Jeffrey Fisher, Annie Lumen, John Latendresse, David Mattie
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Extrapolation of hypothalamic-pituitary-thyroid axis perturbations and associated toxicity in rodents to humans: case study with perchlorate.
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.
期刊介绍：
Journal of Environmental Science and Health, Part C: Environmental Carcinogenesis and Ecotoxicology Reviews aims at rapid publication of reviews on important subjects in various areas of environmental toxicology, health and carcinogenesis. Among the subjects covered are risk assessments of chemicals including nanomaterials and physical agents of environmental significance, harmful organisms found in the environment and toxic agents they produce, and food and drugs as environmental factors. It includes basic research, methodology, host susceptibility, mechanistic studies, theoretical modeling, environmental and geotechnical engineering, and environmental protection. Submission to this journal is primarily on an invitational basis. All submissions should be made through the Editorial Manager site, and are subject to peer review by independent, anonymous expert referees. Please review the instructions for authors for manuscript submission guidance.
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