Derivation, characterisation and analysis of an adverse outcome pathway network for human hepatotoxicity

Adverse outcome pathways (AOPs) and their networks are important tools for the development of mechanistically based non-animal testing approaches, such as in vitro and/or silico assays, to assess toxicity induced by chemicals. In present study, an AOP network connecting 14 linear AOPs related human hepatotoxicity, currently available AOP-Wiki, was derived according established criteria. The characterised analysed with regard its structure topological features. In-depth analysis showed that cell injury/death, oxidative stress, mitochondrial dysfunction accumulation fatty acids most highly connected central key events. Consequently, these events may be considered rational anchored basis selecting, developing and/optimising assays predict hepatotoxicity chemicals view animal-free hazard identification.