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

Our plain-English summary of 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, by D.M. Bernstein, B. Toth, R.A. Rogers, et al (Toxicology and Applied Pharmacology, 2020).

The study

• Authors: D.M. Bernstein, B. Toth, R.A. Rogers, D.E. Kling, P. Kunzendorf, J.I. Phillips, H. Ernst
• Journal: Toxicology and Applied Pharmacology
• Published: 2020;387:114856
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This 90-day repeated-dose inhalation toxicology study of brake-dust (BD) (brakes manufactured with chrysotile) in rats provides a comprehensive understanding of the biokinetics and potential toxicology in the lung and pleura. Exposure was 6 h/d, 5d/wk., 13wks followed by lifetime observation (~20 % survival). Control groups included a particle control (TiO2), chrysotile, commercial crocidolite and amosite asbestos. Aerosol fiber distributions of the chrysotile, crocidolite and amosite were similar (fibers L > 20 μm/cm3: chrysotile-Low/High 29/72; crocidolite 24; amosite 47 fibers/cm3; WHO-fibers/cm3: chrysotile-Low/High 119/233; crocidolite 181; amosite 281 fibers/cm3). The number of particles/cm3 in the BD was similar to that in the chrysotile, crocidolite & amosite exposures (BD 470-715; chrysotile 495-614; crocidolite 415; amosite 417 particles/cm3). In the BD groups, few fibers L > 20 μm were observed in the lungs at the end of exposure and no fibers L > 20 μm at 90d post exposure. In the chrysotile groups, means of 204,000 and 290,000 fibers(L > 20 μm)/lung were measured at 89d. By 180d, means of 1 and 3.9 fibers were counted on the filter corresponding to 14,000 and 55,000 fibers(L > 20 μm)/lung. In the crocidolite and amosite groups mean lung concentrations were 9,055,000 and 11,645,000 fibers(L > 20 μm)/lung at 89d. At 180d the means remained similar with 8,026,000 and 11,591,000 fibers(L > 20 μm)/lung representing 10-13% of the total lung fibers. BAL determined the total number of macrophages, lymphocytes, neutrophils, eosinophils, epithelial-cells and IL-1 beta, TNF-alpha and TGF-beta. At the moderate aerosol concentrations used in this study, neutrophil counts increased ~5 fold in the amphibole asbestos exposure groups. All other groups and parameters showed no important differences at these exposure concentrations. The exposure and lung burden results provide a sound basis for assessing the potential toxicity of the brake dust in comparison to the TiO2 particle control and the chrysotile, crocidolite and amosite asbestos control groups. The BAL results provide an initial indication of the differential response. Part 2 presents the presentation and discussion of the histopathological and confocal microscopy findings in this study through 90 days post exposure.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

In plain English

This experiment in male Wistar rats reported interim lung fiber counts through day 180, three months after exposure ended, and lung-washing results to nine months after exposure ended. Rats breathed, nose-only, for 13 weeks one of: filtered air, dust from grinding chrysotile-containing brake shoes (three doses), titanium dioxide, chrysotile (two doses), crocidolite or amosite. The brake dust air held under 1 fiber longer than 20 μm per cm3, versus 29 and 72 for chrysotile, 24 for crocidolite and 47 for amosite. In the brake dust groups, few long fibers were found in the lungs at the end of exposure and none at 180 days. In the chrysotile groups, long fibers fell from 204,000 and 290,000 per lung to 14,000 and 55,000. In the crocidolite and amosite groups, the 9,055,000 and 11,645,000 long fibers per lung at the end of exposure showed no statistically significant reduction by 180 days. Lung washings showed statistically significant falls in macrophages and rises in neutrophils only in the crocidolite and amosite groups. The authors concluded the exposure and lung burden results provide a sound basis for assessing the brake dust's potential toxicity.

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: Animal experiment: a 90-day repeated-dose (sub-chronic) inhalation toxicology study in rats with planned lifetime follow-up. This paper (Part 1) gives interim results on aerosol exposure, on lung fiber burdens through day 180, and on bronchoalveolar lavage (lung washing) up to 9 months after exposure ended.
• Who was studied: Young adult male Wistar rats, 8 weeks old at the start, in nine exposure groups, studied at Citoxlab Hungary. Lavage was done on three rats per group at 45 and 89 days and at 3 and 9 months after exposure. The total number of rats per group is not stated in the text.
• Exposure: Nose-only inhalation, 6 h/day, 5 days/week, for 13 weeks. Groups and concentrations:
• filtered air
• brake dust from grinding chrysotile-containing drum brake shoes (made for mid-1960s Chevrolet Impala cars; about 30% chrysotile by area) at 0.20, 0.34 and 0.67 mg/m3
• titanium dioxide particle control at 0.70 mg/m3
• chrysotile 7H19 at 0.27 and 0.64 mg/m3
• crocidolite (Voorspoed mine) at 1.28 mg/m3
• amosite at 2.32 mg/m3
• Main results:
  • Exposure air, brake dust groups: fewer than 1 fiber longer than 20 μm per cm3.
  • Exposure air, fibers longer than 20 μm per cm3: chrysotile groups 29 and 72; crocidolite 24; amosite 47.
  • Exposure air, WHO-defined fibers per cm3: brake dust groups 2, 5 and 7; chrysotile groups 119 and 233.
  • Exposure air, brake dust groups: 470 particles per cm3 in the low-dose group to 715 particles per cm3 in the high-dose group.
  • Lungs, brake dust groups: means of 0 to 3524 fibers longer than 20 μm per lung at the end of exposure (89 days). No long fibers were seen in any brake dust group 90 days after exposure ended.
  • Lungs, chrysotile groups: means of 204,000 and 290,000 fibers longer than 20 μm per lung at 89 days fell to 14,000 and 55,000 per lung at 180 days.
  • Lungs, chrysotile groups: 7% (low dose) and 19% (high dose) of the long fibers present at the end of exposure remained three months later.
  • Lungs, crocidolite and amosite groups: means of 9,055,000 and 11,645,000 fibers longer than 20 μm per lung at 89 days.
  • Lungs, crocidolite and amosite groups: no statistically significant reduction by three months after exposure. Means of 8,026,000 and 11,591,000 long fibers per lung remained, 10 to 13% of all lung fibers.
  • Lung washings, crocidolite and amosite groups: statistically significant rises in neutrophils of 545% and 480% on day 45 and 246% and 223% on day 89. The amosite group also had a 307% rise on day 180.
  • Lung washings: statistically significant falls in macrophages in the crocidolite group (days 45 and 89) and the amosite group (days 45, 89 and 180). The falls were 9 and 10% on day 45, 9 and 8% on day 89, and 7% for amosite on day 180.
  • Lung washings: no other measures were statistically significant in any group at any time point.
• The authors' conclusion: The authors concluded that the exposure and lung burden results provide a sound basis for assessing the potential toxicity of the brake dust in comparison with the titanium dioxide, chrysotile, crocidolite and amosite groups. They also concluded that the lavage results give an initial indication of a differing response. Tissue findings are reported in Part 2.
• Limitations the authors state:
  • Crocidolite and amosite were planned to have similar concentrations of fibers longer than 20 μm, but counting logistics at study start-up led to a difference between them.
  • Electron microscope fiber counts were not available quickly, so exposures were set higher than calculated.
  • Stable particle size measurements were not possible for the pure fiber groups.
  • The share of respirable long fibers in the low-dose brake dust group was based on only 7 fibers.
  • These are interim results. They cover the period through 180 days (3 months after exposure), with a stated exception for one data set (the lavage results extend to 9 months after exposure).

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Chrysotile, Crocidolite.

Medical terms in this study, explained in our Lexicon: Dose-response relationship, Pleura, Chrysotile, Crocidolite, Amosite, Macrophage, Amphibole Asbestos.

Related studies

• Evaluation of the 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 2: Histopathological examination, Confocal microscopy and collagen quantification of the lung and pleural cavity — D.M. Bernstein, B. Toth, et al. (2020)
• Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to chrysotile or crocidolite asbestos in a 28-day quantitative inhalation toxicology study — D.M. Bernstein, B. Toth, et al. (2018)
• Final results from a 90-day quantitative inhalation toxicology study evaluating the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos: Histopathological examination, confocal microscopy and collagen quantification of the lung and pleural cavity — D.M. Bernstein, B. Toth, et al. (2021)
• Evaluation of the fate and pathological response in the lung and pleura of brake dust alone and in combination with added chrysotile compared to crocidolite asbestos following short-term inhalation exposure — D.M. Bernstein, R.A. Rogers, et al. (2015)
• The pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite asbestos following short-term inhalation exposure: interim results — D.M. Bernstein, R.A. Rogers, et al. (2010)
• Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure — D.M. Bernstein, R.A. Rogers, et al. (2011)

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