ToxSci Advance Access published online on February 14, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm019
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Recommendation of a GUM working group for a simple and straightforward approach to genotoxicity testing
1 P+G Prestige and Professional, Cosmital SA, Experimental Product Safety, CH-1723 Marly 2 F. Hoffmann-La Roche AG, Department of Toxicology, CH-4070 Basel 3 Kao Professional Salon Services GmbH, D-64297 Darmstadt 4 Bayer Healthcare AG, D-42096 Wuppertal 5 Federal Institute for Risk Assessment (BfR), Safety of Substances and Preparations, D-14195 Berlin 6 Merck KGaA, Institute of Toxicology, D-64271 Darmstadt 7 RCC Cytotest Cell Research GmbH, D-64380 Rossdorf
* Corresponding author: Stefan Pfuhler, P+G Prestige and Professional, COSMITAL SA, Dept. RD-EPS, Rte de Chesalles 21, CH - 1723 Marly, Switzerland, phone: +41 (0)26 435 25 21, fax: +41 (0)26 435 26 66, e-mail: pfuhler.s{at}pg.com
Received December 21, 2006; accepted February 12, 2007
 |
Abstract |
|---|
Based on new scientific developments and on experience of the regulation of chemical compounds, a working group of the GUM (German-speaking section of the European EMS) 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 consist of a bacterial gene mutation test plus an in vitro micronucleus test, therewith covering all mutagenicity endpoints. Stage II testing is in general required only if relevant positive results occur in stage I testing and will usually be in vivo. However, an isolated positive bacterial gene mutation test in stage I can be followed up with a gene mutation assay in mammalian cells. If this assay turns out negative and there are no compound-specific reasons for concern, in vivo follow-up testing may not be required.
In those cases where in vivo testing is indicated, a single study combining the analysis of micronuclei in bone marrow with the comet assay in appropriately selected tissues is suggested. Negative results for both endpoints in relevant tissues will generally provide sufficient evidence to conclude that the test compound is non-genotoxic in vivo. Compounds which were recognized as in vivo somatic cell mutagens / genotoxicants in this hazard identification step will need further testing. In the absence of additional data such compounds will have to be assumed to be potential genotoxic carcinogens and potential germ cell mutagens.