Per- and polyfluoroalkyl substance profiles and associations with thyroid hormones in a coal mining population from Shanxi Province, China

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) exposure may cause endocrine disruption. However, PFAS exposure and their potential associations with thyroid hormones remain unclear in coal mining areas. OBJECTIVES: To characterize PFAS exposure profile and their associations among this population. METHODS: Serum levels of PFASs and thyroid hormones were measured in 760 participants. Multiple linear regression and restricted cubic spline models assessed individual PFAS associations with thyroid hormones, while Bayesian kernel machine regression and quantile-based g-computation evaluated joint effects. Stratification and sensitivity analyses were conducted to verify the validity and robustness of results. RESULTS: PFOA was extraordinarily high (median: 1623 μg/L), reaching 10-fold those of fluorochemical plant workers, and showed a positive correlation with a 0.057 increase in FT4 per ln-unit (95% CI: 0.006, 0.107). Emerging PFAS substitutes showed stronger, non-linear dose-response associations with thyroid hormones than legacy compounds. PFAS mixture exposure was inversely associated with FT3, TT4, TT4/FT3 and TT4/FT4 (β: -4.816 to -0.071, 95% CI: -6.708 to -0.121, -2.923 to -0.021), but positively with FT4/FT3 (β: 0.074, 95% CI: 0.021, 0.126). Age and BMI were important effect modifiers for associations between PFASs and thyroid hormones, with underweight and obese individuals being more susceptible. CONCLUSIONS: PFAS exposure levels were extraordinarily high and significantly associated with thyroid hormones. Emerging substitutes showed stronger effects and complex bidirectional influences, and mixture exposure exerted the same effects. Age and BMI served as important effect modifiers. Notably high PFAS exposure and their strong links to thyroid hormone homeostasis in coal mining population warranted further validation.