Effect of toenail metal concentrations on thyroid function in Bangladeshi children

BACKGROUND AND AIM: The ubiquitous presence of toxic metal exposures in the environment is a global public health concern. Arsenic, cadmium, and mercury are commonly occurring toxic environmental metal exposures in the general population. These metal exposures appear among the top 20 of the Agency for Toxic Substances and Disease Registry Substance Priority List, prioritizing substances based on their frequency, toxicity, and potential for human exposure. The existing experimental literature supports the hypothesis that the disruption of hormone signaling by metals at key developmental time points might underlie health outcomes observed in childhood, adolescence, and adult life. While limited data exist in humans, experimental studies have observed correlations of metals with endocrine function. This study evaluates the associations between toenail metal concentrations and free thyroxine (T4) among 500 Bangladeshi children aged 5-7 years enrolled in the Bangladesh Environmental Research in Children’s Health (BiRCH) cohort. METHODS: We investigated the associations of toenail metal concentrations of arsenic, cadmium, and mercury with free T4 using linear regression models (single-metal and mutually-adjusted models), adjusted for a priori covariates. Additionally, Bayesian kernel machine regression (BKMR) was conducted as a secondary analysis to test the robustness of findings and potential exposure patterns. RESULTS: Arsenic was positively associated with free T4 (Q4 versus Q1 b=0.10, 95% CI=0.03-0.17), and mercury was inversely associated with free T4 (Q4 versus Q1 b= -0.07, 95% CI=-0.14-0.002). No association was observed with cadmium. Secondary analyses examining metal mixtures yielded similar results. CONCLUSIONS: Findings from linear regression modeling and secondary analyses using BKMR suggest thyroid function may serve as an important mechanism for arsenic and mercury toxicity. Future research is needed to evaluate the inter-related roles of metal exposures and thyroid function across the life course. KEYWORDS: metals, thyroid, children’s environmental health