Research progress of adverse outcome pathways

The Organization for Economic Cooperation and Development (OECD) officially launched a new project on the development of Adverse Outcome Pathway (AOP) in 2012 and released an AOP database in 2014 in order to meet the increasing demand of chemical toxicity risk assessment and safety management. AOP is a conceptual framework that connects molecular initiating events (MIE) with adverse outcomes. The core of AOP is to modularize a series of toxic events related to molecules, cells, tissues, organs, individuals, and groups, and to establish a logical chain through the above modularized process. As an important theoretical framework for the development of alternative toxicity testing methods and future environmental health risk assessment, AOP can be used to evaluate a series of key events by establishing qualitative/quantitative relationships between MIEs and adverse outcomes, and further to promote the release and implementation of relevant administrative decisions, regulations, and laws. The paper summarized the AOP developmental process, basic concepts, structure, knowledge base and its main module functions, and classified AOP by MIE. To describe the development status and evaluate the application prospect of AOP, the qualitative AOP mediated by dioxin/dioxin-like activated aromatic hydrocarbon receptor (AhR) and the quantitative AOP of chronic kidney disease induced by oxidative stress were described as examples. This review is expected to provide new ideas and strategies for toxicity testing and risk assessment of new chemicals and compound pollutants, and improve safety management of chemicals in China.