Association study of internal exposure levels of perfluoroalkyl substances and blood lipid levels in the elderly population and adverse Outcome pathway analysis

Previous research on per- and polyfluoroalkyl substances (PFAS) and blood lipids in the elderly is limited, and the mechanisms by which PFAS affect lipid levels remain unclear. This study aims to investigate the association between PFAS exposure and blood lipid levels in the elderly and to construct Adverse Outcome Pathways (AOP) using toxicological databases. The study included 753 individuals aged 65 and above from a rural area in Northwest China. Serum concentrations of 32 PFAS were measured, and 16 of them were included in the statistical analysis. Linear regression models and restricted cubic spline models were used to examine the associations between PFAS exposure and blood lipid levels. Additionally, Bayesian kernel machine regression was applied to assess the mixture effects of PFAS exposure. The results showed that perfluorooctanoic acid (PFOA) was significantly positively correlated with total cholesterol (β = 0.55, 95 % CI: 0.18, 0.92), while perfluoro-2-propoxypropanoic acid (HFPO-DA) was negatively associated with total cholesterol (β = −0.35, 95 % CI: 0.50, −0.20). Through AOP network analysis, the peroxisome proliferator-activated receptor alpha (PPARα) was identified as a key molecular target through which these two PFAS exposure may influence lipid levels. These findings provide new evidence for understanding the impact of PFAS on blood lipid levels in the elderly population.