Comparison of in vitro and in vivo human skin responses to consumer products and ingredients with a range of irritancy potential

Human skin equivalent cultures were investigated as possible pre-clinical s kin irritation screens to aid safety assessments for chemicals and product formulations, and to facilitate design of safe and efficient human studies. In vitro responses in human skin equivalent cultures were compared directl y to in vivo human skin responses from historic or concurrent skin tests fo r representative chemicals and products, including surfactants, cosmetics, antiperspirants, and deodorants. The in vivo data consisted of visual score s (i.e., erythema and edema) from skin-patch tests and diary accounts of sk in irritation from product-use studies. In the in vitro studies, cornified, air-interfaced human skin cultures (EpiDerm(TM) were evaluated using metho ds designed to parallel human clinical protocols with topical dosing of nea t or diluted test substances to the stratum corneum surface of the skin cul tures. The in vitro endpoints have previously been shown to be relevant to human skin irritation in vivo, including the MTT metabolism assay of cell v iability, enzyme release (lactate dehydrogenase and aspartate aminotransfer ase), and inflammatory cytokine expression (Interleukin-1 alpha). For surfa ctants, dose-response curves of MTT cell-viability data clearly distinguish ed strongly-irritating from milder surfactants and rank-ordered irritancy p otential in a manner similar to repeat-application (3x), patch-test results . For the antiperspirant and deodorant products, all the in vitro endpoints correlated well with consumer-reported irritation (r, 0.75-0.94), with Int erleukin-1 alpha (IL-1 alpha) release, showing the greatest capacity to dis tinguish irritancy over a broad range. IL-1 alpha release also showed the b est prediction of human skin scores from 14-day cumulative irritancy tests of cosmetic products. These results confirm the potential value of cornifie d human skin cultures as in vitro pre-clinical screens for prediction of hu man skin irritation responses. A preliminary report of these results has be en published.