| Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes Mark D. Miller,1,2 Kevin M. Crofton,3 Deborah C. Rice,4 and R. Thomas Zoeller5 1Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, California, USA; 2Pediatric Environmental Health Specialty Unit, University of California at San Francisco, San Francisco, California, USA; 3National Health and Environmental Effects Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; 4Maine Center for Disease Control, Augusta, Maine, USA; 5Biology Department, Morrill Science Center, University of Massachusetts at Amherst, Amherst, Massachusetts, USA Abstract
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]
Address correspondence to M. Miller, Office of Environmental Health Hazard Assessment, 1515 Clay St., 16th Floor, Oakland, CA 94612 USA. Telephone: (510) 622-3159. Fax: (510) 622-3210. E-mail: mmiller@oehha.ca.gov This review developed from conversations among the four authors as a result of a workshop sponsored by the California Environmental Protection Agency and the U.S. Environmental Protection Agency (EPA) in May 2007 to explore ways to integrate information from testing for upstream biochemical events when conducting hazard identification and risk assessment. The information in this document has been funded wholly (or in part) by the U.S. EPA. The manuscript has been reviewed following the policy of the National Health and Environmental Effects Research Laboratory, U.S. EPA, and was approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The views expressed by M.D.M. are his and do not necessarily represent those of the Office of Environmental Health Hazard Assessment, the California Environmental Protection Agency, or the State of California. The authors declare they have no competing financial interests. Received 2 October 2008 ; accepted 12 February 2009.
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