Mesotheliomata in rats after inoculation with asbestos and other materials

Our plain-English summary of Mesotheliomata in rats after inoculation with asbestos and other materials, by J.C. Wagner, G. Berry, V. Timbrell (British Journal of Cancer, 1973).

The study

• Authors: J.C. Wagner, G. Berry, V. Timbrell
• Journal: British Journal of Cancer
• Published: 1973;28(2):173-85
• Cited by: 247 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text
• In J-M's library: Johns-Manville's company medical library held a copy.

Abstract

Four experiments in which SPF Wistar rats were inoculated intrapleurally with asbestos or other materials are described. Mesotheliomata were observed in a considerable proportion of animals with all the samples of asbestos used and with a sample of brucite. A few were produced with synthetic aluminium silicate fibres and single ones with barium sulphate, glass powder and aluminium oxide. The risk of developing a mesothelioma at a given time after injection was approximately proportional to the dose. Of the UICC standard reference samples, crocidolite was the most carcinogenic and removal of the oils by benzene extraction did not alter the carcinogenicity of these samples. Chemical properties also seem unlikely to be the main factor producing mesotheliomata but the results support the hypothesis that the finer fibres are the more carcinogenic, and this is additional to the known aerodynamic advantage which the finer fibres have in penetrating to the periphery of the lung.

In plain English

In four experiments at the Medical Research Council's Pneumoconiosis Unit, the authors injected asbestos and other materials into the chest (pleural) cavity of specific pathogen-free Wistar rats between 1965 and 1969, and followed each until death or distress. Materials included chrysotile, crocidolite, amosite and anthophyllite, chrysotiles from eight Canadian mines, brucite (which also contained chrysotile), and non-asbestos materials including ceramic fibre, fibreglass and glass powder. 386 mesotheliomata occurred among the 1112 rats included. The risk of mesothelioma at a given time after injection was approximately proportional to dose. Of the UICC reference samples, crocidolite was the most carcinogenic, and removing oils with benzene made no significant difference (58 versus 56 tumours). Metal content of the Canadian chrysotiles showed no significant correlation with carcinogenicity. This study's fibreglass sample produced no mesotheliomata in 35 rats. Ceramic fibre, barium sulphate, glass powder and aluminium oxide produced occasional ones. The authors concluded chemical properties seemed unlikely to be the main factor and that finer fibres appeared more carcinogenic. They noted that injection is unlike human exposure and that a direct link to physical factors was not demonstrated.

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 experiments (four separate experiments) using intrapleural inoculation in rats
• Who was studied: Specific pathogen-free (SPF) Wistar rats bred at the MRC Pneumoconiosis Unit, Penarth. Inoculation took place between March 1965 and July 1969, and each rat was then kept until it died or appeared distressed. 1112 rats were included in the results after 13 could not be examined histologically.
• Exposure: Experiment 1 gave SFA chrysotile and crocidolite at 0.5, 1, 2, 4 and 8 mg per rat. Experiments 2 to 4 used 20 mg per rat of various materials: UICC amosite, anthophyllite, Canadian chrysotile, Rhodesian chrysotile and crocidolite (normal and benzene-extracted), Canadian chrysotiles from 8 mines, SFA chrysotile, and brucite (which also contained chrysotile). Non-asbestos materials were ceramic fibre (synthetic aluminium silicate), fibreglass, glass powder and aluminium oxide. Barium sulphate and saline were used as controls.
• Main results:
  • Across all experiments, 386 mesotheliomata occurred.
  • In the varying-dose experiment (SFA chrysotile and crocidolite), the risk of mesothelioma at a given time after injection was approximately proportional to the dose.
  • UICC reference samples: there were no significant differences between normal and benzene-extracted (oil-free) samples. There were 58 mesotheliomata with the extracted samples and 56 with the untreated samples.
  • Among the UICC samples, crocidolite was the most carcinogenic, followed in order by amosite, anthophyllite, Canadian chrysotile and Rhodesian chrysotile. The difference between the two chrysotiles was not significant.
  • Among the separate Canadian chrysotile samples, sample C (from British Columbia) was significantly the least carcinogenic (P less than 0.05). No other differences between the Canadian samples were detected.
  • Correlations between carcinogenicity and the content of iron, chromium, cobalt, nickel, scandium and manganese in the Canadian samples were not significant.
  • All the separate, more finely ground Canadian chrysotile samples were more carcinogenic than the composite UICC Canadian chrysotile.
  • The brucite sample was as carcinogenic as the Canadian chrysotile samples.
  • Non-asbestos materials produced only occasional mesotheliomata: ceramic fibre, barium sulphate, glass powder and aluminium oxide.
  • The particular fibreglass sample used in this study produced no mesotheliomata (0 of 35 rats with histology, Table IV).
  • With SFA chrysotile, 69% of rats in Experiment 2 and 64% in Experiment 4 developed mesotheliomata.
• The authors' conclusion: The authors concluded that chemical properties seem unlikely to be the main factor producing mesotheliomata, and that the results support the hypothesis that finer fibres are more carcinogenic. They also stated that a direct association with physical factors had not been demonstrated.
• Limitations the authors state:
  • Intrapleural inoculation may be criticized as unrealistic compared with human exposure.
  • The dose-relationship estimates were not very precise because there were few mesotheliomata.
  • Variation in results for the Canadian samples between experiments was mainly due to the small number of animals in each group.
  • A full quantitative analysis awaits techniques for complete size characterization of the materials.
  • A direct association between physical factors and mesothelioma development was not demonstrated.
  • Differences in carcinogenicity from the authors' earlier experiment could reflect a change in rat susceptibility or a change in the dust during storage.

Topics

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

Medical terms in this study, explained in our Lexicon: Brucite, Silicate, Mesothelioma, UICC, Crocidolite, Carcinogenic.

Related studies

• Mesotheliomas in rats following inoculation with acid-leached chrysotile asbestos and other mineral fibres — G. Monchaux, J. Bignon, et al. (1981)
• Mesotheliomas in rats following inoculation with asbestos — J.C. Wagner, G. Berry (1969)
• Effect of age at inoculation of asbestos on occurrence of mesotheliomas in rats — G. Berry, J.C. Wagner (1976)
• Pluripotential nature of mesotheliomata induced by inhalation of erionite in rats — N.F. Johnson, R.E. Edwards, et al. (1984)
• The effects of the inhalation of asbestos in rats — J.C. Wagner, G. Berry, et al. (1974)
• Chronic effects of dietary exposure to amosite asbestos and tremolite in F344 rats — E.E. McConnell, H.A. Rutter, et al. (1983)

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