Gender and species differences in the metabolism of 1,3-butadiene to butadiene monoepoxide and butadiene diepoxide in rodents following low-level inhalation exposures

Abstract

Levels of butadiene monoepoxide (BDO) and butadiene diepoxide (BDO 2) were compared in tissues of male Sprague-Dawley rats and male B6C3F 1 mice and in tissues of male and female Sprague-Dawley rats following inhalation exposures to 62.5 ppm 1,3-butadiene (BD). In male rats, BDO 2 levels were highest in blood and were present at a concentration of only 5 ± 1 pmol/g. Following a 6-h exposure, the concentration of BDO 2 in the blood, femurs, lung and fat of female rats was 3 to 7-fold that of male rats. Levels of BDO were similar in tissues of female and male rats. Generally, levels of BDO were approximately 3 to 8-fold greater in mouse tissues as compared with rat tissues following 4-h exposures to BD. In blood, 204 ± 15 pmol/g BDO 2 was detected in male mice, while in rats, blood BDO 2 levels were 5 ± 1 pmol/g. This study shows marked species differences in tissue levels of BD epoxides, particularly BDO 2, in rats and mice, and is the first to show gender differences in BD metabolism.