Quantitative assessment of sensitizing potency using a dose–response adaptation of GARDskin

Abstract Hundreds of chemicals have been identified as skin sensitizers. These are chemicals that possess the ability to induce hypersensitivity reactions in humans, giving rise to a condition termed allergic contact dermatitis. The capacity to limit hazardous exposure to such chemicals depends upon...

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Autores principales:	Robin Gradin, Andy Forreryd, Ulrika Mattson, Anders Jerre, Henrik Johansson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/25728b4eb9b24df2acacc8780cd8be62
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spelling	oai:doaj.org-article:25728b4eb9b24df2acacc8780cd8be622021-12-02T18:13:52ZQuantitative assessment of sensitizing potency using a dose–response adaptation of GARDskin10.1038/s41598-021-98247-72045-2322https://doaj.org/article/25728b4eb9b24df2acacc8780cd8be622021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98247-7https://doaj.org/toc/2045-2322Abstract Hundreds of chemicals have been identified as skin sensitizers. These are chemicals that possess the ability to induce hypersensitivity reactions in humans, giving rise to a condition termed allergic contact dermatitis. The capacity to limit hazardous exposure to such chemicals depends upon the ability to accurately identify and characterize their skin sensitizing potency. This has traditionally been accomplished using animal models, but their widespread use offers challenges from both an ethical and a scientific perspective. Comprehensive efforts have been made by the scientific community to develop new approach methodologies (NAMs) capable of replacing in vivo assays, which have successfully yielded several methods that can identify skin sensitizers. However, there is still a lack of new approaches that can effectively measure skin sensitizing potency. We present a novel methodology for quantitative assessment of skin sensitizing potency, which is founded on the already established protocols of the GARDskin assay. This approach analyses dose–response relationships in the GARDskin assay to identify chemical-specific concentrations that are sufficient to induce a positive response in the assay. We here compare results for 22 skin sensitizers analyzed using this method with both human and LLNA potency reference data and show that the results correlate strongly and significantly with both metrics (rLLNA = 0.81, p = 9.1 × 10–5; rHuman = 0.74, p = 1.5 × 10–3). In conclusion, the results suggest that the proposed GARDskin dose–response methodology provides a novel non-animal approach for quantitative potency assessment, which could represent an important step towards reducing the need for in vivo experiments.Robin GradinAndy ForrerydUlrika MattsonAnders JerreHenrik JohanssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Robin Gradin Andy Forreryd Ulrika Mattson Anders Jerre Henrik Johansson Quantitative assessment of sensitizing potency using a dose–response adaptation of GARDskin
description	Abstract Hundreds of chemicals have been identified as skin sensitizers. These are chemicals that possess the ability to induce hypersensitivity reactions in humans, giving rise to a condition termed allergic contact dermatitis. The capacity to limit hazardous exposure to such chemicals depends upon the ability to accurately identify and characterize their skin sensitizing potency. This has traditionally been accomplished using animal models, but their widespread use offers challenges from both an ethical and a scientific perspective. Comprehensive efforts have been made by the scientific community to develop new approach methodologies (NAMs) capable of replacing in vivo assays, which have successfully yielded several methods that can identify skin sensitizers. However, there is still a lack of new approaches that can effectively measure skin sensitizing potency. We present a novel methodology for quantitative assessment of skin sensitizing potency, which is founded on the already established protocols of the GARDskin assay. This approach analyses dose–response relationships in the GARDskin assay to identify chemical-specific concentrations that are sufficient to induce a positive response in the assay. We here compare results for 22 skin sensitizers analyzed using this method with both human and LLNA potency reference data and show that the results correlate strongly and significantly with both metrics (rLLNA = 0.81, p = 9.1 × 10–5; rHuman = 0.74, p = 1.5 × 10–3). In conclusion, the results suggest that the proposed GARDskin dose–response methodology provides a novel non-animal approach for quantitative potency assessment, which could represent an important step towards reducing the need for in vivo experiments.
format	article
author	Robin Gradin Andy Forreryd Ulrika Mattson Anders Jerre Henrik Johansson
author_facet	Robin Gradin Andy Forreryd Ulrika Mattson Anders Jerre Henrik Johansson
author_sort	Robin Gradin
title	Quantitative assessment of sensitizing potency using a dose–response adaptation of GARDskin
title_short	Quantitative assessment of sensitizing potency using a dose–response adaptation of GARDskin
title_full	Quantitative assessment of sensitizing potency using a dose–response adaptation of GARDskin
title_fullStr	Quantitative assessment of sensitizing potency using a dose–response adaptation of GARDskin
title_full_unstemmed	Quantitative assessment of sensitizing potency using a dose–response adaptation of GARDskin
title_sort	quantitative assessment of sensitizing potency using a dose–response adaptation of gardskin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/25728b4eb9b24df2acacc8780cd8be62
work_keys_str_mv	AT robingradin quantitativeassessmentofsensitizingpotencyusingadoseresponseadaptationofgardskin AT andyforreryd quantitativeassessmentofsensitizingpotencyusingadoseresponseadaptationofgardskin AT ulrikamattson quantitativeassessmentofsensitizingpotencyusingadoseresponseadaptationofgardskin AT andersjerre quantitativeassessmentofsensitizingpotencyusingadoseresponseadaptationofgardskin AT henrikjohansson quantitativeassessmentofsensitizingpotencyusingadoseresponseadaptationofgardskin
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Quantitative assessment of sensitizing potency using a dose–response adaptation of GARDskin

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