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Evaluation of Skin Sensitization Using Amino Acid Derivative Reactivity AssayOrganic Solvent (ADRA-OS), an Alternative to Animal Tests: Effects of Epoxy Compound

Ryo Koizumi, Hiroaki Yamaga*, Koichiro Hayashi, Shinichi Watanabe, Shinsuke Kataoka

Skin sensitization is classified as a type IV (delayed) allergy (allergic contact dermatitis) caused by T lymphocyte activation that manifests as an inflammatory reaction within 48 hours of contact with a causative allergen. It can directly decrease the quality of life for those who are afflicted. Therefore, to appropriately determine the potential of chemical substances to sensitize skin is extremely important.

The development of alternatives to animal tests according to the Adverse Outcome Pathways (AOPs) of skin sensitization has recently progressed and test guidelines have been established by the Organization for Economic Cooperation and Development (OECD). The potential of chemicals to sensitize skin is difficult to determine using a single test and an alternative method that precisely reflects the results of animal experiments is not available. The coverage of alternative methods also needs to be precisely determined. Under these circumstances, the OECD issued Defined Approaches (DAs) for skin sensitization, which precisely evaluates skin sensitization by combining in vitro, in chemico and in silico methods. Based on this consideration, various evaluation methods have been combined, and issues such as their coverage have been clarified.

This review outlines the development of alternative skin sensitization tests and global trends in evaluations using such tests. We also review the Amino Acid Derivative Reactivity Assay-Organic Solvent (ADRA-OS), which we developed as an alternative to evaluating the skin sensitization potential of chemicals. The results of epoxy compound evaluations and the influence of chemical structures are considered.