DISPOSITION OF BUTADIENE MONOEPOXIDE AND BUTADIENE DIEPOXIDE IN VARIOUS TISSUES OF RATS AND MICE FOLLOWING A LOW-LEVEL INHALATION EXPOSURE TO 1,3-BUTADIENE

1,3-Butadiene (BD), a chemical used extensively in the production of s tyrene-butadiene rubber, is carcinogenic in Sprague-Dawley rats and E6 C3F(1) mice. Chronic inhalation studies revealed profound species diff erences in the potency and organ-site specificity of BD carcinogenesis between rats and mice. BD is a potent carcinogen in mice and a weak c arcinogen in rats. Previous studies from our laboratory and others hav e shown marked differences between rats and mice in the metabolism of BD, which may account for species differences in carcinogenicity. The purpose of the present study was to examine the production and disposi tion of two mutagenic BD metabolites, butadiene monoepoxide (BDO) and butadiene diepoxide (BDO2), in blood and other tissues of rats and mic e during and following inhalation exposures to a target concentration of 62.5 p.p.m. BD. BDO was increased above background in blood, bone m arrow, heart, lung, fat, spleen and thymus tissues of mice after 2 h a nd 4 h exposures to BD. In rats, levels of BDO were increased in blood , fat, spleen and thymus tissues. No increases in BDO were observed in rat lungs. BDO2, the more mutagenic of the two epoxides, was increase d in the blood of rats and mice at 2 and 4 h after initiation of expos ure to BD. In mice, BDO2 was detected in all tissues examined immediat ely following the 4 h exposure. This metabolite was detected in heart, lung, fat, spleen and thymus of rats, but at levels 40- to 160-fold l ower than those seen in mice. Immediately after the 4 h exposure, bloo d levels of BDO2 were 204 +/- 15 pmol/g for mice but were 41-fold lowe r for rats. In the sensitive mouse target organs, heart and lungs, lev els of BDO2 exceeded BDO levels immediately after the exposure. This s tudy shows that the levels of BD epoxides are markedly greater in the mouse BD target organs. The high concentrations of BDO2 in these organ s suggest that this compound may be particularly important in BD-induc ed carcinogenesis. Thus, although BD is oxidatively metabolized by sim ilar metabolic pathways in rats and mice, the substantial quantitative differences in tissue levels of mutagenic epoxides between species ma y be responsible for the increased sensitivity of mice to BD-induced c arcinogenicity.