Disposition of butadiene monoepoxide and butadiene diepoxide in various tissues of rats and mice following a low-level inhalation exposure to 1,3-butadiene

摘要: 1,3-Butadiene (BD), a chemical used extensively in the production of styrene-butadiene rubber, is carcinogenic Sprague-Dawley rats and B6C3F 1 mice. Chronic inhalation studies revealed profound species differences potency organ-site specificity BD carcinogenesis between potent carcinogen mice weak rats. Previous from our laboratory others have shown marked metabolism BD, which may account for carcinogenicity. The purpose present study was to examine disposition two mutagenic metabolites, butadiene monoepoxide (BDO) diepoxide (BDO 2 ), blood other tissues during following exposures target concentration 62.5 p.p.m. BD. BDO increased above background blood, bone marrow, heart, lung, fat, spleen thymus after h 4 In rats, levels were tissues. No increases observed rat lungs. , more epoxides, at initiation exposure mice, detected all examined immediately exposure. This metabolite but 40- 160-fold lower than those seen Immediately exposure, 204 ± 15 pmol/g 41-fold sensitive mouse organs, heart lungs, exceeded shows that epoxides are markedly greater organs. high concentrations these organs suggest this compound be particularly important BD-induced carcinogenesis. Thus, although oxidatively metabolized by similar metabolic pathways substantial quantitative tissue responsible sensitivity