IS-SKIN as a technically feasible alternative to EpiSkin for in vitro skin sensitization assessment of complex substances using the SENS-IS assay

: The SENS-IS assay is a reliable in vitro method for assessing the skin sensitization potential of chemicals using reconstructed human epidermis (RhE) models. Unlike many other non-animal methods, SENS-IS is uniquely suited for the evaluation of complex formulations, such as emulsions, mixtures, and ingredients with limited solubility. : This study aimed to compare the performance of the new IS-SKIN model, developed in-house by ImmunoSearch, with the reference Episkin model in the SENS-IS assay, using a panel of ten complex cosmetic raw materials : All test items were coded and tested in a fully blinded manner. ImmunoSearch analysts had no knowledge of the substances’ identities or expected classifications. Both RhE models were treated according to the validated SENS-IS protocol, and gene expression was quantified across three biomarker clusters: IRR, REDOX, and SENS-IS. : The two epidermal models showed full concordance in the classification of the ten test items. For sensitizers, gene expression responses obtained from IS-SKIN showed comparable functional activation patterns to those observed with Episkin, confirming the model’s ability to detect biologically relevant responses. : Conducted under blinded conditions, this study demonstrates that the IS-SKIN model performs equivalently to the reference Episkin model in the SENS-IS assay. The results support the suitability of IS-SKIN alternative, and further confirm the unique strength of SENS-IS for the evaluation of complex substances that remain difficult to assess using conventional in vitro approaches.