Research Institute for Fragrance Materials, Inc., 50 Tice Blvd, Woodcliff Lake, NJ 07677, United States.
Firmenich, Inc., 250 Plainsboro Rd, Plainsboro Township, NJ 08536, United States.
Mutagenesis. 2022 Apr 2;37(1):13-23. doi: 10.1093/mutage/geac004.
BlueScreen HC is a mammalian cell-based assay for measuring the genotoxicity and cytotoxicity of chemical compounds and mixtures. The BlueScreen HC assay has been utilized at the Research Institute for Fragrance Materials in a safety assessment program as a screening tool to prioritize fragrance materials for higher-tier testing, as supporting evidence when using a read-across approach, and as evidence to adjust the threshold of toxicological concern. Predictive values for the BlueScreen HC assay were evaluated based on the ability of the assay to predict the outcome of in vitro and in vivo mutagenicity and chromosomal damage genotoxicity assays. A set of 371 fragrance materials was assessed in the BlueScreen HC assay along with existing or newly generated in vitro and in vivo genotoxicity data. Based on a weight-of-evidence approach, the majority of materials in the data set were deemed negative and concluded not to have the potential to be genotoxic, while only a small proportion of materials were determined to show genotoxic effects in these assays. Analysis of the data set showed a combination of high positive agreement but low negative agreement between BlueScreen HC results, in vitro regulatory genotoxicity assays, and higher-tier test results. The BlueScreen HC assay did not generate any false negatives, thereby providing robustness when utilizing it as a high-throughput screening tool to evaluate the large inventory of fragrance materials. From the perspective of protecting public health, it is desirable to have no or minimal false negatives, as a false-negative result may incorrectly indicate the lack of a genotoxicity hazard. However, the assay did have a high percentage of false-positive results, resulting in poor positive predictivity of the in vitro genotoxicity test battery outcome. Overall, the assay generated 100% negative predictivity and 3.9% positive predictivity. In addition to the data set of 371 fragrance materials, 30 natural complex substances were evaluated for BlueScreen HC, Ames, and in vitro micronucleus assay, and a good correlation in all three assays was observed. Overall, while a positive result may have to be further investigated, these findings suggest that the BlueScreen HC assay can be a valuable screening tool to detect the genotoxic potential of fragrance materials and mixtures.
BlueScreen HC 是一种基于哺乳动物细胞的检测方法，用于测量化合物和混合物的遗传毒性和细胞毒性。该 BlueScreen HC 检测方法已在香料研究所以安全评估计划中得到应用，作为对香料材料进行更高层次测试的筛选工具，作为使用读码法的支持证据，以及作为调整毒理学关注阈值的证据。根据该检测方法预测 BlueScreen HC 检测结果的能力，评估了该检测方法预测体外和体内致突变性和染色体损伤遗传毒性检测结果的能力。对 371 种香料材料进行了 BlueScreen HC 检测，同时还提供了现有的或新生成的体外和体内遗传毒性数据。根据综合证据评估方法，数据集的大部分材料被认为是阴性的，结论是它们没有潜在的遗传毒性，而只有一小部分材料被确定在这些检测中显示出遗传毒性作用。对数据集的分析表明，BlueScreen HC 结果、体外监管遗传毒性检测结果和更高层次检测结果之间存在高阳性一致性和低阴性一致性的组合。BlueScreen HC 检测未产生任何假阴性结果，从而在将其用作评估大量香料材料的高通量筛选工具时提供了稳健性。从保护公众健康的角度来看，最好没有或只有最小的假阴性结果，因为假阴性结果可能会错误地表明没有遗传毒性危害。然而，该检测确实有很高的假阳性率，导致体外遗传毒性检测结果的阳性预测性较差。总体而言，该检测产生了 100%的阴性预测性和 3.9%的阳性预测性。除了 371 种香料材料数据集外，还对 30 种天然复杂物质进行了 BlueScreen HC、Ames 和体外微核检测，在所有三个检测中都观察到了良好的相关性。总体而言，虽然阳性结果可能需要进一步调查，但这些发现表明 BlueScreen HC 检测可以成为一种有价值的筛选工具，用于检测香料材料和混合物的遗传毒性潜力。
