S-methylation of O,O-dialkyl phosphorodithioic acids: O,O,S-trimethyl phosphorodithioate and phosphorothiolate as metabolites of dimethoate in mice.
O,O,S-Trimethyl phosphorodithioate and phosphorothiolate [(MeO)2P(S)SMe and (MeO)2P-(O)SMe, respectively are known from earlier studies to be impurities, delayed toxicants, and detoxication inhibitors in several major O,O-dimethyl phosphorodithioate insecticides. Our recent studies show extensive S-methylation of mono- and dithiocarbamic acids in mice, suggesting the possibility that phosphorodithioic acids such as (MeO)2P(S)SH might also undergo S-methylation. This possibility was examined in ip-treated mice with emphasis on the metabolites of dimethoate [(MeO)2P(S)SCH2C(O)NHMe], one of the most important organophosphorus insecticides. The urinary metabolites of dimethoate, which contains no P-SMe substituent, were found to include four compounds with P-SMe moieties identified by 31P NMR spectroscopy as MeO(HS)P(O)SMe, MeO(HO)P(O)SMe, (MeO)2P(S)SMe, and (MeO)2P-(O)SMe; the latter two compounds are also established by GC-MS as dimethoate metabolites in mouse urine, liver, kidney, and lung. Several approaches verified unequivocally that the previously unknown P-SMe metabolites in urine and tissues are due to in vivo S-methylation rather than to impurities. Studies with other O,O-dimethyl and O,O-diethyl phosphorodithioate insecticides established the analogous S-methylation pathway for ethion, malathion, phenthoate, phosalone, and phosmet in mice. Thus, metabolism of O,O-dialkyl phosphorodithioate insecticides in mammals is shown here for the first time to yield S-methyl phosphorodithioates and phosphorothiolates from in vivo S-methylation of the intermediate O,O-dialkyl phosphorodithioic acids.
Department of Environmental Science, Policy, and Management, University of California, Berkeley 94720-3112, USA.
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M
Mahajna
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Quistad
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Casida
D000818:Animals; D004117:Dimethoate / Q000378:metabolism*; D008297:Male; D008745:Methylation / Q000187:drug effects; D051379:Mice; D063086:Organothiophosphates / Q000378:metabolism*; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis*; D010575:Pesticides / Q000378:metabolism; D014226:Triazenes / Q000378:metabolism
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; D010575:Pesticides; D014226:Triazenes; D004117:Dimethoate