Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany.
Laboratoire de Ploufragan-Plouzané-Niort, Site de Plouzané, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail, Plouzané, France.
Integr Environ Assess Manag. 2024 May;20(3):830-845. doi: 10.1002/ieam.4828. Epub 2023 Aug 29.
Given the vital role of thyroid hormones (THs) in vertebrate development, it is essential to identify chemicals that interfere with the TH system. Whereas, among nonmammalian laboratory animals, fish are the most frequently utilized test species in endocrine disruptor research, for example, in guidelines for the detection of effects on the sex hormone system, there is no test guideline (TG) using fish as models for thyroid-related effects; rather, amphibians are used. Therefore, the objective of the present project was to integrate thyroid-related endpoints for fish into a test protocol combining OECD TGs 229 (Fish Short-Term Reproduction Assay) and 234 (Fish Sexual Development Test). The resulting integrated Fish Endocrine Disruption Test (iFEDT) was designed as a comprehensive approach to covering sexual differentiation, early development, and reproduction and to identifying disruption not only of the sexual and/or reproductive system but also the TH system. Two 85-day exposure tests were performed using different well-studied endocrine disruptors: 6-propyl-2-thiouracil (PTU) and 17α-ethinylestradiol (EE2). Whereas the companion Part A of this study presents the findings on effects by PTU and EE2 on endpoints established in existing TGs, the present Part B discusses effects on novel thyroid-related endpoints such as TH levels, thyroid follicle histopathology, and eye development. 6-Propyl-2-thiouracil induced a massive proliferation of thyroid follicles in any life stage, and histopathological changes in the eyes proved to be highly sensitive for TH system disruption especially in younger life stages. For measurement of THs, further methodological development is required. 17-α-Ethinylestradiol demonstrated not only the well-known disruption of the hypothalamic-pituitary-gonadal axis, but also induced effects on thyroid follicles in adult zebrafish (Danio rerio) exposed to higher EE2 concentrations, suggesting crosstalk between endocrine axes. The novel iFEDT has thus proven capable of simultaneously capturing endocrine disruption of both the steroid and thyroid endocrine systems. Integr Environ Assess Manag 2024;20:830-845. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
鉴于甲状腺激素 (THs) 在脊椎动物发育中的重要作用，确定干扰 TH 系统的化学物质至关重要。然而，在非哺乳动物实验室动物中，鱼类是内分泌干扰物研究中最常使用的测试物种，例如，在检测对性激素系统影响的指南中，没有使用鱼类作为甲状腺相关效应模型的测试指南 (TG)；而是使用两栖动物。因此，本项目的目的是将与甲状腺相关的终点纳入一个测试方案，该方案结合了 OECD TG 229（鱼类短期繁殖试验）和 234（鱼类性发育试验）。由此产生的综合鱼类内分泌干扰测试 (iFEDT) 旨在作为一种全面的方法，涵盖性分化、早期发育和繁殖，并不仅识别对性和/或生殖系统的干扰，还识别对 TH 系统的干扰。使用两种经过充分研究的内分泌干扰物进行了为期 85 天的暴露试验：6-丙基-2-硫代尿嘧啶 (PTU) 和 17α-乙炔基雌二醇 (EE2)。本研究的第 A 部分介绍了 PTU 和 EE2 对现有 TG 中确立的终点的影响，而本第 B 部分讨论了对新的甲状腺相关终点的影响，如 TH 水平、甲状腺滤泡组织病理学和眼睛发育。6-丙基-2-硫代尿嘧啶在任何生命阶段都会导致甲状腺滤泡大量增殖，眼睛的组织病理学变化被证明对 TH 系统的破坏非常敏感，尤其是在较年轻的生命阶段。对于 TH 的测量，需要进一步的方法开发。17-α-乙炔基雌二醇不仅显示了众所周知的下丘脑-垂体-性腺轴破坏，而且还在暴露于较高 EE2 浓度的成年斑马鱼 (Danio rerio) 中引起了甲状腺滤泡的影响，表明内分泌轴之间存在串扰。因此，新的 iFEDT 已被证明能够同时捕获类固醇和甲状腺内分泌系统的内分泌干扰。Integr Environ Assess Manag 2024;20:830-845。2023 年，作者。综合环境评估与管理由 Wiley Periodicals LLC 代表环境毒理与化学学会 (SETAC) 出版。
