Extrapolation of hypothalamic-pituitary-thyroid axis perturbations and associated toxicity in rodents to humans: case study with perchlorate.

Q2 Biochemistry, Genetics and Molecular Biology Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews Pub Date : 2012-01-01 DOI:10.1080/10590501.2012.653889

Jeffrey Fisher, Annie Lumen, John Latendresse, David Mattie

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引用次数: 18

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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外推下丘脑-垂体-甲状腺轴扰动和相关的啮齿动物对人类的毒性:高氯酸盐的案例研究。

比较了大鼠和人类下丘脑-垂体-甲状腺(HPT)轴的功能方面，揭示了为什么使用默认风险评估方法无法将毒理学诱导的大鼠HPT轴的干扰外推到人类HPT轴。建议使用计算工具，如HPT轴的基于生物学的剂量反应模型，进行涉及HPT轴的复杂动物到人类的外推。实验和计算证据表明，高氯酸盐直接作用于大鼠甲状腺。本文讨论了高氯酸盐诱导的甲状腺对放射性碘摄取抑制的明显逃逸，以及停用高氯酸盐临床治疗后观察到的“反弹”或甲状腺对放射性碘的摄取增加。

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来源期刊

Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews 环境科学-毒理学

CiteScore

6.20

自引率

0.00%

发文量

审稿时长

>24 weeks

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.