- Publisher:Lhasa Limited
- Publication Date:Sep 2015
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Using In Vitro Structural Alerts For Chromosome Damage to Predict In Vivo Activity and Direct Future Testing
Dr. Alex Cayley, Knowledge Scientist at Lhasa Limited provides an overview on his paper of the same name.
While the in vivo genotoxicity of a compound may not always correlate well with its activity in in vitro test systems, for certain compound classes a good overlap may exist between the two endpoints. The difficulty, however, lies in establishing the cases where this relationship holds true and selecting the most appropriate protocol to highlight any potential in vivo hazard. With this in mind, a project was initiated at Lhasa Limited in collaboration with the National Institute of Health Sciences (NIHS) of Japan in which existing structural alerts for in vitro chromosome damage in the expert system Derek Nexus were assessed for their relevance to in vivo activity. An expert assessment was made of selected alerts and they were updated with information relating to their in vivo relevance. In this presentation the results from this work will be described. General observations will be discussed based on our findings relating to subjects such as the importance of mechanistic interpretation in in vivo test protocol selection and the need to analyse existing data carefully before reaching a conclusion. These will be illustrated with specific examples from the work. We hope that the detailed information relating to in vivo activity and protocol added to the knowledge base in combination with the mechanistic information provided will prove useful in directing the further testing of compounds of interest.