Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea.
College of Pharmacy, Dankook University Dandae-ro, Cheonan, Chungnam, South Korea.
J Toxicol Environ Health A. 2021 Dec 2;84(23):945-959. doi: 10.1080/15287394.2021.1956660. Epub 2021 Aug 1.
The aim of this study was conducted to validate the physicochemical properties of a total of 362 chemicals [305 skin sensitizers (212 in the previous study + 93 additional new chemicals), 57 non-skin sensitizers (38 in the previous study + 19 additional new chemicals)] for skin sensitization risk assessment using quantitative structure-activity relationship (QSAR)/quantitative structure-property relationship (QSPR) approaches. The average melting point (MP), surface tension (ST), and density (DS) of the 305 skin sensitizers and 57 non-sensitizers were used to determine the cutoff values distinguishing positive and negative sensitization, and correlation coefficients were employed to derive effective 3-fold concentration (EC3 (%)) values. QSAR models were also utilized to assess skin sensitization. The sensitivity, specificity, and accuracy were 80, 15, and 70%, respectively, for the Toxtree QSAR model; 88, 46, and 81%, respectively, for Vega; and 56, 61, and 56%, respectively, for Danish EPA QSAR. Surprisingly, the sensitivity, specificity, and accuracy were 60, 80, and 64%, respectively, when MP, ST, and DS (MP+ST+DS) were used in this study. Further, MP+ST+DS exhibited a sensitivity of 77%, specificity 57%, and accuracy 73% when the derived EC3 values were classified into local lymph node assay (LLNA) skin sensitizer and non-sensitizer categories. Thus, MP, ST, and DS may prove useful in predicting EC3 values as not only an alternative approach to animal testing but also for skin sensitization risk assessment.
本研究旨在验证总共 362 种化学物质（305 种皮肤致敏物[212 种在前一项研究中+93 种新化学物质]和 57 种非皮肤致敏物[38 种在前一项研究中+19 种新化学物质]）的物理化学性质，以便使用定量构效关系（QSAR）/定量构效关系（QSPR）方法进行皮肤致敏风险评估。305 种皮肤致敏物和 57 种非致敏物的平均熔点（MP）、表面张力（ST）和密度（DS）用于确定区分阳性和阴性致敏的截断值，并采用相关系数得出有效 3 倍浓度（EC3（%））值。还利用 QSAR 模型来评估皮肤致敏性。Toxtree QSAR 模型的灵敏度、特异性和准确性分别为 80%、15%和 70%；Vega 的灵敏度、特异性和准确性分别为 88%、46%和 81%；丹麦 EPA QSAR 的灵敏度、特异性和准确性分别为 56%、61%和 56%。令人惊讶的是，当本研究中使用 MP、ST 和 DS（MP+ST+DS）时，其灵敏度、特异性和准确性分别为 60%、80%和 64%。此外，当将衍生的 EC3 值分类为体内淋巴节点分析（LLNA）皮肤致敏物和非致敏物类别时，MP+ST+DS 的灵敏度为 77%，特异性为 57%，准确性为 73%。因此，MP、ST 和 DS 可能有助于预测 EC3 值，不仅可以作为动物测试的替代方法，还可以用于皮肤致敏风险评估。
