The EPISKIN Phototoxicity Assay (EPA): Development of an in vitro tiered strategy to predict phototoxic potential

The aim of the study was to investigate the ability of human reconstructed epidermis EpiSkin to assess the phototoxic potential of chemicals following topical or systemic treatment. Three categories of chemicals according to their available human phototoxic potential were evaluated: systemic phototoxic, topical phototoxic and non phototoxic chemicals. Products were applied topically or added to the underlying culture medium (systemic-like administration) at non cytotoxic concentrations. Following treatment, tissues were exposed to a non cytotoxic dose of UVA (50J.cm). Cell viability and pro-inflammatory mediators (IL-1α) were investigated 22h after UVA exposure. Our results showed that the phototoxic potential of chemicals can be assessed using cell viability endpoints combined with pro-inflammatory mediator measurements (cytokine IL-1α) in a 3-D epidermis model. The EPA was able to discriminate efficiently between phototoxic and non phototoxic products. Furthermore, the EPA is sensitive to the administration route in the prediction of the phototoxic potential. Differences observed between the 2 routes of administration (topical or systemic–like) may be linked in part to chemicals bioavailability which depends on specific penetration potential, epidermis barrier function and also on keratinocytes absorption/metabolization processes. The performances of the EPA showed that the EpiSkin model is an efficient tool able to integrate decision-making processes to address the question of phototoxicity linked to the administration route.