50

Diethylamine (August, 2003) 0/50

Methyl isobutyl ketone (May, 2000) 1/50

α-Methylstyrene (August, 2001) 0/50

Propargyl alcohol (October, 2001) 1/49

Tetralin (June, 2003) 0/50

Total (%) 5/349 (1.4%)

Mean ± standard deviation 1.4% ± 2.2%

Range 0%-6%

Overall Historical Incidence: All Routes

Total (%) 35/1,398 (2.5%)

Mean ± standard deviation 2.5% ± 2.3%

Range 0%-6%

a Data as of April 29, 2009

TABLE A3d

Historical Incidence of Pancreatic Islet Neoplasms in Control Male F344/N Ratsa

Study (Study Start) Incidence in Controls

Adenoma Carcinoma Adenoma or Carcinoma

Historical Incidence: Inhalation Studies 

1-Bromopropane (July, 2003) 0/50 3/50 3/50

Cumene (June, 2001) 1/50 2/50 3/50

Diethylamine (August, 2003) 6/50 1/50 7/50

Methyl isobutyl ketone (May, 2000) 3/50 4/50 7/50

α-Methylstyrene (August, 2001) 3/50 1/50 4/50

Propargyl alcohol (October, 2001) 4/49 5/49 9/49

Tetralin (June, 2003) 3/50 1/50 4/50

Total (%) 20/349 (5.7%) 17/349 (4.9%) 37/349 (10.6%)

Mean ± standard deviation 5.7% ± 3.9% 4.9.% ± 3.3% 10.6% ± 4.8%

Range 0%-12% 2%-10% 6%-18%

Overall Historical Incidence: All Routes

Total (%) 90/1,394 (6.5%) 29/1,394 (2.1%) 119/1,394 (8.5%)

Mean ± standard deviation 6.5% ± 3.6% 2.1% ± 2.6% 8.6% ± 4.0%

Range 0%-14% 0%-10% 0%-18%

a Data as of April 29, 2009
1-Bromopropane, NTP TR 564 A-13

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TABLE A4

Summary of the Incidence of Nonneoplastic Lesions in Male Rats

in the 2-Year Inhalation Study of 1-Bromopropanea

Chamber Control 125 ppm 250 ppm 500 ppm

Disposition Summary

Animals initially in study 50 50 50 50

Early deaths

Moribund 24 20 28 35

Natural deaths 3 4 4 2

Survivors

Terminal sacrifice 23 26 18 13

Animals examined microscopically 50 50 50 50

Alimentary System

Esophagus (50) (50) (50) (50)

Intestine large, cecum (47) (47) (47) (48)

Edema 1 (2%)

Inflammation, chronic active 1 (2%)

Necrosis 1 (2%)

Artery, inflammation 1 (2%)

Intestine large, colon (48) (48) (48) (48)

Artery, inflammation 1 (2%)

Intestine large, rectum (48) (48) (48) (49)

Necrosis 1 (2%) 1 (2%)

Intestine small, duodenum (48) (48) (48) (48)

Fibrosis 1 (2%)

Intestine small, ileum (47) (47) (46) (48)

Inflammation, chronic active 1 (2%)

Necrosis 1 (2%) 1 (2%)

Intestine small, jejunum (47) (47) (46) (48)

Liver (50) (50) (50) (50)

Angiectasis 2 (4%) 1 (2%)

Basophilic focus 9 (18%) 9 (18%) 8 (16%) 8 (16%)

Clear cell focus 16 (32%) 25 (50%) 17 (34%) 15 (30%)

Degeneration, cystic 2 (4%) 2 (4%) 1 (2%) 4 (8%)

Eosinophilic focus 1 (2%) 1 (2%) 1 (2%)

Hemorrhage 1 (2%)

Hepatodiaphragmatic nodule 4 (8%) 1 (2%) 2 (4%)

Mixed cell focus 2 (4%) 1 (2%) 3 (6%)

Necrosis 2 (4%) 1 (2%) 1 (2%) 1 (2%)

Thrombosis 1 (2%) 1 (2%)

Vacuolization cytoplasmic 31 (62%) 38 (76%) 32 (64%) 37 (74%)

Serosa, fibrosis 1 (2%)

Mesentery (13) (13) (8) (19)

Necrosis 13 (100%) 13 (100%) 7 (88%) 17 (89%)

Oral mucosa (3) (0) (2) (4)

Foreign body 1 (33%) 1 (50%) 2 (50%)

Hyperplasia, squamous 1 (33%) 1 (50%)

Inflammation, chronic active 1 (33%) 2 (50%)

Pancreas (50) (50) (50) (50)

Basophilic focus 1 (2%) 1 (2%)

Cyst 1 (2%)

Fibrosis 1 (2%)

Necrosis 1 (2%)

Acinus, atrophy 23 (46%) 13 (26%) 20 (40%) 23 (46%)

Artery, inflammation 1 (2%) 1 (2%)

Salivary glands (50) (50) (50) (50)

Hyperplasia 1 (2%)

Inflammation, chronic active 1 (2%) 3 (6%) 2 (4%)

a Number of animals examined microscopically at the site and the number of animals with lesion
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TABLE A4

Summary of the Incidence of Nonneoplastic Lesions in Male Rats

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Alimentary System (continued)

Stomach, forestomach (50) (50) (50) (50)

Erosion 1 (2%)

Hyperplasia, squamous 1 (2%) 1 (2%) 1 (2%) 1 (2%)

Ulcer 7 (14%) 3 (6%) 5 (10%) 4 (8%)

Stomach, glandular (50) (50) (50) (50)

Erosion 1 (2%) 1 (2%)

Ulcer 1 (2%) 2 (4%) 1 (2%)

Artery, inflammation 1 (2%)

Epithelium, hyperplasia 1 (2%)

Tongue (0) (0) (1) (1)

Hyperplasia, squamous 1 (100%) 1 (100%)

Cardiovascular System

Heart (50) (50) (50) (50)

Cardiomyopathy 26 (52%) 23 (46%) 23 (46%) 15 (30%)

Atrium, thrombosis 4 (8%) 2 (4%)

Ventricle, thrombosis 1 (2%)

Endocrine System

Adrenal cortex (50) (50) (50) (50)

Hyperplasia 27 (54%) 21 (42%) 22 (44%) 20 (40%)

Vacuolization cytoplasmic 9 (18%) 16 (32%) 9 (18%) 12 (24%)

Adrenal medulla (50) (50) (50) (50)

Hemorrhage 1 (2%)

Hyperplasia 23 (46%) 18 (36%) 23 (46%) 19 (38%)

Islets, pancreatic (50) (50) (50) (50)

Hyperplasia 10 (20%) 7 (14%) 6 (12%) 9 (18%)

Parathyroid gland (46) (48) (47) (46)

Hyperplasia 2 (4%)

Pituitary gland (50) (50) (50) (49)

Cyst 1 (2%) 2 (4%) 1 (2%)

Hemorrhage 4 (8%) 2 (4%) 5 (10%)

Pars distalis, hyperplasia 8 (16%) 5 (10%) 11 (22%) 7 (14%)

Thyroid gland (50) (50) (50) (49)

Ultimobranchial cyst 1 (2%)

C-cell, hyperplasia 32 (64%) 31 (62%) 29 (58%) 34 (69%)

Follicular cell, hyperplasia 1 (2%)

General Body System

Peritoneum (0) (0) (0) (2)

Inflammation, suppurative, chronic 1 (50%)

Genital System

Coagulating gland (3) (0) (1) (2)

Hyperplasia 1 (33%)

Inflammation, suppurative 2 (67%)

Epididymis (50) (50) (50) (50)

Penis (0) (3) (1) (1)

Concretion 1 (100%)

Hyperplasia, squamous 1 (33%)
1-Bromopropane, NTP TR 564 A-15

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TABLE A4

Summary of the Incidence of Nonneoplastic Lesions in Male Rats

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Genital System (continued)

Preputial gland (50) (50) (49) (50)

Ectasia 1 (2%) 1 (2%)

Hyperplasia 3 (6%) 1 (2%)

Inflammation, suppurative, chronic 1 (2%)

Inflammation, chronic active 30 (60%) 33 (66%) 31 (63%) 37 (74%)

Prostate (50) (50) (50) (50)

Hyperplasia 12 (24%) 13 (26%) 10 (20%) 17 (34%)

Inflammation, suppurative, chronic 1 (2%)

Inflammation, suppurative 38 (76%) 42 (84%) 40 (80%) 36 (72%)

Seminal vesicle (50) (49) (49) (50)

Congestion 1 (2%)

Dilatation 1 (2%)

Hyperplasia 1 (2%)

Inflammation, suppurative 2 (4%) 1 (2%) 2 (4%)

Testes (50) (50) (50) (50)

Mineralization 1 (2%) 1 (2%)

Germinal epithelium, atrophy 12 (24%) 8 (16%) 7 (14%) 6 (12%)

Interstitial cell, hyperplasia 1 (2%) 2 (4%) 1 (2%)

Hematopoietic System

Bone marrow (50) (50) (50) (50)

Thrombosis 1 (2%)

Lymph node (5) (5) (5) (4)

Deep cervical, angiectasis 1 (20%)

Pancreatic, angiectasis 2 (40%)

Pancreatic, hemorrhage 1 (25%)

Lymph node, bronchial (3) (6) (5) (8)

Angiectasis 1 (33%) 2 (33%) 2 (40%)

Fibrosis 1 (17%)

Hemorrhage 1 (33%) 1 (17%) 1 (20%) 1 (13%)

Hyperplasia, lymphoid 4 (50%)

Lymph node, mandibular (3) (1) (0) (6)

Angiectasis 1 (17%)

Lymph node, mediastinal (30) (25) (23) (32)

Angiectasis 1 (4%) 3 (9%)

Hyperplasia, lymphoid 1 (4%) 1 (4%) 2 (6%)

Lymph node, mesenteric (50) (50) (50) (50)

Angiectasis 1 (2%) 1 (2%) 2 (4%)

Hyperplasia, lymphoid 1 (2%)

Infiltration cellular, histiocyte 1 (2%)

Artery, necrosis 1 (2%)

Spleen (50) (50) (49) (50)

Accessory spleen 1 (2%) 1 (2%)

Fibrosis 1 (2%) 2 (4%) 1 (2%)

Hematopoietic cell proliferation 10 (20%) 17 (34%) 13 (27%) 6 (12%)

Hemorrhage, chronic 4 (8%) 1 (2%) 3 (6%)

Hyperplasia, lymphoid 1 (2%)

Infarct, chronic 1 (2%) 2 (4%) 3 (6%)

Infiltration cellular, mononuclear cell 1 (2%)

Thymus (43) (41) (47) (46)

Cyst 1 (2%)
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TABLE A4

Summary of the Incidence of Nonneoplastic Lesions in Male Rats

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Integumentary System

Mammary gland (40) (36) (39) (36)

Galactocele 1 (3%) 1 (3%)

Hyperplasia 1 (3%)

Epithelium, hyperplasia 1 (3%) 1 (3%) 1 (3%)

Skin (50) (50) (50) (50)

Cyst epithelial inclusion 1 (2%) 1 (2%)

Foreign body 1 (2%)

Hyperkeratosis 3 (6%) 2 (4%)

Hyperplasia, squamous 1 (2%)

Inflammation, suppurative, chronic 1 (2%) 2 (4%) 10 (20%)

Inflammation, chronic active 1 (2%) 3 (6%) 3 (6%) 4 (8%)

Thrombosis 1 (2%)

Musculoskeletal System

Bone (50) (50) (50) (50)

Fibrosis 1 (2%)

Hyperostosis 1 (2%)

Inflammation, suppurative, chronic 2 (4%)

Skeletal muscle (1) (1) (3) (3)

Inflammation, suppurative, chronic 1 (33%)

Nervous System

Brain (50) (50) (50) (50)

Hemorrhage 1 (2%) 1 (2%) 2 (4%) 2 (4%)

Spinal cord (1) (1) (2) (1)

Respiratory System

Larynx (50) (50) (50) (50)

Foreign body 6 (12%) 1 (2%) 5 (10%) 1 (2%)

Inflammation, suppurative, chronic 1 (2%)

Inflammation, chronic active 21 (42%) 28 (56%) 31 (62%) 26 (52%)

Metaplasia, squamous 4 (8%) 6 (12%) 8 (16%) 5 (10%)

Respiratory epithelium, hyperplasia 1 (2%) 1 (2%) 1 (2%)

Lung (50) (50) (50) (50)

Foreign body 1 (2%)

Hemorrhage 2 (4%) 5 (10%) 1 (2%) 1 (2%)

Inflammation, suppurative, chronic 1 (2%) 3 (6%)

Inflammation, chronic active 5 (10%) 3 (6%)

Metaplasia, osseous 1 (2%)

Alveolar epithelium, hyperplasia 15 (30%) 11 (22%) 13 (26%) 11 (22%)

Alveolar epithelium, metaplasia, squamous 1 (2%)

Alveolus, infiltration cellular, histiocyte 16 (32%) 14 (28%) 13 (26%) 11 (22%)

Artery, inflammation 1 (2%)
1-Bromopropane, NTP TR 564 A-17

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TABLE A4

Summary of the Incidence of Nonneoplastic Lesions in Male Rats

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Respiratory System (continued)

Nose (50) (48) (48) (50)

Degeneration, hyaline 1 (2%)

Foreign body 11 (22%) 10 (21%) 15 (31%) 11 (22%)

Inflammation, suppurative, chronic 1 (2%) 2 (4%) 7 (14%)

Inflammation, chronic active 29 (58%) 33 (69%) 34 (71%) 35 (70%)

Epithelium, accumulation, hyaline droplet 44 (88%) 39 (81%) 36 (75%) 44 (88%)

Glands, hyperplasia 5 (10%) 14 (29%) 14 (29%) 15 (30%)

Olfactory epithelium, atrophy 1 (2%)

Olfactory epithelium, metaplasia, 

respiratory 7 (14%) 10 (21%) 12 (25%) 12 (24%)

Respiratory epithelium, hyperplasia 14 (28%) 15 (31%) 20 (42%) 17 (34%)

Respiratory epithelium, metaplasia,

squamous 1 (2%) 1 (2%) 2 (4%)

Trachea (50) (50) (50) (50)

Inflammation, chronic active 1 (2%) 1 (2%) 1 (2%) 4 (8%)

Epithelium, hyperplasia 1 (2%) 1 (2%)

Special Senses System

Eye (49) (49) (50) (50)

Inflammation, chronic active 1 (2%) 2 (4%)

Lens, cataract 2 (4%) 3 (6%) 2 (4%)

Retina, degeneration 1 (2%)

Harderian gland (50) (50) (50) (50)

Inflammation, suppurative, chronic 2 (4%)

Lacrimal gland (1) (0) (0) (0)

Inflammation, chronic active 1 (100%)

Zymbal’s gland (0) (1) (2) (2)

Urinary System

Kidney (50) (50) (50) (49)

Cyst 1 (2%) 1 (2%)

Inflammation, suppurative 1 (2%)

Nephropathy, chronic 44 (88%) 45 (90%) 39 (78%) 44 (90%)

Cortex, infarct 1 (2%)

Cortex, renal tubule, casts granular 2 (4%)

Pelvis, inflammation, chronic active 2 (4%)

Urinary bladder (50) (50) (50) (50)

Hemorrhage 1 (2%)

Inflammation, chronic active 1 (2%) 1 (2%)

Transitional epithelium, hyperplasia 1 (2%)
A-18 1-Bromopropane, NTP TR 564

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B-1

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APPENDIX B

SUMMARY OF LESIONS IN FEMALE RATS

IN THE 2-YEAR INHALATION STUDY

OF 1-BROMOPROPANE

TABLE B1 Summary of the Incidence of Neoplasms in Female Rats

in the 2-Year Inhalation Study of 1-Bromopropane .......................................................................B-2

TABLE B2 Statistical Analysis of Primary Neoplasms in Female Rats

in the 2-Year Inhalation Study of 1-Bromopropane .......................................................................B-6

TABLE B3a Historical Incidence of Large Intestine (Colon or Rectum) Neoplasms 

in Control Female F344/N Rats.......................................................................................................B-10

TABLE B3b Historical Incidence of Skin Neoplasms in Control Female F344/N Rats...................................B-11

TABLE B4 Summary of the Incidence of Nonneoplastic Lesions in Female Rats

in the 2-Year Inhalation Study of 1-Bromopropane ....................................................................B-12
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TABLE B1

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Inhalation Study of 1-Bromopropanea

Chamber Control 125 ppm 250 ppm 500 ppm

Disposition Summary

Animals initially in study 50 50 50 50

Early deaths

Accidental deaths 2

Moribund 13 17 17 23

Natural deaths 3 3 1

Survivors

Terminal sacrifice 34 33 30 24

Animals examined microscopically 50 50 50 50

Alimentary System

Intestine large, colon (47) (50) (48) (49)

Adenoma 1 (2%) 1 (2%) 1 (2%)

Carcinoid tumor malignant 1 (2%)

Intestine large, rectum (47) (50) (48) (49)

Adenoma 1 (2%) 4 (8%)

Intestine small, ileum (46) (50) (47) (48)

Carcinoma 1 (2%)

Intestine small, jejunum (47) (50) (47) (48)

Liver (50) (50) (50) (50)

Hepatocellular carcinoma 1 (2%)

Mesentery (13) (26) (17) (23)

Sarcoma 1 (6%)

Sarcoma, metastatic, stomach, forestomach 1 (4%)

Oral mucosa (2) (0) (1) (1)

Pancreas (50) (50) (50) (50)

Sarcoma, metastatic, mesentery 1 (2%)

Salivary glands (50) (50) (50) (50)

Stomach, forestomach (50) (50) (50) (50)

Sarcoma 1 (2%)

Stomach, glandular (50) (50) (50) (50)

Sarcoma 1 (2%)

Tongue (0) (1) (0) (1)

Tooth (0) (0) (1) (0)

Cardiovascular System

Heart (50) (50) (50) (50)

Alveolar/bronchiolar carcinoma, metastatic, 

lung 1 (2%)

Endocrine System

Adrenal cortex (50) (50) (50) (50)

Adenoma 3 (6%) 3 (6%)

Adrenal medulla (50) (50) (50) (50)

Pheochromocytoma benign 2 (4%) 4 (8%) 1 (2%)

Pheochromocytoma complex 1 (2%)

Islets, pancreatic (50) (50) (50) (50)

Adenoma 2 (4%) 1 (2%)

Carcinoma 1 (2%) 1 (2%) 1 (2%)

Pituitary gland (50) (50) (50) (50)

Pars distalis, adenoma 35 (70%) 33 (66%) 28 (56%) 30 (60%)

Pars distalis, carcinoma 1 (2%) 1 (2%)
1-Bromopropane, NTP TR 564 B-3

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TABLE B1

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Endocrine System (continued)

Thyroid gland (50) (50) (50) (50)

C-cell, adenoma 3 (6%) 3 (6%) 3 (6%) 4 (8%)

C-cell, carcinoma 1 (2%) 2 (4%) 2 (4%) 2 (4%)

Follicular cell, adenoma 1 (2%) 1 (2%)

Follicular cell, carcinoma 1 (2%)

General Body System

None

Genital System

Clitoral gland (49) (50) (49) (49)

Adenoma 3 (6%) 9 (18%) 3 (6%) 3 (6%)

Carcinoma 1 (2%) 3 (6%) 2 (4%) 1 (2%)

Ovary (50) (50) (50) (50)

Cystadenoma 1 (2%)

Granulosa cell tumor malignant 1 (2%)

Granulosa-theca tumor malignant 2 (4%)

Uterus (50) (50) (50) (50)

Adenoma 1 (2%)

Polyp stromal 8 (16%) 8 (16%) 8 (16%) 7 (14%)

Sarcoma stromal 2 (4%) 1 (2%) 1 (2%)

Vagina (3) (0) (0) (0)

Sarcoma 1 (33%)

Hematopoietic System

Bone marrow (50) (50) (50) (50)

Lymph node (1) (3) (2) (2)

Lymph node, bronchial (1) (4) (5) (7)

Squamous cell carcinoma, metastatic, lung 1 (25%)

Lymph node, mediastinal (34) (30) (31) (28)

Carcinoma, metastatic, thyroid gland 1 (3%)

Lymph node, mesenteric (49) (49) (50) (50)

Spleen (50) (50) (50) (50)

Thymus (46) (45) (45) (43)

Thymoma benign 1 (2%)

Integumentary System

Mammary gland (50) (50) (50) (50)

Carcinoma 4 (8%) 3 (6%) 3 (6%) 1 (2%)

Fibroadenoma 19 (38%) 14 (28%) 15 (30%) 15 (30%)

Fibroadenoma, multiple 6 (12%) 6 (12%) 6 (12%) 1 (2%)

Skin (50) (50) (50) (50)

Basal cell adenoma 1 (2%) 1 (2%)

Basal cell carcinoma 1 (2%)

Keratoacanthoma 1 (2%) 1 (2%) 1 (2%)

Squamous cell papilloma 1 (2%)

Pinna, neural crest tumor 1 (2%) 1 (2%)

Sebaceous gland, adenoma 1 (2%)

Subcutaneous tissue, fibroma 2 (4%)

Subcutaneous tissue, lipoma 1 (2%)
B-4 1-Bromopropane, NTP TR 564

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TABLE B1

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Musculoskeletal System

Bone (50) (50) (50) (50)

Skeletal muscle (0) (0) (1) (4)

Alveolar/bronchiolar carcinoma, metastatic, 

lung 1 (100%)

Nervous System

Brain (50) (50) (50) (50)

Carcinoma, metastatic, pituitary gland 1 (2%) 1 (2%)

Glioma malignant 1 (2%)

Spinal cord (0) (1) (0) (3)

Respiratory System

Larynx (50) (50) (50) (50)

Lung (50) (50) (50) (50)

Alveolar/bronchiolar adenoma 1 (2%) 4 (8%) 2 (4%)

Alveolar/bronchiolar adenoma, multiple 1 (2%)

Alveolar/bronchiolar carcinoma 1 (2%) 1 (2%) 2 (4%)

Squamous cell carcinoma 1 (2%)

Nose (50) (50) (49) (50)

Fibroma 1 (2%)

Pleura (0) (0) (1) (0)

Alveolar/bronchiolar carcinoma, metastatic, 

lung 1 (100%)

Trachea (50) (50) (50) (50)

Special Senses System

Ear (0) (0) (1) (1)

Eye (50) (50) (50) (50)

Harderian gland (50) (50) (50) (50)

Zymbal’s gland (1) (1) (2) (0)

Carcinoma 1 (100%) 1 (100%) 2 (100%)

Urinary System

Kidney (49) (50) (50) (50)

Sarcoma, metastatic, stomach, forestomach 1 (2%)

Renal tubule, carcinoma 1 (2%)

Systemic Neoplasms

Multiple organsb (50) (50) (50) (50)

Histiocytic sarcoma 1 (2%)

Leukemia mononuclear 16 (32%) 13 (26%) 17 (34%) 15 (30%)

Lymphoma malignant 1 (2%)
1-Bromopropane, NTP TR 564 B-5

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TABLE B1

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Neoplasm Summary

Total animals with primary neoplasmsc 49 48 46 43

Total primary neoplasms 119 120 106 96

Total animals with benign neoplasms 45 46 36 41

Total benign neoplasms 84 90 72 72

Total animals with malignant neoplasms 26 23 28 20

Total malignant neoplasms 34 29 34 24

Total animals with metastatic neoplasms 2 4 1

Total metastatic neoplasms 2 6 2

Total animals with uncertain neoplasmsbenign or malignant 1 1

Total uncertain neoplasms 1 1

a Number of animals examined microscopically at the site and the number of animals with neoplasm

b Number of animals with any tissue examined microscopically

c Primary neoplasms: all neoplasms except metastatic neoplasms
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TABLE B2

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Adrenal Cortex: Adenoma

Overall ratea 3/50 (6%) 3/50 (6%) 0/50 (0%) 0/50 (0%)

Adjusted rateb 6.6% 6.9% 0.0% 0.0%

Terminal ratec 2/34 (6%) 3/33 (9%) 0/30 (0%) 0/24 (0%)

First incidence (days) 701 730 (T) —e —

Poly-3 testd P=0.042N P=0.645 P=0.131N P=0.156N

Adrenal Medulla: Benign Pheochromocytoma

Overall rate 2/50 (4%) 4/50 (8%) 1/50 (2%) 0/50 (0%)

Adjusted rate 4.4% 9.1% 2.3% 0.0%

Terminal rate 2/34 (6%) 3/33 (9%) 0/30 (0%) 0/24 (0%)

First incidence (days) 730 (T) 687 607 —

Poly-3 test P=0.118N P=0.323 P=0.519N P=0.281N

Adrenal Medulla: Benign or Complex Pheochromocytoma

Overall rate 3/50 (6%) 4/50 (8%) 1/50 (2%) 0/50 (0%)

Adjusted rate 6.6% 9.1% 2.3% 0.0%

Terminal rate 2/34 (6%) 3/33 (9%) 0/30 (0%) 0/24 (0%)

First incidence (days) 677 687 607 —

Poly-3 test P=0.062N P=0.481 P=0.327N P=0.156N

Clitoral Gland: Adenoma

Overall rate 3/49 (6%) 9/50 (18%) 3/49 (6%) 3/49 (6%)

Adjusted rate 6.7% 20.5% 7.2% 8.0%

Terminal rate 2/33 (6%) 8/33 (24%) 3/30 (10%) 1/24 (4%)

First incidence (days) 677 719 730 (T) 627

Poly-3 test P=0.390N P=0.054 P=0.631 P=0.583

Clitoral Gland: Carcinoma

Overall rate 1/49 (2%) 3/50 (6%) 2/49 (4%) 1/49 (2%)

Adjusted rate 2.3% 6.8% 4.8% 2.7%

Terminal rate 1/33 (3%) 2/33 (6%) 2/30 (7%) 0/24 (0%)

First incidence (days) 730 (T) 632 730 (T) 724

Poly-3 test P=0.556N P=0.303 P=0.478 P=0.720

Clitoral Gland: Adenoma or Carcinoma

Overall rate 4/49 (8%) 12/50 (24%) 4/49 (8%) 4/49 (8%)

Adjusted rate 9.0% 27.2% 9.6% 10.6%

Terminal rate 3/33 (9%) 10/33 (30%) 4/30 (13%) 1/24 (4%)

First incidence (days) 677 632 730 (T) 627

Poly-3 test P=0.353N P=0.023 P=0.606 P=0.549

Large Intestine (Colon and Rectum): Adenoma

Overall rate 0/50 (0%) 1/50 (2%) 2/50 (4%) 5/50 (10%)

Adjusted rate 0.0% 2.3% 4.7% 13.3%

Terminal rate 0/34 (0%) 1/33 (3%) 1/30 (3%) 4/24 (17%)

First incidence (days) — 730 (T) 607 719

Poly-3 test P=0.004 P=0.493 P=0.225 P=0.018

Lung: Alveolar/bronchiolar Adenoma

Overall rate 1/50 (2%) 4/50 (8%) 1/50 (2%) 2/50 (4%)

Adjusted rate 2.2% 9.1% 2.4% 5.3%

Terminal rate 1/34 (3%) 3/33 (9%) 1/30 (3%) 0/24 (0%)

First incidence (days) 730 (T) 635 730 (T) 627

Poly-3 test P=0.509 P=0.170 P=0.746 P=0.440
1-Bromopropane, NTP TR 564 B-7

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TABLE B2

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Lung: Alveolar/bronchiolar Adenoma or Carcinoma

Overall rate 2/50 (4%) 5/50 (10%) 3/50 (6%) 2/50 (4%)

Adjusted rate 4.4% 11.3% 6.9% 5.3%

Terminal rate 1/34 (3%) 3/33 (9%) 1/30 (3%) 0/24 (0%)

First incidence (days) 694 635 417 627

Poly-3 test P=0.521N P=0.205 P=0.482 P=0.628

Mammary Gland: Fibroadenoma

Overall rate 25/50 (50%) 20/50 (40%) 21/50 (42%) 16/50 (32%)

Adjusted rate 53.8% 42.8% 48.4% 41.3%

Terminal rate 18/34 (53%) 12/33 (36%) 16/30 (53%) 11/24 (46%)

First incidence (days) 638 528 642 501

Poly-3 test P=0.200N P=0.194N P=0.383N P=0.172N

Mammary Gland: Carcinoma

Overall rate 4/50 (8%) 3/50 (6%) 3/50 (6%) 1/50 (2%)

Adjusted rate 8.7% 6.8% 7.0% 2.7%

Terminal rate 0/34 (0%) 2/33 (6%) 2/30 (7%) 1/24 (4%)

First incidence (days) 612 575 684 730 (T)

Poly-3 test P=0.196N P=0.524N P=0.544N P=0.248N

Mammary Gland: Fibroadenoma or Carcinoma

Overall rate 27/50 (54%) 20/50 (40%) 23/50 (46%) 16/50 (32%)

Adjusted rate 57.1% 42.8% 53.1% 41.3%

Terminal rate 18/34 (53%) 12/33 (36%) 18/30 (60%) 11/24 (46%)

First incidence (days) 612 528 642 501

Poly-3 test P=0.149N P=0.115N P=0.428N P=0.102N

Pancreatic Islets: Adenoma or Carcinoma

Overall rate 1/50 (2%) 3/50 (6%) 2/50 (4%) 0/50 (0%)

Adjusted rate 2.2% 6.9% 4.7% 0.0%

Terminal rate 1/34 (3%) 3/33 (9%) 2/30 (7%) 0/24 (0%)

First incidence (days) 730 (T) 730 (T) 730 (T) —

Poly-3 test P=0.315N P=0.293 P=0.477 P=0.537N

Pituitary Gland (Pars Distalis): Adenoma

Overall rate 35/50 (70%) 33/50 (66%) 28/50 (56%) 30/50 (60%)

Adjusted rate 73.9% 68.2% 62.0% 71.3%

Terminal rate 25/34 (74%) 21/33 (64%) 20/30 (67%) 17/24 (71%)

First incidence (days) 633 433 534 450

Poly-3 test P=0.418N P=0.347N P=0.149N P=0.485N

Pituitary Gland (Pars Distalis): Adenoma or Carcinoma

Overall rate 35/50 (70%) 34/50 (68%) 29/50 (58%) 30/50 (60%)

Adjusted rate 73.9% 70.3% 64.1% 71.3%

Terminal rate 25/34 (74%) 22/33 (67%) 20/30 (67%) 17/24 (71%)

First incidence (days) 633 433 534 450

Poly-3 test P=0.404N P=0.433N P=0.206N P=0.485N

Skin: Squamous Cell Papilloma, Keratoacanthoma, Basal Cell Adenoma, or Basal Cell Carcinoma 

Overall rate 1/50 (2%) 1/50 (2%) 1/50 (2%) 4/50 (8%)

Adjusted rate 2.2% 2.3% 2.4% 10.6%

Terminal rate 1/34 (3%) 1/33 (3%) 1/30 (3%) 4/24 (17%)

First incidence (days) 730 (T) 730 (T) 730 (T) 730 (T)

Poly-3 test P=0.050 P=0.753 P=0.746 P=0.128
B-8 1-Bromopropane, NTP TR 564

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TABLE B2

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Thyroid Gland (C-Cell): Adenoma

Overall rate 3/50 (6%) 3/50 (6%) 3/50 (6%) 4/50 (8%)

Adjusted rate 6.6% 6.8% 7.0% 10.6%

Terminal rate 3/34 (9%) 2/33 (6%) 2/30 (7%) 4/24 (17%)

First incidence (days) 730 (T) 659 694 730 (T)

Poly-3 test P=0.310 P=0.649 P=0.634 P=0.400

Thyroid Gland (C-Cell): Adenoma or Carcinoma

Overall rate 4/50 (8%) 5/50 (10%) 5/50 (10%) 6/50 (12%)

Adjusted rate 8.8% 11.4% 11.7% 15.8%

Terminal rate 4/34 (12%) 4/33 (12%) 4/30 (13%) 5/24 (21%)

First incidence (days) 730 (T) 659 694 626

Poly-3 test P=0.212 P=0.482 P=0.462 P=0.264

Uterus: Stromal Polyp

Overall rate 8/50 (16%) 8/50 (16%) 8/50 (16%) 7/50 (14%)

Adjusted rate 17.3% 18.0% 18.5% 17.9%

Terminal rate 6/34 (18%) 6/33 (18%) 5/30 (17%) 3/24 (13%)

First incidence (days) 438 577 607 590

Poly-3 test P=0.519 P=0.573 P=0.551 P=0.584

Uterus: Stromal Polyp or Stromal Sarcoma

Overall rate 10/50 (20%) 8/50 (16%) 8/50 (16%) 8/50 (16%)

Adjusted rate 21.3% 18.0% 18.5% 20.3%

Terminal rate 7/34 (21%) 6/33 (18%) 5/30 (17%) 3/24 (13%)

First incidence (days) 438 577 607 590

Poly-3 test P=0.516N P=0.449N P=0.472N P=0.558N

All Organs: Mononuclear Cell Leukemia

Overall rate 16/50 (32%) 13/50 (26%) 17/50 (34%) 15/50 (30%)

Adjusted rate 34.3% 29.2% 37.6% 38.7%

Terminal rate 9/34 (27%) 10/33 (30%) 8/30 (27%) 10/24 (42%)

First incidence (days) 633 590 541 611

Poly-3 test P=0.294 P=0.385N P=0.453 P=0.423

All Organs: Benign Neoplasms

Overall rate 45/50 (90%) 46/50 (92%) 36/50 (72%) 41/50 (82%)

Adjusted rate 93.3% 92.2% 79.3% 92.9%

Terminal rate 33/34 (97%) 30/33 (91%) 26/30 (87%) 23/24 (96%)

First incidence (days) 438 433 534 450

Poly-3 test P=0.399N P=0.577N P=0.028N P=0.654N

All Organs: Malignant Neoplasms

Overall rate 26/50 (52%) 23/50 (46%) 28/50 (56%) 20/50 (40%)

Adjusted rate 53.3% 50.0% 58.9% 50.4%

Terminal rate 13/34 (38%) 15/33 (46%) 15/30 (50%) 12/24 (50%)

First incidence (days) 493 575 417 578

Poly-3 test P=0.519N P=0.452N P=0.363 P=0.475N
1-Bromopropane, NTP TR 564 B-9

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TABLE B2

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

All Organs: Benign or Malignant Neoplasms

Overall rate 49/50 (98%) 48/50 (96%) 46/50 (92%) 43/50 (86%)

Adjusted rate 98.0% 96.0% 92.7% 96.6%

Terminal rate 33/34 (97%) 31/33 (94%) 27/30 (90%) 24/24 (100%)

First incidence (days) 438 433 417 450

Poly-3 test P=0.415N P=0.500N P=0.211N P=0.613N

(T)Terminal sacrifice

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for adrenal 

gland, clitoral gland, lung, pancreatic islets, pituitary gland, and thyroid gland; for other tissues, denominator is number of animals necropsied.

b Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality

c Observed incidence at terminal kill

d Beneath the chamber control incidence is the P value associated with the trend test. Beneath the exposed group incidence are the P values 

corresponding to pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for the differential 

mortality in animals that do not reach terminal sacrifice. A negative trend or a lower incidence in an exposure group is indicated by N.

e Not applicable; no neoplasms in animal group
B-10 1-Bromopropane, NTP TR 564

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TABLE B3a

Historical Incidence of Large Intestine (Colon or Rectum) Neoplasms in Control Female F344/N Ratsa

Study (Study Start) Incidence in Controls

Adenoma Carcinoma Adenoma or Carcinoma

Historical Incidence: Inhalation Studies 

1-Bromopropane (July, 2003) 0/50 0/50 0/50

Cumene (June, 2001) 0/50 0/50 0/50

Diethylamine (August, 2003) 0/50 0/50 0/50

Methyl isobutyl ketone (May, 2000) 0/50 0/50 0/50

α-Methylstyrene (August, 2001) 0/50 0/50 0/50

Propargyl alcohol (October, 2001) 0/50 0/50 0/50

Tetralin (June, 2003) 0/50 0/50 0/50

Total (%) 0/350 0/350 0/350

Overall Historical Incidence: All Routes

Total (%) 3/1,350 (0.2%) 1/1,350 (0.1%) 4/1,350 (0.3%)

Mean ± standard deviation 0.2% ± 0.6% 0.1% ± 0.4% 0.3% ± 0.7%

Range 0%-2% 0%-2% 0%-2%

a Data as of April 29, 2009
1-Bromopropane, NTP TR 564 B-11

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TABLE B3b

Historical Incidence of Skin Neoplasms in Control Female F344/N Ratsa

Study (Study Start) Incidence in Controls

Squamous Cell Papilloma Keratoacanthoma Basal Cell Adenoma

Historical Incidence: Inhalation Studies 

1-Bromopropane (July, 2003) 0/50 1/50 0/50

Cumene (June, 2001) 0/50 0/50 0/50

Diethylamine (August, 2003) 0/50 1/50 0/50

Methyl isobutyl ketone (May, 2000) 0/50 0/50 0/50

α-Methylstyrene (August, 2001) 0/50 0/50 0/50

Propargyl alcohol (October, 2001) 0/50 0/50 0/50

Tetralin (June, 2003) 0/50 0/50 0/50

Total (%) 0/350 2/350 (0.6%) 0/350

Mean ± standard deviation 0.6.% ± 1.0%

Range 0%-2%

Overall Historical Incidence: All Routes

Total (%) 5/1,350 (0.4%) 8/1,350 (0.6%) 3/1,350 (0.2%)

Mean ± standard deviation 0.4% ± 0.8% 0.6% ± 1.2% 0.2% ± 0.6%

Range 0%-2% 0%-4% 0%-2%

Basal Cell Carcinoma Squamous Cell Papilloma, 

Keratoacanthoma, Basal Cell Adenoma, 

or Basal Cell Carcinoma

Historical Incidence: Inhalation Studies 

1-Bromopropane (July, 2003) 0/50 1/50

Cumene (June, 2001) 0/50 0/50

Diethylamine (August, 2003) 0/50 1/50

Methyl isobutyl ketone (May, 2000) 0/50 0/50

α-Methylstyrene (August, 2001) 0/50 0/50

Propargyl alcohol (October, 2001) 0/50 0/50

Tetralin (June, 2003) 0/50 0/50

Total (%) 0/350 2/350 (0.6%)

Mean ± standard deviation 0.6.% ± 1.0%

Range 0%-2%

Overall Historical Incidence: All Routes

Total (%) 1/1,350 (0.1%) 16/1,350 (1.2%)

Mean ± standard deviation 0.1% ± 0.4% 1.2% ± 1.8%

Range 0%-2% 0%-6%

a Data as of April 29, 2009
B-12 1-Bromopropane, NTP TR 564

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TABLE B4

Summary of the Incidence of Nonneoplastic Lesions in Female Rats

in the 2-Year Inhalation Study of 1-Bromopropanea

Chamber Control 125 ppm 250 ppm 500 ppm

Disposition Summary

Animals initially in study 50 50 50 50

Early deaths

Accidental deaths 2

Moribund 13 17 17 23

Natural deaths 3 3 1

Survivors

Terminal sacrifice 34 33 30 24

Animals examined microscopically 50 50 50 50

Alimentary System

Intestine large, colon (47) (50) (48) (49)

Intestine large, rectum (47) (50) (48) (49)

Inflammation, suppurative 1 (2%)

Necrosis 1 (2%)

Intestine small, ileum (46) (50) (47) (48)

Intestine small, jejunum (47) (50) (47) (48)

Liver (50) (50) (50) (50)

Angiectasis 3 (6%) 2 (4%) 2 (4%) 1 (2%)

Basophilic focus 40 (80%) 43 (86%) 42 (84%) 39 (78%)

Clear cell focus 30 (60%) 34 (68%) 35 (70%) 35 (70%)

Cyst 1 (2%)

Degeneration, cystic 1 (2%)

Eosinophilic focus 1 (2%) 1 (2%)

Hepatodiaphragmatic nodule 4 (8%) 9 (18%) 5 (10%) 5 (10%)

Mixed cell focus 2 (4%) 2 (4%) 3 (6%) 3 (6%)

Necrosis 1 (2%) 1 (2%)

Vacuolization cytoplasmic 40 (80%) 41 (82%) 39 (78%) 47 (94%)

Bile duct, cyst 1 (2%)

Serosa, fibrosis 1 (2%)

Mesentery (13) (26) (17) (23)

Necrosis 13 (100%) 26 (100%) 16 (94%) 22 (96%)

Oral mucosa (2) (0) (1) (1)

Foreign body 1 (100%) 1 (100%)

Hyperplasia, squamous 2 (100%) 1 (100%) 1 (100%)

Inflammation, chronic active 1 (100%)

Pancreas (50) (50) (50) (50)

Acinus, atrophy 9 (18%) 12 (24%) 7 (14%) 7 (14%)

Salivary glands (50) (50) (50) (50)

Hyperplasia 1 (2%)

Inflammation, chronic active 1 (2%)

Necrosis 1 (2%)

Stomach, forestomach (50) (50) (50) (50)

Hyperplasia, basal cell 1 (2%) 1 (2%)

Hyperplasia, squamous 4 (8%) 2 (4%) 2 (4%)

Ulcer 2 (4%) 3 (6%) 3 (6%) 6 (12%)

Stomach, glandular (50) (50) (50) (50)

Erosion 1 (2%)

Ulcer 3 (6%) 1 (2%) 1 (2%) 1 (2%)

Tongue (0) (1) (0) (1)

Hyperplasia, squamous 1 (100%)

Tooth (0) (0) (1) (0)

Inflammation, chronic active 1 (100%)

a Number of animals examined microscopically at the site and the number of animals with lesion
1-Bromopropane, NTP TR 564 B-13

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TABLE B4

Summary of the Incidence of Nonneoplastic Lesions in Female Rats

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Cardiovascular System

Heart (50) (50) (50) (50)

Cardiomyopathy 35 (70%) 32 (64%) 34 (68%) 21 (42%)

Atrium, thrombosis 1 (2%)

Endocrine System

Adrenal cortex (50) (50) (50) (50)

Degeneration, cystic 1 (2%) 1 (2%)

Hyperplasia 27 (54%) 30 (60%) 24 (48%) 26 (52%)

Necrosis 1 (2%)

Vacuolization cytoplasmic 12 (24%) 16 (32%) 16 (32%) 11 (22%)

Adrenal medulla (50) (50) (50) (50)

Hyperplasia 4 (8%) 9 (18%) 7 (14%) 6 (12%)

Metaplasia, osseous 1 (2%)

Islets, pancreatic (50) (50) (50) (50)

Hyperplasia 3 (6%) 4 (8%) 4 (8%)

Metaplasia, hepatocyte 2 (4%) 1 (2%)

Pituitary gland (50) (50) (50) (50)

Cyst 2 (4%) 1 (2%) 2 (4%) 2 (4%)

Hemorrhage 2 (4%) 4 (8%) 5 (10%) 3 (6%)

Pars distalis, hyperplasia 7 (14%) 11 (22%) 7 (14%) 7 (14%)

Thyroid gland (50) (50) (50) (50)

Ultimobranchial cyst 1 (2%) 1 (2%)

C-cell, hyperplasia 39 (78%) 36 (72%) 37 (74%) 37 (74%)

Follicular cell, hyperplasia 1 (2%) 2 (4%)

General Body System

None

Genital System

Clitoral gland (49) (50) (49) (49)

Hyperplasia 3 (6%) 5 (10%) 9 (18%) 4 (8%)

Inflammation, chronic active 22 (45%) 26 (52%) 26 (53%) 18 (37%)

Ovary (50) (50) (50) (50)

Cyst 3 (6%) 1 (2%) 7 (14%) 3 (6%)

Interstitial cell, hyperplasia 1 (2%)

Uterus (50) (50) (50) (50)

Congestion 1 (2%)

Cyst 1 (2%)

Decidual reaction 2 (4%)

Hemorrhage 2 (4%) 1 (2%)

Hydrometra 1 (2%)

Inflammation, chronic active 1 (2%)

Endometrium, hyperplasia 1 (2%)

Vagina (3) (0) (0) (0)

Muscularis, hypertrophy 2 (67%)
B-14 1-Bromopropane, NTP TR 564

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TABLE B4

Summary of the Incidence of Nonneoplastic Lesions in Female Rats

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Hematopoietic System

Bone marrow (50) (50) (50) (50)

Hyperplasia, histiocytic 1 (2%) 1 (2%) 1 (2%) 1 (2%)

Lymph node (1) (3) (2) (2)

Inflammation, chronic active 1 (100%)

Deep cervical, ectasia 1 (33%)

Deep cervical, hyperplasia, lymphoid 1 (33%)

Pancreatic, hemorrhage 1 (50%)

Lymph node, bronchial (1) (4) (5) (7)

Angiectasis 1 (100%) 2 (40%) 1 (14%)

Hemorrhage 1 (20%) 1 (14%)

Lymph node, mediastinal (34) (30) (31) (28)

Angiectasis 2 (6%) 2 (7%)

Hemorrhage 2 (7%)

Lymph node, mesenteric (49) (49) (50) (50)

Hemorrhage 1 (2%)

Hyperplasia, lymphoid 1 (2%)

Infiltration cellular, histiocyte 1 (2%) 1 (2%)

Spleen (50) (50) (50) (50)

Hematopoietic cell proliferation 33 (66%) 32 (64%) 29 (58%) 21 (42%)

Hemorrhage, chronic 1 (2%) 1 (2%) 2 (4%)

Infarct, chronic 1 (2%) 1 (2%) 1 (2%) 1 (2%)

Inflammation, granulomatous 2 (4%)

Lymphoid follicle, atrophy 1 (2%)

Thymus (46) (45) (45) (43)

Cyst 1 (2%)

Integumentary System

Mammary gland (50) (50) (50) (50)

Galactocele 1 (2%) 3 (6%) 1 (2%)

Hyperplasia 1 (2%)

Inflammation, chronic active 1 (2%) 1 (2%)

Skin (50) (50) (50) (50)

Hyperkeratosis 1 (2%) 2 (4%) 2 (4%)

Hyperplasia, squamous 1 (2%)

Inflammation, suppurative, chronic 1 (2%) 1 (2%)

Inflammation, chronic active 1 (2%) 2 (4%) 1 (2%)

Ulcer 1 (2%) 1 (2%)

Musculoskeletal System

Bone (50) (50) (50) (50)

Fracture 1 (2%)

Inflammation, suppurative, chronic 1 (2%)

Skeletal muscle (0) (0) (1) (4)

Nervous System

Brain (50) (50) (50) (50)

Angiectasis 1 (2%)

Hemorrhage 1 (2%)

Spinal cord (0) (1) (0) (3)

Cyst epithelial inclusion 1 (33%)
1-Bromopropane, NTP TR 564 B-15

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TABLE B4

Summary of the Incidence of Nonneoplastic Lesions in Female Rats

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 125 ppm 250 ppm 500 ppm

Respiratory System

Larynx (50) (50) (50) (50)

Foreign body 8 (16%) 6 (12%) 3 (6%) 4 (8%)

Inflammation, suppurative, chronic 3 (6%)

Inflammation, chronic active 18 (36%) 25 (50%) 30 (60%) 32 (64%)

Metaplasia, squamous 3 (6%) 2 (4%) 6 (12%) 21 (42%)

Necrosis 1 (2%)

Respiratory epithelium, hyperplasia 1 (2%)

Lung (50) (50) (50) (50)

Hemorrhage 4 (8%) 6 (12%) 4 (8%) 4 (8%)

Inflammation, suppurative, chronic 4 (8%)

Inflammation, chronic active 6 (12%) 10 (20%) 12 (24%) 2 (4%)

Alveolar epithelium, hyperplasia 11 (22%) 10 (20%) 16 (32%) 8 (16%)

Alveolus, infiltration cellular, histiocyte 30 (60%) 30 (60%) 29 (58%) 26 (52%)

Nose (50) (50) (49) (50)

Foreign body 6 (12%) 6 (12%) 6 (12%) 9 (18%)

Inflammation, suppurative, chronic 1 (2%) 3 (6%) 7 (14%)

Inflammation, chronic active 24 (48%) 37 (74%) 37 (76%) 36 (72%)

Epithelium, accumulation, hyaline droplet 48 (96%) 48 (96%) 48 (98%) 47 (94%)

Glands, hyperplasia 6 (12%) 23 (46%) 28 (57%) 30 (60%)

Olfactory epithelium, hyperplasia 1 (2%)

Olfactory epithelium, metaplasia, 

respiratory 3 (6%) 4 (8%) 6 (12%) 9 (18%)

Respiratory epithelium, hyperplasia 5 (10%) 13 (26%) 9 (18%) 18 (36%)

Respiratory epithelium, metaplasia,

squamous 1 (2%) 1 (2%) 5 (10%) 1 (2%)

Pleura (0) (0) (1) (0)

Trachea (50) (50) (50) (50)

Inflammation, chronic active 4 (8%) 1 (2%) 6 (12%)

Epithelium, hyperplasia 4 (8%)

Epithelium, metaplasia, squamous 1 (2%)

Epithelium, necrosis 1 (2%)

Special Senses System

Ear (0) (0) (1) (1)

Inflammation, suppurative, chronic 1 (100%)

Eye (50) (50) (50) (50)

Cornea, inflammation, chronic active 1 (2%)

Lens, cataract 4 (8%) 3 (6%) 5 (10%) 2 (4%)

Harderian gland (50) (50) (50) (50)

Inflammation, suppurative, chronic 1 (2%)

Inflammation, chronic active 1 (2%) 1 (2%)

Zymbal’s gland (1) (1) (2) (0)

Urinary System

Kidney (49) (50) (50) (50)

Cyst 1 (2%) 1 (2%)

Nephropathy, chronic 35 (71%) 35 (70%) 31 (62%) 29 (58%)

Cortex, infarct 1 (2%)

Cortex, renal tubule, accumulation,

hyaline droplet 1 (2%)

Pelvis, inflammation, suppurative 1 (2%)

Pelvis, inflammation, chronic active 1 (2%)
B-16 1-Bromopropane, NTP TR 564

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C-1

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APPENDIX C

SUMMARY OF LESIONS IN MALE MICE

IN THE 2-YEAR INHALATION STUDY

OF 1-BROMOPROPANE

TABLE C1 Summary of the Incidence of Neoplasms in Male Mice

in the 2-Year Inhalation Study of 1-Bromopropane .......................................................................C-2

TABLE C2 Statistical Analysis of Primary Neoplasms in Male Mice

in the 2-Year Inhalation Study of 1-Bromopropane ......................................................................C-7

TABLE C3 Summary of the Incidence of Nonneoplastic Lesions in Male Mice

in the 2-Year Inhalation Study of 1-Bromopropane ....................................................................C-10
C-2 1-Bromopropane, NTP TR 564

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TABLE C1

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Inhalation Study of 1-Bromopropanea

Chamber Control 62.5 ppm 125 ppm 250 ppm

Disposition Summary

Animals initially in study 50 50 50 50

Early deaths

Moribund 6 13 9 9

Natural deaths 7 4 9 5

Survivors

Terminal sacrifice 37 33 32 36

Animals examined microscopically 50 50 50 50

Alimentary System

Gallbladder (40) (40) (34) (38)

Intestine large, rectum (45) (48) (43) (48)

Intestine small, duodenum (44) (48) (43) (46)

Polyp adenomatous 1 (2%) 1 (2%)

Intestine small, jejunum (44) (48) (43) (46)

Carcinoma 4 (9%) 1 (2%) 1 (2%)

Liver (50) (50) (50) (50)

Hemangiosarcoma 1 (2%) 1 (2%) 1 (2%) 1 (2%)

Hepatoblastoma 1 (2%) 1 (2%) 1 (2%)

Hepatocellular adenoma 16 (32%) 14 (28%) 19 (38%) 15 (30%)

Hepatocellular adenoma, multiple 14 (28%) 18 (36%) 14 (28%) 8 (16%)

Hepatocellular carcinoma 9 (18%) 8 (16%) 15 (30%) 7 (14%)

Hepatocellular carcinoma, multiple 6 (12%) 7 (14%) 4 (8%) 4 (8%)

Hepatocholangiocarcinoma 1 (2%) 1 (2%) 1 (2%) 1 (2%)

Hepatocholangiocarcinoma, multiple 1 (2%)

Capsule, carcinoma, metastatic, pancreas 1 (2%)

Mesentery (9) (11) (6) (7)

Carcinoma, metastatic, pancreas 1 (11%) 1 (17%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (14%)

Pancreas (48) (50) (48) (50)

Carcinoma 1 (2%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Acinar cell, carcinoma 1 (2%)

Salivary glands (49) (50) (49) (50)

Stomach, forestomach (47) (50) (48) (50)

Squamous cell papilloma 2 (4%)

Stomach, glandular (47) (49) (47) (49)

Tooth (8) (8) (9) (11)

Cardiovascular System

Blood vessel (3) (1) (0) (0)

Heart (50) (50) (50) (50)

Alveolar/bronchiolar carcinoma, metastatic,

lung 1 (2%)

Carcinoma, metastatic, pancreas 1 (2%)

Hemangiosarcoma 1 (2%)

Hepatocellular carcinoma, metastatic, liver 1 (2%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%) 1 (2%) 2 (4%)
1-Bromopropane, NTP TR 564 C-3

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TABLE C1

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Endocrine System

Adrenal cortex (49) (50) (49) (50)

Adenoma 1 (2%) 1 (2%)

Carcinoma, metastatic, pancreas 1 (2%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Subcapsular, adenoma 3 (6%) 3 (6%) 1 (2%)

Adrenal medulla (50) (49) (49) (50)

Pheochromocytoma benign 1 (2%) 1 (2%)

Pheochromocytoma malignant 1 (2%)

Islets, pancreatic (48) (50) (48) (50)

Adenoma 1 (2%) 1 (2%)

Pituitary gland (46) (48) (46) (48)

Pars distalis, adenoma 1 (2%) 1 (2%)

Thyroid gland (49) (50) (48) (50)

General Body System

Peritoneum (0) (0) (1) (0)

Carcinoma, metastatic, pancreas 1 (100%)

Genital System

Coagulating gland (1) (0) (0) (0)

Epididymis (50) (50) (50) (50)

Preputial gland (49) (49) (50) (50)

Bilateral, squamous cell carcinoma 1 (2%)

Prostate (49) (50) (48) (50)

Seminal vesicle (48) (50) (49) (50)

Adenoma 1 (2%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Testes (50) (50) (50) (50)

Interstitial cell, adenoma 1 (2%)

Hematopoietic System

Bone marrow (48) (48) (48) (50)

Hemangiosarcoma 1 (2%) 1 (2%)

Mast cell tumor benign 1 (2%)

Lymph node (1) (1) (3) (0)

Alveolar/bronchiolar carcinoma,

metastatic, lung 1 (33%)

Lumbar, carcinoma, metastatic,

uncertain primary site 1 (33%)

Popliteal, carcinoma, metastatic,

uncertain primary site 1 (33%)

Lymph node, bronchial (23) (30) (32) (31)

Carcinoma, metastatic, pancreas 1 (3%)

Hepatocellular carcinoma, metastatic, liver 1 (3%) 1 (3%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (3%) 1 (3%) 2 (6%)

Lymph node, mandibular (27) (28) (21) (26)
C-4 1-Bromopropane, NTP TR 564

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TABLE C1

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Hematopoietic System (continued)

Lymph node, mediastinal (35) (32) (35) (34)

Carcinoma, metastatic, pancreas 1 (3%) 1 (3%)

Hepatocellular carcinoma, metastatic, liver 1 (3%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (3%) 1 (3%) 1 (3%) 2 (6%)

Lymph node, mesenteric (48) (46) (44) (48)

Carcinoma, metastatic, pancreas 1 (2%) 1 (2%)

Hepatocellular carcinoma, metastatic,

liver 1 (2%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Spleen (48) (50) (49) (50)

Hemangiosarcoma 2 (4%) 1 (2%)

Mast cell tumor malignant, metastatic,

uncertain primary site 1 (2%)

Thymus (38) (35) (37) (32)

Hepatocholangiocarcinoma, metastatic,

liver 1 (3%) 1 (3%)

Integumentary System

Skin (50) (50) (50) (50)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Subcutaneous tissue, fibrous histiocytoma 1 (2%)

Subcutaneous tissue, hemangiosarcoma 1 (2%) 1 (2%)

Subcutaneous tissue, sarcoma 1 (2%)

Musculoskeletal System

Bone (50) (49) (50) (50)

Hemangiosarcoma 1 (2%)

Osteosarcoma 1 (2%)

Skeletal muscle (0) (2) (1) (2)

Alveolar/bronchiolar carcinoma, metastatic,

lung 1 (100%)

Hemangiosarcoma 1 (50%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (50%) 1 (50%)

Nervous System

Brain (50) (50) (49) (50)
1-Bromopropane, NTP TR 564 C-5

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

TABLE C1

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Respiratory System

Larynx (48) (50) (48) (50)

Lung (50) (50) (49) (49)

Alveolar/bronchiolar adenoma 6 (12%) 4 (8%) 4 (8%) 4 (8%)

Alveolar/bronchiolar adenoma, multiple 1 (2%) 1 (2%)

Alveolar/bronchiolar carcinoma 8 (16%) 7 (14%) 8 (16%) 9 (18%)

Alveolar/bronchiolar carcinoma, multiple 2 (4%) 1 (2%)

Carcinoma, metastatic, harderian gland 1 (2%)

Carcinoma, metastatic, pancreas 1 (2%) 1 (2%)

Hemangiosarcoma, metastatic, liver 1 (2%)

Hemangiosarcoma, metastatic, spleen 1 (2%)

Hepatocellular carcinoma, metastatic, liver 7 (14%) 10 (20%) 12 (24%) 4 (8%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%) 1 (2%) 1 (2%) 2 (4%)

Osteosarcoma, metastatic, 

uncertain primary site 1 (2%)

Bronchiole, adenoma 1 (2%)

Nose (50) (50) (50) (50)

Carcinoma, metastatic, harderian gland 1 (2%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Pleura (0) (0) (1) (1)

Alveolar/bronchiolar carcinoma,

metastatic, lung 1 (100%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (100%)

Trachea (49) (50) (47) (50)

Special Senses System

Eye (45) (47) (44) (47)

Harderian gland (46) (49) (49) (48)

Adenoma 6 (13%) 3 (6%) 2 (4%) 3 (6%)

Carcinoma 3 (7%) 1 (2%) 7 (14%) 5 (10%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Bilateral, adenoma 1 (2%)

Urinary System

Kidney (49) (50) (50) (49)

Alveolar/bronchiolar carcinoma,

metastatic, lung 1 (2%)

Hepatocellular carcinoma, metastatic, liver 1 (2%) 1 (2%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%) 1 (2%) 1 (2%) 2 (4%)

Urethra (0) (0) (0) (1)

Urinary bladder (47) (50) (47) (48)

Systemic Lesions

Multiple organsb (50) (50) (50) (50)

Histiocytic sarcoma 2 (4%) 1 (2%)

Lymphoma malignant 2 (4%) 3 (6%)
C-6 1-Bromopropane, NTP TR 564

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TABLE C1

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Neoplasm Summary

Total animals with primary neoplasmsc 47 47 46 36

Total primary neoplasms 90 81 90 69

Total animals with benign neoplasms 36 35 35 29

Total benign neoplasms 51 47 43 35

Total animals with malignant neoplasms 30 29 34 24

Total malignant neoplasms 39 34 47 34

Total animals with metastatic neoplasms 9 12 17 6

Total metastatic neoplasms 18 24 39 21

Total animals with malignant neoplasms

of uncertain primary site 2 1

a Number of animals examined microscopically at the site and the number of animals with neoplasm

b Number of animals with any tissue examined microscopically

c Primary neoplasms: all neoplasms except metastatic neoplasms
1-Bromopropane, NTP TR 564 C-7

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TABLE C2

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Adrenal Cortex: Adenoma

Overall ratea 4/49 (8%) 3/50 (6%) 2/49 (4%) 0/50 (0%)

Adjusted rateb 9.1% 6.9% 4.5% 0.0%

Terminal ratec 3/37 (8%) 2/33 (6%) 2/32 (6%) 0/36 (0%)

First incidence (days) 586 655 729 (T) —e

Poly-3 testd P=0.040N P=0.502N P=0.329N P=0.066N

Harderian Gland: Adenoma

Overall rate 7/50 (14%) 3/50 (6%) 2/50 (4%) 3/50 (6%)

Adjusted rate 15.9% 6.9% 4.4% 7.2%

Terminal rate 7/37 (19%) 1/33 (3%) 1/32 (3%) 3/36 (8%)

First incidence (days) 729 (T) 684 702 729 (T)

Poly-3 test P=0.133N P=0.161N P=0.072N P=0.179N

Harderian Gland: Carcinoma

Overall rate 3/50 (6%) 1/50 (2%) 7/50 (14%) 5/50 (10%)

Adjusted rate 6.8% 2.3% 15.1% 12.0%

Terminal rate 3/37 (8%) 1/33 (3%) 3/32 (9%) 5/36 (14%)

First incidence (days) 729 (T) 729 (T) 604 729 (T)

Poly-3 test P=0.123 P=0.312N P=0.178 P=0.327

Harderian Gland: Adenoma or Carcinoma

Overall rate 10/50 (20%) 4/50 (8%) 8/50 (16%) 8/50 (16%)

Adjusted rate 22.7% 9.2% 17.2% 19.1%

Terminal rate 10/37 (27%) 2/33 (6%) 3/32 (9%) 8/36 (22%)

First incidence (days) 729 (T) 684 604 729 (T)

Poly-3 test P=0.547 P=0.074N P=0.350N P=0.446N

Small Intestine (Jejunum): Carcinoma

Overall rate 4/50 (8%) 1/50 (2%) 1/50 (2%) 0/50 (0%)

Adjusted rate 9.1% 2.3% 2.2% 0.0%

Terminal rate 4/37 (11%) 0/33 (0%) 0/32 (0%) 0/36 (0%)

First incidence (days) 729 (T) 631 682 —

Poly-3 test P=0.034N P=0.181N P=0.170N P=0.067N

Liver: Hepatocellular Adenoma

Overall rate 30/50 (60%) 32/50 (64%) 33/50 (66%) 23/50 (46%)

Adjusted rate 62.5% 67.6% 68.3% 53.3%

Terminal rate 23/37 (62%) 24/33 (73%) 21/32 (66%) 20/36 (56%)

First incidence (days) 328 424 537 417

Poly-3 test P=0.186N P=0.377 P=0.347 P=0.248N

Liver: Hepatocellular Carcinoma

Overall rate 15/50 (30%) 15/50 (30%) 19/50 (38%) 11/50 (22%)

Adjusted rate 32.7% 33.1% 39.1% 25.4%

Terminal rate 9/37 (24%) 8/33 (24%) 8/32 (25%) 7/36 (19%)

First incidence (days) 539 520 537 470

Poly-3 test P=0.289N P=0.571 P=0.332 P=0.302N

Liver: Hepatocellular Adenoma or Carcinoma

Overall rate 38/50 (76%) 38/50 (76%) 41/50 (82%) 28/50 (56%)

Adjusted rate 77.7% 78.1% 82.3% 63.1%

Terminal rate 28/37 (76%) 25/33 (76%) 24/32 (75%) 22/36 (61%)

First incidence (days) 328 424 537 417

Poly-3 test P=0.066N P=0.578 P=0.370 P=0.089N
C-8 1-Bromopropane, NTP TR 564

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TABLE C2

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Liver: Hepatocellular Carcinoma or Hepatoblastoma

Overall rate 16/50 (32%) 16/50 (32%) 19/50 (38%) 11/50 (22%)

Adjusted rate 34.9% 35.3% 39.1% 25.4%

Terminal rate 10/37 (27%) 9/33 (27%) 8/32 (25%) 7/36 (19%)

First incidence (days) 539 520 537 470

Poly-3 test P=0.208N P=0.569 P=0.415 P=0.230N

Liver: Hepatocellular Adenoma, Hepatocellular Carcinoma, or Hepatoblastoma

Overall rate 38/50 (76%) 39/50 (78%) 41/50 (82%) 28/50 (56%)

Adjusted rate 77.7% 80.1% 82.3% 63.1%

Terminal rate 28/37 (76%) 26/33 (79%) 24/32 (75%) 22/36 (61%)

First incidence (days) 328 424 537 417

Poly-3 test P=0.055N P=0.479 P=0.370 P=0.089N

Lung: Alveolar/bronchiolar Adenoma

Overall rate 6/50 (12%) 5/50 (10%) 4/49 (8%) 5/49 (10%)

Adjusted rate 13.3% 11.5% 9.0% 11.9%

Terminal rate 4/37 (11%) 5/33 (15%) 4/32 (13%) 4/36 (11%)

First incidence (days) 544 729 (T) 729 (T) 360

Poly-3 test P=0.476N P=0.530N P=0.380N P=0.554N

Lung: Alveolar/bronchiolar Carcinoma

Overall rate 8/50 (16%) 7/50 (14%) 10/49 (20%) 10/49 (20%)

Adjusted rate 17.8% 15.9% 22.0% 24.3%

Terminal rate 6/37 (16%) 6/33 (18%) 5/32 (16%) 9/36 (25%)

First incidence (days) 539 520 617 708

Poly-3 test P=0.209 P=0.518N P=0.407 P=0.317

Lung: Alveolar/bronchiolar Adenoma or Carcinoma

Overall rate 13/50 (26%) 12/50 (24%) 14/49 (29%) 15/49 (31%)

Adjusted rate 28.3% 27.3% 30.8% 35.7%

Terminal rate 9/37 (24%) 11/33 (33%) 9/32 (28%) 13/36 (36%)

First incidence (days) 539 520 617 360

Poly-3 test P=0.225 P=0.552N P=0.484 P=0.301

All Organs: Hemangiosarcoma

Overall rate 2/50 (4%) 4/50 (8%) 2/50 (4%) 2/50 (4%)

Adjusted rate 4.5% 9.2% 4.4% 4.8%

Terminal rate 2/37 (5%) 3/33 (9%) 1/32 (3%) 1/36 (3%)

First incidence (days) 729 (T) 661 718 708

Poly-3 test P=0.477N P=0.331 P=0.684N P=0.675

All Organs: Malignant Lymphoma

Overall rate 2/50 (4%) 0/50 (0%) 3/50 (6%) 0/50 (0%)

Adjusted rate 4.5% 0.0% 6.6% 0.0%

Terminal rate 1/37 (3%) 0/33 (0%) 3/32 (9%) 0/36 (0%)

First incidence (days) 578 — 729 (T) —

Poly-3 test P=0.313N P=0.244N P=0.506 P=0.252N

All Organs: Benign Neoplasms

Overall rate 36/50 (72%) 35/50 (70%) 35/50 (70%) 29/50 (58%)

Adjusted rate 73.2% 73.5% 72.4% 65.9%

Terminal rate 26/37 (70%) 26/33 (79%) 23/32 (72%) 25/36 (69%)

First incidence (days) 328 424 537 360

Poly-3 test P=0.232N P=0.582 P=0.556N P=0.290N
1-Bromopropane, NTP TR 564 C-9

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TABLE C2

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

All Organs: Malignant Neoplasms

Overall rate 30/50 (60%) 30/50 (60%) 34/50 (68%) 24/50 (48%)

Adjusted rate 62.7% 63.5% 69.0% 54.8%

Terminal rate 20/37 (54%) 18/33 (55%) 19/32 (59%) 19/36 (53%)

First incidence (days) 328 520 537 470

Poly-3 test P=0.270N P=0.554 P=0.329 P=0.289N

All Organs: Benign or Malignant Neoplasms

Overall rate 47/50 (94%) 47/50 (94%) 46/50 (92%) 36/50 (72%)

Adjusted rate 94.0% 94.3% 92.4% 78.6%

Terminal rate 34/37 (92%) 31/33 (94%) 29/32 (91%) 28/36 (78%)

First incidence (days) 328 424 537 360

Poly-3 test P=0.005N P=0.640 P=0.529N P=0.024N

(T)Terminal sacrifice

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for adrenal 

cortex, liver, and lung; for other tissues, denominator is number of animals necropsied.

b Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality

c Observed incidence at terminal kill

d Beneath the chamber control incidence is the P value associated with the trend test. Beneath the exposed group incidence are the P values 

corresponding to pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for the differential 

mortality in animals that do not reach terminal sacrifice. A negative trend or a lower incidence in an exposure group is indicated by N.

e Not applicable; no neoplasms in animal group
C-10 1-Bromopropane, NTP TR 564

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TABLE C3

Summary of the Incidence of Nonneoplastic Lesions in Male Mice

in the 2-Year Inhalation Study of 1-Bromopropanea

Chamber Control 62.5 ppm 125 ppm 250 ppm

Disposition Summary

Animals initially in study 50 50 50 50

Early deaths

Moribund 6 13 9 9

Natural deaths 7 4 9 5

Survivors

Terminal sacrifice 37 33 32 36

Animals examined microscopically 50 50 50 50

Alimentary System

Gallbladder (40) (40) (34) (38)

Degeneration, hyaline 2 (5%) 1 (3%)

Hemorrhage 1 (3%)

Hyperplasia 1 (3%)

Infiltration cellular, polymorphonuclear 1 (3%)

Intestine large, rectum (45) (48) (43) (48)

Inflammation, suppurative 1 (2%)

Ulcer 1 (2%)

Artery, inflammation, chronic active 1 (2%)

Intestine small, duodenum (44) (48) (43) (46)

Inflammation, acute 1 (2%)

Intestine small, jejunum (44) (48) (43) (46)

Liver (50) (50) (50) (50)

Angiectasis 3 (6%)

Basophilic focus 1 (2%) 2 (4%) 1 (2%) 3 (6%)

Clear cell focus 9 (18%) 14 (28%) 16 (32%) 12 (24%)

Eosinophilic focus 20 (40%) 16 (32%) 8 (16%) 9 (18%)

Fatty change, focal 1 (2%) 3 (6%) 5 (10%)

Inflammation, chronic 1 (2%) 1 (2%)

Mineralization 1 (2%)

Mixed cell focus 2 (4%) 7 (14%) 1 (2%) 1 (2%)

Necrosis 5 (10%) 4 (8%) 3 (6%) 9 (18%)

Tension lipidosis 4 (8%) 3 (6%) 6 (12%) 2 (4%)

Vacuolization cytoplasmic 1 (2%)

Bile duct, hyperplasia 1 (2%)

Mesentery (9) (11) (6) (7)

Artery, inflammation 1 (14%)

Artery, mineralization 1 (11%)

Fat, necrosis 7 (78%) 11 (100%) 5 (83%) 5 (71%)

Pancreas (48) (50) (48) (50)

Atrophy 1 (2%) 1 (2%)

Basophilic focus 1 (2%) 1 (2%)

Cyst 1 (2%)

Inflammation, chronic active 1 (2%)

Salivary glands (49) (50) (49) (50)

Atrophy 1 (2%) 1 (2%)

Stomach, forestomach (47) (50) (48) (50)

Hyperplasia, squamous 5 (11%) 7 (14%) 5 (10%) 3 (6%)

Inflammation 2 (4%) 2 (4%) 1 (2%)

Ulcer 2 (4%) 4 (8%) 3 (6%) 2 (4%)

Artery, inflammation, chronic active 1 (2%)

a Number of animals examined microscopically at the site and the number of animals with lesion
1-Bromopropane, NTP TR 564 C-11

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

TABLE C3

Summary of the Incidence of Nonneoplastic Lesions in Male Mice

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Alimentary System (continued)

Stomach, glandular (47) (49) (47) (49)

Mineralization 2 (4%)

Artery, inflammation, chronic active 1 (2%)

Tooth (8) (8) (9) (11)

Dysplasia 7 (88%) 8 (100%) 9 (100%) 11 (100%)

Malformation 1 (13%)

Cardiovascular System

Blood vessel (3) (1) (0) (0)

Inflammation, chronic active 1 (33%)

Thrombosis 1 (100%)

Aorta, mineralization 2 (67%)

Heart (50) (50) (50) (50)

Cardiomyopathy 12 (24%) 10 (20%) 14 (28%) 9 (18%)

Hemorrhage 1 (2%)

Inflammation, acute 1 (2%)

Mineralization 2 (4%)

Thrombosis 1 (2%) 2 (4%) 1 (2%)

Artery, inflammation, chronic active 1 (2%) 1 (2%)

Epicardium, inflammation, chronic 1 (2%)

Endocrine System

Adrenal cortex (49) (50) (49) (50)

Hyperplasia 16 (33%) 18 (36%) 14 (29%) 12 (24%)

Hypertrophy 23 (47%) 19 (38%) 22 (45%) 28 (56%)

Subcapsular, hyperplasia 1 (2%)

Adrenal medulla (50) (49) (49) (50)

Hyperplasia 1 (2%) 2 (4%) 1 (2%) 2 (4%)

Islets, pancreatic (48) (50) (48) (50)

Hyperplasia 1 (2%)

Pituitary gland (46) (48) (46) (48)

Cyst 1 (2%) 1 (2%)

Pars distalis, hyperplasia 2 (4%) 2 (4%) 1 (2%) 1 (2%)

Pars intermedia, hyperplasia 1 (2%)

Thyroid gland (49) (50) (48) (50)

Follicular cell, hyperplasia 1 (2%)

General Body System

Peritoneum (0) (0) (1) (0)

Genital System

Coagulating gland (1) (0) (0) (0)

Inflammation, suppurative 1 (100%)

Epididymis (50) (50) (50) (50)

Granuloma sperm 1 (2%) 1 (2%) 1 (2%)

Necrosis 2 (4%)

Preputial gland (49) (49) (50) (50)

Inflammation, suppurative 1 (2%)

Inflammation, granulomatous 1 (2%) 1 (2%)
C-12 1-Bromopropane, NTP TR 564

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TABLE C3

Summary of the Incidence of Nonneoplastic Lesions in Male Mice

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Genital System (continued)

Prostate (49) (50) (48) (50)

Inflammation, suppurative 2 (4%) 2 (4%) 2 (4%)

Inflammation, chronic active 1 (2%) 1 (2%)

Artery, inflammation, chronic active 1 (2%)

Seminal vesicle (48) (50) (49) (50)

Amyloid deposition 1 (2%)

Inflammation, suppurative 1 (2%)

Inflammation, chronic active 1 (2%)

Testes (50) (50) (50) (50)

Atrophy 1 (2%) 1 (2%) 1 (2%) 3 (6%)

Hematopoietic System

Bone marrow (48) (48) (48) (50)

Lymph node (1) (1) (3) (0)

Lymph node, bronchial (23) (30) (32) (31)

Infiltration cellular, mixed cell 1 (3%)

Lymph node, mandibular (27) (28) (21) (26)

Lymph node, mediastinal (35) (32) (35) (34)

Infiltration cellular, mixed cell 1 (3%)

Lymph node, mesenteric (48) (46) (44) (48)

Angiectasis 1 (2%)

Spleen (48) (50) (49) (50)

Angiectasis 1 (2%)

Atrophy 7 (15%) 8 (16%) 2 (4%) 3 (6%)

Congestion 4 (8%) 4 (8%) 1 (2%) 3 (6%)

Hematopoietic cell proliferation 20 (42%) 19 (38%) 14 (29%) 16 (32%)

Hyperplasia, lymphoid 5 (10%) 2 (4%) 5 (10%) 2 (4%)

Infarct 1 (2%)

Necrosis 1 (2%)

Necrosis, lymphoid 1 (2%) 1 (2%) 2 (4%)

Thymus (38) (35) (37) (32)

Atrophy 13 (34%) 12 (34%) 19 (51%) 12 (38%)

Cyst 5 (13%) 1 (3%) 7 (19%) 4 (13%)

Necrosis, lymphoid 1 (3%) 1 (3%) 3 (9%)

Medulla, hyperplasia, lymphoid 16 (42%) 9 (26%) 14 (38%) 6 (19%)

Integumentary System

Skin (50) (50) (50) (50)

Cyst epithelial inclusion 1 (2%)

Inflammation, chronic active 5 (10%) 5 (10%) 3 (6%) 8 (16%)

Ulcer 1 (2%)

Musculoskeletal System

Bone (50) (49) (50) (50)

Hyperostosis 2 (4%) 1 (2%)

Necrosis 1 (2%)

Skeletal muscle (0) (2) (1) (2)

Nervous System

Brain (50) (50) (49) (50)
1-Bromopropane, NTP TR 564 C-13

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TABLE C3

Summary of the Incidence of Nonneoplastic Lesions in Male Mice

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Respiratory System

Larynx (48) (50) (48) (50)

Vacuolization cytoplasmic 5 (10%) 10 (21%) 11 (22%)

Lung (50) (50) (49) (49)

Congestion, chronic 1 (2%) 1 (2%)

Hemorrhage 2 (4%) 2 (4%) 1 (2%)

Inflammation, chronic active 2 (4%)

Mineralization 1 (2%)

Pigmentation 1 (2%)

Thrombosis 1 (2%)

Alveolar epithelium, hyperplasia 2 (4%) 2 (4%) 1 (2%) 5 (10%)

Alveolus, infiltration cellular, histiocyte 3 (6%) 1 (2%) 1 (2%)

Bronchiole, hyperplasia 3 (6%) 1 (2%)

Bronchiole, necrosis 1 (2%)

Bronchiole, regeneration 1 (2%) 44 (88%) 38 (78%) 47 (96%)

Bronchiole, vacuolization cytoplasmic 18 (36%) 19 (39%) 17 (35%)

Nose (50) (50) (50) (50)

Foreign body 1 (2%)

Inflammation, suppurative 2 (4%) 3 (6%) 2 (4%) 3 (6%)

Polyp, inflammatory 3 (6%)

Glands, hyperplasia 1 (2%)

Olfactory epithelium, atrophy 2 (4%) 4 (8%) 7 (14%) 4 (8%)

Olfactory epithelium, metaplasia, 

respiratory 7 (14%) 6 (12%) 3 (6%)

Respiratory epithelium, hyperplasia 16 (32%) 29 (58%) 23 (46%) 26 (52%)

Respiratory epithelium, vacuolization

cytoplasmic 12 (24%) 19 (38%) 20 (40%)

Pleura (0) (0) (1) (1)

Trachea (49) (50) (47) (50)

Vacuolization cytoplasmic 15 (30%) 24 (51%) 24 (48%)

Special Senses System

Eye (45) (47) (44) (47)

Cataract 1 (2%) 1 (2%) 1 (2%)

Degeneration 1 (2%) 1 (2%) 1 (2%)

Cornea, inflammation, acute 1 (2%)

Cornea, inflammation, chronic active 2 (4%) 1 (2%)

Retina, atrophy 1 (2%) 1 (2%)

Harderian gland (46) (49) (49) (48)

Hyperplasia 3 (7%) 4 (8%) 1 (2%) 4 (8%)

Urinary System

Kidney (49) (50) (50) (49)

Amyloid deposition 1 (2%)

Cyst 1 (2%)

Hydronephrosis 1 (2%) 1 (2%)

Infarct 1 (2%) 2 (4%) 3 (6%) 1 (2%)

Inflammation, suppurative 1 (2%) 2 (4%) 2 (4%)

Metaplasia, osseous 2 (4%) 1 (2%)

Mineralization 2 (4%)

Nephropathy 44 (90%) 46 (92%) 47 (94%) 41 (84%)

Papilla, necrosis 1 (2%)

Renal tubule, hyperplasia 2 (4%) 1 (2%) 2 (4%)

Renal tubule, necrosis 1 (2%)
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TABLE C3

Summary of the Incidence of Nonneoplastic Lesions in Male Mice

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Urinary System (continued)

Urethra (0) (0) (0) (1)

Bulbourethral gland, angiectasis 1 (100%)

Urinary bladder (47) (50) (47) (48)

Inflammation, chronic active 1 (2%) 1 (2%) 1 (2%)

Mineralization 1 (2%)
D-1

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APPENDIX D

SUMMARY OF LESIONS IN FEMALE MICE

IN THE 2-YEAR INHALATION STUDY

OF 1-BROMOPROPANE

TABLE D1 Summary of the Incidence of Neoplasms in Female Mice

in the 2-Year Inhalation Study of 1-Bromopropane .......................................................................D-2

TABLE D2 Statistical Analysis of Primary Neoplasms in Female Mice

in the 2-Year Inhalation Study of 1-Bromopropane ......................................................................D-6

TABLE D3 Historical Incidence of Alveolar/bronchiolar Neoplasms 

in Control Female B6C3F1 Mice ....................................................................................................D-10

TABLE D4 Summary of the Incidence of Nonneoplastic Lesions in Female Mice

in the 2-Year Inhalation Study of 1-Bromopropane ....................................................................D-11
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TABLE D1

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Inhalation Study of 1-Bromopropanea

Chamber Control 62.5 ppm 125 ppm 250 ppm

Disposition Summary

Animals initially in study 50 50 50 50

Early deaths

Moribund 10 7 8 8

Natural deaths 4 3 5

Survivors

Died last week of study 1 1

Terminal sacrifice 35 40 37 41

Animals examined microscopically 50 50 50 50

Alimentary System

Esophagus (50) (50) (50) (50)

Squamous cell carcinoma 1 (2%)

Gallbladder (43) (36) (36) (44)

Intestine large, cecum (48) (49) (46) (50)

Leiomyoma 1 (2%) 1 (2%)

Intestine large, colon (48) (49) (46) (50)

Leiomyoma 1 (2%)

Intestine large, rectum (47) (49) (46) (50)

Intestine small, duodenum (46) (49) (46) (50)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Intestine small, ileum (48) (49) (46) (50)

Hemangiosarcoma 1 (2%)

Intestine small, jejunum (46) (49) (46) (50)

Hemangiosarcoma 1 (2%)

Leiomyosarcoma 1 (2%)

Liver (50) (50) (50) (50)

Hemangiosarcoma 1 (2%)

Hepatoblastoma 1 (2%)

Hepatocellular adenoma 13 (26%) 8 (16%) 13 (26%) 9 (18%)

Hepatocellular adenoma, multiple 6 (12%) 5 (10%) 2 (4%) 3 (6%)

Hepatocellular carcinoma 5 (10%) 4 (8%) 7 (14%)

Hepatocholangiocarcinoma 1 (2%)

Mesentery (11) (9) (11) (13)

Hemangiosarcoma 1 (9%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (8%)

Pancreas (50) (49) (50) (50)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Salivary glands (50) (50) (50) (50)

Stomach, forestomach (50) (50) (49) (50)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Squamous cell papilloma 2 (4%)

Stomach, glandular (50) (49) (48) (50)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Leiomyosarcoma, metastatic, 

intestine small, jejunum 1 (2%)

Tongue (0) (0) (1) (0)

Squamous cell carcinoma 1 (100%)

Tooth (0) (1) (0) (0)
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TABLE D1

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Cardiovascular System

Heart (50) (50) (50) (50)

Hemangiosarcoma 1 (2%)

Endocrine System

Adrenal cortex (50) (50) (50) (50)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Adrenal medulla (50) (50) (49) (50)

Pheochromocytoma benign 3 (6%) 2 (4%)

Pheochromocytoma malignant 1 (2%)

Islets, pancreatic (50) (49) (49) (49)

Carcinoma 1 (2%)

Pituitary gland (46) (49) (47) (48)

Pars distalis, adenoma 5 (11%) 7 (14%) 5 (11%) 9 (19%)

Pars distalis, carcinoma 1 (2%)

Pars intermedia, adenoma 4 (9%)

Thyroid gland (49) (50) (46) (50)

General Body System

Peritoneum (0) (0) (0) (1)

Leiomyosarcoma, metastatic, 

intestine small, jejunum 1 (100%)

Genital System

Ovary (50) (50) (50) (49)

Cystadenoma 3 (6%) 1 (2%) 1 (2%) 2 (4%)

Granulosa cell tumor benign 1 (2%)

Granulosa cell tumor malignant 1 (2%)

Luteoma 1 (2%) 1 (2%)

Uterus (50) (50) (50) (50)

Carcinoma 1 (2%)

Choriocarcinoma, metastatic, 

uncertain primary site 1 (2%)

Leiomyosarcoma 1 (2%)

Polyp stromal 2 (4%) 2 (4%) 3 (6%)

Hematopoietic System

Bone marrow (50) (50) (49) (50)

Lymph node (6) (5) (3) (8)

Lymph node, bronchial (37) (32) (39) (34)

Hepatocholangiocarcinoma, metastatic,

liver 1 (3%)

Lymph node, mandibular (45) (30) (30) (37)

Lymph node, mediastinal (45) (39) (41) (37)

Hemangiosarcoma 1 (2%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (3%)

Lymph node, mesenteric (48) (47) (47) (49)

Spleen (50) (49) (50) (50)

Hemangiosarcoma 1 (2%) 1 (2%) 1 (2%)

Thymus (49) (45) (45) (45)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Thymoma benign 1 (2%)
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TABLE D1

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Integumentary System

Mammary gland (50) (50) (50) (50)

Adenosquamous carcinoma 1 (2%) 2 (4%)

Carcinoma 2 (4%) 1 (2%)

Skin (50) (50) (50) (50)

Sebaceous gland, carcinoma 1 (2%)

Subcutaneous tissue, fibrosarcoma 1 (2%)

Subcutaneous tissue, fibrous histiocytoma 1 (2%) 2 (4%)

Subcutaneous tissue, hemangioma 1 (2%)

Subcutaneous tissue, hemangiosarcoma 1 (2%)

Subcutaneous tissue, sarcoma 7 (14%) 2 (4%) 3 (6%) 1 (2%)

Musculoskeletal System

Bone (50) (50) (50) (50)

Hemangiosarcoma 1 (2%)

Skeletal muscle (0) (0) (0) (1)

Hepatocholangiocarcinoma, metastatic,

liver 1 (100%)

Nervous System

Brain (50) (50) (50) (50)

Carcinoma, metastatic, pituitary gland 1 (2%)

Meningioma benign 1 (2%)

Peripheral nerve (1) (1) (1) (1)

Spinal cord (1) (1) (1) (1)

Respiratory System

Larynx (50) (50) (50) (50)

Lung (50) (50) (50) (50)

Alveolar/bronchiolar adenoma 1 (2%) 6 (12%) 4 (8%) 8 (16%)

Alveolar/bronchiolar adenoma, multiple 2 (4%)

Alveolar/bronchiolar carcinoma 5 (10%) 4 (8%) 3 (6%)

Alveolar/bronchiolar carcinoma, multiple 2 (4%) 1 (2%) 1 (2%)

Choriocarcinoma, metastatic, uterus 1 (2%)

Hepatoblastoma, metastatic, liver 1 (2%)

Hepatocellular carcinoma, metastatic,

liver 1 (2%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Osteosarcoma, metastatic, 

uncertain primary site 1 (2%)

Sarcoma, metastatic, skin 1 (2%)

Bronchiole, adenoma 1 (2%) 1 (2%)

Nose (50) (50) (50) (50)

Pleura (0) (0) (1) (0)

Trachea (50) (49) (50) (50)

Special Senses System

Eye (47) (49) (45) (50)

Harderian gland (49) (49) (48) (50)

Adenoma 3 (6%) 2 (4%) 4 (8%) 2 (4%)

Carcinoma 2 (4%) 1 (2%) 1 (2%)

Zymbal’s gland (0) (1) (0) (0)

Carcinoma 1 (100%)
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TABLE D1

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Urinary System

Kidney (50) (49) (49) (50)

Hepatoblastoma, metastatic, liver 1 (2%)

Hepatocholangiocarcinoma, metastatic,

liver 1 (2%)

Urinary bladder (50) (49) (48) (50)

Hemangiosarcoma 1 (2%)

Systemic Lesions

Multiple organsb (50) (50) (50) (50)

Histiocytic sarcoma 1 (2%) 2 (4%) 2 (4%)

Lymphoma malignant 17 (34%) 9 (18%) 15 (30%) 11 (22%)

Neoplasm Summary

Total animals with primary neoplasmsc 42 37 43 34

Total primary neoplasms 79 66 82 67

Total animals with benign neoplasms 22 24 30 28

Total benign neoplasms 35 34 43 41

Total animals with malignant neoplasms 33 27 32 22

Total malignant neoplasms 44 32 39 26

Total animals with metastatic neoplasms 2 2 2 2

Total metastatic neoplasms 2 3 3 14

Total animals with malignant neoplasms

of uncertain primary site 1 1

a Number of animals examined microscopically at the site and the number of animals with neoplasm

b Number of animals with any tissue examined microscopically

c Primary neoplasms: all neoplasms except metastatic neoplasms
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TABLE D2

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Adrenal Medulla: Benign Pheochromocytoma

Overall ratea 3/50 (6%) 0/50 (0%) 2/49 (4%) 0/50 (0%)

Adjusted rateb 6.7% 0.0% 4.5% 0.0%

Terminal ratec 2/36 (6%) 0/40 (0%) 1/37 (3%) 0/41 (0%)

First incidence (days) 708 —e 631 —

Poly-3 testd P=0.123N P=0.110N P=0.503N P=0.109N

Adrenal Medulla: Benign or Malignant Pheochromocytoma

Overall rate 4/50 (8%) 0/50 (0%) 2/49 (4%) 0/50 (0%)

Adjusted rate 9.0% 0.0% 4.5% 0.0%

Terminal rate 3/36 (8%) 0/40 (0%) 1/37 (3%) 0/41 (0%)

First incidence (days) 708 — 631 —

Poly-3 test P=0.060N P=0.054N P=0.340N P=0.054N

Harderian Gland: Adenoma

Overall rate 3/50 (6%) 2/50 (4%) 4/50 (8%) 2/50 (4%)

Adjusted rate 6.7% 4.3% 8.9% 4.2%

Terminal rate 3/36 (8%) 2/40 (5%) 4/37 (11%) 1/41 (2%)

First incidence (days) 731 (T) 731 (T) 731 (T) 663

Poly-3 test P=0.456N P=0.477N P=0.505 P=0.472N

Harderian Gland: Adenoma or Carcinoma

Overall rate 5/50 (10%) 2/50 (4%) 4/50 (8%) 3/50 (6%)

Adjusted rate 11.2% 4.3% 8.9% 6.3%

Terminal rate 5/36 (14%) 2/40 (5%) 4/37 (11%) 2/41 (5%)

First incidence (days) 731 (T) 731 (T) 731 (T) 663

Poly-3 test P=0.372N P=0.196N P=0.494N P=0.323N

Liver: Hepatocellular Adenoma

Overall rate 19/50 (38%) 13/50 (26%) 15/50 (30%) 12/50 (24%)

Adjusted rate 40.8% 27.6% 32.3% 25.4%

Terminal rate 14/36 (39%) 12/40 (30%) 11/37 (30%) 11/41 (27%)

First incidence (days) 481 678 589 703

Poly-3 test P=0.108N P=0.127N P=0.263N P=0.083N

Liver: Hepatocellular Carcinoma

Overall rate 5/50 (10%) 4/50 (8%) 7/50 (14%) 0/50 (0%)

Adjusted rate 11.1% 8.5% 15.4% 0.0%

Terminal rate 3/36 (8%) 3/40 (8%) 5/37 (14%) 0/41 (0%)

First incidence (days) 669 678 589 —

Poly-3 test P=0.047N P=0.471N P=0.388 P=0.027N

Liver: Hepatocellular Adenoma or Carcinoma

Overall rate 24/50 (48%) 15/50 (30%) 20/50 (40%) 12/50 (24%)

Adjusted rate 51.1% 31.8% 43.0% 25.4%

Terminal rate 17/36 (47%) 14/40 (35%) 15/37 (41%) 11/41 (27%)

First incidence (days) 481 678 589 703

Poly-3 test P=0.017N P=0.043N P=0.282N P=0.007N

Lung: Alveolar/bronchiolar Adenoma

Overall rate 1/50 (2%) 6/50 (12%) 4/50 (8%) 10/50 (20%)

Adjusted rate 2.2% 12.8% 8.9% 20.8%

Terminal rate 1/36 (3%) 6/40 (15%) 4/37 (11%) 7/41 (17%)

First incidence (days) 731 (T) 731 (T) 731 (T) 649

Poly-3 test P=0.007 P=0.064 P=0.181 P=0.006
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TABLE D2

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Lung: Alveolar/bronchiolar Carcinoma

Overall rate 0/50 (0%) 7/50 (14%) 5/50 (10%) 4/50 (8%)

Adjusted rate 0.0% 14.9% 11.1% 8.5%

Terminal rate 0/36 (0%) 6/40 (15%) 5/37 (14%) 4/41 (10%)

First incidence (days) — 709 731 (T) 731 (T)

Poly-3 test P=0.277 P=0.009 P=0.031 P=0.068

Lung: Alveolar/bronchiolar Adenoma or Carcinoma

Overall rate 1/50 (2%) 9/50 (18%) 8/50 (16%) 14/50 (28%)

Adjusted rate 2.2% 19.2% 17.8% 29.2%

Terminal rate 1/36 (3%) 8/40 (20%) 8/37 (22%) 11/41 (27%)

First incidence (days) 731 (T) 709 731 (T) 649

Poly-3 test P<0.001 P=0.010 P=0.016 P<0.001

Ovary: Cystadenoma

Overall rate 3/50 (6%) 1/50 (2%) 1/50 (2%) 2/49 (4%)

Adjusted rate 6.7% 2.1% 2.2% 4.3%

Terminal rate 3/36 (8%) 1/40 (3%) 1/37 (3%) 1/40 (3%)

First incidence (days) 731 (T) 731 (T) 731 (T) 730

Poly-3 test P=0.480N P=0.287N P=0.302N P=0.484N

Pituitary Gland (Pars Distalis): Adenoma

Overall rate 5/46 (11%) 7/49 (14%) 5/47 (11%) 9/48 (19%)

Adjusted rate 12.2% 15.2% 11.8% 19.1%

Terminal rate 5/34 (15%) 6/39 (15%) 5/35 (14%) 6/41 (15%)

First incidence (days) 731 (T) 723 731 (T) 470

Poly-3 test P=0.237 P=0.461 P=0.608N P=0.278

Pituitary Gland (Pars Distalis): Adenoma or Carcinoma

Overall rate 6/46 (13%) 7/49 (14%) 5/47 (11%) 9/48 (19%)

Adjusted rate 14.6% 15.2% 11.8% 19.1%

Terminal rate 5/34 (15%) 6/39 (15%) 5/35 (14%) 6/41 (15%)

First incidence (days) 708 723 731 (T) 470

Poly-3 test P=0.322 P=0.586 P=0.477N P=0.391

Pituitary Gland (Pars Intermedia): Adenoma

Overall rate 0/46 (0%) 0/49 (0%) 4/47 (9%) 0/48 (0%)

Adjusted rate 0.0% 0.0% 9.4% 0.0%

Terminal rate 0/34 (0%) 0/39 (0%) 4/35 (11%) 0/41 (0%)

First incidence (days) — — 731 (T) —

Poly-3 test P=0.551 —f P=0.064 —

Skin (Subcutaneous Tissue): Sarcoma

Overall rate 7/50 (14%) 2/50 (4%) 3/50 (6%) 1/50 (2%)

Adjusted rate 15.0% 4.2% 6.6% 2.1%

Terminal rate 1/36 (3%) 0/40 (0%) 2/37 (5%) 1/41 (2%)

First incidence (days) 562 505 610 731 (T)

Poly-3 test P=0.029N P=0.074N P=0.169N P=0.029N

Skin (Subcutaneous Tissue): Fibrous Histiocytoma, Fibrosarcoma, or Sarcoma

Overall rate 8/50 (16%) 4/50 (8%) 4/50 (8%) 1/50 (2%)

Adjusted rate 17.1% 8.3% 8.7% 2.1%

Terminal rate 2/36 (6%) 1/40 (3%) 2/37 (5%) 1/41 (2%)

First incidence (days) 562 505 537 731 (T)

Poly-3 test P=0.014N P=0.164N P=0.184N P=0.015N
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TABLE D2

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Uterus: Stromal Polyp

Overall rate 0/50 (0%) 2/50 (4%) 2/50 (4%) 3/50 (6%)

Adjusted rate 0.0% 4.2% 4.4% 6.4%

Terminal rate 0/36 (0%) 1/40 (3%) 1/37 (3%) 2/41 (5%)

First incidence (days) — 547 589 719

Poly-3 test P=0.121 P=0.252 P=0.241 P=0.129

All Organs: Hemangiosarcoma

Overall rate 4/50 (8%) 2/50 (4%) 2/50 (4%) 1/50 (2%)

Adjusted rate 9.0% 4.3% 4.4% 2.1%

Terminal rate 4/36 (11%) 1/40 (3%) 1/37 (3%) 1/41 (2%)

First incidence (days) 731 (T) 687 603 731 (T)

Poly-3 test P=0.131N P=0.312N P=0.328N P=0.162N

All Organs: Hemangioma or Hemangiosarcoma

Overall rate 4/50 (8%) 3/50 (6%) 2/50 (4%) 1/50 (2%)

Adjusted rate 9.0% 6.4% 4.4% 2.1%

Terminal rate 4/36 (11%) 2/40 (5%) 1/37 (3%) 1/41 (2%)

First incidence (days) 731 (T) 687 603 731 (T)

Poly-3 test P=0.107N P=0.470N P=0.328N P=0.162N

All Organs: Malignant Lymphoma

Overall rate 17/50 (34%) 9/50 (18%) 15/50 (30%) 11/50 (22%)

Adjusted rate 37.2% 19.0% 33.0% 23.2%

Terminal rate 13/36 (36%) 8/40 (20%) 13/37 (35%) 8/41 (20%)

First incidence (days) 591 583 631 649

Poly-3 test P=0.198N P=0.040N P=0.421N P=0.104N

All Organs: Benign Neoplasms

Overall rate 22/50 (44%) 24/50 (48%) 30/50 (60%) 28/50 (56%)

Adjusted rate 47.2% 50.3% 64.0% 57.3%

Terminal rate 17/36 (47%) 21/40 (53%) 25/37 (68%) 21/41 (51%)

First incidence (days) 481 547 589 470

Poly-3 test P=0.150 P=0.463 P=0.072 P=0.217

All Organs: Malignant Neoplasms

Overall rate 33/50 (66%) 28/50 (56%) 33/50 (66%) 22/50 (44%)

Adjusted rate 68.4% 57.0% 67.9% 45.2%

Terminal rate 22/36 (61%) 20/40 (50%) 23/37 (62%) 15/41 (37%)

First incidence (days) 540 505 345 568

Poly-3 test P=0.021N P=0.168N P=0.566N P=0.016N
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TABLE D2

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

All Organs: Benign or Malignant Neoplasms

Overall rate 42/50 (84%) 37/50 (74%) 44/50 (88%) 34/50 (68%)

Adjusted rate 85.0% 74.4% 89.6% 68.8%

Terminal rate 29/36 (81%) 28/40 (70%) 33/37 (89%) 26/41 (63%)

First incidence (days) 481 505 345 470

Poly-3 test P=0.064N P=0.142N P=0.349 P=0.044N

(T)Terminal sacrifice

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for adrenal 

medulla, liver, lung, ovary, and pituitary gland; for other tissues, denominator is number of animals necropsied.

b Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality

c Observed incidence at terminal kill

d Beneath the chamber control incidence is the P value associated with the trend test. Beneath the exposed group incidence are the P values 

corresponding to pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for the differential 

mortality in animals that do not reach terminal sacrifice. A negative trend or a lower incidence in an exposure group is indicated by N.

e Not applicable; no neoplasms in animal group

f Value of statistic cannot be computed.
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TABLE D3

Historical Incidence of Alveolar/bronchiolar Neoplasms in Control Female B6C3F1 Micea

Study (Study Start) Incidence in Controls

Adenoma Carcinoma Adenoma or Carcinoma

Historical Incidence: Inhalation Studies 

1-Bromopropane (July, 2003) 1/50 0/50 1/50

Cumene (June, 2001) 1/50 3/50 4/50

Diethylamine (August, 2003) 2/50 3/50 5/50

Methyl isobutyl ketone (June, 2000) 4/50 0/50 4/50

α-Methylstyrene (July, 2001) 1/50 1/50 2/50

Propargyl alcohol (September, 2001) 3/50 2/50 5/50

Tetralin (June, 2003) 6/50 0/50 6/50

Total (%) 18/350 (5.1%) 9/350 (2.6%) 27/350 (7.7%)

Mean ± standard deviation 5.1% ± 3.8% 2.6% ± 2.8% 7.7% ± 3.6%

Range 2%-12% 0%-6% 2%-12%

Overall Historical Incidence: All Routes

Total (%) 73/1,496 (4.9%) 59/1,496 (3.9%) 128/1,496 (8.6%)

Mean ± standard deviation 4.9% ± 3.4% 3.9% ± 3.4% 8.6% ± 3.7%

Range 0%-12% 0%-12% 2%-18%

a Data as of April 29, 2009
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TABLE D4

Summary of the Incidence of Nonneoplastic Lesions in Female Mice

in the 2-Year Inhalation Study of 1-Bromopropanea

Chamber Control 62.5 ppm 125 ppm 250 ppm

Disposition Summary

Animals initially in study 50 50 50 50

Early deaths

Moribund 10 7 8 8

Natural deaths 4 3 5

Survivors

Died last week of study 1 1

Terminal sacrifice 35 40 37 41

Animals examined microscopically 50 50 50 50

Alimentary System

Esophagus (50) (50) (50) (50)

Gallbladder (43) (36) (36) (44)

Inflammation, chronic active 1 (3%)

Intestine large, cecum (48) (49) (46) (50)

Hemorrhage 1 (2%)

Inflammation, suppurative 1 (2%)

Intestine large, colon (48) (49) (46) (50)

Necrosis 1 (2%)

Intestine large, rectum (47) (49) (46) (50)

Artery, inflammation, chronic active 1 (2%)

Intestine small, duodenum (46) (49) (46) (50)

Intestine small, ileum (48) (49) (46) (50)

Epithelium, hyperplasia 1 (2%)

Intestine small, jejunum (46) (49) (46) (50)

Epithelium, hyperplasia 1 (2%)

Liver (50) (50) (50) (50)

Angiectasis 1 (2%) 1 (2%) 2 (4%)

Basophilic focus 2 (4%) 3 (6%) 2 (4%) 3 (6%)

Clear cell focus 2 (4%) 1 (2%) 2 (4%)

Eosinophilic focus 6 (12%) 7 (14%) 7 (14%) 5 (10%)

Fatty change 1 (2%) 1 (2%) 2 (4%)

Fatty change, focal 2 (4%)

Hematopoietic cell proliferation 1 (2%)

Infarct 1 (2%)

Inflammation, acute 1 (2%)

Inflammation, chronic 1 (2%) 1 (2%)

Malformation, lobular 1 (2%)

Mineralization 1 (2%)

Mixed cell focus 2 (4%) 3 (6%) 3 (6%)

Necrosis 1 (2%) 1 (2%) 2 (4%) 1 (2%)

Tension lipidosis 3 (6%) 10 (20%) 4 (8%) 1 (2%)

Thrombosis 1 (2%)

Vacuolization cytoplasmic 1 (2%)

Bile duct, hyperplasia 1 (2%)

Hepatocyte, mitotic alteration 1 (2%)

Mesentery (11) (9) (11) (13)

Artery, inflammation 1 (9%)

Fat, hemorrhage 1 (11%) 1 (9%)

Fat, necrosis 9 (82%) 9 (100%) 9 (82%) 12 (92%)

Pancreas (50) (49) (50) (50)

Atrophy 7 (14%) 4 (8%) 5 (10%) 2 (4%)

Basophilic focus 1 (2%) 2 (4%)

Inflammation, chronic active 1 (2%) 1 (2%)

Salivary glands (50) (50) (50) (50)

a Number of animals examined microscopically at the site and the number of animals with lesion
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TABLE D4

Summary of the Incidence of Nonneoplastic Lesions in Female Mice

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Alimentary System (continued)

Stomach, forestomach (50) (50) (49) (50)

Hyperplasia, squamous 3 (6%) 2 (4%) 2 (4%) 1 (2%)

Inflammation 1 (2%)

Ulcer 2 (4%) 2 (4%) 2 (4%)

Artery, inflammation, chronic active 1 (2%)

Stomach, glandular (50) (49) (48) (50)

Infiltration cellular, mixed cell 1 (2%)

Infiltration cellular, mononuclear cell 1 (2%)

Mineralization 1 (2%) 1 (2%)

Necrosis 1 (2%) 1 (2%)

Artery, inflammation, chronic active 1 (2%)

Tongue (0) (0) (1) (0)

Tooth (0) (1) (0) (0)

Dysplasia 1 (100%)

Cardiovascular System

Heart (50) (50) (50) (50)

Cardiomyopathy 6 (12%) 12 (24%) 8 (16%) 8 (16%)

Inflammation, suppurative 1 (2%)

Mineralization 3 (6%) 2 (4%)

Necrosis 1 (2%)

Thrombosis 2 (4%)

Artery, inflammation, chronic active 1 (2%) 1 (2%)

Endocrine System

Adrenal cortex (50) (50) (50) (50)

Hyperplasia 3 (6%) 10 (20%) 4 (8%) 6 (12%)

Hypertrophy 4 (8%) 3 (6%) 1 (2%) 9 (18%)

Inflammation, suppurative 1 (2%)

Subcapsular, hyperplasia 1 (2%) 1 (2%)

Adrenal medulla (50) (50) (49) (50)

Hyperplasia 5 (10%) 1 (2%) 4 (8%)

Islets, pancreatic (50) (49) (49) (49)

Hyperplasia 2 (4%) 1 (2%)

Pituitary gland (46) (49) (47) (48)

Pars distalis, angiectasis 1 (2%) 1 (2%) 2 (4%)

Pars distalis, hyperplasia 15 (33%) 14 (29%) 11 (23%) 15 (31%)

Pars intermedia, hyperplasia 1 (2%) 2 (4%)

Pars intermedia, hypertrophy 1 (2%) 1 (2%)

Thyroid gland (49) (50) (46) (50)

Follicular cell, hyperplasia 1 (2%) 1 (2%) 1 (2%) 1 (2%)

General Body System

Peritoneum (0) (0) (0) (1)
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TABLE D4

Summary of the Incidence of Nonneoplastic Lesions in Female Mice

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Genital System

Ovary (50) (50) (50) (49)

Angiectasis 1 (2%) 2 (4%) 2 (4%)

Congestion, chronic 1 (2%)

Cyst 12 (24%) 8 (16%) 12 (24%) 2 (4%)

Hyperplasia, tubular 1 (2%)

Thrombosis 2 (4%) 2 (4%) 1 (2%)

Uterus (50) (50) (50) (50)

Angiectasis 2 (4%) 3 (6%) 6 (12%) 3 (6%)

Fibrosis 1 (2%)

Inflammation, suppurative 1 (2%)

Inflammation, acute 1 (2%)

Thrombosis 1 (2%) 1 (2%) 2 (4%) 1 (2%)

Endometrium, hyperplasia, cystic 39 (78%) 43 (86%) 43 (86%) 41 (82%)

Hematopoietic System

Bone marrow (50) (50) (49) (50)

Angiectasis 2 (4%)

Atrophy 1 (2%)

Lymph node (6) (5) (3) (8)

Iliac, angiectasis 2 (33%) 1 (20%)

Iliac, hyperplasia, lymphoid 1 (17%)

Lumbar, angiectasis 1 (20%) 1 (33%) 1 (13%)

Renal, angiectasis 1 (13%)

Renal, hyperplasia, lymphoid 1 (17%) 1 (20%)

Lymph node, bronchial (37) (32) (39) (34)

Lymph node, mandibular (45) (30) (30) (37)

Hyperplasia, lymphoid 1 (3%)

Lymph node, mediastinal (45) (39) (41) (37)

Hyperplasia, lymphoid 1 (2%)

Lymph node, mesenteric (48) (47) (47) (49)

Angiectasis 2 (4%) 2 (4%) 1 (2%)

Hyperplasia, lymphoid 1 (2%)

Spleen (50) (49) (50) (50)

Atrophy 4 (8%) 1 (2%) 2 (4%) 5 (10%)

Congestion 1 (2%) 2 (4%)

Hematopoietic cell proliferation 13 (26%) 10 (20%) 13 (26%) 16 (32%)

Hemorrhage 1 (2%)

Hyperplasia, histiocytic 2 (4%)

Hyperplasia, lymphoid 7 (14%) 7 (14%) 5 (10%) 3 (6%)

Hyperplasia, plasma cell 1 (2%)

Necrosis, lymphoid 1 (2%) 1 (2%)

Pigmentation, hemosiderin 1 (2%) 2 (4%)

Thymus (49) (45) (45) (45)

Atrophy 14 (29%) 13 (29%) 17 (38%) 16 (36%)

Cyst 5 (10%) 7 (16%) 6 (13%) 9 (20%)

Necrosis, lymphoid 2 (4%) 4 (9%)

Medulla, hyperplasia, lymphoid 25 (51%) 29 (64%) 30 (67%) 26 (58%)

Integumentary System

Mammary gland (50) (50) (50) (50)

Hyperplasia 1 (2%) 1 (2%) 1 (2%)

Skin (50) (50) (50) (50)

Cyst 1 (2%)

Inflammation, chronic active 4 (8%) 2 (4%) 1 (2%)
D-14 1-Bromopropane, NTP TR 564

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TABLE D4

Summary of the Incidence of Nonneoplastic Lesions in Female Mice

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Musculoskeletal System

Bone (50) (50) (50) (50)

Cyst 1 (2%)

Skeletal muscle (0) (0) (0) (1)

Nervous System

Brain (50) (50) (50) (50)

Necrosis 1 (2%) 1 (2%)

Artery, inflammation 1 (2%)

Peripheral nerve (1) (1) (1) (1)

Degeneration 1 (100%)

Spinal cord (1) (1) (1) (1)

Inflammation, chronic active 1 (100%)

Respiratory System

Larynx (50) (50) (50) (50)

Vacuolization cytoplasmic 3 (6%) 2 (4%) 2 (4%)

Artery, inflammation, chronic active 1 (2%)

Lung (50) (50) (50) (50)

Inflammation, chronic active 1 (2%)

Alveolar epithelium, hyperplasia 1 (2%) 1 (2%) 3 (6%)

Alveolus, infiltration cellular, histiocyte 4 (8%) 1 (2%)

Bronchiole, hyperplasia 1 (2%) 1 (2%)

Bronchiole, necrosis 1 (2%)

Bronchiole, regeneration 45 (90%) 43 (86%) 49 (98%)

Bronchiole, vacuolization cytoplasmic 3 (6%) 4 (8%) 3 (6%)

Nose (50) (50) (50) (50)

Inflammation, suppurative 1 (2%)

Olfactory epithelium, atrophy 6 (12%)

Olfactory epithelium, metaplasia, 

respiratory 4 (8%) 5 (10%) 14 (28%)

Respiratory epithelium, hyperplasia 11 (22%) 25 (50%) 28 (56%) 27 (54%)

Respiratory epithelium, vacuolization

cytoplasmic 3 (6%) 5 (10%) 8 (16%)

Pleura (0) (0) (1) (0)

Trachea (50) (49) (50) (50)

Vacuolization cytoplasmic 8 (16%) 7 (14%) 4 (8%)

Special Senses System

Eye (47) (49) (45) (50)

Cataract 3 (6%) 1 (2%) 2 (4%)

Cornea, hyperplasia, squamous 1 (2%)

Cornea, inflammation, chronic active 1 (2%) 2 (4%) 1 (2%)

Cornea, mineralization 1 (2%) 2 (4%) 1 (2%)

Harderian gland (49) (49) (48) (50)

Hyperplasia 3 (6%) 1 (2%) 2 (4%) 6 (12%)

Inflammation, chronic active 1 (2%)

Zymbal’s gland (0) (1) (0) (0)
1-Bromopropane, NTP TR 564 D-15

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TABLE D4

Summary of the Incidence of Nonneoplastic Lesions in Female Mice

in the 2-Year Inhalation Study of 1-Bromopropane

Chamber Control 62.5 ppm 125 ppm 250 ppm

Urinary System

Kidney (50) (49) (49) (50)

Amyloid deposition 1 (2%)

Cyst 1 (2%)

Inflammation, suppurative 1 (2%)

Inflammation, chronic active 1 (2%)

Metaplasia, osseous 3 (6%) 4 (8%) 2 (4%)

Nephropathy 33 (66%) 37 (76%) 40 (82%) 39 (78%)

Renal tubule, hyperplasia 1 (2%)

Transitional epithelium, hyperplasia 1 (2%)

Urinary bladder (50) (49) (48) (50)

Inflammation, chronic active 1 (2%)

Artery, inflammation, chronic active 2 (4%)
D-16 1-Bromopropane, NTP TR 564

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E-1 

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APPENDIX E 

GENETIC TOXICOLOGY

BACTERIAL MUTAGENICITY TEST PROTOCOL .......................................................................................................E-2 

MOUSE PERIPHERAL BLOOD MICRONUCLEUS TEST PROTOCOL...........................................................................E-2 

EVALUATION PROTOCOL .........................................................................................................................................E-3 

RESULTS....................................................................................................................................................................E-3 

TABLE E1 Mutagenicity of 1-Bromopropane in Bacterial Tester Strains.......................................................E-4 

TABLE E2 Frequency of Micronuclei in Peripheral Blood Erythrocytes of Mice 

Following Treatment with 1-Bromopropane by Inhalation for 3 Months....................................E-6 
E-2 1-Bromopropane, NTP TR 564

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GENETIC TOXICOLOGY

BACTERIAL MUTAGENICITY TEST PROTOCOL

Testing at BioReliance Corporation was performed as reported by Zeiger et al. (1992). 1-Bromopropane was sent to 

the laboratory as a coded aliquot. In the tests conducted at BioReliance Corporation, it was incubated with the 

Salmonella typhimurium tester strains TA97, TA98, TA100, and TA1535 either in buffer or S9 mix (metabolic 

activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver) for 

20 minutes at 37° C. Top agar supplemented with L-histidine and d-biotin was added, and the contents of the tubes 

were mixed and poured onto the surfaces of minimal glucose agar plates. Histidine-independent mutant colonies 

arising on these plates were counted following incubation for 2 days at 37° C. The slightly modified protocol used 

at SITEK Research Laboratories tested the same lot (1581313004) of 1-bromopropane used in the 2-year studies, 

used only 10% rat liver S9 for exogenous metabolic activation, and employed Escherichia coli strain 

WP2 uvrA/pKM101 as a bacterial tester strain in addition to S. typhimurium strains TA98 and TA100. Incubation of 

bacterial strains with 1-bromopropane and subsequent plating were carried out as described above for the traditional 

protocol.

Each trial consisted of triplicate plates of concurrent positive and negative controls and five doses of 

1-bromopropane. The high dose was limited by toxicity in some trials and by the limit dose of 10,000 μg/plate in 

those trials where only slight toxicity was observed. All trials were repeated, and those that were conducted with S9 

activation enzymes were repeated using the same or higher concentrations of S9.

In this assay, a positive response is defined as a reproducible, dose-related increase in histidine-independent 

(revertant) colonies in any one strain/activation combination. An equivocal response is defined as an increase in 

revertants that is not dose related, is not reproducible, or is not of sufficient magnitude to support a determination of 

mutagenicity. A negative response is obtained when no increase in revertant colonies is observed following 

chemical treatment. There is no minimum percentage or fold increase required for a chemical to be judged positive 

or weakly positive, although positive calls are typically reserved for increases in mutant colonies that are at least 

twofold over background. 

MOUSE PERIPHERAL BLOOD MICRONUCLEUS TEST PROTOCOL

A detailed discussion of this assay is presented by MacGregor et al. (1990). At the end of the 3-month toxicity 

study, peripheral blood samples were obtained from male and female mice. Smears were immediately prepared and 

fixed in absolute methanol. The methanol-fixed slides were stained with acridine orange and coded. Slides were 

scanned to determine the frequency of micronuclei in 2,000 normochromatic erythrocytes (NCEs; immature 

erythrocytes) per animal. In addition, the percentage of polychromatic erythrocytes (PCEs or reticulocytes) in a

population of 1,000 erythrocytes was determined as a measure of bone marrow toxicity.

The results were tabulated as the mean of the pooled results from all animals within an exposure group plus or 

minus the standard error of the mean. The frequency of micronucleated cells among NCEs was analyzed by a 

statistical software package that tested for increasing trend over exposure groups with a one-tailed 

Cochran-Armitage trend test, followed by pairwise comparisons between each exposed group and the chamber 

control group. In the presence of excess binomial variation, as detected by a binomial dispersion test, the binomial 

variance of the Cochran-Armitage test was adjusted upward in proportion to the excess variation. In the 

micronucleus test, an individual trial is considered positive if the trend test P value is less than or equal to 0.025 or if 

the P value for any single exposed group is less than or equal to 0.025 divided by the number of exposed groups. A 

final call of positive for micronucleus induction is preferably based on reproducibly positive trials (as noted above). 

Results of the 3-month study were accepted without repeat tests, because additional test data could not be obtained. 

Ultimately, the final call is determined by the scientific staff after considering the results of statistical analyses, the 

reproducibility of any effects observed, and the magnitudes of those effects.
1-Bromopropane, NTP TR 564 E-3 

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EVALUATION PROTOCOL

These are the basic guidelines for arriving at an overall assay result for assays performed by the National 

Toxicology Program. Statistical as well as biological factors are considered. For an individual assay, the statistical 

procedures for data analysis have been described in the preceding protocols. There have been instances, however, in 

which multiple aliquots of a chemical were tested in the same assay, and different results were obtained among 

aliquots and/or among laboratories. Results from more than one aliquot or from more than one laboratory are not 

simply combined into an overall result. Rather, all the data are critically evaluated, particularly with regard to 

pertinent protocol variations, in determining the weight of evidence for an overall conclusion of chemical activity in 

an assay. In addition to multiple aliquots, the in vitro assays have another variable that must be considered in 

arriving at an overall test result. In vitro assays are conducted with and without exogenous metabolic activation. 

Results obtained in the absence of activation are not combined with results obtained in the presence of activation; 

each testing condition is evaluated separately. The summary table in the Abstract of this Technical Report presents 

a result that represents a scientific judgment of the overall evidence for activity of the chemical in an assay. 

RESULTS

1-Bromopropane (doses up to 10,000 μg/plate) was not mutagenic in either of two independent bacterial 

mutagenicity assays, with or without exogenous metabolic activation (Table E1). Bacterial strains tested included

S. typhimurium strains TA97, TA98, TA100, and TA1535, as well as E. coli strain WP2 uvrA/pKM101. In addition 

to the negative results in the two bacterial tests, no increases in the frequencies of micronucleated NCEs were seen 

in peripheral blood of male or female B6C3F1 mice exposed for 3 months to 62.5 to 500 ppm 1-bromopropane via 

inhalation (Table E2). The percentage of reticulocytes (PCEs) in the peripheral blood of male and female mice was 

unaltered by 1-bromopropane exposure, suggesting a lack of chemical-associated bone marrow toxicity.
E-4 1-Bromopropane, NTP TR 564

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TABLE E1

Mutagenicity of 1-Bromopropane in Bacterial Tester Strainsa

n Reverta ts/Plateb

Dose −S9 +hamster S9 +rat S9

Strain (μg/Plate) Trial 1 Trial 2 10% 30% 10% 30%

 Study performed at BioReliance Corporation 

 TA100 0 150 ± 4 121 ± 16 104 ± 2 103 ± 9 124 ± 2 140 ± 8 

33

 

115 ± 6 118 ± 6

 

121 ± 7

100 144 ± 10 124 ± 4 109 ± 12 104 ± 8 123 ± 2 133 ± 5 

333 139 ± 7 127 ± 7 92 ± 8 108 ± 6 128 ± 10 117 ± 12

1,000 149 ± 7 128 ± 6 111 ± 7 98 ± 6 144 ± 5 103 ± 7 

3,333 c 117 ± 2 107 ± 11c 98 ± 19c 118 ± 6c c c

10,000 Toxic Toxic

107 ± 7 123 ± 7 

 

Toxic

Trial summary Neg tive a Negative Negative Negative Negative Negative

Positive controld 728 ± 27 279 ± 14 661 ± 22 615 ± 14 523 ± 32 636 ± 27 

TA1535 0 16 ± 2 10 ± 2 10 ± 2 12 ± 2 12 ± 2 14 ± 3 

33

 

9 ± 1 9 ± 2

 

9 ± 2

100 19 ± 2 11 ± 0 12 ± 2 18 ± 2 8 ± 1c 14 ± 2

333 14 ± 3 10 ± 1 11 ± 2 15 ± 4 8 ± 1 18 ± 3 

1,000 14 ± 1 10 ± 1 12 ± 1 17 ± 1 13 ± 2 15 ± 0 e 3,333 6 ± 3 9 ± 1c 8 ± 1c 10 ± 1c 8 ± 2c

 8 ± 0c

10,000 2 ± 1c

 

6 ± 1c

 

4 ± 1c

Trial summary Negative Negative Negative Negative Negative Negative

Positive control 226 ± 10 199 ± 19 60 ± 6 137 ± 9 127 ± 13 80 ± 8 

TA97 0 134 ± 27 105 ± 12 156 ± 6 125 ± 9 161 ± 7 168 ± 13

33 

 

130 ± 12 163 ± 13

 

156 ± 9

100 108 ± 9 121 ± 3 114 ± 17 141 ± 11 141 ± 9 170 ± 9

333 98 ± 5 132 ± 6 124 ± 4 133 ± 12 149 ± 14 168 ± 5 

1,000 117 ± 4 125 ± 6 143 ± 7 166 ± 3c 147 ± 8 180 ± 13 c 3,333 86 ± 3c

 117 ± 7 113 ± 9c 91 ± 16c 122 ± 10c 121 ± 13c

10,000 40 ± 22e

 

53 ± 3c

 

70 ± 15c

Trial summary Negative Negative Negative Negative Negative Negative

Positive control 354 ± 17 211 ± 4 988 ± 30 1,063 ± 138 1,084 ± 32 418 ± 16

TA98 0 23 ± 3 14 ± 1 16 ± 1 29 ± 1 25 ± 2 31 ± 4 

33 

 

18 ± 2 21 ± 3

 

24 ± 3

100 23 ± 2 15 ± 2 24 ± 3 23 ± 2 22 ± 2 27 ± 3 

333 17 ± 2 16 ± 1 14 ± 1 17 ± 2 21 ± 5 23 ± 2 

1,000 19 ± 2 15 ± 1 20 ± 2 22 ± 1 20 ± 2 21 ± 1 

3,333 19 ± 1 17 ± 2c 12 ± 3c

 19 ± 2c 15 ± 1c 15 ± 2c

10,000 Toxic c c

 

11 ± 2 

 

13 ± 0 

Trial summary Negative Negative Negative Negative Negative Negative

Positive control 340 ± 17 166 ± 3 875 ± 24 578 ± 17 302 ± 22 824 ± 28 

 
1-Bromopropane, NTP TR 564 E-5 

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TABLE E1

Mutagenicity of 1-Bromopropane in Bacterial Tester Strains

 

Revertants/Plate 

Dose −S9 +10% rat S9

Strain (μg/Plate) Trial 1 Trial 2 Trial 1 Trial 2

 Study Performed at SITEK Research Laboratories (lot 1581313004 used in the 2-year studies)

TA100 0 62 ± 2 67 ± 4 76 ± 3 65 ± 2 

500 57 ± 6 57 ± 3

1,000 

 

62 ± 4 

1,500 64 ± 3 53 ± 4 

2,500 50 ± 2 35 ± 1 84 ± 2 67 ± 3 

3,500 38 ± 6 16 ± 1c 75 ± 3 63 ± 6 

5,000 11 ± 2c 66 ± 3 66 ± 4 

7,500 62 ± 5 60 ± 4 

10,000 

 

59 ± 7 53 ± 7 

Trial summary Negative Negative Negative Negative

Positive control 488 ± 27 635 ± 35 878 ± 19 982 ± 37

TA98 0 18 ± 1 22 ± 3 29 ± 3 24 ± 2 

500 16 ± 0 16 ± 1 

1,000 

0

19 ± 2

1,50 17 ± 3 18 ± 1 

2,500 18 ± 2 14 ± 1 24 ± 0 23 ± 1

3,500 8 ± 2c

 5 ± 1c 21 ± 4 21 ± 0 c 5,000 2 ± 1 26 ± 4 26 ± 1

7,500 23 ± 3 20 ± 1

10,000 c c

 

6 ± 1 8 ± 2

Trial summary Negative Negative Negative Negative

Positive control 693 ± 26 693 ± 26 1,163 ± 77 742 ± 37

Escherichia coli WP2 uvrA/pKM101 

0 177 ± 3 163 ± 7 185 ± 8 190 ± 23 

500 197 ± 25 190 ± 15

1,500 211 ± 20 194 ± 6 

2,500 153 ± 7 139 ± 12 226 ± 17 214 ± 14

3,500 148 ± 10 124 ± 3 203 ± 14 201 ± 8 

5,000 88 ± 3c c 76 ± 17 192 ± 6 195 ± 10

7,500

10,000 

171 ± 6 164 ± 25

 

149 ± 7 142 ± 4 

Trial summary Negative Negative Negative Negative

Positive control 1,883 ± 20 1,955 ± 18 993 ± 79 1,164 ± 25 

 

a The detailed protocol for the BioReliance Corporation study is presented by Zeiger et al. (1992); the study performed at SITEK Research 

Laboratories used a slight modification of those procedures. 0 μg/plate was the solvent control.

b Revertants are presented as mean ± standard error from three plates.

c Slight toxicity

d The positive controls in the absence of metabolic activation were sodium azide (TA100 and TA1535), 9-aminoacridine (TA97), 

4-nitro-o-phenylenediamine (TA98), and methyl methanesulfonate (E. coli). The positive control for metabolic activation with all strains was 

2-aminoanthracene.

e Slight toxicity and precipitate
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Table E2

Frequency of Micronuclei in Peripheral Blood Erythrocytes of Mice 

Following Treatment with 1-Bromopropane by Inhalation for 3 Monthsa

Exposure Number of Mice Micronucleated NCEs/ Compound Concentration with Erythrocytes val c b P ue PCEs (%)b

1,000 NCEs (ppm) Scored

Male 

 

Aird 0 5 2.00 ± 0.61 2.52 ± 0.30 

1-Bromopropane 62.5 5 3.10 ± 0.81 0.0615 2.16 ± 0.31

125 5 2.70 ± 0.64 0.1533 2.96 ± 0.11 

250 5 1.30 ± 0.41 0.8887 2.80 ± 0.18

500 5 2.30 ± 0.46 0.3235 2.80 ± 0.44 

P=0.757e

Female

Air 0 5 1.80 ± 0.25 2.24 ± 0.52

1-Bromopropane 62.5 5 1.70 ± 0.25 0.5672 2.94 ± 0.23

125 5 1.60 ± 0.19 0.6343 2.74 ± 0.52

250 5 1.40 ± 0.33 0.7604 2.42 ± 0.27 

500 5 1.80 ± 0.20 0.5000 2.48 ± 0.29

 

 

P=0.500

 

a Study was performed at ILS, Inc. The detailed protocol is presented by MacGregor et al. (1990).

PCE=polychromatic erythrocyte; NCE=normochromatic erythrocyte.

b Mean ± standard error

c Pairwise comparison with the chamber control group; significant at P≤0.008 

d Chamber control

e Significance of micronucleated NCEs/1,000 NCEs tested by the one-tailed trend test; significant at P≤0.025
F-1 

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APPENDIX F 

CLINICAL PATHOLOGY RESULTS

TABLE F1 Hematology and Clinical Chemistry Data for Rats in the 3-Month Inhalation Study

of 1-Bromopropane ............................................................................................................................F-2 

TABLE F2 Hematology Data for Mice in the 3-Month Inhalation Study of 1-Bromopropane ......................F-7 
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TABLE F1

Hematology and Clinical Chemistry Data for Rats in the 3-Month Inhalation Study of 1-Bromopropanea

Chamber 

Control 62.5 ppm 125 ppm 250 ppm 500 ppm 1,000 ppm

Male

Hematology

n

Day 3 10 10 10 9 10 10

Day 23 10 10 10 10 10 10

Week 14 10 10 10 10 10 10

Hematocrit (%)

Day 3 45.3 ± 0.5 44.2 ± 0.4 44.7 ± 0.4 44.9 ± 0.5 45.0 ± 0.6 47.0 ± 0.6

Day 23 47.2 ± 0.5 47.2 ± 0.4 47.9 ± 0.4 47.4 ± 0.4 47.2 ± 0.5 47.9 ± 0.5

Week 14 48.2 ± 0.2 48.4 ± 0.4 48.0 ± 0.3 48.5 ± 0.3 47.9 ± 0.3 49.1 ± 0.5

Packed cell volume (mL/dL)

Day 3 44.3 ± 0.6 43.8 ± 0.4 43.8 ± 0.4 44.3 ± 0.4 44.5 ± 0.5 46.5 ± 0.5**

Day 23 46.0 ± 0.6 46.0 ± 0.5 46.8 ± 0.4 46.4 ± 0.5 46.1 ± 0.4 47.1 ± 0.4

Week 14 47.8 ± 0.3 47.8 ± 0.3 47.7 ± 0.4 47.8 ± 0.3 47.6 ± 0.4 48.4 ± 0.5

Hemoglobin (g/dL)

Day 3 13.5 ± 0.2 13.5 ± 0.1 13.6 ± 0.2 13.8 ± 0.2 13.7 ± 0.1 14.3 ± 0.2**

Day 23 14.8 ± 0.2 14.7 ± 0.2 14.9 ± 0.1 14.8 ± 0.2 14.7 ± 0.1 14.9 ± 0.1

Week 14 15.4 ± 0.1 15.5 ± 0.1 15.5 ± 0.1 15.6 ± 0.1 15.5 ± 0.1 15.8 ± 0.2

Erythrocytes (106/μL)

Day 3 7.12 ± 0.10 7.07 ± 0.08 7.14 ± 0.09 7.30 ± 0.08 7.34 ± 0.09 7.71 ± 0.11**

Day 23 7.80 ± 0.10 7.74 ± 0.09 7.84 ± 0.10 7.78 ± 0.07 7.67 ± 0.09 7.84 ± 0.05

Week 14 9.07 ± 0.06 9.02 ± 0.05 9.01 ± 0.05 9.06 ± 0.04 8.98 ± 0.08 9.15 ± 0.09

Reticulocytes (103/μL)

Day 3 360.8 ± 28.8 356.4 ± 32.6 381.7 ± 25.1 350.3 ± 30.4 362.4 ± 33.7 346.3 ± 17.0

Day 23 209.2 ± 19.6 187.6 ± 16.7 233.4 ± 19.1 240.4 ± 15.2 222.6 ± 10.8 222.0 ± 11.8

Week 14 106.1 ± 14.6 131.2 ± 12.4 137.4 ± 12.4 127.6 ± 15.7 97.8 ± 12.6 119.3 ± 10.7

Nucleated erythrocytes/100 leukocytes

Day 3 0.70 ± 0.15 1.10 ± 0.28 0.90 ± 0.35 0.78 ± 0.28 0.20 ± 0.13 0.10 ± 0.10*

Day 23 0.20 ± 0.13 0.00 ± 0.00 0.10 ± 0.10 0.00 ± 0.00 0.30 ± 0.15 0.00 ± 0.00

Week 14 0.00 ± 0.00 0.30 ± 0.15 0.10 ± 0.10 0.30 ± 0.21 0.50 ± 0.22 0.30 ± 0.21

Mean cell volume (fL)

Day 3 62.2 ± 0.2 61.9 ± 0.4 61.4 ± 0.4 60.7 ± 0.3** 60.6 ± 0.4** 60.3 ± 0.4**

Day 23 59.0 ± 0.3 59.4 ± 0.3 59.8 ± 0.4 59.6 ± 0.2 60.2 ± 0.4* 60.0 ± 0.3

Week 14 52.7 ± 0.2 53.0 ± 0.2 52.9 ± 0.2 52.8 ± 0.2 53.0 ± 0.3 52.9 ± 0.2

Mean cell hemoglobin (pg)

Day 3 18.9 ± 0.1 19.0 ± 0.1 19.0 ± 0.1 18.9 ± 0.1 18.7 ± 0.1 18.6 ± 0.1*

Day 23 18.9 ± 0.1 19.0 ± 0.1 19.0 ± 0.1 19.0 ± 0.1 19.2 ± 0.1 19.0 ± 0.1

Week 14 17.1 ± 0.0 17.2 ± 0.1 17.1 ± 0.1 17.2 ± 0.1 17.3 ± 0.1 17.2 ± 0.1

Mean cell hemoglobin concentration (g/dL)

Day 3 30.4 ± 0.1 30.7 ± 0.2 30.8 ± 0.2 31.1 ± 0.2* 30.8 ± 0.2 30.8 ± 0.2 

Day 23 32.1 ± 0.1 32.0 ± 0.1 31.8 ± 0.1 31.8 ± 0.2 31.9 ± 0.1 31.7 ± 0.1

Week 14 32.4 ± 0.1 32.5 ± 0.1 32.4 ± 0.1 32.6 ± 0.2 32.6 ± 0.1 32.5 ± 0.2

Platelets (103/μL)

Day 3 905.9 ± 33.7 875.4 ± 16.8 888.2 ± 16.3 799.0 ± 30.6** 759.8 ± 29.9** 820.9 ± 33.4**

Day 23 754.5 ± 18.1 798.8 ± 14.0 820.2 ± 16.4* 802.4 ± 20.1* 843.3 ± 14.8** 845.8 ± 15.6**

Week 14 678.6 ± 10.6 674.2 ± 8.3 653.8 ± 14.4 661.8 ± 13.9 647.8 ± 16.1 651.7 ± 6.4

Leukocytes (103/μL)

Day 3 10.39 ± 0.50 9.77 ± 0.71 10.77 ± 0.47 10.95 ± 0.56 8.97 ± 0.53 7.79 ± 0.43**

Day 23 7.90 ± 0.53 8.40 ± 0.40 8.13 ± 0.57 7.73 ± 0.32 8.24 ± 0.44 7.68 ± 0.44

Week 14 7.25 ± 0.17 6.78 ± 0.22 7.48 ± 0.41 8.09 ± 0.37 8.07 ± 0.34 8.56 ± 0.33*

Segmented neutrophils (103/μL)

Day 3 1.22 ± 0.06 1.19 ± 0.06 1.34 ± 0.06 1.34 ± 0.09 1.10 ± 0.09 0.92 ± 0.05**

Day 23 1.16 ± 0.03 1.25 ± 0.04 1.15 ± 0.06 1.18 ± 0.04 1.07 ± 0.05 0.93 ± 0.03**

Week 14 1.19 ± 0.09 1.18 ± 0.09 1.34 ± 0.11 1.32 ± 0.07 1.40 ± 0.08 1.37 ± 0.11
1-Bromopropane, NTP TR 564 F-3 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

TABLE F1

Hematology and Clinical Chemistry Data for Rats in the 3-Month Inhalation Study of 1-Bromopropane

Chamber 

Control 62.5 ppm 125 ppm 250 ppm 500 ppm 1,000 ppm

Male (continued)

Hematology (continued)

n

Day 3 10 10 10 9 10 10

Day 23 10 10 10 10 10 10

Week 14 10 10 10 10 10 10

Bands (103/μL)

Day 3 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00

Day 23 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00

Week 14 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00

Lymphocytes (103/μL)

Day 3 8.93 ± 0.46 8.39 ± 0.66 9.19 ± 0.43 9.38 ± 0.49 7.65 ± 0.45 6.72 ± 0.39**

Day 23 6.62 ± 0.50 7.01 ± 0.36 6.86 ± 0.51 6.42 ± 0.29 7.03 ± 0.39 6.63 ± 0.43

Week 14 5.79 ± 0.17 5.35 ± 0.16 5.73 ± 0.35 6.49 ± 0.34 6.33 ± 0.34 6.91 ± 0.27*

Monocytes (103/μL)

Day 3 0.14 ± 0.02 0.09 ± 0.01 0.14 ± 0.02 0.09 ± 0.02 0.14 ± 0.03 0.08 ± 0.02*

Day 23 0.04 ± 0.01 0.06 ± 0.01 0.04 ± 0.01 0.05 ± 0.01 0.05 ± 0.01 0.05 ± 0.01

Week 14 0.17 ± 0.05 0.16 ± 0.04 0.27 ± 0.08 0.18 ± 0.05 0.22 ± 0.07 0.21 ± 0.03

Basophils (103/μL)

Day 3 0.007 ± 0.002 0.004 ± 0.002 0.006 ± 0.002 0.007 ± 0.002 0.003 ± 0.002 0.005 ± 0.002

Day 23 0.007 ± 0.002 0.005 ± 0.002 0.008 ± 0.002 0.006 ± 0.002 0.006 ± 0.002 0.007 ± 0.002 

Week 14 0.002 ± 0.001 0.002 ± 0.002 0.010 ± 0.004 0.004 ± 0.002 0.003 ± 0.002 0.009 ± 0.009

Eosinophils (103/μL)

Day 3 0.09 ± 0.01 0.10 ± 0.01 0.10 ± 0.01 0.13 ± 0.02 0.09 ± 0.01 0.06 ± 0.01 

Day 23 0.08 ± 0.01 0.08 ± 0.01 0.08 ± 0.01 0.07 ± 0.01 0.08 ± 0.01 0.06 ± 0.01

Week 14 0.09 ± 0.01 0.10 ± 0.01 0.13 ± 0.01 0.09 ± 0.03 0.12 ± 0.02 0.07 ± 0.02

Clinical Chemistry

n 10 10 10 10 10 10

Urea nitrogen (mg/dL)

Day 3 8.1 ± 0.4 9.0 ± 0.2* 9.0 ± 0.4* 10.3 ± 0.4** 11.0 ± 0.5** 16.7 ± 0.6**

Day 23 10.7 ± 0.3 11.5 ± 0.6 11.5 ± 0.3 12.3 ± 0.3** 14.6 ± 0.5** 16.5 ± 0.4**

Week 14 16.9 ± 0.3 15.8 ± 0.5 15.6 ± 0.5* 16.3 ± 0.5 17.0 ± 0.3 14.5 ± 0.5**

Creatinine (mg/dL)

Day 3 0.24 ± 0.02 0.26 ± 0.02 0.26 ± 0.02 0.26 ± 0.02 0.26 ± 0.02 0.30 ± 0.00*

Day 23 0.31 ± 0.01 0.30 ± 0.00 0.33 ± 0.02 0.36 ± 0.02* 0.37 ± 0.02** 0.38 ± 0.01**

Week 14 0.61 ± 0.03 0.63 ± 0.02 0.62 ± 0.02 0.62 ± 0.01 0.63 ± 0.02 0.67 ± 0.02

Total protein (g/dL)

Day 3 5.9 ± 0.1 5.8 ± 0.0 5.7 ± 0.1* 5.6 ± 0.1** 5.6 ± 0.1** 5.7 ± 0.1*

Day 23 6.3 ± 0.0 6.2 ± 0.0 6.3 ± 0.0 6.3 ± 0.1 6.2 ± 0.1 6.2 ± 0.1

Week 14 7.3 ± 0.1 7.2 ± 0.1 7.1 ± 0.1 7.3 ± 0.0 7.2 ± 0.1 7.2 ± 0.1

Albumin (g/dL)

Day 3 4.3 ± 0.0 4.2 ± 0.0 4.1 ± 0.0** 4.1 ± 0.0** 4.1 ± 0.0** 4.2 ± 0.0**

Day 23 4.5 ± 0.0 4.4 ± 0.0 4.4 ± 0.0 4.4 ± 0.0 4.3 ± 0.0** 4.3 ± 0.0**

Week 14 4.9 ± 0.0 4.8 ± 0.0 4.7 ± 0.1 4.8 ± 0.0 4.7 ± 0.0 4.8 ± 0.0

Globulin (g/dL)

Day 3 1.6 ± 0.1 1.6 ± 0.0 1.6 ± 0.0 1.5 ± 0.0 1.5 ± 0.0 1.6 ± 0.0

Day 23 1.8 ± 0.0 1.8 ± 0.0 1.9 ± 0.0 1.8 ± 0.0 1.9 ± 0.0 1.8 ± 0.0

Week 14 2.4 ± 0.1 2.5 ± 0.0 2.4 ± 0.0 2.5 ± 0.0 2.5 ± 0.0 2.5 ± 0.0

Albumin/globulin ratio

Day 3 2.7 ± 0.1 2.7 ± 0.0 2.7 ± 0.1 2.7 ± 0.0 2.7 ± 0.1 2.7 ± 0.0

Day 23 2.5 ± 0.0 2.4 ± 0.0 2.4 ± 0.0 2.4 ± 0.1 2.3 ± 0.0** 2.4 ± 0.0**

Week 14 2.0 ± 0.0 2.0 ± 0.0 1.9 ± 0.1 1.9 ± 0.0* 1.9 ± 0.0* 1.9 ± 0.0*
F-4 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

TABLE F1

Hematology and Clinical Chemistry Data for Rats in the 3-Month Inhalation Study of 1-Bromopropane

Chamber 

Control 62.5 ppm 125 ppm 250 ppm 500 ppm 1,000 ppm

Male (continued)

Clinical Chemistry (continued)

n 10 10 10 10 10 10

Alanine aminotransferase (IU/L)

Day 3 56 ± 2 49 ± 1** 40 ± 1** 32 ± 1** 50 ± 7** 31 ± 5**

Day 23 47 ± 1 44 ± 1 38 ± 1** 30 ± 1** 25 ± 1** 22 ± 1**

Week 14 141 ± 16 115 ± 9 121 ± 8 124 ± 9 120 ± 7 71 ± 5**

Alkaline phosphatase (IU/L)

Day 3 689 ± 13 691 ± 15 679 ± 7 686 ± 12 706 ± 22 645 ± 18

Day 23 438 ± 11 467 ± 13 476 ± 9 470 ± 12 429 ± 9 453 ± 9

Week 14 258 ± 6 231 ± 3** 238 ± 6* 236 ± 4* 230 ± 5** 232 ± 5**

Creatine kinase (IU/L)

Day 3 400 ± 43b 385 ± 35b 417 ± 37b 397 ± 44b 400 ± 22b 311 ± 25b

Day 23 417 ± 63 b 350 ± 41b 380 ± 48b 712 ± 190b 363 ± 49b 358 ± 39b

Week 14 355 ± 113 b 191 ± 26b 189 ± 40b 224 ± 46b 223 ± 38b 137 ± 18b

Sorbitol dehydrogenase (IU/L)

Day 23 17 ± 1 17 ± 0 17 ± 1 16 ± 1 18 ± 1 17 ± 0

Week 14 27 ± 2 24 ± 1 27 ± 1 30 ± 1 35 ± 1** 34 ± 1**

Bile salts (μmol/L)

Day 3 19.5 ± 1.0 16.6 ± 0.5 16.4 ± 0.5 16.4 ± 0.9 25.3 ± 2.6 21.6 ± 2.2

Day 23 15.7 ± 0.4 15.0 ± 0.6 15.3 ± 0.3 15.2 ± 0.6 13.5 ± 0.4** 14.6 ± 0.5

Week 14 17.7 ± 0.9 15.7 ± 0.5 18.1 ± 1.2 16.4 ± 0.6 18.7 ± 0.6 17.5 ± 1.1

Female

Hematology

n 10 10 10 10 10 10

Hematocrit (%)

Day 3 48.4 ± 0.5 47.3 ± 0.4 47.7 ± 0.5 47.7 ± 0.5 47.8 ± 0.5 47.4 ± 0.7

Day 23 47.6 ± 0.5 48.1 ± 0.4 47.7 ± 0.5 48.2 ± 0.6 48.7 ± 0.4 50.5 ± 0.4**

Week 14 48.2 ± 0.3 47.8 ± 0.4 47.6 ± 0.5 48.8 ± 0.3 47.3 ± 0.4 48.4 ± 0.4

Packed cell volume (mL/dL)

Day 3 48.2 ± 0.4 47.2 ± 0.4 46.9 ± 0.5 47.5 ± 0.6 47.7 ± 0.6 47.8 ± 0.6

Day 23 47.9 ± 0.5 47.9 ± 0.4 47.5 ± 0.3 48.4 ± 0.5 48.5 ± 0.4 50.1 ± 0.4**

Week 14 48.2 ± 0.4 47.6 ± 0.4 47.5 ± 0.5 48.5 ± 0.3 47.3 ± 0.3 47.7 ± 0.4

Hemoglobin (g/dL)

Day 3 15.0 ± 0.2 14.5 ± 0.1 14.5 ± 0.2 14.5 ± 0.2 14.7 ± 0.2 14.7 ± 0.2

Day 23 15.4 ± 0.2 15.3 ± 0.1 15.4 ± 0.1 15.6 ± 0.2 15.8 ± 0.1* 16.2 ± 0.2**

Week 14 15.7 ± 0.1 15.6 ± 0.1 15.5 ± 0.2 15.8 ± 0.1 15.6 ± 0.1 15.6 ± 0.1

Erythrocytes (106/μL)

Day 3 7.97 ± 0.11 7.69 ± 0.07 7.69 ± 0.12 7.75 ± 0.11 7.87 ± 0.14 7.95 ± 0.11

Day 23 8.16 ± 0.12 8.04 ± 0.06 8.03 ± 0.06 8.08 ± 0.11 8.23 ± 0.10 8.48 ± 0.09

Week 14 8.39 ± 0.07 8.36 ± 0.06 8.34 ± 0.09 8.49 ± 0.05 8.35 ± 0.04 8.45 ± 0.07

Reticulocytes (103/μL)

Day 3 293.9 ± 16.6 295.4 ± 22.4 316.4 ± 10.9 274.5 ± 14.3 294.0 ± 14.6 290.2 ± 18.3

Day 23 156.7 ± 9.9 158.4 ± 11.8 148.5 ± 10.9 160.7 ± 8.2 162.3 ± 8.7 168.4 ± 7.6

Week 14 110.2 ± 11.5 114.7 ± 15.5 112.4 ± 18.5 113.0 ± 8.2 104.9 ± 17.8 115.9 ± 16.8

Nucleated erythrocytes/100 leukocytes

Day 3 0.20 ± 0.20 0.20 ± 0.13 0.20 ± 0.13 0.60 ± 0.22 0.60 ± 0.31 0.20 ± 0.13

Day 23 0.20 ± 0.13 0.00 ± 0.00 0.20 ± 0.13 0.10 ± 0.10 0.00 ± 0.00 0.10 ± 0.10

Week 14 0.70 ± 0.21 0.40 ± 0.22 0.30 ± 0.15 0.50 ± 0.27 0.80 ± 0.39 0.70 ± 0.40
1-Bromopropane, NTP TR 564 F-5

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

TABLE F1

Hematology and Clinical Chemistry Data for Rats in the 3-Month Inhalation Study of 1-Bromopropane

Chamber 

Control 62.5 ppm 125 ppm 250 ppm 500 ppm 1,000 ppm

Female (continued)

Hematology (continued)

n 10 10 10 10 10 10

Mean cell volume (fL)

Day 3 60.5 ± 0.5 61.4 ± 0.2 61.0 ± 0.4 61.3 ± 0.2 60.6 ± 0.4 60.2 ± 0.2

Day 23 58.8 ± 0.4 59.5 ± 0.3 59.2 ± 0.6 59.9 ± 0.4 59.0 ± 0.4 59.1 ± 0.4

Week 14 57.4 ± 0.2 57.0 ± 0.2 56.9 ± 0.1 57.2 ± 0.1 56.6 ± 0.1** 56.5 ± 0.2**

Mean cell hemoglobin (pg)

Day 3 18.8 ± 0.1 18.9 ± 0.1 18.8 ± 0.1 18.8 ± 0.1 18.7 ± 0.1 18.6 ± 0.1

Day 23 18.8 ± 0.1 19.1 ± 0.1 19.1 ± 0.1 19.3 ± 0.1* 19.2 ± 0.2 19.1 ± 0.1

Week 14 18.7 ± 0.1 18.7 ± 0.1 18.6 ± 0.1 18.6 ± 0.1 18.7 ± 0.1 18.4 ± 0.1*

Mean cell hemoglobin concentration (g/dL)

Day 3 31.1 ± 0.1 30.8 ± 0.1 30.8 ± 0.2 30.6 ± 0.1 30.8 ± 0.2 30.8 ± 0.1

Day 23 32.1 ± 0.1 32.0 ± 0.1 32.4 ± 0.2 32.2 ± 0.1 32.5 ± 0.2 32.2 ± 0.1

Week 14 32.6 ± 0.1 32.8 ± 0.1 32.6 ± 0.1 32.6 ± 0.1 33.0 ± 0.1 32.6 ± 0.1

Platelets (103/μL)

Day 3 812.0 ± 25.7 824.1 ± 21.5 796.1 ± 19.3 805.1 ± 35.1 740.4 ± 30.7 778.1 ± 29.5

Day 23 773.3 ± 17.5 791.6 ± 13.7 806.4 ± 10.6 757.4 ± 19.3 791.4 ± 15.1 775.0 ± 21.8

Week 14 681.6 ± 12.3 647.1 ± 10.7 656.6 ± 12.0 660.7 ± 15.7 658.2 ± 13.6 647.5 ± 11.6

Leukocytes (103/μL)

Day 3 12.82 ± 0.51 11.64 ± 0.33 11.75 ± 0.57 11.64 ± 0.51 11.46 ± 0.53 8.41 ± 0.45**

Day 23 7.39 ± 0.54 7.48 ± 0.27 9.13 ± 0.39* 8.90 ± 0.36 9.27 ± 0.41* 7.98 ± 0.36

Week 14 6.34 ± 0.34 6.54 ± 0.26 6.51 ± 0.31 6.55 ± 0.31 6.44 ± 0.32 7.64 ± 0.43

Segmented neutrophils (103/μL)

Day 3 1.41 ± 0.07 1.43 ± 0.07 1.29 ± 0.06 1.40 ± 0.11 1.21 ± 0.07* 1.10 ± 0.14**

Day 23 1.10 ± 0.11 1.09 ± 0.08 1.33 ± 0.19 1.23 ± 0.15 1.28 ± 0.14 1.12 ± 0.12

Week 14 1.03 ± 0.10 0.90 ± 0.05 1.03 ± 0.06 1.10 ± 0.09 0.89 ± 0.05 1.33 ± 0.10

Bands (103/μL)

Day 3 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00

Day 23 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00

Week 14 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00

Lymphocytes (103/μL)

Day 3 11.11 ± 0.50 9.97 ± 0.35 10.20 ± 0.54 9.98 ± 0.41 10.02 ± 0.48 7.10 ± 0.40**

Day 23 6.13 ± 0.49 6.22 ± 0.20 7.59 ± 0.31* 7.46 ± 0.32 7.78 ± 0.35* 6.64 ± 0.30

Week 14 5.04 ± 0.28 5.49 ± 0.24 5.25 ± 0.28 5.19 ± 0.27 5.29 ± 0.31 5.95 ± 0.38

Monocytes (103/μL)

Day 3 0.12 ± 0.01 0.09 ± 0.02 0.12 ± 0.02 0.11 ± 0.02 0.10 ± 0.01 0.08 ± 0.01

Day 23 0.05 ± 0.01 0.07 ± 0.01 0.07 ± 0.02 0.07 ± 0.01 0.06 ± 0.01 0.10 ± 0.02

Week 14 0.17 ± 0.06 0.06 ± 0.02 0.13 ± 0.04 0.16 ± 0.05 0.16 ± 0.04 0.29 ± 0.07

Basophils (103/μL)

Day 3 0.018 ± 0.002 0.013 ± 0.003 0.015 ± 0.004 0.015 ± 0.003 0.013 ± 0.003 0.009 ± 0.002

Day 23 0.008 ± 0.007 0.005 ± 0.002 0.006 ± 0.002 0.006 ± 0.002 0.009 ± 0.002 0.006 ± 0.002

Week 14 0.004 ± 0.002 0.002 ± 0.001 0.015 ± 0.008 0.005 ± 0.002 0.007 ± 0.002 0.007 ± 0.003

Eosinophils (103/μL)

Day 3 0.17 ± 0.02 0.14 ± 0.01 0.12 ± 0.01 0.13 ± 0.02 0.12 ± 0.01 0.12 ± 0.01

Day 23 0.10 ± 0.01 0.10 ± 0.01 0.13 ± 0.01 0.13 ± 0.01 0.15 ± 0.02* 0.10 ± 0.01

Week 14 0.09 ± 0.01 0.10 ± 0.01 0.08 ± 0.01 0.10 ± 0.01 0.10 ± 0.02 0.07 ± 0.01
F-6 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

TABLE F1

Hematology and Clinical Chemistry Data for Rats in the 3-Month Inhalation Study of 1-Bromopropane

Chamber 

Control 62.5 ppm 125 ppm 250 ppm 500 ppm 1,000 ppm

Female (continued)

Clinical Chemistry

n 10 10 10 10 10 10

Urea nitrogen (mg/dL)

Day 3 10.3 ± 0.5 10.4 ± 0.5 8.9 ± 0.5 10.2 ± 0.4 12.4 ± 0.4* 14.5 ± 0.4**

Day 23 11.6 ± 0.4 11.4 ± 0.3 11.5 ± 0.3 11.3 ± 0.2 12.8 ± 0.3** 16.6 ± 0.3**

Week 14 16.2 ± 0.4 17.0 ± 0.7 15.5 ± 0.4 16.4 ± 0.5 16.9 ± 0.4 14.8 ± 0.5

Creatinine (mg/dL)

Day 3 0.27 ± 0.02 0.25 ± 0.02 0.27 ± 0.02 0.27 ± 0.02 0.28 ± 0.01 0.31 ± 0.01

Day 23 0.24 ± 0.02 0.27 ± 0.02 0.28 ± 0.01 0.28 ± 0.01 0.30 ± 0.02** 0.37 ± 0.02**

Week 14 0.70 ± 0.02 0.69 ± 0.01 0.68 ± 0.01 0.68 ± 0.01 0.63 ± 0.02 0.71 ± 0.02

Total protein (g/dL)

Day 3 6.1 ± 0.1 5.8 ± 0.1** 5.9 ± 0.1* 5.8 ± 0.1** 5.7 ± 0.0** 5.7 ± 0.1**

Day 23 6.2 ± 0.0 6.1 ± 0.0 6.3 ± 0.1 6.2 ± 0.1 6.2 ± 0.1 6.1 ± 0.1

Week 14 7.4 ± 0.1 7.4 ± 0.1 7.3 ± 0.1 7.3 ± 0.1 7.4 ± 0.1 7.4 ± 0.1

Albumin (g/dL)

Day 3 4.6 ± 0.0 4.4 ± 0.0** 4.4 ± 0.0** 4.4 ± 0.1** 4.3 ± 0.0** 4.3 ± 0.0**

Day 23 4.6 ± 0.0 4.5 ± 0.0 4.6 ± 0.1 4.5 ± 0.0 4.5 ± 0.0 4.5 ± 0.0

Week 14 5.3 ± 0.0 5.3 ± 0.0 5.2 ± 0.1 5.2 ± 0.1 5.3 ± 0.0 5.2 ± 0.1

Globulin (g/dL)

Day 3 1.5 ± 0.0 1.4 ± 0.0 1.5 ± 0.0 1.4 ± 0.0 1.4 ± 0.0 1.4 ± 0.0

Day 23 1.7 ± 0.0 1.6 ± 0.0 1.8 ± 0.0 1.7 ± 0.0 1.7 ± 0.0 1.6 ± 0.0

Week 14 2.1 ± 0.0 2.1 ± 0.0 2.1 ± 0.1 2.1 ± 0.1 2.1 ± 0.1 2.2 ± 0.0

Albumin/globulin ratio

Day 3 3.2 ± 0.1 3.1 ± 0.1 3.0 ± 0.0 3.1 ± 0.1 3.1 ± 0.1 3.2 ± 0.1

Day 23 2.8 ± 0.1 2.9 ± 0.1 2.6 ± 0.0 2.7 ± 0.0 2.7 ± 0.0 2.9 ± 0.1

Week 14 2.6 ± 0.0 2.5 ± 0.0 2.5 ± 0.0 2.6 ± 0.0 2.5 ± 0.1** 2.4 ± 0.0**

Alanine aminotransferase (IU/L)

Day 3 51 ± 2 41 ± 1** 33 ± 1** 26 ± 1** 25 ± 2** 19 ± 1**

Day 23 44 ± 1 34 ± 1** 29 ± 1** 22 ± 1** 17 ± 1** 20 ± 5**

Week 14 71 ± 8 61 ± 5 57 ± 5 53 ± 3* 41 ± 4** 37 ± 7**

Alkaline phosphatase (IU/L)

Day 3 598 ± 15 589 ± 10 579 ± 17 563 ± 7 529 ± 13** 515 ± 11**

Day 23 326 ± 9 342 ± 8 325 ± 9 326 ± 7 314 ± 9 337 ± 9

Week 14 215 ± 7 191 ± 5** 182 ± 5** 201 ± 6* 179 ± 5** 187 ± 8**

Creatine kinase (IU/L)

Day 3 373 ± 33b 329 ± 48b 326 ± 25b 338 ± 26b 303 ± 29b 217 ± 10**b

Day 23 285 ± 25b 331 ± 25b 334 ± 25b 399 ± 57b 311 ± 17b 296 ± 18b

Week 14 179 ± 20b 182 ± 12b 226 ± 37b 168 ± 23b 192 ± 34b 157 ± 22b

Sorbitol dehydrogenase (IU/L)

Day 23 16 ± 1 17 ± 0 15 ± 1 14 ± 2 16 ± 1 67 ± 27*

Week 14 19 ± 1 18 ± 1 18 ± 1 18 ± 1 18 ± 1 87 ± 33

Bile salts (μmol/L)

Day 3 17.3 ± 0.7 17.8 ± 1.3 16.1 ± 0.9 14.0 ± 0.8** 14.7 ± 0.7** 15.3 ± 0.9*

Day 23 16.9 ± 1.0 13.6 ± 0.5 14.3 ± 0.9 13.1 ± 0.5* 13.3 ± 0.5* 19.2 ± 2.9

Week 14 16.2 ± 0.9 17.7 ± 1.2 15.9 ± 2.1 13.7 ± 0.5 15.7 ± 1.2 30.7 ± 6.3

* Significantly different (P≤0.05) from the chamber control group by Dunn’s or Shirley’s test

** P≤0.01 a Mean ± standard error. Statistical tests were performed on unrounded data. b n=9
1-Bromopropane, NTP TR 564 F-7 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

TABLE F2 

Hematology Data for Mice in the 3-Month Inhalation Study of 1-Bromopropanea

Chamber 

Control 62.5 ppm 125 ppm 250 ppm 500 ppm

Male

n 10 10 10 9 6

Hematocrit (%) 47.8 ± 0.4 48.4 ± 0.3 49.3 ± 0.4* 48.1 ± 0.2 47.9 ± 0.5

Packed cell volume (mL/dL) 47.9 ± 0.5 49.2 ± 0.3 50.1 ± 0.4** 49.1 ± 0.2 48.9 ± 0.7

Hemoglobin (g/dL) 15.2 ± 0.2 15.5 ± 0.1 15.9 ± 0.1** 15.4 ± 0.1 15.1 ± 0.2

Erythrocytes (106/μL) 9.79 ± 0.09 9.91 ± 0.04 9.98 ± 0.09 9.62 ± 0.05 9.46 ± 0.15 

Reticulocytes (103/μL) 143.8 ± 8.9 158.6 ± 12.0 145.6 ± 12.6 130.2 ± 11.7 153.5 ± 26.9

Nucleated erythrocytes 

/100 leukocytes 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00

Howell-Jolly bodies

(%) erythrocytes 0.1 ± 0.0 0.2 ± 0.0 0.2 ± 0.0 0.2 ± 0.1 0.1 ± 0.0

Mean cell volume (fL) 48.9 ± 0.2 49.6 ± 0.2* 50.2 ± 0.3** 51.1 ± 0.2** 51.7 ± 0.2**

Mean cell hemoglobin (pg) 15.5 ± 0.1 15.6 ± 0.1 15.9 ± 0.1** 16.0 ± 0.1** 15.9 ± 0.1**

Mean cell hemoglobin 

concentration (g/dL) 31.7 ± 0.1 31.6 ± 0.1 31.6 ± 0.1 31.4 ± 0.1* 30.9 ± 0.1**

Platelets (103/μL) 891.7 ± 27.6 894.0 ± 17.4 874.9 ± 14.7 870.0 ± 15.5 880.3 ± 43.4

Leukocytes (103/μL) 2.36 ± 0.28 2.50 ± 0.25 2.42 ± 0.22 2.72 ± 0.17 3.86 ± 0.41**

Segmented neutrophils (103/μL) 0.29 ± 0.05 0.31 ± 0.03 0.29 ± 0.04 0.31 ± 0.03 0.43 ± 0.03*

Bands (103/μL) 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00

Lymphocytes (103/μL) 1.94 ± 0.23 2.09 ± 0.21 2.02 ± 0.20 2.28 ± 0.16 3.31 ± 0.36**

Monocytes (103/μL) 0.06 ± 0.01 0.03 ± 0.01 0.04 ± 0.02 0.07 ± 0.02 0.05 ± 0.02

Basophils (103/μL) 0.013 ± 0.002 0.009 ± 0.003 0.012 ± 0.003 0.009 ± 0.002 0.012 ± 0.003 

Eosinophils (103/μL) 0.06 ± 0.01 0.06 ± 0.02 0.05 ± 0.01 0.05 ± 0.01 0.07 ± 0.02

Female

n 10 10 10 10 5

Hematocrit (%) 50.1 ± 0.3 50.1 ± 0.5 49.4 ± 0.3 48.5 ± 0.4** 48.6 ± 0.5*

Packed cell volume (mL/dL) 50.9 ± 0.3 50.7 ± 0.4 50.0 ± 0.2 49.1 ± 0.5** 49.1 ± 0.5*

Hemoglobin (g/dL) 16.2 ± 0.1 16.2 ± 0.1 15.9 ± 0.1 15.6 ± 0.1** 15.6 ± 0.2*

Erythrocytes (106/μL) 10.18 ± 0.08 10.13 ± 0.07 9.92 ± 0.04* 9.60 ± 0.08** 9.53 ± 0.11**

Reticulocytes (103/μL) 153.9 ± 10.6 148.8 ± 10.9 134.9 ± 17.3 123.9 ± 8.0 112.2 ± 10.1

Nucleated erythrocytes

 /100 leukocytes 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00

Howell-Jolly bodies

(%) erythrocytes 0.0 ± 0.0 0.1 ± 0.0 0.1 ± 0.0 0.1 ± 0.0 0.0 ± 0.0

Mean cell volume (fL) 50.0 ± 0.2 50.1 ± 0.1 50.4 ± 0.2 51.1 ± 0.2** 51.6 ± 0.2**

Mean cell hemoglobin (pg) 15.9 ± 0.1 16.0 ± 0.0 16.1 ± 0.1 16.3 ± 0.1** 16.3 ± 0.1**

Mean cell hemoglobin

concentration (g/dL) 31.8 ± 0.1 32.0 ± 0.1 31.9 ± 0.1 31.8 ± 0.1 31.7 ± 0.2

Platelets (103/μL) 846.7 ± 18.9 821.5 ± 30.0 835.0 ± 17.5 819.0 ± 16.9 732.4 ± 50.0

Leukocytes (103/μL) 2.73 ± 0.24 2.81 ± 0.23 2.33 ± 0.16 2.78 ± 0.33 2.57 ± 0.25

Segmented neutrophils (103/μL) 0.32 ± 0.05 0.29 ± 0.03 0.26 ± 0.02 0.31 ± 0.03 0.26 ± 0.03

Bands (103/μL) 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00

Lymphocytes (103/μL) 2.35 ± 0.19 2.45 ± 0.21 1.97 ± 0.14 2.36 ± 0.32 2.25 ± 0.22

Monocytes (103/μL) 0.04 ± 0.01 0.03 ± 0.01 0.05 ± 0.02 0.08 ± 0.02 0.04 ± 0.02

Basophils (103/μL) 0.007 ± 0.002 0.010 ± 0.002 0.009 ± 0.003 0.012 ± 0.002 0.008 ± 0.004 

Eosinophils (103/μL) 0.02 ± 0.01 0.03 ± 0.01 0.04 ± 0.01 0.03 ± 0.00 0.01 ± 0.00

* Significantly different (P≤0.05) from the chamber control group by Dunn’s or Shirley’s test

** P≤0.01 

a Mean ± standard error. Statistical tests were performed on unrounded data.
F-8 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft
G-1

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

APPENDIX G

ORGAN WEIGHTS

AND ORGAN-WEIGHT-TO-BODY-WEIGHT RATIOS

TABLE G1 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats

in the 2-Week Inhalation Study of 1-Bromopropane ..................................................................... G-2

TABLE G2 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats

in the 3-Month Inhalation Study of 1-Bromopropane .................................................................. G-3

TABLE G3 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice

in the 2-Week Inhalation Study of 1-Bromopropane .................................................................... G-4

TABLE G4 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice

in the 3-Month Inhalation Study of 1-Bromopropane .................................................................. G-5
G-2 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

TABLE G1

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats in the 2-Week Inhalation Study 

of 1-Bromopropanea

Chamber 

Control 125 ppm 250 ppm 500 ppm 1,000 ppm 2,000 ppm

Male

n 5 5 5 4 5 5

Necropsy body wt 169 ± 4 167 ± 4 169 ± 5 166 ± 6 164 ± 5 123 ± 4**

Heart

Absolute 0.62 ± 0.01 0.61 ± 0.01 0.63 ± 0.02 0.63 ± 0.02 0.62 ± 0.02 0.56 ± 0.02

Relative 3.686 ± 0.026 3.648 ± 0.116 3.711 ± 0.032 3.779 ± 0.075 3.802 ± 0.046 4.550 ± 0.103**

R. Kidney

Absolute 0.65 ± 0.02 0.70 ± 0.02 0.70 ± 0.02 0.72 ± 0.03 0.79 ± 0.03** 0.63 ± 0.02

Relative 3.843 ± 0.096 4.191 ± 0.076* 4.162 ± 0.074* 4.350 ± 0.095** 4.813 ± 0.091** 5.144 ± 0.090**

Liver

Absolute 7.57 ± 0.14 7.26 ± 0.17 7.61 ± 0.22 7.98 ± 0.22 8.93 ± 0.19** 6.57 ± 0.24**

Relative 44.895 ± 0.729 43.588 ± 0.572 45.158 ± 0.735 48.215 ± 0.754** 54.535 ± 0.909** 53.600 ± 0.936**

Lung

Absolute 1.37 ± 0.15 1.36 ± 0.13 1.26 ± 0.11 1.16 ± 0.11 1.10 ± 0.05 0.90 ± 0.05**

Relative 8.122 ± 0.878 8.241 ± 0.991 7.449 ± 0.556 7.001 ± 0.617 6.674 ± 0.131 7.365 ± 0.314

R. Testis

Absolute 1.000 ± 0.027 1.022 ± 0.019 1.018 ± 0.033 1.016 ± 0.046 1.022 ± 0.037 0.893 ± 0.042

Relative 5.924 ± 0.075 6.142 ± 0.087 6.036 ± 0.100 6.127 ± 0.102 6.229 ± 0.142 7.265 ± 0.119**

Thymus

Absolute 0.461 ± 0.025 0.457 ± 0.016 0.477 ± 0.028 0.523 ± 0.017 0.452 ± 0.016 0.286 ± 0.011**

Relative 2.742 ± 0.189 2.743 ± 0.087 2.826 ± 0.142 3.177 ± 0.200 2.761 ± 0.104 2.342 ± 0.103

Female

n 5 5 5 5 5 5 

Necropsy body wt 120 ± 2 124 ± 3 120 ± 4 124 ± 5 119 ± 2 107 ± 2*

Heart

Absolute 0.48 ± 0.01 0.48 ± 0.01 0.48 ± 0.01 0.54 ± 0.01** 0.48 ± 0.01 0.51 ± 0.01

Relative 3.984 ± 0.068 3.877 ± 0.143 3.982 ± 0.081 4.325 ± 0.069 4.058 ± 0.036 4.759 ± 0.103**

R. Kidney

Absolute 0.48 ± 0.01 0.58 ± 0.01** 0.54 ± 0.02** 0.57 ± 0.03** 0.60 ± 0.02** 0.61 ± 0.02**

Relative 3.999 ± 0.074 4.647 ± 0.116** 4.521 ± 0.036** 4.615 ± 0.067** 5.049 ± 0.107** 5.718 ± 0.161**

Liver

Absolute 4.75 ± 0.12 5.24 ± 0.09 5.22 ± 0.28 6.01 ± 0.26** 6.19 ± 0.19** 5.82 ± 0.13**

Relative 39.548 ± 0.581 42.259 ± 0.673* 43.253 ± 0.977** 48.342 ± 0.856** 52.105 ± 1.280** 54.698 ± 0.832**

Lung

Absolute 0.83 ± 0.03 1.07 ± 0.09* 0.91 ± 0.04 1.22 ± 0.11 0.86 ± 0.04 0.79 ± 0.02

Relative 6.915 ± 0.201 8.609 ± 0.579 7.586 ± 0.377 9.874 ± 1.027** 7.245 ± 0.304 7.395 ± 0.258

Thymus

Absolute 0.360 ± 0.007 0.400 ± 0.012 0.365 ± 0.022 0.424 ± 0.031 0.374 ± 0.023 0.300 ± 0.013

Relative 3.000 ± 0.023 3.220 ± 0.095 3.025 ± 0.086 3.417 ± 0.203 3.138 ± 0.155 2.817 ± 0.116

* Significantly different (P≤0.05) from the chamber control group by Williams’ or Dunnett’s test

** P≤0.01

a Organ weights (absolute weights) and body weights are given in grams; organ-weight-to-body-weight ratios (relative weights) are given as 

mg organ weight/g body weight (mean ± standard error).
1-Bromopropane, NTP TR 564 G-3 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

TABLE G2

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats in the 3-Month Inhalation Study 

of 1-Bromopropanea

Chamber 

Control 62.5 ppm 125 ppm 250 ppm 500 ppm 1,000 ppm

n 10 10 10 10 10 10

Male

Necropsy body wt 345 ± 7 346 ± 5 348 ± 6 350 ± 7 344 ± 10 305 ± 6**

Heart

Absolute 0.93 ± 0.02 0.93 ± 0.02 0.95 ± 0.01 0.93 ± 0.01 0.92 ± 0.02 0.86 ± 0.02*

Relative 2.690 ± 0.023 2.698 ± 0.027 2.727 ± 0.038 2.662 ± 0.037 2.675 ± 0.059 2.819 ± 0.034

R. Kidney

Absolute 1.01 ± 0.02 1.02 ± 0.02 1.06 ± 0.02 1.08 ± 0.03 1.08 ± 0.07 1.02 ± 0.03

Relative 2.929 ± 0.024 2.936 ± 0.041 3.035 ± 0.019 3.102 ± 0.110 3.161 ± 0.209 3.347 ± 0.050**

Liver

Absolute 11.21 ± 0.28 11.21 ± 0.30 11.71 ± 0.33 12.45 ± 0.31* 13.34 ± 0.43** 13.23 ± 0.36**

Relative 32.435 ± 0.387 32.318 ± 0.481 33.674 ± 0.638 35.543 ± 0.696** 38.800 ± 0.435** 43.386 ± 0.496**

Lung

Absolute 1.73 ± 0.06 2.01 ± 0.18 1.82 ± 0.08 1.80 ± 0.04 1.69 ± 0.05 1.55 ± 0.05

Relative 5.007 ± 0.184 5.797 ± 0.465 5.257 ± 0.248 5.152 ± 0.165 4.950 ± 0.202 5.101 ± 0.123

Spleen

Absolute 0.678 ± 0.015 0.682 ± 0.012 0.677 ± 0.015 0.689 ± 0.014 0.691 ± 0.021 0.625 ± 0.015

Relative 1.963 ± 0.024 1.970 ± 0.017 1.947 ± 0.027 1.968 ± 0.031 2.011 ± 0.030 2.053 ± 0.033

R. Testis

Absolute 1.430 ± 0.027 1.434 ± 0.022 1.436 ± 0.034 1.405 ± 0.022 1.320 ± 0.078 1.336 ± 0.017

Relative 4.142 ± 0.050 4.147 ± 0.077 4.132 ± 0.079 4.015 ± 0.044 3.809 ± 0.170 4.396 ± 0.069

Thymus

Absolute 0.346 ± 0.012 0.321 ± 0.010 0.327 ± 0.012 0.338 ± 0.015 0.355 ± 0.016 0.323 ± 0.015

Relative 1.002 ± 0.033 0.927 ± 0.028 0.941 ± 0.028 0.965 ± 0.042 1.029 ± 0.021 1.064 ± 0.050

Female

Necropsy body wt 202 ± 3 203 ± 5 207 ± 4 209 ± 2 205 ± 3 190 ± 4

Heart

Absolute 0.59 ± 0.01 0.60 ± 0.01 0.62 ± 0.01 0.63 ± 0.01 0.63 ± 0.01 0.61 ± 0.01

Relative 2.942 ± 0.064 2.978 ± 0.053 3.009 ± 0.059 3.001 ± 0.028 3.090 ± 0.058 3.207 ± 0.051**

R. Kidney

Absolute 0.65 ± 0.01 0.66 ± 0.02 0.67 ± 0.01 0.68 ± 0.01 0.68 ± 0.01 0.71 ± 0.02**

Relative 3.209 ± 0.037 3.237 ± 0.043 3.252 ± 0.081 3.263 ± 0.045 3.298 ± 0.045 3.719 ± 0.058**

Liver

Absolute 6.02 ± 0.09 6.38 ± 0.20 6.62 ± 0.16* 6.60 ± 0.18* 7.29 ± 0.17** 7.98 ± 0.18**

Relative 29.910 ± 0.219 31.398 ± 0.538 32.001 ± 0.573* 31.497 ± 0.754* 35.490 ± 0.666** 41.895 ± 0.398**

Lung

Absolute 1.16 ± 0.03 1.19 ± 0.03 1.30 ± 0.06 1.24 ± 0.05 1.25 ± 0.05 1.08 ± 0.03

Relative 5.752 ± 0.126 5.904 ± 0.199 6.283 ± 0.276 5.945 ± 0.232 6.089 ± 0.252 5.658 ± 0.172

Spleen

Absolute 0.420 ± 0.009 0.422 ± 0.010 0.446 ± 0.006* 0.461 ± 0.005* 0.451 ± 0.009* 0.439 ± 0.010*

Relative 2.085 ± 0.030 2.084 ± 0.053 2.162 ± 0.048 2.204 ± 0.030 2.200 ± 0.052 2.311 ± 0.057**

Thymus

Absolute 0.261 ± 0.009 0.271 ± 0.008 0.290 ± 0.012 0.301 ± 0.011* 0.302 ± 0.010* 0.271 ± 0.014

Relative 1.296 ± 0.042 1.336 ± 0.039 1.397 ± 0.039 1.437 ± 0.042 1.471 ± 0.050* 1.425 ± 0.073*

* Significantly different (P≤0.05) from the chamber control group by Williams’ or Dunnett’s test

** (P≤0.01) 

a Organ weights (absolute weights) and body weights are given in grams; organ-weight-to-body-weight ratios (relative weights) are given as 

mg organ weight/g body weight (mean ± standard error).
G-4 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

TABLE G3

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice in the 2-Week Inhalation Study 

of 1-Bromopropanea

Chamber 

Control 125 ppm 250 ppm 500 ppm 1,000 ppm 2,000 ppm

Male

n 5 5 5 1 4 0b

Necropsy body wt 28.0 ± 0.4 28.9 ± 0.5 27.0 ± 0.4 25.8 26.6 ± 0.5

Heart

Absolute 0.14 ± 0.01 0.14 ± 0.01 0.12 ± 0.00 0.12 0.11 ± 0.01**

Relative 4.995 ± 0.216 4.906 ± 0.149 4.594 ± 0.075 4.651 4.243 ± 0.232*

R. Kidney

Absolute 0.24 ± 0.01 0.25 ± 0.01 0.24 ± 0.00 0.24 0.24 ± 0.01

Relative 8.641 ± 0.099 8.638 ± 0.301 8.743 ± 0.127 9.302 8.941 ± 0.161

Liver

Absolute 1.46 ± 0.04 1.50 ± 0.05 1.39 ± 0.02 1.44 1.65 ± 0.05* 

Relative 52.109 ± 0.653 51.841 ± 0.992 51.568 ± 0.464 55.814 61.936 ± 1.839**

Lung

Absolute 0.18 ± 0.01 0.19 ± 0.01 0.19 ± 0.00 0.19 0.18 ± 0.01

Relative 6.562 ± 0.238 6.489 ± 0.291 7.116 ± 0.111 7.364 6.679 ± 0.125

R. Testis

Absolute 0.107 ± 0.002 0.102 ± 0.005 0.107 ± 0.002 0.109 0.103 ± 0.003

Relative 3.807 ± 0.029 3.516 ± 0.162 3.955 ± 0.127 4.225 3.863 ± 0.149

Thymus

Absolute 0.059 ± 0.002 0.057 ± 0.004 0.060 ± 0.003 0.049 0.050 ± 0.006

Relative 2.107 ± 0.080 1.960 ± 0.150 2.222 ± 0.109 1.899 1.876 ± 0.191 

Female

n 5 5 5 5 4 3

Necropsy body wt 22.9 ± 0.2 22.2 ± 0.5 22.8 ± 0.2 23.4 ± 0.6 22.8 ± 0.5 22.7 ± 0.3

Heart

Absolute 0.12 ± 0.00 0.12 ± 0.00 0.12 ± 0.01 0.12 ± 0.01 0.11 ± 0.01 0.12 ± 0.00

Relative 5.146 ± 0.129 5.410 ± 0.082 5.258 ± 0.256 4.990 ± 0.314 4.923 ± 0.161 5.152 ± 0.205

R. Kidney

Absolute 0.16 ± 0.00 0.17 ± 0.00 0.18 ± 0.00* 0.17 ± 0.01* 0.19 ± 0.01** 0.19 ± 0.00**

Relative 6.977 ± 0.135 7.762 ± 0.174 7.795 ± 0.169 7.377 ± 0.315 8.355 ± 0.425** 8.235 ± 0.034**

Liver

Absolute 1.19 ± 0.03 1.13 ± 0.03 1.23 ± 0.02 1.35 ± 0.03* 1.52 ± 0.07** 1.69 ± 0.10**

Relative 51.985 ± 0.718 51.014 ± 0.533 53.680 ± 0.826 57.791 ± 1.092** 66.739 ± 2.104** 74.471 ± 3.176**

Lung

Absolute 0.17 ± 0.00 0.18 ± 0.01 0.19 ± 0.01 0.19 ± 0.01 0.19 ± 0.01 0.20 ± 0.01 

Relative 7.506 ± 0.163 8.287 ± 0.259 8.404 ± 0.220 8.147 ± 0.370 8.348 ± 0.330 8.677 ± 0.274*

Thymus

Absolute 0.074 ± 0.004 0.078 ± 0.004 0.077 ± 0.002 0.062 ± 0.006 0.058 ± 0.005* 0.048 ± 0.005**

Relative 3.208 ± 0.169 3.527 ± 0.111 3.389 ± 0.080 2.689 ± 0.319 2.552 ± 0.262* 2.114 ± 0.199**

* Significantly different (P≤0.05) from the chamber control group by Williams’ or Dunnett’s test

** P≤0.01

a Organ weights (absolute weights) and body weights are given in grams; organ-weight-to-body-weight ratios (relative weights) are given as 

mg organ weight/g body weight (mean ± standard error).

b No data were available for the 2,000 ppm males due to 100% mortality.
1-Bromopropane, NTP TR 564 G-5 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

TABLE G4

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice in the 3-Month Inhalation Study 

of 1-Bromopropanea

Chamber 

Control 62.5 ppm 125 ppm 250 ppm 500 ppm

Male

n 10 10 10 9 6

Necropsy body wt 39.6 ± 0.8 39.0 ± 0.9 39.6 ± 0.6 37.9 ± 0.7 37.4 ± 1.4

Heart

Absolute 0.16 ± 0.00 0.16 ± 0.00 0.16 ± 0.00 0.15 ± 0.00 0.16 ± 0.00

Relative 4.051 ± 0.054 4.014 ± 0.050 4.023 ± 0.049 4.080 ± 0.058 4.210 ± 0.148

R. Kidney

Absolute 0.32 ± 0.01 0.31 ± 0.01 0.30 ± 0.00 0.29 ± 0.01** 0.28 ± 0.01**

Relative 8.133 ± 0.216 7.947 ± 0.123 7.669 ± 0.117 7.687 ± 0.208 7.458 ± 0.258*

Liver

Absolute 1.68 ± 0.05 1.66 ± 0.05 1.71 ± 0.03 1.71 ± 0.03 1.80 ± 0.08 

Relative 42.485 ± 0.503 42.584 ± 0.641 43.288 ± 0.379 45.129 ± 0.393** 48.038 ± 1.126**

Lung

Absolute 0.21 ± 0.01 0.21 ± 0.01 0.23 ± 0.01 0.21 ± 0.00 0.21 ± 0.01

Relative 5.236 ± 0.147 5.477 ± 0.168 5.734 ± 0.259 5.505 ± 0.167 5.742 ± 0.302

Spleen

Absolute 0.067 ± 0.002 0.067 ± 0.002 0.069 ± 0.002 0.067 ± 0.002 0.063 ± 0.002

Relative 1.696 ± 0.051 1.724 ± 0.050 1.743 ± 0.032 1.763 ± 0.051 1.699 ± 0.069

R. Testis

Absolute 0.116 ± 0.003 0.120 ± 0.002 0.108 ± 0.009 0.114 ± 0.002 0.115 ± 0.001

Relative 2.933 ± 0.053 3.099 ± 0.051 2.747 ± 0.226 3.014 ± 0.050 3.081 ± 0.098

Thymus

Absolute 0.049 ± 0.005 0.045 ± 0.004 0.047 ± 0.004 0.049 ± 0.003 0.056 ± 0.006

Relative 1.236 ± 0.107 1.154 ± 0.084 1.192 ± 0.087 1.277 ± 0.060 1.481 ± 0.104

Female

n 10 10 10 10 5

Necropsy body wt 30.9 ± 0.7 33.0 ± 1.3 31.9 ± 0.8 30.2 ± 0.9 31.3 ± 1.4. 

Heart

Absolute 0.14 ± 0.00 0.14 ± 0.00 0.14 ± 0.00 0.14 ± 0.01 0.14 ± 0.01

Relative 4.378 ± 0.087 4.332 ± 0.112 4.404 ± 0.078 4.651 ± 0.110 4.365 ± 0.210

R. Kidney

Absolute 0.20 ± 0.00 0.20 ± 0.00 0.21 ± 0.01 0.20 ± 0.01 0.22 ± 0.01**

Relative 6.330 ± 0.155 6.199 ± 0.179 6.552 ± 0.184 6.780 ± 0.164 7.187 ± 0.265**

Liver

Absolute 1.42 ± 0.03 1.49 ± 0.06 1.51 ± 0.03 1.49 ± 0.04 1.65 ± 0.11*

Relative 46.102 ± 0.767 45.104 ± 0.424 47.586 ± 0.880 49.377 ± 0.640** 52.666 ± 1.904**

Lung

Absolute 0.20 ± 0.01 0.22 ± 0.01 0.22 ± 0.01 0.21 ± 0.01 0.26 ± 0.02**

Relative 6.518 ± 0.276 6.642 ± 0.298 7.018 ± 0.222 7.028 ± 0.190 8.497 ± 0.929**

Spleen

Absolute 0.093 ± 0.002 0.098 ± 0.003 0.096 ± 0.004 0.092 ± 0.004 0.082 ± 0.007 

Relative 3.019 ± 0.073 2.980 ± 0.072 3.006 ± 0.079 3.060 ± 0.114 2.643 ± 0.257

Thymus

Absolute 0.058 ± 0.005 0.058 ± 0.003 0.054 ± 0.002 0.054 ± 0.002 0.055 ± 0.004

Relative 1.861 ± 0.145 1.749 ± 0.081 1.692 ± 0.073 1.797 ± 0.062 1.767 ± 0.138

* Significantly different (P≤0.05) from the chamber control group by Williams’ or Dunnett’s test

** P≤0.01 a Organ weights (absolute weights) and body weights are given in grams; organ-weight-to-body-weight ratios (relative weights) are given as 

mg organ weight/g body weight (mean ± standard error).
G-6 1-Bromopropane, NTP TR 564

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H-1

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

APPENDIX H

REPRODUCTIVE TISSUE EVALUATIONS

AND ESTROUS CYCLE CHARACTERIZATION

TABLE H1 Summary of Reproductive Tissue Evaluations for Male Rats 

in the 3-Month Inhalation Study of 1-Bromopropane ................................................................... H-2

TABLE H2 Estrous Cycle Characterization for Female Rats 

in the 3-Month Inhalation Study of 1-Bromopropane .................................................................. H-2

TABLE H3 Summary of Reproductive Tissue Evaluations for Male Mice 

in the 3-Month Inhalation Study of 1-Bromopropane .................................................................. H-3

TABLE H4 Estrous Cycle Characterization for Female Mice 

in the 3-Month Inhalation Study of 1-Bromopropane .................................................................. H-3
H-2 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

TABLE H1

Summary of Reproductive Tissue Evaluations for Male Rats in the 3-Month Inhalation Study

of 1-Bromopropanea

Chamber Control 250 ppm 500 ppm 1,000 ppm

n 10 10 10 10

Weights (g)

Necropsy body wt 345 ± 7 350 ± 7 344 ± 10 305 ± 6**

L. Cauda epididymis 0.1865 ± 0.0039 0.1929 ± 0.0038 0.1740 ± 0.0106 0.1603 ± 0.0067*

L. Epididymis 0.4862 ± 0.0081 0.4994 ± 0.0042 0.4622 ± 0.0192 0.4423 ± 0.0083*

L. Testis 1.5128 ± 0.0313 1.4833 ± 0.0252 1.3867 ± 0.0839 1.4104 ± 0.0269 

Spermatid measurement

Spermatid heads (106/g testis) 123.6 ± 2.3 129.9 ± 6.1 112.9 ± 12.3 130.5 ± 3.8

Spermatid heads (106/testis) 171.8 ± 4.6 172.0 ± 9.2 150.8 ± 16.9 169.5 ± 6.0

Epididymal spermatozoal measurements

Motility (%) 90.99 ± 0.83 84.87 ± 0.94** 81.84 ± 0.80**b 65.82 ± 3.17**

Sperm (106/g cauda epididymis) 699 ± 26 638 ± 34 576 ± 63 523 ± 30**

Sperm (106/cauda epididymis) 130.27 ± 5.19 122.90 ± 6.63 105.27 ± 12.01 82.39 ± 2.51**

* Significantly different (P≤0.05) from the chamber control group by Williams’ test (cauda epididymis and epididymis weights)

** Significantly different (P≤0.01) from the chamber control group by Williams’ test (body weights) or Shirley’s test (epididymal spermatozoal 

measurements)

a Data are presented as mean ± standard error. Differences from the chamber control group are not significant by Dunnett’s test (testis weights) 

or Dunn’s test (spermatid measurements).

b n=9

TABLE H2

Estrous Cycle Characterization for Female Rats in the 3-Month Inhalation Study of 1-Bromopropanea

Chamber Control 250 ppm 500 ppm 1,000 ppm

Number weighed at necropsy 10 10 10 10

Necropsy body wt (g) 202 ± 3 209 ± 2 205 ± 3 190 ± 4

Proportion of regular cycling femalesb 9/10 10/10 10/10 10/10

Estrous cycle length (days) 4.9 ± 0.11c 5.0 ± 0.05 4.9 ± 0.07 5.0 ± 0.05

Estrous stages (% of cycle)d

Diestrus 55.8 43.3 40.0 41.7

Proestrus 17.5 5.0 4.2 6.7

Estrus 20.8 32.5 36.7 33.3

Metestrus 5.0 19.2 19.2 18.3

Uncertain diagnoses 0.8 0.0 0.0 0.0

a Necropsy body weights and estrous cycle length data are presented as mean ± standard error. Differences from the chamber control group are 

not significant by Dunnett’s test (body weight) or Dunn’s test (estrous cycle length).

b Number of females with a regular cycle/number of females cycling

c Estrous cycle was longer than 12 days or unclear in 1 of 10 animals.

d Evidence shows that females exposed to 250, 500, or 1,000 ppm differ significantly (Wilk’s Criterion, P≤0.05) from the chamber control 

females in the relative length of time spent in the estrous stages. The tests for equality of transition probability matrices among exposed 

groups and between the chamber control group and each exposed group indicated that exposed females spent significantly more time in 

extended estrus (P<0.001) and significantly less time in extended diestrus (P<0.005) than the chamber control group.
1-Bromopropane, NTP TR 564 H-3 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

TABLE H3 

Summary of Reproductive Tissue Evaluations for Male Mice in the 3-Month Inhalation Study

of 1-Bromopropanea

Chamber Control 125 ppm 250 ppm 500 ppm

n 10 10 9 6

Weights (g)

Necropsy body wt 39.6 ± 0.8 39.6 ± 0.6 37.9 ± 0.7 37.4 ± 1.4

L. Cauda epididymis 0.0164 ± 0.0008 0.0170 ± 0.0009 0.0179 ± 0.0005 0.0192 ± 0.0007 

L. Epididymis 0.0538 ± 0.0010 0.0492 ± 0.0016* 0.0532 ± 0.0014 0.0535 ± 0.0012

L. Testis 0.1137 ± 0.0020 0.1063 ± 0.0085 0.1104 ± 0.0028 0.1103 ± 0.0010

Spermatid measurement

Spermatid heads (106/g testis) 188.7 ± 8.1 164.9 ± 19.7 180.5 ± 3.7 199.3 ± 8.0

Spermatid heads (106/testis) 19.83 ± 0.89 17.57 ± 2.09 18.17 ± 0.48 20.11 ± 0.59

Epididymal spermatozoal measurements

Motility (%) 91.57 ± 0.73 89.70 ± 0.66b 87.78 ± 1.10* 88.13 ± 0.56**

Sperm (106/g cauda epididymis) 1,237 ± 60 1,204 ± 66b 1,062 ± 70 890 ± 68**

Sperm (106/cauda epididymis) 19.93 ± 0.47 19.66 ± 0.69b 18.92 ± 0.97 16.93 ± 1.15

* Significantly different (P≤0.05) from the chamber control group by Dunnett’s test (epididymis weights) or Shirley’s test (sperm motility)

** Significantly different (P≤0.01) from the chamber control group by Shirley’s test

a Data are presented as mean ± standard error. Differences from the chamber control group are not significant by Dunnett’s test (body, cauda 

epididymis, and testis weights) or Dunn’s test (spermatid measurements and sperm/cauda epididymis).

b n=9

TABLE H4 

Estrous Cycle Characterization for Female Mice in the 3-Month Inhalation Study of 1-Bromopropanea

Chamber Control 125 ppm 250 ppm 500 ppm

Number weighed at necropsy 10 10 10 5

Necropsy body wt (g) 30.9 ± 0.7 31.9 ± 0.8 30.2 ± 0.9 31.3 ± 1.4

Proportion of regular cycling femalesb 9/10 8/10 6/10 5/5

Estrous cycle length (days) 4.2 ± 0.11 4.6 ± 0.50 4.2 ± 0.08 4.6 ± 0.10*

Estrous stages (% of cycle)c

Diestrus 27.5 27.5 25.8 41.7

Proestrus 0.0 0.0 0.0 0.0

Estrus 49.2 48.3 52.5 41.7

Metestrus 23.3 24.2 21.7 16.7

* Significantly different (P≤0.05) from the chamber control group by Dunn’s test

a Necropsy body weights and estrous cycle length data are presented as mean ± standard error. Differences from the chamber control group are 

not significant by Dunnett’s test (body weight).

b Number of females with a regular cycle/number of females cycling

c Evidence shows that females exposed to 500 ppm differ significantly (Wilk’s Criterion, P≤0.05) from the chamber control females in the 

relative length of time spent in the estrous stages. The tests for equality of transition probability matrices among exposed groups and between 

the chamber control group and each exposed group indicated that 500 ppm females spent significantly more time in extended diestrus 

(P=0.035) and 250 ppm females spent significantly more time in extended estrus (P<0.001) than the chamber control group.
H-4 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft
I-1

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

APPENDIX I

CHEMICAL CHARACTERIZATION AND

GENERATION OF CHAMBER CONCENTRATIONS

PROCUREMENT AND CHARACTERIZATION OF 1-BROMOPROPANE .........................................................................I-2

VAPOR GENERATION AND EXPOSURE SYSTEM ........................................................................................................I-2

VAPOR CONCENTRATION MONITORING...................................................................................................................I-3

CHAMBER ATMOSPHERE CHARACTERIZATION .......................................................................................................I-3

FIGURE I1 Infrared Absorption Spectrum of 1-Bromopropane........................................................................I-5

FIGURE I2 1H-Nuclear Magnetic Resonance Spectrum of 1-Bromopropane ...................................................I-6

TABLE I1 Gas Chromatography Systems Used in the Inhalation Studies of 1-Bromopropane ....................I-7

FIGURE I3 Schematic of the Vapor Generation and Delivery System 

in the Inhalation Studies of 1-Bromopropane...................................................................................I-8

TABLE I2 Summary of Chamber Concentrations in the 2-Week Inhalation Studies 

of 1-Bromopropane .............................................................................................................................I-9

TABLE I3 Summary of Chamber Concentrations in the 3-Month Inhalation Studies

of 1-Bromopropane ............................................................................................................................I-9

TABLE I4 Summary of Chamber Concentrations in the 2-Year Inhalation Studies

of 1-Bromopropane ..........................................................................................................................I-10
I-2 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

CHEMICAL CHARACTERIZATION AND

GENERATION OF CHAMBER CONCENTRATIONS

PROCUREMENT AND CHARACTERIZATION OF 1-BROMOPROPANE

1-Bromopropane was obtained in 55-gallon metal drums from Diaz Chemical Corporation (Holley, NY) in one lot 

(106-015) and from Albemarle PCC (Thann, France) in one lot (1581313004). Lot 106-015 was used in the 2-week 

and 3-month studies, and lot 1581313004 was used during the 2-year studies. Identity and purity analyses were 

conducted by the study laboratory at Battelle Toxicology Northwest (Richland, WA), and by Chemir/Polytech 

Laboratories, Inc. (Maryland Heights, MO). Reports on analyses performed in support of the 1-bromopropane

studies are on file at the National Institute of Environmental Health Sciences.

Both lots of the chemical, a colorless to pale yellow liquid with a strong, characteristic odor, were identified as 

1-bromopropane by Chemir/Polytech Laboratories, Inc., by infrared (IR) and 1H-nuclear magnetic resonance (NMR) 

spectroscopy. All spectra were consistent with the literature reference spectra (Aldrich, 1993, 1997) of 

1-bromopropane. Representative IR and 1H-NMR spectra are presented in Figures I1 and I2, respectively. 

The purity of each lot was determined by the study laboratory using gas chromatography (GC) by system A 

(Table I1). In addition, Chemir/Polytech Laboratories, Inc., determined the moisture content of each lot by Karl 

Fischer titration and the purity of each lot by elemental and hydrogen bromide (HBr) analyses. The analyses of the 

bulk chemical for HBr were performed by volumetric extraction of the samples with deionized water subsequent to 

an analysis of the extractables for free bromide ion using ion chromatography (IC). IC was performed on a Dionex 

DX100 ion chromatograph (Dionex Corporation, Sunnyvale, CA) equipped with a conductivity detector and and 

IonPac (Dionex) column.

For lot 106-015, Karl Fischer titration indicated a water content of 39 ppm. Elemental analyses for carbon,

hydrogen, nitrogen, and sulfur were in agreement with the theoretical values for 1-bromopropane; residual HBr was 

determined to be 1.3 ppm. GC indicated one major peak and three impurities with areas exceeding 0.1% of the total

peak area; these peaks matched the retention times for prepared standards of 1-propanol (0.14%), 2-bromopropane 

(0.11%), and di-n-propyl ether (0.74%). Measured purity of the bulk chemical was consistent throughout the 

sampled metal drum, and the overall purity of lot 106-015 was determined to be approximately 99%.

For lot 1581313004, Karl Fischer titration indicated a water content of 119 ppm. Elemental analyses for carbon,

hydrogen, nitrogen, and sulfur were in agreement with the theoretical values for 1-bromopropane; residual HBr was 

determined to be 61.6 ppm. GC detected one major peak and no impurities with areas greater than 0.1% of the total

peak area. Three impurities identified with prepared standards were 1-propanol (0.03%), 2-bromopropane (0.02%), 

and di-n-propyl ether (0.02%). Measured purity of the bulk chemical was consistent throughout the sampled metal 

drums, and the overall purity of lot 1581313004 was determined to be 99.9% or greater.

To ensure stability, the bulk chemical was stored at controlled room temperature in the original shipping containers 

(55-gallon metal drums). Periodic reanalyses of the bulk chemical were performed during the 2-week, 3-month, and 

2-year studies by the study laboratory using GC by system A, and no degradation of the bulk chemical was detected.

VAPOR GENERATION AND EXPOSURE SYSTEM

A diagram of the 1-bromopropane vapor generation and delivery system used in the studies is shown in Figure I3. 

1-Bromopropane was pumped through a preheater (for the 2-week and 3-month studies) and into a heated glass 

column filled with glass beads that increased the surface area for vaporization. Heated nitrogen entered the column 

from below and assisted in vaporizing the chemical while conveying it into a short distribution manifold. 

Concentration in the manifold was determined by the chemical pump rate and nitrogen flow rate. The pressure in 

the distribution manifold was kept fixed to ensure constant flow through the manifold and into all chambers as the 

flow of vapor to each chamber was adjusted.
1-Bromopropane, NTP TR 564 I-3

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

Metering valves at the manifold controlled flow to each chamber through individual Teflon® delivery lines that 

carried the vapor from the manifold to three-way exposure valves at the chamber inlets. The exposure valves 

diverted vapor delivery to exposure chamber exhaust until the generation system was stable and exposures were 

ready to proceed. To initiate exposure, the chamber exposure valves were rotated to allow the 1-bromopropane 

vapor to flow to each exposure chamber inlet duct where it was further diluted with filtered, conditioned air to 

achieve the desired exposure concentration.

The study laboratory designed the inhalation exposure chamber (Harford Systems Division of Lab Products, Inc., 

Aberdeen, MD) so that uniform vapor concentrations could be maintained throughout the chamber with the catch 

pans in place. The total active mixing volume of each chamber was 1.7 m3

. A small particle detector 

(Model 3022A, TSI Incorporated, St. Paul, MN) was used with and without animals in the exposure chambers to 

ensure that 1-bromopropane vapor, and not aerosol, was produced. No particle counts above the minimum 

resolvable level (approximately 200 particles/cm3

) were detected.

VAPOR CONCENTRATION MONITORING

Summaries of the chamber vapor concentrations are given in Tables I2 through I4. Chamber and room 

concentrations of 1-bromopropane were monitored by an on-line gas chromatograph (system B, Table I1). Samples 

were drawn from each exposure chamber approximately every 20 (2-week and 3-month studies) or 30 (2-year 

studies) minutes during each 6-hour exposure period using Hastelloy®-C stream-select and gas-sampling valves 

(VALCO Instruments Company, Houston, TX) in a separate, heated valve oven. The sample lines composing each 

sample loop were made from Teflon® tubing and were connected to the exposure chamber relative humidity 

sampling lines at a location close to the gas chromatograph. A vacuum regulator maintained a constant vacuum in 

the sample loop to compensate for variations in sample line pressure. An in-line flow meter between the vacuum 

regulator and the gas chromatograph allowed digital measurement of sample flow.

The on-line gas chromatograph was checked throughout the day for instrument drift against an on-line standard 

vapor of 1-bromopropane in nitrogen supplied by a standard generator (Kin-Tek; Precision Calibration Systems, 

La Marque, TX). The on-line gas chromatograph was recalibrated as required to meet acceptance criteria. 

Calibration was performed by a comparison of chamber concentration data to data from grab samples that were 

collected with activated coconut charcoal gas sampling tubes (ORBOTM-32; Supelco, Bellefonte, PA), extracted with 

methylene chloride containing 1-bromobutane as an internal standard, and analyzed using an off-line gas 

chromatograph (system C). Known volumes of chamber atmosphere were sampled at a constant flow rate ensured 

by a calibrated critical orifice. The off-line gas chromatograph was calibrated with gravimetrically prepared 

standards of 1-bromopropane containing 1-bromobutane as an internal standard in methylene chloride.

CHAMBER ATMOSPHERE CHARACTERIZATION

Buildup and decay rates for chamber vapor concentrations were determined with and without animals present in the 

chambers. At a chamber airflow rate of 15 air changes per hour, the theoretical value for the time to achieve 90% of 

the target concentration after the beginning of vapor generation (T90) and the time for the chamber concentration to 

decay to 10% of the target concentration after vapor generation was terminated (T10) was approximately 

12.5 minutes. For rats and mice in the 2-week studies, T90 and T10 values ranged from 9 to 10 minutes with animals 

present. For rats and mice in the 3-month studies, T90 values averaged 9 minutes without animals present and 

ranged from 9 to 10 minutes with animals present; T10 values ranged from 8 to 9 minutes without animals present 

and from 9 to 11 minutes with animals present. For rats and mice in the 2-year studies, T90 values ranged from 9 to 

10 minutes without animals present and from 9 to 11 minutes with animals present; T10 values ranged from 9 to 

10 minutes without animals present and from 10 to 11 minutes with animals present. A T90 value of 12 minutes was 

selected for the 2-week studies, and a T90 value of 10 minutes was selected for the 3-month and 2-year studies.

The uniformity of vapor concentration in the inhalation exposure chambers without animals present was evaluated 

before the 3-month and 2-year studies began; in addition, concentration uniformity with animals present in the 

chambers was measured once during the 2-week studies, once during the 3-month studies, and quarterly during the 

2-year studies. The vapor concentration was measured using the on-line gas chromatograph (system B, Table I1) 

with the stream-selection valve fixed in one position to allow continuous monitoring from a single input line. 
I-4 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

During the 2-week studies and prior to the 3-month and 2-year studies, concentrations were measured at 12 chamber 

positions, one in front and one in back for each of the six possible animal cage unit positions per chamber. During 

the 3-month and 2-year studies, concentrations were measured at the regular monitoring port and from sample ports 

at levels where animals were present. Chamber concentration uniformity was maintained throughout the studies.

The persistence of 1-bromopropane in the chambers after vapor delivery ended was determined by monitoring the 

vapor concentration in the 2,000 ppm chambers in the 2-week studies, the 500 ppm (rats and mice) and 1,000 ppm

(rats) chambers in the 3-month studies, and the 250 ppm (mice) and 500 ppm (rats) chambers in the 2-year studies,

with (all studies) and without (3-month and 2-year studies) animals present in the chambers. In the 2-week studies, 

the concentration decreased to 1% of the target concentration within 19 minutes with animals present. In the 

3-month studies, the concentration decreased to 1% of the target concentration within 20 minutes without animals 

present and within 25 (rat and mouse chambers) and 21 (rat chamber) minutes with animals present. In the 2-year 

studies, the concentration decreased to 1% of the target concentration within 19 (rats) and 20 (mice) minutes without 

animals present and within 25 (rats) and 22 (mice) minutes with animals present.

Samples of the test atmosphere from the distribution lines and low and high exposure concentration chambers were 

collected prior to the 3-month and 2-year studies and also at the beginning and end of one generation day during the 

2-week, 3-month, and 2-year studies; the atmosphere samples were collected with adsorbent gas sampling tubes 

containing activated charcoal (ORBOTM-32), followed by a tube containing silica gel (ORBOTM-52; Supelco, Inc.)

and extracted with methylene chloride. Additional samples were collected from the generator reservoir, and all of 

the samples were analyzed using GC by system A to measure the stability and purity of 1-bromopropane in the 

generation and delivery system. To assess whether impurities or degradation products co-eluted with 

1-bromopropane or the solvent, a second GC analysis of the samples was performed using a polar column capable of 

resolving compounds with similar boiling points and polarities (system D). Fourier transform IR was used to 

determine if HBr was present in the atmosphere samples; spectra were generated using a MIDAC I-1101 

spectrometer with a 9.5 m path-length gas cell (MIDAC Corporation, Irvine, CA) and were compared to those of 

prepared HBr standards.

No evidence of degradation of 1-bromopropane was noted in any part of the exposure system. Three impurity peaks 

with areas greater than 0.1% of the total peak area were consistently detected in atmosphere and generator reservoir 

samples collected prior to the 3-month studies and during the 2-week and 3-month studies. These peaks matched the 

retention times for prepared standards of 1-propanol, 2-bromopropane, and di-n-propyl ether and had area percent 

values similar to those measured during the initial bulk purity analyses of lot 106-015. No impurity peaks were 

detected in atmosphere or generator reservoir samples collected prior to or during the 2-year studies. Using the 

polar column, no additional impurities were detected in any of the atmosphere or generator reservoir samples 

collected prior to or during any of the studies. HBr levels in the exposure atmosphere were determined to be less 

than 0.07% during the 2-week studies and less than 1% prior to and during the 3-month and 2-year studies.
1-Bromopropane, NTP TR 564 I-5 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

FIGURE I1

Infrared Absorption Spectrum of 1-Bromopropane
I-6 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

FIGURE I2 

1H-Nuclear Magnetic Resonance Spectrum of 1-Bromopropane
1-Bromopropane, NTP TR 564 I-7 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

TABLE I1

Gas Chromatography Systems Used in the Inhalation Studies of 1-Bromopropanea

Detection System Column Carrier Gas Oven Temperature

Program

System A

Flame ionization DB-5, 30 m × 0.53 mm,

5.0-μm film thickness 

(J&W Scientific, Folsom, CA) or

Rtx-5, 30 m × 0.53 mm, 

5.0-μm film thickness (Restek, 

Bellefonte, PA)

Helium at 4 psi head pressure 35° C for 3 minutes, then

3° C/minute to 65° C, then

7° C/minute to 260° C, held for

1 minute

System B

Flame ionization DB-5, 15 m × 0.53 mm,

1.5-μm film thickness

(J&W Scientific)

Nitrogen at 17 mL/minute Isothermal at 35° C

System C

Flame ionization DB-5, 30 m × 0.53 mm,

5.0-μm film thickness 

(J&W Scientific) or 

Rtx-5, 30 m × 0.53 mm, 

5.0-μm film thickness (Restek)

Helium at 6 psi head pressure 40° C for 1 minute, then

6° C/minute to 95° C, then 

15° C/minute to 150° C, held for

2 minutes 

System D

Flame ionization DB-Wax, 30 m × 0.53 mm,

1.0-μm film thickness

(J&W Scientific) 

Helium 40° C for 1 minute, then

6° C/minute to 95° C, then 

15° C/minute to 150° C, held for

2 minutes

a The gas chromatographs were manufactured by Hewlett-Packard (Palo Alto, CA).
I-8 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

FIGURE I3

Schematic of the Vapor Generation and Delivery System in the Inhalation Studies

of 1-Bromopropane
1-Bromopropane, NTP TR 564 I-9 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

TABLE I2 

Summary of Chamber Concentrations in the 2-Week Inhalation Studies of 1-Bromopropane

Target Concentration 

(ppm) Total Number of Readings Average Concentrationa

(ppm)

Rat Chambers

125 225 127 ± 2

250 226 252 ± 3

500 227 499 ± 4

1,000 226 1,015 ± 12

2,000 228 2,028 ± 17

Mouse Chambers

125 245 127 ± 2

250 246 251 ± 3

500 247 499 ± 3

1,000 246 1,013 ± 13

2,000 248 2,027 ± 17

a Mean ± standard deviation

TABLE I3 

Summary of Chamber Concentrations in the 3-Month Inhalation Studies of 1-Bromopropane

Target Concentration 

(ppm) Total Number of Readings Average Concentrationa

(ppm)

Rat Chambers

62.5 1,222 62.2 ± 1.2

125 1,237 124 ± 2

250 1,247 247 ± 4

500 1,241 497 ± 8

1,000 1,243 1,005 ± 15

Mouse Chambers

62.5 1,264 62.1 ± 1.2

125 1,277 124 ± 2

250 1,287 247 ± 4

500 1,281 497 ± 8

a Mean ± standard deviation
I-10 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

TABLE I4 

Summary of Chamber Concentrations in the 2-Year Inhalation Studies of 1-Bromopropane

Target Concentration 

(ppm) Total Number of Readings Average Concentrationa

(ppm)

Rat Chambers

125 8,018 125 ± 3

250 8,011 250 ± 6

500 8,042 500 ± 11

Mouse Chambers

62.5 8,494 62.5 ± 1.6

125 8,009 125 ± 3

250 8,038 250 ± 5

a Mean ± standard deviation
J-1 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

APPENDIX J 

INGREDIENTS, NUTRIENT COMPOSITION,

AND CONTAMINANT LEVELS

IN NTP-2000 RAT AND MOUSE RATION

TABLE J1 Ingredients of NTP-2000 Rat and Mouse Ration .............................................................................J-2 

TABLE J2 Vitamins and Minerals in NTP-2000 Rat and Mouse Ration..........................................................J-2 

TABLE J3 Nutrient Composition of NTP-2000 Rat and Mouse Ration............................................................J-3 

TABLE J4 Contaminant Levels in NTP-2000 Rat and Mouse Ration ..............................................................J-4 
J-2 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

TABLE J1

Ingredients of NTP-2000 Rat and Mouse Ration

Ingredients Percent by Weight

Ground hard winter wheat 22.26

Ground #2 yellow shelled corn 22.18

Wheat middlings 15.0

Oat hulls 8.5

Alfalfa meal (dehydrated, 17% protein) 7.5

Purified cellulose 5.5

Soybean meal (49% protein) 5.0

Fish meal (60% protein) 4.0

Corn oil (without preservatives) 3.0

Soy oil (without preservatives) 3.0

Dried brewer’s yeast 1.0

Calcium carbonate (USP) 0.9

Vitamin premixa 0.5

Mineral premixb 0.5

Calcium phosphate, dibasic (USP) 0.4

Sodium chloride 0.3

Choline chloride (70% choline) 0.26

Methionine 0.2

a Wheat middlings as carrier

b Calcium carbonate as carrier

TABLE J2

Vitamins and Minerals in NTP-2000 Rat and Mouse Rationa

Amount Source

Vitamins

A 4,000 IU Stabilized vitamin A palmitate or acetate

D 1,000 IU D-activated animal sterol

K 1.0 mg Menadione sodium bisulfite complex

α-Tocopheryl acetate 100 IU

Niacin 23 mg

Folic acid 1.1 mg

d-Pantothenic acid 10 mg d-Calcium pantothenate

Riboflavin 3.3 mg

Thiamine 4 mg Thiamine mononitrate

B12 52 μg

Pyridoxine 6.3 mg Pyridoxine hydrochloride

Biotin 0.2 mg d-Biotin

Minerals

Magnesium 514 mg Magnesium oxide

Iron 35 mg Iron sulfate

Zinc 12 mg Zinc oxide

Manganese 10 mg Manganese oxide

Copper 2.0 mg Copper sulfate

Iodine 0.2 mg Calcium iodate

Chromium 0.2 mg Chromium acetate

a Per kg of finished product
1-Bromopropane, NTP TR 564 J-3 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION

TABLE J3

Nutrient Composition of NTP-2000 Rat and Mouse Ration

Nutrient Mean ± Standard 

Deviation Range Number of Samples

Protein (% by weight) 14.8 ± 0.65 13.7 – 16.1 24 

Crude fat (% by weight) 8.1 ± 0.36 7.4 – 9.0 24

Crude fiber (% by weight) 9.2 ± 0.45 8.2 – 9.9 24

Ash (% by weight) 5.0 ± 0.25 4.4 – 5.4 24

Amino Acids (% of total diet)

Arginine 0.770 ± 0.070 0.670 – 0.970 18

Cystine 0.225 ± 0.023 0.150 – 0.250 18

Glycine 0.706 ± 0.043 0.620 – 0.800 18

Histidine 0.362 ± 0.082 0.310 – 0.680 18

Isoleucine 0.524 ± 0.046 0.430 – 0.660 18

Leucine 1.087 ± 0.066 0.960 – 1.240 18

Lysine 0.712 ± 0.118 0.310 – 0.840 18

Methionine 0.407 ± 0.051 0.260 – 0.490 18

Phenylalanine 0.626 ± 0.043 0.540 – 0.720 18

Threonine 0.500 ± 0.046 0.430 – 0.610 18 

Tryptophan 0.142 ± 0.024 0.110 – 0.200 18

Tyrosine 0.388 ± 0.058 0.280 – 0.540 18

Valine 0.667 ± 0.045 0.550 – 0.730 18

Essential Fatty Acids (% of total diet)

Linoleic 3.92 ± 0.243 3.49 – 4.54 18

Linolenic 0.30 ± 0.035 0.21 – 0.35 18

Vitamins

Vitamin A (IU/kg) 4,870 ± 121 3,230 – 8,900 24

Vitamin D (IU/kg) 1,000a

α-Tocopherol (ppm) 84.2 ± 16.60 52.0 – 110.0 15

Thiamine (ppm)b 9.0 ± 3.71 6.4 – 25.2 24 

Riboflavin (ppm) 6.8 ± 2.11 4.20 – 11.20 15

Niacin (ppm) 79.0 ± 10.50 66.4 – 98.2 15

Pantothenic acid (ppm) 23.9 ± 3.73 17.4 – 29.8 15

Pyridoxine (ppm)b 9.21 ± 2.20 6.4 – 13.7 15

Folic acid (ppm) 1.75 ± 0.54 1.20 – 3.27 15

Biotin (ppm) 0.332 ± 0.12 0.225 – 0.704 15

Vitamin B12 (ppb) 60.5 ± 46.5 18.3 – 174.0 15

Choline (ppm)b 3,064 ± 270 2,700 – 3,790 15

Minerals

Calcium (%) 0.964 ± 0.043 0.884 – 1.030 24

Phosphorus (%) 0.578 ± 0.026 0.535 – 0.623 24

Potassium (%) 0.665 ± 0.023 0.626 – 0.694 15

Chloride (%) 0.376 ± 0.041 0.300 – 0.474 15

Sodium (%) 0.191 ± 0.017 0.160 – 0.222 15

Magnesium (%) 0.201 ± 0.009 0.185 – 0.217 15

Sulfur (%) 0.170 ± 0.029 0.116 – 0.209 15

Iron (ppm) 182 ± 46.7 135 – 311 15

Manganese (ppm) 54.1 ± 7.89 42.1 – 73.1 15

Zinc (ppm) 55.0 ± 9.55 43.3 – 78.5 15

Copper (ppm) 6.65 ± 1.790 3.21 – 10.50 15

Iodine (ppm) 0.512 ± 0.221 0.233 – 0.972 15

Chromium (ppm) 0.604 ± 0.253 0.330 – 1.380 14

Cobalt (ppm) 0.25 ± 0.074 0.20 – 0.47 14

a From formulation

b As hydrochloride (thiamine and pyridoxine) or chloride (choline)
J-4 1-Bromopropane, NTP TR 564

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft

TABLE J4

Contaminant Levels in NTP-2000 Rat and Mouse Rationa

Mean ± Standard

Deviationb Range Number of Samples

Contaminants

Arsenic (ppm) 0.25 ± 0.120 0.14 – 0.50 24

Cadmium (ppm) 0.07 ± 0.022 0.04 – 0.10 24

Lead (ppm) 0.09 ± 0.023 0.05 – 0.13 24 

Mercury (ppm) <0.02 24

Selenium (ppm) 0.21 ± 0.058 0.16 – 0.45 24

Aflatoxins (ppb) <5.00 24

Nitrate nitrogen (ppm)c 13.1 ± 4.17 7.89 – 24.4 24 

Nitrite nitrogen (ppm)c <0.61 24

BHA (ppm)d <1.0 24 

BHT (ppm)d <1.0 24 

Aerobic plate count (CFU/g) 10 ± 0.0 10 24

Coliform (MPN/g) 3.0 ± 0.0 3.0 24

Escherichia coli (MPN/g) <10 24

Salmonella (MPN/g) Negative 24

Total nitrosoamines (ppb)e 4.4 ± 1.73 2.3 – 8.5 24 

N-Nitrosodimethylamine (ppb)e 2.4 ± 1.29 1.1 – 5.6 24

N-Nitrosopyrrolidine (ppb)e 1.9 ± 0.80 0.9 – 4.1 24

Pesticides (ppm)

α-BHC <0.01 24

β-BHC <0.02 24

γ-BHC <0.01 24

δ-BHC <0.01 24

Heptachlor <0.01 24

Aldrin <0.01 24

Heptachlor epoxide <0.01 24

DDE <0.01 24

DDD <0.01 24

DDT <0.01 24

HCB <0.01 24

Mirex <0.01 24

Methoxychlor <0.05 24 

Dieldrin <0.01 24

Endrin <0.01 24

Telodrin <0.01 24

Chlordane <0.05 24

Toxaphene <0.10 24

Estimated PCBs <0.20 24

Ronnel <0.01 24

Ethion <0.02 24

Trithion <0.05 24

Diazinon <0.10 24

Methyl chlorpyrifos 0.122 ± 0.139 0.020 – 0.416 24

Methyl parathion <0.02 24

Ethyl parathion <0.02 24

Malathion 0.165 ± 0.178 0.020 – 0.589 24

Endosulfan I <0.01 24

Endosulfan II <0.01 24

Endosulfan sulfate <0.03 24

a All samples were irradiated. CFU=colony-forming units; MPN=most probable number; BHC=hexachlorocyclohexane or 

benzene hexachloride

b For values less than the limit of detection, the detection limit is given as the mean.

c Sources of contamination: alfalfa, grains, and fish meal

d Sources of contamination: soy oil and fish meal

e All values were corrected for percent recovery.
K-1 

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APPENDIX K 

SENTINEL ANIMAL PROGRAM

Methods................................................................................................................................................................... K-2 

Results...................................................................................................................................................................... K-4 
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SENTINEL ANIMAL PROGRAM

METHODS

Rodents used in the Carcinogenesis Program of the National Toxicology Program are produced in optimally clean 

facilities to eliminate potential pathogens that may affect study results. The Sentinel Animal Program is part of the 

periodic monitoring of animal health that occurs during the toxicologic evaluation of chemical compounds. Under 

this program, the disease state of the rodents is monitored via serology on sera from extra (sentinel) animals in the 

study rooms. These animals and the study animals are subject to identical environmental conditions. The sentinel 

animals come from the same production source and weanling groups as the animals used for the studies of chemical 

compounds.

Serum samples were collected from five male and five female chamber control rats and mice at the end of the 

2-week and 3-month studies, five male and five female sentinel rats and mice 1 week after the start of the 3-month 

and 2-year studies, five male and five female sentinel rats and mice at 6 and 12 months in the 2-year studies, five 

male and four female sentinel rats at 18 months in the 2-year studies, five male and five female mice at 18 months in 

the 2-year studies, and five males and five females from the 500 ppm rats and 250 ppm mice at the end of the 2-year 

studies. Blood from each animal was collected and allowed to clot, and the serum was separated; fecal samples 

were collected from five male and five female mice at 18 months in the 2-year study for Helicobacter species by 

polymerase chain reaction testing. The samples were processed appropriately and sent to MA 

Bioservices/BioReliance (Rockville, MD) for determination of antibody titers. The laboratory serology methods and 

viral agents for which testing was performed are tabulated below; the times at which blood was collected during the 

studies are also listed.

Method and Test Time of Collection

RATS

2-Week Study

ELISA

H-1 (Toolan’s H-1 virus) Study termination

KRV (Kilham rat virus) Study termination

Mycoplasma pulmonis Study termination

PVM (pneumonia virus of mice) Study termination

RCV (rat coronavirus) Study termination

Sendai Study termination

3-Month Study

ELISA

H-1 1 week

KRV 1 week

Mycoplasma arthritidis Study termination

M. pulmonis 1 week, study termination

PVM 1 week, study termination

RCV/SDA 

(rat coronavirus/sialodacryoadenitis virus) 1 week, study termination

Sendai 1 week, study termination

Immunofluorescence Assay

Parvovirus Study termination
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Method and Test Time of Collection

RATS (continued)

2-Year Study

ELISA

H-1 1 week

KRV 1 week

M. pulmonis 1 week, study termination

M. arthritidis Study termination

PVM 1 week, 6, 12, and 18 months, study termination

RCV/SDA 1 week, 6, 12, and 18 months, study termination

Sendai 1 week, 6, 12, and 18 months, study termination

Immunofluorescence Assay

Parvovirus 6, 12, and 18 months, study termination

MICE

2-Week Study

ELISA

GDVII (mouse encephalomyelitis virus) Study termination

MVM (minute virus of mice) Study termination

MHV (mouse hepatitis virus) Study termination

M. pulmonis Study termination

PVM Study termination

Sendai Study termination

3-Month Study

ELISA

Ectromelia virus Study termination

EDIM (epizootic diarrhea of infant mice) Study termination

GDVII 1 week, study termination

LCM (lymphocytic choriomeningitis virus) Study termination

MVM 1 week

Mouse adenoma virus-FL Study termination

MHV 1 week, study termination

M. arthritidis Study termination

M. pulmonis 1 week, study termination

PVM 1 week, study termination

Reovirus 3 Study termination

Sendai 1 week, study termination

Immunofluorescence Assay

MCMV (mouse cytomegalovirus) Study termination

Parvovirus Study termination
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Method and Test Time of Collection

MICE (continued)

2-Year Study

ELISA

Ectromelia virus 6, 12, and 18 months, study termination

EDIM 6, 12, and 18 months, study termination

GDVII 1 week, 6, 12, and 18 months, study termination

LCM 6, 12, and 18 months, study termination

MVM 1 week, 12 and 18 months, study termination

Mouse adenoma virus 6, 12, and 18 months, study termination

MHV 1 week, 6, 12, and 18 months, study termination

M. arthritidis Study termination

M. pulmonis 1 week, study termination

PVM 1 week, 6, 12, and 18 months, study termination

Reovirus 3 6, 12, and 18 months, study termination

Sendai 1 week, 6, 12, and 18 months, study termination

Immunofluorescence Assay

MCMV Study termination

Parvovirus 6, 12, and 18 months, study termination

Polymerase Chain Reaction

Helicobacter species 18 months

RESULTS

All test results were negative.