ROLE OF DETOXICATION PATHWAYS IN ACUTE TOXICITY LEVELS OF PHOSPHOROTHIONATE INSECTICIDES IN THE RAT

Phosphorothionate insecticides and their active oxon metabolites can b e detoxified by a variety of hepatic mechanisms. Cytochrome P450-media ted dearylation activity was higher in males than in females. While de arylation was induced by phenobarbital in both sexes, it was induced b y beta-naphthoflavone in females only. Detoxication of oxons in the pr esence of EDTA was inducible by phenobarbital, was higher in males tha n in females, and paralleled aliesterase activity. In vitro Ca++-depen dent A-esterase-mediated hydrolysis of chlorpyrifos-oxon but not of pa raoxon occurred at biologically relevant nM concentrations. This hydro lysis was also inducible by phenobarbital. Glutathione-mediated conjug ation did not appear to be relevant to the disposition of the phosphor othionates studied here. Hepatic detoxication via dearylation, alieste rase phosphorylation and A-esterase-mediated hydrolysis (for some orga nophosphates) all appear to be relevant reactions in the attenuation o f acute toxicity.