The Benigni / Bossa rulebase for mutagenicity and carcinogenicity - a module of Toxtree

TLDR: This report gives an introduction to currently available QSARs and SAs for carcinogenicity and mutagenicity, and provides details of the Benigni/Bossa rulebase.

Abstract: The Joint Resarch Centre's European Chemicals Bureau has developed a hazard estimation software called Toxtree, capable of making structure-based predictions for a number of toxicological endpoints. One of the modules developed as an extension to Toxtree is aimed at the prediction of carcinogenicity and mutagenicity. This module encodes the Benigni/Bossa rulebase for carcinogenicity and mutagenicity developed by Romualdo Benigni and Cecilia Bossa at the Istituto Superiore di Sanita’, in Rome, Italy. The module was coded by the Toxtree programmer, Ideaconsult Ltd, Bulgaria. In the Toxtree implementation of this rulebase, the processing of a query chemical gives rise to limited number of different outcomes, namely: a) no structural alerts for carcinogenicity are recognised; b) one or more structural alerts (SAs) are recognised for genotoxic or non-genotoxic carcinogenicity; c) SAs relative to aromatic amines or αβ-unsaturated aldehydes are recognised, and the chemical goes through Quantitative Structure-Activity Relationship (QSAR) analysis, which may result in a negative or positive outcome. If the query chemical belongs to the classes of aromatic amines or αβ-unsaturated aldehydes, the appropriate QSAR is applied and provides a more refined assessment than the SAs, and should be given higher importance in a weightof-evidence scheme. This report gives an introduction to currently available QSARs and SAs for carcinogenicity and mutagenicity, and provides details of the Benigni/Bossa rulebase. LIST OF ABBREVIATIONS AD Applicability Domain ECB European Chemicals Bureau FDA US Food and Drug Administration ISSCAN Istituto di Sanita database on chemical carcinogens QSAR Quantitative Structure-Activity Relationship SA Structural Alert