Prospective multicentre study of the U-SENS test method for skin sensitization testing

Alépée, Nathalie; Piroird, C.; Aujoulat, Michel; Dreyfuss, S.; Hoffmann, Sebastian; Hohenstein, A.; Méloni, Marisa; Nardelli, L; Gerbeix, C.; Cotovio, José

doi:10.1016/j.tiv.2015.09.028

Cited by 26 publications

(5 citation statements)

References 17 publications

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“…The final prediction is based on the majority concordant results. 18,19 This simplified prediction model was peer reviewed by EURL ECVAM. The U-SENS underwent an industry-led validation study designed primarily to address the reproducibility of the method [Within Laboratory Reproducibility (WLR) and Between Laboratory Reproducibility (BLR)].…”

Section: In Vitro Methodsmentioning

confidence: 99%

“…Thus the goal for the replacement of in vivo assays by non-animal alternatives appears to have been reached. [15][16][17] In addition, several further methods are in the final stages of review at the OECD, including U-SENSÔ 18,19 (www.oecd.org/env/ehs/testing/TG-Usensdraft-TG_Dec15-2016-clean.pdf) and IL8 Luc 20 (www1.oecd .org/env/ehs/testing/Draft-IL-8-Luc-TG-15Dec_clean.pdf), or under consideration, including LuSens 21 and SENS-IS. 22 Although there remains some debate, the current consensus holds that none of the methods in isolation is sufficient for hazard identification, which means that strategies to combine outputs from these methods must be developed.…”

Section: Introductionmentioning

confidence: 99%

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Alternative Integrated Testing for Skin Sensitization: Assuring Consumer Safety

BufaloAurelia¹,

PauloinThierry²,

Alépée³

et al. 2018

Applied In Vitro Toxicology

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Cosmetics legislation in Europe has driven the validation and acceptance of non-animal alternatives, most recently in the area of skin sensitization. Despite use of these methods to meet regulatory needs, it is also essential that they allow evaluation regarding human safety. For cosmetic product safety, it is necessary to understand how they can be used and with what limitations, and thereby reveal what remains to be addressed. A dataset of 165 ingredients (137 cosmetic ingredients +28 reference substances) has been identified, curated, and subjected to testing using accepted in vitro methods, with additional information, including physicochemical data and in silico results. The inputs from multiple determinants of skin sensitizing activity have been used in five individual supervised classification models (or machine learning approaches), which were then collated in a robust statistical manner, a stacking meta-model, to deliver a prediction with an optimized level of confidence. For the training set, with the probability cutoffs at 70% and 30%, predictive sensitivity was 97%, specificity was 88%, the overall accuracy was 93%, and kappa was 85%. A further 52 substances were used to test the effectiveness of the model: the predictive sensitivity was 89%, specificity was 95%, overall accuracy was 91%, and kappa was 82%. In conclusion, this stacking meta-model delivers improved performance and therefore enhanced confidence in the discrimination of skin sensitizers from nonsensitizers. The key remaining gap, prediction of skin sensitization potency, may benefit from a similar approach, maximizing use of evidence from individual strands of prediction, while minimizing the impact of the limitations from any particular one.

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Section: In Vitro Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alternative Integrated Testing for Skin Sensitization: Assuring Consumer Safety

BufaloAurelia¹,

PauloinThierry²,

Alépée³

et al. 2018

Applied In Vitro Toxicology

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“…Such methods include protein-binding interactions using the direct peptide reactivity assay ( Gerberick et al., 2004 ). Current cell-based tests include those using myeloid cancer cell lines, such as the human cell line activation test that measures changes in CD86 and CD54 expression in THP-1 monocytes ( Ashikaga et al., 2006 ; Sakaguchi et al., 2006 ); U-SENS, based on a similar readout using U937 cells ( Alépée et al., 2015 ; Piroird et al., 2015 ); and those based on monolayer-cultured KC reporter-based assay systems, including KeratinoSens ( Andreas et al., 2011 ; Emter et al., 2010 ) and LuSens ( Ramirez et al., 2014 ), or secretion of IL-18 ( Corsini et al., 2013 ), some of which have been accepted by or are in review at the Organisation for Economic Co-operation and Development as approved standard tests. An in vitro version of the LA stinging test has also been developed ( Sakka et al., 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Determination of Chemical Irritation Potential Using a Defined Gene Signature Set on Tissue-Engineered Human Skin Equivalents

et al. 2021

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There are no physical or visual manifestations that define skin sensitivity or irritation; a subjective diagnosis is made on the basis of the evaluation of clinical presentations, including burning, prickling, erythema, and itching. Adverse skin reaction in response to topically applied products is common and can limit the use of dermatological or cosmetic products. The purpose of this study was to evaluate the use of human skin equivalents based on immortalized skin keratinocytes and evaluate the potential of a 22-gene panel in combination with multivariate analysis to discriminate between chemicals known to act as irritants and those that do not. Test compounds were applied topically to full-thickness human skin equivalent or human ex vivo skin and gene signatures determined for known irritants and nonirritants. Principle component analysis showed the discriminatory potential of the 22-gene panel. Linear discrimination analysis, performed to further refine the gene set for a more high-throughput analysis, identified a putative seven-gene panel (IL-6, PTGS2, ATF3, TRPV3, MAP3K8, HMGB2, and matrix metalloproteinase gene MMP-3) that could distinguish potential irritants from nonirritants. These data offer promise as an in vitro prediction tool, although analysis of a large chemical test set is required to further evaluate the system.

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“… Key event 3: i.e. dendritic cells activation, with the existing DC-surrogates based CD86 activation U-SENS™ assay (Piroird et al, 2015;Alépée et al, 2015).…”

Section: Rationale Underlying the Construction Of The Defined Approachmentioning

confidence: 99%

“…Co-stimulatory molecule CD86 as a marker of cell activation as well as cell viability assessed using propidium iodide exclusion are measured by flow cytometry. Chemicals that induce the expression of CD86 higher than 1.5 fold, at cell viabilities above 70%, compared to the controls are predicted to have a DC activating potential and therefore a sensitisation potential Piroird et al, 2015;Alépée et al, 2015). The test method is under peerreview at EURL-ECVAM and is integrated in OECD TG programme.…”

Section: Description Of the Individual Information Sources Used (See ...mentioning

confidence: 99%

Guidance Document on the Reporting of Defined Approaches and Individual Information Sources to be Used within Integrated Approaches to Testing and Assessment (IATA) for Skin Sensitisation

2017

OECD Series on Testing and Assessment

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This publication was developed in the IOMC context. The contents do not necessarily reflect the views or stated policies of individual IOMC Participating Organisations. The Inter-Organisation Programme for the Sound Management of Chemicals (IOMC) was established in 1995 following recommendations made by the 1992 UN Conference on Environment and Development to strengthen co-operation and increase international co-ordination in the field of chemical safety. The Participating Organisations are FAO, ILO, UNDP, UNEP, UNIDO, UNITAR, WHO, World Bank and OECD. The purpose of the IOMC is to promote co-ordination of the policies and activities pursued by the Participating Organisations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment. ENV/JM/MONO(2016)29 5 This publication is available electronically, at no charge. For this and many other Environment, Health and Safety publications, consult the OECD's World Wide Web site (www.oecd.org/chemicalsafety/)

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Prospective multicentre study of the U-SENS test method for skin sensitization testing

Cited by 26 publications

References 17 publications

Alternative Integrated Testing for Skin Sensitization: Assuring Consumer Safety

Alternative Integrated Testing for Skin Sensitization: Assuring Consumer Safety

Determination of Chemical Irritation Potential Using a Defined Gene Signature Set on Tissue-Engineered Human Skin Equivalents

Guidance Document on the Reporting of Defined Approaches and Individual Information Sources to be Used within Integrated Approaches to Testing and Assessment (IATA) for Skin Sensitisation

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