The long term fibrogenic effects of chrysotile and crocidolite asbestos dust injected into the pleural cavity of experimental animals

Our plain-English summary of The long term fibrogenic effects of chrysotile and crocidolite asbestos dust injected into the pleural cavity of experimental animals, by J.M. Davis (British Journal of Experimental Pathology, 1970).

The study

• Author: J.M. Davis
• Journal: British Journal of Experimental Pathology
• Published: 1970;51(6):617-27
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Free full text
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 003290).

Abstract

In a series of experiments on the effects of chrysotile and crocidolite asbestos dust injected into the pleural cavities of experimental animals, the following results were obtained. Both dusts produced large granulomas in all the species used, but the histological patterns of these lesions varied. In guinea-pigs both chrysotile and crocidolite produced granulomas that consisted mainly of giant cells, mixed with a few macrophages and fibroblasts, and each granuloma was surrounded by a distinct capsule of fibrous tissue. In mice and rats, however, relatively few giant cells were present in the asbestos granulomas, and the lesions consisted only of macrophages with some fibroblasts. In these 2 species the granulomas were not surrounded by a distinct capsule. In all cases the granulomas were eventually replaced by masses of fibrous tissue, but the time sequence of this change was variable. In guinea-pigs the granulomas remained cellular for 6-12 months, and after this period there was evidence of the invasion of the lesions by fresh macrophages which rephagocytosed dust left behind by the death of previous cells. In mice some areas of the granulomas remained cellular for 12-15 months, but others were completely fibrosed by 6-9 months. In rats fibrosis of the asbestos granulomas was very rapid, and most lesions consisted of old almost acellular collagen by 3-4 months. In all species a few animals showed massive pleural fibrosis outside the main granulomas. In some cases this appeared to be associated with an infection spreading from the lung tissue, but in others no such association could be traced.

In plain English

In this animal experiment, the author injected chrysotile or crocidolite asbestos dust into the chest (pleural) cavity of guinea-pigs and rats (25 mg) and mice (10 mg). Animals were examined 7 days to 4 years later; the article does not give animal numbers. At autopsy, every injected animal had granulomas (clusters of inflammatory cells around dust) or fibrous lesions, and both dusts produced large granulomas in all three species. Guinea-pig granulomas were mostly giant cells inside a fibrous capsule; rat and mouse granulomas had few giant cells and seldom a capsule. The granulomas were gradually replaced by fibrous scar tissue: most rat lesions by 3-4 months (chrysotile) or 4-5 months (crocidolite), most guinea-pig chrysotile lesions within 18 months. Some mouse and guinea-pig crocidolite areas stayed cellular much longer. A few animals developed massive pleural fibrosis, some with signs of spreading lung infection. Old guinea-pig chrysotile lesions often calcified, resembling human calcified pleural plaques. All rats died of pneumonia by 13 months. The author concluded that the pleural response resembled the lung's qualitatively, though pleural lesions could be much larger, and that species differed markedly.

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: intrapleural injection of asbestos dust, with light and electron microscope examination of the resulting lesions over time
• Who was studied: Guinea-pigs, rats and mice (numbers not stated), at the Department of Pathology, Cambridge University. Animals were examined from 7 days to 4 years after injection. The oldest guinea-pigs survived 49 months and the oldest mice 25 months. All rats had died by 13 months.
• Exposure: Chrysotile and crocidolite asbestos dust injected into the lower right pleural cavity: 25 mg in 1 ml distilled water for guinea-pigs and rats, and 10 mg for mice. The dust was mostly fiber bundles under 5 microns long and 0.1-1 micron in diameter, supplied by Dr. P. F. Holt of Reading University.
• Main results:
  • At autopsy, granulomas or fibrous lesions were found in the pleural cavities of all injected animals.
  • Both chrysotile and crocidolite produced large granulomas in all the species used, but the microscopic pattern of these lesions varied.
  • Chrysotile in guinea-pigs: the granulomas consisted mainly of giant cells. In rats and mice few giant cells formed, and the lesions were mostly closely packed mononuclear cells.
  • Chrysotile in guinea-pigs: in most animals the granulomas were replaced by fibrous tissue within 18 months, though clumps of giant cells were found in some lesions as late as 2 years.
  • Chrysotile in mice: some parts of the granulomas remained cellular even in the oldest animals.
  • Chrysotile in rats: by 3-4 months most lesions had been replaced by almost acellular collagen.
  • Crocidolite in guinea-pigs: unlike with chrysotile, the whole lesion rarely became acellular, and large cellular areas were found in some animals 3 years after injection.
  • Crocidolite in mice: in some areas of the granulomas, the cells remained alive for up to 18 months after injection.
  • Crocidolite in rats: by 4-5 months after injection most lesions had been converted to fibrous tissue.
  • In the guinea-pig chrysotile section, 6 animals had extremely extensive pleural fibrosis. Of these, 3 died 14 days after injection, apparently from intrapleural haemorrhage. The others died at 5, 9 and 11 months, with evidence of lung infection that had spread to the pleura.
  • In a few mice there was very rapid fibrosis throughout the pleural cavity between 9 and 12 months. Some of these cases showed evidence of spreading lung infection and others did not.
  • Old fibrosed granuloma sites in guinea-pigs frequently calcified from about 18 months after injection, resembling calcified pleural plaques in human asbestosis. No calcification was seen in mouse or rat lesions.
  • With crocidolite, small areas of calcification were found in only 2 guinea-pigs, at 28 and 36 months after injection.
  • Asbestos bodies formed in large numbers in guinea-pig chrysotile granulomas. A few were found in mice, and none in rat granulomas.
  • In guinea-pigs and mice, dust freed by cell death was taken up again by new macrophages from about 6 to 18 months. This was not seen in rats.
  • The author noted that the experimental asbestos lesions so far produced in lung tissue had been relatively small, while those in the pleural cavity could be very large.
• The authors' conclusion: The author concluded that, qualitatively at least, the tissue response to asbestos in the pleural cavity is similar to that in lung tissue, while noting that pleural lesions could be much larger. The author also concluded that examining large pleural granulomas of known age showed marked differences between species. The author suggested that repeated uptake of freed dust by new macrophages may be important in deciding how much fibrosis eventually develops.
• Limitations the authors state:
  • All rats died by 13 months after injection because of a pneumonia outbreak. The author included the rat results because no changes had been seen in rat lesions between 6 and 13 months.
  • No systematic electron microscope study was possible for crocidolite, so crocidolite observations relied on light microscopy alone.
  • The dust was sterilized by heating in water. The author could only hope that chemical changes to the asbestos were kept to a minimum.
  • In 2 guinea-pigs injected with chrysotile, the needle had penetrated the lung, and these animals were excluded.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Fibrogenic, Chrysotile, Crocidolite, Pleural Cavity, Granuloma, Macrophage, Fibroblast, Fibrosis.

Related studies

• Experimental studies on the effects of heated chrysotile asbestos and automobile brake lining dust injected into the body cavities of mice — J.M. Davis, S.W. Coniam (1973)
• Epithelial outgrowths from lung tissue following intrapleural injection of asbestos dust in experimental animals — J.M. Davis (1971)
• The calcification of fibrous pleural lesions produced in guinea-pigs by the injection of chrysotile asbestos dust — J.M. Davis (1971)
• 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 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)
• Tumorigenicity of cellulose fibers injected into the rat peritoneal cavity — R.T. Cullen, B.G. Miller, et al. (2002)

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