Allergic contact dermatitis is one of the most common adverse events associated with cosmetic use. Accordingly, assessment of skin sensitisation hazard is required for safety evaluation of cosmetic ingredients. The transition to the use of alternative methods for testing has made skin sensitisation an intense field in the past decades. The first alternative methods have been in place for almost a decade, but none as stand-alone replacement for the reference murine Local Lymph Node Assay (LLNA). While strategies to combine data from several methods are being evaluated and refined, individual methods face technical limitations. These include issues related to their applicability to highly lipophilic substances and the lack of reliable potency estimation, which remain important obstacles to their widespread adoption as replacement for animal methods. The unique characteristics of in vitro skin models represented an attractive alternative, potentially overcoming these limitations and offering a more physiologically relevant environment for the assessment of the response in keratinocytes and dendritic cells. In this review, we recapitulate how reconstructed human skin models have been used as platforms for skin sensitisation testing, including the latest approaches using organ-on-a-chip and microfluidic technologies, aimed to develop next-generation organotypic skin models with increased complexity and monitoring capabilities.

Allergic contact dermatitis is one of the most common adverse events associated with cosmetic use. Accordingly, assessment of skin sensitisation hazard is required for safety evaluation of cosmetic ingredients. Urged by the European cosmetics legislation ban on animal testing, skin sensitisation has been an intense field in the past two decades, focused on transitioning to the use of alternative methods for hazard prediction. The first alternative methods accepted for regulatory use have been in place for almost a decade, but none as stand-alone replacement for the reference animal method, the murine Local Lymph Node Assay (LLNA). While their strengths and limitations are being evaluated, and the search for new combinations of the adopted methods and other sources of information increase confidence, novel methods based on reconstructed human epidermis (RHE) have recently been validated and joined the available methods. Their unique characteristics provide important advantages that will potentially enhance non-animal testing for skin sensitisation in cosmetics and related industries. In this review, we recapitulate how reconstructed human skin models have been used as platforms for skin sensitisation testing, including the latest approaches using organ-on-a-chip and microfluidic technologies, aimed to develop next-generation organotypic skin models with increased complexity and monitoring capabilities.