Health Effect Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Rd, MS-2015, Morgantown, WV, 26505-2888, USA.
West Virginia University, Morgantown, WV, USA.
Part Fibre Toxicol. 2020 Dec 7;17(1):62. doi: 10.1186/s12989-020-00392-w.
Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer similar toxicity, in particular, genotoxicity. Nine CNT/F (MW #1-7 and CNF #1-2), commonly found in exposure assessment studies of U.S. facilities, were evaluated with reported diameters ranging from 6 to 150 nm. All materials were extensively characterized to include distributions of physical dimensions and prevalence of bundled agglomerates. Human bronchial epithelial cells were exposed to the nine CNT/F (0-24 μg/ml) to determine cell viability, inflammation, cellular oxidative stress, micronuclei formation, and DNA double-strand breakage. Computational modeling was used to understand various permutations of physicochemical characteristics and toxicity outcomes.
Analyses of the CNT/F physicochemical characteristics illustrate that using detailed distributions of physical dimensions provided a more consistent grouping of CNT/F compared to using particle dimension means alone. In fact, analysis of binning of nominal tube physical dimensions alone produced a similar grouping as all characterization parameters together. All materials induced epithelial cell toxicity and micronuclei formation within the dose range tested. Cellular oxidative stress, DNA double strand breaks, and micronuclei formation consistently clustered together and with larger physical CNT/F dimensions and agglomerate characteristics but were distinct from inflammatory protein changes. Larger nominal tube diameters, greater lengths, and bundled agglomerate characteristics were associated with greater severity of effect. The portion of tubes with greater nominal length and larger diameters within a sample was not the majority in number, meaning a smaller percentage of tubes with these characteristics was sufficient to increase toxicity. Many of the traditional physicochemical characteristics including surface area, density, impurities, and dustiness did not cluster with the toxicity outcomes.
Distributions of physical dimensions provided more consistent grouping of CNT/F with respect to toxicity outcomes compared to means only. All CNT/F induced some level of genotoxicity in human epithelial cells. The severity of toxicity was dependent on the sample containing a proportion of tubes with greater nominal lengths and diameters.
碳纳米管和纳米纤维（CNT/F）已知具有毒性，但同时对广泛的材料类别进行比较研究，特别是对直径较大的材料类别进行比较研究，并结合计算分析将毒性与它们的基本材料特性联系起来的研究还很缺乏。目前尚不清楚所有 CNT/F 是否具有相似的毒性，特别是遗传毒性。评估了美国工厂暴露评估研究中常见的 9 种 CNT/F（MW #1-7 和 CNF #1-2），报告的直径范围为 6 至 150nm。对所有材料进行了广泛的表征，包括物理尺寸分布和束状团聚体的存在情况。将 9 种 CNT/F（0-24μg/ml）暴露于人支气管上皮细胞中，以确定细胞活力、炎症、细胞氧化应激、微核形成和 DNA 双链断裂。计算建模用于了解各种物理化学特性和毒性结果的排列组合。
对 CNT/F 物理化学特性的分析表明，使用物理尺寸的详细分布比仅使用颗粒尺寸平均值更能一致地对 CNT/F 进行分组。事实上，仅分析名义管物理尺寸的分组与所有表征参数一起产生了相似的分组。在测试的剂量范围内，所有材料均诱导上皮细胞毒性和微核形成。细胞氧化应激、DNA 双链断裂和微核形成始终与较大的物理 CNT/F 尺寸和团聚体特征一起聚类，但与炎症蛋白变化不同。较大的名义管直径、较长的长度和束状团聚体特征与更大的效应严重程度相关。样品中具有较大名义长度和较大直径的管的部分在数量上并不是大多数，这意味着具有这些特征的管的比例较小足以增加毒性。许多传统的物理化学特性，包括表面积、密度、杂质和扬尘，与毒性结果没有聚类。
与仅使用平均值相比，物理尺寸分布提供了更一致的 CNT/F 分组方式，以达到毒性结果。所有 CNT/F 都在人上皮细胞中引起了一定程度的遗传毒性。毒性的严重程度取决于样品中是否含有一定比例的具有较大名义长度和直径的管。
