Abstract

Incubations of butadiene monoxide (BMO) with mouse, rat, and human liver microsomes or cDNA-expressed human microsomal epoxide hydrolase led to 3-buten-1,2-diol (BDD) detection; the BDD peak exhibited a GC/MS fragmentation pattern similar to that of reference material. Incubations with rat liver cytosol did not lead to BDD detection; however, when mouse or human liver cytosol was used, BDD was detected but at levels lower than those detected with the liver microsomes. The catalytic efficiency (V_max/K_m ratio) of BDD formation in rat liver microsomes was nearly 3-fold higher than the ratio obtained with mouse liver microsomes. Among two human liver microsomal samples, one sample exhibited a ratio that was nearly 3-fold higher than that of rat liver microsomes, and the second sample exhibited a ratio that was similar to that of rat liver microsomes. Although these results suggest epoxide hydrolases may play a role in BMO metabolism in vivo, rats and mice given BMO (71.3–285 μmol/kg) excreted <1% of the dose as BDD into urine within 24 hr. Thus, further studies into the role of epoxide hydrolases in BMO metabolism and disposition and the fate of BDD are warranted.