Predictive performance for human skin sensitizing potential of the human cell line activation test (h-CLAT)
Predictive performance for human skin sensitizing potential of the human cell line activation test (h-CLAT)
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DOI：
10.1111/j.1600-0536.2011.01952.x
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发表时间：
2011-12-01
影响因子：
5.5
通讯作者：
Nishiyama, Naohiro
中科院分区：
文献类型：
--
作者：
Nukada, Yuko;Ashikaga, Takao;Nishiyama, Naohiro
背景最近法规限制的变化和社会对动物毒理学实验的反对推动了对可靠的体外试验的需求，以预测各种工业化学品的皮肤致敏潜力。在此之前，我们开发了人类细胞系激活试验（h-CLAT）作为一种基于细胞的检测方法来预测化学品的皮肤致敏潜力，并显示了h-CLAT与小鼠局部淋巴结检测结果之间的对应性。本研究旨在研究h-CLAT对人类皮肤致敏潜力的预测性能。我们共选择了66种已知具有人体致敏潜力的测试化学品，并使用h-CLAT测试了所有化学品。然后，我们评估了h-CLAT在预测人类致敏潜力方面的性能。在51种检测的致敏物中，有45种在h-CLAT中呈阳性，表明敏感性相对较高。此外，15种非致敏剂中有10种被正确检测为阴性。人类数据和h-CLAT结果之间的总体一致性为83%。此外，h-CLAT可以准确地预测23个测试的化学物质，胺，杂环化合物，或硫化合物的人体致敏潜力。我们的数据表明，实用的h-CLAT预测人类皮肤致敏潜力的各种化学品。
Background. Recent changes in regulatory restrictions and social opposition to animal toxicology experiments have driven the need for reliable in vitro tests for predicting the skin sensitizing potentials of a wide variety of industrial chemicals. Previously, we developed the human cell line activation test (h-CLAT) as a cell-based assay to predict the skin sensitizing potential of chemicals, and showed the correspondence between the h-CLAT and the murine local lymph node assay results.Objectives. This study was conducted to investigate the predictive performance of the h-CLAT for human skin sensitizing potential.Materials/Methods. We selected a total of 66 test chemicals with known human sensitizing potential, and tested all chemicals with the h-CLAT. We then evaluated the performance of the h-CLAT in predicting human sensitizing potential.Results and conclusion. Forty-five of 51 tested sensitizers were positive in the h-CLAT, indicating relatively high sensitivity. Also, 10 of 15 non-sensitizers were correctly detected as negative. The overall agreement between human data and h-CLAT outcome was 83%. Furthermore, the h-CLAT could accurately predict the human sensitizing potential of 23 tested chemicals that were amines, heterocyclic compounds, or sulfur compounds. Our data indicate the utility of the h-CLAT for predicting the human skin sensitizing potential of a variety of chemicals.