Mehta_2025_Toxics_13_

Background: Experimental studies suggest that some insecticides, fungicides, and herbicides can result in liver cell death, but population-based evidence is lacking. We investigated associations between urinary pesticide metabolites and liver biomarkers among adolescents and adults in an Ecuadorian agricultural area. Methods: We examined participants in 2016 (N = 528, 11-17 years) and 2022 (N = 505, 17-24 years). Plasma alanine aminotransferase (ALT), aspartate aminotransferase, soluble cytokeratin-18, and erythrocytic acetylcholinesterase were measured. Urinary biomarkers included four organophosphates, six neonicotinoids, three pyrethroids, two herbicides, and two fungicides. Generalized estimating equation (GEE) models examined associations and introduced sex and age interaction terms and quadratic terms. Quantile g-computation evaluated the effects of pesticide mixtures. Results: No significant associations were observed between pesticide biomarkers and liver biomarkers in longitudinal or cross-sectional analyses. A curvilinear association was found between 3-phenoxybenzoic acid (3-PBA; pyrethroid) and ALT (beta(quadratic) = -0.35, 95% CI: [-0.67, -0.04]) in 2016, but not in 2022. Sex modified the associations of 3-PBA with AST, ALT, and CK18-M65 in adolescents (2016), with non-significant positive associations observed in males and non-significant negative associations observed in females. No pesticide mixture effects were observed. Conclusions: Urinary biomarkers of various insecticides, herbicides, fungicides, and their mixtures were not associated with liver biomarkers among adolescents and young adults in agricultural settings. These largely null findings, consistent across time points, suggest background-level exposures in these settings possibly do not harm liver health in this population, though effects at higher exposures cannot be ruled out.