Application of available alternative methods to predict skin sensitization of preservatives

Allergic disease resulting from industrial or environmental exposure to sensitizers is the most commonmanifestation of immunotoxicity in humans. Allergen risk assessment of chemicals so far relies on animalassays. In the context of the 7th amendment to the Cosmetic Directive and the REACH-legislation onchemicals, the cosmetic industry is concerned by the challenge of finding nonanimal approaches to assessthe sensitizing potential of chemicals.Among the Skin Sensitization Test (MUSST) based on the induction of CD86 on U937 cells. Years in-house experiencewith this assay led us to identify its limits, and to develop further methods (apoptosis assay) and furthermodels (including 3D-models) to overcome these limits. During the past two years, we enlarged our set ofcell-based assays by incorporating the well-described direct peptide reactivity assay (DPRA). Currently,we are addressing the question of the integration of in vitro data that we are now able to produce, togetherwith in silico data, in order to predict skin sensitization potency of cosmetic ingredients. While the generationand the detailed analysis of complete data on a large set of raw materials is ongoing, we present herethe analysis of the results obtained on a benchmark of 25 preservatives. This study allowed us in a verypragmatic approach, to get an insight into the feasibility, but also the actual limitations of using in vitro methods so far available for pre-validation studies, we developed the Myeloid U937in vitromethods for the screening and / or the evaluation of new chemicals for skin sensitization potential.