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

Abstract

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.