Robinson, M.K., M.A. Perkins, and R. Osborne. Comparison of In Vitro and In Vivo Human Skin Response to Consumer Products and Ingredients with a Range of Irritancy Potential. In Vitro Cell. Dev. Biol. - Animal. 1998. 34(3): 8-A. Part II. Abstract T-3. [CopyrightÓ 1998 by the Society of In Vitro Biology (formerly the Tissue Culture Association). Permission to reproduce on website by the copyright owner.]

Human skin equivalent cultures are being investigated as a preclinical skin irritation screen to aid in the design of safe and efficient human studies. Our approach has been to directly compare in vitro to in vivo human skin responses using historic or concurrent skin response data for products and ingredients including surfactants, cosmetics, antiperspirants and deodorants (AP/DO). The in vivo data consisted of visual scores (i.e., erythema and edema) from skin patch tests and diary accounts of skin irritation from product use studies. For the in vitro studies we evaluated cornified, air-interfaced human skin cultures (EpidermÔ ) using methods to parallel human clinical protocols by topical dosing of neat or diluted test substances to the stratum corneum surface of the skin cultures. In the in vitro studies we evaluated endpoints that have been shown previously to be relevant to human skin irritation in vivo, including the MTT metabolism assay of cell viability, enzyme release (lactate dehydrogenase and aspartate aminotransferase) and inflammatory cytokine expression (Interleukin-1a ). For surfactants, dose-response curves of MTT cell viability data clearly distinguished strongly irritating from milder surfactants, and rank ordered irritancy potential in a manner similar to in vivo 3-patch test results. For AP/DO products, all the in vitro endpoints correlated well with consumer reported irritation (r=0.78-0.94), with IL-1a release showing the greatest capacity to distinguish irritancy over a broad range. IL-1a also showed the best prediction of human skin scores from 14-day cumulative irritancy tests of cosmetic products. These results confirm the potential value of cornified human skin cultures as an in vitro preclinical screen for prediction of human skin irritation responses, and identify the need to customize in vitro endpoints for irritancy prediction for different product classes.