Experimental Pathology Laboratories, Inc., 45600 Terminal Drive, Sterling, VA 20166, USA.
John W Green Ecostatistical Consulting, LLC 372 Chickory Way, Newark, DE 19711, USA.
Aquat Toxicol. 2024 Feb;267:106811. doi: 10.1016/j.aquatox.2023.106811. Epub 2023 Dec 20.
The Amphibian Metamorphosis Assay (AMA) is used to determine if a tested chemical has potential to impact the hypothalamic-pituitary-thyroid (HPT) axis of Xenopus laevis tadpoles, while the Fish Short Term Reproduction Assay (FSTRA) assesses potential effects on the hypothalamic-pituitary-gonadal (HPG) axis of fish such as the fathead minnow (Pimephales promelas). Several global regulatory programs routinely require these internationally validated tests be performed to determine the potential endocrine activity of chemicals. As such, they are conducted in accordance with standardized protocols and test criteria, which were originally developed more than a decade ago. Sizeable numbers of AMA and FSTRA studies have since been carried out, which allows for the mining of extensive historical control data (HCD). Such data are useful for investigating the existence of outlier results and aberrant control groups, identifying potential confounding variables, providing context for rare diagnoses, discriminating target from non-target effects, and for refining current testing paradigms. The present paper provides histopathology HCD from 55 AMA studies and 45 fathead minnow FSTRA studies, so that these data may become publicly available and thus aid in the interpretation of future study outcomes. Histopathology is a key endpoint in these assays, in which it is considered to be one of the most sensitive indicators of endocrine perturbation. In the current review, granular explorations of HCD data were used to identify background lesions, to assess the utility of particular diagnostic findings for distinguishing endocrine from non-endocrine effects, and to help determine if specific improvements to established regulatory guidance may be warranted. Knowledge gleaned from this investigation, supplemented by information from other recent studies, provided further context for the interpretation of AMA and FSTRA histopathology results. We recommend HCDs for the AMA and FSTRA be maintained to support the interpretation of study results.
两栖动物变态分析（AMA）用于确定测试化学物质是否有可能影响非洲爪蟾蝌蚪的下丘脑-垂体-甲状腺（HPT）轴，而鱼类短期生殖分析（FSTRA）评估潜在影响对鱼类（如黑头软口鱼）的下丘脑-垂体-性腺（HPG）轴。几个全球监管计划通常需要进行这些国际验证测试，以确定化学物质的潜在内分泌活性。因此，它们是根据标准化协议和测试标准进行的，这些协议和测试标准最初是在十多年前制定的。此后，进行了大量的 AMA 和 FSTRA 研究，从而可以挖掘广泛的历史对照数据（HCD）。这些数据可用于调查异常结果和异常对照组的存在，确定潜在的混杂变量，为罕见诊断提供背景，区分靶标和非靶标效应，并改进当前的测试范例。本文件提供了 55 项 AMA 研究和 45 项黑头软口鱼 FSTRA 研究的组织病理学 HCD，以便这些数据可以公开提供，从而有助于解释未来的研究结果。组织病理学是这些测定中的一个关键终点，它被认为是内分泌干扰最敏感的指标之一。在当前的综述中，对 HCD 数据进行了详细的探索，以确定背景病变，评估特定诊断发现用于区分内分泌和非内分泌效应的效用，并帮助确定是否需要对既定的监管指南进行特定改进。从这项调查中收集的知识，加上其他最近研究的信息，为 AMA 和 FSTRA 组织病理学结果的解释提供了进一步的背景。我们建议维持 AMA 和 FSTRA 的 HCD，以支持对研究结果的解释。
