Integrated approach to testing and assessment for predicting rodent genotoxic carcinogenicity

Knowledge Source Identification
Knowledge source name Integrated approach to testing and assessment for predicting rodent genotoxic carcinogenicity
Owner/Developer John Wiley & Sons, Inc.
Country United States of America
Languages English
Description We investigated the performance of an integrated approach to testing and assessment (IATA), designed to cover different genotoxic mechanisms causing cancer and to replicate measured carcinogenicity data included in a new consolidated database. Genotoxic carcinogenicity was predicted based on positive results from at least two genotoxicity tests: one in vitro and one in vivo (which were associated with mutagenicity categories according to the Globally Harmonized System classification). Substances belonging to double positives mutagenicity categories were assigned to be genotoxic carcinogens. In turn, substances that were positive only in a single mutagenicity test were assigned to be mutagens. Chemicals not classified by the selected genotoxicity endpoints were assigned to be negative genotoxic carcinogens and subsequently evaluated for their capability to elicit non-genotoxic carcinogenicity. However, non-genotoxic carcinogenicity mechanisms were not currently included in the developed IATA. The IATA is docked to the OECD Toolbox and uses measured data for different genotoxicity endpoints when available. Alternatively, the system automatically provides predictions by SAR genotoxicity models using the OASIS Tissue Metabolism Simulator platform. When the developed IATA was tested against the consolidated database, its performance was found to be high, with sensitivity of 74% and specificity of 83%, when measured carcinogenicity data were used along with predictions falling within the models' applicability domains. Performance of the IATA would be slightly changed to a sensitivity of 80% and specificity of 72% when the evaluation by non-genotoxic carcinogenicity mechanisms was taken into account.
Knowledge Source Category
Category Publication
Sub categories Review / Research article
Knowledge Dissemination and Sharing
Dissemination channel Website, Printed
Targeted audience (specified/objective analysis) Scientists, Industry, Researchers
Users access Fee-based access
Knowledge Characterization
3Rs relevance Replacement, Reduction, Refinement
Purpose Documentation and information, Toxicological and safety evaluation, Method development
Technology/Tools Integrated approaches to testing and assessment (IATA), Alternative test methods (in vitro), Non-testing methods (in silico), Animal testing (in vivo)