Legacy, alternative, and precursor PFAS and associations with lipids and liver function biomarkers: results from a cross-sectional analysis of adult females in the MIREC-ENDO study

BACKGROUND: Legacy per- and polyfluoroalkyl substances (PFAS) can promote dyslipidemia; however, evidence is lacking for alternative and precursor PFAS. We investigated associations between serum concentrations of 31 PFAS and concurrently measured lipids and liver function biomarkers. METHODS: PFAS, lipids, and liver function biomarkers were analyzed in serum samples provided by 282 adult females participating in a 2018-2021 follow-up study of a Canadian pregnancy cohort. We examined percent differences in outcomes continuously for 17 PFAS with >50% detection and as detected vs. not detected for 14 PFAS with 10-50% detection. We also examined associations with the sum of 7 PFAS recommended by the National Academies of Sciences, Engineering, and Medicine guidance report on PFAS testing and 17 PFAS. We used weighted quantile sum (WQS) and quantile g-computation models to estimate joint associations. RESULTS: Each two-fold increase in concentrations of PFHxS, PFOS, PFNA, PFDA, PFHpS, and Σ7PFAS were associated with up to 7% higher total and LDL cholesterol and the TC:HDL ratio. Individuals with detectable concentrations of N-EtFOSA, N-MeFOSA, PFBS, and 9Cl-PF3ONS had up to 17% higher total and LDL cholesterol and TC:HDL. Each one-quartile increase in the mixture of 7 PFAS was associated with up to 10% higher total and LDL cholesterol. Adding additional PFAS to the mixture (17 PFAS) made estimates less precise in WQS models and attenuated associations to the null in quantile g-computation models. CONCLUSION: Alternative and precursor PFAS, including replacements for legacy PFAS, are associated with higher cholesterol levels; prospective studies are required to confirm these findings.