EVALUATION OF THE SCIENTIFIC UNDERPINNINGS FOR IDENTIFYING ESTROGENIC CHEMICALS IN NONMAMMALIAN TAXA USING MAMMALIAN TEST SYSTEMS
EVALUATION OF THE SCIENTIFIC UNDERPINNINGS FOR IDENTIFYING ESTROGENIC CHEMICALS IN NONMAMMALIAN TAXA USING MAMMALIAN TEST SYSTEMS
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DOI：
10.1002/etc.3456
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发表时间：
2016-11-01
影响因子：
4.1
通讯作者：
Hornung, Michael W.
中科院分区：
文献类型：
--
作者：
Ankley, Gerald T.;LaLone, Carlie A.;Hornung, Michael W.
美国环境保护署负责评估超过10000种化学品的内分泌活性，这是一项仅通过使用现有的哺乳动物和非哺乳动物体内筛选试验无法合理实现的任务。因此，有人建议，化学品应优先用于体内测试，使用体外高通量试验的数据，为特定的内分泌系统的目标。最近的努力集中在潜在的雌激素化学品-特别是那些激活雌激素受体α（ER α）-已广泛证明该方法的可行性。然而，一个主要的不确定性是基于哺乳动物（主要是人类）高通量检测的优先顺序是否准确地反映了非哺乳动物物种中潜在的化学-ER α相互作用。作者根据雌激素受体的结构属性、ER α的体外结合和反式激活数据以及一系列化学品对体内雌激素信号通路的影响，对化学品-ER α相互作用的跨物种可比性进行了全面分析。总体而言，这一综合分析表明，在哺乳动物系统中具有中度至高度雌激素效力的化学品也应该是非哺乳动物脊椎动物的优先化学品。然而，由于缺乏对在环节动物等门中发现的可能的ER α直系同源物的生物学作用的了解，优先排序方法可能适用于无脊椎动物的程度是不确定的。此外，对鱼类和爬行动物的体外数据的比较分析表明，基于Escherialian的测定可能无法有效捕获所有脊椎动物类别中低亲和力化学品的ER α相互作用。2016年Wiley Periodicals Inc.关于SETAC本条目属于美国政府作品，因此在美国属于公有领域。
The US Environmental Protection Agency has responsibility for assessing endocrine activity of more than 10 000 chemicals, a task that cannot reasonably be achieved solely through use of available mammalian and nonmammalian in vivo screening assays. Hence, it has been proposed that chemicals be prioritized for in vivo testing using data from in vitro high-throughput assays for specific endocrine system targets. Recent efforts focused on potential estrogenic chemicals-specifically those that activate estrogen receptor-alpha (ER alpha)-have broadly demonstrated feasibility of the approach. However, a major uncertainty is whether prioritization based on mammalian (primarily human) high-throughput assays accurately reflects potential chemical-ER alpha interactions in nonmammalian species. The authors conducted a comprehensive analysis of cross-species comparability of chemical-ER alpha interactions based on information concerning structural attributes of estrogen receptors, in vitro binding and transactivation data for ER alpha, and the effects of a range of chemicals on estrogen-signaling pathways in vivo. Overall, this integrated analysis suggests that chemicals with moderate to high estrogenic potency in mammalian systems also should be priority chemicals in nonmammalian vertebrates. However, the degree to which the prioritization approach might be applicable to invertebrates is uncertain because of a lack of knowledge of the biological role(s) of possible ER alpha orthologs found in phyla such as annelids. Further, comparative analysis of in vitro data for fish and reptiles suggests that mammalian-based assays may not effectively capture ER alpha interactions for low-affinity chemicals in all vertebrate classes. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.