Genotoxicity assays with Episkin, a reconstructed skin model: Towards new tools for in vitro risk assessment of dermally applied compounds?

In vitro reconstructed human skin such as Episkin® is a widely used model in safety or efficacy pre-screening tests. It is of growing interest for regulatory purposes as an alternative to animal testing. The reduction and eventually the replacement of In vivo toxicity testing require the development of In vitro models to predict the genotoxic or other endpoint risk. This can be achieved if these new assays take into account the exposure conditions in a more relevant way. To that end, new approaches are proposed using human reconstructed skin model for in vitro toxicology assessment. Reconstructed skin models have not been used for In vitro genotoxicity testing so far, though they present clear advantages over mouse skin for human risk assessment. This work highlights the development of a specific protocol for performing genotoxicity assays. The skin is indeed a biologically active barrier driving the exposure to compounds and their possible metabolites. A specific co-culture system using Episkin® and target cells to perform a regular micronucleus assay is presented. This first step in using human reconstructed skin for genotoxicity testing has aimed at improving the relevance of exposure conditions in In vitro genotoxicity assays for topically applied compounds.