Adverse Outcome Pathways as Tools to Assess Drug-Induced Toxicity.
Adverse outcome pathways (AOPs) are novel tools in toxicology and human 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. Development and evaluation of AOPs ideally complies with guidelines issued by the Organization for Economic Cooperation and Development. AOP frameworks have yet been proposed for major types of drug-induced injury, especially in the liver, including steatosis, fibrosis, and cholestasis. These newly postulated AOPs can serve a number of purposes pertinent to safety assessment of drugs, in particular the establishment of quantitative structure-activity relationships, the development of novel in vitro toxicity screening tests, and the elaboration of prioritization strategies.
Department of In Vitro Toxicology and Dermato-Cosmetology, Pharmaceutical Institute, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels-Jette, 1090, Belgium. mvinken@vub.ac.be.
Mathieu
M
Vinken
D000073931:Adverse Outcome Pathways; D000826:Animal Testing Alternatives; D062313:Databases, Pharmaceutical; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008954:Models, Biological; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment
AOP; Cholestasis; Drug safety; Fibrosis; Steatosis