Lung carcinogenicity of inhaled multi-walled carbon nanotube in rats

Our plain-English summary of Lung carcinogenicity of inhaled multi-walled carbon nanotube in rats, by T. Kasai, Y. Umeda, M. Ohnishi, et al (Particle and Fibre Toxicology, 2016).

The study

• Authors: T. Kasai, Y. Umeda, M. Ohnishi, T. Mine, H. Kondo, T. Takeuchi, M. Matsumoto, S. Fukushima
• Journal: Particle and Fibre Toxicology
• Published: 2016;13(1):53
• Cited by: 168 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Multi-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/m3 using male and female F344 rats.

Results: Lung carcinomas, mainly bronchiolo-alveolar carcinoma, and combined carcinomas and adenomas were significantly increased in males exposed to 0.2 and 2 mg/m3 MWNT-7 and in females exposed to 2 mg/m3 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/m3 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.

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

In plain English

This was an animal experiment on a multi-walled carbon nanotube called MWNT-7, not a study of people or of asbestos. The authors exposed F344 rats, 50 males and 50 females per group, to airborne MWNT-7 for 6 hours a day, 5 days a week, for 104 weeks, at 0, 0.02, 0.2 or 2 mg/m3. Lung carcinomas, mainly bronchiolo-alveolar carcinomas, were significantly increased in males at 0.2 and 2 mg/m3 (8 and 11 of 50 rats, against 1 of 50 controls) and in females at 2 mg/m3 (8 of 50, against 0 of 50). Survival did not differ between groups. Granulomatous change and focal fibrosis in the lungs were increased at 0.2 and 2 mg/m3 in both sexes. No pleural mesothelioma developed. Peritoneal malignant mesotheliomas were listed in 3, 1 and 1 exposed males, and in no controls; the authors did not regard any tumors outside the lung as MWNT-7-related. The authors concluded there was clear evidence that MWNT-7 is carcinogenic to rat lungs. They noted the results do not apply to all MWCNTs.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: 2-year (104-week) whole-body inhalation carcinogenicity study in rats
• Who was studied: F344 rats, 6 weeks old at the start, 50 males and 50 females per exposure group (400 animals in all), at the Japan Bioassay Research Center, Japan
• Exposure: Aerosol of MWNT-7, a fibrous, straight multi-walled carbon nanotube (not asbestos), at target concentrations of 0 (clean air), 0.02, 0.2 or 2 mg/m3, 6 hours a day, 5 days a week, for 104 weeks
• Main results:
  • Lung carcinomas were significantly increased in male rats exposed to 0.2 and 2 mg/m3 and in female rats exposed to 2 mg/m3
  • Total lung carcinomas, out of 50 rats per group: males 1 (control), 1 (0.02), 8 (0.2), 11 (2 mg/m3); females 0, 1, 0, 8
  • Rare lung tumor types appeared only at 2 mg/m3: one adenosquamous carcinoma in each sex, plus one poorly differentiated adenocarcinoma and one squamous cell carcinoma in females
  • Granulomatous change and focal fibrosis of the alveolar wall were significantly increased in male and female rats exposed to 0.2 and 2 mg/m3
  • No pleural mesothelioma was induced in any group
  • Simple mesothelial hyperplasia of the parietal pleura was significantly increased in males exposed to 2 mg/m3. In females at 2 mg/m3 the increase was not statistically significant.
  • The histopathology table lists peritoneal malignant mesothelioma in males at 0, 3, 1 and 1 of 50 (control, 0.02, 0.2, 2 mg/m3) and in no females. The authors reported no MWNT-7-related tumors in the pleural or peritoneal mesothelium.
  • Survival did not differ between exposed and control groups in either sex
  • Absolute and relative lung weights were significantly raised in males at 0.2 and 2 mg/m3 and in all exposed female groups
  • MWNT-7 fibers counted in pleural lavage fluid were 38, 134 and 1468 in males and 23, 240 and 847 in females at 0.02, 0.2 and 2 mg/m3
• The authors' conclusion: The authors concluded there is clear evidence that MWNT-7 is carcinogenic to the lungs of male and female F344 rats exposed by inhalation for 104 weeks. They suggested that a likely factor in the absence of mesothelioma was the low number of fibers reaching the pleura.
• Limitations the authors state:
  • Because different MWCNTs vary in fiber length, shape and rigidity, the authors stated the results do not apply to all MWCNTs
  • The authors stated that further studies are needed to explain why another study using intratracheal instillation produced pleural mesotheliomas when this inhalation study did not

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Carcinoma, Pleural Mesothelioma, Fibrosis, Pleura, Peritoneum, Carcinogenic, Mesothelioma.

Related studies

• Thirteen-week study of toxicity of fiber-like multi-walled carbon nanotubes with whole-body inhalation exposure in rats — T. Kasai, Y. Umeda, et al. (2015)
• 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 — D.M. Saleh, W.T. Alexander, et al. (2020)
• Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats — J. Xu, M. Futakuchi, et al. (2012)
• Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study — D.M. Saleh, S. Luo, et al. (2022)
• Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes — L.M. Sargent, D.W. Porter, et al. (2014)
• Osteopontin mRNA expression by rat mesothelial cells exposed to multi-walled carbon nanotubes as a potential biomarker of chronic neoplastic transformation in vitro — S. Sridharan, A. Taylor-Just, et al. (2021)

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