Genotoxicity and carcinogenicity risk of carbon nanotubes

Our plain-English summary of Genotoxicity and carcinogenicity risk of carbon nanotubes, by S. Toyokuni (Advanced Drug Delivery Reviews, 2013).

The study

• Author: S. Toyokuni
• Journal: Advanced Drug Delivery Reviews
• Published: 2013;65(15):2098-110
• Type of article: Review
• Cited by: 71 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Novel materials are often commercialized without a complete assessment of the risks they pose to human health because such assessments are costly and time-consuming; additionally, sometimes the methodology needed for such an assessment does not exist. Carbon nanotubes have the potential for widespread application in engineering, materials science and medicine. However, due to the needle-like shape and high durability of multiwalled carbon nanotubes (MWCNTs), concerns have been raised that they may induce asbestos-like pathogenicity when inhaled. Indeed, experiments in rodents supported this hypothesis. Notably, the genetic alterations in MWCNT-induced rat malignant mesothelioma were similar to those induced by asbestos. Single-walled CNTs (SWCNTs) cause mitotic disturbances in cultured cells, but thus far, there has been no report that SWCNTs are carcinogenic. This review summarizes the recent noteworthy publications on the genotoxicity and carcinogenicity of CNTs and explains the possible molecular mechanisms responsible for this carcinogenicity. The nanoscale size and needle-like rigid structure of CNTs appear to be associated with their pathogenicity in mammalian cells, where carbon atoms are major components in the backbone of many biomolecules. Publishing adverse events associated with novel materials is critically important for alerting people exposed to such materials. CNTs still have a bright future with superb economic and medical merits. However, appropriate regulation of the production, distribution and secondary manufacturing processes is required, at least to protect the workers.

Copyright © 2013 Elsevier B.V. All rights reserved.

In plain English

This article was a review of published research on whether carbon nanotubes damage DNA (genotoxicity) or cause cancer. It covered single-walled (SWCNTs) and multiwalled carbon nanotubes (MWCNTs) and compared them with asbestos. The reviewed studies reported that one MWCNT product (Mitsui MWCNT-7) caused malignant mesothelioma in genetically altered, cancer-prone (p53 hetero-knockout) mice after injection into the abdomen. It also caused mesothelioma in male Fischer 344 rats after injection into the scrotum. In earlier work from the author's laboratory, MWCNTs 50 nm wide caused mesothelioma in 13 of 13 rats given 1 mg. Tangled 15 nm tubes caused it in 0 of 15 rats. Two other studies reported no increase in cancer. Many genotoxicity tests in mammalian cells and animals were positive. No cancer-causing effect had been reported for SWCNTs, and no human case of MWCNT-induced cancer had been reported. The author concluded that certain MWCNTs are as carcinogenic to mesothelial cells as asbestos fibers, at least in animal experiments. The author noted that the animals were exposed directly and were young and healthy, which differs from real human exposure.

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: Review of published studies (narrative review with summary tables)
• Who was studied: Published animal experiments (mice and rats) and cell-culture studies on carbon nanotubes; no new human or animal data
• Exposure: Single-walled and multiwalled carbon nanotubes of various makers, widths and lengths (e.g. Mitsui MWCNT-7), given by intraperitoneal, intrascrotal, subcutaneous, intratracheal and other routes. Crocidolite asbestos was used as a positive control in several of the animal studies reviewed.
• Main results:
  • A 2008 study (Kanno group) reported that Mitsui MWCNT-7 caused malignant mesothelioma in p53 hetero-knockout mice after intraperitoneal injection: 14/16 mice at day 84, versus 14/18 in the crocidolite positive control.
  • A study by the Nakae group reported mesothelioma after intrascrotal injection of the same MWCNT in male Fischer 344 rats (6/7 at 37-40 weeks).
  • In the author's laboratory's earlier rat study, mesothelioma depended on MWCNT diameter. For 50 nm tubes, 13/13 rats developed it at 1 mg and 49/49 at 10 mg. For 145 nm tubes, 5/29 developed it at 1 mg and 28/30 at 10 mg. For 15 nm tangled tubes, 0/15 developed it at day 350.
  • In that rat study, homozygous deletion of Cdkn2a/2b was found in 92% of MWCNT-induced mesotheliomas, and 86% were of the sarcomatoid subtype. The author wrote that this suggested MWCNT- and asbestos-induced mesothelioma have much in common.
  • Other reviewed studies (Müller; Takanashi et al.) reported no increase in carcinogenesis with the MWCNTs they tested.
  • Bacterial genotoxicity tests were described as ineffective for carbon nanotubes, while many genotoxicity studies using mammalian cells and animals were positive.
  • No carcinogenicity had been reported for SWCNTs.
  • No human case of MWCNT-induced cancer had been reported.
• The authors' conclusion: The author concluded that certain types of MWCNTs are as carcinogenic to mesothelial cells as asbestos fibers, at least in animal experiments, with effects strongly modulated by physical factors such as diameter. No carcinogenicity has been reported for SWCNTs. The author considered an airborne limit of 0.03 mg/m3 appropriate where carbon nanotubes are used.
• Limitations the authors state:
  • In the animal experiments, mesothelial cells were exposed directly to MWCNTs, which does not represent actual human exposure.
  • The experimental animals were young and free of disease, unlike humans with smoking-damaged or otherwise diseased lungs.
  • The positive mouse and rat studies used very sensitive, cancer-prone models.
  • A longer observation period is needed before concluding anything from the absence of human cases.

Topics

Medical terms in this study, explained in our Lexicon: Genotoxicity, Malignant Mesothelioma, Carcinogenic.

Related studies

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• 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)
• Genotoxicity of carbon nanofibers: are they potentially more or less dangerous than carbon nanotubes or asbestos? — E.R. Kisin, A.R. Murray, et al. (2011)
• 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)
• Aspect ratio has no effect on genotoxicity of multi-wall carbon nanotubes — J.S. Kim, K. Lee, et al. (2011)
• Carcinogenicity of fluoro-edenite, silicon carbide fibres and whiskers, and carbon nanotubes — Y. Grosse, D. Loomis, et al. (2014)

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