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MODE OF ACTION: NEUROTOXICITY INDUCED BY THYROID HORMONE DISRUPTION DURING DEVELOPMENT - HEARING LOSS RESULTING FROM EXPOSURE TO PHAHS.
Citation:
CROFTON, K. M. AND R. T. ZOELLER. MODE OF ACTION: NEUROTOXICITY INDUCED BY THYROID HORMONE DISRUPTION DURING DEVELOPMENT - HEARING LOSS RESULTING FROM EXPOSURE TO PHAHS. CRC CRITICAL REVIEWS IN TOXICOLOGY 35:757-769, (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 the neurodevelopmental effects of hypothyroidism to test the framework. Propylthiouracil, an agent that induces hypothyroidism during developmental exposure, was used as a prototypical example. There report concludes that there is a high degree of confidence that the animal MOA for propylthiouracil-induced developmental neurotoxicity is plausible in humans. However, because human exposure is necessarily under strict medical supervision, the doses used are titrated such that this MOA is not likely to occur in humans. Therefore, in principle, no developmental neurotoxicity due to propylthiouracil-induced hypothyroidism should occur in humans.