Recent developments in in vitro toxicology: perspectives of European research and Tox21

2012) and genotoxicity (Kirsch-Volders et al. 2011; Santovito et al. 2011). Since 2008, American funding institutions have supported a different concept, known formally as Tox21 (Betts 2013; Attene-Ramos et al. 2013; Bucher 2013). This concept aims at ‘high-throughput screening, toxicity pathway profiling’ and ‘target-specific, mechanism-based’ performance of in vitro assays (Tice et al. 2013). Practically, large numbers of chemicals are tested for relatively simple endpoints, such as cytotoxicity, cell signalling, DNA damage, inhibition of drug-metabolizing enzymes, interaction with nuclear receptors and isolated molecular targets (Tice et al. 2013). A major difference to previous approaches is that a large number of in vitro assays are used to determine the activation of ‘toxicity pathways’ to help prioritize compounds or even develop predictive models for biological response in humans (Tice et al. 2013). In a recent keynote lecture at the Eurotox 2013 in Interlaken, Franz Oesch summarized the current status of Tox21. Unfortunately, the accuracy of most in vitro assays for predicting human or animal toxicity used in Tox21 was not sufficient to replace in vivo experiments. Recently, relatively critical comments have been published, and Tox21 clearly faces difficulties, mainly due to the following reasons: