The Vitotox and ToxTracker assays: a two-test combination for quick and reliable assessment of genotoxic hazards

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.