Evaluation of the GARD assay in a blind Cosmetics Europe study

Johansson, Henrik; Gradin, Robin; Forreryd, Andy; Agemark, Maria; Zeller, Kathrin S.; Johansson, Angelica; Larne, Olivia; Vliet, Erwin van; Borrebaeck, Carl; Lindstedt, Malin

doi:10.14573/altex.1701121

Cited by 12 publications

(14 citation statements)

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“…the mDPRA, the IL-18 assay, the U-SENS and GARD skin showed the best human correlation for the hair dye ingredients tested here, showing a higher predictive capacity of these methods than of some others based on animal data (eg, in silico models established by the use of LLNA data). Corroborating this, previous studies have shown that these four assays have different predictive capacities in identifying skin sensitizers, 1,10,[57][58][59][60] showing their potential to be applied in a testing approach as a way to overcome the technical limitations found in each technique.…”

Section: Evaluation Of Henna Products In the Testing Approach Estabmentioning

confidence: 83%

“…However, our data showed that all henna products tested were classified as skin sensitizers by the use of different two‐of‐three ITSs, which is a conventional approach that was first introduced by Bauch et al Interestingly, the mDPRA or GARD skin classified the henna colourants as skin sensitizers in the same way as the combined outputs involving different endpoints, questioning the need for combined approaches. Among the techniques evaluated, previous studies showed that the DPRA (accuracy of 80%) and GARD skin (accuracy of 86%) achieved the best accuracies by testing a wide range of chemical datasets . Although no data have yet been published involving mixtures, it has recently been shown that the combination of a high‐performing assay with less accurate techniques reduces the predictive capacity of a two‐of‐three ITS .…”

Section: Discussionmentioning

confidence: 99%

“…Among the techniques evaluated, previous studies showed that the DPRA (accuracy of 80%) and GARD skin (accuracy of 86%) achieved the best accuracies by testing a wide range of chemical datasets. 8,58 Although no data have yet been published involving mixtures, it has recently been shown that the combination of a highperforming assay with less accurate techniques reduces the predictive capacity of a two-of-three ITS. 56,63 Corroborating this, another study evaluated the predictive performances of the DPRA and other two assays, namely KeratinoSens™ (accuracy 77%) and the human cell line activation test (h-CLAT) (accuracy of 85%) on the basis of skin sensitization KE-2 and KE-3, respectively.…”

Section: Evaluation Of Henna Products In the Testing Approach Estabmentioning

confidence: 99%

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Evaluation of in vitro testing strategies for hazard assessment of the skin sensitization potential of “real‐life” mixtures: The case of henna‐based hair‐colouring products containing p‐phenylenediamine

et al. 2019

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Background: Allergic contact dermatitis caused by henna-based hair-colouring products has been associated with adulteration of henna with p-phenylenediamine (PPD).Objectives: To develop a testing approach based on in vitro techniques that address key events within the skin sensitization adverse outcome pathway in order to evaluate the allergenic potential of hair-colouring products. Methods:The following in vitro assays were used to test the sensitizing capacity of hair dye ingredients: the micro-direct peptide reactivity assay (mDPRA); the HaCaT keratinocyte-associated interleukin (IL)-18 assay; the U937 cell line activation test (U-SENS)/IL-8 levels; the blood monocyte-derived dendritic cell test; and genomic allergen rapid detection (GARD skin). Those techniques with better human concordance were selected to evaluate the allergenic potential of 10 hair-colouring products.Results: In contrast to the information on the label, chromatographic analyses identified PPD in all products. The main henna biomarker, lawsone, was not detected in one of the 10 products. Among the techniques evaluated by testing hair dye ingredients, the mDPRA, the IL-18 assay, GARD skin and the U-SENS correlated better with human classification (concordances of 91.7%-100%) and were superior to the animal testing (concordance of 78.5%). Thus, these assays were used to evaluate haircolouring products, which were classified as skin sensitizers by the use of different two-of-three approaches.Conclusions: Our findings highlight the toxicological consequences of, and risks associated with, the undisclosed use of PPD in henna-based "natural" "real-life" products. K E Y W O R D Sallergic contact dermatitis, alternative methods, cosmetics, hair dyes, mixtures, skin sensitization

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Section: Evaluation Of Henna Products In the Testing Approach Estabmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Evaluation Of Henna Products In the Testing Approach Estabmentioning

confidence: 99%

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Evaluation of in vitro testing strategies for hazard assessment of the skin sensitization potential of “real‐life” mixtures: The case of henna‐based hair‐colouring products containing p‐phenylenediamine

et al. 2019

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“…More innovative is the study performed to identify skin sensitizers in henna products using the GARD TM skin assay. The Genomic Allergen Rapid Detection (GARD) platform is a cell-based assay that uses the innate recognition of xenobiotics by dendritic cells, measured by monitoring genomic biomarkers [12]. In the context of henna-based hair dye products, GARD TM skin has been further combined with validated tests such as the micro-direct peptide reactivity assay, the HaCaT keratinocytes-associated IL-18 assay, and the U937 cell line activation test (USENS) [13].…”

Section: Introductionmentioning

confidence: 99%

Chemical Compounds Responsible for Skin Allergy to Complex Mixtures: How to Identify Them?

Giménez‐Arnau

2019

Cosmetics

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In the cosmetics industry, various natural complex mixtures such as botanical extracts and essential oils are used. In addition, finished consumer products may contain a number of constituents of natural origin but many products are derived from organic synthesis too. Hence, finding skin sensitizers within this myriad of chemicals is an arduous task. Nowadays, methods validated by European dedicated instances to evaluate the allergenicity of chemicals are incapable of predicting the sensitization potential of complex mixtures, although research has progressed a lot in this direction recently. In this context, precisely identifying the culprit(s) responsible for skin sensitization in these mixtures is essential for risk assessment. This review is a short summary of approaches that identify allergens in chemical mixtures such as bioassay-guided chemical fractionation, structure-activity relationship studies, and recent methods allowing identification of reactive intermediates in natural extracts exposed to air oxidation. It is shown that substantial progress has been made, although the identification of sensitizers in complex mixtures continues to be puzzling.

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“…Although it has been argued that the GARD platform indeed captures information of relevance for potency subcategorization ( Johansson et al , 2017 ), GARDskin is currently proposed for hazard identification. However, the concept of identifying and utilizing a subset of genomic biomarkers that are specific for sensitizing potency has been explored ( Albrekt et al , 2014 ).…”

mentioning

confidence: 99%

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

Gradin

Johansson

Forreryd

et al. 2020

Toxicological Sciences

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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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Evaluation of the GARD assay in a blind Cosmetics Europe study

Cited by 12 publications

References 12 publications

Evaluation of in vitro testing strategies for hazard assessment of the skin sensitization potential of “real‐life” mixtures: The case of henna‐based hair‐colouring products containing p‐phenylenediamine

Evaluation of in vitro testing strategies for hazard assessment of the skin sensitization potential of “real‐life” mixtures: The case of henna‐based hair‐colouring products containing p‐phenylenediamine

Chemical Compounds Responsible for Skin Allergy to Complex Mixtures: How to Identify Them?

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

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