Metabolic alterations bridge exposure to urinary halogenated phenols and bisphenols to dyslipidemia: Evidence from an e-waste recycling area.

Halogenated phenols and bisphenols are metabolic-disrupting chemicals related to electronic waste (e-waste) dismantling activities. However, their adverse effects on lipid metabolism and the underlying mechanisms remain insufficiently understood. Based on a cross-sectional study of 227 e-waste workers and residents from an e-waste recycling area in China, we measured 11 urinary halogenated phenols and bisphenols, quantified four serum lipid parameters, and performed untargeted serum metabolomics. Dyslipidemia and its subtypes (hypercholesterolemia, hypertriglyceridemia, and hyper low-density lipoprotein cholesterol) were defined according to clinical criteria. After covariate adjustment, six phenolic compounds (PCs) and their mixture were associated with increased odds of dyslipidemia and its subtypes, with 3,5-dichlorophenol contributing most to dyslipidemia, hyper low-density lipoprotein cholesterol, and hypertriglyceridemia, whereas 3,4-dichlorophenol contributed most to hypercholesterolemia. Stronger associations were observed in males, normal-weight individuals, and those aged <60 years. Mediation analysis identified nine metabolites that significantly mediated these associations (proportions mediated: 14.8%-63.7%), annotated to amino acid, energy, and retinol metabolism pathways. Hierarchical partitioning revealed that PC exposure alone explained 4.28% of the variance in lipid metabolism, indicating a meaningful contribution. These findings provide potential mechanistic insights into the associations of halogenated phenol and bisphenol exposure with lipid homeostasis and highlight the need to reduce exposure to these chemicals among e-waste workers and nearby residents.