Associations of per- and polyfluoroalkyl substances and alternatives with thyroid hormones in pregnant women: A cross-sectional study in China

Per- and polyfluoroalkyl substances (PFAS) have been recognized as potential disruptors of thyroid function, but the health implications of their increasingly used emerging alternatives, particularly during pregnancy, remain poorly understood. To address this, we conducted a cross-sectional study involving 492 pregnant women in Zhejiang, China, quantifying thirty PFAS and three thyroid hormones and employing advanced statistical models to assess their associations. The study findings revealed that exposure to perfluorododecanoic acid (PFDoDA) was associated with a 6.37 % decrease in free 3,5,3',5'-tetraiodothyronine (FT4), exposure to perfluoro-2-methoxyacetic acid (PFMOAA) resulted in a 32.52 % increase in thyroid stimulating hormone (TSH) and a 2.33 % decrease in FT4, and exposure to 8:2 Chlorinated polyfluorinated ether sulfonic acid (8:2 Cl-PFESA) led to a 28.46 % increase in TSH. Quantile g-computation (Qgcomp) models demonstrated a significant 21.04 % increase in TSH (95 % CI: 3.11 %, 42.09 %) association with PFAS mixtures, with 8:2 Cl-PFESA (0.25) and PFMOAA (0.23) showing the highest positive weights. These findings were further corroborated by the adaptive elastic net (AENET) models, which confirmed the positive correlation between PFAS mixtures and TSH. Bayesian statistics-based benchmark dose (BBMD) analyses indicated that 8:2 Cl-PFESA (0.01 ng/mL), PFMOAA (0.02 ng/mL), and PFDoDA (0.42 ng/mL) might possess lower safety margin levels for thyroid disruption, warranting more stringent regulatory standards. These findings highlight the necessity of conducting routine biomonitoring and further exploration into the toxicological mechanisms of the emerging PFAS alternatives to address the potential health risks.