The effects of the inhalation of asbestos in rats

Our plain-English summary of The effects of the inhalation of asbestos in rats, by J.C. Wagner, G. Berry, J.W. Skidmore, et al (British Journal of Cancer, 1974).

The study

• Authors: J.C. Wagner, G. Berry, J.W. Skidmore, V. Timbrell
• Journal: British Journal of Cancer
• Published: 1974;29(3):252-69
• Cited by: 461 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

Two experiments in which SPF Wistar rats were exposed by inhalation to dust clouds of the UICC standard reference samples for periods of between one day and 2 years are described. All the samples of asbestos produced asbestosis which continued to progress after removal from exposure but only a little fibrosis was observed in control rats. Lung tumours, ranging in severity from adenomata to squamous carcinomata, were produced by all samples but in the controls there were only a few adenomata and none of the more serious tumours. Of the 20 tumours which metastasized, 16 occurred after exposure to one or other of the 2 chrysotile samples. In addition, a total of 11 mesotheliomata occurred, 4 of which were with crocidolite and 4 with Canadian chrysotile. Two of the mesotheliomata occurred with only one day's exposure to asbestos. There was a positive association between asbestosis and lung tumours.

In plain English

In this animal experiment from the Medical Research Council's Pneumoconiosis Unit in Penarth, Glamorgan, SPF Wistar rats in two experiments breathed dust clouds of five UICC standard reference asbestos samples (amosite, anthophyllite, crocidolite, Canadian chrysotile and Rhodesian chrysotile). Exposure ran 7 hours a day, 5 days a week, for periods from one day to 2 years, and unexposed control rats were included. Every sample produced asbestosis, which kept progressing after exposure ended; amosite produced the least. Lung tumours were found in 247 exposed rats, while controls had only a few adenomata. Of 20 tumours that spread, 16 followed chrysotile exposure. Eleven mesotheliomata occurred, 4 each with crocidolite and Canadian chrysotile. Two followed only one day of exposure, and all but one were pleural. Rats with lung tumours had significantly more asbestosis than those without. Far less chrysotile than amphibole remained in the lungs, yet the authors found no evidence of less tumour production or less asbestosis with chrysotile. They noted that the UICC chrysotile samples were finer than chrysotile used in industry in the past. They concluded that the method is a valid tool for studying the biological effects of asbestos.

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 inhalation experiments in rats, with random allocation to asbestos types, exposure lengths and unexposed control groups
• Who was studied: Caesarean-derived SPF Wistar rats bred at the MRC Pneumoconiosis Unit, Llandough Hospital, Penarth, Glamorgan. There were 1013 rats in all, most aged 5 to 7 weeks at the start, with roughly equal numbers of males and females. Experiment 1 began in 1967 and Experiment 2 ran from January 1969 to January 1971.
• Exposure: Respirable dust clouds of the five UICC standard reference samples: amosite, anthophyllite and crocidolite (amphiboles), and Canadian and Rhodesian chrysotile. Exposure was 7 hours a day, 5 days a week. Dust concentrations were similar across groups, and dose was varied by exposure length: one day (7 hours), 3 months, 6 months, 12 months or 24 months.
• Main results:
  • Asbestosis increased with exposure for all dusts. In rats exposed for 6 months, it continued to progress during the following 18 months without exposure, for all asbestos types.
  • Amosite gave the least asbestosis among the five samples.
  • Rats exposed for one day had no more asbestosis than control rats.
  • Lung tumours were observed in 247 of the asbestos-exposed rats.
  • Among control rats, 7 of 84 survivors in Experiment 1 had adenomata, and none of 42 control rats in Experiment 2 had lung tumours.
  • Of the 20 tumours that metastasized, 16 followed exposure to a chrysotile (10 Rhodesian, 6 Canadian). Three others were with crocidolite and one with anthophyllite.
  • A total of 11 mesotheliomata occurred, 4 with crocidolite and 4 with Canadian chrysotile.
  • Two mesotheliomata occurred after only one day's exposure: one with amosite after 715 days and one with crocidolite after 551 days.
  • The mesothelioma after 3 months' crocidolite exposure was peritoneal. All the others were pleural.
  • Overall, rats with lung tumours had significantly more asbestosis than rats without (P less than 0.001).
  • In the one-day exposure groups (rats surviving at least 600 days), lung tumours occurred in 6 of 157 rats without asbestosis (3.8%), compared with 11 of 44 rats with minimal or slight asbestosis (25%).
  • Much less chrysotile than amphibole dust was retained in the lungs, and chrysotile lung content did not show the same clear increase with dose.
  • The authors found very little indication that exposure affected overall survival of the rats.
  • For tumours at sites other than the lung, using a larger set of controls, the association with ovarian tumours was weak and not significant, and there was no support for an association with male genito-urinary tumours.
• The authors' conclusion: The authors concluded that the results corresponded in several respects to findings in humans, and that this experimental method is a valid tool for investigating the biological effects of asbestos. They also reported no evidence of less carcinogenicity or less asbestosis with chrysotile than with the amphiboles.
• Limitations the authors state:
  • The UICC chrysotile samples were finer than chrysotile used in industry in the past.
  • The lack of significance for ovarian and male genito-urinary tumours could have been due to the relatively small control group.
  • There were insufficient data to reach firm conclusions on whether the asbestosis-tumour relationship differed between dusts.
  • Overcrowding among males in the 24-month groups led to some rats being removed early and counted in the 12-month groups.

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: UICC, Fibrosis, Chrysotile, Crocidolite.

Related studies

• Persistent effects of Libby amphibole and amosite asbestos following subchronic inhalation in rats — S.H. Gavett, C.U. Parkinson, et al. (2016)
• Acute and chronic effects of intraperitoneal injection of two types of asbestos in rats with a study of the histopathogenesis and ultrastructure of resulting mesotheliomas — M.L. Shin, H.I. Firminger (1973)
• Mesotheliomata in rats after inoculation with asbestos and other materials — J.C. Wagner, G. Berry, et al. (1973)
• The sizes, shapes, and mineralogy of asbestos structures that induce lung tumors or mesothelioma in AF/HAN rats following inhalation — D.W. Berman, K.S. Crump, et al. (1995)
• 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)
• Accumulation of mixed mineral dusts in the lungs of rats during chronic inhalation exposure — C.H. McMillan, A.D. Jones, et al. (1989)

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