Weight-of-evidence analysis of human exposures to dioxins and dioxin-like compounds and associations with thyroid hormone levels during early development

Thyroid hormones play a critical role in the proper development of brain function and cell growth. Several epidemiological studies have been conducted to assess potential associations between pre- and post-natal exposure to dioxins or dioxin-like compounds (DLCs) and the levels of circulating thyroid hormones during early development. Dioxins and DLCs include chlorinated dibenzo-p-dioxins, chlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (PCBs). We identified a total of 23 relevant epidemiological studies (21 cohort studies and 1 case–control study) that measured exposures to various types of dioxins and DLCs as well as markers of thyroid function, such as thyroid stimulating hormone (TSH), total thyroxine (T4), free T4, total triiodothyroxine (T3), free T3, and thyroid-binding globulin concentrations in cord blood or circulation. While some of the studies reported associations between concentrations of dioxins and/or DLCs and some biomarkers of thyroid function, the majority of the observed associations were not statistically significant. Moreover, there were no clear and consistent effects across studies for any of the hormone levels examined, and while a number of studies showed a statistically significant association with exposure for a given marker of thyroid function, other studies showed either no change or changes in the opposite direction for the same thyroid function marker. Similarly, when the results were analyzed considering developmental stage, there generally were no clear and consistent effects at any age from birth through 12 years of age. The absence of a clear correlation between background exposures to dioxins and DLCs and thyroid function biomarkers during development is not consistent with the hypothesis that background exposures to these chemicals cause effects on thyroid function during development.