Kandárová Helena, Liebsch Manfred, Schmidt Elisabeth, Genschow Elke, Traue Dieter, Spielmann Horst, Meyer Kirstin, Steinhoff Claudia, Tornier Carine, De Wever Bart, Rosdy Martin
ZEBET, National Centre for the Documentation and Evaluation of Alternative Methods to Animal Experiments, Federal Institute for Risk assessment (BfR), Diedersdorfer Weg 1, D-12277 Berlin, Germany.
Altern Lab Anim. 2006 Aug;34(4):393-406. doi: 10.1177/026119290603400407.
Currently, two reconstructed human skin models, EpiDerm and EPISKIN are being evaluated in an ECVAM skin irritation validation study. A common skin irritation protocol has been developed, differing only in minor technical details for the two models. A small-scale study, applying this common skin irritation protocol to the SkinEthic reconstructed human epidermis (RHE), was performed at ZEBET at the BfR, Berlin, Germany, to consider whether this protocol could be successfully transferred to another epidermal model. Twenty substances from Phase III of the ECVAM prevalidation study on skin irritation were tested with the SkinEthic RHE. After minor, model-specific adaptations for the SkinEthic RHE, almost identical results to those obtained with the EpiDerm and EPISKIN models were achieved. The overall accuracy of the method was more than 80%, indicating a reliable prediction of the skin irritation potential of the tested chemicals when compared to in vivo rabbit data. As a next step, inter laboratory reproducibility was assessed in a study conducted between ZEBET and the Department of Experimental Toxicology, Schering AG, Berlin, Germany. Six coded substances were tested in both laboratories, with three different batches of the SkinEthic model. The assay results showed good reproducibility and correct predictions of the skin irritation potential for all six test chemicals. The results obtained with the SkinEthic RHE and the common protocol were reproducible in both phases, and the overall outcome is very similar to that of earlier studies with the EPISKIN and EpiDerm models. Therefore, the SkinEthic skin irritation assay test protocol can now be evaluated in a formal "catch-up" validation study.
目前，两种重建的人体皮肤模型EpiDerm和EPISKIN正在欧洲替代方法验证中心（ECVAM）的皮肤刺激性验证研究中接受评估。已经制定了一种通用的皮肤刺激方案，两种模型仅在一些小技术细节上有所不同。德国柏林联邦风险评估研究所（BfR）的ZEBET进行了一项小规模研究，将这种通用的皮肤刺激方案应用于SkinEthic重建人表皮（RHE），以考虑该方案是否能成功转移到另一种表皮模型。用SkinEthic RHE对ECVAM皮肤刺激性预验证研究第三阶段的20种物质进行了测试。对SkinEthic RHE进行了一些针对该模型的小调整后，获得了与EpiDerm和EPISKIN模型几乎相同的结果。该方法的总体准确率超过80%，表明与体内兔实验数据相比，能可靠地预测受试化学品的皮肤刺激潜力。下一步，在德国柏林ZEBET和先灵葆雅公司实验毒理学部之间进行的一项研究中评估了实验室间的重现性。在两个实验室中用三批不同的SkinEthic模型对六种编码物质进行了测试。测定结果显示出良好的重现性，并且对所有六种测试化学品的皮肤刺激潜力都做出了正确预测。用SkinEthic RHE和通用方案获得的结果在两个阶段都是可重现的，总体结果与早期使用EPISKIN和EpiDerm模型的研究非常相似。因此，现在可以在正式的“追赶”验证研究中对SkinEthic皮肤刺激试验方案进行评估。
