Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
Arch Toxicol. 2017 Nov;91(11):3697-3707. doi: 10.1007/s00204-017-2020-z. Epub 2017 Jun 28.
Adverse outcome pathways (AOPs) are designed to provide a clear-cut mechanistic representation of critical toxicological effects that propagate over different layers of biological organization from the initial interaction of a chemical with a molecular target to an adverse outcome at the individual or population level. Adverse outcome pathways are currently gaining momentum, especially in view of their many potential applications as pragmatic tools in the fields of human toxicology, ecotoxicology, and risk assessment. A number of guidance documents, issued by the Organization for Economic Cooperation and Development, as well as landmark papers, outlining best practices to develop, assess and use AOPs, have been published in the last few years. The present paper provides a synopsis of the main principles related to the AOP framework for the toxicologist less familiar with this area, followed by two case studies relevant for human toxicology and ecotoxicology.
不良结局途径(AOPs)旨在提供一种清晰的机制表示,阐明从化学物质与分子靶标最初相互作用到个体或群体水平的不良结局的不同层次的生物学组织中传播的关键毒理学效应。不良结局途径目前正在获得动力,特别是考虑到它们作为人类毒理学、生态毒理学和风险评估领域的实用工具的许多潜在应用。在过去几年中,经济合作与发展组织发布了一些指导文件,以及概述了制定、评估和使用 AOP 的最佳实践的标志性文件。本文为毒理学家提供了与该领域不太熟悉的 AOP 框架相关的主要原则概述,然后是两个与人类毒理学和生态毒理学相关的案例研究。