Toxicity and carcinogenicity studies of boric acid in male and female B6C3F1 mice

Abstract

Toxicity and potential carcinogenicity studies of boric acid were investigated in mice to verify in a second rodent species that this was a noncarcinogenic chemical. Earlier chronic studies in rats indicated boric acid was not a carcinogen. The chemical is nominated for testing because over 200 tons are produced annually, there are multiple uses for the product, and there is potential for widespread human exposure, both orally and dermally. Both sexes of B6C3F1 mice were offered diets mixed with boric acid for 14 days, 13 weeks, or 2 years. Dietary doses used in the acute, 14-day study were 0, 0.62, 1.26, 2.5, 5, and 10%; those in the subchronic, 13-week study were 0, 0.12, 0.25, 0.50, 1, and 2%; and doses in the 2-year, chronic study were 0, 0.25, and 0.50% in the diet. Mortality, clinical signs of toxicity, estimates of food consumption, body weight gain, and histopathologic examination of selected tissues constituted the variables measured. In the 14-day study mortality was proportional to dose and time of exposure in both sexes, occurring in dose groups as low as 2.5% and as early as 7 days of exposure. Body weights were depressed more than 10% below controls in the higher dose groups of both sexes. Mortality in the 13-week study was confined to the two highest dose groups in male mice and to the 2%-dose group in females. Body weight depression from 8 to 23% below those of controls occurred in the 0.50% and higher dose groups of both sexes. Minimal to mild extramedullary hematopoiesis in spleens of both sexes was a common occurrence in all dose groups, but the most severe lesion was testicular degeneration or atrophy of the seminiferous tubules in male mice fed 0.50 to 2.0% boric acid. Dietary doses of 0.25 and 0.50% were selected for both sexes of mice in 2-year studies based on body weights and mortality. Survival of male mice was reduced in the high-dose group after week 63, and after week 84 in the low-dose group; survival in female mice was not affected at either dose of boric acid. Reductions in body weight gain occurred in the high-dose group of both sexes. Based on estimates of food consumption, the average amount of boric acid ingested per mouse per day was calculated to be 400 to 500 mg/kg in the low-dose and 1100 to 1200 mg/kg in the high-dose groups of both sexes. Again the most prominent lesion was an increased incidence of testicular atrophy (3/49, 6/50, 27/47) and interstitial cell hyperplasia (0/49, 0/50, 7/47) in high-dose male mice. There was a slight increase in spleen lymphoid depletion in dosed male mice, which was considered secondary to stress and debilitation. Although there were marginal increases in subcutaneous tissue tumors and hepatic tumors in dosed male mice, these fell within the historical control range and were not believed to be related to chemical treatment. These particular tumors are highly variable in historical controls, only occurred in the low-dose group, and were not significant by an incidental tumor test, which is appropriate for tumors that are not a cause of death. There were also no indications that boric acid is genotoxic, since tests with prokaryotic and eukaryotic cells were uniformly negative, and there were no effects on sister-chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells.