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, buta diene monoepoxide and diepoxybutane, were tested in the bacterial muta tion assay using Salmonella typhimurium strain TA100 with and without metabolic activation (S9 mix), All three compounds showed a mutagenic response, The bifunctional epoxide was more effective than the diolepo xide which was more effective than the monoepoxide. Toxicity appeared to follow the ranking of the chemicals for their mutagenic potency, Th e monoepoxide and the diolepoxide were also tested for induction of mi cronuclei in mouse bone marrow erythrocytes and for dominant lethal mu tation induction in postmeiotic male mouse germ cells, The effects of the diepoxide in both in vivo tests have been published earlier. In th e micronucleus assay, the three metabolites gave a positive response w hereby the diepoxide was more effective than the monoepoxide which was more effective than the diolepoxide, In contrast to the diepoxide whi ch was positive at a dose as low as 36 mg/kg, the monoepoxide and the diol did not show an induction of dominant lethal effects up to doses of 120 and 240 mg/kg, respectively, It is concluded that the metabolit es were mutagenic in bacteria without metabolic activation and clastog enic in mouse bone marrow; only the bifunctional diepoxide, however, w as active in postmeiotic male mouse germ cells.