Experimental studies on the effects of heated chrysotile asbestos and automobile brake lining dust injected into the body cavities of mice

Our plain-English summary of Experimental studies on the effects of heated chrysotile asbestos and automobile brake lining dust injected into the body cavities of mice, by J.M. Davis, S.W. Coniam (Experimental and Molecular Pathology, 1973).

The study

• Authors: J.M. Davis, S.W. Coniam
• Journal: Experimental and Molecular Pathology
• Published: 1973;19(3):339-53
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy.

Abstract

A series of experiments with mice involving the intrapleural injection of chrysotile asbestos dust heated to varying temperatures up to 1000°C suggests that the physical shape of the dust particles is more important than the altered chemistry of the dust. Chrysotile heated to no more than 400°C produced dust samples containing many long fibers, and these samples resulted in large pleural granulomas. Chrysotile heated to more than 400°C produced dust containing mainly particles of low aspect ratio, and these produced very small granulomas. The initial size of the granulomas was very closely related to the final degree of fibrosis found in the animals and, therefore, chrysotile heated to 400°C or less was much more fibrogenic than when it was heated to higher temperatures. A sample of automobile brake lining dust was found to contain very little recognizable chrysotile, and consisted mainly of particles with a low aspect ratio. When this dust was injected into the pleural cavities of mice it produced very small granulomas and little fibrosis.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

In plain English

The authors injected Cassiar chrysotile asbestos, unheated or heated to 400, 600, 800 or 1000°C, and automobile brake lining dust into the body cavities of Balb/C mice. Each dust sample went to a batch of 25 mice, and tissues were examined from 7 days to 1 year later. Of 25 mice given 250 mg of chrysotile heated to 1000°C into the peritoneal (abdominal) cavity, seven died within 48 hours, and the rest recovered. After 10 mg injected into the pleural (chest) cavity, no mice died within the first 2 weeks and none showed toxic effects. Unsieved chrysotile heated to no more than 400°C produced large granulomas and more fibrosis. Dust heated to 800 or 1000°C produced small granulomas. The brake lining dust contained very little recognizable chrysotile and produced the smallest granulomas and little fibrosis. No tumors were found. The authors concluded that particle shape mattered more than altered chemistry. They stated this did not settle whether brake lining dust is linked to mesothelioma, as the study ended at 1 year and mice develop few such tumors after such injections.

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: injection of dust samples into the pleural or peritoneal cavities of mice, with light and electron microscopy of the tissues
• Who was studied: Balb/C mice at the Institute of Occupational Medicine, Edinburgh, Scotland, in batches of 25 per dust sample (sieved and unsieved samples each), killed at intervals from 7 days to 1 year after injection; article received February 1973
• Exposure: High-grade Cassiar chrysotile asbestos heated for 4 hours to 400, 600, 800 or 1000°C, plus unheated chrysotile, ground and either sieved or unsieved. Doses were 250 mg intraperitoneally of chrysotile heated to 1000°C (one series) and single 10 mg intrapleural doses of each sample. The study also used 10 mg intrapleural doses of automobile brake lining dust taken from the rear brake drums of two test vehicles; the linings had contained chrysotile, binding resins, chromium oxide and metallic aluminium granules.
• Main results:
  • Of 25 mice given 250 mg of chrysotile heated to 1000°C into the peritoneal cavity, seven had died by 48 hours after showing toxic effects within 24 hours.
  • The remaining mice in the 250 mg series showed signs of disability for several days but all recovered, and none died within 6 months.
  • With 10 mg doses of heated chrysotile or brake lining dust, no animals died within the first 2 weeks after injection and none showed toxic effects.
  • With unheated chrysotile or chrysotile heated to 400°C, unsieved dust produced much larger granulomas than sieved dust at the same dose, often with adhesions.
  • Chrysotile heated to 800 or 1000°C produced granulomas that were always small relative to the dose, with no adhesions, whether sieved or unsieved.
  • Total collagen (fibrosis) after a 10 mg dose was closely related to granuloma size. Unsieved samples heated to no more than 400°C were therefore more fibrogenic than sieved samples or samples heated to higher temperatures.
  • Collagen formed faster in the first weeks in granulomas from chrysotile heated to 800°C or more. By 6 months this difference was no longer apparent.
  • Under the electron microscope, the brake lining dust consisted mainly of dark masses containing no recognizable chrysotile. Particles containing apparently normal chrysotile crystals made up much less than 1% of the dust.
  • Brake lining dust injected into the pleural cavity produced smaller granulomas than any of the asbestos samples, and the amount of collagen produced was never very great.
  • Dead macrophages were found more often with chrysotile heated to 800°C or more and with brake lining dust than with normal chrysotile. They never made up more than a few percent of the total.
  • No tumors were found in mice injected with heated chrysotile or brake lining dust.
  • The authors calculated that the 10 mg mouse dose corresponds to about 30 g for a 12 stone man. They judged it very unlikely that the acute toxic effect of heated chrysotile needs serious consideration for general atmospheric pollution.
• The authors' conclusion: The authors concluded that the physical shape of the dust particles was more important than the altered chemistry in determining the degree of fibrosis. Chrysotile heated to 400°C or less, which kept many long fibers, was much more fibrogenic than chrysotile heated to higher temperatures.
• Limitations the authors state:
  • The authors stated that the study did not settle with certainty whether brake lining dust is associated with mesothelioma.
  • The experiments were mainly concerned with the initial tissue response and were ended after 1 year.
  • Few mesotheliomas are produced by intrapleural asbestos injection in mice (unlike rats), so prolonged experiments of this type would not have given significant results.
  • Because very little of the brake lining dust was recognizable as chrysotile, its results are not directly comparable with those for heated chrysotile.

Mines named here

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

• Cassiar mine, British Columbia

All asbestos mines

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: Chrysotile, Brake Lining, Granuloma, Aspect Ratio (Length-to-diameter ratio), Fibrosis, Fibrogenic.

Related studies

• The long term fibrogenic effects of chrysotile and crocidolite asbestos dust injected into the pleural cavity of experimental animals — J.M. Davis (1970)
• 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)
• 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)
• 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)
• Assessing specific causation of mesothelioma following exposure to chrysotile asbestos-containing brake dust — M.D. Freeman, S.S. Kohles (2012)
• Simple quantitative analysis of asbestos body using the sediment of formalin injected into surgically resected lung cancers — Y. Sakai, C. Ohbayashi, et al. (2010)

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