Mass and number of fibres in the pathogenesis of asbestos-related lung disease in rats

Our plain-English summary of Mass and number of fibres in the pathogenesis of asbestos-related lung disease in rats, by J.M. Davis, S.T. Beckett, R.E. Bolton, et al (British Journal of Cancer, 1978).

The study

• Authors: J.M. Davis, S.T. Beckett, R.E. Bolton, P. Collings, A.P. Middleton
• Journal: British Journal of Cancer
• Published: 1978;37(5):673-88
• Cited by: 170 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Five groups of rats were treated by inhalation for 12 months, with the U.I.C.C. preparations of the 3 main commercially used asbestos types, chrysotile, crocidolite and amosite. The experiment was designed so that the effects of both fibre mass and fibre number could be examined. The results indicated that chrysotile dust caused far more lung fibrosis than either amphibole type even when the fibre numbers in the dust clouds were similar. All malignant pulmonary neoplasms found during this study occurred in animals treated with chrysotile. The fibre-number calculations used for the generation of dust clouds were evaluated using the parameters recommended by the Health and Safety Executive in 1976, by which all fibres over 5 microgram long are counted using a phase-contrast light microscopy. When fibre-length distributions were calculated using a scanning electron microscope, however, it was found that the chrysotile clouds used in this study contained many more fibres over 20 microgram long than either of the amphibole clouds. The results, therefore, support previous suggestions that long asbestos fibres are more dangerous than short. They also indicate that neither a single mass standard, nor the present fibre-number standards are satisfactory.

In plain English

In this animal inhalation experiment, five groups of 48 rats breathed clouds of U.I.C.C. reference samples of chrysotile, crocidolite or amosite asbestos for 7 hours a day, 5 days a week, over one year. Twenty rats served as unexposed controls. Three clouds had equal mass (10 mg/m3). A 2 mg/m3 chrysotile cloud and a 5 mg/m3 crocidolite cloud were meant to match amosite in fibre number, counting fibres longer than 5 µm by light microscope. Chrysotile caused far more lung fibrosis than either amphibole, including at the lower, fibre-matched dose. All malignant lung tumours occurred in chrysotile-exposed rats. Two mesotheliomas were found: one pleural (crocidolite, 5 mg/m3) and one abdominal (chrysotile, 2 mg/m3). Electron microscopy showed the chrysotile clouds had many more fibres over 20 µm long. Much less chrysotile than amphibole was retained in the lungs. The authors concluded that the results support suggestions that long fibres are more dangerous than short ones. They also concluded that neither a single mass standard nor the current fibre-number standards were satisfactory. They noted that the amosite cloud's high fibre count partly spoilt the fibre-number comparison.

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 comparing asbestos types at equal fibre mass and at (intended) equal fibre number
• Who was studied: White SPF rats of the Han strain, Institute of Occupational Medicine, Edinburgh: 5 exposed groups of 48 animals each, aged 3 months at the start, plus 20 control rats. The experiment was ended 860 days after the start of dusting.
• Exposure: U.I.C.C. samples of amosite, chrysotile A (described in the discussion as U.I.C.C. Rhodesian chrysotile) and crocidolite. Equal-mass clouds of 10 mg/m3 were used for all three. The equal-fibre-number clouds were chrysotile at 2 mg/m3 and crocidolite at 5 mg/m3. Exposure was 7 h/day, 5 days a week, for 224 days over one year.
• Main results:
  • Measured mean fibre concentrations (fibres longer than 5 µm) in the equal-number chambers were 550 fibres/ml for amosite, 390 for chrysotile and 430 for crocidolite. The amosite chamber was significantly different from the other two.
  • Chrysotile caused far more lung fibrosis than either amphibole type.
  • At the final kill, the low (2 mg/m3) chrysotile cloud had produced more interstitial fibrosis than any of the amphibole clouds.
  • All malignant lung tumours occurred in chrysotile-treated rats. In the 10 mg/m3 chrysotile group (40 animals) there were 7 adenomas, 6 adenocarcinomas and 2 squamous carcinomas. In the 2 mg/m3 chrysotile group (42 animals) there were 6 adenomas, 1 adenocarcinoma and 1 squamous carcinoma. The amphibole groups had only adenomas (1 or 2 per group), and controls had no lung tumours.
  • Tumour counts for the 10 mg/m3 chrysotile group (40 animals): 7 adenomas, 6 adenocarcinomas, 2 squamous carcinomas, 0 pleural and 0 peritoneal mesotheliomas.
  • Only 2 mesotheliomas were found. One was a pleural tumour in a crocidolite-treated rat. The other was an abdominal (peritoneal) mesothelioma in a chrysotile-treated rat.
  • Scanning electron microscopy showed the chrysotile clouds contained many more fibres over 20 µm long than either amphibole cloud.
  • For the 10 mg/m3 clouds, the lung content of chrysotile at the end of dusting was only 15 to 16% of the amosite and crocidolite content.
  • No laryngeal tumours were found.
• The authors' conclusion: The authors concluded that the results support previous suggestions that long asbestos fibres are more dangerous than short ones. They also concluded that neither a single mass standard nor the present fibre-number standards are satisfactory.
• Limitations the authors state:
  • The comparison on a fibre-number basis was partly spoilt by the higher-than-intended fibre count of the amosite cloud.
  • The fibre-number versus mass correlation used to set the equal-number clouds had a large uncertainty.
  • Interstitial fibrosis figures at 12 months were based on only 4 animals per group and were not considered to show significant differences.
  • Mesotheliomas are rare, so animal studies have not produced enough of them for a statistically meaningful comparison between asbestos types.
  • Differences in tumours outside the lung were not significant, given the small group sizes.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Crocidolite, Amosite, Fibrosis, Amphibole Group, Neoplasm.

Related studies

• Mass, number and size of lung fibres in the pathogenesis of asbestosis in sheep — P. Sébastien, R. Bégin, et al. (1990)
• Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide — K. Donaldson, R.E. Bolton, et al. (1988)
• Experimental studies in rats on the effects of asbestos inhalation coupled with the inhalation of titanium dioxide or quartz — J.M. Davis, A.D. Jones, et al. (1991)
• Pathogenesis of experimentally induced asbestos mesothelioma in rats — L.A. Vasilieva, L.N. Pylev, et al. (1998)
• An overload hypothesis for pulmonary clearance of UICC amosite fibres inhaled by rats — R.E. Bolton, J.H. Vincent, et al. (1983)
• The effects of intermittent high asbestos exposure (peak dose levels) on the lungs of rats — J.M. Davis, S.T. Beckett, et al. (1980)

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