Intraperitoneal administration of tangled multiwalled carbon nanotubes of 15 nm in diameter does not induce mesothelial carcinogenesis in rats

Our plain-English summary of Intraperitoneal administration of tangled multiwalled carbon nanotubes of 15 nm in diameter does not induce mesothelial carcinogenesis in rats, by H. Nagai, Y. Okazaki, S.H. Chew, et al (Pathology International, 2013).

The study

• Authors: H. Nagai, Y. Okazaki, S.H. Chew, N. Misawa, Y. Miyata, H. Shinohara, S. Toyokuni
• Journal: Pathology International
• Published: 2013;63(9):457-62
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Multiwalled carbon nanotubes (MWCNTs) have attracted public attention not only for their potential applications in engineering and materials science but also for possible environmental risks. MWCNTs share similar properties with asbestos, a definite human carcinogen causing malignant mesothelioma (MM), in that they are both biopersistent thin fibers with a high aspect ratio. Certain types of MWCNTs do induce MM in animal experiments. Though there are many different types of MWCNTs awaiting use in industry, there is little evidence about what types of MWCNTs present a high risk for MM in vivo. We have previously shown that the diameter of MWCNTs is one of the critical factors for mesothelial injury, which eventually leads to MM. Because of the extensive commercial use of MWCNTs, the properties of MWCNTs that determine carcinogenic activity should be clarified. Here we report that a high dose (10 mg) of a tangled form of pristine MWCNT (with a diameter of 15 nm) did not induce MM after intraperitoneal administration in rats, which were followed for up to 3 years after injection. This observation strengthens our previous finding that the rigidity, diameter, length and surface properties of MWCNTs are important factors in MM induction in vivo.

© 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

In plain English

This animal experiment from Japan tested whether a tangled form of multiwalled carbon nanotube (NTtngl, about 15 nm in diameter) causes malignant mesothelioma in rats. The authors describe these nanotubes as sharing properties with asbestos, but no asbestos was tested. Six-week-old male Fischer 344/Brown Norway hybrid rats received two 5 mg injections into the abdominal (peritoneal) cavity a week apart, 10 mg in total. Of 21 rats, 9 died soon after the second injection for unknown reasons. Six were examined at one year in the authors' earlier work, and none had mesothelioma. The remaining 6 were followed until they were sacrificed between day 746 and day 1139. None developed mesothelioma. Other tumors were found, including liver, lung, adrenal and testicular tumors. The authors thought these were mostly age-related but said it was difficult to prove the nanotubes had no influence. At least 5 of the 6 rats had granulomas. The authors concluded that this nanotube did not induce mesothelioma in rats. They noted two limitations: the small number of animals, and the use of injection rather than inhalation.

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: lifetime carcinogenesis study with intraperitoneal injection
• Who was studied: 21 six-week-old male Fischer 344/Brown Norway F1 hybrid rats, Nagoya University, Japan. 9 died acutely after the second injection and 6 were sacrificed at one year (reported previously), leaving 6 rats followed over their lifetime
• Exposure: A tangled form of multiwalled carbon nanotube (NTtngl; manufacturer-reported mean diameter 15 nm and length 3000 nm), injected into the peritoneal cavity as two 5 mg doses one week apart (10 mg total). A thin, rigid nanotube (NT50a) that induced mesothelioma was used as a positive control.
• Main results:
  • None of the 6 rats followed over their lifetime developed malignant mesothelioma. They were sacrificed between day 746 and day 1139, mainly for senility or other tumors.
  • Examination of the peritoneal organs found no mesothelioma, but other tumors were found. These included adrenal cortical adenomas, mammary fibroadenomas, pancreatic islet cell tumors, hepatocellular carcinomas, bile duct adenomas, Leydig cell tumors of the testis, and lung adenocarcinomas.
  • The 6 rats sacrificed one year after injection, reported in the authors' earlier study, also did not develop mesothelioma
  • The nanotubes induced many granulomas in at least 5 of the 6 rats. In the sixth rat, granulomas could not be confirmed because of postmortem changes.
  • The granulomas around the tangled nanotubes showed no iron deposition on Perls' iron staining
  • 9 of the 21 rats died acutely after the second injection. The cause was unknown, but the authors suspected arterial and/or lymphatic embolism.
• The authors' conclusion: The authors concluded that this tangled form of multiwalled carbon nanotube did not induce mesothelioma over the rats' lifetime when given intraperitoneally at a high dose. They said inhalation studies are needed to evaluate environmental risk.
• Limitations the authors state:
  • Small number of animals and the route of administration: intraperitoneal injection rather than inhalation, which the authors note is how nanotubes would affect humans
  • The authors could not exclude that the nanotubes influenced the other tumors, which they attributed mostly to age

Topics

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

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Malignant Mesothelioma, Aspect Ratio (Length-to-diameter ratio), Carcinogenic.

Related studies

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• Chronic exposure to carbon nanotubes induces invasion of human mesothelial cells through matrix metalloproteinase-2 — W. Lohcharoenkal, L. Wang, et al. (2013)
• 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)
• Size- and shape-dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes — J. Xu, D.B. Alexander, et al. (2014)
• Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice — A. Takagi, A. Hirose, et al. (2012)

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