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首页> 外文会议>Rapra International Conference on Encocrine Disruptors >ENDOCRINE DISRUPTING CHEMICALS IN FISH: DEVELOPING EXPOSURE INDICATORS AND PREDICTIVE MODELS OF EFFECTS BASED ON MECHANISM OF ACTION
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ENDOCRINE DISRUPTING CHEMICALS IN FISH: DEVELOPING EXPOSURE INDICATORS AND PREDICTIVE MODELS OF EFFECTS BASED ON MECHANISM OF ACTION

机译：内分泌扰乱鱼类化学品：基于行动机制制定曝光指标和效果的预测模型

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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.
机译：了解化学品的动作（MOA）的可能有毒机制（或模式）可以为评估暴露和效果的适当方法提供有价值的见解，从而减少了跨种类，终点和化学结构的外推相关的不确定性。然而，基于MOA的测试很少用于评估化学品的生态风险。这部分是因为过去的监管要求更多地关注化学品的不利影响（减少存活，生长或生殖，生长或繁殖），这些效应引发了这些效应的途径。最近的偏离涉及内分泌破坏化学品（EDC），在那里需要了解MOA和不利结果。为了达到这样的认识，需要在预测方法的进步，从而在分子水平上化学品引起的机械变化可以转化为有意义的生态风险评价心尖响应。在本文中，我们提供了一个概述和说明性结果，来自大型综合项目，评估EDC对两种小鱼模型的影响，Fathead Minnow（Pimephales Promelas）和斑马鱼（Danio Rerio）。对于这项工作，基于系统的方法用于描绘具有不同已知或假设毒性MOA的12种模型EDC的毒性途径。研究采用最先进的基因组（转录组，蛋白质组学，代谢组），生物信息和建模方法的组合，与整个动物检测结合在一起，制定组织生物学水平的响应联系。这种理解形成了物种，终点和化学推销的预测方法的基础。虽然我们的项目专门专注于鱼类的EDC，但我们认为基本的概念方法有用，可以在各种生物系统中系统地评估化学品对其他MOA的暴露和影响。

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