定量有害结局路径(qAOPs)评估环境化学物质毒性的研究进展Ⅰ：模型构建与应用案例
Research Advance of Quantitative Adverse Outcome Pathways (qAOPs) in Environmental Chemicals Toxicity Assessment Ⅰ: Model Building and Application Cases
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摘要: 近年来，有害结局路径（adverse outcome pathway，AOP）框架逐渐发展成熟，将生物信息组织成一种可用于评估化学品对人体健康和生态环境生物毒性的新方法，其开发的目的是用于化学品的评估和监管工作，包括优先级评估和危害性预测，最终实现风险评估并服务于管理决策。尽管AOP框架取得了巨大进展，但将其有效应用于化学品监管需要对分子启动事件、关键事件和有害结局之间的关系进行定量描述，因此发展定量AOPs （quantitative AOPs，qAOPs）至关重要。本文首先概述了AOP框架的现状，包括AOP数据库（AOP Knowledge Base）、定性AOPs （qualitative AOPs）和qAOPs。其次主要介绍了qAOPs构建的基本框架与步骤、方法模型，现阶段已构建的qAOPs案例及其应用现状。最后论述了当前qAOPs发展中存在的问题与潜在解决方案，并展望了未来的发展趋势与潜在应用。Abstract: Over the past decade, the development of adverse outcome pathway (AOP) framework has matured significantly, which has been considered as a new approach for organizing biological information into a format and applicable method for chemical safety evaluation in both human health and ecological contexts. Ultimately, it is developed for use in the assessment and regulation of chemicals, including the priority assessment and hazard prediction. Based on above, AOP will contribute to the realization of the risk assessment and application in regulatory decision making. Although the development of AOP frameworks has made great progress, its effective application to chemical regulation requires a detailed quantitative description of the relationship among the molecular priming events, key events and the adverse outcome. Consequently, quantitative AOPs (qAOPs) is critical for AOP application. At first, this review summarizes the development status of AOP framework, including AOP knowledge base (AOP KB), qualitative AOPs and quantitative AOPs. Secondly, this review describes how qAOP models can be developed and provides examples of how they could be used in a hazard or risk assessment context. Finally, the most important issues and potential solutions in the current qAOPs development process are discussed in this review, the future research and application of qAOPs in the hazard assessment of environment chemicals and environmental mixtures are also prospected.
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