To ensure human health, it is essential to characterize the genotoxic potential of new chemical entities such as pharmaceutical and cosmetic substances. In a first tier a battery of regulatory accepted in vitro tests is recommended. These tests have a relatively high sensitivity, but a low specificity. Furthermore, they are time-consuming, laborious and require large quantities of the individual chemicals. New assays overcoming these drawbacks are under development, the majority of them being reporter-based assays. In this paper we investigate the performance of two in vitro reporter-based assays, namely the Vitotox and the ToxTracker. A set of reference compounds were selected to cover not only different mechanisms of genotoxic action, but also a variety of applicability domains (e.g. pharmaceutical and cosmetic ingredients). Results show that both assays can be valuable tools in genotoxicity hazard assessment, especially when combined in a test battery. An interesting property of both assays for drug-development is the possibility of time-efficient analysis of a large amount of drug-candidates while using small quantities and high throughput (automatized) technologies. Furthermore, the tests are less laborious. For the cosmetic industry, the generated information can be added in a weight-of-evidence approach to derisk false positive results as in vivo follow-up testing is no longer allowed in Europe.