Associations between emerging endocrine-disrupting chemicals and thyroid hormone homeostasis in pregnant women.

Epidemiological evidence on the effects of emerging endocrine-disrupting chemicals (EDCs) on thyroid function during pregnancy is limited. This study investigated associations between 17 emerging EDCs and thyroid hormone (TH) homeostasis in 764 pregnant women from the Jiashan birth cohort, examining oxidative stress as a potential mediator. Urinary concentrations of EDCs (e.g., p-phenylenediamine antioxidants, bisphenol diglycidyl ethers, and benzothiazoles/benzotriazoles), three oxidative stress biomarkers, and plasma levels of five THs were measured at 8-16 weeks of gestation. Multivariable linear regression analyses, adjusted for multiple testing, showed that higher exposure to N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), bisphenol S (BPS), and 1-H-benzotriazole (1-H-BTR) was associated with elevated total triiodothyronine (TT3) levels, with an increase of 5 % (95 % CI: 0.01 to 0.08) for each compound (highest vs. lowest tertile for 6PPD-Q and BPS, middle vs. lowest tertile for 1-H-BTR). Notably, 6PPD-Q and 1-H-BTR were associated with decreased ratios of total thyroxine (TT4) to TT3 and free thyroxine (FT4) to free triiodothyronine (FT3) and increased TT3 to FT3 ratios. Similar associations were observed for BPS, 2-hydroxy-benzothiazole (2-OH-BTH), bisphenol A (2,3-dihydroxypropyl) glycidyl ether (BADGE-H2O), and bisphenol a-bis(2,3-dihydroxypropyl) ether (BADGE-2H2O). Bayesian Kernel Machine Regression analyses showed the EDC mixture linked to decreased TT4/TT3 and FT4/FT3 ratios, with 6PPD-Q as the main contributor. Mediation analyses indicated that oxidative stress, measured by 8-hydroxy-2'-deoxiguanosine (8-OHdG), significantly mediated the association between higher 6PPD-Q exposure (highest vs. lowest tertile) and increased FT3 levels, with a mediation proportion of 33.31 %. These findings highlight the potential health risks of emerging EDCs, warranting further research.