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

Our plain-English summary of 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, by D.M. Saleh, W.T. Alexander, T. Numano, et al (Particle and Fibre Toxicology, 2020).

The study

• Authors: D.M. Saleh, W.T. Alexander, T. Numano, O.H.M. Ahmed, S. Gunasekaran, D.B. Alexander, M. Abdelgied, A.M. El-Gazzar, H. Takase, J. Xu, A. Naiki-Ito, S. Takahashi, A. Hirose, M. Ohnishi, J. Kanno, H. Tsuda
• Journal: Particle and Fibre Toxicology
• Published: 2020;17(1):48
• Cited by: 42 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

In plain English

This was an animal experiment in Japan comparing two kinds of multi-walled carbon nanotubes (MWCNTs) with crocidolite asbestos. Male F344 rats had one of four materials sprayed into their lungs through the windpipe eight times over 7 weeks, and were then observed for 2 years. The materials were a thick, straight nanotube (MWCNT-A, about 150 nm wide), a thin, tangled nanotube (MWCNT-B, about 7.4 nm wide), crocidolite, or the vehicle liquid alone. Total doses were 0.5 or 1.0 mg of each nanotube per rat and 1.0 mg of crocidolite. Survival did not differ between groups. At 104 weeks, lung hyperplasia was significantly increased with MWCNT-B: 6/20 at 0.5 mg and 9/20 at 1.0 mg, versus 0/19 controls. Combined lung adenomas and carcinomas were significantly increased at 1.0 mg MWCNT-B (7/20 versus 1/19). MWCNT-A and crocidolite did not significantly raise hyperplasia or lung tumors on their own. However, all proliferative lesions combined were significantly higher (14 of 40 MWCNT-A rats; 7 of 20 crocidolite rats). No pleural mesotheliomas were found. The authors concluded that MWCNT-B is carcinogenic to the rat lung by this route, while the carcinogenicity of MWCNT-A remains to be determined.

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 carcinogenicity study in rats), with materials given by intra-tracheal intra-pulmonary spraying (TIPS), an interim sacrifice at week 52 and a terminal sacrifice at week 104
• Who was studied: Male F344 rats, 10 weeks old at the start, housed at Nagoya City University Medical School, Japan. Groups of 25 rats: 5 per group were sacrificed at 52 weeks and 20 per group at 104 weeks. The vehicle group had 19 effective rats at 104 weeks because one was sacrificed early at 39 weeks.
• Exposure: A thick, straight-type MWCNT (MWCNT-A, about 150 nm diameter, 213 walls, 0.001% iron) and a thin, tangled-type MWCNT (MWCNT-B, about 7.4 nm diameter, 6 to 7 walls, 1.1% iron), each at total doses of 0.5 or 1.0 mg per rat. Crocidolite asbestos (UICC grade) at 1.0 mg per rat was the reference material, and vehicle (0.5% poloxamer 188 in saline) was the control.
• Main results:
  • Survival did not differ significantly between groups.
  • At the week-52 interim sacrifice (5 rats per group), no tumors were found in the lung, mesothelium or other organs.
  • At week 104, bronchiolo-alveolar hyperplasia was significantly increased in the MWCNT-B groups: 6/20 at 0.5 mg and 9/20 at 1.0 mg, compared with 0/19 in vehicle controls.
  • Combined bronchiolo-alveolar adenoma and carcinoma in the 1.0 mg MWCNT-B group (7/20) was significantly higher than in vehicle controls (1/19). The 0.5 mg MWCNT-B group had 5/20, which was not marked as significant in Table 2.
  • In the MWCNT-A and crocidolite groups, neither hyperplasia nor lung tumors were significantly increased.
  • Hyperplasia, adenoma and carcinoma counted together were significantly higher than in vehicle controls (1/19) in both groups: 14 of 40 rats in the MWCNT-A groups combined and 7 of 20 rats in the crocidolite group.
  • No pleural mesotheliomas were found in any group.
  • Both nanotubes persisted in the lung. The amount of MWCNT-B in the lung at 52 and 104 weeks was markedly higher than MWCNT-A, about 3-fold according to the authors.
  • Macrophage counts, used as an indicator of inflammation, were significantly higher in the MWCNT-A and MWCNT-B groups than in vehicle controls.
• The authors' conclusion: The authors concluded that MWCNT-B is carcinogenic to the rat lung when given via the airway, and they identified it as a potential human health hazard. They found MWCNT-A was not overtly carcinogenic in this study, but said its carcinogenicity in the rat lung and pleural cavity remains to be determined.
• Limitations the authors state:
  • The authors called this an initial study and said the lack of apparent carcinogenicity of MWCNT-A does not mean it is not a carcinogen in rats.
  • The authors said experiments with a wider range of doses and more animals are needed to define the carcinogenicity of MWCNT-A.
  • The authors said pulmonary overload may have contributed to the lung carcinogenicity of MWCNT-B, and that the effect may be specific to rats; they said this requires further investigation.
  • The authors were unable to detect fibers in the pleural cavity itself.

Topics

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

Medical terms in this study, explained in our Lexicon: Carcinogenic, Pleura, Peritoneal Cavity, Mesothelioma, Carcinogenesis, Crocidolite, Adenocarcinoma, Pleural Mesothelioma.

Related studies

• In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes — J. Catalán, K.M. Siivola, et al. (2016)
• MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats — T. Numano, H. Higuchi, et al. (2019)
• Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats — J. Xu, M. Futakuchi, et al. (2012)
• Role of p53 in the chronic pulmonary immune response to tangled or rod-like multi-walled carbon nanotubes — K.S. Duke, E.A. Thompson, et al. (2018)
• Multiwalled carbon nanotubes intratracheally instilled into the rat lung induce development of pleural malignant mesothelioma and lung tumors — M. Suzui, M. Futakuchi, et al. (2016)
• Fullerene and fullerene whisker are not carcinogenic to the lungs and pleura in rat long-term study after 2-week intra-tracheal intrapulmonary administration — A.N. Sheema, A. Naiki-Ito, et al. (2024)

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