An in vitro skin sensitization assay termed EpiSensA for broad sets of chemicals including lipophilic chemicals and pre/pro-haptens

Saito, Kazutoshi; Takenouchi, Osamu; Nukada, Yuko; Miyazawa, Masaaki; Sakaguchi, Hitoshi

doi:10.1016/j.tiv.2016.12.005

Cited by 37 publications

(30 citation statements)

References 60 publications

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“…Characterization of skin sensitivity and irritancy at the gene level is rapidly gaining pace and has driven the development of several gene expression-based assay systems using either reconstituted human epidermis skin equivalents that consist solely of a stratified squamous epidermis ( Hasan et al., 2019 ; Saito et al., 2017 ) or full-thickness HSE (consisting of both epidermis and a fibroblast-populated dermis), with SENS-IS being the most advanced in terms of validation against a large panel of chemicals ( Cottrez et al., 2016 ). We recently reported whole genome expression profiles of reconstituted human epidermis in response to LA, identifying several genes highly associated with irritancy and sensitization ( Hasan et al., 2019 ).…”

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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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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“…Relative to the in vivo conclusions on dermal sensitization, the sensitivity of the EpiSensA was 92%, the specificity was 57%, and the accuracy was 80%. Compared with a recent analysis with a larger data set (72 chemicals; Saito et al, 2017), the sensitivity of the EpiSensA for the current chemicals was similar; however, specificity and accuracy were slightly decreased compared with the larger data set (78% specificity and 90% accuracy; Saito et al, 2017).…”

Section: Discussionmentioning

confidence: 50%

“…The EpiSensA is a RhE model-based assay and addresses the second key event in the AOP for skin sensitization (i.e., keratinocyte activation). The test protocol has been described in Saito et al (2017) except for the potency prediction. An RhE model "LabCyte EPI-MODEL 24" (Japan Tissue Engineering Co. Ltd, Aichi, Japan) was pre-incubated overnight in culture medium.…”

Section: Episensa Protocolmentioning

confidence: 99%

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Characterization of dermal sensitization potential for industrial or agricultural chemicals with EpiSensA

Mizumachi

LeBaron

Settivari

et al. 2020

J of Applied Toxicology

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The regulatory community is transitioning to the use of nonanimal methods for dermal sensitization assessments; however, some in vitro assays have limitations in their domain of applicability depending on the properties of chemicals being tested. This study explored the utility of epidermal sensitization assay (EpiSensA) to evaluate the sensitization potential of complex and/or “difficult to test” chemicals. Assay performance was evaluated by testing a set of 20 test chemicals including 10 methacrylate esters, 5 silicone‐based compounds, 3 crop protection formulations, and 2 surfactant mixtures; each had prior in vivo data plus some in silico and in vitro data. Using the weight of evidence (WoE) assessments by REACH Lead Registrants, 14 of these chemicals were sensitizers and, six were nonsensitizers based on in vivo studies (local lymph node assay [LLNA] and/or guinea pig studies). The EpiSensA correctly predicted 16/20 materials with three test materials as false positive and one silane as false negative. This silane, classified as weak sensitizer via LLNA, also gave a “false negative” result in the KeratinoSens™ assay. Overall, consistent with prior evaluations, the EpiSensA demonstrated an accuracy level of 80% relative to available in vivo WoE assessments. In addition, potency classification based on the concentration showing positive marker gene expression of EpiSensA was performed. The EpiSensA correctly predicted the potency for all seven sensitizing methacrylates classified as weak potency via LLNA (EC3 ≥ 10%). In summary, EpiSensA could identify dermal sensitization potential of these test substances and mixtures, and continues to show promise as an in vitro alternative method for dermal sensitization.

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“…The number of fragrances tested in 3D tissue model based assays is more limited, nevertheless, the results hold promise [20,21,[35][36][37], but dataset must be enhanced to move these models to an OECD guideline stage to complement cell-culture based models. For example, in the IL-18 RhE assay only ten fragrances have been tested [20,21], namely benzyl cinnamate, benzyl salicylate, cinnamaldehyde, cinnamic alcohol, citral, dihydroeugenol, eugenol, isoeugenol, limonene, methyl salicylate, all correctly classified.…”

Section: In Vitro Methods Fragrances and Hazard Identificationmentioning

confidence: 99%

Contact Allergy to Fragrances: In Vitro Opportunities for Safety Assessment

Corsini

Galbiati

2019

Cosmetics

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The majority of cosmetic products contain fragrances to make products more pleasant to the consumer, as we all like goods that smell nice. Unfortunately, contact allergy to fragrance compounds is among the most frequent findings in patients with suspected allergic contact dermatitis. In order to revert this and to reduce contact allergy to cosmetics, it is imperative to improve safety assessment of cosmetic products for skin sensitization. In the era of animal ban for cosmetic ingredients, this represents a challenge. Luckily, in the last decades, substantial progress has been made in the understanding of the mechanism of chemical-induced contact allergy and several in vitro methods are available for hazard identification. The purpose of this manuscript is to explore the possibility of non-animal testing for quantitative risk assessment of fragrance-induced contact allergy, essential for cosmetic products, which cannot be tested on animals.

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An in vitro skin sensitization assay termed EpiSensA for broad sets of chemicals including lipophilic chemicals and pre/pro-haptens

Cited by 37 publications

References 60 publications

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

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

Characterization of dermal sensitization potential for industrial or agricultural chemicals with EpiSensA

Contact Allergy to Fragrances: In Vitro Opportunities for Safety Assessment

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