Abstract：
The Epidermal Sensitization Assay (EpiSensA) is a reconstructed human epidermis (RhE)-based gene expression assay for predicting the skin sensitization potential of chemicals. Since the RhE model is covered by a stratified stratum corneum, various kinds of test chemicals, including lipophilic ones and pre-/pro-haptens, can be tested with a route of exposure akin to an in vivo assay and human exposure. This article presents the results of a formally managed validation study of the EpiSensA that was carried out by three participating laboratories. The purpose of this validation study was to assess transferability of the EpiSensA to new laboratories along with its within- (WLR) and between-laboratory reproducibility (BLR). The validation study was organized into two independent stages. As demonstrated during the first stage, where three sensitizers and one non-sensitizer were correctly predicted by all participating laboratories, the EpiSensA was successfully transferred to all three participating laboratories. For Phase I of the second stage, each participating laboratory performed three experiments with an identical set of 15 coded test chemicals resulting in WLR of 93.3%, 93.3%, and 86.7%, respectively. Furthermore, when the results from the 15 test chemicals were combined with those of the additional 12 chemicals tested in Phase II of the second stage, the BLR for 27 test chemicals was 88.9%. Moreover, the predictive capacity among the three laboratories showed 92.6% sensitivity, 63.0% specificity, 82.7% accuracy, and 77.8% balanced accuracy based on murine local lymph node assay (LLNA) results. Overall, this validation study concluded that EpiSensA is easily transferable and sufficiently robust for assessing the skin sensitization potential of chemicals.
摘要：
表皮致敏测定(EpiSensA)是用于预测化学品的皮肤致敏潜力的基于重建的人表皮(RhE)的基因表达测定。由于RhE模型被分层的角质层覆盖，各种测试化学品，包括亲脂性的和前/前半抗原，可以用类似于体内测定和人体暴露的暴露途径进行测试。本文介绍了三个参与实验室对EpiSensA进行的正式管理验证研究的结果。这项验证研究的目的是评估EpiSensA向新实验室的可转移性，以及其内部（WLR）和实验室间可重复性（BLR）。验证研究分为两个独立的阶段。正如在第一阶段所证明的那样，所有参与实验室都正确预测了三种敏化剂和一种非敏化剂，EpiSensA已成功转移到所有三个参与实验室。第二阶段的第一阶段，每个参与实验室用相同的15种编码测试化学品进行了3次实验，WLR为93.3%，93.3%,和86.7%，分别。此外，当15种测试化学品的结果与第二阶段第二阶段测试的其他12种化学品的结果结合时，27种测试化学品的BLR为88.9%。此外，三个实验室的预测能力显示出92.6%的灵敏度，63.0%特异性，82.7%的准确度,基于小鼠局部淋巴结测定(LLNA)结果的平衡准确度为77.8%。总的来说,这项验证研究的结论是,EpiSensA易于转移,并且对于评估化学品的皮肤致敏潜能具有足够的鲁棒性.
