A. Gray, T. Fukuto
Dec 1, 1984
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Influential Citations
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Journal
Pesticide Biochemistry and Physiology
Abstract
Abstract The in vivo metabolism of [14CH3S]- and [14CH3O]O,O,S-trimethyl phosphorothioate (OOS) was followed in rats after oral administration of threshold or LD50 toxic doses of 20 or 60 mg/kg. Similar metabolic studies were conducted with coadministration of 1% O,O,O-trimethyl phosphorothionate (OOO), which prevented all signs of delayed toxicity, including weight loss. When administered alone, OOS was metabolized mainly (50–60%) via removal of the CH3S moiety, which was largely converted to expired CO2. Approximately 20% of the compound was O-demethylated, presumably by conjugation with glutathione, and then further metabolized to CO2. Major urinary products were identified as O,O-dimethyl phosphoric acid (50–60%) and O,S-dimethyl phosphorothioic acid (∼20%). Coadministration of OOO caused a slight decrease (∼5%) in the cleavage of the CH3S moiety, indicated by a reduction in 14CO2 from [14CH3S]OOS and a quantitatively similar increase in the formation of O,S-dimethyl phosphoric acid. Limited pharmacokinetic studies indicated that OOS was rapidly absorbed and distributed throughout the body. Coadministration of 1% OOO caused a slight increase in the blood half-life of parent OOS when administered at 60 mg/kg. It was concluded that a small proportion of the cleavage of the CH3S moiety from OOS is involved in the intoxication process, and that this intoxication reaction is specifically inhibited by OOO.