In vitro and in vivo mutagenicity of the butadiene metabolites butadiene diolepoxide, butadiene monoepoxide and diepoxybutane

Three metabolites of 1,3-butadiene, namely butadiene diolepoxide,butadiene monoepoxide and diepoxybutane, were tested in thebacterial mutation assay using Salmonella typhimurium strainTA100 with and without metabolic activation (S9 mix). All threecompounds showed a mutagenic response. The bifunctional epoxidewas more effective than the diolepoxide which was more effectivethan the monoepoxide. Toxicity appeared to follow the rankingof the chemicals for their mutagenic potency. The monoepoxideand the diolepoxide were also tested for induction of micronucleiin mouse bone marrow erythrocytes and for dominant lethal mutationinduction in postmeiotic male mouse germ cells. The effectsof the diepoxide in both in vivo tests have been published earlier.In the micronucleus assay, the three metabolites gave a positiveresponse whereby the diepoxide was more effective than the monoepoxidewhich was more effective than the diolepoxide. In contrast tothe diepoxide which was positive at a dose as low as 36 mg/kg,the monoepoxide and the diol did not show an induction of dominantlethal effects up to doses of 120 and 240 mg/kg, respectively.It is concluded that the metabolites were mutagenic in bacteriawithout metabolic activation and clastogenic in mouse bone marrow;only the bifunctional diepoxide, however, was active in postmeioticmale mouse germ cells. ⁴To whom correspondence should be addressed