Omics-based input and output in the development and use of adverse outcome pathways

Abstract

Adverse outcome pathways (AOPs) are pragmatic tools in toxicology and risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of key events connected by key event relationships and an adverse outcome. AOPs can serve a number of purposes pertinent to safety assessment of chemicals, such as the establishment of quantitative structure–activity relationships, the development of novel in vitro toxicity screening tests, and the elaboration of prioritization strategies. Development of AOPs ideally complies with guidelines issued by the Organization for Economic Cooperation and Development. Omics, in particular transcriptomics, plays a major role in the establishment and application of AOPs by defining key events and by providing biomarkers for toxicity screening, respectively.