Oxidation of Thiophosphate Insecticides in the Rat

Abstract

THE problems encountered in assessing the toxicity of the organo-phosphorus insecticides towards mammals have been reviewed in a recent article by Aldridge and Barnes¹. It was pointed out that compounds such as O-p-nitrophenyl O,O-diethyl thiophosphate (parathion, E 605) are considerably more potent in vivo as inhibitors of true cholinesterase than would be expected from their inhibitory activity in vitro; the summarized evidence indicated that thiophosphates of this type are transformed into another more active inhibitor in vivo. It has been shown that the inhibitory action of technical parathion on true cholinesterase in vitro is due mainly, if not entirely, to an impurity of the form O-p-nitrophenyl O,S-diethyl thiophosphate². Thus it was conceivable that the increased potency of parathion in vivo could be due to the formation of this S-ethyl isomer, but recent evidence seems to suggest that isomerization may not be the complete answer to this problem³. In the course of investigations on the selective inhibition of ali-esterase (tributyrinase), we have obtained evidence indicating that the thiophosphate insecticides may be oxidized in vivo to their phosphate analogues.