The Comparative Effect of Three Chrysotile Dust Injection and Inhalation in Rats

Our plain-English summary of The Comparative Effect of Three Chrysotile Dust Injection and Inhalation in Rats, by J.C. Wagner, G. Berry, J.W. Skidmore, et al (1980).

The study

• Authors: J.C. Wagner, G. Berry, J.W. Skidmore, F.D. Pooley
• Published: BIOLOGICAL EFFECTS OF MINERAL FIBRES (J.C. WAGNER, EDITOR), LYON: IARC SCIENTIFIC PUBLICATIONS, VOLUME 30., PP 363-372 (1980)
• Type of article: Conference paper
• Our copy: from Johns-Manville's own medical library. The article is still under copyright, so we describe it here rather than post it.

In plain English

This was an animal experiment in Wistar rats. It compared three Canadian chrysotile asbestos samples: a specially ground superfine sample called SFA, the UICC Canadian chrysotile standard reference sample, and a grade 7 chrysotile from the Bells Mine. Italian cosmetic talc was also tested. All the materials contained impurities, and the grade 7 sample contained traces of tremolite. In the first experiment, groups of 48 rats had 20 mg of dust injected into the right pleural (chest) cavity. Mesotheliomas occurred with all three chrysotiles: 18 with SFA, 13 with grade 7 and five with UICC. Saline controls had none. In the second experiment, rats inhaled the dusts for 3, 6 or 12 months. The UICC chrysotile produced 20 lung tumours, 10 of them malignant. SFA produced 13, four malignant, including the only mesothelioma. Grade 7 produced nine, one malignant. The authors concluded that overtly similar chrysotile samples can differ in biological effect. They warned of clear dangers in extrapolating from injection experiments to humans.

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: an intrapleural injection experiment and an inhalation experiment in rats
• Who was studied: Barrier-protected, caesarian-derived Wistar rats. Injection experiment: 48 rats per material (24 of each sex), aged 8 to 14 weeks, plus 48 saline-injected controls. Inhalation experiment: 96 rats per dust (48 exposed for 3 months, 24 for 6 months, 24 for 12 months), plus the same number of controls, mostly 6 to 8 weeks old at the start. The work was done at the MRC Pneumoconiosis Unit, Penarth, UK. Dates are not given.
• Exposure: Three chrysotile samples: SFA (a specially ground sample from the Normandie Mine, Canada), the UICC Canadian chrysotile standard reference sample (a mixture from eight Canadian mines), and grade 7 chrysotile from the Bells Mine, Canada. Cosmetic grade talc from Italy was also tested. None of the chrysotiles was pure, and the grade 7 sample contained traces of tremolite. Injection: 20 mg of dust in saline, into the right pleural cavity. Inhalation: cumulative doses of 4100, 8200 and 16,400 mg/m3 hours for the 3-, 6- and 12-month exposures, given for 35 hours a week.
• Main results:
  • Dust clouds: the UICC cloud contained the most fibres longer than 5 um (3750 fibres/ml, compared with 1020 for grade 7 and 430 for SFA). The grade 7 fibres were the longest and the UICC fibres the shortest and narrowest.
  • Injection experiment: mesotheliomas occurred in 18 of the 48 SFA-injected rats, 13 of the grade 7 rats and 5 of the UICC rats.
  • Injection experiment: the saline controls had no mesotheliomas, with a mean survival of 691 days. The SFA group had the shortest mean survival, 598 days.
  • Injection experiment: after allowing for different survival times, SFA was about twice as carcinogenic as grade 7, and grade 7 was three times as carcinogenic as UICC. The grade 7 result was significantly different from each of the other two chrysotiles. The exact P value is cut off in the text.
  • Inhalation experiment: deposition and retention of dust in the lungs were low for all the chrysotiles, and there was evidence that chrysotile was eliminated during the year after exposure ended. Much more talc was retained, and the amount was related to length of exposure.
  • Inhalation experiment: fibrosis progressed during the first year after exposure ended for the 6- and 12-month exposures, for all dusts. After 3 months' exposure, fibrosis on average regressed.
  • Inhalation experiment: UICC chrysotile caused at least as much fibrosis as the other two chrysotiles and the talc on all six occasions (P = 0.06).
  • Inhalation experiment: UICC chrysotile produced 20 lung tumours, 10 of them malignant.
  • Inhalation experiment: SFA chrysotile produced 13 tumours, four of them malignant, including the only mesothelioma in the inhalation experiment.
  • Inhalation experiment: grade 7 chrysotile produced nine tumours, only one of them malignant.
  • Inhalation experiment: the tumour yield was significantly greater with UICC chrysotile than with grade 7 (P less than 0.05 for all tumours; P less than 0.01 for malignant tumours).
• The authors' conclusion: The authors concluded that the experiments show differences in biological effects between overtly similar chrysotile samples. UICC chrysotile produced more lung tumours after inhalation than the injection results would suggest. They said there are clear dangers in extrapolating from injection experiments to man, and that a positive injection result may be taken as an indication that an inhalation experiment should be carried out.
• Limitations the authors state:
  • All the test materials contained mineral impurities.
  • Fibre size distributions and counts depend heavily on the counting conventions used and on how aggregates are interpreted.
  • Because fibres aggregated in the bulk samples, the size distributions of the injected materials may have been quite different from those measured in the inhalation chamber clouds. The authors suggested this could partly explain why the two experiments ranked the samples differently.

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile, UICC, Cosmetic Talc, Tremolite, Mesothelioma.

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