Species difference in the ovarian toxicity of 1,3-butadiene epoxides in B6C3F1 mice and Sprague-Dawley rats.
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 B6C3F1 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 ED50 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 ED50 values for BDE in mice were 0.10 and 0.14 mmol/kg b.w. for small and growing follicles, respectively, ED50 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.
Department of Pharmacology and Toxicology, University of Arizona, College of Pharmacy, Tucson 85721, USA.
J K
JK
Doerr
E A
EA
Hollis
I G
IG
Sipes
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000633:toxicity*; D005260:Female; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D010053:Ovary / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D002273:Carcinogens; D004852:Epoxy Compounds; D009153:Mutagens; C024370:3,4-epoxy-1-butene; C007366:diepoxybutane