Abstract：
There has been increasing interest in endocrine-disrupting chemicals (EDCs) among scientists and public authorities over the last 30 years, notably because of their wide use and the increasing evidence of detrimental effects on humans and the environment. However, test systems for the detection of potential EDCs as well as testing strategies still require optimization. Thus, the aim of the present project was the development of an integrated test protocol that merges the existing OECD test guidelines (TGs) 229 (fish short-term reproduction assay) and 234 (fish sexual development test) and implements thyroid-related endpoints for fish. The integrated fish endocrine disruptor test (iFEDT) represents a comprehensive approach for fish testing, which covers reproduction, early development, and sexual differentiation, and will thus allow the identification of multiple endocrine-disruptive effects in fish. Using zebrafish (Danio rerio) as a model organism, two exposure tests were performed with well-studied EDCs: 6-propyl-2-thiouracil (PTU), an inhibitor of thyroid hormone synthesis, and 17α-ethinylestradiol (EE2), an estrogen receptor agonist. In part A of this article, the effects of PTU and EE2 on established endpoints of the two existing TGs are reported, whereas part B focuses on the novel thyroid-related endpoints. Results of part A document that, as expected, both PTU and EE2 had strong effects on various endocrine-related endpoints in zebrafish and their offspring. Merging of TGs 229 and 234 proved feasible, and all established biomarkers and endpoints were responsive as expected, including reproductive and morphometric changes (PTU and EE2), vitellogenin levels, sex ratio, gonad maturation, and histopathology (only for EE2) of different life stages. A validation of the iFEDT with other well-known EDCs will allow verification of the sensitivity and usability and confirm its capacity to improve the existing testing strategy for EDCs in fish. Integr Environ Assess Manag 2024;20:817-829. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
摘要：
在过去的30年中，科学家和公共当局对内分泌干扰化学物质（EDCs）的兴趣越来越大，特别是因为它们的广泛使用以及对人类和环境有害影响的证据越来越多。然而,检测潜在EDC的测试系统以及测试策略仍然需要优化。因此，本项目的目的是制定一项综合检测方案,该方案将现有的OECD检测指南(TG)229(FSTRA-鱼类短期繁殖检测)和234(FSDT-鱼类性发育检测)合并,并对鱼类实施甲状腺相关终点."综合鱼类内分泌干扰物测试"(iFEDT)代表了鱼类测试的综合方法,包括繁殖，早期发育和性别分化，因此可以识别鱼类中的多种内分泌干扰作用。使用斑马鱼（Daniorerio）作为模型生物，使用经过充分研究的EDC进行了两项暴露测试：丙基硫氧嘧啶（PTU），甲状腺激素合成和17α-炔雌醇（EE2）的抑制剂，雌激素受体激动剂.在本出版物的A部分中，报告了PTU和EE2对两个现有TG的既定终点的影响，而B部分(Gölz等人。2023年)关注新的甲状腺相关终点。A部分文件的结果，正如预期的那样，PTU和EE2对斑马鱼及其后代的各种内分泌相关终点均有强烈影响.TG229和234的合并证明是可行的，所有已确定的生物标志物和终点都如预期的那样反应，包括生殖和形态变化（PTU和EE2），卵黄蛋白原水平,性别比例,不同生命阶段的性腺成熟和组织病理学（仅EE2）。iFEDT与其他著名的EDC的验证将允许验证灵敏度和可用性，并确认其改善鱼类EDC现有测试策略的能力。
