Application of an Antioxidant Response Element–Nuclear Factor Erythroid 2 Luciferase Assay for Assessing the Skin Sensitization Potential of Agrochemicals

Abstract

The skin sensitization potential of agrochemicals can be assessed using laboratory methods such as the keratinocyte activation assay so that their use in regulatory toxicology might replace experimental animal testing. Here, we evaluated the skin sensitization potential of 11 agrochemicals by using an antioxidant response element–nuclear factor erythroid 2 luciferase assay in KeratinoSens and LuSens cells and applying a skin sensitization adverse outcome pathway (AOP). The KeratinoSens and LuSens assays consistently evaluated the skin sensitization potential of 10/11 agrochemicals with reference to animal testing databases. Benomyl, pretilachlor, fluazinam, terbufos, butachlor, and carbosulfan were correctly detected as sensitizers, and glufosinate ammonium, oxiadiazon, tebuconazole, and etofenprox were correctly detected as non-sensitizers. For diazinon, the skin sensitizing potential was positive in the KeratinoSens assay but not in the LuSens assay. These results suggest that the evaluation of in vitro skin sensitization using the AOP mechanism can be applied to assess active agrochemicals.

Keywords

• skin sensitization
• agrochemicals
• alternative methods
• antioxidant response element
• nuclear factor erythroid 2 luciferase assay
• adverse outcome pathway