The asbestos-carbon nanotube analogy: An update

Our plain-English summary of The asbestos-carbon nanotube analogy: An update, by A.B. Kane, R.H. Hurt, H. Gao (Toxicology and Applied Pharmacology, 2018).

The study

• Authors: A.B. Kane, R.H. Hurt, H. Gao
• Journal: Toxicology and Applied Pharmacology
• Published: 2018;361:68-80
• Type of article: Review
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Nanotechnology is an emerging industry based on commercialization of materials with one or more dimensions of 100 nm or less. Engineered nanomaterials are currently incorporated into thin films, porous materials, liquid suspensions, or filler/matrix nanocomposites with future applications predicted in energy and catalysis, microelectronics, environmental sensing and remediation, and nanomedicine. Carbon nanotubes are one-dimensional fibrous nanomaterials that physically resemble asbestos fibers. Toxicologic studies in rodents demonstrated that some types of carbon nanotubes can induce mesothelioma, and the World Health Organization evaluated long, rigid multiwall carbon nanotubes as possibly carcinogenic for humans in 2014. This review summarizes key physicochemical similarities and differences between asbestos fibers and carbon nanotubes. The "fiber pathogenicity paradigm" has been extended to include carbon nanotubes as well as other high-aspect-ratio fibrous nanomaterials including metallic nanowires. This paradigm identifies width, length, and biopersistence of high-aspect-ratio fibrous nanomaterials as critical determinants of lung disease, including mesothelioma, following inhalation. Based on recent theoretical modeling studies, a fourth factor, mechanical bending stiffness, will be considered as predictive of potential carcinogenicity. Novel three-dimensional lung tissue platforms provide an opportunity for in vitro screening of a wide range of high aspect ratio fibrous nanomaterials for potential lung toxicity prior to commercialization.

Copyright © 2018 Elsevier Inc. All rights reserved.

In plain English

This was a review comparing asbestos fibers with carbon nanotubes and other high-aspect-ratio fibrous nanomaterials (HARNs), including metallic nanowires. The review set out physicochemical differences: amphibole asbestos was described as highly biopersistent, positively charged and hydrophilic, chrysotile as slowly leaching magnesium ions and splitting into fibrils, and carbon nanotubes as typically negatively charged and hydrophobic, with tensile strength of 0.2 to 5 TPa against 1 to 4 GPa for asbestos. The authors recounted that a 2014 IARC working group, with no human epidemiological data, classified one carbon nanotube type, MWCNT-7, in group 2B and other multiwall and single wall types in group 3. The authors also summarized rodent studies in which long, rigid multiwall nanotubes injected into the peritoneum were more potent in inducing mesothelioma than thinner, flexible or curved ones, while a chronic inhalation study of MWCNT-7 in rats produced lung adenomas and carcinomas but no mesotheliomas. Using Euler buckling theory, the authors proposed mechanical bending stiffness as a fourth factor in the fiber pathogenicity paradigm, and proposed three-dimensional in vitro lung platforms for future testing.

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: narrative review of asbestos fibers and carbon nanotubes, with a proposed theoretical framework and testing strategy
• Who was studied: published laboratory, animal and in vitro literature on asbestos fibers, carbon nanotubes and other one-dimensional engineered high-aspect-ratio nanomaterials; no new subjects studied
• Exposure: asbestos fiber types (chrysotile; the amphiboles crocidolite, tremolite, amosite, actinolite, anthophyllite) compared with single wall and multiwall carbon nanotubes, metallic nanowires, metal oxide nanorods and other fibrous nanomaterials
• Main results:
  • The review reported that the 2014 IARC working group, lacking human epidemiological data, classified only MWCNT-7 in group 2B, with other multiwall and single wall carbon nanotubes in group 3
  • In a cited chronic inhalation assay in rats, MWCNT-7 produced lung adenomas and carcinomas at 0.2 and 2 mg/m3 but no mesotheliomas
  • In a cited rat peritoneal assay, very short, thin, tangled multiwall carbon nanotubes (about 11 nm diameter, 0.7 micrometres length) did not significantly increase mesotheliomas
  • The review reported that, in a rat peritoneal assay, long, rigid multiwall carbon nanotubes were more potent than thinner, flexible or curved ones in inducing mesothelioma
  • In a cited transtracheal intrapulmonary spraying study in rats, longer, rigid multiwall carbon nanotubes reached the parietal pleura and caused inflammation, fibrosis and focal mesothelial cell proliferation to a greater extent than shorter, thinner agglomerates
  • The authors contrasted the stiffness of fibers with lung and pleural tissue: asbestos 1 to 4 GPa and carbon nanotubes 0.2 to 5 TPa, against an alveolar elastic modulus of about 5 kPa and rat visceral pleura less than 1 kPa
  • The authors applied Euler buckling theory, in which the critical buckling load varies with the fourth power of diameter and inversely with the square of length, predicting that very long, thin HARNs buckle more easily
  • The review cited a threshold fiber length of 4 micrometres for pleural pathogenicity after direct intrapleural injection of nanowires or carbon nanotubes in mice
• The authors' conclusion: The authors concluded that mechanical bending stiffness should be added as a fourth parameter to the fiber pathogenicity paradigm, that most carbon nanotube varieties remain unclassifiable as carcinogens, and that tissue-engineered three-dimensional lung models combined with computational modeling could test structure-activity relationships predictive of potential carcinogenicity
• Limitations the authors state:
  • The authors stated that the route by which inhaled fibers or HARNs reach the pleural space is unknown
  • The authors stated that acute genotoxicity assays face conceptual and technical difficulties in predicting carcinogenicity, particularly for mesothelioma with its long latency
  • The authors stated that rodent inhalation assays are expensive and time consuming and that rodent-human anatomic differences, especially in the pleura, limit extrapolation
  • The authors noted that the variable properties of carbon nanotubes complicate interpretation of toxicity testing and prediction of carcinogenicity
  • The authors noted that findings with metallic nanowires after direct injection must be interpreted cautiously because nickel compounds themselves induce mesotheliomas in rats

Topics

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

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