Development of structural alerts for the in vivo micronucleus assay in rodents

In vivo mutagenicity and carcinogenicity studies are posing a high demand for testrelated resources. Among these studies, the micronucleus test in rodents is the most widely used, as follow up to positive in vitro mutagenicity results. A recent survey of the (Q)SAR models for mutagenicity and carcinogenicity has indicated that no (Q)SAR models for in vivo micronucleus are available in the public domain. Therefore, the development and extensive use of estimation techniques such as (Q)SARs, read-across and grouping of chemicals, promises to have a huge animal saving potential for this endpoint. In this report, we describe the identification of structural alerts for the in vivo micronucleus assay, and provide the list of underlying chemical structures. These structural alerts provide a coarse-grain filter for the preliminary screening of potential in vivo mutagens. LIST OF ABBREVIATIONS EPA Environmental Protection Agency EU European Union FDA Food and Drug Administration HOMO Highest Occupied Molecular Orbital ISS Istituto Superiore di Sanita’ JRC Joint Research Centre LUMO Lowest Unccupied Molecular Orbital OECD Organisation for Economic Cooperation and Development (Q)SAR (Quantitative) Structure-Activity Relationship REACH Registration Evaluation and Authorisation of CHemicals ROC Receiver Operating Curve SA Structural Alert SA_BB Benigni-Bossa structural alerts for mutagnicity / carcinogenicity in Toxtree SA_Mic Structural alerts refers for the in vivo micronucleus assay in Toxtree SA_Prot Structural alerts for protein binding in the OECD QSAR Toolbox CONTENTS