[Strategic Establishment of a High-throughput Photosafety Assessment System].

Abstract

Chemical phototoxicity is elicited after exposure of skin to photosensitive chemicals, followed by exposure to sunlight. The intensity of ultraviolet light has increased due to ozone layer destruction; therefore, interest in avoidance of the phototoxicity risk of chemicals has increased in drug discovery and product development. Based on the mechanism of chemical phototoxicity, a photosafety screening strategy focusing on the photoreactivity of chemicals and skin exposure to chemicals was proposed. In an initially-developed photosafety screening system, a reactive oxygen species (ROS) assay and an in vivo cassette-dosing pharmacokinetic study were employed to evaluate the photoreactivity of chemicals and skin exposure to chemicals, respectively, and previous investigations yielded reliable photosafety predictions. On the other hand, the tools in the photosafety screening system have some issues, such as low applicability to poorly water-soluble chemicals in the ROS assay and unsatisfactory animal welfare in in vivo cassette-dosing pharmacokinetic studies. The present study aimed to overcome these issues. A micellar ROS (mROS) assay was newly developed to evaluate photoreactivity of poorly water-soluble chemicals, resulting in an increase in the number of evaluable chemicals by ROS assay systems. An in vitro permeation test was applied to the proposed photosafety screening strategy as an alternative to the in vivo pharmacokinetic study for evaluating chemical exposure of the skin. Combined use of the ROS assay system and in vitro permeation test provided reliable photosafety evaluations. These findings would contribute to drug discovery and product development with high photosafety and improved animal welfare.