Comparative assessment of several in silico systems and models to predict the outcome of the Ames mutagenicity assay
The current step 5 of the International Conference of Harmonization (ICH) M7 guideline on the assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals mandates the initial assessment of their potential mutagenicity using computational tools. The computational analysis should be carried out with two different methodologies: one expert-rule based and one statistical based. In order to comply with such specification, additional commercial in silico tools and novel models have been recently made available to the scientific community. In the present study we evaluated the individual and combined performance of three expert-rule systems (Derek Nexus, ToxTree, Leadscope Expert Alert) and three statistical systems (Sarah, Leadscope Model Applier, CASE Ultra – 3 novel models).
Presented by Alessandro Brigo at SOT, San Diego, USA; 22nd - 26th March 2015.