Fujita Katsuhide, Obara Sawae, Maru Junko
Research Institute of Science for Safety and Sustainability (RISS), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, 305-8569, Japan.
Research Institute of Science for Safety and Sustainability (RISS), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, 305-8569, Japan.
Toxicology. 2022 Jan 30;466:153063. doi: 10.1016/j.tox.2021.153063. Epub 2021 Dec 8.
Submicron-diameter carbon fibers (SCFs) are a type of fine-diameter fibrous carbon material that can be used in various applications. To accelerate their practical application, a hazard assessment of SCFs must be undertaken. This study demonstrated the pulmonary toxicity, cytotoxicity, and genotoxicity of three types of SCFs with different diameters and lengths. The average diameter and length of SCFs were 259.2 nm and 11.7 μm in SCF1 suspensions, 248.5 nm and 6.7 μm in SCF2 suspensions, and 183.0 nm and 13.7 μm in SCF3 suspensions, respectively. The results of pulmonary inflammation and recovery following intratracheal instillation with SCFs at doses of 0.25, 0.5, or 1.0 mg/kg showed that the pulmonary toxicity of SCFs was SCF3 > SCF1 > SCF2. These results suggest that SCF diameter and length are most likely important contributing factors associated with lung SCF clearance, pulmonary inflammation, and recovery. Furthermore, SCFs are less pulmonary toxic than bent multi-walled carbon nanotubes. Cell viability, pro-inflammatory cytokine and intracellular reactive oxygen species productions, morphological changes, gene expression profiling in NR8383 rat alveolar macrophage cells showed that the cytotoxic potency of SCFs is: SCF3 > SCF1 > SCF2. These results showed that SCFs with small diameters had high cytotoxicity, and SCFs with short lengths had low cytotoxicity. We conclude that pulmonary toxicity and cytotoxicity are associated with the diameter and length distributions of SCFs. In addition, a standard battery for genotoxicity testing, namely the Ames test, an in vitro chromosomal aberration test, and a mammalian erythrocyte micronucleus test, demonstrated that the three types of SCFs did not induce genotoxicity. Our findings provide new evidence for evaluating the potential toxicity of not only SCFs used in this study but also various SCFs which differ depending on the manufacturing processes or physicochemical properties.
亚微米级直径的碳纤维(SCFs)是一种细直径的纤维状碳材料,可用于各种应用。为加速其实际应用,必须对SCFs进行危害评估。本研究证明了三种不同直径和长度的SCFs的肺毒性、细胞毒性和遗传毒性。SCF1悬浮液中SCFs的平均直径和长度分别为259.2 nm和11.7μm,SCF2悬浮液中为248.5 nm和6.7μm,SCF3悬浮液中为183.0 nm和13.7μm。以0.25、0.5或1.0 mg/kg的剂量经气管内滴注SCFs后肺部炎症和恢复的结果表明,SCFs的肺毒性为SCF3 > SCF1 > SCF2。这些结果表明,SCF的直径和长度很可能是与肺内SCF清除、肺部炎症和恢复相关的重要因素。此外,SCFs的肺毒性低于弯曲的多壁碳纳米管。NR8383大鼠肺泡巨噬细胞中的细胞活力、促炎细胞因子和细胞内活性氧生成、形态变化、基因表达谱分析表明,SCFs的细胞毒性效力为:SCF3 > SCF1 > SCF2。这些结果表明,直径小的SCFs具有高细胞毒性,长度短的SCFs具有低细胞毒性。我们得出结论,肺毒性和细胞毒性与SCFs的直径和长度分布有关。此外,一套标准的遗传毒性测试,即艾姆斯试验、体外染色体畸变试验和哺乳动物红细胞微核试验,表明这三种类型的SCFs不会诱导遗传毒性。我们的研究结果为评估本研究中使用的SCFs以及因制造工艺或物理化学性质不同的各种SCFs的潜在毒性提供了新的证据。