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under regulatory frameworks such as European REACH (“Registration, Evaluation, Authorisation and Restriction of Chemicals”) or CLP (“Classification, Labelling and Packaging”) regulation, but also in accordance with more specific directives such as those for cosmetics, foods or biocides. State of the art of genotoxicity testing of chemicals is the application of a battery of assays covering gene mutations, structural and numerical chromosomal aberrations. At tier-1, this typically starts with an in vitro testing battery. If a chemical is without any effect in vitro, it might be classified as non-genotoxic in some legislations (REACH, CLP, Cosmetics Directive), while others (i.e., pharmaceuticals, veterinary drugs) usually require an in vivo follow-up investigation. On the other side, a positive outcome in vitro may also call for confirmation by appropriate in vivo testing. Yet, in recent years, in vivo studies in principle became under pressure or even prohibited under certain regulations such as the Cosmetics Directive (Adler et al. 2011). Established in vitro gene mutation assays are the bacterial reverse mutation test, also referred to as Ames test (OECD TG 471) and the mammalian gene mutation tests (OECD TG 476 and 490), of which the latter two have been revised in 2015. The in vitro mammalian chromosomal aberration test, also referred to as CAT assay (OECD TG 473), is an established measure for the frequency of chromosomal aberrations. In addition, the in vitro mammalian cell micronucleus test, i.e., MNT (OECD TG 487), is supposed to detect structural and numerical aberrations and was only recently assessed by the European Centre for the Validation of Alternative Methods (ECVAM; Corvi et al. 2008); the test guideline has been revised thereafter. The MNT was considered less expensive and time consuming, thereby requiring less intense training and allowing a greater statistical validity compared to the CAT. Thus, the Nanomaterials are increasingly used in a variety of applications, and plenty of nanoenabled products are already placed on the market. Nanomaterials often display novel and enhanced features compared to conventional materials. This led to an ongoing debate about the safety of these materials. Often it was concluded that the data pool is incomplete and insufficient to perform meaningful and reliable risk assessments for most of the nanomaterials. Additionally, it was questioned whether the established test methods for chemicals were at all adequate and suitable to assess the safety of nanomaterials. Has this situation changed meanwhile? In this editorial, we want to discuss the genotoxicity testing of nanomaterials by focusing on in vitro methodologies. Genotoxicity describes the property of a chemical compound or of particles to alter the genetic information of a cell. This may occur by different mechanisms like gene mutations and structural or numerical chromosomal aberrations. In the following, such alterations can have severe consequences. In the germline, they can lead to abortions or to heritable damage to the offspring; in somatic cells, they may cause cancer. Furthermore, aging and a variety of diseases such cardiovascular or some neurodegenerative diseases are linked to the accumulation of DNA damage. Thus, genetic alterations are associated with serious health effects and may, in principle, occur even at very low exposure levels against the chemical culprit. Investigating the genotoxic properties therefore represents an important step in the safety assessment of a substance and is required

Genotoxicity of nanomaterials in vitro: treasure or trash?