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- Publication Type:Poster
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Development of an Adverse Outcome Pathway (AOP) Network for Carcinogenicity Using Expert-Derived (Q)SAR Knowledge. Poster
The prediction of carcinogenicity and related toxicity endpoints has always been a principal research area for in silico (Q)SAR systems and, as a result, software relating to these endpoints is well developed. In recent years, predictions provided by these systems have become embedded in regulatory guidance, where they may be used to replace or augment other testing methods. Consequently, it is important that the predictions are as accurate as possible and are provided in such a way that they can be easily integrated with other sources of evidence. For example, suggested revisions to the ICH S1 guidance are under consideration which would negate the need to conduct a two year rodent carcinogenicity assay if there is knowledge of pharmacologic targets and pathways, alongside toxicological and other data, which could provide sufficient information to anticipate the outcome of a carcinogenicity bioassay. This review highlights the work undertaken so far to rearrange knowledge contained within Derek Nexus into an AOP network for carcinogenicity. This will allow for 1) easier interpretation of the evidence available that relates to a prediction, 2) integration of existing and emerging in vitro and in vivo assays, and 3) expansion of the scope of predictions which can be made for this endpoint.