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有害结局路径策略在毒理学研究中的发展和应用
作者:王艳华 段化伟

摘要:

有害结局路径(AOP)是综合已有的毒理学信息,在个人或群体的水平上,关于外源性化学物引发的分子起始事件(MIE)和有害结局之间相互联系的框架。可以通过这个框架将分子起始事件引起损害作用的毒性试验结果外推到人,为收集和评估相关化学、生物学和毒理学信息提供框架,在毒理学风险评估中发挥重要作用。本文对AOP的概念及其框架的建立和评定进行了论述,并列举了已经在毒理学研究中建立的AOP框架的实例,以及其在毒理学应用方面的展望和挑战。

关键词:危险性评估;毒理学;分子生物学;有害结局路径;关键事件

Abstract:

Adverse outcome pathway (AOP) was a conceptual construct that integrated existing knowledge concerning the pathway of causal linkages between a molecular initiating event (MIE) and a final adverse effect at individual or population levels. The AOP methodology could be used as a basis for effects extrapolation and was an approach towards providing a framework for collecting and evaluating relevant chemical, biological and toxicological information. The framework would play an important role in risk assessment. We reviewed the concept of AOP, the development and assessment of the framework and the established models in toxicology researches. And the prospects and challenges of its application in toxicology were also introduced.

Key words: Risk assessment;Toxicology;Molecular biology;Adverse outcome pathway;Key event

发表日期:2015/12

引用本文:

图/表:

  • 10.3760/cma.j.issn.0253-9624.2015.12.019.F001:图1 毒性通路、作用模式、有害结局路径、从源到结局路径概念的理论范围[13]

    10.3760/cma.j.issn.0253-9624.2015.12.019.F001:图1 毒性通路、作用模式、有害结局路径、从源到结局路径概念的理论范围[13]

  • 10.3760/cma.j.issn.0253-9624.2015.12.019.F002:图2 有害结局路径相关生物反应过程[13]

    10.3760/cma.j.issn.0253-9624.2015.12.019.F002:图2 有害结局路径相关生物反应过程[13]

  • 10.3760/cma.j.issn.0253-9624.2015.12.019.F003:图3 皮肤过敏反应有害结局路径框架[13]

    10.3760/cma.j.issn.0253-9624.2015.12.019.F003:图3 皮肤过敏反应有害结局路径框架[13]

  • 10.3760/cma.j.issn.0253-9624.2015.12.019.F004:图4 肝纤维化有害结局路径框架[26]

    10.3760/cma.j.issn.0253-9624.2015.12.019.F004:图4 肝纤维化有害结局路径框架[26]

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