New Approach for In Silico Genotoxicity Testing of Impurities and Degradants
Poster May 05, 2011
Kiril Lanevskij, Liutauras Juska, Remigijus Didziapetris and Pranas Japertas
The list of potentially hazardous structural fragments was compiled from various literature sources and refined by analyzing their performance on data from different assays detecting point mutational and/or clastogenic mechanisms of DNA damage (Ames test, in vitro chromosomal aberrations, micronucleus test, mouse lymphoma assay, sister chromatid exchange). Finally, the expert system was tested on the Carcinogenic Potency Database and FDA carcinogenicity data to ensure detection of common non-genotoxic carcinogens. Selected structural alerts achieved >90% sensitivity for recognizing positive compounds in Ames and Chromosomal Aberrations data sets showing that the absence of alerting groups is a reliable criterion for identifying impurities not posing significant genotoxic/carcinogenic risk.