Comparative carcinogenicity study of a thick, straight-type and a thin, tangled-type multi-walled carbon nanotube administered by intra-tracheal instillation in the rat

• Published in: Particle and fibre toxicology Vol. 17; no. 1; pp. 1 - 14
• Main Authors: Saleh, Dina Mourad, Alexander, William T, Numano, Takamasa, Ahmed, Omnia Hosny Mohamed, Gunasekaran, Sivagami, Alexander, David B, Abdelgied, Mohamed, El-Gazzar, Ahmed M, Takase, Hiroshi, Xu, Jiegou, Naiki-Ito, Aya, Takahashi, Satoru, Hirose, Akihiko, Ohnishi, Makoto, Kanno, Jun, Tsuda, Hiroyuki
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 15-10-2020; BioMed Central; BMC
• Subjects: Adenocarcinoma; Adenoma; Alveoli; Animals; Asbestos; Carbon; Carcinogenesis; Carcinogenicity; Carcinogens; Chemical properties; Comparative studies; Crocidolite; Cytoplasm; Development and progression; Graphene; Health aspects; Homogenization; Hyperplasia; Inflammation; Injection; Intrapulmonary; Intratracheal; Lung cancer; Lungs; Lymphatic system; Mesothelioma; Multi wall carbon nanotubes; MWCNT; Nanotechnology; Nanotubes; Peritoneum; Pleura; Respiratory tract; Risk factors; Rodents; Spraying; Thick and thin; Tumors; Japan
• ISSN: 1743-8977; 1743-8977
• DOI: 10.1186/s12989-020-00382-y

Multi-walled carbon nanotubes can be divided into two general subtypes: tangled and straight. MWCNT-N (60 nm in diameter) and MWCNT-7 (80-90 nm in diameter) are straight-type MWCNTs, and similarly to asbestos, both are carcinogenic to the lung and pleura when administered to rats via the airway. Injection of straight-type MWCNTs into the peritoneal cavity also induces the development of mesothelioma, however, injection of tangled-type MWCNTs into the peritoneal cavity does not induce carcinogenesis. To investigate these effects in the lung we conducted a 2-year comparative study of the potential carcinogenicities of a straight-type MWCNT, MWCNT-A (approximately 150 nm in diameter), and a tangled-type MWCNT, MWCNT-B (7.4 nm in diameter) after administration into the rat lung. Crocidolite asbestos was used as the reference material, and rats administered vehicle were used as the controls. Test materials were administered by intra-Tracheal Intra-Pulmonary Spraying (TIPS) once a week over a 7 week period (8 administrations from day 1 to day 50), followed by a 2-year observation period without further treatment. Rats were administered total doses of 0.5 or 1.0 mg MWCNT-A and MWCNT-B or 1.0 mg asbestos. There was no difference in survival between any of the groups. The rats administered MWCNT-A or asbestos did not have a significant increase in bronchiolo-alveolar hyperplasia or tumors in the lung. However, the rats administered MWCNT-B did have significantly elevated incidences of bronchiolo-alveolar hyperplasia and tumors in the lung: the incidence of bronchiolo-alveolar hyperplasia was 0/20, 6/20, and 9/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively, and the incidence of adenoma and adenocarcinoma combined was 1/19, 5/20, and 7/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively. Malignant pleural mesothelioma was not induced in any of the groups. The results of this initial study indicate that tangled-type MWCNT-B is carcinogenic to the rat lung when administered via the airway, and that straight-type MWCNT-A did not have higher carcinogenic potential in the rat lung than tangled-type MWCNT-B.