Association of organophosphate pesticide exposure with serum lipid profiles in US adults: an analysis of NHANES 2003–2020

Organophosphate (OP) pesticides are extensively used in agricultural and residential environments, resulting in widespread human exposure. However, their effects on lipid metabolism remain unclear. Using cross-sectional data from eight National Health and Nutrition Examination Survey (NHANES) cycles (2003-2020), we examined associations between urinary OP metabolites and serum lipid profiles in a nationally representative sample of 3,769 U.S. adults. Survey-weighted multivariable linear regression, restricted cubic spline models, and subgroup analyses were conducted to account for the complex survey design. Mixture effects were evaluated using weighted quantile sum regression and quantile g-computation, and mediation analysis explored the role of systemic inflammation. Diethyl thiophosphate (DETP) and dimethyl dithiophosphate (DMDP) were positively associated with triglyceride (TG) levels, while dimethyl phosphate (DMP) and diethyl phosphate (DEP) exhibited U-shaped associations with TG and total cholesterol (TC). Mixture analyses confirmed positive associations of OP exposure with TG, with dimethyl thiophosphate (DMTP) and DETP contributing most prominently. No evidence of mediation by inflammatory markers was observed. These findings suggest that OP pesticide is associated with adverse lipid profiles in U.S. adults, emphasizing the need for continued surveillance and mechanistic research on the long-term health effects.