Natural mineral fibers: conducting inhalation toxicology studies - part A: Libby Amphibole aerosol generation and characterization method development

Our plain-English summary of Natural mineral fibers: conducting inhalation toxicology studies - part A: Libby Amphibole aerosol generation and characterization method development, by A. Wang, A. Gupta, M.D. Grimm, et al (Inhalation Toxicology, 2023).

The study

• Authors: A. Wang, A. Gupta, M.D. Grimm, D.T. Pressburger, B.R. Sparrow, J.S. Richey, J.R. Shaw, K.E. Elsass, G.K. Roberts, P.L. Yao, M.D. Stout, B.J. Ellis, R.L. Ray
• Journal: Inhalation Toxicology
• Published: 2023;35(7-8):201-213
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Asbestos has been classified as a human carcinogen, and exposure may increase the risk of diseases associated with impaired respiratory function. As the range of health effects and airborne concentrations that result in health effects across asbestos-related natural mineral fiber types are not fully understood, the National Institute of Environmental Health Sciences has established a series of research studies to characterize hazards of natural mineral fibers after inhalation exposure. This paper presents the method development work of this research project.

Results: A prototype nose-only exposure system was fabricated to explore the feasibility of generating natural mineral fiber aerosol for in vivo inhalation toxicity studies. The prototype system consisted of a slide bar aerosol generator, a distribution/delivery system and an exposure carousel. Characterization tests conducted using Libby Amphibole 2007 (LA 2007) demonstrated the prototype system delivered stable and controllable aerosol concentration to the exposure carousel. Transmission electron microscopy (TEM) analysis of aerosol samples collected at the exposure port showed the average fiber length and width were comparable to the bulk LA 2007. TEM coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis further confirmed fibers from the aerosol samples were consistent with the bulk LA 2007 chemically and physically.

Conclusions: Characterization of the prototype system demonstrated feasibility of generating LA 2007 fiber aerosols appropriate for in vivo inhalation toxicity studies. The methods developed in this study are suitable to apply to a multiple-carousel exposure system for a rat inhalation toxicity testing using LA 2007.

In plain English

This paper described building and testing equipment for future rat inhalation studies. The authors built a prototype nose-only exposure system (an aerosol generator, delivery lines and a 24-port exposure carousel) and tested it with Libby Amphibole 2007 (LA 2007), a reference material representing Libby, Montana amphibole. It reports equipment tests, not health effects. Early tests delivered fibers about 45% shorter on average than the bulk material. The authors therefore halved a buffer chamber (11 L to 5.5 L), changed its airflow direction, and gently brushed the material through a coarser 750-μm sieve. In five daily 3-hour runs at a target of 10 mg/m3, daily mean concentrations were within 20% of target and variability stayed under 15%. Average airborne fiber lengths were 4.44 to 4.79 μm and widths 0.28 to 0.36 μm, compared with about 5.76 μm and 0.33 μm for the bulk material. Electron diffraction and chemical analysis found the airborne fibers consistent with the bulk material. The authors concluded that the system showed it was feasible to generate LA 2007 aerosols appropriate for inhalation toxicity studies.

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: Method development and engineering characterization study of an aerosol generation and nose-only exposure system. No animal or human results are reported.
• Who was studied: No human or animal subjects. The study tested a prototype system built by Battelle with a single 24-port nose-only exposure carousel, designed to be expanded to multiple carousels for rat studies.
• Exposure: Libby Amphibole 2007 (LA 2007) aerosol, described as mixed minerals, primarily winchite and richterite with a small amount of tremolite. The material was sieved, then generated for 3 hours per day over five consecutive days at a target concentration of 10 mg/m3.
• Main results:
  • In initial testing, before modifications, the average fiber length in aerosol samples at the exposure ports was approximately 45% shorter than in the bulk LA 2007 material.
  • To reduce long-fiber loss, the buffer chamber was halved in size from 11 L to 5.5 L and its airflow was redirected from horizontal to vertical. A 100-μm sieve was replaced with a 750-μm sieve, and the material was brushed through gently.
  • In 3-hour tests, sieved LA 2007 gave a measured concentration of 11.6 mg/m3 with a real-time monitor relative standard deviation of 12%. Un-sieved LA 2007 gave 10.0 mg/m3 with 19% (Table 1). The authors judged sieving necessary.
  • Aerosol made from un-sieved LA 2007 had a higher average fiber width (0.61 μm, versus 0.32 μm for sieved; Table 2), which the authors took to imply fiber bundles were present.
  • Over the five-day test, daily mean concentrations ranged from 82% to 108% of the 10 mg/m3 target (Table 3), all within 20% of target. Temporal variability was less than 15%, with the highest value, 13%, on Day 3 because of a concentration adjustment.
  • Average fiber lengths in aerosol samples at the exposure ports ranged from 4.44 to 4.79 μm and widths from 0.28 to 0.36 μm. The bulk material measured approximately 5.76 μm in length and 0.33 μm in width. The authors judged these comparable.
  • Electron diffraction showed the aerosol and bulk material were highly crystalline and consistent with standards of Libby amphibole asbestos. Chemical (EDS) results for the aerosol were consistent across the five days and with the bulk LA 2007.
• The authors' conclusion: The authors concluded that the prototype nose-only exposure system demonstrated the feasibility of generating LA 2007 aerosols appropriate for in vivo inhalation toxicity studies.
• Limitations the authors state:
  • The authors noted that average fiber lengths of the sieved bulk and aerosol samples appeared different. They stated that the length ranges overlap and that the difference could be due to natural variability in LA 2007.

Topics

Medical terms in this study, explained in our Lexicon: Mineral Fiber, Libby amphiboles, Transmission Electron Microscopy (TEM), Fiber Length, Selected Area Electron Diffraction (SAED).

Related studies

• Natural mineral fibers: conducting inhalation toxicology studies-part B: development of a nose-only exposure system for repeat-exposure in vivo study of Libby amphibole aerosol — A. Wang, A. Gupta, et al. (2023)
• Evaluation of the exposure, dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 1: Experimental design, aerosol exposure, lung burdens and BAL — D.M. Bernstein, B. Toth, et al. (2020)
• Separation and characterization of respirable amphibole fibers from Libby, Montana — J.S. Webber, D.J. Blake, et al. (2008)
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• Chronic inhalation studies of man-made vitreous fibres: characterization of fibres in the exposure aerosol and lungs — T.W. Hesterberg, W.C. Miiller, et al. (1995)
• Standardized methods for preparation and bi-variate length & diameter counting/sizing of aerosol and tissue digestion fiber samples — D.M. Bernstein, P. Kunzendorf (2018)

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