Overview on the current status of available test methods and additional promising methods for assessing UV-induced effects

Abstract

Photo-induced effects are based on the photosensitization processes by which a photosensitizer, i.e., a molecule absorbing nontoxic dose of ultraviolet (UV) or visible (VIS) radiation (chromophores), interacts with other molecules leading eventually to an adverse effect. The assessment of photo-induced toxicity is required when chemical preparations are intended to be used on sunlight-exposed skin, i.e., products topically applied to the skin or systemic drugs. It includes evaluation of phototoxic effects and of photoallergy, which will be discussed hereafter. Moreover, the recommended tiered phototoxic strategy, including nonbiological and biological assays, will be reported together with the ICH (International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) recommendations. In this photosafety strategy, UV/VIS spectral analysis should be employed as the first screening to indicate a potential phototoxic risk by measuring the molar extinction coefficient (MEC), followed by the ROS (reactive oxygen species) assay. The biological assays are then carried out to evaluate the phototoxic potential of those materials presenting potential phototoxic risk and include the 3T3 neutral red uptake phototoxicity test (3T3 NRU-PT) followed, if a positive result is obtained, by the human 3D reconstructed skin model phototoxicity test (H3D-PT). The last step is the confirmatory photopatch test to be applied to a group of volunteers and to be performed using the first non-phototoxic concentration determined in the H3D-PT using a margin of safety factor of 10. Finally, some epidemiological data regarding photoallergy will be presented.