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.
Three-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.
Three-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, 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.
Two-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.
Two-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.