Quantitative and qualitative differences in the metabolism of C-14-1,3-butadiene in rats and mice: Relevance to cancer susceptibility

1,3-Butadiene (butadiene) is a potent carcinogen in mice, but not in rats, Metabolic studies may provide an explanation of these species differences a nd their relevance to humans. Male Sprague-Dawley rats and B6C3F1 mice were exposed for 6 h to 200 ppm [2,3-C-14]-butadiene (specific radioactivity [s a] 20 mCi/mmol) in a Cannon nose-only system. Radioactivity in urine, feces , exhaled volatiles and C-14-CO2 were measured during and up to 42 h after exposure. The total uptake of butadiene by rats and mice under these experi mental conditions was 0.19 and 0.38 mmol (equivalent to 3.8 and 7.5 mCi) pe r kg body weight, respectively. In the rat, 40% of the recovered radioactiv ity was exhaled as C-14-CO2, 70% of which was trapped during the 6-h exposu re period. In contrast, only 6% was exhaled as C-14-CO2 by mice, 3% during the 6-h exposure and 97% in the 42 h following cessation of exposure. The f ormation of C-14-CO2 from [2,3-C-14]-labeled butadiene indicated a ready bi odegradability of butadiene. Radioactivity excreted in urine accounted for 42% of the recovered radioactivity from rats and 71% from mice. Small amoun ts of radioactivity were recovered in feces, exhaled volatiles and carcasse s. Although there was a large measure of commonality, the exposure to butad iene also led to the formation of different metabolites in rats and mice. T hese metabolites were not found after administration of [4-C-14] 1,2-epoxy- 3-butene to animals by ip injection. The results show that the species diff erences in the metabolism of butadiene are not simply confined to the quant itative formation of epoxides, but also reflect a species-dependant selecti on of metabolic pathways. No metabolites other than those formed via an epo xide intermediate were identified in the urine of rats or mice after exposu re to C-14-butadiene. These findings may have relevance for the prediction of butadiene toxicity and provide a basis for a revision of the existing ph ysiologically based pharmacokinetic models.