Serial Cross-Sectional Human Biomonitoring Analysis of Pesticide Exposure Patterns and Their Association with Lipid Metabolism Biomarkers: The Mediating Role of Liver Function

Continuous low-level exposure to pesticides is inevitable in daily life. Previous studies have demonstrated the adverse effects of pesticide exposure on lipid metabolism. However, population studies have focused primarily on individual pesticides and have short-term fluctuations, and the animal experiments used doses far higher than those exposed by the general population. In this study, urinary concentrations of metabolites of three classes of pesticides, including organophosphate, pyrethroid, and phenoxy carboxylic acid, were determined in 1858 participants of repeated cross-sectional biomonitoring programs from 2018 to 2022. We comprehensively analyzed the association of pesticide metabolites and pesticide exposure patterns with lipid metabolism biomarkers. The indirect effects of liver function markers in these associations were explored by using the structural equation model analysis. Generalized linear models showed that 3,5,6-trichloro-2-pyridinol and para-nitrophenol were positively correlated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride. In contrast, 3-phenoxybenzoic acid was negatively correlated with apolipoprotein B. Quantile g-computation and Bayesian Kernel Machine Regression showed a consistent gradual increase in high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels but a gradual decrease in apolipoprotein B levels with increasing exposure to pesticide mixtures. By analyzing the exposure patterns of different categories of pesticides, we found that the population has a high level of exposure to organophosphate pesticides, which disrupts lipid metabolism more significantly than other pesticides. Liver function exhibited significant mediating effects in the association between pesticide exposure and lipid metabolism biomarkers. The results indicated that pesticide exposure was significantly associated with lipid metabolism, and this association may be modulated by improvements in liver function.