Minimal inflammogenicity of pristine single-wall carbon nanotubes

Our plain-English summary of Minimal inflammogenicity of pristine single-wall carbon nanotubes, by S. Toyokuni, L.I. Jiang, R. Kitaura, et al (Nagoya Journal of Medical Science, 2015).

The study

• Authors: S. Toyokuni, L.I. Jiang, R. Kitaura, H. Shinohara
• Journal: Nagoya Journal of Medical Science
• Published: 2015;77(1-2):195-202
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Carbon nanotubes (CNTs) are a novel synthetic material comprising only carbon atoms. Based on its rigidity, its electrical and heat conductivity and its applicability to surface manufacturing, this material is expected to have numerous applications in industry. However, due to the material's dimensional similarity to asbestos fibers, its carcinogenicity was hypothesized during the last decade, and indeed, we have shown that multi-wall CNTs (MWCNTs) of 50 nm in diameter are potently carcinogenic to mesothelial cells after intraperitoneal injection. Additionally, we suggested that inflammogenicity after intraperitoneal injection can predict mesothelial carcinogenesis. However, few data have been published on the intraperitoneal inflammogenicity of single-wall CNTs (SWCNTs). Here, we conducted a series of studies on SWCNTs using both intraperitoneal injection into rats and MeT5A mesothelial cells. Intraperitoneal injection of 10 mg SWCNTs caused no remarkable inflammation in the abdominal cavity, and the exposure of MeT5A cells to up to 25 μg/cm(2) SWCNTs did not alter proliferation. MWCNTs of 50 nm in diameter were used as a positive control, and tangled MWCNTs of 15 nm in diameter were used as a negative control. The results suggest that SWCNTs are a low-risk material with respect to mesothelial carcinogenesis.

In plain English

This laboratory study tested single-wall carbon nanotubes (SWCNTs) in rats and a human cell line. No asbestos was tested. Electron microscopy of two lots of pristine SWCNTs from Zeon Corporation showed single- and double-wall tubes with flattened portions. Twenty-four male Wistar rats, 3 per group, each received one abdominal injection of the first lot, SWCNT1 (0.1 to 10 mg), 10 mg of 50 nm multi-wall nanotubes (MWCNT-50, positive control), 10 mg of tangled 15 nm multi-wall nanotubes (negative control), or vehicle, and were examined 4 weeks later. MWCNT-50 caused severe peritonitis and fibrosis over 500 μm thick. SWCNT1 caused no visible change apart from clumps of nanotubes, similar to the negative control, and microscopy found none of the fibrosis seen with MWCNT-50. In human mesothelial cells, both SWCNT lots were not toxic up to 25 μg/cm2, while MWCNT-50 was significantly toxic from 5 μg/cm2. The authors concluded that SWCNTs appear low-risk for mesothelial cancer. They noted this rests on their hypothesis that damage to mesothelial cells is critical for cancer, and that a cancer study would be preferable.

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 (single intraperitoneal injection in rats, examined after 4 weeks) combined with a cell culture experiment and electron microscopy characterization of the nanotubes
• Who was studied: 24 six-week-old male Wistar rats, divided into 8 groups of 3 animals; plus MeT5A, an immortalized human mesothelial cell line
• Exposure: Two lots of pristine single-wall carbon nanotubes (SWCNT1 and SWCNT2) obtained from Zeon Corporation. Only SWCNT1 was used in rats, at 0.1, 0.3, 1.0, 3.0 or 10 mg. Comparison groups received 10 mg of 50 nm multi-wall nanotubes (MWCNT-50, positive control), 10 mg of tangled 15 nm multi-wall nanotubes (MWCNT-tngl, negative control), or vehicle. Cells were exposed to 0.5 to 25 μg/cm2.
• Main results:
  • In rats given 10 mg MWCNT-50, injection caused severe peritonitis, with evident peritoneal fibrosis
  • In MWCNT-50 rats, fibrosis on the surface of abdominal organs and peritoneum was over 500 μm thick
  • In SWCNT1 rats, there was no recognizable change on visual (macroscopic) inspection apart from aggregated nanotubes seen as black foreign bodies; observations were similar to the negative-control MWCNT-tngl group
  • On histology, the fibrotic lesions seen with MWCNT-50 were absent in the SWCNT1 and MWCNT-tngl groups
  • In MeT5A human mesothelial cells, both SWCNT types were not toxic up to 25 μg/cm2, whereas MWCNT-50 was significantly toxic at concentrations as low as 5 μg/cm2
  • SWCNT1 contained both single- and double-wall tubes. The double-wall tubes (mean 4.30, SEM 0.59 nm) were not significantly thicker than the single-wall tubes (3.83, SEM 0.165 nm; P=0.3545).
• The authors' conclusion: The authors concluded that this intraperitoneal injection study suggests SWCNTs have low carcinogenicity to mesothelial cells, and that SWCNTs are a low-risk material with respect to mesothelial carcinogenesis
• Limitations the authors state:
  • The conclusion depends on the authors' hypothesis that toxicity and damage to mesothelial cells are critical factors for mesothelial cancer
  • Cancer itself was not studied; the authors stated that confirmation through a carcinogenesis study is preferable
  • The respiratory system, the route through which humans are exposed, was not considered
  • Effects on the cardiovascular and nervous systems still need study, and there are no effective labeling or detection techniques for SWCNTs
  • The nanotubes were tangled, so their length could not be determined

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenic, Mesothelial Cells, Carcinogenesis, Inflammation.

Related studies

• Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells — M. Pacurari, X.J. Yin, et al. (2008)
• Single- and multi-wall carbon nanotubes versus asbestos: are the carbon nanotubes a new health risk to humans? — M. Pacurari, V. Castranova, et al. (2010)
• Respiratory toxicity of multi-wall carbon nanotubes — J. Muller, F. Huaux, et al. (2005)
• Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube — A. Takagi, A. Hirose, et al. (2008)
• Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice — A. Takagi, A. Hirose, et al. (2012)
• Genotoxicity and cytotoxicity of multi-wall carbon nanotubes in cultured Chinese hamster lung cells in comparison with chrysotile A fibers — M. Asakura, T. Sasaki, et al. (2010)

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