NTP TECHNICAL REPORT
 

ON THE
 

TOXICOLOGY AND CARCINOGENESIS
 

STUDIES OF 1-CHLORO-2-PROPANOL
 (TECHNICAL GRADE)
 

(CAS NO. 127-00-4)
 

IN F344/N RATS AND B6C3F1 MICE

(DRINKING WATER STUDIES) 

NATIONAL TOXICOLOGY PROGRAM
 

P.O. Box 12233
 

Research Triangle Park, NC 27709
 

September 1998
 

NTP TR 477
 

NIH Publication No. 98-3967
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

National Institutes of Health
 
FOREWORD 

The National Toxicology Program (NTP) is made up of four charter agencies of the U.S. Department of 

Health and Human Services (DHHS): the National Cancer Institute (NCI), National Institutes of Health; the 

National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health; the National 

Center for Toxicological Research (NCTR), Food and Drug Administration; and the National Institute for 

Occupational Safety and Health (NIOSH), Centers for Disease Control. In July 1981, the Carcinogenesis 

Bioassay Testing Program, NCI, was transferred to the NIEHS. The NTP coordinates the relevant 

programs, staff, and resources from these Public Health Service agencies relating to basic and applied 

research and to biological assay development and validation. 

The NTP develops, evaluates, and disseminates scientific information about potentially toxic and hazardous 

chemicals. This knowledge is used for protecting the health of the American people and for the primary 

prevention of disease. 

The studies described in this Technical Report were performed under the direction of the NIEHS and were 

conducted in compliance with NTP laboratory health and safety requirements and must meet or exceed all 

applicable federal, state, and local health and safety regulations. Animal care and use were in accordance 

with the Public Health Service Policy on Humane Care and Use of Animals. The prechronic and chronic 

studies were conducted in compliance with Food and Drug Administration (FDA) Good Laboratory Practice 

Regulations, and all aspects of the chronic studies were subjected to retrospective quality assurance audits 

before being presented for public review. 

These studies are designed and conducted to characterize and evaluate the toxicologic potential, including 

carcinogenic activity, of selected chemicals in laboratory animals (usually two species, rats and mice). 

Chemicals selected for NTP toxicology and carcinogenesis studies are chosen primarily on the bases of 

human exposure, level of production, and chemical structure. The interpretive conclusions presented in this 

Technical Report are based only on the results of these NTP studies. Extrapolation of these results to other 

species and quantitative risk analyses for humans require wider analyses beyond the purview of these studies. 

Selection per se is not an indicator of a chemical’s carcinogenic potential. 

Listings of all published NTP reports and ongoing studies are available from NTP Central Data 

Management, NIEHS, P.O. Box 12233, MD E1-02, Research Triangle Park, NC 27709 (919-541-3419). 

The Abstracts and other study information for 2-year studies are also available at the NTP’s World Wide 

Web site: http://ntp-server.niehs.nih.gov. 
NTP TECHNICAL REPORT
 

ON THE
 

TOXICOLOGY AND CARCINOGENESIS
 

STUDIES OF 1-CHLORO-2-PROPANOL
 (TECHNICAL GRADE)
 

(CAS NO. 127-00-4)
 

IN F344/N RATS AND B6C3F1 MICE

(DRINKING WATER STUDIES) 

NATIONAL TOXICOLOGY PROGRAM
 

P.O. Box 12233
 

Research Triangle Park, NC 27709
 

September 1998
 

NTP TR 477
 

NIH Publication No. 98-3967
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

National Institutes of Health
 
2 1-Chloro-2-propanol, NTP TR 477 

CONTRIBUTORS
 

National Toxicology Program 

Evaluated and interpreted results and reported findings 

J.K. Dunnick, Ph.D., Study Scientist 

D.A. Bridge, B.S. 

J.R. Bucher, Ph.D. 

R.E. Chapin, Ph.D. 

J.R. Hailey, D.V.M. 

J.K. Haseman, Ph.D. 

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

G.N. Rao, D.V.M., Ph.D. 

C.S. Smith, Ph.D. 

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

D.B. Walters, Ph.D. 

K.L. Witt, M.S., Integrated Laboratory Systems 

SRI International 

Conducted 14-day and 14-week studies, evaluated pathology 

findings 

J.B. Reid, Ph.D., Principal Investigator 

R.A. Becker, Ph.D. 

J.R. Hill, Ph.D. 

E.F. Meierhenry, Ph.D. 

TSI Mason Laboratories 

Conducted 2-year studies, evaluated pathology findings 

M.R. Osheroff, Ph.D., Principal Investigator 

C. Gamba-Vitalo, Ph.D. 

F.A. Voelker, D.V.M. 

D. Norlin, Ph.D. 

Experimental Pathology Laboratories, Inc. 

Provided pathology quality assurance 

J.F. Hardisty, D.V.M., Principal Investigator 

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

Dynamac Corporation 

Prepared quality assurance audits 

S. Brecher, Ph.D., Principal Investigator 

NTP Pathology Working Group 

Evaluated slides, prepared pathology report on rats 

(24 April 1997) 

J.C. Seely, D.V.M., Chairperson 

PATHCO, Inc. 

R. Brown, D.V.M. 

Glaxo-Wellcome 

V. Geiss, D.V.M., Ph.D., Observer 

National Toxicology Program 

J.R. Hailey, D.V.M. 

National Toxicology Program 

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

National Toxicology Program 

J.R. Leininger, D.V.M., Ph.D. 

National Toxicology Program 

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

Experimental Pathology Laboratories, Inc. 

A. Radovsky, D.V.M., Ph.D. 

National Toxicology Program 

Evaluated slides, prepared pathology report on mice 

(24 April 1997) 

P.K. Hildebrandt, D.V.M., Chairperson 

PATHCO, Inc. 

R. Brown, D.V.M. 

Glaxo-Wellcome 

V. Geiss, D.V.M., Ph.D., Observer 

National Toxicology Program 

J.R. Hailey, D.V.M. 

National Toxicology Program 

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

National Toxicology Program 

J.R. Leininger, D.V.M., Ph.D. 

National Toxicology Program 

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

Experimental Pathology Laboratories, Inc. 

A. Radovsky, D.V.M., Ph.D. 

National Toxicology Program 
1-Chloro-2-propanol, NTP TR 477 3 

Analytical Sciences, Inc. Biotechnical Services, Inc. 

Provided statistical analyses Prepared Technical Report 

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

S.R. Lloyd, M.S. G. Gordon, M.A. 

N.G. Mintz, B.S. L.M. Harper, B.S. 

A.M. Macri-Hanson, M.A., M.F.A. 

S.M. Swift, B.S. 
4 

CONTENTS
 

ABSTRACT ............................................................. 5
 

EXPLANATION OF LEVELS OF EVIDENCE OF CARCINOGENIC ACTIVITY ............. 9
 

TECHNICAL REPORTS REVIEW SUBCOMMITTEE ................................ 10
 

SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS .......... 11
 

INTRODUCTION ......................................................... 13
 

MATERIALS AND METHODS ................................................ 19
 

RESULTS ............................................................... 31
 

DISCUSSION AND CONCLUSIONS ............................................ 57
 

REFERENCES ........................................................... 61
 

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

of 1-Chloro-2-propanol ........................................... 67
 

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

of 1-Chloro-2-propanol ........................................... 99
 

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

of 1-Chloro-2-propanol ........................................... 131
 

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

of 1-Chloro-2-propanol ........................................... 161
 

APPENDIX E Genetic Toxicology ............................................. 199
 

APPENDIX F Continuous Breeding Study in Sprague-Dawley Rats ....................... 211
 

APPENDIX G Hematology, Clinical Chemistry, and Urinalysis Results .................... 223
 

APPENDIX H Organ Weights and Organ-Weight-to-Body-Weight Ratios .................. 229
 

APPENDIX I Reproductive Tissue Evaluations and Estrous Cycle Characterization ........... 235
 

APPENDIX J Chemical Characterization and Dose Formulation Studies ................... 239
 

APPENDIX K Water and Compound Consumption in the 2-Year Drinking Water Studies 

of 1-Chloro-2-propanol ........................................... 251
 

APPENDIX L Ingredients, Nutrient Composition, and Contaminant Levels 

in NIH-07 Rat and Mouse Ration ................................... 257
 

APPENDIX M Sentinel Animal Program ......................................... 261
 
 

5 

ABSTRACT
 

CH2 CH CH3 

Cl OH 

TECHNICAL GRADE 1-CHLORO-2-PROPANOL
 

(~75% 1-CHLORO-2-PROPANOL; ~25% 2-CHLORO-1-PROPANOL)
 

CAS No. 127-00-4
 

Chemical Formula: C 3 7 H ClO Molecular Weight: 94.54

Synonyms: Chlorohydrin, 1-chloro-2-hydroxypropane, 1-chloroisopropyl alcohol, propylene-%-chlorohydrin, sec-propylene chlorohydrin 

1-Chloro-2-propanol and its positional isomer, 

2-chloro-1-propanol, are used as chemical intermediates for the manufacture of propylene oxide, a 

starting material for production of polyurethane 

polyols and propylene glycol. The National Cancer 

Institute nominated 1-chloro-2-propanol for study 

because of potential for human exposure due to its 

residues in various foods that are fumigated with 

ethylene oxide or propylene oxide. Male and female 

F344/N rats and B6C3F1 mice were exposed to 

technical grade 1-chloro-2-propanol (75% to 76% 

1-chloro-2-propanol; 24% to 25% 2-chloro-1­

propanol) in drinking water for 14 days, 14 weeks, or 

2 years. Genetic toxicology studies were conducted in 

Salmonella typhimurium, cultured Chinese hamster 

ovary cells, Drosophila melanogaster, and mouse 

peripheral blood erythrocytes. Continuous breeding 

studies were conducted in Sprague-Dawley rats. 

14-DAY STUDY IN RATS 

Groups of 10 male and 10 female F344/N rats were 

administered 1-chloro-2-propanol in drinking water at 

concentrations of 0, 100, 330, 1,000, 3,300, or 

10,000 ppm for 14 days. Two 10,000 ppm females 

died before the end of the study. The final mean body 

weights and body weight gains of 3,300 and 

10,000 ppm rats were significantly less than those of 

the controls; rats in the 10,000 ppm groups lost 

weight. Water consumption by the 3,300 and 

10,000 ppm groups was significantly less than that by 

the controls throughout the study. The thymus 

weights of 10,000 ppm rats were significantly less 

than those of the controls. Exposure to 1-chloro-2­

propanol caused cytoplasmic alteration and degeneration of the acinar cells and fatty change in the 

pancreas, atrophy of the bone marrow, and atrophy 

and hematopoiesis of the spleen in males and females. 

14-DAY STUDY IN MICE 

Groups of 10 male and 10 female B6C3F1 mice were

administered 1-chloro-2-propanol in drinking water at 

concentrations of 0, 100, 330, 1,000, 3,300, or 

10,000 ppm for 14 days. One male mouse in the 

10,000 ppm group died before the end of the study. 

Mean body weight gains of 10,000 ppm mice were 

significantly less than those of the controls. Water 

consumption by 3,300 and 10,000 ppm males and 

females was significantly less than that by the controls 

throughout the study. Liver weights of 1,000, 3,300, 

or 10,000 ppm males and females were significantly 

greater and thymus weights of 10,000 ppm mice were 

significantly less than those of the controls. Exposure 
6 1-Chloro-2-propanol, NTP TR 477 

to 1-chloro-2-propanol caused hepatocellular vacuolization, cytoplasmic alteration and degeneration of the 

pancreas acinar cells, and atrophy of the spleen in 

males and females. 

14-WEEK STUDY IN RATS 

Groups of 10 male and 10 female F344/N rats were 

administered 1-chloro-2-propanol at concentrations of 

0, 33, 100, 330, 1,000, or 3,300 ppm (equivalent to 

average daily doses of approximately 5, 10, 35, 100, 

or 220 mg/kg) for 14 weeks. All rats survived to the 

end of the study. Mean body weight gains of 

3,300 ppm rats were significantly less than those of 

the controls. Water consumption by the 3,300 ppm 

male and female rats was significantly less than that by 

the controls. A minimal to mild anemia was observed 

in exposed female rats. The cauda epididymis and 

epididymis weights of 3,300 ppm males were 

significantly less than those of the controls. The 

percentage of abnormal sperm in 3,300 ppm males and 

the concentration of epididymal sperm in 330 ppm 

males were significantly increased compared to the 

controls. Kidney and liver weights of males and 

females exposed to 100 ppm or more were generally 

greater than those of the controls. The incidences of 

acinar cell degeneration and fatty change of the 

pancreas in 1,000 and 3,300 ppm rats, hepatocytic 

metaplasia of the pancreatic islets in 3,300 ppm 

females, cytoplasmic vacuolization of the liver in 100, 

1,000 and 3,300 ppm males, and renal tubule 

epithelium regeneration in 3,300 ppm females were 

increased compared to the controls. 

14-WEEK STUDY IN MICE 

Groups of 10 male and 10 female B6C3F mice were 1 

administered 1-chloro-2-propanol in drinking water at 

concentrations of 0, 33, 100, 330, 1,000, or 

3,300 ppm (equivalent to average daily doses of 

approximately 5, 15, 50, 170, or 340 mg/kg to males 

and 7, 20, 70, 260, or 420 mg/kg to females) for 

14 weeks. One 330 ppm male died before the end of 

the study. Mean body weight gains of exposed groups 

were similar to those of the controls. A minimal 

anemia was observed in 3,300 ppm males. The right 

epididymis weight of 3,300 ppm males was significantly greater than that of the controls. Kidney 

weights of 3,300 ppm mice, liver weights of 

1,000 ppm males and of all exposed groups of 

females, and thymus weights of 1,000 and 3,300 ppm 

females were greater than those of the controls. The 

incidences of pancreatic acinar cell degeneration and 

fatty change in 3,300 ppm males and females and 

cytoplasmic vacuolization of the liver in all groups of 

exposed females were significantly increased compared 

to the controls. The severities of renal tubule 

cytoplasmic vacuolization were greater in 1,000 and 

3,300 ppm males than in the controls. 

2-YEAR STUDY IN RATS 

Groups of 50 male and 50 female F344/N rats were 

administered drinking water containing 0, 150, 325, or 

650 ppm 1-chloro-2-propanol (equivalent to average 

daily doses of approximately 15, 30, or 65 mg/kg 

during the first several months of the study and 8, 17, 

or 34 mg/kg for the remainder of the 2-year study) for 

up to 105 weeks. Survival of all exposed groups was 

similar to that of the controls. Mean body weights of 

exposed rats were generally similar to those of the 

controls throughout most of the study. Water 

consumption by all exposed groups was similar to that 

by the controls. No treatment-related neoplasms or 

nonneoplastic lesions were observed in this study. 

2-YEAR STUDY IN MICE 

Groups of 50 male and 50 female B6C3F1 mice were

administered drinking water containing 0, 250, 500, or 

1,000 ppm 1-chloro-2-propanol (equivalent to average 

daily doses of approximately 45, 75, or 150 mg/kg to 

males and 60, 105, or 210 mg/kg to females during 

the first several months of the study and 25, 50, or 

100 mg/kg for the remainder of the 2-year study) for 

up to 105 weeks. Survival of all exposed groups was 

similar to that of the controls. The mean body weights 

of all exposed mice were generally similar to those of 

the controls throughout the study. Water consumption 

by all exposed groups was similar to that by the 

controls. No treatment-related neoplasms or 

nonneoplastic lesions were observed in this study. 

GENETIC TOXICOLOGY 

1-Chloro-2-propanol is a demonstrated mutagen 

in vitro. It was weakly mutagenic in S. typhimurium 

strain TA100 in the presence of hamster or rat liver S9 

activation enzymes and was positive, with and without 

S9, in TA1535. No mutagenic activity was detected in 

strains TA97, TA98, and TA1537, with or without S9. 

In cytogenetic tests with Chinese hamster ovary cells, 

1-chloro-2-propanol induced high levels of sister 
__________ 

1-Chloro-2-propanol, NTP TR 477 7 

chromatid exchanges and chromosomal aberrations in mice administered 1-chloro-2-propanol via drinking 

the presence and the absence of S9. The marked water for 14 weeks. 

ability of 1-chloro-2-propanol to induce chromosomal 

effects in vitro was not seen in vivo. Positive results 

were obtained in a test in D. melanogaster for CONCLUSIONS 

induction of sex-linked recessive lethal mutations in Under the conditions of these 2-year drinking water 

germ cells of males administered 1-chloro-2-propanol studies, there was no evidence of carcinogenic 

via injection; however, negative results were obtained activity* of technical grade 1-chloro-2-propanol in 

when males were administered 1-chloro-2-propanol in male or female F344/N rats exposed to 150, 325, or 

feed. A subsequent germ cell reciprocal translocation 650 ppm. There was no evidence of carcinogenic 

test in D. melanogaster yielded negative results. activity of technical grade 1-chloro-2-propanol in male 

Further, no induction of micronucleated erythrocytes or female B6C3F1 mice exposed to 250, 500, or 

was observed in peripheral blood of male and female 1,000 ppm. 

*	 Explanation of Levels of Evidence of Carcinogenic Activity is on page 9. A summary of the Technical Reports Review Subcommittee 

comments and the public discussion on this Technical Report appears on page 11. 
8 1-Chloro-2-propanol, NTP TR 477 

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

Male Female Male Female 

F344/N Rats F344/N Rats B6C3F Mice B6C3F Mice 1 1 

Concentrations 0, 150, 325, or 0, 150, 325, or 0, 250, 500, or 0, 250, 500, or 

650 ppm 650 ppm 1,000 ppm 1,000 ppm 

Body weights Exposed groups similar Exposed groups similar Exposed groups similar Exposed groups similar 

to control group to control group to control group to control group 

Survival rates 20/50, 23/50, 24/50, 25/50, 33/50, 30/50, 40/50, 44/50, 29/50, 32/50, 32/50, 36/50, 

23/50 31/50 39/50 32/50 

Nonneoplastic effects None None None None 

Neoplastic effects None None None None 

Level of evidence of 

carcinogenic activity 

No evidence No evidence No evidence No evidence 

Genetic toxicology 

Salmonella typhimurium gene mutations: 

Sister chromatid exchanges 

Cultured Chinese hamster ovary cells in vitro: 

Chromosomal aberrations 

Cultured Chinese hamster ovary cells in vitro: 

Sex-linked recessive lethal mutations 

Drosophila melanogaster: 

Reciprocal translocations 

Drosophila melanogaster: 

Micronucleated erythrocytes 

Mouse peripheral blood in vivo: 

Positive or equivocal with S9 in strain TA100; positive with and without S9 in 

strain TA1535; negative with and without S9 in strains TA97, TA98, and TA1537 

Positive with and without S9 

Positive with and without S9 

Positive when administered via injection, negative when administered via feed 

Negative 

Negative 
1-Chloro-2-propanol, NTP TR 477 9 

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 the 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 

in 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.
 

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 in 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. 
__________ 

10 1-Chloro-2-propanol, NTP TR 477 

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-chloro-2-propanol on 

10 December 1997 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. 

Gary P. Carlson, Ph.D., Chairperson John M. Cullen, Ph.D., V.M.D. 

School of Health Sciences Department of Microbiology, Parasitology, and Pathology 

Purdue University College of Veterinary Medicine 

West Lafayette, IN North Carolina State University 

Raleigh, NC 

A. John Bailer, Ph.D. 

Department of Mathematics and Statistics Susan M. Fischer, Ph.D. 

Miami University M.D. Anderson Cancer Center 

Oxford, OH University of Texas 

Smithville, TX 

Steven A. Belinsky, Ph.D.* 

Inhalation Toxicology Research Institute Thomas L. Goldsworthy, Ph.D. 

Kirkland Air Force Base Integrated Laboratory Systems 

Albuquerque, NM Research Triangle Park, NC 

James S. Bus, Ph.D., Principal Reviewer Irma Russo, M.D. 

Health and Environmental Sciences Fox Chase Cancer Center 

Dow Chemical Company Philadelphia, PA 

Midland, MI 

Linda A. Chatman, D.V.M., Principal Reviewer 

Pfizer, Inc. 

Groton, CT 

Special Reviewers 

Stephen S. Hecht, Ph.D. Jose Russo, M.D., Principal Reviewer

University of Minnesota Cancer Centers Fox Chase Cancer Center

Minneapolis, MN Philadelphia, PA

Michele Medinsky, Ph.D. 

Chemical Industry Institute of Toxicology 

Research Triangle Park, NC 

* Did not attend 
1-Chloro-2-propanol, NTP TR 477 11 

SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS
 

On 10 December 1997, the draft Technical Report on lamic damage. Dr. Dunnick said water consumption 

the toxicology and carcinogenesis studies of 1-chloro- was decreased more in the 14-day studies than in the 

2-propanol (technical grade) received public review by 14-week studies, and by 13 weeks, decreases in water 

the National Toxicology Program’s Board of Scientific consumption were much less as animals adapted to the 

Counselors’ Technical Reports Review Subcommittee. taste of the chemical. Dr. Chatman inquired whether 

The meeting was held at the National Institute of exposure concentrations were monitored in view of the 

Environmental Health Sciences, Research Triangle decrease in water consumption. Dr. Dunnick said 

Park, NC. analyses were performed on the drinking water bottles 

and on the dose preparations, and, in general, concenDr. J.K. Dunnick, NIEHS, introduced the toxicology trations were within targeted amounts. 

and carcinogenesis studies of 1-chloro-2-propanol by 

discussing the uses of the chemical and the rationale Dr. Bus, the third principal reviewer, agreed with the 

for study, describing the experimental design, proposed conclusions. 

reporting on any survival and body weight effects, and 

commenting on compound-related neoplastic and Dr. Goldsworthy also thought that the high doses 

nonneoplastic lesions in rats and mice. The proposed may have been below maximal tolerated doses. 

conclusions for the 2-year studies were no evidence of Dr. J.R. Hailey, NIEHS, said that the 2-year study 

carcinogenic activity in male or female F344/N rats or doses were based on the significant pancreatic lesions 

B6C3F mice. in the 14-week studies. Dr. Bus commented that based 1 

on the results of the 14-week studies, the doses for the 

Dr. Chatman, a principal reviewer, agreed with the 2-year studies were chosen properly. Dr. Cullen 

proposed conclusions. She noted that the pancreas asked whether the pancreatic lesions in the 14-week 

was a target tissue in the 14-week studies, and in light studies were metaplastic and if the size of the pancreas 

of epidemiologic reports of higher rates of pancreatic had changed. Dr. Hailey replied that there was no 

cancer in humans working in the chlorohydrin change in size although there was apoptosis of acinar 

industry, she asked if the top doses should have been cells and replacement by adipocytes (fat cells). 

higher in the 2-year studies. Dr. Chatman asked why Dr. Chatman urged the NTP to pursue the evaluation 

inhalation was not the preferred route of exposure. of possible pancreatic effects in view of a possible 

Dr. Dunnick responded that the chemical was admin- association with increased pancreatic cancer in the 

istered orally because of concern about its being workplace. 

present in fumigated foods. 

Dr. Chatman moved that the Technical Report on 

Dr. J. Russo, the second principal reviewer, agreed 1-chloro-2-propanol (technical grade) be accepted with 

with the proposed conclusions. He commented on the the conclusions as written for male and female rats and 

significant decrease in drinking water consumption in mice, no evidence of carcinogenic activity. 

exposed animals in the 14-week studies and asked Dr. Goldsworthy seconded the motion, which was 

whether this could be due to some type of hypotha- accepted unanimously with seven votes. 
12 1-Chloro-2-propanol, NTP TR 477 
 

13 

INTRODUCTION
 

CH2 CH CH3 

Cl OH 

TECHNICAL GRADE 1-CHLORO-2-PROPANOL
 

(~75% 1-CHLORO-2-PROPANOL; ~25% 2-CHLORO-1-PROPANOL)
 

CAS No. 127-00-4
 

Chemical Formula: C 3 7 H ClO Molecular Weight: 94.54

Synonyms: Chlorohydrin, 1-chloro-2-hydroxypropane, 1-chloroisopropyl alcohol, propylene-%-chlorohydrin, sec-propylene chlorohydrin 

CHEMICAL AND PHYSICAL PROPERTIES 

1-Chloro-2-propanol and 2-chloro-1-propanol are the 

isomers of propylene chlorohydrin. The chemical and 

physical properties of the two isomers are summarized 

in Table 1. 

PRODUCTION, USE, 

AND HUMAN EXPOSURE 

Propylene chlorohydrins, organic compounds containing chlorine and hydroxyl groups, are unknown as 

natural products; they are manufactured by the reaction of propylene with hypochlorous acid. The production of a mixture of 1-chloro-2-propanol and 

2-chloro-1-propanol in the United States in 1976 was 8 estimated to be greater than 8.1 × 10 kg or 1.78 billion pounds (USEPA, 1977). 

The chlorine in propylene chlorohydrins is labile; it 

dehydrohalogenates readily through an intermediate 

epoxide, which then hydrolyzes to glycols (KirkOthmer, 1985). Propylene chlorohydrins are used 

commercially as chemical intermediates in the manufacture of propylene oxide, a starting material for the 

production of polyurethane polyols and propylene 

glycol. Approximately half of the propylene oxide 

produced in the United States in 1979 was from 

propylene chlorohydrins. Prior to 1969, all propylene 

oxide and most ethylene oxide produced in the United 

States were manufactured using propylene chlorohydrins (USEPA, 1977; SRI, 1980). 

Propylene chlorohydrins have been identified as 

potential air pollutants from chemical manufacturing 

plants (USEPA, 1976). However, no threshold limit 

values have been set for workplace air in the United 

States, no occupational standard for exposure to 

propylene chlorohydrins has been established by the 

Occupational Safety and Health Administration 

(OSHA), and no allowable limits for water or soil have 

been determined by the U.S. Environmental Protection 

Agency. 

Propylene chlorohydrins are generated from the 

hydrolysis of epichlorohydrin, a widely used chemical 

intermediate (Carr and Rosenkranz, 1978), and 

1-chloro-2-propanol has been identified in the 

headspace above a soil sample contaminated with 
14 1-Chloro-2-propanol, NTP TR 477 

TABLE 1 

Summary of the Chemical and Physical Properties of Isomers of Propylene Chlorohydrina 

1-Chloro-2-propanol 2-Chloro-1-propanol 

(sec-propylene chlorohydrin) (propylene chlorohydrin) 

Property CAS No. 127-00-4 CAS No. 78-89-70 

Molecular weight 94.54 94.54 

Form Colorless liquid Colorless liquid, pleasant odor 

Boiling point 126E to 127E C 133E to 134E C 

Flash point 52E C 52E C 

Density 

Solubilityb 

1.115 at 20E C 

Water, alcohol, diethyl ether 

1.103 at 20E C 

Water, alcohol, diethyl ether 

Refractive index 1.4392 at 20E C 1.4362 at 20E C 

Vapor pressure 4.9 mm Hg at 20E C — 

a Merck Index, 1989 b Lide, 1992 

degradation products of burned polyurethane foam 

used for thermal insulation (Schulting and Wils, 

1977). 

Propylene chlorohydrins are found in a broad spectrum of foodstuffs, including powdered and flaked 

foods, cereals, dried fruits, spices, cocoa, flour, and 

egg powder, that have been fumigated or cold sterilized with propylene oxide (Ragelis et al., 1966; 

Fishbein, 1969). Under conditions necessary for 

effective sterilization, propylene oxide reacts with 

naturally occurring inorganic chlorides in foods, 

forming propylene chlorohydrins (Wesley et al., 

1965). Concentrations of 1-chloro-2-propanol ranging 

from 4 ppm in cocoa to 47 ppm in glazed citron have 

been measured in foods fumigated with propylene 

oxide (Ragelis et al., 1968). Only 5 ppm propylene 

chlorohydrins are permitted as a food additive in 

modified food starch (Fed. Regist., 1969). 

ABSORPTION, DISTRIBUTION, 

METABOLISM, AND EXCRETION 

Experimental Animals 

Data from limited metabolism studies indicate that 

propylene chlorohydrins are partly excreted in 

the conjugated form in the urine of laboratory animals. 

Following oral administration of 140 mg/kg 2-chloro1-propanol to rabbits, 11% of the dose was excreted in 

the urine as its glucuronic acid conjugate (Williams, 

1959). In a study of the metabolism of 

1-halogenopropanes (Barnsley, 1966), 1-chloro-2­

propanol (0.5 mL) was administered as a 3.3% (w/v) 

solution in arachis oil. 2-Hydroxypropylmercapturic 

acid (N-acetyl-S-(2-hydroxypropyl)-L-cysteine) was 

identified as a urinary metabolite of 1-chloro2-propanol in the urine of male rats (strain not 

specified) 24 hours after a single subcutaneous 

injection. Jones and Gibson (1980) conducted in vitro 

studies of the metabolism of 1,2-dichloropropane using 

the methods of Barnsley (1966), proposed 1-chloro2-propanol as an intermediate metabolite to explain the 

presence of the N-acetyl-S-(2-hydroxypropyl)-cysteine 

found in the urine of male rats injected subcutaneously 

with 1,2-dichloropropane. Jones and Gibson (1980) 

also conducted in vivo studies in male Sprague-Dawley 

rats. Following subcutaneous injection of 100 mg 36 [ Cl]-1-chloro-2-propanol to a single rat, 4% of the 

administered radiolabel was excreted unchanged in the 

expired air. In addition, two major urinary 

metabolites identified in rats dosed orally with 

1-chloro-2-propanol (100 mg/kg per day for 4 days) 

were N-acetyl-S-(2-hydroxypropyl)-cysteine and 

$-chlorolactate. 

The disposition of 1-chloro-2-propanol was studied in 

male F344/N rats (aged 11 to 13 weeks) exposed by 

nose-only inhalation to approximately 8 or 80 ppm 

[

14C]-1-chloro-2-propanol for 6 hours (Bond et al., 

1988). The two major routes of 14C elimination were 

urinary and respiratory, which together accounted for 

about 80% of the total radiolabel recovered 70 hours 

after the end of the 6-hour exposure. At both 

exposure concentrations, most of the radiolabel was 

eliminated in urine during the first day after exposure. 

Half-lives for elimination were 3.9 hours for breath 

and 5 hours for urine. The results indicated that 
 

1-Chloro-2-propanol, NTP TR 477 15 

metabolism of 1-chloro-2-propanol was rapid and 

related linearly to the inhaled exposure concentration. 

Following inhalation, 1-chloro-2-propanol was widely distributed to tissues, rapidly metabolized, and 

eliminated. One hour after the end of the 6-hour 

exposure period, the kidney, liver, trachea, and nasal 

turbinates of 8 ppm rats contained 30 to 50 nmol 14C/g 

tissue, and those of 80 ppm rats contained 200 to 

350 nmol 14C/g tissue; other tissues contained less than 14 14 150 nmol C/g tissue. The tissue elimination of C 

was biphasic at both exposure concentrations, with a 

short-term elimination half-life of 1 to 4 hours and a 

long-term elimination half-life of 40 to 126 hours. No 

evidence of unmetabolized 1-chloro-2-propanol was 

seen in the tissues examined. Biliary excretion was a 

major route of elimination of 1-chloro-2-propanol; 

approximately 30% of the administered radiolabel 

was excreted in the bile within 10 hours. Three hours 

after exposure of rats to 80 ppm, two major metabolites were detected in the urine and three major 

metabolites were detected in liver. In both cases, one 

of these metabolites was identified as N-acetyl-S­

(hydroxypropyl)-cysteine and/or S-(2-hydroxypropyl)­

cysteine, which is consistent with data obtained by 

Barnsley (1966) and Jones and Gibson (1980). These 

metabolites appear to be derived from the conjugation 

of 1-chloro-2-propanol with glutathione. Bond et al. 

(1988) also investigated whether the exhaled radiolabeled CO was derived from the second and/or third 2 

carbon atoms using 1-chloro-2-propanol labeled with 14C either at both carbons or only at the second carbon 

atom. Less 14CO2 was detected in rats exposed to 14 [2- C]-1-chloro-2-propanol than in rats exposed 14 to [2,3- C]-1-chloro-2-propanol, indicating that the 

second and third carbon atoms are both metabolized, 

at least in part, to CO . 2 

Humans 

No information on the absorption, distribution, 

metabolism, or excretion of 1-chloro-2-propanol in 

humans was found in the literature. 

TOXICITY 

Experimental Animals 

The acute oral (gavage) LD50 for a commercial grade 

of propylene chlorohydrins was 0.22 mL/kg in 

Carworth-Wistar rats (4 to 5 weeks of age) and 

0.72 g/kg in guinea pigs; narcosis was observed in 

rats and guinea pigs at LD50 doses and greater (Smyth 

et al., 1941, 1969). Data from the Food and Drug 

Administration indicated an acute oral LD50 of 

217 mg/kg for propylene chlorohydrins in the rat 

(strain not specified) (FAO, 1974). The acute oral 

LD50 for 1-chloro-2-propanol in rats was 0.1 to 

0.3 g/kg (Patty’s, 1982). Dogs (number not specified) 

survived an oral dose of 150 mg propylene 

chlorohydrin/kg (FAO, 1974). At 200 mg/kg, one of 

seven treated dogs died; single doses of 250 mg/kg or

greater were lethal to all six dogs in each group. The 

dermal LD50 for propylene chlorohydrin (24-hour 

plastic-covered contact on clipped skin) was 

0.48 mL/kg in male New Zealand rabbits (Smyth 

et al., 1969). 

No skin irritation was observed in a single New 

Zealand rabbit 24 hours after the uncovered topical 

application of 0.01 mL (approximately 10 mg) neat 

propylene chlorohydrins to the clipped skin of the 

abdomen (Smyth et al., 1969). Severe (grade 8 on a 

scale of 1 to 10) corneal injury resulted from instillation of 0.005 mL (approximately 5 mg) neat propylene 

chlorohydrins or an excess of a 40% solution in 

propylene glycol into the eye of albino rabbits 

(Carpenter and Smyth, 1946). 

Inhalation of 500 ppm commercial propylene chlorohydrins resulted in the death of one of six rats after 

a 4-hour exposure period (Smyth et al., 1969). In an 

inhalation study by Bond et al. (1988), there were no 

overt acute toxic effects of 1-chloro-2-propanol at 

exposure concentrations up to 80 ppm. 

In an inhalation study by Gage (1970) using AlderleyPark specific-pathogen-free rats, exposure of two male 

and two female rats to a vapor concentration 

of 1,000 ppm 1-chloro-2-propanol for two 6-hour 

periods at a 3-day interval resulted in lethargy after the 

first exposure and the death of one rat after the second 

exposure. In the animal that died, necropsy findings 

included a pale liver and edematous, congested lungs; 

histopathology findings included swollen, vacuolated 

hepatocytes with nuclear degeneration and pulmonary 

interstitial inflammation. Following fifteen 6-hour 

exposures of two male and two female rats to 

250 ppm, lethargy, irregular weight gain, 

and congestion and perivascular edema of the lungs 

were observed. Fifteen 6-hour exposures to 100 ppm 

resulted in no findings of toxicity in four male and 

four female rats; however, histopathologic findings 

included congestion and perivascular edema of the 
16 1-Chloro-2-propanol, NTP TR 477 

lungs. No toxic or histopathologic effects were 

observed in four males or four females following 

fourteen 6-hour exposures to 30 ppm 1-chloro2-propanol. 

Humans 

No information on toxicity in humans was reported in 

the literature. 

CARCINOGENICITY 

Experimental Animals 

The carcinogenicity of 1-chloro-2-propanol was evaluated in a bioassay system involving induction of pulmonary adenomas in strain A mice (Theiss et al., 

1979). Groups of 10 male and 10 female mice were 

given intraperitoneal injections of 1-chloro-2-propanol 

in tricaprylin three times per week (total of 

24 injections) at concentrations of 0.53, 1.06, or 

2.12 mmol/kg. Twenty-four weeks after the first 

injection, the number of adenomas on the lung surface 

was counted. No statistically significant differences in 

the average number of lung neoplasms per mouse were 

observed between treated and control mice. 

Humans 

Several studies in the literature examined mortality in 

men assigned to a chlorohydrin unit that produced 

ethylene chlorohydrin and/or propylene chlorohydrin 

from 1925 and 1957. Greenberg et al. (1990) reported statistically significant excess mortality due to 

pancreatic cancer and leukemia in men assigned to the 

chlorohydrin unit for 2 years or more during the 

period from 1925 through 1957; six deaths due to 

pancreatic cancer (0.7 expected) and three deaths due 

to leukemia (0.4 expected) occurred. A fourth death 

due to leukemia occurred in a man assigned to the 

chlorohydrin unit for less than 2 years. Nine of the 

ten decedents worked in the chlorohydrin unit between 

1935 and 1945. The six men who died from pancreatic cancer were first assigned to the chlorohydrin 

unit between 1929 and 1944; their cumulative duration 

of assignments ranged from 2 to 30 years and 

averaged 12 years, and they died between 26 and 

48 years after their first chlorohydrin assignment. The 

four men who died from leukemia were first assigned 

to the chlorohydrin unit prior to 1937; the average 

duration of their assignments was 9 years and ranged 

from less than 1 to 16 years. They died between 18 to 

39 years after their first chlorohydrin assignment. 

Significant trends with duration of assignment to the 

chlorohydrin unit were found for both cancers. The 

authors concluded that the observed excesses of 

pancreatic cancer and leukemia were primarily 

associated with the production of ethylene 

chlorohydrin and/or propylene chlorohydrins although 

quantitative measurements of exposure were not 

available. 

A second retrospective study was conducted at the 

same chemical plant to verify the previous findings of 

cancer excesses among 278 men with a mean duration 

of assignment to the chlorohydrin unit of 5.9 years 

and mean duration of follow-up of 36.5 years (Benson 

and Teta, 1993). During 1979 through 1988, two 

additional deaths from pancreatic cancer (0.9 expected) 

were reported, bringing the total to 8 observed versus 

1.6 deaths expected. There were no additional deaths 

from leukemia, but the three- to fourfold increase in 

risk for lymphopoietic cancers persisted due to new 

cases of non-Hodgkin’s lymphoma and multiple 

myeloma. Increases in risk were seen for total cancer, 

pancreatic cancer, all lymphatic and hematopoietic 

cancers, and leukemia with increasing durations of 

assignment to the chlorohydrin unit. The data were 

insufficient to conclusively identify the causative agent 

or combination of agents. However, the authors suggested that high exposure to ethylene dichloride, 

perhaps in combination with other chlorinated 

hydrocarbons, was the most likely agent. IARC has 

found insufficient epidemiological studies for ethylene 

dichloride, bischloro ethylene, ethylene chlorohydrin, 

and propylene chlorohydrin to determine the carcinogenic potential to humans (IARC, 1979). 

REPRODUCTIVE 

AND DEVELOPMENTAL TOXICITY 

Experimental Animals 

Administration of gavage doses of 8, 20, 50, or 

125 mg propylene chlorohydrin/kg body weight per 

day to groups of five female rats on gestation days 6 

to 15 had no effect on maternal growth or the growth 

and survival of fetuses (Exxon Chemical Company, 

1980). There was a slight decrease in embryo survival 

in the 8 and 125 mg/kg groups, and two fetuses (dose 

level not specified) showed gross malformations. The 

investigators concluded that propylene chlorohydrin 

may be a weak teratogen. 
 

1-Chloro-2-propanol, NTP TR 477 17 

Humans 

No information on the reproductive or developmental 

toxicity in humans was reported in the literature. 

GENETIC TOXICITY 

1-Chloro-2-propanol (both 97% pure and 70% technical grade) was mutagenic in Salmonella typhimurium 

strains TA100 and TA1535, with and without induced 

S9 metabolic activation enzymes; no mutagenicity was 

detected in strains TA97, TA98, and TA1537, which 

revert via a frameshift mechanism (Carr and 

Rosenkranz, 1978; Pfeiffer and Dunkelberg, 1980; 

Zeiger et al., 1987). The chemical was also positive 

in the Escherichia coli pol A assay for DNA damage 

(Hyman et al., 1980). 1-Chloro-2-propanol (technical grade) induced sex-linked recessive lethal mutations in germ cells of male Drosophila melanogaster 

when administered by injection; however, results of a 

subsequent test for induction of reciprocal translocations in germ cells of male D. melanogaster were 

negative (Foureman et al., 1994). 

A mixture (proportions not stated) of 2-chloro1-propanol and 1-chloro-2-propanol was tested for 

mutagenicity in S. typhimurium, and positive results 

were reported with strains TA100 and TA1535 in the 

absence of S9 (Pfeiffer and Dunkelberg, 1980). 

Biles and Piper (1983) confirmed this response in 

S. typhimurium with a 75:25 mixture of 1-chloro2-propanol:2-chloro-1-propanol and further reported 

that addition of S9 enhanced the mutagenic response. 

In addition, they reported positive results with 

this mixture in the L5178Y mouse lymphoma 

assay, with and without S9. Finally, these authors 

reported that this mixture in doses of 10, 31, and 

100 mg/kg per day for 5 days induced significant 

dose-related increases in chromosomal aberrations, 

consisting mainly of chromatid breaks, in rat bone 

marrow cells. 

STUDY RATIONALE 

The National Cancer Institute nominated 1-chloro2-propanol and 2-chloro-1-propanol for carcinogenesis 

evaluation because these chemicals may be present in 

food fumigated with propylene oxide. The pure 

chemicals were not available and, therefore, technical 

grade 1-chloro-2-propanol (approximately 75% 

1-chloro-2-propanol and 25% 2-chloro-1-propanol) 

was evaluated in the NTP studies. Drinking water was 

selected as the route of administration because human 

exposure may occur by the oral route. 
18 1-Chloro-2-propanol, NTP TR 477 
19 

MATERIALS AND METHODS
 

PROCUREMENT 

AND CHARACTERIZATION 

OF 1-CHLORO-2-PROPANOL 

Technical grade 1-chloro-2-propanol (approximately 

75% 1-chloro-2-propanol and 25% 2-chloro-1­

propanol) was obtained from Eastman Kodak 

Laboratory Chemicals (Rochester, NY) in one lot 

(B15). Identity, purity, and stability analyses were 

conducted by the analytical chemistry laboratory, 

Midwest Research Institute (Kansas City, MO) 

(Appendix J). Reports on analyses performed in 

support of the 1-chloro-2-propanol studies are on file 

at the National Institute of Environmental Health 

Sciences. 

The major component of the test chemical, a clear, 

colorless liquid, was identified as 1-chloro-2-propanol 

by infrared, ultraviolet/visible, and nuclear magnetic 

resonance spectroscopy. The purity of lot B15 was 

determined by elemental analyses, Karl Fischer water 

analysis, free acid titration, and gas chromatography. 

Elemental analyses for carbon, chlorine, and hydrogen 

were in agreement with the theoretical values for 

1-chloro-2-propanol. Karl Fischer water analysis 

indicated 0.62% ± 0.02% water. Free acid titration 

indicated a hydrochloric acid content of 

1,149 ± 2 ppm, equivalent to 0.0315 ± 0.0001 mEq 

of acid per gram of sample. Gas chromatography 

using one system indicated two major peaks and two 

impurities with a combined area of 0.47% relative to 

the total major peak area. Gas chromatography using 

another system indicated two major peaks and three 

impurities with a combined area of 0.67% relative to 

the total major peak area. No additional impurities 

with areas of 0.1% or greater relative to the major 

peak were detected using either system. The second 

major peak represents 2-chloro-1-propanol, a positional isomer of 1-chloro-2-propanol. The concentrations of 1-chloro-2-propanol and 2-chloro-1-propanol 

were estimated to be approximately 75% to 76% and 

24% to 25%, respectively. 

Stability studies of the bulk chemical were performed 

by the analytical chemistry laboratory using gas chromatography. These studies indicated that 1-chloro-2­

propanol was stable as a bulk chemical for 2 weeks 

when stored protected from light at temperatures up to 

60E C. To ensure stability, the bulk chemical was 

stored at 5.5E C (14-day and 14-week studies) or 1E to 

8E C (2-year studies) protected from light in sealed 

glass containers. Stability was monitored during the 

14-week studies using gas chromatography and free 

acid titration and during the 14-day and 2-year studies 

using gas chromatography. No degradation of the 

bulk chemical was detected. 

PREPARATION AND ANALYSIS 

OF DOSE FORMULATIONS 

The dose formulations were prepared twice during the 

14-day studies, every 2 weeks in the 14-week studies, 

and approximately every 2 weeks in the 2-year studies 

by mixing 1-chloro-2-propanol with ultraviolet lighttreated, deionized water for the 14-day and 14-week 

studies and with deionized water for the 2-year studies 

(Table J1). The dose formulations were stored in 

closed bottles in the dark at room temperature prior to 

use. In the animal rooms, the drinking water bottles 

were changed twice per week. 

Periodic analyses of the dose formulations of 1-chloro2-propanol were conducted at the study laboratory 

using gas chromatography. During the 14-day studies, 

dose formulations were analyzed once per week 

(Table J2). Dose formulations were analyzed at the 

beginning, midpoint, and end of the 14-week studies 

(Table J3). During the 2-year studies, dose 

formulations were analyzed approximately every 

8 weeks (Table J4). Through the 14-day, 14-week, 

and 2-year studies, all but one of the 149 dose 

formulations analyzed was within 10% of the target 

concentration; that formulation was remixed. 

Similarly, all but one of 54 animal room 
 

20 1-Chloro-2-propanol, NTP TR 477 

samples was within 10% of target concentration. One 

250 ppm animal room sample was outside of 

specifications and this was attributed to technical 

error; the dose was contaminated with a 650 ppm rat 

dose formulation. Results of periodic referee analyses 

performed by the analytical chemistry laboratory 

agreed with the results obtained by the study 

laboratory for the 14-week studies (Table J5). 

14-DAY STUDIES 

Male and female F344/N rats and B6C3F1 mice were

obtained from Taconic Farms (Germantown, NY). On 

receipt, the rats and mice were 4 weeks old. Animals 

were quarantined for 11 to 14 days and were 6 weeks 

old on the first day of the studies. Groups of 10 male 

and 10 female rats and mice were exposed to 1-chloro2-propanol at concentrations of 0, 100, 333, 1,000, 

3,300, or 10,000 ppm in drinking water. Feed and 

water were available ad libitum. Rats were housed 

five per cage, and mice were housed individually. 

Clinical findings were recorded daily for rats and 

mice. Water consumption was recorded weekly. The 

animals were weighed initially, weekly, and at the end 

of the studies. Details of the study design and animal 

maintenance are summarized in Table 2. 

A necropsy was performed on all rats and mice. The 

brain, heart, right kidney, liver, lung, right testis, and 

thymus were weighed. Complete histopathologic 

examinations were performed on 0 and 10,000 ppm 

rats and mice. Additionally, the following tissues 

were examined to a no-effect level: bone marrow, 

pancreas, spleen, and uterus of rats and liver, 

pancreas, spleen, and thymus of mice. Table 2 lists 

the tissues and organs examined. 

14-WEEK STUDIES 

The 14-week studies were conducted to evaluate the 

cumulative toxic effects of repeated exposure to 

1-chloro-2-propanol 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 (Germantown, NY). On 

receipt, the rats and mice were approximately 4 weeks 

old. Animals were quarantined for 11 to 

12 days and were 6 weeks old on the first day of the 

studies. Before initiation of the studies, five male and 

five female rats and mice were randomly selected for 

parasite evaluation and gross observation for evidence 

of disease. At the end of the studies, serologic analyses were performed on five male and five female 

control rats and sentinel mice using the protocols of 

the NTP Sentinel Animal Program (Appendix M). 

Groups of 10 male and 10 female rats and mice were 

given drinking water containing 1-chloro-2-propanol 

at concentrations of 0, 33, 100, 330, 1,000, or 

3,300 ppm. Groups of 10 male and 10 female rats 

exposed to the same concentrations were designated as 

special study animals for clinical pathology evaluations. Feed and water were available ad libitum. 

Rats were housed five per cage, and mice were housed 

individually. Clinical findings were recorded weekly 

for rats and mice. Water consumption was recorded 

weekly. The animals were weighed initially, weekly, 

and at the end of the studies. Details of the study 

design and animal maintenance are summarized in 

Table 2. 

On days 3, 15, and 45, clinical chemistry evaluations 

were performed for all male and female rats designated 

for special studies. At study termination, hematology 

and clinical chemistry evaluations were performed for 

all special study rats. Starting on day 14 and the day 

prior to study termination, timed urine collections 

were performed for all special study rats for urine 

chemistry evaluations. Hematology evaluations were 

performed for all core study mice at the end of the 

study. At all time points, rats and mice were 

anesthetized with a CO 2 2 /O mixture and blood was 

drawn from the retroorbital sinus. Blood for hematology determinations was placed in tubes containing 

potassium EDTA as the anticoagulant; blood for 

clinical chemistry analyses was placed in tubes without 

anticoagulant, allowed to clot at room temperature, 

and centrifuged, and the serum was separated. For 

urinalysis studies, rats were placed individually into 

metabolism cages for a 16-hour urine collection. 

During urine collection, containers were kept chilled 

with ice to minimize evaporation and suppress 

bacterial growth. Animals had access to food and 

water during the urine collection period. Table 2 lists 

the hematology, clinical chemistry, and urinalysis 

parameters evaluated. 
1-Chloro-2-propanol, NTP TR 477 21 

Hematology determinations including erythrocyte and 

leukocyte counts, hemoglobin concentration, hematocrit, mean cell volume, mean cell hemoglobin, and 

mean cell hemoglobin concentration were performed 

on a Coulter Hematology Analyzer, Model S560 

(Coulter Electronics, Hialeah, FL). Platelet counts 

were determined with a Baker Series 810 Whole Blood 

Platelet Analyzer (Serono-Baker Diagnostics, 

Allentown, PA). Leukocyte differential and nucleated 

erythrocyte counts and morphologic evaluation of 

blood cells were determined by light microscopic 

examination of blood films stained with Romanowsky 

stain. Blood smears stained with brilliant cresyl blue 

were examined microscopically for the quantitative 

determination of reticulocytes. Clinical chemistry and 

urinalysis evaluations were performed on a Gemini 

Miniature Centrifugal Analyzer (Electronucleonics, 

Inc., Fairfield, NJ) using commercially available 

reagents. Urine specific gravity was determined by 

refractometry; urine volume was a calculated value 

based on measurements of mass and specific gravity. 

At the end of the 14-week studies, samples were 

collected for sperm morphology and vaginal cytology 

evaluations on rats and mice exposed to 0, 33, 330, 

and 3,300 ppm. The parameters evaluated are listed 

in Table 2. Methods used were those described in the 

NTP’s sperm morphology and vaginal cytology 

evaluations protocol (NTP, 1985a). For 7 consecutive 

days prior to the 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 morphology, count, and motility. The right 

testis and right 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 right 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 65E C. Sperm density was then 

determined microscopically with the aid of a 

hemacytometer. Four sperm morphology slides were 

prepared for each animal evaluated. An aliquot of 

killed sperm suspension was stained in a test tube, 

spread on a microscope slide under a coverslip, and 

examined. 

A necropsy was performed on all animals. The brain, 

heart, right kidney, liver, lung, right testis, and 

thymus were weighed. Tissues for microscopic examination were fixed and preserved in 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. A complete histopathologic examination was performed on 0 and 

3,300 ppm rats and mice. In addition, the kidney of 

mice, the liver of male rats and male and female mice, 

and the pancreas of rats and mice were examined in 

33, 100, 330, and 1,000 ppm groups. Table 2 lists 

the tissues and organs routinely examined. 

2-YEAR STUDIES 

Study Design 

Groups of 50 male and 50 female rats were given 

drinking water containing 1-chloro-2-propanol at 

concentrations of 0, 150, 325, or 650 ppm. Groups of 

50 male and 50 female mice were exposed to 1-chloro2-propanol in drinking water at concentrations of 0, 

250, 500, or 1,000 ppm. 

Source and Specification of Animals 

Male and female F344/N rats and B6C3F mice were 1 

obtained from Taconic Farms (Germantown, NY) for 

use in the 2-year studies. Rats and mice were quarantined for 12 to 15 days before the beginning of the 

studies. Five male and five female rats and mice were 

randomly selected for parasite evaluation and gross 

observation of disease. Rats and mice were approximately 7 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 M). 
 

22 1-Chloro-2-propanol, NTP TR 477 

Animal Maintenance 

Rats were housed five per cage, and mice were housed 

individually. Feed and water were available 

ad libitum. Water consumption was measured approximately monthly. Cages were changed three times per 

week for male rats, two times per week for female 

rats, and once per week for mice, and racks were 

rotated once every two weeks. Further details of 

animal maintenance are given in Table 2. Information 

on feed composition and contaminants is provided in 

Appendix L. 

Clinical Examinations and Pathology 

All animals were observed twice daily. Clinical 

findings were recorded monthly, except for an 

additional observation at week 6 for male mice. Body 

weights were recorded initially, weekly for 14 weeks, 

monthly thereafter, and at the end of the studies. 

A complete necropsy and microscopic examination 

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, 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 (i.e., adrenal gland, kidney, ovary), samples 

from each organ were examined. Tissues examined 

microscopically are listed in Table 2. 

Microscopic evaluations were completed by the study 

laboratory pathologist, and the pathology data were 

entered into the Toxicology Data Management 

System. The microscopic slides, paraffin blocks, and 

residual wet tissues were sent to the 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 mammary gland, pancreas (for acinar cell atrophy), 

and pituitary gland of rats, the liver, lung, and 

mesentery lymph nodes of male and female mice, and 

the pituitary gland pars distalis (for hyperplasia) of 

female mice. 

The quality assessment report and the reviewed slides 

were submitted to the NTP Pathology Working Group 

(PWG) chairperson, who reviewed the selected tissues 

and addressed any inconsistencies in the diagnosis 

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 chairperson 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). 
1-Chloro-2-propanol, NTP TR 477 23 

TABLE 2 

Experimental Design and Materials and Methods in the Drinking Water Studies of 1-Chloro-2-propanol 

14-Day Studies 14-Week Studies 2-Year Studies 

Study Laboratory 

SRI International (Menlo Park, CA) SRI International (Menlo Park, CA) TSI Mason Laboratories (Worcester, MA) 

Strain and Species 

Rats: F344/N 

Mice: B6C3F1 

Rats: 

Mice: 

F344/N 

B6C3F1 

Rats: 

Mice: 

F344/N 

B6C3F1 

Animal Source 

Taconic Farms (Germantown, NY) Taconic Farms (Germantown, NY) Taconic Farms (Germantown, NY) 

Time Held Before Studies 

Rats: 11 days (males) or 12 days (females) 

Mice: 13 days (males) or 14 days (females) 

Rats: 

Mice: 

11 days (males) or 12 days (females) 

11 days (males) or 12 days (females) 

Rats: 

Mice: 

12 days (males) or 14 days (females) 

13 days (males) or 15 days (females) 

Average Age When Studies Began 

6 weeks 6 weeks 7 weeks 

Date of First Exposure 

Rats: 15 September 1986 (males) 

16 September 1986 (females) 

Mice: 17 September 1986 (males) 

18 September 1986 (females) 

Rats: 

Mice: 

9 February 1987 (males) 

10 February 1987 (females) 

2 February 1987 (males) 

3 February 1987 (females) 

Rats: 

Mice: 

5 February 1991 (males) 

7 February 1991 (females) 

2 January 1991 (males) 

4 January 1991 (females) 

Duration of Exposure 

14 days 14 weeks 105 weeks 

Date of Last Exposure 

Rats: 29 September 1986 (males) 

30 September 1986 (females) 

Mice: 1 October 1986 (males) 

2 October 1986 (females) 

Rats: 

Mice: 

11 May 1987 (males) 

12 May 1987 (females) 

4 May 1987 (males) 

5 May 1987 (females) 

Rats: 

Mice: 

2 February 1993 (males) 

9-10 February 1993 (females) 

30-31 December 1992 (males) 

7 January 1993 (females) 

Necropsy Dates 

Rats: 29 September 1986 (males) 

30 September 1986 (females) 

Mice: 1 October 1986 (males) 

2 October 1986 (females) 

Rats: 

Mice: 

11 May 1987 (males) 

12 May 1987 (females) 

4 May 1987 (males) 

5 May 1987 (females) 

Rats: 

Mice: 

2 February 1993 (males) 

9-10 February 1993 (females) 

30-31 December 1992 (males) 

7 January 1993 (females) 

Average Age at Necropsy 

8 weeks 19 weeks 111 weeks (males) or 112 weeks (females) 

Size of Study Groups 

10 males and 10 females 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 14-day studies Same as 14-day studies 

Animals per Cage 

Rats: 5 

Mice: 1 

Rats: 

Mice: 

5 

1 

Rats: 

Mice: 

5 

1 
24 1-Chloro-2-propanol, NTP TR 477 

TABLE 2 

Experimental Design and Materials and Methods in the Drinking Water Studies of 1-Chloro-2-propanol 

14-Day Studies 14-Week Studies 2-Year Studies 

Method of Animal Identification 

Toe clip 

Diet 

NIH-07 open formula block diet (Zeigler 

Brothers, Inc., Gardners, PA), available 

ad libitum, changed once per week 

Water 

UV treated, deionized water (Menlo Park 

municipal supply) via glass sipper tube water 

bottles (Lab Products, Rochelle Park, NJ), 

available ad libitum, changed twice per week 

Cages 

Polycarbonate cages (Lab Products, 

Rochelle Park, NJ), changed twice per week 

Bedding 

Sani-Chips (P.J. Murphy Forest Products 

Corp., Rochelle Park, NJ), changed twice 

per week 

Cage Filters 

Spun bonded polyester fabric (Snow 

Filtration, Cincinnati, OH) 

Racks 

Stainless-steel (Lab Products, Rochelle 

Park, NJ) 

Animal Room Environment 

Temperature: 22.2E-25.0E C 

Relative humidity: 41%-60% 

Room fluorescent light: 12 hours/day 

Room air changes: 10/hour 

Exposure Concentrations 

0, 100, 333, 1,000, 3,300, or 10,000 ppm 

in drinking water, available ad libitum 

Toe clip 

Same as 14-day studies 

Same as 14-day studies 

Same as 14-day studies, except changed 

weekly for mice 

Same as 14-day studies 

Same as 14-day studies, except changed 

once every two weeks 

Same as 14-day studies, except changed 

once every two weeks 

Temperature: 18.9E-27.2E C (rats) 

18.9E-25.6E C (mice) 

Relative humidity: 24%-77% (rats) 

18%-65% (mice) 

Room fluorescent light: 12 hours/day 

Room air changes: 10/hour 

0, 33, 100, 330, 1,000, or 3,300 ppm in 

drinking water, available ad libitum 

Tail tattoo 

NIH-07 open formula pelleted diet (Zeigler 

Brothers, Inc., Gardners, PA), available 

ad libitum, changed once per week 

Deionized water (Worcester municipal supply) 

via glass sipper tube water bottles (Allentown 

Cage Co. Inc., Allentown, PA), available 

ad libitum, changed twice per week 

Same as 14-day studies, except changed 

three times per week for male rats, two times 

per week for female rats, and once per week 

for mice 

Same as 14-day studies, except changed 

three times per week for male rats, two times 

per week for female rats, and changed once 

per week for mice 

Same as 14-week studies 

Same as 14-week studies 

Temperature: 18.3E-24.4E C (rats) 

20.6E-24.4E C (mice) 

Relative humidity: 8%-78% (rats) 

10%-68% (mice) 

Room fluorescent light: 12 hours/day 

Room air changes: 10/hour 

Rats: 0, 150, 325, or 650 ppm in drinking 

water, available ad libitum 

Mice: 0, 250, 500, or 1,000 ppm in drinking 

water, available ad libitum 
1-Chloro-2-propanol, NTP TR 477 25 

TABLE 2 

Experimental Design and Materials and Methods in the Drinking Water Studies of 1-Chloro-2-propanol 

14-Day Studies 14-Week Studies 2-Year Studies 

Type and Frequency of Observation 

Observed twice daily; animals were weighed Observed twice daily; animals were weighed Observed twice daily; animals were weighed 

initially, weekly, and at the end of the initially, weekly, and at the end of the initially, weekly for 13 weeks, monthly 

studies; clinical findings were recorded studies; clinical findings were recorded thereafter, and at the end of the studies. 

daily. Water consumption was recorded weekly. Water consumption was recorded Clinical findings were recorded monthly, 

weekly. weekly. except for an additional observation at week 6 

for male mice. Water consumption was 

measured approximately monthly. 

Method of Sacrifice 

CO2 asphyxiation CO asphyxiation 2 CO asphyxiation 2 

Necropsy 

Necropsy performed on all animals. Organs Necropsy performed on all animals. Organs Necropsy performed on all animals. 

weighed were brain, heart, right kidney, weighed were brain, heart, right kidney, 

liver, lung, right testis, and thymus. liver, lung, right testis, and thymus. 

Clinical Pathology 

None Blood was collected from the retroorbital None 

sinus of special study rats and core study 

mice at week 14 for hematology analyses. 

Blood was collected from the retroorbital 

sinus of special study rats on days 3, 15, and 

45, and at 14 weeks for clinical chemistry. 

Rats were placed in metabolism cages for 

16-hour urine collection at the end of the 

study. 

Hematology: hematocrit; hemoglobin 

concentration; erythrocyte, reticulocyte, 

nucleated erythrocyte, and platelet counts; 

mean cell volume; mean cell hemoglobin; 

mean cell hemoglobin concentration; and 

total leukocyte count and differentials 

Clinical chemistry: creatinine, albumin, 

alanine aminotransferase, creatine kinase, 

sorbitol dehydrogenase, and 

(-glutamyltransferase 

Urinalysis: glucose, protein, volume, and 

specific gravity 
26 1-Chloro-2-propanol, NTP TR 477 

TABLE 2 

Experimental Design and Materials and Methods in the Drinking Water Studies of 1-Chloro-2-propanol 

14-Day Studies 14-Week Studies 2-Year Studies 

Histopathology 

Complete histopathology was performed on 

0 and 10,000 ppm rats and mice. In 

addition to gross lesions and tissue masses, 

the following tissues were examined: 

adrenal gland, bone (including marrow), 

brain, clitoral gland, esophagus, gallbladder 

(mice), heart, large intestine (cecum, colon, 

and rectum), small intestine (duodenum, 

jejunum, and ileum), kidney, liver, lung 

(and mainstem bronchi), lymph nodes 

(mandibular and mesenteric), mammary 

gland (with adjacent skin), nose, ovary, 

pancreas, parathyroid gland, pituitary gland, 

preputial gland, prostate gland, salivary 

gland, spleen, stomach (forestomach and 

glandular), testis (with epididymis and 

seminal vesicle), thymus, thyroid gland, 

trachea, urinary bladder, and uterus. In 

addition, bone marrow in 330 ppm female 

rats and 1,000 and 3,300 ppm male and 

female rats; uterus in all female rats; liver in 

all mice; spleen in 1,000 ppm rats and 3,300 

ppm rats and mice; and thymus in 3,300 

ppm female rats and female mice were 

examined. 

Sperm Morphology and Vaginal Cytology 

None 

Complete histopathology was performed on 

0 and 3,300 ppm rats and mice. In addition 

to gross lesions and tissue masses, the 

following tissues were examined: adrenal 

gland, bone (including marrow), brain, 

clitoral gland, esophagus, gallbladder 

(mice), heart, large intestine (cecum, colon, 

and rectum), small intestine (duodenum, 

jejunum, and ileum), kidney, liver, lung 

(and mainstem bronchi), lymph nodes 

(mandibular and mesenteric), mammary 

gland (with adjacent skin), nose, ovary, 

pancreas, parathyroid gland, pituitary gland, 

preputial gland, prostate gland, salivary 

gland, spleen, stomach (forestomach and 

glandular), testis (with epididymis and 

seminal vesicle), thymus, thyroid gland, 

trachea, urinary bladder, and uterus. In 

addition, the kidney of mice, the liver of 

male rats and male and female mice, and the 

pancreas of rats and mice were examined in 

all remaining exposure groups. 

At the end of the studies, sperm samples 

were collected from all male animals in the 

0, 33, 330, and 3,300 ppm exposure groups 

for sperm morphology evaluations. The 

following parameters were evaluated: 

epididymal sperm concentration, 

morphology, and motility. The right cauda 

epididymis, epididymis, and testis were 

weighed. Vaginal samples were collected 

for up to 7 consecutive days prior to the end 

of the studies from all females exposed to 0, 

33, 330, or 3,300 ppm for vaginal cytology 

evaluations. The parameters evaluated were 

relative frequency of estrous stages and 

estrous cycle length. 

Complete histopathology was performed all 

rats and mice. In addition to gross lesions and 

tissue masses, the following tissues were 

examined: adrenal gland, bone (including 

marrow), brain, clitoral gland, esophagus, 

gallbladder (mice), heart, large intestine 

(cecum, colon, and rectum), small intestine 

(duodenum, jejunum, and ileum), kidney, 

liver, lung (and mainstem bronchi), lymph 

nodes (mandibular and mesenteric), mammary 

gland (with adjacent skin), nose, ovary, 

pancreas, parathyroid gland, pituitary gland, 

preputial gland, prostate gland, salivary gland, 

spleen, stomach (forestomach and glandular), 

testis (with epididymis and seminal vesicle), 

thymus, thyroid gland, trachea, urinary 

bladder, and uterus. 

None 
1-Chloro-2-propanol, NTP TR 477 27 

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 from 

the survival analyses; 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 

as presented in Tables A1, A5, B1, B4, C1, C4, D1, 

and D5 are given as the number of animals bearing 

such lesions at a specific anatomic site and the number 

of animals with that site examined microscopically. 

For calculation of statistical significance, the incidences of most neoplasms (Tables A3, B3, C3, and 

D3) 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., harderian gland, intestine, mammary 

gland, and skin) before microscopic evaluation, or 

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 A3, B3, C3, and D3 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, to 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 kù3 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). 

Tests of significance included pairwise comparisons of 

each exposed group with controls and a test for an 

overall exposure-related trend. Continuity-corrected 

tests were used in the analysis of lesion incidence, and 

reported P values are one sided. 

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 have 

approximately normal distributions, were analyzed 

with the parametric multiple comparison procedures of 

Dunnett (1955) and Williams (1971, 1972). Hematology, clinical chemistry, urinalysis, spermatid, and 

epididymal spermatozoal data, which have typically 

skewed distributions, were analyzed using the 

nonparametric multiple comparison methods of Shirley 

(1977) 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 
28 1-Chloro-2-propanol, NTP TR 477 

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 (1951) were examined by NTP 

personnel, and implausible values were eliminated 

from the analysis. Average severity values were analyzed for significance with the Mann-Whitney U test 

(Hollander and Wolfe, 1973). 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. 

Historical Control Data 

Although the concurrent control group is always the 

first and most appropriate control group used for 

evaluation, historical control data can be helpful in the 

overall assessment of neoplasm incidence in certain 

instances. Consequently, neoplasm incidences from 

the NTP historical control database, which is updated 

yearly, are included in the NTP reports for neoplasms 

appearing to show compound-related effects. 

QUALITY ASSURANCE METHODS 

The 14-week 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 covering 

completeness and accuracy of the pathology data, 

pathology specimens, final pathology tables, and a 

draft of this NTP Technical Report were conducted. 

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, so all 

comments had been resolved or were otherwise 

addressed during the preparation of this Technical 

Report. 

GENETIC TOXICOLOGY 

The genetic toxicity of 1-chloro-2-propanol was 

assessed by testing the ability of the chemical to 

induce mutations in various strains of Salmonella 

typhimurium, sister chromatid exchanges and chromosomal aberrations in cultured Chinese hamster ovary 

cells, sex-linked recessive lethal mutations in 

Drosophila melanogaster, and increases in the frequency of micronucleated erythrocytes in peripheral 

blood of mice. The protocols for these studies and the 

results are given in Appendix E. 

The genetic toxicity studies of 1-chloro-2-propanol are 

part of a larger effort by the NTP to develop a database that would permit the evaluation of carcinogenicity in experimental animals from the molecular 

structure and the effects of the chemical in short-term 

in vitro and in vivo genetic toxicity tests. These 

genetic toxicity tests were originally developed to 

study mechanisms of chemical-induced DNA damage 

and to predict carcinogenicity in animals, based on the 

electrophilicity theory of chemical mutagenesis and the 

somatic mutation theory of cancer (Miller and Miller, 

1977; Straus, 1981; Crawford, 1985). 

There is a strong correlation between a chemical’s 

potential electrophilicity (structural alert to DNA 

reactivity), mutagenicity in Salmonella, and carcinogenicity in rodents. The combination of electrophilicity and Salmonella mutagenicity is highly correlated 

with the induction of carcinogenicity in rats and mice 

and/or at multiple tissue sites (Ashby and Tennant, 

1991). Other in vitro genetic toxicity tests correlate 

less well with rodent carcinogenicity (Tennant et al., 

1987; Zeiger et al., 1990), although these other tests 

can provide information on the types of DNA and 

chromosome effects that can be induced by the 

chemical being investigated. Data from NTP studies 

show that a positive response in Salmonella is the 
1-Chloro-2-propanol, NTP TR 477 29 

most predictive in vitro test for rodent carcinogenicity Salmonella test (Shelby et al., 1993; Shelby and Witt, 

(89% of the Salmonella mutagens are rodent carcino- 1995). Positive responses in long-term peripheral 

gens), and that there is no complementarity among the blood micronucleus tests have not been formally evalin vitro genetic toxicity tests. That is, no battery of uated for their predictivity for rodent carcinogenicity. 

tests that included the Salmonella test improved the But, because of the theoretical and observed assopredictivity of the Salmonella test alone. ciations between induced genetic damage and adverse 

effects in somatic and germ cells, the determination of 

The predictivity for carcinogenicity of a positive in vivo genetic effects is important to the overall 

response in bone marrow chromosome aberration understanding of the risks associated with exposure to 

or micronucleus tests appears to be less than the a particular chemical. 
30 1-Chloro-2-propanol, NTP TR 477 
31 

RESULTS
 

R of 100, 330, 1,000, 3,300, or 10,000 ppm 1-chloro-2- ATS 

propanol resulted in average daily doses of approxi14-DAY STUDY mately 15, 45, 140, 260, or 265 mg 1-chloro-2-

Two 10,000 ppm female rats died before the end of propanol/kg body weight. Clinical findings observed 

the study (Table 3). The final mean body weights and in the 10,000 ppm males and females included eye 

body weight gains of 3,300 and 10,000 ppm males and exudate, hypoactivity, thinness, and hunched posture. 

females were significantly less than those of the 

controls; male and female rats in the 10,000 ppm The absolute and relative thymus weights of 

groups lost weight during the study. Water consump- 10,000 ppm males and females were significantly less 

tion by the 3,300 and 10,000 ppm males and females than those of the controls (Table H1). No other 

was significantly less than that by the controls biologically significant organ weight changes were 

throughout the study. Drinking water concentrations observed. 

TABLE 3 

Survival, Body Weights, and Water Consumption of Rats in the 14-Day Drinking Water Study 

of 1-Chloro-2-propanol 

Concentration 

(ppm) 

Survivala Initial 

Mean Body Weight (g) b 

Final Change 

Final Weight 

to Controls 

Relative 

(%) 

Consumption 

Water c 

Week 1 Week 2 

Male 

0 

100 

330 

1,000 

3,300 

10,000 

10/10 

10/10 

10/10 

10/10 

10/10 

10/10 

121 ± 2 

117 ± 3 

117 ± 3 

119 ± 3 

118 ± 2 

123 ± 2 

196 ± 3 

193 ± 5 

198 ± 3 

195 ± 5 

162 ± 4** 

88 ± 2** 

74 ± 2 

75 ± 2 

81 ± 2 

76 ± 3 

44 ± 2** 

–36 ± 3** 

99 

101 

100 

83 

45 

19.9 ± 0.1 

19.4 ± 0.1 

20.1 ± 0.4 

20.2 ± 0.0 

10.8 ± 0.0** 

2.7 ± 0.2** 

22.3 ± 0.1 

21.6 ± 0.7 

23.2 ± 1.6 

22.5 ± 0.1 

13.4 ± 0.2** 

3.2 ± 0.1** 

Female 

0 

100 

330 

1,000 

3,300 

10,000

10/10 

10/10 

10/10 

10/10 

10/10 

8/10d 

105 ± 2 

104 ± 2 

103 ± 2 

105 ± 2 

103 ± 2 

103 ± 2 

136 ± 2 

139 ± 2 

139 ± 2 

139 ± 3 

123 ± 1** 

67 ± 3** 

31 ± 1 

35 ± 1 

36 ± 1 

34 ± 1 

20 ± 1** 

–36 ± 3** 

102 

102 

102 

90 

49 

18.2 ± 0.9 

17.5 ± 0.3 

17.9 ± 0.8 

17.6 ± 0.3 

8.5 ± 0.1** 

2.0 ± 0.2** 

18.0 ± 2.1 

17.9 ± 0.4 

18.7 ± 1.1

17.8 ± 0.2 

9.9 ± 0.2** 

2.2 ± 0.2** 

** Significantly different (P#0.01) from the control group by Williams’ or Dunnett’s test a Number of animals surviving at 14 days/number initially in group. Subsequent calculations are based on animals surviving to the end of 

the study. b	 Weights and weight changes are given as mean ± standard error. 

Water consumption is expressed as grams per animal per day ± standard error. d	 Day of deaths: 12 

c 
32 1-Chloro-2-propanol, NTP TR 477 

The incidences of cytoplasmic alteration and degenera- consisted of mature fat cells that appeared to be within 

tion of the acinar cells of the exocrine pancreas in the interstitium. 

3,300 and 10,000 ppm males and females and 

1,000 ppm females were significantly increased compared to the controls (Table 4). The incidences of 

fatty change in 3,300 ppm males and females and 

10,000 ppm males were significantly increased compared to the controls. Cytoplasmic alteration was 

characterized by basophilic cells having reduced 

amounts of acidophilic cytoplasmic granules (zymogen) and small acini. In some animals, the basophilic 

acinar cells appeared to be hyperplastic or hypertrophic. Degeneration was defined as the presence of 

cellular or nuclear debris within acinar cells (autophagic vacuoles and/or apoptosis). The fatty change 

There were increased incidences of minimal to moderate atrophy of the bone marrow in the 3,300 and 

10,000 ppm male and female rats and in 1,000 ppm 

females compared to the controls (Table 4). Atrophy 

was characterized by a reduction in the number of 

hematopoietic cells with a concomitant increase in the 

amount of adipose tissue within the marrow. 

There were increased incidences of minimal to mild 

diffuse atrophy of the spleen in 10,000 ppm males and 

females compared to the controls (Table 4). Minimal 

to mild hematopoiesis of the spleen occurred in males 

and females in the 3,300 ppm groups. 
33 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE 4 

Incidence of Selected Nonneoplastic Lesions in Rats in the 14-Day Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 10,000 ppm 

Male 

Pancreasa 

Acinar Cell,

 Cytoplasmic

 Alterationb 

Degeneration 

Fatty Change 

10

0 

0 

0 

—c — 10 

0 

0 

0 

10 

10** 

10** 

6** 

10 

9** 

7** 

4* 

Bone Marrow 

Atrophy 

10 

0 

— — 10 

0 

10 

10** (1.0)d 

10 

10** (3.0) 

Spleen 

Atrophy, Diffuse 

Hematopoiesis 

10 

0 

0 

— — 10 

0 

0 

10 

0 

7** (1.0) 

10 

10** 

0 

(1.9) 

Female 

Pancreas 

Acinar Cell,

 Cytoplasmic

 Alteration 

Degeneration 

Fatty Change 

10 

0 

0 

0 

— — 10 

10** 

5* 

0 

10 

10** 

10** 

6** 

10 

5* 

6** 

1 

Bone Marrow 

Atrophy 

10 

0 

— 10 

0 

10 

8** (1.3) 

10 

10** (1.8) 

10 

10** (3.2) 

Spleen 

Atrophy, Diffuse 

Hematopoiesis 

10 

0 

0 

2 

0 

0 

— 10 

0 

0 

10 

0 

6** (2.2) 

10

10** 

0 

(2.0)

* Significantly different (P#0.05) from the control group by the Fisher exact test 

** P#0.01 a Number of animals with tissue examined microscopically b Number of animals with lesion
 

Tissue not examined at this exposure concentration d Average severity grade of lesions in affected animals: 1ùminimal, 2ùmild, 3ùmoderate, 4ùmarked 
34 

c 

1-Chloro-2-propanol, NTP TR 477 

14-WEEK STUDY
 

All rats survived to the end of the study (Table 5). Drinking water concentrations of 33, 100, 330, 1,000, 

The final mean body weights and body weight gains of or 3,300 ppm 1-chloro-2-propanol resulted in average 

3,300 ppm males and females were significantly less daily doses of approximately 5, 10, 35, 100, or 

than those of the controls. Water consumption by the 220 mg 1-chloro-2-propanol/kg body weight. No 

3,300 ppm male and female rats was significantly less clinical findings that could be attributed to 1-chloro-2­

than that by the controls throughout the study. propanol exposure were observed. 

TABLE 5 

Survival, Body Weights, and Water Consumption of Rats in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanol 

Mean Body Weight b (g) Final Weight 

Concentration 

(ppm) 

Survivala Initial Final Change to Controls 

Relative 

(%) 

Consumption 

Water c 

Week 1 Week 13 

Male 

0 

33 

100 

330 

1,000 

3,300 

10/10 

10/10 

10/10 

10/10 

10/10 

10/10 

116 ± 3 

114 ± 3 

120 ± 4 

118 ± 3 

115 ± 2 

116 ± 3 

383 ± 6 

372 ± 9 

373 ± 9 

378 ± 8 

373 ± 5 

312 ± 5** 

267 ± 5 

257 ± 7 

254 ± 6 

260 ± 6 

258 ± 5 

196 ± 4** 

97 

98 

99 

97 

82 

19.5 ± 0.6 

19.7 ± 0.7 

19.6 ± 0.5 

19.3 ± 0.1 

18.5 ± 0.2 

8.7 ± 0.1** 

21.8 ± 0.4 

20.7 ± 0.5 

22.7 ± 1.6 

21.5 ± 1.0 

19.7 ± 0.2 

14.1 ± 0.0** 

Female 

0 

33 

100 

330 

1,000 

3,300 

10/10 

10/10 

10/10 

10/10 

10/10 

10/10 

103 ± 2 

103 ± 2 

103 ± 2 

101 ± 2 

102 ± 2 

100 ± 2 

211 ± 5 

209 ± 3 

212 ± 3 

205 ± 3 

202 ± 3 

182 ± 2** 

108 ± 4 

106 ± 3 

109 ± 2 

104 ± 2 

100 ± 3* 

82 ± 1** 

99 

101 

97 

96 

86

16.2 ± 0.4 

16.7 ± 0.3 

15.8 ± 0.1 

17.1 ± 0.4 

16.3 ± 0.0 

7.0 ± 0.1**

17.7 ± 0.8 

16.9 ± 1.7 

17.4 ± 0.3

18.5 ± 1.2 

16.8 ± 0.8 

8.8 ± 0.6** 

* Significantly different (P#0.05) from the control group by Williams’ or Dunnett’s test 

** P#0.01 a Number of animals surviving at 14 weeks/number initially in group b Weights and weight changes are given as mean ± standard error. 

Water consumption is expressed as grams per animal per day ± standard error. 
 

1-Chloro-2-propanol, NTP TR 477 35 

The hematology, clinical chemistry, and urinalysis reflect a physiologic response of water conservation 

data are listed in Table G1. At study termination, a and would be consistent with the decreased water 

treatment-related anemia occurred in the exposed intake that occurred. 

female rats; the anemia was evidenced by decreases in 

hematocrit values, hemoglobin concentrations, and The cauda epididymis and epididymis weights of 

erythrocyte counts. The anemia was of minimal to 3,300 ppm males were significantly less than those of 

mild severity and was most pronounced in the 1,000 the controls (Table I1). The percentage of abnormal 

and 3,300 ppm groups. The male rats were less sperm in 3,300 ppm males and the concentration of 

affected, and hemoglobin concentrations decreased epididymal sperm in 330 ppm males were significantly 

only in the 3,300 ppm group. Slightly lower water increased compared to the controls. No significant 

consumption by 3,300 ppm males and females differences from the controls in estrous cycle length or 

suggests that dehydration could have occurred. percentage of time spent in estrous cycle stages were 

Dehydration can cause a relative erythrocytosis due to observed in female rats (Table I2). 

decreased blood volume and hemoconcentration. If 

significant dehydration occurred in these animals, the The absolute kidney weights of 100 ppm males and 

severity of the anemia could have been masked. The females and 1,000 ppm females and the relative kidney 

anemia in female rats was characterized as macrocytic, weights of 100 ppm or greater males and females were 

normochromic, and responsive. Macrocytosis was significantly greater than those of the controls 

evidenced by minimal increases in the mean cell (Table H2). The absolute liver weights of 330 and 

volumes in 3,300 ppm females. Normochromatic 1,000 ppm males and 100 and 1,000 ppm females and 

erythrocytes were evidenced by the absence of change the relative liver weights of males and females exposed 

in the mean cell hemoglobin concentrations. Evidence to 100 ppm or greater were significantly greater than 

of an erythropoietic response was demonstrated by those of the controls. 

minimal increases in the reticulocyte counts in the 33, 

100, and 3,300 ppm female groups. The incidences of acinar cell degeneration and fatty 

change of the pancreas in 1,000 and 3,300 ppm males 

An exposure-related decrease in serum alanine amino- and females were significantly increased compared to 

transferase activity occurred at all time points for the controls (Table 6). In the most severely affected 

male and female rats in the 1,000 and 3,300 ppm animals, much of the normal parenchyma was replaced 

groups; transient decreases occurred in the lower by large vacuolated cells (adipocytes) (Plates 1 

exposure groups on day 3 and/or day 15. The through 3). The adipocytes appeared to be of 

decreased enzyme activity could suggest altered interstitial origin and were much less common in the 

enzyme metabolism (e.g., decreased synthesis or 1,000 ppm animals. Within residual acinar cells, the 

increased catabolism) or an enzyme-inhibitory effect of number of zymogen granules was reduced or absent 

1-chloro-2-propanol. A transient decrease in albumin (Plates 4 and 5); cellular or nuclear debris was often 

concentration occurred on day 3 for all exposed observed within or adjacent to these cells (autophagic 

groups. The decreases, while treatment related, were vacuoles and/or apoptosis; Plate 6) and was diagnosed 

not exposure related, and the magnitude of the as degeneration. An increased number of cells in the 

decreases were equal for all exposed groups. interstitium was also observed. 

Decreased albumin concentrations could suggest 

altered albumin/protein metabolism by the liver and In general, pancreatic islets (endocrine pancreas) 

could be consistent with the decreased alanine remained intact; however, hepatocytic metaplasia was 

aminotransferase activity. A marked decrease in the observed in a few islets in five females in the 

16-hour urine volume and concomitant increase in 3,300 ppm group. Within the peripheral region of 

urine specific gravity occurred in 3,300 ppm male affected islets, there was a variably thick band of large 

and female rats on day 15 and at week 14. These polygonal cells with abundant eosinophilic cytoplasm 

alterations in urine volume and specific gravity would which resembled hepatocytes (Plate 7). 
36 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE 6 

Incidence of Selected Nonneoplastic Lesions in Rats in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 33 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 

Male 

Pancreasa 

Acinar Cell,

 Degenerationb 

Fatty Change 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

10** 

10** 

(1.0)c 

(1.4) 

9 

9** 

9** 

(3.0) 

(3.0) 

Liver 

Cytoplasmic

 Vacuolization 

10 

0 

10 

1 (1.0) 

10 

6** (1.2) 

10 

2 (1.0) 

10 

7** (1.0) 

10 

10** (1.4) 

Kidney 

Epithelium,

 Regeneration, 

Tubular 

10 

8 (1.0) 

10 

0 

10 

0 

10 

0 

10 

0 

10 

10 (1.0)

Female 

Pancreas 

Acinar Cell,

 Degeneration 

Fatty Change 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

0 

1 (1.0) 

10 

10** 

10** 

(1.0) 

(1.0) 

10 

10** 

10** 

(3.0) 

(3.0) 

Pancreatic Islets 

Metaplasia, Focal 

10 

0 

10 

0 

10 

0 

10 

0 

10 

0 

10 

5* (1.0) 

Kidney 

Epithelium,

 Regeneration, 

Tubular 

10 

1 (1.0) 

10 

0 

10 

0 

10 

1 (1.0) 

10 

2 (1.0) 

10 

8** (1.0)

* Significantly different (P#0.05) from the control group by the Fisher exact test 

** P#0.01 a Number of animals with tissue examined microscopically b Number of animals with lesions 

Average severity grade of lesions in affected animals: 1ùminimal, 2ùmild, 3ùmoderate, 4ùmarked 
1-Chloro-2-propanol, NTP TR 477 37 

There were increased incidences of cytoplasmic vacu- sent a regenerative response to injury. This change is 

olization of the liver in 100, 1,000, and 3,300 ppm very similar to that observed in the early stages of the 

males compared to the controls. The cytoplasmic background nephropathy that occurs in the F344/N 

vacuolization was primarily observed within hepato- rat. This was an extremely subtle change, and it is not 

cytes in the centrilobular region of the liver. Plate 8 certain if it represents a slight exacerbation of the 

represents one of the more severely affected animals. background nephropathy or a primary insult to the 

Vacuoles were variable in size with the largest slightly kidney. The spontaneous nephropathy that occurs in 

displacing the nucleus. Eosinophilic staining material the F344/N rat is most severe in males, and at 

was often observed within the vacuoles. Vacuolar 14 weeks virtually all males have regenerative tubules 

change is often a nonspecific change in the liver, and while females do not. While a difference was not 

this minimal change is considered of little biologic observed between control and exposed males, 

significance. detection of a subtle increase in regenerative tubules is 

very difficult with the background nephropathy. 

There was an increased incidence of regeneration of 

renal tubule epithelium in the 3,300 ppm female rats Exposure Concentration Selection Rationale: Based 

compared to the controls (Table 6). Within the renal on chemical-related lesions of the pancreas, 1-chlorocortex of the affected kidneys, there were occasional 2-propanol exposure concentrations selected for the 

tubules composed of slightly smaller and more baso- 2-year drinking water study in rats were 150, 325, and 

philic appearing cells which were considered to repre- 650 ppm. 
38 

c 

1-Chloro-2-propanol, NTP TR 477 

2-YEAR STUDY 

Survival 

Estimates of 2-year survival probabilities for male and 

female rats are shown in Table 7 and in the 

Kaplan-Meier survival curves (Figure 1). Survival of 

all exposed groups was similar to that of the controls. 

Body Weights, Water and Compound 

Consumption, and Clinical Findings 

Mean body weights of exposed males and females 

were generally similar to those of the controls 

TABLE 7 

throughout the study (Tables 8 and 9 and Figure 2). 

Water consumption by all groups of exposed rats was 

similar to that by the controls (Tables K1 and K2). 

Drinking water concentrations of 150, 325, or 

650 ppm 1-chloro-2-propanol resulted in average daily 

doses of approximately 15, 30, or 65 mg 1-chloro-2­

propanol/kg body weight to males and females during 

the first several months of the study and 8, 17, or 

34 mg/kg for the remainder of the 2-year study. No 

clinical findings that could be attributed to 1-chloro-2­

propanol exposure were observed. 

Survival of Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Male 

Animals initially in study	 50 50 50 50 

Moribund 12 13 7 10 

Natural deaths 18 14 19 17 

Animals surviving to study termination 20d 23 24 23 a Percent probability of survival at end of study 40 46 48 46 

Mean survival (days)b 659 678 672 680 

c Survival analysis	 Pù0.564N Pù0.476N Pù0.507N Pù0.514N 

Female 

Animals initially in study	 50 50 50 50 

Moribund 12 7 7 5 

Natural deaths 13 10 13 14 

Animals surviving to study termination 25 33 30 31 

Percent probability of survival at end of study 50 66 60 62 

Mean survival (days) 698 705 700 701 

Survival analysis	 Pù0.513N Pù0.137N Pù0.474N Pù0.334N 

a Kaplan-Meier determinations b	 Mean of all deaths (uncensored, censored, and terminal sacrifice) 

The result of the life table trend test (Tarone, 1975) is in the control column, and the results of the life table pairwise comparisons (Cox, 1972) 

with the 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 
 

1-Chloro-2-propanol, NTP TR 477 39 

FIGURE 1
 

Kaplan-Meier Survival Curves for Male and Female Rats Administered 1-Chloro-2-propanol
 

in Drinking Water for 2 Years
 
40 1-Chloro-2-propanol, NTP TR 477 

TABLE 8 

Mean Body Weights and Survival of Male Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

Weeks 0 ppm 150 ppm 325 ppm 650 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 

1 132 50 130 99 50 131 99 50 131 100 50 

2 166 50 163 99 50 166 100 50 167 101 50 

3 194 50 197 102 50 201 104 50 202 104 50 

4 224 50 225 101 50 231 103 50 230 103 50 

5 247 50 249 101 50 256 104 50 253 103 50 

6 263 50 266 101 50 274 104 50 270 103 50 

7 277 50 282 102 50 289 104 50 285 103 50 

8 289 50 293 101 50 296 103 50 294 102 50 

9 306 50 306 100 50 312 102 50 308 101 50 

10 314 50 319 101 50 324 103 50 320 102 50 

11 325 50 328 101 50 332 102 50 329 101 50 

12 337 50 341 101 50 346 103 50 340 101 50 

13 349 50 351 100 50 355 102 50 351 101 50 

17 375 50 378 101 50 383 102 50 382 102 50 

21 410 50 409 100 50 414 101 50 413 101 50 

25 426 50 424 100 50 432 101 50 428 101 50 

29 445 50 444 100 50 451 101 50 450 101 50 

33 454 50 454 100 50 462 102 50 461 102 50 

37 462 50 462 100 50 473 102 50 470 102 50 

41 478 50 478 100 50 491 103 50 488 102 50 

45 488 50 487 100 50 501 103 50 496 102 50 

49 484 50 485 100 50 497 103 50 494 102 50 

53 503 49 500 99 50 516 103 50 507 101 50 

57 504 49 503 100 49 517 103 50 509 101 50 

61 505 49 507 100 49 523 104 49 516 102 50 

65 502 48 502 100 49 518 103 49 508 101 50 

69 502 48 504 100 49 520 104 48 508 101 50 

73 510 46 514 101 48 529 104 48 510 100 49 

77 512 44 513 100 48 524 102 48 509 100 47 

81 513 43 516 101 44 532 104 46 503 98 47 

85 514 38 516 100 44 537 104 41 505 98 42 

89 512 35 504 98 39 524 102 38 497 97 40 

93 516 32 497 96 36 522 101 35 487 94 39 

97 516 29 502 97 34 506 98 31 477 93 35 

101 481 25 492 102 31 495 103 28 468 97 28 

104 464 20 479 103 23 488 105 24 460 99 23 

Mean for weeks 

1-13 263 265 101 270 103 268 102 

14-52 447 447 100 456 102 454 102 

53-104 504 504 100 518 103 497 99 
1-Chloro-2-propanol, NTP TR 477 41 

TABLE 9 

Mean Body Weights and Survival of Female Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

Weeks 0 ppm 150 ppm 325 ppm 650 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 

1 111 50 111 100 50 111 100 50 110 99 50 

2 128 50 128 100 50 128 100 50 127 99 50 

3 144 50 143 99 50 143 100 50 143 100 50 

4 152 50 151 100 50 152 100 50 153 101 50 

5 160 50 160 100 50 161 100 50 163 102 50 

6 169 50 169 100 50 169 100 50 172 101 50 

7 174 50 175 100 50 173 99 50 176 101 50 

8 182 50 180 99 50 180 99 50 182 100 50 

9 188 50 187 99 50 186 99 50 189 101 50 

10 191 50 190 99 50 190 99 50 192 100 50 

11 193 50 192 99 50 193 100 50 195 101 50 

12 198 50 198 100 50 199 100 50 201 101 50 

13 201 50 201 100 50 201 100 50 205 102 50 

17 216 50 216 100 50 213 99 50 218 101 50 

21 224 50 221 99 50 220 98 50 224 100 50 

25 230 50 228 99 50 227 99 50 231 100 50 

29 240 50 238 99 50 238 99 50 242 101 50 

33 246 50 244 99 49 244 99 50 247 100 50 

37 254 50 252 99 49 252 99 50 255 101 50 

41 266 50 265 100 49 266 100 50 268 101 50 

45 269 50 268 99 49 269 100 50 270 100 50 

49 281 50 278 99 49 280 100 50 282 100 50 

53 292 50 293 100 49 290 99 50 297 102 50 

57 296 50 298 101 49 295 100 50 301 102 50 

61 305 50 305 100 49 302 99 50 309 101 50 

65 305 50 307 101 49 303 99 50 311 102 49 

69 315 50 315 100 49 311 99 50 318 101 49 

73 321 50 323 101 48 316 99 50 324 101 48 

77 329 49 332 101 48 328 100 47 333 101 48 

81 326 48 334 102 48 326 100 47 331 102 47 

85 333 47 337 101 48 327 98 46 338 101 46 

89 339 45 343 101 48 337 99 43 348 103 45 

93 338 42 344 102 46 336 100 43 353 105 43 

97 345 36 336 97 46 337 98 38 358 104 40 

101 345 33 341 99 39 333 96 36 367 107 36 

Mean for weeks 

1-13 169 168 99 168 99 170 101 

14-52 247 246 100 245 99 249 101 

53-101 322 324 101 319 99 330 102 
 

42 1-Chloro-2-propanol, NTP TR 477 

FIGURE 2
 

Growth Curves for Male and Female Rats Administered 1-Chloro-2-propanol
 

in Drinking Water for 2 Years
 
1-Chloro-2-propanol, NTP TR 477 43 

Pathology and Statistical Analyses 

This section describes the statistically significant or 

biologically noteworthy changes in the incidences of 

neoplasms of the mammary gland. Summaries of the 

incidences of neoplasms and nonneoplastic lesions, 

individual animal tumor diagnoses, 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. 

There were no significant increases or decreases in the 

incidences of neoplastic or nonneoplastic lesions that 

were attributed to administration of 1-chloro-2­

propanol in drinking water for 2 years. 

Mammary Gland: The incidence of fibroadenoma was 

significantly decreased in 150 ppm males compared to 

the controls (0 ppm, 7/50; 150 ppm, 0/50; 325 ppm, 

6/50; 650 ppm, 6/50; Table A3). The incidence of 

fibroadenoma in control male rats exceeded that 

observed in historical control groups from drinking 

water, feed, corn oil gavage, and inhalation studies 

(Table A4). 
44 1-Chloro-2-propanol, NTP TR 477 

MICE 

14-DAY STUDY 

One male mouse in the 10,000 ppm group died before 

the end of the study (Table 10). The final mean body 

weights and body weight gains of 10,000 ppm males 

and females were significantly less than those of the 

controls, and the male mice in the 10,000 ppm group 

lost weight during the study. Water consumption by 

3,300 and 10,000 ppm males and females was 

significantly less than that by the controls throughout 

the study. Drinking water concentrations of 100, 330, 

1,000, 3,300, or 10,000 ppm 1-chloro-2-propanol 

resulted in average daily doses of approximately 20, 

60, 175, 430, or 630 mg 1-chloro-2-propanol/kg body 

weight to males and 25, 95, 290, 640, or 940 mg/kg 

to females. No clinical findings that could be attributed to 1-chloro-2-propanol exposure were observed. 

TABLE 10 

The relative liver weights of 1,000, 3,300, and 

10,000 ppm males and females were significantly 

greater than those of the controls (Table H3). The 

absolute and relative thymus weights of 10,000 ppm 

males and females were significantly less than those 

of the controls. The relative kidney weights of 

10,000 ppm males and females were significantly 

greater than those of the controls, probably reflecting 

decreased water consumption. 

The incidences of minimal to mild hepatocellular 

vacuolization in 1,000, 3,300, and 10,000 ppm male 

and female mice were significantly increased compared 

to the controls (Table 11). In general, the vacuolar 

change involved hepatocytes scattered throughout the 

liver, but it was sometimes more pronounced in the 

periportal regions. Affected hepatocytes contained 

Survival, Body Weights, and Water Consumption of Mice in the 14-Day Drinking Water Study 

of 1-Chloro-2-propanol 

Concentration 

(ppm) 

Survivala Initial 

Mean Body Weight (g) b 

Final Change 

Final Weight 

to Controls 

Relative 

(%) 

Consumption 

Water c 

Week 1 Week 2 

Male 

0 

100 

330 

1,000 

3,300 

10,000

10/10 

10/10 

10/10 

10/10 

10/10 

9/10d 

26.0 ± 0.6 

25.3 ± 0.5 

24.8 ± 0.7 

25.7 ± 0.4 

25.0 ± 0.4 

24.8 ± 0.4 

28.1 ± 0.6 

27.7 ± 0.5 

27.5 ± 0.7 

28.7 ± 0.4 

28.4 ± 0.5 

24.3 ± 0.6** 

2.0 ± 0.2 

2.5 ± 0.2 

2.7 ± 1.1 

3.0 ± 0.2 

3.4 ± 0.2 

–0.5 ± 0.5** 

99 

98 

102 

101 

87 

4.6 ± 0.2 4.8 ± 0.3 

4.4 ± 0.3 5.2 ± 0.2 

4.7 ± 0.4 5.0 ± 0.3 

4.7 ± 0.2 4.8 ± 0.2 

3.4 ± 0.2** 3.5 ± 0.2** 

1.3 ± 0.1** 1.8 ± 0.1** e e 

Female 

0 

100 

330 

1,000 

3,300 

10,000 

10/10 

10/10 

10/10 

10/10 

10/10 

10/10 

19.3 ± 0.2 

19.5 ± 0.4 

19.0 ± 0.3 

19.1 ± 0.3 

19.8 ± 0.4 

19.5 ± 0.3 

21.6 ± 0.2 

22.0 ± 0.4 

21.6 ± 0.4 

22.0 ± 0.3 

22.9 ± 0.3 

19.8 ± 0.8* 

2.3 ± 0.2 

2.5 ± 0.2 

2.6 ± 0.2 

2.9 ± 0.4 

3.1 ± 0.2 

0.3 ± 0.9** 

102 

100 

102 

106 

92 

5.4 ± 0.3 

5.2 ± 0.3 

5.4 ± 0.5 

5.8 ± 0.5 

3.7 ± 0.2** 

1.5 ± 0.2** 

5.7 ± 0.2 

5.5 ± 0.2 

6.2 ± 0.4

6.2 ± 0.6 

3.9 ± 0.2** 

1.9 ± 0.1** 

* Significantly different (P#0.05) from the control group by Williams’ or Dunnett’s test 

** P#0.01 a Number of animals surviving at 14 days/number initially in group. Subsequent calculations are based on animals surviving to the end of 

the study. b	 Weights and weight changes are given as mean ± standard error. 

Water consumption is expressed as grams per animal per day ± standard error. d	 Day of death: 3 e nù9 

c 
 

 

1-Chloro-2-propanol, NTP TR 477 45 

small, sometimes coalescing vacuoles that often filled females compared to those in the controls (Table 11). 

the cytoplasm but did not displace the nucleus. The lesions were qualitatively similar to those 

described in the rats. Fatty change was not observed 

As was observed in the rats, there were increased in the mice, however. 

incidences of minimal to mild cytoplasmic alteration in 

3,300 and 10,000 ppm male and female mice and Minimal to mild atrophy of red pulp (hematopoietic 

minimal to mild degeneration of the pancreatic acinar cells) was observed in the spleen of four 10,000 ppm 

cells in 3,300 ppm males and 3,300 and 10,000 ppm males and five 10,000 ppm females (Table 11). 

TABLE 11 

Incidence of Selected Nonneoplastic Lesions in Mice in the 14-Day Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 10,000 ppm 

Male 

Livera 

Hepatocyte,

 Cytoplasmic,

 Vacuolizationb 

10 

1 (3.0)c 

10 

3 (1.3) 

10 

5 (1.4) 

10 

10** (2.1) 

10 

10** (2.0) 

10 

10** (2.0) 

Pancreas 

Acinar Cell,

 Cytoplasmic

 Alteration 

Degeneration 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

7** 

10** 

10 

8** 

3 

Spleen 

Atrophy 

10

0 

—d — — 10 

0 

10 

4* (1.5) 

Female 

Liver 

Hepatocyte,

 Cytoplasmic,

 Vacuolization 

10 

0 

10 

0 

10 

3 (2.0) 

10 

8** (1.5) 

10 

10** (1.8) 

10 

9** (1.8) 

Pancreas 

Acinar Cell,

 Cytoplasmic

 Alteration 

Degeneration 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

7** 

9** 

10 

9** 

10** 

Spleen 

Atrophy 

10 

0 

— — — 10 

0 

10

5* (1.6) 

* Significantly different (P#0.05) from the control group by the Fisher exact test 

** P#0.01 a Number of animals with tissue examined microscopically b Number of animals with lesion 

Average severity grade of lesions in affected animals: 1ùminimal, 2ùmild, 3ùmoderate, 4ùmarked 

d Tissue not examined at this exposure concentration 

c 
 

46 1-Chloro-2-propanol, NTP TR 477 

14-WEEK STUDY 

One 330 ppm male died before the end of the study 

(Table 12). Final mean body weights and body weight 

gains of exposed groups were similar to those of the 

controls. Water consumption by exposed groups was 

generally similar to that by the controls, except at 

13 weeks, when water consumption by the 3,300 ppm 

females was less than that by the controls. Drinking 

water concentrations of 33, 100, 330, 1,000, or 

3,300 ppm 1-chloro-2-propanol resulted in average 

daily doses of approximately 5, 15, 50, 170, or 

340 mg 1-chloro-2-propanol/kg body weight to males 

and 7, 20, 70, 260, or 420 mg/kg to females. No 

clinical findings that could be attributed to 1-chloro-2­

propanol exposure were observed. 

TABLE 12 

Hematology data are listed in Table G2. There was 

some evidence of minimal anemia in 3,300 ppm male 

mice; this was characterized by decreased erythrocyte 

count and hemoglobin concentration. The lower water 

consumption by 3,300 ppm mice suggests that 

dehydration may have occurred. Dehydration can 

cause a relative erythrocytosis due to decreased blood 

volumes and hemoconcentration. If significant dehydration occurred in these animals, the severity of the 

anemia could have been masked. The erythrocytes of 

330, 1,000, and 3,300 ppm male mice were minimally 

larger, as evidenced by increases in mean cell volume. 

Increases in mean cell volume usually suggest 

increased numbers of larger immature erythrocytes 

(reticulocytes) in the bloodstream. However, 

Survival, Body Weights, and Water Consumption of Mice in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanol 

Concentration 

(ppm) 

Survivala Initial 

Mean Body Weight (g) b 

Final Change 

Final Weight 

to Controls 

Relative 

(%) 

Consumption 

Water c 

Week 1 Week 13 

Male 

0 

33 

100 

330

1,000 

3,300 

10/10 

10/10 

10/10 

9/10d 

10/10 

10/10 

22.8 ± 0.3 

23.5 ± 0.4 

23.6 ± 0.6 

23.1 ± 0.3 

23.4 ± 0.5 

24.2 ± 0.4 

38.4 ± 0.9 

40.2 ± 1.1 

39.5 ± 1.1 

39.2 ± 1.3 

39.0 ± 0.8 

39.8 ± 0.7 

15.6 ± 0.7 

16.8 ± 1.0 

16.0 ± 1.0 

16.1 ± 1.1 

15.6 ± 0.5 

15.6 ± 0.5 

105 

103 

102 

101 

103 

4.4 ± 0.2 

4.9 ± 0.2 

4.7 ± 0.2e 

5.1 ± 0.4e 

5.1 ± 0.3e 

3.5 ± 0.2* 

4.1 ± 0.2 

5.0 ± 1.0 

4.6 ± 0.5 

4.4 ± 0.4e 

4.2 ± 0.2 

3.1 ± 0.2* 

Female 

0 

33 

100 

330 

1,000 

3,300 

10/10 

10/10 

10/10 

10/10 

10/10 

10/10 

20.0 ± 0.2 

19.3 ± 0.3 

19.1 ± 0.3 

19.7 ± 0.2 

19.9 ± 0.5 

19.4 ± 0.2 

34.0 ± 1.0 

33.8 ± 0.9 

31.5 ± 1.5 

34.8 ± 0.9 

33.5 ± 1.2 

33.5 ± 0.8 

14.0 ± 0.9 

14.5 ± 0.8 

12.4 ± 1.4 

15.1 ± 0.8 

13.7 ± 0.8 

14.1 ± 0.7 

99 

93 

102 

99 

99 

3.8 ± 0.1 

4.0 ± 1.1 

4.1 ± 0.6 

4.3 ± 0.3 

3.8 ± 0.3 

3.0 ± 0.6e 

6.0 ± 0.6 

5.8 ± 0.4 

6.3 ± 0.7

5.6 ± 0.6 

5.1 ± 0.4 

3.4 ± 0.3** 

* Significantly different (P#0.05) from the control group by Williams’ or Dunnett’s test 

** P#0.01 a Number of animals surviving at 14 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. 

Water consumption is expressed as grams per animal per day ± standard error. d Week of death: 7 e nù9 

c 
1-Chloro-2-propanol, NTP TR 477 47 

the reticulocyte counts were not increased, suggesting males and of all exposed groups of females were sigthat the anemia observed in 3,300 ppm males was too nificantly greater than those of the controls. The 

minimal to stimulate a strong bone marrow response. absolute and relative thymus weights of 1,000 ppm 

Other hematologic changes were not considered to be females and the absolute thymus weight of 3,300 ppm 

toxicologically relevant. females were significantly greater than those of the 

controls. 

The right epididymis weight of 3,300 ppm males was 

significantly greater than that of the controls The incidences of pancreatic acinar cell degeneration 

(Table I3). No significant differences from the con- and fatty change in 3,300 ppm males and females were 

trols were observed in the length of estrous cycle or significantly increased compared to the controls (Table 

the percentage of time spent in estrous cycle stages 13). The degeneration and fatty change were 

(Table I4). qualitatively similar to that described for the rats, but 

the lesions were much milder in mice. 

The absolute and relative right kidney weights of 

3,300 ppm males and females were significantly The severities of renal tubule cytoplasmic vacuolgreater than those of the controls (Table H4). The ization were greater in 1,000 and 3,300 ppm males 

absolute and relative liver weights of 1,000 ppm than in the controls (Table 13). 

TABLE 13 

Incidence of Selected Nonneoplastic Lesions in Mice in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 33 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 

Male 

Pancreasa 

Acinar Cell,

 Degenerationb 

Fatty Change 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

2 

2 

(1.0)c 

(1.0) 

10 

10** 

9** 

(1.1) 

(1.1) 

Kidney 

Renal Tubule,

 Vacuolization,

 Cytoplasmic 

10 

10 (1.1) 

10 

10 (1.1) 

10 

10 (1.4) 

10 

8 (1.1) 

10 

10 (1.6) 

10 

10 (1.7) 

Female 

Pancreas 

Acinar Cell,

 Degeneration 

Fatty Change 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

0 

0 

10 

9** 

4* 

(1.0)

(1.0) 

Liver 

Cytoplasmic

 Vacuolization 

10 

0 

10 

7** (1.0) 

10 

10** (1.5) 

10 

7** (1.1) 

10 

9** (1.4) 

10 

10** (2.0) 

* Significantly different (P#0.05) from the control group by the Fisher exact test 

** P#0.01 a Number of animals with tissue examined microscopically b Number of animals with lesions 

Average severity grade of lesions in affected animals: 1ùminimal, 2ùmild, 3ùmoderate, 4ùmarked c 
48 

The incidences of cytoplasmic vacuolization of the 

liver in all groups of exposed females were significantly increased compared to the controls (Table 13). 

The nature of the vacuolization was similar between 

groups and was generally characterized by indistinct 

borders and irregularly shaped clear spaces in the 

cytoplasm. 

1-Chloro-2-propanol, NTP TR 477 

Exposure Concentration Selection Rationale: Based 

on chemical-related lesions of the pancreas in the 

3,300 ppm groups, 1-chloro-2-propanol exposure 

concentrations selected for the 2-year drinking water 

study in mice were 250, 500, and 1,000 ppm. 
1-Chloro-2-propanol, NTP TR 477 49 

2-YEAR STUDY 

Survival 

Estimates of 2-year survival probabilities for male and 

female mice are shown in Table 14 and in the KaplanMeier survival curves (Figure 3). Survival of all 

exposed groups was similar to that of the controls. 

Body Weights, Water and Compound 

Consumption, and Clinical Findings 

The mean body weights of all groups of exposed males 

and females were generally similar to those of the 

TABLE 14 

controls throughout the study (Figure 4 and Tables 15 

and 16). Water consumption by all exposed groups of 

mice was similar to that by the controls (Tables K3 

and K4). Drinking water concentrations of 0, 250, 

500, or 1,000 ppm 1-chloro-2-propanol resulted in 

average daily doses of approximately 45, 75, or 

150 mg 1-chloro-2-propanol/kg body weight to males 

and 60, 105, or 210 mg/kg to females during the first 

several months of the study and 25, 50, or 100 mg/kg 

for the remainder of the 2-year study. No clinical 

findings related to 1-chloro-2-propanol exposure were 

observed. 

Survival of Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Male 

Animals initially in study 50 50 50 50 

Accidental deathsa 0 0 5 3 

Moribund 8 0 7 4 

Natural deaths 2 6 9 4 

Animals surviving to study termination 40 44 29 39 

Percent probability of survival at end of studyb 80 88 65 83 c Mean survival (days) 689 712 624 686 

d Survival analysis Pù0.986 Pù0.386N Pù0.151 Pù0.824N 

Female 

Animals initially in study 50 50 50 50 

Accidental deathsa 3 0 1 2 

Moribund 8 7 3 5 

Natural deaths 7 11 10 11 

Animals surviving to study termination 32 32 36 32 

Percent probability of survival at end of study 68 64 74 67 

Mean survival (days) 692 700 680 662 

Survival analysis Pù0.888 Pù0.650 Pù0.944N Pù0.812 

a Censored from survival analyses; some accidental deaths were attributed to hypothermia due to leakage of water bottles and flooding of cages. b Kaplan-Meier determinations 

Mean of all deaths (uncensored, censored, and terminal sacrifice) d The result of the life table trend test (Tarone, 1975) is in the control column, and the results of the life table pairwise comparisons (Cox, 1972) 

with the controls are in the exposed group columns. A lower mortality in an exposure group is indicated by N. 

c 
 

50 1-Chloro-2-propanol, NTP TR 477 

FIGURE 3
 

Kaplan-Meier Survival Curves for Male and Female Mice Administered 1-Chloro-2-propanol
 

in Drinking Water for 2 Years
 
 

1-Chloro-2-propanol, NTP TR 477 51 

FIGURE 4
 

Growth Curves for Male and Female Mice Administered 1-Chloro-2-propanol
 

in Drinking Water for 2 Years
 
52 1-Chloro-2-propanol, NTP TR 477 

TABLE 15 

Mean Body Weights and Survival of Male Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

Weeks 0 ppm 250 ppm 500 ppm 1,000 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 24.4 50 24.6 101 50 24.7 101 50 24.6 101 50 

2 25.8 50 25.9 100 50 26.5 103 50 26.4 102 50 

3 28.2 50 27.7 98 50 28.4 101 50 28.4 101 50 

4 29.7 50 29.1 98 50 29.6 100 50 29.8 100 50 

5 31.5 50 30.9 98 50 31.7 101 50 31.9 101 50 

6 33.4 50 33.1 99 50 33.5 100 50 33.9 102 50 

7 35.0 50 34.7 99 50 35.2 101 50 35.7 102 50 

8 36.6 50 36.3 99 50 36.9 101 50 37.2 102 50 

9 37.4 50 37.4 100 50 38.3 102 50 38.5 103 50 

10 38.0 50 38.1 100 50 38.7 102 50 39.1 103 50 

11 39.0 50 39.2 101 50 39.5 101 50 39.7 102 50 

12 39.5 50 39.6 100 50 39.8 101 50 40.2 102 50 

13 40.6 50 40.9 101 50 41.6 103 49 41.7 103 50 

17 44.6 50 44.8 100 50 45.3 102 48 45.5 102 50 

21 46.9 50 47.5 101 50 47.7 102 48 47.9 102 50 

25 48.6 50 48.9 101 50 49.6 102 48 49.7 102 50 

29 50.7 50 50.5 100 50 51.0 101 46 50.9 100 50 

33 51.3 49 50.8 99 50 51.1 100 46 51.3 100 50 

37 51.9 49 51.0 98 50 51.2 99 46 51.6 99 48 

41 52.4 49 52.0 99 50 52.7 101 46 52.4 100 48 

45 53.1 49 52.2 98 50 53.5 101 46 53.4 101 48 

49 52.4 49 51.8 99 49 52.7 101 46 52.9 101 48 

53 52.4 49 52.0 99 49 52.9 101 46 53.2 102 48 

57 52.1 48 51.7 99 49 52.5 101 45 52.8 101 48 

61 52.3 48 52.1 100 49 52.7 101 44 53.1 102 48 

65 51.7 48 52.1 101 49 52.3 101 44 52.9 102 47 

69 51.8 47 52.1 101 48 51.8 100 42 51.9 100 47 

73 51.4 46 51.5 100 48 51.4 100 41 51.2 100 47 

77 49.8 45 51.0 102 48 50.3 101 38 49.2 99 47 

81 50.1 44 50.4 101 48 49.7 99 38 48.5 97 45 

85 50.1 43 50.1 100 48 49.5 99 38 47.6 95 44 

89 48.7 43 49.4 101 48 48.0 99 35 47.2 97 44 

93 47.6 43 49.3 104 47 47.4 100 31 45.1 95 43 

97 47.0 42 48.6 103 46 46.8 100 31 44.6 95 40 

101 45.4 42 47.7 105 45 46.9 103 30 44.4 98 39 

104 44.3 40 47.5 107 44 45.5 103 29 43.6 98 39 

Mean for weeks 

1-13 33.8 33.7 100 34.2 101 34.4 102 

14-52 50.2 49.9 99 50.5 101 50.6 101 

53-104 49.6 50.4 102 49.8 100 49.0 99 
1-Chloro-2-propanol, NTP TR 477 53 

TABLE 16 

Mean Body Weights and Survival of Female Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

Weeks 0 ppm 250 ppm 500 ppm 1,000 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 20.3 50 19.6 97 50 19.6 97 50 19.8 98 50 

2 21.9 50 21.6 99 50 21.6 99 50 21.5 98 50 

3 22.7 50 22.1 97 50 21.7 96 50 22.4 99 50 

4 24.1 50 22.8 95 50 23.4 97 50 23.6 98 50 

5 25.5 50 24.2 95 50 24.6 97 50 24.5 96 50 

6 27.2 50 26.3 97 50 26.9 99 50 26.7 98 50 

7 28.8 50 27.3 95 50 28.0 97 50 28.0 97 50 

8 29.6 50 27.4 93 50 28.6 97 49 28.9 98 50 

9 30.8 50 28.9 94 50 29.7 96 49 30.1 98 50 

10 32.6 50 30.1 92 50 31.3 96 49 30.9 95 50 

11 33.5 50 31.4 94 50 32.5 97 49 32.9 98 50 

12 33.9 49 32.0 94 50 33.6 99 49 33.8 100 49 

13 34.6 49 32.6 94 50 34.2 99 49 35.1 101 49 

17 37.6 49 35.8 95 50 37.1 99 48 37.4 100 49 

21 40.7 49 39.1 96 50 40.7 100 48 40.6 100 49 

25 44.0 49 42.2 96 50 43.6 99 48 44.1 100 48 

29 45.7 49 44.1 97 50 45.3 99 48 45.7 100 48 

33 47.4 49 45.1 95 50 46.5 98 48 46.4 98 48 

37 50.0 49 47.6 95 50 49.5 99 48 49.0 98 47 

41 51.1 48 48.9 96 50 50.8 99 48 49.8 98 46 

45 53.0 48 50.9 96 50 52.8 100 48 52.4 99 46 

49 53.3 48 52.0 98 50 53.9 101 48 52.8 99 46 

53 54.4 48 52.7 97 50 55.3 102 48 54.4 100 46 

57 54.7 48 53.5 98 50 55.9 102 48 55.2 101 46 

61 55.8 48 54.9 98 50 58.2 104 47 56.7 102 46 

65 57.4 48 55.6 97 50 59.4 104 47 58.6 102 46 

69 59.1 47 57.4 97 48 60.5 102 47 59.0 100 45 

73 58.7 47 57.8 99 48 61.1 104 47 60.3 103 45 

77 59.3 47 58.1 98 48 61.2 103 47 60.7 102 44 

81 59.5 47 59.3 100 47 62.9 106 45 61.2 103 44 

85 60.1 46 59.8 100 45 62.4 104 45 61.0 102 43 

89 59.8 45 59.5 100 44 61.0 102 45 59.5 100 41 

93 57.6 45 58.6 102 44 60.8 106 43 59.7 104 39 

97 56.2 42 58.9 105 40 61.7 110 38 59.7 106 37 

101 54.2 38 57.6 106 38 59.6 110 36 58.6 108 34 

Mean for weeks 

1-13 28.1 26.6 95 27.4 98 27.6 98 

14-52 47.0 45.1 96 46.7 99 46.5 99 

53-101 57.4 57.2 100 60.0 105 58.8 102 
 

54 1-Chloro-2-propanol, NTP TR 477 

Pathology and Statistical Analyses 

This section describes the statistically significant or 

biologically noteworthy changes in the incidences of 

neoplasms of the liver. Summaries of the incidences 

of neoplasms and nonneoplastic lesions, individual 

animal tumor diagnoses, 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. 

There were no significant increases or decreases in the 

incidences of neoplasms or nonneoplastic lesions that 

were attributed to administration of 1-chloro-2­

propanol in drinking water for 2 years. 

Liver: There were high incidences of hepatocellular 

adenoma, hepatocellular carcinoma, or hepatoblastoma 

(combined) in all groups of male and female mice 

(males: 0 ppm, 40/50; 250 ppm, 39/50; 500 ppm, 

37/50; 1,000 ppm, 36/50; females: 41/50, 41/50, 

43/50, 42/50; Tables C3 and D3). The incidence of 

these combined lesions in the female control group 

(82%) was at the upper limit of the historical control 

range for drinking water studies (32% to 82%; 

Table D4). 

GENETIC TOXICOLOGY 

1-Chloro-2-propanol is genotoxic in vitro. It was 

tested for mutation induction in Salmonella 

typhimurium in three studies at two laboratories, and 

all test responses were similar (Table E1; Zeiger 

et al., 1987). In strain TA100, equivocal responses 

were obtained in the absence of S9; with S9, equivocal 

or weakly positive mutagenic activity was seen. 

Clearly positive, reproducible responses were seen 

across laboratories with strain TA1535, with and 

without S9. No mutagenic activity was detected with 

strain TA97, TA98, or TA1537, with or without S9. 

1-Chloro-2-propanol induced marked increases in 

sister chromatid exchanges (Table E2) and chromosomal aberrations (Table E3) in cultured Chinese 

hamster ovary cells, with and without S9. Cell cycle 

delay was induced in cultures treated with concentrations of 1,700 μg/mL 1-chloro-2-propanol and greater; 

to obtain sufficient cells for scoring, incubation time was extended to up to 34 hours in the 

sister chromatid exchange test. Experimental design 

normally calls for no more than 33 hours exposure to 

BrdU, but, because increases in sister chromatid 

exchange frequencies were also seen at standard 

harvest times, in the absence of S9, the delayed 

harvest results were accepted as confirmatory of the 

results seen in Trial 1. In the sister chromatid exchange test with S9, the only concentration that 

produced a significant increase in sister chromatid 

exchanges was the 1,700 μg/mL dose, which employed a culture time of 33.5 hours. However, 

because the response was so strong, it was accepted 

that even if BrdU exposure contributed to some extent 

to the induction of sister chromatid exchanges, much 

of the increase was due to exposure to 1-chloro-2­

propanol. This trial was not repeated because it was 

apparent from the combined results of the three trials 

that 1-chloro-2-propanol induced sister chromatid 

exchanges in cultured Chinese hamster ovary cells. In 

the cultured Chinese hamster ovary cell chromosomal 

aberrations test with 1-chloro-2-propanol, fewer than 

the usual 200 cells per concentration were scored 

because a marked increase in aberrations as well as in 

the percentage of cells with aberrations was observed. 

The chromosomal effects seen in vitro were not 

apparent in the in vivo studies, but induction of gene 

mutations was observed. Positive results were obtained in the Drosophila melanogaster test for 

induction of sex-linked recessive lethal mutations in 

germ cells of male flies administered 1-chloro-2­

propanol via injection (Table E4; Foureman et al., 

1994). However, a subsequent test for induction of 

reciprocal chromosomal translocations in germ cells of 

male D. melanogaster yielded negative results (Table 

E5; Foureman et al., 1994). Additional negative 

results were obtained for chromosomal effects in mice. 

No induction of micronucleated erythrocytes was 

observed in peripheral blood of male or female mice 

administered 1-chloro-2-propanol in drinking water for 

14 weeks (Table E6). 

CONTINUOUS BREEDING STUDY 

IN SPRAGUE-DAWLEY RATS 

The complete methods and results of the continuous 

breeding study are presented in Appendix F. Exposure to 1-chloro-2-propanol did not cause significant 
1-Chloro-2-propanol, NTP TR 477 55 

reproductive toxicity in rats. All exposed and control 

pairs except one 300 ppm pair were fertile; all pairs 

exposed to 1,300 ppm delivered five litters. The 

average numbers of litters per pair of all exposed 

groups were similar to that of the controls. The 

cumulative number of days to litter for the 1,300 ppm 

group was slightly but significantly greater than that of 

the controls for litter 5. At delivery of each litter, the 

mean body weights of dams in the 650 ppm group 

(except for the second litter) and the 1,300 ppm group 

were significantly less than those of the controls. 

Mean body weights of litter 5 dams in the 650 ppm 

group were significantly less than those of the controls 

from lactation days 0 to 14, and the mean body 

weights of dams in the 1,300 ppm group were 

significantly less than those of the controls throughout 

lactation. 

The survival of the final litters of exposed F pups was 1 

similar to that of the controls throughout lactation. 

Male and female F pup weights were significantly less 1 

than those of the controls in the 1,300 ppm group on 

days 7, 14, and 21 and in the 650 ppm group on days 

14 and 21. 

During the offspring assessment phase of the 

continuous breeding study, the mean body weight of 

dams in the 1,300 ppm group at delivery was 

significantly less than that of the controls. Exposure 

to 1,300 ppm did not affect the number of live pups 

per litter, the sex ratio, or pup or organ weights. The 

percentage of abnormal sperm was significantly 

greater in 1,300 ppm male rats than in the controls. 

There were no significant differences in estrous cycle 

parameters between control and 1,300 ppm females. 
56 1-Chloro-2-propanol, NTP TR 477 
PLATE 1 PLATE 2 

Pancreas from a male F344 rat exposed to 3,300 ppm 1-chloro- Pancreas from a control F344 rat at the same magnification as
 

2-propanol in drinking water for 90 days. Note the diffuse Plate 1. H&E; 13 ×
 

vacuolated appearance of the pancreas compared to a normal
 

pancreas in Plate 2. H&E; 13 ×
 

PLATE 3 

Pancreas from a male F344 rat exposed to 3,300 ppm 1-chloro2-propanol in drinking water for 90 days. Higher magnification 

of Plate 1 showing the large adiposytes (a) and interspersed 

residual exocrine pancreatic tissue. H&E; 125 × 

PLATE 4 

Pancreas from a male F344 rat exposed to 3,300 ppm 1-chloro2-propanol in drinking water for 90 days. Zymogen granules are 

lacking in the apical region of the acinar cells, compared with a 

normal pancreas in Plate 5. H&E; 250 × 
PLATE 5 

Pancreas from a control male F344 rat. The pancreas is normal; 

note the abundant zymogen granules in the apical region of the 

acinar cells (arrows). The structure in the center is an islet (I). 

H&E; 250 × 

PLATE 7 

Pancreas from a female F344 rat exposed to 3,300 ppm 1­

chloro-2-propanol in drinking water for 90 days. Note the large 

polygonal cells (hepatocyte metaplasia) at the border of the 

pancreatic islet (between arrows); compare to the centrally 

located smaller, normal islet cells. H&E; 125 × 

PLATE 6 

Pancreas from a male F344 rat exposed to 3,300 ppm 1-chloro2-propanol in drinking water for 90 days. Note the cellular 

debris (apoptosis) which appears to be within acinar cells 

(arrows). H&E; 500 × 

PLATE 8 

Liver from a male F344 rat exposed to 3,300 ppm 1-chloro-2­

propanol in drinking water for 90 days. Vacuoles (arrows) are 

present within hepatocytes in the centrilobular region of the 

liver. H&E; 125 × 
57 

DISCUSSION AND CONCLUSIONS
 

The NTP conducted toxicology and carcinogenesis 

studies of technical grade 1-chloro-2-propanol (75% to 

76% 1-chloro-2-propanol and 24% to 25% 2-chloro-1­

propanol; also known as chlorohydrins). The National 

Cancer Institute nominated 1-chloro-2-propanol for 

study because of the potential for human exposure to 

chlorohydrins that are formed as a by-product of 

sterilization of various foods fumigated with ethylene 

oxide or propylene oxide. Such fumigation may be 

used for sterilizing foodstuffs including spices, cocoa, 

flour, dried egg powder, desiccated coconut, dried 

fruits, and dehydrated vegetables (Wesley et al., 1965; 

Ragelis et al., 1966; Fishbein, 1969). 

In the 14-day studies, rats and mice received 1-chloro2-propanol in drinking water at concentrations of 0, 

100, 330, 1,000, 3,300, or 10,000 ppm. Two female 

rats and one male mouse in the 10,000 ppm groups 

died before the end of the studies. Minimal to mild 

lesions of the exocrine pancreas were observed in the 

3,300 and 10,000 ppm male and female groups of rats 

and mice. Atrophy and/or hematopoiesis of the bone 

marrow and spleen occurred in 3,300 and 10,000 ppm 

male and female rats. A minimal to mild hepatocellular vacuolization of the liver in 1,000, 3,300, and 

10,000 ppm male and female mice and atrophy of the 

spleen in 10,000 ppm male and female mice were 

observed. 

In the 14-week studies, rats and mice received 0, 33, 

100, 330, 1,000 or 3,300 ppm 1-chloro-2-propanol in 

drinking water. No treatment-related effects on survival occurred. The exocrine pancreatic lesions 

observed in the 14-day studies were also observed in 

the 14-week studies; however, the lesions were more 

severe and occurred in 1,000 and 3,300 ppm male and 

female rats and in 3,300 ppm male and female mice. 

In general, pancreatic islets (endocrine pancreas) 

remained intact; however, metaplasia (hepatocytic) was 

observed in a few islets in five of ten 3,300 ppm 

female rats. Within the peripheral region of affected 

islets, there was a variably thick band of large polygonal cells with abundant eosinophilic cytoplasm which 

resembled hepatocytes (Plate 7). In other studies, 

these cells have been shown to have characteristics of 

hepatocytes, not of exocrine or endocrine pancreatic 

cells. These “pancreatic hepatocytes” may occur 

spontaneously and increases have been observed with 

administration of some chemicals/agents (McDonald 

and Boorman, 1989). In many instances, increased 

incidences have been associated with pancreatic 

atrophy and fibrosis. 

Rodent acinar cells are sensitive to the toxic effects of 

a wide variety of chemicals and also to viruses, nutritional deficit, and trauma (Angiolelli and Rio, 1972; 

Lansdown, 1976; Longnecker, 1982; Rao et al., 

1987). Acute pancreatitis can be caused by direct 

injury of acinar cells, resulting in necrosis and release 

of enzymes into the interstitium, which causes injury 

to adjacent acinar cells. The acinar cells of the pancreas comprise approximately 85% of the pancreas 

volume. These cells synthesize and store digestive 

proenzymes packaged into zymogen granules, and this 

elaborate intercellular compartmentation of enzymes 

protects the cell from destruction by its own enzymes 

(deoxyribonuclease, ribonuclease, lipase, amylase, 

etc.) (Longnecker, 1982). Ingestion of food 

“activates” the zymogen granules into the duct system, 

where the enzymes mix with water and bicarbonate 

ions, and this pancreatic juice is released into the 

duodenoma. 

The exposure concentrations for the 2-year studies 

were set just below the concentrations that were 

known to induce exocrine pancreas lesions in the 

14-day and 14-week studies. The severity of the exocrine pancreatic lesions progressed when treatment 

was lengthened from 14 days to 14 weeks, and it was 

thought that the severities of these lesions would 

continue to progress during the 2-year studies; 

therefore, exposure concentrations at which these 

lesions occurred would not be suitable for the 2-year 

studies. When enzyme secretion from the pancreas is 

reduced more than 10% by necrosis, clinical evidence 

of malabsorption develops (Longnecker, 1982). 
58 1-Chloro-2-propanol, NTP TR 477 

In the 2-year rat study, animals received 0, 150, 325, et al., 1987; Longnecker and Millar, 1990). The 

or 650 ppm 1-chloro-2-propanol in drinking water acinar cell is considered to be the cell of origin for 

(equivalent to average daily doses of approximately pancreatic exocrine tumors in rats. In general, tumors 

15, 30, or 65 mg/kg to males and females during of the exocrine pancreas are more frequent in male rats 

the first several months of the study and 8, 17, or than in female rats (Longnecker and Millar, 1990). 

34 mg/kg for the remainder of the 2-year study). In Acidophilic foci (or acinar cell hyperplasia) were not 

the 2-year mouse study, animals received exposure observed in rats or mice in the 14-week studies of 

concentrations of 0, 250, 500 or 1,000 ppm in 1-chloro-2-propanol, and the lesions observed in the 

drinking water (equivalent to average daily doses of 14-week studies did not occur in the 2-year studies. 

approximately 45, 75, or 150 mg/kg to males and 60, 

105, or 210 mg/kg to females during the first several The following chemicals studied by the NTP have 

months of the study and 25, 50, or 100 mg/kg for the been found to cause some or clear evidence of causing 

remainder of the study). There were no treatment- pancreatic neoplasms [exocrine tumors (acinar cell 

related effects on survival or body weights and no adenoma/adenocarcinoma)] in the rat, most often in 

treatment-related neoplasms or nonneoplastic lesions. males: nitrofen (NCI, 1978), cinnamyl anthranilate 

(NCI, 1980), commercial grade 2,4 (80%)- and 

Inflammatory pancreatic responses occur in humans 2,6 (20%)-toluene diisocyanate (NTP, 1986), 

and may be due to a variety of causes (e.g., alcohol, chlorendic acid (NTP, 1987a), 2-amino-5-nitrophenol 

gall stones, etc.) (Mack et al., 1986; Steinberg and (NTP, 1988a), 2-mercaptobenzothiazole (NTP, 

Tenner, 1994; Steer et al., 1995), but this syndrome 1988b), dichlorvos (NTP, 1989), and 1,2,3­

did not occur with 1-chloro-2-propanol at the time trichloropropane (NTP, 1993). In the NTP historical 

points evaluated, although there was significant loss of database there are no chemicals reported to cause 

exocrine pancreatic tissue and replacement by mature pancreatic neoplasms in mice. Other chemicals, paradipocytes. In the 1-chloro-2-propanol studies, the ticularly N-nitroso compounds, have been reported to 

pancreatic changes were suggestive of a mild insult cause pancreatic neoplasms in rats (Longnecker et al., 

rather than acute pancreatitis in which the released 1984). The NTP has found increased incidences of 

enzymes and necrotic debris incite an acute inflam- focal acinar hyperplasia and acinar adenoma in male 

mation and pancreatitis. With chemicals that cause a rats administered corn oil by gavage for 2 years as 

subtle insult, the only histologic evidence of injury compared to male rats not administered corn oil 

may be autophagic vacuoles and/or apoptotic bodies (Eustis and Boorman, 1985). 

and little to no inflammatory response. In these 

studies, acinar cells containing minimal zymogen With these pancreatic carcinogens studied by the NTP, 

granules and autophagic vacuoles and/or apoptotic with corn oil, and with azaserine and other rodent 

bodies were commonly observed. pancreatic carcinogens, increased preneoplastic acinar 

cell hyperplasia may occur at various time points after 

In 13-week NTP studies of another chlorohydrin, treatment. In the studies of pancreatic carcinogens by 

ethylene chlorohydrin (NTP, 1985b), exocrine pancre- the NTP, acinar cell hyperplasia was often observed at 

atic lesions were also observed in rats and mice. The the end of the 2-year studies. No lesions of the 

pancreatic lesions were composed of minimal to mild exocrine pancreas similar to those observed at 

vacuolar changes within acinar cells and an apparent 13 weeks in the current study were seen in NTP 

reduction of zymogen granules. The extensive fatty studies of chemicals that caused pancreatic neoplasms. 

change and acinar cell degeneration seen in the In the 1-chloro-2-propanol rat studies, acinar cell 

1-chloro-2-propanol studies did not occur. hyperplasia occurred in three males in the 650 ppm 

group, but there was no evidence of a neoplasm 

Several studies have been conducted to characterize response. While there is no established database for 

the putative preneoplastic pancreatic lesions in rodents nonneoplastic pancreatic lesions, the incidence of 

following exposure to pancreatic carcinogens. With pancreatic hyperplasia in untreated male F344/N rats 

azaserine, a pancreatic carcinogen in rats, a small from 17 NTP feed studies was 2.6%, with a range of 

proportion of acidophilic foci and/or focal acinar cell 0% to 10% (Eustis and Boorman, 1985). This minihyperplasia is thought to progress to adenocarcinoma mal incidence of pancreatic hyperplasia was not 

in lifetime studies (Longnecker et al., 1984; Roebuck considered to be related to chemical administration. 
1-Chloro-2-propanol, NTP TR 477 59 

In the United States, carcinoma of the exocrine 

pancreas ranks fifth among all cancers and is the 

fourth leading cause of cancer deaths (Benson and 

Teta, 1993). The etiology of pancreatic carcinoma is 

not known, although some studies have shown an 

association between smoking and pancreatic cancer 

(Mack et al., 1986). It would be of interest to study 

the progression of pancreatic lesions seen in the 

14-day and 14-week studies of 1-chloro-2-propanol. 

That pancreatic cancer is rising in incidence suggests 

that environmental factors may play a role in this 

disease (Longnecker, 1982; Longnecker and Millar, 

1990). The incidence of pancreatic cancer is low in 

the Japanese population, but Japanese who have 

migrated to the United States have a higher incidence 

of pancreatic cancer, which supports the hypothesis 

that environmental factors play a role in the etiology 

of this cancer (Longnecker, 1982). 

In the workplace (at a chlorohydrin plant in South 

Carolina), where chlorohydrins are one of several 

chemicals to which exposures are possible, there is 

evidence for increased mortality from pancreatic 

cancer (type of pancreatic cancer not specified) and 

lymphocytic leukemia (Greenberg et al., 1990; Benson 

and Teta, 1993). Studies of other chlorohydrin 

production facilities in Louisiana and Texas did not 

find any association between work in the plant and an 

increase in pancreatic cancer incidences (Olsen et al., 

1997), although the duration of follow-up was 

25 years versus 36 years in the studies of the South 

Carolina workers. In addition, other differences in the 

plant processes were noted (e.g., closed facility versus 

open facility at the South Carolina plant). Other 

epidemiological studies have implicated short-chain 

hydrocarbons in the occurrence of pancreatic cancer 

(Benson and Teta, 1993). 

1-Chloro-2-propanol (technical grade) was weakly 

mutagenic in Salmonella typhimurium with and without metabolic activation in strains TA100 and TA1535 

but not in strain TA97, TA98, or TA1537 (the strains 

that revert via frameshift mutation) (Carr and 

Rosenkranz, 1978; Pfeiffer and Dunkelberg, 1980; 

Zeiger et al., 1987). In addition, 1-chloro-2-propanol 

was positive in the mouse lymphoma assay and 

induced significant chromosomal aberrations consisting mainly of chromatid breaks in rat bone marrow 

cells at doses of 10, 31, or 100 mg/kg per day (Biles 

and Piper, 1983). In general, these mutagenicity 

studies used the same technical grade 1-chloro-2­

propanol as was used in the 14-day, 14-week, and 

2-year studies. Assay systems are available to detect 

damage to the DNA in pancreatic acinar cells 

(Curphey et al., 1987), and testing chlorinated hydrocarbons in these assay systems may be warranted. 

In the 14-week studies, sperm morphology results 

showed a greater percentage of abnormal sperm and 

lower cauda epididymis and epididymis weights in 

3,300 ppm male rats than those in the controls. In 

mice, there was no effect on sperm morphology or 

concentration, although there was a significantly lower 

epididymis weight in 3,300 ppm males than in the 

controls. This effect may have been related in part to 

body weights lower than those of the controls. 

However, to more completely examine the potential of 

1-chloro-2-propanol to affect fertility, a rat continuous 

breeding study was conducted according to an NTP 

study design (Gulati et al., 1991). Morrissey et al. 

(1989) and Chapin et al. (1997) have found that the 

organ weight change that best correlates with reduced 

fertility is reduced epididymal weight. 

In the NTP CD BR outbred Sprague-Dawley albino rat 

continuous breeding study, 1-chloro-2-propanol did 

not affect fertility or reproduction when given in the 

drinking water at exposure concentrations of 300, 650, 

or 1,300 ppm. The percentage of abnormal sperm was 

significantly greater in 1,300 ppm F1 rats than in the

controls. Therefore, in these follow-up rat continuous 

breeding studies, which used a study design sensitive 

to small changes (8%) in fertility, there were no 

changes in fertility after exposure to 1-chloro-2­

propanol. 
__________ 

60 1-Chloro-2-propanol, NTP TR 477 

CONCLUSIONS 

Under the conditions of these 2-year drinking water 650 ppm. There was no evidence of carcinogenic 

studies, there was no evidence of carcinogenic activity of technical grade 1-chloro-2-propanol in male 

activity* of technical grade 1-chloro-2-propanol in or female B6C3F1 mice exposed to 250, 500, or 

male or female F344/N rats exposed to 150, 325, or 1,000 ppm. 

*	 Explanation of Levels of Evidence of Carcinogenic Activity is on page 9. A summary of the Technical Reports Review Subcommittee 

comments and the public discussion on this Technical Report appears on page 11. 
61 

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67 

APPENDIX A
 

SUMMARY OF LESIONS IN MALE RATS
 

IN THE 2-YEAR DRINKING WATER STUDY
 

OF 1-CHLORO-2-PROPANOL
 

TABLE A1 Summary of the Incidence of Neoplasms in Male Rats 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

TABLE A2 Individual Animal Tumor Pathology of Male Rats 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

TABLE A3 Statistical Analysis of Primary Neoplasms in Male Rats 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

TABLE A4 Historical Incidence of Mammary Gland Fibroadenoma 

................... 68 

................... 72 

................... 88 

in Untreated Male F344/N Rats ....................................... 92

TABLE A5 Summary of the Incidence of Nonneoplastic Lesions in Male Rats 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 93
 
 

 

 

 

 

 

 

 

68 1-Chloro-2-propanol, NTP TR 477 

TABLE A1 

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanola 

0 ppm 150 ppm 325 ppm 650 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 12 13 7 10 

Natural deaths 18 14 19 17 

Survivors 

Died last week of study 1 

Terminal sacrifice 19 23 24 23 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Esophagus (50) (50) (50) (50) 

Squamous cell carcinoma 1 (2%) 

Intestine large, colon (46) (46) (48) (47) 

Squamous cell carcinoma, metastatic, skin 1 (2%) 

Intestine large, cecum (45) (46) (45) (44) 

Intestine small, duodenum (46) (45) (46) (48) 

Intestine small, jejunum (39) (42) (41) (42) 

Intestine small, ileum (39) (41) (41) (43) 

Liver (50) (50) (50) (50) 

Hepatocellular carcinoma 1 (2%) 1 (2%) 

Hepatocellular adenoma 1 (2%) 3 (6%) 1 (2%) 2 (4%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Mesentery (12) (11) (10) (14) 

Lipoma 1 (7%) 

Oral mucosa (2) 

Squamous cell papilloma 1 (50%) 

Pancreas (48) (45) (46) (48) 

Acinus, adenoma 1 (2%) 1 (2%) 1 (2%) 1 (2%) 

Salivary glands (50) (50) (49) (50) 

Histiocytic sarcoma 1 (2%) 

Stomach, forestomach (50) (49) (48) (49) 

Stomach, glandular (50) (49) (48) (50) 

Cardiovascular System 

Blood vessel (48) (50) (50) (50) 

Heart (50) (50) (50) (50) 

Endocrine System 

Adrenal cortex (50) (49) (49) (50) 

Carcinoma 1 (2%) 

Adrenal medulla (50) (49) (49) (50) 

Pheochromocytoma malignant 1 (2%) 1 (2%) 2 (4%) 

Pheochromocytoma benign 7 (14%) 13 (27%) 13 (27%) 11 (22%) 

Bilateral, pheochromocytoma benign 6 (12%) 1 (2%) 4 (8%) 1 (2%) 

Islets, pancreatic (49) (45) (46) (47) 

Adenoma 2 (4%) 1 (2%) 2 (4%) 3 (6%) 

Carcinoma 1 (2%) 

Pituitary gland (48) (49) (49) (50) 

Pars distalis, adenoma 15 (31%) 20 (41%) 25 (51%) 24 (48%) 
 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 69 

TABLE A1 

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Endocrine System (continued) 

Thyroid gland (50) (50) (50) (50) 

C-cell, adenoma 5 (10%) 1 (2%) 6 (12%) 3 (6%) 

C-cell, carcinoma 2 (4%) 1 (2%) 

Follicular cell, adenoma 1 (2%) 1 (2%) 

General Body System 

Peritoneum (3) (1) 

Genital System 

Epididymis (50) (49) (50) (50) 

Preputial gland (50) (50) (50) (49) 

Adenoma 1 (2%) 1 (2%) 2 (4%) 2 (4%) 

Carcinoma 1 (2%) 4 (8%) 4 (8%) 3 (6%) 

Bilateral, carcinoma 1 (2%) 

Prostate (50) (50) (50) (50) 

Adenoma 1 (2%) 

Seminal vesicle (50) (50) (50) (50) 

Testes (50) (49) (50) (50) 

Bilateral, interstitial cell, adenoma 36 (72%) 32 (65%) 31 (62%) 34 (68%) 

Interstitial cell, adenoma 10 (20%) 11 (22%) 9 (18%) 12 (24%) 

Hematopoietic System 

Bone marrow (47) (45) (47) (49) 

Lymph node (24) (23) (23) (24) 

Iliac, squamous cell carcinoma, metastatic,

 skin 1 (4%) 

Lymph node, mandibular (50) (50) (50) (50) 

Carcinoma, metastatic, Zymbal’s gland 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Squamous cell carcinoma, metastatic,

 uncertain primary site 1 (2%) 

Lymph node, mesenteric (49) (50) (50) (50) 

Spleen (50) (50) (50) (50) 

Thymus (49) (47) (48) (47) 

Thymoma benign 1 (2%) 

Integumentary System 

Mammary gland (50) (45) (48) (47) 

Fibroadenoma 7 (14%) 5 (10%) 6 (13%) 

Fibroadenoma, multiple 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

70 1-Chloro-2-propanol, NTP TR 477 

TABLE A1 

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Integumentary System (continued) 

Skin (50) (50) (50) (50) 

Basal cell carcinoma 1 (2%) 

Keratoacanthoma 2 (4%) 3 (6%) 3 (6%) 6 (12%) 

Keratoacanthoma, multiple 1 (2%) 

Squamous cell carcinoma, multiple 1 (2%) 

Squamous cell papilloma 1 (2%) 

Trichoepithelioma 1 (2%) 

Subcutaneous tissue, fibroma 3 (6%) 8 (16%) 7 (14%) 6 (12%) 

Subcutaneous tissue, fibrosarcoma 1 (2%) 1 (2%) 

Subcutaneous tissue, histiocytic sarcoma 1 (2%) 

Subcutaneous tissue, lipoma 1 (2%) 

Subcutaneous tissue, melanoma malignant 1 (2%) 

Subcutaneous tissue, sarcoma 1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) (50) 

Osteosarcoma 1 (2%) 

Vertebra, osteosarcoma 1 (2%) 

Skeletal muscle (2) (1) 

Histiocytic sarcoma 1 (100%) 

Nervous System 

Brain (50) (50) (50) (50) 

Carcinoma, metastatic, Zymbal’s gland 1 (2%) 

Respiratory System 

Lung (50) (50) (50) (50) 

Alveolar/bronchiolar adenoma 2 (4%) 1 (2%) 

Alveolar/bronchiolar carcinoma 2 (4%) 1 (2%) 

Carcinoma, metastatic, uncertain primary site 1 (2%) 

Hepatocellular carcinoma, metastatic, liver 1 (2%) 

Osteosarcoma, metastatic, bone 1 (2%) 

Osteosarcoma, metastatic, uncertain primary

 site 1 (2%) 

Nose (50) (47) (49) (50) 

Histiocytic sarcoma 1 (2%) 

Respiratory epithelium, adenoma 1 (2%) 

Special Senses System 

Harderian gland (1) 

Histiocytic sarcoma 1 (100%) 

Zymbal’s gland (1) (3) (3) 

Carcinoma 1 (100%) 3 (100%) 3 (100%) 

Urinary System 

Kidney (50) (49) (49) (50) 

Renal tubule, adenoma 1 (2%) 1 (2%) 

Renal tubule, carcinoma 1 (2%) 

Urinary bladder (48) (50) (49) (49) 
 

 

71 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE A1 

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Systemic Lesions 

Multiple organsb (50) (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Leukemia mononuclear 32 (64%) 33 (66%) 30 (60%) 31 (62%) 

Mesothelioma malignant 3 (6%) 1 (2%) 2 (4%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 48 50 50 50 

Total primary neoplasms 141 148 156 161 

Total animals with benign neoplasms 48 48 48 50 

Total benign neoplasms 99 101 112 116 

Total animals with malignant neoplasms 39 38 37 37 

Total malignant neoplasms 42 47 44 45 

Total animals with metastatic neoplasms 3 4 1 

Total metastatic neoplasms 3 5 1 

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 

Primary neoplasms: all neoplasms except metastatic neoplasms 
 

 

 

 

 

 

 

 

 

 

 

 

72 1-Chloro-2-propanol, NTP TR 477 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 0 ppm 

3 4 4 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 

Number of Days on Study	 6 4 9 0 2 3 5 7 7 7 8 8 9 1 1 2 3 3 5 5 7 8 9 9 9 

2 5 4 2 9 2 1 8 9 9 0 5 9 1 6 9 5 7 5 8 3 7 3 3 7 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

Carcass ID Number 0 0 0 3 1 2 1 4 1 4 0 0 3 0 2 1 4 0 3 2 3 1 4 4 1 

7 8 4 2 3 2 9 6 8 2 1 9 3 5 8 1 8 3 4 1 5 5 5 9 7 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 

Squamous cell carcinoma X 

Intestine large, colon + + + + + + + A + + + + + + + + + + + + + + + + A 

Intestine large, rectum + + + + + + + A A A + + + + + + + + + A + + + + + 

Intestine large, cecum + + + + + + + A A A + + + + + + + + + + A + + + + 

Intestine small, duodenum + + + + + + + + + + A + + + + + A + + + A + + + + 

Intestine small, jejunum + + + + + + + A A A A + + + + + A + + A A + A + A 

Intestine small, ileum M + + + + + + A + A A + + + + + A + + A A A A + + 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 

Hepatocellular adenoma 

Mesentery + + + + 

Oral mucosa + + 

Squamous cell papilloma X 

Pancreas A + + + + + + + + + + + + + + + + + + + + + + + + 

Acinus, adenoma 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 

Cardiovascular System 

Blood vessel + + + + + + + + + M + + + + + + M + + + + + + + + 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Pheochromocytoma malignant X 

Pheochromocytoma benign X X 

Bilateral, pheochromocytoma benign 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma X 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + M + 

Pituitary gland + + + + M M + + + + + + + + + + + + + + + + + + + 

Pars distalis, adenoma X X X X X X 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

C-cell, adenoma X 

Follicular cell, adenoma X 

General Body System 

Peritoneum + + 

Tissue NOS 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Penis + 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma 

Carcinoma 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma 

+: Tissue examined microscopically M: Missing tissue X: Lesion present 

A: Autolysis precludes examination I: Insufficient tissue Blank: Not examined 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 73 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 0 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 0 0 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

3 9 4 6 6 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Total 

Carcass ID Number 2 4 3 0 5 0 1 1 1 1 2 2 2 2 2 2 3 3 3 3 3 4 4 4 4 Tissues/ 

3 3 7 2 0 6 0 2 4 6 0 4 5 6 7 9 0 1 6 8 9 0 1 4 7 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Squamous cell carcinoma 1 

Intestine large, colon + M A + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine large, rectum + + A + + + + + + + + + + + + + + + + + + + + + + 45 

Intestine large, cecum + + A + + + + + + + + + + + + + + + + + + + + + + 45 

Intestine small, duodenum + + A + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, jejunum + + A A + + + + + + + + + + + + + + + + + + + + + 39 

Intestine small, ileum + A A + + + + + + + + + + + + + + + + + + + + + + 39 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocellular adenoma X 1 

Mesentery + + + + + + + + 12 

Oral mucosa 2 

Squamous cell papilloma 1 

Pancreas + + A + + + + + + + + + + + + + + + + + + + + + + 48 

Acinus, adenoma X 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma malignant 1 

Pheochromocytoma benign X X X X X 7 

Bilateral, pheochromocytoma benign X X X X X X 6 

Islets, pancreatic + + A + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma X 2 

Parathyroid gland + + + + + M + + + + + + + + + + + + + + + + + + + 48 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Pars distalis, adenoma X X X X X X X X X 15 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, adenoma X X X X 5 

Follicular cell, adenoma 1 

General Body System 

Peritoneum + 3 

Tissue NOS + 1 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Penis 1 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Carcinoma X 1 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

74 1-Chloro-2-propanol, NTP TR 477 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 0 ppm 

3 4 4 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 

Number of Days on Study	 6 4 9 0 2 3 5 7 7 7 8 8 9 1 1 2 3 3 5 5 7 8 9 9 9 

2 5 4 2 9 2 1 8 9 9 0 5 9 1 6 9 5 7 5 8 3 7 3 3 7 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

Carcass ID Number 0 0 0 3 1 2 1 4 1 4 0 0 3 0 2 1 4 0 3 2 3 1 4 4 1 

7 8 4 2 3 2 9 6 8 2 1 9 3 5 8 1 8 3 4 1 5 5 5 9 7 

Genital System (continued) 

Seminal vesicle 

Testes 

Bilateral, interstitial cell, adenoma 

Interstitial cell, adenoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X X X X X X X 

X X X X X X X X 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, mandibular 

Squamous cell carcinoma, metastatic,

 uncertain primary site 

Lymph node, mesenteric 

Spleen 

Thymus 

+ + + + + + + A + + A + + + + + A + + + + + + + + 

+ + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + A + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + M 

Integumentary System 

Mammary gland 

Fibroadenoma 

Skin 

Basal cell carcinoma 

Keratoacanthoma 

Subcutaneous tissue, fibroma 

Subcutaneous tissue, sarcoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X X 

X 

Musculoskeletal System 

Bone 

Vertebra, osteosarcoma 

Skeletal muscle 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + +
 

Peripheral nerve + +
 

Spinal cord + +
 

Respiratory System 

Lung 

Carcinoma, metastatic, uncertain primary site 

Osteosarcoma, metastatic, bone 

Nose 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Zymbal’s gland 

Carcinoma 

+ 

X 

Urinary System 

Kidney 

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + A + + + + + + + + + + + + + + 

Systemic Lesions 

Multiple organs 

Leukemia mononuclear 

Mesothelioma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X X X X X X 

X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 75 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 0 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 0 0 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

3 9 4 6 6 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Total 

Carcass ID Number 2 

3 

4 

3 

3 

7 

0 

2 

5 

0 

0 

6 

1 

0 

1 

2 

1 

4 

1 

6 

2 

0 

2 

4 

2 

5 

2 

6 

2 

7 

2 

9 

3 

0 

3 

1 

3 

6 

3 

8 

3 

9 

4 

0 

4 

1 

4 

4 

4 

7 

Tissues/ 

Tumors 

Genital System (continued) 

Seminal vesicle 

Testes 

Bilateral, interstitial cell, adenoma 

Interstitial cell, adenoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X X X X X X X X X X X X X X X X X 

X X 

50 

50 

36 

10 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, mandibular 

Squamous cell carcinoma, metastatic,

 uncertain primary site

Lymph node, mesenteric 

Spleen 

Thymus 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

47 

24 

50 

1 

49 

50 

49 

Integumentary System 

Mammary gland 

Fibroadenoma 

Skin 

Basal cell carcinoma 

Keratoacanthoma 

Subcutaneous tissue, fibroma 

Subcutaneous tissue, sarcoma

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

X

X

50 

7 

50 

1 

2 

3 

1 

Musculoskeletal System 

Bone 

Vertebra, osteosarcoma

Skeletal muscle 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+

50 

1 

2 

Nervous System 

Brain 

Peripheral nerve

Spinal cord

+ + + + + + + + + + + + + + + + + + + + + + + + + 50 

2 

2 

Respiratory System 

Lung 

Carcinoma, metastatic, uncertain primary site 

Osteosarcoma, metastatic, bone

Nose 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

1 

1 

50 

50 

Special Senses System 

Zymbal’s gland

Carcinoma

 1 

1 

Urinary System 

Kidney 

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + A + + + + + + + + + + + + + + + + + + + + + + 

50 

48 

Systemic Lesions 

Multiple organs 

Leukemia mononuclear 

Mesothelioma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X X X X X X X X X X X X X X 

X X

50 

32 

3 
 

 

 

 

 

 

 

76 1-Chloro-2-propanol, NTP TR 477 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

150 ppm 

Number of Days on Study 

3 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 

8 0 4 4 5 5 9 9 0 1 1 3 3 4 5 5 7 9 9 0 0 1 1 1 2 

8 2 4 8 5 5 2 3 9 1 3 0 6 3 5 7 5 3 7 6 7 1 6 8 1 

Carcass ID Number 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

5 7 5 9 7 8 5 5 7 5 7 5 7 8 6 9 7 6 6 9 5 9 8 7 6 

3 6 8 6 7 6 6 7 3 5 4 2 9 1 4 3 0 1 0 9 4 8 9 8 2 

Alimentary System 

Esophagus 

Intestine large, colon 

Squamous cell carcinoma, metastatic, skin 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Hepatocellular adenoma 

Histiocytic sarcoma 

Mesentery 

Pancreas 

Acinus, adenoma 

Salivary glands 

Stomach, forestomach 

Stomach, glandular 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + A + A A + + + + + 

X 

+ + + + + + + + + + + + + + + + A + + A + + + + + 

+ + + + + + + + + + + + + + + + A + A A + + + + + 

+ + + + + + + + A + A + + + + A A + + + + + + + + 

+ + + + + + + + A + A + + + + A A A A A + + + + + 

+ + + + + + + A A + A + + + + A A A A + + + + A + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + 

+ + + + + + + + A + A + + + + A A + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + A + + + + + + + + 

+ + + + + + + + + + + + + + + + A + + + + + + + + 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Endocrine System 

Adrenal cortex + + + + + + + + + + A + + + + + + + + + + + + + + 

Carcinoma 

Adrenal medulla + + + + + + + + + + A + + + + + + + + + + + + + + 

Pheochromocytoma benign X X X X X X 

Bilateral, pheochromocytoma benign 

Islets, pancreatic + + + + + + + + A + A + + + + A A + + + + + + + + 

Adenoma 

Parathyroid gland + + + M + + + + + + + + + + + + + + + + + + + + + 

Pituitary gland + + + + + + + + + + A + + + + + + + + + + + + + + 

Pars distalis, adenoma X X X X X X X 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

C-cell, adenoma 

C-cell, carcinoma 

General Body System 

None 

Genital System 

Epididymis + + + + + + + M + + + + + + + + + + + + + + + + + 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma 

Carcinoma 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 

Testes + + + + + + + M + + + + + + + + + + + + + + + + + 

Bilateral, interstitial cell, adenoma X X X X X X X X X X X 

Interstitial cell, adenoma X X X X X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 77 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

150 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

3 8 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Total 

Carcass ID Number 6 9 5 5 6 6 6 6 6 7 7 7 8 8 8 8 8 8 8 9 9 9 9 9 0 Tissues/ 

5 1 1 9 3 6 7 8 9 1 2 5 0 2 3 4 5 7 8 0 2 4 5 7 0 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, colon + A + + + + + + + + + + + + + + + + + + + + + + + 46 

Squamous cell carcinoma, metastatic, skin 1 

Intestine large, rectum + A + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine large, cecum + A + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, duodenum + A + + + + + + + + + + + + + + + + + + + + + + + 45 

Intestine small, jejunum + A + + + + + + + + + + + + + + + + + + + + + + + 42 

Intestine small, ileum + A + + + + + + + + + + + + + + + + + + + + + + + 41 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocellular adenoma X X 3 

Histiocytic sarcoma X 1 

Mesentery + + + + 11 

Pancreas + A + + + + + + + + + + + + + + + + + + + + + + + 45 

Acinus, adenoma X 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Carcinoma X 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pheochromocytoma benign X X X X X X X 13 

Bilateral, pheochromocytoma benign X 1 

Islets, pancreatic + A + + + + + + + + + + + + + + + + + + + + + + + 45 

Adenoma X 1 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pars distalis, adenoma X X X X X X X X X X X X X 20 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, adenoma X 1 

C-cell, carcinoma X X 2 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Carcinoma X X X X 4 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Bilateral, interstitial cell, adenoma X X X X X X X X X X X X X X X X X X X X X 32 

Interstitial cell, adenoma X X 11 
 

 

 

 

 

 

 

 

 

 

 

78 1-Chloro-2-propanol, NTP TR 477 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

150 ppm 

3 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 

Number of Days on Study 8 0 4 4 5 5 9 9 0 1 1 3 3 4 5 5 7 9 9 0 0 1 1 1 2 

8 2 4 8 5 5 2 3 9 1 3 0 6 3 5 7 5 3 7 6 7 1 6 8 1 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

Carcass ID Number 5 7 5 9 7 8 5 5 7 5 7 5 7 8 6 9 7 6 6 9 5 9 8 7 6 

3 6 8 6 7 6 6 7 3 5 4 2 9 1 4 3 0 1 0 9 4 8 9 8 2 

Hematopoietic System 

Bone marrow + + + + + + + + A + A + + + + A + A + + + + + + + 

Lymph node + + + + + + + + + + + + + + + 

Iliac, squamous cell carcinoma, metastatic, skin X 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, Zymbal’s gland X 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 

Thymus + I + + + + + + + + + M + + + + + + + + + + + + + 

Thymoma benign 

Integumentary System 

Mammary gland + + M + + + + + + + M + + + M + + + M + + + + M + 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 

Keratoacanthoma X X 

Keratoacanthoma, multiple 

Squamous cell carcinoma, multiple X 

Trichoepithelioma 

Subcutaneous tissue, fibroma X X X X X 

Subcutaneous tissue, fibrosarcoma X 

Subcutaneous tissue, histiocytic sarcoma 

Subcutaneous tissue, melanoma malignant 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, Zymbal’s gland X 

Peripheral nerve 

Spinal cord 

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 

Alveolar/bronchiolar adenoma X 

Osteosarcoma, metastatic, uncertain primary site 

Nose + + + + + + A + + + A + + + + A + + + + + + + + + 

Respiratory epithelium, adenoma 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Ear + 

Eye + 

Zymbal’s gland + + + 

Carcinoma X X X 

Urinary System 

Kidney + + + + + + + + + + A + + + + + + + + + + + + + + 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma 

Leukemia mononuclear X X X X X X X X X X X X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 79 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

150 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 

3 

2 

8 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Total 

Carcass ID Number 6 

5 

9 

1 

5 

1 

5 

9 

6 

3 

6 

6 

6 

7 

6 

8 

6 

9 

7 

1 

7 

2 

7 

5 

8 

0 

8 

2 

8 

3 

8 

4 

8 

5 

8 

7 

8 

8 

9 

0 

9 

2 

9 

4 

9 

5 

9 

7 

0 

0 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow + A + + + + + + + + + + + + + + + + + + + + + + + 45 

Lymph node 

Iliac, squamous cell carcinoma, metastatic, skin

Lymph node, mandibular 

Carcinoma, metastatic, Zymbal’s gland

Lymph node, mesenteric 

Spleen 

Thymus 

Thymoma benign 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

M 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

23 

1 

50 

1 

50 

50 

47 

1 

Integumentary System 

Mammary gland 

Skin 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

45 

50 

Keratoacanthoma X 3 

Keratoacanthoma, multiple 

Squamous cell carcinoma, multiple

Trichoepithelioma 

Subcutaneous tissue, fibroma 

Subcutaneous tissue, fibrosarcoma

Subcutaneous tissue, histiocytic sarcoma 

Subcutaneous tissue, melanoma malignant 

X X X

X

X

X

X

 1 

1 

1 

8 

1 

1 

1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, Zymbal’s gland

Peripheral nerve 

Spinal cord 

+

+

 1 

1 

1 

Respiratory System 

Lung + 

Alveolar/bronchiolar adenoma 

Osteosarcoma, metastatic, uncertain primary site 

Nose + 

Respiratory epithelium, adenoma 

Trachea + 

Special Senses System 

Ear

Eye

Zymbal’s gland

Carcinoma

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X

+ 

+ 

X

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 50 

2 

1 

+ 47 

1 

+ 50 

1 

1 

3 

3 

Urinary System 

Kidney + 

Urinary bladder + 

Systemic Lesions 

Multiple organs + 

Histiocytic sarcoma 

Leukemia mononuclear X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

X

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 49 

+ 50 

+ 50 

1 

33 
 

 

 

 

 

 

 

 

 

80 1-Chloro-2-propanol, NTP TR 477 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

325 ppm 

Number of Days on Study 

4 4 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 

0 5 3 5 6 7 7 7 8 9 0 0 2 3 4 4 5 6 6 8 9 9 1 1 2 

8 7 3 9 4 1 2 3 2 2 3 6 7 9 1 8 3 7 8 6 0 5 0 4 0 

Carcass ID Number 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

3 1 4 0 2 2 1 0 0 4 3 3 0 0 2 4 1 4 2 2 2 0 5 4 3 

8 3 3 2 5 3 6 8 6 4 2 1 1 9 2 6 5 1 7 1 9 5 0 9 9 

Alimentary System 

Esophagus 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Hepatocellular carcinoma 

Hepatocellular adenoma 

Mesentery 

Pancreas 

Acinus, adenoma 

Salivary glands 

Stomach, forestomach 

Stomach, glandular 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + A + + + + + + + + + + + + + + + + A 

+ + + + + + + A + + + + + + + + + + + + A + + A A 

+ + + + + + + A + + + + + + + + + + + + A + + A A 

+ + + A + + + A A + + + + + + + + + + + + + + + A 

+ A + A + A A A A + + + + + + + + + + + A + + A A 

+ A + A + + A A A + + + + + + + + + + + A + + A A 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + 

+ + + A + + + A A + + + + + + + + + + + + + + + A 

+ + + + + + + + A + + + + + + + + + + + + + + + + 

+ + + + + + + + A + + + + + + + + + + + A + + + + 

+ + + + + + + + A + + + + + + + + + + + A + + + + 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Endocrine System 

Adrenal cortex + + + + + + + + A + + + + + + + + + + + + + + + + 

Adrenal medulla + + + + + + + + A + + + + + + + + + + + + + + + + 

Pheochromocytoma malignant 

Pheochromocytoma benign X X X 

Bilateral, pheochromocytoma benign X X 

Islets, pancreatic + + + A + + + A A + + + + + + + + + + + + + + + A 

Adenoma X 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Pituitary gland + + + + + + + + A + + + + + + + + + + + + + + + + 

Pars distalis, adenoma X X X X X X X X X X X 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

C-cell, adenoma X X X X 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma 

Carcinoma X X X 

Bilateral, carcinoma 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 

Bilateral, interstitial cell, adenoma X X X X X X X X X X X X 

Interstitial cell, adenoma X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 81 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

325 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

8 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 1 0 0 0 1 1 1 1 1 1 2 2 2 2 3 3 3 3 3 3 4 4 4 4 4 Tissues/ 

4 3 4 7 0 1 2 7 8 9 0 4 6 8 0 3 4 5 6 7 0 2 5 7 8 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine large, cecum A + + + + + + + + + + + + + + + + + + + + + + + + 45 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 41 

Intestine small, ileum A + + + + + + + + + + + + + + + + + + + + + + + + 41 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocellular carcinoma X 1 

Hepatocellular adenoma X 1 

Mesentery + + + + + 10 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Acinus, adenoma X 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pheochromocytoma malignant X 1 

Pheochromocytoma benign X X X X X X X X X X 13 

Bilateral, pheochromocytoma benign X X 4 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Adenoma X 2 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pars distalis, adenoma X X X X X X X X X X X X X X 25 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, adenoma X X 6 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X X 2 

Carcinoma X 4 

Bilateral, carcinoma X 1 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Bilateral, interstitial cell, adenoma X X X X X X X X X X X X X X X X X X X 31 

Interstitial cell, adenoma X X X X X 9 
 

 

 

 

 

 

 

 

 

82 1-Chloro-2-propanol, NTP TR 477 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

325 ppm 

4 4 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 

Number of Days on Study 0 5 3 5 6 7 7 7 8 9 0 0 2 3 4 4 5 6 6 8 9 9 1 1 2 

8 7 3 9 4 1 2 3 2 2 3 6 7 9 1 8 3 7 8 6 0 5 0 4 0 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

Carcass ID Number 3 1 4 0 2 2 1 0 0 4 3 3 0 0 2 4 1 4 2 2 2 0 5 4 3 

8 3 3 2 5 3 6 8 6 4 2 1 1 9 2 6 5 1 7 1 9 5 0 9 9 

Hematopoietic System 

Bone marrow + + + A + + + + A + + + + + + + + + + + + + + + A 

Lymph node + + + + + + + + + + + + + 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + M M + + + + + + + + + 

Fibroadenoma X 

Fibroadenoma, multiple 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 

Keratoacanthoma X 

Subcutaneous tissue, fibroma X X X 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 

Peripheral nerve + 

Spinal cord + 

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar carcinoma X 

Nose + + + + + + + + + + A + + + + + + + + + + + + + + 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Zymbal’s gland + 

Carcinoma X 

Urinary System 

Kidney + + + + + + + + A + + + + + + + + + + + + + + + + 

Renal tubule, adenoma 

Renal tubule, carcinoma 

Urinary bladder + + + + + + + + A + + + + + + + + + + + + + + + + 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 

Leukemia mononuclear X X X X X X X X X X X X X X X X X 

Mesothelioma malignant X 
 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 83 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

325 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

8 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 1 0 0 0 1 1 1 1 1 1 2 2 2 2 3 3 3 3 3 3 4 4 4 4 4 Tissues/ 

4 3 4 7 0 1 2 7 8 9 0 4 6 8 0 3 4 5 6 7 0 2 5 7 8 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Lymph node + + + + + + + + + + 23 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Thymus + + + M + + + + + + + + + + + + + + + + I + + + + 48 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Fibroadenoma X X X X 5 

Fibroadenoma, multiple X 1 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Keratoacanthoma X X 3 

Subcutaneous tissue, fibroma X X X X 7 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Peripheral nerve 1 

Spinal cord 1 

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar adenoma X 1 

Alveolar/bronchiolar carcinoma X 2 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Zymbal’s gland + + 3 

Carcinoma X X 3 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Renal tubule, adenoma X 1 

Renal tubule, carcinoma X 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Leukemia mononuclear X X X X X X X X X X X X X 30 

Mesothelioma malignant 1 

50 
 

 

 

 

 

 

 

 

 

 

 

 

 

84 1-Chloro-2-propanol, NTP TR 477 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

650 ppm 

5 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 

Number of Days on Study 0 2 2 6 6 6 8 8 9 0 3 4 4 6 7 7 7 8 8 8 9 9 0 0 1 

2 0 0 4 9 9 2 5 7 5 0 8 8 3 2 6 6 2 3 6 0 7 7 9 4 

1 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

Carcass ID Number 7 6 9 5 8 9 5 0 9 8 8 5 7 9 8 8 9 7 9 5 5 6 6 8 9 

1 6 0 8 8 3 1 0 8 7 9 5 4 6 3 6 7 2 5 7 9 5 9 4 1 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 

Intestine large, colon + + + + + + + + + + + + + A + + + + + + A A + + + 

Intestine large, rectum + + + + A + + + + + + + + A + + + + + + A + + + + 

Intestine large, cecum + + + + + + + + + + + + + A + + + A + + A A A + + 

Intestine small, duodenum + + + + + + + + + + + + + A + + + + + + A + + + + 

Intestine small, jejunum + + + + A + + A + + + + + A + + + + A + A A + A + 

Intestine small, ileum + + + + A + + A + + + + + A + + + + + + A A + A + 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 

Hepatocellular carcinoma X 

Hepatocellular adenoma X 

Histiocytic sarcoma X 

Mesentery + + + + + + + + + + 

Lipoma 

Pancreas + + + + + + + + + + + + + + + + + + + + A + A + + 

Acinus, adenoma 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Stomach, forestomach + + + + + + + + + + + + + + + + A + + + + + + + + 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Pheochromocytoma malignant 

Pheochromocytoma benign X X X 

Bilateral, pheochromocytoma benign 

Islets, pancreatic + + + + + + + + + + + + + A + + + + + + A + A + + 

Adenoma 

Carcinoma 

Parathyroid gland + M + + + + + + + + M + + + + + + + + + + + + + + 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Pars distalis, adenoma X X X X X X X X 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

C-cell, adenoma X X 

C-cell, carcinoma X 

Follicular cell, adenoma 

General Body System 

Peritoneum + 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Preputial gland + + + + + + + + + + + M + + + + + + + + + + + + + 

Adenoma 

Carcinoma X 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 

Bilateral, interstitial cell, adenoma X X X X X X X X X X X X X 

Interstitial cell, adenoma X X X X X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 85 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

650 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

1 8 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 7 7 5 5 5 5 6 6 6 6 6 6 6 7 7 7 7 7 8 8 8 8 9 9 9 Tissues/ 

9 3 2 3 4 6 0 1 2 3 4 7 8 0 5 6 7 8 0 1 2 5 2 4 9 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine large, cecum + A + + + + + + + + + + + + + + + + + + + + + + + 44 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, jejunum + A + + + + + + + + + + + + + + + + + + + + + + + 42 

Intestine small, ileum + A + + + + + + + + + + + + + + + + + + + + + + + 43 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocellular carcinoma 1 

Hepatocellular adenoma X 2 

Histiocytic sarcoma 1 

Mesentery + + + + 14 

Lipoma X 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Acinus, adenoma X 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma malignant X X 2 

Pheochromocytoma benign X X X X X X X X 11 

Bilateral, pheochromocytoma benign X 1 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Adenoma X X X 3 

Carcinoma X 1 

Parathyroid gland + + M + + + + + + + + + + + + + + + + + + + + + + 47 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pars distalis, adenoma X X X X X X X X X X X X X X X X 24 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, adenoma X 3 

C-cell, carcinoma 1 

Follicular cell, adenoma X 1 

General Body System 

Peritoneum 1 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma X X 2 

Carcinoma X X 3 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Bilateral, interstitial cell, adenoma X X X X X X X X X X X X X X X X X X X X X 34 

Interstitial cell, adenoma X X X 12 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

86 1-Chloro-2-propanol, NTP TR 477 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

650 ppm 

5 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 

Number of Days on Study 0 

2 

2 

0 

2 

0 

6 

4 

6 

9 

6 

9 

8 

2 

8 

5 

9 

7 

0 

5 

3 

0 

4 

8 

4 

8 

6 

3 

7 

2 

7 

6 

7 

6 

8 

2 

8 

3 

8 

6 

9 

0 

9 

7 

0 

7 

0 

9 

1 

4 

1 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

Carcass ID Number 7 6 9 5 8 9 5 0 9 8 8 5 7 9 8 8 9 7 9 5 5 6 6 8 9 

1 6 0 8 8 3 1 0 8 7 9 5 4 6 3 6 7 2 5 7 9 5 9 4 1 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, mandibular 

Histiocytic sarcoma 

Lymph node, mesenteric 

Spleen 

Thymus 

+ + + + + + + + + + + + + + + + + + + + + + + A + 

+ + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + M + + M + + + + + + + + + + + + + + 

Integumentary System 

Mammary gland 

Fibroadenoma 

Skin 

Keratoacanthoma 

Squamous cell papilloma 

Subcutaneous tissue, fibroma 

Subcutaneous tissue, fibrosarcoma 

Subcutaneous tissue, lipoma 

+ + + + + + + + + + M + + + + + + + M + + + + M + 

X X X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X 

X 

X X 

X 

X 

Musculoskeletal System 

Bone 

Osteosarcoma 

Skeletal muscle 

Histiocytic sarcoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ 

X 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 

Respiratory System 

Lung 

Alveolar/bronchiolar carcinoma 

Hepatocellular carcinoma, metastatic, liver 

Nose 

Histiocytic sarcoma 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Eye 

Harderian gland 

Histiocytic sarcoma 

+ 

+ 

X 

Urinary System 

Kidney 

Renal tubule, adenoma 

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + A + + + 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Leukemia mononuclear 

Mesothelioma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X X X X X X X X X X X X X X X X X 

X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 87 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

650 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 

1 

2 

8 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 7 

9 

7 

3 

5 

2 

5 

3 

5 

4 

5 

6 

6 

0 

6 

1 

6 

2 

6 

3 

6 

4 

6 

7 

6 

8 

7 

0 

7 

5 

7 

6 

7 

7 

7 

8 

8 

0 

8 

1 

8 

2 

8 

5 

9 

2 

9 

4 

9 

9 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, mandibular 

Histiocytic sarcoma

Lymph node, mesenteric 

Spleen 

Thymus 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + M + + + + + + + + + + + + + + + + + 

49 

24 

50 

1 

50 

50 

47 

Integumentary System 

Mammary gland 

Fibroadenoma 

Skin 

Keratoacanthoma 

Squamous cell papilloma

Subcutaneous tissue, fibroma 

Subcutaneous tissue, fibrosarcoma

Subcutaneous tissue, lipoma

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X

X X X X

47 

6 

50 

6 

1 

6 

1 

1 

Musculoskeletal System 

Bone 

Osteosarcoma

Skeletal muscle

Histiocytic sarcoma

+ + + + + + + + + + + + + + + + + + + + + + + + + 50 

1 

1 

1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Respiratory System 

Lung 

Alveolar/bronchiolar carcinoma 

Hepatocellular carcinoma, metastatic, liver

Nose 

Histiocytic sarcoma

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

1 

1 

50 

1 

50 

Special Senses System 

Eye 

Harderian gland

Histiocytic sarcoma

+ 2 

1 

1 

Urinary System 

Kidney 

Renal tubule, adenoma 

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

1 

49 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma

Leukemia mononuclear 

Mesothelioma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X X X X X X X X 

X

50 

1 

31 

2 
88 1-Chloro-2-propanol, NTP TR 477 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Adrenal Medulla: Benign Pheochromocytoma a Overall rate 13/50 (26%) 14/49 (29%) 17/49 (35%) 12/50 (24%) 

Adjusted rateb 32.7% 33.5% 41.4% 28.1% c Terminal rate 8/20 (40%) 8/23 (35%) 11/24 (46%) 8/23 (35%) 

First incidence (days) 580 609 627 585 

d Poly-3 test Pù0.375N Pù0.585 Pù0.295 Pù0.433N 

Adrenal Medulla: Benign or Malignant Pheochromocytoma 

Overall rate 14/50 (28%) 14/49 (29%) 18/49 (37%) 13/50 (26%)
 

Adjusted rate 35.1% 33.5% 43.8% 30.4%
 

Terminal rate 8/20 (40%) 8/23 (35%) 12/24 (50%) 9/23 (39%)
 

First incidence (days) 580 609 627 585
 

Poly-3 test Pù0.413N Pù0.552N Pù0.295 Pù0.432N
 

Liver: Hepatocellular Adenoma 

Overall rate 1/50 (2%) 3/50 (6%) 1/50 (2%) 2/50 (4%) 

Adjusted rate 2.6% 7.1% 2.5% 4.8% 

Terminal rate 1/20 (5%) 2/23 (9%) 1/24 (4%) 1/23 (4%) 

First incidence (days) 729 (T) 630 729 (T) 676 

Poly-3 test Pù0.588 Pù0.379 Pù0.805N Pù0.583 

Liver: Hepatocellular Adenoma or Carcinoma 

Overall rate 1/50 (2%) 3/50 (6%) 2/50 (4%) 3/50 (6%) 

Adjusted rate 2.6% 7.1% 4.9% 7.1% 

Terminal rate 1/20 (5%) 2/23 (9%) 2/24 (8%) 1/23 (4%) 

First incidence (days) 729 (T) 630 729 (T) 569 

Poly-3 test Pù0.360 Pù0.379 Pù0.576 Pù0.382 

Lung: Alveolar/bronchiolar Adenoma or Carcinoma 

Overall rate 0/50 (0%) 2/50 (4%) 3/50 (6%) 1/50 (2%) 

Adjusted rate 0.0% 4.7% 7.3% 2.4% 

Terminal rate 0/20 (0%) 1/23 (4%) 2/24 (8%) 1/23 (4%) e First incidence (days) — 388 686 729 (T) 

Poly-3 test Pù0.509 Pù0.314 Pù0.161 Pù0.611 

Mammary Gland: Fibroadenoma 

Overall rate 7/50 (14%) 0/50 (0%) 6/50 (12%) 6/50 (12%)
 

Adjusted rate 17.7% 0.0% 14.6% 14.2%
 

Terminal rate 5/20 (25%) 0/23 (0%) 5/24 (21%) 3/23 (13%)
 

First incidence (days) 585 — 573 648
 

Poly-3 test Pù0.394 Pù0.007N Pù0.496N Pù0.474N
 

Pancreatic Islets: Adenoma 

Overall rate 2/49 (4%) 1/45 (2%) 2/46 (4%) 3/47 (6%) 

Adjusted rate 5.2% 2.6% 5.2% 7.7% 

Terminal rate 0/20 (0%) 1/23 (4%) 1/24 (4%) 3/23 (13%) 

First incidence (days) 637 729 (T) 667 729 (T) 

Poly-3 test Pù0.333 Pù0.557N Pù0.734N Pù0.555 

Pancreatic Islets: Adenoma or Carcinoma 

Overall rate 2/49 (4%) 1/45 (2%) 2/46 (4%) 4/47 (9%) 

Adjusted rate 5.2% 2.6% 5.2% 10.2% 

Terminal rate 0/20 (0%) 1/23 (4%) 1/24 (4%) 4/23 (17%) 

First incidence (days) 637 729 (T) 667 729 (T) 

Poly-3 test Pù0.176 Pù0.557N Pù0.734N Pù0.386 
1-Chloro-2-propanol, NTP TR 477 89 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Pituitary Gland (Pars Distalis): Adenoma 

Overall rate 15/48 (31%) 20/49 (41%) 25/49 (51%) 24/50 (48%)
 

Adjusted rate 37.4% 46.9% 57.2% 53.2%
 

Terminal rate 7/20 (35%) 12/23 (52%) 13/24 (54%) 15/23 (65%)
 

First incidence (days) 502 502 559 502
 

Poly-3 test Pù0.090 Pù0.264 Pù0.052 Pù0.106 

Preputial Gland: Carcinoma 

Overall rate 1/50 (2%) 4/50 (8%) 5/50 (10%) 3/49 (6%) 

Adjusted rate 2.6% 9.6% 12.0% 7.2% 

Terminal rate 1/20 (5%) 4/23 (17%) 2/24 (8%) 2/23 (9%) 

First incidence (days) 729 (T) 729 (T) 592 585 

Poly-3 test Pù0.394 Pù0.232 Pù0.138 Pù0.373 

Preputial Gland: Adenoma or Carcinoma 

Overall rate 2/50 (4%) 5/50 (10%) 7/50 (14%) 5/49 (10%)
 

Adjusted rate 5.1% 12.0% 16.8% 12.0%
 

Terminal rate 1/20 (5%) 5/23 (22%) 4/24 (17%) 4/23 (17%)
 

First incidence (days) 709 729 (T) 592 585
 

Poly-3 test Pù0.267 Pù0.273 Pù0.109 Pù0.271 

Skin: Keratoacanthoma 

Overall rate 2/50 (4%) 4/50 (8%) 3/50 (6%) 6/50 (12%)
 

Adjusted rate 5.1% 9.5% 7.4% 14.2%
 

Terminal rate 1/20 (5%) 2/23 (9%) 2/24 (8%) 3/23 (13%)
 

First incidence (days) 697 636 720 582
 

Poly-3 test Pù0.138 Pù0.410 Pù0.567 Pù0.182 

Skin: Squamous Cell Papilloma or Keratoacanthoma 

Overall rate 2/50 (4%) 4/50 (8%) 3/50 (6%) 7/50 (14%)
 

Adjusted rate 5.1% 9.5% 7.4% 16.5%
 

Terminal rate 1/20 (5%) 2/23 (9%) 2/24 (8%) 3/23 (13%)
 

First incidence (days) 697 636 720 582
 

Poly-3 test Pù0.072 Pù0.410 Pù0.567 Pù0.114 

Skin: Squamous Cell Papilloma, Keratoacanthoma, or Squamous Cell Carcinoma 

Overall rate 2/50 (4%) 5/50 (10%) 3/50 (6%) 7/50 (14%)
 

Adjusted rate 5.1% 11.7% 7.4% 16.5%
 

Terminal rate 1/20 (5%) 2/23 (9%) 2/24 (8%) 3/23 (13%)
 

First incidence (days) 697 544 720 582
 

Poly-3 test Pù0.101 Pù0.282 Pù0.567 Pù0.114 

Skin: Squamous Cell Papilloma, Keratoacanthoma, Trichoepithelioma, Basal Cell Carcinoma, or Squamous Cell Carcinoma 

Overall rate 3/50 (6%) 6/50 (12%) 3/50 (6%) 7/50 (14%)
 

Adjusted rate 7.7% 14.1% 7.4% 16.5%
 

Terminal rate 2/20 (10%) 3/23 (13%) 2/24 (8%) 3/23 (13%)
 

First incidence (days) 697 544 720 582
 

Poly-3 test Pù0.216 Pù0.314 Pù0.683N Pù0.214 

Skin (Subcutaneous Tissue): Fibroma 

Overall rate 3/50 (6%) 8/50 (16%) 7/50 (14%) 6/50 (12%)
 

Adjusted rate 7.6% 18.7% 16.7% 14.1%
 

Terminal rate 1/20 (5%) 2/23 (9%) 4/24 (17%) 3/23 (13%)
 

First incidence (days) 635 555 592 520
 

Poly-3 test Pù0.406 Pù0.140 Pù0.202 Pù0.308 
90 1-Chloro-2-propanol, NTP TR 477 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Skin (Subcutaneous Tissue): Fibroma, Fibrosarcoma, or Sarcoma 

Overall rate 4/50 (8%) 9/50 (18%) 7/50 (14%) 7/50 (14%)
 

Adjusted rate 10.1% 21.0% 16.7% 16.3%
 

Terminal rate 1/20 (5%) 2/23 (9%) 4/24 (17%) 3/23 (13%)
 

First incidence (days) 635 555 592 520
 

Poly-3 test Pù0.436 Pù0.161 Pù0.318 Pù0.336 

Testes: Adenoma 

Overall rate 46/50 (92%) 43/49 (88%) 40/50 (80%) 46/50 (92%)
 

Adjusted rate 97.2% 91.8% 87.1% 94.2%
 

Terminal rate 20/20 (100%) 21/23 (91%) 23/24 (96%) 22/23 (96%)
 

First incidence (days) 445 548 457 502
 

Poly-3 test Pù0.400N Pù0.221N Pù0.041N Pù0.411N
 

Thyroid Gland (C-cell): Adenoma 

Overall rate 5/50 (10%) 1/50 (2%) 6/50 (12%) 3/50 (6%) 

Adjusted rate 12.7% 2.4% 14.5% 7.1% 

Terminal rate 4/20 (20%) 1/23 (4%) 2/24 (8%) 1/23 (4%) 

First incidence (days) 532 729 (T) 592 676 

Poly-3 test Pù0.488N Pù0.105N Pù0.567 Pù0.351N 

Thyroid Gland (C-cell): Adenoma or Carcinoma 

Overall rate 5/50 (10%) 3/50 (6%) 6/50 (12%) 4/50 (8%) 

Adjusted rate 12.7% 7.2% 14.5% 9.4% 

Terminal rate 4/20 (20%) 3/23 (13%) 2/24 (8%) 1/23 (4%) 

First incidence (days) 532 729 (T) 592 648 

Poly-3 test Pù0.517N Pù0.358N Pù0.567 Pù0.486N 

Zymbal’s Gland: Carcinoma 

Overall rate 1/50 (2%) 3/50 (6%) 3/50 (6%) 0/50 (0%)
 

Adjusted rate 2.5% 7.0% 7.2% 0.0%
 

Terminal rate 0/20 (0%) 0/23 (0%) 1/24 (4%) 0/23 (0%)
 

First incidence (days) 599 388 408 —
 

Poly-3 test Pù0.264N Pù0.380 Pù0.370 Pù0.582N
 

All Organs: Mononuclear Cell Leukemia 

Overall rate 32/50 (64%) 33/50 (66%) 30/50 (60%) 31/50 (62%)
 

Adjusted rate 73.7% 71.1% 65.4% 66.4%
 

Terminal rate 15/20 (75%) 15/23 (65%) 12/24 (50%) 12/23 (52%)
 

First incidence (days) 445 548 533 502
 

Poly-3 test Pù0.239N Pù0.494N Pù0.265N Pù0.299N
 

All Organs: Malignant Mesothelioma 

Overall rate 3/50 (6%) 0/50 (0%) 1/50 (2%) 2/50 (4%) 

Adjusted rate 7.7% 0.0% 2.4% 4.8% 

Terminal rate 2/20 (10%) 0/23 (0%) 0/24 (0%) 1/23 (4%) 

First incidence (days) 673 — 667 683 

Poly-3 test Pù0.592N Pù0.136N Pù0.333N Pù0.511N 

All Organs: Benign Neoplasms 

Overall rate 48/50 (96%) 48/50 (96%) 48/50 (96%) 50/50 (100%)
 

Adjusted rate 99.1% 98.1% 98.6% 100.0%
 

Terminal rate 20/20 (100%) 23/23 (100%) 24/24 (100%) 23/23 (100%)
 

First incidence (days) 445 388 457 502
 

Poly-3 test Pù0.391 Pù0.749N Pù0.903N Pù0.957 
91 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

All Organs: Malignant Neoplasms 

Overall rate 40/50 (80%) 38/50 (76%) 37/50 (74%) 37/50 (74%) 

Adjusted rate 87.6% 78.8% 78.1% 77.6% 

Terminal rate 17/20 (85%) 16/23 (70%) 16/24 (67%) 15/23 (65%) 

First incidence (days) 

Poly-3 test 

445 

Pù0.175N 

388 

Pù0.187N 

408 

Pù0.162N 

502 

Pù0.147N 

All Organs: Benign or Malignant Neoplasms 

Overall rate 48/50 (96%) 50/50 (100%) 50/50 (100%) 50/50 (100%) 

Adjusted rate 99.1% 100.0% 100.0% 100.0% 

Terminal rate 20/20 (100%) 23/23 (100%) 24/24 (100%) 23/23 (100%) 

First incidence (days) 

Poly-3 test 

445 

Pù0.702 

388 

Pù0.957 

408 

Pù0.957 

502 

Pù0.957 

(T)Terminal sacrifice 

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for adrenal gland, liver, 

lung, pancreatic islets, pituitary gland, preputial gland, testis, and thyroid gland; for other tissues, denominator is number of animals necropsied. b	 Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality 

Observed incidence at terminal kill 

d	 Beneath the 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 controls and that exposed group. The Poly-3 test accounts for 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 
92 1-Chloro-2-propanol, NTP TR 477 

TABLE A4 

Historical Incidence of Mammary Gland Fibroadenoma in Untreated Male F344/N Ratsa 

Study Incidence in Controls 

Historical Incidence at TSI Mason Research Institute: Feed Study 

Phenolphthalein 6/50 

Overall Historical Incidence: Drinking Water Studies 

Total 13/281 (4.6%) 

Standard deviation 2.2% 

Range 2%-8% 

Overall Historical Incidence: Feed Studies 

Total 58/1,354 (4.3%) 

Standard deviation 3.3% 

Range 0%-12% 

Overall Historical Incidence: Gavage (Corn Oil) Studies 

Total 44/772 (5.7%) 

Standard deviation 2.5% 

Range 2%-12% 

Overall Historical Incidence: Inhalation Studies 

Total 17/905 (1.9%) 

Standard deviation 2.0% 

Range 0%-6% 

Data as of 15 October 1996 a 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 93 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 150 ppm 325 ppm 650 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 12 13 7 10 

Natural deaths 18 14 19 17 

Survivors 

Died last week of study 1 

Terminal sacrifice 19 23 24 23 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Intestine large, colon (46) (46) (48) (47) 

Hemorrhage 1 (2%) 

Parasite metazoan 1 (2%) 3 (7%) 1 (2%) 2 (4%) 

Intestine large, rectum (45) (47) (46) (47) 

Parasite metazoan 3 (7%) 3 (6%) 3 (7%) 2 (4%) 

Intestine large, cecum (45) (46) (45) (44) 

Inflammation, chronic active 1 (2%) 

Necrosis 1 (2%) 

Parasite metazoan 1 (2%) 

Intestine small, jejunum (39) (42) (41) (42) 

Fibrosis 1 (2%) 

Intestine small, ileum (39) (41) (41) (43) 

Parasite metazoan 1 (2%) 

Liver (50) (50) (50) (50) 

Angiectasis 5 (10%) 11 (22%) 7 (14%) 9 (18%) 

Basophilic focus 3 (6%) 

Clear cell focus 7 (14%) 8 (16%) 7 (14%) 3 (6%) 

Congestion 2 (4%) 

Cyst 1 (2%) 

Deformity 1 (2%) 2 (4%) 1 (2%) 

Degeneration, cystic 12 (24%) 8 (16%) 12 (24%) 12 (24%) 

Eosinophilic focus 4 (8%) 10 (20%) 10 (20%) 3 (6%) 

Hemorrhage 2 (4%) 

Hepatodiaphragmatic nodule 2 (4%) 3 (6%) 5 (10%) 

Inflammation, chronic active 1 (2%) 1 (2%) 

Mixed cell focus 6 (12%) 6 (12%) 2 (4%) 5 (10%) 

Necrosis 1 (2%) 2 (4%) 

Vacuolization cytoplasmic 2 (4%) 4 (8%) 1 (2%) 

Bile duct, hyperplasia 1 (2%) 2 (4%) 3 (6%) 

Centrilobular, congestion 1 (2%) 

Centrilobular, degeneration 1 (2%) 1 (2%) 

Centrilobular, vacuolization cytoplasmic 1 (2%) 2 (4%) 1 (2%) 1 (2%) 

Kupffer cell, pigmentation 1 (2%) 

Vein, dilatation 1 (2%) 

Mesentery (12) (11) (10) (14) 

Accessory spleen 1 (7%) 

Inflammation, chronic active 1 (9%) 

Necrosis 1 (8%) 

Pigmentation 1 (8%) 

Fat, necrosis 9 (75%) 10 (91%) 9 (90%) 12 (86%) 

Fat, pigmentation 1 (10%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

94 1-Chloro-2-propanol, NTP TR 477 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Alimentary System (continued) 

Oral mucosa (2) 

Hyperplasia 1 (50%) 

Pancreas (48) (45) (46) (48) 

Acinus, atrophy 10 (21%) 9 (20%) 13 (28%) 12 (25%) 

Acinus, hyperplasia 1 (2%) 3 (6%) 

Artery, hyperplasia 2 (4%) 

Salivary glands (50) (50) (49) (50) 

Atrophy 1 (2%) 

Duct, hyperplasia 1 (2%) 

Stomach, forestomach (50) (49) (48) (49) 

Diverticulum 1 (2%) 

Hemorrhage 1 (2%) 

Inflammation, chronic active 3 (6%) 2 (4%) 2 (4%) 

Ulcer 10 (20%) 10 (20%) 8 (17%) 13 (27%) 

Epithelium, hyperplasia 3 (6%) 4 (8%) 2 (4%) 1 (2%) 

Stomach, glandular (50) (49) (48) (50) 

Atrophy 1 (2%) 

Hyperplasia, lymphoid 2 (4%) 1 (2%) 

Inflammation, chronic active 1 (2%) 1 (2%) 

Mineralization 1 (2%) 1 (2%) 

Necrosis 17 (34%) 14 (29%) 13 (27%) 17 (34%) 

Cardiovascular System 

Blood vessel (48) (50) (50) (50) 

Aorta, inflammation, chronic active 1 (2%) 

Aorta, mineralization 1 (2%) 

Heart (50) (50) (50) (50) 

Cardiomyopathy 35 (70%) 41 (82%) 42 (84%) 33 (66%) 

Fibrosis 1 (2%) 

Mineralization 2 (4%) 1 (2%) 

Thrombosis 1 (2%) 

Artery, inflammation, chronic active 1 (2%) 

Atrium, thrombosis 3 (6%) 6 (12%) 4 (8%) 

Ventricle, pigmentation 1 (2%) 

Endocrine System 

Adrenal cortex (50) (49) (49) (50) 

Angiectasis 1 (2%) 

Cytoplasmic alteration 2 (4%) 2 (4%) 

Degeneration, cystic 1 (2%) 

Hemorrhage 1 (2%) 1 (2%) 1 (2%) 

Hyperplasia 1 (2%) 

Necrosis 1 (2%) 1 (2%) 

Vacuolization cytoplasmic 3 (6%) 

Adrenal medulla (50) (49) (49) (50) 

Angiectasis 1 (2%) 

Hemorrhage 1 (2%) 

Hyperplasia 10 (20%) 8 (16%) 8 (16%) 4 (8%) 

Islets, pancreatic (49) (45) (46) (47) 

Hyperplasia 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 95 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Endocrine System (continued) 

Parathyroid gland (48) (49) (50) (47) 

Hyperplasia 1 (2%) 2 (4%) 1 (2%) 

Pituitary gland (48) (49) (49) (50) 

Pars distalis, angiectasis 3 (6%) 1 (2%) 3 (6%) 5 (10%) 

Pars distalis, cyst 1 (2%) 3 (6%) 2 (4%) 2 (4%) 

Pars distalis, hemorrhage 1 (2%) 

Pars distalis, hyperplasia 8 (17%) 5 (10%) 5 (10%) 7 (14%) 

Pars intermedia, cyst 1 (2%) 1 (2%) 

Pars nervosa, hemorrhage 1 (2%) 

Thyroid gland (50) (50) (50) (50) 

Cyst 1 (2%) 

C-cell, hyperplasia 4 (8%) 6 (12%) 5 (10%) 4 (8%) 

Follicular cell, hyperplasia 1 (2%) 

General Body System 

Peritoneum (3) (1) 

Necrosis 1 (33%) 

Tissue NOS (1) 

Abdominal, hemorrhage 1 (100%) 

Genital System 

Epididymis (50) (49) (50) (50) 

Inflammation, chronic active 1 (2%) 

Penis (1) 

Inflammation, chronic active 1 (100%) 

Preputial gland (50) (50) (50) (49) 

Cyst 3 (6%) 1 (2%) 2 (4%) 3 (6%) 

Fibrosis 1 (2%) 

Inflammation, chronic 1 (2%) 1 (2%) 1 (2%) 1 (2%) 

Inflammation, chronic active 5 (10%) 1 (2%) 3 (6%) 5 (10%) 

Prostate (50) (50) (50) (50) 

Hyperplasia 1 (2%) 2 (4%) 1 (2%) 2 (4%) 

Inflammation, chronic active 4 (8%) 5 (10%) 7 (14%) 5 (10%) 

Seminal vesicle (50) (50) (50) (50) 

Hyperplasia 1 (2%) 

Inflammation, chronic active 1 (2%) 

Testes (50) (49) (50) (50) 

Atrophy 8 (16%) 9 (18%) 12 (24%) 8 (16%) 

Artery, inflammation, chronic active 2 (4%) 2 (4%) 

Interstitial cell, hyperplasia 8 (16%) 11 (22%) 10 (20%) 8 (16%) 

Hematopoietic System 

Bone marrow (47) (45) (47) (49) 

Atrophy 4 (9%) 1 (2%) 3 (6%) 

Fibrosis 2 (4%) 

Hyperplasia 2 (4%) 4 (9%) 2 (4%) 1 (2%) 

Myeloid cell, hyperplasia 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

96 1-Chloro-2-propanol, NTP TR 477 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Hematopoietic System (continued) 

Lymph node (24) (23) (23) (24) 

Hemorrhage 1 (4%) 1 (4%) 1 (4%) 

Iliac, hemorrhage 1 (4%) 1 (4%) 

Iliac, hyperplasia, lymphoid 1 (4%) 

Iliac, hyperplasia, plasma cell 1 (4%) 

Mediastinal, congestion 1 (4%) 

Mediastinal, ectasia 1 (4%) 

Mediastinal, hemorrhage 11 (46%) 11 (48%) 8 (35%) 11 (46%) 

Mediastinal, hyperplasia, lymphoid 3 (13%) 2 (9%) 

Mediastinal, hyperplasia, plasma cell 1 (4%) 

Mediastinal, infiltration cellular, histiocyte 1 (4%) 1 (4%) 

Mediastinal, pigmentation 3 (13%) 2 (9%) 1 (4%) 

Pancreatic, ectasia 1 (4%) 

Pancreatic, hemorrhage 1 (4%) 4 (17%) 2 (9%) 5 (21%) 

Pancreatic, hyperplasia, lymphoid 1 (4%) 

Renal, ectasia 3 (13%) 

Renal, hemorrhage 3 (13%) 3 (13%) 1 (4%) 8 (33%) 

Renal, hyperplasia, lymphoid 1 (4%) 

Renal, hyperplasia, plasma cell 1 (4%) 

Renal, pigmentation 3 (13%) 4 (17%) 2 (9%) 7 (29%) 

Lymph node, mandibular (50) (50) (50) (50) 

Ectasia 1 (2%) 8 (16%) 2 (4%) 3 (6%) 

Hemorrhage 3 (6%) 1 (2%) 3 (6%) 2 (4%) 

Hyperplasia, lymphoid 5 (10%) 2 (4%) 3 (6%) 2 (4%) 

Hyperplasia, plasma cell 2 (4%) 4 (8%) 5 (10%) 2 (4%) 

Infiltration cellular, histiocyte 1 (2%) 

Lymph node, mesenteric (49) (50) (50) (50) 

Ectasia 3 (6%) 1 (2%) 2 (4%) 1 (2%) 

Hemorrhage 4 (8%) 4 (8%) 4 (8%) 6 (12%) 

Hyperplasia, lymphoid 4 (8%) 2 (4%) 2 (4%) 

Inflammation, chronic active 1 (2%) 

Spleen (50) (50) (50) (50) 

Angiectasis 2 (4%) 

Atrophy 1 (2%) 

Congestion 3 (6%) 2 (4%) 

Cyst 1 (2%) 

Fibrosis 10 (20%) 16 (32%) 19 (38%) 14 (28%) 

Hematopoietic cell proliferation 3 (6%) 5 (10%) 2 (4%) 2 (4%) 

Necrosis 3 (6%) 1 (2%) 2 (4%) 1 (2%) 

Pigmentation 2 (4%) 2 (4%) 2 (4%) 

Capsule, fibrosis 2 (4%) 2 (4%) 2 (4%) 

Capsule, pigmentation 1 (2%) 1 (2%) 

Thymus (49) (47) (48) (47) 

Atrophy 30 (61%) 19 (40%) 18 (38%) 27 (57%) 

Hemorrhage 3 (6%) 3 (6%) 2 (4%) 

Epithelial cell, hyperplasia 5 (10%) 3 (6%) 2 (4%) 3 (6%) 

Integumentary System 

Mammary gland (50) (45) (48) (47) 

Dilatation 8 (16%) 13 (29%) 9 (19%) 6 (13%) 

Hyperplasia 1 (2%) 3 (7%) 5 (10%) 6 (13%) 

Inflammation, chronic active 2 (4%) 

Pigmentation 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 97 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Integumentary System (continued) 

Skin (50) (50) (50) (50) 

Cyst epithelial inclusion 1 (2%) 1 (2%) 

Hyperkeratosis 2 (4%) 1 (2%) 

Inflammation, chronic active 2 (4%) 1 (2%) 1 (2%) 

Ulcer 2 (4%) 

Epidermis, hyperplasia 1 (2%) 

Hair follicle, atrophy 1 (2%) 

Subcutaneous tissue, fibrosis 1 (2%) 

Subcutaneous tissue, foreign body 1 (2%) 

Subcutaneous tissue, inflammation,

 chronic active 1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) (50) 

Hyperostosis 1 (2%) 1 (2%) 1 (2%) 

Nervous System 

Brain (50) (50) (50) (50) 

Hemorrhage 1 (2%) 2 (4%) 1 (2%) 4 (8%) 

Mineralization 1 (2%) 

Necrosis 1 (2%) 

Meninges, angiectasis 1 (2%) 

Respiratory System 

Lung (50) (50) (50) (50) 

Hemorrhage 1 (2%) 1 (2%) 4 (8%) 

Inflammation, acute 1 (2%) 1 (2%) 

Inflammation, chronic active 3 (6%) 1 (2%) 

Alveolar epithelium, hyperplasia 4 (8%) 1 (2%) 6 (12%) 1 (2%) 

Alveolus, metaplasia, squamous 1 (2%) 

Nose (50) (47) (49) (50) 

Foreign body 2 (4%) 1 (2%) 

Nasopharyngeal duct, inflammation,

 chronic active 1 (2%) 

Olfactory epithelium, degeneration, hyaline 1 (2%) 2 (4%) 

Olfactory epithelium, foreign body 1 (2%) 1 (2%) 

Olfactory epithelium, hyperplasia 1 (2%) 

Olfactory epithelium, inflammation,

 chronic active 10 (20%) 2 (4%) 6 (12%) 5 (10%) 

Olfactory epithelium, metaplasia 1 (2%) 

Respiratory epithelium, degeneration, hyaline 2 (4%) 1 (2%) 

Respiratory epithelium, foreign body 3 (6%) 

Respiratory epithelium, hyperplasia 22 (44%) 20 (43%) 16 (33%) 28 (56%) 

Respiratory epithelium, inflammation 1 (2%) 

Respiratory epithelium, inflammation, chronic 1 (2%) 1 (2%) 1 (2%) 

Respiratory epithelium, inflammation,

 chronic active 22 (44%) 15 (32%) 22 (45%) 27 (54%) 

Respiratory epithelium, metaplasia 1 (2%) 

Respiratory epithelium, metaplasia, squamous 2 (4%) 1 (2%) 

Respiratory epithelium, thrombosis 4 (8%) 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

98 1-Chloro-2-propanol, NTP TR 477 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Special Senses System 

Eye (1) (2) 

Atrophy 2 (100%) 

Hemorrhage 1 (100%) 

Lens, cataract 1 (100%) 

Urinary System 

Kidney (50) (49) (49) (50) 

Angiectasis 1 (2%) 

Atrophy 1 (2%) 

Cyst 3 (6%) 2 (4%) 3 (6%) 

Fibrosis 1 (2%) 

Hemorrhage 1 (2%) 

Hydronephrosis 1 (2%) 

Infiltration cellular, polymorphonuclear 1 (2%) 

Mineralization 2 (4%) 1 (2%) 

Necrosis 1 (2%) 

Nephropathy 46 (92%) 46 (94%) 46 (94%) 49 (98%) 

Renal tubule, hyperplasia 1 (2%) 1 (2%) 

Renal tubule, pigmentation 4 (8%) 3 (6%) 4 (8%) 3 (6%) 

Urinary bladder (48) (50) (49) (49) 

Hemorrhage 1 (2%) 1 (2%) 

Inflammation, acute 1 (2%) 

Inflammation, chronic active 1 (2%) 
99 

APPENDIX B 

SUMMARY OF LESIONS IN FEMALE RATS 

IN THE 2-YEAR DRINKING WATER STUDY 

OF 1-CHLORO-2-PROPANOL 

TABLE B1 Summary of the Incidence of Neoplasms in Female Rats 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 100 

TABLE B2 Individual Animal Tumor Pathology of Female Rats 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 104 

TABLE B3 Statistical Analysis of Primary Neoplasms in Female Rats 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 122 

TABLE B4 Summary of the Incidence of Nonneoplastic Lesions in Female Rats 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 125 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

100 1-Chloro-2-propanol, NTP TR 477 

TABLE B1 

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanola 

0 ppm 150 ppm 325 ppm 650 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 12 7 7 5 

Natural deaths 13 10 13 14 

Survivors 

Terminal sacrifice 25 33 30 31 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Intestine large, cecum (47) (49) (48) (48) 

Intestine small, jejunum (44) (44) (43) (46) 

Intestine small, ileum (42) (45) (43) (45) 

Liver (50) (50) (50) (50) 

Hepatocellular adenoma 1 (2%) 1 (2%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Mesentery (9) (11) (12) (10) 

Histiocytic sarcoma 1 (11%) 

Oral mucosa (1) (1) 

Squamous cell carcinoma 1 (100%) 

Squamous cell papilloma 1 (100%) 

Pancreas (47) (49) (49) (48) 

Histiocytic sarcoma 1 (2%) 

Acinus, adenoma 1 (2%) 

Salivary glands (50) (50) (50) (50) 

Stomach, forestomach (50) (50) (50) (50) 

Stomach, glandular (50) (50) (50) (50) 

Tongue (2) (2) (1) 

Squamous cell carcinoma, metastatic, oral

 mucosa 1 (50%) 

Squamous cell papilloma 2 (100%) 1 (50%) 1 (100%) 

Cardiovascular System 

Heart (50) (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Endocrine System 

Adrenal cortex (49) (50) (50) (50) 

Carcinoma 1 (2%) 

Adrenal medulla (49) (50) (50) (50) 

Ganglioneuroma 1 (2%) 

Pheochromocytoma malignant 1 (2%) 1 (2%) 1 (2%) 

Pheochromocytoma complex 1 (2%) 

Pheochromocytoma benign 2 (4%) 4 (8%) 1 (2%) 4 (8%) 

Bilateral, pheochromocytoma benign 1 (2%) 

Islets, pancreatic (46) (49) (48) (48) 

Adenoma 1 (2%) 1 (2%) 1 (2%) 

Carcinoma 1 (2%) 

Pituitary gland (49) (50) (50) (50) 

Pars distalis, adenoma 29 (59%) 30 (60%) 32 (64%) 35 (70%) 

Pars distalis, carcinoma 1 (2%) 

Pars distalis, histiocytic sarcoma 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 101 

TABLE B1 

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Endocrine System (continued) 

Thyroid gland (50) (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

C-cell, adenoma 2 (4%) 8 (16%) 5 (10%) 3 (6%) 

C-cell, carcinoma 1 (2%) 2 (4%) 

Follicular cell, adenoma 1 (2%) 

General Body System 

Tissue NOS (1) 

Abdominal, sarcoma 1 (100%) 

Genital System 

Clitoral gland (49) (49) (49) (49) 

Adenoma 1 (2%) 2 (4%) 4 (8%) 

Carcinoma 2 (4%) 3 (6%) 2 (4%) 3 (6%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Bilateral, carcinoma 2 (4%) 1 (2%) 

Ovary (50) (50) (50) (50) 

Cystadenoma 1 (2%) 

Granulosa cell tumor benign 1 (2%) 

Granulosa-theca tumor malignant 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Uterus (50) (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Polyp stromal 6 (12%) 6 (12%) 6 (12%) 4 (8%) 

Bilateral, polyp stromal 1 (2%) 

Hematopoietic System 

Bone marrow (47) (50) (47) (49) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Lymph node (11) (9) (15) (7) 

Mediastinal, histiocytic sarcoma 1 (7%) 

Pancreatic, histiocytic sarcoma 1 (7%) 

Lymph node, mandibular (50) (50) (50) (49) 

Histiocytic sarcoma 1 (2%) 

Lymph node, mesenteric (50) (50) (49) (50) 

Histiocytic sarcoma 1 (2%) 

Spleen (50) (50) (50) (49) 

Histiocytic sarcoma 1 (2%) 

Thymus (48) (49) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Thymoma benign 1 (2%) 1 (2%) 

Integumentary System 

Mammary gland (50) (50) (49) (50) 

Adenoma 1 (2%) 

Carcinoma 1 (2%) 1 (2%) 1 (2%) 

Fibroadenoma 21 (42%) 21 (42%) 26 (53%) 14 (28%) 

Fibroadenoma, multiple 8 (16%) 7 (14%) 5 (10%) 9 (18%) 

Histiocytic sarcoma 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

102 1-Chloro-2-propanol, NTP TR 477 

TABLE B1 

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Integumentary System (continued) 

Skin 

Squamous cell papilloma

Subcutaneous tissue, fibroma

Subcutaneous tissue, fibrous histiocytoma

Subcutaneous tissue, histiocytic sarcoma

Subcutaneous tissue, melanoma malignant

Subcutaneous tissue, sarcoma

Subcutaneous tissue, schwannoma malignant

(50) 

 1 (2%) 

 1 (2%) 

 1 (2%) 

 1 (2%) 

(50) 

 1 (2%) 

 1 (2%) 

(50) 

 1 (2%) 

 1 (2%) 

 1 (2%) 

 1 (2%) 

(50) 

 2 (4%) 

 1 (2%) 

Musculoskeletal System 

Bone 

Osteosarcoma

(50) (50) (50) 

 1 (2%) 

(50) 

Nervous System 

None 

Respiratory System 

Lung (50) (50) (50) (50) 

Alveolar/bronchiolar adenoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Melanoma malignant, metastatic, skin 1 (2%) 

Osteosarcoma, metastatic, bone 1 (2%) 

Pheochromocytoma complex, metastatic,

 adrenal medulla 1 (2%) 

Nose (50) (48) (49) (49) 

Respiratory epithelium, histiocytic sarcoma 1 (2%) 

Special Senses System 

Zymbal’s gland (1) (1) 

Carcinoma 1 (100%) 

Urinary System 

Kidney (46) (49) (50) (50) 

Mesenchymal tumor malignant 1 (2%) 

Transitional epithelium, papilloma 1 (2%) 

Urinary bladder (49) (50) (50) (49) 

Histiocytic sarcoma 1 (2%) 

Papilloma 1 (2%) 

Systemic Lesions 

Multiple organsb (50) (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 1 (2%) 1 (2%) 1 (2%) 

Leukemia mononuclear 19 (38%) 19 (38%) 18 (36%) 13 (26%) 
103 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE B1 

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Neoplasm Summary 

Total animals with primary neoplasmsc 48 46 49 48 

Total primary neoplasms 107 111 112 104 

Total animals with benign neoplasms 43 42 48 42 

Total benign neoplasms 76 81 83 83 

Total animals with malignant neoplasms 26 24 26 18 

Total malignant neoplasms 31 30 29 21 

Total animals with metastatic neoplasms 1 2 1 

Total metastatic neoplasms 1 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 

Primary neoplasms: all neoplasms except metastatic neoplasms 
 

 

 

 

 

 

 

 

 

 

 

 

104 1-Chloro-2-propanol, NTP TR 477 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 

Number of Days on Study 1 4 8 9 0 2 3 4 4 5 5 7 7 7 8 9 0 0 1 1 2 2 2 2 2 

9 1 2 7 9 9 5 1 6 3 9 0 2 2 0 8 1 9 2 9 0 2 7 9 9 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

Carcass ID Number 5 5 6 3 4 4 4 6 6 4 5 2 2 2 2 5 5 3 1 6 2 5 4 3 4 

0 4 5 7 3 7 9 1 4 5 7 1 6 7 8 2 9 4 9 0 9 6 8 0 4 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 

Intestine large, colon + + + + + A + + + + + A + + + A + + + + + + + + + 

Intestine large, rectum + + + + + + + + + + + + + + + A + + + + + + + + + 

Intestine large, cecum + + + + + A + + + + + A + + + A + + + + + + + + + 

Intestine small, duodenum + + + + + A + A + + + A + + + A + + + + + + + + + 

Intestine small, jejunum + + + + + A + A + + + A + + + A A A + + + + + + + 

Intestine small, ileum + + + + + A + A + + + A + + A A A A + A + + + + + 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Mesentery + + + + + + + 

Histiocytic sarcoma X 

Pancreas + + + + + A + + + + + A + + + A + + + + + + + + + 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 

Tongue 

Squamous cell papilloma 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Endocrine System 

Adrenal cortex + + + + + + + + + + + A + + + + + + + + + + + + + 

Carcinoma X 

Adrenal medulla + + + + + + + + + + + A + + + + + + + + + + + + + 

Pheochromocytoma malignant X 

Pheochromocytoma complex X 

Pheochromocytoma benign X X 

Islets, pancreatic + + + + + A + + + + + A + + A A + + + + + + + + + 

Adenoma X 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Pituitary gland + + + + + A + + + + + + + + + + + + + + + + + + + 

Pars distalis, adenoma X X X X X X X X X X X X 

Pars distalis, carcinoma X 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

C-cell, adenoma 

General Body System 

Tissue NOS + 

Abdominal, sarcoma X 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + M + + + + + 

Adenoma 

Carcinoma 

Histiocytic sarcoma X 

Bilateral, carcinoma 

+: Tissue examined microscopically M: Missing tissue X: Lesion present 

A: Autolysis precludes examination I: Insufficient tissue Blank: Not examined 
 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 105 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Total 

Carcass ID Number 1 1 2 2 2 3 4 4 4 4 5 5 5 6 6 1 2 2 3 3 3 3 3 3 5 Tissues/ 

7 8 0 3 4 1 0 1 2 6 3 5 8 2 3 6 2 5 2 3 5 6 8 9 1 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 44 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 42 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Mesentery + + 9 

Histiocytic sarcoma 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Tongue + + 2 

Squamous cell papilloma X X 2 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Carcinoma 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pheochromocytoma malignant 1 

Pheochromocytoma complex 1 

Pheochromocytoma benign 2 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Adenoma 1 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X 29 

Pars distalis, carcinoma 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

C-cell, adenoma X X 2 

General Body System 

Tissue NOS 1 

Abdominal, sarcoma 1 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma X 1 

Carcinoma X X 2 

Histiocytic sarcoma 1 

Bilateral, carcinoma X X 2 
 

 

 

 

 

 

 

 

 

 

 

106 1-Chloro-2-propanol, NTP TR 477 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

Number of Days on Study 

5 

1 

9 

5 

4 

1 

5 

8 

2 

5 

9 

7 

6 

0 

9 

6 

2 

9 

6 

3 

5 

6 

4 

1 

6 

4 

6 

6 

5 

3 

6 

5 

9 

6 

7 

0 

6 

7 

2 

6 

7 

2 

6 

8 

0 

6 

9 

8 

7 

0 

1 

7 

0 

9 

7 

1 

2 

7 

1 

9 

7 

2 

0 

7 

2 

2 

7 

2 

7 

7 

2 

9 

7 

2 

9 

Carcass ID Number 

2 

5 

0 

2 

5 

4 

2 

6 

5 

2 

3 

7 

2 

4 

3 

2 

4 

7 

2 

4 

9 

2 

6 

1 

2 

6 

4 

2 

4 

5 

2 

5 

7 

2 

2 

1 

2 

2 

6 

2 

2 

7 

2 

2 

8 

2 

5 

2 

2 

5 

9 

2 

3 

4 

2 

1 

9 

2 

6 

0 

2 

2 

9 

2 

5 

6 

2 

4 

8 

2 

3 

0 

2 

4 

4 

Genital System (continued) 

Ovary 

Uterus 

Polyp stromal 

Bilateral, polyp stromal 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Thymus 

+ + + + + A + + + + + A + + + A + + + + + + + + + 

+ + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + M + + A + + + + + + + + + + + + + 

Integumentary System 

Mammary gland 

Carcinoma 

Fibroadenoma 

Fibroadenoma, multiple 

Skin 

Squamous cell papilloma 

Subcutaneous tissue, fibroma 

Subcutaneous tissue, histiocytic sarcoma 

Subcutaneous tissue, sarcoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X X X X X X X X X 

X X X X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 

Peripheral nerve + + 

Spinal cord + + 

Respiratory System 

Lung 

Histiocytic sarcoma 

Pheochromocytoma complex, metastatic,

 adrenal medulla 

Nose 

Trachea 

Special Senses System 

None 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Urinary System 

Kidney 

Transitional epithelium, papilloma 

Urinary bladder 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Leukemia mononuclear 

+ + + + + A + + + + + A + + A A + + + + + + + + + 

+ + + + + + + + + + + A + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X X X X X X X X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 107 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Total 

Carcass ID Number 1 1 2 2 2 3 4 4 4 4 5 5 5 6 6 1 2 2 3 3 3 3 3 3 5 Tissues/ 

7 8 0 3 4 1 0 1 2 6 3 5 8 2 3 6 2 5 2 3 5 6 8 9 1 Tumors 

Genital System (continued) 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Polyp stromal X 6 

Bilateral, polyp stromal X 1 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Lymph node + + + 11 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma 1 

Fibroadenoma X X X X X X X X X X X X 21 

Fibroadenoma, multiple X X X X 8 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Squamous cell papilloma X 1 

Subcutaneous tissue, fibroma X 1 

Subcutaneous tissue, histiocytic sarcoma 1 

Subcutaneous tissue, sarcoma X 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Peripheral nerve 2 

Spinal cord 2 

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Pheochromocytoma complex, metastatic,

 adrenal medulla 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

None 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Transitional epithelium, papilloma X 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Leukemia mononuclear X X X X X X X 19 

50 
 

 

 

 

 

 

 

 

 

 

 

 

 

108 1-Chloro-2-propanol, NTP TR 477 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

150 ppm 

Number of Days on Study 

2 4 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

1 8 2 3 7 7 7 7 8 9 9 0 0 1 1 1 2 3 3 3 3 3 3 3 3 

7 4 7 6 6 7 8 8 2 1 9 8 8 2 2 6 8 4 4 4 4 4 4 4 4 

Carcass ID Number 

2 3 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

9 0 8 9 7 6 9 9 7 9 6 7 8 6 8 9 8 6 7 7 7 7 7 7 7 

3 6 0 9 1 6 7 8 3 1 9 6 1 8 4 6 3 7 0 2 4 5 7 8 9 

Alimentary System 

Esophagus 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Mesentery 

Oral mucosa 

Squamous cell carcinoma 

Pancreas 

Salivary glands 

Stomach, forestomach 

Stomach, glandular 

Tongue 

Squamous cell carcinoma, metastatic,

 oral mucosa 

Squamous cell papilloma 

Tooth 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + A + + + + + + + + + + + 

+ + + + + + + + + + + + + A + + + + + + + + + + + 

+ + + + + + + + + + + + + A + + + + + + + + + + + 

+ + + + + + + + + + + + + A + + + + + + + + + + + 

+ + A + + + + + + A A + + A A + A + + + + + + + + 

+ + + + + + + + + A A + + A A + A + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + 

+ 

X 

+ + + + + + + + + + + + + A + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ 

X 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Pheochromocytoma malignant X 

Pheochromocytoma benign X X 

Bilateral, pheochromocytoma benign X 

Islets, pancreatic + + + + + + + + + + + + + A + + + + + + + + + + + 

Adenoma 

Carcinoma 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Pars distalis, adenoma X X X X X X X X X X X X X 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

C-cell, adenoma X X X X X 

General Body System 

None 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma X X 

Bilateral, carcinoma X 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 

Polyp stromal X X X 

Vagina + + 
 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 109 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

150 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 

2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 8 8 8 8 8 8 9 9 9 9 0 0 0 0 0 0 0 0 0 1 1 1 1 1 1 Tissues/ 

2 5 6 7 8 9 0 2 4 5 0 1 2 3 4 5 7 8 9 0 1 2 3 4 5 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 44 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 45 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Mesentery + + + + + + + + 11 

Oral mucosa 1 

Squamous cell carcinoma 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Tongue + 2 

Squamous cell carcinoma, metastatic,

 oral mucosa 1 

Squamous cell papilloma X 1 

Tooth + 1 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma malignant 1 

Pheochromocytoma benign X X 4 

Bilateral, pheochromocytoma benign 1 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma X 1 

Carcinoma X 1 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X 30 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, adenoma X X X 8 

General Body System 

None 

Genital System 

Clitoral gland + + + + + + + + + + + + M + + + + + + + + + + + + 49 

Carcinoma X 3 

Bilateral, carcinoma 1 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Polyp stromal X X X 6 

Vagina 2 
 

 

 

 

 

 

110 1-Chloro-2-propanol, NTP TR 477 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

150 ppm 

2 4 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 1 

7 

8 

4 

2 

7 

3 

6 

7 

6 

7 

7 

7 

8 

7 

8 

8 

2 

9 

1 

9 

9 

0 

8 

0 

8 

1 

2 

1 

2 

1 

6 

2 

8 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

2 3 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

Carcass ID Number 9 

3 

0 

6 

8 

0 

9 

9 

7 

1 

6 

6 

9 

7 

9 

8 

7 

3 

9 

1 

6 

9 

7 

6 

8 

1 

6 

8 

8 

4 

9 

6 

8 

3 

6 

7 

7 

0 

7 

2 

7 

4 

7 

5 

7 

7 

7 

8 

7 

9 

Hematopoietic System 

Bone marrow 

Histiocytic sarcoma 

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Thymus 

Thymoma benign 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + M + + + + + + + + + + + + 

Integumentary System 

Mammary gland 

Adenoma 

Carcinoma 

Fibroadenoma 

Fibroadenoma, multiple 

Skin 

Subcutaneous tissue, melanoma malignant 

Subcutaneous tissue, schwannoma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X X X X X X X X 

X X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

Musculoskeletal System 

Bone 

Skeletal muscle 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ 

Nervous System 

Brain 

Peripheral nerve 

Spinal cord 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ 

+ 

Respiratory System 

Lung 

Melanoma malignant, metastatic, skin 

Nose 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + A + + + + + + + + A + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Ear 

Zymbal’s gland 

+ 

+ 

Urinary System 

Kidney 

Urinary bladder 

+ + + + + + + + + + A + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Leukemia mononuclear 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 111 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

150 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 

2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 8 8 8 8 8 8 9 9 9 9 0 0 0 0 0 0 0 0 0 1 1 1 1 1 1 Tissues/ 

2 5 6 7 8 9 0 2 4 5 0 1 2 3 4 5 7 8 9 0 1 2 3 4 5 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma X 1 

Lymph node + + 9 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Thymoma benign X 1 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Carcinoma 1 

Fibroadenoma X X X X X X X X X X X X X 21 

Fibroadenoma, multiple X X X X X 7 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Subcutaneous tissue, melanoma malignant X 1 

Subcutaneous tissue, schwannoma malignant 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Skeletal muscle 1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Peripheral nerve 1 

Spinal cord 1 

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Melanoma malignant, metastatic, skin X 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Ear 1 

Zymbal’s gland 1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma X 1 

Leukemia mononuclear X X X X X X X X 19 
 

 

 

 

 

 

 

112 1-Chloro-2-propanol, NTP TR 477 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

325 ppm 

Number of Days on Study 

5 5 5 5 5 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 

0 2 2 7 9 0 1 5 5 6 6 6 9 9 0 1 1 1 2 3 3 3 3 3 3 

6 5 8 1 7 8 3 5 9 1 3 8 4 7 8 4 7 8 1 3 4 4 4 4 4 

Carcass ID Number 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 5 3 3 5 2 4 2 5 6 1 3 6 4 6 5 2 2 6 5 1 1 1 2 2 

8 3 4 3 4 2 1 3 8 1 6 1 2 2 0 1 4 0 3 0 7 8 9 1 5 

Alimentary System 

Esophagus 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Hepatocellular adenoma 

Histiocytic sarcoma 

Mesentery 

Oral mucosa 

Squamous cell papilloma 

Pancreas 

Histiocytic sarcoma 

Salivary glands 

Stomach, forestomach 

Stomach, glandular 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + A + + + + + + + + + + + + + + + + + + 

+ + + + + + A + + + + + + + + + + + + A + + + + + 

+ + + + + + A + + + + + + + + + + + + A + + + + + 

+ + + + + + A + + + A + + A + + A + + + + + + + + 

+ A + + + + A + + + A + + A + + A A + A + + + + + 

+ A + + + + A + + + A + + A + + A A + A + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + 

+ + + + + + + + + + A + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Cardiovascular System 

Blood vessel 

Heart 

Histiocytic sarcoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Pheochromocytoma benign X 

Islets, pancreatic + + + + + + A + + + A + + + + + + + + + + + + + + 

Adenoma 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X 

Pars distalis, histiocytic sarcoma X 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

C-cell, adenoma 

C-cell, carcinoma 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 113 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

325 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 5 5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 5 5 5 5 5 6 6 4 4 Tissues/ 

6 7 8 9 0 2 5 6 7 8 9 0 3 4 5 6 2 5 6 7 9 4 5 7 9 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 43 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 43 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocellular adenoma X 1 

Histiocytic sarcoma 1 

Mesentery + + + + + 12 

Oral mucosa + 1 

Squamous cell papilloma X 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Histiocytic sarcoma 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma benign 1 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Adenoma X 1 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pars distalis, adenoma X X X X X X X X X X X X X X X 32 

Pars distalis, histiocytic sarcoma 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, adenoma X X X X X 5 

C-cell, carcinoma X 1 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

114 1-Chloro-2-propanol, NTP TR 477 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

325 ppm 

5 5 5 5 5 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 0 2 2 7 9 0 1 5 5 6 6 6 9 9 0 1 1 1 2 3 3 3 3 3 3 

6 5 8 1 7 8 3 5 9 1 3 8 4 7 8 4 7 8 1 3 4 4 4 4 4 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

Carcass ID Number 4 5 3 3 5 2 4 2 5 6 1 3 6 4 6 5 2 2 6 5 1 1 1 2 2 

8 3 4 3 4 2 1 3 8 1 6 1 2 2 0 1 4 0 3 0 7 8 9 1 5 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + M + + 

Adenoma X 

Carcinoma 

Histiocytic sarcoma X 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 

Cystadenoma X 

Granulosa cell tumor benign X 

Granulosa-theca tumor malignant 

Histiocytic sarcoma X 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Polyp stromal X X X X 

Hematopoietic System 

Bone marrow + + + A + + + + + A + + + + + + + A + + + + + + + 

Lymph node + + + + + + + + + + + + 

Mediastinal, histiocytic sarcoma X 

Pancreatic, histiocytic sarcoma X 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + A + + + + + 

Histiocytic sarcoma X 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Integumentary System 

Mammary gland + + + M + + + + + + + + + + + + + + + + + + + + + 

Carcinoma X 

Fibroadenoma X X X X X X X X X X 

Fibroadenoma, multiple X X X 

Histiocytic sarcoma X 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 

Subcutaneous tissue, fibroma X 

Subcutaneous tissue, histiocytic sarcoma X 

Subcutaneous tissue, melanoma malignant X 

Subcutaneous tissue, sarcoma X 

Musculoskeletal System 

Bone 

Osteosarcoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 
 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 115 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

325 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 5 5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 5 5 5 5 5 6 6 4 4 Tissues/ 

6 7 8 9 0 2 5 6 7 8 9 0 3 4 5 6 2 5 6 7 9 4 5 7 9 Tumors 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma X 2 

Carcinoma X X 2 

Histiocytic sarcoma 1 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cystadenoma 1 

Granulosa cell tumor benign 1 

Granulosa-theca tumor malignant X 1 

Histiocytic sarcoma 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Polyp stromal X X 6 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Lymph node + + + 15 

Mediastinal, histiocytic sarcoma 1 

Pancreatic, histiocytic sarcoma 1 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Histiocytic sarcoma 1 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Carcinoma 1 

Fibroadenoma X X X X X X X X X X X X X X X X 26 

Fibroadenoma, multiple X X 5 

Histiocytic sarcoma 1 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Subcutaneous tissue, fibroma 1 

Subcutaneous tissue, histiocytic sarcoma 1 

Subcutaneous tissue, melanoma malignant 1 

Subcutaneous tissue, sarcoma 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Osteosarcoma 1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 
 

 

 

 

 

 

 

116 1-Chloro-2-propanol, NTP TR 477 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

325 ppm 

Number of Days on Study 

5 

0 

6 

5 

2 

5 

5 

2 

8 

5 

7 

1 

5 

9 

7 

6 

0 

8 

6 

1 

3 

6 

5 

5 

6 

5 

9 

6 

6 

1 

6 

6 

3 

6 

6 

8 

6 

9 

4 

6 

9 

7 

7 

0 

8 

7 

1 

4 

7 

1 

7 

7 

1 

8 

7 

2 

1 

7 

3 

3 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

Carcass ID Number 

3 

4 

8 

3 

5 

3 

3 

3 

4 

3 

3 

3 

3 

5 

4 

3 

2 

2 

3 

4 

1 

3 

2 

3 

3 

5 

8 

3 

6 

1 

3 

1 

6 

3 

3 

1 

3 

6 

2 

3 

4 

2 

3 

6 

0 

3 

5 

1 

3 

2 

4 

3 

2 

0 

3 

6 

3 

3 

5 

0 

3 

1 

7 

3 

1 

8 

3 

1 

9 

3 

2 

1 

3 

2 

5 

Respiratory System 

Lung 

Histiocytic sarcoma 

Osteosarcoma, metastatic, bone 

Nose 

Respiratory epithelium, histiocytic sarcoma 

Pleura 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X 

+ + + + + + + + + + A + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Zymbal’s gland 

Carcinoma 

+ 

X 

Urinary System 

Kidney 

Mesenchymal tumor malignant 

Urinary bladder 

Histiocytic sarcoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Leukemia mononuclear 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X X X X X X X X X X 
 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 117 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

325 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

5 

3 

5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 2 

6 

2 

7 

2 

8 

2 

9 

3 

0 

3 

2 

3 

5 

3 

6 

3 

7 

3 

8 

3 

9 

4 

0 

4 

3 

4 

4 

4 

5 

4 

6 

5 

2 

5 

5 

5 

6 

5 

7 

5 

9 

6 

4 

6 

5 

4 

7 

4 

9 

Tissues/ 

Tumors 

Respiratory System 

Lung 

Histiocytic sarcoma

Osteosarcoma, metastatic, bone

Nose 

Respiratory epithelium, histiocytic sarcoma

Pleura 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

1 

1 

49 

1 

1 

50 

Special Senses System 

Zymbal’s gland

Carcinoma

 1 

1 

Urinary System 

Kidney 

Mesenchymal tumor malignant 

Urinary bladder 

Histiocytic sarcoma

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

1 

50 

1 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma

Leukemia mononuclear 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X X 

50 

1 

18 
 

 

 

 

 

 

 

 

 

 

 

 

118 1-Chloro-2-propanol, NTP TR 477 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

650 ppm 

Number of Days on Study 

4 4 5 5 5 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 

4 8 6 6 9 3 3 4 5 6 9 9 9 0 0 1 2 3 3 3 3 3 3 3 3 

9 9 1 2 2 4 9 9 6 8 1 3 8 0 8 4 2 1 3 4 4 4 4 4 4 

Carcass ID Number 

3 4 3 3 3 4 3 4 3 3 3 3 3 3 3 4 3 3 3 3 3 3 3 3 3 

9 0 8 7 8 0 8 1 8 9 9 9 7 6 8 1 6 9 7 7 7 7 7 7 7 

4 7 7 5 3 6 0 0 1 6 9 2 1 6 4 4 9 5 2 0 4 6 7 8 9 

Alimentary System 

Esophagus 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Hepatocellular adenoma 

Mesentery 

Pancreas 

Acinus, adenoma 

Salivary glands 

Stomach, forestomach 

Stomach, glandular 

Tongue 

Squamous cell papilloma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + A + + + + + + + + + A + + + + + + + + + + 

+ + + + A + + + + + + + + + + + + + + + + + + + + 

+ + + + A + + + + + A + + + + + + + + + + + + + + 

A A + + A + + + + + + + + + + + + + + + + + + + + 

+ A A + A + A + + + + + + + + + + + + + + + + + + 

A + + + A + A + + + A + + + + + + + A + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + 

+ A + + A + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Ganglioneuroma X 

Pheochromocytoma malignant X 

Pheochromocytoma benign X 

Islets, pancreatic + A + + A + + + + + + + + + + + + + + + + + + + + 

Parathyroid gland + + + + + + + + + + + + + M + + + + + + + + + + + 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X X 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

C-cell, adenoma 

C-cell, carcinoma X 

Follicular cell, adenoma X 

General Body System 

None 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + M + + + + + + + 

Adenoma X 

Carcinoma X 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 

Polyp stromal X 
 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 119 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

650 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 5 5 5 5 5 5 

3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 4 4 3 3 3 3 3 3 Total 

Carcass ID Number 8 8 9 9 9 9 9 0 0 0 0 0 0 0 0 1 1 1 1 6 6 7 8 8 8 Tissues/ 

2 8 0 1 3 7 8 0 1 2 3 4 5 8 9 1 2 3 5 7 8 3 5 6 9 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 45 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocellular adenoma 1 

Mesentery + + 10 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Acinus, adenoma 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Tongue + 1 

Squamous cell papilloma X 1 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Ganglioneuroma 1 

Pheochromocytoma malignant 1 

Pheochromocytoma benign X X X 4 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X 35 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, adenoma X X X 3 

C-cell, carcinoma X 2 

Follicular cell, adenoma 1 

General Body System 

None 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma X X X 4 

Carcinoma X X 3 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Polyp stromal X X X 4 
 

 

 

 

 

 

 

120 1-Chloro-2-propanol, NTP TR 477 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

650 ppm 

Number of Days on Study 

4 

4 

9 

4 

8 

9 

5 

6 

1 

5 

6 

2 

5 

9 

2 

6 

3 

4 

6 

3 

9 

6 

4 

9 

6 

5 

6 

6 

6 

8 

6 

9 

1 

6 

9 

3 

6 

9 

8 

7 

0 

0 

7 

0 

8 

7 

1 

4 

7 

2 

2 

7 

3 

1 

7 

3 

3 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

Carcass ID Number 

3 

9 

4 

4 

0 

7 

3 

8 

7 

3 

7 

5 

3 

8 

3 

4 

0 

6 

3 

8 

0 

4 

1 

0 

3 

8 

1 

3 

9 

6 

3 

9 

9 

3 

9 

2 

3 

7 

1 

3 

6 

6 

3 

8 

4 

4 

1 

4 

3 

6 

9 

3 

9 

5 

3 

7 

2 

3 

7 

0 

3 

7 

4 

3 

7 

6 

3 

7 

7 

3 

7 

8 

3 

7 

9 

Hematopoietic System 

Bone marrow 

Histiocytic sarcoma 

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Thymus 

Thymoma benign 

+ + + + A + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + 

+ + + + + + + + + + + + + + + + M + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ A + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Integumentary System 

Mammary gland 

Fibroadenoma 

Fibroadenoma, multiple 

Skin 

Subcutaneous tissue, fibroma 

Subcutaneous tissue, fibrous histiocytoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X 

X X X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Nose 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + A + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Ear + 

Urinary System 

Kidney 

Urinary bladder 

Papilloma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + A + + + + + + + + + + + + + + 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Leukemia mononuclear 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 121 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

650 ppm 

Number of Days on Study 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

Carcass ID Number 

3 

8 

2 

3 

8 

8 

3 

9 

0 

3 

9 

1 

3 

9 

3 

3 

9 

7 

3 

9 

8 

4 

0 

0 

4 

0 

1 

4 

0 

2 

4 

0 

3 

4 

0 

4 

4 

0 

5 

4 

0 

8 

4 

0 

9 

4 

1 

1 

4 

1 

2 

4 

1 

3 

4 

1 

5 

3 

6 

7 

3 

6 

8 

3 

7 

3 

3 

8 

5 

3 

8 

6 

3 

8 

9 

Total 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow 

Histiocytic sarcoma 

Lymph node

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Thymus 

Thymoma benign 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

49 

1 

7 

49 

50 

49 

50 

1 

Integumentary System 

Mammary gland 

Fibroadenoma 

Fibroadenoma, multiple 

Skin 

Subcutaneous tissue, fibroma

Subcutaneous tissue, fibrous histiocytoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X 

X X X X X X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

50 

14 

9 

50 

2 

1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma

Nose 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

1 

49 

50 

Special Senses System 

Ear + 2 

Urinary System 

Kidney 

Urinary bladder 

Papilloma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

50 

49 

1 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Leukemia mononuclear 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

X X X X 

50 

1 

13 
122 1-Chloro-2-propanol, NTP TR 477 

TABLE B3 

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Adrenal Medulla: Benign Pheochromocytoma a Overall rate 2/49 (4%) 5/50 (10%) 1/50 (2%) 4/50 (8%) 

Adjusted rateb 4.6% 10.8% 2.3% 8.9% c Terminal rate 0/25 (0%) 3/33 (9%) 1/30 (3%) 3/31 (10%) 

First incidence (days) 659 627 734 (T) 693 

d Poly-3 test Pù0.451 Pù0.256 Pù0.524N Pù0.370 

Adrenal Medulla: Benign, Complex, or Malignant Pheochromocytoma 

Overall rate 4/49 (8%) 5/50 (10%) 1/50 (2%) 5/50 (10%)
 

Adjusted rate 9.1% 10.8% 2.3% 11.2%
 

Terminal rate 0/25 (0%) 3/33 (9%) 1/30 (3%) 4/31 (13%)
 

First incidence (days) 629 627 734 (T) 693
 

Poly-3 test Pù0.535 Pù0.547 Pù0.191N Pù0.528 

Clitoral Gland: Adenoma 

Overall rate 1/49 (2%) 0/49 (0%) 2/49 (4%) 4/49 (8%) 

Adjusted rate 2.3% 0.0% 4.6% 9.1% 

Terminal rate 1/25 (4%) 0/32 (0%) 1/29 (3%) 3/31 (10%) e First incidence (days) 734 (T) — 608 649 

Poly-3 test Pù0.039 Pù0.539N Pù0.537 Pù0.202 

Clitoral Gland: Carcinoma 

Overall rate 4/49 (8%) 4/49 (8%) 2/49 (4%) 3/49 (6%) 

Adjusted rate 9.3% 8.9% 4.6% 6.9% 

Terminal rate 4/25 (16%) 2/32 (6%) 2/29 (7%) 2/31 (7%) 

First incidence (days) 734 (T) 708 734 (T) 693 

Poly-3 test Pù0.371N Pù0.634N Pù0.354N Pù0.510N 

Clitoral Gland: Adenoma or Carcinoma 

Overall rate 5/49 (10%) 4/49 (8%) 4/49 (8%) 7/49 (14%)
 

Adjusted rate 11.7% 8.9% 9.2% 15.9%
 

Terminal rate 5/25 (20%) 2/32 (6%) 3/29 (10%) 5/31 (16%)
 

First incidence (days) 734 (T) 708 608 649
 

Poly-3 test Pù0.268 Pù0.487N Pù0.507N Pù0.413 

Mammary Gland: Fibroadenoma 

Overall rate 29/50 (58%) 28/50 (56%) 31/50 (62%) 23/50 (46%)
 

Adjusted rate 62.1% 59.3% 67.6% 50.6%
 

Terminal rate 16/25 (64%) 21/33 (64%) 22/30 (73%) 17/31 (55%)
 

First incidence (days) 541 627 608 561
 

Poly-3 test Pù0.175N Pù0.479N Pù0.371 Pù0.182N
 

Mammary Gland: Fibroadenoma, Adenoma, or Carcinoma 

Overall rate 30/50 (60%) 28/50 (56%) 31/50 (62%) 23/50 (46%)
 

Adjusted rate 64.2% 59.3% 67.6% 50.6%
 

Terminal rate 16/25 (64%) 21/33 (64%) 22/30 (73%) 17/31 (55%)
 

First incidence (days) 541 627 608 561
 

Poly-3 test Pù0.133N Pù0.395N Pù0.456 Pù0.130N
 

Pituitary Gland (Pars Distalis): Adenoma 

Overall rate 29/49 (59%) 30/50 (60%) 32/50 (64%) 35/50 (70%)
 

Adjusted rate 62.9% 63.6% 66.5% 73.5%
 

Terminal rate 17/25 (68%) 21/33 (64%) 19/30 (63%) 23/31 (74%)
 

First incidence (days) 541 676 506 489
 

Poly-3 test Pù0.132 Pù0.565 Pù0.444 Pù0.185 
1-Chloro-2-propanol, NTP TR 477 123 

TABLE B3 

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Pituitary Gland (Pars Distalis): Adenoma or Carcinoma 

Overall rate 30/49 (61%) 30/50 (60%) 32/50 (64%) 35/50 (70%)
 

Adjusted rate 65.0% 63.6% 66.5% 73.5%
 

Terminal rate 17/25 (68%) 21/33 (64%) 19/30 (63%) 23/31 (74%)
 

First incidence (days) 541 676 506 489
 

Poly-3 test Pù0.173 Pù0.537N Pù0.528 Pù0.247 

Skin (Subcutaneous Tissue): Fibroma, Fibrous Histiocytoma, or Sarcoma 

Overall rate 2/50 (4%) 0/50 (0%) 2/50 (4%) 3/50 (6%) 

Adjusted rate 4.6% 0.0% 4.5% 6.7% 

Terminal rate 2/25 (8%) 0/33 (0%) 0/30 (0%) 2/31 (6%) 

First incidence (days) 734 (T) — 659 708 

Poly-3 test Pù0.235 Pù0.254N Pù0.710N Pù0.533 

Thyroid Gland (C-cell): Adenoma 

Overall rate 2/50 (4%) 8/50 (16%) 5/50 (10%) 3/50 (6%) 

Adjusted rate 4.6% 17.3% 11.3% 6.7% 

Terminal rate 2/25 (8%) 5/33 (15%) 5/30 (17%) 3/31 (10%) 

First incidence (days) 734 (T) 678 734 (T) 734 (T) 

Poly-3 test Pù0.446N Pù0.058 Pù0.235 Pù0.532 

Thyroid Gland (C-cell): Adenoma or Carcinoma 

Overall rate 2/50 (4%) 8/50 (16%) 6/50 (12%) 5/50 (10%)
 

Adjusted rate 4.6% 17.3% 13.6% 11.2%
 

Terminal rate 2/25 (8%) 5/33 (15%) 6/30 (20%) 4/31 (13%)
 

First incidence (days) 734 (T) 678 734 (T) 668
 

Poly-3 test Pù0.396 Pù0.058 Pù0.146 Pù0.240 

Uterus: Stromal Polyp 

Overall rate 7/50 (14%) 6/50 (12%) 6/50 (12%) 4/50 (8%)
 

Adjusted rate 15.7% 13.0% 13.3% 9.0%
 

Terminal rate 2/25 (8%) 4/33 (12%) 4/30 (13%) 3/31 (10%)
 

First incidence (days) 635 636 528 731
 

Poly-3 test Pù0.230N Pù0.484N Pù0.507N Pù0.274N
 

All Organs: Mononuclear Cell Leukemia 

Overall rate 19/50 (38%) 19/50 (38%) 18/50 (36%) 13/50 (26%)
 

Adjusted rate 40.6% 40.1% 38.5% 27.8%
 

Terminal rate 7/25 (28%) 11/33 (33%) 9/30 (30%) 4/31 (13%)
 

First incidence (days) 519 627 528 562
 

Poly-3 test Pù0.099N Pù0.572N Pù0.510N Pù0.141N
 

All Organs: Benign Neoplasms 

Overall rate 43/50 (86%) 42/50 (84%) 48/50 (96%) 42/50 (84%)
 

Adjusted rate 89.1% 87.1% 96.6% 88.2%
 

Terminal rate 23/25 (92%) 28/33 (85%) 29/30 (97%) 29/31 (94%)
 

First incidence (days) 541 627 506 489
 

Poly-3 test Pù0.512 Pù0.506N Pù0.131 Pù0.584N
 

All Organs: Malignant Neoplasms 

Overall rate 26/50 (52%) 24/50 (48%) 26/50 (52%) 18/50 (36%)
 

Adjusted rate 54.9% 49.6% 53.9% 38.5%
 

Terminal rate 10/25 (40%) 14/33 (42%) 13/30 (43%) 9/31 (29%)
 

First incidence (days) 519 217 525 562
 

Poly-3 test Pù0.078N Pù0.378N Pù0.548N Pù0.081N
 
124 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE B3 

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

All Organs: Benign or Malignant Neoplasms 

Overall rate 48/50 (96%) 46/50 (92%) 49/50 (98%) 48/50 (96%) 

Adjusted rate 96.0% 93.3% 98.0% 97.5% 

Terminal rate 23/25 (92%) 30/33 (91%) 29/30 (97%) 30/31 (97%) 

First incidence (days) 

Poly-3 test 

519 

Pù0.306 

217 

Pù0.443N 

506 

Pù0.500 

489 

Pù0.560 

(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, pituitary gland, thyroid gland, and uterus; for other tissues, denominator is number of animals necropsied. b	 Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality 

Observed incidence at terminal kill 

d	 Beneath the 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 controls and that exposed group. The Poly-3 test accounts for 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 
 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 125 

TABLE B4 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 150 ppm 325 ppm 650 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths

 Moribund 12 7 7 5

 Natural deaths 13 10 13 14 

Survivors

 Terminal sacrifice 25 33 30 31 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Intestine large, colon (47) (49) (49) (48) 

Dilatation 1 (2%) 

Inflammation, chronic active 1 (2%) 

Parasite metazoan 3 (6%) 2 (4%) 2 (4%) 1 (2%) 

Intestine large, rectum (49) (49) (48) (49) 

Parasite metazoan 6 (12%) 4 (8%) 3 (6%) 7 (14%) 

Intestine large, cecum (47) (49) (48) (48) 

Dilatation 1 (2%) 

Hemorrhage 1 (2%) 

Inflammation, chronic active 1 (2%) 

Mineralization 1 (2%) 

Parasite metazoan 1 (2%) 

Ulcer 1 (2%) 

Intestine small, jejunum (44) (44) (43) (46) 

Hemorrhage 1 (2%) 

Intestine small, ileum (42) (45) (43) (45) 

Hemorrhage 1 (2%) 

Liver (50) (50) (50) (50) 

Angiectasis 1 (2%) 5 (10%) 3 (6%) 7 (14%) 

Basophilic focus 29 (58%) 33 (66%) 27 (54%) 32 (64%) 

Clear cell focus 3 (6%) 7 (14%) 7 (14%) 2 (4%) 

Congestion 2 (4%) 

Deformity 3 (6%) 6 (12%) 3 (6%) 

Eosinophilic focus 6 (12%) 3 (6%) 7 (14%) 4 (8%) 

Fibrosis 1 (2%) 

Hemorrhage 2 (4%) 

Hepatodiaphragmatic nodule 2 (4%) 3 (6%) 12 (24%) 4 (8%) 

Infiltration cellular, lymphocyte 1 (2%) 1 (2%) 1 (2%) 

Inflammation, granulomatous 12 (24%) 5 (10%) 9 (18%) 11 (22%) 

Mixed cell focus 4 (8%) 8 (16%) 5 (10%) 6 (12%) 

Necrosis 3 (6%) 2 (4%) 5 (10%) 1 (2%) 

Pigmentation, bile 1 (2%) 

Vacuolization cytoplasmic 1 (2%) 2 (4%) 3 (6%) 3 (6%) 

Artery, thrombosis 1 (2%) 

Bile duct, hyperplasia 1 (2%) 

Centrilobular, necrosis 1 (2%) 

Kupffer cell, pigmentation 1 (2%) 

Mesentery (9) (11) (12) (10) 

Hemorrhage 1 (11%) 

Fat, necrosis 8 (89%) 10 (91%) 11 (92%) 9 (90%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

126 1-Chloro-2-propanol, NTP TR 477 

TABLE B4 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Alimentary System (continued) 

Pancreas (47) (49) (49) (48) 

Infiltration cellular, mixed cell 1 (2%) 

Inflammation, acute 1 (2%) 

Acinus, atrophy 12 (26%) 4 (8%) 3 (6%) 5 (10%) 

Acinus, hyperplasia 1 (2%) 1 (2%) 

Salivary glands (50) (50) (50) (50) 

Atrophy 1 (2%) 

Stomach, forestomach (50) (50) (50) (50) 

Inflammation, chronic active 5 (10%) 1 (2%) 3 (6%) 

Ulcer 2 (4%) 2 (4%) 3 (6%) 4 (8%) 

Epithelium, hyperplasia 4 (8%) 3 (6%) 3 (6%) 3 (6%) 

Stomach, glandular (50) (50) (50) (50) 

Inflammation, chronic active 1 (2%) 

Necrosis 12 (24%) 6 (12%) 7 (14%) 7 (14%) 

Ulcer 2 (4%) 

Tooth (1) 

Developmental malformation 1 (100%) 

Cardiovascular System 

Heart (50) (50) (50) (50) 

Cardiomyopathy 18 (36%) 21 (42%) 15 (30%) 11 (22%) 

Hemorrhage 1 (2%) 

Inflammation, chronic active 1 (2%) 

Artery, inflammation, chronic active 1 (2%) 

Atrium, inflammation, chronic active 1 (2%) 

Atrium, thrombosis 4 (8%) 2 (4%) 3 (6%) 3 (6%) 

Endocrine System 

Adrenal cortex (49) (50) (50) (50) 

Angiectasis 7 (14%) 8 (16%) 9 (18%) 10 (20%) 

Cytoplasmic alteration 5 (10%) 3 (6%) 1 (2%) 4 (8%) 

Degeneration, cystic 1 (2%) 1 (2%) 

Hemorrhage 2 (4%) 3 (6%) 

Vacuolization cytoplasmic 4 (8%) 5 (10%) 7 (14%) 8 (16%) 

Adrenal medulla (49) (50) (50) (50) 

Hyperplasia 5 (10%) 1 (2%) 2 (4%) 

Infiltration cellular, lymphocyte 1 (2%) 

Necrosis 1 (2%) 

Islets, pancreatic (46) (49) (48) (48) 

Hyperplasia 1 (2%) 

Metaplasia 1 (2%) 

Parathyroid gland (50) (50) (50) (49) 

Angiectasis 1 (2%) 

Hyperplasia 1 (2%) 

Pituitary gland (49) (50) (50) (50) 

Necrosis 1 (2%) 

Pars distalis, angiectasis 1 (2%) 4 (8%) 1 (2%) 

Pars distalis, cyst 13 (27%) 11 (22%) 11 (22%) 13 (26%) 

Pars distalis, hemorrhage 2 (4%) 1 (2%) 

Pars distalis, hyperplasia 4 (8%) 6 (12%) 6 (12%) 

Pars distalis, pigmentation 1 (2%) 

Pars nervosa, cyst 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 127 

TABLE B4 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Endocrine System (continued) 

Thyroid gland 

Infiltration cellular, mixed cell

Inflammation, chronic active

C-cell, hyperplasia

Follicle, cyst

(50) 

 1 (2%) 

 1 (2%) 

 10 (20%) 

(50) 

 11 (22%) 

(50) 

 6 (12%) 

(50) 

 8 (16%) 

 1 (2%) 

General Body System 

None 

Genital System 

Clitoral gland (49) (49) (49) (49) 

Atrophy 2 (4%) 

Cyst 4 (8%) 4 (8%) 4 (8%) 6 (12%) 

Hyperplasia 1 (2%) 1 (2%) 1 (2%) 

Inflammation, chronic active 3 (6%) 1 (2%) 

Bilateral, cyst 1 (2%) 

Ovary (50) (50) (50) (50) 

Angiectasis 1 (2%) 

Cyst 6 (12%) 4 (8%) 10 (20%) 8 (16%) 

Hyperplasia, histiocytic 1 (2%) 

Inflammation, granulomatous 1 (2%) 

Bilateral, cyst 1 (2%) 

Interstitial cell, hyperplasia 1 (2%) 

Uterus (50) (50) (50) (50) 

Abscess 1 (2%) 

Cyst 1 (2%) 2 (4%) 

Fibrosis 1 (2%) 

Hemorrhage 1 (2%) 1 (2%) 1 (2%) 

Hydrometra 4 (8%) 3 (6%) 4 (8%) 

Hyperplasia, cystic 1 (2%) 1 (2%) 1 (2%) 

Inflammation, chronic active 1 (2%) 3 (6%) 

Bilateral, hydrometra 1 (2%) 

Epithelium, hyperplasia 1 (2%) 

Vagina (2) 

Hemorrhage 1 (50%) 

Infiltration cellular, polymorphonuclear 1 (50%) 

Inflammation, chronic active 1 (50%) 

Pigmentation 1 (50%) 

Hematopoietic System 

Bone marrow (47) (50) (47) (49) 

Atrophy 2 (4%) 

Fibrosis 1 (2%) 

Hyperplasia 1 (2%) 3 (6%) 1 (2%) 

Inflammation, chronic active 1 (2%) 

Myeloid cell, hyperplasia 3 (6%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

128 1-Chloro-2-propanol, NTP TR 477 

TABLE B4 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Hematopoietic System (continued) 

Lymph node (11) (9) (15) (7) 

Hemorrhage 1 (9%) 2 (22%) 1 (7%) 

Hyperplasia, lymphoid 1 (7%) 

Pigmentation 1 (7%) 

Deep cervical, hemorrhage 1 (9%) 1 (7%) 

Deep cervical, hyperplasia, plasma cell 1 (7%) 

Deep cervical, pigmentation 1 (7%) 

Iliac, amyloid deposition 1 (11%) 

Iliac, hemorrhage 2 (18%) 1 (11%) 

Iliac, pigmentation 1 (11%) 

Mediastinal, hemorrhage 4 (36%) 2 (22%) 7 (47%) 1 (14%) 

Mediastinal, hyperplasia, lymphoid 1 (7%) 

Mediastinal, hyperplasia, plasma cell 1 (7%) 

Mediastinal, inflammation, acute 1 (11%) 

Mediastinal, pigmentation 2 (18%) 5 (33%) 

Pancreatic, hemorrhage 2 (18%) 2 (13%) 1 (14%) 

Pancreatic, hyperplasia, histiocytic 1 (9%) 1 (7%) 

Pancreatic, hyperplasia, lymphoid 1 (7%) 

Renal, hemorrhage 3 (27%) 2 (22%) 4 (27%) 1 (14%) 

Renal, hyperplasia, histiocytic 1 (9%) 

Renal, pigmentation 1 (9%) 2 (22%) 1 (7%) 1 (14%) 

Lymph node, mandibular (50) (50) (50) (49) 

Amyloid deposition 1 (2%) 

Atrophy 1 (2%) 

Ectasia 1 (2%) 1 (2%) 

Hemorrhage 6 (12%) 4 (8%) 4 (8%) 2 (4%) 

Hyperplasia, lymphoid 1 (2%) 2 (4%) 

Hyperplasia, plasma cell 1 (2%) 4 (8%) 1 (2%) 

Inflammation, chronic active 1 (2%) 

Pigmentation 1 (2%) 1 (2%) 1 (2%) 

Lymph node, mesenteric (50) (50) (49) (50) 

Atrophy 2 (4%) 

Hemorrhage 7 (14%) 3 (6%) 6 (12%) 5 (10%) 

Hyperplasia, histiocytic 3 (6%) 4 (8%) 2 (4%) 

Hyperplasia, lymphoid 1 (2%) 

Pigmentation 1 (2%) 1 (2%) 

Spleen (50) (50) (50) (49) 

Accessory spleen 1 (2%) 

Atrophy 1 (2%) 

Congestion 1 (2%) 

Fibrosis 3 (6%) 2 (4%) 2 (4%) 1 (2%) 

Hematopoietic cell proliferation 7 (14%) 2 (4%) 3 (6%) 1 (2%) 

Hyperplasia, histiocytic 1 (2%) 

Necrosis 1 (2%) 

Pigmentation 7 (14%) 11 (22%) 8 (16%) 10 (20%) 

Capsule, cyst 1 (2%) 

Capsule, fibrosis 2 (4%) 

Thymus (48) (49) (50) (50) 

Atrophy 16 (33%) 10 (20%) 17 (34%) 14 (28%) 

Ectopic parathyroid gland 1 (2%) 

Hemorrhage 1 (2%) 1 (2%) 1 (2%) 3 (6%) 

Epithelial cell, hyperplasia 7 (15%) 6 (12%) 9 (18%) 4 (8%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 129 

TABLE B4 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Integumentary System 

Mammary gland (50) (50) (49) (50) 

Dilatation 34 (68%) 33 (66%) 25 (51%) 27 (54%) 

Hyperplasia 20 (40%) 23 (46%) 14 (29%) 19 (38%) 

Inflammation, chronic active 1 (2%) 

Pigmentation 1 (2%) 

Skin (50) (50) (50) (50) 

Exudate 1 (2%) 

Inflammation, chronic active 1 (2%) 1 (2%) 

Ulcer 1 (2%) 1 (2%) 

Subcutaneous tissue, edema 1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) (50) 

Hyperostosis 6 (12%) 7 (14%) 7 (14%) 4 (8%) 

Malformation 1 (2%) 

Femur, callus 1 (2%) 

Femur, hyperostosis 2 (4%) 1 (2%) 

Nervous System 

Brain (50) (50) (50) (50) 

Hemorrhage 2 (4%) 2 (4%) 3 (6%) 2 (4%) 

Spinal cord (2) (1) 

Hemorrhage 1 (50%) 

Respiratory System 

Lung (50) (50) (50) (50) 

Congestion 1 (2%) 

Hemorrhage 1 (2%) 2 (4%) 2 (4%) 

Inflammation, acute 1 (2%) 

Inflammation, chronic active 3 (6%) 1 (2%) 2 (4%) 

Alveolus, infiltration cellular, histiocyte 1 (2%) 3 (6%) 2 (4%) 

Artery, inflammation, chronic active 1 (2%) 1 (2%) 

Mediastinum, necrosis 1 (2%) 

Nose (50) (48) (49) (49) 

Foreign body 1 (2%) 

Olfactory epithelium, atrophy 1 (2%) 

Olfactory epithelium, degeneration, hyaline 2 (4%) 9 (19%) 4 (8%) 3 (6%) 

Olfactory epithelium, inflammation,

 chronic active 2 (4%) 2 (4%) 

Respiratory epithelium, degeneration, hyaline 6 (12%) 3 (6%) 8 (16%) 12 (24%) 

Respiratory epithelium, hyperplasia 1 (2%) 10 (21%) 1 (2%) 5 (10%) 

Respiratory epithelium, inflammation,

 chronic active 13 (26%) 9 (19%) 18 (37%) 6 (12%) 

Respiratory epithelium, thrombosis 1 (2%) 

Special Senses System 

Ear (1) (2) 

External ear, hyperplasia 1 (50%) 

Zymbal’s gland (1) (1) 

Hyperplasia 1 (100%) 
 

 

 

 

 

 

 

130 1-Chloro-2-propanol, NTP TR 477 

TABLE B4 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Urinary System 

Kidney (46) (49) (50) (50) 

Casts 1 (2%) 

Cyst 1 (2%) 2 (4%) 

Hydronephrosis 1 (2%) 

Infarct 1 (2%) 

Inflammation, acute 1 (2%) 

Inflammation, chronic active 1 (2%) 1 (2%) 

Mineralization 24 (52%) 28 (57%) 26 (52%) 30 (60%) 

Nephropathy 23 (50%) 23 (47%) 15 (30%) 20 (40%) 

Pelvis, mineralization 1 (2%) 

Renal tubule, degeneration, hyaline 1 (2%) 1 (2%) 

Renal tubule, pigmentation 2 (4%) 2 (4%) 4 (8%) 1 (2%) 

Transitional epithelium, hyperplasia 1 (2%) 

Urinary bladder (49) (50) (50) (49) 

Dilatation 1 (2%) 
131 

APPENDIX C 

SUMMARY OF LESIONS IN MALE MICE 

IN THE 2-YEAR DRINKING WATER STUDY 

OF 1-CHLORO-2-PROPANOL 

TABLE C1 Summary of the Incidence of Neoplasms in Male Mice 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 132 

TABLE C2 Individual Animal Tumor Pathology of Male Mice 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 136 

TABLE C3 Statistical Analysis of Primary Neoplasms in Male Mice 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 154 

TABLE C4 Summary of the Incidence of Nonneoplastic Lesions in Male Mice 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 157 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

132 1-Chloro-2-propanol, NTP TR 477 

TABLE C1 

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanola 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Accidental deaths 5 3 

Moribund 8 7 4 

Natural deaths 2 6 9 4 

Survivors 

Terminal sacrifice 40 44 29 39 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Gallbladder (45) (45) (42) (47) 

Adenoma 1 (2%) 

Intestine large, rectum (50) (50) (50) (50) 

Fibrous histiocytoma, metastatic, skin 1 (2%) 

Fibrous histiocytoma, metastatic, uncertain

 primary site 1 (2%) 

Intestine large, cecum (49) (50) (48) (47) 

Intestine small, duodenum (49) (49) (47) (47) 

Intestine small, jejunum (49) (49) (44) (47) 

Liver (50) (50) (50) (50) 

Fibrous histiocytoma 1 (2%) 

Hemangiosarcoma 2 (4%) 1 (2%) 2 (4%) 

Hemangiosarcoma, multiple 1 (2%) 1 (2%) 

Hepatoblastoma 6 (12%) 2 (4%) 6 (12%) 

Hepatoblastoma, multiple 1 (2%) 

Hepatocellular carcinoma 12 (24%) 6 (12%) 5 (10%) 7 (14%) 

Hepatocellular carcinoma, multiple 1 (2%) 1 (2%) 1 (2%) 

Hepatocellular adenoma 7 (14%) 13 (26%) 21 (42%) 11 (22%) 

Hepatocellular adenoma, multiple 28 (56%) 22 (44%) 13 (26%) 19 (38%) 

Histiocytic sarcoma 2 (4%) 1 (2%) 

Pancreas (50) (50) (50) (50) 

Fibrous histiocytoma 1 (2%) 

Fibrous histiocytoma, metastatic, uncertain

 primary site 1 (2%) 

Salivary glands (50) (50) (50) (50) 

Stomach, forestomach (49) (50) (49) (50) 

Squamous cell papilloma 1 (2%) 1 (2%) 1 (2%) 

Stomach, glandular (49) (50) (50) (49) 

Mast cell tumor benign 1 (2%) 

Cardiovascular System 

Heart (50) (50) (50) (50) 

Fibrous histiocytoma, metastatic, uncertain

 primary site 1 (2%) 

Hemangiosarcoma 1 (2%) 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 133 

TABLE C1 

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Endocrine System 

Adrenal cortex (50) (50) (50) (50) 

Adenoma 1 (2%) 

Capsule, adenoma 1 (2%) 2 (4%) 1 (2%) 

Islets, pancreatic (50) (50) (50) (50) 

Adenoma 1 (2%) 2 (4%) 

Pituitary gland (50) (49) (49) (47) 

Pars distalis, adenoma 1 (2%) 

Thyroid gland (50) (50) (50) (50) 

C-cell, carcinoma 1 (2%) 

Follicular cell, adenoma 1 (2%) 1 (2%) 1 (2%) 1 (2%) 

General Body System 

None 

Genital System 

Epididymis (50) (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Prostate (50) (50) (49) (50) 

Hemangiosarcoma 1 (2%) 

Seminal vesicle (50) (50) (50) (50) 

Testes (50) (50) (50) (50) 

Interstitial cell, adenoma 2 (4%) 

Hematopoietic System 

Bone marrow (50) (50) (50) (50) 

Hemangiosarcoma 1 (2%) 1 (2%) 1 (2%) 

Lymph node (4) (5) (2) (3) 

Fibrous histiocytoma 1 (20%) 

Iliac, fibrous histiocytoma 1 (20%) 

Mediastinal, fibrous histiocytoma 1 (20%) 

Pancreatic, fibrous histiocytoma 1 (20%) 

Renal, fibrous histiocytoma 1 (20%) 1 (33%) 

Lymph node, mandibular (50) (50) (50) (50) 

Carcinoma, metastatic, harderian gland 1 (2%) 

Fibrous histiocytoma 1 (2%) 

Lymph node, mesenteric (49) (50) (50) (50) 

Fibrous histiocytoma 1 (2%) 

Hemangiosarcoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Spleen (50) (50) (50) (50) 

Fibrous histiocytoma 1 (2%) 1 (2%) 

Hemangiosarcoma 1 (2%) 1 (2%) 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Thymus (37) (47) (45) (41) 

Thymoma benign 1 (2%) 

Thymoma malignant 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

134 1-Chloro-2-propanol, NTP TR 477 

TABLE C1 

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Integumentary System 

Skin 

Subcutaneous tissue, fibrous histiocytoma

Subcutaneous tissue, hemangioma

Subcutaneous tissue, hemangiosarcoma

(50) 

 1 (2%) 

 1 (2%) 

 1 (2%) 

(50) 

 1 (2%) 

(50) (50) 

Musculoskeletal System 

Bone 

Osteosarcoma

Skeletal muscle

Hemangiosarcoma

Sarcoma

(50) 

 1 (2%) 

(50) 

(1)

 1 (100%) 

(50) (50) 

(1) 

 1 (100%) 

Nervous System 

None 

Respiratory System 

Lung (50) (50) (50) (50) 

Alveolar/bronchiolar adenoma 11 (22%) 5 (10%) 4 (8%) 4 (8%) 

Alveolar/bronchiolar adenoma, multiple 1 (2%) 3 (6%) 1 (2%) 

Alveolar/bronchiolar carcinoma 4 (8%) 2 (4%) 4 (8%) 4 (8%) 

Alveolar/bronchiolar carcinoma, multiple 1 (2%) 1 (2%) 

Carcinoma, metastatic, harderian gland 1 (2%) 

Fibrous histiocytoma 1 (2%) 

Hepatoblastoma, metastatic, liver 1 (2%) 1 (2%) 

Hepatocellular carcinoma, metastatic, liver 6 (12%) 2 (4%) 1 (2%) 2 (4%) 

Histiocytic sarcoma 1 (2%) 

Nose (50) (50) (50) (50) 

Carcinoma, metastatic, harderian gland 1 (2%) 1 (2%) 

Hemangiosarcoma 1 (2%) 

Special Senses System 

Harderian gland (1) (5) (3) (1) 

Adenoma 1 (100%) 4 (80%) 2 (67%) 1 (100%) 

Carcinoma 1 (100%) 1 (20%) 1 (33%) 

Urinary System 

Kidney (50) (50) (50) (50) 

Renal tubule, adenoma 1 (2%) 

Urinary bladder (50) (50) (49) (50) 

Fibrous histiocytoma, metastatic, uncertain

 primary site 1 (2%) 

Hemangioma 1 (2%) 

Systemic Lesions 

Multiple organsb (50) (50) (50) (50) 

Histiocytic sarcoma 2 (4%) 1 (2%) 

Lymphoma malignant 1 (2%) 1 (2%) 4 (8%) 
135 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE C1 

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Neoplasm Summary 

Total animals with primary neoplasmsc 48 44 40 42 

Total primary neoplasms 90 80 65 75 

Total animals with benign neoplasms 41 39 36 34 

Total benign neoplasms 53 52 47 43 

Total animals with malignant neoplasms 32 17 15 24 

Total malignant neoplasms 37 28 18 32 

Total animals with metastatic neoplasms 8 4 2 3 

Total metastatic neoplasms 8 7 4 3 

Total animals with malignant neoplasms

 of uncertain primary site 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 

Primary neoplasms: all neoplasms except metastatic neoplasms 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

136 1-Chloro-2-propanol, NTP TR 477 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

2 3 4 5 5 5 5 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 8 6 0 1 4 7 4 0 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

0 0 4 1 8 7 8 6 8 4 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

Carcass ID Number 0 2 2 3 4 4 2 1 4 4 0 0 0 0 0 0 1 1 1 1 1 1 1 1 2 

3 5 4 4 1 9 3 6 5 4 1 4 5 7 8 9 0 1 2 3 4 7 8 9 0 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 

Gallbladder + + + + A + + + + + + + + + + M + + + + + + + + M 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 

Fibrous histiocytoma, metastatic, skin 

Intestine large, cecum + + + + + + A + + + + + + + + + + + + + + + + + + 

Intestine small, duodenum + + + + A + + + + + + + + + + + + + + + + + + + + 

Intestine small, jejunum + + + + + + A + + + + + + + + + + + + + + + + + + 

Intestine small, ileum + + + + + + A + + + + + + + + + + + + + + + + + + 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 

Hemangiosarcoma X X 

Hemangiosarcoma, multiple X 

Hepatoblastoma X X 

Hepatocellular carcinoma X X X X 

Hepatocellular carcinoma, multiple 

Hepatocellular adenoma X X X X X 

Hepatocellular adenoma, multiple X X X X X X X X X X 

Histiocytic sarcoma 

Mesentery + + 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 

Stomach, forestomach + + + + A + + + + + + + + + + + + + + + + + + + + 

Squamous cell papilloma X 

Stomach, glandular + + + + A + + + + + + + + + + + + + + + + + + + + 

Tooth + 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

C-cell, carcinoma 

Follicular cell, adenoma X 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 

Hemangiosarcoma X 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 

+: Tissue examined microscopically M: Missing tissue X: Lesion present 

A: Autolysis precludes examination I: Insufficient tissue Blank: Not examined 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 137 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 

9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 0 0 0 0 0 0 0 0 0 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Total 

Carcass ID Number 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 0 0 1 2 2 3 3 4 5 Tissues/ 

1 2 7 9 0 1 2 3 5 8 9 0 2 3 6 7 2 6 5 6 8 6 7 8 0 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder + M + + + + + + + + + + + + + + + + + + M + + + + 45 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Fibrous histiocytoma, metastatic, skin X 1 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma 2 

Hemangiosarcoma, multiple 1 

Hepatoblastoma X X X X 6 

Hepatocellular carcinoma X X X X X X X X 12 

Hepatocellular carcinoma, multiple X 1 

Hepatocellular adenoma X X 7 

Hepatocellular adenoma, multiple X X X X X X X X X X X X X X X X X X 28 

Histiocytic sarcoma X X 2 

Mesentery + + 4 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Squamous cell papilloma 1 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Tooth + + + 4 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Parathyroid gland + + + + + + + + + + M + M + + + + + + + + + + + + 48 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, carcinoma X 1 

Follicular cell, adenoma 1 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma X 1 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma 1 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 

50 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

138 1-Chloro-2-propanol, NTP TR 477 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

2 3 4 5 5 5 5 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 

0 

8 

0 

6 

4 

0 

1 

1 

8 

4 

7 

7 

8 

4 

6 

0 

8 

1 

4 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

Carcass ID Number 0 2 2 3 4 4 2 1 4 4 0 0 0 0 0 0 1 1 1 1 1 1 1 1 2 

3 5 4 4 1 9 3 6 5 4 1 4 5 7 8 9 0 1 2 3 4 7 8 9 0 

Hematopoietic System 

Bone marrow 

Hemangiosarcoma 

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Histiocytic sarcoma 

Spleen 

Histiocytic sarcoma 

Thymus 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + M + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + M + + + + + + + + M + + + + + M + + + + M 

Integumentary System 

Mammary gland 

Skin 

Subcutaneous tissue, fibrous histiocytoma 

Subcutaneous tissue, hemangioma 

Subcutaneous tissue, hemangiosarcoma 

M M M M M M M M M M M M M M M M M M M M M M M M M 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Musculoskeletal System 

Bone 

Osteosarcoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

Nervous System 

Brain 

Spinal cord 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar adenoma, multiple 

Alveolar/bronchiolar carcinoma 

Hepatocellular carcinoma, metastatic, liver 

Nose 

Carcinoma, metastatic, harderian gland 

Hemangiosarcoma 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X 

X 

X 

X X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Ear 

Harderian gland 

Adenoma 

Carcinoma 

+ 

+ 

X 

X 

Urinary System 

Kidney 

Urethra 

Urinary bladder 

Hemangioma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Lymphoma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 139 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Total 

Carcass ID Number 2 

1 

2 

2 

2 

7 

2 

9 

3 

0 

3 

1 

3 

2 

3 

3 

3 

5 

3 

8 

3 

9 

4 

0 

4 

2 

4 

3 

4 

6 

4 

7 

0 

2 

0 

6 

1 

5 

2 

6 

2 

8 

3 

6 

3 

7 

4 

8 

5 

0 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Histiocytic sarcoma 

Spleen 

Histiocytic sarcoma 

Thymus 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

M 

+ 

+ 

+ 

M 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

M 

+ 

+ 

+ 

M 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

M 

+ 

+ 

X

+ 

X

M 

+ 

+ 

+ 

M 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

M 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

M 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

1 

4 

50 

49 

1 

50 

1 

37 

Integumentary System 

Mammary gland 

Skin 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

+ 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

+ 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

M 

+ 

M

+ 

2 

50 

Subcutaneous tissue, fibrous histiocytoma 

Subcutaneous tissue, hemangioma 

Subcutaneous tissue, hemangiosarcoma 

X 

X

X

1 

1 

1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Osteosarcoma 1 

Nervous System 

Brain + 

Spinal cord

Respiratory System 

Lung + 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar adenoma, multiple 

Alveolar/bronchiolar carcinoma 

Hepatocellular carcinoma, metastatic, liver 

Nose + 

Carcinoma, metastatic, harderian gland 

Hemangiosarcoma

Trachea + 

Special Senses System 

Ear

Harderian gland

Adenoma

Carcinoma

+ 

+ 

X 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

X

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 50 

1 

+ 50 

11 

1 

4 

X 6 

+ 50 

1 

1 

+ 50 

1 

1 

1 

1 

Urinary System 

Kidney + 

Urethra

Urinary bladder + 

Hemangioma 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 50 

1 

+ 50 

1 

Systemic Lesions 

Multiple organs + 

Histiocytic sarcoma 

Lymphoma malignant 

+ + + + 

X

+ + + + + + 

X 

+ + + + + + + + 

X

+ + + + + + 50 

2 

1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

140 1-Chloro-2-propanol, NTP TR 477 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

Number of Days on Study 

3 4 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

3 7 4 6 0 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

5 1 5 5 0 0 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

Carcass ID Number 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

7 6 9 5 8 8 5 5 5 5 5 6 6 6 6 6 7 7 7 7 7 7 7 8 8 

4 9 5 7 3 9 4 5 6 8 9 0 2 3 5 6 0 1 2 3 6 7 8 0 2 

Alimentary System 

Esophagus 

Gallbladder 

Adenoma 

Intestine large, colon 

Intestine large, rectum 

Fibrous histiocytoma, metastatic,

 uncertain primary site 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Fibrous histiocytoma 

Hepatoblastoma 

Hepatoblastoma, multiple 

Hepatocellular carcinoma 

Hepatocellular adenoma 

Hepatocellular adenoma, multiple 

Histiocytic sarcoma 

Mesentery 

Pancreas 

Fibrous histiocytoma, metastatic,

 uncertain primary site 

Salivary glands 

Stomach, forestomach 

Stomach, glandular 

Tooth 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

M A + A A + M + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ A + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + A + + + + + + + + + + + + + + + + + + + + 

+ + A + A + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X 

X X X 

X X X X X X X 

X X X X X X X X X X 

X 

+ + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ 

Cardiovascular System 

Heart 

Fibrous histiocytoma, metastatic,

 uncertain primary site 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Capsule, adenoma 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 

Parathyroid gland + + + + + + + + + + + + + M + + + + + + + + + + + 

Pituitary gland + + + + + + + + + + + + + + + + + + + + M + + + + 

Pars distalis, adenoma X 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Follicular cell, adenoma X 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 141 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

9 9 9 9 9 9 9 9 9 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Total 

Carcass ID Number 8 8 8 9 9 9 9 9 9 9 5 5 5 6 6 6 6 7 7 8 8 8 9 9 0 Tissues/ 

4 5 7 0 1 2 3 7 8 9 1 2 3 1 4 7 8 5 9 1 6 8 4 6 0 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder + + + + + + + + + + + + + + + + + + + + + + + + + 45 

Adenoma X 1 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Fibrous histiocytoma, metastatic,

 uncertain primary site X 1 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Fibrous histiocytoma X 1 

Hepatoblastoma X 2 

Hepatoblastoma, multiple 1 

Hepatocellular carcinoma X X X 6 

Hepatocellular adenoma X X X X X X 13 

Hepatocellular adenoma, multiple X X X X X X X X X X X X 22 

Histiocytic sarcoma 1 

Mesentery 2 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Fibrous histiocytoma, metastatic,

 uncertain primary site X 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Tooth + + 3 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Fibrous histiocytoma, metastatic,

 uncertain primary site X 1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Capsule, adenoma X 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pars distalis, adenoma 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Follicular cell, adenoma 1 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

142 1-Chloro-2-propanol, NTP TR 477 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

3 4 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 7 4 6 0 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

5 1 5 5 0 0 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

Carcass ID Number 7 6 9 5 8 8 5 5 5 5 5 6 6 6 6 6 7 7 7 7 7 7 7 8 8 

4 9 5 7 3 9 4 5 6 8 9 0 2 3 5 6 0 1 2 3 6 7 8 0 2 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 

Lymph node + + + 

Fibrous histiocytoma 

Iliac, fibrous histiocytoma 

Mediastinal, fibrous histiocytoma 

Pancreatic, fibrous histiocytoma 

Renal, fibrous histiocytoma 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 

Fibrous histiocytoma 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 

Fibrous histiocytoma 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 

Fibrous histiocytoma 

Hemangiosarcoma 

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 

Thymoma benign X 

Integumentary System 

Mammary gland M M M M M M M M M M M M M + M M M M M M M M M M M 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 

Subcutaneous tissue, hemangiosarcoma X 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 

Skeletal muscle 

Hemangiosarcoma 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 

Alveolar/bronchiolar adenoma X X X 

Alveolar/bronchiolar adenoma, multiple X X X 

Alveolar/bronchiolar carcinoma X X 

Alveolar/bronchiolar carcinoma, multiple 

Fibrous histiocytoma 

Hepatoblastoma, metastatic, liver X 

Hepatocellular carcinoma, metastatic, liver X 

Histiocytic sarcoma X 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Harderian gland 

Adenoma 

Carcinoma 

+ 

X 
 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 143 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

2 

9 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

3 

0 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Total 

Carcass ID Number 8 

4 

8 

5 

8 

7 

9 

0 

9 

1 

9 

2 

9 

3 

9 

7 

9 

8 

9 

9 

5 

1 

5 

2 

5 

3 

6 

1 

6 

4 

6 

7 

6 

8 

7 

5 

7 

9 

8 

1 

8 

6 

8 

8 

9 

4 

9 

6 

0 

0 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node 

Fibrous histiocytoma 

Iliac, fibrous histiocytoma 

Mediastinal, fibrous histiocytoma 

Pancreatic, fibrous histiocytoma 

Renal, fibrous histiocytoma 

Lymph node, mandibular 

Fibrous histiocytoma 

Lymph node, mesenteric 

Fibrous histiocytoma 

Spleen 

Fibrous histiocytoma 

Hemangiosarcoma 

Thymus 

Thymoma benign

+ +

X

X

X

X

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

X

+ + + + + + + + + M + + M M + + + + + + + + + + + 

5 

1 

1 

1 

1 

1 

50 

1 

50 

1 

50 

1 

1 

47 

1 

Integumentary System 

Mammary gland 

Skin 

M M M M + M M M M M + M M + M M M M M M M M M + M

+ + + + + + + + + + + + + + + + + + + + + + + + + 

5 

50 

Subcutaneous tissue, hemangiosarcoma 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Skeletal muscle + 1 

Hemangiosarcoma X 1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar adenoma, multiple 

Alveolar/bronchiolar carcinoma

Alveolar/bronchiolar carcinoma, multiple 

Fibrous histiocytoma 

Hepatoblastoma, metastatic, liver

Hepatocellular carcinoma, metastatic, liver 

Histiocytic sarcoma

Nose 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X

X 

X

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

5 

3 

2 

1 

1 

1 

2 

1 

50 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Harderian gland 

Adenoma 

+ 

X 

+ 

X 

+ +

X

 5 

4 

Carcinoma X 1 
 

 

 

144 1-Chloro-2-propanol, NTP TR 477 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

3 4 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 7 4 6 0 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

5 1 5 5 0 0 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

Carcass ID Number 7 6 9 5 8 8 5 5 5 5 5 6 6 6 6 6 7 7 7 7 7 7 7 8 8 

4 9 5 7 3 9 4 5 6 8 9 0 2 3 5 6 0 1 2 3 6 7 8 0 2 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 

Fibrous histiocytoma, metastatic,

 uncertain primary site 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Lymphoma malignant X 
 

 

 

1-Chloro-2-propanol, NTP TR 477 145 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

9 9 9 9 9 9 9 9 9 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Total 

Carcass ID Number 8 8 8 9 9 9 9 9 9 9 5 5 5 6 6 6 6 7 7 8 8 8 9 9 0 Tissues/ 

4 5 7 0 1 2 3 7 8 9 1 2 3 1 4 7 8 5 9 1 6 8 4 6 0 Tumors 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Fibrous histiocytoma, metastatic,

 uncertain primary site X 1 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Lymphoma malignant 1 
 

 

 

 

 

 

 

 

 

 

146 1-Chloro-2-propanol, NTP TR 477 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

500 ppm 

Number of Days on Study 

0 0 1 1 3 4 4 4 4 5 5 5 6 6 6 6 6 6 6 7 7 7 7 7 7 

7 9 8 8 7 0 5 5 8 1 1 1 0 0 0 2 3 3 4 0 1 2 2 2 2 

9 2 0 9 7 8 8 8 4 1 9 9 2 7 8 5 7 8 5 0 4 9 9 9 9 

Carcass ID Number 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

0 4 4 4 3 1 0 2 2 3 3 3 4 0 1 0 4 0 3 5 2 0 0 0 0 

2 3 5 0 7 6 3 2 6 8 1 9 7 5 0 4 1 7 2 0 1 1 6 8 9 

Alimentary System 

Esophagus 

Gallbladder 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Hemangiosarcoma 

Hemangiosarcoma, multiple 

Hepatocellular carcinoma 

Hepatocellular carcinoma, multiple 

Hepatocellular adenoma 

Hepatocellular adenoma, multiple 

Mesentery 

Pancreas 

Salivary glands 

Stomach, forestomach 

Squamous cell papilloma 

Stomach, glandular 

Mast cell tumor benign 

Tooth 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

M + + + + A + + + + M + + A + A + + M A + + + + + 

+ + + + + + + + + + + + + + + + + + + A + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + A + + + + + A + + + + + 

+ + + + A + + + + + + + + A + + + + + A + + + + + 

A + + + A A + + + + + + + A + A + + + A + + + + + 

+ A + + + + + A + + + + + A + A + + + A + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X 

X X X X 

X 

X X X X X X X X X 

X X X X X 

+ 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + A + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Hemangiosarcoma X 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Capsule, adenoma 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 

Parathyroid gland + + + M + + + + + + + M + + + + + + + + + + + + + 

Pituitary gland + + + + + + + + + + + + + + + + + + + M + + + + + 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Follicular cell, adenoma 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + +
 

Penis +
 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + +
 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + +
 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + +
 

Testes + + + + + + + + + + + + + + + + + + + + + + + + +
 

Interstitial cell, adenoma 
 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 147 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

500 ppm 

Number of Days on Study 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

3 

0 

Carcass ID Number 

1 

1 

1 

1 

1 

2 

1 

1 

3 

1 

1 

4 

1 

1 

5 

1 

1 

7 

1 

1 

8 

1 

1 

9 

1 

2 

0 

1 

2 

3 

1 

2 

4 

1 

2 

5 

1 

2 

7 

1 

2 

8 

1 

2 

9 

1 

3 

0 

1 

3 

3 

1 

3 

4 

1 

3 

5 

1 

3 

6 

1 

4 

2 

1 

4 

4 

1 

4 

6 

1 

4 

8 

1 

4 

9 

Total 

Tissues/ 

Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder + + + + + + + + + + + + + + + + + + + M + + + + + 42 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 44 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 45 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma 1 

Hemangiosarcoma, multiple 1 

Hepatocellular carcinoma X 5 

Hepatocellular carcinoma, multiple 1 

Hepatocellular adenoma X X X X X X X X X X X X 21 

Hepatocellular adenoma, multiple X X X X X X X X 13 

Mesentery + + + + + 6 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Squamous cell papilloma X 1 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Mast cell tumor benign X 1 

Tooth + + + + 4 

Cardiovascular System 

Heart 

Hemangiosarcoma

Endocrine System 

Adrenal cortex 

Capsule, adenoma 

Adrenal medulla 

Islets, pancreatic 

Parathyroid gland 

Pituitary gland 

Thyroid gland 

Follicular cell, adenoma 

General Body System 

None 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + M + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

50 

1 

50 

2 

50 

50 

47 

49 

50 

1 

Genital System 

Epididymis 

Penis 

Preputial gland 

Prostate 

Seminal vesicle 

Testes 

Interstitial cell, adenoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + M + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X

50 

2 

50 

49 

50 

50 

2 
 

 

 

 

 

 

 

 

 

 

 

148 1-Chloro-2-propanol, NTP TR 477 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

500 ppm 

Number of Days on Study 

0 

7 

9 

0 

9 

2 

1 

8 

0 

1 

8 

9 

3 

7 

7 

4 

0 

8 

4 

5 

8 

4 

5 

8 

4 

8 

4 

5 

1 

1 

5 

1 

9 

5 

1 

9 

6 

0 

2 

6 

0 

7 

6 

0 

8 

6 

2 

5 

6 

3 

7 

6 

3 

8 

6 

4 

5 

7 

0 

0 

7 

1 

4 

7 

2 

9 

7 

2 

9 

7 

2 

9 

7 

2 

9 

Carcass ID Number 

1 

0 

2 

1 

4 

3 

1 

4 

5 

1 

4 

0 

1 

3 

7 

1 

1 

6 

1 

0 

3 

1 

2 

2 

1 

2 

6 

1 

3 

8 

1 

3 

1 

1 

3 

9 

1 

4 

7 

1 

0 

5 

1 

1 

0 

1 

0 

4 

1 

4 

1 

1 

0 

7 

1 

3 

2 

1 

5 

0 

1 

2 

1 

1 

0 

1 

1 

0 

6 

1 

0 

8 

1 

0 

9 

Hematopoietic System 

Bone marrow 

Hemangiosarcoma 

Lymph node 

Lymph node, mandibular 

Carcinoma, metastatic, harderian gland 

Lymph node, mesenteric 

Hemangiosarcoma 

Spleen 

Hemangiosarcoma 

Thymus 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + M + M + + + + 

Integumentary System 

Mammary gland 

Skin 

M M M M M M M M + M M + M M M M M M M M M M M M M 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar carcinoma 

Alveolar/bronchiolar carcinoma, multiple 

Carcinoma, metastatic, harderian gland 

Hepatocellular carcinoma, metastatic, liver 

Nose 

Carcinoma, metastatic, harderian gland 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X 

X X 

X 

X 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Harderian gland 

Adenoma 

Carcinoma 

+ 

X 

Urinary System 

Kidney 

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + A + + + + + + + + + + + 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 
 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 149 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

500 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 

9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 0 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 3 3 3 3 3 4 4 4 4 4 Tissues/ 

1 2 3 4 5 7 8 9 0 3 4 5 7 8 9 0 3 4 5 6 2 4 6 8 9 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma 1 

Lymph node + + 2 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, harderian gland 1 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma X 1 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma 1 

Thymus M + + + + + M M + + + + + + + + + + + + + + + + + 45 

Integumentary System 

Mammary gland M M M M M M M M + M M M M M M M M M M M M M M M M 3 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar adenoma X X 4 

Alveolar/bronchiolar carcinoma X X 4 

Alveolar/bronchiolar carcinoma, multiple 1 

Carcinoma, metastatic, harderian gland 1 

Hepatocellular carcinoma, metastatic, liver 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, harderian gland 1 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Harderian gland + + 3 

Adenoma X X 2 

Carcinoma 1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 

50 

50 

50 
 

 

 

 

 

 

 

 

 

 

 

150 1-Chloro-2-propanol, NTP TR 477 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 1,000 ppm 

2 2 4 5 5 5 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 3 4 4 4 5 6 1 4 5 5 0 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

3 6 3 3 6 8 7 5 2 7 0 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

Carcass ID Number 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

5 8 9 6 7 7 8 5 8 9 5 5 5 5 5 5 5 6 6 6 6 6 6 6 7 

2 0 0 3 7 2 3 3 6 1 6 1 4 5 7 8 9 0 1 2 4 5 6 8 1 

Alimentary System 

Esophagus 

Gallbladder 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Hemangiosarcoma 

Hepatoblastoma 

Hepatocellular carcinoma 

Hepatocellular carcinoma, multiple 

Hepatocellular adenoma 

Hepatocellular adenoma, multiple 

Mesentery 

Oral mucosa 

Pancreas 

Fibrous histiocytoma 

Salivary glands 

Stomach, forestomach 

Squamous cell papilloma 

Stomach, glandular 

Tooth 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

A + M + + + + + + A + + + + + + + + + + + + + + + 

+ + + + + + + + + A + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

A + + + A + + + + A + + + + + + + + + + + + + + + 

+ A + + A + + + + A + + + + + + + + + + + + + + + 

A + + + A + + + + A + + + + + + + + + + + + + + + 

A + + + A + + + + A + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X X X X X 

X X X X X 

X X X X X 

X X X X X X X 

+ + + + + + + 

+ 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

A + + + + + + + + + + + + + + + + + + + + + + + + 

+ + 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Hemangiosarcoma 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma X 

Capsule, adenoma X 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma X 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Pituitary gland M + + + + + + + + + + + + + + + + + + + + + + + + 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Follicular cell, adenoma 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 
 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 151 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 1,000 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 

9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 0 0 0 0 0 0 0 0 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 7 7 7 7 7 8 8 8 8 8 8 9 9 9 9 9 0 6 6 7 7 8 9 9 9 Tissues/ 

3 5 6 8 9 1 2 4 7 8 9 3 4 7 8 9 0 7 9 0 4 5 2 5 6 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma X 2 

Hepatoblastoma X 6 

Hepatocellular carcinoma X X 7 

Hepatocellular carcinoma, multiple X 1 

Hepatocellular adenoma X X X X X X 11 

Hepatocellular adenoma, multiple X X X X X X X X X X X X 19 

Mesentery + 8 

Oral mucosa 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Fibrous histiocytoma X 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Squamous cell papilloma X 1 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Tooth + + + + + 7 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma X 1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma 1 

Capsule, adenoma 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 2 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pituitary gland + + + + + + M + + + M + + + + + + + + + + + + + + 47 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Follicular cell, adenoma X 1 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 
 

 

 

 

 

 

 

 

 

 

152 1-Chloro-2-propanol, NTP TR 477 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 1,000 ppm 

2 2 4 5 5 5 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 3 4 4 4 5 6 1 4 5 5 0 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

3 6 3 3 6 8 7 5 2 7 0 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

Carcass ID Number 5 8 9 6 7 7 8 5 8 9 5 5 5 5 5 5 5 6 6 6 6 6 6 6 7 

2 0 0 3 7 2 3 3 6 1 6 1 4 5 7 8 9 0 1 2 4 5 6 8 1 

Hematopoietic System 

Bone marrow 

Hemangiosarcoma 

Lymph node 

Renal, fibrous histiocytoma 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Fibrous histiocytoma 

Hemangiosarcoma 

Thymus 

Thymoma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + M + M + + M M + + + M + + + + + M + + 

Integumentary System 

Mammary gland 

Skin 

M M M M M M M M M M M M M M M M M M M M M M M M M 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Musculoskeletal System 

Bone 

Skeletal muscle 

Sarcoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar adenoma, multiple 

Alveolar/bronchiolar carcinoma 

Hepatoblastoma, metastatic, liver 

Hepatocellular carcinoma, metastatic, liver 

Nose 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X 

X 

X X X 

X 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Ear 

Harderian gland 

Adenoma 

+ 

+ 

X 

Urinary System 

Kidney 

Renal tubule, adenoma 

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Systemic Lesions 

Multiple organs 

Lymphoma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X 
 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 153 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 1,000 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 

9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 0 0 0 0 0 0 0 0 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 7 7 7 7 7 8 8 8 8 8 8 9 9 9 9 9 0 6 6 7 7 8 9 9 9 Tissues/ 

3 5 6 8 9 1 2 4 7 8 9 3 4 7 8 9 0 7 9 0 4 5 2 5 6 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma X 1 

Lymph node + + 3 

Renal, fibrous histiocytoma X 1 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Fibrous histiocytoma X 1 

Hemangiosarcoma X 1 

Thymus + + + + + + M + + M + + + + + + + + M + + + + + + 41 

Thymoma malignant X 1 

Integumentary System 

Mammary gland M + M M M M M M M M M M M M M M M M M M M M M M M 1 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Skeletal muscle + 1 

Sarcoma X 1 

Nervous System 

Brain	 + + + + + + + + + + + + + + + + + + + + + + + + + 

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar adenoma X 4 

Alveolar/bronchiolar adenoma, multiple 1 

Alveolar/bronchiolar carcinoma X 4 

Hepatoblastoma, metastatic, liver 1 

Hepatocellular carcinoma, metastatic, liver X 2 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Ear

Harderian gland

Adenoma

 1 

1 

1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Renal tubule, adenoma X 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymphoma malignant X X 4 

50 
154 1-Chloro-2-propanol, NTP TR 477 

TABLE C3 

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Harderian Gland: Adenoma 

Overall ratea 

Adjusted rateb 

Terminal ratec 

1/50 (2%) 

2.2% 

1/40 (3%) 

4/50 (8%) 

8.4% 

4/44 (9%) 

2/50 (4%) 

5.3% 

2/29 (7%) 

1/50 (2%) 

2.3% 

1/39 (3%) 

First incidence (days) 

Poly-3 testd 729 (T) 

Pù0.428N 

729 (T) 

Pù0.211 

729 (T) 

Pù0.494 

729 (T) 

Pù0.786 

Harderian Gland: Adenoma or Carcinoma 

Overall rate 1/50 (2%) 5/50 (10%) 3/50 (6%) 1/50 (2%) 

Adjusted rate 2.2% 10.5% 7.9% 2.3% 

Terminal rate 1/40 (3%) 5/44 (11%) 2/29 (7%) 1/39 (3%) 

First incidence (days) 

Poly-3 test 

729 (T) 

Pù0.393N 

729 (T) 

Pù0.125 

608 

Pù0.288 

729 (T) 

Pù0.786 

Liver: Hemangiosarcoma 

Overall rate 3/50 (6%) 0/50 (0%) 2/50 (4%) 2/50 (4%) 

Adjusted rate 6.6% 0.0% 5.3% 4.5% 

Terminal rate 

First incidence (days) 

Poly-3 test 

2/40 (5%) 

501 

Pù0.613 

0/44 (0%) 

—e 

Pù0.119N 

1/29 (3%) 

602 

Pù0.620N 

2/39 (5%) 

729 (T) 

Pù0.532N 

Liver: Hepatocellular Adenoma 

Overall rate 35/50 (70%) 35/50 (70%) 34/50 (68%) 30/50 (60%) 

Adjusted rate 76.0% 72.9% 79.6% 65.1% 

Terminal rate 32/40 (80%) 33/44 (75%) 23/29 (79%) 25/39 (64%) 

First incidence (days) 

Poly-3 test 

464 

Pù0.151N 

645 

Pù0.460N 

377 

Pù0.451 

556 

Pù0.176N 

Liver: Hepatocellular Carcinoma 

Overall rate 13/50 (26%) 6/50 (12%) 6/50 (12%) 8/50 (16%) 

Adjusted rate 29.0% 12.2% 15.0% 17.7% 

Terminal rate 12/40 (30%) 4/44 (9%) 1/29 (3%) 4/39 (10%) 

First incidence (days) 

Poly-3 test 

646 

Pù0.228N 

335 

Pù0.038N 

458 

Pù0.109N 

617 

Pù0.159N 

Liver: Hepatocellular Adenoma or Carcinoma 

Overall rate 39/50 (78%) 38/50 (76%) 37/50 (74%) 32/50 (64%) 

Adjusted rate 84.2% 76.5% 83.8% 69.0% 

Terminal rate 35/40 (88%) 34/44 (77%) 23/29 (79%) 26/39 (67%) 

First incidence (days) 

Poly-3 test 

464 

Pù0.068N 

335 

Pù0.247N 

377 

Pù0.608N 

556 

Pù0.064N 

Liver: Hepatoblastoma 

Overall rate 6/50 (12%) 3/50 (6%) 0/50 (0%) 6/50 (12%) 

Adjusted rate 13.1% 6.3% 0.0% 13.3% 

Terminal rate 4/40 (10%) 3/44 (7%) 0/29 (0%) 4/39 (10%) 

First incidence (days) 

Poly-3 test 

518 

Pù0.483 

729 (T) 

Pù0.231N 

— 

Pù0.037N 

568 

Pù0.621 

Liver: Hepatocellular Carcinoma or Hepatoblastoma 

Overall rate 18/50 (36%) 9/50 (18%) 6/50 (12%) 13/50 (26%) 

Adjusted rate 39.0% 18.3% 15.0% 28.4% 

Terminal rate 15/40 (38%) 7/44 (16%) 1/29 (3%) 8/39 (21%) 

First incidence (days) 

Poly-3 test 

518 

Pù0.280N 

335 

Pù0.020N 

458 

Pù0.012N 

568 

Pù0.199N 
1-Chloro-2-propanol, NTP TR 477 155 

TABLE C3 

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Liver: Hepatocellular Adenoma, Hepatocellular Carcinoma, or Hepatoblastoma 

Overall rate 40/50 (80%) 39/50 (78%) 37/50 (74%) 36/50 (72%)
 

Adjusted rate 85.3% 78.6% 83.8% 77.6%
 

Terminal rate 35/40 (88%) 35/44 (80%) 23/29 (79%) 30/39 (77%)
 

First incidence (days) 464 335 377 556
 

Poly-3 test Pù0.271N Pù0.277N Pù0.549N Pù0.245N
 

Lung: Alveolar/bronchiolar Adenoma 

Overall rate 12/50 (24%) 8/50 (16%) 4/50 (8%) 5/50 (10%)
 

Adjusted rate 26.3% 16.8% 10.5% 11.2%
 

Terminal rate 10/40 (25%) 8/44 (18%) 3/29 (10%) 4/39 (10%)
 

First incidence (days) 220 729 (T) 511 568
 

Poly-3 test Pù0.040N Pù0.199N Pù0.067N Pù0.059N
 

Lung: Alveolar/bronchiolar Carcinoma 

Overall rate 4/50 (8%) 3/50 (6%) 5/50 (10%) 4/50 (8%) 

Adjusted rate 9.0% 6.3% 13.0% 8.9% 

Terminal rate 4/40 (10%) 2/44 (5%) 2/29 (7%) 3/39 (8%) 

First incidence (days) 729 (T) 710 519 543 

Poly-3 test Pù0.487 Pù0.477N Pù0.438 Pù0.656N 

Lung: Alveolar/bronchiolar Adenoma or Carcinoma 

Overall rate 16/50 (32%) 11/50 (22%) 9/50 (18%) 9/50 (18%)
 

Adjusted rate 35.1% 23.1% 23.0% 19.8%
 

Terminal rate 14/40 (35%) 10/44 (23%) 5/29 (17%) 7/39 (18%)
 

First incidence (days) 220 710 511 543
 

Poly-3 test Pù0.087N Pù0.150N Pù0.177N Pù0.084N
 

All Organs: Hemangiosarcoma 

Overall rate 5/50 (10%) 3/50 (6%) 4/50 (8%) 4/50 (8%) 

Adjusted rate 11.0% 6.3% 10.6% 9.0% 

Terminal rate 3/40 (8%) 3/44 (7%) 3/29 (10%) 4/39 (10%) 

First incidence (days) 501 729 (T) 602 729 (T) 

Poly-3 test Pù0.548N Pù0.340N Pù0.641N Pù0.531N 

All Organs: Hemangioma or Hemangiosarcoma 

Overall rate 7/50 (14%) 3/50 (6%) 4/50 (8%) 4/50 (8%) 

Adjusted rate 15.4% 6.3% 10.6% 9.0% 

Terminal rate 5/40 (13%) 3/44 (7%) 3/29 (10%) 4/39 (10%) 

First incidence (days) 501 729 (T) 602 729 (T) 

Poly-3 test Pù0.324N Pù0.144N Pù0.400N Pù0.287N 

All Organs: Malignant Lymphoma 

Overall rate 1/50 (2%) 1/50 (2%) 0/50 (0%) 4/50 (8%) 

Adjusted rate 2.2% 2.1% 0.0% 9.0% 

Terminal rate 1/40 (3%) 1/44 (2%) 0/29 (0%) 3/39 (8%) 

First incidence (days) 729 (T) 729 (T) — 617 

Poly-3 test Pù0.057 Pù0.765N Pù0.627N Pù0.194 

All Organs: Benign Neoplasms 

Overall rate 41/50 (82%) 39/50 (78%) 36/50 (72%) 34/50 (68%)
 

Adjusted rate 87.1% 81.2% 84.3% 72.3%
 

Terminal rate 36/40 (90%) 37/44 (84%) 25/29 (86%) 27/39 (69%)
 

First incidence (days) 220 645 377 543
 

Poly-3 test Pù0.044N Pù0.307N Pù0.485N Pù0.058N
 
156 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE C3 

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

All Organs: Malignant Neoplasms 

Overall rate 32/50 (64%) 17/50 (34%) 15/50 (30%) 24/50 (48%) 

Adjusted rate 66.9% 34.3% 36.2% 51.7% 

Terminal rate 26/40 (65%) 13/44 (30%) 6/29 (21%) 18/39 (46%) 

First incidence (days) 

Poly-3 test 

220 

Pù0.237N 

335 

P<0.001N 

458 

Pù0.003N 

543 

Pù0.098N 

All Organs: Benign or Malignant Neoplasms 

Overall rate 48/50 (96%) 44/50 (88%) 40/50 (80%) 42/50 (84%) 

Adjusted rate 98.7% 88.2% 89.9% 88.8% 

Terminal rate 40/40 (100%) 39/44 (89%) 25/29 (86%) 34/39 (87%) 

First incidence (days) 

Poly-3 test 

220 

Pù0.106N 

335 

Pù0.039N 

377 

Pù0.068N 

543 

Pù0.048N 

(T)Terminal sacrifice 

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for liver and lung; for 

other tissues, denominator is number of animals necropsied. b	 Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality 

Observed incidence at terminal kill 

d	 Beneath the 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 controls and that exposed group. The Poly-3 test accounts for 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 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 157 

TABLE C4 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Accidental deaths 5 3 

Moribund 8 7 4 

Natural deaths 2 6 9 4 

Survivors 

Terminal sacrifice 40 44 29 39 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Intestine large, colon (50) (50) (49) (49) 

Serosa, inflammation, chronic 1 (2%) 

Intestine large, cecum (49) (50) (48) (47) 

Serosa, inflammation, chronic 1 (2%) 

Intestine small, jejunum (49) (49) (44) (47) 

Diverticulum 1 (2%) 

Liver (50) (50) (50) (50) 

Angiectasis 1 (2%) 1 (2%) 

Clear cell focus 2 (4%) 11 (22%) 6 (12%) 3 (6%) 

Eosinophilic focus 27 (54%) 34 (68%) 33 (66%) 29 (58%) 

Erythrophagocytosis 1 (2%) 

Inflammation, chronic 2 (4%) 1 (2%) 1 (2%) 

Mixed cell focus 2 (4%) 5 (10%) 1 (2%) 3 (6%) 

Necrosis 6 (12%) 3 (6%) 1 (2%) 3 (6%) 

Vacuolization cytoplasmic 1 (2%) 2 (4%) 

Hepatocyte, centrilobular, vacuolization

 cytoplasmic 1 (2%) 

Mesentery (4) (2) (6) (8) 

Fat, necrosis 4 (100%) 2 (100%) 6 (100%) 8 (100%) 

Pancreas (50) (50) (50) (50) 

Hemorrhage 1 (2%) 

Inflammation, chronic 1 (2%) 

Acinus, atrophy 3 (6%) 1 (2%) 2 (4%) 2 (4%) 

Duct, cyst 2 (4%) 

Duct, hemorrhage 1 (2%) 

Duct, inflammation, chronic 1 (2%) 

Salivary glands (50) (50) (50) (50) 

Metaplasia, squamous 1 (2%) 

Stomach, forestomach (49) (50) (49) (50) 

Angiectasis 1 (2%) 

Hyperplasia, squamous 4 (8%) 3 (6%) 2 (4%) 

Inflammation, chronic 1 (2%) 

Ulcer 1 (2%) 

Serosa, inflammation, acute 1 (2%) 

Stomach, glandular (49) (50) (50) (49) 

Cyst 1 (2%) 1 (2%) 

Erosion 3 (6%) 1 (2%) 1 (2%) 2 (4%) 

Hyperplasia 1 (2%) 1 (2%) 1 (2%) 

Inflammation, chronic 1 (2%) 1 (2%) 

Metaplasia, squamous 1 (2%) 

Ulcer 1 (2%) 

Glands, hyperplasia 1 (2%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

158 1-Chloro-2-propanol, NTP TR 477 

TABLE C4 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Alimentary System (continued) 

Tooth (4) (3) (4) (7) 

Degeneration 4 (100%) 3 (100%) 4 (100%) 7 (100%) 

Inflammation, chronic active 1 (25%) 

Cardiovascular System 

Heart (50) (50) (50) (50) 

Cardiomyopathy 6 (12%) 2 (4%) 2 (4%) 2 (4%) 

Mineralization 2 (4%) 

Atrium, thrombosis 1 (2%) 

Valve, inflammation, acute 1 (2%) 

Endocrine System 

Adrenal cortex (50) (50) (50) (50) 

Hemorrhage 1 (2%) 

Hyperplasia 2 (4%) 

Hypertrophy, focal 18 (36%) 25 (50%) 21 (42%) 17 (34%) 

Capsule, hyperplasia 39 (78%) 42 (84%) 38 (76%) 38 (76%) 

Adrenal medulla (50) (50) (50) (50) 

Hemorrhage 1 (2%) 

Islets, pancreatic (50) (50) (50) (50) 

Hyperplasia 48 (96%) 47 (94%) 45 (90%) 47 (94%) 

Pituitary gland (50) (49) (49) (47) 

Pars distalis, cyst 2 (4%) 3 (6%) 2 (4%) 

Pars distalis, hyperplasia 1 (2%) 

Thyroid gland (50) (50) (50) (50) 

Cyst 1 (2%) 3 (6%) 

Follicular cell, hyperplasia 6 (12%) 9 (18%) 3 (6%) 5 (10%) 

General Body System 

None 

Genital System 

Epididymis (50) (50) (50) (50) 

Granuloma sperm 1 (2%) 

Hemorrhage 1 (2%) 

Inflammation, chronic 1 (2%) 3 (6%) 3 (6%) 

Spermatocele 2 (4%) 1 (2%) 

Penis (2) 

Congestion 1 (50%) 

Preputial gland (50) (50) (50) (50) 

Atrophy 1 (2%) 1 (2%) 

Cyst 30 (60%) 33 (66%) 26 (52%) 30 (60%) 

Inflammation, acute 1 (2%) 

Inflammation, chronic 1 (2%) 7 (14%) 5 (10%) 5 (10%) 

Inflammation, chronic active 6 (12%) 6 (12%) 4 (8%) 7 (14%) 

Pigmentation 1 (2%) 

Prostate (50) (50) (49) (50) 

Inflammation, acute 1 (2%) 

Inflammation, chronic 3 (6%) 1 (2%) 3 (6%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 159 

TABLE C4 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Genital System (continued) 

Seminal vesicle (50) (50) (50) (50) 

Atrophy 1 (2%) 

Hypertrophy 1 (2%) 1 (2%) 

Inflammation, chronic 3 (6%) 9 (18%) 8 (16%) 1 (2%) 

Inflammation, chronic active 1 (2%) 

Mineralization 1 (2%) 

Testes (50) (50) (50) (50) 

Germinal epithelium, degeneration 1 (2%) 1 (2%) 2 (4%) 

Interstitial cell, hyperplasia 1 (2%) 

Hematopoietic System 

Bone marrow (50) (50) (50) (50) 

Angiectasis 1 (2%) 

Hyperplasia, mast cell 1 (2%) 

Myeloid cell, hyperplasia 2 (4%) 

Lymph node (4) (5) (2) (3) 

Infiltration cellular, plasma cell 1 (20%) 

Iliac, infiltration cellular, plasma cell 1 (20%) 

Iliac, infiltration cellular, histiocyte 1 (25%) 

Iliac, pigmentation 3 (75%) 1 (20%) 

Inguinal, hyperplasia, lymphoid 1 (20%) 

Mediastinal, hyperplasia, lymphoid 1 (50%) 

Mediastinal, infiltration cellular, plasma cell 1 (20%) 

Mediastinal, pigmentation 1 (25%) 

Renal, angiectasis 1 (20%) 

Renal, hyperplasia, lymphoid 1 (50%) 

Lymph node, mandibular (50) (50) (50) (50) 

Hyperplasia, lymphoid 2 (4%) 1 (2%) 1 (2%) 

Infiltration cellular, plasma cell 1 (2%) 1 (2%) 1 (2%) 

Lymph node, mesenteric (49) (50) (50) (50) 

Angiectasis 7 (14%) 8 (16%) 3 (6%) 5 (10%) 

Hemorrhage 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 1 (2%) 

Spleen (50) (50) (50) (50) 

Hematopoietic cell proliferation 9 (18%) 8 (16%) 5 (10%) 6 (12%) 

Hyperplasia, lymphoid 1 (2%) 3 (6%) 

Lymphoid follicle, atrophy 2 (4%) 

Integumentary System 

Skin (50) (50) (50) (50) 

Epidermis, cyst 1 (2%) 

Epidermis, necrosis 1 (2%) 

Subcutaneous tissue, edema 1 (2%) 

Subcutaneous tissue, hemorrhage 1 (2%) 1 (2%) 

Subcutaneous tissue, inflammation, acute 1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) (50) 

Callus 1 (2%) 

Fibrous osteodystrophy 1 (2%) 

Hyperostosis 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

160 1-Chloro-2-propanol, NTP TR 477 

TABLE C4 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Nervous System 

Brain (50) (50) (50) (50) 

Demyelination 1 (2%) 

Hemorrhage 1 (2%) 

Thalamus, mineralization 30 (60%) 25 (50%) 23 (46%) 26 (52%) 

Spinal cord (1) 

Demyelination 1 (100%) 

Respiratory System 

Lung (50) (50) (50) (50) 

Hemorrhage 2 (4%) 1 (2%) 2 (4%) 

Infiltration cellular, histiocyte 2 (4%) 2 (4%) 4 (8%) 5 (10%) 

Inflammation, chronic 2 (4%) 

Leukocytosis 1 (2%) 

Necrosis 1 (2%) 

Alveolar epithelium, hyperplasia 5 (10%) 5 (10%) 2 (4%) 3 (6%) 

Nose (50) (50) (50) (50) 

Foreign body 1 (2%) 

Inflammation, acute 4 (8%) 1 (2%) 

Glands, amyloid deposition 1 (2%) 

Nasolacrimal duct, inflammation, acute 1 (2%) 

Special Senses System 

None 

Urinary System 

Kidney (50) (50) (50) (50) 

Cyst 11 (22%) 13 (26%) 10 (20%) 15 (30%) 

Hemorrhage 1 (2%) 

Hydronephrosis 2 (4%) 1 (2%) 3 (6%) 1 (2%) 

Inflammation, acute 1 (2%) 

Mineralization 5 (10%) 2 (4%) 

Nephropathy, acute 1 (2%) 1 (2%) 6 (12%) 1 (2%) 

Nephropathy, chronic 43 (86%) 45 (90%) 38 (76%) 46 (92%) 

Arteriole, thrombosis 1 (2%) 

Papilla, necrosis 1 (2%) 

Pelvis, calculus microscopic observation only 1 (2%) 

Renal tubule, hyperplasia 4 (8%) 1 (2%) 

Transitional epithelium, hyperplasia 1 (2%) 

Urethra (1) 

Inflammation, acute 1 (100%) 

Urinary bladder (50) (50) (49) (50) 

Calculus, gross observation 1 (2%) 

Calculus, microscopic observation only 1 (2%) 

Hemorrhage 1 (2%) 

Inflammation, acute 1 (2%) 3 (6%) 1 (2%) 

Inflammation, chronic 1 (2%) 
161 

APPENDIX D
 

SUMMARY OF LESIONS IN FEMALE MICE
 

IN THE 2-YEAR DRINKING WATER STUDY
 

OF 1-CHLORO-2-PROPANOL
 

TABLE D1	 Summary of the Incidence of Neoplasms in Female Mice 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 163
 

TABLE D2 Individual Animal Tumor Pathology of Female Mice 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 168
 

TABLE D3 Statistical Analysis of Primary Neoplasms in Female Mice 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 190
 

TABLE D4 Historical Incidence of Liver Neoplasms in Untreated Female B6C3F1
 Mice .......... 193

TABLE D5	 Summary of the Incidence of Nonneoplastic Lesions in Female Mice 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 194
 
162 1-Chloro-2-propanol, NTP TR 477 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 163 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanola 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Accidental deaths 3 1 2 

Moribund 8 7 3 5 

Natural deaths 7 11 10 11 

Survivors 

Terminal sacrifice 32 32 36 32 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Esophagus (50) (50) (50) (50) 

Gallbladder (42) (44) (45) (40) 

Carcinoma, metastatic, uncertain primary site 1 (2%) 

Carcinoma, metastatic, urinary bladder 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Intestine large, cecum (44) (46) (48) (49) 

Intestine small, duodenum (43) (46) (46) (47) 

Intestine small, jejunum (46) (45) (47) (46) 

Carcinoma 1 (2%) 

Leiomyosarcoma, metastatic, uncertain

 primary site 1 (2%) 

Intestine small, ileum (46) (44) (45) (45) 

Liver (50) (50) (50) (50) 

Alveolar/bronchiolar carcinoma, metastatic, 

lung 1 (2%) 

Carcinoma, metastatic, uncertain primary site 1 (2%) 

Carcinoma, metastatic, urinary bladder 1 (2%) 

Carcinoma, metastatic, intestine small, 

jejunum 1 (2%) 

Fibrous histiocytoma, metastatic, uncertain

 primary site 1 (2%) 

Hemangiosarcoma 1 (2%) 1 (2%) 1 (2%) 

Hepatoblastoma 1 (2%) 1 (2%) 1 (2%) 

Hepatocellular carcinoma 6 (12%) 9 (18%) 7 (14%) 9 (18%) 

Hepatocellular carcinoma, multiple 2 (4%) 1 (2%) 

Hepatocellular adenoma 12 (24%) 12 (24%) 10 (20%) 10 (20%) 

Hepatocellular adenoma, multiple 28 (56%) 27 (54%) 32 (64%) 30 (60%) 

Histiocytic sarcoma 2 (4%) 1 (2%) 2 (4%) 

Leiomyosarcoma, metastatic, uncertain

 primary site 1 (2%) 

Lipoma 1 (2%) 

Mesentery (20) (19) (16) (12) 

Carcinoma, metastatic, uncertain primary site 2 (11%) 

Carcinoma, metastatic, urinary bladder 1 (6%) 

Carcinoma, metastatic, intestine small, 

jejunum 1 (5%) 

Hemangioma 1 (5%) 

Hemangiosarcoma, metastatic, uterus 1 (5%) 

Histiocytic sarcoma 1 (5%) 1 (6%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

164 1-Chloro-2-propanol, NTP TR 477 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Alimentary System (continued) 

Pancreas (50) (50) (50) (50) 

Carcinoma, metastatic, uncertain primary site 2 (4%) 

Carcinoma, metastatic, urinary bladder 1 (2%) 

Fibrous histiocytoma, metastatic, uncertain

 primary site 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Leiomyosarcoma, metastatic, uncertain

 primary site 1 (2%) 

Acinus, adenoma 1 (2%) 

Salivary glands (50) (50) (49) (50) 

Stomach, forestomach (50) (50) (50) (50) 

Carcinoma, metastatic, urinary bladder 1 (2%) 

Squamous cell papilloma 1 (2%) 1 (2%) 

Stomach, glandular (50) (50) (48) (50) 

Carcinoma, metastatic, uncertain primary site 1 (2%) 

Carcinoma, metastatic, urinary bladder 1 (2%) 

Cardiovascular System 

Heart (50) (50) (50) (50) 

Alveolar/bronchiolar carcinoma, metastatic, 

lung 1 (2%) 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Endocrine System 

Adrenal cortex (50) (50) (50) (50) 

Adenoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Adrenal medulla (50) (50) (50) (50) 

Pheochromocytoma malignant 1 (2%) 

Islets, pancreatic (50) (50) (50) (50) 

Adenoma 1 (2%) 

Pituitary gland (49) (49) (47) (46) 

Pars distalis, adenoma 6 (12%) 5 (10%) 3 (6%) 4 (9%) 

Pars intermedia, adenoma 1 (2%) 1 (2%) 

Thyroid gland (50) (50) (50) (50) 

Follicular cell, adenoma 1 (2%) 2 (4%) 1 (2%) 

General Body System 

Tissue NOS (3) (1) (2) 

Histiocytic sarcoma 1 (33%) 

Leiomyosarcoma, metastatic, uncertain

 primary site 1 (50%) 

Pelvic, hemangiosarcoma 1 (33%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 165 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Genital System 

Clitoral gland (50) (49) (48) (49) 

Histiocytic sarcoma 1 (2%) 

Ovary (50) (49) (50) (50) 

Carcinoma, metastatic, uncertain primary site 1 (2%) 

Carcinoma, metastatic, urinary bladder 1 (2%) 

Cystadenoma 1 (2%) 1 (2%) 2 (4%) 

Granulosa cell tumor benign 1 (2%) 

Granulosa-theca tumor benign 1 (2%) 

Hemangioma 1 (2%) 1 (2%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 2 (4%) 

Uterus (50) (50) (50) (50) 

Hemangioma 1 (2%) 

Hemangiosarcoma 1 (2%) 1 (2%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 2 (4%) 

Polyp stromal 1 (2%) 2 (4%) 1 (2%) 

Sarcoma stromal 1 (2%) 1 (2%) 1 (2%) 

Hematopoietic System 

Bone marrow (50) (50) (50) (50) 

Hemangiosarcoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Lymph node (8) (12) (15) (9) 

Histiocytic sarcoma 1 (13%) 

Deep cervical, histiocytic sarcoma 1 (13%) 

Iliac, hemangiosarcoma 1 (8%) 

Iliac, hemangiosarcoma, metastatic, uterus 1 (13%) 

Iliac, histiocytic sarcoma 2 (25%) 1 (8%) 

Inguinal, histiocytic sarcoma 1 (13%) 

Mediastinal, histiocytic sarcoma 1 (13%) 1 (8%) 

Pancreatic, fibrous histiocytoma, metastatic, 

uncertain primary site 1 (7%) 

Pancreatic, histiocytic sarcoma 1 (13%) 

Renal, histiocytic sarcoma 1 (13%) 1 (7%) 

Lymph node, mandibular (50) (49) (49) (50) 

Carcinoma, metastatic, harderian gland 1 (2%) 

Carcinoma, metastatic, urinary bladder 1 (2%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Lymph node, mesenteric (49) (48) (47) (49) 

Fibrous histiocytoma, metastatic, uncertain

 primary site 1 (2%) 

Hemangioma 1 (2%) 

Histiocytic sarcoma 2 (4%) 1 (2%) 2 (4%) 

Leiomyosarcoma, metastatic, uncertain

 primary site 1 (2%) 

Spleen (49) (50) (50) (50) 

Fibrous histiocytoma, metastatic, uncertain

 primary site 1 (2%) 

Hemangiosarcoma 1 (2%) 2 (4%) 1 (2%) 2 (4%) 

Histiocytic sarcoma 1 (2%) 

Thymus (48) (48) (45) (49) 

Carcinoma, metastatic, harderian gland 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

166 1-Chloro-2-propanol, NTP TR 477 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Integumentary System 

Skin (50) (50) (50) (50) 

Subcutaneous tissue, fibrosarcoma 1 (2%) 1 (2%) 1 (2%) 

Subcutaneous tissue, fibrosarcoma, multiple 1 (2%) 

Subcutaneous tissue, fibrous histiocytoma 1 (2%) 

Subcutaneous tissue, hemangiosarcoma 1 (2%) 2 (4%) 1 (2%) 

Subcutaneous tissue, sarcoma 1 (2%) 1 (2%) 

Musculoskeletal System 

Skeletal muscle (1) (2) 

Alveolar/bronchiolar carcinoma, metastatic, 

lung 1 (50%) 

Sarcoma, metastatic, skin 1 (50%) 

Nervous System 

Brain (50) (49) (50) (50) 

Carcinoma, metastatic, harderian gland 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Respiratory System 

Lung (50) (50) (50) (50) 

Alveolar/bronchiolar adenoma 4 (8%) 1 (2%) 4 (8%) 4 (8%) 

Alveolar/bronchiolar carcinoma 5 (10%) 1 (2%) 2 (4%) 3 (6%) 

Carcinoma, metastatic, harderian gland 2 (4%) 1 (2%) 

Carcinoma, metastatic, uncertain primary site 1 (2%) 1 (2%) 

Carcinoma, metastatic, urinary bladder 1 (2%) 

Hemangiosarcoma, metastatic, uterus 1 (2%) 

Hepatocellular carcinoma, metastatic, liver 2 (4%) 4 (8%) 3 (6%) 1 (2%) 

Histiocytic sarcoma 2 (4%) 1 (2%) 2 (4%) 

Nose (50) (50) (50) (50) 

Carcinoma, metastatic, harderian gland 1 (2%) 1 (2%) 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Trachea (50) (50) (50) (50) 

Special Senses System 

Harderian gland (5) (3) (2) (1) 

Adenoma 3 (60%) 1 (33%) 1 (50%) 

Carcinoma 2 (40%) 2 (67%) 1 (50%) 1 (100%) 

Urinary System 

Kidney (50) (50) (50) (50) 

Alveolar/bronchiolar carcinoma, metastatic, 

lung 1 (2%) 

Carcinoma, metastatic, uncertain primary site 1 (2%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 1 (2%) 

Urinary bladder (48) (49) (48) (49) 

Fibrous histiocytoma, metastatic, uncertain

 primary site 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Transitional epithelium, carcinoma 1 (2%) 
 

 

167 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Systemic Lesions 

Multiple organsb 

Histiocytic sarcoma

Lymphoma malignant

(50) 

 2 (4%) 

 10 (20%) 

(50) 

 1 (2%) 

 14 (28%) 

(50) 

 2 (4%) 

 10 (20%) 

(50) 

 11 (22%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 

Total primary neoplasms 

Total animals with benign neoplasms 

Total benign neoplasms 

Total animals with malignant neoplasms 

Total malignant neoplasms 

Total animals with metastatic neoplasms 

Total metastatic neoplasms 

Total animals with malignant neoplasms

 of uncertain primary site 

46 

94 

42 

60 

28 

34 

8 

14 

1 

49 

95 

43 

57 

30 

38 

6 

17 

2 

46 

86 

43 

55 

25 

31 

6 

24 

2 

44 

84 

41 

52 

22 

32 

3 

6 

a Number of animals examined microscopically at the site and the number of animals with neoplasms b Number of animals with any tissue examined microscopically 

Primary neoplasms: all neoplasms except metastatic neoplasms 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

168 1-Chloro-2-propanol, NTP TR 477 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

0 2 4 5 5 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 7 6 6 8 9 5 7 7 7 8 8 9 1 2 2 3 3 3 3 3 3 3 3 3 3 

6 4 5 7 3 7 0 3 7 3 3 8 4 1 6 1 2 3 5 5 5 5 5 5 5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

Carcass ID Number 6 4 2 5 2 3 4 5 5 2 2 3 5 3 3 3 3 3 1 1 1 1 2 2 2 

2 2 8 1 7 0 6 8 4 1 6 1 5 6 8 7 5 9 6 7 8 9 0 2 3 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 

Gallbladder + A + + A + + + A A + A + + A + M A + + + + + + + 

Histiocytic sarcoma X 

Intestine large, colon + + + + + + + + A + + + + + A A + + + + + + + + + 

Intestine large, rectum + + + + + + + + + + + + + + A A + + + + + + + + + 

Intestine large, cecum + + + + A + A + A + + + + + A A + A + + + + + + + 

Intestine small, duodenum + A + + A + A + A + + A + + A A + + + + + + + + + 

Intestine small, jejunum + A + + + + + + + + + A + + A A + + + + + + + + + 

Carcinoma X 

Intestine small, ileum + + + + + + A + A + + + + + A A + + + + + + + + + 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, intestine

 small, jejunum X 

Hemangiosarcoma 

Hepatocellular carcinoma X X 

Hepatocellular adenoma X X X X X X 

Hepatocellular adenoma, multiple X X X X X X X X X X X X 

Histiocytic sarcoma X X 

Mesentery + + + + + + + 

Carcinoma, metastatic, intestine

 small, jejunum X 

Hemangiosarcoma, metastatic, uterus X 

Histiocytic sarcoma X 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 

Squamous cell papilloma 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Alveolar/bronchiolar carcinoma,

 metastatic, lung X 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Pheochromocytoma malignant X 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma 

Parathyroid gland + + + + + + + + + + + + M + + + + + + + + + + + + 

Pituitary gland + + + + M + + + + + + + + + + + + + + + + + + + + 

Pars distalis, adenoma X X 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Follicular cell, adenoma 

+: Tissue examined microscopically M: Missing tissue X: Lesion present 

A: Autolysis precludes examination I: Insufficient tissue Blank: Not examined 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 169 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Total 

Carcass ID Number 2 2 2 3 3 3 4 4 4 4 4 4 4 4 5 5 5 5 5 5 6 6 6 6 6 Tissues/ 

4 5 9 2 3 4 0 1 3 4 5 7 8 9 0 2 3 6 7 9 0 1 3 4 5 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder + + + + + + + + + + + + + + + + + + + + + + + + + 42 

Histiocytic sarcoma 1 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 44 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 43 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Carcinoma 1 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, intestine

 small, jejunum 1 

Hemangiosarcoma X 1 

Hepatocellular carcinoma X X X X 6 

Hepatocellular adenoma X X X X X X 12 

Hepatocellular adenoma, multiple X X X X X X X X X X X X X X X X 28 

Histiocytic sarcoma 2 

Mesentery + + + + + + + + + + + + + 20 

Carcinoma, metastatic, intestine

 small, jejunum 1 

Hemangiosarcoma, metastatic, uterus 1 

Histiocytic sarcoma 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Squamous cell papilloma X 1 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar carcinoma,

 metastatic, lung 1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma malignant 1 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pars distalis, adenoma X X X X 6 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Follicular cell, adenoma X 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

170 1-Chloro-2-propanol, NTP TR 477 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

0 2 4 5 5 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 7 6 6 8 9 5 7 7 7 8 8 9 1 2 2 3 3 3 3 3 3 3 3 3 3 

6 4 5 7 3 7 0 3 7 3 3 8 4 1 6 1 2 3 5 5 5 5 5 5 5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

Carcass ID Number 6 4 2 5 2 3 4 5 5 2 2 3 5 3 3 3 3 3 1 1 1 1 2 2 2 

2 2 8 1 7 0 6 8 4 1 6 1 5 6 8 7 5 9 6 7 8 9 0 2 3 

General Body System 

Tissue NOS + + 

Histiocytic sarcoma X 

Pelvic, hemangiosarcoma 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 

Cystadenoma 

Granulosa cell tumor benign 

Hemangioma X 

Histiocytic sarcoma X 

Oviduct + 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 

Hemangiosarcoma X 

Histiocytic sarcoma X 

Polyp stromal 

Sarcoma stromal 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Lymph node + + + + + + + 

Histiocytic sarcoma X 

Deep cervical, histiocytic sarcoma X 

Iliac, hemangiosarcoma, metastatic, uterus X 

Iliac, histiocytic sarcoma X X 

Inguinal, histiocytic sarcoma X 

Mediastinal, histiocytic sarcoma X 

Pancreatic, histiocytic sarcoma X 

Renal, histiocytic sarcoma X 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, harderian gland X 

Histiocytic sarcoma X 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X X 

Spleen + + + + + + + + + + + + + + A + + + + + + + + + + 

Hemangiosarcoma X 

Histiocytic sarcoma X 

Thymus + + + + + + + + + + + + + + + + M + + + + + + + + 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 

Subcutaneous tissue, fibrosarcoma, multiple 

Subcutaneous tissue, hemangiosarcoma X 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 
 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 171 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Total 

Carcass ID Number 2 2 2 3 3 3 4 4 4 4 4 4 4 4 5 5 5 5 5 5 6 6 6 6 6 Tissues/ 

4 5 9 2 3 4 0 1 3 4 5 7 8 9 0 2 3 6 7 9 0 1 3 4 5 Tumors 

General Body System 

Tissue NOS + 3 

Histiocytic sarcoma 1 

Pelvic, hemangiosarcoma X 1 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cystadenoma X 1 

Granulosa cell tumor benign X 1 

Hemangioma 1 

Histiocytic sarcoma 1 

Oviduct 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma 1 

Histiocytic sarcoma 1 

Polyp stromal X 1 

Sarcoma stromal X 1 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Lymph node + 8 

Histiocytic sarcoma 1 

Deep cervical, histiocytic sarcoma 1 

Iliac, hemangiosarcoma, metastatic, uterus 1 

Iliac, histiocytic sarcoma 2 

Inguinal, histiocytic sarcoma 1 

Mediastinal, histiocytic sarcoma 1 

Pancreatic, histiocytic sarcoma 1 

Renal, histiocytic sarcoma 1 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, harderian gland 1 

Histiocytic sarcoma 1 

Lymph node, mesenteric + + + + + + + + + + + + + M + + + + + + + + + + + 49 

Histiocytic sarcoma 2 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hemangiosarcoma 1 

Histiocytic sarcoma 1 

Thymus + + + + + + + + + + + + + + + + M + + + + + + + + 48 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Subcutaneous tissue, fibrosarcoma, multiple X 1 

Subcutaneous tissue, hemangiosarcoma 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 
 

 

 

 

 

 

 

 

 

 

 

 

 

172 1-Chloro-2-propanol, NTP TR 477 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

0 2 4 5 5 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 7 

6 

6 

4 

6 

5 

8 

7 

9 

3 

5 

7 

7 

0 

7 

3 

7 

7 

8 

3 

8 

3 

9 

8 

1 

4 

2 

1 

2 

6 

3 

1 

3 

2 

3 

3 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

Carcass ID Number 6 4 2 5 2 3 4 5 5 2 2 3 5 3 3 3 3 3 1 1 1 1 2 2 2 

2 2 8 1 7 0 6 8 4 1 6 1 5 6 8 7 5 9 6 7 8 9 0 2 3 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, harderian gland 

Histiocytic sarcoma 

Peripheral nerve 

Spinal cord 

X 

+ 

+ 

X 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar carcinoma 

Carcinoma, metastatic, harderian gland 

Carcinoma, metastatic, uncertain primary site 

Hemangiosarcoma, metastatic, uterus 

Hepatocellular carcinoma, metastatic, liver 

Histiocytic sarcoma 

Nose 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X 

X X X X 

X X 

X 

X 

X X 

X X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, harderian gland 

Trachea 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Harderian gland 

Adenoma 

+ 

X 

+ + 

X 

+ 

Carcinoma X X 

Urinary System 

Kidney 

Histiocytic sarcoma 

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + M + + + + + + + A + + + + + + + + + + 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Lymphoma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X 

X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 173 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

0 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Total 

Carcass ID Number 2 

4 

2 

5 

2 

9 

3 

2 

3 

3 

3 

4 

4 

0 

4 

1 

4 

3 

4 

4 

4 

5 

4 

7 

4 

8 

4 

9 

5 

0 

5 

2 

5 

3 

5 

6 

5 

7 

5 

9 

6 

0 

6 

1 

6 

3 

6 

4 

6 

5 

Tissues/ 

Tumors 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, harderian gland 

Histiocytic sarcoma

Peripheral nerve 

Spinal cord 

+

+

1 

1 

2 

2 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar carcinoma 

Carcinoma, metastatic, harderian gland 

Carcinoma, metastatic, uncertain primary site 

Hemangiosarcoma, metastatic, uterus

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma

Nose 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

4 

5 

2 

1 

1 

2 

2 

50 

Carcinoma, metastatic, harderian gland 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 

1 

50 

Special Senses System 

Harderian gland 

Adenoma 

+

X

 5 

3 

Carcinoma 2 

Urinary System 

Kidney 

Histiocytic sarcoma

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

1 

48 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma

Lymphoma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X 

50 

2 

10 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

174 1-Chloro-2-propanol, NTP TR 477 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

Number of Days on Study 

4 4 5 5 5 5 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 

4 4 3 7 8 9 4 6 6 6 9 9 0 0 0 1 1 3 3 3 3 3 3 3 3 

9 9 8 5 2 4 7 2 3 8 1 5 3 4 7 0 2 2 5 5 5 5 5 5 5 

Carcass ID Number 

2 2 2 3 2 3 3 3 3 2 2 3 3 3 2 2 2 2 2 2 2 2 2 2 2 

8 9 7 0 6 1 0 1 1 8 7 0 0 0 9 9 9 7 6 6 6 7 7 7 7 

4 2 5 7 8 2 2 4 5 6 1 3 6 8 0 7 5 7 6 7 9 0 2 3 4 

Alimentary System 

Esophagus 

Gallbladder 

Carcinoma, metastatic, uncertain primary site 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Carcinoma, metastatic, uncertain primary site 

Hepatoblastoma 

Hepatocellular carcinoma 

Hepatocellular adenoma 

Hepatocellular adenoma, multiple 

Histiocytic sarcoma 

Lipoma 

Mesentery 

Carcinoma, metastatic, uncertain primary site 

Hemangioma 

Pancreas 

Carcinoma, metastatic, uncertain primary site 

Acinus, adenoma 

Salivary glands 

Stomach, forestomach 

Squamous cell papilloma 

Stomach, glandular 

Carcinoma, metastatic, uncertain primary site 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + A A + A + + + A + A + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + A A + A + A + + + + + + + + + + + 

+ + + + + + + + A A + A + A + + + + + + + + + + + 

+ + + + + + + + A A + A + A + + + A + + + + + + + 

+ + + + + + + + A A A A + A + + + A + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X X X X X X X X 

X X X X X X X X X 

X X X X X X X X X 

X 

X 

+ + + + + + + 

X X 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Pituitary gland + + + + + + M + + + + + + + + + + + + + + + + + + 

Pars distalis, adenoma X X 

Pars intermedia, adenoma 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Follicular cell, adenoma 

General Body System 

Tissue NOS 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 175 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 7 7 7 8 8 8 8 8 8 8 8 9 9 9 9 9 9 0 0 0 0 0 1 1 1 Tissues/ 

6 8 9 0 1 2 3 5 7 8 9 1 3 4 6 8 9 0 1 4 5 9 0 1 3 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder + + + + + + M + + + + + + + + + + + + + + + + + + 44 

Carcinoma, metastatic, uncertain primary site 1 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 45 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 44 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, uncertain primary site 1 

Hepatoblastoma X 1 

Hepatocellular carcinoma X 9 

Hepatocellular adenoma X X X 12 

Hepatocellular adenoma, multiple X X X X X X X X X X X X X X X X X X 27 

Histiocytic sarcoma 1 

Lipoma 1 

Mesentery + + + + + + + + + + + + 19 

Carcinoma, metastatic, uncertain primary site 2 

Hemangioma 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, uncertain primary site 2 

Acinus, adenoma X 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Squamous cell papilloma X 1 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, uncertain primary site 1 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Parathyroid gland + + + + + + + + + + M + + + + + + + + + + + + + + 49 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pars distalis, adenoma X X X 5 

Pars intermedia, adenoma X 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Follicular cell, adenoma X X 2 

General Body System 

Tissue NOS + 1 
 

 

 

 

 

 

 

 

 

 

 

 

176 1-Chloro-2-propanol, NTP TR 477 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

4 4 5 5 5 5 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 4 

9 

4 

9 

3 

8 

7 

5 

8 

2 

9 

4 

4 

7 

6 

2 

6 

3 

6 

8 

9 

1 

9 

5 

0 

3 

0 

4 

0 

7 

1 

0 

1 

2 

3 

2 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

2 2 2 3 2 3 3 3 3 2 2 3 3 3 2 2 2 2 2 2 2 2 2 2 2 

Carcass ID Number 8 9 7 0 6 1 0 1 1 8 7 0 0 0 9 9 9 7 6 6 6 7 7 7 7 

4 2 5 7 8 2 2 4 5 6 1 3 6 8 0 7 5 7 6 7 9 0 2 3 4 

Genital System 

Clitoral gland 

Ovary 

Carcinoma, metastatic, uncertain primary site 

Hemangioma 

Histiocytic sarcoma 

Uterus 

+ + + + + + + + + + M + + + + + + + + + + + + + + 

+ + + M + + + + + + + + + + + + + + + + + + + + + 

X 

X 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma 

Polyp stromal 

Sarcoma stromal 

X 

X 

X 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 

Hemangiosarcoma 

Lymph node 

Iliac, hemangiosarcoma 

Iliac, histiocytic sarcoma 

Mediastinal, histiocytic sarcoma 

Lymph node, mandibular 

Histiocytic sarcoma 

Lymph node, mesenteric 

Histiocytic sarcoma 

Spleen 

Hemangiosarcoma 

Thymus 

Carcinoma, metastatic, harderian gland 

X 

+ + + + + + + + + + 

X 

X 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + M + + + + + M + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X 

+ + + + + + + + + + + + M + + + + M + + + + + + + 

X 

Integumentary System 

Mammary gland 

Skin 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Subcutaneous tissue, fibrosarcoma 

Subcutaneous tissue, fibrous histiocytoma 

Subcutaneous tissue, hemangiosarcoma 

Subcutaneous tissue, sarcoma 

X X 

X 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 

Skeletal muscle + 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + M + + + + 
 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 177 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 7 7 7 8 8 8 8 8 8 8 8 9 9 9 9 9 9 0 0 0 0 0 1 1 1 Tissues/ 

6 8 9 0 1 2 3 5 7 8 9 1 3 4 6 8 9 0 1 4 5 9 0 1 3 Tumors 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Carcinoma, metastatic, uncertain primary site 1 

Hemangioma 1 

Histiocytic sarcoma 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Polyp stromal X 2 

Sarcoma stromal 1 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma 1 

Lymph node + + 12 

Iliac, hemangiosarcoma 1 

Iliac, histiocytic sarcoma 1 

Mediastinal, histiocytic sarcoma 1 

Lymph node, mandibular + + + + + + + M + + + + + + + + + + + + + + + + + 49 

Histiocytic sarcoma 1 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Histiocytic sarcoma 1 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma 2 

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Carcinoma, metastatic, harderian gland 1 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Subcutaneous tissue, fibrosarcoma 1 

Subcutaneous tissue, fibrous histiocytoma X 1 

Subcutaneous tissue, hemangiosarcoma 2 

Subcutaneous tissue, sarcoma X 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Skeletal muscle 1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 49 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

178 1-Chloro-2-propanol, NTP TR 477 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

4 4 5 5 5 5 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 4 

9 

4 

9 

3 

8 

7 

5 

8 

2 

9 

4 

4 

7 

6 

2 

6 

3 

6 

8 

9 

1 

9 

5 

0 

3 

0 

4 

0 

7 

1 

0 

1 

2 

3 

2 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

2 2 2 3 2 3 3 3 3 2 2 3 3 3 2 2 2 2 2 2 2 2 2 2 2 

Carcass ID Number 8 9 7 0 6 1 0 1 1 8 7 0 0 0 9 9 9 7 6 6 6 7 7 7 7 

4 2 5 7 8 2 2 4 5 6 1 3 6 8 0 7 5 7 6 7 9 0 2 3 4 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar carcinoma 

Carcinoma, metastatic, harderian gland 

Carcinoma, metastatic, uncertain primary site 

Hepatocellular carcinoma, metastatic,

 liver 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X 

X 

X X X X 

Histiocytic sarcoma 

Nose 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, harderian gland 

Trachea 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Harderian gland 

Adenoma 

+ + 

X 

Carcinoma X 

Lacrimal gland + 

Urinary System 

Kidney 

Carcinoma, metastatic, uncertain primary site 

Histiocytic sarcoma 

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Lymphoma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 179 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

250 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 7 

6 

7 

8 

7 

9 

8 

0 

8 

1 

8 

2 

8 

3 

8 

5 

8 

7 

8 

8 

8 

9 

9 

1 

9 

3 

9 

4 

9 

6 

9 

8 

9 

9 

0 

0 

0 

1 

0 

4 

0 

5 

0 

9 

1 

0 

1 

1 

1 

3 

Tissues/ 

Tumors 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar carcinoma

Carcinoma, metastatic, harderian gland 

Carcinoma, metastatic, uncertain primary site 

Hepatocellular carcinoma, metastatic,

 liver

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

50 

1 

1 

1 

1 

4 

Histiocytic sarcoma

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 

1 

50 

Carcinoma, metastatic, harderian gland 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 

1 

50 

Special Senses System 

Harderian gland 

Adenoma

+ 3 

1 

Carcinoma X 2 

Lacrimal gland 1 

Urinary System 

Kidney 

Carcinoma, metastatic, uncertain primary site 

Histiocytic sarcoma

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + M + + 

50 

1 

1 

49 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma

Lymphoma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X X 

50 

1 

14 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

180 1-Chloro-2-propanol, NTP TR 477 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

500 ppm 

0 1 3 5 5 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 5 1 9 4 4 2 3 4 4 4 4 5 8 9 3 3 3 3 3 3 3 3 3 3 3 

0 3 3 0 3 2 3 5 5 6 9 5 9 7 5 5 5 5 5 5 5 5 5 5 5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

Carcass ID Number 4 1 5 2 6 2 1 5 6 6 3 3 5 3 1 1 2 2 2 2 2 2 2 2 3 

5 9 5 8 2 3 6 9 4 0 9 3 4 8 7 8 0 1 2 4 5 6 7 9 0 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 

Gallbladder M A + + A + + + + + + + A + + + + + + + + + + + + 

Carcinoma, metastatic, urinary bladder X 

Intestine large, colon + A + + + + + + + + + + + + + + + + + + + + + + + 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 

Intestine large, cecum + A + + + + + + + + + + A + + + + + + + + + + + + 

Intestine small, duodenum + A + + + + + + + + A + A A + + + + + + + + + + + 

Intestine small, jejunum + A + + + + + + + + A + A + + + + + + + + + + + + 

Leiomyosarcoma, metastatic,

 uncertain primary site X 

Intestine small, ileum + A + + + + A + + + A + A A + + + + + + + + + + + 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, urinary bladder X 

Fibrous histiocytoma, metastatic,

 uncertain primary site X 

Hemangiosarcoma 

Hepatoblastoma 

Hepatocellular carcinoma X X X 

Hepatocellular carcinoma, multiple X 

Hepatocellular adenoma X X X X X X X 

Hepatocellular adenoma, multiple X X X X X X X X X X 

Histiocytic sarcoma X X 

Leiomyosarcoma, metastatic,

 uncertain primary site X 

Mesentery + + + + + + + + 

Carcinoma, metastatic, urinary bladder X 

Histiocytic sarcoma X 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, urinary bladder X 

Fibrous histiocytoma, metastatic,

 uncertain primary site X 

Leiomyosarcoma, metastatic,

 uncertain primary site X 

Salivary glands + + + + + + + + + + + + + + + + + + + M + + + + + 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, urinary bladder X 

Stomach, glandular + A + + + + + + + + + + A + + + + + + + + + + + + 

Carcinoma, metastatic, urinary bladder X 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 

Parathyroid gland + M + + + + + + + + + + M + M M + + + + + + + + + 

Pituitary gland + + + + + + + + + M M + + + + + + + + + + + + + + 

Pars distalis, adenoma 

Pars intermedia, adenoma 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Follicular cell, adenoma 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 181 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

500 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 5 5 5 5 5 5 5 6 6 6 Tissues/ 

1 2 4 5 6 7 0 1 2 3 4 6 7 8 9 0 1 2 3 6 7 8 1 3 5 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder + + + + + M + + + + + + + + + + + + + + + + + + + 45 

Carcinoma, metastatic, urinary bladder 1 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Leiomyosarcoma, metastatic,

 uncertain primary site 1 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 45 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, urinary bladder 1 

Fibrous histiocytoma, metastatic,

 uncertain primary site 1 

Hemangiosarcoma X 1 

Hepatoblastoma X 1 

Hepatocellular carcinoma X X X X 7 

Hepatocellular carcinoma, multiple X 2 

Hepatocellular adenoma X X X 10 

Hepatocellular adenoma, multiple X X X X X X X X X X X X X X X X X X X X X X 32 

Histiocytic sarcoma 2 

Leiomyosarcoma, metastatic,

 uncertain primary site 1 

Mesentery + + + + + + + + 16 

Carcinoma, metastatic, urinary bladder 1 

Histiocytic sarcoma 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, urinary bladder 1 

Fibrous histiocytoma, metastatic,

 uncertain primary site 1 

Leiomyosarcoma, metastatic,

 uncertain primary site 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, urinary bladder 1 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Carcinoma, metastatic, urinary bladder 1 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Pituitary gland + + + + + + + + + + + + M + + + + + + + + + + + + 47 

Pars distalis, adenoma X X X 3 

Pars intermedia, adenoma X 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Follicular cell, adenoma X 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

182 1-Chloro-2-propanol, NTP TR 477 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

500 ppm 

0 1 3 5 5 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 5 1 9 4 4 2 3 4 4 4 4 5 8 9 3 3 3 3 3 3 3 3 3 3 3 

0 3 3 0 3 2 3 5 5 6 9 5 9 7 5 5 5 5 5 5 5 5 5 5 5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

Carcass ID Number 4 1 5 2 6 2 1 5 6 6 3 3 5 3 1 1 2 2 2 2 2 2 2 2 3 

5 9 5 8 2 3 6 9 4 0 9 3 4 8 7 8 0 1 2 4 5 6 7 9 0 

General Body System 

Tissue NOS + + 

Leiomyosarcoma, metastatic,

 uncertain primary site X 

Genital System 

Clitoral gland M + + + + + + + + + + M + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, urinary bladder X 

Cystadenoma 

Histiocytic sarcoma X X 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 

Hemangiosarcoma X 

Histiocytic sarcoma X X 

Polyp stromal 

Vagina + 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Lymph node + + + + + + + 

Pancreatic, fibrous histiocytoma,

 metastatic, uncertain primary site X 

Renal, histiocytic sarcoma X 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + M + + + + + 

Carcinoma, metastatic, urinary bladder X 

Lymph node, mesenteric + A + + + + + + + + + + A + + + + + + + + + + + + 

Fibrous histiocytoma, metastatic,

 uncertain primary site X 

Hemangioma 

Histiocytic sarcoma X X 

Leiomyosarcoma, metastatic,

 uncertain primary site X 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 

Fibrous histiocytoma, metastatic,

 uncertain primary site X 

Hemangiosarcoma 

Thymus + + + + + + + + + + M M + + + + + + + I + + + + + 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 

Subcutaneous tissue, fibrosarcoma 

Subcutaneous tissue, hemangiosarcoma 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 183 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

500 ppm 

Number of Days on Study 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

Carcass ID Number 

3 

3 

1 

3 

3 

2 

3 

3 

4 

3 

3 

5 

3 

3 

6 

3 

3 

7 

3 

4 

0 

3 

4 

1 

3 

4 

2 

3 

4 

3 

3 

4 

4 

3 

4 

6 

3 

4 

7 

3 

4 

8 

3 

4 

9 

3 

5 

0 

3 

5 

1 

3 

5 

2 

3 

5 

3 

3 

5 

6 

3 

5 

7 

3 

5 

8 

3 

6 

1 

3 

6 

3 

3 

6 

5 

Total 

Tissues/ 

Tumors 

General Body System 

Tissue NOS

Leiomyosarcoma, metastatic,

 uncertain primary site 

Genital System 

Clitoral gland 

Histiocytic sarcoma

Ovary 

Carcinoma, metastatic, urinary bladder 

Cystadenoma 

Histiocytic sarcoma

Uterus 

Hemangiosarcoma

Histiocytic sarcoma

Polyp stromal 

Vagina

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

 2 

1 

48 

1 

50 

1 

1 

2 

50 

1 

2 

1 

1 

Hematopoietic System 

Bone marrow 

Histiocytic sarcoma

Lymph node 

Pancreatic, fibrous histiocytoma,

 metastatic, uncertain primary site 

Renal, histiocytic sarcoma

Lymph node, mandibular 

Carcinoma, metastatic, urinary bladder 

Lymph node, mesenteric 

Fibrous histiocytoma, metastatic,

 uncertain primary site

Hemangioma 

Histiocytic sarcoma

Leiomyosarcoma, metastatic,

 uncertain primary site 

Spleen 

Fibrous histiocytoma, metastatic,

 uncertain primary site

Hemangiosarcoma 

Thymus 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + M + + + + + + + + + 

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

+ + + + + + + + + M + + + + + + + + M + + + + + + 

50 

1 

15 

1 

1 

49 

1 

47 

1 

1 

2 

1 

50 

1 

1 

45 

Integumentary System 

Mammary gland 

Skin 

Subcutaneous tissue, fibrosarcoma 

Subcutaneous tissue, hemangiosarcoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

X

50 

50 

1 

1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 
 

 

 

 

 

 

 

 

 

 

 

 

184 1-Chloro-2-propanol, NTP TR 477 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

500 ppm 

Number of Days on Study 

0 

5 

0 

1 

1 

3 

3 

9 

3 

5 

4 

0 

5 

4 

3 

6 

2 

2 

6 

3 

3 

6 

4 

5 

6 

4 

5 

6 

4 

6 

6 

4 

9 

6 

5 

5 

6 

8 

9 

6 

9 

7 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

Carcass ID Number 

3 

4 

5 

3 

1 

9 

3 

5 

5 

3 

2 

8 

3 

6 

2 

3 

2 

3 

3 

1 

6 

3 

5 

9 

3 

6 

4 

3 

6 

0 

3 

3 

9 

3 

3 

3 

3 

5 

4 

3 

3 

8 

3 

1 

7 

3 

1 

8 

3 

2 

0 

3 

2 

1 

3 

2 

2 

3 

2 

4 

3 

2 

5 

3 

2 

6 

3 

2 

7 

3 

2 

9 

3 

3 

0 

Nervous System 

Brain 

Spinal cord 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ 

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 

Alveolar/bronchiolar adenoma X X X 

Alveolar/bronchiolar carcinoma 

Carcinoma, metastatic, urinary bladder X 

Hepatocellular carcinoma, metastatic, liver X X 

Histiocytic sarcoma X X 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, harderian gland X 

Histiocytic sarcoma X 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Harderian gland + + 

Adenoma X 

Carcinoma X 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X 

Urinary bladder + A + + + + + + + + + + + + + + + + + + + + + + + 

Fibrous histiocytoma, metastatic,

 uncertain primary site X 

Histiocytic sarcoma X 

Transitional epithelium, carcinoma X 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 

Histiocytic sarcoma X X 

Lymphoma malignant X X 
 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 185 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

500 ppm 

Number of Days on Study 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

Carcass ID Number 

3 

3 

1 

3 

3 

2 

3 

3 

4 

3 

3 

5 

3 

3 

6 

3 

3 

7 

3 

4 

0 

3 

4 

1 

3 

4 

2 

3 

4 

3 

3 

4 

4 

3 

4 

6 

3 

4 

7 

3 

4 

8 

3 

4 

9 

3 

5 

0 

3 

5 

1 

3 

5 

2 

3 

5 

3 

3 

5 

6 

3 

5 

7 

3 

5 

8 

3 

6 

1 

3 

6 

3 

3 

6 

5 

Total 

Tissues/ 

Tumors 

Nervous System 

Brain 

Spinal cord

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar carcinoma 

Carcinoma, metastatic, urinary bladder 

Hepatocellular carcinoma, metastatic, liver 

Histiocytic sarcoma

Nose 

Carcinoma, metastatic, harderian gland 

Histiocytic sarcoma

Trachea 

Special Senses System 

Harderian gland

Adenoma

Carcinoma

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

X X

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

1 

50 

4 

2 

1 

3 

2 

50 

1 

1 

50 

2 

1 

1 

Urinary System 

Kidney 

Histiocytic sarcoma

Urinary bladder 

Fibrous histiocytoma, metastatic,

 uncertain primary site

Histiocytic sarcoma

Transitional epithelium, carcinoma

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + 

50 

1 

48 

1 

1 

1 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma

Lymphoma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X X X 

50 

2 

10 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

186 1-Chloro-2-propanol, NTP TR 477 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

1,000 ppm 

Number of Days on Study 

0 1 2 2 4 5 5 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 

7 5 3 6 6 2 6 0 1 2 4 4 6 8 8 0 1 3 3 3 3 3 3 3 3 

7 0 8 1 6 3 9 6 6 9 2 6 4 1 1 1 7 4 5 5 5 5 5 5 5 

Carcass ID Number 

4 3 3 4 3 3 4 3 3 4 3 3 4 3 3 3 4 4 3 3 3 3 3 3 3 

0 9 8 0 9 7 0 9 7 1 7 9 0 7 8 8 1 0 6 6 6 6 7 7 7 

5 1 5 9 9 1 6 4 7 0 9 7 4 4 6 8 4 8 6 7 8 9 0 2 3 

Alimentary System 

Esophagus 

Gallbladder 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Alveolar/bronchiolar carcinoma,

 metastatic, lung 

Hemangiosarcoma 

Hepatoblastoma 

Hepatocellular carcinoma 

Hepatocellular carcinoma, multiple 

Hepatocellular adenoma 

Hepatocellular adenoma, multiple 

Mesentery 

Pancreas 

Salivary glands 

Stomach, forestomach 

Stomach, glandular 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

A + + + A A + + + + A M + + A + A A + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + A + + + + + + + + + + + + + + + + + + + + 

+ + + + A + + + + + A + + A + + + + + + + + + + + 

+ + + + + + + + + + A + + A + + A A + + + + + + + 

+ + + + A + + + + + A A + + A + + A + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

X 

X X X X X 

X X X X 

X X X X X X X X X X X X X X 

+ + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Cardiovascular System 

Heart 

Alveolar/bronchiolar carcinoma,

 metastatic, lung 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 

Parathyroid gland + + + + + + + + M + + + + + + + + + + + + + + + M 

Pituitary gland + + + + + + + + M + + + + + M + + + + + + + + + + 

Pars distalis, adenoma 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

General Body System 

None 

Genital System 

Clitoral gland + M + + + + + + + + + + + + + + + + + + + + + + + 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 

Cystadenoma X X 

Granulosa-theca tumor benign X 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 

Hemangioma X 

Sarcoma stromal 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 187 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

1,000 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 Total 

Carcass ID Number 7 7 7 8 8 8 8 8 8 8 9 9 9 9 9 9 0 0 0 0 0 1 1 1 1 Tissues/ 

5 6 8 0 1 2 3 4 7 9 0 2 3 5 6 8 0 1 2 3 7 1 2 3 5 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder + + + + + + + + + + + + M + + M + + + + + + + + + 40 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 45 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar carcinoma,

 metastatic, lung 1 

Hemangiosarcoma 1 

Hepatoblastoma X 1 

Hepatocellular carcinoma X X X X 9 

Hepatocellular carcinoma, multiple X 1 

Hepatocellular adenoma X X X X X X 10 

Hepatocellular adenoma, multiple X X X X X X X X X X X X X X X X 30 

Mesentery + + + + + + + + 12 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar carcinoma,

 metastatic, lung 1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Pituitary gland + + + + + + + + + + + + + M + + + + M + + + + + + 46 

Pars distalis, adenoma X X X X 4 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

General Body System 

None 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cystadenoma 2 

Granulosa-theca tumor benign 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangioma 1 

Sarcoma stromal X 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

188 1-Chloro-2-propanol, NTP TR 477 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

1,000 ppm 

0 1 2 2 4 5 5 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 7 

7 

5 

0 

3 

8 

6 

1 

6 

6 

2 

3 

6 

9 

0 

6 

1 

6 

2 

9 

4 

2 

4 

6 

6 

4 

8 

1 

8 

1 

0 

1 

1 

7 

3 

4 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

4 3 3 4 3 3 4 3 3 4 3 3 4 3 3 3 4 4 3 3 3 3 3 3 3 

Carcass ID Number 0 

5 

9 

1 

8 

5 

0 

9 

9 

9 

7 

1 

0 

6 

9 

4 

7 

7 

1 

0 

7 

9 

9 

7 

0 

4 

7 

4 

8 

6 

8 

8 

1 

4 

0 

8 

6 

6 

6 

7 

6 

8 

6 

9 

7 

0 

7 

2 

7 

3 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Hemangiosarcoma 

Thymus 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + M + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Integumentary System 

Mammary gland 

Skin 

Subcutaneous tissue, fibrosarcoma 

Subcutaneous tissue, sarcoma 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

Musculoskeletal System 

Bone 

Skeletal muscle 

Alveolar/bronchiolar carcinoma,

 metastatic, lung 

Sarcoma, metastatic, skin 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + 

X 

X 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar carcinoma 

Hepatocellular carcinoma, metastatic, liver 

Nose 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X 

X X 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Ear 

Eye 

Harderian gland 

Carcinoma 

+ 

+ + 

Urinary System 

Kidney 

Alveolar/bronchiolar carcinoma,

 metastatic, lung 

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X 

+ + + + + + + + + + + + + A + + + + + + + + + + + 

Systemic Lesions 

Multiple organs 

Lymphoma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 189 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol: 

1,000 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 

5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 Total 

Carcass ID Number 7 

5 

7 

6 

7 

8 

8 

0 

8 

1 

8 

2 

8 

3 

8 

4 

8 

7 

8 

9 

9 

0 

9 

2 

9 

3 

9 

5 

9 

6 

9 

8 

0 

0 

0 

1 

0 

2 

0 

3 

0 

7 

1 

1 

1 

2 

1 

3 

1 

5 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Hemangiosarcoma

Thymus 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + +

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + M 

50 

9 

50 

49 

50 

2 

49 

Integumentary System 

Mammary gland 

Skin 

Subcutaneous tissue, fibrosarcoma 

Subcutaneous tissue, sarcoma

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X

50 

50 

1 

1 

Musculoskeletal System 

Bone 

Skeletal muscle

Alveolar/bronchiolar carcinoma,

 metastatic, lung 

Sarcoma, metastatic, skin

+ + + + + + + + + + + + + + + + + + + + + + + + + 50 

2 

1 

1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar carcinoma 

Hepatocellular carcinoma, metastatic, liver 

Nose 

Trachea 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X

X

X

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

4 

3 

1 

50 

50 

Special Senses System 

Ear

Eye 

Harderian gland 

Carcinoma 

+

+

X

 1 

3 

1 

1 

Urinary System 

Kidney 

Alveolar/bronchiolar carcinoma,

 metastatic, lung 

Urinary bladder 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

50 

1 

49 

Systemic Lesions 

Multiple organs 

Lymphoma malignant 

+ + + + + + + + + + + + + + + + + + + + + + + + + 

X X X X X X 

50 

11 
190 1-Chloro-2-propanol, NTP TR 477 

TABLE D3 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Harderian Gland: Adenoma a Overall rate 3/50 (6%) 1/50 (2%) 1/50 (2%) 0/50 (0%) 

Adjusted rateb 6.7% 2.3% 2.3% 0.0% c Terminal rate 2/32 (6%) 1/32 (3%) 0/36 (0%) 0/32 (0%) e First incidence (days) 587 735 (T) 655 — d Poly-3 test Pù0.089N Pù0.333N Pù0.341N Pù0.156N 

Harderian Gland: Adenoma or Carcinoma 

Overall rate 5/50 (10%) 3/50 (6%) 2/50 (4%) 1/50 (2%) 

Adjusted rate 11.0% 6.7% 4.6% 2.4% 

Terminal rate 3/32 (9%) 2/32 (6%) 1/36 (3%) 1/32 (3%) 

First incidence (days) 587 647 655 735 (T) 

Poly-3 test Pù0.082N Pù0.380N Pù0.248N Pù0.138N 

Liver: Hepatocellular Adenoma 

Overall rate 40/50 (80%) 39/50 (78%) 42/50 (84%) 40/50 (80%)
 

Adjusted rate 85.2% 82.3% 92.4% 88.7%
 

Terminal rate 29/32 (91%) 27/32 (84%) 36/36 (100%) 29/32 (91%)
 

First incidence (days) 587 449 543 466
 

Poly-3 test Pù0.237 Pù0.465N Pù0.211 Pù0.430 

Liver: Hepatocellular Carcinoma 

Overall rate 6/50 (12%) 9/50 (18%) 9/50 (18%) 10/50 (20%)
 

Adjusted rate 13.4% 19.4% 20.3% 23.4%
 

Terminal rate 4/32 (13%) 3/32 (9%) 5/36 (14%) 7/32 (22%)
 

First incidence (days) 726 575 645 466
 

Poly-3 test Pù0.168 Pù0.326 Pù0.294 Pù0.186 

Liver: Hepatocellular Adenoma or Carcinoma 

Overall rate 41/50 (82%) 41/50 (82%) 43/50 (86%) 42/50 (84%)
 

Adjusted rate 87.3% 85.1% 93.9% 92.7%
 

Terminal rate 29/32 (91%) 27/32 (84%) 36/36 (100%) 30/32 (94%)
 

First incidence (days) 587 449 543 466
 

Poly-3 test Pù0.140 Pù0.503N Pù0.219 Pù0.301 

Liver: Hepatocellular Carcinoma or Hepatoblastoma 

Overall rate 6/50 (12%) 10/50 (20%) 10/50 (20%) 10/50 (20%)
 

Adjusted rate 13.4% 21.5% 22.5% 23.4%
 

Terminal rate 4/32 (13%) 4/32 (13%) 6/36 (17%) 7/32 (22%)
 

First incidence (days) 726 575 645 466
 

Poly-3 test Pù0.186 Pù0.239 Pù0.210 Pù0.186 

Liver: Hepatocellular Adenoma, Hepatocellular Carcinoma, or Hepatoblastoma 

Overall rate 41/50 (82%) 41/50 (82%) 43/50 (86%) 42/50 (84%)
 

Adjusted rate 87.3% 85.1% 93.9% 92.7%
 

Terminal rate 29/32 (91%) 27/32 (84%) 36/36 (100%) 30/32 (94%)
 

First incidence (days) 587 449 543 466
 

Poly-3 test Pù0.140 Pù0.503N Pù0.219 Pù0.301 

Lung: Alveolar/bronchiolar Adenoma 

Overall rate 4/50 (8%) 1/50 (2%) 4/50 (8%) 4/50 (8%) 

Adjusted rate 9.0% 2.3% 9.1% 9.5% 

Terminal rate 3/32 (9%) 1/32 (3%) 2/36 (6%) 2/32 (6%) 

First incidence (days) 733 735 (T) 645 466 

Poly-3 test Pù0.388 Pù0.195N Pù0.653 Pù0.634 
1-Chloro-2-propanol, NTP TR 477 191 

TABLE D3 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Lung: Alveolar/bronchiolar Carcinoma 

Overall rate 5/50 (10%) 1/50 (2%) 2/50 (4%) 3/50 (6%) 

Adjusted rate 10.8% 2.2% 4.6% 7.1% 

Terminal rate 1/32 (3%) 0/32 (0%) 2/36 (6%) 2/32 (6%) 

First incidence (days) 465 710 735 (T) 466 

Poly-3 test Pù0.435N Pù0.120N Pù0.259N Pù0.429N 

Lung: Alveolar/bronchiolar Adenoma or Carcinoma 

Overall rate 9/50 (18%) 2/50 (4%) 5/50 (10%) 6/50 (12%)
 

Adjusted rate 19.4% 4.5% 11.4% 14.2%
 

Terminal rate 4/32 (13%) 1/32 (3%) 3/36 (8%) 4/32 (13%)
 

First incidence (days) 465 710 645 466
 

Poly-3 test Pù0.461N Pù0.032N Pù0.233N Pù0.373N
 

Pituitary Gland (Pars Distalis): Adenoma 

Overall rate 6/49 (12%) 5/49 (10%) 3/47 (6%) 4/46 (9%) 

Adjusted rate 13.6% 11.4% 7.3% 10.5% 

Terminal rate 5/32 (16%) 4/32 (13%) 3/35 (9%) 4/30 (13%) 

First incidence (days) 733 695 735 (T) 735 (T) 

Poly-3 test Pù0.374N Pù0.519N Pù0.295N Pù0.487N 

Skin (Subcutaneous Tissue): Fibrous Histiocytoma, Fibrosarcoma, or Sarcoma 

Overall rate 1/50 (2%) 3/50 (6%) 1/50 (2%) 2/50 (4%) 

Adjusted rate 2.2% 6.8% 2.3% 4.8% 

Terminal rate 1/32 (3%) 3/32 (9%) 1/36 (3%) 2/32 (6%) 

First incidence (days) 735 (T) 735 (T) 735 (T) 735 (T) 

Poly-3 test Pù0.513 Pù0.326 Pù0.784 Pù0.513 

Uterus: Stromal Polyp or Stromal Sarcoma 

Overall rate 2/50 (4%) 3/50 (6%) 1/50 (2%) 1/50 (2%) 

Adjusted rate 4.5% 6.7% 2.3% 2.4% 

Terminal rate 2/32 (6%) 2/32 (6%) 1/36 (3%) 1/32 (3%) 

First incidence (days) 735 (T) 695 735 (T) 735 (T) 

Poly-3 test Pù0.322N Pù0.521 Pù0.542N Pù0.564N 

All Organs: Hemangiosarcoma 

Overall rate 4/50 (8%) 2/50 (4%) 3/50 (6%) 2/50 (4%) 

Adjusted rate 8.9% 4.5% 6.9% 4.8% 

Terminal rate 3/32 (9%) 0/32 (0%) 2/36 (6%) 0/32 (0%) 

First incidence (days) 673 691 655 664 

Poly-3 test Pù0.365N Pù0.357N Pù0.536N Pù0.397N 

All Organs: Hemangioma or Hemangiosarcoma 

Overall rate 5/50 (10%) 3/50 (6%) 4/50 (8%) 3/50 (6%) 

Adjusted rate 11.1% 6.7% 9.2% 7.1% 

Terminal rate 3/32 (9%) 1/32 (3%) 3/36 (8%) 0/32 (0%) 

First incidence (days) 673 691 655 616 

Poly-3 test Pù0.390N Pù0.377N Pù0.538N Pù0.416N 

All Organs: Malignant Lymphoma 

Overall rate 10/50 (20%) 14/50 (28%) 10/50 (20%) 11/50 (22%)
 

Adjusted rate 22.3% 29.9% 22.9% 25.5%
 

Terminal rate 8/32 (25%) 9/32 (28%) 9/36 (25%) 8/32 (25%)
 

First incidence (days) 683 449 645 238
 

Poly-3 test Pù0.525 Pù0.287 Pù0.587 Pù0.474 
192 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE D3 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Drinking Water Study of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

All Organs: Benign Neoplasms 

Overall rate 42/50 (84%) 43/50 (86%) 43/50 (86%) 41/50 (82%) 

Adjusted rate 89.0% 89.5% 93.9% 90.5% 

Terminal rate 30/32 (94%) 29/32 (91%) 36/36 (100%) 29/32 (91%) 

First incidence (days) 

Poly-3 test 

587 

Pù0.428 

449 

Pù0.612 

543 

Pù0.314 

466 

Pù0.553 

All Organs: Malignant Neoplasms 

Overall rate 28/50 (56%) 30/50 (60%) 26/50 (52%) 22/50 (44%) 

Adjusted rate 59.2% 60.4% 56.8% 49.2% 

Terminal rate 17/32 (53%) 16/32 (50%) 18/36 (50%) 14/32 (44%) 

First incidence (days) 

Poly-3 test 

465 

Pù0.162N 

449 

Pù0.534 

540 

Pù0.496N 

238 

Pù0.231N 

All Organs: Benign or Malignant Neoplasms 

Overall rate 46/50 (92%) 49/50 (98%) 47/50 (94%) 44/50 (88%) 

Adjusted rate 95.9% 98.0% 99.7% 94.6% 

Terminal rate 31/32 (97%) 31/32 (97%) 36/36 (100%) 30/32 (94%) 

First incidence (days) 

Poly-3 test 

465 

Pù0.431N 

449 

Pù0.499 

540 

Pù0.293 

238 

Pù0.587N 

(T)Terminal sacrifice 

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for liver, lung, pituitary 

gland, and uterus; for other tissues, denominator is number of animals necropsied. b	 Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality 

Observed incidence at terminal kill 

d	 Beneath the 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 controls and that exposed group. The Poly-3 test accounts for 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 
1-Chloro-2-propanol, NTP TR 477 193 

TABLE D4 

Historical Incidence of Liver Neoplasms in Untreated Female B6C3F a 1 Mice

Incidence in Controls 

Study Hepatocellular 

Adenoma 

Hepatocellular 

Carcinoma Hepatoblastoma 

Hepatocellular Adenoma, 

Hepatocellular Carcinoma, 

or Hepatoblastoma 

Historical Incidence at TSI Mason Research Institute: Drinking Water Study 

Pyridine 37/49 13/49 1/49 41/49 

Overall Historical Incidence: Drinking Water Studies 

Total 

Standard deviation 

Range 

147/288 (51.0%) 

19.5% 

26%-74% 

62/288 (21.5%) 

13.6% 

8%-42% 

1/288 (0.3%) 

0.9% 

0%-2% 

173/288 (60.1%) 

21.9% 

32%-82% 

Data as of 15 October 1997 a 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

194 1-Chloro-2-propanol, NTP TR 477 

TABLE D5 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Accidental deaths 3 1 2 

Moribund 8 7 3 5 

Natural deaths 7 11 10 11 

Survivors 

Terminal sacrifice 32 32 36 32 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Gallbladder (42) (44) (45) (40) 

Inflammation, acute 1 (2%) 

Necrosis 1 (3%) 

Intestine large, cecum (44) (46) (48) (49) 

Lymphoid tissue, hyperplasia 1 (2%) 

Serosa, inflammation, chronic active 1 (2%) 

Intestine small, jejunum (46) (45) (47) (46) 

Hyperplasia, lymphoid 1 (2%) 

Peyer’s patch, hyperplasia, lymphoid 2 (4%) 1 (2%) 1 (2%) 1 (2%) 

Peyer’s patch, inflammation, acute 1 (2%) 

Serosa, inflammation, chronic active 1 (2%) 

Intestine small, ileum (46) (44) (45) (45) 

Serosa, inflammation, chronic active 1 (2%) 

Liver (50) (50) (50) (50) 

Amyloid deposition 1 (2%) 

Angiectasis 1 (2%) 1 (2%) 

Clear cell focus 2 (4%) 3 (6%) 2 (4%) 2 (4%) 

Cyst 1 (2%) 1 (2%) 

Eosinophilic focus 29 (58%) 24 (48%) 29 (58%) 31 (62%) 

Fibrosis 1 (2%) 

Hematopoietic cell proliferation 1 (2%) 2 (4%) 

Infiltration cellular, polymorphonuclear 1 (2%) 

Inflammation, chronic 1 (2%) 1 (2%) 

Inflammation, suppurative 1 (2%) 

Leukocytosis 1 (2%) 1 (2%) 

Mixed cell focus 2 (4%) 1 (2%) 

Necrosis 1 (2%) 3 (6%) 1 (2%) 

Bile duct, hyperplasia 1 (2%) 

Hepatocyte, vacuolization cytoplasmic 1 (2%) 1 (2%) 

Hepatocyte, portal, vacuolization cytoplasmic 1 (2%) 

Hepatocyte, centrilobular, vacuolization

 cytoplasmic 1 (2%) 

Serosa, inflammation, chronic active 1 (2%) 1 (2%) 

Mesentery (20) (19) (16) (12) 

Inflammation, chronic active 1 (6%) 

Fat, necrosis 19 (95%) 17 (89%) 14 (88%) 11 (92%) 

Pancreas (50) (50) (50) (50) 

Acinus, atrophy 1 (2%) 1 (2%) 3 (6%) 

Acinus, hyperplasia 1 (2%) 1 (2%) 

Duct, cyst 1 (2%) 2 (4%) 

Serosa, inflammation, chronic active 1 (2%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 195 

TABLE D5 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Alimentary System (continued) 

Stomach, forestomach (50) (50) (50) (50) 

Hyperplasia, squamous 3 (6%) 2 (4%) 

Inflammation, chronic 1 (2%) 

Ulcer 1 (2%) 2 (4%) 3 (6%) 

Stomach, glandular (50) (50) (48) (50) 

Erosion 5 (10%) 2 (4%) 2 (4%) 2 (4%) 

Mineralization 1 (2%) 

Glands, hyperplasia 1 (2%) 

Serosa, inflammation, chronic active 1 (2%) 

Cardiovascular System 

Heart (50) (50) (50) (50) 

Angiectasis 1 (2%) 

Cardiomyopathy 5 (10%) 2 (4%) 2 (4%) 

Inflammation, acute 1 (2%) 

Inflammation, chronic 1 (2%) 1 (2%) 

Inflammation, chronic active 1 (2%) 1 (2%) 

Mineralization 1 (2%) 1 (2%) 2 (4%) 

Atrium, thrombosis 1 (2%) 1 (2%) 

Endocrine System 

Adrenal cortex (50) (50) (50) (50) 

Angiectasis 1 (2%) 1 (2%) 

Cyst 1 (2%) 

Hyperplasia 1 (2%) 

Capsule, hyperplasia 48 (96%) 50 (100%) 49 (98%) 48 (96%) 

Adrenal medulla (50) (50) (50) (50) 

Hyperplasia 2 (4%) 

Islets, pancreatic (50) (50) (50) (50) 

Hyperplasia 28 (56%) 30 (60%) 30 (60%) 31 (62%) 

Hypertrophy 1 (2%) 

Pituitary gland (49) (49) (47) (46) 

Hemorrhage 1 (2%) 

Pars distalis, angiectasis 2 (4%) 1 (2%) 1 (2%) 2 (4%) 

Pars distalis, cyst 1 (2%) 

Pars distalis, hemorrhage 1 (2%) 

Pars distalis, hyperplasia 5 (10%) 3 (6%) 8 (17%) 10 (22%) 

Pars intermedia, hemorrhage 1 (2%) 

Thyroid gland (50) (50) (50) (50) 

C-cell, hyperplasia 1 (2%) 

Follicular cell, hyperplasia 13 (26%) 6 (12%) 15 (30%) 13 (26%) 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

196 1-Chloro-2-propanol, NTP TR 477 

TABLE D5 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Genital System 

Clitoral gland (50) (49) (48) (49) 

Cyst 1 (2%) 1 (2%) 

Pigmentation 2 (4%) 1 (2%) 3 (6%) 1 (2%) 

Ovary (50) (49) (50) (50) 

Angiectasis 2 (4%) 2 (4%) 

Cyst 11 (22%) 9 (18%) 9 (18%) 11 (22%) 

Hemorrhage 1 (2%) 1 (2%) 2 (4%) 

Inflammation, chronic active 1 (2%) 1 (2%) 

Oviduct (1) 

Cyst 1 (100%) 

Uterus (50) (50) (50) (50) 

Angiectasis 1 (2%) 1 (2%) 3 (6%) 

Hemorrhage 1 (2%) 1 (2%) 

Hyperplasia, cystic 41 (82%) 46 (92%) 43 (86%) 44 (88%) 

Inflammation, acute 1 (2%) 1 (2%) 1 (2%) 

Inflammation, chronic 1 (2%) 

Vagina (1) 

Fibrosis 1 (100%) 

Hematopoietic System 

Bone marrow (50) (50) (50) (50) 

Angiectasis 1 (2%) 

Depletion cellular 2 (4%) 

Myelofibrosis 1 (2%) 

Lymph node (8) (12) (15) (9) 

Iliac, angiectasis 2 (13%) 

Iliac, hemorrhage 1 (11%) 

Iliac, hyperplasia, lymphoid 2 (25%) 2 (17%) 2 (13%) 

Iliac, infiltration cellular, plasma cell 1 (13%) 1 (8%) 1 (7%) 

Mediastinal, angiectasis 1 (7%) 

Mediastinal, hemorrhage 1 (13%) 

Mediastinal, inflammation, acute 1 (13%) 

Mediastinal, pigmentation 1 (11%) 

Renal, angiectasis 1 (8%) 

Renal, ectasia 1 (8%) 

Renal, hemorrhage 1 (7%) 

Renal, hyperplasia, lymphoid 4 (27%) 

Renal, infiltration cellular, plasma cell 1 (7%) 

Lymph node, mandibular (50) (49) (49) (50) 

Angiectasis 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 1 (2%) 2 (4%) 2 (4%) 

Infiltration cellular, plasma cell 1 (2%) 1 (2%) 1 (2%) 

Infiltration cellular, histiocyte 1 (2%) 

Lymph node, mesenteric (49) (48) (47) (49) 

Angiectasis 1 (2%) 2 (4%) 3 (6%) 1 (2%) 

Ectasia 1 (2%) 1 (2%) 

Fibrosis 1 (2%) 

Hemorrhage 1 (2%) 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 1 (2%) 

Infiltration cellular, plasma cell 1 (2%) 

Inflammation, acute 1 (2%) 

Inflammation, granulomatous 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-Chloro-2-propanol, NTP TR 477 197 

TABLE D5 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Hematopoietic System (continued) 

Spleen (49) (50) (50) (50) 

Congestion 1 (2%) 

Hematopoietic cell proliferation 13 (27%) 9 (18%) 16 (32%) 11 (22%) 

Hyperplasia, lymphoid 3 (6%) 1 (2%) 

Infiltration cellular, histiocyte 1 (2%) 

Metaplasia, osseous 1 (2%) 1 (2%) 

Pigmentation 1 (2%) 

Integumentary System 

Skin (50) (50) (50) (50) 

Ulcer 1 (2%) 1 (2%) 1 (2%) 

Subcutaneous tissue, inflammation, acute 1 (2%) 1 (2%) 

Subcutaneous tissue, inflammation, chronic 1 (2%) 1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) (50) 

Fibrous osteodystrophy 8 (16%) 6 (12%) 5 (10%) 4 (8%) 

Hyperplasia 2 (4%) 

Skeletal muscle (1) (2) 

Inflammation, chronic 1 (100%) 

Nervous System 

Brain (50) (49) (50) (50) 

Demyelination 1 (2%) 1 (2%) 

Hemorrhage 1 (2%) 1 (2%) 

Thalamus, mineralization 22 (44%) 27 (55%) 22 (44%) 22 (44%) 

Peripheral nerve (2) 

Demyelination 1 (50%) 

Spinal cord (2) (1) 

Cyst epithelial inclusion 1 (100%) 

Respiratory System 

Lung (50) (50) (50) (50) 

Hemorrhage 4 (8%) 3 (6%) 6 (12%) 3 (6%) 

Infiltration cellular, lymphocyte 1 (2%) 

Infiltration cellular, histiocyte 4 (8%) 2 (4%) 2 (4%) 4 (8%) 

Inflammation, acute 1 (2%) 

Inflammation, chronic 1 (2%) 1 (2%) 

Thrombosis 1 (2%) 1 (2%) 1 (2%) 

Alveolar epithelium, hyperplasia 1 (2%) 1 (2%) 

Nose (50) (50) (50) (50) 

Hemorrhage 1 (2%) 

Inflammation, acute 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

198 1-Chloro-2-propanol, NTP TR 477 

TABLE D5 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Special Senses System 

Ear

External ear, inflammation, chronic

Eye

Atrophy

Inflammation, acute

Cornea, inflammation, acute

Cornea, necrosis

 (1) 

 1 (100%) 

(3) 

 1 (33%) 

 1 (33%) 

 1 (33%) 

 1 (33%) 

Urinary System 

Kidney (50) (50) (50) (50) 

Cyst 1 (2%) 1 (2%) 

Hydronephrosis 1 (2%) 3 (6%) 1 (2%) 

Inflammation, acute 1 (2%) 

Inflammation, chronic 1 (2%) 1 (2%) 

Metaplasia, osseous 2 (4%) 1 (2%) 1 (2%) 

Mineralization 1 (2%) 1 (2%) 1 (2%) 

Nephropathy, acute 1 (2%) 

Nephropathy, chronic 16 (32%) 6 (12%) 9 (18%) 11 (22%) 

Pigmentation 1 (2%) 

Renal tubule, accumulation, hyaline droplet 3 (6%) 3 (6%) 1 (2%) 

Renal tubule, dilatation 1 (2%) 

Urinary bladder (48) (49) (48) (49) 

Inflammation, acute 1 (2%) 
199 

APPENDIX E
 

GENETIC TOXICOLOGY
 

SALMONELLA TYPHIMURIUM MUTAGENICITY TEST PROTOCOL .............................. 200
 

CHINESE HAMSTER OVARY CELL CYTOGENETICS PROTOCOLS .............................. 200
 

DROSOPHILA MELANOGASTER TEST PROTOCOLS ........................................ 201
 

MOUSE PERIPHERAL BLOOD MICRONUCLEUS TEST PROTOCOL ............................. 202
 

RESULTS ................................................................ 203
 

TABLE E1 Mutagenicity of 1-Chloro-2-propanol in Salmonella typhimurium .................. 204
 

TABLE E2 Induction of Sister Chromatid Exchanges in Chinese Hamster Ovary Cells 

by 1-Chloro-2-propanol ............................................. 207
 

TABLE E3 Induction of Chromosomal Aberrations in Chinese Hamster Ovary Cells 

by 1-Chloro-2-propanol ............................................. 208
 

TABLE E4 Induction of Sex-Linked Recessive Lethal Mutations in Drosophila melanogaster
 

by 1-Chloro-2-propanol ............................................. 209
 

TABLE E5 Induction of Reciprocal Translocations in Drosophila melanogaster
 

by 1-Chloro-2-propanol ............................................. 209
 

TABLE E6 Frequency of Micronuclei in Mouse Peripheral Blood Erythrocytes 

Following Treatment with 1-Chloro-2-propanol in Drinking Water 

for 14 Weeks ..................................................... 210
 
 

200 1-Chloro-2-propanol, NTP TR 477 

GENETIC TOXICOLOGY 

SALMONELLA TYPHIMURIUM MUTAGENICITY TEST PROTOCOL 

Testing was performed as reported by Zeiger et al. (1987). 1-Chloro-2-propanol was sent to the laboratory as 

a coded aliquot from Radian Corporation (Austin, TX). It was incubated with the Salmonella typhimurium 

tester strains TA97, TA98, TA100, TA1535, and TA1537 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 37E 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 37E C. 

Each trial consisted of triplicate plates of concurrent positive and negative controls and five doses of 

1-chloro-2-propanol. In the absence of toxicity, 10,000 μg/plate was selected as the high dose. All positive 

trials were repeated under the conditions that elicited the positive response. 

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. 

CHINESE HAMSTER OVARY CELL CYTOGENETICS PROTOCOLS 

Testing was performed as reported by Galloway et al. (1987). 1-Chloro-2-propanol was sent to the 

laboratory as a coded aliquot by Radian Corporation. It was tested in cultured Chinese hamster ovary (CHO) 

cells for induction of sister chromatid exchanges (SCEs) and chromosomal aberrations (Abs), both in the 

presence and absence of Aroclor 1254-induced male Sprague-Dawley rat liver S9 and cofactor mix. Cultures 

were handled under gold lights to prevent photolysis of bromodeoxyuridine-substituted DNA. Each test 

consisted of concurrent solvent and positive controls and of three doses of 1-chloro-2-propanol; the high 

dose was limited to 5,000 μg/mL. A single flask per dose was used. 

Sister Chromatid Exchange Test: In the SCE test without S9, CHO cells were incubated for 25.5 hours with 

1-chloro-2-propanol in supplemental McCoy’s 5A medium. Bromodeoxyuridine (BrdU) was added 2 hours 

after culture initiation. After 25.5 hours, the medium containing 1-chloro-2-propanol was removed and 

replaced with fresh medium plus BrdU and Colcemid, and incubation was continued for 2 hours. Cells were 

then harvested by mitotic shake-off, fixed, and stained with Hoechst 33258 and Giemsa. In the SCE test 

with S9, cells were incubated with 1-chloro-2-propanol, serum-free medium, and S9 for 2 hours. The 

medium was then removed and replaced with medium containing serum and BrdU and no 1-chloro2-propanol. Incubation proceeded for an additional 25.5 hours, with Colcemid present for the final 2 hours. 

Harvesting and staining were the same as for cells treated without S9. All slides were scored blind and those 

from a single test were read by the same person. Up to 50 second-division metaphase cells were scored for 

frequency of SCEs/cell from each dose level. Because significant chemical-induced cell cycle delay was seen 

with and without S9 at 1,700 μg/mL and greater, incubation time was lengthened to ensure a sufficient 

number of scorable (second-division metaphase) cells. 

Statistical analyses were conducted on the slopes of the dose-response curves and the individual dose points 

(Galloway et al., 1987). An SCE frequency 20% above the concurrent solvent control value was chosen as a 

statistically conservative positive response. The probability of this level of difference occurring by chance at 

one dose point is less than 0.01; the probability for such a chance occurrence at two dose points is less than 
 

 

1-Chloro-2-propanol, NTP TR 477 201 

0.001. An increase of 20% or greater at any single dose was considered weak evidence of activity; increases 

at two or more doses resulted in a determination that the trial was positive. A statistically significant trend 

(P<0.005) in the absence of any responses reaching 20% above background led to a call of equivocal. 

Chromosomal Aberrations Test: In the Abs test without S9, cells were incubated in McCoy’s 5A medium 

with 1-chloro-2-propanol for 18.5 hours; Colcemid was added and incubation continued for 2 hours. The 

cells were then harvested by mitotic shake-off, fixed, and stained with Giemsa. For the Abs test with S9, 

cells were treated with 1-chloro-2-propanol and S9 for 2 hours, after which the treatment medium was 

removed and the cells were incubated for 18.5 hours in fresh medium, with Colcemid present for the final 

2 hours. Cells were harvested in the same manner as for the treatment without S9. The harvest time for the 

Abs test was based on the cell cycle information obtained in the SCE test: because cell cycle delay was 

anticipated, the incubation period was extended from the normal duration of approximately 12 hours. 

Cells were selected for scoring on the basis of good morphology and completeness of karyotype 

(21 ± 2 chromosomes). All slides were scored blind and those from a single test were read by the same 

person. Twenty or fifty first-division metaphase cells were scored at each concentration. Normally 200 cells 

are scored, but due to the high percentage of aberrant cells observed after treatment with 1-chloro2-propanol, few metaphase cells were scored. Classes of aberrations included simple (breaks and terminal 

deletions), complex (rearrangements and translocations), and other (pulverized cells, despiralized 

chromosomes, and cells containing 10 or more aberrations). 

Chromosomal aberration data are presented as percentage of cells with aberrations. To arrive at a statistical 

call for a trial, analyses were conducted on both the dose response curve and individual dose points. For a 

single trial, a statistically significant (P#0.05) difference for one dose point and a significant trend (P#0.015) 

were considered weak evidence for a positive response; significant differences for two or more doses 

indicated the trial was positive. A positive trend test in the absence of a statistically significant increase at 

any one dose resulted in an equivocal call (Galloway et al., 1987). Ultimately, the trial calls were based on 

a consideration of the statistical analyses as well as the biological information available to the reviewers. 

DROSOPHILA MELANOGASTER TEST PROTOCOLS 

The assays for induction of sex-linked recessive lethal (SLRL) mutations and chromosomal reciprocal 

translocations (RTs) were performed with adult flies as described by Foureman et al. (1994). 1-Chloro2-propanol was supplied as a coded aliquot by Radian Corporation. 

Sex-Linked Recessive Lethal Mutation Test: 1-Chloro-2-propanol was assayed in the SLRL test by feeding 

for 3 days to adult Canton-S wild-type males no more than 24 hours old at the beginning of treatment. 

Because no response was obtained, 1-chloro-2-propanol was retested by injection into adult males. 

To administer 1-chloro-2-propanol by injection, a glass Pasteur pipette was drawn out in a flame to a 

microfine filament, and the tip was broken off to allow delivery of the test solution. Injection was performed 

either manually, by attaching a rubber bulb to the other end of the pipette and forcing through sufficient 

solution (0.2 to 0.3 μL) to slightly distend the abdomen of the fly, or by attaching the pipette to a 

microinjector that automatically delivered a calibrated volume. Flies were anesthetized with ether and 

immobilized on a strip of tape. Injection into the thorax, under the wing, was performed with the aid of a 

dissecting microscope. 

Toxicity tests were performed to set concentrations of 1-chloro-2-propanol at a level that would induce 

30% mortality after 72 hours of feeding or 24 hours after injection, while keeping induced sterility at an 

acceptable level. Canton-S males were allowed to feed for 72 hours on a solution of 1-chloro-2-propanol in 

5% sucrose. In the injection experiments, 24- to 72-hour old Canton-S males were treated with a solution of 
 

202 1-Chloro-2-propanol, NTP TR 477 

1-chloro-2-propanol dissolved in saline and allowed to recover for 24 hours. A concurrent saline control 

group was also included. Treated males were mated to three Basc females for 3 days and were given fresh 

females at 2-day intervals to produce three matings of 3, 2, and 2 days (in each case, sample sperm from 

successive matings was treated at successively earlier postmeiotic stages). F1 heterozygous females were

mated with their siblings and then placed in individual vials. F1 daughters from the same parental male were

kept together to identify clusters. (A cluster occurs when a number of mutants from a given male result from 

a single spontaneous premeiotic mutation event and is identified when the number of mutants from that male 

exceeds the number predicted by a Poisson distribution.) If a cluster was identified, all data from the male in 

question were discarded. Presumptive lethal mutations were identified as vials containing fewer than 5% of 

the expected number of wild-type males after 17 days; these were retested to confirm the response. 

SLRL data were analyzed by simultaneous comparison with the concurrent and historical controls (Mason 

et al., 1992) using a normal approximation to the binomial test (Margolin et al., 1983). A test result was 

considered positive if the P value was less than or equal to 0.01 and the mutation frequency in the tested 

group was greater than 0.10% or if the P value was less than or equal to 0.05 and the frequency in the 

treatment group was greater than 0.15%. A test was considered to be inconclusive if the P value was 

between 0.05 and 0.01 but the frequency in the treatment group was between 0.10% and 0.15% or if the 

P value was between 0.10 and 0.05 but the frequency in the treatment group was greater than 0.10%. A test 

was considered negative if the P value was greater than or equal to 0.10 or if the frequency in the treatment 

group was less than 0.10%. 

Reciprocal Translocation Test: Because the injection route produced a positive result in the SLRL test, 

1-chloro-2-propanol was assayed for induction of RTs using the same method of exposure. The treatment 

regimen was essentially the same as that for the SLRL test, except that Canton-S males were mated en masse 

to marker (bw;st) females. The females were transferred to fresh medium every 3 to 4 days for a period of 

about 3 weeks to produce a total of six broods. The results of the SLRL test were used to determine the 

germ cell stages most likely to be affected by 1-chloro-2-propanol. F1 heterozygous males were backcrossed

individually to bw;st females, and the F2 progeny were screened for pseudolinkage, which results from the

induction of a translocation in a germ cell of the parental male. Flies suspected of carrying RTs were 

retested to confirm the findings. The translocation data were compared to the concurrent and historical 

controls, and significance was analyzed according to the conditional binomial response of Kastenbaum and 

Bowman (1970). 

MOUSE PERIPHERAL BLOOD MICRONUCLEUS TEST PROTOCOL 

A detailed discussion of this assay is presented in MacGregor et al. (1990). At the end of the 14-week 

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 a 

chromatin-specific fluorescent dye mixture of Hoechst 33258/pyronin Y (MacGregor et al., 1983) and 

coded. Slides were scanned to determine the frequency of micronuclei in 2,000 polychromatic erythrocytes 

(PCEs) and 10,000 normochromatic erythrocytes (NCEs) in each of 10 animals per exposure group. 

Log transformation of the NCE data, testing for normality by the Shapiro-Wilk test, and testing for 

heterogeneity of variance by Cochran’s test were performed before statistical analyses. The frequency of 

micronucleated cells among NCEs was determined by analysis of variance with the SAS GLM procedure. 

The NCE data for each exposure group were compared with the concurrent solvent control by Student’s 

t-test. The frequency of micronucleated cells among PCEs was analyzed by the Cochran-Armitage trend test, 

and individual exposure groups were compared to the concurrent solvent control by Kastenbaum-Bowman’s 

binomial test. The percentage of PCEs among total erythrocytes was determined by an analysis of variance 

on ranks (classed by sex), and individual exposure groups were compared with the concurrent solvent 

control with a t-test on ranks. 
1-Chloro-2-propanol, NTP TR 477 203 

RESULTS 

1-Chloro-2-propanol is genotoxic in vitro. It was tested for mutation induction in Salmonella typhimurium in 

three studies at two laboratories, and all test responses were similar (Table E1; Zeiger et al., 1987). In 

strain TA100, equivocal responses were obtained in the absence of S9; with S9, equivocal or weakly positive 

mutagenic activity was seen. Clearly positive, reproducible responses were seen across studies with strain 

TA1535, with and without S9. No mutagenic activity was detected with strain TA97, TA98, or TA1537, 

with or without S9. 

1-Chloro-2-propanol induced marked increases in SCEs (Table E2) and Abs (Table E3) in cultured CHO 

cells, with and without S9. Cell cycle delay was induced in cultures treated with concentrations of 

1,700 μg/mL 1-chloro-2-propanol and greater; to obtain sufficient cells for scoring, incubation time was 

extended to up to 34 hours in the SCE test. Experimental design normally calls for no more than 33 hours 

of exposure to BrdU, but, because increases in SCE frequencies were also seen at standard harvest times, in 

the absence of S9, the delayed harvest results were accepted as confirmatory of the results seen in Trial 1. In 

the SCE test with S9, the only concentration that produced a significant increase in SCEs was the 

1,700 μg/mL dose, which employed a culture time of 33.5 hours. However, because the response was so 

strong, it was accepted that even if BrdU exposure contributed to some extent to the induction of SCEs, 

much of the increase was due to exposure to 1-chloro-2-propanol. This trial was not repeated because it was 

apparent from the combined results of the three trials that 1-chloro-2-propanol induced SCEs in cultured 

CHO cells. In the cultured CHO cell Abs test with 1-chloro-2-propanol, fewer than the usual 200 cells per 

concentration were scored because a marked increase in aberrations as well as in the percentage of cells with 

aberrations were observed. 

The chromosomal effects seen in vitro were not apparent in the in vivo studies, but induction of gene 

mutations was observed. Positive results were obtained in the Drosophila melanogaster test for induction of 

SLRL mutations in germ cells of male flies administered 1-chloro-2-propanol via injection (Table E4; 

Foureman et al., 1994). However, a subsequent test for induction of reciprocal chromosomal translocations 

in germ cells of male D. melanogaster yielded negative results (Table E5; Foureman et al., 1994). 

Additional negative results were obtained for chromosomal effects in mice. No increase in the frequency of 

micronucleated erythrocytes was observed in peripheral blood of male or female mice administered 1-chloro2-propanol in drinking water for 14 weeks (Table E6). 
204 1-Chloro-2-propanol, NTP TR 477 

TABLE E1 

Mutagenicity of 1-Chloro-2-propanol in Salmonella typhimuriuma 

Revertants/plateb 

Strain Dose 

(μg/plate) Trial 1 

!S9 

Trial 2 

+10% hamster S9 

Trial 1 Trial 2 

+10% rat S9 

Trial 1 Trial 2 

Study 1 Performed at SRI International 

TA100 0 119 ± 3.8 120 ± 4.4 

100 120 ± 7.8 

333 117 ± 4.7 147 ± 7.1 

1,000 116 ± 3.5 

1,666 153 ± 4.3 

3,333 144 ± 21.7 147 ± 2.8 

6,666 160 ± 6.0 

10,000 188 ± 4.9 172 ± 10.4 

129 ± 3.8 

144 ± 10.1 

143 ± 11.4 

142 ± 2.4 

133 ± 4.4 

151 ± 2.3 

128 ± 5.9 

124 ± 3.8 

129 ± 6.2 

158 ± 4.7 

195 ± 11.8 

201 ± 11.7 

133 ± 4.8 

131 ± 3.2 

126 ± 5.9 

136 ± 3.1 

162 ± 13.0 

197 ± 7.4 

136 ± 4.9 

146 ± 7.8 

138 ± 13.7 

161 ± 8.7 

200 ± 5.2 

227 ± 9.3 

Trial summary 

Positive controlc Equivocal 

229 ± 34.4 

Equivocal 

274 ± 6.4 

Negative 

790 ± 67.8 

Weakly positive 

718 ± 68.9 

Equivocal 

326 ± 7.6 

Weakly positive 

352 ± 26.3 

TA1535 0 

100 

333 

1,000 

1,666 

3,333 

6,666 

10,000 

14 ± 2.3 

21 ± 5.2 

17 ± 2.3 

18 ± 5.8 

29 ± 0.9 

58 ± 9.7 

19 ± 3.8 

30 ± 3.4 

54 ± 6.0 

69 ± 6.3 

93 ± 5.2 

122 ± 4.6 

9 ± 2.3 

12 ± 1.7 

7 ± 2.8 

16 ± 0.6 

26 ± 5.5 

41 ± 1.8 

10 ± 2.7 

12 ± 1.8 

21 ± 1.5 

37 ± 4.4 

78 ± 2.2 

108 ± 4.2 

8 ± 2.0 

11 ± 1.5 

7 ± 0.9 

16 ± 1.3 

21 ± 3.2 

47 ± 5.2 

9 ± 2.6 

14 ± 2.9 

22 ± 2.2 

60 ± 6.2 

73 ± 8.5 

112 ± 9.0 

Trial summary 

Positive control 

Positive 

134 ± 10.7 

Positive 

236 ± 12.4 

Positive 

161 ± 9.0 

Positive 

216 ± 9.7 

Positive 

152 ± 4.3 

Positive 

172 ± 8.7 

TA1537 0 

100 

333 

1,000 

3,333 

10,000 

5 ± 1.2 

5 ± 0.6 

5 ± 1.5 

6 ± 1.3 

7 ± 2.6 

5 ± 0.7 

7 ± 1.2 

4 ± 0.9 

4 ± 0.9 

3 ± 0.9 

5 ± 0.6 

3 ± 1.2 

4 ± 1.0 

6 ± 0.7 

5 ± 0.9 

6 ± 1.7 

5 ± 0.3 

3 ± 0.3 

Trial summary 

Positive control 

Negative 

143 ± 13.3 

Negative 

253 ± 40.8 

Negative 

160 ± 10.6 

TA98 0 

100 

333 

1,000 

3,333 

10,000 

17 ± 2.4 

15 ± 3.5 

16 ± 1.2 

13 ± 2.3 

20 ± 2.7 

14 ± 3.5 

25 ± 3.0 

33 ± 4.8 

24 ± 3.8 

26 ± 3.5 

19 ± 1.2 

20 ± 5.2 

17 ± 1.7 

30 ± 7.1 

30 ± 5.2 

31 ± 3.2 

22 ± 2.3 

25 ± 2.2 

Trial summary 

Positive control 

Negative 

913 ± 42.2 

Negative 

620 ± 90.5 

Negative 

255 ± 12.2 
1-Chloro-2-propanol, NTP TR 477 205 

TABLE E1 

Mutagenicity of 1-Chloro-2-propanol in Salmonella typhimurium 

Revertants/plate 

Strain Dose 

(μg/plate) Trial 1 

!S9 

Trial 2 

+10% hamster S9 

Trial 1 Trial 2 

+10% rat S9 

Trial 1 Trial 2 

Study 2 Performed at SRI International 

TA100 0 127 ± 7.5 

100 135 ± 16.5 

333 131 ± 8.3 

1,000 127 ± 5.9 

3,333 130 ± 1.3 

10,000 149 ± 10.7 

153 ± 3.5 

135 ± 12.4 

136 ± 8.1 

144 ± 14.1 

161 ± 10.4 

159 ± 15.8 

124 ± 14.5 

134 ± 6.7 

123 ± 3.3 

132 ± 4.6 

148 ± 5.0 

177 ± 5.5 

Trial summary 

Positive control 

Negative 

444 ± 11.0 

Negative 

875 ± 68.8 

Equivocal 

719 ± 59.3 

TA1535 0 

100 

333 

1,000 

3,333 

6,666 

10,000 

20 ± 1.5 

30 ± 3.3 

37 ± 2.4 

39 ± 2.7 

37 ± 0.6 

64 ± 2.5 

34 ± 0.7 

29 ± 2.8 

29 ± 0.3 

34 ± 2.4 

49 ± 5.0 

67 ± 15.0 

13 ± 2.4 

10 ± 2.1 

11 ± 0.9 

14 ± 0.9 

27 ± 2.3 

39 ± 4.7 

11 ± 2.2 

11 ± 3.0 

16 ± 2.6 

40 ± 6.4 

53 ± 0.9 

55 ± 1.2 

15 ± 2.2 

9 ± 1.2 

10 ± 4.3 

13 ± 1.0 

17 ± 1.7 

48 ± 1.7 

13 ± 3.2 

11 ± 1.8 

13 ± 1.0 

21 ± 2.0 

42 ± 5.5 

52 ± 1.5 

Trial summary 

Positive control 

Weakly positive 

344 ± 18.5 

Equivocal 

347 ± 43.9 

Positive 

331 ± 11.7 

Positive 

134 ± 10.1 

Equivocal 

217 ± 1.3 

Positive 

89 ± 4.0 

TA97 0 

100 

333 

1,000 

3,333 

10,000 

152 ± 22.8 

151 ± 15.5 

142 ± 14.7 

139 ± 5.5 

148 ± 10.1 

156 ± 4.5 

179 ± 16.9 

186 ± 18.0 

196 ± 4.5 

178 ± 17.9 

69 ± 24.0 

0 ± 0.0d 

206 ± 4.4 

199 ± 7.8 

191 ± 12.2 

209 ± 5.5 

214 ± 15.5 

175 ± 20.0 

Trial summary 

Positive control 

Negative 

479 ± 28.3 

Negative 

628 ± 35.9 

Negative 

589 ± 27.5 

TA98 0 

100 

333 

1,000 

3,333 

10,000 

24 ± 3.8 

14 ± 1.5 

25 ± 3.8 

22 ± 2.3 

22 ± 1.0 

17 ± 1.2 

32 ± 3.6 

29 ± 1.7 

25 ± 0.9 

29 ± 4.9 

26 ± 1.5 

18 ± 2.0 

41 ± 4.9 

28 ± 4.9 

34 ± 3.4 

28 ± 2.5 

24 ± 1.2 

27 ± 0.6 

Trial summary 

Positive control 

Negative 

746 ± 39.0 

Negative 

577 ± 51.1 

Negative 

424 ± 11.4 
206 1-Chloro-2-propanol, NTP TR 477 

TABLE E1 

Mutagenicity of 1-Chloro-2-propanol in Salmonella typhimurium 

Revertants/plate 

Strain Dose !S9 +10% hamster S9 +10% rat S9 

(μg/plate) Trial 1 Trial 2 Trial 1 Trial 2 Trial 1 Trial 2 

Study 3 Performed at Microbiological Associates, Inc. 

TA100 0 89 ± 7.3 115 ± 8.0 85 ± 7.3 112 ± 14.9 93 ± 2.4 93 ± 5.5 

100 100 ± 5.3 97 ± 4.1 90 ± 0.7 94 ± 8.8 94 ± 7.9 101 ± 5.1 

333 102 ± 4.1 113 ± 5.3 104 ± 6.4 127 ± 6.4 101 ± 4.0 104 ± 2.5 

1,000 98 ± 3.2 106 ± 3.3 93 ± 4.3 122 ± 2.6 85 ± 1.9 122 ± 7.7 

3,333 111 ± 3.5 141 ± 8.4 112 ± 4.3 156 ± 6.1 120 ± 6.2 149 ± 13.4 

6,667 128 ± 5.0 151 ± 4.7 176 ± 5.9 

10,000 194 ± 0.7 195 ± 6.4	 163 ± 7.6 

Trial summary Equivocal Equivocal Equivocal Equivocal Equivocal Weakly positive 

Positive control 343 ± 19.5 329 ± 7.3 721 ± 11.4 363 ± 20.8 452 ± 20.0 466 ± 47.8 

TA1535 0 18 ± 0.3 17 ± 2.2 13 ± 2.2 9 ± 1.0 7 ± 1.5 6 ± 0.3 

100 19 ± 1.9 21 ± 3.5 10 ± 1.2 15 ± 4.0 10 ± 1.9 10 ± 2.1 

333 21 ± 2.0 25 ± 3.8 14 ± 3.2 19 ± 0.9 10 ± 0.6 13 ± 1.5 

1,000 29 ± 3.7 25 ± 1.3 22 ± 3.0 23 ± 1.8 22 ± 1.5 21 ± 1.7 

3,333 51 ± 2.9 62 ± 3.5 51 ± 1.2 67 ± 3.5 50 ± 2.2 44 ± 3.5 

6,667 67 ± 3.2 110 ± 2.8 83 ± 3.5 65 ± 2.1 

10,000 92 ± 2.3 125 ± 10.8 

Trial summary Positive Positive Positive Positive Positive Positive 

Positive control 199 ± 11.4 171 ± 16.5 79 ± 7.0 69 ± 11.8 116 ± 8.1 124 ± 2.0 

TA97 0 102 ± 9.2 135 ± 4.2 102 ± 7.8 

100 85 ± 12.1 108 ± 8.1 130 ± 7.2 

333 71 ± 9.8 97 ± 8.5 104 ± 3.5 

1,000 76 ± 1.0 68 ± 4.2 79 ± 9.2 

3,333 81 ± 11.3 97 ± 4.1 111 ± 10.0 

6,667 17 ± 4.3 104 ± 9.3 

10,000 102 ± 0.6 

Trial summary Negative Negative Negative 

Positive control 276 ± 16.2 783 ± 65.7 848 ± 48.6 

TA98 0 18 ± 2.0 22 ± 4.4 27 ± 3.2 

100 14 ± 4.3 26 ± 0.6 21 ± 2.2 

333 19 ± 2.0 28 ± 0.0 21 ± 3.9 

1,000 18 ± 4.5 17 ± 0.3 21 ± 0.9 

3,333 20 ± 1.8 17 ± 2.6 20 ± 4.1 

6,667 14 ± 1.5 27 ± 1.2 

10,000 16 ± 0.9 

Trial summary Negative Negative Negative 

Positive control 117 ± 0.9 115 ± 5.9 157 ± 10.1 

a The detailed protocol and these data are presented in Zeiger et al. (1987). 0 μg/plate was the solvent control. b	 Revertants are presented as mean ± standard error from three plates. 

The positive controls in the absence of metabolic activation were sodium azide (TA100 and TA1535), 9-aminoacridine (TA97 and 

TA1537), and 4-nitro-o-phenylenediamine (TA98). The positive control for metabolic activation with all strains was 2-aminoanthracene. d	 Slight toxicity 

c 
1-Chloro-2-propanol, NTP TR 477 207 

TABLE E2 

Induction of Sister Chromatid Exchanges in Chinese Hamster Ovary Cells by 1-Chloro-2-propanola 

Compound 

Concentration 

(μg/mL) 

Total 

Cells 

Scored 

No. of 

Chromosomes No. of 

SCEs 

SCEs/ 

Chromosome SCEs/ 

Cell 

Hrs 

in BrdU 

Relative 

Change of SCEs/ 

Chromosomeb 

(%) 

!S9 

Trial 1 

Summary: Positive 

Mediumc 50 1,025 366 0.35 7.3 25.5 

Mitomycin-Cd 0.001 

0.01 

50 

5 

1,035 

104 

637 

236 

0.61 

2.26 

12.7 

47.2 

25.5 

25.5 

72.36 

535.51 

1-Chloro-2-propanol 167 

500 

1,700 

50 

25 

25 

1,051 

517 

527 

506 

543 

675 

0.48 

1.05 

1.28 

10.1 

21.7 

27.0 

25.5 

25.5 

33.5 

34.83* 

194.14* 

258.71* 

P#0.000e 

Trial 2 

Summary: Positive 

Medium 50 1,052 357 0.33 7.1 26.0 

Mitomycin-C 0.001 

0.01 

50 

5 

1,050 

105 

599 

223 

0.57 

2.12 

12.0 

44.6 

26.0 

26.0

68.11 

525.84 

1-Chloro-2-propanol 1,700 

3,000 

4,000 

10 

5 

5 

211 

105 

106 

309 

175 

185 

1.46 

1.66 

1.74 

30.9 

35.0 

37.0 

34.0 

34.0 

34.0 

331.55* 

391.13* 

414.30* 

P#0.000 

+S9 

Summary: Positive 

Medium 50 1,039 398 0.38 8.0 25.5 

Cyclophosphamided 0.4 

2 

50 

5 

1,046 

105 

626 

218 

0.59 

2.07 

12.5 

43.6 

25.5 

25.5 

56.23 

442.00 

1-Chloro-2-propanol 167 

500 

1,700 

50 

50 

50 

1,046 

1,041 

1,041 

373 

431 

664 

0.35 

0.41 

0.63 

7.5 

8.6 

13.3 

25.5 

25.5 

33.5 

–6.91 

8.08 

66.51* 

P#0.000 

* Positive response ( 20% increase over solvent control) a Study was performed at Litton Bionetics, Inc. A detailed description of the protocol is presented in Galloway et al. (1987). SCEùsister 

chromatid exchange; BrdUùbromodeoxyuridine b SCEs/chromosome in treated cells versus SCEs/chromosome in solvent control cells 

Solvent control 

d Positive control e Significance of SCEs/chromosome tested by the linear regression trend test versus log of the dose 

c 
208 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE E3 

Induction of Chromosomal Aberrations in Chinese Hamster Ovary Cells by 1-Chloro-2-propanola 

Concentration Total Cells Number Aberrations/ Cells with 

Compound (μg/mL) Scored of Aberrations Cell Aberrations (%) 

!S9 

Harvest time: 20.5 hoursb 

Summary: Positive 

Mediumc	 100 3 0.03 3.0 

Mitomycin-Cd	 0.05 50 27 0.54 32.0 

0.08 25 22 0.88 52.0 

1-Chloro-2-propanol	 3,000 50 5 0.10 10.0 

4,000 50 11 0.22 18.0* 

5,000 50 12 0.24 22.0* 

P#0.000e 

+S9 

Harvest time: 20.5 hoursb 

Summary: Positive 

Medium	 200 10 0.05 4.0 

Cyclophosphamided	 6.25 200 57 0.29 22.0 

12.5 25 18 0.72 40.0 

1-Chloro-2-propanol	 3,000 20 47 2.35 75.0* 

4,000 20 74 3.70 95.0* 

5,000 20 79 3.95 90.0* 

P#0.000 

*	 Positive response (P#0.05) versus the solvent control a Study was performed at Litton Bionetics, Inc. The detailed protocol is presented in Galloway et al. (1987). b	 Due to cell cycle delay, harvest time was extended to maximize the number of first-division metaphase cells available for analysis. 

Solvent control 

d Positive control e Significance of percent cells with aberrations tested by the linear regression trend test versus log of the dose 
209 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE E4 

Induction of Sex-Linked Recessive Lethal Mutations in Drosophila melanogaster by 1-Chloro-2-propanola 

Route of 

Exposure 

Dose 

(ppm) 

Incidence of 

Death (%) 

Incidence of 

Sterility (%) 

No. of Lethals/No. of X Chromosomes Tested 

Mating 1 Mating 2 Mating 3 Totalb 

Feed 200 

0 

16 5 0/1,948 

3/3,060 

1/1,645 

9/2,972 

1/1,556 

6/2,679 

2/5,149 (0.04%) 

18/8,711 (0.21%) 

Pù0.994c 

Injection 1,000 

0 

24 12 3/2,044 

1/2,001 

3/1,607 

1/1,967 

3/1,735 

1/1,988 

9/5,386 (0.17%) 

3/5,956 (0.05%) 

Pù0.028c 

a Study was performed at the University of Wisconsin, Madison. The detailed protocol and these data are presented in Foureman et al. 

(1994). The mean mutant frequency from 518 negative control experiments is 0.074% (Mason et al., 1992). b	 Total number of lethal mutations/total number of X chromosomes tested for three mating trials 

Significance of total number of lethal mutations/total number of X chromosomes tested by a normal approximation to the binomial test 

(Margolin et al., 1983). 

TABLE E5 

Induction of Reciprocal Translocations in Drosophila melanogaster by 1-Chloro-2-propanola 

Route of 

Exposure 

Dose 

(ppm) 1 

Translocations/Total F Tested 1 

2 3 4 5 6 

No. of 

Tests 

Total 

No. of 

Translocations 

Total 

Translocations 

(%) 

Injection 1,000 0/2,268 1/1,941 0/768 0/308 0/26 0/9 5,312 1 0.00 

Concurrent control 77,700 1 0.00 

Historical control 116,163 2 0.00 

Pù0.126 

a Study was performed at the University of Wisconsin, Madison. The detailed protocol and these data are presented in Foureman et al. 

(1994). Results were not significant at the 5% level (Kastenbaum and Bowman, 1970). 
210 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE E6 

Frequency of Micronuclei in Mouse Peripheral Blood Erythrocytes Following Treatment 

with 1-Chloro-2-propanol in Drinking Water for 14 Weeksa 

Compound Dose 

(ppm) 

Number of 

Mice 

Micronucleated Cells/1,000 Cellsb 

PCEs NCEs PCEsb (%) 

Male 

Waterc 10 1.21 ± 0.19 1.34 ± 0.13 2.19 ± 0.11 

1-Chloro-2­ 33 

100 

330 

1,000 

3,000 

9 

10 

9 

10 

10 

2.08 ± 0.53 

1.79 ± 0.26 

1.26 ± 0.17 

1.41 ± 0.16 

1.81 ± 0.36 

Pù0.290d 

1.42 ± 0.12 

1.43 ± 0.13 

1.11 ± 0.06 

1.40 ± 0.09 

1.31 ± 0.08 

Pù0.635 

2.35 ± 0.14 

2.07 ± 0.08 

2.39 ± 0.16 

2.17 ± 0.09 

2.59 ± 0.12 

Female 

Water 10 2.15 ± 0.38 0.98 ± 0.08 1.99 ± 0.12 

1-Chloro-2­ 33 

100 

330 

1,000 

3,000 

10 

10 

10 

10 

10 

1.12 ± 0.26 

1.64 ± 0.30 

1.24 ± 0.26 

1.58 ± 0.34 

1.51 ± 0.30 

Pù0.559 

1.20 ± 0.08 

1.12 ± 0.07 

1.03 ± 0.09 

1.03 ± 0.07 

1.09 ± 0.05 

Pù0.503 

2.05 ± 0.11 

2.08 ± 0.16 

2.11 ± 0.19 

1.97 ± 0.08 

2.45 ± 0.09 

a Study was performed at the United States Department of Agriculture. The detailed protocol is presented in MacGregor et al. (1990). 

PCEùpolychromatic erythrocyte; NCEùnormochromatic erythrocyte. b Mean ± standard error 

Vehicle control 

d Significance of micronucleated cells/1,000 cells tested by the one-tailed trend test, significant at P#0.025 (Margolin et al., 1990) 
 

 

211 

APPENDIX F 

CONTINUOUS BREEDING STUDY 

IN SPRAGUE-DAWLEY RATS 

INTRODUCTION ............................................................ 212 

MATERIALS AND METHODS .................................................... 212 

RESULTS 214 

TABLE F1 Fertility, Reproductive Performance, Length of Gestation, 

and Body Weight Data for F and F Sprague-Dawley Rats 0 1 

in the Continuous Breeding Study of 1-Chloro-2-propanol ..................... 215 

TABLE F2 Litter and Body Weight Data for F Sprague-Dawley Rat Pups 1 

in the Continuous Breeding Study of 1-Chloro-2-propanol ..................... 217 

TABLE F3 Survival and Body Weight Data for F Sprague-Dawley Rat Pups (Final Litter) 1 

in the Continuous Breeding Study of 1-Chloro-2-propanol ..................... 218 

TABLE F4 Fertility, Reproductive Performance, Length of Gestation, 

and Body Weight Data for F and F Sprague-Dawley Rats 1 2 

in the Offspring Assessment Phase of the Continuous Breeding Study 

of 1-Chloro-2-propanol ............................................. 219 

TABLE F5 Organ Weights and Organ-Weight-to-Body-Weight Ratios 

for F Sprague-Dawley Rats in the Offspring Assessment Phase 1 

of the Continuous Breeding Study of 1-Chloro-2-propanol ..................... 220 

TABLE F6 Sperm Parameters and Estrous Cycle Characterization 

for F Sprague-Dawley Rats in the Offspring Assessment Phase 1 

of the Continuous Breeding Study of 1-Chloro-2-propanol .................... 221 
212 1-Chloro-2-propanol, NTP TR 477 

CONTINUOUS BREEDING STUDY 

IN SPRAGUE-DAWLEY RATS 

INTRODUCTION 

The potential reproductive toxicity of 1-chloro-2-propanol was evaluated by Research Triangle Institute 

(Research Triangle Park, NC) in Sprague-Dawley rats because evidence in the literature suggests that 

exposure to 1-chloro-2-propanol may have reproductive effects (NTP, 1987b) and because data collected at 

the end of the 14-week NTP study in F344/N rats indicated chemical-related effects in male rats 

(Appendix I). 

Reproductive assessment by the methods presented in Lamb (1985), NTP (1987b), and Heindel et al., (1989) 

consists of four phases: dose setting, continuous breeding, identification of the affected sex (crossover 

mating trial), and offspring assessment. A 2-week dose-setting phase is conducted to determine exposure 

concentrations for the continuous breeding phase. During the continuous breeding phase, the effects of the 

maximum tolerated exposure concentration estimated in the dose-setting phase and two lower exposure 

concentrations on fertility and reproduction of first-generation (F ) animals are determined. If fertility is 0 

significantly affected during the continuous breeding phase, crossover mating trials are performed to 

determine if males or females, or both, are affected. Offspring assessment includes evaluation of 

reproductive performance of second-generation (F 1 ) animals from the final litters of the continuous breeding

phase. The F animals are raised to sexual maturity while receiving the same exposure concentrations as 1 

their parents, are mated, and are allowed to deliver the third generation (F ) offspring. 2 

Because fertility was not significantly affected during the continuous breeding phase of the 1-chloro2-propanol study, crossover mating trials were not conducted. The 0 and 1,300 ppm groups of the F1 

generation were assessed for fertility measures in the offspring assessment phase. 

MATERIALS AND METHODS 

Technical grade 1-chloro-2-propanol was obtained from Eastman Kodak Laboratory Chemicals (Rochester, 

NY) in one lot (B15), which was also used in the 14-day, 14-week, and 2-year studies conducted at SRI 

International (Menlo Park, CA) and TSI Mason Laboratories (Worcester, MA). Results of purity and 

stability analyses of lot B15 are given in Appendix J. Dose formulations of 1-chloro-2-propanol in deionized 

water were prepared at least every 3 weeks, and analyses by the study laboratory indicated that the dose 

formulations were within 10% of the target concentration. 

Male and female VAF Crl:CD BR outbred Sprague-Dawley albino rats were obtained from Charles River 

Breeding Laboratories, Inc. (Portage, MI). Upon receipt, serum samples were collected from sentinel male 

and female rats, and the serum samples were analyzed for antibody titers to rodent viruses. All sera were 

negative. Rats were quarantined for approximately 2 weeks and were 10 weeks old at the start of the dosesetting phase and the continuous breeding phase. Rats were housed two per cage by sex during quarantine 

and the dose-setting phase. NIH-07 open formula pelleted diet and deionized water containing the 

appropriate concentrations of 1-chloro-2-propanol were available ad libitum for all phases of the study. 

For the 2-week dose-setting phase, groups of eight male and eight female rats received 0, 1,000, 2,000, 

4,000, 6,000, or 8,000 ppm 1-chloro-2-propanol in drinking water. Survival, clinical findings, body 

weights, and water consumption were recorded. 

During the continuous breeding phase, rats were housed two per cage by sex for 1 week while being exposed 

to 0, 300, 650, or 1,300 ppm 1-chloro-2-propanol; rats were then housed in breeding pairs (40 control pairs 
1-Chloro-2-propanol, NTP TR 477 213 

and 20 dosed pairs per group) for 112 days during exposure. After the mating period, rats continued to be 

exposed while housed separately for approximately 21 days to allow delivery of the final litter of pups. 

Clinical observations, water consumption, pregnancy index, litters per pair, cumulative number of days to 

litter, dam body weights, live pups per litter, proportion of pups born alive, sex of live pups, and pup body 

weights were recorded. For the last litter, pup survival and body weights were recorded on lactation days 0, 

4, 7, 14, and 21. 

To assess the offspring of exposed rats, the final litter of pups born to each F0 rat in the 0 and 1,300 ppm

groups was raised to sexual maturity. After weaning, siblings were housed two per cage by sex and were 

administered the same exposure concentrations as their parents. At sexual maturity (88 ± 10 days of age), 

nonsibling male and female rats from within the same exposure group (20 pairs per group) were housed as 

breeding pairs for 7 days. Female rats were examined for a copulatory plug or sperm, and rats were then 

housed individually through the delivery of the pups. Clinical observations, water consumption, mating 

index, pregnancy index, fertility index, dam body weights, length of gestation, live pups per litter, 

proportion of pups born alive, sex of live pups, and pup body weights were recorded. For the 12 days 

before necropsy of the F1 rats, estrous cycle data were collected. At necropsy, epididymal spermatozoal data

were collected, and the following organs were weighed: right cauda epididymis, right epididymis, kidneys, 

liver, right ovary, prostate gland, seminal vesicles, and right testis. Selected organs were fixed in 10% 

neutral buffered formalin or Bouin’s fixative (ovaries only) and embedded in plastic or paraffin. Sections 

were stained with hematoxylin and eosin (testis only) or PAS and hematoxylin. 

For data expressed as proportions (fertility, mating, and pregnancy indices), the Cochran-Armitage test 

(Armitage, 1971) was used to test for exposure-related trends, and pairwise comparisons were performed 

with a chi-square test (Conover, 1971). The number of litters and the number of live pups per litter were 

determined per fertile pair and then exposure group means were determined. The proportion of live pups 

was defined as the number of pups born alive divided by the total number of pups produced by each pair. 

The sex ratio was expressed as the number of male pups born alive divided by the total number of live pups 

born to each fertile pair. 

Exposure group means for data with skewed distributions were analyzed by the nonparametric multiple 

comparisons methods of Shirley (1977) or Dunn (1964). Jonkheere’s test (Jonkheere, 1954) or Wilcoxon’s 

test (Conover, 1971) was used to assess the significance of exposure-response trends and to determine 

whether a trend-sensitive test (Shirley’s) was more appropriate for pairwise comparisons than a test that does 

not assume a monotonic exposure-related trend (Dunn’s). Multiple comparisons in the offspring assessment 

phase were made with Dunn’s test or Wilcoxon’s test (Conover, 1971). 

Analysis of covariance (Neter and Wasserman, 1974), with average litter size as the covariate, was 

performed to remove the potential effect of number of pups per litter on average pup weight. Analysis of 

covariance was also used to adjust organ weights for total body weight. Least-square estimates of exposure 

group means adjusted for litter size were tested for overall equality by an F-test and for pairwise equality by 

Dunnett’s test (Dunnett, 1955) or a t-test; these tests were performed on the data from males, females, and 

males and females (combined) to analyze potential sex differences. Unadjusted body and organ weights were 

analyzed by the Kruskal-Wallis (Kruskal and Wallis, 1952) and the Mann-Whitney-U test (Mann and 

Whitney, 1947). 

For vaginal cytology data, 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. 
214 1-Chloro-2-propanol, NTP TR 477 

RESULTS 

All rats survived to the end of the dose setting study. Final mean body weights were less in 8,000 ppm 

males and females than in the controls; rats in these two groups lost weight during the study. Water 

consumption decreased with increasing exposure concentration throughout the study. Estimated daily 

exposure concentrations ranged from 0.9 to 0.16 g 1-chloro-2-propanol/kg body weight. Based on the 

adverse effects on mean body weights and water consumption, the exposure concentrations selected for the 

continuous breeding phase were 0, 300, 650, and 1,300 ppm. 

During the continuous breeding phase, exposure to 1-chloro-2-propanol did not cause significant 

reproductive toxicity in rats (Table F1). All exposed and control pairs except one 300 ppm pair were fertile; 

all pairs exposed to 1,300 ppm delivered five litters. The average numbers of litters per pair of all exposed 

groups were similar to that of the controls. The cumulative number of days to litter for the 1,300 ppm group 

was slightly but significantly greater than that of the controls for litter 5. At delivery of each litter, the mean 

body weights of dams in the 650 ppm group (except for the second litter) and the 1,300 ppm group were 

significantly less than those of the controls. Mean body weights of litter 5 dams in the 650 ppm exposure 

group were significantly less than those of the controls from lactation days 0 to 14, and the mean body 

weights of dams in the 1,300 ppm group were significantly less than those of the controls throughout 

lactation. Total and adjusted pup weights, sex ratios, and number of live pups per litter were similar to those 

of the controls for all exposed groups for all litters (Tables F1 and F2). 

The survival of the final litters of exposed F1 pups was similar to that of the controls throughout lactation

(Table F3). Male and female F1 pup weights were significantly less than those of the controls in the

1,300 ppm group on days 7, 14, and 21 and in the 650 ppm group on days 14 and 21 (Table F3). 

During the offspring assessment phase of the continuous breeding study, the mean body weight of dams in 

the 1,300 ppm group at delivery was significantly less than that of the controls (Table F4). Exposure to 

1,300 ppm 1-chloro-2-propanol did not affect the number of live pups per litter, the sex ratio, or pup weights 

(Table F4) or organ weights (Table F5). The percentage of abnormal sperm was significantly greater in 

1,300 ppm male rats than in the controls (Table F6). There were no significant differences in estrous cycle 

parameters between control and 1,300 ppm females. 
 

1-Chloro-2-propanol, NTP TR 477 215 

TABLE F1 

Fertility, Reproductive Performance, Length of Gestation, and Body Weight Data a for F and F Sprague-Dawley Rats in the Continuous Breeding Study of 1-Chloro-2-propanol 0 1 

0 ppm 300 ppm 650 ppm 1,300 ppm 

F0 Adult Data

Pregnancy indexb 

Litter 1 40/40 (100%) 18/19 (95%) 20/20 (100%) 20/20 (100%) 

Litter 2 40/40 (100%) 18/19 (95%) 20/20 (100%) 20/20 (100%) 

Litter 3 39/40 (98%) 18/19 (95%) 20/20 (100%) 20/20 (100%) 

Litter 4 38/40 (95%) 17/19 (89%) 20/20 (100%) 20/20 (100%) 

Litter 5 34/40 (85%) 17/19 (89%) 19/20 (95%) 20/20 (100%) 

Average litters/pair 4.8 ± 0.1 4.9 ± 0.1 5.0 ± 0.1 5.0 ± 0.0 

Cumulative days to litter 

Litter 1 27.00 ± 1.92 25.78 ± 0.92 25.80 ± 0.87 26.05 ± 0.91 

Litter 2 50.13 ± 2.04 49.94 ± 1.63 48.50 ± 0.90 48.95 ± 0.86 

Litter 3 71.10 ± 1.06 73.89 ± 2.92 71.55 ± 0.95 71.65 ± 0.89 

Litter 4 94.11 ± 1.06 94.24 ± 0.98 95.60 ± 1.42 94.75 ± 0.91 

Litter 5 116.74 ± 1.08 118.24 ± 1.33 118.74 ± 1.24 118.75 ± 1.00* 

Dam weight at delivery (g) 

n 40 18 20 20 

Litter 1 282 ± 4 277 ± 6 269 ± 5* 253 ± 5** 

Litter 2 305 ± 5 303 ± 7 293 ± 6 272 ± 7** 

Litter 3 330 ± 6c 322 ± 8 311 ± 7* 287 ± 8** 

Litter 4 355 ± 7d 343 ± 10e 331 ± 8* 303 ± 7** 

Litter 5 370 ± 7f 361 ± 11e 342 ± 9*g 314 ± 9** 

Dam weight during lactation of litter 5 (g) 

n 35 18 20 19 

Lactation day 0 372 ± 7 363 ± 10 342 ± 8* 315 ± 9* 

Lactation day 4 370 ± 6 362 ± 1 347 ± 7* 311 ± 8* 

Lactation day 7 374 ± 5 368 ± 8 351 ± 7* 319 ± 9* 

Lactation day 14 379 ± 5 370 ± 8 355 ± 7* 316 ± 9* 

Lactation day 21 355 ± 6 349 ± 7 342 ± 7 303 ± 7* 
 

216 1-Chloro-2-propanol, NTP TR 477 

TABLE F1 

Fertility, Reproductive Performance, Length of Gestation, and Body Weight Data 

for F and F Sprague-Dawley Rats in the Continuous Breeding Study of 1-Chloro-2-propanol 0 1 

0 ppm 300 ppm 650 ppm 1,300 ppm 

F Pup Data (Litters 1 Through 5) 1 

Number of breeding pairs 40 18 20 20 

Live male pups/litter 5.7 ± 0.2 6.3 ± 0.3 5.5 ± 0.2 5.5 ± 0.2 

Live female pups/litter 6.4 ± 0.2 6.3 ± 0.3 6.3 ± 0.3 6.1 ± 0.2 

Total live pups/litter 12.2 ± 0.2 12.7 ± 0.6 11.8 ± 0.4 11.6 ± 0.3 

Average live pups/litter (%) 

Sex ratio (%) h 

97 ± 0 

47 ± 0 

98 ± 0 

50 ± 0 

98 ± 0 

47 ± 0 

98 ± 0 

48 ± 0 

Male pup weight (g) 6.22 ± 0.06 6.36 ± 0.09 6.23 ± 0.10 6.22 ± 0.09 

Female pup weight (g) 

Total live pup weight (g) i 

Adjusted total pup weight (g) j 

5.85 ± 0.05 

6.01 ± 0.05 

6.02 ± 0.06 

5.85 ± 0.08 

6.11 ± 0.09 

6.13 ± 0.09 

5.96 ± 0.09 

6.08 ± 0.09 

6.07 ± 0.08 

5.93 ± 0.10 

6.07 ± 0.09 

6.04 ± 0.08 

* Significantly different (P#0.05) from the control group by Shirley’s test 

** P#0.01 a Data for average litters/pair, cumulative days to litter, body weights, live pups/litter, and sex ratio are given as mean ± standard error. 

Differences from the control group were not significant by the chi-square test (pregnancy index), Shirley’s test (average litters/pair), Dunn’s 

test (live pups/litter, sex ratio, and pup weights), or Dunnett’s test (adjusted total pup weight). b Pregnant females/cohabiting pairs c nù39 

d nù38 e nù17 

f nù34 

g nù19 

h Live male pups/live pups i Mean of average live pup weight for each fertile pair j Least-squares estimate of the mean of the average pup weight for each fertile pair, adjusted for average litter size 
217 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE F2 

Litter and Body Weight Data for F Sprague-Dawley Rat Pups in the Continuous Breeding Study 1 

of 1-Chloro-2-propanola 

0 ppm 300 ppm 650 ppm 1,300 ppm 

Litter 1 

Number of pairs delivering 

Live pups/litterb 

Total live pup weight (g) c 

Adjusted total live pup weight (g) d 

40 

14.05 ± 0.35 

5.72 ± 0.07 

5.78 ± 0.07 

18 

14.50 ± 0.53 

5.69 ± 0.10 

5.78 ± 0.11 

20 

12.85 ± 0.89 

5.93 ± 0.16 

5.82 ± 0.11 

20 

12.85 ± 0.50 

5.87 ± 0.14 

5.78 ± 0.11 

Litter 2 

Number of pairs delivering 40 18 20 20 

Live pups/litter 13.00 ± 0.44 11.03 ± 0.92 11.35 ± 0.75 12.40 ± 0.52 

Total live pup weight (g) 5.91 ± 0.11 6.23 ± 0.13 6.28 ± 0.17 6.03 ± 0.15 

Adjusted total live pup weight (g) 6.00 ± 0.09 6.16 ± 0.13 6.15 ± 0.13 6.04 ± 0.12 

Litter 3 

Number of pairs delivering 39 18 20 20 

Live pups/litter 12.31 ± 0.58 12.03 ± 0.80 11.60 ± 0.59 11.45 ± 0.44 

Total live pup weight (g) 6.20 ± 0.10 6.10 ± 0.11 6.16 ± 0.11 6.19 ± 0.11 

Adjusted total live pup weight (g) 6.22 ± 0.08 6.15 ± 0.12 6.13 ± 0.11 6.14 ± 0.11 

Litter 4 

Number of pairs delivering 38 17 20 20 

Live pups/litter 10.26 ± 0.53 12.53 ± 0.66 10.70 ± 0.76 11.45 ± 0.63 

Total live pup weight (g) 6.44 ± 0.09 6.35 ± 0.14 6.39 ± 0.16 6.29 ± 0.11 

Adjusted total live pup weight (g) 6.36 ± 0.08 6.52 ± 0.12 6.37 ± 0.11 6.33 ± 0.11 

Litter 5 

Number of pairs delivering 34 17 19 20 

Live pups/litter 10.68 ± 0.53 12.18 ± 0.89 12.74 ± 0.62 9.80 ± 0.79 

Total live pup weight (g) 6.33 ± 0.11 6.52 ± 0.17 6.13 ± 0.14 6.29 ± 0.15 

Adjusted total live pup weight (g) 6.29 ± 0.09 6.61 ± 0.13 6.29 ± 0.12 6.12 ± 0.12 

Litters 1 Through 5 

Number of pairs delivering 40 18 20 20 

Live pups/litter 12.16 ± 0.21 12.65 ± 0.55 11.80 ± 0.44 11.59 ± 0.31 

Total live pup weight (g) 

Adjusted total live pup weight (g) e 6.01 ± 0.05 

6.02 ± 0.06 

6.11 ± 0.09 

6.13 ± 0.09 

6.08 ± 0.09 

6.07 ± 0.08 

6.07 ± 0.09 

6.04 ± 0.08 

a Data given as mean ± standard error. Differences from the control group were not significant by Shirley’s or Dunn’s test (live pups/litter), 

Dunn’s test (weights), or Dunnett’s test (adjusted weights) b	 Mean of average number of live pups/litter for each fertile pair 

Mean of average live pup weight for each fertile pair d	 Least-squares estimate of the mean pup weight adjusted for average litter size e Least-squares estimate of the mean of the average pup weight for each fertile pair, adjusted for average litter size 
218 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE F3
 

Survival and Body Weight Data for F Sprague-Dawley Rat Pups (Final Litter) 1 

in the Continuous Breeding Study of 1-Chloro-2-propanola

 0 ppm 300 ppm 650 ppm 1,300 ppm 

Day 0 

Number of litters 35 18 20 19b 

Male pup weight (g) 6.51 ± 0.14 6.64 ± 0.15 6.33 ± 0.14 6.37 ± 0.15 

Female pup weight (g) 6.16 ± 0.10 6.33 ± 0.17 5.91 ± 0.13 6.22 ± 0.17 

Day 4 

Male survival (%) 98 ± 0 98 ± 0 99 ± 0 97 ± 0 

Female survival (%) 98 ± 0 100 ± 0 98 ± 0 100 ± 0 

Total survival (%) 98 ± 0 99 ± 0 99 ± 0 99 ± 0 

Male pup weight (g) 10.61 ± 0.25 10.67 ± 0.47 10.08 ± 0.34 10.04 ± 0.30 

Female pup weight (g) 10.15 ± 0.19 10.36 ± 0.51 9.35 ± 0.28 9.61 ± 0.36 

Day 7 

Male survival (%) 97 ± 0 96 ± 0 96 ± 0 95 ± 0 

Female survival (%) 98 ± 0 100 ± 0 95 ± 0 99 ± 0 

Total survival (%) 98 ± 0 98 ± 0 95 ± 0 98 ± 0 

Male pup weight (g) 15.62 ± 0.38 15.78 ± 0.75 14.89 ± 0.54 14.06 ± 0.58* 

Female pup weight (g) 15.00 ± 0.35 15.10 ± 0.77 13.88 ± 0.45 13.17 ± 0.55* 

Day 14 

Male survival (%) 95 ± 0 91 ± 0 92 ± 0 90 ± 0 

Female survival (%) 93 ± 0 95 ± 0 92 ± 0 91 ± 0 

Total survival (%) 94 ± 0 94 ± 0 91 ± 0 90 ± 0 

Male pup weight (g) 

Female pup weight (g) 

30.24 ± 0.72 

29.47 ± 0.58c 30.80 ± 1.18 

29.67 ± 1.11 

20.04 ± 0.75* 

26.30 ± 0.58* 

24.52 ± 1.39* 

24.00 ± 1.21* 

Day 21 

Male survival (%) 94 ± 0 91 ± 0 92 ± 0 90 ± 0 

Female survival (%) 93 ± 0 94 ± 0 91 ± 0 89 ± 0 

Total survival (%) 93 ± 0 93 ± 0 91 ± 0 89 ± 0 

Male pup weight (g) 

Female pup weight (g) 

48.90 ± 1.22 

46.96 ± 0.92d 

49.44 ± 1.88 

46.78 ± 1.88 

45.31 ± 1.40* 

41.82 ± 1.07* 

37.83 ± 2.87* 

37.52 ± 2.37* 

* Significantly different (P#0.05) from the control group by Shirley’s test a Data are given as mean ± standard error. Differences from the control group for survival were not significant by Shirley’s or Dunn’s test. b Because no live male pups were born in two litters, nù17 for male pup survival and body weights.
 

nù34
 d nù33 
 

219 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE F4 

Fertility, Reproductive Performance, Length of Gestation, and Body Weight Data 

for F and F Sprague-Dawley Rats in the Offspring Assessment Phase 1 2 

of the Continuous Breeding Study of 1-Chloro-2-propanola

 0 ppm 1,300 ppm 

F1 Adult Data

Mating indexb 

Pregnancy indexc 

Fertility indexd 

18/20 (90%) 

17/20 (85%) 

17/18 (94%) 

18/20 (90%) 

18/20 (90%) 

18/18 (100%) 

Mean dam weight at delivery (g) 317 ± 9 264 ± 4** 

Days to litter 22.2 ± 0.1 22.1 ± 0.1 

F2 Pup Data

Number of litters 17 18 

Live male pups/litter 7.1 ± 0.7 7.1 ± 0.6 

Live female pups/litter 7.1 ± 0.6 6.7 ± 0.4 

Total live pups/litter 14.1 ± 0.8 13.8 ± 0.5 

Total live pups/litter (%) 

Sex ratio (%) e 99 ± 0 

50 ± 0 

100 ± 0 

51 ± 0 

Male pup weight (g) 6.18 ± 0.16 6.04 ± 0.12 

Female pup weight (g) 5.84 ± 0.16 5.72 ± 0.10 

Total live pup weight (g) 

Adjusted total live pup weight (g) f 

6.01 ± 0.15 

6.03 ± 0.12 

5.88 ± 0.11 

5.87 ± 0.11 

** Significantly different (P#0.01) from the controls by Wilcoxon’s test a Data for body weights, days to litter, live pups/litter, and sex ratio are given as mean ± standard error. Differences from the control group 

were not significant by the chi-square test (mating and fertility indexes), Wilcoxon’s test (days to litter, pups/litter, live pups, and weights), or 

Dunnett’s test (adjusted pup weight). b	 Females with sperm plug/cohabiting pairs 

Pregnant females/cohabiting pairs d	 Pregnant females/females with sperm plug e Live male pups/live pups f Least-squares estimate of the mean pup weight adjusted for average litter size 
220 1-Chloro-2-propanol, NTP TR 477 

TABLE F5 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for F Sprague-Dawley Rats 1 

in the Offspring Assessment Phase of the Continuous Breeding Study of 1-Chloro-2-propanola

 0 ppm 1,300 ppm 

n 20 20 

Male 

Necropsy body wt 520 ± 8 448 ± 8 

R. Cauda Epididymis 

Absolute 224.74 ± 6.64 215.17 ± 6.61 

Relative 0.434 ± 0.013 0.481 ± 0.014 

R. Epididymis 

Absolute 550.86 ± 10.15 509.08 ± 10.75 

Relative 1.06 ± 0.022 1.14 ± 0.022 

Kidneys 

Absolute 3.85 ± 0.082 3.54 ± 0.077 

Relative 7.40 ± 0.133 7.91 ± 0.070 

Liver 

Absolute 22.41 ± 0.593 19.39 ± 0.554 

Relative 43.12 ± 1.14 43.20 ± 0.672 

Prostate Gland 

Absolute 644.88 ± 33.74 594.45 ± 31.88 

Relative 1.25 ± 0.071 1.33 ± 0.073 

Seminal Vesicles 

Absolute 2,424.71 ± 78.25 2,224.54 ± 72.94 

Relative 4.67 ± 0.152 4.99 ± 0.175 

R. Testis 

Absolute 1,741.02 ± 43.95 1,594.86 ± 36.26 

Relative 3.35 ± 0.084 3.57 ± 0.066 

Female 

Necropsy body wt 316 ± 8 280 ± 4 

Kidneys 

Absolute 2.44 ± 0.057 2.33 ± 0.034 

Relative 7.76 ± 0.131 8.36 ± 0.137 

Liver 

Absolute 12.74 ± 0.416 11.43 ± 0.249 

Relative 40.35 ± 0.776 40.81 ± 0.600 

R. Ovary 

Absolute 56.26 ± 2.44 47.84 ± 1.79 

Relative 0.181 ± 0.008 0.171 ± 0.006 

a Liver, kidney, and body weights are given in grams; all other organ weights (absolute weights) are in milligrams; organ weights and organweight-to-body-weight ratios (relative weights) are given as mg organ weight/g body weight (mean ± standard error). Differences from the 

controls were not significant by Wilcoxon’s test. 
1-Chloro-2-propanol, NTP TR 477 221 

TABLE F6 

Sperm Parameters and Estrous Cycle Characterization for F Sprague-Dawley Rats 1 

in the Offspring Assessment Phase of the Continuous Breeding Study of 1-Chloro-2-propanola

 0 ppm 1,300 ppm 

Male 

n 19 20 

Epididymal spermatozoal measurements 

Motility (%) 85.0 ± 1.4b 86.7 ± 1.7 

Abnormal (%) 0.78 ± 0.11 2.4 ± 0.53* 

Concentration (10 /g cauda epididymal tissue) 6 497 ± 25 488 ± 20 

Female 

n 20 20 

Estrous cycle length (days) 4.20 ± 0.08 4.55 ± 0.18 

Estrous stages (% of cycle) 

Diestrus 30.8 38.3 

Proestrus 22.1 19.6 

Estrus 26.2 24.6 

Metestrus 20.4 16.2 

Uncertain diagnosis 0.4 1.2 

* Significantly different (P#0.05) from the control group by Wilcoxon’s test a Epididymal spermatozoal measurements and estrous cycle length data are given as mean ± standard error. Differences from the control group 

are not significant by Dunn’s test (motility and concentration) or Wilcoxon’s test (estrous cycle length). By multivariate analysis of variance, 

exposed females do not differ significantly from control females in the relative length of time spent in estrous stages. b nù20 
222 1-Chloro-2-propanol, NTP TR 477 
223 

APPENDIX G 

HEMATOLOGY, CLINICAL CHEMISTRY, 

AND URINALYSIS RESULTS 

TABLE G1 

TABLE G2 

Hematology, Clinical Chemistry, and Urinalysis Data for Rats 

in the 14-Week Drinking Water Study of 1-Chloro-2-propanol .................. 

Hematology Data for Mice in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanol ............................................. 

224 

228 
224 1-Chloro-2-propanol, NTP TR 477 

TABLE G1 

Hematology, Clinical Chemistry, and Urinalysis Data for Rats in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 33 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 

Male 

n 10 10 10 10 10 10 

Hematology 

Hematocrit (%) 45.7 ± 0.6 46.7 ± 0.4 45.2 ± 0.5 47.1 ± 0.7 46.7 ± 0.4 45.8 ± 0.5 

Hemoglobin (g/dL) 

Erythrocytes (10 /μL) 6 

Reticulocytes (10 /μL) 6 

Nucleated erythrocytes (10 /μL) 3 

16.4 ± 0.2 

8.71 ± 0.12 

0.26 ± 0.03 

0.01 ± 0.01 

16.7 ± 0.1 

8.92 ± 0.08 

0.22 ± 0.02 

0.00 ± 0.00 

16.5 ± 0.1 

8.72 ± 0.09 

0.21 ± 0.02 

0.01 ± 0.01 

16.7 ± 0.3 

9.05 ± 0.16 

0.22 ± 0.01 

0.02 ± 0.01 

16.4 ± 0.1 

8.94 ± 0.07 

0.22 ± 0.02 

0.01 ± 0.01 

15.7 ± 0.1** 

8.59 ± 0.08 

0.27 ± 0.02 

0.01 ± 0.01 

Mean cell volume (fL) 51.4 ± 0.3 51.3 ± 0.2 50.9 ± 0.2 51.4 ± 0.3 51.1 ± 0.3 52.3 ± 0.2 

Mean cell hemoglobin (pg) 18.8 ± 0.1 18.6 ± 0.2 18.8 ± 0.3 18.3 ± 0.2 18.1 ± 0.1** 18.0 ± 0.0** 

Mean cell hemoglobin 

concentration (g/dL) 

Platelets (10 /μL) 3 36.0 ± 0.0 

687.0 ± 22.1 

36.0 ± 0.1 

687.4 ± 21.8 

36.7 ± 0.4 

708.0 ± 17.0 

35.3 ± 0.2* 

649.8 ± 15.8 

35.1 ± 0.2** 

667.4 ± 10.7 

34.2 ± 0.1** 

615.0 ± 21.1 

Mean platelet volume (fL) 

Leukocytes (10 /μL) 3 

Segmented neutrophils (10 /μL) 3 

Lymphocytes (10 /μL) 3 

Monocytes (10 /μL) 3 

Eosinophils (10 /μL) 3 

7.35 ± 0.03 

10.36 ± 0.36 

1.16 ± 0.11 

8.91 ± 0.35 

0.21 ± 0.06 

0.07 ± 0.02 

7.18 ± 0.07 

10.04 ± 0.38 

1.10 ± 0.17 

8.47 ± 0.35 

0.43 ± 0.09 

0.05 ± 0.02 

7.32 ± 0.08 

10.24 ± 0.34 

1.54 ± 0.12 

8.12 ± 0.31 

0.50 ± 0.16 

0.07 ± 0.03 

7.23 ± 0.07 

9.53 ± 0.42 

1.04 ± 0.12 

8.29 ± 0.43 

0.08 ± 0.03 

0.05 ± 0.02 

7.17 ± 0.06 

9.93 ± 0.33 

1.25 ± 0.19 

8.15 ± 0.28 

0.42 ± 0.15 

0.06 ± 0.02 

7.36 ± 0.08 

7.72 ± 0.37** 

1.04 ± 0.07 

6.50 ± 0.36** 

0.05 ± 0.02* 

0.07 ± 0.03 

Clinical Chemistry 

Creatinine (mg/dL) 

Day 3 0.66 ± 0.03 0.55 ± 0.04 0.45 ± 0.02** 0.47 ± 0.02** 0.51 ± 0.01* 0.53 ± 0.02b 

Day 15 0.35 ± 0.02 0.47 ± 0.02* 0.50 ± 0.05 0.55 ± 0.02** 0.36 ± 0.02 0.34 ± 0.02 

Day 45 

Week 14 

0.68 ± 0.03 

0.56 ± 0.03 

0.58 ± 0.03 

0.58 ± 0.05 

0.58 ± 0.05 

0.58 ± 0.06b 

0.62 ± 0.03 

0.66 ± 0.04 

0.63 ± 0.03 

0.60 ± 0.05 

0.67 ± 0.03 

0.63 ± 0.03 

Albumin (g/dL) 

Day 3 

Day 15 

4.5 ± 0.1 

4.4 ± 0.1b 

4.0 ± 0.1**b 

4.7 ± 0.1 

4.0 ± 0.1** 

4.6 ± 0.1 

3.8 ± 0.0** 

4.5 ± 0.1b 

4.0 ± 0.1** 

4.3 ± 0.1b 

4.0 ± 0.1**b 

4.0 ± 0.1* 

Day 45 

Week 14 

4.3 ± 0.1 

4.9 ± 0.1b 

4.3 ± 0.2 

4.8 ± 0.1c 4.4 ± 0.2 4.7 ± 0.1b 

4.4 ± 0.1 

4.7 ± 0.1 

4.3 ± 0.1 

4.9 ± 0.1 

4.4 ± 0.1 

4.6 ± 0.1 

Alanine aminotransferase (IU/L) 

Day 3 33 ± 1 31 ± 1 33 ± 1 30 ± 2 19 ± 1** 16 ± 1** 

Day 15 31 ± 1 28 ± 1* 24 ± 1** 22 ± 1** 16 ± 0** 6 ± 1** 

Day 45 34 ± 2 35 ± 2 34 ± 1 31 ± 1 20 ± 1** 11 ± 0** 

Week 14 30 ± 1 34 ± 1 31 ± 1 33 ± 2 22 ± 1** 12 ± 2** 

Creatine kinase (IU/L) 

Day 3 266 ± 41 462 ± 129 334 ± 76 478 ± 124 413 ± 121 444 ± 92 

Day 15 619 ± 122 831 ± 244 368 ± 58 588 ± 161 719 ± 119 579 ± 141 

Day 45 267 ± 47 305 ± 31 476 ± 88 305 ± 33 245 ± 32 315 ± 54 

Week 14 175 ± 36 236 ± 41 220 ± 37 227 ± 54 226 ± 32 154 ± 15 

Sorbitol dehydrogenase (IU/L) 

Day 3 

Day 15 

14 ± 1b 

20 ± 3b 

15 ± 1 

14 ± 0 

14 ± 0 

13 ± 0 

14 ± 1 

14 ± 1 

13 ± 1 

16 ± 1c 23 ± 2** 14 ± 1 

Day 45 25 ± 2 22 ± 1 22 ± 1 19 ± 1** 20 ± 1* 18 ± 2** 

Week 14 20 ± 2 21 ± 2 19 ± 1 18 ± 1 19 ± 2 19 ± 2 
1-Chloro-2-propanol, NTP TR 477 225 

TABLE G1 

Hematology, Clinical Chemistry, and Urinalysis Data for Rats in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 33 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 

Male (continued) 

n 10 10 10 10 10 10 

Clinical Chemistry (continued) 

(-Glutamyltransferase (IU/L) 

Day 3 

Day 15

2.3 ± 0.7b 

—f 

1.7 ± 0.2b 

— 

1.8 ± 0.3d 

— 

2.3 ± 0.2e 

— 

2.3 ± 0.4 

— 

2.4 ± 0.3c 

— 

Day 45 — — — — — — 

Week 14 — — — — — — 

Urinalysis 

Glucose (mg/100 g per 16 hr) 

Day 15 0.599 ± 0.028 0.884 ± 0.021** 0.622 ± 0.055 0.680 ± 0.044 0.695 ± 0.034 0.491 ± 0.044 

Week 14 0.441 ± 0.046 0.430 ± 0.029 0.417 ± 0.026 0.424 ± 0.032 0.389 ± 0.022 0.618 ± 0.038* 

Protein (mg/100 g per 16 hr) 

Day 15 2.048 ± 0.220 2.391 ± 0.086 1.872 ± 0.234 1.364 ± 0.153* 1.423 ± 0.145* 0.486 ± 0.082** 

Week 14 0.985 ± 0.104 1.217 ± 0.096 1.145 ± 0.088 1.199 ± 0.103 1.006 ± 0.131 0.829 ± 0.073 

Volume (mL/16 hr) 

Day 15 5.6 ± 0.8 8.0 ± 0.1 6.6 ± 0.8 5.0 ± 0.6 4.5 ± 0.6 0.9 ± 0.1** 

Week 14 5.9 ± 0.9 6.8 ± 0.7 6.2 ± 0.6 5.6 ± 0.5 4.7 ± 0.4 2.7 ± 0.3** 

Specific gravity 

Day 15 1.030 ± 0.003 1.024 ± 0.002 1.025 ± 0.003 1.033 ± 0.003 1.038 ± 0.004 1.099 ± 0.012** 

Week 14 1.039 ± 0.004 1.034 ± 0.004 1.040 ± 0.004 1.039 ± 0.002 1.047 ± 0.004 1.070 ± 0.004** 

Female 

n 10 10 10 10 9 10 

Hematology 

Hematocrit (%) 47.6 ± 0.4 45.2 ± 0.5** 45.7 ± 0.4** 46.5 ± 0.3** 44.7 ± 0.3** 45.6 ± 0.4** 

Hemoglobin (g/dL) 

Erythrocytes (10 /μL) 6 

Reticulocytes (10 /μL) 6 

Nucleated erythrocytes (10 /μL) 3 

16.9 ± 0.1 

8.34 ± 0.07 

0.15 ± 0.01 

0.01 ± 0.01 

16.3 ± 0.1** 

8.14 ± 0.08 

0.20 ± 0.02* 

0.02 ± 0.01 

16.7 ± 0.1 

8.29 ± 0.06 

0.20 ± 0.02* 

0.00 ± 0.00 

16.7 ± 0.1 

8.27 ± 0.06 

0.19 ± 0.02 

0.00 ± 0.00 

15.9 ± 0.1** 

7.83 ± 0.05** 

0.18 ± 0.02 

0.01 ± 0.01 

16.0 ± 0.1** 

7.61 ± 0.06** 

0.33 ± 0.03** 

0.01 ± 0.01 

Mean cell volume (fL) 55.8 ± 0.2 54.4 ± 0.3 53.8 ± 0.1 54.9 ± 0.2 56.1 ± 0.4 58.2 ± 0.2* 

Mean cell hemoglobin (pg) 20.0 ± 0.0 20.0 ± 0.1 20.0 ± 0.0 20.0 ± 0.0 20.1 ± 0.1 21.0 ± 0.0** 

Mean cell hemoglobin 

concentration (g/dL) 

Platelets (10 /μL) 3 

Mean platelet volume (fL) 

Leukocytes (10 /μL) 3 

Segmented neutrophils (10 /μL) 3 

Lymphocytes (10 /μL) 3 

Monocytes (10 /μL) 3 

Eosinophils (10 /μL) 3 

35.6 ± 0.2 

633.8 ± 20.8 

6.88 ± 0.05 

8.41 ± 0.38 

0.98 ± 0.10 

7.13 ± 0.33 

0.27 ± 0.06 

0.04 ± 0.02 

36.3 ± 0.3 

668.6 ± 23.5 

7.19 ± 0.06** 

8.78 ± 0.48 

1.23 ± 0.14 

7.36 ± 0.48 

0.09 ± 0.02 

0.07 ± 0.02 

36.5 ± 0.2 

674.2 ± 25.5 

7.15 ± 0.06* 

9.49 ± 0.33 

1.08 ± 0.12 

7.97 ± 0.25 

0.34 ± 0.07 

0.06 ± 0.02 

36.1 ± 0.2 

727.2 ± 16.2** 

6.89 ± 0.06 

9.16 ± 0.35 

0.93 ± 0.13 

7.97 ± 0.33 

0.21 ± 0.06 

0.02 ± 0.01 

35.6 ± 0.2 

738.4 ± 14.2** 

7.10 ± 0.05g 

9.16 ± 0.50 

0.96 ± 0.15 

8.08 ± 0.48 

0.08 ± 0.02 

0.03 ± 0.02 

35.1 ± 0.1 

672.8 ± 15.0 

7.09 ± 0.06 

9.46 ± 0.30 

1.30 ± 0.14 

7.69 ± 0.37 

0.36 ± 0.05 

0.07 ± 0.03 
226 1-Chloro-2-propanol, NTP TR 477 

TABLE G1 

Hematology, Clinical Chemistry, and Urinalysis Data for Rats in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 33 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 

Female (continued) 

n 10 10 10 10 10 10 

Clinical Chemistry 

Creatinine (mg/dL) 

Day 3 0.58 ± 0.03 0.55 ± 0.02 0.58 ± 0.02 0.45 ± 0.03* 0.57 ± 0.03 0.49 ± 0.02 

Day 15 0.57 ± 0.03 0.50 ± 0.04 0.56 ± 0.04 0.52 ± 0.03 0.57 ± 0.03 0.64 ± 0.02 

Day 45 

Week 14 

0.49 ± 0.03 

0.57 ± 0.02 

0.36 ± 0.02* 

0.62 ± 0.03b 

0.49 ± 0.05 

0.58 ± 0.06 

0.51 ± 0.02 

0.66 ± 0.03 

0.42 ± 0.02 

0.59 ± 0.04b 

0.55 ± 0.03 

0.64 ± 0.04 

Albumin (g/dL) 

Day 3 

Day 15 

4.7 ± 0.1 

4.8 ± 0.1 

4.3 ± 0.1** 

4.7 ± 0.1b 

4.3 ± 0.0* 

4.6 ± 0.1 

4.4 ± 0.1 

4.3 ± 0.1**b 

4.4 ± 0.1* 

4.6 ± 0.1b 

4.3 ± 0.1** 

5.0 ± 0.1 

Day 45 

Week 14 

5.2 ± 0.1 

5.1 ± 0.1b 

4.8 ± 0.1* 

4.5 ± 0.4b 

4.7 ± 0.1** 

5.0 ± 0.1 

4.9 ± 0.1 

5.0 ± 0.1 

5.0 ± 0.1 

4.8 ± 0.1*b 

4.9 ± 0.1 

5.2 ± 0.1 

Alanine aminotransferase (IU/L) 

Day 3 29 ± 1 28 ± 1 22 ± 1** 22 ± 2** 16 ± 1** 17 ± 1** 

Day 15 23 ± 2 26 ± 1 24 ± 1 19 ± 1* 11 ± 1** 7 ± 1** 

Day 45 

Week 14 

25 ± 1 

28 ± 2 

24 ± 2 

36 ± 3 

22 ± 1* 

29 ± 2 

23 ± 2 

24 ± 1 

16 ± 1** 

18 ± 1** 

10 ± 1** 

9 ± 1**b 

Creatine kinase (IU/L) 

Day 3 347 ± 75 416 ± 69 670 ± 331 731 ± 272 246 ± 57 251 ± 32 

Day 15 

Day 45 

306 ± 76 

197 ± 26 

396 ± 113 

200 ± 32 

285 ± 31 

134 ± 14h 

318 ± 61 

286 ± 76h 

318 ± 78 

263 ± 45h 

296 ± 63 

186 ± 34 

Week 14 186 ± 40 214 ± 59 160 ± 27 178 ± 17 176 ± 30 278 ± 63 

Sorbitol dehydrogenase (IU/L) 

Day 3 12 ± 0 12 ± 1 12 ± 0 11 ± 0 11 ± 0 16 ± 2 

Day 15 18 ± 1 19 ± 2 17 ± 1 20 ± 2 17 ± 1 16 ± 1 

Day 45 19 ± 1 18 ± 2 21 ± 1 23 ± 2 21 ± 1 21 ± 2 

Week 14 18 ± 2 16 ± 1 15 ± 1 17 ± 1 16 ± 1 18 ± 2 

(-Glutamyltransferase (IU/L) 

Day 3 1.8 ± 0.2 3.2 ± 0.4*b 1.8 ± 0.3b 3.4 ± 0.4*c 2.6 ± 0.2b 2.7 ± 0.4b 

Day 15 — — — — — — 

Day 45 — — — — — — 

Week 14 — — — — — — 
227 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE G1 

Hematology, Clinical Chemistry, and Urinalysis Data for Rats in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 33 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 

Female (continued) 

n 

Day 15 10 10 10 10 10 10 

Week 14 10 10 10 10 10 9 

Urinalysis 

Glucose (mg/100 g per 16 hr) 

Day 15 0.781 ± 0.072 0.403 ± 0.056** 0.676 ± 0.049 0.724 ± 0.040 0.732 ± 0.030 0.787 ± 0.043 

Week 14 0.495 ± 0.022 0.529 ± 0.040 0.405 ± 0.029 0.484 ± 0.036 0.487 ± 0.032 0.418 ± 0.046 

Protein (mg/100 g per 16 hr) 

Day 15 6.311 ± 0.614 5.386 ± 0.680 6.520 ± 0.517 5.479 ± 0.468 4.332 ± 0.185 4.805 ± 0.358 

Week 14 0.359 ± 0.029 0.418 ± 0.027 0.318 ± 0.029 0.330 ± 0.031 0.299 ± 0.017 0.262 ± 0.041 

Volume (mL/16 hr) 

Day 15 8.7 ± 1.2 10.9 ± 1.7 9.5 ± 1.0 7.7 ± 0.8 8.5 ± 0.8 3.3 ± 0.3** 

Week 14 6.7 ± 1.1 5.2 ± 0.7 3.8 ± 1.0* 7.3 ± 1.4 4.5 ± 0.9 1.8 ± 0.4** 

Specific gravity 

Day 15 1.021 ± 0.002 1.016 ± 0.002 1.019 ± 0.002 1.022 ± 0.003 1.019 ± 0.001 1.040 ± 0.003** 

Week 14 1.031 ± 0.004 1.031 ± 0.004 1.043 ± 0.006 1.027 ± 0.005 1.036 ± 0.004 1.072 ± 0.007** 

* Significantly different (P#0.05) from the control group by Dunn’s or Shirley’s test 

** P#0.01 a Mean ± standard error. Statistical tests were performed on unrounded data. b nù9 

nù8 

d nù6 e nù7 

f Data for (-glutamyltransferase were below 1 IU/L; therefore, no mean or standard error was calculated. g nù10 

h nù5 
228 1-Chloro-2-propanol, NTP TR 477 

TABLE G2 

Hematology Data for Mice in the 14-Week Drinking Water Study of 1-Chloro-2-propanola 

0 ppm 33 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 

Male 

n 10 10 10 9 10 9 

Hematocrit (%) 52.9 ± 0.9 53.0 ± 0.8 52.5 ± 0.7 54.5 ± 0.8 52.4 ± 0.4 49.4 ± 1.3 

Hemoglobin (g/dL) 

Erythrocytes (10 /μL) 6 

Reticulocytes (10 /μL) 6 

Nucleated erythrocytes (10 /μL) 3 

17.6 ± 0.3 

10.46 ± 0.16 

0.23 ± 0.02 

0.00 ± 0.00 

17.6 ± 0.3 

10.49 ± 0.19 

0.26 ± 0.02 

0.00 ± 0.00 

17.5 ± 0.1 

10.31 ± 0.16 

0.19 ± 0.02 

0.01 ± 0.01 

17.7 ± 0.3 

10.53 ± 0.17 

0.22 ± 0.03 

0.00 ± 0.00 

17.1 ± 0.1* 

10.17 ± 0.07 

0.24 ± 0.03 

0.00 ± 0.00 

15.9 ± 0.4** 

9.49 ± 0.24** 

0.25 ± 0.03 

0.00 ± 0.00 

Mean cell volume (fL) 49.3 ± 0.2 49.5 ± 0.4 49.9 ± 0.2 50.7 ± 0.3** 50.2 ± 0.1** 50.9 ± 0.3** 

Mean cell hemoglobin (pg) 17.0 ± 0.0 16.8 ± 0.1 17.2 ± 0.2 16.8 ± 0.1 17.0 ± 0.0 16.9 ± 0.1 

Mean cell hemoglobin 

concentration (g/dL) 

Platelets (10 /μL) 3 33.5 ± 0.2 

1,058.2 ± 18.4b 

32.9 ± 0.2 

1,005.6 ± 22.8 

33.4 ± 0.3 

1,059.2 ± 23.0 

32.4 ± 0.2** 

1,033.6 ± 28.7 

32.6 ± 0.2** 

1,053.8 ± 15.6 

32.2 ± 0.2** 

917.0 ± 22.2** 

Mean platelet volume (fL) 

Leukocytes (10 /μL) 3 

Segmented neutrophils (10 /μL) 3 

Lymphocytes (10 /μL) 3 

Monocytes (10 /μL) 3 

Eosinophils (10 /μL) 3 

5.66 ± 0.05 

5.19 ± 0.28 

0.64 ± 0.07 

4.49 ± 0.24 

0.02 ± 0.01 

0.03 ± 0.01 

5.75 ± 0.02 

4.84 ± 0.33 

0.49 ± 0.03 

4.13 ± 0.32 

0.16 ± 0.06* 

0.02 ± 0.01 

5.73 ± 0.04 

5.18 ± 0.34 

0.63 ± 0.12 

4.41 ± 0.25 

0.05 ± 0.01 

0.05 ± 0.02 

5.58 ± 0.03 

3.09 ± 0.28** 

0.32 ± 0.04** 

2.67 ± 0.24** 

0.09 ± 0.03 

0.01 ± 0.00 

5.72 ± 0.04 

4.52 ± 0.28 

0.43 ± 0.03 

3.99 ± 0.25 

0.04 ± 0.01 

0.03 ± 0.02 

5.66 ± 0.06 

4.56 ± 0.26 

0.47 ± 0.04 

3.96 ± 0.24 

0.04 ± 0.01 

0.05 ± 0.02 

Female 

n 10 10 10 9 10 10 

Hematocrit (%) 51.4 ± 1.3 55.0 ± 0.9 54.9 ± 0.6 54.8 ± 0.7 53.9 ± 1.1 56.0 ± 1.7 

Hemoglobin (g/dL) 

Erythrocytes (10 /μL) 6 

Reticulocytes (10 /μL) 6 

Nucleated erythrocytes (10 /μL) 3 

18.6 ± 0.3 

9.62 ± 0.30 

0.20 ± 0.01 

0.00 ± 0.00 

18.2 ± 0.2 

10.28 ± 0.14 

0.18 ± 0.02 

0.00 ± 0.00 

17.8 ± 0.2 

10.16 ± 0.15 

0.17 ± 0.01 

0.00 ± 0.00 

18.4 ± 0.2 

10.36 ± 0.15 

0.19 ± 0.02 

0.00 ± 0.00 

17.3 ± 0.3* 

9.97 ± 0.20 

0.18 ± 0.01 

0.00 ± 0.00 

18.0 ± 0.5 

10.52 ± 0.29* 

0.24 ± 0.01 

0.00 ± 0.00 

Mean cell volume (fL) 51.8 ± 0.3 52.3 ± 0.3 52.8 ± 0.4 51.8 ± 0.4 53.0 ± 0.3 52.2 ± 0.2 

Mean cell hemoglobin (pg) 19.5 ± 0.4 17.7 ± 0.2** 17.3 ± 0.2** 17.7 ± 0.2** 17.4 ± 0.2** 17.1 ± 0.1** 

Mean cell hemoglobin 

concentration (g/dL) 

Platelets (10 /μL) 3 

Mean platelet volume (fL) 

Leukocytes (10 /μL) 3 

Segmented neutrophils (10 /μL) 3 

Lymphocytes (10 /μL) 3 

Monocytes (10 /μL) 3 

Eosinophils (10 /μL) 3 

36.4 ± 0.6 

893.1 ± 32.2b 

5.54 ± 0.04 

5.18 ± 0.20 

0.58 ± 0.06 

4.32 ± 0.17 

0.21 ± 0.05 

0.04 ± 0.01 

32.9 ± 0.2** 

942.4 ± 36.4 

5.79 ± 0.03** 

6.14 ± 0.33 

0.62 ± 0.06 

5.18 ± 0.32 

0.29 ± 0.10 

0.02 ± 0.01 

32.5 ± 0.3** 

912.2 ± 31.5 

5.77 ± 0.05* 

5.22 ± 0.29 

0.63 ± 0.07 

4.30 ± 0.24 

0.25 ± 0.08 

0.02 ± 0.02 

33.8 ± 0.3** 

882.8 ± 17.1c 

5.70 ± 0.06c 

5.24 ± 0.51 

0.51 ± 0.09 

4.50 ± 0.46 

0.18 ± 0.05 

0.05 ± 0.03 

32.2 ± 0.2** 

915.8 ± 34.5 

5.58 ± 0.04 

5.86 ± 0.28 

0.46 ± 0.05 

5.04 ± 0.28 

0.32 ± 0.10 

0.02 ± 0.01 

32.2 ± 0.2** 

804.2 ± 73.8 

5.85 ± 0.05** 

3.62 ± 0.26 

0.24 ± 0.05** 

3.18 ± 0.25 

0.14 ± 0.04 

0.03 ± 0.01 

* Significantly different (P#0.05) from the control group by Dunn’s or Shirley’s test 

** P#0.01 a Mean ± standard error. Statistical tests were performed on unrounded data. b nù9
 

nù10
 c 
229 

APPENDIX H
 

ORGAN WEIGHTS 

AND ORGAN-WEIGHT-TO-BODY-WEIGHT RATIOS
 

TABLE H1 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats 

in the 14-Day Drinking Water Study of 1-Chloro-2-propanol ................... 230 

TABLE H2 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats 

in the 14-Week Drinking Water Study of 1-Chloro-2-propanol .................. 231 

TABLE H3 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice 

in the 14-Day Drinking Water Study of 1-Chloro-2-propanol ................... 232 

TABLE H4 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice 

in the 14-Week Drinking Water Study of 1-Chloro-2-propanol .................. 233 
230 1-Chloro-2-propanol, NTP TR 477 

TABLE H1 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats in the 14-Day Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 10,000 ppm 

Male 

n 10 10 10 10 10 10 

Necropsy body wt 196 ± 3 193 ± 5 198 ± 3 195 ± 5 162 ± 4** 88 ± 2** 

Brain 

Absolute 1.899 ± 0.011 1.875 ± 0.012 1.848 ± 0.027 1.888 ± 0.014 1.804 ± 0.020** 1.740 ± 0.012** 

Relative 9.73 ± 0.11 9.78 ± 0.23 9.35 ± 0.13 9.72 ± 0.25 11.16 ± 0.23** 19.99 ± 0.48** 

Heart 

Absolute 0.805 ± 0.033 0.787 ± 0.015 0.810 ± 0.012 0.822 ± 0.027 0.636 ± 0.014** 0.417 ± 0.013** 

Relative 4.11 ± 0.13 4.10 ± 0.09 4.10 ± 0.07 4.21 ± 0.09 3.93 ± 0.08 4.77 ± 0.12** 

R. Kidney 

Absolute 1.044 ± 0.020 1.031 ± 0.020 1.074 ± 0.038 1.041 ± 0.025 0.967 ± 0.014* 0.686 ± 0.016** 

Relative 5.34 ± 0.08 5.37 ± 0.13 5.42 ± 0.14 5.34 ± 0.10 5.98 ± 0.09** 7.85 ± 0.14** 

Liver 

Absolute 10.796 ± 0.288 11.039 ± 0.307 11.440 ± 0.262 11.638 ± 0.387 9.613 ± 0.187** 4.562 ± 0.176** 

Relative 55.21 ± 1.16 57.36 ± 1.22 57.76 ± 0.66 59.46 ± 0.82* 59.35 ± 0.76* 52.02 ± 0.94 

Lung 

Absolute 1.232 ± 0.035 1.217 ± 0.035 1.200 ± 0.030 1.177 ± 0.035 0.955 ± 0.020** 0.709 ± 0.017** 

Relative 6.30 ± 0.16 6.34 ± 0.20 6.07 ± 0.14 6.03 ± 0.15 5.90 ± 0.11 8.15 ± 0.27** 

R. Testis 

Absolute 1.181 ± 0.021 1.135 ± 0.024 1.163 ± 0.020 1.143 ± 0.025 1.110 ± 0.028 0.898 ± 0.036** 

Relative 6.04 ± 0.10 5.90 ± 0.10 5.88 ± 0.10 5.87 ± 0.13 6.85 ± 0.14** 10.24 ± 0.22** 

Thymus 

Absolute 0.517 ± 0.012 0.540 ± 0.019 0.557 ± 0.019 0.553 ± 0.013 0.455 ± 0.018** 0.136 ± 0.013** 

Relative 2.64 ± 0.05 2.81 ± 0.12 2.82 ± 0.09 2.84 ± 0.09 2.81 ± 0.11 1.54 ± 0.12** 

Female 

n 10 10 10 10 10 8 

Necropsy body wt 136 ± 2 139 ± 2 139 ± 2 139 ± 3 123 ± 1** 67 ± 3** 

Brain 

Absolute 1.781 ± 0.022 1.829 ± 0.013 1.797 ± 0.017 1.793 ± 0.015 1.753 ± 0.016 1.625 ± 0.022** 

Relative 13.09 ± 0.22 13.18 ± 0.29 12.98 ± 0.17 12.96 ± 0.25 14.28 ± 0.14* 24.39 ± 0.90** 

Heart 

Absolute 0.605 ± 0.014 0.596 ± 0.015 0.612 ± 0.011 0.616 ± 0.013 0.559 ± 0.009* 0.356 ± 0.016** 

Relative 4.44 ± 0.07 4.28 ± 0.10 4.42 ± 0.09 4.44 ± 0.06 4.55 ± 0.06 5.31 ± 0.16** 

R. Kidney 

Absolute 0.733 ± 0.017 0.739 ± 0.017 0.753 ± 0.019 0.789 ± 0.022 0.774 ± 0.017 0.556 ± 0.019** 

Relative 5.38 ± 0.09 5.31 ± 0.12 5.43 ± 0.09 5.69 ± 0.10 6.30 ± 0.10** 8.30 ± 0.21** 

Liver 

Absolute 6.775 ± 0.123 7.025 ± 0.098 7.430 ± 0.148* 7.656 ± 0.173** 6.789 ± 0.104 3.471 ± 0.246** 

Relative 49.73 ± 0.71 50.50 ± 0.55 53.58 ± 0.52** 55.20 ± 0.73** 55.27 ± 0.57** 51.19 ± 2.07** 

Lung 

Absolute 0.995 ± 0.015 0.988 ± 0.016 0.969 ± 0.026 0.997 ± 0.021 0.839 ± 0.011** 0.641 ± 0.018** 

Relative 7.31 ± 0.15 7.11 ± 0.13 6.98 ± 0.11 7.20 ± 0.13 6.83 ± 0.06 9.58 ± 0.25** 

Thymus 

Absolute 0.420 ± 0.015 0.413 ± 0.013 0.465 ± 0.014 0.435 ± 0.015 0.421 ± 0.014 0.093 ± 0.026** 

Relative 3.08 ± 0.10 2.97 ± 0.09 3.36 ± 0.08 3.13 ± 0.08 3.42 ± 0.10 1.32 ± 0.35** 

* Significantly different (P#0.05) from the 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-Chloro-2-propanol, NTP TR 477 231 

TABLE H2 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 33 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 

n 10 10 10 10 10 10 

Male 

Necropsy body wt 379 ± 6 377 ± 9 377 ± 9 385 ± 8 383 ± 6 322 ± 5** 

Brain 

Absolute 1.985 ± 0.023 2.004 ± 0.027 2.036 ± 0.019 1.999 ± 0.024 1.986 ± 0.016 1.937 ± 0.015 

Relative 5.24 ± 0.05 5.34 ± 0.09 5.42 ± 0.11 5.20 ± 0.08 5.20 ± 0.09 6.02 ± 0.08** 

Heart 

Absolute 1.148 ± 0.029 1.112 ± 0.032 1.167 ± 0.038 1.147 ± 0.028 1.124 ± 0.017 1.034 ± 0.032* 

Relative 3.03 ± 0.04 2.95 ± 0.03 3.09 ± 0.06 2.98 ± 0.04 2.94 ± 0.05 3.20 ± 0.07 

R. Kidney 

Absolute 1.268 ± 0.029 1.238 ± 0.041 1.448 ± 0.049** 1.316 ± 0.035 1.393 ± 0.035 1.258 ± 0.022 

Relative 3.35 ± 0.05 3.28 ± 0.04 3.84 ± 0.09** 3.42 ± 0.06** 3.64 ± 0.05** 3.90 ± 0.06** 

Liver 

Absolute 14.030 ± 0.355 14.181 ± 0.404 15.281 ± 0.696 16.100 ± 0.468* 16.374 ± 0.292** 14.103 ± 0.444 

Relative 37.01 ± 0.65 37.64 ± 0.37 40.53 ± 1.51** 41.76 ± 0.54** 42.79 ± 0.56** 43.73 ± 1.16** 

Lung 

Absolute 1.648 ± 0.048 1.656 ± 0.065 1.524 ± 0.031 1.724 ± 0.030 1.542 ± 0.056 1.422 ± 0.041** 

Relative 4.35 ± 0.12 4.40 ± 0.13 4.05 ± 0.07 4.49 ± 0.10 4.03 ± 0.13 4.41 ± 0.12 

R. Testis 

Absolute 1.514 ± 0.028 1.489 ± 0.033 1.561 ± 0.034 1.547 ± 0.031 1.505 ± 0.024 1.487 ± 0.025 

Relative 4.00 ± 0.03 3.96 ± 0.06 4.14 ± 0.05 4.02 ± 0.05 3.93 ± 0.03 4.61 ± 0.05** 

Thymus 

Absolute 0.290 ± 0.009 0.314 ± 0.013 0.283 ± 0.008 0.304 ± 0.009 0.312 ± 0.010 0.285 ± 0.011 

Relative 0.77 ± 0.02 0.83 ± 0.03 0.75 ± 0.02 0.79 ± 0.03 0.82 ± 0.03 0.88 ± 0.03* 

Female 

Necropsy body wt 212 ± 7 207 ± 4 218 ± 4 209 ± 3 207 ± 3 185 ± 3** 

Brain 

Absolute 1.816 ± 0.016 1.819 ± 0.015 1.835 ± 0.010 1.834 ± 0.013 1.816 ± 0.013 1.770 ± 0.025 

Relative 8.66 ± 0.33 8.83 ± 0.10 8.43 ± 0.14 8.81 ± 0.14 8.80 ± 0.12 9.60 ± 0.11** 

Heart 

Absolute 0.730 ± 0.016 0.714 ± 0.011 0.764 ± 0.017 0.729 ± 0.015 0.709 ± 0.012 0.644 ± 0.011** 

Relative 3.49 ± 0.18 3.46 ± 0.05 3.51 ± 0.07 3.50 ± 0.04 3.43 ± 0.06 3.49 ± 0.03 

R. Kidney 

Absolute 0.720 ± 0.019 0.743 ± 0.018 0.821 ± 0.014** 0.758 ± 0.023 0.797 ± 0.010* 0.762 ± 0.019 

Relative 3.40 ± 0.05 3.60 ± 0.08* 3.77 ± 0.04** 3.63 ± 0.09** 3.86 ± 0.05** 4.13 ± 0.08** 

Liver 

Absolute 7.273 ± 0.221 7.286 ± 0.204 7.963 ± 0.170* 7.785 ± 0.154 8.077 ± 0.168* 6.777 ± 0.150 

Relative 34.37 ± 0.59 35.27 ± 0.68 36.52 ± 0.56* 37.40 ± 0.83** 39.06 ± 0.51** 36.72 ± 0.63** 

Lung 

Absolute 1.155 ± 0.052 1.210 ± 0.044 1.110 ± 0.019 1.211 ± 0.037 1.048 ± 0.023* 0.960 ± 0.013** 

Relative 5.45 ± 0.18 5.86 ± 0.20 5.09 ± 0.06 5.82 ± 0.18 5.07 ± 0.09 5.21 ± 0.06 

Thymus 

Absolute 0.261 ± 0.011 0.237 ± 0.009 0.261 ± 0.006 0.254 ± 0.010 0.238 ± 0.007 0.227 ± 0.008* 

Relative 1.24 ± 0.06 1.15 ± 0.04 1.20 ± 0.02 1.22 ± 0.04 1.16 ± 0.04 1.23 ± 0.03 

* Significantly different (P#0.05) from the 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). 
232 1-Chloro-2-propanol, NTP TR 477 

TABLE H3 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice in the 14-Day Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 10,000 ppm 

Male 

n 10 10 10 10 10 9 

Necropsy body wt 28.1 ± 0.6 27.7 ± 0.5 27.5 ± 0.7 28.7 ± 0.4 28.4 ± 0.5 24.3 ± 0.6** 

Brain 

Absolute 0.525 ± 0.009 0.515 ± 0.010 0.509 ± 0.009 0.534 ± 0.009 0.502 ± 0.008 0.510 ± 0.009 

Relative 18.75 ± 0.34 18.61 ± 0.42 18.60 ± 0.54 18.65 ± 0.43 17.73 ± 0.34 21.10 ± 0.71** 

Heart 

Absolute 0.167 ± 0.005 0.150 ± 0.005 0.154 ± 0.008 0.159 ± 0.006 0.156 ± 0.009 0.141 ± 0.009 

Relative 5.97 ± 0.20 5.41 ± 0.14 5.58 ± 0.21 5.55 ± 0.22 5.49 ± 0.29 5.82 ± 0.37 

R. Kidney 

Absolute 0.325 ± 0.010 0.319 ± 0.012 0.321 ± 0.012 0.356 ± 0.010 0.337 ± 0.012 0.336 ± 0.017 

Relative 11.59 ± 0.30 11.48 ± 0.28 11.66 ± 0.29 12.41 ± 0.28 11.85 ± 0.26 13.76 ± 0.44** 

Liver 

Absolute 1.697 ± 0.042 1.723 ± 0.038 1.749 ± 0.071 1.966 ± 0.051* 2.041 ± 0.045* 1.671 ± 0.081 

Relative 60.52 ± 1.09 62.11 ± 0.69 63.42 ± 1.61 68.44 ± 0.98** 71.98 ± 1.33** 68.46 ± 1.91** 

Lung 

Absolute 0.217 ± 0.007 0.221 ± 0.008 0.223 ± 0.006 0.220 ± 0.004 0.219 ± 0.006 0.214 ± 0.013 

Relative 7.77 ± 0.31 7.99 ± 0.32 8.14 ± 0.28 7.68 ± 0.16 7.72 ± 0.16 8.81 ± 0.46 

R. Testis 

Absolute 0.120 ± 0.003 0.116 ± 0.002 0.118 ± 0.002 0.116 ± 0.002 0.115 ± 0.004 0.113 ± 0.003 

Relative 4.27 ± 0.06 4.19 ± 0.07 4.30 ± 0.10 4.06 ± 0.08 4.05 ± 0.11 4.64 ± 0.09* 

Thymus 

Absolute 0.065 ± 0.004 0.070 ± 0.004 0.062 ± 0.004 0.070 ± 0.003 0.065 ± 0.004 0.031 ± 0.002** 

Relative 2.32 ± 0.13 2.53 ± 0.14 2.24 ± 0.13 2.43 ± 0.13 2.28 ± 0.14 1.26 ± 0.09** 

Female 

n 10 10 10 10 10 10 

Necropsy body wt 21.6 ± 0.2 22.0 ± 0.4 21.6 ± 0.4 22.0 ± 0.3 22.9 ± 0.3 19.8 ± 0.8* 

Brain 

Absolute 0.507 ± 0.006 0.518 ± 0.008 0.510 ± 0.006 0.508 ± 0.008 0.516 ± 0.005 0.519 ± 0.016 

Relative 23.55 ± 0.44 23.53 ± 0.21 23.64 ± 0.41 23.13 ± 0.43 22.59 ± 0.33 27.09 ± 2.39 

Heart 

Absolute 0.132 ± 0.009 0.129 ± 0.005 0.132 ± 0.004 0.134 ± 0.005 0.139 ± 0.005 0.130 ± 0.006 

Relative 6.12 ± 0.38 5.85 ± 0.15 6.10 ± 0.16 6.09 ± 0.19 6.08 ± 0.18 6.68 ± 0.46 

R. Kidney 

Absolute 0.214 ± 0.005 0.212 ± 0.004 0.214 ± 0.005 0.209 ± 0.004 0.229 ± 0.005 0.224 ± 0.007 

Relative 9.93 ± 0.21 9.64 ± 0.16 9.90 ± 0.21 9.50 ± 0.11 10.01 ± 0.17 11.48 ± 0.50** 

Liver 

Absolute 1.412 ± 0.017 1.390 ± 0.022 1.486 ± 0.031 1.551 ± 0.030* 1.704 ± 0.032* 1.427 ± 0.084 

Relative 65.51 ± 0.61 63.13 ± 0.56 68.79 ± 1.26 70.59 ± 1.27** 74.50 ± 0.98** 71.69 ± 2.05** 

Lung 

Absolute 0.204 ± 0.008 0.217 ± 0.007 0.213 ± 0.006 0.206 ± 0.007 0.205 ± 0.007 0.203 ± 0.007 

Relative 9.45 ± 0.30 9.86 ± 0.28 9.87 ± 0.32 9.39 ± 0.37 8.95 ± 0.25 10.43 ± 0.52 

Thymus 

Absolute 0.094 ± 0.003 0.096 ± 0.003 0.096 ± 0.002 0.095 ± 0.007 0.099 ± 0.003 0.066 ± 0.009** 

Relative 4.37 ± 0.16 4.37 ± 0.10 4.44 ± 0.12 4.31 ± 0.29 4.31 ± 0.12 3.20 ± 0.40** 

* Significantly different (P#0.05) from the 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-Chloro-2-propanol, NTP TR 477 233 

TABLE H4 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 33 ppm 100 ppm 330 ppm 1,000 ppm 3,300 ppm 

Male 

n 10 10 10 9 10 10 

Necropsy body wt 39.2 ± 1.0 41.0 ± 1.2 40.3 ± 1.1 40.3 ± 1.3 40.0 ± 0.8 40.2 ± 0.8 

Brain 

Absolute 0.460 ± 0.007 0.472 ± 0.005 0.477 ± 0.007 0.477 ± 0.014 0.460 ± 0.005 0.456 ± 0.005 

Relative 11.80 ± 0.27 11.62 ± 0.38 11.90 ± 0.33 11.86 ± 0.25 11.54 ± 0.30 11.38 ± 0.24 

Heart 

Absolute 0.202 ± 0.009 0.189 ± 0.011 0.202 ± 0.009 0.187 ± 0.007 0.212 ± 0.006 0.214 ± 0.011 

Relative 5.18 ± 0.22 4.64 ± 0.29 5.04 ± 0.26 4.66 ± 0.18 5.30 ± 0.13 5.32 ± 0.24 

R. Kidney 

Absolute 0.316 ± 0.010 0.334 ± 0.018 0.357 ± 0.013 0.321 ± 0.012 0.352 ± 0.011 0.389 ± 0.008** 

Relative 8.08 ± 0.21 8.22 ± 0.49 8.87 ± 0.29 7.99 ± 0.27 8.80 ± 0.27 9.69 ± 0.20** 

Liver 

Absolute 1.812 ± 0.063 1.762 ± 0.096 1.999 ± 0.094 1.624 ± 0.082 2.094 ± 0.048* 1.915 ± 0.019 

Relative 46.29 ± 1.07 42.84 ± 1.46 49.69 ± 2.22 40.36 ± 1.63* 52.30 ± 0.52* 47.74 ± 0.75 

Lung 

Absolute 0.293 ± 0.013 0.339 ± 0.015 0.325 ± 0.021 0.319 ± 0.022 0.315 ± 0.012 0.323 ± 0.012 

Relative 7.47 ± 0.25 8.37 ± 0.52 8.04 ± 0.39 7.91 ± 0.44 7.87 ± 0.24 8.04 ± 0.26 

R. Testis 

Absolute 0.121 ± 0.003 0.120 ± 0.002 0.136 ± 0.004 0.121 ± 0.003 0.137 ± 0.004** 0.127 ± 0.001** 

Relative 3.10 ± 0.11 2.95 ± 0.10 3.38 ± 0.11 3.01 ± 0.08 3.44 ± 0.11 3.18 ± 0.06 

Thymus 

Absolute 0.039 ± 0.003 0.043 ± 0.003 0.048 ± 0.005 0.040 ± 0.002 0.047 ± 0.004 0.041 ± 0.003 

Relative 1.00 ± 0.06 1.06 ± 0.07 1.21 ± 0.14 0.99 ± 0.03 1.16 ± 0.08 1.02 ± 0.08 

Female 

n 10 10 10 10 10 10 

Necropsy body wt 33.2 ± 0.9 32.6 ± 0.9 32.6 ± 1.6 33.5 ± 0.9 34.7 ± 1.2 33.3 ± 0.9 

Brain 

Absolute 0.482 ± 0.004 0.481 ± 0.007 0.483 ± 0.005 0.477 ± 0.006 0.484 ± 0.008 0.469 ± 0.004 

Relative 14.62 ± 0.47 14.87 ± 0.45 15.09 ± 0.66 14.31 ± 0.42 14.13 ± 0.60 14.17 ± 0.35 

Heart 

Absolute 0.157 ± 0.004b 0.166 ± 0.006 0.168 ± 0.008 0.170 ± 0.010 0.166 ± 0.005 0.177 ± 0.006 

Relative 4.76 ± 0.14b 5.14 ± 0.24 5.28 ± 0.39 5.08 ± 0.28 4.83 ± 0.19 5.32 ± 0.15 

R. Kidney 

Absolute 0.210 ± 0.005 0.216 ± 0.006 0.218 ± 0.007 0.212 ± 0.006 0.225 ± 0.008 0.246 ± 0.008** 

Relative 6.37 ± 0.26 6.65 ± 0.17 6.77 ± 0.24 6.35 ± 0.21 6.51 ± 0.17 7.39 ± 0.18** 

Liver 

Absolute 1.430 ± 0.025 1.597 ± 0.054* 1.725 ± 0.054* 1.478 ± 0.030* 1.698 ± 0.056** 1.783 ± 0.049** 

Relative 43.23 ± 0.87 49.10 ± 1.20** 53.44 ± 1.52** 44.21 ± 0.90** 49.11 ± 1.01** 53.65 ± 1.21** 

Lung 

Absolute 0.312 ± 0.013 0.325 ± 0.018 0.352 ± 0.015 0.313 ± 0.010 0.325 ± 0.015 0.340 ± 0.011 

Relative 9.45 ± 0.45 9.99 ± 0.48 10.94 ± 0.56 9.35 ± 0.23 9.44 ± 0.44 10.22 ± 0.22 

Thymus 

Absolute 0.046 ± 0.002 0.051 ± 0.003 0.055 ± 0.003 0.050 ± 0.003 0.060 ± 0.003** 0.056 ± 0.003** 

Relative 1.39 ± 0.08 1.58 ± 0.09 1.70 ± 0.10* 1.50 ± 0.10 1.74 ± 0.06* 1.68 ± 0.06 

* Significantly different (P#0.05) from the 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 nù9 
234 1-Chloro-2-propanol, NTP TR 477 
235 

APPENDIX I
 

REPRODUCTIVE TISSUE EVALUATIONS 

AND ESTROUS CYCLE CHARACTERIZATION
 

TABLE I1 Summary of Reproductive Tissue Evaluations for Male Rats 

in the 14-Week Drinking Water Study of 1-Chloro-2-propanol .................. 236 

TABLE I2 Summary of Estrous Cycle Characterization for Female Rats 

in the 14-Week Drinking Water Study of 1-Chloro-2-propanol .................. 236 

TABLE I3 Summary of Reproductive Tissue Evaluations for Male Mice 

in the 14-Week Drinking Water Study of 1-Chloro-2-propanol .................. 237 

TABLE I4 Summary of Estrous Cycle Characterization for Female Mice 

in the 14-Week Drinking Water Study of 1-Chloro-2-propanol .................. 237 
236 1-Chloro-2-propanol, NTP TR 477 

TABLE I1 

Summary of Reproductive Tissue Evaluations for Male Rats in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 33 ppm 330 ppm 3,300 ppm 

n 10 10 10 10 

Weights (g) 

Necropsy body wt 379 ± 6 376 ± 9 385 ± 8 322 ± 5** 

R. cauda epididymis 0.1490 ± 0.0051 0.1370 ± 0.0061 0.1371 ± 0.0051 0.1152 ± 0.0046** 

R. epididymis 0.4650 ± 0.0091 0.4501 ± 0.0197 0.4720 ± 0.0092 0.4188 ± 0.0077* 

R. testis 1.5141 ± 0.0284 1.4878 ± 0.0336 1.5465 ± 0.0311 1.4871 ± 0.0252 

Epididymal spermatozoal measurements 

Motility (%) 67.20 ± 2.00 64.20 ± 2.59 64.20 ± 3.82 67.00 ± 3.28 

Abnormal (%) 0.78 ± 0.17 0.90 ± 0.11 0.86 ± 0.11 1.50 ± 0.16** 

Concentration 

 (10 /g cauda epididymal tissue) 6 742 ± 45 812 ± 46 887 ± 32* 725 ± 41 

* Significantly different (P#0.05) from the control group by Dunnett’s test (right epididymis weight) or by Dunn’s test (concentration) 

** Significantly different (P#0.01) from the control group by Williams’ test (body and tissue weights) or by Shirley’s test (abnormal sperm) a Data are presented as mean ± standard error. 

TABLE I2 

Summary of Estrous Cycle Characterization for Female Rats in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 33 ppm 330 ppm 3,300 ppm 

n 10 10 10 10 

Necropsy body wt (g) 

Estrous cycle length (days) 

212 ± 7 

4.89 ± 0.2b 

206 ± 4 

4.78 ± 0.15b 

208 ± 3 

5.22 ± 0.22b 

185 ± 3** 

4.40 ± 0.22 

Estrous stages (% of cycle) 

Diestrus 34.3 24.3 31.4 30.0 

Proestrus 15.7 14.3 11.4 21.4 

Estrus 31.4 40.0 37.1 30.0 

Metestrus 18.6 20.0 20.0 18.6 

Uncertain diagnoses 0.0 1.4 0.0 0.0 

** Significantly different (P#0.01) from the control group by Williams’ test a Necropsy body weight and estrous cycle length data are presented as mean ± standard error. Differences from the control group for 

estrous cycle length are not significant by Dunn’s test. By multivariate analysis of variance, exposed females do not differ significantly 

from the control females in the relative length of time spent in the estrous stages. b Estrous cycle was longer than 12 days or unclear in 1 of 10 animals. 
1-Chloro-2-propanol, NTP TR 477 237 

TABLE I3 

Summary of Reproductive Tissue Evaluations for Male Mice in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 33 ppm 330 ppm 3,300 ppm 

n 10 10 9 10 

Weights (g) 

Necropsy body wt 39.0 ± 1.0 41.0 ± 1.2 40.3 ± 1.3 40.2 ± 0.8 

R. cauda epididymis 0.0113 ± 0.0012 0.0108 ± 0.0005 0.0111 ± 0.0006 0.0123 ± 0.0010 

R. epididymis 0.0530 ± 0.0021 0.0493 ± 0.0012 0.0484 ± 0.0009 0.0586 ± 0.0014* 

R. testis 0.1205 ± 0.0028 0.1198 ± 0.0022 0.1203 ± 0.0027 0.1273 ± 0.0011 

Epididymal spermatozoal measurements 

Motility (%) 

Abnormal (%) 

74.22 ± 4.31b 

1.40 ± 0.26b 

76.60 ± 4.58 

1.82 ± 0.23 

70.22 ± 4.47 

1.64 ± 0.16 

71.00 ± 4.14 

1.66 ± 0.16 

Concentration 

 (10 /g cauda epididymal tissue) 6 1,237 ± 208b 1,504 ± 134 1,285 ± 87 1,140 ± 126 

*	 Significantly different (P#0.05) from the control group by Dunnett’s test a Data are presented as mean ± standard error. Differences from the control group are not significant by Dunnett’s test (body weight) or 

Dunn’s test (epididymal spermatozoal measurements). b nù9 

TABLE I4 

Summary of Estrous Cycle Characterization for Female Mice in the 14-Week Drinking Water Study 

of 1-Chloro-2-propanola 

0 ppm 33 ppm 330 ppm 3,300 ppm 

n 10 10 10 10 

Necropsy body wt (g) 

Estrous cycle length (days) 

33.2 ± 0.9 

4.25 ± 0.16b 

32.6 ± 0.9 

4.13 ± 0.13b 

33.5 ± 0.9 

4.33 ± 0.17c 33.3 ± 0.9 4.60 ± 0.16 

Estrous stages (% of cycle) 

Diestrus 24.3 31.4 25.7 14.3 

Proestrus 18.6 22.9 18.6 25.7 

Estrus 30.0 32.9 34.3 37.1 

Metestrus 27.1 12.9 21.4 22.9 

a Weights and estrous cycle lengths are presented as mean ± standard error. Differences from the control group are not significant by 

Dunnett’s test (body weight) or Dunn’s test (estrous cycle length). By multivariate analysis of variance, exposed females do not differ 

significantly from the control females in the relative length of time spent in the estrous stages. b	 Estrous cycle was longer than 12 days or unclear in 2 of 10 animals. 

Estrous cycle was longer than 12 days or unclear in 1 of 10 animals. c 
238 1-Chloro-2-propanol, NTP TR 477 
239 

APPENDIX J
 

CHEMICAL CHARACTERIZATION AND
 

DOSE FORMULATION STUDIES
 

PROCUREMENT AND CHARACTERIZATION OF 1-CHLORO-2-PROPANOL .......................... 240
 

PREPARATION AND ANALYSIS OF DOSE FORMULATIONS ................................... 241
 

FIGURE J1 Infrared Absorption Spectrum of 1-Chloro-2-propanol ........................ 242
 

FIGURE J2 Nuclear Magnetic Resonance Spectrum of 1-Chloro-2-propanol .................. 243
 

TABLE J1 Preparation and Storage of Dose Formulations in the Drinking Water Studies 

of 1-Chloro-2-propanol .............................................. 244
 

TABLE J2 Results of Analyses of Dose Formulations Administered to Rats and Mice
 

in the 14-Day Drinking Water Studies of 1-Chloro-2-propanol ................... 245
 

TABLE J3 Results of Analyses of Dose Formulations Administered to Rats and Mice
 

in the 14-Week Drinking Water Studies of 1-Chloro-2-propanol .................. 246
 

TABLE J4 Results of Analyses of Dose Formulations Administered to Rats and Mice
 

in the 2-Year Drinking Water Studies of 1-Chloro-2-propanol .................... 247
 

TABLE J5 Results of Referee Analyses of Dose Formulations Administered to Rats and Mice
 

in the 14-Week Drinking Water Studies of 1-Chloro-2-propanol .................. 250
 
240 1-Chloro-2-propanol, NTP TR 477 

CHEMICAL CHARACTERIZATION 

AND DOSE FORMULATION STUDIES 

PROCUREMENT AND CHARACTERIZATION OF 1-CHLORO-2-PROPANOL 

Technical grade 1-chloro-2-propanol (approximately 75% 1-chloro-2-propanol and 25% 2-chloro-1-propanol) 

was obtained from Eastman Kodak Laboratory Chemicals (Rochester, NY) in one lot (B15), which was used 

during the 14-day, 14-week, and 2-year studies. Identity, purity, and stability analyses were conducted by 

the analytical chemistry laboratory, Midwest Research Institute (Kansas City, MO). Reports on analyses 

performed in support of the 1-chloro-2-propanol studies are on file at the National Institute of Environmental 

Health Sciences. 

The major component of the test chemical, a clear, colorless liquid, was identified as 1-chloro-2-propanol by 

infrared, ultraviolet/visible, and nuclear magnetic resonance (NMR) spectroscopy. The infrared and 

ultraviolet/visible spectra were consistent with those expected for 1-chloro-2-propanol; the NMR spectrum 

was consistent with a mixture of isomers (1-chloro-2-propanol and 2-chloro-1-propanol). The NMR and 

infrared spectra were also consistent with a literature reference (Sadtler Standard Spectra). The infrared and 

nuclear magnetic spectra are presented in Figures J1 and J2. The boiling point and density of lot B15 were 

consistent with a literature reference (Merck Index, 1989). 

The purity of lot B15 was determined by elemental analyses, Karl Fischer water analysis, free acid titration, 

and gas chromatography. For free acid titration, samples were dissolved in methanol and titrated with 0.01N 

sodium hydroxide to a potentiometric endpoint; free acid was detected with a combination pH/mV electrode 

filled with aqueous 4M potassium chloride. Gas chromatography was performed using a flame ionization 

detector with a nitrogen carrier gas at a flow rate of 70 mL/minute. Two systems were used: 

A) 10% SP-1000 on 80/100 Supelcoport glass column, with an oven temperature program of 

50E C for 5 minutes, then 50E to 250E C at 10E C per minute, and 

B)	 20% SP-2100/0.1% Carbowax 1500 on 100/120 Supelcoport glass column, with an oven 

temperature program of 30E C for 5 minutes, then 30E to 175E C at 10E C per minute. 

Elemental analyses for carbon, chlorine, and hydrogen were in agreement with the theoretical values for 

1-chloro-2-propanol. Karl Fischer water analysis indicated 0.62% ± 0.02% water. Free acid titration 

indicated a hydrochloric acid content of 1,149 ± 2 ppm, equivalent to 0.0315 ± 0.0001 mEq of acid per 

gram of sample. Gas chromatography using system A indicated two major peaks and two impurities with a 

combined area of 0.47% relative to the total major peak area. Gas chromatography using system B indicated 

two major peaks and three impurities with a combined area of 0.67% relative to the total major peak area. 

No additional impurities with areas of 0.1% or greater relative to the major peak were detected using either 

system. The second major peak represents 2-chloro-1-propanol, a positional isomer of 1-chloro-2-propanol. 

The concentrations of 1-chloro-2-propanol and 2-chloro-1-propanol were estimated to be approximately 75% 

to 76% and 24% to 25%, respectively. 

Stability studies of the bulk chemical were performed by the analytical chemistry laboratory. Gas 

chromatography was performed using system A as described above with an oven temperature program of 

100E C for 5 minutes, then 100E to 110E C at 30E C per minute with a 2-minute hold at 110E C. Heptyl 

alcohol was added as an internal standard. These studies indicated that 1-chloro-2-propanol was stable as a 

bulk chemical for 2 weeks when stored protected from light at temperatures up to 60E C. To ensure 

stability, the bulk chemical was stored at 5.5E C (14-day and 14-week studies) or 1E to 8E C (2-year studies) 

protected from light in sealed glass containers. Stability was monitored during the 14-week studies using gas 
1-Chloro-2-propanol, NTP TR 477 241 

chromatography and free acid titration and during the 14-day and 2-year studies using gas chromatography. 

No degradation of the bulk chemical was detected. 

PREPARATION AND ANALYSIS OF DOSE FORMULATIONS 

The dose formulations were prepared twice during the 14-day studies, every 2 weeks in the 14-week studies, 

and as needed in the 2-year studies by mixing 1-chloro-2-propanol with ultraviolet light-treated, deionized 

water for the 14-day and 14-week studies and with deionized water for the 2-year studies (Table J1). 

Formulations were stored in amber glass jars at room temperature. 

Stability studies of the 100 ppm dose formulation were performed at the analytical chemistry laboratory using 

gas chromatography with flame ionization detection with system A with a flow rate of 55 mL/minute and an 

isothermal column oven temperature of 105E C. The isothermal column oven temperature was changed to 

87E C and the nitrogen flow rate was changed to 30 mL/minute for the analyses conducted during the 2-year 

studies. The internal standard was 1-heptanol for the 14-day and 14-week studies. The stability of the dose 

formulation was confirmed for 3 weeks when stored at room temperature protected from light and for 

72 hours when stored in drinking water bottles at room temperature exposed to light. 

Periodic analyses of the dose formulations of 1-chloro-2-propanol were conducted at the study laboratory 

using gas chromatography with the same system used for the stability studies. During the 14-day studies, 

formulations were analyzed once per week (Table J2). For the 14-week studies, formulations were analyzed 

at the beginning, midpoint, and end of the studies (Table J3). During the 2-year studies, formulations were 

analyzed approximately every 8 weeks (Table J4). Of the dose formulations analyzed and used during the 

14-day studies, 95% (19/20) were within 10% of the target concentration, with no value greater than 10% of 

the target concentration. A 1,000 ppm dose prepared on 10 September 1986 was !39% of the target and 

was remixed; the reformulated dose was found to be within the acceptable range. All five of the animal 

room samples analyzed were within 10% of the target concentration. All 25 of the dose formulations 

analyzed and used during the 14-week studies were within 10% of the target concentration with no value 

greater than 106% of the target concentration, and all 15 of the animal room samples analyzed were within 

10% of the target concentration. All 104 of the dose formulations analyzed and used during the 2-year 

studies were within 10% of the target concentration with no value greater than 104% of the target 

concentration, and 33/34 of the animal room samples analyzed were within 10% of the target concentration. 

The high concentration determined for the 250 ppm animal room sample was attributed to technical error; the 

sample was contaminated with the 650 ppm rat dose formulation. Results of periodic referee analyses 

performed by the analytical chemistry laboratory agreed with the results obtained by the study laboratory for 

the 14-week studies (Table J5). 
242 1-Chloro-2-propanol, NTP TR 477
 

FIGURE J1 

Infrared Absorption Spectrum of 1-Chloro-2-propanol 
1-Chloro-2-propanol, NTP TR 477
 243 

FIGURE J2 

Nuclear Magnetic Resonance Spectrum of 1-Chloro-2-propanol 
244 1-Chloro-2-propanol, NTP TR 477 

TABLE J1 

Preparation and Storage of Dose Formulations in the Drinking Water Studies of 1-Chloro-2-propanol 

14-Day Studies 14-Week Studies 2-Year Studies 

Preparation 

A mixture of ultraviolet light-treated 

deionized water and 1-chloro-2-propanol 

was prepared. Doses were prepared 

weekly. 

A mixture of ultraviolet light-treated 

deionized water and 1-chloro-2-propanol 

was prepared. Doses were prepared every 

2 weeks. 

A mixture of deionized water and 1-chloro2-propanol was prepared. Doses were 

prepared as needed. 

Chemical Lot Number 

B15 B15 B15 

Maximum Storage Time 

Approximately 15 days 3 weeks 3 weeks 

Storage Conditions 

Stored in amber glass bottles, protected 

from light, at room temperature 

Same as 14-day studies Same as 14-day studies 

Study Laboratory 

SRI International 

(Menlo Park, CA) 

SRI International 

(Menlo Park, CA) 

TSI Mason Laboratories 

(Worcester, MA) 

Referee Laboratory 

None Midwest Research Institute 

(Kansas City, MO) 

None 
245 

c 

1-Chloro-2-propanol, NTP TR 477 

TABLE J2 

Results of Analyses of Dose Formulations Administered to Rats and Mice 

in the 14-Day Drinking Water Studies of 1-Chloro-2-propanol 

Target Determined Difference a Concentration Concentration from Target 

Date Prepared (ppm) (ppm) (%) 

10 September 1986 100 105 +5 

100 96 !4 

330 335 +2 

330 334 +1 

1,000 614 !39 

1,000 993 !1 

3,300 3,213 !3 

3,300 3,206 !3 

10,000 9,727 !3 

10,000 9,252 !7 

16 September 1986 1,000 1,062b +6 

c 23 September 1986 100 98 !2 

330 316 !4 

1,000 974 !3 

3,300 3,120 !5 

10,000 9,460 !5 

17 September 1986 100 103 +3 

100 106 +6 

330 339 +3 

330 342 +4 

1,000 998 0 

1,000 970 !3 

3,300 3,325 +1 

3,300 3,309 0 

10,000 9,814 !2 

10,000 10,181 +2 

a Results of duplicate analyses b Results of remix
 

Animal room samples (taken from first batch of dose formulations prepared and from 16 September 1986 remix)
 
246 1-Chloro-2-propanol, NTP TR 477 

TABLE J3 

Results of Analyses of Dose Formulations Administered to Rats and Mice 

in the 14-Week Drinking Water Studies of 1-Chloro-2-propanol 

Target Determined Difference 

Concentration Concentrationa from Target 

Date Prepared (ppm) (ppm) (%) 

28 January 1987 33 32 !3 

100 95 !5 

330 323 !2 

1,000 982 !2 

3,300 3,246 !2 

17 February 1987b 33 33 0 

100 101 +1 

330 343 +4 

1,000 1,007 +1 

3,300 3,315 0 

12 March 1987 33 33 0 

33 35 +6 

100 98 !2 

100 98 !2 

330 323 !2 

330 325 !2 

1,000 998 0 

1,000 1,017 +2 

3,300 3,200 !3 

3,300 3,230 !2 

1 April 1987b 33 30 !9 

100 94 !6 

330 315 !5 

1,000 978 !2 

3,300 3,395 +3 

23 April 1987 33 32 !3 

33 33 0 

100 99 !1 

100 98 !2 

330 323 !2 

330 323 !2 

1,000 1,008 +1 

1,000 998 0 

3,300 3,375 +2 

3,300 3,275 !1 

12 May 1987b 33 30 !9 

100 96 !4 

330 321 !3 

1,000 964 !4 

3,300 3,320 +1 

a 

b Results of duplicate analyses 

Animal room samples (taken from first batch of dose formulations prepared) 
1-Chloro-2-propanol, NTP TR 477 247 

TABLE J4 

Results of Analyses of Dose Formulations Administered to Rats and Mice 

in the 2-Year Drinking Water Studies of 1-Chloro-2-propanol 

Target Determined Difference a Concentration Concentration from Target 

Date Prepared Date Analyzed (ppm) (ppm) (%) 

Rats 

23 January 1991 23 January 1991	 150 147 !2 

325 319 !2 

650 631 !3 

7 February 1991b	 150 144 !4 

325 322 !1 

650 644 !1 

27 March 1991 28 March 1991	 150 146 !3 

150 146 !3 

325 316 !3 

325 317 !2 

650 638 !2 

650 631 !3 

22 May 1991 23 May 1991	 150 147 !2 

150 148 !1 

325 320 !2 

650 640 !2 

17 July 1991 17 July 1991	 150 151 +1 

325 324 0 

650 644 !1 

31 July 1991b	 150 146 !3 

325 314 !3 

650 630 !3 

11 September 1991 12!13 September 1991	 150 150 0 

325 321 !1 

650 647 0 

6 November 1991 7 November 1991	 150 147 !2 

325 314 !3 

650 617 !5 

31 December 1991 2 January 1992	 150 147 !2 

325 316 !3 

650 632 !3 

15 January 1992b	 150 147 !2 

325 318 !2 

650 643 !1 

26 February 1992 27 February 1992	 150 147 !2 

150 149 !1 

325 319 !2 

325 323 !1 

650 638 !2 

650 640 !2 
248 1-Chloro-2-propanol, NTP TR 477 

TABLE J4 

Results of Analyses of Dose Formulations Administered to Rats and Mice 

in the 2-Year Drinking Water Studies of 1-Chloro-2-propanol 

Target Determined Difference 

Concentration Concentration from Target 

Date Prepared Date Analyzed (ppm) (ppm) (%) 

Rats (continued) 

22 April 1992 23 April 1992	 150 147 !2 

325 316 !3 

650 628 !3 

17 June 1992 18 June 1992	 150 150 0 

325 314 !3 

650 628 !3 

12 August 1992 13 August 1992	 150 150 0 

325 327 +1 

650 649 0 

9 September 1992b	 150 147 !2 

325 320 !2 

650 642 !1 

13 October 1992 14 October 1992	 150 148 !1 

325 319 !2 

650 637 !2 

2 December 1992 3 December 1992	 150 148 !1 

150 148 !1 

325 322 !1 

325 325 0 

650 639 !2 

650 640 !2 

14 January 1993 14 January 1993	 150 147 !2 

325 323 !1 

650 644 !1 

3 February 1993b	 150 149 !1 

325 323 !1 

650 643 !1 

Mice 

19 December 1990 19 December 1990 250 246 !2 

500 492 !2 

1,000 984 !2 

9 January 1991b 250 244 !2 

500 477 !5 

1,000 969 !3 

6 February 1991 7 February 1991 250 243 !3 

500 490 !2 

1,000 1,002 0 

27 March 1991 28 March 1991 250 247 !1 

500 491 !2 

1,000 990 !1 
1-Chloro-2-propanol, NTP TR 477 249 

TABLE J4 

Results of Analyses of Dose Formulations Administered to Rats and Mice 

in the 2-Year Drinking Water Studies of 1-Chloro-2-propanol 

Target Determined Difference 

Concentration Concentration from Target 

Date Prepared Date Analyzed (ppm) (ppm) (%) 

Mice (continued) 

22 May 1991 23 May 1991 250 248 !1 

500 487 !3 

1,000 990 !1 

1,000 991 !1 

b 5 June 1991 250 240 !4 

500 490 !2 

1,000 982 !2 

1,000 989 !1 

17 July 1991 17 July 1991 250 261 +4 

500 499 0 

1,000 991 !1 

11 September 1991 12!13 September 1991 250 250 0 

500 496 !1 

1,000 999 0 

6 November 1991 7 November 1991 250 246 !2 

500 486 !3 

1,000 983 !2 

b 22 November 1991 250 247 !1 

500 492 !2 

1,000 975 !2 

31 December 1991 2 January 1992 250 244 !2 

500 482 !4 

1,000 992 !1 

26 February 1992 27 February 1992 250 252 +1 

500 489 !2 

1,000 983 !2 

22 April 1992 23 April 1992 250 243 !3 

250 244 !2 

500 481 !4 

500 484 !3 

1,000 969 !3 

1,000 980 !2 

14 May 1992 b 250 250 0 

250 420 +68 

500 487 !3 

500 495 !1 

1,000 993 !1 

1,000 1,005 +1 
250 1-Chloro-2-propanol, NTP TR 477 

TABLE J4 

Results of Analyses of Dose Formulations Administered to Rats and Mice 

in the 2-Year Drinking Water Studies of 1-Chloro-2-propanol 

Date Prepared Date Analyzed 

Target 

Concentration 

(ppm) 

Determined 

Concentration 

(ppm) 

Difference 

from Target 

(%) 

Mice (continued) 

17 June 1992 18 June 1992 250 

250 

500 

500 

1,000 

1,000 

246 

240 

481 

482 

971 

969 

!2 

!4 

!4 

!4 

!3 

!3 

12 August 1992 13 August 1992 250 

500 

1,000 

251 

497 

998 

0 

!1 

0 

13 October 1992 14 October 1992 250 

500 

1,000 

246 

497 

989 

!2 

!1 

!1 

2 November 1992b 250 

500 

1,000 

242 

491 

1,004 

!3 

!2 

0 

2 December 1992 3 December 1992 250 

250 

500 

500 

1,000 

1,000 

251 

248 

492 

496 

982 

989 

0 

!1 

!2 

!1 

!2 

!1 

a Results of duplicate analyses b Animal room samples 

TABLE J5 

Results of Referee Analyses of Dose Formulations Administered to Rats and Mice 

in the 14-Week Drinking Water Studies of 1-Chloro-2-propanol 

Date Prepared 

Target Concentration 

(ppm) 

Determined Concentration (ppm) 

Study Referee 

Laboratory Laboratory a b 

28 January 1987 

23 April 1987 

1,000 

100 

982 

99 

992 ± 8 

96.4 ± 1.9 

a 

b Results of duplicate analyses 

Results of triplicate analyses 
251 

APPENDIX K 

WATER AND COMPOUND CONSUMPTION 

IN THE 2-YEAR DRINKING WATER STUDIES 

OF 1-CHLORO-2-PROPANOL 

TABLE K1 Water and Compound Consumption by Male Rats 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 252 

TABLE K2 Water and Compound Consumption by Female Rats 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 253 

TABLE K3 Water and Compound Consumption by Male Mice 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 254 

TABLE K4 Water and Compound Consumption by Female Mice 

in the 2-Year Drinking Water Study of 1-Chloro-2-propanol ................... 255 
252 1-Chloro-2-propanol, NTP TR 477 

TABLE K1 

Water and Compound Consumption by Male Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Water 

(g/day)a Body 

Weight 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Dayb 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Day 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Day 

Week (g) (g) (mg/kg) (g) (mg/kg) (g) (mg/kg) 

1 18.3 132 18.2 130 21 18.1 131 45 18.8 131 93 

2 23.4 166 23.3 163 21 24.2 166 47 23.6 167 92 

4 19.2 224 20.2 225 13 21.9 231 31 21.0 230 59 

5 18.0 247 18.3 249 11 19.0 256 24 19.7 253 51 

8 24.0 289 23.2 293 12 22.5 296 25 22.7 294 50 

9 22.1 306 22.6 306 11 21.7 312 23 21.7 308 46 

12 18.0 337 18.1 341 8 19.7 346 19 19.8 340 38 

13 22.1 349 21.3 351 9 22.8 355 21 24.6 351 46 

17 22.1 375 21.2 378 8 22.8 383 19 21.3 382 36 

21 21.0 410 20.4 409 7 20.0 414 16 20.4 413 32 

25 21.1 426 19.8 424 7 21.8 432 16 22.5 428 34 

29 19.8 445 20.7 444 7 22.1 451 16 22.7 450 33 

33 22.1 454 21.2 454 7 23.6 462 17 22.7 461 32 

37 20.8 462 20.2 462 7 21.3 473 15 22.2 470 31 

41 23.6 478 22.5 478 7 23.3 491 15 22.9 488 31 

45 24.4 488 24.8 487 8 23.9 501 15 27.2 496 36 

49 25.4 484 22.8 485 7 25.9 497 17 27.4 494 36 

53 24.4 503 23.4 500 7 22.9 516 14 24.9 507 32 

57 21.8 504 20.3 503 6 22.2 517 14 23.0 509 29 

61 21.7 505 20.2 507 6 21.1 523 13 22.2 516 28 

65 22.9 502 22.2 502 7 24.1 518 15 23.8 508 30 

69 22.6 502 21.4 504 6 24.4 520 15 23.6 508 30 

73 20.9 510 20.6 514 6 25.5 529 16 24.4 510 31 

77 23.6 512 25.3 513 7 25.9 524 16 28.8 509 37 

81 20.0 513 20.3 516 6 21.7 532 13 21.0 503 27 

85 24.2 514 25.9 516 8 26.0 537 16 26.3 505 34 

89 22.5 512 21.4 504 6 28.5 524 18 25.3 497 33 

93 23.4 516 23.1 497 7 25.5 522 16 27.9 487 37 

97 28.7 516 26.1 502 8 29.1 506 19 31.3 477 43 

101 28.2 481 24.1 492 7 30.8 495 20 30.9 468 43 

104 26.0 464 26.1 479 8 30.3 488 20 26.9 460 38 

Mean for weeks 

1-13 20.6 256 20.6 257 13 21.2 262 29 21.5 260 59 

14-52 22.3 447 21.5 447 7 22.8 456 16 23.3 454 33 

53-104 23.6 504 22.9 504 7 25.6 518 16 25.7 498 34 

a 

b Grams of water consumed per animal per day 

Milligrams of 1-chloro-2-propanol consumed per kilogram body weight per day 
1-Chloro-2-propanol, NTP TR 477 253 

TABLE K2 

Water and Compound Consumption by Female Rats in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 150 ppm 325 ppm 650 ppm 

Water 

(g/day)a Body 

Weight 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Dayb 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Day 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Day 

Week (g) (g) (mg/kg) (g) (mg/kg) (g) (mg/kg) 

1 16.3 111 16.0 111 22 15.7 111 46 16.1 110 95 

2 17.8 128 16.9 128 20 18.9 128 48 17.8 127 91 

4 13.4 152 14.1 151 14 14.5 152 31 14.5 153 61 

8 14.5 182 14.8 180 12 15.5 180 28 15.0 182 54 

12 12.0 198 13.7 198 10 13.3 199 22 13.1 201 42 

17 14.2 216 15.9 216 11 15.5 213 24 14.7 218 44 

21 12.5 224 13.9 221 9 15.2 220 22 14.6 224 42 

25 13.2 230 13.6 228 9 13.7 227 20 13.6 231 38 

29 12.8 240 14.5 238 9 14.2 238 19 14.5 242 39 

33 13.1 246 13.9 244 9 14.3 244 19 14.5 247 38 

37 13.5 254 14.1 252 8 14.0 252 18 14.4 255 37 

41 14.2 266 15.9 265 9 16.6 266 20 16.6 268 40 

45 12.9 269 13.9 268 8 13.7 269 16 13.7 270 33 

49 13.7 281 14.9 278 8 14.9 280 17 14.8 282 34 

53 13.3 292 13.9 293 7 14.5 290 16 14.2 297 31 

57 13.7 296 14.4 298 7 15.1 295 17 14.6 301 31 

61 13.0 305 14.3 305 7 14.9 302 16 15.0 309 31 

65 14.1 305 14.9 307 7 15.6 303 17 15.9 311 33 

69 15.7 315 16.2 315 8 17.0 311 18 17.1 318 35 

73 15.3 321 16.7 323 8 16.7 316 17 16.7 324 33 

77 15.7 329 16.9 332 8 17.2 328 17 17.3 333 34 

81 15.9 326 16.6 334 7 16.6 326 17 16.5 331 32 

85 17.3 333 17.7 337 8 17.5 327 17 17.7 338 34 

89 16.4 339 17.3 343 8 18.5 337 18 18.0 348 34 

93 16.5 338 18.1 344 8 18.7 336 18 17.9 353 33 

97 18.0 345 19.9 336 9 20.5 337 20 20.7 358 38 

101 16.5 345 18.1 341 8 19.4 333 19 18.5 367 33 

105 18.9 348 18.8 354 8 20.8 334 20 20.3 350 38 

Mean for weeks 

1-13 14.8 154 15.1 153 16 15.6 154 35 15.3 155 69 

14-52 13.3 247 14.5 246 9 14.7 246 20 14.6 249 38 

53-105 15.7 324 16.7 326 8 17.4 320 18 17.2 331 34 

a 

b Grams of water consumed per animal per day 

Milligrams of 1-chloro-2-propanol consumed per kilogram body weight per day 
254 1-Chloro-2-propanol, NTP TR 477 

TABLE K3 

Water and Compound Consumption by Male Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Water 

(g/day)a Body 

Weight 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Dayb 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Day 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Day 

Week (g) (g) (mg/kg) (g) (mg/kg) (g) (mg/kg) 

2 6.8 25.8 7.2 25.9 70 5.7 26.5 107 5.8 26.4 221 

5 5.1 31.5 5.4 30.9 44 4.9 31.7 77 4.6 31.9 145 

8 4.5 36.6 5.3 36.3 36 4.4 36.9 59 4.5 37.2 121 

12 4.2 39.5 4.4 39.6 28 4.1 39.8 52 4.4 40.2 108 

17 4.6 44.6 4.2 44.8 24 4.3 45.3 47 4.2 45.5 93 

21 4.4 46.9 4.3 47.5 23 4.4 47.7 46 4.3 47.9 90 

25 5.0 48.6 4.5 48.9 23 4.6 49.6 46 4.3 49.7 87 

29 4.9 50.7 4.7 50.5 24 4.7 51.0 46 4.6 50.9 91 

33 4.6 51.3 4.8 50.8 24 4.7 51.1 46 4.7 51.3 92 

37 4.5 51.9 4.5 51.0 22 4.5 51.2 44 4.6 51.6 89 

41 4.4 52.4 4.6 52.0 22 4.7 52.7 45 4.6 52.4 87 

45 5.1 53.1 5.0 52.2 24 4.8 53.5 45 4.7 53.4 89 

49 5.2 52.4 5.0 51.8 24 4.9 52.7 46 4.9 52.9 93 

53 5.8 52.4 5.7 52.0 27 5.7 52.9 54 5.3 53.2 99 

57 5.6 52.1 5.3 51.7 26 5.3 52.5 51 5.3 52.8 100 

61 5.7 52.3 5.0 52.1 24 5.6 52.7 53 5.2 53.1 98 

65 5.6 51.7 5.0 52.1 24 5.3 52.3 50 5.1 52.9 97 

69 5.2 51.8 4.9 52.1 24 5.1 51.8 50 5.0 51.9 97 

73 5.4 51.4 5.1 51.5 25 5.6 51.4 55 5.1 51.2 100 

77 5.7 49.8 5.3 51.0 26 5.8 50.3 58 5.4 49.2 110 

81 5.4 50.1 5.0 50.4 25 5.2 49.7 52 5.0 48.5 103 

85 5.8 50.1 5.2 50.1 26 5.8 49.5 59 6.3 47.6 133 

89 6.1 48.7 5.6 49.4 28 5.3 48.0 55 5.8 47.2 123 

93 5.9 47.6 5.1 49.3 26 5.4 47.4 57 5.6 45.1 125 

97 6.2 47.0 5.2 48.6 27 5.2 46.8 55 5.4 44.6 120 

104 6.6 44.3 5.4 47.5 28 5.2 45.5 57 5.6 43.6 129 

Mean for weeks 

1-13 5.2 33.3 5.6 33.2 44 4.8 33.7 74 4.8 33.9 149 

14-52 4.7 50.2 4.6 50.0 23 4.6 50.6 46 4.6 50.6 90 

53-104 5.8 49.9 5.2 50.6 26 5.4 50.1 54 5.4 49.3 110 

a 

b Grams of water consumed per animal per day 

Milligrams of 1-chloro-2-propanol consumed per kilogram body weight per day 
1-Chloro-2-propanol, NTP TR 477 255 

TABLE K4 

Water and Compound Consumption by Female Mice in the 2-Year Drinking Water Study 

of 1-Chloro-2-propanol 

0 ppm 250 ppm 500 ppm 1,000 ppm 

Water 

(g/day)a Body 

Weight 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Dayb 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Day 

Water 

(g/day) 

Body 

Weight 

Dose/ 

Day 

Week (g) (g) (mg/kg) (g) (mg/kg) (g) (mg/kg) 

2 4.9 21.9 6.3 21.6 73 5.2 21.6 121 5.4 21.5 250 

5 4.9 25.5 5.8 24.2 60 5.4 24.6 110 5.8 24.5 236 

7 5.0 28.8 6.4 27.3 58 6.5 28.0 117 6.2 28.0 222 

8 5.2 29.6 6.0 27.4 55 5.6 28.6 98 5.4 28.9 186 

12 5.2 33.9 5.4 32.0 43 5.2 33.6 77 5.3 33.8 157 

17 5.2 37.6 5.0 35.8 35 4.8 37.1 65 5.0 37.4 132 

21 4.6 40.7 5.1 39.1 33 4.6 40.7 56 4.5 40.6 111 

25 4.8 44.0 5.0 42.2 29 4.9 43.6 56 4.9 44.1 111 

29 4.5 45.7 4.9 44.1 28 4.8 45.3 53 4.0 45.7 88 

33 4.5 47.4 4.9 45.1 27 4.7 46.5 51 4.5 46.4 97 

37 4.1 50.0 4.3 47.6 23 4.2 49.5 43 4.3 49.0 88 

41 4.5 51.1 4.4 48.9 23 4.4 50.8 43 4.4 49.8 89 

45 4.6 53.0 4.5 50.9 22 4.5 52.8 42 5.1 52.4 97 

49 4.7 53.3 4.7 52.0 22 4.6 53.9 42 4.4 52.8 84 

53 4.7 54.4 4.7 52.7 22 4.8 55.3 43 4.6 54.4 85 

57 5.0 54.7 4.8 53.5 23 4.9 55.9 44 4.9 55.2 89 

61 4.6 55.8 5.0 54.9 23 4.9 58.2 42 4.8 56.7 85 

65 4.8 57.4 4.9 55.6 22 5.1 59.4 43 4.9 58.6 83 

69 4.8 59.1 4.9 57.4 21 4.9 60.5 40 4.6 59.0 78 

73 5.3 58.7 5.4 57.8 23 5.2 61.1 43 5.0 60.3 84 

77 5.6 59.3 5.5 58.1 23 5.7 61.2 47 5.6 60.7 92 

81 4.9 59.5 5.3 59.3 22 5.0 62.9 40 4.7 61.2 78 

85 5.2 60.1 5.4 59.8 23 5.1 62.4 41 4.8 61.0 78 

89 5.7 59.8 5.2 59.5 22 5.4 61.0 45 5.2 59.5 87 

93 5.7 57.6 5.3 58.6 23 5.7 60.8 47 5.5 59.7 92 

97 5.8 56.2 5.3 58.9 23 5.3 61.7 43 5.5 59.7 92 

101 5.8 54.2 5.9 57.6 26 5.7 59.6 48 5.6 58.6 96 

105 5.9 52.1 5.8 54.5 26 6.3 55.4 57 6.2 55.5 111 

Mean for weeks 

1-13 5.0 27.9 6.0 26.5 58 5.6 27.3 104 5.6 27.3 210 

14-52 4.6 47.0 4.8 45.1 27 4.6 46.7 50 4.6 46.5 100 

53-105 5.3 57.1 5.2 57.0 23 5.3 59.7 44 5.1 58.6 88 

a 

b Grams of water consumed per animal per day 

Milligrams of 1-chloro-2-propanol consumed per kilogram body weight per day 
256 1-Chloro-2-propanol, NTP TR 477 
257 

APPENDIX L 

INGREDIENTS, NUTRIENT COMPOSITION, 

AND CONTAMINANT LEVELS 

IN NIH-07 RAT AND MOUSE RATION 

TABLE L1 

TABLE L2 

TABLE L3 

TABLE L4 

Ingredients of NIH-07 Rat and Mouse Ration .............................. 

Vitamins and Minerals in NIH-07 Rat and Mouse Ration ...................... 

Nutrient Composition of NIH-07 Rat and Mouse Ration ...................... 

Contaminant Levels in NIH-07 Rat and Mouse Ration ........................ 

258 

258 

259 

260 
258 1-Chloro-2-propanol, NTP TR 477 

TABLE L1 

Ingredients of NIH-07 Rat and Mouse Rationa 

Ingredientsb Percent by Weight 

Ground #2 yellow shelled corn 24.50

Ground hard winter wheat 23.00 

Soybean meal (49% protein) 12.00 

Fish meal (60% protein) 10.00 

Wheat middlings 10.00 

Dried skim milk 5.00 

Alfalfa meal (dehydrated, 17% protein) 4.00 

Corn gluten meal (60% protein) 3.00 

Soy oil 2.50 

Dried brewer’s yeast 2.00 

Dry molasses 1.50 

Dicalcium phosphate 1.25 

Ground limestone 0.50 

Salt 0.50 

Premixes (vitamin and mineral) 0.25 

a NCI, 1976; NIH, 1978 b Ingredients were ground to pass through a U.S. Standard Screen No. 16 before being mixed. 

TABLE L2 

Vitamins and Minerals in NIH-07 Rat and Mouse Rationa 

Amount Source 

Vitamins 

A 5,500,000 IU Stabilized vitamin A palmitate or acetate 

D3 4,600,000 IU D-activated animal sterol 

K3 

d-"-Tocopheryl acetate 

2.8 g 

20,000 IU 

Menadione 

Choline 560.0 g Choline chloride 

Folic acid 2.2 g 

Niacin 30.0 g 

d-Pantothenic acid 18.0 g d-Calcium pantothenate 

Riboflavin 3.4 g 

Thiamine 10.0 g Thiamine mononitrate 

B12 4,000 μg 

Pyridoxine 1.7 g Pyridoxine hydrochloride 

Biotin 140.0 mg d-Biotin 

Minerals 

Iron 120.0 g Iron sulfate 

Manganese 60.0 g Manganous oxide 

Zinc 16.0 g Zinc oxide 

Copper 4.0 g Copper sulfate 

Iodine 1.4 g Calcium iodate 

Cobalt 0.4 g Cobalt carbonate 

a Per ton (2,000 lb) of finished product 
1-Chloro-2-propanol, NTP TR 477 259 

TABLE L3 

Nutrient Composition of NIH-07 Rat and Mouse Ration 

Mean ± Standard 

Nutrient Deviation Range Number of Samples 

Protein (% by weight) 23.44 ± 0.51 22.2 ) 24.3 25 

Crude fat (% by weight) 5.32 ± 0.19 5.00 ) 5.90 25 

Crude fiber (% by weight) 3.34 ± 0.32 2.60 ) 4.30 25 

Ash (% by weight) 6.45 ± 0.18 6.12 ) 6.81 25 

Amino Acids (% of total diet) 

Arginine 1.273 ± 0.083 1.100 ) 1.390 12 

Cystine 0.307 ± 0.068 0.181 ) 0.400 12 

Glycine 1.152 ± 0.051 1.060 ) 1.220 12 

Histidine 0.581 ± 0.029 0.531 ) 0.630 12 

Isoleucine 0.913 ± 0.034 0.867 ) 0.965 12 

Leucine 1.969 ± 0.053 1.850 ) 2.040 12 

Lysine 1.269 ± 0.050 1.200 ) 1.370 12 

Methionine 0.436 ± 0.104 0.306 ) 0.699 12 

Phenylalanine 0.999 ± 0.114 0.665 ) 1.110 12 

Threonine 0.899 ± 0.059 0.824 ) 0.985 12 

Tryptophan 0.216 ± 0.146 0.107 ) 0.671 12 

Tyrosine 0.690 ± 0.091 0.564 ) 0.794 12 

Valine 1.079 ± 0.057 0.962 ) 1.170 12 

Essential Fatty Acids (% of total diet) 

Linoleic 2.389 ± 0.223 1.830 ) 2.570 11 

Linolenic 0.273 ± 0.034 0.210 ) 0.320 11 

Vitamins 

Vitamin A (IU/kg) 6,584 ± 1,215 5,280 ) 11,450 25 

Vitamin D (IU/kg) 4,450 ± 1,382 3,000 ) 6,300 4 

"-Tocopherol (ppm) 35.24 ± 8.58 22.5 ) 48.9 12 

Thiamine (ppm) 17.28 ± 2.03 14.0 ) 22.0 25 

Riboflavin (ppm) 7.78 ± 0.899 6.10 ) 9.00 12 

Niacin (ppm) 98.73 ± 23.21 65.0 ) 150.0 12 

Pantothenic acid (ppm) 32.94 ± 8.92 23.0 ) 59.2 12 

Pyridoxine (ppm) 9.28 ± 2.49 5.60 ) 14.0 12 

Folic acid (ppm) 2.56 ± 0.70 1.80 ) 3.70 12 

Biotin (ppm) 0.265 ± 0.046 0.190 ) 0.354 12 

Vitamin B12 (ppb) 41.6 ± 18.6 10.6 ) 65.0 12 

Choline (ppm) 2,995 ± 382 2,300 ) 3,430 11 

Minerals 

Calcium (%) 1.17 ± 0.06 1.09 ) 1.31 25 

Phosphorus (%) 0.92 ± 0.05 0.760 ) 1.00 25 

Potassium (%) 0.886 ± 0.059 0.772 ) 0.971 10 

Chloride (%) 0.531 ± 0.082 0.380 ) 0.635 10 

Sodium (%) 0.316 ± 0.031 0.258 ) 0.370 12 

Magnesium (%) 0.165 ± 0.010 0.148 ) 0.180 12 

Sulfur (%) 0.266 ± 0.060 0.208 ) 0.420 11 

Iron (ppm) 348.0 ± 83.7 255.0 ) 523.0 12 

Manganese (ppm) 93.27 ± 5.62 81.7 ) 102.0 12 

Zinc (ppm) 59.42 ± 9.73 46.1 ) 81.6 12 

Copper (ppm) 11.63 ± 2.46 8.09 ) 15.4 12 

Iodine (ppm) 3.49 ± 1.14 1.52 ) 5.83 11 

Chromium (ppm) 1.57 ± 0.53 0.60 ) 2.09 12 

Cobalt (ppm) 0.81 ± 0.27 0.49 ) 1.23 8 
260 1-Chloro-2-propanol, NTP TR 477 

TABLE L4 

Contaminant Levels in NIH-07 Rat and Mouse Rationa 

Mean ± Standard 

Deviationb Range Number of Samples 

Contaminants 

Arsenic (ppm) 0.47 ± 0.18 0.10 ) 0.70 25 

Cadmium (ppm) 0.14 ± 0.07 0.04 ) 0.20 25 

Lead (ppm) 0.36 ± 0.24 0.10 ) 1.00 25 c Mercury (ppm) 0.02 0.02 ) 0.03 25 

Selenium (ppm) 0.33 ± 0.11 0.05 ) 0.40 25 

Aflatoxins (ppb) <5.0 25 

Nitrate nitrogen (ppm)d 7.92 ± 4.09 2.90 ) 17.0 25 

Nitrite nitrogen (ppm)d 0.14 ± 0.06 0.10 ) 0.30 25 e BHA (ppm) 1.76 ± 1.92 1.00 ) 10.0 25 e BHT (ppm) 1.60 ± 1.58 1.0 ) 8.00 25 

Aerobic plate count (CFU/g) 97,244 ± 161,922 6,500 ) 710,000 25 

Coliform (MPN/g) 3 ± 0.3 3 ) 4 25 

Escherichia coli (MPN/g) <3 25 

Salmonella (MPN/g) Negative 25 

Total nitrosoamines (ppb)f 7.52 ± 1.84 4.7 ) 11.4 25 

N-Nitrosodimethylamine (ppb)f 5.46 ± 1.24 2.9 ) 8.2 25 

N-Nitrosopyrrolidine (ppb)f 2.06 ± 1.08 1.0 ) 4.3 25 

Pesticides (ppm) 

"-BHC <0.01 25 

$-BHC <0.02 25 

(-BHC <0.01 25 

*-BHC <0.01 25 

Heptachlor <0.01 25 

Aldrin <0.01 25 

Heptachlor epoxide <0.01 25 

DDE <0.01 25 

DDD <0.01 25 

DDT <0.01 25 

HCB <0.01 25 

Mirex <0.01 25 

Methoxychlor <0.05 25 

Dieldrin <0.01 25 

Endrin <0.01 25 

Telodrin <0.01 25 

Chlordane <0.05 25 

Toxaphene <0.10 25 

Estimated PCBs <0.20 25 

Ronnel <0.01 25 

Ethion <0.02 25 

Trithion <0.05 25 

Diazinon <0.10 25 

Methyl parathion <0.02 25 

Ethyl parathion <0.02 25 

Malathion 0.25 ± 0.24 0.05 ) 0.97 25 

Endosulfan I <0.01 25 

Endosulfan II <0.01 25 

Endosulfan sulfate <0.03 25 

a CFUùcolony-forming units; MPNùmost probable number; BHCùhexachlorocyclohexane or benzene hexachloride b For values less than the limit of detection, the detection limit is given as the mean. 

All values except for lots milled November and December 1991 were less than the detection limit. The detection limit is given as the 

mean. d Sources of contamination: alfalfa, grains, and fish meal e Sources of contamination: soy oil and fish meal f All values were corrected for percent recovery. 

c 
261 

APPENDIX M 

SENTINEL ANIMAL PROGRAM 

METHODS .............................................................. 

TABLE M1 Murine Virus Antibody Determinations for Rats and Mice 

in the 14-Week and 2-Year Studies of 1-Chloro-2-propanol ..................... 

262 

264 
 

 

262 1-Chloro-2-propanol, NTP TR 477 

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 randomly selected rats and mice during the 14-week and 2-year studies. 

Blood from each animal was collected and allowed to clot, and the serum was separated. The samples were 

processed appropriately and sent to Microbiological Associates, Inc. (Bethesda, 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 Analysis 

RATS 

14-Week Study 

ELISA

 PVM (pneumonia virus of mice) 

RCV/SDA (rat coronavirus/

 sialodacryoadenitis virus) 

Sendai 

Study termination

Study termination

Study termination 

Hemagglutination Inhibition

 H-1 (Toolan’s H-1 virus) 

KRV (Kilham rat virus) 

Study termination

Study termination 

2-Year Study 

ELISA 

Mycoplasma arthritidis 

Mycoplasma pulmonis 

PVM 

RCV/SDA 

Sendai 

22 months 

22 months

6, 10, 12, 18, and 22 months, study termination

6, 10, 12, 18, and 22 months, study termination

6, 10, 12, 18, and 22 months, study termination 

Hemagglutination Inhibition

 H-1 

KRV 

6, 10, 12, 18, and 22 months, study termination

6, 10, 12, 18, and 22 months, study termination 
1-Chloro-2-propanol, NTP TR 477 263 

Method and Test 

MICE 

14-Week Study 

ELISA

 Ectromelia virus 

GDVII (mouse encephalomyelitis virus) 

LCM (lymphocytic choriomeningitis virus) 

MVM (minute virus of mice) 

PVM 

Reovirus 3 

Sendai 

Hemagglutination Inhibition

 Polyoma virus 

2-Year Study 

ELISA

 Ectromelia virus 

EDIM (epizootic diarrhea of infant mice) 

GDVII 

LCM 

Mouse adenoma virus-FL 

MHV (mouse hepatitis virus) 

PVM 

Reovirus 3 

Sendai 

Immunofluorescence Assay

 Ectromelia virus 

EDIM 

LCM 

Reovirus 3 

Hemagglutination Inhibition

 K (papovavirus) 

MVM 

Polyoma virus 

Results of serology tests are presented in Table M1. 

Time of Analysis 

Study termination

Study termination

Study termination

Study termination

Study termination

Study termination

Study termination 

Study termination 

6, 12, and 18 months, study termination

12 and 18 months, study termination

6, 12, and 18 months, study termination

6, 12, and 18 months, study termination

6, 12, and 18 months, study termination

6, 12, and 18 months, study termination

6, 12, and 18 months, study termination

6, 12, and 18 months, study termination

6, 12, and 18 months, study termination 

6 and 12 months

6, 12, and 18 months

6 months

12 months 

6, 12, and 18 months, study termination

6, 12, and 18 months, study termination

6, 12, and 18 months, study termination 
264 1-Chloro-2-propanol, NTP TR 477 

TABLE M1 

Murine Virus Antibody Determinations for Rats and Mice in the 14-Week and 2-Year Studies 

of 1-Chloro-2-propanol 

Incidence of Antibody Positive Serologic 

Interval in Sentinel Animals Reaction for 

14-Week Studies 

Rats 

Study termination 0/10 None positive 

Mice 

Study termination	 0/10 None positive 

2-Year Studies 

Rats 

6 Months 0/10 None positive 

10 Months 0/10 None positive 

12 Months 0/10 None positive 

18 Months 0/11 None positive a 22 Months 1/1 M. arthritidis 

Study termination 0/16 None positive 

Mice 

6 Months 0/10 None positive 

12 Months 1/10b Reovirus 3 

18 Months 0/8 None positive 

Study termination 0/10 None positive 

a One rat with clinical symptoms that could be due to an infectious disease was evaluated for murine virus antibody titers. The serum 

sample from this rat had a low antibody titer for M. arthritidis. A larger set of samples (16) evaluated at study termination was negative 

for the panel of viruses included in the sentinel animal program including M. arthritidis. Evaluation of samples positive for M. arthritidis 

in various studies by immunoblot and Western blot procedures indicated that positive titers may be due to cross reaction with antibodies of 

nonpathogenic Mycoplasma or other agents. Only one sample was positive in this study, and there were no clinical findings or 

histopathologic changes of M. arthritidis infection in the animal with the positive titer. Accordingly, the M. arthritidis-positive titer was 

considered a false positive. b	 Only one sample was positive for Reovirus 3 at 12 months with a low antibody titer. Samples from the same colony at 18 months and 

2 years were negative. Sporadic low-titer positive reactions have been associated with false positives for Reovirus 3. Accordingly, the 

Reovirus 3 positive titer was considered a false positive.