Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System

Our plain-English summary of Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System, by M. Barbarino, A. Giordano (Cancers, 2021).

The study

• Authors: M. Barbarino, A. Giordano
• Journal: Cancers
• Published: 2021;13(6)
• Type of article: Review
• Cited by: 39 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In 2014, the International Agency for Research on Cancer (IARC) classified the first type of carbon nanotubes (CNTs) as possibly carcinogenic to humans, while in the case of other CNTs, it was not possible to ascertain their toxicity due to lack of evidence. Moreover, the physicochemical heterogeneity of this group of substances hamper any generalization on their toxicity. Here, we review the recent relevant toxicity studies produced after the IARC meeting in 2014 on an homogeneous group of CNTs, highlighting the molecular alterations that are relevant for the onset of mesothelioma. Methods: The literature was searched on PubMed and Web of Science for the period 2015-2020, using different combinations keywords. Only data on normal cells of the respiratory system after exposure to fully characterized CNTs for their physico-chemical characteristics were included. Recent studies indicate that CNTs induce a sustained inflammatory response, oxidative stress, fibrosis and histological alterations. The development of mesothelial hyperplasia, mesothelioma, and lungs tumors have been also described in vivo. The data support a strong inflammatory potential of CNTs, similar to that of asbestos, and provide evidence that CNTs exposure led to molecular alterations known to have a key role in mesothelioma onset. These evidences call for an urgent improvement of studies on exposed human populations and adequate systems for monitoring the health of workers exposed to this putative carcinogen.

In plain English

This article is a review, not a new experiment. The authors searched PubMed and Web of Science for studies from 2015 to 2020, after the 2014 International Agency for Research on Cancer (IARC) meeting on carbon nanotubes. They covered well-characterized single-walled and multi-walled carbon nanotubes, including the reference materials NM-400 to NM-403, using data from normal respiratory-system cells, animals, and fluids from exposed workers. The authors reported that animal studies showed sustained inflammation and oxidative stress. They also reported that mesothelial hyperplasia, mesothelioma and lung tumors had been described with single-walled nanotubes and with long fibers of both asbestos and multi-walled nanotubes. In one reviewed mouse study, long multi-walled nanotubes were instilled directly into the pleural cavity, and lesions progressed to pleural mesothelioma in 10–25% of these animals. The authors noted nine studies of exposed workers since 2014 that reported changes such as markers of fibrosis. They wrote that evidence on genotoxicity was still far from a consensus. The authors concluded that a new evaluation of the danger of carbon nanotubes is urgently needed and that exposed workers' health should be monitored.

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: Literature review of toxicity studies published after the 2014 IARC meeting on carbon nanotubes
• Who was studied: Studies found on PubMed and Web of Science, published 2015 to 2020, in English. They covered normal respiratory-system cells (pleural cells, lung cells, fibroblasts, lung macrophages), animal studies of the respiratory system, and biological fluids collected from exposed workers. The total number of studies reviewed is not stated.
• Exposure: Carbon nanotubes: the reference materials NM-400, NM-401, NM-402 and NM-403, plus single-walled (SWCNTs) and multi-walled (MWCNTs) nanotubes made by catalytic carbon vapor deposition and fully characterized. Chemically modified nanotubes for medical use were excluded. Some reviewed studies also used asbestos (amosite, chrysotile, crocidolite) for comparison.
• Main results:
  • The authors reported that animal studies found carbon nanotubes induced a sustained inflammatory response and oxidative stress.
  • Mesothelial hyperplasia, mesothelioma and lung tumors had been described in animals with SWCNTs and with long fibers of both asbestos and MWCNTs.
  • In one reviewed study, long MWCNTs and long-fiber amosite asbestos were instilled into the pleural cavity of mice. Lesions progressed to pleural mesothelioma in 10–25% of the animals exposed to long MWCNTs.
  • In the same study, mice exposed to commercial long MWCNTs showed epigenetic silencing of the CDKN2A locus. The authors described this locus as a well-known driver in asbestos-induced mesothelioma.
  • Since the 2014 IARC evaluation, nine new studies had been done on workers exposed to carbon nanotubes. They reported findings such as markers of fibrosis, profibrotic inflammatory mediators and immune markers.
  • One reviewed study of workers exposed to carbon nanotubes reported an 18.3% increase in telomere length and a 35.2% increase in mitochondrial DNA copy number in peripheral blood.
  • Evidence on cytotoxicity and genotoxicity was more limited, and the authors stated there was no consensus yet.
• The authors' conclusion: The authors concluded that the danger of carbon nanotubes to human health urgently needs a new, case-by-case evaluation. They called for a repository of biological samples from exposed workers and a system for monitoring these workers' health.
• Limitations the authors state:
  • Carbon nanotube exposure in workers has not been completely characterized.
  • Epidemiological studies used widely varying instruments for sampling and analysis, and had few participants.
  • The authors stated that data on the carcinogenicity of carbon nanotubes are not yet available.

Topics

Medical terms in this study, explained in our Lexicon: IARC, Carcinogenic, Mesothelioma, Oxidative Stress, Fibrosis, Reactive Mesothelial Hyperplasia.

Related studies

• Carcinogenicity of fluoro-edenite, silicon carbide fibres and whiskers, and carbon nanotubes — Y. Grosse, D. Loomis, et al. (2014)
• Genotoxicity and carcinogenicity risk of carbon nanotubes — S. Toyokuni (2013)
• Biocompatibility and Carcinogenicity of Carbon Nanotubes as Biomaterials — K. Aoki, N. Saito (2020)
• 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)
• Respiratory toxicity of multi-wall carbon nanotubes — J. Muller, F. Huaux, et al. (2005)
• Review of carbon nanotubes toxicity and exposure--appraisal of human health risk assessment based on open literature — K. Aschberger, H.J. Johnston, et al. (2010)

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