Enantioselective disposition and metabolic products of isofenphos-methyl in rats and the hepatotoxic effects
2020
Abstract Isofenphos-methyl (IFP), a chiral organophosphorus pesticide, is one of the main chemicals used to control underground insects and nematodes. Recently, the use of IFP on vegetables and fruits has been prohibited due to its high toxicity. In this study, we investigated the enantioselective distribution and metabolism of IFP and its metabolites, namely, isofenphos-methyl oxon (IFPO) and isocarbophos oxon (ICPO), in male Sprague Dawley (SD) rats. Forty eight hours (48 h) after exposure, ICPO was the main detectable compound in blood (up to 75%) and urine (up to 77%), and we found that (S)-ICPO was significantly more stable than (R)-ICPO (p 0.05). We found that cytochrome P450 (CYP) (i.e. CYP2C11, CYP2D2 and CYP3A2 enzymes and carboxylesterases) is responsible for the enantioselective metabolism of IFP in liver. In addition, rats exposed to (S)-IFP exhibited hepatic lipid peroxidation, liver inflammation and hepatic fibrosis. This study provides useful information and a reference for the biomonitoring and risk assessment of IFP and organophosphorus pesticide exposure.
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