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首页> 外文期刊>Journal of applied toxicology >Approaches to the assessment of toxicity data with endpoints related to endocrine disruption.
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Approaches to the assessment of toxicity data with endpoints related to endocrine disruption.

机译：评估毒性数据的方法，其终点与内分泌干扰有关。

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There has been a substantial proliferation in the number of studies reporting endocrine effects as an endpoint. The vast majority have focused on oestrogenicity in vitro but, with recent recommendations by the USEPA Endocrine Disrupter Screening and Testing Advisory Committee, tests are now being developed for (anti)-androgenicity and effects on the thyroid, largely because of the potential for altering reproduction or development via these mechanisms. Despite being a vital organ and involved in reproduction and development, there is currently no provision for assessing adrenocortical function. Similarly, the entire process of steroidogenesis poses multiple molecular targets for toxic disruption that are not included in current test strategies and at present there is no clear position on the significance of the data being generated. This review provides a framework for approaching endocrine data: that all the glands, tissues, receptors, transporter proteins and enzymes that comprise the endocrine system are targets for toxicity. They should be considered in much the same way as other target organs, with appropriate provision for the special cases of carcinogenesis and teratogenesis, and a pragmatic weight of evidence approach should be adopted considering all available data and recognizing its limitations. In this approach, structure-activity relationships and in vitro and targeted in vivo screens provide useful data but repeat-dose regulatory studies with defined endpoints provide the most powerful tools for hazard assessment. Pragmatic consideration should be given to exposure issues (which may highlight the practical irrelevance, for example, of very low potency oestrogens) and subsequently whether endocrine disruption is the critical or most sensitive endpoint for a compound. Finally, endocrine disruption may be considered a mechanism and, as with other toxic endpoints, knowledge of effect and no-observable-effect levels and reversibility is as important as identifying the target tissue or any inherent hormone-like property.
机译：报告内分泌作用作为终点的研究数量已经大量增加。绝大多数研究集中在体外雌激素上，但是根据USEPA内分泌干扰物筛查和测试咨询委员会的最新建议，目前正在开发针对（抗）雄激素及其对甲状腺的影响的试验，这在很大程度上是因为有可能改变生殖或通过这些机制进行开发。尽管是重要的器官并参与生殖和发育，但目前尚无评估肾上腺皮质功能的规定。同样，类固醇生成的整个过程为毒性破坏提供了多个分子靶标，而这些分子靶标并未包括在当前的测试策略中，并且目前对于所生成数据的重要性尚无明确立场。这篇综述提供了一种处理内分泌数据的框架：构成内分泌系统的所有腺体，组织，受体，转运蛋白和酶都是毒性的靶标。应当以与其他目标器官几乎相同的方式来考虑它们，并为致癌和致畸的特殊情况提供适当的规定，并且应考虑所有可用数据并认识到其局限性，采用务实的证据权重方法。在这种方法中，结构-活性关系以及体外和靶向体内筛选提供了有用的数据，但是具有确定终点的重复剂量调节研究提供了用于危害评估的最强大工具。务实考虑暴露问题（可能会突出实际的无关性，例如，效力很低的雌激素），然后考虑内分泌干扰是化合物的关键还是最敏感的终点。最后，内分泌干扰可能被认为是一种机制，并且与其他毒性终点一样，了解作用和不可观察的作用水平以及可逆性与确定靶组织或任何固有的类激素性质一样重要。

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