COLIPA validation of the Reconstructed Human Skin Micronucleus Assay (RSMN): A novel micronucleus assay in a 3D human skin model
Current mammalian cell in vitro genotoxicity assays induce a high level of false positive results leading to a large number of costly and time consuming followup in vivo genotoxicity studies. As of March 2009, the 7th Amendment to the EU Cosmetics Directive prohibits the use of in vivo genotoxicity tests in safety assessments for cosmetics, greatly impacting the assessment of genotoxicity of new ingredients. To address this, the European Cosmetic Toiletry and Perfumery Association (COLIPA) initiated an international project to establish and evaluate more predictive in vitro genotoxicity assays using 3D human tissues. One focus has been on the 3D human skin micronucleus assay (RSMN) in EpiDermTM. Since skin is the first site of contact with maximum exposure to many different products including cosmetics, the RSMN assay offers the potential for a more realistic application/metabolism of test compounds for evaluating genotoxicity (1,2,3). The COLIPA RSMN project is a multi-lab initiative involving Procter & Gamble (US), LOreal (France), Henkel (Germany), and the Institute for In Vitro Sciences (IIVS, US). Intra-laboratory and inter-laboratory reproducibility have been investigated with model genotoxins mitomycin C and vinblastine sulfate as well as a variety of chemicals that require metabolic activation. In addition studies with coded chemicals are in progress. This model is a promising new in vitro method for detecting micronuclei induction in human skin. This work is funded by the European Cosmetic Industry Association COLIPA.