Abstract:
:The toxicological assessment of genotoxic impurities is important in the regulatory framework for pharmaceuticals. In this context, the application of promising computational methods (e.g. Quantitative Structure-Activity Relationships (QSARs), Structure-Activity Relationships (SARs) and/or expert systems) for the evaluation of genotoxicity is needed, especially when very limited information on impurities is available. To gain an overview of how computational methods are used internationally in the regulatory assessment of pharmaceutical impurities, the current regulatory documents were reviewed. The software recommended in the guidelines (e.g. MCASE, MC4PC, Derek for Windows) or used practically by various regulatory agencies (e.g. US Food and Drug Administration, US and Danish Environmental Protection Agencies), as well as other existing programs were analysed. Both statistically based and knowledge-based (expert system) tools were analysed. The overall conclusions on the available in silico tools for genotoxicity and carcinogenicity prediction are quite optimistic, and the regulatory application of QSAR methods is constantly growing. For regulatory purposes, it is recommended that predictions of genotoxicity/carcinogenicity should be based on a battery of models, combining high-sensitivity models (low rate of false negatives) with high-specificity ones (low rate of false positives) and in vitro assays in an integrated manner.
journal_name
SAR QSAR Environ Resjournal_title
SAR and QSAR in environmental researchauthors
Fioravanzo E,Bassan A,Pavan M,Mostrag-Szlichtyng A,Worth APdoi
10.1080/1062936X.2012.657236subject
Has Abstractpub_date
2012-01-01 00:00:00pages
257-77issue
3-4eissn
1062-936Xissn
1029-046Xjournal_volume
23pub_type
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