Developing an adverse outcome pathway framework for carcinogenicity from alerts in an expert rule-based system.

Derek Nexus is an in silico, expert rule-based system capable of predicting for multiple toxicity endpoints. Accompanying the predictions are informative descriptions highlighting known toxicants and a plausible biological mechanism of action. Structural alerts are currently organised and presented to the user according to a hierarchy of toxicity endpoints. An alternative approach to organising this knowledge is the use of adverse outcome pathways (AOPs). An AOP is a mechanistic representation linking a molecular initiating event (MIE) to an adverse outcome (AO) through sequential key events (KEs). KEs are described at a defined level of biological organisation and linked together according to known biological mechanisms which are supported by empirical evidence.