Academic journal article Environmental Health Perspectives

Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes

Academic journal article Environmental Health Perspectives

Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes

Article excerpt

BACKGROUND: There is increasing evidence in humans and in experimental animals for a relationship between exposure to specific environmental chemicals and perturbations in levels of critically important thyroid hormones (THs). Identification and proper interpretation of these relationships are required for accurate assessment of risk to public health.

OBJECTIVES: We review the role of TH in nervous system development and specific outcomes in adults, the impact of xenobiotics on thyroid signaling, the relationship between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in thyroid signaling by xenobiotic chemicals.

DATA SOURCES: We drew on an extensive body of epidemiologic, toxicologic, and mechanistic studies.

DATA SYNTHESIS: THs are critical for normal nervous system development, and decreased maternal TH levels are associated with adverse neuropsychological development in children. In adult humans, increased thyroid-stimulating hormone is associated with increased blood pressure and poorer blood lipid profiles, both risk factors for cardiovascular disease and death. These effects of thyroid suppression are observed even within the "normal" range for the population. Environmental chemicals may affect thyroid homeostasis by a number of mechanisms, and multiple chemicals have been identified that interfere with thyroid function by each of the identified mechanisms.

CONCLUSIONS: Individuals are potentially vulnerable to adverse effects as a consequence of exposure to thyroid-disrupting chemicals. Any degree of thyroid disruption that affects TH levels on a population basis should be considered a biomarker of adverse outcomes, which may have important societal outcomes.

KEY WORDS: children's health, endocrine disruption, hazard identification, risk assessment, science policy, thyroid hormone, toxicologic assessments. Environ Health Perspect 117:1033-1041 (2009). doi:10.1289/ehp.0800247 available via http://dx.doi.org/ [Online 12 February 2009]

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Recent epidemiologic studies have demonstrated significant relationships between circulating levels of thyroid hormones (THs) and exposures to environmental chemicals (Blount et al. 2006; Boas et al. 2006; Longnecker et al. 2003; Steinmaus et al. 2007). In controlled animal studies, environmental chemicals have been shown to cause a reduction in serum TH levels, also supporting a causal association (Boas et al. 2006; Brucker-Davis 1998; DeVito et al. 1999; Zoeller 2007). In this article we review the role of THs in development and adult life, the impact of xenobiotics on thyroid status, the relationships between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in THs by xenobiotic chemicals.

The Role of THs in Development

THs include both thyroxine ([T.sub.4]) and triiodothyronine ([T.sub.3]). The independent regulation of circulating levels of these two forms of TH is complex, but in this review we refer generally to both forms as TH. THs are evolutionarily conserved molecules present in all extant vertebrates and some invertebrates (Heyland and Moroz 2005). Molecular signaling pathways regulated by these hormones affect development, energy balance, and metabolism in all taxonomic groups. For example, TH induces metamorphosis in the sand dollar (Heyland et al. 2004), flounder (Yamano et al. 1994), and frogs (Buchholz et al. 2005), and TH is essential for development in birds (McNabb 2006) and mammals (Zoeller and Rovet 2004). In humans, TH is important for normal development of brain (Bernal 2007; Oerbeck et al. 2007), lungs (Bizzarro and Gross 2004; van Tuyl et al. 2004), heart (Danzi et al. 2005; Grover et al. 2005; Stoykov et al. 2006), and other organs. Likewise, the mechanism(s) by which THs exert their actions through nuclear receptors that influence gene expression is highly conserved across the vertebrate taxa (Bertrand et al. …

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