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不良结局途径作为肝毒性测试中的多功能工具。

Adverse Outcome Pathways as Versatile Tools in Liver Toxicity Testing.

机构信息

Department of Pharmaceutical and Pharmacological Sciences, Entity of In Vitro Toxicology, Vrije Universiteit Brussel, Brussels, Belgium.

出版信息

Methods Mol Biol. 2022;2425:521-535. doi: 10.1007/978-1-0716-1960-5_20.

Abstract

Adverse outcome pathways (AOPs) are tools to capture and visualize mechanisms driving toxicological effects. They share a common structure consisting of a molecular initiating event, a series of key events connected by key event relationships and an adverse outcome. Development and evaluation of AOPs ideally comply with guidelines issued by the Organization for Economic Cooperation and Development. AOPs have been introduced for major types of hepatotoxicity, which is not a surprise, as the liver is a frequent target for systemic adversity. Various applications for AOPs have been proposed in the areas of toxicology and chemical risk assessment, in particular in relation to the establishment of quantitative structure-activity relationships, the elaboration of prioritization strategies, and the development of novel in vitro toxicity screening tests and testing strategies.

摘要

不良结局途径(AOP)是用于捕获和可视化驱动毒理学效应的机制的工具。它们具有由分子起始事件、通过关键事件关系连接的一系列关键事件以及不良结局组成的共同结构。AOP 的开发和评估理想情况下应符合经济合作与发展组织发布的准则。AOP 已被引入各种主要类型的肝毒性,这并不奇怪,因为肝脏是全身逆境的常见靶标。AOP 在毒理学和化学风险评估领域提出了各种应用,特别是在建立定量结构-活性关系、制定优先级策略以及开发新型体外毒性筛选测试和测试策略方面。

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