Combined exposure risk of emamectin benzoate and cyantraniliprole mixture to nonalcoholic fatty liver disease

Evidence links pesticides to nonalcoholic fatty liver disease (NAFLD), but the combined effects of dietary pesticide residue mixture exposure on NAFLD remain poorly documented. This study employed a 42-day subchronic exposure in mice at the National Estimated Daily Intake (NEDI), calculated from the residue levels of emamectin benzoate and cyantraniliprole detected in the 290 collected samples of rice, maize, tomato, cowpea, and cotton. Histopathological and biochemical analyses revealed that subchronic co-exposure to emamectin benzoate and cyantraniliprole increased NAFLD risk, as evidenced by abdominal fat accumulation, pathological alterations, inflammatory responses, oxidative injury, and glucose tolerance impairment in mice. Integrated omics analyses suggest that the observed synergism is driven primarily by disruptions in lipid and glucose metabolism, with significant contributions from the PPAR pathway. These findings suggest a potential synergistic effect of emamectin benzoate and cyantraniliprole mixture exposure on NAFLD risk, highlighting the need to update pesticide mixture risk assessments.