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Updated: May 23, 2026

In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
Extrapolation of hypothalamic-pituitary-thyroid axis perturbations and associated toxicity in rodents to humans: case
Jeffrey Fisher1, Annie Lumen, John Latendresse
1Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA. jeffrey.fisher@fda.hhs.gov
Abstract:
Functional aspects of the Hypothalamic-Pituitary-Thyroid (HPT) axis in rats and humans are compared, exposing why extrapolation of toxicant-induced perturbations in the rat HPT axis to the human HPT axis cannot be accomplished using default risk assessment methodology. Computational tools, such as biologically based dose response models for the HPT axis, are recommended to perform complex animal to human extrapolations involving the HPT axis. Experimental and computational evidence are presented that suggest perchlorate acts directly on the thyroid gland in rats. The apparent escape from perchlorate-induced inhibition of thyroidal uptake of radioactive iodide in humans is discussed along with "rebound" or increased thyroidal uptake of radioactive iodide observed after discontinued clinical treatment with perchlorate.
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