423. THE COLIPA STRATEGY FOR THE DEVELOPMENT OF IN VITRO ALTERNATIVES: GENOTOXICITY.

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Pfuhler¹, S., Meunier², J-R., Aardema³, M., Banduhn⁴, N., Fautz⁵, R., Manou⁶, I., Wolfreys⁷, A. ¹Wella AG, Darmstadt, Germany, ²L’Oreal, Paris, France, ³Procter & Gamble, Cincinnati, OH, ⁴Henkel, Düsseldorf, Germany, ⁵Kao Professional Salon Services, Darmstadt, Germany, ⁶COLIPA, Brussels, Belgium, ⁷Unilever, Bedford, England. Presented at the 5th World Congress, Berlin, Germany, August 21-25, (2005).

Summary:
This report by the COLIPA Genotoxicity Task Force, comprised of researchers from Wella AG, L’Oreal, Procter & Gamble, Henkel, and Unilever, presents details of a concept developed for testing dermally exposed substances, including the use of MatTek’s EpiDerm human skin tissue equivalent, that will be part of a strategy for replacement of animal genotoxicity experiments.

The basic in vitro genotoxicity tests like the Ames test, mouse lymphoma test, chromosomal aberration or micronucleus test, exhibit major limitations such as the lack of human-like metabolic capacity, toxicokinetics, use of cell lines that are not relevant to the target organs and oversensitivity compared to in vivo situations.

A recent analysis of over 700 chemicals tested in the current in vitro genotoxicity tests demonstrated that, whilst they are efficient at detecting rodent carcinogens, 75%-95% of rodent non-carcinogens also induce false positive results in one or more of these assays (Kirkland et al. 2005 in press) which leads to most chemicals requiring in vivo animal tests.

Acknowledging these limitations of the present in vitro assays, a task force initiated by the European Commission and led by ECVAM recommended the introduction of an additional in vitro step using skin models (Maurici et al. 2005, in press) including MatTek’s EpiDerm human skin tissue equivalent.

Taking on this recommendation, the COLIPA Genotoxicity Task Force that includes researchers from Wella AG, L’Oreal, Procter & Gamble, Henkel, and Unilever, has developed a concept for dermally exposed substances that should form part of a strategy for replacement of animal experiments. A preliminary work plan based on this concept will be presented. This aims at clarifying positive results from in vitro genotoxicity tests on the basis of in vitro experiments that adequately cover skin metabolism, skin penetration and genotoxicity.

Ideally, the development and future validation of these methods will not only lead to replacement of animal experiments but also to the generation of results with higher significance for the dermal route of exposure.

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Applications: 7th Amendment Cosmetics Directive, Genotoxicity, Metabolism - skin, Micronucleus assay, Validation - in vitro tissue models

Keywords: 3D models, 7th Amendment to the Cosmetics Directive, COLIPA, COLIPA Task Force Genotoxicity, COLIPA-SCAAT Genotoxicity Task Force, Comet assay, ECVAM, EpiDerm, European Cosmetic Toiletry and Perfume Association (COLIPA), Genotoxicity, Genotoxicity assay, Genotoxicity testing, Genotoxins, Metabolism, Micronucleus assay, P450, Permeability, Safety assessments, Skin metabolism, Toxicokinetics

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