Lung carcinogenicity of inhaled multi-walled carbon nanotube in ratsReport as inadecuate

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Particle and Fibre Toxicology

, 13:53

First Online: 13 October 2016Received: 07 April 2016Accepted: 30 September 2016DOI: 10.1186-s12989-016-0164-2

Cite this article as: Kasai, T., Umeda, Y., Ohnishi, M. et al. Part Fibre Toxicol 2015 13: 53. doi:10.1186-s12989-016-0164-2


BackgroundMulti-walled carbon nanotubes MWCNTs constitute one of the most promising types of nanomaterials in industry today. With their increasing use, the potential toxicity and carcinogenicity of MWCNT needs to be evaluated in bioassay studies using rodents. Since humans are mainly exposed to MWCNT by inhalation, we performed a 104-week carcinogenicity study using whole-body inhalation exposure chambers with a fibrous straight type of MWCNT at concentrations of 0, 0.02, 0.2, and 2 mg-m using male and female F344 rats.

ResultsLung carcinomas, mainly bronchiolo-alveolar carcinoma, and combined carcinomas and adenomas were significantly increased in males exposed to 0.2 and 2 mg-m MWNT-7 and in females exposed to 2 mg-m MWNT-7 compared to the clean air control group. However, no development of pleural mesothelioma was observed. Concentration-dependent toxic effects in the lung such as epithelial hyperplasia, granulomatous change, localized fibrosis, and alteration in BALF parameters were found in MWNT-7 treatment groups of both sexes. There were no MWNT-7-specific macroscopic findings in the other organs, including the pleura and peritoneum. Absolute and relative lung weights were significantly elevated in male rats exposed to 0.2 and 2 mg-m MWNT-7 and in all exposed female groups. The lung burdens of MWNT-7 were clearly increased in a concentration-dependent as well as a duration-dependent manner.

ConclusionThere is clear evidence that MWNT-7 is carcinogenic to the lungs of male and female F344 rats, however no plural mesothelioma was observed.

KeywordsLung carcinoma Lung carcinogenicity Multi-walled carbon nanotube MWCNT MWNT-7 Inhalation carcinogenicity Whole body inhalation Rat AbbreviationsALPAlkaline phosphatase

BALFBronchoalveolar lavage fluid

BALTBronchus-associated lymphoid tissue

CNTCarbon nanotube

CVDChemical vapor deposition

GSDGeometric standard deviation

HandEHematoxylin and eosin

HPLCHigh performance liquid chromatography

LDHLactate dehydrogenase

MHLWMinistry of Health, Labour, and Welfare

MMADMass median aerodynamic diameter

MOUDIMicro-orifice uniform deposit cascade impactor

MTDMaximum tolerated dose

MWCNTMulti-walled carbon nanotube

OECDOrganisation for Economic Co-operation and Development

OPCOptical particle controller

PAHPolycyclic aromatic hydrocarbon

SEMScanning electron microscope

TPTotal protein

Electronic supplementary materialThe online version of this article doi:10.1186-s12989-016-0164-2 contains supplementary material, which is available to authorized users.

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