The objectives of this research were to examine the metabolism in vivo of the pesticide leptophos in the rat under normal conditions and during inhibition of the mixed-function oxidases and during depletion of glutathione. Glutathione is a cofactor in the conjugation reactions of the glutathione-S-transferases. Both the mixed-function oxidase system and the glutathione-S-transferases have been shown to be important in the biotransformation of other organophosphate pesticides. Urinary

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... of leptophos were extracted, derivatized and subsequently analyzed by gas-liquid chromatography. The methods used to analyze for alkyl phosphonates were subject to several shortcomings and modifications of the original procedure were necessary. With the modifications the method gave reliable and reproducible results. The results of this study showed that the distribution of leptophos metabolites excreted in the urine of normal rats was methyl phenylthiophosphonate 63%, methyl phenylphosphonate 23%, and phenyl phosphonic acid 14%. These metabolites were both qualitatively and quantitatively similar to those reported for the mouse. In addition, manipulation of metabolic pathways supported the predictions made as to the nature (i.e., oxidative or conjugative) of the various pathways of leptophos metabolism. The results indicate that demethylation and possibly dearylation of leptophos axon are GSH-dependent reactions and that dearylation of leptophos is an MFO-mediated detoxification pathway.