The HaCaT/THP-1 Cocultured Activation Test (COCAT) for Skin Sensitization: A Study of Intra-Laboratory Reproducibility and Predictivity
The HaCaT/THP-1 Cocultured Activation Test (COCAT) for Skin Sensitization: A Study of Intra-Laboratory Reproducibility and Predictivity
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DOI：
10.14573/altex.1905031
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发表时间：
2019-01-01
影响因子：
5.6
通讯作者：
Bloemeke, Brunhilde
中科院分区：
文献类型：
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作者：
Eskes, Chantra;Hennen, Jennifer;Bloemeke, Brunhilde
共培养活化试验（COCAT）由共培养的HaCaT（人角质形成细胞系）和THP-1细胞（抗原呈递细胞的替代物）组成。单独地，这些细胞系用于解决皮肤致敏不良结果途径（AOP）的关键事件2和3。发现它们在共培养物中的暴露有可能增加它们对致敏化学品的反应，能够检测前半抗原，并支持皮肤致敏效力的鉴定。本研究旨在评估COCAT对皮肤致敏危害和效力的预测能力，并基于化学品的盲法试验评估COCAT的实验室内重现性。结果显示，15种编码化学品的运行之间的再现性为80%。皮肤致敏危险预测的敏感性为100%（9/9），特异性为75%（3/4），准确性为92.3%（12/13），而两种化学品的试验结果不确定。除了盲测化学品外，包括优化阶段测试的其他化学品，85.7%（12/14）的1A类化学品、83.3%（10/12）的1B类化学品和92.3%（12/13）的无类别化学品的皮肤致敏性UN GHS子类别预测正确。总准确率为87.4%（34/39）。本研究表明，COCAT是一种有前途的方法，根据联合国全球统一制度分类识别皮肤致敏危害和效力亚类。
The Cocultured Activation Test (COCAT) consists of cocultured HaCaT (human keratinocyte cell line) and THP-1 cells (surrogate of antigen presenting cells). Individually, these cell lines are used to address key events 2 and 3 of the skin sensitization adverse outcome pathway (AOP). Their exposure in coculture was found to have the potential to increase their response to sensitizing chemicals, enable the detection of pro-haptens, and support the identification of skin sensitization potency. The present study was undertaken to assess the predictive capacity of COCAT of both skin sensitization hazard and potency and to assess the intra-laboratory reproducibility of COCAT based on the blind testing of chemicals. Results showed a reproducibility between runs of 80% for 15 coded chemicals. Skin sensitization hazard prediction had 100% sensitivity (9/9), 75% specificity (3/4), and 92.3% accuracy (12/13), while the tests of two chemicals were inconclusive. Including additional chemicals tested during the optimization phase in addition to the blind tested chemicals, the skin sensitization UN GHS sub-categories were correctly predicted for 85.7% (12/14) sub-category 1A chemicals, 83.3% (10/12) sub-category 1B chemicals, and 92.3% (12/13) no category chemicals, resulting in an overall accuracy of 87.4% (34/39). The present study shows the COCAT to be a promising method for the identification of skin sensitization hazard and potency sub-categorization according to the UN GHS classification.