Current Limitations and Recommendations to Improve Testing for the Environmental Assessment of Endocrine Active Substances
Current Limitations and Recommendations to Improve Testing for the Environmental Assessment of Endocrine Active Substances
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DOI：
10.1002/ieam.1862
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发表时间：
2017-03-01
影响因子：
3.1
通讯作者：
Ankley, Gerald T.
中科院分区：
文献类型：
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作者：
Coady, Katherine K.;Biever, Ronald C.;Ankley, Gerald T.
在本研究中，描述了评估潜在内分泌活性化学品的现有监管框架和测试系统，并讨论了相关挑战，以及应对这些挑战的拟议方法。不同地区的监管框架略有不同，但都基本上评估一种化学物质是否具有内分泌活性，以及这种活动是否会导致对人类或环境的不利后果。目前的测试系统包括硅胶、体外和体内技术，重点是检测潜在的内分泌活动，以及体内测试，收集尖端数据以检测可能的不良反应。这些测试系统目前被设计用来强有力地评估雌激素、雄激素和甲状腺激素信号通路中的内分泌活动和/或不良影响；然而，目前的测试系统在评估内分泌危险和风险方面存在一些局限性。这些局限性包括缺乏以下方面的确定性：1)足够敏感的物种和生命阶段；2)对所关注的内分泌途径具有诊断作用的机械性终点；以及3)机械性反应与顶端不良后果之间的联系。此外，一些现有的测试方法在时间、成本和动物使用方面都是资源密集型的。然而，根据最近的经验，有机会改进对现有测试方法的做法和指导，并减少不确定性。例如，体外高通量筛选可以用来确定测试化学品的优先顺序，并为确定危险和风险的特征提供最合适的分析方法。其他建议包括增加终点，用于阐明机制效应和不良后果之间的联系，确定目前尚不存在检测方法的潜在敏感类群，以及解决与雌激素、雄激素和甲状腺信号相关的可能关注的关键内分泌途径。综合环境评估马纳格2017；13：302-316。(C)2016年提交人。综合环境评估和管理，由Wiley期刊公司代表环境毒理学和化学学会(SETAC)出版
In the present study, existing regulatory frameworks and test systems for assessing potential endocrine active chemicals are described, and associated challenges are discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or to the environment. Current test systems include in silico, in vitro, and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life stages; 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern; and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive with regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to and guidance for existing test methods and to reduce uncertainty. For example, in vitro high-throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assays for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen, and thyroid signaling. Integr Environ Assess Manag 2017;13:302-316. (C) 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)