Estimates of carbon nanotube deposition in the lung: improving quality and robustness

Our plain-English summary of Estimates of carbon nanotube deposition in the lung: improving quality and robustness, by M.D. Wright, A.J. Buckley, R. Smith (Inhalation Toxicology, 2020).

The study

• Authors: M.D. Wright, A.J. Buckley, R. Smith
• Journal: Inhalation Toxicology
• Published: 2020;32(7):282-298
• Type of article: Review
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Carbon nanotube (CNT) in vivo inhalation studies are increasingly providing estimates of the quantity of material deposited in the lung, generally estimated using standard formulae and pulmonary deposition models. These models have typically been developed and validated using data from studies using sphere-like particles. Given the importance of particle morphology to pulmonary deposition, the appropriateness of such an approach was explored to identify any potential limitations. Aerosolized CNT particles typically form 'fiber-like' and/or 'broadly spherical' agglomerates. A review of currently used deposition models indicates that none have been directly validated against results for CNT, however, models for spherical particles have been extensively validated against a wide range of particle sizes and materials and are thus expected to provide reasonable estimates for most 'broadly spherical' CNT particles, although experimental confirmation of this would be of benefit, especially given their low density. The validation of fiber deposition models is significantly less extensive and, in general, focused on larger particles, e.g. asbestos. This raises concerns about the accuracy of deposition estimates for 'fiber-like' CNT particles and recommendations are made for future research to address this. An appreciation of the uncertainties on CNT deposition estimates is important for their interpretation and thus it is recommended that model sensitivity and uncertainty assessments be undertaken. Issues surrounding the measurement and derivation of model input data are also addressed, including instrument responses and particle density assessment options. Recommendations are also made for aerosol characterization to 'future-proof' CNT inhalation studies regarding advances in deposition modeling and toxicological understanding.

In plain English

This review looked at how scientists estimate the amount of carbon nanotube (CNT) material that settles in the lungs during animal inhalation studies. It asked whether lung deposition models, developed mainly with data for sphere-like particles, are suitable for CNT. Drawing on published workplace and laboratory studies, the authors reported that most airborne CNT particles are bent and tangled clumps rather than straight needles. They found no deposition model that had been checked against experimental data for CNT aerosols. Data used to check fiber models came mainly from fibers larger and thicker than typical fiber-like CNT, such as asbestos. The authors explained that, unlike asbestos, fiber-like CNT are expected to settle more by diffusion as they get thinner and shorter. In their own basic sensitivity check of one model (MPPD), ignoring the low density of clumped CNT could overestimate deposition of the smallest particles by a factor of 2 to 3 in humans and rats. The authors called for short-term animal studies to test the models, for studies of model uncertainty, and for fuller reporting of model inputs.

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 and lung deposition models, with a basic model sensitivity analysis by the authors
• Who was studied: No people or animals were studied directly. The review covered published studies of airborne CNT, mainly workplace exposure assessments and animal inhalation studies, and existing lung deposition models.
• Exposure: Airborne carbon nanotubes (single-walled and multi-walled), compared with asbestos fibers in size and deposition behavior
• Main results:
  • Most airborne CNT particles seen in real exposure situations were bent and tangled, forming low-density clumps
  • As far as the authors knew, none of the whole-lung deposition models had been validated against experimental deposition data for CNT aerosols
  • Fiber deposition data used for fiber models came mainly from fibers larger and thicker than typical fiber-like CNT, such as asbestos
  • Unlike asbestos, fiber-like CNT are expected to settle increasingly by diffusion as fiber diameter and length decrease
  • In the alveolar region, models predicted deposition efficiency for fiber-like CNT ranging from a few percent for the largest fibers to around 30% for the shortest and thinnest. Asbestos fibers deposit there mostly by aerodynamic mechanisms, at about 10 to 20%. The authors said these estimates should be regarded with caution.
  • In the authors' sensitivity analysis with the MPPD model, failing to account for the lower density of broadly spherical CNT could overestimate deposition efficiency for the smallest particles (below 100 nm) by a factor of 2 to 3 in humans and rats. The effect was less apparent for large particles.
• The authors' conclusion: The authors concluded that several things are needed: short-term animal studies to provide deposition data for testing the models (especially for fiber-like particles), systematic uncertainty studies, research on how measuring instruments perform with CNT, and full reporting of the models and input values used.
• Limitations the authors state:
  • CNT released bound within composite materials were not considered
  • Changes in lung deposition in people with conditions such as COPD or asthma were noted as somewhat beyond the scope of the review

Topics

Medical terms in this study, explained in our Lexicon: Deposition.

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