An epidermal equivalent assay for identification and ranking potency of contact sensitizers

Gibbs, Susan; Corsini, Emanuela; Spiekstra, Sander W.; Galbiati, Valentina; Fuchs, Horst W.; DeGeorge, George; Troese, Matthew J.; Hayden, Patrick; Deng, Wei; Roggen, Erwin L.

doi:10.1016/j.taap.2013.07.003

Cited by 97 publications

(93 citation statements)

References 48 publications

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“…Previously, we have shown that IL-18 production by epidermal keratinocytes (NCTC2544 cell line) is a biomarker for distinguishing a sensitizer from a non-sensitizer (Corsini et al, 2009Galbiati et al, 2011). Parallel to this study, we found that the ee-eC50 potency assay could be combined with IL-18 release by ee in a single assay, thus greatly increasing the value of this assay that uses commercially available ee in the future (Gibbs et al, 2013a). Alternatively, the EE potency assay can be combined with any other assay or test battery that can distinguish a sensitizer from a non-sensitizer in a tiered or integrated approach (Corsini et al, 2009;Johansson et al, 2013;Natsch et al, 2013).…”

Section: Discussionsupporting

confidence: 66%

“…Even though 2 weak sensitizing chemicals (benzocaine, α-hexylcinnamaldehyde) showed poor reproducibility in the duplicate FD runs, these chemicals were still correctly ranked by all laboratories as weak sensitizers. Of note, the EE potency assay appears not only to be reproducible between laboratories but also to a certain extent between different EE cultures (dos Santos et al, 2011;Gibbs et al, 2013a). For example, the EC50 value obtained for DNCB was 0.3 mg/ml in this present study and 1.3 mg/ml in our previous study using in-house VUMC EE, which, when plotted on a log scale, represents very little variation.…”

Section: Discussionsupporting

confidence: 58%

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International ring trial of the epidermal equivalent sensitizer potency assay: reproducibility and predictive capacity

Teunis

2014

ALTEX

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Summary This study describes the international ring trial of the epidermal-equivalent (EE) sensitizer potency assay. This assay does not distinguish a sensitizer from a non-sensitizer, but may classify known skin sensitizers according to their potency. It assesses the chemical concentration resulting in 50% cytotoxicity (EE-EC50)or the 2-fold increase in Abbreviations: AOO, acetone:olive oil (4:1); BD, broad dose; EE, epidermal equivalent; EC 50 , chemical concentration in mg/ml that results in a decrease in cell viability to 50% compared to vehicle treated epidermal equivalents; DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Milan University, Milan; DMSO, 1% dimethylsulfoxide; DSA 05 , chemical dose per skin area in µg/cm 2 leading to a sensitization incidence of 5% in the human tested population; FD, fine dose; GPMT, Guinea Pig Maximization Test; HU, University of Applied Sciences, Utrecht; HRIPT, Human Repeat Insult Patch Test; IL-1α 2x , Chemical concentration in mg/ml resulting in a 2-fold increase in IL-1α release into culture supernatant of EE compared to supernatant of vehicle-exposed EE; LLNA, Local Lymph Node Assay; NOEL, human threshold level (no observed effect level) expressed in µg/cm 2 ; OECD, Organisation for Economic Co-operation and Development; SOP, standard operating procedure; VUMC, VU University Medical Center, Amsterdam

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Section: Discussionsupporting

confidence: 66%

Section: Discussionsupporting

confidence: 58%

International ring trial of the epidermal equivalent sensitizer potency assay: reproducibility and predictive capacity

Teunis

2014

ALTEX

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“…Therefore, an increase in IL‐18 concentration is indicative of a skin sensitizer in both the RHS model and the RHE model 23. As our previous studies used RHE (rather than RHS), we cannot directly use the same prediction model for labelling and classifying sensitizers 22, 23. The current results indicate that the threshold for distinguishing between sensitizers and irritants is slightly higher with RHS than the RHE IL‐18 SI threshold of 5, as lactic acid in RHS has an IL‐18 SI of 8.3 ± 3.9.…”

Section: Discussionmentioning

confidence: 99%

“…Cytokine levels determined in the exposed RHS were transformed into an SI relative to the vehicle (fold increase), according to the procedure described in reference 23.…”

Section: Methodsmentioning

confidence: 99%

Comparison of the skin sensitization potential of 3 red and 2 black tattoo inks using interleukin‐18 as a biomarker in a reconstructed human skin model

et al. 2018

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BackgroundDuring the last decade, the number of people with ≥1 tattoo has increased noticeably within the European population. Despite this, limited safety information is available for tattoo inks.ObjectivesTo test the skin sensitization potential of 5 tattoo inks in vitro by using reconstructed human skin (RHS) and the contact sensitization biomarker interleukin (IL)‐18.MethodsTwo red and 3 black tattoo inks, 1 additive (Hamamelis virginiana extract) and 1 irritant control (lactic acid) were tested. The culture medium of RHS (reconstructed epidermis on a fibroblast‐populated collagen hydrogel) was supplemented with test substances in a dose‐dependent manner for 24 hours, after which cytotoxicity (histology; thiazolyl blue tetrazolium bromide assay) and skin sensitization potential (IL‐18 secretion; enzyme‐linked immunosorbent assay) were assessed.ResultsAll but 1 ink showed cytotoxicity. Notably, 1 red ink and 1 black ink were able to cause an inflammatory response, indicated by substantial release of IL‐18, suggesting that these inks may be contact sensitizers.ConclusionsThe in vitro RHS model showed that 4 tattoo inks were cytotoxic and 2 were able to cause an inflammatory IL‐18 response, indicating that an individual may develop allergic contact dermatitis when exposed to these tattoo inks, as they contain contact sensitizers.

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“…Concordant results were obtained for all 20 chemicals. Comparison of the in vitro potency data with human DSA 05 (lg/cm2) data revealed a good correlation (Spearman r = 0.8500; p > 0.01) [35]. DSA 05 is the induction dose per skin area that produces a positive response in 5% of the tested population.…”

Section: Available Animal-free Testing Approaches Cover the Moa For Smentioning

confidence: 90%

In Vitro Approaches for Detection of Chemical Sensitization

Roggen

2014

Basic Clin Pharma Tox

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Concerns, legislation and research needs have precipitated developments such as the mode of action concept, the Tox21 strategy, the concept of pathways of toxicity and the adverse outcome pathway framework. New technologies and paradigms are currently transforming these concepts into applicable animal-free toxicity testing systems. The adverse outcome pathway framework provides a structure for collecting, organizing and evaluating the available data that describe the compound and the events resulting in an adverse outcome at a biological level of organization. The current chapter intends to provide a nonexhaustive review of (i) our current understanding of the molecular mechanisms driven the key events of the mode of action for sensitization induction by chemicals, (ii) the tools that were developed on the basis of the available knowledge and (iii) the major gaps that need to be filled.

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An epidermal equivalent assay for identification and ranking potency of contact sensitizers

Cited by 97 publications

References 48 publications

International ring trial of the epidermal equivalent sensitizer potency assay: reproducibility and predictive capacity

International ring trial of the epidermal equivalent sensitizer potency assay: reproducibility and predictive capacity

Comparison of the skin sensitization potential of 3 red and 2 black tattoo inks using interleukin‐18 as a biomarker in a reconstructed human skin model

In Vitro Approaches for Detection of Chemical Sensitization

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