Overview on current status

Abstract

The assessment of the genotoxicity hazard of chemicals is a central requirement in many legislations which often decides on the fate of raw materials during product development. Genotoxicity defines the potential of a chemical to damage DNA, and such DNA-damaging agents are differentiated into three classes: mutagens, clastogens, and aneugens. No single in vitro or in vivo assay is able to detect all types of genotoxins, and assessment of the genotoxic potential of a compound therefore usually is done using two or more assays, a so-called test battery. Such a battery approach, however, has shown to exhibit a high rate of “false” or “misleading” positives, which can lead to unnecessary in vivo follow-up testing. Such in vivo testing would today, in a modern testing strategy, consider the anticipated route of human exposure, which for dermally exposed substances is the skin. As a surrogate or replacement for in vivo follow-up assays, more complex alternative assays do now exist and base on human 3D skin models, namely, the 3D Skin Comet assay and the reconstructed skin micronucleus assay (RSMN). They allow for identification of DNA lesions resulting from mutagens, clastogens, and aneugens and are composed of human primary cells which eliminate the species barrier and, at the same time, resemble human skin in terms of bioavailability of a dermally exposed substance as well as in terms of an organ- and species-specific xenobiotic metabolism.