A Prevalidation Study on <i>In Vitro</i> Skin Corrosivity Testing

Botham, Philip A.; Chamberlain, M.; Barratt, Martin D.; Curren, Rodger; Esdaile, David J.; Gardner, John R.; Gordon, Virginia C.; Hildebrand, B.; Lewis, Richard; Liebsch, Manfred; Logemann, Pamela; Osborne, Rosemarie; Ponec, Maria; Régnier, Jean-François; Steiling, W.; Walker, A.P.; Balls, Michael

doi:10.1177/026119299502300207

Cited by 18 publications

(6 citation statements)

References 12 publications

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“…Meanwhile, at the Meeting of the Competent Authorities for the 27th Adaptation to Technical Progress of Directive 67/548/EEC, held on 4 February 2000 in Brussels, the test method B.40 Skin Corrosion was accepted for inclusion in Annex V. It must be emphasised at this point that, based on the knowledge of the promising outcome of the present "catch-up" study, the second part of the guideline, in which the skin model test is described, intentionally does not define specific exposure times and classification cut-off values for tissue viability in the MTT test. As already suggested from previous studies (2,7), the present study has confirmed that, provided that the structural criteria for a skin model are met (5,6), a fine tuning of the test protocol and prediction model are sufficient to meet the performance criteria of the validated EPISKIN test.…”

Section: Status and Future Perspective Of The Testsupporting

confidence: 87%

“…Finally, it must be mentioned that, based on previous experience (2,15), it was not anticipated that a sufficient separation into three skin corrosion potency categories could be achieved with any kind of biological in vitro test. Although current regulations for packing and transport of dangerous goods, as originated by the UN (18), still request a classification into three packing groups (I, II, and III), investigations of the database for corrosion packing groups made in the context of the ECVAM skin corrosivity validation study, showed that such classifications were often not based on the standard rabbit test according to OECD Test Guideline 404, so no in vitro/in vivo comparison could be performed.…”

Section: Prediction Of Classificationsmentioning

confidence: 99%

“…In 1993/1994, two in vitro assays (Corrosi-tex™ and Skin²™ ZK1350) had achieved limited regulatory acceptance (exemptions for being used with specified chemical classes) by the US Department of Transport. A prevalidation study on three in vitro tests for skin corrosivity was performed in 1994 (2), and a well-designed formal validation study, initiated and sponsored by ECVAM, was conducted in 1996/1997 (3,4), in which four tests were evaluated: the rat skin transcutaneous electrical resistance test (TER), CORROSITEX, and the Skin² ZK1350 and EPISKIN™ tests. Of the two human skin models, Skin² proved to be highly specific but far too insensitive, whereas EPISKIN showed acceptable predictions and a balanced rate of about 15% over-prediction and under-prediction (4).…”

Section: Introductionmentioning

confidence: 99%

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The ECVAM Prevalidation Study on the Use of EpiDerm for Skin Corrosivity Testing

Liebsch¹,

Traue²,

Barrabas³

et al. 2000

Altern Lab Anim

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In 1996 and 1997, ECVAM supported a formal validation study on in vitro methods for predicting skin corrosivity. Two of the in vitro tests included in the study employed human skin models, the Skin2™ ZK1350 and EPISKIN™ models. In the ECVAM validation study, BASF, Huntingdon Life Sciences (HLS) and ZEBET tested the Skin2 human skin model, production of which ceased in October 1996, while the validation study was still in progress. Since both of the skin models had shown basic usefulness for corrosivity testing and, in particular, the EPISKIN corrosivity test had proved to be a scientifically valid test, the three laboratories decided to conduct a study to determine whether another commercially available human skin model, EpiDerm™, could also be successfully used to predict skin corrosivity. The study was performed according to the ECVAM prevalidation scheme, to allow for refinement of the test protocol and the prediction model, as well as for independent assessment of the performance of the refined methodology in a final blind trial in the three laboratories. In phase I of the study, ZEBET (Laboratory 1) drafted a Standard Operating Procedure (SOP), including a prediction model (PM1), and the project plan for the study. It was a major task to simplify an existing EpiDerm test protocol, which used the time-course of cytotoxicity as its endpoint. To evaluate the predictivity of the simplified method, which used only a 3-minute exposure to test chemicals, 50 chemicals representing a wide spectrum of chemical entities were tested, revealing that the test sensitivity was too low (65%), whereas the specificity was very high (88%). In addition, acceptance criteria for the negative and positive controls were established. Before proceeding to the next phase of the study, ZEBET distributed a refined SOP, data-recording software and documentation sheets, which allowed Good Laboratory Practice (GLP)-compliant quality assurance for each assay. The main goal of phase II was to produce sufficient data to assess the reproducibility of the EpiDerm skin corrosivity test after transfer to Laboratory 2 (HLS). Repeated testing of several chemicals in both laboratories revealed excellent intralaboratory and interlaboratory reproducibility. In addition, chemicals classified as “non-corrosive” (NC) with a 3-minute exposure in phase I, were re-tested by ZEBET with extended exposure periods of 1 hour and 4 hours. The test sensitivity could be significantly increased, if chemicals classified NC with a 3-minute exposure were tested with a 1-hour exposure. Before proceeding to the final blind trial, a refined SOP was drafted, according to which all chemicals had to be tested with exposure times of 3 minutes and 1 hour, and data for these two exposure times were used in the refined hierarchical prediction model, PM2. In phase III, the blind trial, BASF (Laboratory 3) joined the study. ECVAM selected 24 chemicals from the test chemical set used in the ECVAM skin corrosivity validation study, and BIBRA International (UK) purchased, coded and di...

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Section: Status and Future Perspective Of The Testsupporting

confidence: 87%

Section: Prediction Of Classificationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The ECVAM Prevalidation Study on the Use of EpiDerm for Skin Corrosivity Testing

Liebsch¹,

Traue²,

Barrabas³

et al. 2000

Altern Lab Anim

Self Cite

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show abstract

“…The skin corrosion test was performed to assess the cytotoxic effects of compound 1 immediately following short-term exposure to the stratum corneum of the epidermis using an in vitro skin model. [29][30][31] Cytotoxicity to the skin model was expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). To ensure that the presence of compound 1 did not interfere with the test system, it was checked for direct reduction of MTT and colour interference.…”

Section: Skin Corrosion Test Using a Human Skin Modelmentioning

confidence: 99%

Safety Evaluation of a Prototypical Diazirine-Based Covalent Crosslinker and Molecular Adhesive

Baran¹,

Hof

Groot

et al. 2023

Preprint

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bis-Diazirine reagents are increasingly being used as polymer crosslinkers, adhesives, and photopatterning agents in the materials sciences literature, but little effort has been made thus far to document their chemical safety profile. Here we describe the results of a detailed toxicity assessment of a representative bis-diazirine. Safety was evaluated by a series of in vitro assays, which found the product to be non-mutagenic in bacterial tester strains TA98 and TA100, non-corrosive and non-irritating to skin, and requiring no classification for eye irritation or serious damage. While these results do not completely rule out the possibility of adverse responses to bis-diazirine reagents, they suggest a desirable safety profile for this compound class.

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“…Five validated test methods using commercially available RhE models are included in this Test Guideline, as described below. Prevalidation studies (7), followed by a formal validation study for assessing skin corrosion (8) (9) (10) have been conducted (11) (12) for two of these commercially available test methods, EpiSkin™ Standard Model (SM), and EpiDerm™ Skin Corrosivity Test (SCT) (EPI-200) (referred to in the following text as the Validated Reference Methods -VRMs, EpiSkin TM =VRM1, EpiDerm TM = VRM2). The outcome of these studies led to the recommendation that the two VRMs mentioned above could be used for regulatory purposes for distinguishing corrosive (C) from non-corrosive (NC) substances, and that the EpiSkin™ could moreover be used to support subcategorisation of corrosive substances (13) (14) (15).…”

mentioning

confidence: 99%

Test No. 431: In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method

2013

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A Prevalidation Study on In Vitro Skin Corrosivity Testing

Cited by 18 publications

References 12 publications

The ECVAM Prevalidation Study on the Use of EpiDerm for Skin Corrosivity Testing

The ECVAM Prevalidation Study on the Use of EpiDerm for Skin Corrosivity Testing

Safety Evaluation of a Prototypical Diazirine-Based Covalent Crosslinker and Molecular Adhesive

Test No. 431: In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method

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