Mesotheliomas in rats following inoculation with asbestos

Our plain-English summary of Mesotheliomas in rats following inoculation with asbestos, by J.C. Wagner, G. Berry (British Journal of Cancer, 1969).

The study

• Authors: J.C. Wagner, G. Berry
• Journal: British Journal of Cancer
• Published: 1969;23(3):567-81
• Cited by: 170 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

SPF and Standard rats were inoculated intrapleurally with samples of amosite, chrysotile, crocidolite (natural and with the oils extracted) and saline. With all types of asbestos an appreciable proportion of animals developed a mesothelioma but none of the saline controls developed such a tumour. The histological features of these tumours are described. The survival times have been analysed by sub-dividing the mortality into two independent components, one due to mesotheliomas and the other to natural causes. For all types of asbestos there was a rapid onset of mesotheliomas after an initial period during which none occurred, but this initial period was dependent on the type of asbestos, being longer for amosite than for chrysotile or crocidolite. No evidence was provided of any difference in effect between the natural and oil extracted forms of crocidolite.

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

In plain English

This was an animal experiment at the Medical Research Council's Pneumoconiosis Research Unit in Wales. Specific pathogen-free (SPF) Wistar rats and Standard rats were each given a single injection, intended for the pleural (chest) cavity, of 20 mg of amosite, chrysotile, crocidolite, crocidolite with its oils extracted, or silica, or of saline only. In some rats the dust went into the chest wall instead. The analysis included 572 SPF and 533 Standard rats, each kept until it died or appeared distressed. Every type of asbestos produced mesotheliomas, and no saline-injected control developed one. Amosite produced the fewest: 40% of SPF and 31% of Standard rats. With the other three asbestos samples, 59% to 69% of rats developed mesotheliomas, and amosite tumours took longer to appear. Extracting oils from crocidolite made no apparent difference, although the authors later learned that the extraction had not removed all oils. The authors called the high chrysotile result unexpected. They stated that injecting asbestos into the pleura is unrealistic compared with human experience and that inhalation results would be more valid.

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 (two parallel experiments, in SPF and Standard rats) using injections intended for the pleural cavity, with random allocation of rats to six treatments
• Who was studied: 600 SPF Wistar rats from Imperial Chemical Industries and a similar number of Standard rats from a dealer. 572 SPF and 533 Standard rats were included in the analysis. SPF rats were delivered November 1962 to May 1963 and Standard rats September 1963 to February 1964. The work took place at the Pneumoconiosis Research Unit, Penarth.
• Exposure: A single injection, intended for the pleural cavity, of 20 mg of one of the following: amosite (Transvaal), superfine chrysotile (Canadian mine), crocidolite (North West Cape), crocidolite with oils extracted by cyclohexane, or alkaline-washed silica. A control group received sterile saline only.
• Main results:
  • All asbestos types produced mesotheliomas, and no saline controls did. Amosite produced the fewest: 40% of SPF rats (38 of 96) and 31% of Standard rats (26 of 84).
  • SPF rats with mesothelioma: chrysotile 64% (61 of 96), crocidolite 59% (55 of 94), extracted crocidolite 59% (56 of 95). Standard rats: chrysotile 69% (62 of 90), crocidolite 68% (62 of 91), extracted crocidolite 64% (57 of 89).
  • With amosite, the time between injection and tumour development was longer than with the other asbestos types, in both experiments.
  • The presence or absence of oils in the crocidolite did not affect the incidence of tumours.
  • Mesotheliomas occurred equally in both sexes: of the 210 in SPF rats, 105 were in each sex, and of the 207 in Standard rats, 104 were in males and 103 in females.
  • The tumours were mainly in the chest. Only one animal had a tumour almost entirely in the peritoneum.
  • In both experiments, tubulo-papillary tumours were more frequent among mesotheliomas from chrysotile than from the other dusts (P less than 0.01).
  • Some injections did not reach the pleural cavity. Injection-site tumours showed that in those rats the dust had been deposited in the chest wall.
  • Injection-site tumours (17 in SPF rats, 2 in Standard rats) occurred only with amosite or the crocidolites. Among SPF rats in which the dust did not reach the pleural cavity, they occurred in 5 of 10 given amosite, 4 of 4 given crocidolite and 8 of 10 given extracted crocidolite.
  • About half of the silica-injected rats developed intrapleural tumours, which were histiocytic reticulum celled sarcomata rather than mesotheliomas.
• The authors' conclusion: The authors concluded that with all types of asbestos an appreciable proportion of animals developed a mesothelioma, while none of the saline controls did. They found the high incidence with chrysotile unexpected.
• Limitations the authors state:
  • Injecting asbestos into the pleura is unrealistic compared with human experience; results from inhalation would be more valid.
  • The 20 mg dose may be too high.
  • The delay between a mesothelioma developing and causing death was unknown, and no adjustment was made for it.
  • The cyclohexane extraction did not remove all oils from the crocidolite, and the dusts, stored in plastic bags, were later found to be contaminated.
  • The chrysotile was a specially prepared batch, and it was not yet known whether the findings are typical of chrysotile.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Amosite, Chrysotile, Crocidolite.

Related studies

• Effect of age at inoculation of asbestos on occurrence of mesotheliomas in rats — G. Berry, J.C. Wagner (1976)
• Mesotheliomas in rats following inoculation with acid-leached chrysotile asbestos and other mineral fibres — G. Monchaux, J. Bignon, et al. (1981)
• Mesotheliomata in rats after inoculation with asbestos and other materials — J.C. Wagner, G. Berry, et al. (1973)
• Pathogenesis of experimentally induced asbestos mesothelioma in rats — L.A. Vasilieva, L.N. Pylev, et al. (1998)
• The effects of the inhalation of asbestos in rats — J.C. Wagner, G. Berry, et al. (1974)
• 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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