Comparison of the disposition of butadiene epoxides in Sprague–Dawley rats and B6C3F1 mice following a single and repeated exposures to 1,3-butadiene via inhalation

Abstract

1,3-Butadiene (BD), a compound used extensively in the rubber industry, is a potent carcinogen in mice and a weak carcinogen in rats in chronic carcinogenicity bioassays. While many chemicals are known to alter their own metabolism after repeated exposures, the effect of exposure prior to BD on its in vivo metabolism has not been reported. The purpose of the present research was to examine the effect of repeated exposure to BD on tissue concentrations of two mutagenic BD metabolites, butadiene monoepoxide (BDO) and butadiene diepoxide (BDO2). Concentrations of BD epoxides were compared in several tissues of rats and mice following a single exposure or ten repeated exposures to a target concentration of 62.5 ppm BD. Female Sprague–Dawley rats and female B6C3F1 mice were exposed to BD for 6 h or 6 h×10 days. BDO and BDO2 were quantified in blood and several other tissues following preparation by cryogenic vacuum distillation and analysis by multidimensional gas chromatography–mass spectrometry. Blood and lung BDO concentrations did not differ significantly (P≤0.05) between the two exposure regimens in either species. Following multiple exposures to BD, BDO levels were 5- and 1.6-fold higher (P≤0.05) in mammary tissue and 2- and 1.4-fold higher in fat tissue of rats and mice, respectively, as compared with single exposures. BDO2 levels also increased in rat fat tissue following multiple exposures to BD. However, in mice, levels of this metabolite decreased by 15% in fat, by 28% in mammary tissue and by 34% in lung tissue following repeated exposures to BD. The finding that the mutagenic epoxide BDO, which is the precursor to the highly mutagenic BDO2, accumulates in rodent fat may be important in assessing the potential risk to humans from inhalation of BD.