BackgroundAlthough studies have assessed the association of metals and bisphenols with lipid metabolism, the observed results have been controversial, and limited knowledge exists about the combined and interactive effects of metals and bisphenols exposure on lipid metabolism. MethodsPlasma metals and serum bisphenols concentrations were evaluated in 888 participants. Multiple linear regression and logistic regression models were conducted to assess individual associations of 18 metals and 3 bisphenols with 5 lipid profiles and dyslipidemia risk, respectively. The dose-response relationships of targeted contaminants with lipid profiles and dyslipidemia risk were captured by applying a restriction cubic spline (RCS) function. The bayesian kernel machine regression (BKMR) model was used to assess the overall effects of metals and bisphenols mixture on lipid profiles and dyslipidemia risk. The interactive effects of targeted contaminants on interested outcomes were explored by constructing an interaction model. ResultsSingle-contaminant analyses revealed that exposure to iron (Fe), nickel (Ni), copper (Cu), arsenic (As), selenium (Se), strontium (Sr), and tin (Sn) was associated with elevated lipid levels. Cobalt (Co) showed a negative association with high density lipoprotein cholesterol (HDL-C). Bisphenol A (BPA) and bisphenol AF (BPAF) were associated with decreased HDL-C levels, with nonlinear associations observed. Vanadium (V), lead (Pb), and silver (Ag) displayed U-shaped dose-response relationships with most lipid profiles. Multi-contaminant analyses indicated positive trends between contaminants mixture and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C). The interaction analyses showed that Se-Fe exhibited synergistic effects on LDL-C and non-HDL-C, and Se-Sn showed a synergistic effect on HDL-C. ConclusionsOur study suggested that exposure to metals and bisphenols was associated with changes in lipid levels, and demonstrated their combined and interactive effects.