Kandárová Helena, Liebsch Manfred, Spielmann Horst, Genschow Elke, Schmidt Elisabeth, Traue Dieter, Guest Robert, Whittingham Andrew, Warren Neil, Gamer Armin O, Remmele Marina, Kaufmann Tanja, Wittmer Elke, De Wever Bart, Rosdy Martin
ZEBET, Bundesinstitut für Risikobewertung, BfR, Diedersdorfer Weg 1, D-12277 Berlin, Germany.
Toxicol In Vitro. 2006 Aug;20(5):547-59. doi: 10.1016/j.tiv.2005.11.008. Epub 2006 Feb 7.
Based on two successfully completed ECVAM validation studies for in vitro skin corrosion testing of chemicals, the National Co-ordinators of OECD Test Guideline Programme endorsed in 2002 two new test guidelines: TG 430 'Transcutaneous Electrical Resistance assay' and TG 431 'Human Skin Model Test'. To allow all suitable in vitro human reconstructed (dermal or epidermal) models to be used for skin corrosion testing, the OECD TG 431 defines general and functional conditions that the model must meet before it will be routinely used for skin corrosion testing. In addition, the guideline requires correct prediction of 12 reference chemicals and assessment of intra- and inter-laboratory variability. To show that the OECD TG 431 concept works, in 2003 ZEBET tested several chemicals from the ECVAM validation trials on the SkinEthic reconstituted human epidermal (RHE) model. Based on knowledge that reconstructed human skin models perform similarly in toxicological studies, it was decided to adopt the validated EpiDerm skin corrosion test protocol and prediction model to the SkinEthic model. After minor technical changes, classifications were obtained in concordance with those reported for the validated human skin models EPISKIN and EpiDerm. To allow adequate determination of inter-laboratory reproducibility, a blind trial was conducted in three laboratories -- ZEBET (D), Safepharm (UK) and BASF (D), in which the 12 endorsed reference chemicals were tested. Results obtained with the SkinEthic epidermal model were reproducible, both within and between laboratories, and over time. Concordance between the in vitro predictions of skin corrosivity potential obtained with the SkinEthic model and the predictions obtained with the accepted tests of OECD TG 430 and TG 431 was very good. The new test was able to distinguish between corrosive and non-corrosive reference chemicals with an accuracy of 93%.
基于两项成功完成的关于化学品体外皮肤腐蚀性测试的欧洲替代方法验证中心（ECVAM）验证研究，经济合作与发展组织（OECD）测试指南计划的国家协调员于2002年认可了两项新的测试指南：TG 430“经皮电阻测定法”和TG 431“人体皮肤模型测试”。为使所有合适的体外人重建（真皮或表皮）模型可用于皮肤腐蚀性测试，OECD TG 431定义了该模型在常规用于皮肤腐蚀性测试之前必须满足的一般条件和功能条件。此外，该指南要求正确预测12种参考化学品，并评估实验室内和实验室间的变异性。为证明OECD TG 431概念可行，2003年德国联邦风险评估研究所（ZEBET）在SkinEthic重组人表皮（RHE）模型上测试了来自ECVAM验证试验的几种化学品。基于重建人皮肤模型在毒理学研究中表现相似的认识，决定将经过验证的EpiDerm皮肤腐蚀性测试方案和预测模型应用于SkinEthic模型。经过微小的技术更改后，得到的分类结果与已验证的人体皮肤模型EPISKIN和EpiDerm报告的结果一致。为充分确定实验室间的重现性，在三个实验室——德国的ZEBET、英国的Safepharm和德国的巴斯夫进行了一项盲法试验，其中对12种认可的参考化学品进行了测试。使用SkinEthic表皮模型获得的结果在实验室内、实验室间以及随时间都是可重现的。SkinEthic模型获得的皮肤腐蚀性潜在体外预测结果与OECD TG 430和TG 431认可测试获得的预测结果之间的一致性非常好。新测试能够以93%的准确率区分腐蚀性和非腐蚀性参考化学品。
