Associations between serum per- and polyfluoroalkyl substances and thyroid hormones in Chinese adults: A nationally representative cross-sectional study

Disruption of thyroid homeostasis has been indicated in human studies on the effects of per- and polyfluoroalkyl substances (PFASs). However, limited research exists on this topic within the general Chinese population. Based on a substantial and representative sample of the Chinese adult population, our study provides insight into how PFASs specifically affect thyroid homeostasis. The study included 10 853 participants, aged 18 years and above, sampled from nationally representative data provided by the China National Human Biomonitoring (CNHBM). Weighted multiple linear regression and restricted cubic spline (RCS) models were used to explore the associations between eight individual PFAS concentrations and total thyroxine (T4), total triiodothyronine (T3), and the T4/T3 ratio. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (qgcomp) were employed to explore the joint and independent effects of PFASs on thyroid homeostasis. Both individual PFASs and PFAS mixtures exhibited a significant inverse association with serum T3 and T4 levels, and displayed a positive association with the T4/T3 ratio. Perfluoroundecanoic acid (PFUnDA) [-0.07 (95 % confidence interval (CI): -0.08, -0.05)] exhibited the largest change in T3 level. PFUnDA also exhibited a higher weight compared to other PFAS compounds in qgcomp models. Additionally, a critical exposure threshold for each PFAS was identified based on nonlinear dose-response associations; beyond these thresholds, the decreases in T3 and T4 levels plateaued. Specifically, for perfluoroheptane sulfonic acid (PFHpS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an initial decline in hormone levels was observed, followed by a slight increase when concentrations surpassed 0.7 ng/mL and 2.5 ng/mL, respectively. Sex-specific effects were more pronounced in females, and significant associations were observed predominantly in younger age groups. These insights contribute to our understanding of how PFAS compounds impact thyroid health and emphasize the need for further research and environmental management measures to address these complexities.