The Colipa Research and Method Development Program for Identifying and Characterizing Skin Sensitizers without Animal Testing

151 Allergic contact dermatitis (ACD) is the clinical condition resulting from skin sensitization, which is a delayed-type hypersensitivity reaction induced by small reactive chemicals (haptens). to ensure that ingredients in cosmetic products do not induce skin sensitization (and hence do not cause ACD in consumers), a risk assessment is performed to evaluate the risk to humans and to substantiate the safety decision. to make a safety decision the risk assessor uses information on the concentration of the ingredient in the product and how the product is used by consumers, as well as available hazard characterization data (Loretz et al., 2005, 2006). At present, if significant skin exposure to a new ingredient is predicted, animal test data (e.g. mouse local lymph node assay (llNA) data) may need to be generated to characterize the skin sensitizer potential/potency of the ingredient and thereby inform the risk assessment decision. Given the increasing public and political concerns surrounding the generation of data on cosmetic ingredients in animals, the development of non-animal (in vitro, in chemico, and in silico) test methods and non-animal risk assessment approaches for skin sensitization remains a high priority for the cosmetic industry. Non-animal test methods for skin sensitization need to cover the complex interactions of a chemical with the different compartments of the immune system. the chemical must penetrate the skin and react with endogenous proteins. Some chemicals, termed prohaptens, require activation through skin metabolism in order to become haptens capable of binding to skin proteins. Haptenated carrier-proteins are internalized and processed by immature dendritic cells (DCs) that become activated. the activated DCs start to migrate from the epidermis into the draining lymph node, complete maturation, and present fragments of the haptenated carrier-proteins to t-cells, resulting in an antigenspecific immune response (Enk and Katz, 1992; Cumberbatch et al., 1992). there are several large programs of ongoing research that aim to deliver new non-animal test methods for skin sensitization. Colipa, the european cosmetics industry trade association, participates intensively in this international research effort through continuous funding of research to explore the toxicity pathways governing the induction of skin sensitization, the development of new methods incorporating the acquired knowledge, and as a member of the Sens-it-iv consortium (Aeby et al., 2010; Maxwell et al., 2011). Our ongoing research portfolio (direct funding of eight research and method-development projects and participation in Colipa-affiliated projects) continues to provide new insights into the biological processes driving skin sensitization. three in vitro test methods for the detection of potential sensitizers, i.e., the Direct Peptide Reactivity Assay (DPRA) (Gerberick et al., 2007), the human Cell line Activation test (h-ClAt) (Ashikaga The Colipa Research and Method Development Program for Identifying and Characterizing Skin Sensitizers without Animal Testing Pierre Aeby 1, Natalie Alépée 2, Takao Ashikaga 3, Sandrine Bessou-Touya 4, Eric Dufour 2, Frank Gerberick 5, Nicola Gilmour 6, Carsten Goebel 5, Petra Kern 5, Monique Marrec-Fairley 1, Silvia Martinozzi-Teissier 2, Gavin Maxwell 6, Hitoshi Sakaguchi 7, Julia Scheel 8, Andreas Schepky 9, Kerstin Reisinger 8, Magalie Tailhardat 10, and Petra Winkler 11 1Colipa, Brussels, Belgium; 2L’Oréal, Aulnay-sous-Bois, France; 3Shiseido Research Centre, Yokohama-Shi, Japan; 4Pierre Fabre, Castres, France; 5The Procter & Gamble Company, Cincinnati, OH, USA and Strombeek-Bever, Belgium; 6Unilever, Sharnbrook, UK; 7Kao Corporation, Tochigi, Japan; 8Henkel AG & Co. KGaA, Duesseldorf, Germany; 9Beiersdorf, Hamburg, Germany; 10LVMH Recherche, Saint Jean de Braye, France; 11Johnson & Johnson, Neuss, Germany