NTP TECHNICAL REPORT

ON THE

TOXICOLOGY AND CARCINOGENESIS

STUDIES OF SODIUM CHLORATE

(CAS NO. 7775-09-9)

IN F344/N RATS AND B6C3F1 MICE

(DRINKING WATER STUDIES)

NATIONAL TOXICOLOGY PROGRAM

P.O. Box 12233

Research Triangle Park, NC 27709

December 2005

NTP TR 517

NIH Publication No. 06-4457

National Institutes of Health

Public Health Service

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
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 and Prevention. 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.

Details about ongoing and completed NTP studies, abstracts of all NTP Technical Reports, and full versions of the

completed reports are available at the NTP’s World Wide Web site: http://ntp.niehs.nih.gov. In addition, printed

copies of these reports are available from NTP as supplies last by contacting (919) 541-3419.
NTP TECHNICAL REPORT

ON THE

TOXICOLOGY AND CARCINOGENESIS

STUDIES OF SODIUM CHLORATE

(CAS NO. 7775-09-9)

IN F344/N RATS AND B6C3F1 MICE

(DRINKING WATER STUDIES)

NATIONAL TOXICOLOGY PROGRAM

P.O. Box 12233

Research Triangle Park, NC 27709

December 2005

NTP TR 517

NIH Publication No. 06-4457

National Institutes of Health

Public Health Service

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
2

National Toxicology Program

Evaluated and interpreted results and reported findings

M.J. Hooth, Ph.D., Study Scientist

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

G.D. Hill, D.V.M., Ph.D., Study Pathologist

D.W. Bristol, Ph.D.

J.R. Bucher, Ph.D.

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

G.E. Kissling, Ph.D.

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

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

S.D. Peddada, Ph.D.

J.H. Roycroft, Ph.D.

C.S. Smith, Ph.D.

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

K.L. Witt, M.S.

Southern Research Institute

Conducted studies and evaluated pathology findings

J.D. Prejean, Ph.D., Principal Investigator,

3-week and 2-year studies

W.R. Richter, D.V.M., M.S., Principal Investigator,

2-year studies

C.D. Hébert, Ph.D., Principal Investigator,

2-year studies

D.R. Farnell, D.V.M., M.S., Ph.D.

J.E. Heath, D.V.M.

R.B. Thompson, D.V.M., Ph.D.

Experimental Pathology Laboratories, Inc.

Provided pathology review

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

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

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

G.A. Willson, B.V.M. & S.

Dynamac Corporation

Prepared quality assurance audits

S. Brecher, Ph.D., Principal Investigator

CONTRIBUTORS

NTP Pathology Working Group

Evaluated slides and prepared pathology report

(October 3 and November 19, 2002)

W.G. Lieuallen, B.S., D.V.M., Ph.D., Chairperson

Pathology Associates International

B.J. Davis, V.M.D., Ph.D.

National Toxicology Program

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

National Toxicology Program

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

National Toxicology Program

M.P. Jokinen, D.V.M.

Pathology Associates International

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

Experimental Pathology Laboratories, Inc.

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

Experimental Pathology Laboratories, Inc.

Y. Tani, D.V.M., Ph.D., Observer

National Toxicology Program

G.A. Willson, B.V.M. & S.

Experimental Pathology Laboratories, Inc.

Constella Group, Inc.

Provided statistical analyses

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

L.J. Betz, M.S.

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

Biotechnical Services, Inc.

Prepared Technical Report

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

P.H. Carver, B.A.

L.M. Harper, B.S.

D.C. Serbus, Ph.D.
3

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

EXPLANATION OF LEVELS OF EVIDENCE OF CARCINOGENIC ACTIVITY . . . . . . . . . . . . . . . . 8

TECHNICAL REPORTS REVIEW SUBCOMMITTEE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS . . . . . . . . . . . . 10

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

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

RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

DISCUSSION AND CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

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

of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61

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

of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

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

of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141

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

of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177

APPENDIX E Genetic Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217

APPENDIX F Clinical Pathology Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223

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

APPENDIX H Chemical Characterization and Dose Formulation Studies . . . . . . . . . . . . . . . . . . . . . . . . 233

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

of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243

APPENDIX J Ingredients, Nutrient Composition, and Contaminant Levels 

in NTP-2000 Rat and Mouse Ration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249

APPENDIX K Sentinel Animal Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253

CONTENTS
4 Sodium Chlorate, NTP TR 517 

SUMMARY

Background

Sodium chlorate occurs when drinking water is disinfected by chlorine dioxide. We studied the effects of sodium

chlorate in rats and mice to identify potential toxic or carcinogenic hazards to humans.

Methods

We gave groups of male and female rats drinking water containing 125, 1,000, or 2,000 milligrams (mg) of sodium

chlorate per liter (L) of water for two years. Male and female mice received 500, 1,000, or 2,000 mg/L. Other

groups of animals received plain tap water and served as the control groups. At the end of the study, tissues from

more than 40 sites were examined for every animal.

Results

Male and female rats receiving sodium chlorate had higher rates of follicular cell hypertrophy of the thyroid gland,

and the groups receiving 2,000 mg/L had higher rates of thyroid gland cancer, compared with the control groups.

Female mice exposed to sodium chlorate had a few pancreatic islet cell tumors.

Conclusions

We conclude that sodium chlorate caused some thyroid gland neoplasms in male and female rats. The pancreatic

islet cell tumors in female mice may have been related to sodium chlorate exposure.
ABSTRACT

SODIUM CHLORATE

CAS No. 7775-09-9

Chemical Formula: NaClO3 Molecular Weight: 106.44

Synonyms: Chlorate of soda; chloric acid, sodium salt; soda chlorate

Trade names: Atlacide, Chlorax, Defol, De-Fol-Ate, Dervan, Drop-Leaf, Fall, Harvest-Aid, Kusatol, Leafex, Shed-A-Leaf ‘L’, Tumbleaf

5

Sodium chlorate is used as an oxidizing agent and bleach

for paper pulp; to make chlorine dioxide used in water

disinfection; in ore processing; in the manufacture of

matches and explosives; in dye making and the printing

and dyeing of fabrics; in leather finishing and tanning; to

make perchlorates; in toothpaste and mouthwash; and as

a nonselective herbicide, defoliant, and harvest aid.

Chlorate is found as a stable by-product in drinking

water that has been disinfected with chlorine dioxide.

Sodium chlorate was nominated for study by the

United States Environmental Protection Agency because

of widespread consumer exposure to treated drinking

water and lack of carcinogenicity data. Male and female

F344/N rats and B6C3F1 mice were exposed to sodium

chlorate (at least 99% pure) in drinking water for

3 weeks and 2 years. Genetic toxicology studies were

conducted in Salmonella typhimurium and mouse

peripheral blood erythrocytes.

3-WEEK STUDY IN RATS

Groups of 10 male and 10 female rats were exposed to

drinking water containing 0, 125, 250, 500, 1,000, or

2,000 mg/L sodium chlorate for 3 weeks (equivalent to

average daily doses of approximately 20, 35, 75, 170,

and 300 mg sodium chlorate/kg body weight per day for

males and 20, 40, 75, 150, and 340 mg/kg per day 

for females). All rats survived to the end of the study.

Mean body weights of exposed groups were similar to

those of control groups. Water consumption by exposed

rats was generally similar to that by control groups

throughout the study. An exposure concentration-related

decrease in segmented neutrophil counts occurred in

male and female rats on days 4 and 22. Heart weights

were significantly decreased in 2,000 mg/L males. The

incidences of minimal to mild thyroid gland follicular

cell hypertrophy were significantly increased in males

and females exposed to 500 mg/L or greater.

3-WEEK STUDY IN MICE

Groups of 10 male and 10 female mice were exposed to

drinking water containing 0, 125, 250, 500, 1,000, or

2,000 mg/L sodium chlorate for 3 weeks (equivalent to

average daily doses of approximately 20, 45, 90, 175,

and 350 mg/kg per day for male mice and 20, 45, 95,

O

Na+ Cl O

O
6 Sodium Chlorate, NTP TR 517 

190, and 365 mg/kg per day for female mice). All mice

survived to the end of the study. Mean body weights of

exposed groups were generally similar to those of control groups. Water consumption by exposed mice was

generally similar to that by control groups throughout

the study. No exposure-related lesions occurred in male

or female mice.

2-YEAR STUDY IN RATS

Groups of 50 male and 50 female rats were exposed to

drinking water containing 0, 125, 1,000, or 2,000 mg/L

sodium chlorate for 2 years (equivalent to average daily

doses of approximately 5, 35, and 75 mg/kg per day for

male rats and 5, 45, and 95 mg/kg per day for female

rats). Survival of exposed rats was similar to that of the

control groups. Mean body weights of all exposed

groups were similar to those of the control groups

throughout the study. Water consumption by exposed

rats was generally similar to that by controls throughout

the study. 

Serum concentrations of thyroxine and triiodothyronine

were significantly reduced in 1,000 and 2,000 mg/L

males and females on day 4 and in 2,000 mg/L males and

females at week 3. Serum concentrations of thyroid

stimulating hormone were significantly increased in

1,000 and 2,000 mg/L males on day 4 and at week 3, in

1,000 and 2,000 mg/L females on day 4, in 2,000 mg/L

females at week 3, and in 2,000 mg/L males and females

at week 14. 

All special study rats in the 1,000 and 2,000 mg/L

groups had thyroid gland follicular cell hypertrophy at 3

and 14 weeks. There were positive trends in the incidences of thyroid gland follicular cell carcinoma in male

rats and of thyroid gland follicular cell adenoma or carcinoma (combined) in males and females. The incidences of thyroid gland follicular cell hypertrophy were

significantly increased in all exposed groups of males

and in 1,000 and 2,000 mg/L females. Thyroid gland

focal follicle mineralization occurred in most 1,000 and

2,000 mg/L female rats. The incidences of hematopoietic cell proliferation in the spleen of 2,000 mg/L males

and bone marrow hyperplasia in 1,000 and 2,000 mg/L

males were significantly greater than those in the 

controls.

2-YEAR STUDY IN MICE

Groups of 50 male and 50 female mice were exposed to

drinking water containing 0, 500, 1,000, or 2,000 mg/L

sodium chlorate for 2 years (equivalent to average daily

doses of approximately 40, 80, and 160 mg/kg per day

for male mice and 30, 60, and 120 mg/kg per day for

female mice). Survival of exposed mice was similar to

that of the control groups. Mean body weights of

exposed females were generally less than those of the

control groups after week 84 of the study. Water consumption by exposed mice was generally similar to that

by controls throughout the study. 

There was a positive trend in the incidences of pancreatic islet cell adenoma or carcinoma (combined) in

female mice. Thyroid gland follicular cell hypertrophy

was significantly increased in 2,000 mg/L females. The

incidences of bone marrow hyperplasia were significantly increased in all exposed groups of females.

GENETIC TOXICOLOGY

Sodium chlorate was not mutagenic in Salmonella

typhimurium strains TA97, TA98, TA100, TA102,

TA104, or TA1535; all tests were conducted with and

without exogenous metabolic activation (induced rat or

hamster liver S9 enzymes). In vivo, no increases in the

frequencies of micronucleated normochromatic erythrocytes were seen in peripheral blood samples from male

and female B6C3F1 mice exposed to sodium chlorate in

drinking water for 3 weeks.

CONCLUSIONS

Under the conditions of this 2-year drinking water study,

there was some evidence of carcinogenic activity* of

sodium chlorate in male and female F344/N rats based

on increased incidences of thyroid gland neoplasms.

There was no evidence of carcinogenic activity of

sodium chlorate in male B6C3F1 mice exposed to 500,

1,000, or 2,000 mg/L. There was equivocal evidence of

carcinogenic activity of sodium chlorate in female

B6C3F1 mice based on marginally increased incidences

of pancreatic islet neoplasms.

Exposure to sodium chlorate resulted in nonneoplastic

lesions in the thyroid gland of male and female rats and

female mice, bone marrow of male rats and female mice,

and spleen of male rats.

__________

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

comments and public discussion on this Technical Report appears on page 11.
Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies of Sodium Chlorate

Male Female Male Female

F344/N Rats F344/N Rats B6C3F1 Mice B6C3F1 Mice

Concentrations in

drinking water

Body weights

Survival rates

Nonneoplastic effects

Neoplastic effects

Equivocal findings

Level of evidence of

carcinogenic activity

0, 125, 1,000 or

2,000 mg/L

Exposed groups similar

to the control group

36/50, 27/50, 31/50,

28/50

Thyroid gland: follicular

cell hypertrophy (4/47,

13/44, 33/43, 40/47)

Spleen: hematopoietic

cell proliferation (2/48,

6/49, 4/49, 11/50)

Bone marrow:

hyperplasia (28/48,

35/48, 41/50, 40/49)

Thyroid gland: follicular

cell carcinoma (0/47,

0/44, 0/43, 4/47);

follicular cell adenoma or

carcinoma (1/47, 0/44,

0/43, 6/47)

None

Some evidence

0, 125, 1,000 or

2,000 mg/L

Exposed groups similar

to the control group

37/50, 36/50, 33/50,

41/50

Thyroid gland: follicular

cell hypertrophy (3/47,

7/47, 27/43, 42/46);

follicular cell

mineralization (25/47,

26/47, 40/43, 44/46)

Thyroid gland: follicular 

cell adenoma or

carcinoma (1/47, 0/47,

1/43, 4/46)

None

Some evidence

0, 500, 1,000, or

2,000 mg/L

Exposed groups similar

to the control group

38/50, 41/50, 41/50,

33/50

None

None

None

No evidence

0, 500, 1,000, or

2,000 mg/L

Exposed groups less than

the control group

36/49, 35/50, 31/49,

35/50

Thyroid gland: follicular

cell hypertrophy (3/48,

2/50, 5/49, 14/50)

Bone marrow:

hyperplasia (14/50, 28/50,

29/50, 31/50)

None

Pancreatic islets:

adenoma or carcinoma

(0/46, 2/47, 2/49, 4/49)

Equivocal evidence

Genetic toxicology

Salmonella typhimurium gene mutations:

Micronucleated erythrocytes

Mouse peripheral blood in vivo:

Negative in strains TA97, TA98, TA100, TA102, TA104, and TA1535 with and

without S9

Negative in male and female mice

Sodium Chlorate, NTP TR 517 7
8 Sodium Chlorate, NTP TR 517 

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.

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

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

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

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

indicated as “may have been” related to chemical exposure.

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

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

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

two adjacent levels. These considerations should include:

• adequacy of the experimental design and conduct;

• occurrence of common versus uncommon neoplasia;

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

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

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

neoplasms of those types have the potential to become malignant;

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

• latency in tumor induction;

• multiplicity in site-specific neoplasia;

• metastases;

• supporting information from proliferative lesions (hyperplasia) in the same site of neoplasia or 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. 
Sodium Chlorate, NTP TR 517 9

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 sodium chlorate on

December 9, 2004, 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.

Mary Anna Thrall, D.V.M., M.S., Chairperson

Department of Microbiology, Immunology and Pathology 

Colorado State University

Fort Collins, CO

Diane F. Birt, Ph.D., Principal Reviewer

Department of Food Science & Human Nutrition

Iowa State University

Ames, IA

Kim Boekelheide, M.D., Ph.D.

Division of Biology and Medicine

Department of Pathology and Laboratory Medicine

Brown University

Providence, RI

Michael R. Elwell, D.V.M., Ph.D. 

Pathology, Drug Safety Evaluation

Pfizer Global Research and Development

Groton, CT

Thomas A. Gasiewicz, Ph.D, Principal Reviewer

Department of Environmental Medicine

Environmental Health Sciences Center

University of Rochester School of Medicine

Rochester, NY

James E. Klaunig, Ph.D.

Division of Toxicology

Indiana University School of Medicine

Indianapolis, IN

Stephen M. Roberts, Ph.D.

Center for Environmental & Human Toxicology

University of Florida

Gainesville, FL

Richard D. Storer, M.P.H., Ph.D.

Department of Genetic and Cellular Toxicology

Merck Research Laboratories

West Point, PA

Mary Vore, Ph.D., Principal Reviewer

Graduate Center for Toxicology

University of Kentucky 

Lexington, KY

Cheryl Lyn Walker, Ph.D.

Department of Carcinogenesis

M.D. Anderson Cancer Center

The University of Texas

Smithville, TX
10 Sodium Chlorate, NTP TR 517 

On December 9, 2004, the draft Technical Report on the

toxicology and carcinogenesis studies of sodium chlorate received public review by the National Toxicology

Program’s Board of Scientific Counselors’ Technical

Reports Review Subcommittee. The review meeting

was held at the National Institute of Environmental

Health Sciences, Research Triangle Park, NC.

Dr. M.J. Hooth, NIEHS, introduced the toxicology and

carcinogenesis studies of sodium chlorate by describing

its use as a bleach and occurrence after water disinfection, the design of the drinking water studies, and the

toxic and neoplastic responses in the study animals. The

proposed conclusions were some evidence of carcinogenic activity of sodium chlorate in male and female

F344/N rats, no evidence of carcinogenic activity of

sodium chlorate in male B6C3F1 mice, and equivocal

evidence of carcinogenic activity of sodium chlorate in

female B6C3F1 mice.

Dr. Birt, the first principal reviewer, thought the study

was designed and reported well, and she agreed with the

proposed conclusions.

Dr. Gasiewicz, the second principal reviewer, agreed

with most of the proposed conclusions but thought the

pancreatic islet neoplasms merited a conclusion of some

evidence rather than equivocal evidence.

Dr. Vore, the third principal reviewer, agreed with the

proposed conclusions and inquired about the presence of

chlorate in the tap water.

Dr. Hooth replied that no chlorate was found above the

level of detection (0.11 parts per million) in any of the

water samples assayed. She explained that the pancreatic islet neoplasms were considered equivocal evidence

because they were seen only in one sex of one species,

and the decreased incidences of hyperplasia were not

supportive of an effect. She noted that the NTP had

never made a call of carcinogenicity in mice based on

pancreatic islet neoplasms.

Dr. C. Capen, representing EKA Chemical Company,

spoke about the perturbation of thyroid hormone economy by sodium chlorate above a certain threshold as a

possible link to the genesis of the observed thyroid gland

neoplasms.

Dr. Birt moved and Dr. Vore seconded that the proposed

conclusions be accepted as written. The motion was carried unanimously with nine votes.

Dr. W.T. Allaben, NCTR, asked if the concept of a

threshold effect in the thyroid gland would be added to

the discussion. Drs. Birt and Gasiewicz replied that this

was a hypothesis that required more testing, and they did

not feel the data yet supported their inclusion 

in the discussion.

SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS
11

INTRODUCTION

SODIUM CHLORATE

CAS No. 7775-09-9

Chemical Formula: NaClO3 Molecular Weight: 106.44

Synonyms: Chlorate of soda; chloric acid, sodium salt; soda chlorate

Trade names: Atlacide, Chlorax, Defol, De-Fol-Ate, Dervan, Drop-Leaf, Fall, Harvest-Aid, Kusatol, Leafex, Shed-A-Leaf ‘L’, Tumbleaf

CHEMICAL AND PHYSICAL PROPERTIES

Sodium chlorate occurs as colorless, odorless crystals or

white granules with a salty taste (Merck Index, 1996;

HSDB, 2003). It has a melting point of 248° C, a boiling point of 300° C, and a density of 2.49 g/mL. It is soluble in water, liquid ammonia, glycerin, and alcohol

(Merck Index, 1996; HSDB, 2003). Sodium chlorate

decomposes on heating above 300° C, producing oxygen

and chlorine. It is a strong oxidant and reacts with combustible, reducing, and organic materials, causing fire

and explosion hazards.

PRODUCTION, USE,

AND HUMAN EXPOSURE

Sodium chlorate is manufactured from sodium chloride

by electrolysis (HSDB, 2003). The production capacities of the United States and Canada in 1999 were

946,000 and 1,193,000 short tons per year, respectively

(Chemical Market Reporter, 1999). The demand for

sodium chlorate from the United States and Canada was

1.75 million tons in 1997 and 1.85 million tons in 1998

and was estimated to be 2.35 million tons in 2002

(Chemical Market Reporter, 1999). United States production for 1991 was 639,000 metric tons; imports and

exports in 1984 equaled 124,000 and 1,720 metric tons,

respectively (HSDB, 2003). Between the years 1983

and 1990, the commercial use of sodium chlorate in

North America was estimated to be 565,000 to

967,000 tons per year (Mendiratta and Duncan, 1993),

and 28,583 workers were estimated to have been occupationally exposed in 1983 (Perry et al., 1994).

Sodium chlorate is used as an oxidizing agent and bleach

for paper pulp, to make chlorine dioxide used in water

disinfection, in ore processing (especially uranium ore),

in the manufacture of matches and explosives, in dye

making and the printing and dyeing of fabrics, in leather

finishing and tanning, to make perchlorates, and in

toothpaste and mouthwash (Merck Index, 1996; HSDB,

2003). The consumption pattern for sodium chlorate in

the United States in the 1990s indicated 95% was used

for wood pulp bleaching in the paper industry; 3% for

O

Na+ Cl O

O
12 Sodium Chlorate, NTP TR 517 

the production of other chlorates, perchlorates, and chlorites; and 2% for other uses, including herbicides, water

treatment, and uranium mining (HSDB, 2003).

Sodium chlorate has been widely used as a nonselective

herbicide, defoliant, and harvest aid (Sheahan et al.,

1971; Perry et al., 1994; HSDB, 2003). It is considered

phytotoxic to all green plant parts and can kill through

root absorption. Sodium chlorate may be used to control

morning glory, Canada thistle, Johnson grass, and

St. John’s wort (EXTOXNET, 1995). It is used as a total

weed control on noncrop land where it is applied at up to

600 kg/hectare (HSDB, 2003). Sodium chlorate is also

used as a defoliant and desiccant for cotton, safflower,

corn, flax, peppers, soybeans, grain sorghum, southern

peas, dry beans, rice, and sunflowers. Sodium chlorate

may be used in combination with other herbicides,

including atrazine, 2,4-D, bromacil, diuron, and sodium

metaborate (EXTOXNET, 1995; HSDB, 2003). The

total estimated annual agricultural use of sodium chlorate in the United States in 1992 for eight crops was over

5,200,000 pounds applied. Use of sodium chlorate on

crops of cotton and dry beans accounted for greater than

98% of the national agricultural use (USGS, 1992).

Chlorate is also found as a stable by-product in drinking

water that has been disinfected with chlorine dioxide

(Condie, 1986; Pfaff and Brockhoff, 1990; Singer,

1993). Chlorine dioxide is more effective than chlorine

for killing most microorganisms, produces fewer chlorinated by-products, and does not produce significant levels of trihalomethanes (Richardson, 1998). Chlorate

may be formed by inefficient chlorine dioxide generation, if the pH of the reaction mixture has not been

adjusted properly, or as a result of the reaction between

residual chlorite in finished water and free chlorine in

the distribution system (Singer, 1993; Gallagher et al.,

1994). In addition, chlorine dioxide disproportionates to

form chlorite and chlorate in alkaline solutions and

decomposes to form chlorate in acidic solutions with

exposure to sunlight (Condie, 1986).

In the United States, between 500 and 900 drinking

water treatment facilities used chlorine dioxide either

seasonally or year-round, and as many as 25 million people may be drinking water treated with chlorine dioxide

(Gallagher et al., 1994). Laboratory studies estimate

that 10% to 30% of the chlorine dioxide added to

water is converted to chlorate (Moore et al., 1978;

Michael et al., 1981). For water treatment plants using

chlorine dioxide, chlorate concentrations in four treated

water samples ranged from 21 to 330 μg/L, with a mean

of 200 μg/L (USEPA, 1994). Evaluation of a United

States public water supply, which was disinfected solely

by chlorine dioxide, indicated average weekly

chlorate levels in treated water of 0.34 to 1.13 mg/L

(Michael et al., 1981). For water treatment systems that

used hypochlorite for disinfection, chlorate concentrations ranged from 11 to 660 μg/L (USEPA, 1994).

Chlorate has been detected in source waters and may

result from commercial wastewater from paper and pulp

mills, from the use of chlorate salts as herbicides, and

from the use of free chlorine to disinfect wastewater

prior to its release to receiving waters (Bolyard et al.,

1993). High levels of chlorate (0.2 to 42 g/L) have also

been found in hypochlorite solutions used for drinking

water disinfection (Bolyard and Fair, 1992). In addition,

swimming pool water has been found to contain an average concentration of 16 mg/L chlorate, with a maximum

of 124 mg/L (Beech et al., 1980). 

ABSORPTION, DISTRIBUTION,

METABOLISM, AND EXCRETION

Experimental Animals

Most of the data on the absorption, distribution, metabolism, and excretion of chlorine dioxide, chlorite, and

chlorate have been published by Abdel-Rahman et al.

(1980a, 1982, 1984). These investigators utilized 36Cl as

a tracer for the chlorine and utilized a fractionation

method to separate the 36Cl compounds in various body

fluids. In the rat, chlorine dioxide is metabolized to

chloride, chlorite, and chlorate. Abdel-Rahman et al.

(1984) administered 0.065 mg/kg 36ClO3 (0.85 μCi) in

3 mL of a 5 mg/L solution orally to male SpragueDawley rats. The radiolabeled chlorate was rapidly

absorbed from the gastrointestinal tract. A peak 36Cl

plasma level of 185 ng/mL was reached at 30 minutes.

Distribution of radioactivity at 72 hours after administration indicated that the highest concentrations were in

the plasma, followed by whole blood, stomach, testes,

lung, kidney, skin, duodenum, spleen, brain, packed

cells, ileum, carcass, liver, and bone marrow.

Elimination from the plasma occurred in two phases; the

half-life for the rapid elimination phase was about

6 hours, followed by a slower phase that had a half-life

of 36.7 hours. Radioactivity first appeared in the urine,

and urinary excretion accounted for up to 42% of the

total initial dose in 72 hours. Approximately 2% to 4%

of the initial dose was excreted in the feces at 72 hours

postdosing. Chlorate was metabolized, and 20%, 4%,
Sodium Chlorate, NTP TR 517 13

and 13% of the initial dose was excreted as chloride,

chlorite, and chlorate, respectively. Daily administration

of 100 mg/L chlorate to male rats in drinking water for 

1 year resulted in an increase in the chloroform 

concentration in the liver but not in the blood

(Abdel-Rahman et al., 1982).

Steffen and Wetzel (1993) administered 1 g/kg sodium

chlorate to rabbits by gavage and determined serum and

urine concentrations of chlorate. The highest serum concentrations were observed 90 minutes after dosing and

remained high (10 to 20 mM) for at least 12 hours. Peak

concentrations of chlorate (246 ± 99 mM) were observed

in the urine at 6 hours; the elimination half-life was

approximately 20 hours. 

Humans

No reports were found in the literature on the absorption,

distribution, metabolism, or excretion of sodium chlorate

by humans.

TOXICITY

Experimental Animals

The oral LD50 for sodium chlorate is reported to be

8,350 mg/kg in mice, 1,200 mg/kg in rats, 1,350 mg/kg

in cats, 7,200 mg/kg in rabbits, and 700 mg/kg in dogs

(Lewis, 1996; HSDB, 2003). In laboratory studies,

the LD50 for intravenous administration of sodium 

chlorate to male and female Sprague-Dawley rats

was 2,229 mg chlorate/kg (1,743 to 2,638 mg/kg)

(Jeng and Woodworth, 1990).

Chlorate toxicosis has been reported in horses, pigs,

cows, sheep, chickens, and dogs and is caused primarily

by accidental ingestion through the inadequate handling

or disposal of herbicides or through accidental inclusion

in animal feed (Gregory et al., 1993). Ingestion of chlorates causes local irritation of the gastrointestinal tract.

Hemolysis and methemoglobin formation, followed by

intravascular coagulation, are also frequently observed.

The kidney is a target organ, with the renal tubules being

most susceptible. Clinical signs in animals have

included vomiting, ataxia, dyspnea, cyanosis, hematuria,

hemoglobinuria, and hemoglobinemia. Anuria, coma,

and death can follow. Animals that survive chlorate poisoning may die from chronic renal failure.

Male Sprague-Dawley rats were given 10 or 100 mg/L

chlorate per day in drinking water for 4 months

(Abdel-Rahman et al., 1980b). At 2 months, blood glutathione levels were decreased significantly in both

exposed groups. At 4 months, blood osmotic fragility

was decreased significantly in the 100 mg/L group, and

abnormal erythrocyte morphology, including the presence of codocytes and echinocytes, was observed in both

exposed groups. 

Couri and Abdel-Rahman (1980) studied the 

glutathione-dependent enzyme system in the erythrocytes of male Sprague-Dawley rats after exposure to

chlorate in drinking water at 0, 10, or 100 mg/L for up to

12 months. At 6 months, rats exhibited no change in

glutathione reductase activity, an increase in glutathione

peroxidase at 100 mg/L, a decrease in catalase activity at

100 mg/L, and a decrease in glutathione concentration at

both 10 and 100 mg/L. After 12 months of treatment,

there were no significant differences in the activity of

glutathione reductase, glutathione peroxidase, or catalase in either exposed group, and the glutathione concentration was significantly higher in both exposed

groups.

Male Sprague-Dawley rats were exposed to drinking

water containing 0, 10, or 100 mg chlorate/L for up to

1 year (Couri et al., 1982; Abdel-Rahman et al., 1985).

Mean body weights were significantly decreased (10%

to 20%) in both treatment groups throughout the experiment. Blood osmotic fragility was significantly

decreased in both exposed groups after 7 or 9 months of

treatment. Reduced fragility of red blood cells was

attributed to cross-linking of membrane components

with hemoglobin and subsequent precipitation of hemoglobin. Reductions in blood glutathione levels were

observed in the 100 mg/L group after 7 and 9 months of

treatment and in the 10 mg/L group after 9 months of

treatment. After 9 months of treatment, red blood cell

count, hematocrit, and hemoglobin content were all significantly decreased at both 10 and 100 mg/L.

Evaluation of 3

H-thymidine incorporation into the

organs of rats exposed to 10 mg/L chlorate for 3 months

indicated a decrease in incorporation in the testes but not

in the liver, kidney, or intestinal mucosa.

McCauley et al. (1995) conducted a subchronic (90-day)

study on sodium chlorate in male and female SpragueDawley rats. Animals were exposed to 3, 12, or 48 mM

(250, 1,001, or 4,005 mg/L, respectively) sodium chlorate in the drinking water, resulting in doses of 30 to

512 mg/kg per day for males and 42 to 801 mg/kg per

day for females. There were no compound-related
14 Sodium Chlorate, NTP TR 517 

deaths, but males and females in the highest exposure

group had significantly lower weights (76% and 84% of

that of control values, respectively). Significant

decreases in heart, kidney, and liver relative weights

were observed in 4,005 mg/L males, whereas significant

decreases in adrenal, thymus, and spleen relative weights

were observed in 4,005 mg/L females. Red blood cell

counts and percent hematocrit were decreased in

4,005 mg/L males and females. Microscopic evaluation

of tissues revealed treatment-related changes in the pituitary and thyroid glands. The severity, but not the incidence, of pituitary gland vacuolization was increased in

4,005 mg/L males, whereas both the incidence and

severity were increased in 4,005 mg/L females. Thyroid

gland colloid depletion was present in both sexes; males

and females in the 1,001 and 4,005 mg/L groups exhibited 100% incidence with moderate to marked severity.

No-observed-adverse-effect-levels of 0.36 mM/kg per

day (30 mg/kg per day) and 0.50 mM/kg per day

(42 mg/kg per day) were established in male and female

Sprague-Dawley rats, respectively.

Bercz et al. (1982) exposed 12 African green monkeys

to drinking water containing 25, 50, 100, 200, or

400 mg chlorine dioxide equivalent/L (about 4, 8, 16,

31, or 62 mg chlorate/kg per day, respectively, based 

on water intake of 125 mL/kg per day) in a rising dose

protocol using 30 to 60 day exposures for each concentration. Chlorate did not induce significant changes in

hematological parameters or thyroid hormone levels.

Bio/dynamics, Inc. (cited in USEPA, 1994), gave

Sprague-Dawley rats (14/sex per dose) sodium chlorate

at doses of 0, 7.8, 78, or 784 mg/kg per day by gavage

for up to 3 months. No treatment-related effects were

observed in mortality, physical appearance or behavior,

body weight, food consumption, clinical chemistry,

gross necropsy, or organ histopathology. In the

784 mg/kg group, hematological changes indicative of

anemia included decreases in erythrocyte count, hemoglobin concentration, and percent hematocrit.

Steffen and Wetzel (1993) administered 1 g/kg sodium

chlorate to New Zealand white rabbits by gavage. No

methemoglobin was detected in the blood. No changes

in serum values of urea, creatinine, aspartate, or alanine

aminotransferase were observed. No adverse histopathological effects were observed in the kidneys 7 days

after dosing.

Heywood et al. (1972) repeatedly administered 200 to

326 mg sodium chlorate/kg per day to four male and four

female beagle dogs by gavage over a 5-day period. Two

animals receiving more than 300 mg/kg displayed loss of

appetite and body weight and had blood in their urine or

feces, and one died after 4 days of exposure. The surviving animal was allowed a 7-day recovery period.

Postmortem examination of both animals revealed classic signs of chlorate poisoning, including cyanotic kidney surface and evidence of hemolysis in the liver. Dogs

receiving less than 300 mg/kg sodium chlorate survived

the exposure period and were allowed a week of recovery before necropsy. Some of these dogs exhibited

extramedullary hematopoiesis in the spleen and evidence

of hemolysis in the liver. Packed cell volume, hemoglobin content, and red blood cell count were all reduced in

animals treated with greater than 200 mg/kg compared to

pretreatment values for each animal.

Bio/dynamics, Inc. (cited in USEPA, 1994), exposed

beagle dogs (four/sex per dose) by gavage to sodium

chlorate at doses of 0, 10, 60, or 360 mg/kg per day for

3 months. There was no significant effect at any dose

concentration on body weight, food consumption, clinical chemistry, organ weights, gross necropsy, or tissue

histopathology.

Most of the potential adverse health effects of sodium

chlorate exposure are associated with blood oxidation,

including increased methemoglobin formation,

decreased hematocrit, red blood cell membrane damage,

and reduction in red blood cell glutathione levels.

Incubation of human and rabbit erythrocytes with

sodium chlorate induces a concentration-dependent oxidation of hemoglobin (Steffen and Wetzel, 1993).

In vitro, rabbit erythrocytes are less sensitive to methemoglobin formation than human erythrocytes; approximately twice as much sodium chlorate is required to

mimic the time course of methemoglobin formation

observed for human erythrocytes. At 30 mM sodium

chlorate, significant concentrations of methemoglobin

were formed in rabbit erythrocytes 1 hour later than

human erythrocytes incubated with the same concentration of sodium chlorate.

Sodium chlorate is known to be an inhibitor of sulfation

(Baeuerle and Huttner, 1986; Humphries and Silbert,

1988; Roy et al., 1988) and has been used as a research

tool to elucidate molecular mechanisms in which sulfation, specifically proteoglycan sulfation, appears to

play an important role. Davies et al. (1995) used

sodium chlorate, an inhibitor of glycosaminoglycan sulfation, to study the morphological development of the

urinary-collecting ducts and nephrons in mouse 
Sodium Chlorate, NTP TR 517 15

embryonic kidneys. Sodium chlorate has been shown to

inhibit fibroblast-growth-factor-mediated cardiogenesis

in chick heart precardiac mesoderm (Zhu et al., 1996)

and to inhibit extracellular matrix deposition during

skeletal muscle differentiation (Melo et al., 1996).

Sodium chlorate also inhibits tyrosine sulfation

(Beinfeld, 1994; Mintz et al., 1994).

Humans

The oral LD50 in adult women is reported to be

800 mg/kg (Lewis, 1996). Concern about the acute 

toxicity of sodium chlorate to humans stemmed from

reports of death or illness resulting from accidental 

or intentional ingestion of large amounts of herbicides 

containing sodium chlorate (Timperman and Maes,

1966; Stoodley and Rowe, 1970; Jansen and Zeldenrust,

1972; Oliver et al., 1972; Vakili, 1977; Stavrou et al.,

1978; Bloxham et al., 1979; Helliwell and Nunn, 1979;

Proudfoot et al., 1979; Steffen and Seitz, 1981;

Cunningham, 1982; Casey and Vale, 1994). Sodium

chlorate ingestion has been associated with 

more than 100 cases of fatal poisoning in humans

(Singelmann et al., 1984). Chlorate toxicity after ingestion can be characterized primarily by gastrointestinal

irritation, massive intravascular hemolysis, disseminated

intravascular coagulation, cyanosis, and renal failure.

Gastrointestinal irritation appears to be the result of a

direct effect of the chlorate ion on the gastrointestinal

mucosa. The intravascular hemolysis occurs subsequent

to the formation of methemoglobin in exposed 

erythrocytes, eventually resulting in cyanosis. In addition, chlorate exerts a direct toxic effect on the proximal

tubule of the kidney, causing necrosis and preventing the

formation of urine and subsequent elimination of chlorate from the blood stream, thus prolonging exposure of

the erythrocytes. Supportive management aimed at

removing or deactivating the chlorate ion includes gastric lavage, administration of activated charcoal, and oral

or intravascular administration of sodium thiosulfate.

Reversal of hemoglobinemia may be accomplished with

methylene blue during the very early stages of poisoning

(Proudfoot et al., 1979; Steffen and Seitz, 1981).

Transfusions, bicarbonate infusion containing sodium

thiosulfate, anticoagulation with heparin, and substitution of clotting factors may be called for to counteract

the oxidizing effects of the chlorate on the erythrocytes

(Steffen and Seitz, 1981). Peritoneal dialysis or

hemodialysis is effective in treating renal failure. Death

has been most frequently associated with doses of 

20 g or greater, although recovery has been noted in

patients who ingested as much as 200 g.

Human epidemiology studies investigating doses of

chlorate more relevant to those found in drinking water

have not identified any significant exposure-related

effects (Michael et al., 1981; Lubbers et al., 1982,

1984a,b; Lubbers and Bianchine, 1984). A prospective

epidemiology study was conducted on 197 volunteers

during a 12-week period when the primary water disinfectant in the community was changed from chlorine to

chlorine dioxide. Chlorate levels obtained from 42 samples ranged from 0.17 to 1.79 ppm, with a mean of

0.73 ppm (Michael et al., 1981), and chlorate exposure

was estimated to be 0.010 to 0.032 mg/kg per day

(USEPA, 1994). Thyroid function, as measured by

serum thyroxine levels, did not appear to be altered in

the human population (Bercz et al., 1982).

Chlorine dioxide and its by-products were also administered to normal, healthy, adult-male volunteers in controlled clinical studies to determine the physiological

effects of chronic ingestion of these compounds. A

three-phase study was conducted to characterize the

effects of chronically ingested chlorate in drinking water

(Lubbers et al., 1982, 1984a,b; Lubbers and Bianchine,

1984). In Phase I, tolerance of a rising dose of chlorate

in drinking water was evaluated through serum chemistry, blood counts, urinalysis, clinical chemistry, and a

physical examination. Ten normal, healthy, male volunteers drank two 500-mL aliquots of chlorate-treated

water 4 hours apart. A control group received the same

volume of untreated water. A physical examination was

conducted on each of the 2 days following water consumption. The 3-day study was repeated using successively higher doses of chlorate. Concentrations of 0.01,

0.1, 0.5, 1.0, 1.8, and 2.4 mg chlorate/L yielded total

intakes equivalent to 0.143, 1.43, 7.14, 14.3, 25.7, and

34.3 μg/kg for a 70 kg man. No adverse health effects

were noted. 

In Phase II, 10 healthy male volunteers ingested a 

daily aliquot of 500 mL of drinking water containing

5 mg chlorate/L (35.7 μg/kg) for 12 weeks. Physical

examinations and laboratory measurements were made

on a weekly basis during the treatment period and for

8 weeks following cessation of treatment. There was no

effect of chlorate treatment on any parameter measured.

Phase III used the treatment protocol of Phase II to 
16 Sodium Chlorate, NTP TR 517 

evaluate the effect of chlorate ingestion on three 

glucose-6-phosphate dehydrogenase-deficient subjects.

No adverse effects were noted.

Incubation of human erythrocytes with 30 mM sodium

chlorate resulted in methemoglobin formation and a 

dramatic increase in filtration time, beginning after

2 hours of exposure (Steffen and Singelmann, 1983).

The increase in filtration time, indicating increased

rigidity of the cells, suggests an explanation for the

hemolysis, disseminated intravascular coagulation, and

renal failure observed in humans after chlorate poisoning, since erythrocyte rigidity may lead to impairment of

the microcirculation and to the destruction of the red

cells by the spleen. Further study of the effect of sodium

chlorate on human erythrocytes revealed that sodium

chlorate indirectly induces methemoglobinemia 

by inactivating glucose-6-phosphate dehydrogenase

(Singelmann et al., 1984; Steffen and Wetzel, 1993).

REPRODUCTIVE

AND DEVELOPMENTAL TOXICOLOGY

Experimental Animals

Female Sprague-Dawley rats were given 0, 1, or

10 mg chlorate/L daily in the drinking water for

2.5 months prior to mating with untreated males

(Suh et al., 1983). Administration of the treated water to

pregnant females (six to nine per group) continued until

gestation day 20, when they were killed and evaluated

for status of uterine implants. Live fetuses were

weighed, measured (crown-rump length), and evaluated

for external malformations. Fetuses were then examined

for visceral and skeletal malformations. All animals survived to scheduled necropsy. Maternal body weight was

not affected by treatment. There was no statistically significant effect on pregnancy rate, total number of

implantations per dam, or the number of live, resorbed,

or dead fetuses. Fetal body weight was not adversely

affected by treatment. Crown-rump length was significantly increased in male fetuses exposed to 10 mg/L.

There was no statistically significant increase in the incidence of external, visceral, or skeletal anomalies.

Pregnant Sprague-Dawley (CD) rats were given 0, 10,

100, or 1,000 mg sodium chlorate/kg per day in distilled

water by gavage on gestation days 6 through 15

(Bio/dynamics, Inc., 1987). Females were killed and

evaluated on gestation day 20. There were no maternal

deaths in treated animals. No treatment-related effects

were evident in maternal body weight or weight gain,

food consumption, physical observations, number of

uterine implantations, or gross necropsy. Examination

of fetuses on day 20 revealed no effects on fetal body

weight or sex ratio, and no treatment-related effects on

external, visceral, or skeletal abnormalities were

detected.

Due to the absence of nonrodent toxicity data in the literature, the National Toxicology Program conducted

developmental toxicity studies of sodium chlorate in rabbits. Female New Zealand white (NZW) rabbits

(24/group) were given 100, 250, or 475 mg sodium chlorate/kg per day by gavage or vehicle (deionized/distilled

water) on gestation days 6 through 29 (NTP, 2002).

Dams were necropsied on gestation day 30. One maternal death occurred in each dose group, but these were not

considered to be treatment related. Transient changes in

maternal food intake, urine color, and/or output were

noted at doses of 100 mg/kg per day and greater, but

clear evidence of maternal toxicity was observed only at

doses greater than 475 mg/kg per day in the screening

study (NTP, 1998). Sodium chlorate exposure did not

affect resorptions, fetal viability, fetal body weight, or

fetal external, visceral, or skeletal alterations. Sodium

chlorate did not cause any significant treatment-related

developmental toxicity under the conditions of this

study.

Sodium chlorate was negative in the mouse sperm head

abnormality assay (Meier et al., 1985). Sodium chlorate

was administered by gavage at doses of 8, 20, or

40 mg/kg per day for 5 days to male B6C3F1 mice

(10/group). The animals were sacrificed at 1, 3, and

5 weeks after the last dose, and the sperm were examined for abnormal shapes in the head region. No evidence of an increased incidence of abnormal sperm

heads was found at any dose or time of sacrifice.

Humans

No reproductive or developmental toxicity studies of

sodium chlorate in humans were found in the literature.

CARCINOGENICITY

Experimental Animals

Sodium chlorate was tested in male F344 rats (15/group)

for potential promoting effects in two-stage rat renal carcinogenesis studies (Kurokawa et al., 1985). Renal 

carcinogenesis was initiated with 0.05% N-ethyl-Nhydroxyethylnitrosamine in the drinking water three
Sodium Chlorate, NTP TR 517 17

times per week for 2 weeks. Control animals 

received distilled water. Rats were then treated with

1% sodium chlorate (1 g/100 mL; mean consumption;

686 mg/kg per day) in the drinking water for 25 weeks.

No animals died during the course of the experiment.

Animals were necropsied at 27 weeks. Sodium chlorate

showed no promoting effect on the incidences of renal

neoplastic lesions, including dysplastic foci and renal

cell tumors.

Humans

No epidemiology studies of sodium chlorate in humans

were found in the literature.

GENETIC TOXICITY

The published data from investigations of sodium chlorate genetic toxicity are limited. Gocke et al. (1981),

reporting results from a large screening study, listed

sodium chlorate (12 μmoles per plate) as positive in a

Salmonella mutagenicity assay (strain TA1535 with S9),

weakly positive in a Drosophila sex-linked recessive

lethal assay (0.25 M solution administered by feeding),

and negative in an acute bone marrow micronucleus test

in NMRI mice (2,100 mg/kg intraperitoneal or

4,200 mg/kg gavage). The report did not include data

tables, and the methods and results presentations lacked

detail. However, the authors pointed out that the

S. typhimurium TA1535 strain that demonstrated the

mutagenic response was obtained several years prior to

the experiment, and that replicate trials in a more

recently acquired sample of TA1535 did not demonstrate

the same strength of response. In addition, the mutagenic response observed in TA1535 occurred in cultures

grown on “ZLM” medium, a modified Escherichia coli

medium with different salt concentrations than the standard Vogel Bonner medium typically used in Ames testing. Salmonella cultured on the standard Vogel Bonner

medium did not demonstrate a pronounced reversion.

Moriya et al. (1983) observed no mutagenicity with

sodium chlorate in several strains of Salmonella, including TA1535, or in E. coli strain WP2 hcr; Vogel Bonner

medium was used in these Salmonella assays. A publication of results from in vivo cytogenetics tests with several drinking water disinfectants reported a lack of

activity with sodium chlorate (up to 40 mg/kg by gavage

for 5 days) in tests for induction of micronuclei or 

chromosomal aberrations in bone marrow cells of male

and female CD-1 Swiss mice (Meier et al., 1985). The 

concentrations of test chemicals used in these experiments were below the maximum tolerated dose.

Therefore, the tests may be considered inadequate 

indicators of the absence of genetic toxicity.

Further evidence in support of a lack of mutagenic activity for sodium chlorate in vivo and in vitro is provided by

several industry reports from Life Science Research,

Suffolk, England, cited in an Environmental Protection

Agency criteria document (USEPA, 1994). Negative

results were reported for gene reversion in

S. typhimurium tester strains, with and without S9 activation enzymes, at sodium chlorate doses up to

5,000 μg/plate. No induction of unscheduled DNA synthesis (an indicator of DNA damage repair) was

observed in cultured HeLa cells in the presence or

absence of S9 liver enzymes. No consistent, reproducible induction of gene mutations at the HGPRT locus

of cultured Chinese hamster V79 lung cells exposed to

sodium chlorate (up to 5,000 μg/mL) was reported.

However, lethality, an indicator of induced primary

DNA damage, was seen in repair deficient E. coli strains

WP67 and CM871, but not in the repair proficient strain

WP2, with and without S9, at sodium chlorate doses of

1,000 μg/mL and higher. Results of in vivo studies

demonstrated no induction of micronuclei in bone marrow erythrocytes of male and female CD-1 mice treated

with up to 5,000 mg/kg sodium chlorate.

STUDY RATIONALE

Sodium chlorate was nominated for toxicity and carcinogenicity studies by the United States Environmental

Protection Agency and by the American Water Works

Association and Research Council based on the presence

of sodium chlorate in drinking water disinfected with

chlorine dioxide. A large segment of the United States

population is potentially exposed to sodium chlorate in

the drinking water and from its use as a herbicide. The

3-week and 2-year studies were performed in male and

female F344/N rats and B6C3F1 mice to evaluate the

toxicity and carcinogenicity of sodium chlorate.

Drinking water was chosen as the route of exposure

because it is the most likely route of human exposure.
18 Sodium Chlorate, NTP TR 517 
19

PROCUREMENT

AND CHARACTERIZATION

OF SODIUM CHLORATE

A single lot of sodium chlorate (14019PQ) was obtained

from Aldrich Chemical Company, Inc. (Milwaukee,

WI), by the analytical chemistry laboratory, Battelle

Columbus (Columbus, OH), and provided to the study

laboratory, Southern Research Institute (Birmingham,

AL). Lot 14019PQ was used in the 3-week and 2-year

studies. Identity, purity, and stability analyses were conducted by the analytical chemistry laboratory and the

study laboratory. Reports on analyses performed in support of the sodium chlorate studies are on file at the

National Institute of Environmental Health Sciences.

Lot 14019PQ, a white crystalline solid, was identified as

sodium chlorate by infrared spectroscopy and melting

point determination. The purity of lot 14019PQ was

determined by argentimetric titration, anion exchange

ion chromatography (IC), and elemental analysis.

Karl Fischer titration indicated a moisture content of less

than 0.05%. Elemental analysis for chlorine was in

agreement with the theoretical value for sodium chlorate. However, elemental analysis for sodium was

higher (108%) than the theoretical value. Argentimetric

titration indicated a purity of 99.7%. IC indicated one

major peak with no reportable impurities by one system

and a relative purity of 101% based on major peak comparison with a frozen reference standard of the same lot

by a second system. Major peak area percent by the second system indicated a purity of 100%. The overall

purity of lot 14019PQ was determined to be greater than

99%.

Stability studies of the bulk chemical were performed by

the analytical chemistry laboratory using IC. These

studies indicated that sodium chlorate was stable as a

bulk chemical for 15 days when stored under a minimal

headspace protected from light at temperatures up to

60° C. To ensure stability, the bulk chemical was stored

at room temperature in amber glass containers with

Teflon®-lined lids and protected from light. Stability

was monitored by the study laboratory during the 2-year 

studies with IC. No degradation of the bulk chemical

was detected.

PREPARATION AND ANALYSIS

OF DOSE FORMULATIONS

The dose formulations were prepared once during the

3-week studies and every 4 weeks during the 2-year

studies by mixing sodium chlorate with tap water

(Table H1). Homogeneity studies of 125 and

2,000 mg/L dose formulations were performed by the

study laboratory using IC. Stability studies of a 2 mg/L

dose formulation were performed by the analytical

chemistry laboratory using IC. Homogeneity was confirmed. Stability was confirmed for at least 44 days for

dose formulations stored in sealed NALGENE® containers at temperatures up to 25° C and for at least 7 days

when stored in drinking water bottles under simulated

animal room conditions. 

Periodic analyses of the dose formulations of sodium

chlorate were conducted by the study laboratory using

IC. During the 3-week studies, the dose formulations

were analyzed once; all five of the dose formulations for

rats and mice were within 10% of the target concentrations (Table H2). During the 2-year studies, the dose

formulations were analyzed approximately every

10 weeks (Table H3). Of the dose formulations used for

rats and mice, 40 of 42 were within 10% of the target

concentrations; one dose formulation for rats and one

dose formulation for mice were inadvertently used at

14% and 11% of target, respectively.

3-WEEK STUDIES

Male and female F344/N rats and B6C3F1 mice were

obtained from Taconic Laboratory Animals and Services

(Germantown, NY). On receipt, the rats and mice were

3 to 4 weeks old. Rats were quarantined for 11 (males)

MATERIALS AND METHODS
20 Sodium Chlorate, NTP TR 517 

or 12 (females) days, and mice were quarantined for

13 (males) or 14 (females) days; animals were 5 to

6 weeks old on the first day of the studies. Groups of

10 male and 10 female core study rats and mice and

groups of 10 male and 10 female clinical pathology

study rats were exposed to drinking water containing 0,

125, 250, 500, 1,000, or 2,000 mg/L sodium chlorate for

22 days. Feed and water were available ad libitum. Rats

and female mice were housed five per cage; male mice

were housed individually. Clinical findings were

recorded weekly for core study rats and mice. Water

consumption by core and special study animals was

recorded weekly by cage until day 22. 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 1.

Blood was collected from the retroorbital sinus of clinical pathology study rats on day 4 and from core study

rats and mice at the end of the 3-week studies for hematology (rats and mice) and clinical chemistry (rats)

analyses. Animals were anesthetized with a CO2/O2

mixture. The parameters measured are listed in Table 1.

Blood samples for hematology analyses were placed in

tubes containing EDTA. Erythrocyte, platelet, and

leukocyte counts; hematocrit values; hemoglobin concentrations; and mean cell volume, hemoglobin, and

hemoglobin concentration were determined using a

Technicon H-1TM (Bayer HealthCare LLC, Tarrytown,

NY) with reagents from R&D Systems, Inc.

(Minneapolis, MN), Bayer, Inc. (Tustin, CA), and Fisher

Scientific (Norcross, GA). Reticulocytes were counted

using a Coulter Model Elite Flow Cytometer (Coulter

Corp., Miami, FL) with reagents supplied by the manufacturer and Molecular Probes (Eugene, OR).

Methemoglobin concentration was determined using a

spectrophotometric method and reagents from

J.T. Baker, Inc. (Phillipsburg, NJ) and Fisher Scientific.

Samples for clinical chemistry analyses were placed in

tubes with no anticoagulant. Samples were analyzed

using a Hitachi 911 clinical chemistry analyzer (Roche

Diagnostics Corporation, Indianapolis, IN) with

reagents from Boehringer Mannheim Biochemicals

(Indianapolis, IN) and Sigma Chemical Co. (St. Louis,

MO), except sorbitol dehydrogenase was measured

using a Cobas Fara chemistry analyzer (Roche) with

reagents from Sigma Chemical Co. after serum was

frozen at –20° C.

Necropsies were performed on all core study rats and

mice. The heart, right kidney, liver, lungs, right

testis, and thymus were weighed. Histopathologic 

examinations were performed on core study vehicle 

control and 2,000 mg/L rats and mice. Table 1 lists the

tissues and organs examined to the no-effect level.

2-YEAR STUDIES

Study Design

Groups of 50 male and 50 female rats were exposed to

drinking water containing 0, 125, 1,000, or 2,000 mg/L

sodium chlorate for 105 to 106 weeks. Additional

groups of 20 male and 20 female special study rats were

exposed to the same concentrations for up to 14 weeks

for thyroid hormone evaluations and histopathology.

Groups of 50 male and 50 female mice were exposed to

drinking water containing 0, 500, 1,000, or 2,000 mg/L

sodium chlorate for 105 to 106 weeks.

Source and Specification of Animals

Male and female F344/N rats and B6C3F1 mice were

obtained from Taconic Laboratory Animals and Services

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

Five male and five female core study rats and mice and

five male and five female special study rats were randomly selected for parasite evaluation and gross observation of disease. Rats and mice were approximately

6 weeks old at the beginning of the studies. The health

of the animals was monitored during the studies according to the protocols of the NTP Sentinel Animal Program

(Appendix K).

Animal Maintenance

Male rats were housed three per cage. Female rats and

mice were housed five per cage. Male mice were housed

individually. Feed and water were available ad libitum.

Water consumption was recorded every 4 weeks by cage.

Cages and racks were rotated every two weeks. Further

details of animal maintenance are given in Table 1.

Information on feed composition and contaminants is

provided in Appendix J.

Clinical Examinations and Pathology

All animals were observed twice daily. Clinical findings

were recorded every 4 weeks. Body weights were

recorded initially, every 4 weeks, and at the end of the

studies.

Ten male and 10 female special study rats per exposure

group were designated for thyroid hormone evaluations

at day 4 and week 3. Additional groups of 10 male and
Sodium Chlorate, NTP TR 517 21

10 female special study rats were designated for thyroid

hormone evaluation at week 14. Rats were anesthetized

with CO2/O2 for each blood collection. Blood was taken

from the retroorbital sinus and collected into tubes containing no anticoagulant. The blood samples were

processed for serum, and the serum was aliquoted into

clean tubes and stored frozen (approximately –70° C or

below) until analyzed for thyroid hormones. Rats bled at

week 3 or week 14 were sacrificed and necropsied, and

the thyroid gland was examined histopathologically. See

Table 1 for a list of the parameters measured.

Complete necropsies and microscopic examinations

were performed on all core study 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 (except

eyes), processed and trimmed, embedded in paraffin,

sectioned to a thickness of 5 μm, and stained with 

hematoxylin and eosin for microscopic examination.

For all paired organs (e.g., adrenal gland, kidney, ovary),

samples from each organ were examined. See Table 1

for a list of the tissues examined microscopically.

Microscopic evaluations were completed by the study

laboratory pathologist, and the pathology data were

entered into the Toxicology Data Management System.

The slides, paraffin blocks, and residual wet tissues were

sent to the 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 thyroid gland of male and female rats and female

mice; the forestomach of male and female mice; the

bone marrow, liver, preputial gland, and spleen of male

rats; the liver and pancreas of female rats; and the bone

marrow, mammary gland, ovary, and pancreatic islets 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 diagnoses 

made by the laboratory and quality assessment pathologists. Representative histopathology slides containing

examples of lesions related to chemical administration,

examples of disagreements in diagnoses between the

laboratory and quality assessment pathologists, or

lesions of general interest were presented by the 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).
22 Sodium Chlorate, NTP TR 517 

TABLE 1

Experimental Design and Materials and Methods in the Drinking Water Studies of Sodium Chlorate

3-Week Studies 2-Year Studies

Study Laboratory

Southern Research Institute (Birmingham, AL)

Strain and Species

F344/N rats

B6C3F1 mice

Animal Source

Taconic Laboratory Animals and Services (Germantown, NY)

Time Held Before Studies

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

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

Average Age When Studies Began

6 weeks

Date of First Exposure

Rats: May 18 (males) or 19 (females), 1998

Mice: May 20 (males) or 21 (females), 1998

Duration of Exposure

22 (core study) or 27 (special study) days 

Date of Last Exposure

Rats: June 8 (males) or 9 (females), 1998

Mice: June 10 (males) or 11 (females), 1998 

Necropsy Dates

Rats: June 8 (males) or 9 (females), 1998

Mice: June 10 (males) or 11 (females), 1998 

Average Age at Necropsy

9 weeks 

Size of Study Groups

10 males and 10 females 

Method of Distribution

Animals were distributed randomly into groups of approximately

equal initial mean body weights.

Animals per Cage

Rats: 5

Mice: 1 (males) or 5 (females)

Method of Animal Identification

Tail tattoo

Southern Research Institute (Birmingham, AL)

F344/N rats

B6C3F1 mice

Taconic Laboratory Animals and Services (Germantown, NY)

13 days

6 weeks

Rats: September 16, 1998

Mice: September 30, 1998

105 to 106 weeks

Rats: September 21, 2000

Mice: October 5, 2000

Rats: September 13-21, 2000

Mice: September 27 to October 5, 2000

110-111 weeks

50 males and 50 females

Animals were distributed randomly into groups of approximately

equal initial mean body weights.

Rats: 3 (males) or 5 (females)

Mice: 1 (males) or 5 (females)

Tail tattoo
Sodium Chlorate, NTP TR 517 23

TABLE 1

Experimental Design and Materials and Methods in the Drinking Water Studies of Sodium Chlorate

3-Week Studies 2-Year Studies

Diet

NTP-2000 irradiated pelleted diet (Zeigler Brothers, Inc., Gardners,

PA), available ad libitum, changed weekly

Water

Tap water (Birmingham municipal supply) via amber glass water

bottles with stainless steel screw caps (Kerr Glass Manufacturing

Corp., Plainfield, IL), available ad libitum, changed twice weekly

Cages

Solid-bottom polycarbonate (Lab Products, Maywood, NJ), changed

twice weekly (rats and female mice) or weekly (male mice)

Bedding

Irradiated hardwood chips (mice) or heat-treated irradiated

hardwood chips (rats) (P.J. Murphy Forest Products Corp.,

Montville, NJ), changed once (male mice) or twice (rats and female

mice) weekly

Rack Filters

Reemay® spun bonded polyester (Andico, Birmingham, AL),

changed every 2 weeks

Racks

Stainless steel (Lab Products, Inc., Maywood, NJ), changed every

2 weeks

Animal Room Environment

Temperature: 72° ± 3° F

Relative humidity: 50% ± 15%

Room fluorescent light: 12 hours/day

Room air changes: 10/hour

Exposure Concentrations

0, 125, 250, 500, 1,000, or 2,000 mg/L in water, available ad libitum

Type and Frequency of Observation

Observed twice daily and clinical findings recorded weekly. Water

consumption was recorded weekly by cage for core and special

study animals until day 22. Animals were weighed initially, weekly,

and at the end of the studies.

NTP-2000 irradiated wafer rodent feed (Zeigler Brothers, Inc.,

Gardners, PA), available ad libitum, changed weekly

Tap water (Birmingham municipal supply) via amber glass water

bottles with Teflon®-lined plastic screw caps (Wheaton Scientific

Products, Millville, NJ), available ad libitum, changed twice weekly

Same as 3-week studies

Heat-treated irradiated hardwood chips (P.J. Murphy Forest Products

Corp., Montville, NJ), changed once (male mice) or twice (rats and

female mice) weekly

Same as 3-week studies

Same as 3-week studies

Temperature: 72° ± 3° F

Relative humidity: 50% ± 15%

Room fluorescent light: 12 hours/day

Room air changes: 10/hour 

Rats: 0, 125, 1,000, or 2,000 mg/L in drinking water, available

ad libitum

Mice: 0, 500, 1,000, or 2,000 mg/L in drinking water, available

ad libitum

Observed twice daily; clinical findings and water consumption by

cage were recorded every 4 weeks; core study animals were weighed

initially, every 4 weeks, and at the end of the studies.
24 Sodium Chlorate, NTP TR 517 

TABLE 1

Experimental Design and Materials and Methods in the Drinking Water Studies of Sodium Chlorate

3-Week Studies 2-Year Studies

Method of Sacrifice

Carbon dioxide asphyxiation

Necropsy

Necropsies were performed on all core study animals. Organs

weighed were heart, right kidney, liver, lungs, right testis, and thymus

of core study animals and liver of special study animals.

Clinical Pathology

Blood was collected from the retroorbital sinus of special study rats

on day 4 and from all core study animals at the end of the studies for

hematology (rats and mice) and clinical chemistry (rats). 

Hematology: hematocrit; hemoglobin concentration; erythrocyte,

reticulocyte, and platelet counts; erythrocyte morphology; mean cell

volume; mean cell hemoglobin; mean cell hemoglobin concentration;

and leukocyte count and differentials

Clinical chemistry: urea nitrogen, creatinine, total protein, albumin,

alanine aminotransferase, alkaline phosphatase, creatine kinase,

sorbitol dehydrogenase, and bile acids

Histopathology

Complete histopathology was performed on all core study control

and 2,000 mg/L rats and mice. In addition to gross lesions and tissue

masses, the following tissues were examined to the no-effect level:

adrenal gland, bone with marrow, brain, clitoral gland, esophagus,

gallbladder (mice), heart and aorta, large intestine (cecum, colon,

rectum), small intestine (duodenum, jejunum, ileum), kidney, liver,

lung, lymph nodes (mandibular and mesenteric), mammary gland,

nose, ovary, pancreas, parathyroid gland, pituitary gland, preputial

gland, prostate gland, salivary gland, seminal vesicle, skin, spleen,

stomach (forestomach and glandular), testis (with epididymis),

thymus, thyroid gland, trachea, urinary bladder, and uterus.

Thyroid Hormone Analysis

None

Same as 3-week studies

Necropsies were performed on all animals. 

None

Complete histopathology was performed on all core study rats and

mice. In addition to gross lesions and tissue masses, the following

tissues were examined: adrenal gland, bone with marrow, brain,

clitoral gland, esophagus, gallbladder (mice), harderian gland, heart

and aorta, large intestine (cecum, colon, rectum), small intestine

(duodenum, jejunum, ileum), kidney, liver, lung, lymph nodes

(mandibular and mesenteric), mammary gland, nose, ovary, pancreas,

parathyroid gland, pituitary gland, preputial gland, prostate gland,

salivary gland, seminal vesicle, skin, spleen, stomach (forestomach

and glandular), testis (with epididymis), thymus, thyroid gland,

trachea, urinary bladder, and uterus. In addition, the thyroid gland of

special study rats was examined at 3 and 14 weeks.

At 4 days, 3 weeks, and 14 weeks, blood was collected from the

retroorbital sinus of up to 10 special study male and female rats per

group for determinations of thyroid stimulating hormone (TSH),

triiodothyronine (T3), and thyroxine (T4). 
Sodium Chlorate, NTP TR 517 25

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 or missing 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

are presented in Tables A1, A5, B1, B5, C1, C4, D1, and

D5 as the numbers of animals bearing such lesions at a

specific anatomic site and the numbers of animals with

that site examined microscopically. For calculation of

statistical significance, the incidences of most neoplasms

(Tables 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 (i.e., 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, only to 

site-specific, lesion-free animals that do not reach 

terminal sacrifice.

Analysis of Neoplasm

and Nonneoplastic Lesion Incidences

The Poly-k test (Bailer and Portier, 1988; Portier and

Bailer, 1989; Piegorsch and Bailer, 1997) was used to

assess neoplasm and nonneoplastic lesion prevalence.

This test is a survival-adjusted quantal-response procedure that modifies the Cochran-Armitage linear trend

test to take survival differences into account. More

specifically, this method modifies the denominator in the 

quantal estimate of lesion incidence to approximate

more closely the total number of animal years at risk.

For analysis of a given site, each animal is assigned a

risk weight. This value is one if the animal had a lesion

at that site or if it survived until terminal sacrifice; if the

animal died prior to terminal sacrifice and did not have a

lesion at that site, its risk weight is the fraction of the

entire study time that it survived, raised to the kth power.

This method yields a lesion prevalence rate that depends

only upon the choice of a shape parameter for a Weibull

hazard function describing cumulative lesion incidence

over time (Bailer and Portier, 1988). Unless otherwise

specified, a value of k=3 was used in the analysis of sitespecific 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 Poly-3

tests were used in the analysis of lesion incidence, and

reported P values are one sided. The significance of

lower incidences or decreasing trends in lesions is represented as 1–P with the letter N added (e.g., P=0.99 is

presented as P=0.01N). 

Analysis of Continuous Variables

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

control groups in the analysis of continuous variables.

Organ and body weight data, which historically have

approximately normal distributions, were analyzed with

the parametric multiple comparison procedures of

Dunnett (1955) and Williams (1971, 1972).

Hematology, clinical chemistry, and thyroid hormone

data, which have typically skewed distributions,
26 Sodium Chlorate, NTP TR 517 

were analyzed using the nonparametric multiple 

comparison methods of Shirley (1977) (as modified by

Williams, 1986) and Dunn (1964). Jonckheere’s test

(Jonckheere, 1954) was used to assess the significance

of the dose-related trends and to determine whether a

trend-sensitive test (Williams’ or Shirley’s test) was

more appropriate for pairwise comparisons than a test

that does not assume a monotonic dose-related trend

(Dunnett’s or Dunn’s test). Prior to statistical analysis,

extreme values identified by the outlier test of Dixon and

Massey (1957) were examined by NTP personnel, and

implausible values were eliminated from the analysis.

Average severity values were analyzed for significance

with the Mann-Whitney U test (Hollander and Wolfe,

1973).

Historical Control Data

The concurrent control group represents the most valid

comparison to the treated groups and is the only control

group analyzed statistically in NTP bioassays. However,

historical control data are often helpful in interpreting

potential treatment-related effects, particularly for

uncommon or rare neoplasm types. For meaningful

comparisons, the conditions for studies in the historical

database must be generally similar. One significant factor affecting the background incidence of neoplasms at a

variety of sites is diet. In 1995, the NTP incorporated a

new diet (NTP-2000) that contains less protein and more

fiber and fat than the NIH-07 diet previously used in toxicity and carcinogenicity studies (Rao, 1996, 1997). The

current NTP historical database contains all 23 studies

that use the NTP-2000 diet with histopathology findings

completed up to the present. A second potential source

of variability is route of administration. In general, the

historical database for a given study will include studies

using the same route of administration, and the overall

incidences of neoplasms for all routes of administration

are included for comparison.

QUALITY ASSURANCE METHODS

The 3-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 covered completeness and accuracy of the pathology data, pathology specimens, final

pathology tables, and a draft of this NTP Technical

Report. Audit procedures and findings are presented in

the reports and are on file at NIEHS. The audit findings

were reviewed and assessed by NTP staff, and all 

comments were resolved or otherwise addressed during

the preparation of this Technical Report.

GENETIC TOXICOLOGY

The genetic toxicity of sodium chlorate was assessed by

testing the ability of the chemical to induce mutations in

various strains of Salmonella typhimurium and increases

in the frequency of micronucleated erythrocytes in

mouse peripheral blood. The protocols for these studies

and the results are given in Appendix E.

The genetic toxicity studies have evolved from an earlier

effort by the NTP to develop a comprehensive database

permitting a critical anticipation of a chemical’s carcinogenicity in experimental animals based on numerous

considerations, including the molecular structure of the

chemical and its observed effects in short-term in vitro

and in vivo genetic toxicity tests (structure-activity 

relationships). The short-term tests were originally

developed to clarify proposed mechanisms of chemicalinduced DNA damage based on the relationship between

electrophilicity and mutagenicity (Miller and Miller,

1977) and the somatic mutation theory of cancer (Straus,

1981; Crawford, 1985). However, it should be noted

that not all cancers arise through genotoxic mechanisms.

DNA reactivity combined with Salmonella mutagenicity

is highly correlated with induction of carcinogenicity in

multiple species/sexes of rodents and at multiple tissue

sites (Ashby and Tennant, 1991). A positive response in

the Salmonella test was shown to be the most predictive

in vitro indicator for rodent carcinogenicity (89% of 

the Salmonella mutagens are rodent carcinogens)

(Tennant et al., 1987; Zeiger et al., 1990). Additionally,

no battery of tests that included the Salmonella test

improved the predictivity of the Salmonella test alone.

However, these other tests can provide useful information on the types of DNA and chromosomal damage

induced by the chemical under investigation. 

The predictivity for carcinogenicity of a positive

response in acute in vivo bone marrow chromosome

aberration or micronucleus tests appears to be less than

that in the Salmonella test (Shelby et al., 1993; Shelby

and Witt, 1995). However, clearly positive results in

long-term peripheral blood micronucleus tests have high
Sodium Chlorate, NTP TR 517 27

predictivity for rodent carcinogenicity (Witt et al.,

2000); negative results in this assay do not correlate 

well with either negative or positive results in 

rodent carcinogenicity studies. Because of the 

theoretical and observed associations between induced

genetic damage and adverse effects in somatic and germ

cells, the determination of in vivo genetic effects is

important to the overall understanding of the risks 

associated with exposure to a particular chemical. Most

organic chemicals that are identified by the 

International Agency for Research on Cancer as human

carcinogens, other than hormones, are genotoxic. The

vast majority of these are detected by both the

Salmonella assay and rodent bone marrow 

cytogenetics tests (Shelby, 1988; Shelby and Zeiger,

1990).
28 Sodium Chlorate, NTP TR 517 
29

RATS

3-WEEK STUDY

All rats survived to the end of the study (Table 2). Final

mean body weights and body weight gains of all exposed

groups were similar to those of the control groups.

Water consumption by exposed rats was generally similar to that by control groups throughout the study.

Drinking water concentrations of 125, 250, 500, 1,000,

and 2,000 mg/L resulted in average daily doses of

approximately 20, 35, 75, 170, and 300 mg sodium chlorate/kg body weight per day for male rats and 20, 40, 75, 

150, and 340 mg/kg per day for female rats. No clinical 

findings attributed to sodium chlorate exposure were

observed.

The hematology and clinical chemistry data are shown in

Table F1. An exposure concentration-related decrease in

segmented neutrophil counts occurred in male and

female rats on days 4 and 22. In 2,000 mg/L rats, segmented neutrophil counts were decreased by approximately 64% in males and 51% in females on day 22.

The cause of the decrease is unknown, but the decrease

RESULTS

TABLE 2

Survival, Body Weights, and Water Consumption of Rats 

in the 3-Week Drinking Water Study of Sodium Chlorate

Final Weight

Mean Body Weightb (g) Relative Water

Concentration Survivala Initial Final Change to Controls Consumptionc

(mg/L) (%) Week 1 Week 3

Male

0 10/10 87 ± 1 149 ± 3 61 ± 2 14 19

125 10/10 87 ± 1 148 ± 3 60 ± 2 99 14 21

250 10/10 88 ± 2 153 ± 4 65 ± 3 103 15 20

500 10/10 85 ± 1 149 ± 3 64 ± 2 100 15 20

1,000 10/10 85 ± 1 146 ± 2 61 ± 2 98 17 20

2,000 10/10 86 ± 1 144 ± 2 57 ± 2 97 16 19

Female

0 10/10 81 ± 1 118 ± 1 36 ± 1 12 15

125 10/10 82 ± 1 118 ± 1 36 ± 2 100 13 20

250 10/10 81 ± 1 118 ± 1 37 ± 1 100 13 18

500 10/10 80 ± 1 117 ± 2 38 ± 2 100 12 16

1,000 10/10 82 ± 2 118 ± 2 35 ± 2 100 13 16

2,000 10/10 81 ± 2 117 ± 2 36 ± 1 99 14 20

a Number of animals surviving at 22 days/number initially in group b Weights and weight changes are given as mean ± standard error. Differences from the control group are not significant by Dunnett’s test. c Water consumption is expressed as grams per animal per day.
30 Sodium Chlorate, NTP TR 517 

may represent a redistribution of the neutrophils from the

circulating pool to the marginal neutrophil pool. At day

22, there were minimal decreases (approximately 6%) in

the hematocrit value, hemoglobin concentration, and

erythrocyte count in the 2,000 mg/L males. No chemical-related changes in clinical chemistry parameters

occurred.

Absolute and relative heart weights of 2,000 mg/L males

were significantly less than those of the control group

(Table G1).

Significantly increased incidences of minimal to mild

thyroid gland follicular cell hypertrophy occurred in

males and females receiving 500 mg/L or greater

(males: 0 mg/L, 0/10; 125 mg/L, 0/10; 250 mg/L, 1/10;

500 mg/L, 5/10; 1,000 mg/L, 10/10; 2,000 mg/L, 10/10;

females: 0/10, 0/10, 1/10, 8/10, 6/10, 10/10).

Exposure Concentration Selection Rationale: Because

there were no effects of sodium chlorate on survival or

body weights of male or female F344/N rats, the highest

exposure concentration selected for the 2-year study was

2,000 mg/L. Although follicular cell hypertrophy was

observed at 1,000 and 2,000 mg/L, it was not considered

a potential threat to the health of the rats during a 2-year

study. A low dose of 125 mg/L was selected because it

was anticipated to be a no-observed-adverse-effect level

for thyroid gland effects.
Sodium Chlorate, NTP TR 517 31

2-YEAR STUDY

Survival

Estimates of 2-year survival probabilities for male and

female rats are shown in Table 3 and in the KaplanMeier survival curves (Figure 1). Survival of exposed

rats was similar to that of the control groups.

Body Weights, Water and Compound

Consumption, and Clinical Findings

The mean body weights of all exposed groups were 

similar to those of the control groups throughout the 

study (Figure 2; Tables 4 and 5). Water consumption by

exposed rats was generally similar to that by controls

throughout the study (Tables I1 and I2). Drinking water

concentrations of 125, 1,000, and 2,000 mg/L resulted in

average daily doses of approximately 5, 35, and

75 mg/kg per day for male rats and 5, 45, and 95 mg/kg

per day for female rats. No clinical findings were attributed to sodium chlorate exposure.

TABLE 3

Survival of Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Male

Animals initially in study 50 50 50 50

Accidental deatha 100 0

Moribund 10 13 11 14

Natural deaths 3 10 8 8

Animals surviving to study termination 36 27 31 28

Percent probability of survival at end of studyb 74 54 62 56

Mean survival (days)c 687 693 688 689

Survival analysisd P=0.412 P=0.108 P=0.353 P=0.146

Female

Animals initially in study 50 50 50 50

Moribund 10 11 11 4

Natural deaths 3 3 6 5

Animals surviving to study termination 37 36e 33f 41f

Percent probability of survival at end of study 74 72 66 82

Mean survival (days) 695 687 687 711

Survival analysis P=0.368N P=0.945 P=0.498 P=0.426N

a Censored from survival analyses b Kaplan-Meier determinations c 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 negative trend or lower mortality in an exposed group is indicated by N. e Includes two moribund sacrifice animals from the last week of the study f Includes one animal that died during the last week of the study 
32 Sodium Chlorate, NTP TR 517 

FIGURE 1

Kaplan-Meier Survival Curves for Male and Female Rats Exposed 

to Sodium Chlorate in Drinking Water for 2 Years
Sodium Chlorate, NTP TR 517 33

FIGURE 2

Growth Curves for Male and Female Rats Exposed

to Sodium Chlorate in Drinking Water for 2 Years
34 Sodium Chlorate, NTP TR 517 

TABLE 4

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

Weeks 0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

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

1 102 50 103 101 50 103 101 50 103 101 50

4 187 50 187 100 50 185 99 50 186 99 50

8 261 50 263 101 50 266 102 50 270 104 50

12 312 50 315 101 50 319 102 50 322 103 50

16 348 50 351 101 50 357 103 50 358 103 50

20 373 50 374 100 50 379 102 50 382 102 50

24 393 50 396 101 50 402 102 50 403 103 50

28 420 50 423 101 50 429 102 50 428 102 50

32 437 50 439 101 50 445 102 49 446 102 50

36 442 50 445 101 50 452 102 49 451 102 50

40 459 50 461 100 50 466 102 49 468 102 50

44 467 50 474 101 50 477 102 49 478 102 50

48 475 50 479 101 50 482 102 49 486 102 50

52 487 50 491 101 50 493 101 49 494 101 50

56 489 49 493 101 50 497 102 49 498 102 50

60 495 49 499 101 50 501 101 49 501 101 50

64 499 48 503 101 50 505 101 49 505 101 50

68 500 47 503 101 50 504 101 49 505 101 48

72 497 47 502 101 50 506 102 48 504 102 47

76 508 45 506 100 50 508 100 48 509 100 47

80 508 44 506 100 49 507 100 48 508 100 46

84 512 43 508 99 45 513 100 45 510 100 45

88 509 43 501 99 44 516 101 43 510 100 44

92 514 40a 501 98 41 514 100 42 508 99 43

96 507 40 500 99 38 505 100 40 498 98 40

100 497 40 486 98 35 504 101 37 488 98 36

104 490 36 497 101 28 500 102 31 496 101 28

Mean for weeks

1-13 216 217 101 218 101 220 102

14-52 430 433 101 438 102 439 102

53-104 502 500 100 506 101 503 100

a Number of animals weighed is less than the number of animals surviving.
Sodium Chlorate, NTP TR 517 35

TABLE 5

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

Weeks 0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

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 91 50 91 99 50 91 100 50 89 98 50

4 140 50 141 101 50 140 100 50 138 99 50

8 169 50 171 101 50 170 101 50 169 100 50

12 186 50 187 101 50 188 101 50 186 100 50

16 197 50 200 101 50 199 101 50 196 100 50

20 205 50 208 101 50 208 101 50 204 100 50

24 213 50 215 101 50 216 101 50 212 100 50

28 228 50 230 101 50 232 102 50 226 99 50

32 232 50 236 102 50 237 102 50 231 100 50

36 235 50 239 101 50 240 102 50 236 100 50

40 246 50 250 102 50 248 101 50 244 99 50

44 259 50 268 103 50 265 102 50 259 100 50

48 260 50 266 102 50 263 101 50 259 100 50

52 271 50 277 102 50 276 102 50 267 98 50

56 278 50 283 102 49 284 102 50 276 99 50

60 285 50 287 101 49 293 103 49 283 99 50

64 294 49 301 102 47 304 103 49 291 99 50

68 304 48 310 102 47 309 102 49 298 98 50

72 308 48 313 102 47 316 102 49 305 99 49

76 322 47 325 101 46 328 102 47 317 98 49

80 327 46 331 101 45 332 102 46 323 99 48

84 331 45 337 102 44 337 102 45 330 100 48

88 337 43 338 101 44 341 101 43 331 98 48

92 340 42 342 101 40 345 102 38 339 100 46

96 340 40 343 101 38 352 104 37 332 98 45

100 342 40 350 103 38 351 103 37 337 99 42

104 339 38 351 104 37 359 106 33 341 101 41

Mean for weeks

1-13 147 148 101 147 101 146 99

14-52 235 239 102 238 102 233 100

53-104 319 324 102 327 103 316 99
36 Sodium Chlorate, NTP TR 517 

Thyroid Hormone Concentrations

Assays for thyroxine (T4), triiodothyronine (T3), and thyroid stimulating hormone (TSH) were conducted using

special study rats on day 4, at week 3, and at week 14

(Table 6). Serum concentrations of T4 and T3 were significantly reduced in 1,000 and 2,000 mg/L males and

females on day 4 and in 2,000 mg/L males and females 

at week 3. Serum concentrations of TSH generally

increased with exposure concentration and were significantly increased in 1,000 and 2,000 mg/L males on

day 4 and at week 3, in 1,000 and 2,000 mg/L females 

on day 4, in 2,000 mg/L females at week 3, and in

2,000 mg/L males and females at week 14.

TABLE 6

Serum Concentrations of Thyroid Hormones in Rats

in the 2-Year Drinking Water Study of Sodium Chloratea

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

n 10 10 10 10

Male

Day 4

T4 (μg/dL) 4.67 ± 0.17 5.13 ± 0.20 3.60 ± 0.12** 2.62 ± 0.17**

T3 (ng/dL) 124.60 ± 3.70 136.40 ± 4.67 95.800 ± 2.33** 80.50 ± 4.26**

TSH (ng/mL) 3.33 ± 0.14 2.75 ± 0.15 7.47 ± 0.81** 12.09 ± 0.63**

Week 3

T4 (μg/dL) 4.63 ± 0.17 4.54 ± 0.21 4.08 ± 0.18 2.71 ± 0.12**

T3 (ng/dL) 88.10 ± 4.47 84.20 ± 4.15 77.80 ± 3.63 55.60 ± 3.16**

TSH (ng/mL) 3.34 ± 0.29b 2.58 ± 0.24 7.77 ± 1.21** 31.03 ± 4.72**

Week 14

T4 (μg/dL) 4.81 ± 0.23 4.63 ± 0.20 4.81 ± 0.15 4.89 ± 0.18

T3 (ng/dL) 103.60 ± 5.82 99.70 ± 6.13 99.80 ± 5.33 96.80 ± 3.16

TSH (ng/mL) 2.75 ± 0.29 3.41 ± 0.36 3.64 ± 0.49 5.22 ± 0.60**

Female

Day 4

T4 (μg/dL) 4.12 ± 0.19 4.41 ± 0.13 3.41 ± 0.11** 2.13 ± 0.21**

T3 (ng/dL) 113.10 ± 2.97 120.20 ± 2.95 95.90 ± 2.82** 76.30 ± 4.26**

TSH (ng/mL) 2.46 ± 0.22 2.67 ± 0.19 4.57 ± 0.40** 10.96 ± 1.14**

Week 3

T4 (μg/dL) 3.87 ± 0.27 3.63 ± 0.15 3.79 ± 0.17 2.35 ± 0.14**

T3 (ng/dL) 88.00 ± 6.27c 84.20 ± 2.90 80.22 ± 3.60b 60.00 ± 2.95**

TSH (ng/mL) 1.99 ± 0.20 1.75 ± 0.13 2.85 ± 0.37 13.77 ± 1.79**

Week 14

T4 (μg/dL) 3.63 ± 0.20 3.87 ± 0.15 3.60 ± 0.28 3.19 ± 0.22

T3 (ng/dL) 100.90 ± 2.70 106.80 ± 4.43 102.70 ± 7.18 94.60 ± 3.32

TSH (ng/mL) 2.10 ± 0.32 2.71 ± 0.26 2.38 ± 0.32 3.74 ± 0.61*

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

** P#0.01 a Data are presented as mean ± standard error. Statistical tests were performed on unrounded data. T4=thyroxine; T3=triiodothyronine; 

TSH=thyroid stimulating hormone b n=9 c n=7
Sodium Chlorate, NTP TR 517 37

Pathology and Statistical Analyses

This section describes the statistically significant or biologically noteworthy changes in the incidences of

mononuclear cell leukemia and neoplasms and/or nonneoplastic lesions of the thyroid gland, spleen, and bone

marrow. 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 the historical incidences for the neoplasms mentioned in this section are presented in 

Appendix A for male rats and Appendix B for female

rats.

Thyroid Gland: Slightly enlarged thyroid glands were

observed in 1,000 and 2,000 mg/L special study male

rats and 2,000 mg/L special study female rats at

14 weeks. All special study rats in the 1,000 and

2,000 mg/L groups had follicular cell hypertrophy at 3

and 14 weeks; this lesion did not occur in control

rats (Table 7). 

There were positive trends in the incidences of follicular

cell carcinoma in male rats and in follicular cell adenoma or carcinoma (combined) in males and females

(Tables 8, A3, and B3). The incidences of follicular cell 

adenoma, follicular cell carcinoma, and follicular cell

adenoma or carcinoma (combined) in 2,000 mg/L males

and females exceeded the historical ranges for drinking

water controls (Tables 8, A4, and B4). Microscopically,

adenomas were well demarcated, focal, expansile

masses consisting of well-differentiated thyroid follicular epithelial cells forming follicular structures with 

central colloid. Increased cell density occasionally led to

the formation of papillary projections into the lumens of

the follicle (Plate 1). Histologically, carcinomas were

less well demarcated and less well differentiated and

consisted of glandular to solid hypercellular masses of

pleomorphic thyroid epithelial cells (Plate 2).

Occasionally, invasion into the peripheral thyroid was

noted.

The incidences of follicular cell hypertrophy in all

exposed groups of males and in 1,000 and 2,000 mg/L

females at 2 years were significantly greater than those

in the control groups and the severity was increased in

2,000 mg/L males and females (Tables 8, A5, and B5).

Histologically, the normal thyroid gland is composed of

variably-sized follicles containing eosinophilic material

(colloid) within the lumens (Plate 3). These follicles

range in size from very small (approximately

TABLE 7

Incidences of Thyroid Gland Follicular Cell Hypertrophy in Special Study Rats

at Week 3 and Week 14 in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Male

Number Examined Microscopically 10 10 10 10

Week 3a,b 0 0 10** (2.0)c 10** (2.0)

Week 14 0 0 10** (2.0) 10** (2.0)

Female

Number Examined Microscopically 10 10 10 10

Week 3b 0 0 10** (2.0) 10** (2.0)

Week 14 0 0 10** (1.0) 10** (2.0)

** Significantly different (P#0.01) from the control group by the Fisher exact test a Number of animals with lesion b In Hooth et al. (2001), thyroid gland follicular cell hyperplasia was diagnosed. c Average severity grade of lesions of affected animals: 1=minimal, 2=mild
38 Sodium Chlorate, NTP TR 517 

TABLE 8

Incidences of Neoplasms and Nonneoplastic Lesions of the Thyroid Gland in Rats 

in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Male

Number Examined Microscopically 47 44 43 47

Follicular Cell, Hypertrophya 4 (1.3)b 13* (1.2) 33** (1.5) 40** (2.0)

Follicular Cell, Adenomac 1002

Follicular Cell, Carcinomad

Overall ratee 0/47 (0%) 0/44 (0%) 0/43 (0%) 4/47 (9%)

Adjusted ratef 0.0% 0.0% 0.0% 9.6%

Terminal rateg 0/36 (0%) 0/27 (0%) 0/31 (0%) 4/28 (14%)

First incidence (days) —h — — 729 (T)

Poly-3 testi P=0.003 —j — P=0.058

Follicular Cell, Adenoma or Carcinomak

Overall rate 1/47 (2%) 0/44 (0%) 0/43 (0%) 6/47 (13%)

Adjusted rate 2.4% 0.0% 0.0% 14.4%

Terminal rate 0/36 (0%) 0/27 (0%) 0/31 (0%) 6/28 (21%)

First incidence (days) 705 — — 729 (T)

Poly-3 test P=0.002 P=0.512N P=0.513N P=0.052

Female

Number Examined Microscopically 47 47 43 46

Follicular Cell, Hypertrophy 3 (1.3) 7 (1.0) 27** (1.2) 42** (1.8)

Follicular Cell, Mineralization 25 (1.0) 26 (1.0) 40** (1.3) 44** (2.1)

Follicular Cell, Adenomal 0002

Follicular Cell, Carcinomam 1012

Follicular Cell, Adenoma or Carcinoman

Overall rate 1/47 (2%) 0/47 (0%) 1/43 (2%) 4/46 (9%)

Adjusted rate 2.3% 0.0% 2.6% 9.1%

Terminal rate 1/36 (3%) 0/36 (0%) 0/32 (0%) 2/40 (5%)

First incidence (days) 729 (T) — 703 644

Poly-3 test P=0.026 P=0.503N P=0.741 P=0.189

* Significantly different (P#0.05) from the control group by the Poly-3 test 

** P#0.01

(T)Terminal sacrifice

a Number of animals with lesion b Average severity grade of lesions in affected animals: 1=minimal, 2=mild, 3=moderate, 4=marked c Historical incidence for 2-year drinking water studies with controls given NTP-2000 diet (mean ± standard deviation): 3/139 (2.2% ± 0.3%),

range 2% d Historical incidence: 1/139 (1.0% ± 1.4%), range 0%-2% e Number of animals with neoplasm per number of animals with thyroid gland examined microscopically f Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality g Observed incidence at terminal kill h Not applicable; no neoplasms in animal group i Beneath the control incidence is the P value associated with the trend test. Beneath the exposed group incidences 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 lower incidence in an exposed group is indicated by N. j Value of statistic cannot be computed. k Historical incidence: 4/139 (3.2% ± 1.1%), range 2%-4% l Historical incidence: 1/142 (1.0% ± 1.4%), range 0%-2% m Historical incidence: 3/142 (2.1% ± 0.2%), range 2% n Historical incidence: 4/142 (3.1% ± 1.3%), range 2%-4%
Sodium Chlorate, NTP TR 517 39

50 microns) containing little colloid to relatively large

(several hundred microns) filled with colloid. In smaller

follicles, the epithelium is generally cuboidal, while

more attenuated in glands distended with colloid.

Following sodium chlorate administration, there was an

exposure concentration-related increase in the percentage of smaller follicles, and these follicles contained

sparse amounts of generally pale, often vacuolated

appearing colloid (colloid depletion). The lining epithelium of affected glands appeared more prominent, 

ranging from cuboidal to somewhat columnar (Plate 4).

The incidences of focal follicle mineralization in 1,000

and 2,000 mg/L females were significantly greater than

that in the control group (Tables 8 and B5), and the

severity was increased in the 2,000 mg/L group. This

lesion consisted of basophilic, ovoid-shaped bodies in

the colloid of some of the thyroid follicles. This is a

common aging change, but the increased incidences may

have been exacerbated by exposure to sodium chlorate.

Spleen: The incidence of hematopoietic cell proliferation was significantly increased in 2,000 mg/L males

when compared to the control group (0 mg/L, 2/48,

severity grade 2.5; 125 mg/L, 6/49, severity grade 2.3;

1,000 mg/L, 4/49, severity grade 2.5; 2,000 mg/L, 11/50,

severity grade 2.5; Table A5). Histologically, this lesion

was characterized by an increase in erythroid and

myeloid cells within the red pulp. While the increase in

hematopoietic cell proliferation was modest and not

observed in the 3-week study, this finding is consistent

with hematological effects observed in humans and

other animal species administered sodium chlorate.

Bone Marrow: The incidences of bone marrow hyperplasia were significantly increased in 1,000 and

2,000 mg/L males when compared to the control group

(0 mg/L, 28/48; 125 mg/L, 35/48; 1,000 mg/L, 41/50;

2,000 mg/L, 40/49; Table A5). The severity grades of

this lesion were greater in all treatment groups 

when compared to controls (1.9, 2.3, 2.4, 2.7).

Microscopically, bone marrow hyperplasia was characterized by an increase of hematopoietic cells in the marrow cavity. Though histological evaluation of bone

marrow sections is generally a crude assessment of 

erythroid and/or myeloid response, the increases in

hyperplasia incidence and severity suggest this was a

treatment-related effect. 

Mononuclear Cell Leukemia: The incidence of mononuclear cell leukemia was significantly increased in the

male 2,000 mg/L group when compared to controls

(13/50, 21/50, 16/50, 23/50; Table A3). However, the

incidences of this lesion in all exposed groups fell within

the historical range in controls (all routes)

[514/1,159 (43.1% ± 12.8%), range 22% to 68%].

Because the incidence of mononuclear cell leukemia in

the control group was at the low end of the historical

control range and near average in the exposed groups,

this lesion was not attributed to sodium chlorate 

administration.
40 Sodium Chlorate, NTP TR 517 

TABLE 9

Survival, Body Weights, and Water Consumption of Mice 

in the 3-Week Drinking Water Study of Sodium Chlorate

Final Weight

Mean Body Weightb (g) Relative Water

Concentration Survivala Initial Final Change to Controls Consumptionc

(mg/L) (%) Week 1 Week 3

Male

0 10/10 24.5 ± 0.2 27.7 ± 0.3 3.3 ± 0.2 4.6 4.9

125 10/10 24.2 ± 0.3 28.0 ± 0.3 3.8 ± 0.2 101 4.6 4.7

250 10/10 24.4 ± 0.2 28.0 ± 0.4 3.7 ± 0.2 101 4.6 4.5

500 10/10 23.9 ± 0.4 28.0 ± 0.3 4.1 ± 0.5 101 4.6 4.6

1,000 10/10 24.2 ± 0.3 27.5 ± 0.3 3.3 ± 0.2 99 4.4 4.7

2,000 10/10 24.3 ± 0.3 27.9 ± 0.4 3.6 ± 0.2 101 4.3 5.0

Female

0 10/10 19.1 ± 0.2 21.3 ± 0.3 2.2 ± 0.3 2.8 3.6

125 10/10 18.9 ± 0.3 21.3 ± 0.2 2.4 ± 0.3 100 2.8 3.5

250 10/10 18.8 ± 0.3 20.9 ± 0.1 2.1 ± 0.2 98 3.3 3.7

500 10/10 19.1 ± 0.1 20.4 ± 0.2 1.3 ± 0.2* 96 3.0 4.7

1,000 10/10 19.0 ± 0.3 21.1 ± 0.3 2.1 ± 0.2 99 3.5 4.8

2,000 10/10 18.3 ± 0.2 20.7 ± 0.3 2.3 ± 0.3 97 2.7 3.8

* Significantly different (P#0.05) from the control group by Dunnett’s test a Number of animals surviving at 22 days/number initially in group b Weights and weight changes are given as mean ± standard error. c Water consumption is expressed as grams per animal per day.

MICE

3-WEEK STUDY

All mice survived to the end of the study (Table 9). Final

mean body weights and body weight gains (except 

body weight gain of 500 mg/L females) of all exposed

groups of mice were similar to those of the control

groups. Water consumption by exposed mice was generally similar to that by the control groups throughout

the study. Drinking water concentrations of 125, 250,

500, 1,000, and 2,000 mg/L resulted in average daily

doses of approximately 20, 45, 90, 175, and 350 mg/kg

per day for male mice and 20, 45, 95, 190, and

365 mg/kg per day for female mice. No clinical findings

attributed to sodium chlorate exposure were observed.

At the exposure concentrations selected, no chemicalrelated changes in hematology parameters occurred

(Table F2). There were no significant differences in

organ weights between control and exposed groups

(Table G2). No exposure-related lesions occurred in

male or female mice.

Exposure Concentration Selection Rationale: Because

sodium chlorate produced no biologically significant

changes in any of the parameters examined in male or

female B6C3F1 mice, exposure concentrations of 500,

1,000, and 2,000 mg/L were selected for the 2-year study

in B6C3F1 mice.
Sodium Chlorate, NTP TR 517 41

2-YEAR STUDY

Survival

Estimates of 2-year survival probabilities for male and

female mice are shown in Table 10 and in the 

Kaplan-Meier survival curves (Figure 3). Survival of

exposed mice was similar to that of the control groups.

TABLE 10

Survival of Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L

Male

Animals initially in study 50 50 50 50

Moribund 5 5 4 10

Natural deaths 7 4 5 7

Animals surviving to study termination 38 41 41 33

Percent probability of survival at end of studya 76 82 82 66

Mean survival (days)b 694 712 708 689

Survival analysisc P=0.192 P=0.538N P=0.577N P=0.423

Female

Animals initially in study 50 50 50 50

Accidental deathd 100 0

Otherd 001 0

Moribund 3 5 6 8

Natural deaths 10 10 12 7

Animals surviving to study termination 36 35e 31 35

Percent probability of survival at end of study 74 70 63 70

Mean survival (days) 687 700 679 682

Survival analysis P=0.728 P=0.937 P=0.426 P=0.871

a Kaplan-Meier determinations b Mean of all deaths (uncensored, censored, and terminal sacrifice) c The result of the life table trend test (Tarone, 1975) is in the control column, and the results of the life table pairwise comparisons 

(Cox, 1972) with the controls are in the exposed group columns. Lower mortality in an exposed group is indicated by N. d Censored from survival analysis e Includes one moribund sacrifice animal from the last week of the study 
42 Sodium Chlorate, NTP TR 517 

FIGURE 3

Kaplan-Meier Survival Curves for Male and Female Mice Exposed 

to Sodium Chlorate in Drinking Water for 2 Years
Sodium Chlorate, NTP TR 517 43

Body Weights, Water and Compound

Consumption, and Clinical Findings

The mean body weights of exposed groups of males

were similar to those of the control group throughout 

the study (Table 11 and Figure 4). Body weights of 500

and 1,000 mg/L females were less than those of the 

controls after week 84, and those of 2,000 mg/L females

were less after week 88 of the study (Table 12 and 

Figure 4).

Water consumption by exposed mice was generally similar to that by controls throughout the study (Tables I3

and I4). Drinking water concentrations of 500, 1,000,

and 2,000 mg/L resulted in average daily doses of

approximately 40, 80, and 160 mg/kg per day for male

mice and 30, 60, and 120 mg/kg per day for female 

mice. No clinical findings related to sodium chlorate

exposure were observed.
44 Sodium Chlorate, NTP TR 517 

TABLE 11

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

Weeks 0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L

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 22 50 22 101 50 22 100 50 22 101 50

4 28 50 28 99 50 28 100 50 28 100 50

8 34 50 33 98 50 34 99 50 34 100 50

12 39 50 38 99 50 38 99 50 39 100 50

16 44 50 43 99 50 44 100 50 44 100 50

20 47 50 47 99 50 47 101 50 47 100 50

24 50 50 49 99 50 49 99 50 50 100 50

28 51 50 50 99 50 50 99 50 50 99 50

32 51 50 50 98 50 50 98 50 50 99 50

36 51 50 51 99 50 51 99 50 51 100 50

40 52 50 51 99 50 51 99 50 52 100 50

44 52 49 51 98 50 51 98 50 52 100 49

48 53 49 52 98 50 52 98 50 53 100 49

52 53 49 52 99 50 52 99 50 53 101 49

56 53 49 52 99 50 52 99 50 53 100 49

60 53 49 52 99 50 53 99 50 53 100 49

64 53 49 53 100 49 53 99 50 53 100 49

68 53 49 54 101 49 53 100 50 55 102 48

72 54 48 53 99 49 53 98 50 54 100 48

76 54 48 53 99 49 52 97 50 54 101 48

80 53 48 52 100 49 52 99 49 53 101 47

84 53 45 52 99 47 53 100 46 52 98 46

88 52 44 51 99 46 52 101 45 51 98 44

92 51 41 51 99 46 51 101 45 50 97 42

96 51 39 50 98 45 50 99 44 50 98 37

100 49 39 47 97 45 48 99 41 48 99 36

104 47 38 45 97 41 47 100 41 49 104 33

Mean for weeks

1-13 31 30 99 31 100 31 100

14-52 50 50 99 50 99 50 100

53-104 52 51 99 51 99 52 100
Sodium Chlorate, NTP TR 517 45

TABLE 12

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

Weeks 0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L

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 18 50 18 99 50 18 100 50 18 100 50

4 22 50 22 100 50 22 100 50 22 99 50

8 27 50 27 97 50 27 99 48 26 96 50

12 32 50 31 98 50 32 99 48 30 94 50

16 37 50 36 98 50 36 99 48 35 96 50

20 42 50 42 99 50 42 100 48 41 97 50

24 47 50 47 99 50 47 100 48 45 96 49

28 50 50 50 100 50 50 101 48 49 97 49

32 53 50 52 99 50 53 100 48 51 98 49

36 54 50 54 100 50 54 100 48 53 97 49

40 58 49 58 100 50 57 99 48 56 97 49

44 58 49 59 100 50 57 98 48 57 97 49

48 60 49 60 99 50 59 97 48 59 98 49

52 61 49 61 100 50 60 98 48 61 99 49

56 61 49 61 100 50 60 98 48 61 100 49

60 62 49 61 98 50 61 98 48 62 100 49

64 63 48 62 99 50 63 100 48 62 99 49

68 63 48 62 98 49 63 99 48 64 101 47

72 64 48 62 96 48 63 98 47 65 101 46

76 65 47 64 98 47 64 99 45 65 99 46

80 67 47 65 97 46 65 98 44 65 98 44

84 66 46 65 99 44 64 98 43 65 99 44

88 66 41 63 95 44 62 94 42 64 97 43

92 65 39 60 93 44 62 96 39 62 95 42

96 64 38 58 90 44 60 94 37 59 91 41

100 63 37 56 89 41 57 91 36 59 93 36

104 61 36 54 88 36 55 90 31 55 90 35

Mean for weeks

1-13 25 25 99 25 100 24 97

14-52 52 52 99 52 99 51 97

53-104 64 61 95 61 96 62 97
46 Sodium Chlorate, NTP TR 517 

FIGURE 4

Growth Curves for Male and Female Mice Exposed

to Sodium Chlorate in Drinking Water for 2 Years
Sodium Chlorate, NTP TR 517 47

Pathology and Statistical Analyses

This section describes the statistically significant or 

biologically noteworthy changes in the incidences of

neoplasms and/or nonneoplastic lesions of the pancreatic

islets, liver, thyroid gland, bone marrow, and ovary.

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.

Pancreatic Islets: There was a positive trend in the incidences of pancreatic islet cell adenoma or carcinoma

(combined) (Tables 13, D1, and D3) in female mice that

was composed primarily of adenomas (three of four neoplasms in the 2,000 mg/L group). The incidences of

pancreatic islet adenoma and adenoma or carcinoma

(combined) in 2,000 mg/L females exceeded the historical ranges for drinking water controls (Tables 13, D1,

D3, and D4a). The incidences of hyperplasia decreased

with increasing exposure concentration. Histologically,

islet cell adenomas were characterized by enlarged islets

composed of focal accumulations of well-differentiated

islet cells with variable stromal components that compressed the adjacent parenchyma. On occasion, normal

acinar cells were entrapped within the tumor. Because

size is often considered an important criterion for discerning adenomas of endocrine organs, including the

islets, it was noted that adenomas diagnosed in this study

were significantly larger than those considered to be

hyperplastic. In general, the hyperplastic lesions were

smaller, affected multiple islets, and did not compress

surrounding acinar tissue.

Liver: The incidences of hepatocellular carcinoma were

significantly greater in 500 and 1,000 mg/L females than

in the control group (0 mg/L, 3/49; 500 mg/L, 13/50;

1,000 mg/L, 15/49; 2,000 mg/L, 9/50; Tables D1 and

D3). Although not statistically significant, the incidence

in 2,000 mg/L females was also increased. The incidences in all exposed groups of females exceeded the

historical range for drinking water controls [12/149

(8%), range 4% to 14%; Table D4b]. Microscopically,

these neoplasms were not well demarcated, primarily

trabecular in growth pattern, and characterized by cords

of atypical hepatocytes. When incidences of hepatocellular adenoma (30/49, 19/50, 26/49, 23/50) and carcinoma were combined (31/49, 26/50, 31/49, 26/50), there

was no chemical effect. Due to this fact and because the 

increases were not exposure concentration-related, these

carcinomas were not considered to be induced by

sodium chlorate. 

Thyroid Gland: The incidence of minimal follicular cell

hypertrophy was significantly increased in 2,000 mg/L

female mice when compared to the control group

(0 mg/L, 3/48, severity grade 1.3; 500 mg/L, 2/50, severity grade 2.0; 1,000 mg/L, 5/49, severity grade 1.0;

2,000 mg/L, 14/50, severity grade 1.4; Table D5).

Histologically, affected follicles appeared small and

were lined by slightly enlarged epithelial cells. The

lumens of these follicles contained sparse amounts of

generally pale colloid.

The incidence of thyroid gland cystic degeneration was

significantly increased in 1,000 mg/L females when

compared to the control group (25/48, 28/50, 34/49,

32/50; Table D5). Microscopically, there were variations in follicle size, often with coalescence of contiguous, large follicles to form multilocular cysts. These

cysts were usually lined by flattened epithelial cells, separated by variable amounts of connective tissue, and

filled with pale colloid. Thyroid gland cystic degeneration was considered an aging change and not related to

sodium chlorate administration.

Bone Marrow: The incidences of bone marrow hyperplasia were significantly increased in all exposed groups

of female mice when compared to the control group

(14/50, 28/50, 29/50, 31/50; Table D5). The severity of

this lesion in exposed females was slightly greater than

in the controls (2.4, 2.6, 2.9, 2.7). Microscopically, bone

marrow hyperplasia was characterized by an increase of

hematopoietic cells in the marrow cavity. As in the rat,

the increases in incidence and severity suggest a 

treatment-related effect.

Ovary: The incidence of granulosa cell hyperplasia of

the ovary was significantly increased in 2,000 mg/L

female mice when compared to the control group (0/45,

0/45, 3/47, 7/50; Table D5). Microscopically, granulosa

cell hyperplasia was characterized by one or more foci or

a diffuse increase in the number of granulosa or luteal

cells as pure or mixed populations. It was often difficult

to discern focal hyperplastic changes from enlarged

copora lutea. In general, these were not considered to be

preneoplastic lesions.
48 Sodium Chlorate, NTP TR 517 

TABLE 13

Incidences of Neoplasms and Nonneoplastic Lesions of the Pancreatic Islets in Mice 

in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L

Male

Number Examined Microscopically 48 50 50 50

Hyperplasiaa 31 (2.4)b 25 (2.3) 28 (2.5) 23 (2.3)

Female

Number Examined Microscopically 46 47 49 49

Hyperplasia 9 (1.7) 6 (2.0) 4 (2.3) 3 (2.0)

Adenomac

Overall rated 0/46 (0%) 2/47 (4%) 2/49 (4%) 3/49 (6%)

Adjusted ratee 0.0% 4.5% 4.8% 6.8%

Terminal ratef 0/36 (0%) 1/35 (3%) 2/31 (7%) 1/35 (3%)

First incidence (days) —g 706 729 (T) 475

Poly-3 testh P=0.112 P=0.248 P=0.235 P=0.125

Adenoma or Carcinomac

Overall rate 0/46 (0%) 2/47 (4%) 2/49 (4%) 4/49 (8%)

Adjusted rate 0.0% 4.5% 4.8% 9.1%

Terminal rate 0/36 (0%) 1/35 (3%) 2/31 (7%) 2/35 (6%)

First incidence (days) — 706 729 (T) 475

Poly-3 test P=0.045 P=0.248 P=0.235 P=0.065

(T)Terminal sacrifice

a Number of animals with lesion b Average severity grade of lesions in affected animals: 1=minimal, 2=mild, 3=moderate, 4=marked c Historical incidence for 2-year drinking water studies with controls given NTP-2000 diet (mean ± standard deviation):

2/146 (1.4% ± 2.3%), range 0%-4%. d Number of animals with neoplasm per number of animals with pancreatic islets examined microscopically e Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality f Observed incidence at terminal kill

g Not applicable; no neoplasms in animal group h Beneath the control incidence is the P value associated with the trend test. Beneath the exposed group incidences 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.
Sodium Chlorate, NTP TR 517 49

GENETIC TOXICOLOGY

Sodium chlorate (100 to 10,000 μg/plate) was not mutagenic in Salmonella typhimurium strains TA97, TA98,

TA100, TA102, TA104, and TA1535, with or without

induced rat or hamster liver S9 enzymes. In vivo, no

increases in the frequencies of micronucleated 

normochromatic erythrocytes (NCEs) were seen 

in peripheral blood samples from male and female

B6C3F1 mice exposed to concentrations of 

125 to 2,000 mg/L sodium chlorate in drinking water for

3 weeks. The abbreviated exposure duration of 

3 weeks may not have allowed steady state to be 

reached in the circulating NCE population, but the 

data are clearly negative, with no indication of an exposure concentration-related increase in NCEs. Steady

state is usually established by day 35 of continuous

exposure.
50 Sodium Chlorate, NTP TR 517 
PLATE 1

Follicular cell adenoma (arrows) in the thyroid gland of a male F344/N rat

exposed to 2,000 mg/L sodium chlorate in drinking water for 2 years. Note the

normal portion of the thyroid gland to the upper left (asterisk). H&E; 4×

PLATE 2

Follicular cell carcinoma in the thyroid gland of a male F344/N rat exposed to

2,000 mg/L sodium chlorate in drinking water for 2 years. H&E; 8×

PLATE 3

Thyroid gland of a control male F344/N rat in the 2-year drinking water study

of sodium chlorate. Note the variably-sized follicles lined by cuboidal

(arrowhead) to attenuated (arrow) epithelium. H&E; 40×

PLATE 4

Follicular cell hypertrophy in the thyroid gland of a male F344/N rat exposed

to 2,000 mg/L sodium chlorate in drinking water for 2 years. Note the

predominance of small follicles lined by enlarged epithelial cells (arrows)

when compared to follicles in Plate 3. H&E; 40×
51

Sodium chlorate is found as a stable by-product in drinking water that has been disinfected with chlorine 

dioxide. Disinfection with chlorine dioxide, a strong

oxidant, is being considered as an alternative to chlorine,

which produces trihalomethanes in finished drinking

water. Chlorine dioxide is more effective than chlorine

for killing most microorganisms, produces fewer chlorinated by-products, and does not produce significant 

levels of trihalomethanes (Richardson, 1998). However,

sodium chlorate has been identified as a by-product of

chlorine dioxide disinfection. Sodium chlorate was

nominated for study by the United States Environmental

Protection Agency (USEPA) because of widespread consumer exposure to treated drinking water and a lack of

carcinogenicity data.

In the 3-week and 2-year rat studies, there were no

chemical-related deaths. Administration of sodium

chlorate did not produce any clinical findings of toxicity

and had no significant effect on body weights or water

consumption of rats of either sex. The thyroid gland was

considered to be a target organ for sodium chlorate toxicity in the 3-week study because of the significantly

increased incidences of thyroid gland follicular cell

hypertrophy in 500 mg/L or greater males and females. 

Administration of sodium chlorate to male and female

rats caused significant exposure concentration-related

decreases in serum concentrations of triiodothyronine

(T3

) and thyroxine (T4) and significant increases in

serum concentrations of thyroid stimulating hormone

(TSH) that were evident by day 4 and persisted through

week 3 of the 2-year study. The higher concentrations of

circulating TSH appear to have effectively restored T3

and T4 concentrations nearly to control levels by

week 14 in all exposed groups. By week 14, serum TSH

concentrations in 2,000 mg/L rats had declined significantly from the peak levels observed at week 3 but

remained slightly elevated compared to control 

animals. Hormone levels may return to normal because

of a homeostatic compensatory increase in cell proliferation with subsequent thyroid hormone production.

Hood et al. (1999) demonstrated that small increases in

serum TSH (between 10 and 20 ng/mL) can be sufficient

to stimulate thyroid cell proliferation and thyroid gland

growth. In fact, several special study rats had enlarged

thyroid glands at the 14-week evaluation, indicating

increased cellular growth. Although thyroid hormone

levels were not measured after week 14, chronic stimulation of the thyroid gland by TSH has been shown to

increase the susceptibility of rats to follicular-cellderived tumors in long-term bioassays (Capen, 1997).

Significant changes in serum hormone levels were

observed within a few days of exposure, providing 

early evidence that sodium chlorate disrupts the 

hypothalamic-thyroid-pituitary axis. Bercz et al. (1982)

reported that exposure of African green monkeys to

chlorine dioxide, but not chlorate, resulted in decreased

serum T4 levels. In a subsequent study, Harrington et al.

(1986) noted a decrease in T4 levels in both

Sprague-Dawley rats and African green monkeys

exposed to drinking water containing 0.1 g/L chlorine

dioxide. Decreased T4 levels were associated with

increased binding of dietary iodide to gastrointestinal 

tissue and contents. These observations led to the

hypothesis that chlorine dioxide oxidizes iodide in food

to a reactive species that binds to tissues of the digestive

tract, preventing absorption of dietary iodide. This

effect produces a functional state of iodine deficiency

that promotes increased iodide uptake by the thyroid

gland.

In the 2-year rat study, there were positive trends in the

incidences of thyroid gland follicular cell carcinoma 

in males and in follicular cell adenoma or carcinoma

(combined) in males and females. The incidences of 

follicular cell adenoma, carcinoma, and adenoma or carcinoma (combined) in 2,000 mg/L males and females

exceeded the historical ranges for drinking water controls. Additional thyroid gland effects were observed,

including alterations in thyroid hormone levels, follicular cell hypertrophy in males and females in the 3-week

study, follicular cell hypertrophy at 3 and 14 weeks in

special study rats, and increased incidences of follicular

cell hypertrophy in all exposed groups of males and in

DISCUSSION AND CONCLUSIONS
52 Sodium Chlorate, NTP TR 517 

1,000 and 2,000 mg/L females in the 2-year study.

Furthermore, the incidence of follicular cell hypertrophy

was significantly increased in 2,000 mg/L female mice.

Based on these data, the increased incidences of thyroid

gland neoplasms were considered to be related to sodium

chlorate exposure.

Chlorate is chemically similar to perchlorate and bromate; both are thyroid gland toxicants and chemical 

oxidants. Perchlorate (ClO4

–

) is an anion that originates

as a contaminant in groundwater and surface water from

the dissolution of its ammonium, potassium, magnesium, or sodium salt. The primary target tissue for 

perchlorate toxicity is the thyroid gland, as indicated by

perturbations of T3, T4, and TSH and by histopathology.

Benign tumors and follicular cell carcinomas have been

reported in the thyroid gland of male Wistar rats and

female BALB/c mice after repeated high exposures

(2 years at 1,339 mg/kg per day and 46 weeks at 2,147

mg/kg per day, respectively) of potassium perchlorate in

drinking water (Kessler and Krunkemper, 1966; Pajer

and Kalisnik, 1991). The mode-of-action for perchlorate

toxicity is the competitive inhibition of iodide anion

uptake by the sodium-iodide symporter, a carrier protein

responsible for the active transport of iodide across the

basolateral membrane of the thyroid gland epithelial

cells (Wolff, 1998). Thyroid hormone synthesis is inhibited, resulting in decreased levels of T3 and T4, increased

TSH levels, and stimulation of thyroid cell proliferation. 

Bromate is one of the most prevalent water disinfection

by-products associated with ozonation (Glaze, 1986;

Cavanagh et al., 1992). Potassium bromate is carcinogenic in the rat thyroid gland, producing adenomas and

carcinomas at water concentrations as low as 0.02 g/L

(20 ppm; 1.5 mg/kg/day; DeAngelo et al., 1998;

Wolf et al., 1998). The mechanism by which potassium

bromate induces thyroid gland tumors is not known.

Bromide binds to the sodium-iodide symporter of the

thyroid gland with low affinity (Van Sande et al., 2003).

High levels of bromide result in a decrease in iodide

accumulation in the thyroid gland and a rise in iodide

excretion by the kidneys, resulting in decreased thyroid

hormone synthesis and stimulation of thyroid cell proliferation (Pavelka, 2004).

The mechanism by which sodium chlorate induces thyroid gland follicular cell adenomas and carcinomas has

not been determined. Chlorate may interfere with iodide

uptake indirectly or directly, in a similar manner to chlorine dioxide or perchlorate, respectively, resulting in

stimulation of thyroid follicular cell proliferation mediated by TSH secondary to decreases in T3 and T4.

Sodium chlorate was not mutagenic in several strains of

Salmonella typhimurium, with or without exogenous

metabolic activation, and did not induce chromosomal

aberrations in the bone marrow of CD-1 mice

(Meier et al., 1985) or micronucleated erythrocytes in

peripheral blood of B6C3F1 mice (Table E2). Therefore,

it is unlikely that sodium chlorate induces thyroid gland

follicular cell tumors through a direct genotoxic mechanism. However, sodium chlorate could potentially alter

genes via oxidative damage.

Investigators at USEPA conducted a 90-day study on

sodium chlorate administered in the drinking water to

male F344 rats and B6C3F1 mice (Hooth et al., 2001).

However, hematology and clinical chemistry were not

included in this study. For this reason, a 3-week study of

sodium chlorate was initiated by NTP for the collection

of hematology and clinical chemistry data on days 4 and

22, the early time points for these data collections in

NTP 13-week toxicity studies. Hematotoxicity, primarily methemoglobin formation, is a characteristic 

symptom of chlorate poisoning in humans and animals,

including horses, pigs, cows, sheep, chickens, and dogs

(Gregory et al., 1993). Sodium chlorate is a potent 

oxidizing agent and oxidizes ferrous hemoglobin (Fe2+)

to ferric-hemoglobin (Fe3+ or methemoglobin), which is

unable to bind oxygen. The formation of methemoglobin is prevented by reduction of Fe3+ to Fe2+ by

methemoglobin reductase. There were minimal effects

on hematological parameters in rats in the 3-week

sodium chlorate study. The effects were similar 

to those reported previously (Couri et al., 1982;

Abdel-Rahman et al., 1985; McCauley et al., 1995).

However, there were no effects on methemoglobin 

formation in rats or mice in the 3-week studies. Rat and

mouse erythrocytes have high rates of methemoglobin

reductase compared to human erythrocytes (Smith,

1996), with the mouse having 9.5-fold activity relative to

that in human erythrocytes. There was also no evidence

of the subsequent kidney damage described in other

species, including humans, poisoned with sodium 

chlorate.

Although hematological effects were not observed in the

3-week studies, nonneoplastic lesions of the hematopoietic system were evident in the 2-year rat and mouse

studies. The incidences of bone marrow hyperplasia

were significantly increased in 1,000 and 2,000 mg/L

male rats and all exposed groups of female mice when
Sodium Chlorate, NTP TR 517 53

compared to the control groups. Hematopoietic cell proliferation of the spleen was significantly increased in

2,000 mg/L male rats. Although the severities were minimal to mild, these lesions were considered to be related

to sodium chlorate administration and indicated potential

hematotoxicity.

In the 3-week and 2-year studies in mice, there were no

chemical-related deaths. Administration of sodium

chlorate did not produce any clinical findings of toxicity

and had no significant effect on body weights of males

or water consumption by mice of either sex. Male mice

may have been able to tolerate slightly higher exposure

concentrations. Target organs for sodium chlorate toxicity in the 2-year study included the pancreatic islets and

thyroid gland in female mice. The thyroid gland was

considered to be a target organ for sodium chlorate 

toxicity because of the increases in the incidences of follicular cell hypertrophy in 1,000 and 2,000 mg/L female

mice; the incidence was significantly increased at

2,000 mg/L. There was no evidence of thyroid gland

effects in male or female mice after 3 weeks of exposure. 

Several arguments support an association of pancreatic

islet neoplasms with sodium chlorate administration.

Spontaneous pancreatic islet cell tumors are rare in the

B6C3F1 mouse (Boorman and Sills, 1999). In the 2-year

mouse study, there was a positive trend in the incidences

of pancreatic islet cell adenoma or carcinoma (combined) in females. The incidences of adenoma and 

adenoma or carcinoma (combined) in the 2,000 mg/L

group exceeded the NTP historical range for drinking

water controls. However, the incidences of these lesions

were not increased in male mice. Furthermore, the incidences of pancreatic islet hyperplasia were not increased

significantly in exposed mice of either sex. Based on

these data, the pancreatic islet cell response in female

mice was considered an equivocal finding. Only one

other NTP study, 2,4- and 2,6-toluene diisocyanate

(NTP, 1986), demonstrated clear or some evidence of

carcinogenicity in female rats based on an increased

incidence of pancreatic islet adenomas. 

CONCLUSIONS

Under the conditions of this 2-year drinking water study,

there was some evidence of carcinogenic activity* of

sodium chlorate in male and female F344/N rats based

on increased incidences of thyroid gland neoplasms.

There was no evidence of carcinogenic activity of

sodium chlorate in male B6C3F1 mice exposed to 500,

1,000, or 2,000 mg/L. There was equivocal evidence of

carcinogenic activity of sodium chlorate in female

B6C3F1 mice based on marginally increased incidences

of pancreatic islet neoplasms.

Exposure to sodium chlorate resulted in nonneoplastic

lesions in the thyroid gland of male and female rats and

female mice, bone marrow of male rats and female mice,

and spleen of male rats.

__________

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

comments and public discussion on this Technical Report appears on page 11.
54 Sodium Chlorate, NTP TR 517 
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61

APPENDIX A

SUMMARY OF LESIONS IN MALE RATS

IN THE 2-YEAR DRINKING WATER STUDY

OF SODIUM CHLORATE

TABLE A1 Summary of the Incidence of Neoplasms in Male Rats

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62

TABLE A2 Individual Animal Tumor Pathology of Male Rats

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

TABLE A3 Statistical Analysis of Primary Neoplasms in Male Rats

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

TABLE A4 Historical Incidence of Thyroid Gland Neoplasms in Control Male F344/N Rats . . . . . . . . 95

TABLE A5 Summary of the Incidence of Nonneoplastic Lesions in Male Rats

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
62 Sodium Chlorate, NTP TR 517 

TABLE A1

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Drinking Water Study of Sodium Chloratea

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Disposition Summary 

Animals initially in study 50 50 50 50

Early deaths 

Accidental death 1 

Moribund 10 13 11 14

Natural deaths 3 10 8 8

Survivors 

Terminal sacrifice 36 27 31 28 

Animals examined microscopically 50 50 50 50

Alimentary System

Intestine large, colon (48) (47) (44) (49)

Intestine large, cecum (47) (46) (43) (47)

Intestine small, duodenum (49) (46) (46) (47)

Intestine small, jejunum (47) (46) (42) (44)

Intestine small, ileum (47) (46) (42) (47)

Liver (50) (50) (48) (50)

Hemangiosarcoma 1 (2%) 

Hepatocellular adenoma 3 (6%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Mesentery (19) (20) (19) (23)

Carcinoma, metastatic, pancreas 1 (5%) 

Hemangiosarcoma, metastatic, liver 1 (5%) 

Histiocytic sarcoma 1 (5%) 1 (5%) 

Osteosarcoma 1 (5%) 

Pancreas (49) (49) (49) (50)

Hemangiosarcoma, metastatic, liver 1 (2%) 

Acinus, adenoma 2 (4%) 1 (2%) 

Acinus, adenoma, multiple 1 (2%) 

Acinus, carcinoma 1 (2%) 

Salivary glands (49) (50) (50) (50)

Fibrosarcoma 1 (2%) 

Stomach, forestomach (50) (50) (50) (50)

Schwannoma malignant 1 (2%) 

Squamous cell papilloma 1 (2%) 

Stomach, glandular (49) (48) (48) (50)

Tongue (1) (1) (1) (1)

Sarcoma 1 (100%)

Squamous cell carcinoma 1 (100%)

Squamous cell papilloma 1 (100%)

Cardiovascular System

Blood vessel (1) (2)

Aorta, osteosarcoma 1 (100%)

Heart (50) (50) (50) (50)

Carcinoma, metastatic, Zymbal’s gland 1 (2%) 

Schwannoma benign 1 (2%) 
Sodium Chlorate, NTP TR 517 63

TABLE A1

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Endocrine System

Adrenal cortex (49) (49) (50) (50)

Carcinoma 1 (2%) 

Osteosarcoma, metastatic, bone 1 (2%) 

Adrenal medulla (49) (49) (50) (50)

Ganglioneuroma 1 (2%) 

Pheochromocytoma malignant 3 (6%) 1 (2%) 1 (2%) 

Pheochromocytoma benign 6 (12%) 3 (6%) 3 (6%) 5 (10%) 

Bilateral, ganglioneuroma 1 (2%) 

Bilateral, pheochromocytoma benign 1 (2%) 3 (6%) 

Islets, pancreatic (50) (49) (49) (50)

Adenoma 3 (6%) 4 (8%) 3 (6%) 5 (10%) 

Carcinoma 2 (4%) 1 (2%) 2 (4%) 

Pituitary gland (48) (50) (49) (50)

Pars distalis, adenoma 16 (33%) 15 (30%) 20 (41%) 15 (30%) 

Pars intermedia, adenoma 1 (2%) 1 (2%) 

Thyroid gland (47) (44) (43) (47)

Bilateral, C-cell, adenoma, multiple 1 (2%) 

C-cell, adenoma 9 (19%) 9 (20%) 5 (12%) 9 (19%) 

C-cell, carcinoma 2 (4%) 2 (5%) 1 (2%) 

Follicular cell, adenoma 1 (2%) 2 (4%) 

Follicular cell, carcinoma 4 (9%) 

General Body System

Peritoneum (1) (1)

Tissue NOS (5) (6) (2) (7)

Abdominal, paraganglioma 1 (20%) 

Mediastinum, carcinoma, metastatic, Zymbal’s gland 1 (17%) 

Mediastinum, squamous cell carcinoma, metastatic, lung 1 (17%) 

Pelvic, leiomyoma 1 (20%) 

Thoracic, fibroma 1 (14%) 

Genital System

Epididymis (50) (50) (50) (50)

Preputial gland (48) (49) (50) (50)

Adenoma 1 (2%) 6 (12%) 5 (10%) 5 (10%) 

Carcinoma 3 (6%) 1 (2%) 2 (4%) 2 (4%) 

Prostate (50) (49) (50) (50)

Seminal vesicle (50) (49) (50) (50)

Testes (50) (50) (50) (50)

Bilateral, interstitial cell, adenoma 1 (2%) 

Bilateral, interstitial cell, adenoma, multiple 40 (80%) 43 (86%) 42 (84%) 39 (78%) 

Interstitial cell, adenoma 2 (4%) 1 (2%) 2 (4%) 

Interstitial cell, adenoma, multiple 3 (6%) 5 (10%) 2 (4%) 3 (6%) 

Hematopoietic System

Bone marrow (48) (48) (50) (49)

Lymph node (34) (24) (26) (34)

Histiocytic sarcoma 1 (3%) 

Deep cervical, histiocytic sarcoma 1 (3%) 

Mediastinal, carcinoma, metastatic, Zymbal’s gland 1 (4%) 

Lymph node, mandibular (3) (2) (3) (4)
64 Sodium Chlorate, NTP TR 517 

TABLE A1

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Hematopoietic System (continued)

Lymph node, mesenteric (49) (50) (49) (50)

Spleen (48) (49) (49) (50)

Histiocytic sarcoma 1 (2%) 

Capsule, carcinoma, metastatic, pancreas 1 (2%) 

Thymus (48) (48) (49) (47)

Carcinoma, metastatic, Zymbal’s gland 1 (2%) 

Thymoma benign 1 (2%) 

Integumentary System

Mammary gland (45) (43) (47) (44)

Carcinoma 1 (2%) 1 (2%) 

Fibroadenoma 2 (4%) 1 (2%) 4 (9%) 4 (9%) 

Skin (50) (50) (50) (50)

Basal cell carcinoma 1 (2%) 2 (4%) 

Basal cell carcinoma, multiple 1 (2%) 

Keratoacanthoma 4 (8%) 2 (4%) 1 (2%) 1 (2%) 

Trichoepithelioma 1 (2%) 

Subcutaneous tissue, fibroma 9 (18%) 9 (18%) 4 (8%) 7 (14%) 

Subcutaneous tissue, fibroma, multiple 1 (2%) 1 (2%) 1 (2%) 

Subcutaneous tissue, fibrosarcoma 1 (2%) 2 (4%) 

Subcutaneous tissue, histiocytic sarcoma 1 (2%) 

Subcutaneous tissue, lipoma 1 (2%) 

Subcutaneous tissue, neural crest tumor 1 (2%) 

Subcutaneous tissue, osteosarcoma 1 (2%) 

Subcutaneous tissue, sarcoma 1 (2%) 

Subcutaneous tissue, schwannoma malignant 1 (2%) 1 (2%) 

Musculoskeletal System

Bone (50) (50) (50) (50)

Osteosarcoma 1 (2%) 

Periosteum, cranium, fibrosarcoma, metastatic, skin 1 (2%) 

Nervous System

Brain (50) (50) (50) (50)

Carcinoma, metastatic, Zymbal’s gland 1 (2%) 

Glioma malignant 1 (2%) 

Respiratory System

Lung (50) (50) (50) (50)

Alveolar/bronchiolar adenoma 1 (2%) 1 (2%) 2 (4%) 

Alveolar/bronchiolar carcinoma 2 (4%) 2 (4%) 1 (2%) 

Alveolar/bronchiolar carcinoma, multiple 1 (2%) 

Carcinoma, metastatic, Zymbal’s gland 1 (2%) 

Histiocytic sarcoma, metastatic, uncertain primary site 1 (2%) 

Osteosarcoma, metastatic, bone 1 (2%) 

Squamous cell carcinoma 1 (2%) 

Nose (49) (49) (49) (50)

Trachea (50) (49) (50) (50)
Sodium Chlorate, NTP TR 517 65

TABLE A1

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Special Senses System

Eye (50) (48) (46) (50)

Retrobulbar, fibrosarcoma, metastatic, skin 1 (2%) 

Harderian gland (49) (49) (49) (50)

Carcinoma 1 (2%) 

Zymbal’s gland (1) (1) (3)

Carcinoma 1 (100%) 1 (100%) 1 (33%) 

Urinary System

Kidney (47) (46) (49) (49)

Lipoma 1 (2%) 1 (2%) 

Mesenchymal tumor benign 1 (2%) 

Renal tubule, adenoma 1 (2%) 

Urinary bladder (48) (49) (47) (50)

Systemic Lesions

Multiple organsb (50) (50) (50) (50)

Histiocytic sarcoma 1 (2%) 1 (2%) 

Leukemia mononuclear 13 (26%) 21 (42%) 16 (32%) 23 (46%) 

Lymphoma malignant 1 (2%) 

Mesothelioma malignant 1 (2%) 2 (4%) 2 (4%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 49 50 50 50 

Total primary neoplasms 135 152 124 150 

Total animals with benign neoplasms 48 49 47 47 

Total benign neoplasms 100 112 97 108 

Total animals with malignant neoplasms 27 32 24 32 

Total malignant neoplasms 34 40 27 42 

Total animals with metastatic neoplasms 2 5 1 

Total metastatic neoplasms 3 10 3 

Total animals with malignant neoplasms 

of uncertain primary site 1

Total animals with uncertain neoplasms 

benign or malignant 1 

Total uncertain neoplasms 1 

a Number of animals examined microscopically at the site and the number of animals with neoplasm b Number of animals with any tissue examined microscopically c Primary neoplasms: all neoplasms except metastatic neoplasms
66 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Intestine large, colon + A + A +++++++++++++++++++++

Intestine large, rectum + A + A +++++++++++++++++++++

Intestine large, cecum + A + A ++++++++A++++++++++++

Intestine small, duodenum + + + A +++++++++++++++++++++

Intestine small, jejunum + A + A ++++++++A++++++++++++

Intestine small, ileum + A + A ++++++++A++++++++++++

Liver +++++++++++++++++++++++++

Histiocytic sarcoma X

Mesentery ++++++ ++ ++

Histiocytic sarcoma X

Osteosarcoma X

Pancreas + + + A +++++++++++++++++++++

Salivary glands + + + A +++++++++++++++++++++

Stomach, forestomach +++++++++++++++++++++++++

Schwannoma malignant X

Stomach, glandular + + + A +++++++++++++++++++++

Tongue

Cardiovascular System 

Blood vessel +

Aorta, osteosarcoma X

Heart +++++++++++++++++++++++++

Endocrine System 

Adrenal cortex + + + A +++++++++++++++++++++

Osteosarcoma, metastatic, bone X

Adrenal medulla + + + A +++++++++++++++++++++

Pheochromocytoma malignant X

Pheochromocytoma benign X

Islets, pancreatic +++++++++++++++++++++++++

Adenoma X

Carcinoma

Parathyroid gland + + + A +++++++++++++++++++++

Pituitary gland ++++A+++++++A++++++++++++

Pars distalis, adenoma X X X X

Thyroid gland + A + A +++++++++A+++++++++++

C-cell, adenoma X X X X X X

C-cell, carcinoma

Follicular cell, adenoma X

General Body System 

Tissue NOS + + +

Abdominal, paraganglioma X

Pelvic, leiomyoma X

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

3445555666667777777777777

Number of Days on Study 8260147333990022222233333

1393154066595699999900000

0000000000000000000000000

Carcass ID Number 1332330424254411111100000

2910827560401634567812389

+: Tissue examined microscopically M: Missing tissue X: Lesion present

A: Autolysis precludes examination. I: Insufficient tissue Blank: Not examined
Sodium Chlorate, NTP TR 517 67

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 48

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 49

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 1

Mesentery + + + + + + + + + 19

Histiocytic sarcoma 1

Osteosarcoma 1

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 49

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Schwannoma malignant 1

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49

Tongue + 1

Cardiovascular System 

Blood vessel 1

Aorta, osteosarcoma 1

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 49

Osteosarcoma, metastatic, bone 1

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 49

Pheochromocytoma malignant X X 3

Pheochromocytoma benign X X X X X 6

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X X 3

Carcinoma X X 2

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 48

Pars distalis, adenoma X X X X X X X X X X X X 16

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 47

C-cell, adenoma X X X 9

C-cell, carcinoma XX 2

Follicular cell, adenoma 1

General Body System 

Tissue NOS + +5

Abdominal, paraganglioma 1

Pelvic, leiomyoma 1

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0000111111111111111144444

0000000000000000000000000 Total

Carcass ID Number 2234111222333334444400022 Tissues/

5739019189045672347845623 Tumors
68 Sodium Chlorate, NTP TR 517 

Genital System 

Epididymis +++++++++++++++++++++++++

Preputial gland + + + A +++++++++++++++++++++

Adenoma

Carcinoma X X

Prostate +++++++++++++++++++++++++

Seminal vesicle +++++++++++++++++++++++++

Testes +++++++++++++++++++++++++

Bilateral, interstitial cell, adenoma, multiple X X X X XXXXXXXXXXXXXXX

Interstitial cell, adenoma X

Interstitial cell, adenoma, multiple X X

Hematopoietic System 

Bone marrow + + A +++++++++++++++++++++

Lymph node +++++++++ +++ +++ + +

Histiocytic sarcoma X

Deep cervical, histiocytic sarcoma X

Lymph node, mandibular MMMM + + MMMMMMMMMMMMMMM + MMM

Lymph node, mesenteric + + + M +++++++++++++++++++++

Spleen + A ++++++++++A++++++++++++

Histiocytic sarcoma X

Thymus + + + A + + + +M+ + + + + + + + + + + + + + + +

Integumentary System 

Mammary gland M + + A + + + +M+ + + + + + + + + + + + + + + +

Fibroadenoma

Skin +++++++++++++++++++++++++

Keratoacanthoma X X X

Trichoepithelioma X

Subcutaneous tissue, fibroma X X X X X

Subcutaneous tissue, fibrosarcoma X

Subcutaneous tissue, neural crest tumor

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Osteosarcoma X

Skeletal muscle

Nervous System 

Brain +++++++++++++++++++++++++

Peripheral nerve + +

Spinal cord + +

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

3445555666667777777777777

Number of Days on Study 8260147333990022222233333

1393154066595699999900000

0000000000000000000000000

Carcass ID Number 1332330424254411111100000

2910827560401634567812389
Sodium Chlorate, NTP TR 517 69

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + M 48

Adenoma X 1

Carcinoma X 3

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50

Bilateral, interstitial cell, adenoma, multiple X X X X X X X X X X X X X X X X X X X X X 40

Interstitial cell, adenoma X 2

Interstitial cell, adenoma, multiple X 3

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 48

Lymph node + + + + + + + + + + + + + + + + + 34

Histiocytic sarcoma 1

Deep cervical, histiocytic sarcoma 1

Lymph node, mandibular MMMMMMMMMMMMMMMMMMMMMMMMM 3

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 49

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 48

Histiocytic sarcoma 1

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 48

Integumentary System 

Mammary gland + + M + + + + + + + + + M + + + + + + + + + + + + 45

Fibroadenoma X X 2

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Keratoacanthoma X 4

Trichoepithelioma 1

Subcutaneous tissue, fibroma X X X X 9

Subcutaneous tissue, fibrosarcoma 1

Subcutaneous tissue, neural crest tumor X 1

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Osteosarcoma 1

Skeletal muscle + 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Peripheral nerve 2

Spinal cord 2

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0000111111111111111144444

0000000000000000000000000 Total

Carcass ID Number 2234111222333334444400022 Tissues/

5739019189045672347845623 Tumors
70 Sodium Chlorate, NTP TR 517 

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar carcinoma

Alveolar/bronchiolar carcinoma, multiple

Histiocytic sarcoma, metastatic,

uncertain primary site X

Osteosarcoma, metastatic, bone X

Nose + + A + + + + + + + + + + + + + + + + + + + + + +

Trachea +++++++++++++++++++++++++

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + +

Harderian gland + + + A +++++++++++++++++++++

Carcinoma

Urinary System 

Kidney + A + A ++++++++A++++++++++++

Urinary bladder + A + A +++++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Histiocytic sarcoma X

Leukemia mononuclear X X X X X X X X

Lymphoma malignant X

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

3445555666667777777777777

Number of Days on Study 8260147333990022222233333

1393154066595699999900000

0000000000000000000000000

Carcass ID Number 1332330424254411111100000

2910827560401634567812389
Sodium Chlorate, NTP TR 517 71

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X 1

Alveolar/bronchiolar carcinoma XX 2

Alveolar/bronchiolar carcinoma, multiple X 1

Histiocytic sarcoma, metastatic,

uncertain primary site 1

Osteosarcoma, metastatic, bone 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 49

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 50

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Carcinoma X 1

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 47

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 48

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 1

Leukemia mononuclear X X X X X 13

Lymphoma malignant 1

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0000111111111111111144444

0000000000000000000000000 Total

Carcass ID Number 2234111222333334444400022 Tissues/

5739019189045672347845623 Tumors
72 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Intestine large, colon ++++A+A+A++++++++++++++++

Intestine large, rectum ++++A+A+A++++++++++++++++

Intestine large, cecum + + A + A + A + A ++++++++++++++++

Intestine small, duodenum + + A + A + A + A ++++++++++++++++

Intestine small, jejunum + + A + A + A + A ++++++++++++++++

Intestine small, ileum + + A + A + A + A ++++++++++++++++

Liver +++++++++++++++++++++++++

Hemangiosarcoma

Hepatocellular adenoma X

Histiocytic sarcoma

Mesentery + + + + + + + + + + +

Carcinoma, metastatic, pancreas

Hemangiosarcoma, metastatic, liver

Histiocytic sarcoma

Pancreas ++++++A++++++++++++++++++

Hemangiosarcoma, metastatic, liver

Acinus, adenoma X X

Acinus, adenoma, multiple

Acinus, carcinoma

Salivary glands +++++++++++++++++++++++++

Stomach, forestomach +++++++++++++++++++++++++

Stomach, glandular + + A + + + A ++++++++++++++++++

Tongue +

Squamous cell carcinoma X

Tooth +

Cardiovascular System 

Heart +++++++++++++++++++++++++

Endocrine System 

Adrenal cortex ++++++A++++++++++++++++++

Adrenal medulla ++++++A++++++++++++++++++

Ganglioneuroma X

Pheochromocytoma benign X

Bilateral, pheochromocytoma benign X

Islets, pancreatic ++++++A++++++++++++++++++

Adenoma XX X

Carcinoma

Parathyroid gland +++++++++++++++++++++++++

Pituitary gland +++++++++++++++++++++++++

Pars distalis, adenoma X X X X

Pars intermedia, adenoma X

Thyroid gland + + A + A + A + A + + A ++++++++++A++

C-cell, adenoma X X X

C-cell, carcinoma

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

5555566666666666677777777

Number of Days on Study 4567801135666799901112222

2524254982038235934441699

0000000000000000000000000

Carcass ID Number 5877986656568959858896655

2518236244550119488943937
Sodium Chlorate, NTP TR 517 73

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 46

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 46

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 46

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 46

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hemangiosarcoma X 1

Hepatocellular adenoma X X 3

Histiocytic sarcoma X 1

Mesentery + + + + + + + + + 20

Carcinoma, metastatic, pancreas X 1

Hemangiosarcoma, metastatic, liver X 1

Histiocytic sarcoma X 1

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49

Hemangiosarcoma, metastatic, liver X 1

Acinus, adenoma 2

Acinus, adenoma, multiple X 1

Acinus, carcinoma X 1

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 48

Tongue 1

Squamous cell carcinoma 1

Tooth 1

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 49

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 49

Ganglioneuroma 1

Pheochromocytoma benign XX 3

Bilateral, pheochromocytoma benign 1

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49

Adenoma X 4

Carcinoma X 1

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pars distalis, adenoma X X X X X X X X X X X 15

Pars intermedia, adenoma 1

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 44

C-cell, adenoma X X X X X X 9

C-cell, carcinoma X X 2

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

7777777777777777777777777

Number of Days on Study 2222222222333333333333333

9999999999000000000011111

0000000000000000000100000 Total

Carcass ID Number 5777888999566777999066778 Tissues/

9234127035678567678001096 Tumors
74 Sodium Chlorate, NTP TR 517 

General Body System 

Peritoneum +

Tissue NOS + + + + + +

Mediastinum, carcinoma, metastatic,

Zymbal’s gland X

Mediastinum, squamous cell carcinoma,

metastatic, lung X

Genital System 

Epididymis +++++++++++++++++++++++++

Penis +

Preputial gland ++++++A++++++++++++++++++

Adenoma X

Carcinoma

Prostate ++++++A++++++++++++++++++

Seminal vesicle ++++++A++++++++++++++++++

Testes +++++++++++++++++++++++++

Bilateral, interstitial cell, adenoma, multiple X X X X X X X X X X X X X X X X X X X 

Interstitial cell, adenoma X

Interstitial cell, adenoma, multiple X X X X

Hematopoietic System 

Bone marrow ++++++++A++A+++++++++++++

Lymph node + ++++ + ++ ++++ ++

Mediastinal, carcinoma, metastatic,

Zymbal’s gland X

Lymph node, mandibular MMMMMMMMMMMMMMMMM + MMMMMMM

Lymph node, mesenteric +++++++++++++++++++++++++

Spleen ++++++A++++++++++++++++++

Capsule, carcinoma, metastatic,

Pancreas

Thymus + + + + + + + + + + + + + +MI + + + + + + + + +

Carcinoma, metastatic, Zymbal’s gland X

Integumentary System 

Mammary gland + M + M A M M + + + +M+ + + + + +M+ + + + + +

Carcinoma X

Fibroadenoma

Skin +++++++++++++++++++++++++

Basal cell carcinoma

Basal cell carcinoma, multiple

Keratoacanthoma X X

Subcutaneous tissue, fibroma X X X

Subcutaneous tissue, fibroma, multiple X

Subcutaneous tissue, fibrosarcoma X

Subcutaneous tissue, histiocytic sarcoma

Subcutaneous tissue, lipoma X

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

5555566666666666677777777

Number of Days on Study 4567801135666799901112222

2524254982038235934441699

0000000000000000000000000

Carcass ID Number 5877986656568959858896655

2518236244550119488943937
Sodium Chlorate, NTP TR 517 75

General Body System 

Peritoneum 1

Tissue NOS 6

Mediastinum, carcinoma, metastatic,

Zymbal’s gland 1

Mediastinum, squamous cell carcinoma,

metastatic, lung 1

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50

Penis + 2

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Adenoma X X X X X 6

Carcinoma X 1

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 49

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 49

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50

Bilateral, interstitial cell, adenoma, multiple X X X X X X X X X X X X X X X X X X X X X X X X 43

Interstitial cell, adenoma 1

Interstitial cell, adenoma, multiple X 5

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 48

Lymph node + + + + + + + + + + 24

Mediastinal, carcinoma, metastatic,

Zymbal’s gland 1

Lymph node, mandibular MMMMMMMMMMMMMMMMMMMM + MMMM 2

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 49

Capsule, carcinoma, metastatic,

Pancreas X 1

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 48

Carcinoma, metastatic, Zymbal’s gland 1

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 43

Carcinoma 1

Fibroadenoma X 1

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Basal cell carcinoma X 1

Basal cell carcinoma, multiple X 1

Keratoacanthoma 2

Subcutaneous tissue, fibroma X X X X X X 9

Subcutaneous tissue, fibroma, multiple 1

Subcutaneous tissue, fibrosarcoma X 2

Subcutaneous tissue, histiocytic sarcoma X 1

Subcutaneous tissue, lipoma 1

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

7777777777777777777777777

Number of Days on Study 2222222222333333333333333

9999999999000000000011111

0000000000000000000100000 Total

Carcass ID Number 5777888999566777999066778 Tissues/

9234127035678567678001096 Tumors
76 Sodium Chlorate, NTP TR 517 

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Periosteum, cranium, fibrosarcoma,

metastatic, skin X

Nervous System 

Brain +++++++++++++++++++++++++

Glioma malignant X

Peripheral nerve +

Spinal cord +

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar carcinoma X

Squamous cell carcinoma X

Nose ++++++A++++++++++++++++++

Trachea ++++++A++++++++++++++++++

Special Senses System 

Eye + + + + A + A + + + + + + + + + + + + + + + + + +

Retrobulbar, fibrosarcoma, metastatic, skin X

Harderian gland ++++++A++++++++++++++++++

Lacrimal gland +

Zymbal’s gland +

Carcinoma X

Urinary System 

Kidney ++++++A+A++A++++++++++A++

Lipoma

Renal tubule, adenoma X

Urinary bladder ++++++A++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Histiocytic sarcoma

Leukemia mononuclear X X X X X X XXXXX XX X

Mesothelioma malignant X

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

5555566666666666677777777

Number of Days on Study 4567801135666799901112222

2524254982038235934441699

0000000000000000000000000

Carcass ID Number 5877986656568959858896655

2518236244550119488943937
Sodium Chlorate, NTP TR 517 77

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Periosteum, cranium, fibrosarcoma,

metastatic, skin 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Glioma malignant 1

Peripheral nerve 1

Spinal cord 1

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X 1

Alveolar/bronchiolar carcinoma X 2

Squamous cell carcinoma 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 49

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 49

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 48

Retrobulbar, fibrosarcoma, metastatic, skin 1

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Lacrimal gland 1

Zymbal’s gland 1

Carcinoma 1

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 46

Lipoma X 1

Renal tubule, adenoma 1

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 49

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma X 1

Leukemia mononuclear X X X X X X X 21

Mesothelioma malignant 1

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

7777777777777777777777777

Number of Days on Study 2222222222333333333333333

9999999999000000000011111

0000000000000000000100000 Total

Carcass ID Number 5777888999566777999066778 Tissues/

9234127035678567678001096 Tumors
78 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Intestine large, colon + A + A A + A A + + + A +++++++++++++

Intestine large, rectum + + + + + +AA+ + +A+ + + + + + + + + + + + +

Intestine large, cecum + A A + A + A A + + + A + + A ++++++++++

Intestine small, duodenum + A + + + +AA+ + + + + +A+ + + + + + + + + +

Intestine small, jejunum + A A A + + A A A + + A + + A ++++++++++

Intestine small, ileum + AAAA+AA+ + +A+ +A ++++++++++

Liver + A ++++A++++++++++++++++++

Mesentery + + +++++ + + ++

Pancreas + A +++++++++++++++++++++++

Acinus, adenoma X

Salivary glands +++++++++++++++++++++++++

Fibrosarcoma

Stomach, forestomach +++++++++++++++++++++++++

Stomach, glandular + A ++++A++++++++++++++++++

Tongue +

Sarcoma X

Tooth

Cardiovascular System 

Blood vessel + +

Heart +++++++++++++++++++++++++

Schwannoma benign X

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++

Adrenal medulla +++++++++++++++++++++++++

Pheochromocytoma malignant X

Pheochromocytoma benign X X

Islets, pancreatic + A +++++++++++++++++++++++

Adenoma X

Parathyroid gland +++++++++++++++++++++++++

Pituitary gland + M +++++++++++++++++++++++

Pars distalis, adenoma X X X X X X X X X X X

Thyroid gland + A A A + + A A + + + A + + A ++++++++++

Bilateral, C-cell, adenoma, multiple

C-cell, adenoma X X X

General Body System 

Peritoneum +

Tissue NOS +

Genital System 

Epididymis +++++++++++++++++++++++++

Preputial gland +++++++++++++++++++++++++

Adenoma X X X

Carcinoma X X

Prostate +++++++++++++++++++++++++

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

2455566666666667777777777

Number of Days on Study 0766700246677990012222222

9516657670735583341999999

Carcass ID Number 1111111111111111111111111

0401342400113101300222224

6572645842594786031234893
Sodium Chlorate, NTP TR 517 79

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 44

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 43

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 46

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 42

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 42

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 48

Mesentery + + + + + + + + 19

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49

Acinus, adenoma 1

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Fibrosarcoma X 1

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 48

Tongue 1

Sarcoma 1

Tooth + 1

Cardiovascular System 

Blood vessel 2

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Schwannoma benign 1

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pheochromocytoma malignant 1

Pheochromocytoma benign X 3

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49

Adenoma X X 3

Parathyroid gland M + + + M + M + + + + + + + + + + + + + + + + + + 47

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Pars distalis, adenoma X X X X X X X X X 20

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 43

Bilateral, C-cell, adenoma, multiple X 1

C-cell, adenoma X X 5

General Body System 

Peritoneum 1

Tissue NOS + 2

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma XX 5

Carcinoma 2

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0000000000011111111111111

1111111111111111111111111 Total

Carcass ID Number 1133334444500111222233344 Tissues/

3412350129059018016778967 Tumors
80 Sodium Chlorate, NTP TR 517 

Genital System (continued)

Seminal vesicle +++++++++++++++++++++++++

Testes +++++++++++++++++++++++++

Bilateral, interstitial cell, adenoma, multiple X X X X X X X X X X X X X X X X X X X 

Interstitial cell, adenoma, multiple X

Hematopoietic system 

Bone marrow +++++++++++++++++++++++++

Lymph node + + + + + + + +++++ ++ +

Lymph node, mandibular MMMM + MMMM + MMMM + MMMMMMMMMM

Lymph node, mesenteric +++++++++++++++++++++++++

Spleen ++++++A++++++++++++++++++

Thymus +++++++++I+++++++++++++++

Thymoma benign

Integumentary system 

Mammary gland + + + + + + + +M+ + + +M+ + + + + + + + + + +

Carcinoma

Fibroadenoma X X

Skin +++++++++++++++++++++++++

Keratoacanthoma

Subcutaneous tissue, fibroma X X

Subcutaneous tissue, fibroma, multiple X

Subcutaneous tissue, sarcoma X

Subcutaneous tissue, schwannoma malignant X

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Skeletal muscle

Nervous System 

Brain +++++++++++++++++++++++++

Peripheral nerve + + + +

Spinal cord + + + +

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma X

Nose ++++++A++++++++++++++++++

Trachea +++++++++++++++++++++++++

Special Senses System 

Eye + M + A + + A A + + + + + + + + + + + + + + + + +

Harderian gland + A +++++++++++++++++++++++

Lacrimal gland +

Zymbal’s gland +

Carcinoma X

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

2455566666666667777777777

Number of Days on Study 0766700246677990012222222

9516657670735583341999999

1111111111111111111111111

Carcass ID Number 0401342400113101300222224

6572645842594786031234893
Sodium Chlorate, NTP TR 517 81

Genital System (continued)

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50

Bilateral, interstitial cell, adenoma, multiple X X X X X X X X X X X X X X X X X X X X X X X 42

Interstitial cell, adenoma, multiple X 2

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50

Lymph node + + + + + + + + + + + 26

Lymph node, mandibular MMMMMMMMMMMMMMMMMMMMMMMMM 3

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + I + + + + + 49

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 49

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 49

Thymoma benign X 1

Integumentary System 

Mammary gland + + + + + M + + + + + + + + + + + + + + + + + + + 47

Carcinoma X 1

Fibroadenoma XX 4

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Keratoacanthoma X 1

Subcutaneous tissue, fibroma X X 4

Subcutaneous tissue, fibroma, multiple 1

Subcutaneous tissue, sarcoma 1

Subcutaneous tissue, schwannoma malignant 1

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skeletal muscle + 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Peripheral nerve 4

Spinal cord + 5

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X 2

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 49

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 46

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Lacrimal gland 1

Zymbal’s gland 1

Carcinoma 1

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0000000000011111111111111

1111111111111111111111111 Total

Carcass ID Number 1133334444500111222233344 Tissues/

3412350129059018016778967 Tumors
82 Sodium Chlorate, NTP TR 517 

Urinary System 

Kidney + A +++++++++++++++++++++++

Mesenchymal tumor benign X

Urinary bladder + A + + + +AA+ + + + + + + + + + + + + + + + +

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Leukemia mononuclear X X X X X X X X X X X

Mesothelioma malignant X X

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

2455566666666667777777777

Number of Days on Study 0766700246677990012222222

9516657670735583341999999

1111111111111111111111111

Carcass ID Number 0401342400113101300222224

6572645842594786031234893
Sodium Chlorate, NTP TR 517 83

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49

Mesenchymal tumor benign 1

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 47

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Leukemia mononuclear X X X X X 16

Mesothelioma malignant 2

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0000000000011111111111111

1111111111111111111111111 Total

Carcass ID Number 1133334444500111222233344 Tissues/

3412350129059018016778967 Tumors
84 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Intestine large, colon + + A ++++++++++++++++++++++

Intestine large, rectum +++++++++++++++++++++++++

Intestine large, cecum + + A + A +++++++A++++++++++++

Intestine small, duodenum + + A ++++A+++++++++++++A+++

Intestine small, jejunum A + A + A + + A ++++A++++++++A+++

Intestine small, ileum + + A +++++++++++++A++++A+++

Liver +++++++++++++++++++++++++

Mesentery +++++++ + +++ + ++++

Pancreas +++++++++++++++++++++++++

Salivary glands +++++++++++++++++++++++++

Stomach, forestomach +++++++++++++++++++++++++

Squamous cell papilloma

Stomach, glandular +++++++++++++++++++++++++

Tongue

Squamous cell papilloma

Cardiovascular System 

Heart +++++++++++++++++++++++++

Carcinoma, metastatic, Zymbal’s gland X

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++

Carcinoma

Adrenal medulla +++++++++++++++++++++++++

Pheochromocytoma malignant

Pheochromocytoma benign X X

Bilateral, ganglioneuroma X

Bilateral, pheochromocytoma benign X 

Islets, pancreatic +++++++++++++++++++++++++

Adenoma X

Carcinoma X

Parathyroid gland +++++++++++++++++++++++++

Pituitary gland +++++++++++++++++++++++++

Pars distalis, adenoma X X X X X X X X X

Pars intermedia, adenoma X

Thyroid gland + + A + A ++++++++++++++++A+++

C-cell, adenoma X

C-cell, carcinoma X

Follicular cell, adenoma

Follicular cell, carcinoma X

General Body System 

Tissue NOS + + + + +

Thoracic, fibroma

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

4445556666666666777777777

Number of Days on Study 4684693455777899000112222

3525209411128199133080999

1111111111111111111111111

Carcass ID Number 9858665556797658557877666

2477795491391586126584023
Sodium Chlorate, NTP TR 517 85

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 44

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Mesentery + + + + + + + 23

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Squamous cell papilloma X 1

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50

Tongue + 1

Squamous cell papilloma X 1

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Carcinoma, metastatic, Zymbal’s gland 1

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Carcinoma X 1

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pheochromocytoma malignant X 1

Pheochromocytoma benign X X X 5

Bilateral, ganglioneuroma 1

Bilateral, pheochromocytoma benign X X 3

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X X X X 5

Carcinoma X 2

Parathyroid gland + + + + + + + + + + + + + + + + M + + + + + + + + 49

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pars distalis, adenoma X X X X X X 15

Pars intermedia, adenoma 1

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 47

C-cell, adenoma X X X X X X X X 9

C-cell, carcinoma 1

Follicular cell, adenoma X X 2

Follicular cell, carcinoma X X X 4

General Body System 

Tissue NOS + + 7

Thoracic, fibroma X 1

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 2222222222333333333333333

9999999999000001111111111

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 Total

Carcass ID Number 6788899999778885566779990 Tissues/

4212301678090893668573450 Tumors
86 Sodium Chlorate, NTP TR 517 

Genital System 

Epididymis +++++++++++++++++++++++++

Preputial gland +++++++++++++++++++++++++

Adenoma X X

Carcinoma X

Prostate +++++++++++++++++++++++++

Seminal vesicle +++++++++++++++++++++++++

Testes +++++++++++++++++++++++++

Bilateral, interstitial cell, adenoma

Bilateral, interstitial cell, adenoma, multiple X X X X X X X X X X X X X X X X X 

Interstitial cell, adenoma X X

Interstitial cell, adenoma, multiple X X

Hematopoietic System 

Bone marrow + + + A +++++++++++++++++++++

Lymph node ++++ +++ ++++++++ ++++

Lymph node, mandibular M M + MMMMM + MMMMMMMMMMMMMMMM

Lymph node, mesenteric +++++++++++++++++++++++++

Spleen +++++++++++++++++++++++++

Thymus + + + I + + + + + + + + + + + + + + + +M+M+ +

Integumentary system

Mammary gland + + + + + + + M + + + + M + MM + + M + + + + + +

Fibroadenoma X

Skin +++++++++++++++++++++++++

Basal cell carcinoma

Keratoacanthoma X

Subcutaneous tissue, fibroma X X X

Subcutaneous tissue, fibroma, multiple

Subcutaneous tissue, osteosarcoma X

Subcutaneous tissue, schwannoma malignant

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Nervous System 

Brain +++++++++++++++++++++++++

Carcinoma, metastatic, Zymbal’s gland X

Peripheral nerve + + +

Spinal cord + + +

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar carcinoma

Carcinoma, metastatic, Zymbal’s gland X

Nose +++++++++++++++++++++++++

Trachea +++++++++++++++++++++++++

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

4445556666666666777777777

Number of Days on Study 4684693455777899000112222

3525209411128199133080999

1111111111111111111111111

Carcass ID Number 9858665556797658557877666

2477795491391586126584023
Sodium Chlorate, NTP TR 517 87

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X X X 5

Carcinoma X 2

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50

Bilateral, interstitial cell, adenoma X 1

Bilateral, interstitial cell, adenoma, multiple X X X X X X X X X X X X X X X X X X X X X X 39

Interstitial cell, adenoma 2

Interstitial cell, adenoma, multiple X 3

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 49

Lymph node ++++++++ + + + + + + + 34

Lymph node, mandibular MMMMMMMM + MMMMMMMMM + MMMMMM 4

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 47

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + M 44

Fibroadenoma X X X 4

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Basal cell carcinoma X X 2

Keratoacanthoma 1

Subcutaneous tissue, fibroma X X X X 7

Subcutaneous tissue, fibroma, multiple X 1

Subcutaneous tissue, osteosarcoma 1

Subcutaneous tissue, schwannoma malignant X 1

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Carcinoma, metastatic, Zymbal’s gland 1

Peripheral nerve 3

Spinal cord + + 5

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar carcinoma X 1

Carcinoma, metastatic, Zymbal’s gland 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 2222222222333333333333333

9999999999000001111111111

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 Total

Carcass ID Number 6788899999778885566779990 Tissues/

4212301678090893668573450 Tumors
88 Sodium Chlorate, NTP TR 517 

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + +

Harderian gland +++++++++++++++++++++++++

Lacrimal gland +

Zymbal’s gland + + +

Carcinoma X

Urinary System 

Kidney + + + A +++++++++++++++++++++

Lipoma

Urinary bladder +++++++++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Leukemia mononuclear XXXX XX X X XX X XX X

Mesothelioma malignant

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

4445556666666666777777777

Number of Days on Study 4684693455777899000112222

3525209411128199133080999

1111111111111111111111111

Carcass ID Number 9858665556797658557877666

2477795491391586126584023
Sodium Chlorate, NTP TR 517 89

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 50

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Lacrimal gland 1

Zymbal’s gland 3

Carcinoma 1

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49

Lipoma X 1

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Leukemia mononuclear X X X X X X X X X 23

Mesothelioma malignant X X 2

TABLE A2

Individual Animal Tumor Pathology of Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 2222222222333333333333333

9999999999000001111111111

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 Total

Carcass ID Number 6788899999778885566779990 Tissues/

4212301678090893668573450 Tumors
90 Sodium Chlorate, NTP TR 517 

TABLE A3

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Adrenal Medulla: Benign Pheochromocytoma

Overall ratea 6/49 (12%) 4/49 (8%) 3/50 (6%) 8/50 (16%)

Adjusted rateb 13.8% 9.1% 6.8% 18.3%

Terminal ratec 6/36 (17%) 3/27 (11%) 2/31 (7%) 5/28 (18%)

First incidence (days) 729 (T) 555 698 699

Poly-3 testd P=0.229 P=0.364N P=0.236N P=0.391

Adrenal Medulla: Malignant Pheochromocytoma

Overall rate 3/49 (6%) 0/49 (0%) 1/50 (2%) 1/50 (2%)

Adjusted rate 6.9% 0.0% 2.3% 2.3%

Terminal rate 3/36 (8%) 0/27 (0%) 0/31 (0%) 1/28 (4%)

First incidence (days) 729 (T) —e 667 729 (T)

Poly-3 test P=0.404N P=0.119N P=0.300N P=0.305N

Adrenal Medulla: Benign or Malignant Pheochromocytoma 

Overall rate 9/49 (18%) 4/49 (8%) 4/50 (8%) 9/50 (18%)

Adjusted rate 20.7% 9.1% 9.1% 20.6%

Terminal rate 9/36 (25%) 3/27 (11%) 2/31 (7%) 6/28 (21%)

First incidence (days) 729 (T) 555 667 699

Poly-3 test P=0.331 P=0.110N P=0.107N P=0.598N

Liver: Hepatocellular Adenoma

Overall rate 0/50 (0%) 3/50 (6%) 0/48 (0%) 0/50 (0%)

Adjusted rate 0.0% 6.9% 0.0% 0.0%

Terminal rate 0/36 (0%) 3/27 (11%) 0/31 (0%) 0/28 (0%)

First incidence (days) — 729 (T) — —

Poly-3 test P=0.141N P=0.119 —f —

Lung: Alveolar/bronchiolar Carcinoma

Overall rate 3/50 (6%) 2/50 (4%) 0/50 (0%) 1/50 (2%)

Adjusted rate 6.9% 4.6% 0.0% 2.3%

Terminal rate 3/36 (8%) 2/27 (7%) 0/31 (0%) 1/28 (4%)

First incidence (days) 729 (T) 729 (T) — 729 (T)

Poly-3 test P=0.159N P=0.499N P=0.118N P=0.307N

Lung: Alveolar/bronchiolar Adenoma or Carcinoma

Overall rate 4/50 (8%) 3/50 (6%) 2/50 (4%) 1/50 (2%)

Adjusted rate 9.2% 6.9% 4.6% 2.3%

Terminal rate 4/36 (11%) 3/27 (11%) 2/31 (7%) 1/28 (4%)

First incidence (days) 729 (T) 729 (T) 729 (T) 729 (T)

Poly-3 test P=0.119N P=0.499N P=0.337N P=0.180N

Mammary Gland: Fibroadenoma

Overall rate 2/50 (4%) 1/50 (2%) 4/50 (8%) 4/50 (8%)

Adjusted rate 4.6% 2.3% 9.0% 9.2%

Terminal rate 2/36 (6%) 1/27 (4%) 3/31 (10%) 3/28 (11%)

First incidence (days) 729 (T) 729 (T) 566 718

Poly-3 test P=0.118 P=0.499N P=0.343 P=0.334

Mammary Gland: Fibroadenoma or Carcinoma

Overall rate 2/50 (4%) 2/50 (4%) 5/50 (10%) 4/50 (8%)

Adjusted rate 4.6% 4.6% 11.3% 9.2%

Terminal rate 2/36 (6%) 1/27 (4%) 4/31 (13%) 3/28 (11%)

First incidence (days) 729 (T) 726 566 718

Poly-3 test P=0.173 P=0.693N P=0.221 P=0.334
Sodium Chlorate, NTP TR 517 91

Pancreas: Adenoma

Overall rate 0/49 (0%) 3/49 (6%) 1/49 (2%) 0/50 (0%)

Adjusted rate 0.0% 6.9% 2.3% 0.0%

Terminal rate 0/36 (0%) 3/27 (11%) 1/31 (3%) 0/28 (0%)

First incidence (days) — 729 (T) 729 (T) —

Poly-3 test P=0.214N P=0.118 P=0.500 —

Pancreas: Adenoma or Carcinoma

Overall rate 0/49 (0%) 4/49 (8%) 1/49 (2%) 0/50 (0%)

Adjusted rate 0.0% 9.3% 2.3% 0.0%

Terminal rate 0/36 (0%) 4/27 (15%) 1/31 (3%) 0/28 (0%)

First incidence (days) — 729 (T) 729 (T) —

Poly-3 test P=0.138N P=0.059 P=0.500 —

Pancreatic Islets: Adenoma

Overall rate 3/50 (6%) 4/49 (8%) 3/49 (6%) 5/50 (10%)

Adjusted rate 6.9% 9.2% 6.9% 11.5%

Terminal rate 3/36 (8%) 2/27 (7%) 2/31 (7%) 4/28 (14%)

First incidence (days) 729 (T) 663 714 681

Poly-3 test P=0.335 P=0.498 P=0.661 P=0.355

Pancreatic Islets: Adenoma or Carcinoma

Overall rate 5/50 (10%) 5/49 (10%) 3/49 (6%) 7/50 (14%)

Adjusted rate 11.4% 11.5% 6.9% 16.0%

Terminal rate 5/36 (14%) 3/27 (11%) 2/31 (7%) 5/28 (18%)

First incidence (days) 729 (T) 663 714 681

Poly-3 test P=0.331 P=0.629 P=0.358N P=0.379

Pituitary Gland (Pars Distalis): Adenoma

Overall rate 16/48 (33%) 15/50 (30%) 20/49 (41%) 15/50 (30%)

Adjusted rate 37.2% 33.8% 43.8% 33.6%

Terminal rate 13/36 (36%) 11/27 (41%) 12/31 (39%) 8/28 (29%)

First incidence (days) 630 652 561 651

Poly-3 test P=0.516N P=0.457N P=0.337 P=0.449N

Preputial Gland: Adenoma

Overall rate 1/48 (2%) 6/49 (12%) 5/50 (10%) 5/50 (10%)

Adjusted rate 2.4% 13.7% 11.3% 11.3%

Terminal rate 1/35 (3%) 5/27 (19%) 3/31 (10%) 3/28 (11%)

First incidence (days) 729 (T) 542 626 465

Poly-3 test P=0.287 P=0.060 P=0.111 P=0.111

Preputial Gland: Carcinoma

Overall rate 3/48 (6%) 1/49 (2%) 2/50 (4%) 2/50 (4%)

Adjusted rate 7.0% 2.3% 4.6% 4.6%

Terminal rate 2/35 (6%) 1/27 (4%) 1/31 (3%) 1/28 (4%)

First incidence (days) 511 729 (T) 721 590

Poly-3 test P=0.555N P=0.304N P=0.492N P=0.491N

Preputial Gland: Adenoma or Carcinoma

Overall rate 4/48 (8%) 7/49 (14%) 7/50 (14%) 6/50 (12%)

Adjusted rate 9.3% 16.0% 15.8% 13.4%

Terminal rate 3/35 (9%) 6/27 (22%) 4/31 (13%) 3/28 (11%)

First incidence (days) 511 542 626 465

Poly-3 test P=0.461 P=0.270 P=0.276 P=0.395

TABLE A3

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
92 Sodium Chlorate, NTP TR 517 

Skin: Keratoacanthoma

Overall rate 4/50 (8%) 2/50 (4%) 1/50 (2%) 1/50 (2%)

Adjusted rate 9.1% 4.6% 2.3% 2.3%

Terminal rate 2/36 (6%) 0/27 (0%) 1/31 (3%) 0/28 (0%)

First incidence (days) 636 695 729 (T) 718

Poly-3 test P=0.132N P=0.338N P=0.181N P=0.183N

Skin: Keratoacanthoma, Trichoepithelioma, or Basal Cell Carcinoma

Overall rate 5/50 (10%) 4/50 (8%) 1/50 (2%) 3/50 (6%)

Adjusted rate 11.3% 9.1% 2.3% 6.9%

Terminal rate 3/36 (8%) 2/27 (7%) 1/31 (3%) 2/28 (7%)

First incidence (days) 636 695 729 (T) 718

Poly-3 test P=0.224N P=0.502N P=0.103N P=0.364N

Skin: Fibroma

Overall rate 9/50 (18%) 10/50 (20%) 5/50 (10%) 8/50 (16%)

Adjusted rate 20.5% 22.1% 11.3% 18.2%

Terminal rate 7/36 (19%) 6/27 (22%) 3/31 (10%) 5/28 (18%)

First incidence (days) 695 555 607 651

Poly-3 test P=0.300N P=0.528 P=0.187N P=0.498N

Skin: Fibroma, Fibrosarcoma, or Sarcoma

Overall rate 10/50 (20%) 12/50 (24%) 6/50 (12%) 8/50 (16%)

Adjusted rate 22.3% 26.4% 13.3% 18.2%

Terminal rate 7/36 (19%) 7/27 (26%) 3/31 (10%) 5/28 (18%)

First incidence (days) 381 555 209 651

Poly-3 test P=0.180N P=0.420 P=0.198N P=0.412N

Testes: Adenoma

Overall rate 45/50 (90%) 49/50 (98%) 44/50 (88%) 45/50 (90%)

Adjusted rate 93.8% 99.1% 93.3% 92.8%

Terminal rate 34/36 (94%) 27/27 (100%) 30/31 (97%) 27/28 (96%)

First incidence (days) 469 542 561 443

Poly-3 test P=0.198N P=0.164 P=0.644N P=0.593N

Thyroid Gland (C-Cell): Adenoma

Overall rate 9/47 (19%) 9/44 (20%) 6/43 (14%) 9/47 (19%)

Adjusted rate 21.1% 22.2% 15.0% 21.6%

Terminal rate 7/36 (19%) 7/27 (26%) 4/31 (13%) 8/28 (29%)

First incidence (days) 636 619 660 718

Poly-3 test P=0.485N P=0.553 P=0.334N P=0.583

Thyroid Gland (C-Cell): Carcinoma

Overall rate 2/47 (4%) 2/44 (5%) 0/43 (0%) 1/47 (2%)

Adjusted rate 4.7% 5.0% 0.0% 2.4%

Terminal rate 2/36 (6%) 2/27 (7%) 0/31 (0%) 1/28 (4%)

First incidence (days) 729 (T) 729 (T) — 729 (T)

Poly-3 test P=0.254N P=0.673 P=0.251N P=0.505N

Thyroid Gland (C-Cell): Adenoma or Carcinoma

Overall rate 11/47 (23%) 11/44 (25%) 6/43 (14%) 10/47 (21%)

Adjusted rate 25.7% 27.2% 15.0% 23.9%

Terminal rate 9/36 (25%) 9/27 (33%) 4/31 (13%) 9/28 (32%)

First incidence (days) 636 619 660 718

Poly-3 test P=0.339N P=0.539 P=0.174N P=0.524N

TABLE A3

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 93

Thyroid Gland (Follicular Cell): Carcinoma

Overall rate 0/47 (0%) 0/44 (0%) 0/43 (0%) 4/47 (9%)

Adjusted rate 0.0% 0.0% 0.0% 9.6%

Terminal rate 0/36 (0%) 0/27 (0%) 0/31 (0%) 4/28 (14%)

First incidence (days) — — — 729 (T)

Poly-3 test P=0.003 — — P=0.058

Thyroid Gland (Follicular Cell): Adenoma or Carcinoma

Overall rate 1/47 (2%) 0/44 (0%) 0/43 (0%) 6/47 (13%)

Adjusted rate 2.4% 0.0% 0.0% 14.4%

Terminal rate 0/36 (0%) 0/27 (0%) 0/31 (0%) 6/28 (21%)

First incidence (days) 705 — — 729 (T)

Poly-3 test P=0.002 P=0.512N P=0.513N P=0.052

All Organs: Mononuclear Cell Leukemia

Overall rate 13/50 (26%) 21/50 (42%) 16/50 (32%) 23/50 (46%)

Adjusted rate 28.5% 45.0% 35.0% 48.4%

Terminal rate 8/36 (22%) 8/27 (30%) 8/31 (26%) 10/28 (36%)

First incidence (days) 545 574 561 465

Poly-3 test P=0.111 P=0.074 P=0.328 P=0.036

All Organs: Osteosarcoma

Overall rate 3/50 (6%) 0/50 (0%) 0/50 (0%) 1/50 (2%)

Adjusted rate 6.7% 0.0% 0.0% 2.3%

Terminal rate 0/36 (0%) 0/27 (0%) 0/31 (0%) 1/28 (4%)

First incidence (days) 469 — — 729 (T)

Poly-3 test P=0.344N P=0.122N P=0.122N P=0.315N

All Organs: Benign Neoplasms

Overall rate 48/50 (96%) 49/50 (98%) 47/50 (94%) 47/50 (94%)

Adjusted rate 99.3% 99.1% 97.7% 96.3%

Terminal rate 36/36 (100%) 27/27 (100%) 31/31 (100%) 27/28 (96%)

First incidence (days) 469 542 561 443

Poly-3 test P=0.128N P=0.955N P=0.608N P=0.346N

All Organs: Malignant Neoplasms

Overall rate 27/50 (54%) 32/50 (64%) 24/50 (48%) 32/50 (64%)

Adjusted rate 55.4% 66.7% 49.7% 66.5%

Terminal rate 16/36 (44%) 14/27 (52%) 11/31 (36%) 16/28 (57%)

First incidence (days) 381 562 209 465

Poly-3 test P=0.365 P=0.175 P=0.360N P=0.181

TABLE A3

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
94 Sodium Chlorate, NTP TR 517 

All Organs: Benign or Malignant Neoplasms

Overall rate 49/50 (98%) 50/50 (100%) 50/50 (100%) 50/50 (100%)

Adjusted rate 99.6% 100.0% 100.0% 100.0%

Terminal rate 36/36 (100%) 27/27 (100%) 31/31 (100%) 28/28 (100%)

First incidence (days) 381 542 209 443

Poly-3 test P=0.987 P=1.000 P=1.000 P=1.000

(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, pancreas, pancreatic islets, pituitary gland, preputial gland, testes, and thyroid gland; for other tissues, denominator is number of animals necropsied. b Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality c Observed incidence at terminal kill d Beneath the control incidence is the P value associated with the trend test. Beneath the exposed group incidence are the P values corresponding to pairwise 

comparisons between the controls and that exposed group. The Poly-3 test accounts for the differential mortality in animals that do not reach terminal 

sacrifice. A negative trend or a lower incidence in an exposed group is indicated by N. e Not applicable; no neoplasms in animal group f Value of statistic cannot be computed.

TABLE A3

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 95

TABLE A4

Historical Incidence of Thyroid Gland Neoplasms in Control Male F344/N Ratsa

Incidence in Controls

Follicular Cell Follicular Cell Follicular Cell

Adenoma Carcinoma Adenoma 

Study or Carcinoma

Historical Incidence in Drinking Water Controls Given NTP-2000 Diet

Dipropylene glycol 1/42 0/42 1/42

Sodium chlorate 1/47 0/47 1/47

Sodium nitrite 1/50 1/50 2/50

Overall Historical Incidence: Drinking Water Studies

Total (%) 3/139 (2.2%) 1/139 (0.7%) 4/139 (2.9%)

Mean ± standard deviation 2.2% ± 0.3% 1.0% ± 1.4% 3.2% ± 1.1%

Range 2% 0%-2% 2%-4%

Overall Historical Incidence: All Routes

Total (%) 12/1,140 (1.1%) 11/1,140 (1.0%) 23/1,140 (2.0%)

Mean ± standard deviation 1.0% ± 1.3% 0.9% ± 1.2% 1.9% ± 1.5%

Range 0%-4% 0%-4% 0%-4%

a Data as of April 19, 2004
96 Sodium Chlorate, NTP TR 517 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Accidental death 1 

Moribund 10 13 11 14 

Natural death 3 10 8 8 

Survivors 

Terminal sacrifice 36 27 31 28 

Animals examined microscopically 50 50 50 50 

Alimentary System

Intestine large, colon (48) (47) (44) (49)

Edema 2 (4%) 

Intestine large, rectum (48) (47) (47) (50)

Congestion 1 (2%) 

Edema 1 (2%) 

Hemorrhage 1 (2%) 

Intestine large, cecum (47) (46) (43) (47)

Edema 1 (2%) 1 (2%) 

Ulcer 1 (2%) 

Intestine small, duodenum (49) (46) (46) (47)

Ulcer 1 (2%) 

Epithelium, hyperplasia 1 (2%) 

Intestine small, jejunum (47) (46) (42) (44)

Epithelium, necrosis 1 (2%) 

Intestine small, ileum (47) (46) (42) (47)

Ulcer 1 (2%) 

Liver (50) (50) (48) (50)

Angiectasis, focal 2 (4%) 1 (2%) 1 (2%) 3 (6%) 

Basophilic focus 27 (54%) 30 (60%) 33 (69%) 29 (58%) 

Cholangiofibrosis 2 (4%) 1 (2%) 1 (2%) 1 (2%) 

Clear cell focus 21 (42%) 18 (36%) 29 (60%) 15 (30%) 

Congestion 2 (4%) 

Degeneration, cystic, focal 13 (26%) 9 (18%) 12 (25%) 14 (28%) 

Eosinophilic focus 2 (4%) 3 (6%) 2 (4%) 

Fibrosis, focal 1 (2%) 1 (2%) 

Hemorrhage, focal 1 (2%) 

Hepatodiaphragmatic nodule 6 (12%) 2 (4%) 3 (6%) 5 (10%) 

Hyperplasia, focal, histiocytic 6 (12%) 2 (4%) 8 (17%) 5 (10%) 

Hyperplasia, focal, lymphoid 1 (2%) 1 (2%) 

Infarct 1 (2%) 

Infiltration cellular, mixed cell 36 (72%) 29 (58%) 33 (69%) 28 (56%) 

Mixed cell focus 13 (26%) 11 (22%) 3 (6%) 8 (16%) 

Bile duct, hyperplasia 48 (96%) 49 (98%) 46 (96%) 50 (100%)

Centrilobular, congestion 1 (2%) 

Hepatocyte, necrosis, focal 1 (2%) 2 (4%) 

Hepatocyte, vacuolization cytoplasmic, diffuse 3 (6%) 3 (6%) 4 (8%) 

Hepatocyte, vacuolization cytoplasmic, focal 26 (52%) 15 (30%) 14 (29%) 18 (36%) 

Hepatocyte, periportal, necrosis 1 (2%) 

a Number of animals examined microscopically at the site and the number of animals with lesion

TABLE A5

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of Sodium Chloratea

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 97

Alimentary System (continued)

Liver (continued) (50) (50) (48) (50)

Hepatocyte, periportal, vacuolization cytoplasmic 1 (2%) 1 (2%) 

Hepatocyte, centrilobular, atrophy 1 (2%)

Hepatocyte, centrilobular, necrosis 1 (2%) 3 (6%) 6 (13%) 4 (8%) 

Hepatocyte, centrilobular, vacuolization cytoplasmic 4 (8%) 9 (18%) 12 (25%) 11 (22%) 

Hepatocyte, midzonal, necrosis 1 (2%) 

Hepatocyte, midzonal, vacuolization cytoplasmic 6 (12%) 1 (2%) 1 (2%) 

Hepatocyte, midzonal, vacuolization cytoplasmic, focal 1 (2%) 

Portal, fibrosis 1 (2%) 

Portal, hemorrhage 1 (2%) 

Mesentery (19) (20) (19) (23)

Angiectasis 1 (5%) 

Hemorrhage 1 (5%) 1 (5%) 

Inflammation, chronic 1 (5%) 

Inflammation, chronic, focal 1 (4%) 

Fat, necrosis 2 (11%) 2 (11%) 2 (9%) 

Fat, necrosis, focal 12 (63%) 10 (50%) 13 (68%) 14 (61%) 

Pancreas (49) (49) (49) (50)

Inflammation, chronic 1 (2%) 

Acinus, atrophy, diffuse 1 (2%) 

Acinus, atrophy, focal 23 (47%) 23 (47%) 27 (55%) 15 (30%) 

Acinus, hyperplasia, focal 1 (2%) 1 (2%) 

Duct, cyst, focal 1 (2%) 1 (2%) 

Duct, cyst, focal, multiple 15 (31%) 13 (27%) 18 (37%) 15 (30%) 

Salivary glands (49) (50) (50) (50)

Atrophy 1 (2%) 

Hyperplasia, focal, histiocytic 1 (2%) 

Stomach, forestomach (50) (50) (50) (50)

Edema 1 (2%) 1 (2%) 4 (8%) 

Erosion 1 (2%) 

Inflammation, chronic 4 (8%) 1 (2%) 

Inflammation, chronic, focal 1 (2%) 

Inflammation, focal 1 (2%) 1 (2%) 

Ulcer 1 (2%) 5 (10%) 2 (4%) 4 (8%) 

Epithelium, cyst 1 (2%) 

Epithelium, hyperplasia 2 (4%) 8 (16%) 1 (2%) 7 (14%) 

Epithelium, hyperplasia, focal 1 (2%) 

Stomach, glandular (49) (48) (48) (50)

Erosion 3 (6%) 2 (4%) 4 (8%) 4 (8%) 

Perforation 1 (2%) 

Pigmentation, focal 1 (2%) 1 (2%) 

Ulcer 1 (2%) 3 (6%) 

Epithelium, hyperplasia, focal 1 (2%) 

Tongue (1) (1) (1) (1)

Epithelium, hyperplasia 1 (100%) 

Tooth (1) (1)

Malformation 1 (100%)

Peridontal tissue, hyperplasia, squamous 1 (100%)

TABLE A5

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
98 Sodium Chlorate, NTP TR 517 

Cardiovascular System

Heart (50) (50) (50) (50)

Cardiomyopathy 6 (12%) 3 (6%) 7 (14%) 10 (20%) 

Infiltration cellular, mixed cell 2 (4%) 1 (2%) 2 (4%) 

Inflammation, chronic, focal 1 (2%) 

Thrombosis 1 (2%) 1 (2%) 2 (4%) 2 (4%) 

Artery, inflammation, chronic, focal 1 (2%) 

Endocardium, valve, inflammation, chronic, focal 1 (2%) 

Endocrine System

Adrenal cortex (49) (49) (50) (50)

Accessory adrenal cortical nodule 1 (2%) 7 (14%) 4 (8%) 3 (6%) 

Atrophy 1 (2%) 

Cytoplasmic alteration, focal 3 (6%) 3 (6%) 2 (4%) 4 (8%) 

Degeneration, cystic, focal 2 (4%) 

Hyperplasia, diffuse 1 (2%) 

Infiltration cellular, mixed cell 1 (2%) 

Necrosis, focal 1 (2%) 

Vacuolization cytoplasmic, diffuse 1 (2%) 

Vacuolization cytoplasmic, focal 12 (24%) 8 (16%) 7 (14%) 6 (12%) 

Capsule, fibrosis, focal 1 (2%) 

Adrenal medulla (49) (49) (50) (50)

Hyperplasia, focal 5 (10%) 12 (24%) 9 (18%) 13 (26%) 

Islets, pancreatic (50) (49) (49) (50)

Hyperplasia 2 (4%) 

Hyperplasia, focal 1 (2%) 1 (2%) 

Parathyroid gland (49) (50) (47) (49)

Hyperplasia, focal 1 (2%) 

Pituitary gland (48) (50) (49) (50)

Angiectasis 2 (4%) 4 (8%) 1 (2%) 3 (6%) 

Hemorrhage 1 (2%) 

Hemorrhage, focal 1 (2%) 

Pars distalis, cyst 2 (4%) 1 (2%) 1 (2%) 1 (2%) 

Pars distalis, cytoplasmic alteration, focal 3 (6%) 7 (14%) 3 (6%) 8 (16%) 

Pars distalis, degeneration, cystic, focal 2 (4%) 2 (4%) 

Pars distalis, hemorrhage, focal 2 (4%) 2 (4%) 1 (2%) 3 (6%) 

Pars distalis, hyperplasia, focal 4 (8%) 2 (4%) 3 (6%) 1 (2%) 

Pars distalis, pars nervosa, hemorrhage, focal 1 (2%) 

Pars intermedia, hemorrhage, focal 1 (2%) 

Rathke’s cleft, cyst 1 (2%) 

Rathke’s cleft, hemorrhage 1 (2%) 2 (4%) 2 (4%) 

Rathke’s cleft, hyperplasia, cystic 1 (2%) 

Thyroid gland (47) (44) (43) (47)

C-cell, hyperplasia 45 (96%) 42 (95%) 41 (95%) 44 (94%) 

C-cell, hyperplasia, focal 1 (2%) 

Follicle, cyst 1 (2%) 1 (2%) 2 (4%) 

Follicle, degeneration, cystic, focal 2 (4%) 

Follicle, mineralization, focal 45 (96%) 43 (98%) 42 (98%) 42 (89%) 

Follicular cell, hypertrophy 4 (9%) 13 (30%) 33 (77%) 40 (85%) 

Follicular cell, hypertrophy, focal 1 (2%) 

TABLE A5

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 99

General Body System

Tissue NOS (5) (6) (2) (7)

Abdominal, fibrosis 1 (50%) 

Mediastinum, hemorrhage 1 (17%) 

Genital System

Epididymis (50) (50) (50) (50)

Fibrosis 1 (2%) 

Inflammation, chronic 1 (2%) 1 (2%) 2 (4%) 

Penis (2)

Thrombosis 1 (50%) 

Preputial gland (48) (49) (50) (50)

Atrophy 1 (2%) 

Cyst 1 (2%) 1 (2%) 

Degeneration, cystic 2 (4%) 1 (2%) 2 (4%) 

Hyperplasia, cystic 1 (2%) 1 (2%) 

Inflammation, chronic 22 (46%) 12 (24%) 18 (36%) 20 (40%) 

Necrosis 1 (2%) 

Prostate (50) (49) (50) (50)

Inflammation, chronic 21 (42%) 23 (47%) 29 (58%) 30 (60%) 

Mineralization, focal 3 (6%) 2 (4%) 3 (6%) 4 (8%) 

Epithelium, hyperplasia, focal 11 (22%) 4 (8%) 2 (4%) 11 (22%) 

Testes (50) (50) (50) (50)

Atrophy 4 (8%) 10 (20%) 9 (18%) 6 (12%) 

Bilateral, atrophy 1 (2%) 

Germinal epithelium, atrophy 1 (2%) 

Germinal epithelium, degeneration 1 (2%) 

Interstitial cell, hyperplasia, focal 1 (2%) 1 (2%) 1 (2%) 3 (6%) 

Hematopoietic System

Bone marrow (48) (48) (50) (49)

Angiectasis 1 (2%) 

Atrophy 1 (2%) 

Fibrosis 2 (4%) 

Hyperplasia 28 (58%) 35 (73%) 41 (82%) 40 (82%) 

Myeloid cell, erythroid cell, hyperplasia 2 (4%) 

Lymph node (34) (24) (26) (34)

Ectasia 1 (3%) 

Hemorrhage 1 (3%) 

Deep cervical, hemorrhage 1 (4%) 

Deep cervical, hyperplasia, plasma cell 1 (3%) 

Mediastinal, angiectasis 1 (4%) 

Mediastinal, ectasia 5 (15%) 7 (29%) 5 (19%) 3 (9%) 

Mediastinal, hemorrhage 3 (9%) 2 (8%) 2 (8%) 1 (3%) 

Mediastinal, hyperplasia, histiocytic 3 (13%) 2 (8%) 1 (3%) 

Mediastinal, hyperplasia, lymphoid 1 (3%) 1 (4%) 3 (9%) 

Mediastinal, hyperplasia, plasma cell 1 (3%) 2 (8%) 

Mediastinal, infiltration cellular, polymorphonuclear 1 (4%) 

Mediastinal, inflammation, chronic active 1 (3%) 

Mediastinal, inflammation, suppurative 1 (4%) 

Pancreatic, angiectasis 2 (6%) 

Pancreatic, ectasia 3 (9%) 3 (13%) 3 (12%) 6 (18%) 

Pancreatic, hemorrhage 5 (15%) 3 (13%) 1 (4%) 1 (3%) 

TABLE A5

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
100 Sodium Chlorate, NTP TR 517 

Hematopoietic System (continued)

Lymph node (continued) (34) (24) (26) (34)

Pancreatic, hyperplasia, histiocytic 8 (24%) 5 (21%) 9 (35%) 6 (18%) 

Pancreatic, hyperplasia, lymphoid 1 (3%) 1 (4%) 

Pancreatic, pigmentation 1 (3%) 1 (4%) 1 (4%) 

Renal, hemorrhage 1 (4%) 

Renal, hyperplasia, focal, histiocytic 1 (4%) 

Renal, hyperplasia, lymphoid 1 (4%) 

Lymph node, mesenteric (49) (50) (49) (50)

Amyloid deposition 1 (2%) 

Ectasia 1 (2%) 1 (2%) 1 (2%) 3 (6%) 

Hemorrhage 2 (4%) 3 (6%) 

Hyperplasia, focal, histiocytic 1 (2%) 

Hyperplasia, histiocytic 3 (6%) 3 (6%) 1 (2%) 

Hyperplasia, lymphoid 2 (4%) 1 (2%) 1 (2%) 

Spleen (48) (49) (49) (50)

Amyloid deposition 1 (2%) 

Angiectasis, focal 2 (4%) 1 (2%) 3 (6%) 

Atrophy 1 (2%) 

Congestion 1 (2%) 1 (2%) 

Fibrosis, focal 2 (4%) 2 (4%) 4 (8%) 

Hematopoietic cell proliferation 2 (4%) 6 (12%) 4 (8%) 11 (22%) 

Hemorrhage 1 (2%) 1 (2%) 

Hyperplasia, focal, histiocytic 1 (2%) 1 (2%) 2 (4%) 1 (2%) 

Infarct, multiple 1 (2%) 

Metaplasia, focal, lipocyte 1 (2%) 

Necrosis 1 (2%) 

Pigmentation 1 (2%) 

Pigmentation, focal 1 (2%) 

Capsule, accessory spleen, focal 1 (2%) 

Capsule, fibrosis, focal 1 (2%) 

Lymphoid follicle, atrophy 1 (2%) 

Thymus (48) (48) (49) (47)

Angiectasis 1 (2%) 

Cyst 1 (2%) 

Hemorrhage 1 (2%) 2 (4%) 3 (6%) 

Hyperplasia, lymphoid 2 (4%) 1 (2%) 

Integumentary System

Mammary gland (45) (43) (47) (44)

Cyst 1 (2%) 

Dilatation 7 (16%) 7 (16%) 7 (15%) 2 (5%) 

Hyperplasia 1 (2%) 2 (4%) 2 (5%) 

Inflammation, chronic, focal 1 (2%) 1 (2%) 

Skin (50) (50) (50) (50)

Cyst epithelial inclusion 3 (6%) 1 (2%) 3 (6%) 1 (2%) 

Fibrosis, focal 2 (4%) 

Hyperkeratosis, focal 1 (2%) 1 (2%) 

Inflammation, chronic, focal 2 (4%) 

Ulcer 1 (2%) 

Artery, subcutaneous tissue, thrombosis 1 (2%) 

Epidermis, hyperplasia, focal 1 (2%) 

Lip, inflammation, chronic, focal 1 (2%) 

Subcutaneous tissue, cyst 1 (2%) 

TABLE A5

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 101

Integumentary System (continued)

Skin (continued) (50) (50) (50) (50)

Subcutaneous tissue, cyst epithelial inclusion 1 (2%) 

Subcutaneous tissue, hyperplasia, focal, histiocytic 1 (2%) 

Subcutaneous tissue, inflammation, chronic, focal 1 (2%) 

Subcutaneous tissue, inflammation, chronic, 

focal, suppurative 1 (2%) 

Musculoskeletal System

Bone (50) (50) (50) (50)

Cranium, hyperostosis 1 (2%) 

Nervous System

Brain (50) (50) (50) (50)

Compression, focal 6 (12%) 6 (12%) 7 (14%) 6 (12%) 

Hemorrhage, focal 2 (4%) 2 (4%) 4 (8%) 6 (12%) 

Cerebrum, ventricle, hydrocephalus 1 (2%) 

Respiratory System

Lung (50) (50) (50) (50)

Congestion 2 (4%) 1 (2%) 3 (6%) 

Foreign body, focal 1 (2%) 

Hemorrhage 1 (2%) 

Hemorrhage, focal 3 (6%) 1 (2%) 2 (4%) 2 (4%) 

Hyperplasia, focal, histiocytic 1 (2%) 1 (2%) 

Hyperplasia, histiocytic 2 (4%) 1 (2%) 1 (2%) 2 (4%) 

Infiltration cellular, mixed cell 1 (2%) 3 (6%) 1 (2%) 2 (4%) 

Inflammation, chronic, focal 5 (10%) 2 (4%) 3 (6%) 3 (6%) 

Inflammation, focal, suppurative 1 (2%) 

Alveolar epithelium, hyperplasia, focal 8 (16%) 5 (10%) 3 (6%) 4 (8%) 

Alveolar epithelium, metaplasia, squamous 1 (2%) 

Alveolus, edema, focal 1 (2%) 

Alveolus, hyperplasia, focal, histiocytic 1 (2%) 

Interstitium, edema 1 (2%) 1 (2%) 

Mediastinum, edema 1 (2%) 1 (2%) 

Nose (49) (49) (49) (50)

Foreign body 1 (2%) 2 (4%) 1 (2%) 

Inflammation, chronic 1 (2%) 

Inflammation, suppurative 1 (2%) 1 (2%) 6 (12%) 1 (2%) 

Nasolacrimal duct, inflammation 1 (2%) 3 (6%) 1 (2%) 

Olfactory epithelium, hyperplasia, focal 1 (2%) 

Respiratory epithelium, hyperplasia, focal 1 (2%) 

Trachea (50) (49) (50) (50)

Peritracheal tissue, edema 1 (2%) 

Special Senses System

Eye (50) (48) (46) (50)

Atrophy 2 (4%) 

Cataract 2 (4%) 1 (2%) 2 (4%) 

Exudate 1 (2%) 

Cornea, inflammation, chronic 1 (2%) 

Cornea, retrobulbar, inflammation, chronic active 1 (2%) 

Retina, degeneration 2 (4%) 1 (2%) 2 (4%) 

TABLE A5

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
102 Sodium Chlorate, NTP TR 517 

Special Senses System (continued)

Harderian gland (49) (49) (49) (50)

Fibrosis, focal 1 (2%) 

Hyperplasia, focal, histiocytic 1 (2%) 1 (2%) 1 (2%) 

Inflammation, chronic, focal 1 (2%) 1 (2%) 1 (2%) 

Inflammation, chronic active, diffuse 1 (2%) 

Epithelium, hyperplasia, focal 1 (2%) 

Urinary System

Kidney (47) (46) (49) (49)

Cyst 1 (2%) 

Cyst, multiple 1 (2%) 

Hydronephrosis 1 (2%) 

Infarct 1 (2%) 

Infarct, multiple 1 (2%) 1 (2%) 

Metaplasia, focal, lipocyte 1 (2%) 

Nephropathy 45 (96%) 44 (96%) 48 (98%) 47 (96%) 

Cortex, medulla, atrophy 1 (2%) 

Pelvis, infiltration cellular, mixed cell 1 (2%) 

Pelvis, transitional epithelium, hyperplasia 1 (2%) 1 (2%) 

Renal tubule, accumulation, hyaline droplet 1 (2%) 4 (8%) 2 (4%) 

Renal tubule, hyperplasia, focal 1 (2%) 

Renal tubule, pigmentation 4 (9%) 4 (9%) 1 (2%) 4 (8%) 

Urinary bladder (48) (49) (47) (50)

Calculus microscopic observation only 1 (2%) 

Edema 2 (4%) 

Hemorrhage 2 (4%) 

Inflammation, chronic 1 (2%) 

Serosa, inflammation, focal 1 (2%) 

Transitional epithelium, hyperplasia, diffuse 1 (2%) 

TABLE A5

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
103

APPENDIX B

SUMMARY OF LESIONS IN FEMALE RATS

IN THE 2-YEAR DRINKING WATER STUDY

OF SODIUM CHLORATE

TABLE B1 Summary of the Incidence of Neoplasms in Female Rats

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

TABLE B2 Individual Animal Tumor Pathology of Female Rats

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108

TABLE B3 Statistical Analysis of Primary Neoplasms in Female Rats

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130

TABLE B4 Historical Incidence of Thyroid Gland Neoplasms in Control Female F344/N Rats . . . . . . 134

TABLE B5 Summary of the Incidence of Nonneoplastic Lesions in Female Rats

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
104 Sodium Chlorate, NTP TR 517 

TABLE B1

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Drinking Water Study of Sodium Chloratea

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 10 11 11 4 

Natural deaths 3 3 6 5 

Survivors 

Died last week of study 2 1 1

Terminal sacrifice 37 34 32 40

Animals examined microscopically 50 50 50 50 

Alimentary System

Intestine large, colon (50) (48) (46) (49)

Leiomyosarcoma 1 (2%) 

Intestine small, jejunum (49) (47) (44) (45)

Leiomyoma 1 (2%) 

Liver (50) (50) (50) (50)

Cholangiocarcinoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Histiocytic sarcoma, metastatic, skeletal muscle 1 (2%) 

Mesentery (18) (10) (13) (16)

Carcinoma 1 (6%) 

Oral mucosa (1) (1)

Squamous cell carcinoma 1 (100%)

Pancreas (50) (49) (49) (49)

Acinus, adenoma 2 (4%) 

Salivary glands (50) (50) (50) (50)

Stomach, forestomach (50) (50) (50) (50)

Tooth (2) (2) (1)

Odontoma 1 (50%) 

Cardiovascular System

Heart (50) (50) (50) (50)

Endocrine System

Adrenal cortex (50) (50) (50) (50)

Adrenal medulla (50) (50) (50) (50)

Pheochromocytoma malignant 1 (2%) 1 (2%) 

Pheochromocytoma complex 1 (2%) 

Pheochromocytoma benign 2 (4%) 1 (2%) 1 (2%) 1 (2%) 

Islets, pancreatic (50) (49) (49) (50)

Adenoma 2 (4%) 1 (2%) 

Carcinoma 1 (2%) 1 (2%) 1 (2%) 

Pituitary gland (49) (49) (50) (50)

Pars distalis, adenoma 23 (47%) 18 (37%) 17 (34%) 24 (48%) 

Pars distalis, adenoma, multiple 1 (2%) 

Pars distalis, carcinoma 1 (2%) 3 (6%) 

Pars intermedia, adenoma 1 (2%) 1 (2%) 1 (2%) 

Thyroid gland (47) (47) (43) (46)

Bilateral, C-cell, adenoma 1 (2%) 2 (4%) 

C-cell, adenoma 11 (23%) 8 (17%) 11 (26%) 9 (20%) 

C-cell, carcinoma 1 (2%) 3 (6%) 1 (2%) 3 (7%) 

Follicular cell, adenoma 2 (4%) 

Follicular cell, carcinoma 1 (2%) 1 (2%) 2 (4%) 
Sodium Chlorate, NTP TR 517 105

General Body System

Tissue NOS (1) (2) (4) (6)

Mediastinum, carcinoma, metastatic, thyroid gland 1 (50%) 

Mediastinum, carcinoma, metastatic, Zymbal’s gland 1 (25%) 

Mediastinum, histiocytic sarcoma 1 (25%) 

Mediastinum, sarcoma 1 (17%) 

Genital System

Clitoral gland (49) (50) (50) (49)

Adenoma 11 (22%) 5 (10%) 12 (24%) 4 (8%) 

Carcinoma 3 (6%) 1 (2%) 

Sarcoma 1 (2%) 

Ovary (50) (50) (49) (50)

Granulosa cell tumor benign 1 (2%) 

Sarcoma 1 (2%) 

Oviduct (2)

Uterus (50) (50) (49) (50)

Carcinoma, metastatic, mesentery 1 (2%) 

Sarcoma stromal 1 (2%) 

Endometrium, polyp stromal 8 (16%) 8 (16%) 7 (14%) 7 (14%) 

Endometrium, polyp stromal, multiple 1 (2%) 2 (4%) 

Endometrium, sarcoma 1 (2%) 

Hematopoietic System

Bone marrow (50) (49) (50) (50)

Lymph node (36) (34) (30) (39)

Mediastinal, histiocytic sarcoma 1 (3%) 

Mediastinal, sarcoma 1 (3%) 

Lymph node, mandibular (4) (6) (4) (5)

Lymph node, mesenteric (50) (49) (49) (50)

Spleen (50) (50) (50) (50)

Sarcoma 1 (2%) 

Thymus (49) (48) (48) (48)

Sarcoma 1 (2%) 

Integumentary System

Mammary gland (50) (50) (50) (50)

Adenoma 3 (6%) 2 (4%) 

Carcinoma 2 (4%) 1 (2%) 2 (4%) 

Carcinoma, multiple 1 (2%) 

Fibroadenoma 23 (46%) 26 (52%) 23 (46%) 27 (54%) 

Fibroadenoma, multiple 10 (20%) 3 (6%) 8 (16%) 6 (12%) 

Histiocytic sarcoma, metastatic, skeletal muscle 1 (2%) 

Skin (50) (50) (50) (50)

Basal cell carcinoma 1 (2%) 

Keratoacanthoma 1 (2%) 

Trichoepithelioma 2 (4%) 

Pinna, neural crest tumor 1 (2%) 

Subcutaneous tissue, carcinoma, metastatic, 

mammary gland 1 (2%) 

Subcutaneous tissue, fibroma 4 (8%) 1 (2%) 1 (2%) 1 (2%) 

TABLE B1

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
106 Sodium Chlorate, NTP TR 517 

Integumentary System (continued)

Skin (continued) (50) (50) (50) (50)

Subcutaneous tissue, fibrosarcoma 1 (2%) 

Subcutaneous tissue, histiocytic sarcoma 1 (2%) 

Subcutaneous tissue, histiocytic sarcoma, 

metastatic, skeletal muscle 1 (2%) 

Subcutaneous tissue, lipoma 1 (2%) 

Subcutaneous tissue, sarcoma 1 (2%) 

Musculoskeletal System

Bone (50) (50) (50) (50)

Osteosarcoma 1 (2%) 

Skeletal muscle (2) (1) (1)

Histiocytic sarcoma 1 (50%) 

Rhabdomyosarcoma 1 (50%) 

Nervous System

Brain (49) (50) (50) (50)

Carcinoma, metastatic, pituitary gland 2 (4%) 

Respiratory System

Lung (50) (50) (50) (50)

Alveolar/bronchiolar adenoma 1 (2%) 1 (2%) 

Alveolar/bronchiolar carcinoma 1 (2%) 

Carcinoma, metastatic, mammary gland 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Histiocytic sarcoma, metastatic, skeletal muscle 1 (2%) 

Sarcoma 1 (2%) 

Nose (50) (50) (50) (50)

Special Senses System

Eye (50) (49) (47) (50)

Harderian gland (50) (50) (50) (50)

Histiocytic sarcoma 1 (2%) 

Squamous cell carcinoma, metastatic, oral mucosa 1 (2%) 

Zymbal’s gland (1) (1) (1)

Carcinoma 1 (100%)

Urinary System

Kidney (50) (49) (47) (47)

Sarcoma 1 (2%) 

Urinary bladder (50) (48) (50) (50)

Transitional epithelium, papilloma 1 (2%) 

Systemic Lesions

Multiple organsb (50) (50) (50) (50)

Histiocytic sarcoma 2 (4%) 1 (2%) 

Leukemia mononuclear 11 (22%) 9 (18%) 13 (26%) 9 (18%) 

Lymphoma malignant 1 (2%) 

Mesothelioma malignant 1 (2%) 

TABLE B1

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 107

Neoplasm Summary 

Total animals with primary neoplasmsc 49 48 46 48 

Total primary neoplasms 133 102 101 118 

Total animals with benign neoplasms 46 42 44 47 

Total benign neoplasms 107 77 82 87 

Total animals with malignant neoplasms 21 22 19 22 

Total malignant neoplasms 25 25 19 31 

Total animals with metastatic neoplasms 1 5 2 2 

Total metastatic neoplasms 1 8 2 2 

Total animals with uncertain neoplasmsbenign or malignant 1 

Total uncertain neoplasms 1 

a Number of animals examined microscopically at the site and the number of animals with neoplasm b Number of animals with any tissue examined microscopically c Primary neoplasms: all neoplasms except metastatic neoplasms

TABLE B1

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
108 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Intestine large, colon +++++++++++++++++++++++++

Leiomyosarcoma

Intestine large, rectum +++++++++++++++++++++++++

Intestine large, cecum +++++++++++++++++++++++++

Intestine small, duodenum +++++++++++++++++++++++++

Intestine small, jejunum ++++++A++++++++++++++++++

Intestine small, ileum ++++++A++++++++++++++++++

Liver +++++++++++++++++++++++++

Mesentery + + + + + + + + + + + +

Pancreas +++++++++++++++++++++++++

Acinus, adenoma X

Salivary glands +++++++++++++++++++++++++

Stomach, forestomach +++++++++++++++++++++++++

Stomach, glandular +++++++++++++++++++++++++

Cardiovascular System 

Heart +++++++++++++++++++++++++

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++

Adrenal medulla +++++++++++++++++++++++++

Pheochromocytoma benign

Islets, pancreatic +++++++++++++++++++++++++

Adenoma

Carcinoma

Parathyroid gland + + + + + + + + + + + + + + + + + +M+ +M+ + +

Pituitary gland + + + + + + + + + + + + + + + + + +M+ + + + + +

Pars distalis, adenoma X X X X X X X X X XXXX

Pars distalis, carcinoma X

Pars intermedia, adenoma

Thyroid gland + + + + +AA+ + + + + + + + + + +M+ + + + + +

Bilateral, C-cell, adenoma

C-cell, adenoma X X X X X

C-cell, carcinoma X

Follicular cell, carcinoma

General Body System 

Tissue NOS +

Genital System 

Clitoral gland +++++++++++++++++++++++++

Adenoma X X X X

Carcinoma X

Ovary +++++++++++++++++++++++++

Granulosa cell tumor benign X

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

4455555666777777777777777

Number of Days on Study 2615699246112333333333333

3215645341787444444444444

2222222222222222222222222

Carcass ID Number 4110434240431000111122222

2803567765001124234512345

+: Tissue examined microscopically M: Missing tissue X: Lesion present

A: Autolysis precludes examination I: Insufficient tissue Blank: Not examined
Sodium Chlorate, NTP TR 517 109

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 50

Leiomyosarcoma X 1

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 49

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 49

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Mesentery + + + + + + 18

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50

Acinus, adenoma X 2

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pheochromocytoma benign X X 2

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X X 2

Carcinoma X 1

Parathyroid gland + + + + + + + + + M + + + + + + + + + + + + + + + 47

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Pars distalis, adenoma X X X X X X X X X X 23

Pars distalis, carcinoma 1

Pars intermedia, adenoma X 1

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 47

Bilateral, C-cell, adenoma X 1

C-cell, adenoma X X X X X X 11

C-cell, carcinoma 1

Follicular cell, carcinoma X 1

General Body System 

Tissue NOS 1

Genital System 

Clitoral gland + + + + M + + + + + + + + + + + + + + + + + + + + 49

Adenoma X X X X X X X 11

Carcinoma XX 3

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50

Granulosa cell tumor benign 1

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

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 3333333333333333333333333

4444445556666666677777777

2222222222222222222222222 Total

Carcass ID Number 3334452220000111233333444 Tissues/

7898906896789679012345134 Tumors
110 Sodium Chlorate, NTP TR 517 

Genital System (continued)

Uterus +++++++++++++++++++++++++

Sarcoma stromal

Endometrium, polyp stromal X X

Endometrium, polyp stromal, multiple X

Vagina + + + +

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++

Lymph node + + ++++ +++++ +++++ ++

Lymph node, mandibular MMMMMM + MMMMMMMMMMMMMMMMMM

Lymph node, mesenteric +++++++++++++++++++++++++

Spleen +++++++++++++++++++++++++

Thymus + + + + + + + + + + + + + + + + + +M+ + + + + +

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Adenoma X

Carcinoma X X

Carcinoma, multiple X

Fibroadenoma X X X X XXXX X

Fibroadenoma, multiple X XXXX X

Skin +++++++++++++++++++++++++

Basal cell carcinoma X

Trichoepithelioma X

Pinna, neural crest tumor X

Subcutaneous tissue, fibroma X

Subcutaneous tissue, lipoma

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Nervous System 

Brain + + + + + + + + + +M+ + + + + + + + + + + + + +

Peripheral nerve +

Spinal cord +

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar carcinoma

Carcinoma, metastatic, mammary gland X

Nose +++++++++++++++++++++++++

Trachea +++++++++++++++++++++++++

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + +

Harderian gland +++++++++++++++++++++++++

Zymbal’s gland +

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

4455555666777777777777777

Number of Days on Study 2615699246112333333333333

3215645341787444444444444

2222222222222222222222222

Carcass ID Number 4110434240431000111122222

2803567765001124234512345
Sodium Chlorate, NTP TR 517 111

Genital System (continued)

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Sarcoma stromal X 1

Endometrium, polyp stromal X X X X X X 8

Endometrium, polyp stromal, multiple 1

Vagina + + 6

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50

Lymph node + + + + + + + + + + + + + + + + + + 36

Lymph node, mandibular MMMMM + MMMMMMMM + MMMMM + MMMM 4

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 49

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma XX 3

Carcinoma 2

Carcinoma, multiple 1

Fibroadenoma XXXXX XXX X X X X X X 23

Fibroadenoma, multiple X X X X 10

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Basal cell carcinoma 1

Trichoepithelioma X 2

Pinna, neural crest tumor 1

Subcutaneous tissue, fibroma X X X 4

Subcutaneous tissue, lipoma X 1

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 49

Peripheral nerve 1

Spinal cord 1

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X 1

Alveolar/bronchiolar carcinoma X 1

Carcinoma, metastatic, mammary gland 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 50

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Zymbal’s gland 1

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

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 3333333333333333333333333

4444445556666666677777777

2222222222222222222222222 Total

Carcass ID Number 3334452220000111233333444 Tissues/

7898906896789679012345134 Tumors
112 Sodium Chlorate, NTP TR 517 

Urinary System 

Kidney +++++++++++++++++++++++++

Urinary bladder +++++++++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Leukemia mononuclear X X X X X X X X

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

4455555666777777777777777

Number of Days on Study 2615699246112333333333333

3215645341787444444444444

2222222222222222222222222

Carcass ID Number 4110434240431000111122222

2803567765001124234512345
Sodium Chlorate, NTP TR 517 113

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Leukemia mononuclear X X X 11

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

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 3333333333333333333333333

4444445556666666677777777

2222222222222222222222222 Total

Carcass ID Number 3334452220000111233333444 Tissues/

7898906896789679012345134 Tumors
114 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Intestine large, colon +++++A+++A+++++++++++++++

Intestine large, rectum +++++++++++++++++++++++++

Intestine large, cecum +++++A+++A+++++++++++++++

Intestine small, duodenum +++++++++A+++++++++++++++

Intestine small, jejunum + + + + +AA+ +A+ + + + + + + + + + + + + + +

Leiomyoma X

Intestine small, ileum +++++A+++A+++++++++++++++

Liver +++++++++++++++++++++++++

Cholangiocarcinoma X

Histiocytic sarcoma X

Histiocytic sarcoma, metastatic, skeletal muscle

Mesentery + + + + + + +

Pancreas +++++++++A+++++++++++++++

Salivary glands +++++++++++++++++++++++++

Stomach, forestomach +++++++++++++++++++++++++

Stomach, glandular +++++++++A+++++++++++++++

Tooth + +

Odontoma X

Cardiovascular System 

Blood vessel +

Heart +++++++++++++++++++++++++

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++

Adrenal medulla +++++++++++++++++++++++++

Pheochromocytoma malignant X

Pheochromocytoma benign

Islets, pancreatic +++++++++A+++++++++++++++

Adenoma

Carcinoma

Parathyroid gland + + + + + + + + + + + + + + + + +M+ + + + + + +

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + +

Pars distalis, adenoma X X X X X X X

Pars distalis, carcinoma X X

Pars intermedia, adenoma

Thyroid gland + + + + +AA+ +A+ + + + + + + + + + + + + + +

Bilateral, C-cell, adenoma

C-cell, adenoma X X X X

C-cell, carcinoma X X

General Body System 

Tissue NOS +

Mediastinum, carcinoma, metastatic,

thyroid gland X

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

3445556666667777777777777

Number of Days on Study 6231462233451233333333333

5331133669474734444444455

2222222222222222222222222

Carcass ID Number 6987858598567755556666966

5066781452201871351234967
Sodium Chlorate, NTP TR 517 115

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 48

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 49

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Leiomyoma 1

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 48

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Cholangiocarcinoma 1

Histiocytic sarcoma 1

Histiocytic sarcoma, metastatic, skeletal muscle X 1

Mesentery + + + 10

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49

Tooth 2

Odontoma 1

Cardiovascular System 

Blood vessel 1

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pheochromocytoma malignant 1

Pheochromocytoma benign X 1

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49

Adenoma X 1

Carcinoma X 1

Parathyroid gland + + + + M + + + + + + + + + + + + + + + + + M + + 47

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Pars distalis, adenoma X X X X X X X X X X X 18

Pars distalis, carcinoma X 3

Pars intermedia, adenoma X 1

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 47

Bilateral, C-cell, adenoma X X 2

C-cell, adenoma X X X X 8

C-cell, carcinoma X 3

General Body System 

Tissue NOS + 2

Mediastinum, carcinoma, metastatic,

thyroid gland 1

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5555555556666666666667777

2222222222222222222222223 Total

Carcass ID Number 6678899995577777788889990 Tissues/

8908912346923457903456780 Tumors
116 Sodium Chlorate, NTP TR 517 

Genital System 

Clitoral gland +++++++++++++++++++++++++

Adenoma X X

Carcinoma X

Ovary +++++++++++++++++++++++++

Uterus +++++++++++++++++++++++++

Endometrium, polyp stromal X X

Vagina + +

Hematopoietic System 

Bone marrow +++++++++A+++++++++++++++

Lymph node ++++ + ++ +++++ +++++++

Lymph node, mandibular MMMMMMM + MMMMMMM + + MMMMMMMM

Lymph node, mesenteric +++++++++A+++++++++++++++

Spleen +++++++++++++++++++++++++

Thymus + + + + + + + + +A+ + + + + + + + + + + +M+ +

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Carcinoma X

Fibroadenoma X X X X X XXXXX X

Fibroadenoma, multiple X

Histiocytic sarcoma, metastatic,

skeletal muscle

Skin +++++++++++++++++++++++++

Subcutaneous tissue, carcinoma, metastatic,

mammary gland X

Subcutaneous tissue, fibroma X

Subcutaneous tissue, fibrosarcoma X

Subcutaneous tissue, histiocytic sarcoma X

Subcutaneous tissue, histiocytic sarcoma,

metastatic, skeletal muscle

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Osteosarcoma X

Skeletal muscle

Histiocytic sarcoma

Rhabdomyosarcoma

Nervous System 

Brain +++++++++++++++++++++++++

Carcinoma, metastatic, pituitary gland X

Peripheral nerve + +

Spinal cord + +

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

3445556666667777777777777

Number of Days on Study 6231462233451233333333333

5331133669474734444444455

2222222222222222222222222

Carcass ID Number 6987858598567755556666966

5066781452201871351234967
Sodium Chlorate, NTP TR 517 117

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X X X 5

Carcinoma 1

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Endometrium, polyp stromal X X X X X X 8

Vagina + 3

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 49

Lymph node + + + + + +++ + + + + + + + 34

Lymph node, mandibular M M + MMMMMMMM + MMMMMMMMMM + MM 6

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 49

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 48

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Carcinoma 1

Fibroadenoma X X X X X X X X X X X X X X X 26

Fibroadenoma, multiple XX 3

Histiocytic sarcoma, metastatic,

skeletal muscle X 1

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Subcutaneous tissue, carcinoma, metastatic,

mammary gland 1

Subcutaneous tissue, fibroma 1

Subcutaneous tissue, fibrosarcoma 1

Subcutaneous tissue, histiocytic sarcoma 1

Subcutaneous tissue, histiocytic sarcoma,

metastatic, skeletal muscle X 1

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Osteosarcoma 1

Skeletal muscle + +2

Histiocytic sarcoma X 1

Rhabdomyosarcoma X 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Carcinoma, metastatic, pituitary gland X 2

Peripheral nerve + 3

Spinal cord + 3

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5555555556666666666667777

2222222222222222222222223 Total

Carcass ID Number 6678899995577777788889990 Tissues/

8908912346923457903456780 Tumors
118 Sodium Chlorate, NTP TR 517 

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma

Histiocytic sarcoma X

Histiocytic sarcoma, metastatic,

skeletal muscle

Nose +++++++++++++++++++++++++

Trachea +++++++++++++++++++++++++

Special Senses System 

Eye + + + + + + + + + A + + + + + + + + + + + + + + +

Harderian gland +++++++++++++++++++++++++

Histiocytic sarcoma X

Urinary System 

Kidney +++++++++A+++++++++++++++

Urinary bladder +++++++++A+++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Histiocytic sarcoma X

Leukemia mononuclear X X X X

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

3445556666667777777777777

Number of Days on Study 6231462233451233333333333

5331133669474734444444455

2222222222222222222222222

Carcass ID Number 6987858598567755556666966

5066781452201871351234967
Sodium Chlorate, NTP TR 517 119

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X 1

Histiocytic sarcoma 1

Histiocytic sarcoma, metastatic,

skeletal muscle X 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 49

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 1

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49

Urinary bladder + + + + + + + + M + + + + + + + + + + + + + + + + 48

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma X 2

Leukemia mononuclear X X X X X 9

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate: 125 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5555555556666666666667777

2222222222222222222222223 Total

Carcass ID Number 6678899995577777788889990 Tissues/

8908912346923457903456780 Tumors
120 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Intestine large, colon + + + A + + + A A +++++A++++++++++

Intestine large, rectum + + + A + + + A A +++++A++++++++++

Intestine large, cecum + + + A A + + A A +++++A+++A++++++

Intestine small, duodenum + + + A + + + A A +++++A+++A++++++

Intestine small, jejunum + + + A A + + A A +++++A+++A++++++

Intestine small, ileum + + + A A + + A A +++++A+++A++++++

Liver +++++++++++++++++++++++++

Mesentery + + +++++ + +

Oral mucosa +

Pancreas ++++++++++++++++++A++++++

Salivary glands +++++++++++++++++++++++++

Stomach, forestomach +++++++++++++++++++++++++

Stomach, glandular + + + + A + + + + + + + + + + + + + + + + + + + +

Tooth + +

Cardiovascular System 

Heart +++++++++++++++++++++++++

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++

Adrenal medulla +++++++++++++++++++++++++

Pheochromocytoma benign

Islets, pancreatic ++++++++++++++++++A++++++

Parathyroid gland + + + + + + + + + + + + + + + + + +M+ + + + + +

Pituitary gland +++++++++++++++++++++++++

Pars distalis, adenoma X X X X X X X X X

Thyroid gland + + A A A + + A A +++++A+++A++++++

C-cell, adenoma XXXX

C-cell, carcinoma X

Follicular cell, carcinoma X

General Body System 

Tissue NOS + + + +

Mediastinum, carcinoma, metastatic,

Zymbal’s gland X

Mediastinum, histiocytic sarcoma X

Genital System 

Clitoral gland +++++++++++++++++++++++++

Adenoma X X X X X X X

Ovary ++++++++++++++++++A++++++

Oviduct + +

Uterus ++++++++++++++++++++++++

Endometrium, polyp stromal X X X

Endometrium, polyp stromal, multiple X X

Vagina + +

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study

of Sodium Chlorate: 1,000 mg/L

4555555666666667777777777

Number of Days on Study 0114788112335990033333333

1147377556661993344444444

3333333333333333333333333

Carcass ID Number 5201234243002141322233334

0848451594690162867906790
Sodium Chlorate, NTP TR 517 121

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 46

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 46

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 44

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 45

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 44

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 44

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Mesentery + + + + 13

Oral mucosa 1

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49

Tooth 2

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pheochromocytoma benign X 1

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + M + + 48

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pars distalis, adenoma X X X X X X X X 17

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 43

C-cell, adenoma X X X X X X X 11

C-cell, carcinoma 1

Follicular cell, carcinoma 1

General Body System 

Tissue NOS 4

Mediastinum, carcinoma, metastatic,

Zymbal’s gland 1

Mediastinum, histiocytic sarcoma 1

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X X X X X 12

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 49

Oviduct 2

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 49

Endometrium, polyp stromal X X X X 7

Endometrium, polyp stromal, multiple 2

Vagina + 3

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate: 1,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

4444445556666666666777777

3333333333333333333333333 Total

Carcass ID Number 4444443330000111222001111 Tissues

2345781231235679123780345 Tumors
122 Sodium Chlorate, NTP TR 517 

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++

Lymph node ++++++++ ++ +++ +++ +

Mediastinal, histiocytic sarcoma X

Lymph node, mandibular M M M + MMMMMMMMMMM + MMMMMMMMM

Lymph node, mesenteric + + + + + + +M+ + + + + + + + + + + + + + + + +

Spleen +++++++++++++++++++++++++

Thymus + + + + + + + + + + +M+ + + + + +M+ + + + + +

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Fibroadenoma X X X X X X X X X X

Fibroadenoma, multiple X X X X X

Skin +++++++++++++++++++++++++

Subcutaneous tissue, fibroma X

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Skeletal muscle +

Mesothelioma malignant, metastatic, mesentery X

Nervous System 

Brain +++++++++++++++++++++++++

Peripheral nerve

Respiratory System 

Lung +++++++++++++++++++++++++

Nose +++++++++++++++++++++++++

Trachea +++++++++++++++++++++++++

Special Senses System 

Eye + + + + + + + A + + + + + + A + + + A + + + + + +

Harderian gland +++++++++++++++++++++++++

Lacrimal gland

Zymbal’s gland +

Carcinoma X

Urinary System 

Kidney ++++A+++A+++++++++A++++++

Urinary bladder +++++++++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Histiocytic sarcoma X

Leukemia mononuclear X X X X X X X X

Lymphoma malignant X

Mesothelioma malignant X

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate: 1,000 mg/L

4555555666666667777777777

Number of Days on Study 0114788112335990033333333

1147377556661993344444444

3333333333333333333333333

Carcass ID Number 5201234243002141322233334

0848451594690162867906790
Sodium Chlorate, NTP TR 517 123

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50

Lymph node + + + + + + ++ + + + + + 30

Mediastinal, histiocytic sarcoma 1

Lymph node, mandibular MMMMMMMMMMMMMMMMMMMM + M + MM 4

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 49

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 48

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Fibroadenoma X X X X X X X X X X X X X 23

Fibroadenoma, multiple X X X 8

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Subcutaneous tissue, fibroma 1

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skeletal muscle 1

Mesothelioma malignant, metastatic, mesentery 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Peripheral nerve + 1

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 47

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Lacrimal gland + 1

Zymbal’s gland 1

Carcinoma 1

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 47

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 1

Leukemia mononuclear X X X X X 13

Lymphoma malignant 1

Mesothelioma malignant 1

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate: 1,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

4444445556666666666777777

3333333333333333333333333 Total

Carcass ID Number 4444443330000111222001111 Tissues

2345781231235679123780345 Tumors
124 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Intestine large, colon +++++++A+++++++++++++++++

Intestine large, rectum + + A + + + A A +++++++++A+++++++

Intestine large, cecum + + + + + +AA+ + + + + + + + +A+ + + + + + +

Intestine small, duodenum ++++++A++++++++++++++++++

Intestine small, jejunum + + A + A + A A +++++++++A+++++++

Intestine small, ileum + + A + + + A A +++++++++++++++++

Liver +++++++++++++++++++++++++

Mesentery + + + + + + + +

Carcinoma X

Oral mucosa +

Squamous cell carcinoma X

Pancreas + + A ++++++++++++++++++++++

Salivary glands +++++++++++++++++++++++++

Stomach, forestomach +++++++++++++++++++++++++

Stomach, glandular +++++++++++++++++++++++++

Tooth +

Cardiovascular System 

Blood vessel

Heart +++++++++++++++++++++++++

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++

Adrenal medulla +++++++++++++++++++++++++

Pheochromocytoma malignant X

Pheochromocytoma complex

Pheochromocytoma benign X

Islets, pancreatic +++++++++++++++++++++++++

Carcinoma X

Parathyroid gland + + + + + + + + + + + + +M+M+ + + + + + + + +

Pituitary gland +++++++++++++++++++++++++

Pars distalis, adenoma X X X X X X X X X X X X X X

Pars distalis, adenoma, multiple X

Pars intermedia, adenoma

Thyroid gland + + A + + + A A +++++++++A+++++++

C-cell, adenoma X X X

C-cell, carcinoma X

Follicular cell, adenoma X X

Follicular cell, carcinoma X

General Body System 

Tissue NOS + + + + +

Mediastinum, sarcoma X

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

4566666677777777777777777

Number of Days on Study 7433467902222222233333333

5256480339999999905555555

3333333333333333333333333

Carcass ID Number 5898696787777888995555555

1018375016789679052345678
Sodium Chlorate, NTP TR 517 125

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49

Intestine large, rectum + + + + + + + + + + + + I + + + + + + + + + + + + 45

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 49

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 45

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Mesentery + + + + + + + + 16

Carcinoma 1

Oral mucosa 1

Squamous cell carcinoma 1

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50

Tooth 1

Cardiovascular System 

Blood vessel + 1

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pheochromocytoma malignant 1

Pheochromocytoma complex X 1

Pheochromocytoma benign 1

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50

Carcinoma 1

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + M + + 47

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pars distalis, adenoma XXXX X X X X X X 24

Pars distalis, adenoma, multiple 1

Pars intermedia, adenoma X 1

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 46

C-cell, adenoma X X X X X X 9

C-cell, carcinoma X X 3

Follicular cell, adenoma 2

Follicular cell, carcinoma X 2

General Body System 

Tissue NOS + 6

Mediastinum, sarcoma 1

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5555555555566666666667777

3333333333433333333333333 Total

Carcass ID Number 5677777999066688889996666 Tissues/

9012345689012423452346789 Tumors
126 Sodium Chlorate, NTP TR 517 

Genital System 

Clitoral gland +++++++++++++++++++++++++

Adenoma X

Sarcoma X

Ovary +++++++++++++++++++++++++

Sarcoma X

Uterus +++++++++++++++++++++++++

Carcinoma, metastatic, mesentery X

Endometrium, polyp stromal X X X X X

Endometrium, sarcoma X

Vagina

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++

Lymph node +++++++++++ ++++++++ ++

Mediastinal, sarcoma X

Lymph node, mandibular MMMMMMMMMM + M + MMMM + MMMMMMM

Lymph node, mesenteric +++++++++++++++++++++++++

Spleen +++++++++++++++++++++++++

Sarcoma X

Thymus + + + + +M+ + + + + + + + + + + + + + + + + + +

Sarcoma X

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Adenoma

Carcinoma X

Fibroadenoma X X X X X X X XXXXXXX

Fibroadenoma, multiple X X

Skin +++++++++++++++++++++++++

Keratoacanthoma X

Subcutaneous tissue, fibroma X

Subcutaneous tissue, sarcoma X

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Skeletal muscle +

Nervous System 

Brain +++++++++++++++++++++++++

Respiratory System 

Lung +++++++++++++++++++++++++

Sarcoma X

Nose +++++++++++++++++++++++++

Trachea +++++++++++++++++++++++++

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

4566666677777777777777777

Number of Days on Study 7433467902222222233333333

5256480339999999905555555

3333333333333333333333333

Carcass ID Number 5898696787777888995555555

1018375016789679052345678
Sodium Chlorate, NTP TR 517 127

Genital System 

Clitoral gland + + + + + + + + + + M + + + + + + + + + + + + + + 49

Adenoma X X X 4

Sarcoma 1

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50

Sarcoma 1

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Carcinoma, metastatic, mesentery 1

Endometrium, polyp stromal X X 7

Endometrium, sarcoma 1

Vagina + 1

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50

Lymph node + + + + + + + + + + + + + + + + + + 39

Mediastinal, sarcoma 1

Lymph node, mandibular M M M + MMMMMMMMMMMM + MMMMMMMM 5

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50

Sarcoma 1

Thymus + + + + + + + + + + + + + + + + + + + + + I + + + 48

Sarcoma 1

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X X 2

Carcinoma X 2

Fibroadenoma X X X X X X X X X X X X X 27

Fibroadenoma, multiple X X X X 6

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Keratoacanthoma 1

Subcutaneous tissue, fibroma 1

Subcutaneous tissue, sarcoma 1

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skeletal muscle 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Sarcoma 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5555555555566666666667777

3333333333433333333333333 Total

Carcass ID Number 5677777999066688889996666 Tissues/

9012345689012423452346789 Tumors
128 Sodium Chlorate, NTP TR 517 

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + +

Harderian gland +++++++++++++++++++++++++

Squamous cell carcinoma, metastatic,

oral mucosa X

Lacrimal gland +

Zymbal’s gland +

Urinary System 

Kidney + + A + A ++++++++++++A+++++++

Sarcoma X

Urinary bladder +++++++++++++++++++++++++

Transitional epithelium, papilloma

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Leukemia mononuclear X X X X X X

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

4566666677777777777777777

Number of Days on Study 7433467902222222233333333

5256480339999999905555555

3333333333333333333333333

Carcass ID Number 5898696787777888995555555

1018375016789679052345678
Sodium Chlorate, NTP TR 517 129

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 50

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Squamous cell carcinoma, metastatic,

oral mucosa 1

Lacrimal gland + 2

Zymbal’s gland 1

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 47

Sarcoma 1

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50

Transitional epithelium, papilloma X 1

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Leukemia mononuclear X X X 9

TABLE B2

Individual Animal Tumor Pathology of Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5555555555566666666667777

3333333333433333333333333 Total

Carcass ID Number 5677777999066688889996666 Tissues/

9012345689012423452346789 Tumors
130 Sodium Chlorate, NTP TR 517 

TABLE B3

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Adrenal Medulla: Benign, Complex, or Malignant Pheochromocytoma 

Overall ratea 2/50 (4%) 2/50 (4%) 1/50 (2%) 3/50 (6%)

Adjusted rateb 4.5% 4.5% 2.3% 6.4%

Terminal ratec 2/37 (5%) 1/36 (3%) 1/33 (3%) 3/41 (7%)

First incidence (days) 729 (T) 541 729 (T) 729 (T)

Poly-3 testd P=0.430 P=0.690 P=0.512N P=0.522

Clitoral Gland: Adenoma

Overall rate 11/49 (22%) 5/50 (10%) 12/50 (24%) 4/49 (8%)

Adjusted rate 24.9% 11.4% 26.9% 8.7%

Terminal rate 10/36 (28%) 5/36 (14%) 8/33 (24%) 4/40 (10%)

First incidence (days) 595 729 (T) 511 729 (T)

Poly-3 test P=0.131N P=0.085N P=0.512 P=0.035N

Clitoral Gland: Carcinoma

Overall rate 3/49 (6%) 1/50 (2%) 0/50 (0%) 0/49 (0%)

Adjusted rate 6.9% 2.3% 0.0% 0.0%

Terminal rate 3/36 (8%) 1/36 (3%) 0/33 (0%) 0/40 (0%)

First incidence (days) 729 (T) 729 (T) —e —

Poly-3 test P=0.054N P=0.305N P=0.120N P=0.110N

Clitoral Gland: Adenoma or Carcinoma

Overall rate 14/49 (29%) 6/50 (12%) 12/50 (24%) 4/49 (8%)

Adjusted rate 31.7% 13.7% 26.9% 8.7%

Terminal rate 13/36 (36%) 6/36 (17%) 8/33 (24%) 4/40 (10%)

First incidence (days) 595 729 (T) 511 729 (T)

Poly-3 test P=0.036N P=0.037N P=0.395N P=0.005N

Mammary Gland: Fibroadenoma

Overall rate 33/50 (66%) 29/50 (58%) 31/50 (62%) 33/50 (66%)

Adjusted rate 69.8% 63.5% 68.7% 69.0%

Terminal rate 26/37 (70%) 25/36 (69%) 24/33 (73%) 29/41 (71%)

First incidence (days) 423 365 547 636

Poly-3 test P=0.437 P=0.333N P=0.544N P=0.557N

Mammary Gland: Adenoma

Overall rate 3/50 (6%) 0/50 (0%) 0/50 (0%) 2/50 (4%)

Adjusted rate 6.7% 0.0% 0.0% 4.3%

Terminal rate 3/37 (8%) 0/36 (0%) 0/33 (0%) 2/41 (5%)

First incidence (days) 729 (T) — — 729 (T)

Poly-3 test P=0.609 P=0.123N P=0.125N P=0.478N

Mammary Gland: Fibroadenoma or Adenoma

Overall rate 35/50 (70%) 29/50 (58%) 31/50 (62%) 34/50 (68%)

Adjusted rate 74.0% 63.5% 68.7% 71.1%

Terminal rate 28/37 (76%) 25/36 (69%) 24/33 (73%) 30/41 (73%)

First incidence (days) 423 365 547 636

Poly-3 test P=0.466 P=0.184N P=0.362N P=0.464N

Mammary Gland: Carcinoma

Overall rate 3/50 (6%) 1/50 (2%) 0/50 (0%) 2/50 (4%)

Adjusted rate 6.5% 2.3% 0.0% 4.3%

Terminal rate 0/37 (0%) 0/36 (0%) 0/33 (0%) 2/41 (5%)

First incidence (days) 462 541 — 729 (T)

Poly-3 test P=0.483N P=0.323N P=0.132N P=0.495N
Sodium Chlorate, NTP TR 517 131

Mammary Gland: Adenoma or Carcinoma

Overall rate 6/50 (12%) 1/50 (2%) 0/50 (0%) 4/50 (8%)

Adjusted rate 12.9% 2.3% 0.0% 8.5%

Terminal rate 3/37 (8%) 0/36 (0%) 0/33 (0%) 4/41 (10%)

First incidence (days) 462 541 — 729 (T)

Poly-3 test P=0.494N P=0.064N P=0.019N P=0.362N

Mammary Gland: Fibroadenoma, Adenoma, or Carcinoma

Overall rate 37/50 (74%) 30/50 (60%) 31/50 (62%) 35/50 (70%)

Adjusted rate 76.0% 64.9% 68.7% 73.2%

Terminal rate 28/37 (76%) 25/36 (69%) 24/33 (73%) 31/41 (76%)

First incidence (days) 423 365 547 636

Poly-3 test P=0.466 P=0.161N P=0.280N P=0.466N

Pancreatic Islets: Adenoma or Carcinoma

Overall rate 3/50 (6%) 2/49 (4%) 0/49 (0%) 1/50 (2%)

Adjusted rate 6.7% 4.7% 0.0% 2.1%

Terminal rate 3/37 (8%) 2/36 (6%) 0/32 (0%) 1/41 (2%)

First incidence (days) 729 (T) 729 (T) — 729 (T)

Poly-3 test P=0.153N P=0.518N P=0.129N P=0.288N

Pituitary Gland (Pars Distalis): Adenoma

Overall rate 23/49 (47%) 18/49 (37%) 17/50 (34%) 25/50 (50%)

Adjusted rate 49.9% 41.0% 36.5% 51.3%

Terminal rate 16/36 (44%) 15/36 (42%) 9/33 (27%) 20/41 (49%)

First incidence (days) 511 626 511 475

Poly-3 test P=0.367 P=0.261N P=0.134N P=0.526

Pituitary Gland (Pars Distalis): Carcinoma

Overall rate 1/49 (2%) 3/49 (6%) 0/50 (0%) 0/50 (0%)

Adjusted rate 2.3% 6.8% 0.0% 0.0%

Terminal rate 0/36 (0%) 1/36 (3%) 0/33 (0%) 0/41 (0%)

First incidence (days) 644 636 — —

Poly-3 test P=0.074N P=0.304 P=0.504N P=0.487N

Pituitary Gland (Pars Distalis): Adenoma or Carcinoma

Overall rate 24/49 (49%) 21/49 (43%) 17/50 (34%) 25/50 (50%)

Adjusted rate 51.7% 47.1% 36.5% 51.3%

Terminal rate 16/36 (44%) 16/36 (44%) 9/33 (27%) 20/41 (49%)

First incidence (days) 511 626 511 475

Poly-3 test P=0.527N P=0.409N P=0.099N P=0.566N

Skin: Trichoepithelioma or Basal Cell Carcinoma

Overall rate 3/50 (6%) 0/50 (0%) 0/50 (0%) 0/50 (0%)

Adjusted rate 6.7% 0.0% 0.0% 0.0%

Terminal rate 3/37 (8%) 0/36 (0%) 0/33 (0%) 0/41 (0%)

First incidence (days) 729 (T) — — —

Poly-3 test P=0.084N P=0.123N P=0.125N P=0.110N

Skin: Keratoacanthoma, Trichoepithelioma, or Basal Cell Carcinoma

Overall rate 3/50 (6%) 0/50 (0%) 0/50 (0%) 1/50 (2%)

Adjusted rate 6.7% 0.0% 0.0% 2.1%

Terminal rate 3/37 (8%) 0/36 (0%) 0/33 (0%) 0/41 (0%)

First incidence (days) 729 (T) — — 635

Poly-3 test P=0.337N P=0.123N P=0.125N P=0.285N

TABLE B3

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
132 Sodium Chlorate, NTP TR 517 

Skin: Fibroma

Overall rate 4/50 (8%) 1/50 (2%) 1/50 (2%) 1/50 (2%)

Adjusted rate 8.9% 2.3% 2.3% 2.1%

Terminal rate 3/37 (8%) 0/36 (0%) 1/33 (3%) 1/41 (2%)

First incidence (days) 623 714 729 (T) 729 (T)

Poly-3 test P=0.175N P=0.188N P=0.191N P=0.167N

Skin: Fibroma, Fibrosarcoma, or Sarcoma

Overall rate 4/50 (8%) 2/50 (4%) 1/50 (2%) 2/50 (4%)

Adjusted rate 8.9% 4.6% 2.3% 4.2%

Terminal rate 3/37 (8%) 0/36 (0%) 1/33 (3%) 1/41 (2%)

First incidence (days) 623 714 729 (T) 670

Poly-3 test P=0.277N P=0.351N P=0.191N P=0.316N

Thyroid Gland (C-Cell): Adenoma

Overall rate 12/47 (26%) 9/47 (19%) 11/43 (26%) 9/46 (20%)

Adjusted rate 28.0% 21.2% 28.3% 20.6%

Terminal rate 10/36 (28%) 6/36 (17%) 11/32 (34%) 9/40 (23%)

First incidence (days) 661 644 729 (T) 729 (T)

Poly-3 test P=0.368N P=0.317N P=0.585 P=0.292N

Thyroid Gland (C-Cell): Carcinoma

Overall rate 1/47 (2%) 3/47 (6%) 1/43 (2%) 3/46 (7%)

Adjusted rate 2.3% 7.1% 2.5% 6.9%

Terminal rate 1/36 (3%) 2/36 (6%) 0/32 (0%) 3/40 (8%)

First incidence (days) 729 (T) 626 587 729 (T)

Poly-3 test P=0.394 P=0.302 P=0.743 P=0.314

Thyroid Gland (C-Cell): Adenoma or Carcinoma

Overall rate 13/47 (28%) 11/47 (23%) 12/43 (28%) 12/46 (26%)

Adjusted rate 30.3% 25.7% 30.5% 27.5%

Terminal rate 11/36 (31%) 7/36 (19%) 11/32 (34%) 12/40 (30%)

First incidence (days) 661 626 587 729 (T)

Poly-3 test P=0.526N P=0.406N P=0.588 P=0.479N

Thyroid Gland (Follicular Cell): Adenoma or Carcinoma

Overall rate 1/47 (2%) 0/47 (0%) 1/43 (2%) 4/46 (9%)

Adjusted rate 2.3% 0.0% 2.6% 9.1%

Terminal rate 1/36 (3%) 0/36 (0%) 0/32 (0%) 2/40 (5%)

First incidence (days) 729 (T) — 703 644

Poly-3 test P=0.026 P=0.503N P=0.741 P=0.189

Uterus: Stromal Polyp

Overall rate 9/50 (18%) 8/50 (16%) 9/50 (18%) 7/50 (14%)

Adjusted rate 20.0% 18.2% 20.0% 14.7%

Terminal rate 8/37 (22%) 7/36 (19%) 4/33 (12%) 5/41 (12%)

First incidence (days) 644 636 514 635

Poly-3 test P=0.318N P=0.521N P=0.603 P=0.347N

Uterus: Stromal Polyp or Stromal Sarcoma

Overall rate 10/50 (20%) 8/50 (16%) 9/50 (18%) 7/50 (14%)

Adjusted rate 22.2% 18.2% 20.0% 14.7%

Terminal rate 9/37 (24%) 7/36 (19%) 4/33 (12%) 5/41 (12%)

First incidence (days) 644 636 514 635

Poly-3 test P=0.255N P=0.417N P=0.501N P=0.255N

TABLE B3

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 133

All Organs: Mononuclear Cell Leukemia

Overall rate 11/50 (22%) 9/50 (18%) 13/50 (26%) 9/50 (18%)

Adjusted rate 24.0% 20.4% 29.0% 18.8%

Terminal rate 7/37 (19%) 8/36 (22%) 7/33 (21%) 6/41 (15%)

First incidence (days) 594 623 615 636

Poly-3 test P=0.408N P=0.437N P=0.385 P=0.359N

All Organs: Benign Neoplasms

Overall rate 46/50 (92%) 42/50 (84%) 44/50 (88%) 47/50 (94%)

Adjusted rate 94.3% 88.7% 90.1% 95.1%

Terminal rate 35/37 (95%) 33/36 (92%) 29/33 (88%) 39/41 (95%)

First incidence (days) 423 365 511 475

Poly-3 test P=0.319 P=0.248N P=0.342N P=0.609

All Organs: Malignant Neoplasms

Overall rate 21/50 (42%) 22/50 (44%) 19/50 (38%) 22/50 (44%)

Adjusted rate 44.2% 47.3% 40.4% 45.5%

Terminal rate 14/37 (38%) 14/36 (39%) 8/33 (24%) 17/41 (42%)

First incidence (days) 462 541 547 635

Poly-3 test P=0.497N P=0.465 P=0.432N P=0.533

All Organs: Benign or Malignant Neoplasms

Overall rate 49/50 (98%) 48/50 (96%) 46/50 (92%) 48/50 (96%)

Adjusted rate 98.0% 97.5% 93.6% 97.1%

Terminal rate 36/37 (97%) 35/36 (97%) 30/33 (91%) 40/41 (98%)

First incidence (days) 423 365 511 475

Poly-3 test P=0.429N P=0.706N P=0.271N P=0.652N

(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, pancreatic islets, pituitary gland, and thyroid gland; for other tissues, denominator is number of animals necropsied. b Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality c Observed incidence at terminal kill d Beneath the control incidence is the P value associated with the trend test. Beneath the exposed group incidence are the P values corresponding to pairwise 

comparisons between the controls and that exposed group. The Poly-3 test accounts for the differential mortality in animals that do not reach terminal 

sacrifice. A negative trend or a lower incidence in an exposed group is indicated by N. e Not applicable; no neoplasms in animal group

TABLE B3

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
134 Sodium Chlorate, NTP TR 517 

TABLE B4

Historical Incidence of Thyroid Gland Neoplasms in Control Female F344/N Ratsa

Incidence in Controls

Follicular Cell Follicular Cell Follicular Cell

Adenoma Carcinoma Adenoma 

Study or Carcinoma

Historical Incidence in Drinking Water Controls Given NTP-2000 Diet

Dipropylene glycol 0/45 1/45 1/45

Sodium chlorate 0/47 1/47 1/47

Sodium nitrite 1/50 1/50 2/50

Overall Historical Incidence: Drinking Water Studies

Total (%) 1/142 (0.7%) 3/142 (2.1%) 4/142 (2.8%)

Mean ± standard deviation 1.0% ± 1.4% 2.1% ± 0.2% 3.1% ± 1.3%

Range 0%-2% 2% 2%-4%

Overall Historical Incidence: All Routes

Total (%) 3/1,192 (0.3%) 13/1,192 (1.1%) 16/1,192 (1.3%)

Mean ± standard deviation 0.2% ± 0.6% 1.2% ± 1.2% 1.5% ± 1.3%

Range 0%-2% 0%-4% 0%-4%

a Data as of April 19, 2004
Sodium Chlorate, NTP TR 517 135

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 10 11 11 4 

Natural deaths 3 3 6 5 

Survivors 

Died last week of study 2 1 1

Terminal sacrifice 37 34 32 40 

Animals examined microscopically 50 50 50 50 

Alimentary System

Intestine small, duodenum (50) (49) (45) (49)

Amyloid deposition 1 (2%) 

Epithelium, cyst 1 (2%) 

Liver (50) (50) (50) (50)

Angiectasis, focal 2 (4%) 

Basophilic focus 42 (84%) 44 (88%) 41 (82%) 42 (84%) 

Cholangiofibrosis 1 (2%) 1 (2%) 3 (6%) 

Clear cell focus 6 (12%) 16 (32%) 18 (36%) 10 (20%) 

Congestion 6 (12%) 2 (4%) 2 (4%) 1 (2%) 

Degeneration, cystic, focal 1 (2%) 1 (2%) 3 (6%) 

Eosinophilic focus 1 (2%) 1 (2%) 2 (4%) 

Fibrosis, focal 1 (2%) 

Hemorrhage 1 (2%) 

Hepatodiaphragmatic nodule 7 (14%) 4 (8%) 8 (16%) 3 (6%) 

Hyperplasia, focal, histiocytic 20 (40%) 19 (38%) 16 (32%) 23 (46%) 

Hyperplasia, focal, regenerative 1 (2%) 1 (2%) 

Hyperplasia, regenerative 2 (4%) 

Infarct, multiple 1 (2%) 

Infiltration cellular, focal, polymorphonuclear 1 (2%) 

Infiltration cellular, polymorphonuclear 1 (2%) 

Infiltration cellular, mixed cell 39 (78%) 38 (76%) 35 (70%) 41 (82%) 

Mixed cell focus 12 (24%) 6 (12%) 7 (14%) 8 (16%) 

Thrombosis 1 (2%) 

Bile duct, cyst 1 (2%) 

Bile duct, hyperplasia 29 (58%) 24 (48%) 34 (68%) 26 (52%) 

Capsule, cyst 1 (2%) 

Hepatocyte, karyomegaly 1 (2%) 

Hepatocyte, necrosis, focal 2 (4%) 1 (2%) 

Hepatocyte, vacuolization cytoplasmic 2 (4%) 

Hepatocyte, vacuolization cytoplasmic, diffuse 1 (2%) 2 (4%) 1 (2%) 2 (4%) 

Hepatocyte, vacuolization cytoplasmic, focal 17 (34%) 10 (20%) 10 (20%) 10 (20%) 

Hepatocyte, periportal, vacuolization cytoplasmic 2 (4%) 

Hepatocyte, periportal, centrilobular,

vacuolization cytoplasmic 1 (2%) 

Hepatocyte, centrilobular, necrosis 2 (4%) 1 (2%) 1 (2%) 2 (4%) 

Hepatocyte, centrilobular, vacuolization cytoplasmic 5 (10%) 3 (6%) 8 (16%) 3 (6%) 

Hepatocyte, midzonal, vacuolization cytoplasmic 2 (4%) 

a Number of animals examined microscopically at the site and the number of animals with lesion

TABLE B5

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of Sodium Chloratea

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
136 Sodium Chlorate, NTP TR 517 

Alimentary System (continued)

Mesentery (18) (10) (13) (16)

Inflammation, chronic, focal 1 (10%) 

Fat, necrosis 4 (22%) 2 (20%) 1 (8%) 

Fat, necrosis, focal 12 (67%) 5 (50%) 9 (69%) 13 (81%) 

Pancreas (50) (49) (49) (49)

Lipomatosis 1 (2%) 

Acinus, atrophy, diffuse 1 (2%) 

Acinus, atrophy, focal 15 (30%) 8 (16%) 9 (18%) 16 (33%) 

Duct, cyst, focal 1 (2%) 2 (4%) 4 (8%) 1 (2%) 

Duct, cyst, focal, multiple 10 (20%) 14 (29%) 11 (22%) 18 (37%) 

Duct, hyperplasia, focal 1 (2%) 

Salivary glands (50) (50) (50) (50)

Atrophy, focal 2 (4%) 

Stomach, forestomach (50) (50) (50) (50)

Edema 1 (2%) 1 (2%) 1 (2%) 

Erosion 1 (2%) 

Inflammation, chronic 2 (4%) 1 (2%) 

Inflammation, chronic, focal 1 (2%) 

Perforation 1 (2%) 

Ulcer 2 (4%) 7 (14%) 1 (2%) 

Epithelium, hyperplasia 2 (4%) 4 (8%) 6 (12%) 1 (2%) 

Stomach, glandular (50) (49) (49) (50)

Erosion 2 (4%) 2 (4%) 2 (4%) 

Erosion, focal 1 (2%) 

Inflammation, chronic 1 (2%) 

Necrosis, focal 1 (2%) 

Pigmentation, focal 1 (2%) 

Ulcer 1 (2%) 

Tooth (2) (2) (1)

Malformation 1 (50%) 

Dentine, malformation 1 (50%) 

Peridontal tissue, inflammation, chronic 1 (50%) 2 (100%)

Peridontal tissue, inflammation, chronic, focal 1 (100%)

Cardiovascular System

Blood vessel (1) (1)

Thrombosis 1 (100%)

Heart (50) (50) (50) (50)

Cardiomyopathy 4 (8%) 2 (4%) 2 (4%) 

Infiltration cellular, mixed cell 1 (2%) 1 (2%) 4 (8%) 

Thrombosis 1 (2%) 

Endocrine System

Adrenal cortex (50) (50) (50) (50)

Accessory adrenal cortical nodule 2 (4%) 3 (6%) 5 (10%) 2 (4%) 

Angiectasis 2 (4%) 1 (2%) 1 (2%) 2 (4%) 

Cytoplasmic alteration, focal 1 (2%) 2 (4%) 3 (6%) 2 (4%) 

Degeneration, cystic, focal 1 (2%) 1 (2%) 

Fibrosis, focal 1 (2%) 

Hematopoietic cell proliferation 1 (2%) 

TABLE B5

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 137

Endocrine System (continued)

Adrenal cortex (continued) (50) (50) (50) (50)

Hemorrhage 1 (2%) 1 (2%) 2 (4%) 

Infiltration cellular, mixed cell 1 (2%) 

Necrosis, focal 1 (2%) 

Vacuolization cytoplasmic, focal 7 (14%) 13 (26%) 7 (14%) 8 (16%) 

Adrenal medulla (50) (50) (50) (50)

Angiectasis 1 (2%) 

Hyperplasia, focal 3 (6%) 4 (8%) 1 (2%) 1 (2%) 

Infiltration cellular, focal, lymphoid 1 (2%) 

Islets, pancreatic (50) (49) (49) (50)

Hyperplasia, focal 1 (2%) 

Parathyroid gland (47) (47) (48) (47)

Hyperplasia, focal 1 (2%) 

Pituitary gland (49) (49) (50) (50)

Angiectasis 10 (20%) 6 (12%) 2 (4%) 13 (26%) 

Pigmentation, focal 1 (2%) 

Pars distalis, angiectasis 1 (2%) 2 (4%) 2 (4%) 

Pars distalis, cyst 2 (4%) 2 (4%) 1 (2%) 2 (4%) 

Pars distalis, cytoplasmic alteration, focal 3 (6%) 1 (2%) 2 (4%) 3 (6%) 

Pars distalis, degeneration, cystic, focal 11 (22%) 14 (29%) 11 (22%) 3 (6%) 

Pars distalis, hemorrhage, focal 9 (18%) 6 (12%) 10 (20%) 2 (4%) 

Pars distalis, hyperplasia, focal 7 (14%) 5 (10%) 10 (20%) 4 (8%) 

Pars distalis, infiltration cellular, focal 1 (2%) 

Pars nervosa, hyperplasia, atypical, focal 1 (2%) 

Rathke’s cleft, cyst 1 (2%) 2 (4%) 

Rathke’s cleft, hemorrhage 1 (2%) 2 (4%) 2 (4%) 6 (12%) 

Rathke’s cleft, hyperplasia, cystic 1 (2%) 

Thyroid gland (47) (47) (43) (46)

Congestion 1 (2%) 

Ultimobranchial cyst 1 (2%) 1 (2%) 

C-cell, hyperplasia 43 (91%) 45 (96%) 43 (100%) 44 (96%) 

Follicle, mineralization, focal 25 (53%) 26 (55%) 40 (93%) 44 (96%) 

Follicular cell, hyperplasia, cystic, focal 1 (2%) 

Follicular cell, hypertrophy 3 (6%) 7 (15%) 27 (63%) 42 (91%) 

General Body System

Tissue NOS (1) (2) (4) (6)

Mediastinum, cyst 1 (25%) 

Mediastinum, thrombosis 1 (17%) 

Oral, foreign body, focal 1 (17%) 

Oral, necrosis, focal 1 (17%) 

Genital System

Clitoral gland (49) (50) (50) (49)

Cyst 1 (2%) 

Degeneration, cystic 5 (10%) 2 (4%) 6 (12%) 1 (2%) 

Hyperplasia 1 (2%) 

Hyperplasia, cystic 1 (2%) 4 (8%) 3 (6%) 1 (2%) 

Hyperplasia, cystic, focal 1 (2%) 

Inflammation, chronic 6 (12%) 2 (4%) 1 (2%) 3 (6%) 

Duct, inflammation, chronic 1 (2%) 

TABLE B5

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
138 Sodium Chlorate, NTP TR 517 

Genital System (continued)

Ovary (50) (50) (49) (50)

Cyst 5 (10%) 1 (2%) 1 (2%) 4 (8%) 

Corpus luteum, hyperplasia 1 (2%) 

Interstitial cell, hyperplasia 1 (2%) 1 (2%) 

Periovarian tissue, cyst 4 (8%) 4 (8%) 2 (4%) 1 (2%) 

Uterus (50) (50) (49) (50)

Hemorrhage 1 (2%) 1 (2%) 

Hydrometra 1 (2%) 

Inflammation, chronic 1 (2%) 

Inflammation, focal, suppurative 1 (2%) 

Inflammation, suppurative 1 (2%) 1 (2%) 

Ulcer, chronic active 1 (2%) 

Endometrium, hyperplasia, cystic 16 (32%) 7 (14%) 16 (33%) 11 (22%) 

Vagina (6) (3) (3) (1)

Cyst 2 (33%) 1 (33%) 1 (33%) 1 (100%)

Inflammation, chronic 1 (17%) 

Inflammation, suppurative 1 (33%) 1 (33%) 

Hematopoietic System

Bone marrow (50) (49) (50) (50)

Angiectasis 1 (2%) 

Hemorrhage 1 (2%) 

Hyperplasia 2 (4%) 1 (2%) 1 (2%) 

Hyperplasia, focal, histiocytic 2 (4%) 2 (4%) 

Myeloid cell, hyperplasia 7 (14%) 3 (6%) 2 (4%) 6 (12%) 

Myeloid cell, erythroid cell, hyperplasia 2 (4%) 2 (4%) 3 (6%) 

Lymph node (36) (34) (30) (39)

Hyperplasia, plasma cell 1 (3%) 

Pigmentation 1 (3%) 

Deep cervical, hemorrhage 1 (3%) 

Deep cervical, hyperplasia, lymphoid 1 (3%) 

Deep cervical, hyperplasia, plasma cell 1 (3%) 

Mediastinal, angiectasis 1 (3%) 

Mediastinal, congestion 1 (3%) 

Mediastinal, ectasia 2 (6%) 4 (12%) 2 (7%) 4 (10%) 

Mediastinal, hemorrhage 6 (17%) 6 (18%) 5 (17%) 3 (8%) 

Mediastinal, hyperplasia, histiocytic 1 (3%) 4 (12%) 2 (7%) 3 (8%) 

Mediastinal, hyperplasia, lymphoid 1 (3%) 2 (6%) 2 (7%) 3 (8%) 

Mediastinal, hyperplasia, plasma cell 1 (3%) 

Mediastinal, infiltration cellular, mixed cell 1 (3%) 

Mediastinal, pigmentation 1 (3%) 

Pancreatic, angiectasis 1 (3%) 

Pancreatic, ectasia 1 (3%) 1 (3%) 

Pancreatic, hemorrhage 5 (14%) 3 (9%) 5 (13%) 

Pancreatic, hyperplasia, histiocytic 31 (86%) 22 (65%) 15 (50%) 25 (64%) 

Pancreatic, hyperplasia, lymphoid 1 (3%) 

Pancreatic, pigmentation 1 (3%) 7 (21%) 3 (10%) 6 (15%) 

Lymph node, mandibular (4) (6) (4) (5)

Ectasia 1 (17%) 

TABLE B5

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 139

Hematopoietic System (continued)

Lymph node, mesenteric (50) (49) (49) (50)

Hemorrhage 1 (2%) 

Hyperplasia, focal, histiocytic 1 (2%) 

Hyperplasia, histiocytic 2 (4%) 4 (8%) 4 (8%) 

Hyperplasia, lymphoid 1 (2%) 

Spleen (50) (50) (50) (50)

Angiectasis, focal 1 (2%) 1 (2%) 

Fibrosis, focal 1 (2%) 1 (2%) 

Hematopoietic cell proliferation 16 (32%) 21 (42%) 8 (16%) 17 (34%) 

Hemorrhage 1 (2%) 1 (2%) 1 (2%) 2 (4%) 

Hyperplasia, focal, histiocytic 2 (4%) 4 (8%) 2 (4%) 5 (10%) 

Infarct 1 (2%) 

Pigmentation, focal 1 (2%) 

Red pulp, fibrosis, diffuse 1 (2%) 

Thymus (49) (48) (48) (48)

Angiectasis 2 (4%) 1 (2%) 

Cyst 1 (2%) 

Hemorrhage 1 (2%) 2 (4%) 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 1 (2%) 

Integumentary System

Mammary gland (50) (50) (50) (50)

Dilatation 37 (74%) 39 (78%) 34 (68%) 38 (76%) 

Ectasia 4 (8%) 1 (2%) 3 (6%) 2 (4%) 

Fibrosis 2 (4%) 1 (2%) 1 (2%) 4 (8%) 

Fibrosis, focal 1 (2%) 

Hyperplasia 7 (14%) 11 (22%) 10 (20%) 9 (18%) 

Hyperplasia, focal 1 (2%) 1 (2%) 

Inflammation, chronic 1 (2%) 

Skin (50) (50) (50) (50)

Inflammation, chronic, focal 1 (2%) 

Ulcer 1 (2%) 

Subcutaneous tissue, fibrosis, focal 1 (2%) 

Musculoskeletal System

None

Nervous System

Brain (49) (50) (50) (50)

Compression, focal 9 (18%) 9 (18%) 10 (20%) 9 (18%) 

Hemorrhage, focal 4 (8%) 3 (6%) 2 (4%) 

Necrosis, focal 1 (2%) 

Thalamus, mineralization, focal 1 (2%) 

Thalamus, necrosis, focal 1 (2%) 

TABLE B5

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
140 Sodium Chlorate, NTP TR 517 

Respiratory System

Lung (50) (50) (50) (50)

Congestion 2 (4%) 1 (2%) 

Hemorrhage, focal 1 (2%) 1 (2%) 2 (4%) 

Hyperplasia, focal, histiocytic 1 (2%) 1 (2%) 2 (4%) 

Hyperplasia, histiocytic 4 (8%) 6 (12%) 5 (10%) 2 (4%) 

Infiltration cellular, polymorphonuclear 1 (2%) 

Infiltration cellular, mixed cell 2 (4%) 3 (6%) 2 (4%) 1 (2%) 

Inflammation, chronic, focal 2 (4%) 4 (8%) 2 (4%) 

Metaplasia, focal, osseous 1 (2%) 

Alveolar epithelium, hyperplasia 1 (2%) 

Alveolar epithelium, hyperplasia, focal 4 (8%) 2 (4%) 3 (6%) 2 (4%) 

Interstitium, edema 1 (2%) 

Mediastinum, edema 1 (2%) 

Peribronchiolar, hyperplasia, lymphoid 1 (2%) 

Nose (50) (50) (50) (50)

Inflammation, suppurative 1 (2%) 2 (4%) 

Nasolacrimal duct, inflammation 1 (2%) 1 (2%) 

Respiratory epithelium, metaplasia, focal, squamous 1 (2%) 

Special Senses System

Eye (50) (49) (47) (50)

Atrophy 1 (2%) 

Cataract 2 (4%) 3 (6%) 1 (2%) 2 (4%) 

Hemorrhage 1 (2%) 

Retinal detachment 1 (2%) 

Bilateral, atrophy 1 (2%) 

Cornea, inflammation, chronic 1 (2%) 1 (2%) 

Cornea, necrosis, focal 1 (2%) 

Retina, degeneration 1 (2%) 2 (4%) 1 (2%) 2 (4%) 

Harderian gland (50) (50) (50) (50)

Hyperplasia, cystic, focal 1 (2%) 

Hyperplasia, focal 1 (2%) 

Hyperplasia, focal, histiocytic 2 (4%) 1 (2%) 

Inflammation, chronic, focal 1 (2%) 1 (2%) 2 (4%) 

Metaplasia, focal, squamous 1 (2%) 

Epithelium, hyperplasia, focal 1 (2%) 

Urinary System

Kidney (50) (49) (47) (47)

Atrophy, diffuse 1 (2%) 

Atrophy, focal 1 (2%) 2 (4%) 

Cyst 1 (2%) 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 

Infarct 1 (2%) 1 (2%) 

Infiltration cellular, polymorphonuclear 1 (2%) 

Inflammation, chronic 1 (2%) 2 (4%) 

Inflammation, chronic, focal, granulomatous 1 (2%) 

Nephropathy 43 (86%) 41 (84%) 37 (79%) 38 (81%) 

Pelvis, inflammation, chronic 1 (2%) 

Pelvis, transitional epithelium, hyperplasia 1 (2%) 

Renal tubule, accumulation, hyaline droplet 5 (10%) 12 (24%) 11 (23%) 5 (11%) 

Renal tubule, pigmentation 2 (4%) 1 (2%) 4 (9%) 4 (9%) 

TABLE B5

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L
141

APPENDIX C

SUMMARY OF LESIONS IN MALE MICE

IN THE 2-YEAR DRINKING WATER STUDY

OF SODIUM CHLORATE

TABLE C1 Summary of the Incidence of Neoplasms in Male Mice

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142

TABLE C2 Individual Animal Tumor Pathology of Male Mice

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146

TABLE C3 Statistical Analysis of Primary Neoplasms in Male Mice

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168

TABLE C4 Summary of the Incidence of Nonneoplastic Lesions in Male Mice

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
142 Sodium Chlorate, NTP TR 517 

TABLE C1

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Drinking Water Study of Sodium Chloratea

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 5 5 4 10 

Natural deaths 7 4 5 7 

Survivors 

Terminal sacrifice 38 41 41 33 

Animals examined microscopically 50 50 50 50 

Alimentary System

Intestine large, colon (48) (50) (50) (50)

Histiocytic sarcoma, metastatic, liver 1 (2%) 

Intestine large, cecum (47) (49) (49) (48)

Carcinoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Histiocytic sarcoma, metastatic, liver 1 (2%) 

Intestine small, duodenum (48) (50) (49) (49)

Adenoma 1 (2%) 

Carcinoma 1 (2%) 

Carcinoma, metastatic, islets, pancreatic 1 (2%) 

Polyp adenomatous 2 (4%) 

Intestine small, jejunum (47) (49) (50) (50)

Adenoma 1 (2%) 1 (2%) 

Carcinoma 2 (4%) 2 (4%) 2 (4%) 

Liver (48) (50) (50) (50)

Carcinoma, metastatic, islets, pancreatic 1 (2%) 

Cholangiocarcinoma 1 (2%) 1 (2%) 

Hemangioma 1 (2%) 

Hemangiosarcoma 1 (2%) 2 (4%) 1 (2%) 2 (4%) 

Hemangiosarcoma, metastatic, spleen 1 (2%) 

Hepatoblastoma 5 (10%) 3 (6%) 1 (2%) 3 (6%) 

Hepatoblastoma, multiple 1 (2%) 

Hepatocellular carcinoma 14 (29%) 13 (26%) 14 (28%) 12 (24%) 

Hepatocellular carcinoma, multiple 6 (13%) 1 (2%) 5 (10%) 1 (2%) 

Hepatocellular adenoma 16 (33%) 15 (30%) 13 (26%) 14 (28%) 

Hepatocellular adenoma, multiple 14 (29%) 17 (34%) 23 (46%) 16 (32%) 

Histiocytic sarcoma 1 (2%) 2 (4%) 2 (4%) 

Ito cell tumor malignant 1 (2%) 

Leiomyosarcoma, metastatic, mesentery 1 (2%) 

Mesentery (9) (10) (10) (8)

Cholangiocarcinoma, metastatic, liver 1 (11%) 

Hepatocellular carcinoma, metastatic, liver 1 (10%) 1 (13%) 

Histiocytic sarcoma 2 (25%) 

Histiocytic sarcoma, metastatic, liver 1 (11%) 

Ito cell tumor malignant, metastatic, liver 1 (10%) 

Leiomyosarcoma 1 (11%) 

Liposarcoma 1 (10%) 

Pancreas (48) (50) (50) (50)

Cholangiocarcinoma, metastatic, liver 1 (2%) 

Hepatocellular carcinoma, metastatic, liver 1 (2%) 1 (2%) 

Histiocytic sarcoma, metastatic, liver 1 (2%) 

Salivary glands (50) (50) (50) (50)

Histiocytic sarcoma 1 (2%) 
Sodium Chlorate, NTP TR 517 143

Alimentary System (continued)

Stomach, forestomach (49) (50) (50) (50)

Leiomyosarcoma, metastatic, mesentery 1 (2%) 

Squamous cell papilloma 2 (4%) 2 (4%) 

Stomach, glandular (48) (50) (50) (50)

Adenoma 2 (4%) 

Histiocytic sarcoma, metastatic, liver 1 (2%) 

Leiomyosarcoma, metastatic, mesentery 1 (2%) 

Cardiovascular System

Heart (50) (50) (50) (50)

Cholangiocarcinoma, metastatic, liver 1 (2%) 

Endocrine System

Adrenal cortex (50) (50) (50) (50)

Adenoma 1 (2%) 1 (2%) 1 (2%) 1 (2%) 

Hepatocellular carcinoma, metastatic, liver 1 (2%) 

Bilateral, subcapsular, adenoma 1 (2%) 

Subcapsular, adenoma 1 (2%) 3 (6%) 4 (8%) 2 (4%) 

Islets, pancreatic (48) (50) (50) (50)

Adenoma 1 (2%) 1 (2%) 

Carcinoma 1 (2%) 

Pituitary gland (47) (47) (45) (49)

Pars distalis, adenoma 1 (2%) 

General Body System

None

Genital System

Epididymis (50) (50) (50) (50)

Cholangiocarcinoma, metastatic, liver 1 (2%) 

Histiocytic sarcoma, metastatic, liver 1 (2%) 

Prostate (50) (50) (50) (50)

Seminal vesicle (50) (50) (50) (50)

Histiocytic sarcoma, metastatic, liver 1 (2%) 

Testes (50) (50) (50) (50)

Interstitial cell, adenoma 2 (4%) 

Hematopoietic System

Bone marrow (49) (50) (50) (50)

Hemangiosarcoma, metastatic, spleen 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Lymph node (3) (1) (3)

Mediastinal, carcinoma, metastatic, harderian gland 1 (33%) 

Mediastinal, hepatocellular carcinoma, metastatic, liver 1 (100%) 1 (33%) 

Mediastinal, histiocytic sarcoma, metastatic, liver 1 (33%) 

Mediastinal, leiomyosarcoma, metastatic, mesentery 1 (33%) 

Pancreatic, hepatocellular carcinoma, metastatic, liver 1 (100%)

Pancreatic, histiocytic sarcoma, metastatic, liver 1 (33%) 

Renal, hepatocellular carcinoma, metastatic, liver 1 (100%)

Renal, histiocytic sarcoma, metastatic, liver 1 (33%) 

Renal, leiomyosarcoma, metastatic, mesentery 1 (33%) 

TABLE C1

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
144 Sodium Chlorate, NTP TR 517 

Hematopoietic System (continued)

Lymph node, mandibular (49) (48) (45) (49)

Histiocytic sarcoma 1 (2%) 

Lymph node, mesenteric (47) (50) (50) (50)

Hepatocellular carcinoma, metastatic, liver 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Leiomyosarcoma, metastatic, mesentery 1 (2%) 

Spleen (48) (50) (50) (50)

Hemangiosarcoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Histiocytic sarcoma, metastatic, liver 1 (2%) 

Leiomyosarcoma, metastatic, mesentery 1 (2%) 

Thymus (43) (43) (40) (44)

Alveolar/bronchiolar carcinoma, metastatic, lung 1 (3%) 

Hepatocellular carcinoma, metastatic, liver 1 (3%) 

Leiomyosarcoma, metastatic, mesentery 1 (2%) 

Integumentary System

Skin (50) (50) (50) (50)

Subcutaneous tissue, fibrous histiocytoma 1 (2%) 

Subcutaneous tissue, lipoma 1 (2%) 

Musculoskeletal System

Bone (50) (50) (50) (50)

Carcinoma, metastatic, harderian gland 1 (2%) 

Skeletal muscle (3) (1) (3) (2)

Alveolar/bronchiolar carcinoma, metastatic, lung 2 (67%) 

Hepatocellular carcinoma, metastatic, liver 1 (50%) 

Histiocytic sarcoma, metastatic, liver 1 (33%) 

Leiomyosarcoma, metastatic, mesentery 1 (33%) 

Rhabdomyosarcoma 1 (50%) 

Nervous System

None

Respiratory System

Lung (50) (50) (50) (50)

Alveolar/bronchiolar adenoma 6 (12%) 4 (8%) 7 (14%) 6 (12%) 

Alveolar/bronchiolar carcinoma 4 (8%) 5 (10%) 6 (12%) 4 (8%) 

Alveolar/bronchiolar carcinoma, multiple 1 (2%) 

Carcinoma, metastatic, harderian gland 1 (2%) 

Carcinoma, metastatic, kidney 1 (2%) 

Hemangiosarcoma 1 (2%) 

Hepatoblastoma, metastatic, liver 1 (2%) 2 (4%) 

Hepatocellular carcinoma, metastatic, liver 9 (18%) 2 (4%) 4 (8%) 6 (12%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Histiocytic sarcoma, metastatic, liver 1 (2%) 

Leiomyosarcoma, metastatic, mesentery 1 (2%) 

TABLE C1

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 145

Special Senses System

Harderian gland (50) (50) (50) (49)

Adenoma 6 (12%) 4 (8%) 4 (8%) 6 (12%) 

Carcinoma 1 (2%) 1 (2%) 

Urinary System

Kidney (49) (50) (50) (50)

Alveolar/bronchiolar carcinoma, metastatic, lung 1 (2%) 

Hepatocellular carcinoma, metastatic, liver 1 (2%) 

Renal tubule, adenoma 1 (2%) 

Renal tubule, carcinoma 1 (2%) 

Systemic Lesions

Multiple organsb (50) (50) (50) (50)

Histiocytic sarcoma 1 (2%) 2 (4%) 3 (6%) 

Lymphoma malignant 3 (6%) 1 (2%) 3 (6%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 45 45 47 45 

Total primary neoplasms 86 76 95 87 

Total animals with benign neoplasms 34 38 37 34 

Total benign neoplasms 47 48 59 51 

Total animals with malignant neoplasms 29 22 30 27 

Total malignant neoplasms 39 28 36 36 

Total animals with metastatic neoplasms 12 5 9 8 

Total metastatic neoplasms 38 5 20 14 

a Number of animals examined microscopically at the site and the number of animals with neoplasm b Number of animals with any tissue examined microscopically c Primary neoplasms: all neoplasms except metastatic neoplasms

TABLE C1

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
146 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Gallbladder A + + + A + A M + + M M +++++++++++++

Intestine large, colon A +++++A++++++++++++++++++

Histiocytic sarcoma, metastatic, liver X

Intestine large, rectum A +++++++++++++I++++++++++

Intestine large, cecum A +++++A+++A++++++++++++++

Histiocytic sarcoma, metastatic, liver X

Intestine small, duodenum A +++++A++++++++++++++++++

Adenoma

Intestine small, jejunum A ++++A+++++A+++++++++++++

Carcinoma

Intestine small, ileum A +++++A++++++++++++++++++

Liver A +++++A++++++++++++++++++

Cholangiocarcinoma X

Hemangiosarcoma

Hepatoblastoma X X X

Hepatoblastoma, multiple

Hepatocellular carcinoma X X X X X X X

Hepatocellular carcinoma, multiple X X

Hepatocellular adenoma X X X X X X X X X

Hepatocellular adenoma, multiple X X X X X

Histiocytic sarcoma X

Leiomyosarcoma, metastatic, mesentery X

Mesentery + + + + + +

Cholangiocarcinoma, metastatic, liver X

Histiocytic sarcoma, metastatic, liver X

Leiomyosarcoma X

Pancreas A +++++A++++++++++++++++++

Cholangiocarcinoma, metastatic, liver X

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma, metastatic, liver X

Salivary glands +++++++++++++++++++++++++

Stomach, forestomach A ++++++++++++++++++++++++

Leiomyosarcoma, metastatic, mesentery X

Stomach, glandular A +++++A++++++++++++++++++

Histiocytic sarcoma, metastatic, liver X

Leiomyosarcoma, metastatic, mesentery X

Tooth +

Cardiovascular System 

Heart +++++++++++++++++++++++++

Cholangiocarcinoma, metastatic, liver X

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

3455566666667777777777777

Number of Days on Study 0866602236692222222233333

1411233581399999999900000

0000000000000000000000000

Carcass ID Number 0513122303110233444402223

7048585991088656258922372

+: Tissue examined microscopically M: Missing tissue X: Lesion present

A: Autolysis precludes examination I: Insufficient tissue Blank: Not examined
Sodium Chlorate, NTP TR 517 147

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Gallbladder + + + + + + + + + + + + + + + + + + + + + + + + + 44

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48

Histiocytic sarcoma, metastatic, liver 1

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 48

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Histiocytic sarcoma, metastatic, liver 1

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 48

Adenoma X 1

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Carcinoma X X 2

Intestine small, ileum + + + + + M + + + + + + + + + + + + + + + + + + + 47

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 48

Cholangiocarcinoma 1

Hemangiosarcoma X 1

Hepatoblastoma XX 5

Hepatoblastoma, multiple X 1

Hepatocellular carcinoma X X X X X X X 14

Hepatocellular carcinoma, multiple X X X X 6

Hepatocellular adenoma X X X X X X X 16

Hepatocellular adenoma, multiple X X X X X X X X X 14

Histiocytic sarcoma 1

Leiomyosarcoma, metastatic, mesentery 1

Mesentery + + + 9

Cholangiocarcinoma, metastatic, liver 1

Histiocytic sarcoma, metastatic, liver 1

Leiomyosarcoma 1

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 48

Cholangiocarcinoma, metastatic, liver 1

Hepatocellular carcinoma, metastatic, liver 1

Histiocytic sarcoma, metastatic, liver 1

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 49

Leiomyosarcoma, metastatic, mesentery 1

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 48

Histiocytic sarcoma, metastatic, liver 1

Leiomyosarcoma, metastatic, mesentery 1

Tooth + 2

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Cholangiocarcinoma, metastatic, liver 1

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0011111111111111111444444

0000000000000000000000000 Total

Carcass ID Number 4400000111112223344123344 Tissues/

4713456236790194706140313 Tumors
148 Sodium Chlorate, NTP TR 517 

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++

Adenoma X

Bilateral, subcapsular, adenoma X

Subcapsular, adenoma

Adrenal medulla ++++++A++++++++++++++++++

Islets, pancreatic A +++++A++++++++++++++++++

Adenoma

Parathyroid gland M + + + + MM + + + + + + + + + + + + + + + + + +

Pituitary gland + + + + + +M+ + + +M+ + + + + + + + +M+ + +

Thyroid gland I + + + + +M+ + + + + + + + + + + + + + + + + +

General Body System 

None

Genital System 

Epididymis +++++++++++++++++++++++++

Histiocytic sarcoma, metastatic, liver X

Preputial gland +++++++++++++++++++++++++

Prostate +++++++++++++++++++++++++

Seminal vesicle +++++++++++++++++++++++++

Histiocytic sarcoma, metastatic, liver X

Testes +++++++++++++++++++++++++

Hematopoietic System 

Bone marrow A ++++++++++++++++++++++++

Lymph node + + +

Mediastinal, histiocytic sarcoma,

metastatic, liver X

Mediastinal, leiomyosarcoma,

metastatic, mesentery X

Pancreatic, histiocytic sarcoma, metastatic, liver X

Renal, histiocytic sarcoma, metastatic, liver X

Renal, leiomyosarcoma, metastatic, mesentery X

Lymph node, mandibular + + + + + + + M + + + + + + + + + + + + + + + + +

Lymph node, mesenteric A + + I + + A ++++++++++++++++++

Hepatocellular carcinoma, metastatic, liver X

Leiomyosarcoma, metastatic, mesentery X

Spleen A +++++A++++++++++++++++++

Histiocytic sarcoma, metastatic, liver X

Leiomyosarcoma, metastatic, mesentery X

Thymus M + + + + + + + + MM + + + + + + + + + M + + + +

Leiomyosarcoma, metastatic, mesentery X

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

3455566666667777777777777

Number of Days on Study 0866602236692222222233333

1411233581399999999900000

0000000000000000000000000

Carcass ID Number 0513122303110233444402223

7048585991088656258922372
Sodium Chlorate, NTP TR 517 149

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma 1

Bilateral, subcapsular, adenoma 1

Subcapsular, adenoma X 1

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 49

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 48

Adenoma X 1

Parathyroid gland + + + + + M + + + + + + + + + + + + + + + + + + + 46

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 47

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 48

General Body System 

None

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma, metastatic liver 1

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma, metastatic, liver 1

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 49

Lymph node 3

Mediastinal, histiocytic sarcoma,

metastatic, liver 1

Mediastinal, leiomyosarcoma,

metastatic, mesentery 1

Pancreatic, histiocytic sarcoma, metastatic, liver 1

Renal, histiocytic sarcoma, metastatic, liver 1

Renal, leiomyosarcoma, metastatic, mesentery 1

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 49

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 47

Hepatocellular carcinoma, metastatic, liver 1

Leiomyosarcoma, metastatic, mesentery 1

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 48

Histiocytic sarcoma, metastatic, liver 1

Leiomyosarcoma, metastatic, mesentery 1

Thymus M + + + + + + + M + + + + + + + + + + + + M + + + 43

Leiomyosarcoma, metastatic, mesentery 1

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0011111111111111111444444

0000000000000000000000000 Total

Carcass ID Number 4400000111112223344123344 Tissues/

4713456236790194706140313 Tumors
150 Sodium Chlorate, NTP TR 517 

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Skin +++++++++++++++++++++++++

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Skeletal muscle + +

Histiocytic sarcoma, metastatic, liver X

Leiomyosarcoma, metastatic, mesentery X

Nervous System 

Brain +++++++++++++++++++++++++

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma X X

Alveolar/bronchiolar carcinoma X X X X

Hepatoblastoma, metastatic, liver

Hepatocellular carcinoma, metastatic, liver X X X X X X X

Histiocytic sarcoma, metastatic, liver X

Leiomyosarcoma, metastatic, mesentery X

Nose +++++++++++++++++++++++++

Trachea +++++++++++++++++++++++++

Special Senses System 

Eye + + + + + + + + + M + + + + + + + + + + + + + + +

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + +

Adenoma X X X

Urinary System 

Kidney A ++++++++++++++++++++++++

Urinary bladder ++++++A++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Histiocytic sarcoma X

Lymphoma malignant X

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

3455566666667777777777777

Number of Days on Study 0866602236692222222233333

1411233581399999999900000

0000000000000000000000000

Carcass ID Number 0513122303110233444402223

7048585991088656258922372
Sodium Chlorate, NTP TR 517 151

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skeletal muscle + 3

Histiocytic sarcoma, metastatic, liver 1

Leiomyosarcoma, metastatic, mesentery 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X X X X 6

Alveolar/bronchiolar carcinoma 4

Hepatoblastoma, metastatic, liver X 1

Hepatocellular carcinoma, metastatic, liver X X 9

Histiocytic sarcoma, metastatic, liver 1

Leiomyosarcoma, metastatic, mesentery 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 49

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X X X 6

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 49

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 1

Lymphoma malignant X X 3

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0011111111111111111444444

0000000000000000000000000 Total

Carcass ID Number 4400000111112223344123344 Tissues/

4713456236790194706140313 Tumors
152 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Gallbladder + M M + M A + + + + + + + + + + + + + + +M+ I +

Intestine large, colon +++++++++++++++++++++++++

Intestine large, rectum +++++++++++++++++++++++++

Intestine large, cecum +++++++++++++++++++++++++

Intestine small, duodenum +++++++++++++++++++++++++

Intestine small, jejunum M ++++++++++++++++++++++++

Carcinoma

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + +M

Liver +++++++++++++++++++++++++

Hemangiosarcoma X X

Hepatoblastoma X X

Hepatocellular carcinoma X X X X X

Hepatocellular carcinoma, multiple

Hepatocellular adenoma X X X X

Hepatocellular adenoma, multiple X X X X X X X X X X

Ito cell tumor malignant X

Mesentery + + + +

Ito cell tumor malignant, metastatic, liver X

Pancreas +++++++++++++++++++++++++

Salivary glands +++++++++++++++++++++++++

Stomach, forestomach +++++++++++++++++++++++++

Stomach, glandular +++++++++++++++++++++++++

Adenoma X X

Tooth + +

Cardiovascular System 

Heart +++++++++++++++++++++++++

Endocrine system 

Adrenal cortex +++++++++++++++++++++++++

Adenoma

Subcapsular, adenoma X X

Adrenal medulla +++++++++++++++++++++++++

Islets, pancreatic +++++++++++++++++++++++++

Parathyroid gland + + + +M+ + + +M+ + + + + + + + + + + + + + +

Pituitary gland +++++++++++++++++++++++++

Pars distalis, adenoma

Thyroid gland +++++++++++++++++++++++++

General Body System 

None

Genital System 

Epididymis +++++++++++++++++++++++++

Preputial gland +++++++++++++++++++++++++

Prostate +++++++++++++++++++++++++

Seminal vesicle +++++++++++++++++++++++++

Testes +++++++++++++++++++++++++

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 500 mg/L

4556667777777777777777777

Number of Days on Study 3770691222222223333333333

1474883129999990000000000

0000000000000000000000000

Carcass ID Number 6899658587788995555677779

1529513923478683478456791
Sodium Chlorate, NTP TR 517 153

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Gallbladder + + + + + + + + + M + + + + + + + + + + M + I + + 41

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, cecum + + + + + + + + + + + M + + + + + + + + + + + + + 49

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 49

Carcinoma X X 2

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 49

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hemangiosarcoma 2

Hepatoblastoma X 3

Hepatocellular carcinoma X X X X X X X X 13

Hepatocellular carcinoma, multiple X 1

Hepatocellular adenoma X X X X X X X X X X X 15

Hepatocellular adenoma, multiple X X X X X X X 17

Ito cell tumor malignant 1

Mesentery + + + + + + 10

Ito cell tumor malignant, metastatic, liver 1

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma 2

Tooth + + 4

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X 1

Subcapsular, adenoma X 3

Adrenal medulla + + + + + + + + + + + + + + + + + + + M + + + + M 48

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 48

Pituitary gland + M + + + + + + M + + + + + I + + + + + + + + + + 47

Pars distalis, adenoma X 1

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

General Body System 

None

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 500 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0111111111111114444444444

1000000000000000000000000 Total

Carcass ID Number 0555666677888896667789999 Tissues/

0256026901046943782810357 Tumors
154 Sodium Chlorate, NTP TR 517 

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++

Lymph node, mandibular M + I ++++++++++++++++++++++

Lymph node, mesenteric +++++++++++++++++++++++++

Spleen +++++++++++++++++++++++++

Thymus M + + + I + + + + +M+ + + + + + + + + + +M+ +

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Skin +++++++++++++++++++++++++

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Skeletal muscle +

Nervous System 

Brain +++++++++++++++++++++++++

Peripheral nerve +

Spinal cord +

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma X

Alveolar/bronchiolar carcinoma X X

Hepatoblastoma, metastatic, liver X

Hepatocellular carcinoma, metastatic, liver X

Nose +++++++++++++++++++++++++

Trachea +++++++++++++++++++++++++

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + +

Harderian gland +++++++++++++++++++++++++

Adenoma X X

Urinary System 

Kidney +++++++++++++++++++++++++

Renal tubule, adenoma

Urinary bladder +++++++++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Lymphoma malignant

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 500 mg/L

4556667777777777777777777

Number of Days on Study 3770691222222223333333333

1474883129999990000000000

0000000000000000000000000

Carcass ID Number 6899658587788995555677779

1529513923478683478456791
Sodium Chlorate, NTP TR 517 155

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 48

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50

Thymus + + + + + + + + M + + I + + M + + + + + + + + + + 43

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skeletal muscle 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Peripheral nerve 1

Spinal cord 1

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X X X 4

Alveolar/bronchiolar carcinoma X X X 5

Hepatoblastoma, metastatic, liver X 2

Hepatocellular carcinoma, metastatic, liver X 2

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 50

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X X 4

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50

Renal tubule, adenoma X 1

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Lymphoma malignant X 1

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 500 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0111111111111114444444444

1000000000000000000000000 Total

Carcass ID Number 0555666677888896667789999 Tissues/

0256026901046943782810357 Tumors
156 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Gallbladder + + I + + + + +M+ + + + +M+ + + + + + + + + +

Intestine large, colon +++++++++++++++++++++++++

Intestine large, rectum +++++++++++++++++++++++++

Intestine large, cecum +++++A+++++++++++++++++++

Intestine small, duodenum +++++A+++++++++++++++++++

Polyp adenomatous

Intestine small, jejunum +++++++++++++++++++++++++

Adenoma

Intestine small, ileum +++++++++++++++++++++++++

Liver +++++++++++++++++++++++++

Cholangiocarcinoma X

Hemangioma X

Hemangiosarcoma X

Hemangiosarcoma, metastatic, spleen X

Hepatoblastoma X

Hepatocellular carcinoma X X X X X X X X X

Hepatocellular carcinoma, multiple X X 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

Mesentery + + + + + +

Hepatocellular carcinoma, metastatic, liver X

Liposarcoma X

Pancreas +++++++++++++++++++++++++

Hepatocellular carcinoma, metastatic, liver X

Salivary glands +++++++++++++++++++++++++

Stomach, forestomach +++++++++++++++++++++++++

Squamous cell papilloma X

Stomach, glandular +++++++++++++++++++++++++

Tooth

Cardiovascular System 

Heart +++++++++++++++++++++++++

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + +

Adenoma

Subcapsular, adenoma X

Adrenal medulla +++++++++++++++++++++++++

Islets, pancreatic +++++++++++++++++++++++++

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + +M

Pituitary gland + + M M + + + + + + + +M+ + + + + + + + + + + +

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + +M

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

5555666667777777777777777

Number of Days on Study 4567066772222222222223333

3820778239999999999990000

1111111111111111111111111

Carcass ID Number 0224132000112233344440011

9480707438266914912482503
Sodium Chlorate, NTP TR 517 157

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Gallbladder + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, rectum + + + + + I + + + + + + + + + + + + + + + + + + + 49

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 49

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 49

Polyp adenomatous X X 2

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X 1

Intestine small, ileum + + + + + + + + + + + + + + + M + + + + + + + + + 49

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Cholangiocarcinoma 1

Hemangioma 1

Hemangiosarcoma 1

Hemangiosarcoma, metastatic, spleen 1

Hepatoblastoma 1

Hepatocellular carcinoma X X X X X 14

Hepatocellular carcinoma, multiple XX 5

Hepatocellular adenoma X X X X X X 13

Hepatocellular adenoma, multiple X X X X X X X X X X X X X 23

Histiocytic sarcoma X 2

Mesentery + + + + 10

Hepatocellular carcinoma, metastatic, liver 1

Liposarcoma 1

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hepatocellular carcinoma, metastatic, liver 1

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Squamous cell papilloma X 2

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50

Tooth + 1

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X 1

Subcapsular, adenoma X X X 4

Adrenal medulla + + + + + + + + M + + + + + + + + + + + + + + + + 49

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50

Parathyroid gland + + + + + + M + + + + + + + + + + + + M + + + + + 47

Pituitary gland + + + + + + + + + + + + + + + + + + M + M + + + + 45

Thyroid gland + + + + + + M + + + + + + + + + + + + + + + + + + 48

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0000000011111111144444444

1111111111111111111111111 Total

Carcass ID Number 1223344400112334501122334 Tissues/

5032656717192579064815383 Tumors
158 Sodium Chlorate, NTP TR 517 

General Body System 

None

Genital System 

Epididymis +++++++++++++++++++++++++

Cholangiocarcinoma, metastatic, liver X

Preputial gland +++++++++++++++++++++++++

Prostate +++++++++++++++++++++++++

Seminal vesicle +++++++++++++++++++++++++

Testes +++++++++++++++++++++++++

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++

Hemangiosarcoma, metastatic, spleen X

Lymph node +

Mediastinal, hepatocellular

Carcinoma, metastatic, liver X

Pancreatic, hepatocellular carcinoma,

metastatic, liver X

Renal, hepatocellular carcinoma,

metastatic, liver X

Lymph node, mandibular + + + M ++++++++++++ MMMM +++++

Lymph node, mesenteric +++++++++++++++++++++++++

Spleen +++++++++++++++++++++++++

Hemangiosarcoma X

Histiocytic sarcoma X

Thymus + + M + + + M + + + M + + + +M+ + +M+ + + +M

Alveolar/bronchiolar carcinoma,

Metastatic, lung X

Hepatocellular carcinoma, metastatic, liver X

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Skin +++++++++++++++++++++++++

Subcutaneous tissue, fibrous

Histiocytoma

Subcutaneous tissue, lipoma

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Carcinoma, metastatic, harderian gland

Skeletal muscle + + +

Alveolar/bronchiolar carcinoma,

Metastatic, lung X X

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

5555666667777777777777777

Number of Days on Study 4567066772222222222223333

3820778239999999999990000

1111111111111111111111111

Carcass ID Number 0224132000112233344440011

9480707438266914912482503
Sodium Chlorate, NTP TR 517 159

General Body System 

None

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50

Cholangiocarcinoma, metastatic, liver 1

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hemangiosarcoma, metastatic, spleen 1

Lymph node 1

Mediastinal, hepatocellular carcinoma,

metastatic, liver 1

Pancreatic, hepatocellular carcinoma, 

metastatic, liver 1

Renal, hepatocellular carcinoma, 

metastatic, liver 1

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 45

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hemangiosarcoma 1

Histiocytic sarcoma 1

Thymus + + M + + + + + + + + + + + + M + + M + M + + + + 40

Alveolar/bronchiolar carcinoma,

metastatic, lung 1

Hepatocellular carcinoma, metastatic, liver 1

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Subcutaneous tissue, fibrous

Histiocytoma X 1

Subcutaneous tissue, lipoma X 1

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Carcinoma, metastatic, harderian gland X 1

Skeletal muscle 3

Alveolar/bronchiolar carcinoma,

metastatic, lung 2

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0000000011111111144444444

1111111111111111111111111 Total

Carcass ID Number 1223344400112334501122334 Tissues/

5032656717192579064815383 Tumors
160 Sodium Chlorate, NTP TR 517 

Nervous System 

Brain +++++++++++++++++++++++++

Peripheral nerve + +

Spinal cord + +

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma X X X

Alveolar/bronchiolar carcinoma X X X X X X

Alveolar/bronchiolar carcinoma, multiple

Carcinoma, metastatic, kidney

Hepatocellular carcinoma, metastatic, liver X X X

Histiocytic sarcoma X

Nose +++++++++++++++++++++++++

Trachea +++++++++++++++++++++++++

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + +

Harderian gland +++++++++++++++++++++++++

Adenoma X X

Carcinoma

Urinary System 

Kidney +++++++++++++++++++++++++

Alveolar/bronchiolar carcinoma,

metastatic, lung X

Hepatocellular carcinoma, metastatic, liver X

Renal tubule, carcinoma

Urethra +

Urinary bladder +++++++++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Histiocytic sarcoma X

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

5555666667777777777777777

Number of Days on Study 4567066772222222222223333

3820778239999999999990000

1111111111111111111111111

Carcass ID Number 0224132000112233344440011

9480707438266914912482503
Sodium Chlorate, NTP TR 517 161

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Peripheral nerve 2

Spinal cord 2

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X X X X 7

Alveolar/bronchiolar carcinoma 6

Alveolar/bronchiolar carcinoma, multiple X 1

Carcinoma, metastatic, kidney X 1

Hepatocellular carcinoma, metastatic, liver X 4

Histiocytic sarcoma 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 50

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X X 4

Carcinoma X 1

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar carcinoma,

metastatic, lung 1

Hepatocellular carcinoma, metastatic, liver

Renal tubule, carcinoma X 1

Urethra 1

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma X 2

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 1,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

0000000011111111144444444

1111111111111111111111111 Total

Carcass ID Number 1223344400112334501122334 Tissues/

5032656717192579064815383 Tumors
162 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Gallbladder + + + + I + + IM+ + +A+ + + + + + + + + + + +

Intestine large, colon +++++++++++++++++++++++++

Intestine large, rectum +++++++++++++++++++++++++

Intestine large, cecum +++++A++++++A++++++++++++

Carcinoma

Histiocytic sarcoma X

Intestine small, duodenum +++++I+++++++++++++++++++

Carcinoma

Carcinoma, metastatic, islets, pancreatic

Intestine small, jejunum +++++++++++++++++++++++++

Adenoma X

Carcinoma X X

Intestine small, ileum +++++A+++++++++++++++++++

Liver + + + + + + + + + + + + + + + + + + + + + + ++ +

Carcinoma, metastatic, islets, pancreatic

Hemangiosarcoma

Hepatoblastoma X

Hepatocellular carcinoma X X X X X X X X X

Hepatocellular carcinoma, multiple X

Hepatocellular adenoma X X X X X X X X X

Hepatocellular adenoma, multiple X X X X X

Histiocytic sarcoma X X

Mesentery + + + + + +

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma X

Pancreas +++++++++++++++++++++++++

Salivary glands +++++++++++++++++++++++++

Histiocytic sarcoma X

Stomach, forestomach +++++++++++++++++++++++++

Squamous cell papilloma X X

Stomach, glandular +++++++++++++++++++++++++

Tooth +

Cardiovascular System 

Blood vessel

Heart +++++++++++++++++++++++++

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++

Adenoma

Hepatocellular carcinoma, metastatic, liver X

Subcapsular, adenoma X

Adrenal medulla +++++++++++++++++++++++++

Islets, pancreatic +++++++++++++++++++++++++

Adenoma X

Carcinoma

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

2455566666666677777777777

Number of Days on Study 8637901144556911222222222

8550556800274419199999999

1111211111111111111111111

Carcass ID Number 5799066769858778556778889

6719070138244569819243570
Sodium Chlorate, NTP TR 517 163

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Gallbladder + + + + + + + + + + + + + + + + + + + + + I + + + 45

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, rectum + M + + + + + + + + + + + + + + + + + + + + + + + 49

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 48

Carcinoma X 1

Histiocytic sarcoma 1

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 49

Carcinoma X 1

Carcinoma, metastatic, islets, pancreatic X 1

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma 1

Carcinoma 2

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 49

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Carcinoma, metastatic, islets, pancreatic X 1

Hemangiosarcoma X X 2

Hepatoblastoma X X 3

Hepatocellular carcinoma X X X 12

Hepatocellular carcinoma, multiple 1

Hepatocellular adenoma X X X X X 14

Hepatocellular adenoma, multiple X X X X X X X X X X X 16

Histiocytic sarcoma 2

Mesentery ++ 8

Hepatocellular carcinoma, metastatic, liver 1

Histiocytic sarcoma X 2

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 1

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Squamous cell papilloma 2

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50

Tooth + + 3

Cardiovascular System 

Blood vessel + 1

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X 1

Hepatocellular carcinoma, metastatic, liver 1

Subcapsular, adenoma X 2

Adrenal medulla + + + + + + + + + + + + + + + + + I + + + + + + + 49

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma 1

Carcinoma X 1

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 2233333333333333333333333

9900000001111111114444444

1111111111111111111111111 Total

Carcass ID Number 9956788995666777895556689 Tissues/

2671001352246389873595864 Tumors
164 Sodium Chlorate, NTP TR 517 

Endocrine System (continued)

Parathyroid gland + + + + + + + +M+ + + + + + + + + + + + + + + +

Pituitary gland + + + + + + + + + + + + + + + + + + +M+ + + + +

Thyroid gland +++++++++++++++++++++++++

General Body System 

None

Genital System 

Epididymis +++++++++++++++++++++++++

Preputial gland +++++++++++++++++++++++++

Prostate +++++++++++++++++++++++++

Seminal vesicle +++++++++++++++++++++++++

Testes +++++++++++++++++++++++++

Interstitial cell, adenoma X

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++

Histiocytic sarcoma X

Lymph node + + +

Mediastinal, carcinoma, metastatic,

Harderian gland X

Mediastinal, hepatocellular carcinoma,

metastatic, liver X

Lymph node, mandibular + + + + + + + + + + + + + +M+ + + + + + + + + +

Histiocytic sarcoma X

Lymph node, mesenteric +++++++++++++++++++++++++

Histiocytic sarcoma X

Spleen +++++++++++++++++++++++++

Histiocytic sarcoma X

Thymus + + + + +M+ + + I + + + +M+ + + + + + + + + +

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Skin +++++++++++++++++++++++++

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Skeletal muscle + +

Hepatocellular carcinoma, metastatic, liver X

Rhabdomyosarcoma X

Nervous System 

Brain +++++++++++++++++++++++++

Peripheral nerve +

Spinal cord +

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

2455566666666677777777777

Number of Days on Study 8637901144556911222222222

8550556800274419199999999

1111211111111111111111111

Carcass ID Number 5799066769858778556778889

6719070138244569819243570
Sodium Chlorate, NTP TR 517 165

Endocrine System (continued)

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

General Body System 

None

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50

Interstitial cell, adenoma X 2

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 1

Lymph node 3

Mediastinal, carcinoma, metastatic,

Harderian gland 1

Mediastinal, hepatocellular carcinoma

metastatic, liver 1

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 49

Histiocytic sarcoma 1

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 1

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 1

Thymus + + + M + M + + + + + + + + + + + + + + + + M + + 44

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skeletal muscle 2

Hepatocellular carcinoma, metastatic, liver 1

Rhabdomyosarcoma 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Peripheral nerve 1

Spinal cord 1

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 2233333333333333333333333

9900000001111111114444444

1111111111111111111111111 Total

Carcass ID Number 9956788995666777895556689 Tissues/

2671001352246389873595864 Tumors
166 Sodium Chlorate, NTP TR 517 

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma X X X X

Alveolar/bronchiolar carcinoma X X

Carcinoma, metastatic, harderian gland X

Hemangiosarcoma

Hepatocellular carcinoma, metastatic, liver X X X X X X

Histiocytic sarcoma X

Nose +++++++++++++++++++++++++

Trachea +++++++++++++++++++++++++

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + +

Harderian gland ++++++++I++++++++++++++++

Adenoma X X X

Carcinoma X

Urinary System 

Kidney +++++++++++++++++++++++++

Urinary bladder +++++++++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Histiocytic sarcoma X X

Lymphoma malignant X

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

2455566666666677777777777

Number of Days on Study 8637901144556911222222222

8550556800274419199999999

1111211111111111111111111

Carcass ID Number 5799066769858778556778889

6719070138244569819243570
Sodium Chlorate, NTP TR 517 167

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X X 6

Alveolar/bronchiolar carcinoma X X 4

Carcinoma, metastatic, harderian gland 1

Hemangiosarcoma X 1

Hepatocellular carcinoma, metastatic, liver 6

Histiocytic sarcoma 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 50

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Adenoma X X X 6

Carcinoma 1

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma X 3

Lymphoma malignant X X 3

TABLE C2

Individual Animal Tumor Pathology of Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 2233333333333333333333333

9900000001111111114444444

1111111111111111111111111 Total

Carcass ID Number 9956788995666777895556689 Tissues/

2671001352246389873595864 Tumors
168 Sodium Chlorate, NTP TR 517 

Adrenal Cortex: Adenoma

Overall ratea 3/50 (6%) 4/50 (8%) 5/50 (10%) 3/50 (6%)

Adjusted rateb 6.7% 8.5% 10.8% 6.9%

Terminal ratec 3/38 (8%) 4/41 (10%) 5/41 (12%) 3/33 (9%)

First incidence (days) 729 (T) 729 (T) 729 (T) 729 (T)

Poly-3 testd P=0.566 P=0.532 P=0.379 P=0.654

Harderian Gland: Adenoma

Overall rate 6/50 (12%) 4/50 (8%) 4/50 (8%) 6/50 (12%)

Adjusted rate 13.2% 8.4% 8.5% 13.5%

Terminal rate 4/38 (11%) 3/41 (7%) 2/41 (5%) 3/33 (9%)

First incidence (days) 562 698 543 605

Poly-3 test P=0.478 P=0.344N P=0.345N P=0.606

Harderian Gland: Adenoma or Carcinoma

Overall rate 6/50 (12%) 4/50 (8%) 5/50 (10%) 7/50 (14%)

Adjusted rate 13.2% 8.4% 10.6% 15.6%

Terminal rate 4/38 (11%) 3/41 (7%) 3/41 (7%) 3/33 (9%)

First incidence (days) 562 698 543 595

Poly-3 test P=0.335 P=0.344N P=0.473N P=0.491

Intestine Small (Duodenum or Jejunum): Carcinoma

Overall rate 2/50 (4%) 2/50 (4%) 0/50 (0%) 3/50 (6%)

Adjusted rate 4.5% 4.2% 0.0% 6.8%

Terminal rate 2/38 (5%) 2/41 (5%) 0/41 (0%) 1/33 (3%)

First incidence (days) 729 (T) 729 (T) —e 570

Poly-3 test P=0.418 P=0.673N P=0.228N P=0.498

Intestine Small (Duodenum or Jejunum): Adenoma or Carcinoma

Overall rate 3/50 (6%) 2/50 (4%) 1/50 (2%) 4/50 (8%)

Adjusted rate 6.7% 4.2% 2.2% 9.0%

Terminal rate 3/38 (8%) 2/41 (5%) 1/41 (2%) 2/33 (6%)

First incidence (days) 729 (T) 729 (T) 729 (T) 570

Poly-3 test P=0.362 P=0.473N P=0.291N P=0.497

Liver: Hepatocellular Adenoma

Overall rate 30/48 (63%) 32/50 (64%) 36/50 (72%) 30/50 (60%)

Adjusted rate 64.5% 67.6% 74.9% 65.5%

Terminal rate 25/38 (66%) 31/41 (76%) 32/41 (78%) 24/33 (73%)

First incidence (days) 484 722 543 535

Poly-3 test P=0.478 P=0.459 P=0.184 P=0.546

Liver: Hepatocellular Carcinoma

Overall rate 20/48 (42%) 14/50 (28%) 19/50 (38%) 13/50 (26%)

Adjusted rate 43.3% 28.6% 39.2% 28.4%

Terminal rate 14/38 (37%) 10/41 (24%) 14/41 (34%) 5/33 (15%)

First incidence (days) 484 431 558 570

Poly-3 test P=0.159N P=0.099N P=0.421N P=0.100N

Liver: Hepatocellular Adenoma or Carcinoma

Overall rate 41/48 (85%) 42/50 (84%) 44/50 (88%) 40/50 (80%)

Adjusted rate 86.0% 85.8% 89.2% 84.2%

Terminal rate 32/38 (84%) 37/41 (90%) 37/41 (90%) 27/33 (82%)

First incidence (days) 484 431 543 535

Poly-3 test P=0.477N P=0.604N P=0.434 P=0.517N

TABLE C3

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 169

Liver: Hepatoblastoma

Overall rate 6/48 (13%) 3/50 (6%) 1/50 (2%) 3/50 (6%)

Adjusted rate 13.5% 6.3% 2.1% 6.8%

Terminal rate 5/38 (13%) 1/41 (2%) 0/41 (0%) 2/33 (6%)

First incidence (days) 561 577 668 719

Poly-3 test P=0.179N P=0.207N P=0.048N P=0.248N

Liver: Hepatocellular Carcinoma or Hepatoblastoma

Overall rate 23/48 (48%) 16/50 (32%) 20/50 (40%) 16/50 (32%)

Adjusted rate 49.2% 32.7% 41.0% 34.9%

Terminal rate 16/38 (42%) 11/41 (27%) 14/41 (34%) 7/33 (21%)

First incidence (days) 484 431 558 570

Poly-3 test P=0.180N P=0.074N P=0.276N P=0.117N

Liver: Hepatocellular Adenoma, Hepatocellular Carcinoma, or Hepatoblastoma

Overall rate 41/48 (85%) 43/50 (86%) 45/50 (90%) 40/50 (80%)

Adjusted rate 86.0% 87.7% 90.8% 84.2%

Terminal rate 32/38 (84%) 37/41 (90%) 37/41 (90%) 27/33 (82%)

First incidence (days) 484 431 543 535

Poly-3 test P=0.448N P=0.522 P=0.337 P=0.517N

Lung: Alveolar/bronchiolar Adenoma

Overall rate 6/50 (12%) 4/50 (8%) 7/50 (14%) 6/50 (12%)

Adjusted rate 13.5% 8.4% 14.9% 13.7%

Terminal rate 6/38 (16%) 3/41 (7%) 6/41 (15%) 4/33 (12%)

First incidence (days) 729 (T) 604 570 711

Poly-3 test P=0.423 P=0.328N P=0.540 P=0.610

Lung: Alveolar/bronchiolar Carcinoma

Overall rate 4/50 (8%) 5/50 (10%) 7/50 (14%) 4/50 (8%)

Adjusted rate 8.9% 10.6% 14.7% 9.1%

Terminal rate 2/38 (5%) 5/41 (12%) 4/41 (10%) 2/33 (6%)

First incidence (days) 638 729 (T) 543 640

Poly-3 test P=0.534 P=0.528 P=0.293 P=0.631

Lung: Alveolar/bronchiolar Adenoma or Carcinoma

Overall rate 10/50 (20%) 8/50 (16%) 13/50 (26%) 9/50 (18%)

Adjusted rate 22.1% 16.8% 27.0% 20.3%

Terminal rate 8/38 (21%) 7/41 (17%) 9/41 (22%) 5/33 (15%)

First incidence (days) 638 604 543 640

Poly-3 test P=0.505 P=0.349N P=0.383 P=0.520N

All Organs: Hemangioma or Hemangiosarcoma 

Overall rate 1/50 (2%) 2/50 (4%) 3/50 (6%) 2/50 (4%)

Adjusted rate 2.2% 4.2% 6.4% 4.6%

Terminal rate 1/38 (3%) 2/41 (5%) 2/41 (5%) 2/33 (6%)

First incidence (days) 729 (T) 729 (T) 667 729 (T)

Poly-3 test P=0.386 P=0.520 P=0.322 P=0.494

All Organs: Histiocytic Sarcoma

Overall rate 1/50 (2%) 0/50 (0%) 2/50 (4%) 3/50 (6%)

Adjusted rate 2.2% 0.0% 4.3% 6.8%

Terminal rate 0/38 (0%) 0/41 (0%) 2/41 (5%) 1/33 (3%)

First incidence (days) 661 — 729 (T) 595

Poly-3 test P=0.097 P=0.489N P=0.512 P=0.301

TABLE C3

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
170 Sodium Chlorate, NTP TR 517 

All Organs: Malignant Lymphoma 

Overall rate 3/50 (6%) 1/50 (2%) 0/50 (0%) 3/50 (6%)

Adjusted rate 6.6% 2.1% 0.0% 6.8%

Terminal rate 2/38 (5%) 1/41 (2%) 0/41 (0%) 2/33 (6%)

First incidence (days) 301 729 (T) — 616

Poly-3 test P=0.514 P=0.292N P=0.115N P=0.649

All Organs: Benign Neoplasms

Overall rate 34/50 (68%) 38/50 (76%) 37/50 (74%) 34/50 (68%)

Adjusted rate 70.7% 79.4% 76.7% 72.5%

Terminal rate 27/38 (71%) 35/41 (85%) 32/41 (78%) 24/33 (73%)

First incidence (days) 484 604 543 535

Poly-3 test P=0.528N P=0.223 P=0.330 P=0.515

All Organs: Malignant Neoplasms

Overall rate 29/50 (58%) 22/50 (44%) 30/50 (60%) 27/50 (54%)

Adjusted rate 59.1% 44.9% 60.0% 56.7%

Terminal rate 19/38 (50%) 17/41 (42%) 21/41 (51%) 14/33 (42%)

First incidence (days) 301 431 543 535

Poly-3 test P=0.435 P=0.113N P=0.544 P=0.487N

All Organs: Benign or Malignant Neoplasms

Overall rate 45/50 (90%) 45/50 (90%) 47/50 (94%) 45/50 (90%)

Adjusted rate 90.7% 91.0% 94.0% 93.1%

Terminal rate 34/38 (90%) 38/41 (93%) 38/41 (93%) 30/33 (91%)

First incidence (days) 301 431 543 535

Poly-3 test P=0.355 P=0.618 P=0.402 P=0.470

(T)Terminal sacrifice

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for adrenal gland, 

liver, and lung; for other tissues, denominator is number of animals necropsied. b Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality c Observed incidence at terminal kill d Beneath the control incidence is the P value associated with the trend test. Beneath the exposed group incidence are the P values corresponding to pairwise 

comparisons between the controls and that exposed group. The Poly-3 test accounts for the differential mortality in animals that do not reach terminal 

sacrifice. A negative trend or a lower incidence in an exposed group is indicated by N. e Not applicable; no neoplasms in animal group

TABLE C3

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 171

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 5 5 4 10 

Natural deaths 7 4 5 7 

Survivors 

Terminal sacrifice 38 41 41 33

Animals examined microscopically 50 50 50 50 

Alimentary System

Intestine large, cecum (47) (49) (49) (48)

Edema 1 (2%) 3 (6%) 4 (8%) 2 (4%) 

Inflammation, chronic 1 (2%) 1 (2%) 

Intestine small, duodenum (48) (50) (49) (49)

Ulcer 1 (2%) 1 (2%) 

Epithelium, hyperplasia 1 (2%) 1 (2%) 

Intestine small, jejunum (47) (49) (50) (50)

Epithelium, hyperplasia 2 (4%) 

Intestine small, ileum (47) (49) (49) (49)

Cyst 1 (2%) 

Liver (48) (50) (50) (50)

Angiectasis 2 (4%) 2 (4%) 

Basophilic focus 2 (4%) 3 (6%) 4 (8%) 

Clear cell focus 12 (25%) 19 (38%) 19 (38%) 13 (26%) 

Cyst 1 (2%) 1 (2%) 

Eosinophilic focus 11 (23%) 10 (20%) 5 (10%) 11 (22%) 

Hematopoietic cell proliferation 1 (2%) 4 (8%) 

Hemorrhage 1 (2%) 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 1 (2%) 

Infarct 1 (2%) 

Infiltration cellular, mixed cell 2 (4%) 1 (2%) 1 (2%) 

Mixed cell focus 2 (4%) 9 (18%) 8 (16%) 7 (14%) 

Necrosis, focal 4 (8%) 6 (12%) 7 (14%) 6 (12%) 

Regeneration, focal 1 (2%) 

Tension lipidosis 1 (2%) 1 (2%) 

Bile duct, hyperplasia 2 (4%) 

Centrilobular, necrosis 1 (2%) 2 (4%) 

Hepatocyte, karyomegaly 1 (2%) 1 (2%) 

Hepatocyte, vacuolization cytoplasmic 2 (4%) 3 (6%) 

Kupffer cell, pigmentation 2 (4%) 1 (2%) 

Mesentery (9) (10) (10) (8)

Infarct 1 (10%) 

Inflammation, chronic 1 (11%) 2 (25%) 

Fat, necrosis 3 (33%) 8 (80%) 6 (60%) 5 (63%) 

Pancreas (48) (50) (50) (50)

Cyst 2 (4%) 

Acinus, cytoplasmic alteration 1 (2%) 1 (2%) 

Salivary glands (50) (50) (50) (50)

Atrophy 1 (2%) 2 (4%) 

Hyperplasia, lymphoid 7 (14%) 3 (6%) 6 (12%) 4 (8%) 

a Number of animals examined microscopically at the site and the number of animals with lesion

TABLE C4

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Drinking Water Study 

of Sodium Chloratea

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
172 Sodium Chlorate, NTP TR 517 

Alimentary System (continued)

Stomach, forestomach (49) (50) (50) (50)

Cyst 2 (4%) 

Diverticulum 1 (2%) 1 (2%) 2 (4%) 

Erosion 1 (2%) 

Inflammation, chronic active 2 (4%) 2 (4%) 4 (8%) 2 (4%) 

Ulcer 1 (2%) 1 (2%) 2 (4%) 1 (2%) 

Epithelium, hyperplasia 3 (6%) 7 (14%) 2 (4%) 4 (8%) 

Stomach, glandular (48) (50) (50) (50)

Cyst 1 (2%) 2 (4%) 1 (2%) 

Ulcer 1 (2%) 

Tooth (2) (4) (1) (3)

Malformation 2 (100%) 4 (100%) 2 (67%) 

Cardiovascular System

Heart (50) (50) (50) (50)

Cardiomyopathy 2 (4%) 

Inflammation, chronic 2 (4%) 1 (2%) 1 (2%) 1 (2%) 

Mineralization 1 (2%) 2 (4%) 

Thrombosis 1 (2%) 1 (2%) 

Endocrine System

Adrenal cortex (50) (50) (50) (50)

Accessory adrenal cortical nodule 6 (12%) 5 (10%) 3 (6%) 5 (10%) 

Degeneration, fatty 1 (2%) 1 (2%) 2 (4%) 

Hyperplasia, focal 4 (8%) 6 (12%) 7 (14%) 9 (18%) 

Hypertrophy 1 (2%) 

Hypertrophy, focal 9 (18%) 16 (32%) 11 (22%) 11 (22%) 

Capsule, hyperplasia 5 (10%) 3 (6%) 1 (2%) 8 (16%) 

Adrenal medulla (49) (48) (49) (49)

Hyperplasia 1 (2%) 1 (2%) 1 (2%) 

Islets, pancreatic (48) (50) (50) (50)

Hyperplasia 31 (65%) 25 (50%) 28 (56%) 23 (46%) 

Parathyroid gland (46) (48) (47) (49)

Cyst 1 (2%) 2 (4%) 1 (2%) 

Pituitary gland (47) (47) (45) (49)

Pars distalis, cyst 1 (2%) 1 (2%) 2 (4%) 5 (10%) 

Pars intermedia, cyst 1 (2%) 

Thyroid gland (48) (50) (48) (50)

Degeneration, cystic 13 (27%) 17 (34%) 14 (29%) 15 (30%) 

Follicular cell, hypertrophy 2 (4%) 1 (2%) 2 (4%) 

General Body System

None

Genital System

Epididymis (50) (50) (50) (50)

Atypia cellular 1 (2%) 6 (12%) 4 (8%) 3 (6%) 

Granuloma sperm 1 (2%) 1 (2%) 

Inflammation, chronic 1 (2%) 1 (2%) 1 (2%) 

TABLE C4

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 173

Genital System (continued)

Preputial gland (50) (50) (50) (50)

Cyst 22 (44%) 26 (52%) 15 (30%) 29 (58%) 

Inflammation, chronic 28 (56%) 27 (54%) 18 (36%) 21 (42%) 

Prostate (50) (50) (50) (50)

Inflammation, chronic 1 (2%) 4 (8%) 3 (6%) 5 (10%) 

Seminal vesicle (50) (50) (50) (50)

Degeneration 1 (2%) 2 (4%) 

Dilatation 1 (2%) 

Inflammation, chronic 3 (6%) 1 (2%) 

Testes (50) (50) (50) (50)

Angiectasis 1 (2%) 1 (2%) 

Atrophy 1 (2%) 1 (2%) 1 (2%) 

Necrosis 1 (2%) 

Germinal epithelium, atrophy 1 (2%) 5 (10%) 3 (6%) 4 (8%) 

Hematopoietic System

Bone marrow (49) (50) (50) (50)

Hyperplasia 21 (43%) 12 (24%) 13 (26%) 15 (30%) 

Lymph node (3) (1) (3)

Mediastinal, hemorrhage 1 (33%) 

Lymph node, mandibular (49) (48) (45) (49)

Atrophy 1 (2%) 1 (2%) 

Hyperplasia, lymphoid 14 (29%) 14 (29%) 16 (36%) 16 (33%) 

Pigmentation 7 (14%) 10 (21%) 9 (20%) 9 (18%) 

Lymph node, mesenteric (47) (50) (50) (50)

Atrophy 2 (4%) 1 (2%) 1 (2%) 

Hematopoietic cell proliferation 2 (4%) 4 (8%) 1 (2%) 

Hemorrhage 4 (9%) 6 (12%) 2 (4%) 4 (8%) 

Hyperplasia, lymphoid 11 (23%) 6 (12%) 6 (12%) 9 (18%) 

Spleen (48) (50) (50) (50)

Depletion lymphoid 1 (2%) 

Hematopoietic cell proliferation 21 (44%) 17 (34%) 18 (36%) 21 (42%) 

Hyperplasia, lymphoid 8 (17%) 9 (18%) 10 (20%) 8 (16%) 

Pigmentation 3 (6%) 1 (2%) 1 (2%) 

Lymphoid follicle, atrophy 1 (2%) 1 (2%) 3 (6%) 

Thymus (43) (43) (40) (44)

Atrophy 11 (26%) 13 (30%) 4 (10%) 13 (30%) 

Cyst 1 (2%) 3 (7%) 4 (10%) 4 (9%) 

Hyperplasia, lymphoid 2 (5%) 1 (2%) 

Integumentary System

Skin (50) (50) (50) (50)

Cyst epithelial inclusion 1 (2%) 

Edema 3 (6%) 

Inflammation, chronic 1 (2%) 1 (2%) 

Ulcer 2 (4%) 

Epidermis, hyperplasia 1 (2%) 1 (2%) 

TABLE C4

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
174 Sodium Chlorate, NTP TR 517 

Musculoskeletal System

Bone (50) (50) (50) (50)

Fracture 1 (2%) 1 (2%) 2 (4%) 

Hyperostosis 1 (2%) 1 (2%) 

Skeletal muscle (3) (1) (3) (2)

Atrophy 1 (100%)

Infiltration cellular, lipocyte 1 (33%) 

Nervous System

Peripheral nerve (1) (2) (1)

Atrophy 1 (100%)

Respiratory System

Lung (50) (50) (50) (50)

Edema 6 (12%) 11 (22%) 7 (14%) 8 (16%) 

Foreign body 1 (2%) 1 (2%) 

Hemorrhage 5 (10%) 3 (6%) 4 (8%) 5 (10%) 

Hyperplasia, lymphoid 4 (8%) 5 (10%) 7 (14%) 6 (12%) 

Infiltration cellular, histiocyte 8 (16%) 5 (10%) 9 (18%) 10 (20%) 

Metaplasia, osseous 2 (4%) 

Alveolar epithelium, hyperplasia 2 (4%) 3 (6%) 1 (2%) 5 (10%) 

Nose (50) (50) (50) (50)

Foreign body 1 (2%) 1 (2%) 2 (4%) 

Inflammation, chronic 1 (2%) 2 (4%) 1 (2%) 5 (10%) 

Respiratory epithelium, hyperplasia 1 (2%) 1 (2%) 

Special Senses System

Eye (49) (50) (50) (50)

Cataract 1 (2%) 

Inflammation, chronic 3 (6%) 

Harderian gland (50) (50) (50) (49)

Hyperplasia, focal 1 (2%) 1 (2%) 

Inflammation, chronic 1 (2%) 3 (6%) 3 (6%) 2 (4%) 

Urinary System

Kidney (49) (50) (50) (50)

Cyst 14 (29%) 10 (20%) 9 (18%) 10 (20%) 

Hydronephrosis 1 (2%) 2 (4%) 2 (4%) 1 (2%) 

Hyperplasia, lymphoid 8 (16%) 6 (12%) 4 (8%) 11 (22%) 

Infarct 5 (10%) 1 (2%) 4 (8%) 5 (10%) 

Inflammation, chronic 1 (2%) 1 (2%) 

Metaplasia, osseous 7 (14%) 5 (10%) 3 (6%) 4 (8%) 

Nephropathy 37 (76%) 42 (84%) 43 (86%) 36 (72%) 

Renal tubule, accumulation, hyaline droplet 1 (2%) 1 (2%) 

Renal tubule, dilatation 1 (2%) 2 (4%) 3 (6%) 

Renal tubule, hyperplasia 1 (2%) 1 (2%) 1 (2%) 

Renal tubule, necrosis 1 (2%) 2 (4%) 

Renal tubule, pigmentation 2 (4%) 1 (2%) 1 (2%) 

Urethra (1)

Angiectasis 1 (100%)

TABLE C4

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 175

Urinary System (continued)

Urinary bladder (49) (50) (50) (50)

Edema 1 (2%) 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 1 (2%) 

Inflammation, chronic 1 (2%) 

Transitional epithelium, hyperplasia 2 (4%) 1 (2%) 

TABLE C4

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
176 Sodium Chlorate, NTP TR 517 
177

APPENDIX D

SUMMARY OF LESIONS IN FEMALE MICE

IN THE 2-YEAR DRINKING WATER STUDY

OF SODIUM CHLORATE

TABLE D1 Summary of the Incidence of Neoplasms in Female Mice

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178

TABLE D2 Individual Animal Tumor Pathology of Female Mice

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182

TABLE D3 Statistical Analysis of Primary Neoplasms in Female Mice

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206

TABLE D4a Historical Incidence of Pancreatic Islet Neoplasms in Control Female B6C3F1 Mice . . . . . 210

TABLE D4b Historical Incidence of Liver Neoplasms in Control Female B6C3F1 Mice . . . . . . . . . . . . . . 210

TABLE D5 Summary of the Incidence of Nonneoplastic Lesions in Female Mice

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
178 Sodium Chlorate, NTP TR 517 

TABLE D1

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Drinking Water Study of Sodium Chloratea

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L

Disposition Summary 

Animals initially in study 50 50 50 50

Early deaths 

Accidental death 1 

Moribund sacrifice 3 5 6 8 

Natural deaths 10 10 12 7 

Survivors 

Died last week of study 1 

Terminal sacrifice 36 34 31 35 

Other 1 

Animals examined microscopically 50 50 50 50 

Alimentary System

Esophagus (49) (50) (50) (50)

Gallbladder (40) (44) (44) (48)

Intestine large, cecum (44) (47) (47) (47)

Hemangioma 1 (2%) 

Intestine small, duodenum (46) (47) (47) (50)

Adenoma 1 (2%) 

Polyp adenomatous 1 (2%) 

Intestine small, jejunum (45) (47) (47) (47)

Histiocytic sarcoma 1 (2%) 

Intestine small, ileum (42) (45) (46) (47)

Liver (49) (50) (49) (50)

Hemangioma 2 (4%) 

Hemangiosarcoma 1 (2%) 2 (4%) 

Hemangiosarcoma, metastatic, spleen 1 (2%) 

Hepatoblastoma 1 (2%) 

Hepatocellular carcinoma 2 (4%) 6 (12%) 11 (22%) 6 (12%) 

Hepatocellular carcinoma, multiple 1 (2%) 7 (14%) 4 (8%) 3 (6%) 

Hepatocellular adenoma 15 (31%) 9 (18%) 14 (29%) 8 (16%) 

Hepatocellular adenoma, multiple 15 (31%) 10 (20%) 12 (24%) 15 (30%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Mesentery (30) (32) (27) (24)

Fibrosarcoma 1 (4%) 

Fibrous histiocytoma 1 (3%) 

Hemangiosarcoma 1 (4%) 

Hepatocellular carcinoma, metastatic, liver 1 (4%) 

Histiocytic sarcoma 1 (4%) 

Sarcoma, metastatic, skin 1 (4%) 

Schwannoma malignant, metastatic, skin 1 (3%) 

Oral mucosa (2) (1)

Squamous cell carcinoma 1 (50%) 

Squamous cell papilloma 1 (100%)

Pancreas (46) (47) (49) (48)

Fibrosarcoma, metastatic, mesentery 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Sarcoma, metastatic, skin 1 (2%) 

Acinus, sarcoma 1 (2%) 

Salivary glands (48) (47) (49) (50)

Hepatocellular carcinoma, metastatic, liver 1 (2%) 

Histiocytic sarcoma 1 (2%) 
Sodium Chlorate, NTP TR 517 179

Alimentary System (continued)

Stomach, forestomach (49) (50) (50) (49)

Squamous cell carcinoma 1 (2%) 1 (2%) 

Squamous cell papilloma 1 (2%) 1 (2%) 

Squamous cell papilloma, multiple 1 (2%) 

Stomach, glandular (49) (48) (50) (49)

Hepatocellular carcinoma, metastatic, liver 1 (2%) 

Tongue (2)

Cardiovascular System

Heart (49) (50) (49) (50)

Hemangiosarcoma, metastatic, spleen 1 (2%) 

Hepatocellular carcinoma, metastatic, liver 1 (2%) 

Endocrine System

Adrenal cortex (50) (49) (49) (50)

Histiocytic sarcoma 1 (2%) 

Osteosarcoma, metastatic, bone 1 (2%) 

Subcapsular, adenoma 1 (2%) 

Adrenal medulla (50) (49) (49) (50)

Pheochromocytoma malignant 2 (4%) 

Pheochromocytoma complex 1 (2%) 

Pheochromocytoma benign 1 (2%) 1 (2%) 

Islets, pancreatic (46) (47) (49) (49)

Adenoma 2 (4%) 2 (4%) 3 (6%) 

Carcinoma 1 (2%) 

Pituitary gland (46) (45) (48) (50)

Histiocytic sarcoma 1 (2%) 

Pars distalis, adenoma 3 (7%) 2 (4%) 4 (8%) 4 (8%) 

Thyroid gland (48) (50) (49) (50)

Follicular cell, adenoma 1 (2%) 

General Body System

None

Genital System

Clitoral gland (47) (47) (47) (49)

Ovary (45) (45) (47) (50)

Choriocarcinoma 2 (4%) 

Cystadenoma 1 (2%) 4 (9%) 1 (2%) 1 (2%) 

Granulosa cell tumor malignant 1 (2%) 

Granulosa cell tumor benign 1 (2%) 1 (2%) 1 (2%) 5 (10%) 

Histiocytic sarcoma 2 (4%) 1 (2%) 

Luteoma 3 (7%) 1 (2%) 

Yolk sac carcinoma 1 (2%) 

Uterus (50) (50) (50) (50)

Hemangiosarcoma 1 (2%) 

Histiocytic sarcoma 2 (4%) 1 (2%) 

Leiomyosarcoma 1 (2%) 

Polyp stromal 1 (2%) 3 (6%) 

Yolk sac carcinoma, metastatic, ovary 1 (2%) 

TABLE D1

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
180 Sodium Chlorate, NTP TR 517 

Hematopoietic System

Bone marrow (50) (50) (50) (50)

Hemangiosarcoma 1 (2%) 1 (2%) 2 (4%) 

Histiocytic sarcoma 1 (2%) 

Lymph node (7) (5) (11) (9)

Histiocytic sarcoma 1 (9%) 

Liposarcoma, metastatic, skin 1 (20%) 

Iliac, histiocytic sarcoma 2 (18%) 

Iliac, liposarcoma, metastatic, skin 1 (20%) 

Mediastinal, sarcoma, metastatic, pancreas 1 (9%) 

Pancreatic, histiocytic sarcoma 1 (9%) 

Renal, histiocytic sarcoma 1 (9%) 1 (11%) 

Lymph node, mandibular (46) (46) (49) (49)

Histiocytic sarcoma 2 (4%) 

Squamous cell carcinoma, metastatic, 

uncertain primary site 1 (2%) 

Lymph node, mesenteric (47) (49) (49) (49)

Histiocytic sarcoma 1 (2%) 2 (4%) 

Histiocytic sarcoma, metastatic, mesentery 1 (2%) 

Yolk sac carcinoma, metastatic, ovary 1 (2%) 

Spleen (49) (48) (49) (50)

Hemangiosarcoma 2 (4%) 1 (2%) 1 (2%) 

Histiocytic sarcoma 2 (4%) 

Sarcoma, metastatic, skin 1 (2%) 

Thymus (48) (44) (48) (48)

Hepatocellular carcinoma, metastatic, liver 1 (2%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Integumentary System

Mammary gland (50) (50) (50) (50)

Adenoma 1 (2%) 

Carcinoma 1 (2%) 

Skin (48) (50) (50) (50)

Hemangioma 1 (2%) 

Squamous cell carcinoma 1 (2%) 

Subcutaneous tissue, fibrosarcoma 1 (2%) 2 (4%) 

Subcutaneous tissue, hemangioma 1 (2%) 

Subcutaneous tissue, hemangiosarcoma 1 (2%) 

Subcutaneous tissue, liposarcoma 1 (2%) 

Subcutaneous tissue, sarcoma 1 (2%) 

Subcutaneous tissue, schwannoma malignant 3 (6%) 1 (2%) 1 (2%) 

Musculoskeletal System

Bone (50) (50) (50) (50)

Osteosarcoma 1 (2%) 1 (2%) 2 (4%) 

Sarcoma 1 (2%) 

Skeletal muscle (2) (4) (6)

Histiocytic sarcoma, metastatic, mesentery 1 (25%) 

Rhabdomyosarcoma 1 (50%) 1 (25%) 2 (33%) 

Sarcoma, metastatic, pancreas 1 (25%) 

Sarcoma, metastatic, skin 1 (17%) 

Yolk sac carcinoma, metastatic, ovary 1 (17%) 

Table D1

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 181

Nervous System

Brain (50) (50) (50) (50)

Osteosarcoma, metastatic, bone 1 (2%) 

Respiratory System

Lung (50) (50) (49) (50)

Alveolar/bronchiolar adenoma 3 (6%) 1 (2%) 3 (6%) 

Alveolar/bronchiolar carcinoma 1 (2%) 1 (2%) 1 (2%) 1 (2%) 

Alveolar/bronchiolar carcinoma, multiple 1 (2%) 

Hepatocellular carcinoma, metastatic, liver 1 (2%) 3 (6%) 5 (10%) 2 (4%) 

Histiocytic sarcoma 1 (2%) 1 (2%) 

Liposarcoma, metastatic, skin 1 (2%) 

Osteosarcoma, metastatic, bone 1 (2%) 

Sarcoma, metastatic, skin 1 (2%) 

Nose (50) (50) (50) (50)

Carcinoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Special Senses System

Eye (50) (48) (50) (50)

Harderian gland (50) (50) (50) (49)

Adenoma 11 (22%) 9 (18%) 5 (10%) 6 (12%) 

Carcinoma 1 (2%) 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Urinary System

Kidney (50) (49) (49) (50)

Hepatocellular carcinoma, metastatic, liver 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Osteosarcoma, metastatic, bone 1 (2%) 

Urinary bladder (49) (50) (50) (50)

Systemic Lesions

Multiple organsb (50) (50) (50) (50)

Histiocytic sarcoma 1 (2%) 4 (8%) 2 (4%) 

Leukemia granulocytic 1 (2%) 

Lymphoma malignant 23 (46%) 19 (38%) 28 (56%) 27 (54%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 47 45 46 47 

Total primary neoplasms 99 87 108 105 

Total animals with benign neoplasms 38 27 33 31 

Total benign neoplasms 58 40 44 53

Total animals with malignant neoplasms 33 38 41 41 

Total malignant neoplasms 41 47 64 52

Total animals with metastatic neoplasms 2 5 10 5

Total metastatic neoplasms 2 8 20 11

a Number of animals examined microscopically at the site and the number of animals with neoplasm b Number of animals with any tissue examined microscopically c Primary neoplasms: all neoplasms except metastatic neoplasms

Table D1

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
182 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Gallbladder A A + + A + + A + AAAAA +++++++++++

Intestine large, colon A ++++++++A+++++++++++++++

Intestine large, rectum ++++++++A++++++++++++++++

Intestine large, cecum + A + + A + + + AAAA +++++++++++++

Intestine small, duodenum A ++++++A+A+A+++++++++++++

Intestine small, jejunum A A + + + + + + I AA+ + + + + + + + + + + + + +

Intestine small, ileum A M + + A + + A M A A + + + + + + + + + + + +M+

Liver A ++++++++++++++++++++++++

Hemangioma X

Hemangiosarcoma

Hepatoblastoma

Hepatocellular carcinoma X

Hepatocellular carcinoma, multiple

Hepatocellular adenoma X X X X

Hepatocellular adenoma, multiple X X X X X X

Mesentery A +++++++ +++++ + +++++

Fibrous histiocytoma

Schwannoma malignant, metastatic, skin X

Oral mucosa + +

Squamous cell carcinoma X

Pancreas A A + + A + + M +++++++++++++++++

Salivary glands + + + +M+ + +M+ + + + + + + + + + + + + + + +

Stomach, forestomach A ++++++++++++++++++++++++

Stomach, glandular A ++++++++++++++++++++++++

Cardiovascular System 

Blood vessel

Heart + + + + + + + +M+ + + + + + + + + + + + + + + +

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++

Subcapsular, adenoma

Adrenal medulla +++++++++++++++++++++++++

Pheochromocytoma malignant X

Pheochromocytoma benign X

Islets, pancreatic A A + + A + + M +++++++++++++++++

Parathyroid gland M M +++++++++++++++++++++++

Pituitary gland M + + + I M +++++++++++++++++++

Pars distalis, adenoma

Thyroid gland M ++++++++++++++++++++++++

Follicular cell, adenoma

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

2455555566666777777777777

Number of Days on Study 7427899903367133333333333

1046811760904055555555555

2222222222222222222222222

Carcass ID Number 1122004023432400011111112

3787456653202512312456890

+: Tissue examined microscopically M: Missing tissue X: Lesion present

A: Autolysis precludes examination I: Insufficient tissue Blank: Not examined
Sodium Chlorate, NTP TR 517 183

Alimentary System 

Esophagus + + + + + + + + + + + + + M + + + + + + + + + + + 49

Gallbladder + + + + + + + + + + + + + + M + + + + + + + + + + 40

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48

Intestine large, rectum + + + + + + + + + + + + + + + + + + I + + + + + + 48

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 44

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 46

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 45

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 42

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 49

Hemangioma X 2

Hemangiosarcoma X 1

Hepatoblastoma X 1

Hepatocellular carcinoma X 2

Hepatocellular carcinoma, multiple X 1

Hepatocellular adenoma X X X X X X X X X X X 15

Hepatocellular adenoma, multiple X X X X X X X X X 15

Mesentery + + + + + + + + + + + + 30

Fibrous histiocytoma X 1

Schwannoma malignant, metastatic, skin 1

Oral mucosa 2

Squamous cell carcinoma 1

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 46

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 48

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 49

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49

Cardiovascular System 

Blood vessel + 1

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 49

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Subcapsular, adenoma X 1

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pheochromocytoma malignant X 2

Pheochromocytoma benign 1

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 46

Parathyroid gland M M + + + + + + + + + + + + + + + + M + + + + + + 45

Pituitary gland + + + + + + + + + + + + + + + + + + + M + + + + + 46

Pars distalis, adenoma X X X 3

Thyroid gland + + + + + + + + + + + + + + + + + + M + + + + + + 48

Follicular cell, adenoma X 1

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5555556666666666666667777

2222222222222222222222222 Total

Carcass ID Number 2244450001222333344443333 Tissues/

6978907890134678901341245 Tumors
184 Sodium Chlorate, NTP TR 517 

General Body System 

None

Genital System 

Clitoral gland I ++++++++++++++++++++++++

Ovary A + + + + + + + + + + + + + + +MIM+ + + + + +

Cystadenoma

Granulosa cell tumor benign

Luteoma X X

Uterus +++++++++++++++++++++++++

Polyp stromal

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++

Hemangiosarcoma X

Lymph node + + + +

Lymph node, mandibular + + + +M+ + +M+ + + + + + + + + + + + + + + +

Lymph node, mesenteric A + + + + + + + + + + + + + + + + +M+ + +M+ +

Spleen A ++++++++++++++++++++++++

Hemangiosarcoma X

Thymus + + + + + + + +M+ + + + + + + + + + + + + + + +

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Skin ++++++I++++++++++++++++++

Subcutaneous tissue, schwannoma

malignant X X

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Nervous System 

Brain +++++++++++++++++++++++++

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma X X

Alveolar/bronchiolar carcinoma

Hepatocellular carcinoma, metastatic, liver

Nose +++++++++++++++++++++++++

Carcinoma X

Trachea I + + + M ++++++++++++++++++++

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + +

Harderian gland +++++++++++++++++++++++++

Adenoma X X X X

Carcinoma X

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

2455555566666777777777777

Number of Days on Study 7427899903367133333333333

1046811760904055555555555

2222222222222222222222222

Carcass ID Number 1122004023432400011111112

3787456653202512312456890
Sodium Chlorate, NTP TR 517 185

General Body System 

None

Genital System 

Clitoral gland + M + I + + + + + + + + + + + + + + + + + + + + + 47

Ovary + + + + + + + + + + + + + + + + + + + + + + + I + 45

Cystadenoma X 1

Granulosa cell tumor benign X 1

Luteoma X 3

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Polyp stromal X 1

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hemangiosarcoma 1

Lymph node + + + 7

Lymph node, mandibular + + + + + + + + I + + + + + + + + I + + + + + + + 46

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 47

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 49

Hemangiosarcoma X 2

Thymus + + + + + + + + + + + + + + + + I + + + + + + + + 48

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skin + + + + + + + + + + + + + + + + I + + + + + + + + 48

Subcutaneous tissue, schwannoma

malignant X 3

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X 3

Alveolar/bronchiolar carcinoma X 1

Hepatocellular carcinoma, metastatic, liver X 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Carcinoma 1

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 48

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 50

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma X X X X X X X 11

Carcinoma 1

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5555556666666666666667777

2222222222222222222222222 Total

Carcass ID Number 2244450001222333344443333 Tissues/

6978907890134678901341245 Tumors
186 Sodium Chlorate, NTP TR 517 

Urinary System 

Kidney +++++++++++++++++++++++++

Urinary bladder A ++++++++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Lymphoma malignant X X X X X X X X X X X

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

2455555566666777777777777

Number of Days on Study 7427899903367133333333333

1046811760904055555555555

2222222222222222222222222

Carcass ID Number 1122004023432400011111112

3787456653202512312456890
Sodium Chlorate, NTP TR 517 187

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 49

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Lymphoma malignant X X X X X X X X X X X X 23

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 0 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5555556666666666666667777

2222222222222222222222222 Total

Carcass ID Number 2244450001222333344443333 Tissues/

6978907890134678901341245 Tumors
188 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Gallbladder + M A A + + + + + + + +MAA + + + + + + + + + +

Intestine large, colon + + + A +++++++++++++++++++++

Intestine large, rectum +++++++++++++++++++++++++

Intestine large, cecum + A + A ++++++++++A++++++++++

Intestine small, duodenum + A + A ++++++++++A++++++++++

Adenoma X

Intestine small, jejunum + + + A ++++++++A+A++++++++++

Intestine small, ileum + A A A +++++++A++A++++++++++

Liver +++++++++++++++++++++++++

Hemangiosarcoma X

Hemangiosarcoma, metastatic, spleen X

Hepatocellular carcinoma X X X

Hepatocellular carcinoma, multiple X X X

Hepatocellular adenoma X X X X

Hepatocellular adenoma, multiple X X

Mesentery + + + + +++++++ + +++ +

Pancreas + A A A +++++++++++++++++++++

Salivary glands + M M + + + + + + + + + +M+ + + + + + + + + + +

Stomach, forestomach +++++++++++++++++++++++++

Squamous cell carcinoma

Stomach, glandular + A + A +++++++++++++++++++++

Cardiovascular System 

Blood vessel + + +

Heart +++++++++++++++++++++++++

Hemangiosarcoma, metastatic, spleen X

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + +M+

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + +M+

Islets, pancreatic + A A A +++++++++++++++++++++

Adenoma X

Parathyroid gland + + + + + +M+ + + + +M+ + + + + + + + +M+ +

Pituitary gland + M + + + + +M+ + + + + + + + + +M+ + + + + +

Pars distalis, adenoma X X

Thyroid gland +++++++++++++++++++++++++

General Body System 

None

Genital System 

Clitoral gland + + M +++++++++++++++I++++++

Ovary + M + I + + + + + +M+ +M+ + + + + + + + + + +

Cystadenoma X

Granulosa cell tumor benign

Uterus +++++++++++++++++++++++++

Hemangiosarcoma X

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 500 mg/L

4455556667777777777777777

Number of Days on Study 6915667780111123333333333

1232183426347973444444445

2222223222222222222222222

Carcass ID Number 9698960788958995556666795

3868930765284707690679081
Sodium Chlorate, NTP TR 517 189

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Gallbladder + + + + + + + + + + + + + + + + + + + + + + + + + 44

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Adenoma 1

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 45

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hemangiosarcoma X 2

Hemangiosarcoma, metastatic, spleen 1

Hepatocellular carcinoma X X X 6

Hepatocellular carcinoma, multiple X X X X 7

Hepatocellular adenoma X X X X X 9

Hepatocellular adenoma, multiple X X X X X X X X 10

Mesentery + ++++ + + + + ++ + + + + + 32

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 47

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 47

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Squamous cell carcinoma X 1

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 48

Cardiovascular System 

Blood vessel 3

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hemangiosarcoma, metastatic, spleen 1

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 49

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 49

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 47

Adenoma X 2

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 47

Pituitary gland + + M + + + + + + + + + + + M + + + + + + + + + + 45

Pars distalis, adenoma 2

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

General Body System 

None

Genital System 

Clitoral gland + + + + + + + + + + + + + M + + + + + + + + + + + 47

Ovary + + + + + + + + + I + + + + + + + + + + + + + + + 45

Cystadenoma X X X 4

Granulosa cell tumor benign X 1

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hemangiosarcoma 1

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 500 mg/L

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 3333333333333333333333333

5555555555555566666667777

2222222222222222222222222 Total

Carcass ID Number 5555777888899977777886666 Tissues/

2345689012314512345791245 Tumors
190 Sodium Chlorate, NTP TR 517 

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++

Hemangiosarcoma X

Lymph node + + + +

Liposarcoma, metastatic, skin X

Iliac, liposarcoma, metastatic, skin X

Lymph node, mandibular + M M + + + + + + + + + +M+ + + + + + + + + + +

Lymph node, mesenteric + + + M +++++++++++++++++++++

Histiocytic sarcoma

Spleen + A + A +++++++++++++++++++++

Hemangiosarcoma X

Thymus + + M + M + + + + + I + + MM + + + + + + + + + +

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Carcinoma X

Skin +++++++++++++++++++++++++

Hemangioma

Subcutaneous tissue, fibrosarcoma X

Subcutaneous tissue, liposarcoma X

Subcutaneous tissue, schwannoma malignant X

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + +

Osteosarcoma X

Skeletal muscle + +

Rhabdomyosarcoma X

Nervous System 

Brain +++++++++++++++++++++++++

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar carcinoma

Hepatocellular carcinoma, metastatic, liver X X

Liposarcoma, metastatic, skin X

Nose +++++++++++++++++++++++++

Trachea + + + + + + + + + + + + + + + + + + + + + + + + +

Special Senses System 

Eye + A + A + + + + + + + + + + + + + + + + + + + + +

Harderian gland +++++++++++++++++++++++++

Adenoma X X X

Carcinoma X

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 500 mg/L

4455556667777777777777777

Number of Days on Study 6915667780111123333333333

1232183426347973444444445

2222223222222222222222222

Carcass ID Number 9698960788958995556666795

3868930765284707690679081
Sodium Chlorate, NTP TR 517 191

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hemangiosarcoma 1

Lymph node + 5

Liposarcoma, metastatic, skin 1

Iliac, liposarcoma, metastatic, skin 1

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + M + + + + 46

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 49

Histiocytic sarcoma X 1

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 48

Hemangiosarcoma 1

Thymus + + + + + + + + + + + + + + + + + I + + + + + + + 44

Integumentary system 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Carcinoma 1

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hemangioma X 1

Subcutaneous tissue, fibrosarcoma 1

Subcutaneous tissue, liposarcoma 1

Subcutaneous tissue, schwannoma malignant 1

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Osteosarcoma 1

Skeletal muscle 2

Rhabdomyosarcoma 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X 1

Alveolar/bronchiolar carcinoma X 1

Hepatocellular carcinoma, metastatic, liver X 3

Liposarcoma, metastatic, skin 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 48

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma XXXX X X 9

Carcinoma 1

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 500 mg/L

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 3333333333333333333333333

5555555555555566666667777

2222222222222222222222222 Total

Carcass ID Number 5555777888899977777886666 Tissues/

2345689012314512345791245 Tumors
192 Sodium Chlorate, NTP TR 517 

Urinary System 

Kidney + + + A +++++++++++++++++++++

Urinary bladder +++++++++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Histiocytic sarcoma

Lymphoma malignant X X X X X X X X X

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 500 mg/L

4455556667777777777777777

Number of Days on Study 6915667780111123333333333

1232183426347973444444445

2222223222222222222222222

Carcass ID Number 9698960788958995556666795

3868930765284707690679081
Sodium Chlorate, NTP TR 517 193

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma X 1

Lymphoma malignant X X X X X X X X X X 19

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate: 500 mg/L

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 3333333333333333333333333

5555555555555566666667777

2222222222222222222222222 Total

Carcass ID Number 5555777888899977777886666 Tissues/

2345689012314512345791245 Tumors
194 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Gallbladder + + + A + + + + + +M+ +AAA+ + + + + + + + +

Intestine large, colon + + + A + + + A +++++++++++++++++

Intestine large, rectum +++++++++++++++++++++++++

Intestine large, cecum + + + A ++++++A+++A++++++++++

Hemangioma

Intestine small, duodenum + + + A + + + + + +M+ +A+ + + + + + + + + + +

Intestine small, jejunum + A + + + + + + + + + + +AA+ + + + + + + + + +

Histiocytic sarcoma

Intestine small, ileum + + + A + + + + + +A+ +AA+ + + + + + + + + +

Liver + + + A +++++++++++++++++++++

Hepatocellular carcinoma X X X X X

Hepatocellular carcinoma, multiple X

Hepatocellular adenoma X X X X X X X

Hepatocellular adenoma, multiple X X X

Histiocytic sarcoma X

Mesentery + + +++++++++++ ++ + +

Fibrosarcoma X

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma X

Pancreas + + + A +++++++++++++++++++++

Fibrosarcoma, metastatic, mesentery X

Histiocytic sarcoma

Acinus, sarcoma X

Salivary glands +++++++++++++++++I+++++++

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma

Stomach, forestomach +++++++++++++++++++++++++

Squamous cell carcinoma

Squamous cell papilloma

Squamous cell papilloma, multiple X

Stomach, glandular +++++++++++++++++++++++++

Hepatocellular carcinoma, metastatic, liver X

Tongue + +

Cardiovascular System 

Heart + + + + + + + + + +M+ + + + + + + + + + + + + +

Hepatocellular carcinoma, metastatic, liver X

Endocrine System 

Adrenal cortex + + + A +++++++++++++++++++++

Histiocytic sarcoma

Osteosarcoma, metastatic, bone X

Adrenal medulla + + + A +++++++++++++++++++++

Islets, pancreatic + + + A +++++++++++++++++++++

Adenoma

Parathyroid gland + + + M + + + + + + + + + + + + + + + + + + + +M

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 1,000 mg/L

0045555666666677777777777

Number of Days on Study 2380047011266811122333333

7463324288212312903444444

3333333333333333333333333

Carcass ID Number 3021230044102213234223444

9343651739625244930780678
Sodium Chlorate, NTP TR 517 195

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Gallbladder + + + + + + + + + + + + + + + I + + + + + + + + + 44

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Hemangioma X 1

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Histiocytic sarcoma X 1

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 46

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 49

Hepatocellular carcinoma X X X X X X 11

Hepatocellular carcinoma, multiple X X X 4

Hepatocellular adenoma X X X X X X X 14

Hepatocellular adenoma, multiple X X X X X X X X X 12

Histiocytic sarcoma 1

Mesentery + + + + + + + + + + 27

Fibrosarcoma 1

Hepatocellular carcinoma, metastatic, liver 1

Histiocytic sarcoma 1

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49

Fibrosarcoma, metastatic, mesentery 1

Histiocytic sarcoma X 1

Acinus, sarcoma 1

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 49

Hepatocellular carcinoma, metastatic, liver 1

Histiocytic sarcoma X 1

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50

Squamous cell carcinoma X 1

Squamous cell papilloma X 1

Squamous cell papilloma, multiple 1

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hepatocellular carcinoma, metastatic, liver 1

Tongue 2

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 49

Hepatocellular carcinoma, metastatic, liver 1

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 49

Histiocytic sarcoma X 1

Osteosarcoma, metastatic, bone 1

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 49

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49

Adenoma X X 2

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 48

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 1,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

4555556666666666677777777

3333333333333333333333333 Total

Carcass ID Number 5111220000013333311124444 Tissues/

0125134568901267878901245 Tumors
196 Sodium Chlorate, NTP TR 517 

Endocrine System (continued)

Pituitary gland + + + + + + + + + +M+ + + + + + + + + + + + + +

Histiocytic sarcoma

Pars distalis, adenoma

Thyroid gland + + + M +++++++++++++++++++++

General Body System 

None

Genital System 

Clitoral gland + + + + + + + + + + + +M+ + + + + + + + + + + +

Ovary + + + M + + + + + + + +M+ + + + + + + + + + + +

Choriocarcinoma X

Cystadenoma X

Granulosa cell tumor benign

Histiocytic sarcoma X

Luteoma

Uterus +++++++++++++++++++++++++

Histiocytic sarcoma X

Leiomyosarcoma

Vagina +

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + +

Hemangiosarcoma X X

Lymph node + + + + + +

Histiocytic sarcoma

Iliac, histiocytic sarcoma X

Mediastinal, sarcoma, metastatic, pancreas X

Pancreatic, histiocytic sarcoma

Renal, histiocytic sarcoma

Lymph node, mandibular + + + + + + + + + + + + + + + + +M+ + + + + + +

Histiocytic sarcoma X

Lymph node, mesenteric +++++++++++++++++++++++++

Histiocytic sarcoma X

Histiocytic sarcoma, metastatic, mesentery X

Spleen + + + A +++++++++++++++++++++

Hemangiosarcoma X

Histiocytic sarcoma X

Thymus + + + + + + + + + +M+ + + + + + + + + + + + + +

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Adenoma X

Skin +++++++++++++++++++++++++

Squamous cell carcinoma

Subcutaneous tissue, hemangiosarcoma X

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 1,000 mg/L

0045555666666677777777777

Number of Days on Study 2380047011266811122333333

7463324288212312903444444

3333333333333333333333333

Carcass ID Number 3021230044102213234223444

9343651739625244930780678
Sodium Chlorate, NTP TR 517 197

Endocrine System (continued)

Pituitary gland + + + + + + + + + + + + + + + I + + + + + + + + + 48

Histiocytic sarcoma X 1

Pars distalis, adenoma X X X X 4

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

General Body System 

None

Genital System 

Clitoral gland + + + + + I + + + + + + I + + + + + + + + + + + + 47

Ovary + + + + + + + + + + + + + + + + + + + + I + + + + 47

Choriocarcinoma X 2

Cystadenoma 1

Granulosa cell tumor benign X 1

Histiocytic sarcoma X 2

Luteoma X 1

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma X 2

Leiomyosarcoma X 1

Vagina 1

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hemangiosarcoma 2

Lymph node + + + + + 11

Histiocytic sarcoma X 1

Iliac, histiocytic sarcoma X 2

Mediastinal, sarcoma, metastatic, pancreas 1

Pancreatic, histiocytic sarcoma X 1

Renal, histiocytic sarcoma X 1

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 49

Histiocytic sarcoma X 2

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + I 49

Histiocytic sarcoma X 2

Histiocytic sarcoma, metastatic, mesentery 1

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 49

Hemangiosarcoma 1

Histiocytic sarcoma X 2

Thymus + + + + + + + + + + + + M + + + + + + + + + + + + 48

Hepatocellular carcinoma, metastatic, liver 1

Histiocytic sarcoma X 1

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma 1

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Squamous cell carcinoma X 1

Subcutaneous tissue, hemangiosarcoma 1

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 1,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

4555556666666666677777777

3333333333333333333333333 Total

Carcass ID Number 5111220000013333311124444 Tissues/

0125134568901267878901245 Tumors
198 Sodium Chlorate, NTP TR 517 

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Osteosarcoma X

Sarcoma X

Skeletal muscle + + +

Histiocytic sarcoma, metastatic, mesentery X

Rhabdomyosarcoma

Sarcoma, metastatic, pancreas X

Nervous System 

Brain +++++++++++++++++++++++++

Osteosarcoma, metastatic, bone X

Peripheral nerve + +

Spinal cord + + +

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar carcinoma X

Alveolar/bronchiolar carcinoma, multiple

Hepatocellular carcinoma, metastatic, liver X X

Histiocytic sarcoma X

Osteosarcoma, metastatic, bone X

Nose +++++++++++++++++++++++++

Histiocytic sarcoma

Trachea +++++++++++++++++++++++++

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + +

Harderian gland +++++++++++++++++++++++++

Adenoma X XX

Histiocytic sarcoma

Urinary System 

Kidney + + + A +++++++++++++++++++++

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma

Osteosarcoma, metastatic, bone X

Urinary bladder +++++++++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Histiocytic sarcoma X X X

Leukemia granulocytic X

Lymphoma malignant X X X X X XXXXXX

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 1,000 mg/L

0045555666666677777777777

Number of Days on Study 2380047011266811122333333

7463324288212312903444444

3333333333333333333333333

Carcass ID Number 3021230044102213234223444

9343651739625244930780678
Sodium Chlorate, NTP TR 517 199

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Osteosarcoma 1

Sarcoma 1

Skeletal muscle + 4

Histiocytic sarcoma, metastatic, mesentery 1

Rhabdomyosarcoma X 1

Sarcoma, metastatic, pancreas 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Osteosarcoma, metastatic, bone 1

Peripheral nerve 2

Spinal cord 3

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + 49

Alveolar/bronchiolar carcinoma 1

Alveolar/bronchiolar carcinoma, multiple X 1

Hepatocellular carcinoma, metastatic, liver X X X 5

Histiocytic sarcoma 1

Osteosarcoma, metastatic, bone 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma X 1

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 50

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adenoma XX 5

Histiocytic sarcoma X 1

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49

Hepatocellular carcinoma, metastatic, liver 1

Histiocytic sarcoma X 1

Osteosarcoma, metastatic, bone 1

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma X 4

Leukemia granulocytic 1

Lymphoma malignant XXXX X XXXX X X X X X X X X 28

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 1,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

4555556666666666677777777

3333333333333333333333333 Total

Carcass ID Number 5111220000013333311124444 Tissues/

0125134568901267878901245 Tumors
200 Sodium Chlorate, NTP TR 517 

Alimentary System 

Esophagus +++++++++++++++++++++++++

Gallbladder ++++++++++++++A++++++++++

Intestine large, colon +++++++++++++++++++++++++

Intestine large, rectum +++++++++++++++++++++++++

Intestine large, cecum + + + +M+A+ + +A+ + + + + + + + + + + + + +

Intestine small, duodenum +++++++++++++++++++++++++

Polyp adenomatous X

Intestine small, jejunum +++++A++++A+++A++++++++++

Intestine small, ileum + + + + +A+ + + + + + + + + + + + + + +M+ + +

Liver +++++++++++++++++++++++++

Hepatocellular carcinoma X X

Hepatocellular carcinoma, multiple X X

Hepatocellular adenoma X X X X

Hepatocellular adenoma, multiple X X X X X

Histiocytic sarcoma X

Mesentery + + +++++ + ++++

Hemangiosarcoma

Sarcoma, metastatic, skin

Oral mucosa +

Squamous cell papilloma X

Pancreas + + + + +MA + + + + + + + + + + + + + + + + + +

Sarcoma, metastatic, skin

Salivary glands +++++++++++++++++++++++++

Stomach, forestomach + + + M +++++++++++++++++++++

Squamous cell papilloma X

Stomach, glandular + + + M +++++++++++++++++++++

Cardiovascular System 

Blood vessel

Heart +++++++++++++++++++++++++

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++

Adrenal medulla +++++++++++++++++++++++++

Pheochromocytoma complex X

Pheochromocytoma benign X

Islets, pancreatic ++++++A++++++++++++++++++

Adenoma X X

Carcinoma

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + MM

Pituitary gland +++++++++++++++++++++++++

Pars distalis, adenoma X X

Thyroid gland +++++++++++++++++++++++++

General Body System 

None

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

1444555666666677777777777

Number of Days on Study 4457349146888802222222223

2755507867155859999999995

3333333333333333333333333

Carcass ID Number 5599987696878685555666678

2929796053890171345678906
Sodium Chlorate, NTP TR 517 201

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Gallbladder + + + + + + + + + + + I + + + + + + + + + + + + + 48

Intestine large, colon M + + + + + + + + + + + + + + + + + + + + + + + + 49

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 50

Polyp adenomatous 1

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47

Intestine small, ileum + + + + + + + + + + + + + + + + + + M + + + + + + 47

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50

Hepatocellular carcinoma X X X X 6

Hepatocellular carcinoma, multiple X 3

Hepatocellular adenoma X X X X 8

Hepatocellular adenoma, multiple X X X X X X X X X X 15

Histiocytic sarcoma 1

Mesentery + + + + + + + + + + + + 24

Hemangiosarcoma X 1

Sarcoma, metastatic, skin X 1

Oral mucosa 1

Squamous cell papilloma 1

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 48

Sarcoma, metastatic, skin X 1

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 49

Squamous cell papilloma 1

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49

Cardiovascular System 

Blood vessel + 1

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pheochromocytoma complex 1

Pheochromocytoma benign 1

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49

Adenoma X 3

Carcinoma X 1

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + M + 47

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Pars distalis, adenoma X X 4

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

General Body System 

None

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5666666666666677777777777

3333333333333333333333334 Total

Carcass ID Number 9666778888899955577777990 Tissues/

0245781234513467812345680 Tumors
202 Sodium Chlorate, NTP TR 517 

Genital System 

Clitoral gland +++++++++++++++++++++++++

Ovary +++++++++++++++++++++++++

Cystadenoma X

Granulosa cell tumor malignant X

Granulosa cell tumor benign

Histiocytic sarcoma X

Yolk sac carcinoma X

Uterus +++++++++++++++++++++++++

Histiocytic sarcoma X

Polyp stromal

Yolk sac carcinoma, metastatic, ovary X

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++

Histiocytic sarcoma X

Lymph node + + + + +

Renal, histiocytic sarcoma X

Lymph node, mandibular +++++++++++++++++++++++++

Squamous cell carcinoma, metastatic,

uncertain primary site

Lymph node, mesenteric +++++++++++++++++++++++++

Yolk sac carcinoma, metastatic, ovary X

Spleen +++++++++++++++++++++++++

Sarcoma, metastatic, skin

Thymus + + + +M+ + + + + + + + +M+ + + + + + + + + +

Histiocytic sarcoma X

Integumentary System 

Mammary gland +++++++++++++++++++++++++

Skin +++++++++++++++++++++++++

Subcutaneous tissue, fibrosarcoma X X

Subcutaneous tissue, hemangioma X

Subcutaneous tissue, sarcoma

Subcutaneous tissue, schwannoma malignant X

Musculoskeletal System 

Bone +++++++++++++++++++++++++

Osteosarcoma X X

Skeletal muscle + + + + +

Rhabdomyosarcoma X X

Sarcoma, metastatic, skin

Yolk sac carcinoma, metastatic, ovary X

Nervous System 

Brain +++++++++++++++++++++++++

Peripheral nerve + +

Spinal cord + +

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

1444555666666677777777777

Number of Days on Study 4457349146888802222222223

2755507867155859999999995

3333333333333333333333333

Carcass ID Number 5599987696878685555666678

2929796053890171345678906
Sodium Chlorate, NTP TR 517 203

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + I 49

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50

Cystadenoma 1

Granulosa cell tumor malignant 1

Granulosa cell tumor benign X X X X X 5

Histiocytic sarcoma 1

Yolk sac carcinoma 1

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 1

Polyp stromal X X X 3

Yolk sac carcinoma, metastatic, ovary 1

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 1

Lymph node + + + + 9

Renal, histiocytic sarcoma 1

Lymph node, mandibular + + + + + + + + + + + + + M + + + + + + + + + + + 49

Squamous cell carcinoma, metastatic,

uncertain primary site X 1

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + M + + + + 49

Yolk sac carcinoma, metastatic, ovary 1

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50

Sarcoma, metastatic, skin X 1

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 48

Histiocytic sarcoma 1

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50

Subcutaneous tissue, fibrosarcoma 2

Subcutaneous tissue, hemangioma 1

Subcutaneous tissue, sarcoma X 1

Subcutaneous tissue, schwannoma malignant 1

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50

Osteosarcoma 2

Skeletal muscle + 6

Rhabdomyosarcoma 2

Sarcoma, metastatic, skin X 1

Yolk sac carcinoma, metastatic, ovary 1

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50

Peripheral nerve 2

Spinal cord 2

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5666666666666677777777777

3333333333333333333333334 Total

Carcass ID Number 9666778888899955577777990 Tissues/

0245781234513467812345680 Tumors
204 Sodium Chlorate, NTP TR 517 

Respiratory System 

Lung +++++++++++++++++++++++++

Alveolar/bronchiolar adenoma X

Alveolar/bronchiolar carcinoma

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma X

Sarcoma, metastatic, skin

Nose +++++++++++++++++++++++++

Trachea +++++++++++++++++++++++++

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + +

Harderian gland + + + +M+ + + + + + + + + + + + + + + + + + + +

Adenoma X X X X

Urinary system 

Kidney +++++++++++++++++++++++++

Urinary bladder +++++++++++++++++++++++++

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++

Histiocytic sarcoma X X

Lymphoma malignant X X X X X XXXXXX

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

1444555666666677777777777

Number of Days on Study 4457349146888802222222223

2755507867155859999999995

3333333333333333333333333

Carcass ID Number 5599987696878685555666678

2929796053890171345678906
Sodium Chlorate, NTP TR 517 205

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50

Alveolar/bronchiolar adenoma X X 3

Alveolar/bronchiolar carcinoma X 1

Hepatocellular carcinoma, metastatic, liver X 2

Histiocytic sarcoma 1

Sarcoma, metastatic, skin X 1

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 50

Harderian gland + + + + + + + + + + + + + + + + + + + + + + + + + 49

Adenoma X X6

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50

Histiocytic sarcoma 2

Lymphoma malignant X X X X X X X X X X X X X X X X 27

TABLE D2

Individual Animal Tumor Pathology of Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate: 2,000 mg/L

7777777777777777777777777

Number of Days on Study 3333333333333333333333333

5666666666666677777777777

3333333333333333333333334 Total

Carcass ID Number 9666778888899955577777990 Tissues/

0245781234513467812345680 Tumors
206 Sodium Chlorate, NTP TR 517 

Adrenal Medulla: Benign, Complex, or Malignant Pheochromocytoma

Overall ratea 3/50 (6%) 0/49 (0%) 0/49 (0%) 2/50 (4%)

Adjusted rateb 6.8% 0.0% 0.0% 4.6%

Terminal ratec 2/36 (6%) 0/34 (0%) 0/31 (0%) 1/35 (3%)

First incidence (days) 660 —e — 681

Poly-3 testd P=0.538N P=0.117N P=0.126N P=0.503N

Harderian Gland: Adenoma

Overall rate 11/50 (22%) 9/50 (18%) 5/50 (10%) 6/50 (12%)

Adjusted rate 24.9% 19.7% 11.8% 13.7%

Terminal rate 10/36 (28%) 7/35 (20%) 4/31 (13%) 5/35 (14%)

First incidence (days) 576 673 712 597

Poly-3 test P=0.093N P=0.368N P=0.095N P=0.142N

Harderian Gland: Adenoma or Carcinoma

Overall rate 12/50 (24%) 10/50 (20%) 5/50 (10%) 6/50 (12%)

Adjusted rate 27.2% 21.7% 11.8% 13.7%

Terminal rate 11/36 (31%) 7/35 (20%) 4/31 (13%) 5/35 (14%)

First incidence (days) 576 568 712 597

Poly-3 test P=0.053N P=0.358N P=0.060N P=0.094N

Liver: Hepatocellular Adenoma

Overall rate 30/49 (61%)f 19/50 (38%) 26/49 (53%) 23/50 (46%)

Adjusted rate 66.1% 41.5% 59.9% 51.4%

Terminal rate 26/36 (72%) 17/35 (49%) 19/31 (61%) 20/35 (57%)

First incidence (days) 524 674 602 475

Poly-3 test P=0.252N P=0.013N P=0.348N P=0.108N

Liver: Hepatocellular Carcinoma

Overall rate 3/49 (6%) 13/50 (26%) 15/49 (31%) 9/50 (18%)

Adjusted rate 6.9% 28.5% 35.6% 20.3%

Terminal rate 2/36 (6%) 9/35 (26%) 12/31 (39%) 7/35 (20%)

First incidence (days) 710 682 711 475

Poly-3 test P=0.158 P=0.007 P<0.001 P=0.061

Liver: Hepatocellular Carcinoma or Hepatoblastoma

Overall rate 4/49 (8%) 13/50 (26%) 15/49 (31%) 9/50 (18%)

Adjusted rate 9.2% 28.5% 35.6% 20.3%

Terminal rate 3/36 (8%) 9/35 (26%) 12/31 (39%) 7/35 (20%)

First incidence (days) 710 682 711 475

Poly-3 test P=0.219 P=0.018 P=0.002 P=0.119

Liver: Hepatocellular Adenoma or Carcinoma

Overall rate 31/49 (63%)f 26/50 (52%) 31/49 (63%) 26/50 (52%)

Adjusted rate 68.1% 56.7% 71.3% 57.9%

Terminal rate 26/36 (72%) 21/35 (60%) 23/31 (74%) 22/35 (63%)

First incidence (days) 524 674 602 475

Poly-3 test P=0.287N P=0.174N P=0.461 P=0.207N

Lung: Alveolar/bronchiolar Adenoma

Overall rate 3/50 (6%) 1/50 (2%) 0/49 (0%) 3/50 (6%)

Adjusted rate 6.8% 2.2% 0.0% 6.9%

Terminal rate 2/36 (6%) 1/35 (3%) 0/30 (0%) 3/35 (9%)

First incidence (days) 630 729 (T) — 729 (T)

Poly-3 test P=0.513 P=0.294N P=0.130N P=0.657

TABLE D3

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 207

Lung: Alveolar/bronchiolar Adenoma or Carcinoma

Overall rate 4/50 (8%) 2/50 (4%) 2/49 (4%) 4/50 (8%)

Adjusted rate 9.1% 4.4% 4.8% 9.2%

Terminal rate 3/36 (8%) 2/35 (6%) 1/30 (3%) 4/35 (11%)

First incidence (days) 630 729 (T) 712 729 (T)

Poly-3 test P=0.482 P=0.323N P=0.365N P=0.636

Ovary: Cystadenoma

Overall rate 1/45 (2%) 4/45 (9%) 1/47 (2%) 1/50 (2%)

Adjusted rate 2.5% 9.6% 2.5% 2.3%

Terminal rate 1/32 (3%) 3/34 (9%) 1/30 (3%) 1/35 (3%)

First incidence (days) 729 (T) 682 729 (T) 729 (T)

Poly-3 test P=0.336N P=0.196 P=0.757N P=0.740N

Ovary: Benign Granulosa Cell Tumor

Overall rate 1/45 (2%) 1/45 (2%) 1/47 (2%) 5/50 (10%)

Adjusted rate 2.5% 2.4% 2.5% 11.5%

Terminal rate 1/32 (3%) 1/34 (3%) 1/30 (3%) 5/35 (14%)

First incidence (days) 729 (T) 729 (T) 729 (T) 729 (T)

Poly-3 test P=0.031 P=0.749N P=0.757N P=0.123

Ovary: Benign or Malignant Granulosa Cell Tumor

Overall rate 1/45 (2%) 1/45 (2%) 1/47 (2%) 6/50 (12%)

Adjusted rate 2.5% 2.4% 2.5% 13.5%

Terminal rate 1/32 (3%) 1/34 (3%) 1/30 (3%) 5/35 (14%)

First incidence (days) 729 (T) 729 (T) 729 (T) 142

Poly-3 test P=0.012 P=0.749N P=0.757N P=0.075

Ovary: Luteoma

Overall rate 3/45 (7%) 0/45 (0%) 1/47 (2%) 0/50 (0%)

Adjusted rate 7.5% 0.0% 2.5% 0.0%

Terminal rate 2/32 (6%) 0/34 (0%) 1/30 (3%) 0/35 (0%)

First incidence (days) 674 — 729 (T) —

Poly-3 test P=0.079N P=0.110N P=0.300N P=0.103N

Ovary: Benign Granulosa Cell Tumor, Malignant Granulosa Cell Tumor, or Luteoma

Overall rate 4/45 (9%) 1/45 (2%) 2/47 (4%) 6/50 (12%)

Adjusted rate 10.1% 2.4% 5.0% 13.5%

Terminal rate 3/32 (9%) 1/34 (3%) 2/30 (7%) 5/35 (14%)

First incidence (days) 674 729 (T) 729 (T) 142

Poly-3 test P=0.185 P=0.164N P=0.331N P=0.440

Pancreatic Islets: Adenoma

Overall rate 0/46 (0%) 2/47 (4%) 2/49 (4%) 3/49 (6%)

Adjusted rate 0.0% 4.5% 4.8% 6.8%

Terminal rate 0/36 (0%) 1/35 (3%) 2/31 (7%) 1/35 (3%)

First incidence (days) — 706 729 (T) 475

Poly-3 test P=0.112 P=0.248 P=0.235 P=0.125

Pancreatic Islets: Adenoma or Carcinoma

Overall rate 0/46 (0%) 2/47 (4%) 2/49 (4%) 4/49 (8%)

Adjusted rate 0.0% 4.5% 4.8% 9.1%

Terminal rate 0/36 (0%) 1/35 (3%) 2/31 (7%) 2/35 (6%)

First incidence (days) — 706 729 (T) 475

Poly-3 test P=0.045 P=0.248 P=0.235 P=0.065

TABLE D3

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
208 Sodium Chlorate, NTP TR 517 

Pituitary Gland (Pars Distalis): Adenoma

Overall rate 3/46 (7%) 2/45 (4%) 4/48 (8%) 4/50 (8%)

Adjusted rate 7.2% 4.9% 9.8% 9.2%

Terminal rate 3/35 (9%) 2/32 (6%) 4/30 (13%) 3/35 (9%)

First incidence (days) 729 (T) 729 (T) 729 (T) 688

Poly-3 test P=0.356 P=0.503N P=0.489 P=0.526

Skin: Fibrosarcoma or Sarcoma

Overall rate 0/50 (0%) 1/50 (2%) 0/50 (0%) 3/50 (6%)

Adjusted rate 0.0% 2.2% 0.0% 6.9%

Terminal rate 0/36 (0%) 0/35 (0%) 0/31 (0%) 2/35 (6%)

First incidence (days) — 513 — 705

Poly-3 test P=0.041 P=0.511 —g P=0.118

Skin: Schwannoma Malignant

Overall rate 3/50 (6%) 1/50 (2%) 0/50 (0%) 1/50 (2%)

Adjusted rate 6.8% 2.2% 0.0% 2.3%

Terminal rate 2/36 (6%) 0/35 (0%) 0/31 (0%) 0/35 (0%)

First incidence (days) 591 561 — 685

Poly-3 test P=0.207N P=0.291N P=0.126N P=0.309N

Stomach (Forestomach): Squamous Cell Papilloma or Squamous Cell Carcinoma

Overall rate 0/50 (0%) 1/50 (2%) 3/50 (6%) 1/50 (2%)

Adjusted rate 0.0% 2.2% 7.0% 2.3%

Terminal rate 0/36 (0%) 1/35 (3%) 2/31 (7%) 1/35 (3%)

First incidence (days) — 729 (T) 574 729 (T)

Poly-3 test P=0.343 P=0.508 P=0.115 P=0.499

Uterus: Stromal Polyp

Overall rate 1/50 (2%) 0/50 (0%) 0/50 (0%) 3/50 (6%)

Adjusted rate 2.3% 0.0% 0.0% 6.9%

Terminal rate 1/36 (3%) 0/35 (0%) 0/31 (0%) 3/35 (9%)

First incidence (days) 729 (T) — — 729 (T)

Poly-3 test P=0.081 P=0.492N P=0.506N P=0.303

All Organs: Hemangiosarcoma

Overall rate 3/50 (6%) 4/50 (8%) 2/50 (4%) 1/50 (2%)

Adjusted rate 6.8% 8.8% 4.7% 2.3%

Terminal rate 2/36 (6%) 3/35 (9%) 1/31 (3%) 1/35 (3%)

First incidence (days) 606 674 662 729 (T)

Poly-3 test P=0.170N P=0.518 P=0.515N P=0.310N

All Organs: Hemangioma or Hemangiosarcoma

Overall rate 5/50 (10%) 5/50 (10%) 3/50 (6%) 2/50 (4%)

Adjusted rate 11.4% 11.0% 7.1% 4.6%

Terminal rate 4/36 (11%) 4/35 (11%) 2/31 (7%) 1/35 (3%)

First incidence (days) 606 674 662 618

Poly-3 test P=0.134N P=0.609N P=0.375N P=0.218N

All Organs: Histiocytic Sarcoma

Overall rate 0/50 (0%) 1/50 (2%) 4/50 (8%) 2/50 (4%)

Adjusted rate 0.0% 2.2% 9.3% 4.6%

Terminal rate 0/36 (0%) 1/35 (3%) 1/31 (3%) 1/35 (3%)

First incidence (days) — 729 (T) 503 535

Poly-3 test P=0.163 P=0.508 P=0.058 P=0.239

TABLE D3

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 209

All Organs: Malignant Lymphoma

Overall rate 23/50 (46%) 19/50 (38%) 28/50 (56%) 27/50 (54%)

Adjusted rate 50.5% 41.0% 63.8% 59.5%

Terminal rate 19/36 (53%) 16/35 (46%) 23/31 (74%) 22/35 (63%)

First incidence (days) 440 492 503 447

Poly-3 test P=0.089 P=0.238N P=0.138 P=0.254

All Organs: Benign Neoplasms

Overall rate 38/50 (76%) 27/50 (54%) 33/50 (66%) 31/50 (62%)

Adjusted rate 81.6% 58.6% 74.5% 67.9%

Terminal rate 31/36 (86%) 22/35 (63%) 24/31 (77%) 25/35 (71%)

First incidence (days) 524 673 574 475

Poly-3 test P=0.234N P=0.010N P=0.273N P=0.090N

All Organs: Malignant Neoplasms

Overall rate 33/50 (66%) 38/50 (76%) 41/50 (82%) 41/50 (82%)

Adjusted rate 69.9% 76.9% 88.8% 84.1%

Terminal rate 24/36 (67%) 24/35 (69%) 27/31 (87%) 29/35 (83%)

First incidence (days) 440 461 503 142

Poly-3 test P=0.041 P=0.289 P=0.018 P=0.073

All Organs: Benign or Malignant Neoplasms

Overall rate 47/50 (94%) 45/50 (90%) 46/50 (92%) 47/50 (94%)

Adjusted rate 95.8% 91.0% 98.5% 95.4%

Terminal rate 34/36 (94%) 31/35 (89%) 31/31 (100%) 33/35 (94%)

First incidence (days) 440 461 503 142

Poly-3 test P=0.439 P=0.288N P=0.427 P=0.659N

(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, ovary, pancreatic islets, and pituitary gland; for other tissues, denominator is number of animals necropsied. b Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality c Observed incidence at terminal kill d Beneath the control incidence is the P value associated with the trend test. Beneath the exposed group incidence are the P values corresponding to pairwise 

comparisons between the controls and that exposed group. The Poly-3 test accounts for the differential mortality in animals that do not reach terminal 

sacrifice. A negative trend or a lower incidence in an exposed group is indicated by N. e Not applicable; no neoplasms in animal group f A single incidence of hepatoblastoma occurred in an animal that also had an adenoma. g Value of statistic cannot be computed.

TABLE D3

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Drinking Water Study of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
210 Sodium Chlorate, NTP TR 517 

TABLE D4b

Historical Incidence of Liver Neoplasms in Control Female B6C3F1 Micea

Incidence in Controls

Hepatocellular Hepatocellular Hepatocellular

Adenoma Carcinoma Adenoma 

Study or Carcinoma

Historical Incidence in Drinking Water Controls Given NTP-2000 Diet

Dipropylene glycol 11/50 7/50 17/50

Sodium chlorate 30/49 3/49 31/49

Sodium nitrite 9/50 2/50 10/50

Overall Historical Incidence: Drinking Water Studies

Total (%) 50/149 (33.6%) 12/149 (8.1%) 58/149 (38.9%)

Mean ± standard deviation 20% ± 2.8% 9% ± 7.1% 27% ± 9.9%

Range 18%-61% 4%-14% 20%-63%

Overall Historical Incidence: All Routes

Total (%) 214/1,251 (17.1%) 90/1,251 (7.2%) 286/1,251 (22.9%)

Mean ± standard deviation 18.0% ± 11.6% 7.6% ± 4.4% 24.1% ± 12.8%

Range 6%-61% 0%-16% 8%-63%

a Data as of April 19, 2004

TABLE D4a

Historical Incidence of Pancreatic Islet Neoplasms in Control Female B6C3F1 Micea

Incidence in Controls

Adenoma Carcinoma Adenoma 

Study or Carcinoma

Historical Incidence in Drinking Water Controls Given NTP-2000 Diet

Dipropylene glycol 2/50 0/50 2/50

Sodium chlorate 0/46 0/46 0/46

Sodium nitrite 0/50 0/50 0/50

Overall Historical Incidence: Drinking Water Studies

Total (%) 2/146 (1.4%) 0/146 2/146 (1.4%)

Mean ± standard deviation 1.4% ± 2.3% 1.3% ± 2.3%

Range 0%-4% 0%-4%

Overall Historical Incidence: All Routes

Total (%) 8/1,230 (0.7%) 1/1,230 (0.1%) 9/1,230 (0.7%)

Mean ± standard deviation 0.7% ± 1.2% 0.1% ± 0.4% 0.8% ± 1.2%

Range 0%-4% 0%-2% 0%-4%

a Data as of April 19, 2004
Sodium Chlorate, NTP TR 517 211

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Accidental death 1 

Moribund 3 5 6 8 

Natural death 10 10 12 7 

Survivors 

Died last week of study 1

Terminal sacrifice 36 34 31 35 

Other 1

Animals examined microscopically 50 50 50 50

Alimentary System

Intestine large, colon (48) (49) (48) (49)

Hemorrhage 1 (2%) 

Intestine large, cecum (44) (47) (47) (47)

Edema 4 (9%) 6 (13%) 6 (13%) 6 (13%) 

Hemorrhage 1 (2%) 

Inflammation, chronic 1 (2%) 

Ulcer 1 (2%) 

Intestine small, duodenum (46) (47) (47) (50)

Ulcer 1 (2%) 1 (2%) 

Epithelium, hyperplasia 2 (4%) 

Intestine small, ileum (42) (45) (46) (47)

Inflammation, chronic 1 (2%) 1 (2%) 

Epithelium, hyperplasia 1 (2%) 1 (2%) 

Liver (49) (50) (49) (50)

Angiectasis 2 (4%) 2 (4%) 1 (2%) 

Basophilic focus 5 (10%) 4 (8%) 1 (2%) 

Clear cell focus 3 (6%) 1 (2%) 

Eosinophilic focus 9 (18%) 9 (18%) 13 (27%) 7 (14%) 

Hematopoietic cell proliferation 7 (14%) 4 (8%) 3 (6%) 8 (16%) 

Hemorrhage 1 (2%) 

Hepatodiaphragmatic nodule 1 (2%) 

Hyperplasia, lymphoid 4 (8%) 7 (14%) 3 (6%) 5 (10%) 

Infarct 1 (2%) 

Infiltration cellular, mixed cell 7 (14%) 7 (14%) 8 (16%) 7 (14%) 

Mixed cell focus 7 (14%) 2 (4%) 3 (6%) 3 (6%) 

Necrosis, focal 5 (10%) 1 (2%) 4 (8%) 1 (2%) 

Tension lipidosis 2 (4%) 3 (6%) 1 (2%) 

Centrilobular, necrosis 2 (4%) 2 (4%) 2 (4%) 2 (4%) 

Hepatocyte, karyomegaly 3 (6%) 

Hepatocyte, vacuolization cytoplasmic 4 (8%) 3 (6%) 6 (12%) 4 (8%) 

Kupffer cell, hyperplasia 1 (2%) 1 (2%) 2 (4%) 

Kupffer cell, pigmentation 3 (6%) 4 (8%) 4 (8%) 7 (14%) 

Mesentery (30) (32) (27) (24)

Angiectasis 1 (3%) 1 (4%) 

Hemorrhage 1 (3%) 

Inflammation, chronic 1 (4%) 

Fat, necrosis 21 (70%) 24 (75%) 20 (74%) 16 (67%) 

a Number of animals examined microscopically at the site and the number of animals with lesion

TABLE D5

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Drinking Water Study 

of Sodium Chloratea

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
212 Sodium Chlorate, NTP TR 517 

Alimentary System (continued)

Pancreas (46) (47) (49) (48)

Atrophy 2 (4%) 1 (2%) 1 (2%) 

Cyst 1 (2%) 1 (2%) 

Acinus, hyperplasia, focal 1 (2%) 

Salivary glands (48) (47) (49) (50)

Hyperplasia, lymphoid 16 (33%) 21 (45%) 15 (31%) 18 (36%) 

Stomach, forestomach (49) (50) (50) (49)

Diverticulum 2 (4%) 1 (2%) 1 (2%) 2 (4%) 

Edema 3 (6%) 

Erosion 1 (2%) 2 (4%) 2 (4%) 

Hyperplasia 1 (2%) 

Inflammation, chronic active 2 (4%) 2 (4%) 

Ulcer 2 (4%) 3 (6%) 3 (6%) 

Epithelium, hyperplasia 3 (6%) 4 (8%) 9 (18%) 6 (12%) 

Stomach, glandular (49) (48) (50) (49)

Erosion 1 (2%) 2 (4%) 

Ulcer 1 (2%) 

Cardiovascular System

Blood vessel (1) (3) (1)

Aorta, mineralization 1 (33%) 

Heart (49) (50) (49) (50)

Cardiomyopathy 1 (2%) 1 (2%) 1 (2%) 

Mineralization 1 (2%) 1 (2%) 2 (4%) 

Endocrine System

Adrenal cortex (50) (49) (49) (50)

Accessory adrenal cortical nodule 4 (8%) 2 (4%) 7 (14%) 7 (14%) 

Hyperplasia, focal 1 (2%) 

Capsule, hyperplasia 1 (2%) 2 (4%) 

Zona reticularis, vacuolization cytoplasmic 1 (2%) 1 (2%) 

Adrenal medulla (50) (49) (49) (50)

Hyperplasia 2 (4%) 2 (4%) 1 (2%) 

Islets, pancreatic (46) (47) (49) (49)

Hyperplasia 9 (20%) 6 (13%) 4 (8%) 3 (6%) 

Parathyroid gland (45) (47) (48) (47)

Cyst 1 (2%) 1 (2%) 2 (4%) 2 (4%) 

Pituitary gland (46) (45) (48) (50)

Pars distalis, angiectasis 1 (2%) 2 (4%) 2 (4%) 

Pars distalis, cyst 1 (2%) 

Pars distalis, hyperplasia, focal 3 (7%) 3 (7%) 3 (6%) 1 (2%) 

Thyroid gland (48) (50) (49) (50)

Degeneration, cystic 25 (52%) 28 (56%) 34 (69%) 32 (64%) 

Follicle, cyst 1 (2%) 1 (2%) 1 (2%) 

Follicular cell, cyst 2 (4%) 

Follicular cell, hypertrophy 3 (6%) 2 (4%) 5 (10%) 14 (28%) 

General Body System

None

TABLE D5

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 213

Genital System

Clitoral gland (47) (47) (47) (49)

Inflammation, chronic 2 (4%) 4 (8%) 

Ovary (45) (45) (47) (50)

Angiectasis 3 (7%) 2 (4%) 4 (9%) 3 (6%) 

Cyst 9 (20%) 14 (31%) 14 (30%) 13 (26%) 

Cyst, hemorrhagic 1 (2%) 

Hemorrhage 1 (2%) 

Thrombosis 3 (7%) 1 (2%) 1 (2%) 

Bilateral, cyst 1 (2%) 

Follicle, hemorrhage 1 (2%) 4 (9%) 4 (9%) 9 (18%) 

Granulosa cell, hyperplasia 3 (6%) 7 (14%) 

Uterus (50) (50) (50) (50)

Angiectasis 1 (2%) 2 (4%) 1 (2%) 

Hyperplasia, atypical 1 (2%) 

Hyperplasia, cystic 45 (90%) 45 (90%) 40 (80%) 41 (82%) 

Inflammation, chronic 2 (4%) 

Inflammation, suppurative 1 (2%) 

Metaplasia, squamous 2 (4%) 1 (2%) 

Endometrium, hyperplasia, atypical 1 (2%) 

Hematopoietic System

Bone marrow (50) (50) (50) (50)

Hyperplasia 14 (28%) 28 (56%) 29 (58%) 31 (62%) 

Myelofibrosis 1 (2%) 2 (4%) 1 (2%) 2 (4%) 

Lymph node (7) (5) (11) (9)

Iliac, hemorrhage 1 (9%) 

Iliac, hyperplasia, lymphoid 1 (14%) 1 (11%) 

Mediastinal, hyperplasia, lymphoid 1 (14%) 1 (20%) 2 (18%) 

Mediastinal, pigmentation 1 (14%) 

Pancreatic, hemorrhage 1 (11%) 

Renal, hemorrhage 1 (14%) 1 (11%) 

Lymph node, mandibular (46) (46) (49) (49)

Atrophy 1 (2%) 1 (2%) 

Hematopoietic cell proliferation 1 (2%) 1 (2%) 1 (2%) 

Hyperplasia, lymphoid 12 (26%) 7 (15%) 7 (14%) 10 (20%) 

Pigmentation 18 (39%) 16 (35%) 18 (37%) 15 (31%) 

Lymph node, mesenteric (47) (49) (49) (49)

Atrophy 1 (2%) 1 (2%) 2 (4%) 

Ectasia 2 (4%) 1 (2%) 

Hematopoietic cell proliferation 2 (4%) 2 (4%) 1 (2%) 2 (4%) 

Hemorrhage 4 (9%) 2 (4%) 1 (2%) 

Hyperplasia, lymphoid 10 (21%) 8 (16%) 11 (22%) 6 (12%) 

Pigmentation 1 (2%) 2 (4%) 

Spleen (49) (48) (49) (50)

Accessory spleen 1 (2%) 

Hematopoietic cell proliferation 39 (80%) 39 (81%) 35 (71%) 39 (78%) 

Hyperplasia, lymphoid 11 (22%) 10 (21%) 5 (10%) 9 (18%) 

Pigmentation 28 (57%) 30 (63%) 28 (57%) 27 (54%) 

Lymphoid follicle, atrophy 1 (2%) 2 (4%) 1 (2%) 2 (4%) 

Thymus (48) (44) (48) (48)

Atrophy 5 (10%) 7 (16%) 5 (10%) 9 (19%) 

Cyst 3 (6%) 1 (2%) 1 (2%) 

Hyperplasia, lymphoid 5 (10%) 3 (7%) 4 (8%) 2 (4%) 

TABLE D5

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
214 Sodium Chlorate, NTP TR 517 

Integumentary System

Mammary gland (50) (50) (50) (50)

Hyperplasia 5 (10%) 11 (22%) 8 (16%) 10 (20%) 

Skin (48) (50) (50) (50)

Edema 1 (2%) 1 (2%) 

Epidermis, hyperplasia 1 (2%) 1 (2%) 

Subcutaneous tissue, edema 1 (2%) 2 (4%) 

Musculoskeletal System

Bone (50) (50) (50) (50)

Callus 1 (2%) 

Fracture 1 (2%) 1 (2%) 

Hyperostosis 1 (2%) 1 (2%) 4 (8%) 3 (6%) 

Cranium, osteopetrosis 1 (2%) 

Femur, osteopetrosis 1 (2%) 1 (2%) 

Skeletal muscle (2) (4) (6)

Angiectasis 1 (17%) 

Atrophy 1 (17%) 

Nervous System

Brain (50) (50) (50) (50)

Compression 1 (2%) 1 (2%) 1 (2%) 

Inflammation, chronic 1 (2%) 

Necrosis 1 (2%) 1 (2%) 

Peripheral nerve (2) (2)

Atrophy 1 (50%) 2 (100%)

Respiratory System

Lung (50) (50) (49) (50)

Edema 5 (10%) 8 (16%) 3 (6%) 5 (10%) 

Foreign body 2 (4%) 

Hemorrhage 5 (10%) 8 (16%) 6 (12%) 4 (8%) 

Hyperplasia, lymphoid 10 (20%) 8 (16%) 3 (6%) 9 (18%) 

Infiltration cellular, polymorphonuclear 1 (2%) 

Infiltration cellular, histiocyte 1 (2%) 1 (2%) 3 (6%) 5 (10%) 

Metaplasia, osseous 1 (2%) 2 (4%) 

Thrombosis 1 (2%) 4 (8%) 1 (2%) 

Alveolar epithelium, hyperplasia 2 (4%) 2 (4%) 1 (2%) 2 (4%) 

Special Senses System

Eye (50) (48) (50) (50)

Inflammation, chronic 3 (6%) 3 (6%) 

Cornea, hyperplasia 2 (4%) 1 (2%) 

Harderian gland (50) (50) (50) (49)

Cyst 1 (2%) 

Hyperplasia, focal 1 (2%) 1 (2%) 1 (2%) 

TABLE D5

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 215

Urinary System

Kidney (50) (49) (49) (50)

Hydronephrosis 1 (2%) 1 (2%) 

Hyperplasia, lymphoid 8 (16%) 9 (18%) 6 (12%) 8 (16%) 

Infarct 3 (6%) 2 (4%) 4 (8%) 5 (10%) 

Metaplasia, osseous 1 (2%) 3 (6%) 2 (4%) 

Nephropathy 14 (28%) 11 (22%) 14 (29%) 12 (24%) 

Renal tubule, accumulation, hyaline droplet 2 (4%) 1 (2%) 2 (4%) 1 (2%) 

Renal tubule, dilatation 1 (2%) 1 (2%) 

Renal tubule, necrosis 1 (2%) 1 (2%) 

Renal tubule, pigmentation 3 (6%) 1 (2%) 1 (2%) 

Transitional epithelium, hyperplasia 1 (2%) 

Urinary bladder (49) (50) (50) (50)

Hyperplasia, lymphoid 4 (8%) 12 (24%) 4 (8%) 5 (10%) 

Transitional epithelium, hyperplasia 1 (2%) 

TABLE D5

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
216 Sodium Chlorate, NTP TR 517 
217

APPENDIX E

GENETIC TOXICOLOGY

SALMONELLA TYPHIMURIUM MUTAGENICITY TEST PROTOCOL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218

MOUSE PERIPHERAL BLOOD MICRONUCLEUS TEST PROTOCOL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218

EVALUATION PROTOCOL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218

RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219

TABLE E1 Mutagenicity of Sodium Chlorate in Salmonella typhimurium . . . . . . . . . . . . . . . . . . . . . . . . 220

TABLE E2 Frequency of Micronuclei in Peripheral Blood Erythrocytes of Mice

Following Administration of Sodium Chlorate in Drinking Water for 3 Weeks . . . . . . . . . 222
218 Sodium Chlorate, NTP TR 517 

GENETIC TOXICOLOGY

SALMONELLA TYPHIMURIUM MUTAGENICITY TEST PROTOCOL

Testing was performed as reported by Zeiger et al. (1992). Sodium chlorate was sent to the laboratory as a coded

aliquot. It was incubated with the Salmonella typhimurium tester strains TA97, TA98, TA100, TA102, TA104, and

TA1535 either in buffer or S9 mix (metabolic activation enzymes and cofactors from Aroclor 1254-induced male

Sprague-Dawley rat or Syrian hamster liver) for 20 minutes at 37° C. Top agar supplemented with L-histidine and

d-biotin was added, and the contents of the tubes were mixed and poured onto the surfaces of minimal glucose agar

plates. Histidine-independent mutant colonies arising on these plates were counted following incubation for 2 days

at 37° C.

Each trial consisted of triplicate plates of concurrent positive and negative controls and at least five doses of

sodium chlorate. In the absence of toxicity, 10,000 μg/plate was selected as the high dose. All trials were repeated

at the same or a higher S9 fraction. 

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. 

MOUSE PERIPHERAL BLOOD MICRONUCLEUS TEST PROTOCOL

A detailed discussion of this assay is presented by MacGregor et al. (1990). At the end of the 3-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 acridine orange and coded. Slides

were scanned to determine the frequency of micronuclei in 2,000 normochromatic erythrocytes (NCEs) in each of

10 animals per exposure group. In addition, the percentage of polychromatic erythrocytes (PCEs) in a population

of 1,000 erythrocytes was determined as a measure of bone marrow toxicity.

The results were tabulated as the mean of the pooled results from all animals within a treatment group plus or

minus the standard error of the mean. The frequency of micronucleated cells among NCEs was analyzed by a

statistical software package that tested for increasing trend over exposure groups with a one-tailed CochranArmitage trend test, followed by pairwise comparisons between each exposure group and the control group (ILS,

1990). In the presence of excess binomial variation, as detected by a binomial dispersion test, the binomial

variance of the Cochran-Armitage test was adjusted upward in proportion to the excess variation. In the

micronucleus test, an individual trial is considered positive if the trend test P value is less than or equal to 0.025 or

if the P value for any single exposed group is less than or equal to 0.025 divided by the number of exposed groups.

A final call of positive for micronucleus induction is preferably based on reproducibly positive trials (as noted

above). Results of the 3-week studies were accepted without repeat tests, because additional test data could not be

obtained. Ultimately, the final call is determined by the scientific staff after considering the results of statistical

analyses, the reproducibility of any effects observed, and the magnitudes of those effects.

EVALUATION PROTOCOL

These are the basic guidelines for arriving at an overall assay result for assays performed by the National

Toxicology Program. Statistical as well as biological factors are considered. For an individual assay, the statistical

procedures for data analysis have been described in the preceding protocols. There have been instances, however,
Sodium Chlorate, NTP TR 517 219

in which multiple aliquots of a chemical were tested in the same assay, and different results were obtained among

aliquots and/or among laboratories. Results from more than one aliquot or from more than one laboratory are not

simply combined into an overall result. Rather, all the data are critically evaluated, particularly with regard to

pertinent protocol variations, in determining the weight of evidence for an overall conclusion of chemical activity

in an assay. In addition to multiple aliquots, the in vitro assays have another variable that must be considered in

arriving at an overall test result. In vitro assays are conducted with and without exogenous metabolic activation.

Results obtained in the absence of activation are not combined with results obtained in the presence of activation;

each testing condition is evaluated separately. The summary table in the Abstract of this Technical Report presents

a result that represents a scientific judgement of the overall evidence for activity of the chemical in an assay.

RESULTS

Sodium chlorate (100 to 10,000 μg/plate) was not mutagenic in S. typhimurium strains TA97, TA98, TA100,

TA102, TA104, or TA1535, with or without induced rat or hamster liver S9 enzymes. In vivo, no increases in the

frequencies of micronucleated NCEs were seen in peripheral blood samples from male and female B6C3F1 mice

exposed to concentrations of 125 to 2,000 mg/L sodium chlorate in drinking water for 3 weeks. The abbreviated

exposure duration of 3 weeks may not have allowed steady state to be reached in the circulating NCE population,

but the data are clearly negative, with no indication of an exposure concentration-related increase in NCEs. Steady

state is usually established by day 35 of continuous exposure.
220 Sodium Chlorate, NTP TR 517 

TABLE E1

Mutagenicity of Sodium Chlorate in Salmonella typhimuriuma

Revertants/Plateb

Strain Dose –S9 hamster S9 rat S9

(μg/plate) Trial 1 Trial 2 + 10% + 30% + 10% + 30%

TA102 0 216 ± 5.2 233 ± 20.7 331 ± 9.8 264 ± 4.3 309 ± 27.7 275 ± 11.5

100 210 ± 5.2 220 ± 16.4 359 ± 16.0 250 ± 3.3 340 ± 40.5 264 ± 23.0

333 219 ± 3.3 225 ± 14.6 331 ± 7.2 259 ± 13.9 347 ± 31.0 254 ± 20.0

1,000 233 ± 12.5 233 ± 16.9 305 ± 13.3 286 ± 5.8 357 ± 23.1 291 ± 9.6

3,333 242 ± 22.7 238 ± 6.5 349 ± 4.5 291 ± 6.5 373 ± 34.6 274 ± 8.6

10,000 209 ± 5.2 248 ± 19.3 392 ± 7.9 252 ± 20.8 322 ± 32.4 257 ± 11.6

Trial summary Negative Negative Negative Negative Negative Negative

Positive controlc 737 ± 24.1 898 ± 41.7 1,211 ± 42.0 784 ± 15.3 1,110 ± 60.9 768 ± 24.3

TA104 0 298 ± 8.0 334 ± 16.8 430 ± 10.4 430 ± 11.2 397 ± 15.2 405 ± 10.0

100 289 ± 29.1 328 ± 6.4 411 ± 2.7 432 ± 14.7 377 ± 25.2 411 ± 1.7

333 285 ± 32.8 324 ± 26.7 426 ± 12.2 408 ± 11.4 368 ± 22.2 399 ± 7.5

1,000 262 ± 18.1 364 ± 28.0 365 ± 2.3 406 ± 16.6 425 ± 20.0 398 ± 17.3

3,333 314 ± 9.8 326 ± 16.2 363 ± 12.3 411 ± 3.8 427 ± 22.8 416 ± 9.8

10,000 302 ± 8.2 342 ± 17.9 384 ± 40.0 407 ± 1.5 410 ± 4.9 412 ± 0.9

Trial summary Negative Negative Negative Negative Negative Negative

Positive control 939 ± 17.9 921 ± 42.5 1,254 ± 25.9 974 ± 31.5 1,266 ± 29.0 826 ± 47.6

TA100 0 145 ± 6.9 137 ± 8.7 120 ± 7.3 126 ± 9.5 133 ± 5.2 122 ± 12.4

100 125 ± 3.8 117 ± 4.4 130 ± 1.3 130 ± 9.3 162 ± 2.0 124 ± 9.5

333 134 ± 7.3 127 ± 9.1 124 ± 0.0 135 ± 5.5 131 ± 3.3 148 ± 2.9

1,000 131 ± 7.6 126 ± 9.1 137 ± 7.4 152 ± 8.5 134 ± 7.0 125 ± 2.0

3,333 135 ± 8.7 121 ± 3.8 126 ± 11.2 134 ± 8.8 139 ± 13.4 134 ± 9.5

10,000 144 ± 4.9 132 ± 5.5 128 ± 8.9 126 ± 10.1 122 ± 1.7 131 ± 12.5

Trial summary Negative Negative Negative Negative Negative Negative

Positive control 900 ± 12.3 844 ± 5.1 695 ± 18.5 664 ± 21.1 635 ± 24.8 624 ± 15.4

TA1535 0 13 ± 2.4 11 ± 2.3 12 ± 0.9 12 ± 2.0 12 ± 1.5 13 ± 1.2

100 11 ± 0.3 8 ± 1.2 10 ± 0.3 12 ± 0.7 13 ± 0.6 15 ± 2.0

333 9 ± 0.6 11 ± 2.3 9 ± 1.2 15 ± 1.8 9 ± 0.0 10 ± 1.8

1,000 12 ± 2.0 11 ± 1.3 10 ± 2.7 10 ± 1.2 7 ± 0.6 10 ± 1.2

3,333 11 ± 1.7 7 ± 0.7 9 ± 0.6 12 ± 3.4 8 ± 0.7 10 ± 3.2

10,000 9 ± 1.0 9 ± 1.7 10 ± 1.8 8 ± 0.7 6 ± 1.9 12 ± 2.7

Trial summary Negative Negative Negative Negative Negative Negative

Positive control 938 ± 15.5 940 ± 16.2 126 ± 14.0 141 ± 5.0 130 ± 15.1 115 ± 6.9

TA97 0 128 ± 10.5 139 ± 9.5 146 ± 4.5 169 ± 3.3 154 ± 5.3 174 ± 6.3

100 117 ± 11.1 147 ± 14.3 148 ± 18.1 151 ± 7.5 157 ± 9.8 191 ± 13.8

333 127 ± 14.3 132 ± 10.8 157 ± 12.1 177 ± 10.4 132 ± 3.3 191 ± 14.0

1,000 145 ± 11.4 126 ± 9.6 136 ± 5.2 155 ± 3.7 140 ± 15.5 167 ± 25.2

3,333 121 ± 7.8 149 ± 10.6 138 ± 13.3 160 ± 6.6 158 ± 13.2 210 ± 9.3

10,000 121 ± 6.1 125 ± 4.0 88 ± 45.6 142 ± 10.7 131 ± 8.2 173 ± 19.8

Trial summary Negative Negative Negative Negative Negative Negative

Positive control 572 ± 16.9 640 ± 21.1 710 ± 8.9 660 ± 6.7 653 ± 15.0 650 ± 23.7
Sodium Chlorate, NTP TR 517 221

TABLE E1

Mutagenicity of Sodium Chlorate in Salmonella typhimurium

Revertants/Plate

Strain Dose –S9 hamster S9 rat S9

(μg/plate) Trial 1 Trial 2 + 10% + 30% + 10% + 30%

TA98 0 12 ± 0.9 21 ± 2.7 18 ± 2.4 11 ± 1.5 30 ± 3.2 15 ± 2.6

100 12 ± 1.5 22 ± 1.8 19 ± 5.0 13 ± 1.7 26 ± 1.8 10 ± 1.2

333 10 ± 0.3 19 ± 4.1 24 ± 1.5 9 ± 2.6 23 ± 1.2 12 ± 1.2

1,000 11 ± 2.1 21 ± 3.2 25 ± 0.7 14 ± 2.4 21 ± 2.0 8 ± 0.9

3,333 12 ± 1.0 24 ± 4.3 26 ± 2.3 10 ± 1.9 30 ± 0.9 13 ± 1.9

10,000 13 ± 1.5 21 ± 6.1 27 ± 1.7 10 ± 1.2 27 ± 4.3 13 ± 2.7

Trial summary Negative Negative Negative Negative Negative Negative

Positive control 380 ± 8.3 443 ± 16.9 534 ± 11.4 478 ± 6.7 466 ± 15.8 431 ± 7.8

a Study performed at SRI International. The detailed protocol is presented by Zeiger et al. (1992). 0 μg/plate was the solvent control. b Revertants are presented as mean ± standard error from three plates. c The positive controls in the absence of metabolic activation were sodium azide (TA100 and TA1535), 9-aminoacridine (TA97), 4-nitro-ophenylenediamine (TA98), mitomycin-C (TA102), and methyl methanesulfonate (TA104). The positive control for metabolic activation with

all strains was 2-aminoanthracene, and 2-aminoanthracene or sterigmatocystin was used for TA102. 
222 Sodium Chlorate, NTP TR 517 

TABLE E2

Frequency of Micronuclei in Peripheral Blood Erythrocytes of Mice Following Administration 

of Sodium Chlorate in Drinking Water for 3 Weeksa

Number of Mice 

Concentration with Erythrocytes Micronucleated NCEs/ P Valuec PCEs (%)

(mg/L) Scored 1,000 NCEsb

Male

Tap waterd 10 1.20 ± 0.20 2.510 ± 0.15

Sodium chlorate 125 10 1.25 ± 0.13 0.4432 2.350 ± 0.10

250 10 1.10 ± 0.16 0.6160 2.190 ± 0.08

500 10 0.75 ± 0.21 0.9253 2.260 ± 0.11

1,000 10 1.05 ± 0.14 0.6727 2.080 ± 0.11

2,000 10 1.25 ± 0.23 0.4432 2.040 ± 0.08

P=0.406e

Female

Tap water 10 0.95 ± 0.16 1.890 ± 0.07

Sodium chlorate 125 10 1.05 ± 0.24 0.3759 1.820 ± 0.11

250 10 1.00 ± 0.18 0.4364 1.750 ± 0.14

500 10 0.65 ± 0.18 0.8557 1.680 ± 0.10

1,000 10 0.85 ± 0.17 0.6306 1.840 ± 0.10

2,000 10 1.15 ± 0.18 0.2684 2.040 ± 0.12

P=0.285

a Study was performed at SITEK Research Laboratories, Inc. The detailed protocol is presented by MacGregor et al. (1990).

NCE=normochromatic erythrocyte; PCE=polychromatic erythrocyte b Mean ± standard error c Pairwise comparison with the vehicle control, significant at P#0.005 (ILS, 1990) d Vehicle control e Significance of micronucleated NCEs/1,000 NCEs tested by the one-tailed trend test, significant at P#0.025 (ILS, 1990)
223

APPENDIX F

CLINICAL PATHOLOGY RESULTS

TABLE F1 Hematology and Clinical Chemistry Data for Rats 

in the 3-Week Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . 224

TABLE F2 Hematology Data for Mice

in the 3-Week Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
224 Sodium Chlorate, NTP TR 517 

Male

Hematology

n 10 10 10 10 10 10

Hematocrit (%) 

Day 4 42.7 ± 1.1 41.8 ± 0.8 42.4 ± 0.8 42.9 ± 1.2 42.5 ± 1.2 41.2 ± 0.8 

Day 22 44.7 ± 0.5 44.8 ± 0.5 44.1 ± 0.7 43.3 ± 0.8 44.1 ± 0.5 42.1 ± 0.6**

Hemoglobin (g/dL) 

Day 4 14.1 ± 0.3 13.8 ± 0.2 14.1 ± 0.2 14.3 ± 0.4 14.1 ± 0.4 13.7 ± 0.2 

Day 22 14.9 ± 0.2 15.1 ± 0.1 14.9 ± 0.2 14.7 ± 0.2 14.7 ± 0.2 14.0 ± 0.2** 

Erythrocytes (106/μL) 

Day 4 7.22 ± 0.17 7.08 ± 0.13 7.24 ± 0.11 7.24 ± 0.18 7.21 ± 0.18 7.04 ± 0.14

Day 22 8.05 ± 0.09 8.05 ± 0.07 7.91 ± 0.14 7.80 ± 0.11 7.86 ± 0.09 7.53 ± 0.11** 

Reticulocytes (106/μL) 

Day 4 0.76 ± 0.02 0.74 ± 0.02 0.73 ± 0.03 0.77 ± 0.03 0.77 ± 0.03 0.73 ± 0.02

Day 22 0.43 ± 0.01 0.44 ± 0.01 0.44 ± 0.01 0.46 ± 0.01 0.46 ± 0.01 0.41 ± 0.01 

Mean cell volume (fL) 

Day 4 59.1 ± 0.4 59.0 ± 0.4 58.6 ± 0.3 59.3 ± 0.2 58.9 ± 0.3 58.5 ± 0.2 

Day 22 55.5 ± 0.3 55.6 ± 0.2 55.7 ± 0.2 55.4 ± 0.4 56.1 ± 0.2 55.9 ± 0.2 

Mean cell hemoglobin (pg) 

Day 4 19.6 ± 0.1 19.5 ± 0.1 19.5 ± 0.1 19.7 ± 0.1 19.6 ± 0.2 19.5 ± 0.1 

Day 22 18.6 ± 0.1 18.7 ± 0.1 18.9 ± 0.1 18.9 ± 0.1 18.7 ± 0.1 18.6 ± 0.1 

Mean cell hemoglobin concentration (g/dL) 

Day 4 33.1 ± 0.2 33.1 ± 0.1 33.3 ± 0.3 33.2 ± 0.2 33.3 ± 0.2 33.2 ± 0.2 

Day 22 33.4 ± 0.3 33.7 ± 0.2 33.8 ± 0.3 34.1 ± 0.2 33.3 ± 0.2 33.3 ± 0.1

Platelets (103/μL) 

Day 4 850.4 ± 14.0 859.4 ± 15.7 820.7 ± 9.1 866.1 ± 20.0 888.2 ± 13.4 869.2 ± 20.5 

Day 22 925.5 ± 16.4 958.0 ± 19.0 934.4 ± 18.7 954.9 ± 13.0 908.9 ± 19.7 837.3 ± 11.8** 

Leukocytes (103/μL) 

Day 4 8.05 ± 0.39 7.91 ± 0.27 8.20 ± 0.21 7.89 ± 0.30 7.06 ± 0.45 7.71 ± 0.29 

Day 22 10.82 ± 0.50 10.28 ± 0.14 9.73 ± 0.29 10.10 ± 0.25 9.52 ± 0.31 9.71 ± 0.33 

Segmented neutrophils (103/μL) 

Day 4 1.09 ± 0.05 1.01 ± 0.04 0.91 ± 0.05* 0.63 ± 0.04** 0.48 ± 0.04** 0.47 ± 0.04** 

Day 22 1.05 ± 0.04 0.85 ± 0.04** 0.70 ± 0.03** 0.66 ± 0.04** 0.54 ± 0.03** 0.38 ± 0.02** 

Lymphocytes (103/μL) 

Day 4 6.69 ± 0.36 6.63 ± 0.26 7.01 ± 0.19 6.98 ± 0.30 6.34 ± 0.43 6.96 ± 0.26 

Day 22 9.49 ± 0.47 9.15 ± 0.12 8.77 ± 0.26 9.20 ± 0.27 8.74 ± 0.30 9.10 ± 0.31 

Activated lymphocytes (103/μL) 

Day 4 0.10 ± 0.01 0.11 ± 0.01 0.11 ± 0.01 0.12 ± 0.01 0.10 ± 0.01 0.14 ± 0.01* 

Day 22 0.09 ± 0.02 0.08 ± 0.01 0.07 ± 0.01 0.08 ± 0.01 0.08 ± 0.01b 0.10 ± 0.01 

Monocytes (103/μL) 

Day 4 0.12 ± 0.01 0.11 ± 0.00 0.12 ± 0.01 0.10 ± 0.01 0.10 ± 0.01 0.10 ± 0.01 

Day 22 0.15 ± 0.02 0.15 ± 0.01 0.15 ± 0.02 0.12 ± 0.01 0.12 ± 0.01b 0.07 ± 0.01** 

Basophils (103/μL) 

Day 4 0.005 ± 0.002 0.006 ± 0.002 0.008 ± 0.002 0.013 ± 0.004 0.007 ± 0.002 0.007 ± 0.002 

Day 22 0.012 ± 0.003 0.012 ± 0.001 0.010 ± 0.001 0.010 ± 0.002 0.010 ± 0.002b 0.012 ± 0.001 

Eosinophils (103/μL) 

Day 4 0.05 ± 0.01 0.04 ± 0.01 0.05 ± 0.01 0.07 ± 0.03 0.03 ± 0.00 0.04 ± 0.00 

Day 22 0.04 ± 0.01 0.04 ± 0.00 0.03 ± 0.00 0.04 ± 0.01 0.05 ± 0.01 0.04 ± 0.00 

Methemoglobin (g/dL) 

Day 4 0.17 ± 0.04 0.34 ± 0.15 0.20 ± 0.04 0.20 ± 0.05b 0.27 ± 0.04 0.22 ± 0.04 

Day 22 0.20 ± 0.03 0.27 ± 0.02 0.20 ± 0.03 0.18 ± 0.03 0.17 ± 0.03 0.21 ± 0.06 

TABLE F1

Hematology and Clinical Chemistry Data for Rats in the 3-Week Drinking Water Study of Sodium Chloratea

0 mg/L 125 mg/L 250 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 225

Male (continued)

Clinical Chemistry

Day 4 10 10 10 10 9 10

Day 22 10 10 10 10 10 10

Urea nitrogen (mg/dL) 

Day 4 10.0 ± 0.9 11.2 ± 0.7 9.5 ± 0.5 9.1 ± 0.7 10.3 ± 0.8 10.8 ± 0.5 

Day 22 10.7 ± 0.4 10.4 ± 0.4 10.7 ± 0.5 10.9 ± 0.4 10.1 ± 0.4 10.3 ± 0.5 

Creatinine (mg/dL) 

Day 4 0.39 ± 0.01 0.38 ± 0.02 0.34 ± 0.02 0.38 ± 0.02 0.40 ± 0.02 0.38 ± 0.01 

Day 22 0.41 ± 0.01 0.42 ± 0.01 0.42 ± 0.02 0.41 ± 0.01 0.40 ± 0.02 0.44 ± 0.02 

Total protein (g/dL) 

Day 4 5.4 ± 0.1 5.5 ± 0.1 5.4 ± 0.1 5.4 ± 0.1 5.5 ± 0.2 5.6 ± 0.1 

Day 22 5.8 ± 0.1 5.9 ± 0.1 5.8 ± 0.1 5.8 ± 0.1 5.8 ± 0.1 5.8 ± 0.1 

Albumin (g/dL) 

Day 4 4.0 ± 0.1 4.0 ± 0.1 3.9 ± 0.1b 3.9 ± 0.1 4.0 ± 0.1 4.1 ± 0.1 

Day 22 4.3 ± 0.1 4.5 ± 0.0 4.3 ± 0.0 4.3 ± 0.0 4.3 ± 0.0 4.4 ± 0.0 

Alanine aminotransferase (IU/L) 

Day 4 69 ± 2 66 ± 1 64 ± 1 69 ± 2 62 ± 2 64 ± 2 

Day 22 52 ± 1 54 ± 2 52 ± 1 54 ± 1 54 ± 1 51 ± 1

Alkaline phosphatase (IU/L) 

Day 4 740 ± 21 720 ± 34 682 ± 17 730 ± 31 733 ± 26 706 ± 16 

Day 22 536 ± 8 548 ± 8 531 ± 6 541 ± 7 544 ± 9 489 ± 10* 

Creatine kinase (IU/L) 

Day 4 236 ± 23 224 ± 27 238 ± 27 274 ± 26 252 ± 39 228 ± 25 

Day 22 104 ± 19 78 ± 11b 83 ± 10 109 ± 17c 68 ± 7b 99 ± 17c

Sorbitol dehydrogenase (IU/L)

Day 22 6 ± 0d 8 ± 0*d 8 ± 2b 8 ± 2c 7 ± 1c 6 ± 1c

Bile acids (μmol/L) 

Day 4 34.3 ± 5.7 28.1 ± 2.3 27.5 ± 1.9 30.4 ± 4.2 30.5 ± 2.5 26.0 ± 2.6

Day 22 32.6 ± 2.7 28.5 ± 3.0 28.0 ± 1.9 25.3 ± 1.1 26.0 ± 1.0 38.6 ± 4.3

Female

n 10 10 10 10 10 10

Hematology

Hematocrit (%) 

Day 4 43.4 ± 0.6 43.6 ± 0.7 43.9 ± 0.9 42.1 ± 0.9 43.1 ± 0.8 42.7 ± 0.6 

Day 22 43.9 ± 0.6 43.7 ± 0.6 44.1 ± 1.1 44.4 ± 0.6 44.8 ± 0.3 43.4 ± 0.7

Hemoglobin (g/dL) 

Day 4 14.2 ± 0.2 14.2 ± 0.2 14.6 ± 0.3 13.8 ± 0.3 14.2 ± 0.3 14.0 ± 0.1 

Day 22 14.8 ± 0.2 14.6 ± 0.2 14.8 ± 0.3 14.9 ± 0.2 14.9 ± 0.1 14.3 ± 0.2 

Erythrocytes (106/μL) 

Day 4 7.60 ± 0.09 7.61 ± 0.13 7.65 ± 0.17 7.30 ± 0.15 7.51 ± 0.14 7.40 ± 0.08

Day 22 8.41 ± 0.13 8.28 ± 0.11 8.34 ± 0.24 8.47 ± 0.12 8.47 ± 0.08 8.20 ± 0.13 

Reticulocytes (106/μL) 

Day 4 0.60 ± 0.03 0.63 ± 0.02 0.60 ± 0.02 0.66 ± 0.02 0.62 ± 0.02 0.60 ± 0.03 

Day 22 0.24 ± 0.01b 0.24 ± 0.01 0.29 ± 0.07 0.24 ± 0.01 0.25 ± 0.01 0.26 ± 0.01 

Mean cell volume (fL) 

Day 4 57.1 ± 0.3 57.4 ± 0.1 57.5 ± 0.3 57.8 ± 0.1 57.5 ± 0.3 57.7 ± 0.3 

Day 22 52.3 ± 0.2 52.8 ± 0.1 53.0 ± 0.5 52.4 ± 0.2 52.8 ± 0.2 52.9 ± 0.2 

TABLE F1

Hematology and Clinical Chemistry Data for Rats in the 3-Week Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 250 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
226 Sodium Chlorate, NTP TR 517 

Female (continued)

n 10 10 10 10 10 10

Hematology (continued)

Mean cell hemoglobin (pg) 

Day 4 18.7 ± 0.1 18.7 ± 0.1 19.0 ± 0.1 19.0 ± 0.1 18.9 ± 0.1 18.9 ± 0.1 

Day 22 17.6 ± 0.1 17.6 ± 0.1 17.7 ± 0.2 17.6 ± 0.1 17.6 ± 0.1 17.5 ± 0.1 

Mean cell hemoglobin concentration (g/dL) 

Day 4 32.8 ± 0.2 32.6 ± 0.2 33.1 ± 0.2 32.8 ± 0.3 32.9 ± 0.1 32.8 ± 0.3 

Day 22 33.7 ± 0.2 33.4 ± 0.2 33.5 ± 0.2 33.5 ± 0.1 33.3 ± 0.1 33.0 ± 0.1*

Platelets (103/μL) 

Day 4 834.0 ± 19.3 846.3 ± 21.4 832.7 ± 7.6 818.1 ± 18.5 866.9 ± 24.6 843.4 ± 10.2 

Day 22 846.0 ± 16.9 871.8 ± 14.2 844.3 ± 13.7 803.3 ± 17.8 842.2 ± 19.3 860.5 ± 18.8 

Leukocytes (103/μL) 

Day 4 8.83 ± 0.41 8.57 ± 0.47 8.94 ± 0.40 8.44 ± 0.30 8.24 ± 0.51 8.53 ± 0.34 

Day 22 10.14 ± 0.35 9.32 ± 0.29 9.71 ± 0.61 10.63 ± 0.39 10.28 ± 0.51 10.63 ± 0.43 

Segmented neutrophils (103/μL) 

Day 4 1.02 ± 0.08 0.87 ± 0.08 0.82 ± 0.03* 0.67 ± 0.04** 0.58 ± 0.05** 0.46 ± 0.03** 

Day 22 0.93 ± 0.05 0.63 ± 0.03** 0.66 ± 0.05** 0.61 ± 0.04** 0.57 ± 0.07** 0.46 ± 0.04** 

Lymphocytes (103/μL) 

Day 4 7.54 ± 0.37 7.50 ± 0.42 7.84 ± 0.39 7.51 ± 0.28 7.40 ± 0.47 7.80 ± 0.31 

Day 22 8.94 ± 0.31 8.45 ± 0.26 8.75 ± 0.56 9.72 ± 0.35 9.40 ± 0.46 9.88 ± 0.40 

Activated lymphocytes (103/μL) 

Day 4 0.10 ± 0.01 0.11 ± 0.01 0.11 ± 0.01 0.11 ± 0.01 0.10 ± 0.02 0.13 ± 0.01 

Day 22 0.08 ± 0.01 0.07 ± 0.01 0.09 ± 0.01 0.09 ± 0.01 0.10 ± 0.01 0.10 ± 0.01* 

Monocytes (103/μL) 

Day 4 0.12 ± 0.02 0.11 ± 0.01 0.11 ± 0.01 0.10 ± 0.01 0.08 ± 0.01* 0.09 ± 0.01* 

Day 22 0.11 ± 0.01 0.10 ± 0.01 0.13 ± 0.01 0.14 ± 0.01 0.13 ± 0.01 0.10 ± 0.01 

Basophils (103/μL) 

Day 4 0.006 ± 0.002 0.008 ± 0.002 0.007 ± 0.002 0.008 ± 0.002 0.010 ± 0.001 0.008 ± 0.001 

Day 22 0.016 ± 0.003 0.013 ± 0.003 0.017 ± 0.003 0.015 ± 0.002 0.019 ± 0.004 0.016 ± 0.003 

Eosinophils (103/μL) 

Day 4 0.05 ± 0.01 0.03 ± 0.01 0.05 ± 0.01 0.05 ± 0.01 0.06 ± 0.01 0.05 ± 0.01 

Day 22 0.06 ± 0.01 0.06 ± 0.01 0.07 ± 0.01 0.06 ± 0.01 0.06 ± 0.01 0.07 ± 0.01 

Methemoglobin (g/dL) 

Day 4 0.14 ± 0.02 0.14 ± 0.03 0.19 ± 0.03 0.15 ± 0.02 0.14 ± 0.02 0.18 ± 0.02 

Day 22 0.21 ± 0.03 0.20 ± 0.03 0.21 ± 0.02 0.21 ± 0.02 0.21 ± 0.03 0.19 ± 0.02 

Clinical Chemistry

Urea nitrogen (mg/dL) 

Day 4 11.1 ± 0.7 10.6 ± 7.5 11.6 ± 0.6 10.0 ± 0.6 10.3 ± 0.7 11.4 ± 0.7 

Day 22 15.0 ± 0.4 14.3 ± 0.4 14.0 ± 0.6 13.8 ± 0.3 13.9 ± 0.5 12.53 ± 0.4** 

Creatinine (mg/dL) 

Day 4 0.37 ± 0.02 0.37 ± 0.02 0.37 ± 0.02 0.37 ± 0.02 0.36 ± 0.02 0.38 ± 0.01 

Day 22 0.51 ± 0.01 0.54 ± 0.01 0.52 ± 0.02 0.50 ± 0.02 0.53 ± 0.02 0.50 ± 0.00 

Total protein (g/dL) 

Day 4 5.4 ± 0.1 5.3 ± 0.1 5.3 ± 0.1 5.3 ± 0.1 5.4 ± 0.1 5.4 ± 0.1 

Day 22 6.1 ± 0.1 5.9 ± 0.1 6.1 ± 0.1 5.8 ± 0.1 6.1 ± 0.1 6.0 ± 0.1 

Albumin (g/dL) 

Day 4 4.2 ± 0.1 4.2 ± 0.1 4.2 ± 0.1 4.1 ± 0.1 4.2 ± 0.1 4.2 ± 0.1 

Day 22 4.7 ± 0.1 4.7 ± 0.0 4.7 ± 0.1 4.5 ± 0.0 4.7 ± 0.0 4.6 ± 0.1 

TABLE F1

Hematology and Clinical Chemistry Data for Rats in the 3-Week Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 250 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
Sodium Chlorate, NTP TR 517 227

Female (continued)

n 10 10 10 10 10 10

Clinical Chemistry (continued)

Alanine aminotransferase (IU/L)

Day 4 49 ± 2 51 ± 2 49 ± 2 47 ± 1 57 ± 6b 52 ± 2 

Day 22 40 ± 2 41 ± 1 43 ± 1 42 ± 1 41 ± 1 39 ± 1

Alkaline phosphatase (IU/L) 

Day 4 557 ± 17 564 ± 12 554 ± 15 572 ± 14 551 ± 13 570 ± 20b

Day 22 388 ± 11 377 ± 6 367 ± 10 374 ± 7 360 ± 8 366 ± 8

Creatine kinase (IU/L) 

Day 4 294 ± 63 254 ± 30 242 ± 36 208 ± 19 298 ± 76 248 ± 30

Day 22 152 ± 15 116 ± 8 160 ± 26 120 ± 19 148 ± 18 114 ± 12

Sorbitol dehydrogenase (IU/L) 

Day 22 4 ± 1 3 ± 0 3 ± 0 4 ± 0 4 ± 0 3 ± 0

Bile acids (μmol/L) 

Day 4 30.6 ± 3.0 30.2 ± 2.2 28.9 ± 1.2 29.4 ± 2.1 30.8 ± 2.4 31.6 ± 2.2 

Day 22 23.3 ± 2.6 23.1 ± 1.8 22.8 ± 1.9 20.4 ± 1.1 24.8 ± 1.9 17.9 ± 1.0

* Significantly different (P#0.05) from the chamber control group by Dunn’s or Shirley’s test

** P#0.01 a Mean ± standard error. Statistical tests were performed on unrounded data. b n=9 c n=8 d n=7

TABLE F1

Hematology and Clinical Chemistry Data for Rats in the 3-Week Drinking Water Study of Sodium Chlorate

0 mg/L 125 mg/L 250 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L
228 Sodium Chlorate, NTP TR 517 

TABLE F2

Hematology Data for Mice in the 3-Week Drinking Water Study of Sodium Chloratea

0 mg/L 125 mg/L 250 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L

Male

n 10 10 10 10 10 10

Hematocrit (%) 49.6 ± 1.1 48.0 ± 0.5 47.7 ± 0.5 48.9 ± 0.6 49.2 ± 0.8 49.1 ± 0.4

Hemoglobin (g/dL) 16.5 ± 0.4 16.0 ± 0.1 15.9 ± 0.2 16.3 ± 0.2 16.1 ± 0.3 15.9 ± 0.1 

Erythrocytes (106/μL) 10.46 ± 0.25 10.16 ± 0.11 10.09 ± 0.11 10.44 ± 0.13 10.38 ± 0.17 10.21 ± 0.08 

Reticulocytes (106/μL) 0.33 ± 0.00 0.34 ± 0.01 0.35 ± 0.01 0.34 ± 0.01 0.34 ± 0.01 0.34 ± 0.01 

Mean cell volume (fL) 47.5 ± 0.2 47.2 ± 0.2 47.3 ± 0.1 46.9 ± 0.2 47.4 ± 0.2 48.1 ± 0.1 

Mean cell hemoglobin (pg) 15.8 ± 0.1 15.8 ± 0.1 15.7 ± 0.1 15.6 ± 0.1 15.6 ± 0.1 15.6 ± 0.1 

Mean cell hemoglobin 

concentration (g/dL) 33.3 ± 0.1 33.4 ± 0.1 33.2 ± 0.2 33.3 ± 0.3 32.8 ± 0.2* 32.5 ± 0.2**

Platelets (103/μL) 1,204.5 ± 55.6 1,182.6 ± 37.7 1,224.0 ± 39.9 1,197.4 ± 49.1 1,198.5 ± 53.0 1,273.0 ± 43.0

Leukocytes (103/μL) 5.38 ± 0.32 5.04 ± 0.44 5.41 ± 0.56 5.36 ± 0.59 5.12 ± 0.29 4.39 ± 0.51 

Segmented neutrophils 

(103/μL) 0.61 ± 0.10 0.58 ± 0.09 0.53 ± 0.07 0.63 ± 0.14 0.44 ± 0.05 0.40 ± 0.05 

Lymphocytes (103/μL) 4.64 ± 0.29 4.32 ± 0.35 4.74 ± 0.49 4.59 ± 0.51 4.57 ± 0.25 3.89 ± 0.45 

Activated lymphocytes 

(103/μL) 0.01 ± 0.00 0.01 ± 0.00 0.01 ± 0.0 0.01 ± 0.00 0.01 ± 0.00 0.01 ± 0.00 

Monocytes (103/μL) 0.07 ± 0.01 0.07 ± 0.01 0.08 ± 0.01 0.08 ± 0.01 0.07 ± 0.01 0.06 ± 0.01

Basophils (103/μL) 0.003 ± 0.002 0.000 ± 0.000 0.004 ± 0.002 0.005 ± 0.002 0.000 ± 0.000 0.002 ± 0.001 

Eosinophils (103/μL) 0.04 ± 0.01 0.05 ± 0.01 0.05 ± 0.01 0.05 ± 0.01 0.03 ± 0.00* 0.02 ± 0.01* 

Methemoglobin (g/dL) 0.23 ± 0.02 0.19 ± 0.02 0.21 ± 0.03 0.23 ± 0.02 0.19 ± 0.03 0.26 ± 0.01 

Female

n 9 10 10 10 10 10

Hematocrit (%) 49.0 ± 0.6 48.4 ± 0.8 49.4 ± 0.4 49.1 ± 0.7 47.5 ± 0.8 48.1 ± 0.5

Hemoglobin (g/dL) 16.2 ± 0.3 15.9 ± 0.2 16.0 ± 0.1 16.0 ± 0.2 15.6 ± 0.2 15.4 ± 0.2 

Erythrocytes (106/μL) 10.21 ± 0.17 10.14 ± 0.16 10.27 ± 0.10 10.20 ± 0.15 9.83 ± 0.17 9.86 ± 0.14 

Reticulocytes (106/μL) 0.31 ± 0.01 0.30 ± 0.01 0.31 ± 0.01 0.31 ± 0.01 0.33 ± 0.02 0.33 ± 0.02 

Mean cell volume (fL) 48.0 ± 0.3 47.7 ± 0.2 48.1 ± 0.2 48.2 ± 0.2 48.4 ± 0.2 48.8 ± 0.2* 

Mean cell hemoglobin (pg) 15.8 ± 0.1 15.7 ± 0.1 15.6 ± 0.1 15.7 ± 0.1 15.9 ± 0.1 15.6 ± 0.1 

Mean cell hemoglobin 

concentration (g/dL) 33.0 ± 0.3 33.0 ± 0.3 32.5 ± 0.2 32.7 ± 0.2 32.8 ± 0.2 32.0 ± 0.1**

Platelets (103/μL) 888.6 ± 34.5 970.8 ± 50.0 879.70 ± 56.5 863.7 ± 49.6 961.1 ± 56.5 948.1 ± 41.6

Leukocytes (103/μL) 4.61 ± 0.45 4.44 ± 0.20 4.90 ± 0.34 4.64 ± 0.44 4.76 ± 0.28 4.39 ± 0.28 

Segmented neutrophils 

(103/μL) 0.43 ± 0.06 0.49 ± 0.04 0.48 ± 0.05 0.49 ± 0.05 0.46 ± 0.05 0.40 ± 0.04 

Lymphocytes (103/μL) 4.04 ± 0.39 3.81 ± 0.19 4.28 ± 0.29 4.02 ± 0.39 4.16 ± 0.24 3.86 ± 0.26 

Activated lymphocytes 

(103/μL) 0.01 ± 0.00 0.01 ± 0.00 0.01 ± 0.00 0.01 ± 0.00 0.01 ± 0.00 0.01 ± 0.00 

Monocytes (103/μL) 0.07 ± 0.01 0.06 ± 0.01 0.06 ± 0.01 0.07 ± 0.01 0.07 ± 0.01 0.06 ± 0.01

Basophils (103/μL) 0.004 ± 0.002 0.003 ± 0.002 0.006 ± 0.002 0.005 ± 0.002 0.003 ± 0.002 0.007 ± 0.002 

Eosinophils (103/μL) 0.06 ± 0.01 0.06 ± 0.01 0.07 ± 0.01 0.05 ± 0.01 0.06 ± 0.01 0.06 ± 0.01

Methemoglobin (g/dL) 0.18 ± 0.02 0.13 ± 0.04 0.19 ± 0.04 0.19 ± 0.05 0.15 ± 0.03 0.15 ± 0.04 

* Significantly different (P#0.05) from the chamber control group by Dunn’s or Shirley’s test

** P#0.01 a Mean ± standard error. Statistical tests were performed on unrounded data. 
229

APPENDIX G

ORGAN WEIGHTS

AND ORGAN-WEIGHT-TO-BODY-WEIGHT RATIOS

TABLE G1 Organ Weights and Organ-Weight-to-Body-Weight Ratios for F344/N Rats

in the 3-Week Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . 230

TABLE G2 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice

in the 3-Week Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
230 Sodium Chlorate, NTP TR 517 

TABLE G1

Organ Weights and Organ-Weight-to-Body-Weight Ratios for F344/N Rats 

in the 3-Week Drinking Water Study of Sodium Chloratea

0 mg/L 125 mg/L 250 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L

n 10 10 10 10 10 10

Male

Necropsy body wt 184 ± 3 183 ± 4 191 ± 4 189 ± 3 183 ± 2 177 ± 2 

Heart

Absolute 0.644 ± 0.012 0.631 ± 0.014 0.650 ± 0.018 0.669 ± 0.026 0.623 ± 0.010 0.544 ± 0.015**

Relative 3.509 ± 0.056 3.444 ± 0.036 3.411 ± 0.057 3.538 ± 0.105 3.402 ± 0.037 3.071 ± 0.067**

R. Kidney

Absolute 0.705 ± 0.013 0.700 ± 0.017 0.733 ± 0.023 0.740 ± 0.012 0.702 ± 0.012 0.637 ± 0.020* 

Relative 3.842 ± 0.064 3.822 ± 0.063 3.846 ± 0.075 3.925 ± 0.069 3.834 ± 0.043 3.593 ± 0.087 

Liver

Absolute 7.680 ± 0.191 7.920 ± 0.206 8.110 ± 0.266 8.562 ± 0.345 7.868 ± 0.169 7.501 ± 0.240b

Relative 41.856 ± 1.050 43.210 ± 0.592 42.514 ± 0.728 45.248 ± 1.262 42.959 ± 0.696 42.612 ± 1.349b

Lung

Absolute 1.123 ± 0.081b 1.113 ± 0.062 1.169 ± 0.041 1.245 ± 0.095 1.172 ± 0.052 0.988 ± 0.030 

Relative 6.141 ± 0.492b 6.078 ± 0.315 6.154 ± 0.231 6.562 ± 0.424 6.399 ± 0.270 5.584 ± 0.171

R. Testis

Absolute 1.085 ± 0.036 1.075 ± 0.030 1.091 ± 0.023 1.100 ± 0.026 1.089 ± 0.024 1.036 ± 0.032 

Relative 5.893 ± 0.131 5.863 ± 0.093 5.735 ± 0.094 5.835 ± 0.135 5.949 ± 0.113 5.850 ± 0.162

Thymus

Absolute 0.384 ± 0.013 0.349 ± 0.028 0.385 ± 0.012 0.397 ± 0.016 0.377 ± 0.012 0.378 ± 0.012 

Relative 2.089 ± 0.065 1.915 ± 0.156 2.025 ± 0.065 2.100 ± 0.068 2.058 ± 0.066 2.133 ± 0.062

Female

Necropsy body wt 130 ± 1 132 ± 2 130 ± 1 131 ± 2 132 ± 2 131 ± 2 

Heart

Absolute 0.468 ± 0.012 0.482 ± 0.019 0.469 ± 0.008 0.482 ± 0.009 0.486 ± 0.007 0.464 ± 0.011

Relative 3.611 ± 0.078 3.649 ± 0.133 3.623 ± 0.064 3.693 ± 0.061 3.704 ± 0.086 3.541 ± 0.069

R. Kidney

Absolute 0.531 ± 0.010 0.539 ± 0.018 0.518 ± 0.009 0.537 ± 0.010 0.553 ± 0.012 0.523 ± 0.012 

Relative 4.099 ± 0.071 4.077 ± 0.106 4.003 ± 0.077 4.111 ± 0.045 4.204 ± 0.061 3.990 ± 0.070 

Liver

Absolute 5.046 ± 0.089 5.010 ± 0.126 4.963 ± 0.064 5.091 ± 0.110 5.171 ± 0.163 5.035 ± 0.177 

Relative 38.941 ± 0.539 37.918 ± 0.748 38.338 ± 0.444 38.992 ± 0.691 39.284 ± 0.975 38.390 ± 1.171

Lung

Absolute 0.821 ± 0.030 0.821 ± 0.031 0.804 ± 0.025 0.895 ± 0.034 0.807 ± 0.025 0.785 ± 0.027 

Relative 6.338 ± 0.230 6.210 ± 0.197 6.207 ± 0.174 6.838 ± 0.182 6.129 ± 0.134 5.990 ± 0.192

Thymus

Absolute 0.314 ± 0.010 0.322 ± 0.007 0.329 ± 0.008 0.333 ± 0.011 0.316 ± 0.013 0.313 ± 0.010 

Relative 2.423 ± 0.081 2.440 ± 0.044 2.539 ± 0.057 2.545 ± 0.070 2.399 ± 0.090 2.388 ± 0.085

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

** P#0.01 a Organ weights (absolute weights) and body weights are given in grams; organ-weight-to-body-weight ratios (relative weights) are given as 

mg organ weight/g body weight (mean ± standard error). b n=9
Sodium Chlorate, NTP TR 517 231

TABLE G2

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice 

in the 3-Week Drinking Water Study of Sodium Chloratea

0 mg/L 125 mg/L 250 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L

n 10 10 10 10 10 10

Male

Necropsy body wt 29.8 ± 0.3 29.8 ± 0.3 30.0 ± 0.5 29.8 ± 0.4 29.8 ± 0.4 30.2 ± 0.4 

Heart

Absolute 0.155 ± 0.005 0.146 ± 0.004 0.150 ± 0.006 0.148 ± 0.004 0.149 ± 0.004 0.144 ± 0.004

Relative 5.209 ± 0.172 4.894 ± 0.177 4.999 ± 0.182 4.970 ± 0.107 4.996 ± 0.145 4.769 ± 0.131

R. Kidney

Absolute 0.283 ± 0.006 0.274 ± 0.005 0.282 ± 0.010 0.285 ± 0.008 0.284 ± 0.007 0.276 ± 0.007 

Relative 9.506 ± 0.176 9.182 ± 0.117 9.410 ± 0.332 9.570 ± 0.190 9.522 ± 0.216 9.151 ± 0.268 

Liver

Absolute 1.438 ± 0.058 1.399 ± 0.036 1.443 ± 0.043 1.439 ± 0.035 1.427 ± 0.041 1.369 ± 0.026

Relative 48.321 ± 1.956 46.832 ± 0.832 48.080 ± 1.172 48.327 ± 0.838 47.777 ± 1.043 45.392 ± 1.010

Lung

Absolute 0.207 ± 0.014 0.181 ± 0.010 0.189 ± 0.014 0.196 ± 0.012 0.201 ± 0.019 0.178 ± 0.006

Relative 6.986 ± 0.549 6.066 ± 0.324 6.308 ± 0.452 6.599 ± 0.424 6.711 ± 0.589 5.881 ± 0.138

R. Testis

Absolute 0.107 ± 0.002b 0.110 ± 0.002 0.111 ± 0.002 0.110 ± 0.002 0.110 ± 0.002 0.111 ± 0.002 

Relative 3.610 ± 0.051b 3.689 ± 0.057 3.709 ± 0.046 3.700 ± 0.063 3.688 ± 0.070 3.663 ± 0.052

Thymus

Absolute 0.046 ± 0.001 0.042 ± 0.001 0.047 ± 0.001 0.044 ± 0.003 0.043 ± 0.002 0.044 ± 0.002 

Relative 1.548 ± 0.053 1.389 ± 0.039 1.562 ± 0.030 1.475 ± 0.079 1.439 ± 0.055 1.464 ± 0.069

Female

Necropsy body wt 22.8 ± 0.4 22.8 ± 0.1 23.0 ± 0.3 22.5 ± 0.2 23.4 ± 0.5 22.6 ± 0.6 

Heart

Absolute 0.118 ± 0.003 0.118 ± 0.004 0.118 ± 0.002 0.119 ± 0.004 0.121 ± 0.004 0.117 ± 0.002

Relative 5.185 ± 0.122 5.178 ± 0.181 5.134 ± 0.110 5.292 ± 0.136 5.183 ± 0.149 5.197 ± 0.134

R. Kidney

Absolute 0.167 ± 0.004 0.171 ± 0.004 0.170 ± 0.005 0.170 ± 0.003 0.173 ± 0.005 0.166 ± 0.005 

Relative 7.332 ± 0.146 7.505 ± 0.189 7.387 ± 0.209 7.568 ± 0.157 7.407 ± 0.205 7.351 ± 0.200 

Liver

Absolute 1.048 ± 0.026 1.024 ± 0.021 1.025 ± 0.039 1.006 ± 0.024 1.020 ± 0.038 1.038 ± 0.030 

Relative 46.035 ± 0.975 44.940 ± 0.893 44.446 ± 1.292 44.733 ± 0.863 43.521 ± 0.927 45.895 ± 0.562

Lung

Absolute 0.167 ± 0.010 0.168 ± 0.006 0.175 ± 0.010 0.187 ± 0.009 0.165 ± 0.008 0.175 ± 0.010 

Relative 7.400 ± 0.575 7.377 ± 0.282 7.579 ± 0.363 8.318 ± 0.372 7.082 ± 0.372 7.745 ± 0.396

Thymus

Absolute 0.061 ± 0.001 0.056 ± 0.003 0.063 ± 0.002 0.062 ± 0.002 0.061 ± 0.001 0.061 ± 0.002 

Relative 2.677 ± 0.075 2.461 ± 0.148 2.722 ± 0.072 2.773 ± 0.111 2.632 ± 0.087 2.708 ± 0.078

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 n=9
232 Sodium Chlorate, NTP TR 517 
233

APPENDIX H

CHEMICAL CHARACTERIZATION

AND DOSE FORMULATION STUDIES

PROCUREMENT AND CHARACTERIZATION OF SODIUM CHLORATE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234

PREPARATION AND ANALYSIS OF DOSE FORMULATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235

FIGURE H1 Infrared Absorption Spectrum of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236

TABLE H1 Preparation and Storage of Dose Formulations 

in the 3-Week and 2-Year Drinking Water Studies of Sodium Chlorate . . . . . . . . . . . . . . . 237

TABLE H2 Results of Analyses of Dose Formulations Administered to Rats and Mice

in the 3-Week Drinking Water Studies of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . 238

TABLE H3 Results of Analyses of Dose Formulations Administered to Rats and Mice

in the 2-Year Drinking Water Studies of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . 239
234 Sodium Chlorate, NTP TR 517 

CHEMICAL CHARACTERIZATION

AND DOSE FORMULATION STUDIES

PROCUREMENT AND CHARACTERIZATION OF SODIUM CHLORATE

A single lot of sodium chlorate (14019PQ) was obtained from Aldrich Chemical Company, Inc. (Milwaukee, WI),

by the analytical chemistry laboratory, Battelle Columbus (Columbus, OH), and provided to the study laboratory,

Southern Research Institute (Birmingham, AL). Lot 14019PQ was used in the 3-week and 2-year studies. Identity,

purity, and stability analyses were conducted by the analytical chemistry laboratory and the study laboratory.

Reports on analyses performed in support of the sodium chlorate studies are on file at the National Institute of

Environmental Health Sciences.

Lot 14019PQ, a white crystalline solid, was identified as sodium chlorate by the analytical chemistry laboratory

and the study laboratory using infrared spectroscopy and by Galbraith Laboratories, Inc. (Knoxville, TN) using

melting point determination. All spectra were consistent with a literature spectrum (Aldrich, 1985) of sodium

chlorate. The infrared spectrum is presented in Figure H1. The determined melting point agreed with the range of

values reported in the literature (MSDS, 1986; Sax’s, 1996; Hawley’s, 1997; MDL, 1997)

The moisture content of lot 14019PQ was determined by Galbraith Laboratories, Inc., using Karl Fischer titration.

The purity of lot 14019PQ was determined by the analytical chemistry laboratory using argentimetric titration, by

the analytical chemistry laboratory and the study laboratory using anion exchange ion chromatography (IC), and by

Galbraith Laboratories, Inc., using elemental analysis. Argentimetric titration was performed by heating samples

of sodium chlorate in solutions of sulfurous and nitric acids, adding solutions of 0.1 N silver nitrate and ferric

ammonium sulfate indicator after cooling, and titrating to the end point with 0.1 N ammonium thiocyanate. IC was

performed by the analytical chemistry laboratory using system A and by the study laboratory using system B. 

A) Dionex Corp. (Sunnyvale, CA), an Ionpac AS9-SC ion exchange column (250 mm × 4 mm;

and a mobile phase of A) 40 mM boric acid and 20 mM sodium hydroxide and B) 200 mM boric acid and

100 mM NaOH. Following 6 minutes of isocratic elution with 50% A:50 % B, the mobile phase was

linearly changed to 30% A and 70% B in 2 minutes; and to 100% B in 2 minutes Following a 3-minute 

hold, the gradient was linearly changed to 50% A:50% B in 1 minute, followed by a 4-minute hold. The 

flow rate was 1.5 mL/minute and suppressed conductivity detection was used.

B) Alltech Associates, Inc. (Deerfield, CA), Odyssey Basic Ion Chromatograph, an Alltech Anion HC ion

exchange column (150 mm × 4.6 mm, Alltech Associates), using an isocratic mobile phase

of 2.8 mM sodium bicarbonate and 4.4 mM sodium carbonate in deionized organic-free water. The flow

rate was 1.4 mL/minute, the column temperature was 50° C, and suppressed conductivity detection was

used.

Karl Fischer titration indicated a moisture content of less than 0.05%. Elemental analysis for chlorine was in

agreement with the theoretical value for sodium chlorate; however, elemental analysis for sodium was higher

(108%) than the theoretical value. Argentimetric titration indicated a purity of 99.7%. IC by system A indicated

one major peak with no reportable impurities. IC by system B indicated a relative purity of 101% based on major

peak comparison with a frozen reference standard of the same lot. Major peak area percent indicated a purity of

100%. The overall purity of lot 14019PQ was determined to be greater than 99%.

Stability studies of the bulk chemical were performed by the analytical chemistry laboratory. IC by system A

indicated that sodium chlorate was stable as a bulk chemical for 15 days when stored under a minimal headspace

protected from light at temperatures up to 60° C. To ensure stability, the bulk chemical was stored at room

temperature, protected from light, in amber glass containers with Teflon®-lined lids. Stability was monitored by
Sodium Chlorate, NTP TR 517 235

the study laboratory during the 2-year studies with IC by system B. No degradation of the bulk chemical was

detected.

PREPARATION AND ANALYSIS OF DOSE FORMULATIONS

The dose formulations were prepared once during the 3-week studies and every 4 weeks during the 2-year studies

by mixing sodium chlorate with tap water (Table H1). Formulations were stored at room temperature in

NALGENE® containers and protected from light.

Homogeneity studies of 125 and 2,000 mg/L dose formulations were performed by the study laboratory with IC by

a system similar to system B. Stability studies of a 2 mg/L dose formulation were performed by the analytical

chemistry laboratory with IC by a system similar to system A. Homogeneity was confirmed and stability was

confirmed for at least 44 days for dose formulations stored in sealed NALGENE® containers at temperatures up to

25° C, and for at least 7 days when stored in drinking water bottles under simulated animal room conditions. 

Periodic analyses of the dose formulations of sodium chlorate were conducted by the study laboratory using IC by

systems similar to system B. During the 3-week studies, the dose formulations were analyzed once; all five of the

dose formulations for rats and mice were within 10% of the target concentrations (Table H2). Animal room

samples of these dose formulations were also analyzed; all five of the animal room samples for rats and mice were

within 10% of the target concentrations.

During the 2-year studies, the dose formulations were analyzed approximately every 10 weeks (Table H3). Of the

dose formulations used for rats and mice, 40 of 42 were within 10% of the target concentrations. One dose

formulation for rats and one dose formulation for mice were inadvertently used at 14% and 11% of target,

respectively. All 12 of the animal room samples analyzed for rats and mice were within 10% of the target

concentrations. 
236 Sodium Chlorate, NTP TR 517 

FIGURE H1

Infrared Absorption Spectrum of Sodium Chlorate
Sodium Chlorate, NTP TR 517 237

TABLE H1

Preparation and Storage of Dose Formulations in the 3-Week and 2-Year Drinking Water Studies 

of Sodium Chlorate

Preparation

A premix was prepared in a beaker with tap water and then thoroughly mixed with additional tap water in a NALGENE® mixing tank for

approximately 15 minutes. Dose formulations were prepared once during the 3-week studies and every 4 weeks during the 2-year studies.

Chemical Lot Number

14019PQ

Maximum Storage Time

44 days

Storage Conditions

Stored in NALGENE® containers at room temperature in the dark

Study Laboratory

Southern Research Institute (Birmingham, AL)
238 Sodium Chlorate, NTP TR 517 

TABLE H2

Results of Analyses of Dose Formulations Administered to Rats and Mice 

in the 3-Week Drinking Water Studies of Sodium Chlorate

Target Determined Difference

Date Prepared Date Analyzed Concentration Concentrationa from Target

(mg/L) (mg/L) (%)

Rats

May 11, 1998 May 13, 1998 125 131 +5

250 253 +1

500 510 +2

1,000 1,015 +2

2,000 1,976 –1

June 11, 1998b 125 133 +7

250 260 +4

500 522 +4

1,000 1,027 +3

2,000 2,022 +1

Mice

May 11, 1998 May 13, 1998 125 131 +5

250 253 +1

500 510 +2

1,000 1,015 +2

2,000 1,976 –1

June 12, 1998b 125 134 +8

250 265 +6

500 528 +6

1,000 1,032 +3

2,000 2,075 +4

a Results of duplicate analyses b Animal room samples
Sodium Chlorate, NTP TR 517 239

TABLE H3

Results of Analyses of Dose Formulations Administered to Rats and Mice 

in the 2-Year Drinking Water Studies of Sodium Chlorate

Target Determined Difference

Date Prepared Date Analyzed Concentration Concentrationa from Targetb

(mg/L) (mg/L) (%)

Rats

September 10, 1998 September 11, 1998 125 125 +1

1,000 1,041 +4

2,000 2,025 +1

October 19-20, 1998c 125 123 –2

1,000 990 –1

2,000 1,963 –2

November 6, 1998 November 9, 1998 125 127 +2

1,000 1,004 0

1,000 995 –1

2,000 1,976 –1

2,000 1,976 –1

January 29, 1999 February 1, 1999 125 142 +14

1,000 1,095 +10

2,000 2,125 +6

March 26, 1999 March 29-31, 1999 125 128 +3

1,000 991 –1d

2,000 1,982 –1d

April 30, 1999c 125 137 +10

1,000 1,042 +4

2,000 2,103 +5

April 1, 1999 April 1, 1999 1,000 993 –1e

2,000 1,966 –2e

June 18, 1999 June 21-22, 1999 125 125 0

1,000 973 –3

2,000 1,963 –2

August 13, 1999 August 16-17, 1999 125 132 +5

1,000 1,016 +2

2,000 2,045 +2

November 5, 1999 November 8, 1999 125 125 0

1,000 1,004 0

2,000 1,994 0

December 13, 1999c 125 129 +3

1,000 1,037 +4

2,000 2,045 +2

December 28, 1999 January 3, 2000 125 135 +8

1,000 1,076 +8

2,000 2,133 +7

March 23, 2000 March 24, 2000 125 127 +1

1,000 1,007 +1

2,000 1,991 0
240 Sodium Chlorate, NTP TR 517 

Rats (continued)

May 18, 2000 May 19, 2000 125 127 +2

1,000 1,047 +5

2,000 2,014 +1

June 26, 2000c 125 122 –2

1,000 1,034 +3

2,000 2,016 +1

August 10, 2000 August 11, 2000 125 113 –10

1,000 985 –2

2,000 1,955 –2

Mice

September 10, 1998 September 11, 1998 500 504 +2

1,000 1,041 +4

2,000 2,025 +1

October 19-20, 1998c 500 493 –1

1,000 1,013 +1

2,000 1,971 –1

November 6, 1998 November 9, 1998 500 506 +1

1,000 1,004 0

1,000 995 –1

2,000 1,976 –1

2,000 1,976 –1

January 29, 1999 February 1, 1999 500 556 +11

1,000 1,095 +10

2,000 2,125 +6

March 26, 1999 March 29-31, 1999 500 537 +7

1,000 991 –1d

2,000 1,982 –1d

April 30, 1999c 500 544 +9

1,000 1,051 +5

2,000 2,076 +4

April 1, 1999 April 1, 1999 1,000 993 –1e

2,000 1,966 –2e

June 18, 1999 June 21-22, 1999 500 471 –6

1,000 973 –3

2,000 1,963 –2

August 13, 1999 August 16-17, 1999 500 503 +1

1,000 1,016 +2

2,000 2,045 +2

TABLE H3

Results of Analyses of Dose Formulations Administered to Rats and Mice 

in the 2-Year Drinking Water Studies of Sodium Chlorate

Target Determined Difference

Date Prepared Date Analyzed Concentration Concentration from Target

(mg/L) (mg/L) (%)
Sodium Chlorate, NTP TR 517 241

Mice (continued)

November 5, 1999 November 8, 1999 500 509 +2

1,000 1,004 0

2,000 1,994 0

December 13, 1999c 500 512 +2

1,000 1,020 +2

2,000 2,008 0

December 28, 1999 January 3, 2000 500 534 +7

1,000 1,076 +8

2,000 2,133 +7

March 23, 2000 March 24, 2000 500 527 +5

1,000 1,007 +1

2,000 1,991 0

May 18, 2000 May 19, 2000 500 527 +5

1,000 1,047 +5

2,000 2,014 +1

June 26, 2000c 500 535 +7

1,000 1,036 +4

2,000 2,052 +3

August 10, 2000 August 11, 2000 500 478 –4

1,000 985 –2

2,000 1,955 –2

a Results of duplicate analyses b Reported percentages are based on unrounded raw data; therefore, some percentages may not be reproducible when calculated from the 

rounded concentration values presented here. c Animal room samples d Remixed, not used in study e Results of remix; not used in study

TABLE H3

Results of Analyses of Dose Formulations Administered to Rats and Mice 

in the 2-Year Drinking Water Studies of Sodium Chlorate

Target Determined Difference

Date Prepared Date Analyzed Concentration Concentration from Target

(mg/L) (mg/L) (%)
242 Sodium Chlorate, NTP TR 517 
243

APPENDIX I

WATER AND COMPOUND CONSUMPTION

IN THE 2-YEAR DRINKING WATER STUDIES

OF SODIUM CHLORATE

TABLE I1 Water and Compound Consumption by Male Rats

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244

TABLE I2 Water and Compound Consumption by Female Rats

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245

TABLE I3 Water and Compound Consumption by Male Mice

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246

TABLE I4 Water and Compound Consumption by Female Mice

in the 2-Year Drinking Water Study of Sodium Chlorate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
244 Sodium Chlorate, NTP TR 517 

TABLE I1 

Water and Compound Consumption by Male Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Water Body Water Body Dose Water Body Dose Water Body Dose

(g)a Weight (g) Weight (mg/kg)b (g) Weight (mg/kg) (g) Weight (mg/kg)

Week (g) (g) (g) (g)

4 15.9 187 16.8 187 11.3 16.2 185 87.5 17.1 186 183.5

8 16.4 261 16.3 263 7.8 17.2 266 64.7 17.5 270 129.3

12 16.0 312 15.9 315 6.3 16.5 319 51.7 16.6 322 103.2

16 15.6 348 14.6 351 5.2 15.5 357 43.5 15.3 358 85.6

20 15.3 373 15.5 374 5.2 15.6 379 41.2 15.8 382 83.0

24 14.8 393 14.7 396 4.6 15.3 402 38.1 15.8 403 78.4

28 15.3 420 15.6 423 4.6 16.3 429 37.9 17.4 428 81.3

32 14.1 437 14.2 439 4.1 14.3 445 32.2 14.7 446 66.2

36 13.5 442 13.4 445 3.8 13.2 452 29.3 14.1 451 62.5

40 14.3 459 14.8 461 4.0 14.4 466 30.9 14.6 468 62.4

44 13.2 467 14.4 474 3.8 14.4 477 30.3 14.6 478 61.2

48 13.3 475 13.7 479 3.6 13.8 482 28.7 13.8 486 56.7

52 13.4 487 13.8 491 3.5 13.5 493 27.4 13.8 494 55.7

56 14.2 489 14.7 493 3.7 14.7 497 29.6 15.1 498 60.8

60 15.0 495 15.2 499 3.8 15.4 501 30.7 15.6 501 62.1

64 15.2 499 15.1 503 3.8 15.2 505 30.1 15.7 505 62.1

68 14.8 500 15.0 503 3.7 15.1 504 30.0 15.5 505 61.2

72 14.7 497 15.4 502 3.8 15.8 506 31.3 15.5 504 61.5

76 15.4 508 15.6 506 3.9 16.1 508 31.7 16.1 509 63.3

80 14.6 508 14.4 506 3.6 14.8 507 29.1 15.6 508 61.4

84 15.2 512 15.6 508 3.8 16.1 513 31.4 16.7 510 65.6

88 15.7 509 15.7 501 3.9 15.8 516 30.6 17.2 510 67.5

92 14.8 514 15.8 501 3.9 15.1 514 29.4 16.2 508 63.9

96 14.9 507 14.9 500 3.7 15.2 505 30.1 15.7 498 63.0

100 14.1 497 14.7 486 3.8 15.5 504 30.7 16.4 488 67.2

104 15.0 490 16.5 497 4.2 15.7 500 31.4 17.2 496 69.3

Mean for weeks

1-13 16.1 254 16.4 255 8.5 16.6 257 68.0 17.1 259 138.7

14-52 14.3 430 14.5 433 4.2 14.6 438 34.0 15.0 439 69.3

53-104 14.9 502 15.3 500 3.8 15.4 506 30.5 16.0 503 63.8

a Grams of water consumed per animal per day b Milligrams of sodium chlorate consumed per kilogram body weight per day
Sodium Chlorate, NTP TR 517 245

TABLE I2 

Water and Compound Consumption by Female Rats in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 125 mg/L 1,000 mg/L 2,000 mg/L

Water Body Water Body Dose Water Body Dose Water Body Dose

(g)a Weight (g) Weight (mg/kg)b (g) Weight (mg/kg) (g) Weight (mg/kg)

Week (g) (g) (g) (g)

4 12.7 140 12.9 141 11.5 12.8 140 91.8 12.6 138 182.8

8 12.2 169 12.5 171 9.1 12.6 170 74.2 12.8 169 151.6

12 11.5 186 12.0 187 8.0 11.8 188 62.6 11.6 186 124.8

16 11.1 197 11.3 200 7.1 11.1 199 55.6 10.6 196 107.7

20 10.6 205 11.3 208 6.8 10.9 208 52.6 10.9 204 106.6

24 10.8 213 11.1 215 6.4 10.8 216 50.3 11.3 212 106.3

28 11.5 228 11.7 230 6.3 11.7 232 50.5 11.9 226 105.6

32 10.5 232 11.1 236 5.9 10.9 237 45.9 11.0 231 94.8

36 10.1 235 10.4 239 5.5 9.7 240 40.5 10.1 236 86.0

40 10.7 246 10.9 250 5.4 10.8 248 43.4 10.9 244 89.4

44 10.1 259 10.9 268 5.1 10.5 265 39.8 11.0 259 84.6

48 10.4 260 10.6 266 5.0 10.3 263 39.3 10.4 259 80.4

52 10.5 271 11.3 277 5.1 10.3 276 37.2 10.5 267 79.1

56 11.1 278 11.5 283 5.1 11.9 284 41.8 11.7 276 85.0

60 11.3 285 12.0 287 5.2 12.6 293 43.1 12.8 283 90.3

64 11.9 294 12.3 301 5.1 12.5 304 41.2 12.7 291 87.2

68 11.8 304 12.1 310 4.9 12.0 309 38.9 12.4 298 83.3

72 12.1 308 12.4 313 4.9 12.8 316 40.5 12.7 305 83.2

76 12.8 322 13.2 325 5.1 12.8 328 39.1 13.3 317 83.8

80 12.4 327 11.8 331 4.5 12.0 332 36.1 12.4 323 76.6

84 12.9 331 13.1 337 4.8 13.2 337 39.1 13.7 330 83.0

88 13.4 337 13.6 338 5.0 13.7 341 40.1 13.7 331 83.2

92 13.2 340 12.4 342 4.5 13.4 345 38.9 13.5 339 79.5

96 13.8 340 14.0 343 5.1 13.5 352 38.5 14.2 332 85.5

100 13.5 342 13.4 350 4.8 13.9 351 39.5 14.5 337 86.0

104 13.4 339 13.1 351 4.7 14.7 359 41.0 14.1 341 82.5

Mean for weeks

1-13 12.1 165 12.5 166 9.5 12.4 166 76.2 12.3 164 153.1

14-52 10.6 235 11.1 239 5.9 10.7 238 45.5 10.9 234 94.1

53-104 12.6 319 12.7 324 4.9 13.0 327 39.8 13.2 316 83.8

a Grams of water consumed per animal per day b Milligrams of sodium chlorate consumed per kilogram body weight per day
246 Sodium Chlorate, NTP TR 517 

TABLE I3 

Water and Compound Consumption by Male Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L

Water Body Water Body Dose Water Body Dose Water Body Dose

(g)a Weight (g) Weight (mg/kg)b (g) Weight (mg/kg) (g) Weight (mg/kg)

Week (g) (g) (g) (g)

4 3.6 28.1 4.0 27.7 72 3.8 28.2 136 3.9 28.2 274

8 3.3 33.9 3.6 33.3 54 3.3 33.5 100 3.3 33.8 197

12 3.1 38.7 3.3 38.2 43 3.0 38.4 78 3.3 38.6 171

16 3.2 43.6 3.2 43.0 37 3.1 43.5 71 2.9 43.6 134

20 2.8 47.1 2.9 46.5 31 2.9 47.4 61 2.8 47.0 120

24 3.0 49.5 3.0 48.8 31 3.0 49.1 61 3.1 49.6 125

28 3.4 50.5 3.3 49.8 33 3.3 49.9 67 3.4 50.2 135

32 3.3 50.7 3.3 49.7 33 3.3 49.8 67 3.4 50.4 137

36 3.5 51.3 3.6 50.7 35 3.6 50.6 72 3.6 51.2 141

40 3.8 51.8 3.7 51.1 37 4.0 51.4 79 3.8 51.8 145

44 3.7 52.2 3.7 50.9 36 3.6 51.3 71 3.7 52.1 140

48 3.9 53.0 3.7 51.8 36 3.8 51.7 73 3.8 52.8 142

52 3.8 52.6 3.6 51.8 34 3.7 52.1 71 3.7 52.9 140

56 4.1 52.7 3.9 52.1 38 4.0 52.2 76 4.0 52.5 151

60 4.1 53.0 4.1 52.2 39 4.3 52.6 81 4.0 53.0 152

64 4.2 53.4 4.2 53.2 39 4.5 52.7 85 4.2 53.4 157

68 4.2 53.2 4.3 53.5 40 4.3 53.2 81 4.2 54.5 153

72 3.8 54.1 4.0 53.4 37 4.0 52.8 75 3.9 54.2 144

76 3.9 53.6 4.0 53.0 38 4.1 52.2 79 4.0 54.0 149

80 4.2 52.5 4.0 52.4 39 4.4 51.8 84 4.1 52.9 155

84 4.1 53.0 4.2 52.4 40 4.1 53.0 77 4.1 51.7 157

88 4.1 51.7 3.9 51.4 38 3.9 52.3 74 3.9 50.6 156

92 4.9 50.9 4.3 50.6 43 4.3 51.4 83 4.2 49.6 169

96 4.8 50.7 4.3 49.7 43 4.0 50.3 80 4.1 49.6 164

100 4.3 48.6 4.0 47.1 43 3.8 48.1 79 3.9 48.1 161

104 4.2 46.6 4.2 45.1 46 4.1 46.5 89 4.0 48.5 166

Mean for weeks

1-13 3.4 33.6 3.6 33.1 57 3.4 33.3 105 3.5 33.5 214

14-52 3.5 50.2 3.4 49.4 34 3.4 49.7 69 3.4 50.2 136

53-104 4.2 51.8 4.1 51.2 40 4.1 51.5 80 4.0 51.7 156

a Grams of water consumed per animal per day b Milligrams of sodium chlorate consumed per kilogram body weight per day
Sodium Chlorate, NTP TR 517 247

TABLE I4 

Water and Compound Consumption by Female Mice in the 2-Year Drinking Water Study 

of Sodium Chlorate

0 mg/L 500 mg/L 1,000 mg/L 2,000 mg/L

Water Body Water Body Dose Water Body Dose Water Body Dose

(g)a Weight (g) Weight (mg/kg)b (g) Weight (mg/kg) (g) Weight (mg/kg)

Week (g) (g) (g) (g)

4 3.5 22.3 3.4 22.2 78 3.4 22.4 151 3.9 22.0 356

8 2.9 27.3 3.1 26.6 58 3.2 27.1 117 3.5 26.3 266

12 3.1 32.0 3.2 31.4 51 3.1 31.6 98 3.5 30.2 234

16 3.0 36.5 3.1 35.9 43 3.6 36.0 100 3.1 35.0 175

20 2.4 42.3 2.4 41.9 29 2.4 42.3 57 2.5 41.2 123

24 2.5 46.9 2.3 46.5 25 2.3 46.8 50 2.4 45.1 106

28 2.4 49.9 2.7 49.7 27 2.3 50.3 46 2.9 48.6 118

32 2.5 52.5 2.4 51.9 23 2.4 52.7 45 2.4 51.4 93

36 2.3 54.4 2.5 54.2 23 2.3 54.3 43 2.5 53.0 94

40 2.3 57.8 2.3 58.0 20 2.2 57.4 39 2.4 56.1 87

44 2.5 58.4 2.7 58.5 23 2.4 57.2 42 2.8 56.6 99

48 2.3 60.2 2.4 59.6 20 2.4 58.6 41 2.7 59.0 90

52 2.4 61.0 2.4 60.8 19 2.4 59.9 40 2.5 60.5 82

56 2.5 61.2 2.5 61.0 20 2.5 60.1 42 2.6 61.4 83

60 2.6 62.2 2.6 61.1 22 2.8 60.9 46 2.8 62.1 89

64 2.8 62.8 2.7 62.4 22 2.7 62.7 43 3.2 62.0 103

68 2.6 63.4 2.7 62.3 21 2.8 62.9 44 2.5 63.7 80

72 2.4 64.2 2.8 61.8 23 2.5 63.1 40 2.7 64.5 84

76 2.7 65.0 2.8 63.9 22 2.9 64.3 44 2.8 64.6 86

80 2.9 66.5 2.8 64.7 22 3.0 65.0 46 2.9 65.2 89

84 2.8 65.7 2.8 64.9 22 3.1 64.3 49 2.8 65.1 87

88 2.6 65.9 3.0 62.9 24 3.3 61.7 54 2.7 63.7 86

92 3.1 64.9 3.8 60.2 32 3.7 62.3 60 3.0 61.9 96

96 3.2 64.3 3.5 57.8 30 4.0 60.1 67 3.2 58.5 110

100 3.4 63.3 4.2 56.3 37 4.5 57.3 79 3.4 58.6 116

104 3.6 61.0 3.7 53.7 35 5.1 55.0 93 4.1 54.6 150

Mean for weeks

1-13 3.2 27.2 3.2 26.7 62 3.2 27.0 122 3.6 26.2 285

14-52 2.5 52.0 2.5 51.7 25 2.5 51.6 50 2.6 50.7 107

53-104 2.9 63.9 3.1 61.0 25 3.3 61.5 54 3.0 62.0 97

a Grams of water consumed per animal per day b Milligrams of sodium consumed per kilogram body weight per day
248 Sodium Chlorate, NTP TR 517 
249

APPENDIX J

INGREDIENTS, NUTRIENT COMPOSITION,

AND CONTAMINANT LEVELS

IN NTP-2000 RAT AND MOUSE RATION

TABLE J1 Ingredients of NTP-2000 Rat and Mouse Ration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250

TABLE J2 Vitamins and Minerals in NTP-2000 Rat and Mouse Ration . . . . . . . . . . . . . . . . . . . . . . . . . 250

TABLE J3 Nutrient Composition of NTP-2000 Rat and Mouse Ration . . . . . . . . . . . . . . . . . . . . . . . . . . 251

TABLE J4 Contaminant Levels in NTP-2000 Rat and Mouse Ration . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
250 Sodium Chlorate, NTP TR 517 

TABLE J1

Ingredients of NTP-2000 Rat and Mouse Ration

Ingredients Percent by Weight

Ground hard winter wheat 22.26

Ground #2 yellow shelled corn 22.18

Wheat middlings 15.0

Oat hulls 8.5

Alfalfa meal (dehydrated, 17% protein) 7.5

Purified cellulose 5.5

Soybean meal (49% protein) 5.0

Fish meal (60% protein) 4.0

Corn oil (without preservatives) 3.0

Soy oil (without preservatives) 3.0

Dried brewer’s yeast 1.0

Calcium carbonate (USP) 0.9

Vitamin premixa 0.5

Mineral premixb 0.5

Calcium phosphate, dibasic (USP) 0.4

Sodium chloride 0.3

Choline chloride (70% choline) 0.26

Methionine 0.2

a Wheat middlings as carrier b Calcium carbonate as carrier

TABLE J2

Vitamins and Minerals in NTP-2000 Rat and Mouse Rationa

Amount Source

Vitamins

A 4,000 IU Stabilized vitamin A palmitate or acetate

D 1,000 IU D-activated animal sterol

K 1.0 mg Menadione sodium bisulfite complex

"-Tocopheryl acetate 100 IU

Niacin 23 mg

Folic acid 1.1 mg

d-Pantothenic acid 10 mg d-Calcium pantothenate

Riboflavin 3.3 mg

Thiamine 4 mg Thiamine mononitrate

B12 52 μg

Pyridoxine 6.3 mg Pyridoxine hydrochloride

Biotin 0.2 mg d-Biotin

Minerals

Magnesium 514 mg Magnesium oxide

Iron 35 mg Iron sulfate

Zinc 12 mg Zinc oxide

Manganese 10 mg Manganese oxide

Copper 2.0 mg Copper sulfate

Iodine 0.2 mg Calcium iodate

Chromium 0.2 mg Chromium acetate

a Per kg of finished product
Sodium Chlorate, NTP TR 517 251

TABLE J3

Nutrient Composition of NTP-2000 Rat and Mouse Ration

Mean ± Standard

Nutrient Deviation Range Number of Samples

Protein (% by weight) 13.5 ± 0.44 12.7 – 14.5 25

Crude fat (% by weight) 8.1 ± 0.26 7.6 – 8.6 25

Crude fiber (% by weight) 9.2 ± 0.66 7.9 – 10.5 25

Ash (% by weight) 4.9 ± 0.19 4.7 – 5.4 25

Amino Acids (% of total diet)

Arginine 0.748 ± 0.053 0.670 – 0.850 12

Cystine 0.223 ± 0.027 0.150 – 0.250 12

Glycine 0.702 ± 0.043 0.620 – 0.750 12

Histidine 0.343 ± 0.023 0.310 – 0.390 12

Isoleucine 0.534 ± 0.041 0.430 – 0.590 12

Leucine 1.078 ± 0.059 0.960 – 1.140 12

Lysine 0.729 ± 0.065 0.620 – 0.830 12

Methionine 0.396 ± 0.053 0.260 – 0.460 12

Phenylalanine 0.611 ± 0.038 0.540 – 0.660 12

Threonine 0.492 ± 0.045 0.430 – 0.590 12

Tryptophan 0.129 ± 0.016 0.110 – 0.160 12

Tyrosine 0.378 ± 0.054 0.280 – 0.460 12

Valine 0.658 ± 0.049 0.550 – 0.710 12

Essential Fatty Acids (% of total diet)

Linoleic 3.89 ± 0.278 3.49 – 4.54 12

Linolenic 0.30 ± 0.038 0.21 – 0.35 12

Vitamins

Vitamin A (IU/kg) 5,694 ± 1,010 3,700 – 7,790 25

Vitamin D (IU/kg) 1,000a

"-Tocopherol (ppm) 84.3 ± 17.06 52.0 – 110.0 12

Thiamine (ppm)b 7.9 ± 0.83 6.3 – 9.3 25

Riboflavin (ppm) 6.4 ± 2.11 4.20 – 11.20 12

Niacin (ppm) 78.6 ± 10.86 66.4 – 98.2 12

Pantothenic acid (ppm) 23.1 ± 3.61 17.4 – 29.1 12

Pyridoxine (ppm)b 8.88 ± 2.05 6.4 – 12.4 12

Folic acid (ppm) 1.84 ± 0.56 1.26 – 3.27 12

Biotin (ppm) 0.337 ± 0.13 0.225 – 0.704 12

Vitamin B12 (ppb) 64.8 ± 50.9 18.3 – 174.0 12

Choline (ppm)b 3,094 ± 292 2,700 – 3,790 12

Minerals

Calcium (%) 0.998 ± 0.045 0.903 – 1.090 25

Phosphorus (%) 0.564 ± 0.028 0.505 – 0.618 25

Potassium (%) 0.668 ± 0.023 0.627 – 0.694 12

Chloride (%) 0.368 ± 0.033 0.300 – 0.423 12

Sodium (%) 0.189 ± 0.016 0.160 – 0.212 12

Magnesium (%) 0.200 ± 0.009 0.185 – 0.217 12

Sulfur (%) 0.176 ± 0.026 0.116 – 0.209 12

Iron (ppm) 177 ± 46.2 135 – 311 12

Manganese (ppm) 53.4 ± 6.42 42.1 – 63.1 12

Zinc (ppm) 52.5 ± 6.95 43.3 – 66.0 12

Copper (ppm) 6.64 ± 1.283 5.08 – 9.92 12

Iodine (ppm) 0.535 ± 0.242 0.233 – 0.972 12

Chromium (ppm) 0.545 ± 0.125 0.330 – 0.751 12

Cobalt (ppm) 0.23 ± 0.041 0.20 – 0.30 12

a From formulation b As hydrochloride (thiamine and pyridoxine) or chloride (choline)
252 Sodium Chlorate, NTP TR 517 

TABLE J4

Contaminant Levels in NTP-2000 Rat and Mouse Rationa

Mean ± Standard

Nutrient Deviationb Range Number of Samples

Contaminants

Arsenic (ppm) 0.16 ± 0.070 0.10 – 0.33 25

Cadmium (ppm) 0.04 ± 0.006 0.04 – 0.07 25

Lead (ppm) 0.11 ± 0.104 0.05 – 0.54 25

Mercury (ppm) <0.02 25

Selenium (ppm) 0.19 ± 0.033 0.14 – 0.28 25

Aflatoxins (ppb) <5.00 25

Nitrate nitrogen (ppm)c 10.8 ± 2.98 9.04 – 21.1 25

Nitrite nitrogen (ppm)c <0.61 25

BHA (ppm)d <1.0 25

BHT (ppm)d <1.0 25

Aerobic plate count (CFU/g) 10 ± 2 10 – 20 25

Coliform (MPN/g) 0.4 ± 1.2 0.0 – 3.6 25

Escherichia coli (MPN/g) <10 25

Salmonella (MPN/g) Negative 25

Total nitrosoamines (ppb)e 4.6 ± 1.64 2.1 – 8.8 25

N-Nitrosodimethylamine (ppb)e 1.8 ± 0.86 1.0 – 5.1 25

N-Nitrosopyrrolidine (ppb)e 2.8 ± 1.10 1.0 – 5.6 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 chlorpyrifos 0.145 ± 0.124 0.023 – 0.499 25

Methyl parathion <0.02 25

Ethyl parathion <0.02 25

Malathion 0.217 ± 0.188 0.020 – 0.826 25

Endosulfan I <0.01 25

Endosulfan II <0.01 25

Endosulfan sulfate <0.03 25

a All samples were irradiated. CFU=colony-forming units; MPN=most probable number; BHC=hexachlorocyclohexane or benzene 

hexachloride b For values less than the limit of detection, the detection limit is given as the mean. c Sources of contamination: alfalfa, grains, and fish meal d Sources of contamination: soy oil and fish meal e All values were corrected for percent recovery.
253

APPENDIX K

SENTINEL ANIMAL PROGRAM

METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254

RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
254 Sodium Chlorate, NTP TR 517 

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.

During the 2-year studies, serum samples were collected from randomly selected sentinel rats and mice at 6, 12,

and 18 months and 2,000 mg/L rats and mice at study termination. Blood from each animal was collected and

allowed to clot, and the serum was separated. Samples were processed appropriately and sent to BioReliance

Corporation, Rockville, MD, for determination of antibody titers. The laboratory serology methods and viral

agents for which testing was performed are tabulated below; the times at which blood was collected during the

studies are also listed.

Method and Test Time of Analysis

RATS

ELISA

Mycoplasma arthritidis 6 months, study termination

Mycoplasma pulmonis 6 months, study termination

PVM (pneumonia virus of mice) 6, 12, and 18 months, study termination

RCV/SDA (rat coronavirus/sialodacryoadentis virus) 6, 12, and 18 months, study termination

Sendai 6, 12, and 18 months, study termination

Immunofluorescence Assay

Parvovirus 6, 12, and 18 months, study termination
Sodium Chlorate, NTP TR 517 255

Method and Test Time of Analysis

MICE

ELISA

Ectromelia virus 6, 12, and 18 months, study termination

EDIM (epizootic diarrhea of infant mice) 6, 12, and 18 months, study termination

GDVII (mouse encephalomyelitis virus) 6, 12, and 18 months, study termination

LCM (lymphocytic choriomeningitis virus) 6, 12, and 18 months, study termination

Mouse adenoma virus-FL 6, 12, and 18 months, study termination

MHV (mouse hepatitis virus) 6, 12, and 18 months, study termination

M. arthritidis 6 months, study termination

M. pulmonis 6 months, study termination

PVM 6, 12, and 18 months, study termination

Reovirus 3 6, 12, and 18 months, study termination

Sendai 6, 12, and 18 months, study termination

Immunofluorescence Assay

Ectromelia virus 18 months

EDIM 18 months

GDVII 18 months

LCM 18 months

Mouse adenoma virus-FL 12 and 18 months

MCMV (mouse cytomegalovirus) 6 months, study termination

MHV 18 months

M. arthritidis 6 months, study termination

Parvovirus 6, 12, and 18 months, study termination

PVM 18 months

Reovirus 3 18 months

RESULTS

For the 2-year studies in rats and mice, all serology tests were negative. 
256 Sodium Chlorate, NTP TR 517