Stereoselective <i>In Vitro</i> Metabolism,\nHepatotoxicity, and Cytotoxic Effects of Four Enantiomers of the Fungicide\nPropiconazole

Propiconazole (PRO) is a chiral triazole fungicide that\nhas been\nwidely used for several years. However, its metabolic characteristics\nand hepatotoxicity in the chiral level environment remain unclear.\nIn this study, the stereoselective behavior of PRO was investigated\nby using liver microsome incubation, cell viability assay, inhalation\nexposure, and molecular docking. Our results demonstrated that the\nisomers <i>trans</i> (−)-2<i>R</i>,4<i>R</i>-PRO and <i>cis</i> (+)-2<i>R</i>,4<i>S</i>-PRO exhibited slower metabolic rates in rat liver microsomes.\nThe cytochrome P450 family 1 subfamily A polypeptide 2 enzyme was\nfound to play a key role in the metabolism of PRO, contributing to\nits stereoselective behavior. Histopathological and cell viability\nresults showed that exposure to <i>rac</i>-PRO could induce\nsevere hepatotoxicity in mice. This effect might be related to the\naccumulation of <i>cis</i> (+)-2<i>R</i>,4<i>S</i>-PRO in the liver, which has a slow metabolism and is highly\ntoxic. Our findings indicate that avoiding the application of <i>cis</i> (+)-2<i>R</i>,4<i>S</i>-PRO in agriculture\ncan significantly reduce adverse effects on nontarget organisms.