Development, quantification and application of an adverse outcome pathway network of cholestatic liver injury 

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. Because of its  unique location and function in the organism, the liver is a frequent target for systemic toxicity. 

Several AOPs related to liver toxicity have been introduced over the fast few years, yet only  one focuses on accumulation of noxious bile acids. Nevertheless, this so-called cholestatic  hepatotoxicity underlies a majority of drug-induced liver injury cases and has also been  associated with various other types of chemicals, including food additives, cosmetics and  biocides. The present presentation will give an overview of the development of an AOP  network on cholestatic liver injury. Furthermore, recent testing of the robustness and  applicability domain as well as efforts to quantify the AOP network will be presented. This  quantification exercise is focused on the establishment of a benchmark, denoted the cholestatic  index, that can used for hazard identification and potency ranking.