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 presence of light are called photoallergens or photo sensitizers. The Direct Peptide Reactivity Assay (DPRA, OECD N⁰ 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 skin sensitization potential of several chemical substances. In order to study the combined effect of a chemical compound and UV light, we modified DPRA (photo-DPRA) as well as 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.
Highlights
Allergic contact dermatitis (ACD) induced by repeated skin exposure of low molecular weight chemicals is characterized by skin rash, itch, and other complications such as erythema and edema
3.1 Fulfillment of Direct Peptide Reactivity Assay (DPRA) acceptance criteria as per OECD TG 442C Synthetic Cys- and Lys-peptides with purities of 98.2% and 98.4%, respectively, were obtained and stock solutions of 0.667 mM were prepared for both peptides
Several in chemico reactivity assays that can be used to assess the molecular initiating event (MIE) in the skin sensitization adverse outcome pathway (AOP) have been reported in the literature (Aptula et al, 2006; Natsch and Gfeller, 2008; Avonto et al, 2015; Nepal et al, 2018; Zhang et al, 2018)
Summary
Allergic contact dermatitis (ACD) induced by repeated skin exposure of low molecular weight chemicals is characterized by skin rash, itch, and other complications such as erythema and edema. Chronic exposure may lead to skin thickening and eczema with cracks from itching. Exposure to allergens causes T-cell activation and proliferation that triggers adverse effects resulting in the dermal symptoms of ACD (Silvestre et al, 2018). Skin allergens can be identified using epidemiological data, clinical case studies, and sensitization/allergy tests (patch or maximization test) in humans (Basketter and Safford, 2016). Animal based in vivo methods such as the mouse Local Lymph Node Assay (LLNA) and the guinea pig maximization test were used for the same purpose (Kimber et al, 2001). Regulatory requirements borne out of ethical considerations are driving the development of non-animal alternative tests
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
