Thyroid Function Effects of Mixed Exposure to Urinary Trihalomethanes and Haloacetic Acids: Based on an Integrated Framework of Exposure Assessment, Qualitative Association, and Quantitative Attribution

Toxicological studies have demonstrated that disinfection byproducts (DBPs) can disrupt thyroid function; however, human epidemiological evidence remains limited. The existing studies focus on a limited number of compounds and lack detailed investigation of mixed exposure effects. To address these gaps, we developed a three-tier analytical approach that includes exposure assessment, qualitative association, and quantitative attribution. A total of 435 community-dwelling adults in Shanghai, China, were enrolled, and urinary concentrations of 16 DBPs, including halomethanes (HMs) and haloacetic acids (HAAs), and five serum thyroid function indicators were measured. We detected HAAs at higher concentrations than HMs and chlorinated DBPs, generally exceeding brominated and iodinated species. Key DBP exposure risk factors include age, occupation, education, indoor time, occupational water contact, income, body mass index, and sex. Both individual and mixture-based DBP exposures were significantly associated with thyroid hormone indicators (triiodothyronine and free thyroxine) and immune-related markers (thyroglobulin antibody and thyroid peroxidase antibody). HAAs contributed more to thyroid disruption, with trichloroacetic acid identified as a compound of particular concern. This study offers the first systematic assessment of HAA and HM mixture effects on thyroid function indicators and provides an analytical framework for evaluating the health impacts of pollutant mixture exposures.