Genetic Toxicity Assessment: Employing the Best Science for Human Safety Evaluation Part IV:Recommendation of a Working Group of the Gesellschaft fuer Umwelt-Mutationsforschung (GUM) for a Simple and Straightforward Approach to Genotoxicity Testing

Based on new scientific developments and experience of the regulation of chemical compounds, a working group of the Gesellschaft fuer Umweltmutationsforschung (GUM), a German-speaking section of the European Environmental Mutagen Society, proposes a simple and straightforward approach to genotoxicity testing. This strategy is divided into basic testing (stage I) and follow-up testing (stage II).Stage I consistsof a bacterial genemutation test plus anin vitro micronucleus test, therewith covering all mutagenicity endpoints. Stage II testing is in general required only if relevant positive resultsoccurinstageItestingandwillusuallybeinvivo.However,an isolated positive bacterial gene mutation test in stage I can be followedupwithagenemutationassayinmammaliancells.Ifthisassay turns out negative and there are no compound-specific reasons for concern,in vivofollow-up testing may not be required. Inthose cases whereinvivotestingisindicated,asinglestudycombiningtheanalysis of micronuclei in bone marrow with the comet assay in appropriately selected tissues is suggested. Negative results for both end points in relevant tissues will generally provide sufficient evidence to conclude that the test compound is nongenotoxic in vivo. Compounds which