Oxidative bioactivation of S-alkyl phosphorothiolate pesticides: stereospecificity of profenofos insecticide activation.

The mouse liver microsomal mixed-function oxidase system converts several phosphorothiolate pesticides with S-ethyl, S-propyl, or S-butyl groups to more potent inhibitors of acetylcholinesterase. This activation is stereospecific for the chiral isomers of O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothiolate (profenofos insecticide); the more toxic (-) isomer becomes a 34-fold better inhibitor of acetylcholinesterase in vitro, whereas the less toxic (+) isomer is deactivated by a factor of 2. Prior treatment of the microsomes with piperonyl butoxide or another mixed-function oxidase inhibitor markedly decreases the activation. Piperonyl butoxide also protects against brain acetylcholinesterase inhibition and cholinergic symptoms in chicks resulting from (-)-profenofos administration, thus establishing the importance of the oxidative bioactivation of S-alkyl phosphorothiolate pesticides in vivo.