Abstract
Metabolism of isofenphos (O-[1-14C]ethyl O-2-isopropoxycarbonylphenyl N-isopropylphosphoramidothioate) was examined under in vitro conditions of rat liver. In each fraction of mitochondria, microsomes and supernatant, isofenphos was metabolized enzymatically with NADPH, and the formation of polar metabolites was especially accelerated in the microsome-NADPH system. When the metabolites were partitioned between benzene and water, isofenphos-oxon and aminoisofenphos were identified as benzene soluble metabolites, and O-ethyl O-2-isopropoxycarbonylphenyl hydrogen phosphorothioate, O-ethyl O-2-isopropoxycarbonylphenyl hydrogen phosphate, O-ethyl hydrogen N-isopropylphosphoramidothioate and O-ethyl hydrogen N-isopropylphosphoramidate as water soluble metabolites. Isofenphos was metabolized rapidly into O-ethyl hydrogen N-isopropylphosphoramidate through isofenphos-oxon by the microsome fraction of rat liver, but it was unlikely that isofenphos-oxon could accumulate in the presence of NADPH. The conversion to water soluble metabolites was more dominant in the cleavage of P-O-C(aryl) bond than in that of P-N linkage. None of benzene soluble metabolites inhibited insect acetylcholinesterase (AChE) at the concentration of 10-7M.
