Enantioselective hepatotoxicity of rac- epoxiconazole and epoxiconazole enantiomers in lizards (Eremias argus).

Epoxiconazole (EPX) is widely applied to control various fungal diseases in crops. However, the toxicological effects of EPX on reptiles remain unknown, especially at the enantiomer level. In this study, lizards were repeatedly exposed to rac-EPX, (+)-EPX, and (-)-EPX at doses of 10 and 100 mg/kg bw for 21 days. Low-dose exposure resulted in hepatic steatosis, while high-dose treatment caused more severe pathological changes, including large areas of cell necrosis, loss of cellular structure, and nucleus disappearance. The elevation of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) indicated hepatocyte impairment after high-dose exposure. Furthermore, increased levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) suggested oxidative damage to lipids and DNA in cells, respectively. In addition, the EPX-induced hepatotoxicity exhibited significant enantioselectivity, with injury severity ranked as follows: rac-EPX > (-)-EPX > (+)-EPX. Notably, the highest hepatotoxicity in lizards was attributed to rac-EPX, suggesting a synergistic effect of rac-(+)-EPX and rac-(-)-EPX. The hepatotoxicity induced by (+)-EPX in lizards was lower than that of (-)-EPX, but with higher fungicidal activity. Therefore, it is advisable to utilize (+)-EPX in agricultural production. This study provides a scientific basis for the environmental risk assessment of EPX and the development of future optically pure pesticides.