School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Republic of Korea.
Biotoxtech, 53, Cheongju, Chungcheongbuk-do 28115, Republic of Korea.
Toxicol In Vitro. 2021 Sep;75:105136. doi: 10.1016/j.tiv.2021.105136. Epub 2021 Mar 4.
Although in vivo inhalation toxicity tests have been widely conducted, the testing of many chemicals is limited for economic and ethical reasons. Therefore, we previously developed an in vitro acute inhalation toxicity test method. The goal of the present pre-validation study was to evaluate the transferability, reproducibility, and predictive capacity of this method. After confirming the transferability of the Calu-3 epithelium cytotoxicity assay, reproducibility was evaluated using 20 test substances at three independent institutions. Cytotoxicity data were analyzed using statistical methods, including the intra-class correlation coefficient and Bland-Altman plots for within- and between-laboratory reproducibility. The assay for the 20 test substances showed excellent agreement within and between laboratories. To evaluate the predictive capacity, 77 test substances were analyzed for acute inhalation toxicity. Accuracy was measured using a cutoff of 40%, and the relevance was analyzed as a receiver-operating characteristic (ROC) curve. An accuracy of 72.73% was obtained, and the area under the ROC curve was 0.77, indicating moderate performance. In this study, we found that the in vitro acute inhalation toxicity test method demonstrated good reliability and relevance for predicting the acute toxicity of inhalable chemicals. Hence, this assay has potential as an alternative test for screening acutely toxic inhalants.
虽然已经广泛开展了体内吸入毒性测试，但出于经济和伦理原因，许多化学物质的测试受到限制。因此，我们之前开发了一种体外急性吸入毒性测试方法。本预验证研究的目的是评估该方法的可转移性、重现性和预测能力。在确认 Calu-3 上皮细胞细胞毒性测定的可转移性之后，使用三种独立机构的 20 种测试物质评估了重现性。使用统计方法分析细胞毒性数据，包括内类相关系数和 Bland-Altman 图，用于评估实验室内部和实验室之间的重现性。对 20 种测试物质的测定表明，实验室内部和实验室之间具有极好的一致性。为了评估预测能力，对 77 种测试物质进行了急性吸入毒性分析。使用 40%的截止值来衡量准确性，并作为接收者操作特征（ROC）曲线来分析相关性。获得了 72.73%的准确性，ROC 曲线下面积为 0.77，表明具有中等性能。在这项研究中，我们发现体外急性吸入毒性测试方法在预测可吸入化学品的急性毒性方面具有良好的可靠性和相关性。因此，该测定法具有作为急性毒性吸入物筛选的替代测试方法的潜力。
