Recent advances in the metabolism of organophosphorus insecticides

Rat metabolism studies were conducted with three organophosphorus ester insecticides: [phenyl- or ethoxy-14C]Dyfonate, O-ethyl S-phenyl ethylphosphonodithioate; [phenyl-14C]Trithion, S-[(4-chlorophenylthio)methyl]O,O-diethylphosphorodithioate; and [phenyl-14C]R-14805, 4-[O,0-diethyl phosphorothioyl)]-acetophenoneoxime-N'-methylcarbamate. Compounds were administered orally to rats at 2 to 8 mg/kg, and biotransformation pathways were established from identified metabolites. Metabolites were isolated from O-96 hr urine and identified by using one or more methods including thin-layer chromatography, radio-gas-liquid chromatography, mass spectrometry, and nuclear magnetic resonance. Each of these model insecticides displayed a distinct bioactivation and detoxification pathway. Conversion to potent acetylcholinesterase inhibitors resulted from desulfuration of Dyfonate, desulfuration and thioether oxidation of Trithion, and desulfuration and a variety of modifications of the leaving group of R-14805. The compounds were deactivated primarily via cleavage of an organophosphorus ester group. All three compounds and their metabolites were rapidly excreted primarily in urine without any bioaccumulation in tissues.