Sakamoto Yoshimitsu, Hojo Motoki, Kosugi Yuki, Watanabe Kimiyo, Hirose Akihiko, Inomata Akiko, Suzuki Toshinari, Nakae Dai
Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health.
Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences.
J Toxicol Sci. 2018;43(10):587-600. doi: 10.2131/jts.43.587.
The present study comparatively examined carcinogenicity of 7 different multi-wall carbon nanotubes (MWCNTs) with different physicochemical characteristics. Physicochemical characteristics of MWCNTs (referred to as M-, N-, WL-, SD1-, WS-, SD2- and T-CNTs in the present study) were determined using scanning electron and light microscopes and a collision type inductively coupled plasma mass spectrometer. Male Fischer 344 rats (10 weeks old, 15 animals per group) were administered MWCNTs at a single intraperitoneal dose of 1 mg/kg body weight, and sacrificed up to 52 weeks after the commencement. Fibers of M-, N-, WL- and SD1-CNTs were straight and acicular in shape, and contained few agglomerates. They were relatively long (38-59% of fibers were longer than 5 μm) and thick (33% to more than 70% of fibers were thicker than 60 nm). All of these 4 MWCNTs induced mesotheliomas at absolute incidences of 100%. Fibers of WS-, SD2- and T-CNTs were curled and tightly tangled to form frequent agglomerates. They were relatively short and thin (more than 90% of measured fibers were thinner than 50 nm). WS- CNT did not induce mesothelioma, and only one of 15 rat given SD2- or T-CNT developed tumor. Any correlations existed between the metal content and neither the size or form of fibers, nor the carcinogenicity. It is thus indicated that the physicochemical characteristics of MWCNTs are critical for their carcinogenicity. The straight and acicular shape without frequent agglomerates, and the relatively long and thick size, but not the iron content, may be critical factors. The present data can contribute to the risk management, practical use and social acceptance of MWCNTs.
本研究比较了7种具有不同物理化学特性的多壁碳纳米管(MWCNT)的致癌性。使用扫描电子显微镜、光学显微镜和碰撞型电感耦合等离子体质谱仪测定了MWCNT(本研究中称为M -、N -、WL -、SD1 -、WS -、SD2 -和T - CNT)的物理化学特性。对雄性Fischer 344大鼠(10周龄,每组15只动物)单次腹腔注射剂量为1 mg/kg体重的MWCNT,并在开始给药后长达52周处死动物。M -、N -、WL -和SD1 - CNT的纤维呈直形且为针状,团聚体较少。它们相对较长(38% - 59%的纤维长度超过5μm)且较粗(33%至超过70%的纤维直径超过60nm)。所有这4种MWCNT均以100%的绝对发病率诱发了间皮瘤。WS -、SD2 -和T - CNT的纤维卷曲且紧密缠结形成频繁的团聚体。它们相对较短且较细(超过90%的测量纤维直径小于50nm)。WS - CNT未诱发间皮瘤,给予SD2 -或T - CNT的15只大鼠中只有1只发生了肿瘤。金属含量与纤维的尺寸、形态或致癌性之间均不存在任何相关性。因此表明,MWCNT的物理化学特性对其致癌性至关重要。直形和针状且无频繁团聚体,以及相对较长和较粗的尺寸,而非铁含量,可能是关键因素。本数据有助于MWCNT的风险管理、实际应用和社会接受度。