METABOLISM OF 1,3-BUTADIENE - SPECIES-DIFFERENCES

Species differences in the metabolism of 1,3-butadiene (ED) have been studied in an effort to explain the major differences observed in the responses of mice, the sensitive species, and rats, the resistant spec ies, to the toxicity of inhaled ED. ED is metabolized by the same meta bolic pathways in ail species studied, but there are major species dif ferences in the quantitative aspects of those pathways. Of the species studied, mice are the most efficient at metabolizing ED to the initia l metabolite, the monoepoxide (BDO). Mice either convert most of the B DO to the diepoxide (BDO2), the most mutagenic of the ED metabolites, or form conjugates of the BDO with glutathione (GSH). Rats, on the oth er hand, are less active at forming BDO, oxidize very little of the BD O to BDO2, and form GSH conjugates with either the BDO or its hydrolys is product, butenediol Primates convert even less of inhaled ED to BDO and hydrolyze most of the BDO to the butenediol. The extent to which primates form BDO2 is unknown. Because of the association of high leve ls of the highly mutagenic BDO2 with the sensitive rodent strain, it i s important to determine the production of this metabolite in primates , particularly humans.