Experimental asbestosis. The development of lung cancer in rats with pulmonary deposits of chrysotile asbestos dust

Our plain-English summary of Experimental asbestosis. The development of lung cancer in rats with pulmonary deposits of chrysotile asbestos dust, by P. Gross, R.T. DeTreville, E.B. Tolker, et al (Archives of Environmental Health, 1967).

The study

• Authors: P. Gross, R.T. DeTreville, E.B. Tolker, M. Kaschak, M.A. Babyak
• Journal: Archives of Environmental Health
• Published: 1967;15(3):343-55
• Cited by: 72 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 001481).

In plain English

This animal experiment at the Industrial Hygiene Foundation, Mellon Institute, Pittsburgh, was designed to study asbestosis. 131 male white rats breathed hammer-milled Canadian chrysotile asbestos dust six hours a day, five days a week, for up to 62 weeks, at an average of 86 mg/cu m. Of these, 70 first had lye (sodium hydroxide) put into the windpipe to impair dust clearance from the lungs. Another 64 rats had chrysotile injected into the windpipe. Of 91 rats living 16 months or longer, 28 (31%) had primary malignant lung tumors, counting one pleural mesothelioma and three adenocarcinomas the authors called questionable but probable. Rates were 48% of 31 lye-treated inhalation rats, 24% of 41 inhalation rats without lye, and 16% of 19 injected rats. Control rats had no lung cancer apart from spontaneous lymphoblastoma. No tumor-bearing rat had diffuse asbestosis. Milling raised the dust's nickel, cobalt and chromium content. The authors concluded that the results experimentally confirmed a cause-and-effect relationship between chrysotile dust and lung cancer. They proposed that trace metals from milling were involved, which they said needed further study.

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: rats exposed to chrysotile dust by inhalation in a chamber, or by injection into the windpipe (intratracheal injection), compared with unexposed control rats
• Who was studied: Male white rats at the Industrial Hygiene Foundation, Mellon Institute, Pittsburgh. The inhalation chamber held 131 rats: 70 treated with intratracheal sodium hydroxide and 61 not treated. A further 64 rats received intratracheal chrysotile injections. Controls were 30 untreated rats, 15 rats given sodium hydroxide without asbestos, and 10 rats given intratracheal water. Tumor rates were calculated for rats surviving 16 months or longer: 72 from the chamber and 19 from the injection group. Study dates are not stated.
• Exposure: Canadian chrysotile asbestos, ball-milled and then hammer-milled so that much of the dust was ultramicroscopic. Chamber concentrations were 42 to 106 mg/cu m in the first year, 67 to 146 mg/cu m in the second year, and 86 mg/cu m on average. The injection group received 3.5 mg doses suspended in 1 ml water, from one to six injections per rat.
• Main results:
  • The earliest lung cancer was found in a rat that died 16 months after chrysotile exposure began.
  • Of all 91 rats surviving 16 months or longer, 31% (28 rats) had primary malignant lung tumors. This count excludes spontaneous lymphoblastoma but includes one malignant pleural mesothelioma and three questionable but probable adenocarcinomas.
  • Of the 28 rats with malignant lung tumors, 25 were in the inhalation group, a prevalence of 35% among the 72 inhalation survivors.
  • In the intratracheal injection group, 3 rats had lung cancer, a prevalence of 16% among 19 survivors.
  • Among inhalation rats that also had lye applied to the windpipe, 15 had lung cancer, a prevalence of 48% among 31 survivors.
  • Among inhalation rats without lye treatment, 10 had lung cancer, a prevalence of 24% among 41 survivors.
  • The tumors included 17 certain and 3 questionable but probable adenocarcinomas, 7 fibrosarcomatous tumors, 4 squamous cell cancers, and one malignant mesothelioma of the pleura. Some rats had more than one type.
  • No control rat had lung cancer other than spontaneously occurring lymphoblastoma.
  • No tumor-bearing rat had diffuse asbestosis. Asbestotic involvement was multifocal, with normal or near-normal lung tissue between the affected areas.
  • Hammer milling raised the trace-metal content of the chrysotile dust by 82% for nickel, 145% for cobalt and 34% for chromium.
• The authors' conclusion: The authors concluded that the development of lung cancer in rats with chrysotile deposits confirmed experimentally a cause-and-effect relationship between chrysotile dust exposure and lung cancer. They proposed that cancer production in this study appeared to involve trace metals (nickel, chromium, cobalt) introduced during hammer milling. They also wrote that the higher cancer rate in lye-treated rats underlined the importance of the airways' clearance mechanism.
• Limitations the authors state:
  • Some lung lesions were hard to diagnose. A few were classed only as questionable but probably correct, and intermediate lesions between cancer and atypical metaplasia were fairly common.
  • The authors said the trace-metal finding needed to be validated by further studies.
  • The authors were not certain that the dust used in an earlier rat study, which found no lung cancer, had a lower trace-metal content than their own dust.

Topics

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

Medical terms in this study, explained in our Lexicon: Lung Cancer, Chrysotile.

Related studies

• Pulmonary and systemic immunoregulatory changes during the development of experimental asbestosis — M. Rola-Pleszczynski, S. Gouin, et al. (1984)
• Changes in pulmonary surfactant and phosphatidylcholine metabolism in rats exposed to chrysotile asbestos dust — T.D. Tetley, R.J. Richards, et al. (1977)
• Experimental lung tumors following specific intrabronchial application of chrysotile asbestos. Longitudinal light and electron microscopic investigations in rats — E. Fasske (1988)
• Chrysotile-induced asbestosis: changes in the free cell population, pulmonary surfactant and whole lung tissue of rats — T.D. Tetley, P.M. Hext, et al. (1976)
• 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)
• Experimental lesions in rats corresponding to advanced human asbestosis — J.M. Davis, R.E. Bolton, et al. (1986)

Browse more research in Archives of Environmental Health, or return to medical research.