Species difference in the ovarian toxicity of 1,3-butadiene epoxides in B6C3F 1 mice and Sprague-Dawley rats

Abstract

1,3-Butadiene (BD) is an ovarian carcinogen in mice, but not in rats. Since species variation in metabolism of BD has been associated with the greater sensitivity of mice to BD-induced carcinogenicity, the extent of biotransformation and detoxification of BD and its epoxides may play a critical role in other ovotoxic effects of this compound. Thus, the ovotoxic potency of the BD epoxides was determined. Butadiene monoepoxide (BMO, 0.005–1.43 mmol/kg b.w.), butadiene diepoxide (BDE, 0.002–0.29 mmol/kg b.w.), or vehicle was administered i.p. to female B6C3F 1 mice and Sprague-Dawley rats for 30 days. Following day 30, tissues were removed and weighed, and the number of pre-antral ovarian follicles counted. BMO was ovotoxic in mice as demonstrated by decreases in reproductive organ weights (1.43 mmol/kg b.w.) and follicular counts, but not in rats at any dose tested. In mice the ED 50 values for BMO for small and growing follicles were 0.29 and 0.40 mmol/kg b.w., respectively. BDE was ovotoxic in both species, however mice were more sensitive to BDE than rats. Ovarian and uterine weights were decreased in mice at 0.14 and 0.29 mmol/kg b.w. of BDE treatment, and in rats at 0.29 mmol/kg b.w. only. The ED 50 values for BDE in mice were 0.10 and 0.14 mmol/kg b.w. for small and growing follicles, respectively. ED 50 values could not be determined in rats since only 32% of the follicular population was depleted at the highest concentration tested. Thus, BMO and BDE exhibited a greater ovotoxic potential in mice, as compared to rats. In addition, in each species the diepoxide was the most potent ovotoxicant.