Fiber localization and its relationship to lung reaction in rats after chronic inhalation of chrysotile asbestos

Our plain-English summary of Fiber localization and its relationship to lung reaction in rats after chronic inhalation of chrysotile asbestos, by K.E. Pinkerton, P.C. Pratt, A.R. Brody, et al (The American Journal of Pathology, 1984).

The study

• Authors: K.E. Pinkerton, P.C. Pratt, A.R. Brody, J.D. Crapo
• Journal: The American Journal of Pathology
• Published: 1984;117(3):484-98
• Cited by: 68 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Inhalation of chrysotile asbestos fibers causes interstitial lung disease in animals and man. For examination of the anatomic localization of inhaled asbestos and its relationship to alveolar tissue responses of the lung during and after chronic exposure, male and female Fischer 344 rats were exposed to aerosolized chrysotile for 7 hours/day, 5 days/week for 3 or 12 months. A number of exposed animals were kept in filtered air for an additional 12 months. Lung tissue from randomly selected animals in each group was studied by morphometric analysis of electron micrographs. Our findings show that during exposure to asbestos fibers, macrophages and alveolar epithelial cells contain statistically significant amounts of asbestos and are associated with histologic changes indicating marked epithelial injury. Increased amounts of fibers are also localized in the lung interstitium with continued exposure to asbestos and are associated with a progressive interstitial fibrotic reaction. Following cessation of exposure, macrophages and epithelial cells are cleared of fibers and resolve toward normal proportions. However, significant clearance of fibers from the lung interstitium does not occur after cessation of exposure, and there is a continuing process of fibrogenesis. These data provide new insights related to the pathogenesis of diffuse lung disease and the role each alveolar tissue compartment plays in the early and late phases of the disease.

In plain English

This was an animal experiment in Fischer 344 rats. Male and female rats breathed aerosolized Jeffrey Mine chrysotile asbestos for 7 hours a day, 5 days a week, while control rats breathed filtered air. Eight rats per group were examined after 3 or 12 months of exposure, or after 12 months of exposure plus 12 months in filtered air. The authors used electron microscopy to measure how much asbestos sat in each major tissue compartment of the alveolar region (the air-sac part of the lung) and how those compartments changed. After 3 months, alveolar macrophages (scavenger cells) held about 60 percent of the asbestos. Exposure increased lung tissue volume and thickened the alveolar walls, and all 16 rats exposed for 12 months showed bronchiolar metaplasia. After exposure stopped, macrophages and alveolar lining (epithelial) cells largely cleared fibers, but fiber amounts in the interstitium did not change significantly. The fibrotic reaction there persisted but did not significantly progress. One year after exposure ended, about 90 percent of the remaining asbestos was in the interstitium. The authors noted that the exposure levels were substantially higher than those allowed at work.

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 with control and exposed groups, using morphometric (measurement-based) analysis of electron micrographs of lung tissue
• Who was studied: Male and female Fischer 344 rats from the Charles River Laboratory. Of 170 rats, 10 were killed for a health check and 160 were divided into control and exposure groups. Four animals of each sex (8 per group) were examined from the control and exposure chambers at 3 months, at 12 months, and 12 months after the end of 12 months of exposure. The work was done at Duke University, the Durham Veterans Administration Medical Center and NIEHS in North Carolina.
• Exposure: Aerosolized Jeffrey Mine chrysotile (greater than 96% chrysotile by volume), 7 hours/day, 5 days/week for 12 months. The mean chamber concentration was 11.36 mg/cu m and the mean respirable concentration was 9.06 mg/cu m. Control rats breathed filtered air.
• Main results:
  • After 3 months of exposure, alveolar macrophages in exposed rats nearly doubled in number and volume and contained almost two-thirds of the total asbestos fiber burden in the alveolar region (60 percent).
  • In exposed rats, the total volume of fibers in the noncellular interstitial matrix increased from 0.044 cu mm/both lungs at 3 months to 0.168 cu mm/both lungs at 12 months of exposure.
  • In rats kept 12 months in filtered air after 12 months of exposure, fiber density and total fiber volume in the alveolar interstitium did not change significantly. Interstitial cell number and interstitial matrix volume remained significantly elevated.
  • One year after exposure ended, two-thirds of the inhaled asbestos was still in the lungs, and 90% of it was in the interstitium, mainly in the noncellular portions.
  • In exposed rats, the interstitial fibrotic reaction persisted after exposure ended but did not significantly progress during the post-exposure period.
  • The epithelium of exposed rats was most altered after 12 months of exposure. Alveolar Type II cells showed ultrastructural abnormalities that did not resolve after 12 more months in filtered air, even though these cells contained very little asbestos.
  • All 16 rats exposed for 12 months (examined immediately or after 12 months' recovery) showed bronchiolar metaplasia. None of the control animals did. These areas were excluded from the measurements.
  • In exposed rats, the alveolar walls thickened, and the tissue component of the lung's diffusion capacity (a measure of gas exchange) decreased.
  • At 26 months of age, survival was 50% among rats that had been exposed to chrysotile and 60% among control rats. Most deaths resulted from renal disease, and none from pneumonia.
• The authors' conclusion: The authors concluded that epithelial injury largely resolved after exposure ended, while fibers in the interstitium were not removed. They found this failure of removal was associated with persistence of the interstitial fibrotic reaction (asbestosis). They stated that the mechanisms by which interstitial asbestos causes fibrotic disease require further study.
• Limitations the authors state:
  • The exposure levels were substantially higher than those allowed in occupational settings. They were chosen to produce disease in an animal with a relatively short life span.
  • Areas of metaplastic change were left out of the analysis, although they were probably the most intensely injured areas.
  • Fixed lung volume is not a physiologic measure, especially in abnormal lungs. Trapped gas in exposed lungs may have affected inflation.
  • Some macrophages counted in the alveolar air spaces may have been washed in from the airways when the fixative was instilled.

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

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Interstitial Lung Disease, Macrophage, Interstitial.

Related studies

• Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats — T.W. Hesterberg, W.C. Miiller, et al. (1994)
• Alveolar type II cell responses to chronic inhalation of chrysotile asbestos in rats — K.E. Pinkerton, S.L. Young, et al. (1990)
• The importance of fiber biopersistence and lung dose in determining the chronic inhalation effects of X607, RCF1, and chrysotile asbestos in rats — T.W. Hesterberg, G.A. Hart, et al. (1998)
• Reaction of rat lungs to inhaled chrysotile asbestos following acute and subchronic exposures — B.E. Barry, K.C. Wong, et al. (1983)
• Chronic inhalation toxicity of size-separated glass fibers in Fischer 344 rats — T.W. Hesterberg, W.C. Miiller, et al. (1993)
• Chronic mesothelial reaction and toxicity of potassium octatitanate fibers in the pleural cavity in mice and F344 rats — M. Yokohira, Y. Nakano-Narusawa, et al. (2016)

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