Serum synthetic phenolic antioxidants, transformation products, and thyroid homeostasis in adults from eastern China: Association and benchmark dose assessment.

Although toxicological studies suggest that synthetic phenolic antioxidants and their transformation products (SPAs/TPs) may disrupt thyroid function, epidemiological evidence and exposure safety thresholds remain limited. This study included 810 adults from Jiangsu Province, China, and measured serum concentrations of 12 SPAs, 3 TPs, and 7 thyroid function indicators (TFIs). Multiple linear regression (MLR) and restricted cubic spline (RCS) analyses were used to evaluate associations between individual SPAs/TPs and TFIs, whereas quantile g-computation (qgcomp) and Bayesian kernel machine regression (BKMR) were applied to assess the joint effects of mixed exposure. In addition, the Benchmark Dose Software (BMDS) was used to estimate the benchmark dose (BMD) and its lower confidence limit (BMDL) for serum SPAs/TPs, and to derive the corresponding reference doses (RfDs). The results showed widespread exposure to multiple SPAs/TPs among the study participants. Both individual and mixed exposure to SPAs/TPs were significantly associated with increased levels of free thyroxine (FT4) and total triiodothyronine (T3), as well as decreased levels of thyroid-stimulating hormone (TSH) and the T4/T3 ratio. Among the detected compounds, BHT-COOH (3,5-di-tert-butyl-4-hydroxybenzoic acid) and AO245 (triethylene glycol bis(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate) were the primary contributors to elevated FT4 and T3 levels. Under a benchmark response (BMR) of 5%, the estimated RfDs were 0.018 mg/kg/day for BHT-COOH and 0.181 mg/kg/day for AO245, and potential health risks may exist (HQc > 1). This study is the first to evaluate the effects of exposure to SPAs/TPs on thyroid homeostasis, providing a scientific basis for the formulation and improvement of targeted regulatory policies.