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THYROID HORMONE DISRUPTION: FROM KINETICS TO DYNAMICS.
CROFTON, K. M. THYROID HORMONE DISRUPTION: FROM KINETICS TO DYNAMICS. Presented at Society of Toxicology, Charlotte, NC, March 25 - 29, 2007.
A wide range of chemicals with diverse structures act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are chemicals that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormones (THs), or change circulating or tissue concentrations of THs. These structurally diverse chemicals act through a variety of mechanisms. Chemicals such as perchlorate, inhibit the uptake of iodide into the thyroid and subsequently decrease TH synthesis. Other chemicals decrease TH synthesis by inhibition of thyroid peroxidase. A number of chemicals also alter the catabolism of THs. One such class of chemicals induce TH glucuronidation, increasing elimination of these hormones. An adverse consequence of concern for TDC exposure is developmental neurotoxicity. While serum concentrations of THs are useful bio-indicators of TDCs, the relationship between alternations in serum concentration of THs and developmental toxicities is uncertain, particularly at low doses. This symposium will focus on recent collaborative research aimed at reducing the uncertainties by delineating the relationship between developmental neurotoxicity of the brain and perturbation in the maternal/fetal and neonatal hypothalamic-pituitary-thyroid (HPT) axis. A biologically-based model for the HPT axis is under development which describes highly nonlinear responses in this axis. The application of such models to risk assessment may provide a platform to better quantify the dose-response relationships for developmental neurotoxicants. This abstract does not necessarily reflect the policy of the US EPA
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
NEUROBEHAVIORAL TOXICOLOGY BRANCH