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The GARDpotency Assay for Potency-Associated Subclassification of Chemical Skin Sensitizers—Rationale, Method Development, and Ring Trial Results of Predictive Performance and Reproducibility

Proactive identification and characterization of hazards attributable to chemicals are central aspects of risk assessments. Current legislations and trends in predictive toxicology advocate a transition from in vivo methods to nonanimal alternatives. For skin sensitization assessment, several OECD v...

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Autores principales: Gradin, Robin, Johansson, Angelica, Forreryd, Andy, Aaltonen, Emil, Jerre, Anders, Larne, Olivia, Mattson, Ulrika, Johansson, Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416325/
https://www.ncbi.nlm.nih.gov/pubmed/32421796
http://dx.doi.org/10.1093/toxsci/kfaa068
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author Gradin, Robin
Johansson, Angelica
Forreryd, Andy
Aaltonen, Emil
Jerre, Anders
Larne, Olivia
Mattson, Ulrika
Johansson, Henrik
author_facet Gradin, Robin
Johansson, Angelica
Forreryd, Andy
Aaltonen, Emil
Jerre, Anders
Larne, Olivia
Mattson, Ulrika
Johansson, Henrik
author_sort Gradin, Robin
collection PubMed
description Proactive identification and characterization of hazards attributable to chemicals are central aspects of risk assessments. Current legislations and trends in predictive toxicology advocate a transition from in vivo methods to nonanimal alternatives. For skin sensitization assessment, several OECD validated alternatives exist for hazard identification, but nonanimal methods capable of accurately characterizing the risks associated with sensitizing potency are still lacking. The GARD (Genomic Allergen Rapid Detection) platform utilizes exposure-induced gene expression profiles of a dendritic-like cell line in combination with machine learning to provide hazard classifications for different immunotoxicity endpoints. Recently, a novel genomic biomarker signature displaying promising potency-associated discrimination between weak and strong skin sensitizers was proposed. Here, we present the adaptation of the defined biomarker signature on a gene expression analysis platform suited for routine acquisition, confirm the validity of the proposed biomarkers, and define the GARDpotency assay for prediction of skin sensitizer potency. The performance of GARDpotency was validated in a blinded ring trial, in accordance with OECD guidance documents. The cumulative accuracy was estimated to 88.0% across 3 laboratories and 9 independent experiments. The within-laboratory reproducibility measures ranged between 62.5% and 88.9%, and the between-laboratory reproducibility was estimated to 61.1%. Currently, no direct or systematic cause for the observed inconsistencies between the laboratories has been identified. Further investigations into the sources of introduced variability will potentially allow for increased reproducibility. In conclusion, the in vitro GARDpotency assay constitutes a step forward for development of nonanimal alternatives for hazard characterization of skin sensitizers.
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spelling pubmed-74163252020-08-12 The GARDpotency Assay for Potency-Associated Subclassification of Chemical Skin Sensitizers—Rationale, Method Development, and Ring Trial Results of Predictive Performance and Reproducibility Gradin, Robin Johansson, Angelica Forreryd, Andy Aaltonen, Emil Jerre, Anders Larne, Olivia Mattson, Ulrika Johansson, Henrik Toxicol Sci Immunotoxicology Proactive identification and characterization of hazards attributable to chemicals are central aspects of risk assessments. Current legislations and trends in predictive toxicology advocate a transition from in vivo methods to nonanimal alternatives. For skin sensitization assessment, several OECD validated alternatives exist for hazard identification, but nonanimal methods capable of accurately characterizing the risks associated with sensitizing potency are still lacking. The GARD (Genomic Allergen Rapid Detection) platform utilizes exposure-induced gene expression profiles of a dendritic-like cell line in combination with machine learning to provide hazard classifications for different immunotoxicity endpoints. Recently, a novel genomic biomarker signature displaying promising potency-associated discrimination between weak and strong skin sensitizers was proposed. Here, we present the adaptation of the defined biomarker signature on a gene expression analysis platform suited for routine acquisition, confirm the validity of the proposed biomarkers, and define the GARDpotency assay for prediction of skin sensitizer potency. The performance of GARDpotency was validated in a blinded ring trial, in accordance with OECD guidance documents. The cumulative accuracy was estimated to 88.0% across 3 laboratories and 9 independent experiments. The within-laboratory reproducibility measures ranged between 62.5% and 88.9%, and the between-laboratory reproducibility was estimated to 61.1%. Currently, no direct or systematic cause for the observed inconsistencies between the laboratories has been identified. Further investigations into the sources of introduced variability will potentially allow for increased reproducibility. In conclusion, the in vitro GARDpotency assay constitutes a step forward for development of nonanimal alternatives for hazard characterization of skin sensitizers. Oxford University Press 2020-08 2020-05-18 /pmc/articles/PMC7416325/ /pubmed/32421796 http://dx.doi.org/10.1093/toxsci/kfaa068 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Immunotoxicology
Gradin, Robin
Johansson, Angelica
Forreryd, Andy
Aaltonen, Emil
Jerre, Anders
Larne, Olivia
Mattson, Ulrika
Johansson, Henrik
The GARDpotency Assay for Potency-Associated Subclassification of Chemical Skin Sensitizers—Rationale, Method Development, and Ring Trial Results of Predictive Performance and Reproducibility
title The GARDpotency Assay for Potency-Associated Subclassification of Chemical Skin Sensitizers—Rationale, Method Development, and Ring Trial Results of Predictive Performance and Reproducibility
title_full The GARDpotency Assay for Potency-Associated Subclassification of Chemical Skin Sensitizers—Rationale, Method Development, and Ring Trial Results of Predictive Performance and Reproducibility
title_fullStr The GARDpotency Assay for Potency-Associated Subclassification of Chemical Skin Sensitizers—Rationale, Method Development, and Ring Trial Results of Predictive Performance and Reproducibility
title_full_unstemmed The GARDpotency Assay for Potency-Associated Subclassification of Chemical Skin Sensitizers—Rationale, Method Development, and Ring Trial Results of Predictive Performance and Reproducibility
title_short The GARDpotency Assay for Potency-Associated Subclassification of Chemical Skin Sensitizers—Rationale, Method Development, and Ring Trial Results of Predictive Performance and Reproducibility
title_sort gardpotency assay for potency-associated subclassification of chemical skin sensitizers—rationale, method development, and ring trial results of predictive performance and reproducibility
topic Immunotoxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416325/
https://www.ncbi.nlm.nih.gov/pubmed/32421796
http://dx.doi.org/10.1093/toxsci/kfaa068
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