Endocrine disrupting chemicals in fish: Developing exposure indicators and predictive models of effects based on mechanism of action
Endocrine disrupting chemicals in fish: Developing exposure indicators and predictive models of effects based on mechanism of action
复制标题
DOI：
10.1016/j.aquatox.2009.01.013
复制
发表时间：
2009-05-05
影响因子：
4.5
通讯作者：
Watanabe, Karen H.
中科院分区：
文献类型：
--
作者：
Ankley, Gerald T.;Bencic, David C.;Watanabe, Karen H.
了解化学品可能的毒性作用机制（或方式），可以为评估接触和影响的适当方法提供宝贵的见解，从而减少与跨物种、终点和化学结构外推有关的不确定性。然而，基于MOA的测试很少被用于评估化学品的生态风险。这部分是因为过去的管制任务更多地关注化学品的不利影响（生存、生长或繁殖的减少），而不是引起这些影响的途径。最近的一个偏离涉及内分泌干扰化学品（EDCs），其中有必要了解MOA和不良后果。为了实现这一理解，需要在预测方法的进展，从而在分子水平上的化学品引起的机械变化可以转化为顶端的生态风险评估有意义的反应。在本文中，我们提供了一个概述和说明性的结果，从一个大型的综合项目，评估了内分泌干扰物对两种小鱼模型，黑头呆鱼（黑头呆鱼）和斑马鱼（斑马鱼）的影响。对于这项工作，基于系统的方法被用来描绘不同的已知或假设的毒性MOA的12个模型内分泌干扰物的毒性途径。这些研究采用了最先进的基因组学（转录组学，蛋白质组学，代谢组学），生物信息学和建模方法的组合，结合整体动物试验，以开发跨生物组织水平的反应联系。这种理解构成了物种、终点和化学外推的预测方法的基础。虽然我们的项目是专门集中在鱼类内分泌干扰物，我们认为，基本的概念方法有效用，系统地评估暴露和化学品的影响与其他MOA在各种生物系统。由爱思唯尔公司出版
Knowledge of possible toxic mechanisms (or modes) of action (MOA) of chemicals can provide valuable insights as to appropriate methods for assessing exposure and effects, thereby reducing uncertainties related to extrapolation across species, endpoints and chemical structure. However, MOA-based testing seldom has been used for assessing the ecological risk of chemicals. This is in part because past regulatory mandates have focused more on adverse effects of chemicals (reductions in survival, growth or reproduction) than the pathways through which these effects are elicited. A recent departure from this involves endocrine-disrupting chemicals (EDCs), where there is a need to understand both MOA and adverse outcomes. To achieve this understanding, advances in predictive approaches are required whereby mechanistic changes caused by chemicals at the molecular level can be translated into apical responses meaningful to ecological risk assessment. In this paper we provide an overview and illustrative results from a large, integrated project that assesses the effects of EDCs on two small fish models, the fathead minnow (Pimephales promelas) and zebrafish (Danio rerio). For this work a systems-based approach is being used to delineate toxicity pathways for 12 model EDCs with different known or hypothesized toxic MOA. The studies employ a combination of state-of-the-art genomic (transcriptomic, proteomic, metabolomic), bioinformatic and modeling approaches, in conjunction with whole animal testing, to develop response linkages across biological levels of organization. This understanding forms the basis for predictive approaches for species, endpoint and chemical extrapolation. Although our project is focused specifically on EDCs in fish, we believe that the basic conceptual approach has utility for systematically assessing exposure and effects of chemicals with other MOA across a variety of biological systems. Published by Elsevier B.V.