Aardema1, M., Khambatta1, Z., Barnett1, B., Reisinger, K., Ouedraogo3, G., Faquet3, B., Ginestet3, A.C., Mun4, G., Dahl4, E., Curren4, R., Carmichael5, P., Diembeck6, W., Fautz7, R., Harvey8, J., Hewitt9, N., Latil10, A., Pfuhler11, S., Marrec-Fairley12, M. 1The Procter & Gamble Co., Cincinnati, OH, USA; 2Henkel AG & Co KGaA, Duesseldorf, Germany; 3L’Oreal Life Sciences Research, Aulnay sous Bois, France; 4Institute for In Vitro Sciences, Inc., Gaithersburg, MD, USA; 5Unilever, Sharnbrook UK; 6Beiersdorf AG, Hamburg, Germany; 7KPSS - Kao Professional Salon Services, Darmstadt, Germany; 8GSK, Ware, UK; 9Erzhausen, Germany; 10Pierre Fabre, Toulouse, France; 11The Procter & Gamble Co., Marly, Switzerland; 12COLIPA, Brussels, Belgium.

This COLIPA-funded study by scientists at Procter and Gamble, Henkel AG and Co KGaA, L’Oreal, the Institute for In Vitro Sciences (IIVS), Unilever, Beiersdorf AG, KPSS (Kao Professional Salon Services), GlaxoSmithKline (GSK) and Pierre Fabre demonstrated that MatTek’s EpiDerm in vitro 3-D human skin tissue equivalent, when used as the basis for a human skin micronucleus assay (RSMN), provides a more realistic application/metabolism of test compounds for evaluating the genotoxicity of topically appliced cosmetics. 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 follow-up 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 EpiDerm™. 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), L’Oreal (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).


7th Amendment to the EU Cosmetics Directive, Assay transferability, Assay validation, COLIPA, EPI-200-MNA, EpiDerm, Genotoxicity, Genotoxicity assays, Inter-laboratory reproducibility, RSMN, Reconstructed human skin micronucleus assay

Materials Tested

Acetone, Cyclohexanone, Mitomycin C, N-Ethyl-N-nitrosourea, Vinblastine sulfate

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