This study investigated the utility of combining in vitro alternatives to animal use in tests for skin sensitization (also known as allergic contact dermatitis). Four promising alternative methods are currently being developed for testing skin sensitization to chemicals. Fifty-four substances were tested with combinations of the four alternative methods, and the results from these combinations were compared with previous results from animal and human tests. A predictive model combining three of the alternative tests showed higher accuracy in predicting skin sensitization than current animal methods. The authors concluded these alternative tests have the potential to replace animal tests in the future.

“Allergic contact dermatitis is a common skin disease and is elicited by repeated skin contact with an allergen. In the regulatory context, currently only data from animal experiments are acceptable to assess the skin sensitizing potential of substances. Animal welfare and EU Cosmetic Directive/Regulation call for the implementation of animal-free alternatives for safety assessments. The mechanisms that trigger skin sensitization are complex and various steps are involved. Therefore, a single in vitro method may not be able to accurately assess this endpoint.”

“Non-animal methods are being developed and validated and can be used for testing strategies that ensure a reliable prediction of skin sensitization potentials. In this study, the predictivities of four in vitro assays, one in chemico and one in silico method addressing three different steps in the development of skin sensitization were assessed using 54 test substances of known sensitizing potential. The predictivity of single tests and combinations of these assays were compared.”

“These data were used to develop an in vitro testing scheme and prediction model for the detection of skin sensitizers based on protein reactivity, activation of the Keap-1/Nrf2 signaling pathway and dendritic cell activation.”