Zuang1, V., Balls1, M., Bothan2, P.A., Coquette3, A., Corsini4, E., Curren5, R.D., Elliott6, G.R., Fentem7, J.H., Heylings2, J.R., Liebsch8, M., Medina9, J., Roguet10, R., van de Sandt11, J.J.M., Wiemann12, C., Worth1, A.P. 1ECVAM, Institute for Health & Consumer Protection, European Commission Joint Research Centre, Italy. 2Syngenta, Central Toxicology Laboratory, Cheshire, UK. 3SGS BioPharma, Wavre, Belgium. 4Laboratory of Toxicology, Milan, Italy. 5Institute for In Vitro Sciences, Inc., Gaithersburg, MD, USA. 6TNO-PML, Rijswijk, The Netherlands. 7SEAC Toxicology Unit, Unilever Research, Bedfordshire, UK. 8ZEBET, Berlin, Germany. 9Instituto de Salud Carlos III, Ciudad Unibersitaria, Madrid, Spain. 10L’Oreal Life Sciences Research, Cedex, France. 11TNO Nutrition & Food Research, Zeist, The Netherlands. 12BASF AG, Ludwigshafen, Germany.

The European Centre for the Validation of Alternative Methods (ECVAM) Skin Irritation Task Force was established in 1996, to review the status of the development and validation of alternative tests for skin irritation and corrosion, and to identify appropriate non-animal tests for predicting human skin irritation that were sufficiently well-developed to be prevalidated and validated by ECVAM. The EpiDerm method, based on a reconstituted human skin model, was proposed as being sufficiently well advanced to enter a prevalidation (PV) study. Based on a review of test protocols, prediction models (PMs), and data submitted by test developers on ten specified chemicals, with 20% sodium lauryl sulphate as a reference standard, the task force recommended the inclusion of four other tests: EPISKIN and PREDISKIN, based on reconstituted human epidermis or on human skin; the non-perfused pig-ear test, based on pig skin; and the skin integrity function test (SIFT), with ex vivo mouse skin. The prevalidation study on these methods was funded by ECVAM, and took place during 1999-2000. The outcome of the PV study was that none of the methods was ready to enter a formal validation study, and that the protocols and PMs of the methods had to be improved in order to increase their predictive abilities. Improved protocols and PMs for the EpiDerm and EPISKIN methods, the pig ear test, and the SIFT were presented at an extended Task Force meeting held in May 2001. It was agreed that, in the short term, the performance of the revised and harmonised EpiDerm and EPISKIN methods, as well as the modified SIFT, should be evaluated in a further study with a new set of 20 test chemicals. In addition, it was decided that the SIFT and the pig ear test would be compared to see if common endpoints (transepidermal water loss, methyl green-pyronine stain) could be identified.


Allergens, Alternative methods, Contact sensitization, Contact sensitizers, Corrosion, Differential display-polymerease chain reaction (DD-PCR), Dose response studies, ECETOC, ECVAM, ECVAM, EPISKIN, ET50, Electrical resistance (ER), EpiDerm, European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) , European Centre for the Validation of Alternative Methods (ECVAM), Ex vivo mouse skin, Function test , In vitro, Keratinocytes, LC, Langerhans cells, MTT, MTT ET-50 tissue viability assay, MTT assay, OECD, Optical density (OD), PREDISKIN, Pig-ear test, Predictive ability , Prevalidation, Reconstituted human skin model, Reproducibility, Reverse transcription-PCR (RT-PCR), SIFT, Skin integrity function test (SIFT), Skin irritation, Skin sensitisation, TEWL, Topical toxicity, Validation

Materials Tested

1,1, 1-Trichloroethane, 1-Bromopentane, 10-Undecanoic acid, 2,4,-Xylidine, 2-Methyl-4-phenyl-2-butanol, 3,3’-Dithiodipropionic, 3-Chloronitrobenzene, 4,4-Methylenebis-(2,6-di-tert-butyl)phenol, 4-Amnio-1,2,4-trizole, Cis-Cyclooctene, Dimethyl sulphide, Heptanal, Hydroxycitronellal, Liestralis/Lillial, Methyl palmitate, Potassium hydroxide (5%), Soap from 20/80 coconut oil/tallow, Sodim lauryl sulphate (50%) (SLS), d-Limonene, dl-Citronellol

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