Comparison of Esterase Sensitivity, Metabolic Efficiency, and Toxicity Levels of Two Organophosphorus Insecticides: Parathion and Chlorpyrifos

摘要

Parathion and chlorpyrifos are phosphorothionate insecticides, and parathion is about an order of magnitude more toxic than chlorpyrifos. Our laboratories have investigated several aspects of the biochemical reactivity and the metabolism of these two insecticides in rats to identify factors that influence the acute toxicity level. Both insecticides are bioactivated by cytochromes P450 to potent oxon metabolites by desulfuration, with bioactivation of parathion more efficient than that of chlorpyrifos. P450-mediated detoxication, dearylation, can also occur, and is more effective against chlorpyrifos than parathion. The oxons can persistently inhibit serine esterases, including nervous system acetylcholinesterase (the target enzyme for acute toxicity) and protective B-esterases such as carboxylesterases; chlorpyrifos-oxon is a more potent inhibitor of both acetylcholinesterase and carboxylesterases than paraoxon. The oxons can be hydrolyzed by paraoxonase (PON) which is much more efficient towards chlorpyrifos-oxon than paraoxon. Chlorpyrifos, because of its high lipophilicity, results in more persistent inhibition of serine esterases than does parathion. The lower toxicity of chlorpyrifos than parathion seems to be the result largely of less effective bioactivation and more effective detoxication by P450, carboxylesterases and paraoxonase, despite the greater affinity of chlorpyrifos-oxon than paraoxon toward acetylcholinesterase. These factors can be useful in PBPK modeling.