Identifying the pulmonary hazard of high aspect ratio nanoparticles to enable their safety-by-design

Our plain-English summary of Identifying the pulmonary hazard of high aspect ratio nanoparticles to enable their safety-by-design, by K. Donaldson, F. Murphy, A. Schinwald, et al (Nanomedicine, 2011).

The study

• Authors: K. Donaldson, F. Murphy, A. Schinwald, R. Duffin, C.A. Poland
• Journal: Nanomedicine
• Published: 2011;6(1):143-56
• Type of article: Review
• Cited by: 124 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

High aspect ratio, or fiber-shaped, nanoparticles (HARNs) represent a growth area in nanotechnology as their useful properties become more apparent. Carbon nanotubes, the best known and studied of the HARNs are handled on an increasingly large scale, with subsequent potential for human inhalation exposure. Their resemblance to asbestos fibers precipitated fears that they might show the same type of pathology as that caused by asbestos and there is emerging evidence to support this possibility. The large number of other HARNs, including nanorods, nanowires and other nanofibers, require similar toxicological scrutiny. In this article we describe the unusual hazard associated with fibers, with special reference to asbestos, and address the features of fibers that dictate their pathogenicity as developed in the fiber pathogenicity paradigm. This paradigm is a robust structure:toxicity model that identifies thin, long, biopersistent fibers as the effective dose for fiber-type pathogenic effects. It is likely that HARNs will in general conform to the paradigm and such an understanding of the features that make fibers pathogenic should enable us to design safer HARNs.

In plain English

This article was a review, not a new study. The authors described what was known about lung hazards from fibers, especially asbestos, and asked whether high aspect ratio nanoparticles (HARNs) might behave the same way. HARNs include carbon nanotubes, nanowires and nanorods. They described the 'fiber pathogenicity paradigm', a model built from decades of research on asbestos and synthetic vitreous fibers. It identifies thin, long, biopersistent fibers as the dose that causes fiber-type disease. They summarized evidence that long fibers cannot be fully engulfed by lung scavenger cells (macrophages), and that fibers longer than the pleural drainage openings may be retained in the pleural space. They cited their group's earlier mouse study, in which long carbon nanotubes injected into the abdominal cavity caused persistent inflammation similar to long amosite asbestos. They also described an unpublished pleural-injection study with a similar result. In their own PubMed count, where the HARN category excluded carbon nanotubes, toxicity studies made up 6% of HARN publications. The authors concluded that HARNs will likely follow the paradigm, which should help in designing safer HARNs, though further research is needed.

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 article (narrative review of fiber and nanoparticle toxicology), with a PubMed count of publications by the authors
• Who was studied: No human or animal population was studied directly. The authors reviewed published research on asbestos, synthetic vitreous fibers and high aspect ratio nanoparticles, chiefly carbon nanotubes, including rodent experiments.
• Exposure: Asbestos fibers (chrysotile, amosite, crocidolite, tremolite and others), synthetic vitreous fibers, and high aspect ratio nanoparticles (nanotubes including single-walled and multiwalled carbon nanotubes, nanowires, nanorods)
• Main results:
  • The fiber pathogenicity paradigm, as described by the authors, identifies fiber width, length and biopersistence as the factors that determine whether a fiber is pathogenic. Thin, long, biopersistent fibers are the effective dose for fiber-type effects.
  • The authors reported that long fibers (more than about 15 micrometers) cannot be fully engulfed by macrophages, while short fibers are effectively cleared.
  • The authors described clearance from the pleural space as length dependent. Fibers longer than the diameter of the drainage openings (stomata, approximately 3 to 10 micrometers) are caught at those openings and retained.
  • The authors cited their group's earlier study, in which 50 micrograms of carbon nanotubes were injected into the abdominal cavity of mice. Long, fiber-like carbon nanotubes produced a strong, persistent inflammatory response similar to long amosite asbestos. Short carbon nanotubes and short amosite (under 5 micrometers) did not.
  • The authors described a study from their laboratory, not yet published at the time (manuscript in preparation), in which multiwalled carbon nanotubes were injected into the pleural space of animals and followed for up to 6 months. Acute inflammation followed by progressive fibrosis and granuloma development occurred only with the long multiwalled carbon nanotubes and the long amosite asbestos control.
  • The authors cited a 2-year rat study by Muller and colleagues that found no carcinogenic response to multiwalled carbon nanotubes injected into the abdominal cavity, with crocidolite as the positive control. The carbon nanotubes used in that study were all shorter than 0.7 micrometers.
  • In the authors' PubMed search, the HARN category counted nanofibers, nanowires, nanorods and nanotubes made of materials other than carbon, so it excluded carbon nanotubes. Publications in this category rose from 86 in 2000 to 1822 in 2009.
  • In the same PubMed count, toxicity studies made up 6% of publications in the HARN category (which excluded carbon nanotubes). They made up 19% of nanoparticle publications.
• The authors' conclusion: The authors concluded that HARNs are likely, in general, to conform to the fiber pathogenicity paradigm. In their view, understanding what makes fibers pathogenic should allow safer HARNs to be designed, for example short, thick or nonbiopersistent ones.
• Limitations the authors state:
  • The authors stated that further research is needed to confirm that all HARNs conform to the paradigm.
  • The authors stated that the fiber length above which frustrated phagocytosis occurs is not known exactly; they placed it somewhere between 10 and 20 micrometers.
  • The authors noted that no published study had yet reported HARN fibers moving into the pleural space after being placed in the lung.
  • The authors noted that the rodent peritoneal (abdominal cavity) injection model is not a model of inhalation exposure.
  • The authors noted that it is currently difficult to measure the dimensions of very thin fibers in workplace air.

Topics

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

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