The transition to include in vitro-based data in chemical hazard assessment has resulted in the development and implementation of screening assays to cover a diversity of biological pathways, including recently added assays to interrogate chemical disruption of proteins relevant to thyroid signaling pathways. Iodotyrosine deiodinase (IYD), the iodide recycling enzyme, is one such thyroid-relevant endpoint for which a human-based screening assay has recently been developed and used to screen large libraries of chemicals. Presented here is the development of an amphibian IYD inhibition assay and its implementation to conduct a cross-species comparison between chemical inhibition of mammalian and non-mammalian IYD enzyme activity. The successful development of an amphibian IYD inhibition assay was based on demonstration of sufficient IYD enzyme activity in several tissues collected from larval Xenopus laevis. With this new assay, 154 chemicals were tested in concentration-response to provide a basis for comparison of relative chemical potency to results obtained from the human IYD assay. Most chemicals exhibited similar inhibition in both assays, with less than 25% variation in median inhibition for 120 of 154 chemicals and 85% concordance in categorization of “active” (potential IYD inhibitor) versus “inactive”. For chemicals that produced 50% or greater inhibition in both assays, rank-order potency was similar, with the majority of the IC50s varying by less than 2-fold (and all within an order of magnitude). Most differences resulted from greater maximum inhibition or higher chemical potency observed with human IYD. This strong cross-species agreement suggests that results from the human-based assay would be conservatively predictive of chemical effects on amphibian IYD.

将基于体外的数据纳入化学危害评估的转变导致了筛选测定的开发和实施，以涵盖多种生物途径，包括最近添加的用于询问与甲状腺信号传导途径相关的蛋白质的化学破坏的测定。碘酪氨酸脱碘酶 (IYD) 是一种碘化物回收酶，是此类甲状腺相关终点之一，最近开发了一种基于人体的筛选测定法，并用于筛选大型化学品库。本文介绍了两栖动物 IYD 抑制测定的开发及其实施，以对哺乳动物和非哺乳动物 IYD 酶活性的化学抑制进行跨物种比较。两栖动物 IYD 抑制测定的成功开发是基于从非洲爪蟾幼虫收集的几种组织中证明了足够的 IYD 酶活性。通过这种新测定，对 154 种化学物质进行了浓度响应测试，为相对化学效力与人类 IYD 测定结果的比较提供了基础。大多数化学物质在两种测定中都表现出相似的抑制作用，154 种化学物质中有 120 种的中值抑制变化小于 25%，“​​活性”（潜在的 IYD 抑制剂）与“非活性”分类的一致性为 85%。对于在两种测定中产生 50% 或更高抑制率的化学物质，排序效力相似，大多数 IC50 变化小于 2 倍（且全部在一个数量级内）。大多数差异是由于人类 IYD 观察到的最大抑制更大或化学效力更高造成的。这种强烈的跨物种一致性表明，基于人体的检测结果将保守地预测化学对两栖动物 IYD 的影响。