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

Our plain-English summary of 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, 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):214-229
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series of studies to address fundamental questions on the toxicology of naturally occurring asbestos and related mineral fibers after inhalation exposure. A prototype nose-only exposure system was previously developed and validated. The prototype system was expanded to a large-scale exposure system in this study for conducting subsequent in vivo rodent inhalation studies of Libby amphibole (LA) 2007, selected as a model fiber.

Results: The exposure system consisting of six exposure carousels was able to independently deliver stable LA 2007 aerosol to individual carousels at target concentrations of 0 (control group), 0.1, 0.3, 1, 3, or 10 mg/m3. A single aerosol generator was used to provide aerosol to all carousels to ensure that exposure atmospheres were chemically and physically similar, with aerosol concentration as the only major variable among the carousels. Transmission electron microscopy (TEM) coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis of aerosol samples collected at the exposure ports indicated the fiber dimensions, chemical composition, and mineralogy were equivalent across exposure carousels and were comparable to the bulk LA 2007 material.

Conclusion: The exposure system developed is ready for use in conducting nose-only inhalation toxicity studies of LA 2007 in rats. The exposure system is anticipated to have applicability for the inhalation toxicity evaluation of other natural mineral fibers of concern.

In plain English

This paper described the building and testing of an inhalation exposure system for later rat studies. The tests reported here measured the airborne material, not animals. The test material was Libby amphibole 2007 (LA 2007), from Libby, Montana. A single aerosol generator supplied LA 2007 aerosol to five nose-only carousels set to 0.1, 0.3, 1, 3 or 10 mg/m3, and a sixth control carousel received filtered air. In three days of three-hour tests, daily mean concentrations were within 20% of target except for one data point. Electron microscopy found average fiber lengths of 4.42 to 4.88 μm and widths of 0.35 to 0.40 μm in the aerosols, compared with 4.55 μm and 0.29 μm in the bulk material. Winchite was the main mineral type in both, with richterite and tremolite also predominant. The authors concluded the system was ready for nose-only studies of LA 2007 in rats. They noted that operators had to remain in the exposure room throughout testing and that LA 2007 fiber sizes vary naturally.

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: Methods-development study: design, building and characterization testing of a nose-only inhalation exposure system for later rodent studies. No animals were exposed in the tests reported.
• Who was studied: No human or animal subjects. The tested system had six exposure carousels with 96 ports each. Aerosol generation tests ran over three consecutive days, three hours per day.
• Exposure: Libby amphibole 2007 (LA 2007) aerosol from a single generator, supplied to five exposure carousels at target concentrations of 0.1, 0.3, 1, 3 or 10 mg/m3. A sixth carousel was a control exposed to HEPA-filtered air. A sample of about 10 kg of bulk material was provided by the US EPA.
• Main results:
  • In all exposure carousels, daily mean aerosol concentrations were within 20% of target except for one data point. Table 1 shows 131% of target for the 0.1 mg/m3 carousel on the first test day.
  • Concentration variability (relative standard deviation) was above 30% on Day 1, which the authors attributed to concentration adjustment. Variability improved on Day 2.
  • In the 1, 3 and 10 mg/m3 carousels, the mass median aerodynamic diameter was 2.5 to 2.6 μm and the geometric standard deviation was 2.7 to 2.9. The authors described this as within the respirable size range for rodents.
  • Aerosol samples from the exposure ports had average fiber lengths of 4.42 to 4.88 μm and average widths of 0.35 to 0.40 μm. The bulk material had 4.55 μm length and 0.29 μm width.
  • The average aspect ratio (length to width) was about 15 for each set of aerosol samples. Table 3 gives 19 for the bulk sample.
  • The element oxide composition of the aerosol fibers was comparable to the bulk sample and to results from a US Geological Survey report.
  • Winchite was the major mineral type in both bulk and aerosol samples: 52.0 to 66.3% in aerosol samples versus 49.0% in bulk. Winchite and tremolite were slightly higher in aerosol samples, and richterite was lower: 10.7 to 17.7% in aerosol samples versus 28.7% in bulk.
  • Air flow variability across the 96 ports was 5% or less for all six carousels. The underlying data were not shown.
  • In the laboratory, no personal breathing zone or exposure room air sample exceeded the action level while the engineering controls were in place.
• The authors' conclusion: The authors concluded that the exposure system was ready for nose-only inhalation toxicity studies of LA 2007 in rats. They expected it to be applicable to other natural mineral fibers.
• Limitations the authors state:
  • Because of the system's size and complexity, operators in protective equipment had to stay in the exposure room for the entire test to run and adjust it.
  • Particle size (MMAD) was not measured for the 0.1 and 0.3 mg/m3 carousels because of their low concentrations.
  • Fiber dimensions varied widely, which the authors attributed to natural variability in the LA 2007 material despite mixing.
  • Fiber sizes were measured with different technology and counting rules than in an earlier EPA study of LA 2007, so the two are not directly comparable.

Topics

Medical terms in this study, explained in our Lexicon: Mineral Fiber, Libby amphiboles, naturally occurring asbestos (NOA), Transmission Electron Microscopy (TEM), Selected Area Electron Diffraction (SAED), Fiber Dimensions, Mineralogy.

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