Objectif The testing of cosmetological (and pharmaceutical) preparations will have to be performed in a near future by procedures alternative to animal experiments to comply with the Sixth Amendment (93-35-EEC) to the EC Cosmetic Directive (976- 768-EEC). In vitro recombined skin using human cells represents an elegant procedure for this purpose. The presently available models suffer imperfections that will be addressed in the present project to aim at the preparation of an in-vitro test for skin irritancy. It will display meaningful endpoints, should prove reproducible by the use of chemically defined culture products and immortalised cell lines and be easy-to-use by introducing adequate markers of the irritant reaction. The programme will be a shared activity of six academic research units representing a large part of the scientific european potential in the domain and associated industrial laboratories experts in the use of reconstructed skin for irritant testing. The project will be developed in four partially overlapping steps addressing to defined problems. Step 1- improvement of the quality of the stratum corneum in-vitro, introduction of endothelial cells in the dermal compartment and determination of in-vivo related endpoints of irritancy. Step 2 - replacement of the human cell strains by immortalised human cell lines and determination of the conditions required to obtain near physiological functions and the above determined selected end-points of the irritant reaction. Step 3 introduction of the markers of the irritant reaction by infection or transfection of constructions made of a reporter gene driven by the promoter of a protein participating in the process in the different lines of cells (keratinocytes, fibroblasts and endothelial cells). Step 4 - preparation of a model suitable for prevalidation testing in collaboration with industrial partners. The benefits of the project is scientific by the european collaboration required to address to the specific know-how of the different types of cells included in the model, economical by helping the industry to comply to the EEC directives and ethical by a contribution to the faster suppression of testing in animals by an alternative procedure. Champ scientifique sciences naturellessciences biologiquesbiochimiebiomoléculeprotéines Programme(s) FP4-BIOTECH 2 - Specific research, technological development and demonstration programme in the field of biotechnology, 1994-1998 Thème(s) 070104 - Cell cultures for the development of in vitro tests Appel à propositions Data not available Régime de financement CSC - Cost-sharing contracts Coordinateur Université de Liège Adresse 4000 Liège Belgique Voir sur la carte Contribution de l’UE € 0,00 Participants (5) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire Institut National de la Santé et de la Recherche Médicale France Contribution de l’UE € 0,00 Adresse Avenue claude vellefaux 75475 Paris Voir sur la carte Istituto di Ricerche Farmacologiche Mario Negri Italie Contribution de l’UE € 0,00 Adresse Via eritrea 62 20157 Milano Voir sur la carte Rijksuniversiteit Leiden Pays-Bas Contribution de l’UE € 0,00 Adresse 10,rijnsburgerweg 2300 RC Leiden Voir sur la carte Stiftung Deutsches Krebsforschungszentrum Allemagne Contribution de l’UE € 0,00 Adresse 280,im neuenheimer feld 69120 Heidelberg Voir sur la carte Universität Köln Allemagne Contribution de l’UE € 0,00 Adresse 9,joseph stelzmann straße 50931 Köln Voir sur la carte