Carcinogenicity of multi-walled carbon nanotubes : challenging issue on hazard assessment

• Published in: Journal of Occupational Health Vol. 60; no. 1; pp. 10 - 30
• Main Authors: Fukushima, Shoji, Kasai, Tatsuya, Umeda, Yumi, Ohnishi, Makoto, Sasaki, Toshiaki, Matsumoto, Michiharu
• Format: Journal Article
• Language: English
• Published: Australia JAPAN SOCIETY FOR OCCUPATIONAL HEALTH 01.01.2018; Oxford University Press; Japan Society for Occupational Health
• Subjects: Animals; Cancer; Carcinogenesis; Carcinogenesis - drug effects; Carcinogenicity; Carcinogens; Carcinoma - chemically induced; Exposure limits; Fibers; Gastric cancer; Hazard assessment; Humans; Inhalation; Inhalation Exposure; Injection; Lung - drug effects; Lung burden; Lung carcinogenicity; Lung carcinoma; Lung Neoplasms - chemically induced; Macrophages; Maximum Allowable Concentration; Mesothelioma; Mesothelioma - chemically induced; Mesothelioma, Malignant; Mice; Mode of action; Multi wall carbon nanotubes; Multi‐walled carbon nanotube; MWCNT; Nanotechnology; Nanotubes; Nanotubes, Carbon - toxicity; Occupational exposure; Occupational Exposure - standards; Occupational health; Peritoneal Neoplasms - chemically induced; Peritoneum; Phagocytosis; Phagocytosis - drug effects; Pleural Neoplasms - chemically induced; Rats; Respiration; Review; Rodents; Shape effects; Trachea; Mesothelioma; Lung burden; MWCNT; Inhalation exposure; Multi-walled carbon nanotube; Lung carcinogenicity
• ISSN: 1341-9145; 1348-9585; 1348-9585
• DOI: 10.1539/joh.17-0102-ra

[Abstract]: [Objectives]: This report reviews the carcinogenicity of multi-walled carbon nanotubes (MWCNTs) in experimental animals, concentrating on MWNT-7, a straight fibrous MWCNT. [Methods]: MWCNTs were administered to mice and rats by intraperitoneal injection, intrascrotal injection, subcutaneous injection, intratracheal instillation and inhalation. [Results]: Intraperitoneal injection of MWNT-7 induced peritoneal mesothelioma in mice and rats. Intrascrotal injection induced peritoneal mesothelioma in rats. Intratracheal instillation of MWCNT-N (another straight fibrous MWCNT) induced both lung carcinoma and pleural mesothelioma in rats. In the whole body inhalation studies, in mice MWNT-7 promoted methylcholanthrene-initiated lung carcinogenesis. In rats, inhalation of MWNT-7 induced lung carcinoma and lung burdens of MWNT-7 increased with increasing concentration of airborne MWNT-7 and increasing duration of exposure. [Conclusions]: Straight, fibrous MWCNTs exerted carcinogenicity in experimental animals. Phagocytosis of MWCNT fibers by macrophages was very likely to be a principle factor in MWCNT lung carcinogenesis. Using no-observed-adverse-effect level-based approach, we calculated that the occupational exposure limit (OEL) of MWNT-7 for cancer protection is 0.15 μg/m3 for a human worker. Further studies on the effects of the shape and size of MWCNT fibers and mode of action on the carcinogenicity are required.