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THYROID DISRUPTING CHEMICALS: CHALLENGES IN ASSESSING NEUROTOXIC RISK FROM ENVIRONMENTAL MIXTURES.
Citation:
CROFTON, K. M. THYROID DISRUPTING CHEMICALS: CHALLENGES IN ASSESSING NEUROTOXIC RISK FROM ENVIRONMENTAL MIXTURES. Presented at International Conference on Food Contaminants and Neurodevelopmental Disorders, Valencia, SPAIN, December 03 - 05, 2006.
Description:
Environmental contaminants are known to act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are xenobiotics that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeostasis, or change circulating or tissue concentrations of THs. TDCs include a wide range chemical structures that act through a variety of mechanisms. Concern about TDCs has increased due to the critical role that thyroid hormones play in brain development. A major uncertainty regarding the endocrine disrupting potential of environmental xenobiotics is the potential for additive or synergistic effects of exposure to mixtures. The US EPA default process is to use dose-addition in cumulative assessment for chemicals that share common "mechanisms of toxicity". Recent results suggest that this default method may be adequate for assessing cumulative risk for chemicals with similar mechanisms-of-action. It is currently unknown how to predict effects of TDC mixtures that contain xenobiotics with different mechanisms-of-action. In addition, there are a number of uncertainties in both interpretation and extrapolation of results from studies of TDC mixtures. Differences in sensitivity between species in thyrotoxic effects make extrapolation of laboratory animals to humans difficult. Furthermore, since TDCs alter thyroid homeostasis via a variety of mechanisms, it is difficult to determine the level of organization at which to cumulate results. Should it be at the molecular level, which could be chemical class or molecular target specific, or at the level of a downstream consequence (e.g., circulating hormone levels, brain biochemistry, behavior) which could be mechanism-independent? Assessing the health risks of thyroid disruption by environmental xenobiotics necessitates an improved understanding of how divergent mechanisms alter THs and consequent adverse impacts of these perturbations on nervous system development.