Predictivity of an in vitro model for acute and chronic skin irritation (SkinEthic) applied to the testing of topical vehicles

An in vitro human reconstructed epidermis model (SkinEthic) used for screen ing acute and chronic skin irritation potential was validated against in vi vo data from skin tolerability studies. The irritation potential of sodium lauryl sulfate (SLS), calcipotriol and trans-retinoic acid was investigated . The in vitro epidermis-like model consists of cultures of keratinocytes f rom human foreskin on a polycarbonate filter. The modulation of cell viabil ity, the release and gene expression of proinflammatory cytokines, interleu kins 1 alpha and 8, and morphological changes were evaluated during 3 days as endpoints representative for an inflammatory reaction. The cumulative ir ritation potential of the topical products was evaluated in a human clinica l study by visual scoring and biophysical measurement of inflammatory skin reaction after repeated 24 h applications over 3 weeks under Finn chamber p atches. All topical products that were nonirritating in the human study wer e noncytotoxic and did not induce cytokine expression in the in vitro acute model (day 1 exposure). All irritating controls exhibited specific cell vi ability and cytokine patterns, which were predictive of the in vivo human d ata. The ranking of mild to moderate skin irritation potential was based on the lack of cytotoxicity and the presence of cytokine patterns including g ene expression specific for each irritant, using the chronic in vitro model (up to 3 days exposure). The human reconstructed epidermis model SkinEthic was shown to be a reliabl e preclinical tool predicting the irritation potential of topical products. Moreover, it is a useful model in a two-step tiered strategy for screening acute and chronic irritation potential for the selection of vehicles for n ew topical drugs.