COMPARISONS OF IN VITRO AND IN VIVO SKIN RESPONSES TO SURFACTANTS WITH A RANGE OF IRRITANCY POTENTIAL.

Scientists at Procter & Gamble Co. previously reported the development of a battery of endpoints in human skin cultures that correlate with human skin irritation responses to selected prototype surfactants. The purpose of the present study was to directly compare dose-response characteristics for surfactant-induced irritation in intact human skin exposed in vivo with the responses of in vitro cornified human skin cultures using their previously developed methods. In these studies, P&G scientists examined the effects of 7 surfactants representing a range of skin irritancy potential from mild to strong. Test materials included nonionic, anionic and amphoteric surfactants. For the in vivo studies twelve healthy volunteers were skin patch tested using 3 applications of Webril patches (2.25 cm2) with 0.25 ml of 5 dilutions of each surfactant. Surfactant concentrations were selected to produce an erythema response in human skin in vivo. Patches were applied for 24 hours and then test sites rinsed with water at patch removal before visual grading scores were assigned. Grades were assigned before each reapplication of patches and 24 hours after removal of the third set of patches using a 0-4 scale (0 representing no cutaneous involvement). For the in vitro studies, P&G scientists evaluated cornified, air-interfaced human skin cultures (EpiDerm™ – MatTek Corp. and Skin2 Model ZK1301 – Advanced Tissue Sciences). To parallel the human clinical methods, the in vitro studies used the same lot of surfactant, dose solution preparation, topical dosing method and dose volume adjusted for skin surface area. In the in vitro studies, the endpoint evaluated was the MTT assay of cell viability, which we have shown previously to correlate well with in vivo skin responses. The results indicate that: 1) in vivo human skin response curves for each surfactant could be generated and these curves can be used to assess surfactants for irritancy potential in vivo; and 2) dose response curves could be generated in vitro in which increases in cytotoxicity (MTT assay) in response to topically-applied dilutions of the surfactants, could be used to distinguish the degree of skin irritancy similar to the in vivo human skin responses. These results indicate the potential value of cornified human skin cultures for in vitro evaluations of human skin irritation responses to surfactants.

Contact Dermatitis, Cutaneous irritancy, Cutaneous irritation, Cutaneous toxicity, Cytotoxicity, Dermal irritancy, Dermal irritancy testing, Dermal irritation, Dermatitis, Contact, Endpoints, MTT, EpiDerm, Erythema Response, MTT, MTT ET-50 tissue viability assay, MTT assay, Skin irritancy, Skin irritation, Surfactants, Surfactants, irritancy/irritancy potential, Viability