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Roberts, DW (2022) A critical review of the kinetic direct peptide reactivity assay (kDPRA) for skin sensitizer potency assessment - taking it forward. Critical Reviews in Toxicology, 51 (10). pp. 805-819. ISSN 1040-8444
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A critical review of the kinetic direct peptide reactivity assay kDPRA for skin sensitizer potency assessment taking it forward.pdf - Published Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (2MB) | Preview |
Abstract
It is widely recognized that the ability of chemicals to sensitize, and the potency of those chemicals that are sensitizers, is related to their ability to covalently modify protein in the skin. With the object of putting non-animal-based prediction of skin sensitization on a more quantitative footing, a recent paper describes the development of the kinetic Direct Protein Reactivity Assay (kDPRA), in which a matrix of peptide depletion values for different reaction times and test chemical concentrations is generated and analyzed so as to derive a reactivity parameter, logk max, which is used to classify chemicals into one of two potency categories. The present paper demonstrates that the reaction chemistry is not always consistent with the mathematical analysis of the data matrix and the kDPRA protocol does not identify such cases. Consequently the derived logk max value is not always mechanistically meaningful and its application to predict potency can lead to misleading conclusions. It is shown that by adopting a data analysis protocol based on conventional kinetics practice, the kDPRA can be made to provide more reliably meaningful and more extensive information that can be used for purposes such as potency estimation for deriving No Expected Sensitization Induction Level (NESILs) required for quantitative risk assessment (QRA), deriving quality specifications in terms of acceptable impurity levels, and development of structure-activity relationships. Secondly, the paper addresses applicability domain issues, in particular the problem of deciding whether or not the kDPRA is applicable for a given chemical.
| Item Type: | Article |
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| Uncontrolled Keywords: | ALLERGY; APPLICABILITY DOMAIN; applicability domains; chemical reaction mechanisms; IN-VITRO; Life Sciences & Biomedicine; LYMPH-NODE ASSAY; non-animal methods; OXIDATION; PREDICTION; QUANTITATIVE RISK-ASSESSMENT; Reaction kinetics; Science & Technology; structure-activity relationships; Toxicology; Science & Technology; Life Sciences & Biomedicine; Toxicology; Reaction kinetics; applicability domains; chemical reaction mechanisms; non-animal methods; structure-activity relationships; LYMPH-NODE ASSAY; QUANTITATIVE RISK-ASSESSMENT; IN-VITRO; APPLICABILITY DOMAIN; PREDICTION; OXIDATION; ALLERGY; Skin; Animals; Dermatitis, Allergic Contact; Peptides; Allergens; Risk Assessment; Kinetics; Animal Testing Alternatives; Reaction kinetics; applicability domains; chemical reaction mechanisms; non-animal methods; structure–activity relationships; Allergens; Animal Testing Alternatives; Animals; Dermatitis, Allergic Contact; Kinetics; Peptides; Risk Assessment; Skin; Toxicology; 1115 Pharmacology and Pharmaceutical Sciences |
| Subjects: | R Medicine > RS Pharmacy and materia medica |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Taylor & Francis |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 21 Sep 2022 07:40 |
| Last Modified: | 21 Sep 2022 10:15 |
| DOI or ID number: | 10.1080/10408444.2021.2020212 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/17622 |
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