Reaction of rat lungs to inhaled chrysotile asbestos following acute and subchronic exposures

Our plain-English summary of Reaction of rat lungs to inhaled chrysotile asbestos following acute and subchronic exposures, by B.E. Barry, K.C. Wong, A.R. Brody, et al (Experimental Lung Research, 1983).

The study

• Authors: B.E. Barry, K.C. Wong, A.R. Brody, J.D. Crapo
• Journal: Experimental Lung Research
• Published: 1983;5(1):1-21
• Cited by: 53 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Inhalation of asbestos fibers can cause fibrotic and neoplastic diseases in the lung. The early in vivo interactions between fibers and lung tissue that initiate these diseases have received little study. Male and female Fischer 344 rats were placed in inhalation chambers and exposed to 9.06 +/- 1.83 mg/m3 (average respirable mass) of chrysotile asbestos for 1 hr, 1 day, 7 hr/day for 5 days, or 5 days/week for 3 months. Qualitative examination of the tissue showed that, after 1 day, fibers were found not only in the alveolar macrophages, but also in the epithelium and interstitium of the alveolar region. After 3 months, numerous fibers were present in the epithelium and interstitium. Morphometric analysis of this tissue showed that these compartments were also the most significantly changed as a result of asbestos exposure. The majority of epithelial changes were attributable to a 57% increase in the number of type II cells and a 90% increase in their average cell volume. The interstitial cell population increased 58% with a 40% increase in the average cell volume. There was no significant increase in the volume of noncellular interstitium. A morphologic characterization of the interstitial cells showed that interstitial macrophages accounted for almost the entire increase in this population and that 88% of the fiber-containing cells were macrophages. Several interstitial macrophages contained membrane-bound inclusions which were shown by x-ray energy spectrometry to be microcalcifications. They were composed of rings of calcium phosphate granules around asbestos fibers. These microcalcifications may indicate sublethal cell injury caused by the presence of asbestos fibers in the cell cytoplasm. Fibers which enter but do not kil alveolar cells may be an essential component for the pathogenesis of lung disease caused by asbestos inhalation.

In plain English

In this animal experiment, Fischer 344 rats breathed chrysotile asbestos from Quebec in inhalation chambers at an average respirable mass of 9.06 plus or minus 1.83 mg/m3. Male rats were exposed for 1 hour, 7 hours, or 7 hours a day for 5 days. Four male and four female rats were exposed 7 hours a day, 5 days a week for 3 months, alongside matched air-exposed controls. After 1 hour, fibers were seen only in the air spaces. In rats examined 16 hours after a 7-hour exposure, fibers were occasionally found inside type I epithelial cells and interstitial cells. Little acute inflammation was seen after 5 days. After 3 months, compared with controls, type II epithelial cells rose 57% in number. Interstitial cells rose 58%, from 149 million to 235 million, almost entirely due to interstitial macrophages, and 88% of fiber-containing interstitial cells were macrophages. A 27% rise in non-cellular interstitium was not statistically significant. Some interstitial macrophages contained rings of calcium phosphate around fibers. The authors concluded that fibers entering and accumulating in alveolar wall cells may cause changes essential to fibrotic and pulmonary disease.

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 inhalation experiment in rats, with qualitative light and electron microscopy at four exposure times and morphometric (quantitative microscopic) analysis after 3 months
• Who was studied: Fischer 344 rats from Charles River Laboratory. In the acute study, 6 male rats were exposed for 1 hour and killed immediately. Another 6 male rats were exposed for 7 hours and killed 16 hours later. A further 12 male rats were exposed 7 hours a day for 5 days and killed on the sixth day. There were 8 control animals. In the subchronic study, 4 male and 4 female rats were exposed for 3 months, with 8 matched controls.
• Exposure: Grade 4 chrysotile asbestos from Quebec (Plastibest-20, Jeffrey Mine), aerosolized at an average respirable mass of 9.06 plus or minus 1.83 mg/m3. Approximately 92% of fibers were less than 10 micrometers long, and the mean diameter was 0.29 micrometers. Exposures lasted 1 hour, 7 hours, 7 hours a day for 5 days, or 7 hours a day, 5 days a week for 3 months.
• Main results:
  • Rats exposed for 1 hour: no changes were seen in lung tissue, and fibers were found only in the air spaces.
  • Rats exposed for 7 hours and then kept 16 hours in air: fibers were occasionally found in type I epithelial cells and interstitial cells, and rarely in an endothelial cell.
  • Rats exposed for 5 days: few polymorphonuclear leukocytes were seen, and the authors interpreted this as little acute inflammatory response.
  • Rats exposed for 3 months, compared with controls: type II epithelial cells rose 57% in number with a 90% increase in average cell volume. The share of alveolar surface they covered went from 3% to 7%.
  • Rats exposed for 3 months: total interstitial cells increased 58%, from 149 million to 235 million, and mean interstitial cell volume increased 40%.
  • Rats exposed for 3 months: interstitial macrophages increased fivefold, from about 22 million to 113 million, accounting for almost the entire increase in interstitial cells. Fibroblasts decreased from about 100 million to 85 million.
  • Rats exposed for 3 months: asbestos fibers were found in 7% of all interstitial cells. Of these fiber-containing cells, 88% were interstitial macrophages and the remainder were fibroblasts.
  • Rats exposed for 3 months: plasma cells rose from about 0.4% of interstitial cells in controls to 4%, and none contained asbestos fibers.
  • Rats exposed for 3 months: alveolar macrophages increased 88%, from 24 to 45 million cells, with no significant change in mean cell volume.
  • Rats exposed for 3 months: the volume of noncellular interstitium increased 27%, but this was not statistically significant because of large animal-to-animal variability.
  • Rats exposed for 3 months: harmonic mean thickness of the air-blood barrier increased 23%, from 0.36 to 0.44 micrometers.
  • Rats exposed for 3 months: Masson's trichrome staining showed denser collagen staining in thickened areas near terminal bronchioles, and a slight increase in collagen in the distal alveolar region.
  • Rats exposed for 3 months: some interstitial macrophages contained membrane-bound inclusions. X-ray analysis showed these were rings of calcium phosphate around a chrysotile fiber (microcalcifications). No true asbestos bodies were found.
  • Rats exposed for 3 months: in one instance, a small cluster of fibers was found inside the nucleus of a type II epithelial cell.
• The authors' conclusion: The authors concluded that fibers which enter and accumulate in the cells of the alveolar septa may cause changes essential for the pathogenesis of fibrotic and pulmonary disease. They also suggested that the microcalcifications in healthy-appearing cells indicate that fibers may cause sublethal cell injury.
• Limitations the authors state:
  • It was often difficult to tell whether fibers were truly free in the cell cytoplasm or enclosed in a membrane, partly because of tears in the embedding resin next to fibers.
  • Fibers in the epithelium, interstitium and capillaries after 5 days were relatively infrequent, so the volume of fibers in each tissue compartment was not quantified.
  • Large animal-to-animal variability meant the 27% increase in noncellular interstitium did not reach statistical significance.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Jeffrey mine, Asbestos, Quebec

All asbestos mines

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile, Alveolar Macrophage, Epithelium, Asbestos Exposure, Interstitial, Macrophage.

Related studies

• Fiber localization and its relationship to lung reaction in rats after chronic inhalation of chrysotile asbestos — K.E. Pinkerton, P.C. Pratt, et al. (1984)
• Progressive lung cell reactions and extracellular matrix production after a brief exposure to asbestos — L.Y. Chang, L.H. Overby, et al. (1988)
• Exposure to low levels of ozone results in enhanced pulmonary retention of inhaled asbestos fibers — K.E. Pinkerton, A.R. Brody, et al. (1989)
• Persistent effects of Libby amphibole and amosite asbestos following subchronic inhalation in rats — S.H. Gavett, C.U. Parkinson, et al. (2016)
• Impact of acute and subchronic asbestos exposure on some parameters of antioxidant defense system and lung tissue injury — A. Kaiglová, Z. Kováciková, et al. (1999)
• Changes in numbers and dimensions of chrysotile asbestos fibers in lungs of rats following short-term exposure — V.L. Roggli, A.R. Brody (1984)

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