Comparison of in chemico skin sensitization methods and development of an in chemico skin photosensitization assay

Abstract

Chemical substances that induce an allergic response in skin upon contact are called skin allergens or sensitizers, while chemical substances that elicit an allergic response only in the presence of light are called photoallergens or photo sensitizers. The Direct Peptide Reactivity Assay (DPRA, OECD TG 442C, 2015) and the Amino Acid Derivative Reactivity Assay (ADRA) are in chemico assays used to discriminate between allergens and non-allergens. The DPRA and the ADRA respectively monitor the depletion of model peptides and modified amino acids induced by crosslinking with test chemicals. In the current study, we compared these two assays and analyzed their suitability to predict the skin sensitization potential of several chemical substances. In order to study the combined effect of a chemical compound and UV light, we modified the DPRA (photo-DPRA) as well as the ADRA (photo-ADRA) by introduction of a photo-irradiation parameter. Analysis using photo-DPRA and photo-ADRA correctly distinguished known photoallergens from non-photoallergens. Upon irradiation, photoallergens selectively showed higher depletion of model peptides or modified amino acids. Thus, photo-DPRA and/or photo-ADRA can serve as non-animal in vitro methods for the identification and assessment of photoallergens/photosensitizers.