Can a Genetic Toxicity Profile Inform In Vivo Testing Strategies

A positive result from a bacterial reporter assay would lower the ranking of the compound for development. The compound file should be aimotated with an alert for a confirmatory in vitro test (if the compound remains hve), in this case it might be a screening Ames at a later stage. There should also be a second alert to the lead optimization chemists. A third alert should still notify the genotoxicity safety assessment team that the compound is a priority for mechanistic investigation if the series continues, with the associated need for coordination of in vivo studies, this would be a lower priority than an Ames profiling positive. 

A positive result from a eukaryotic reporter assay would lower the ranking of a compound for development, alert lead optimization chemists and similarly trigger a confirmatory assay and alert safety assessment. 

Can a Genetic Toxicity Profile Inform In Vivo Testing Strategies  

A positive result from a chromosome aberration assay (MNT, cytogenetic analysis or small colonies in MLA) suggests a second in vivo assay for clastogenesis or aneugenesis. Centromere staining of mitotic cells allows the distinction of aneugens and clastogens. 

Eollow-up for positive results in reporter assays specifically developed for profiling screening would by default be in vivo MNT, though additional information might 

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