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MODE OF ACTION: NEUROTOXICITY INDUCED BY DEVELOPMENTAL THYROID HORMONE INSUFFICIENCY -- NEUROLOGICAL ABNORMALITIES RESULTING FROM EXPOSURE TO PROPYLTHIOURACIL.
Citation:
ZOELLER, R. T. AND K. M. CROFTON. MODE OF ACTION: NEUROTOXICITY INDUCED BY DEVELOPMENTAL THYROID HORMONE INSUFFICIENCY -- NEUROLOGICAL ABNORMALITIES RESULTING FROM EXPOSURE TO PROPYLTHIOURACIL. CRC CRITICAL REVIEWS IN TOXICOLOGY 35:771-781, (2005).
Impact/Purpose:
To summarize a workshop aimed at developing a framework to determine the relevancy of animal modes-of-action for extrapolation to humans
Description:
A manuscript summarizes a workshop aimed at developing a framework to determine the relevancy of animal modes-of-action for extrapolation to humans. This specific report used animal data on neurodevelopmental effects of thyroid hormone disruption to test the framework. Polyhalogenated aromatic hydrocarbons(PHAH), a class of environmental contaminants that disrupt thyroid hormones during developmental exposure, were used as prototypical examples. This report concludes that a high degree of confidence exists for the mode-of-action PHAH-induced hearing loss in the rat. The report also concludes that there is medium confidence for the interspecies concordance for the key events in the MOA for the hearing loss that results from thyrotoxic PHAHs. Toxicodynamic and toxicokinetic uncertainties temper confidence in the concordance of the mode-of-action between rats and humans. This mode-of-action may occur in humans for compounds that have a high degree of ambient exposure during development and/or are highly antagonistic to fetal thyroid hormone homeostasis.