Monooxygenase-mediated metabolism and binding of ethylene thiourea to mouse liver microsomal protein

Ethylenethiourea (ETU), a metabolite and degradation product of the ethylenebisdithiocarbamate fungicides, is a substrate for the flavin-dependent monooxygenase (FMO), a microsomal NADPH requiring enzyme that can oxidize ETU, as well as for the cytochrome P-450 enzyme system. The present study shows that the mouse metabolises ETU preferentially via the FMO system. FMO activity decreases as male, but not female mice, increase in age to 30 weeks. This difference in activity is reflected in decreased overall metabolism of ETU and in a decreased FMO-mediated binding of radiolabelled ETU to mouse liver microsomal protein. The rapid metabolism of ETU by the FMO system may contribute to the lack of acute toxicity and teratogenicity exhibited by the mouse relative to the rat. However, the FMO-mediated binding of ETU metabolites to mouse liver protein is consistent with the chronic hepatotoxicity exhibited by ETU in this species.