In vivo and in vitro metabolism of ethylenethiourea in the rat and the cat

Ethylenethiourea (ETU), a degradation product of the ethylenebisdithiocarbamate fungicides, is known to be teratogenic in the rat but not the cat. Administration of [ 14C]ETU at 4.0 mg/kg po produces several metabolites in the 24-hr urine of male rats. Compounds tentatively identified were imidazoline, ethylene urea (EU), 4-imidazolin-2-one (imidazolone) and unchanged ETU. [ 14C]ETU was also administered iv to two female cats at 4 mg/kg. Radioactivity in the blood declines with a half-life of 3.5 hr. ETU, EU, and S-methyl ETU were present in the 24-hr urine, with the latter compound comprising 64% of total urinary radioactivity. In vitro metabolism of [ 14C]ETU by cat and rat liver microsomes produced EU, imidazoline, and other unidentified compounds. S-Methyl ETU was produced when [ 14C]ETU was incubated with a 20,000 g cat liver supernatant containing S-adenosyl methionine. The results suggest that the ability of the cat to extensively metabolize ETU to its S-methyl derivative may contribute to the absence of teratogenic effects in this species.