Variations in the carcinogenicity of tremolite dust samples of differing morphology

Our plain-English summary of Variations in the carcinogenicity of tremolite dust samples of differing morphology, by J.M. Davis, J. Addison, C. McIntosh, et al (Annals of the New York Academy of Sciences, 1991).

The study

• Authors: J.M. Davis, J. Addison, C. McIntosh, B.G. Miller, K. Niven
• Journal: Annals of the New York Academy of Sciences
• Published: 1991;643:473-90
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Six samples of tremolite of different morphological type were prepared as dusts of respirable size and used in intraperitoneal injection studies in rats. Three "asbestiform" tremolites produced mesotheliomas in almost all animals, although with significantly different tumor-induction periods. A brittle type of fibrous tremolite which, when manipulated to prepare "respirable dust," produced a sample with relatively few asbestiform fibers remaining nonetheless produced tumors in 70% of rats. Two samples of nonfibrous tremolite produced respirable dust samples containing numerous elongated fragments with aspect ratios greater than 3:1, which therefore fitted the definition of respirable fibers. Both these samples produced relatively few tumors, although one had more long "fibers" than did the brittle tremolite that produced 70% of tumors. This study has therefore demonstrated that different morphologic forms of tremolite produce dusts with very different carcinogenic potential. Carcinogenicity does not depend simply on the number of elongated particles injected, and we need to develop methods of distinguishing carcinogenic tremolite fibers from relatively innocuous tremolite dusts, with similar numbers of elongated particles of similar aspect ratios.

In plain English

Edinburgh researchers tested six tremolite dust samples of different physical forms in rats. Three were asbestiform tremolites: Californian, Korean, and one supplied by a Swansea laboratory whose country of origin was uncertain. One was a brittle fibrous tremolite from Italy. Two, from Dornie and Shinness in Scotland, were made up mostly of cleavage fragments. Each dust was injected once, at 10 mg, into the abdominal cavity of 33 or 36 rats, which lived out their lives. Peritoneal mesothelioma developed in 36 of 36 rats given California tremolite, 35 of 36 given Swansea, 32 of 33 given Korean, 24 of 36 given Italian, 4 of 33 given Dornie and 2 of 36 given Shinness tremolite. The Italian sample caused far more tumors than the Dornie sample, even though the Italian dose had only about one-third as many fibers longer than 8 micrometers. No single fiber-size measure fully explained the differences. The authors concluded that different forms of tremolite produce dusts with very different carcinogenic potential, and that methods are needed to tell carcinogenic fibers from relatively harmless dusts.

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: single intraperitoneal (abdominal cavity) injection of tremolite dusts in rats, followed for life, with electron-microscope sizing of the fibers and particles in each dust
• Who was studied: Groups of 33 or 36 three-month-old AF/Han strain rats, one group for each of six tremolite samples
• Exposure: Six respirable-size tremolite dusts. Three were asbestiform: a California tremolite (listed as from Jamestown), a Korean tremolite, and a sample donated by the British Coal Laboratory in Swansea whose country of origin was uncertain. The fourth was a brittle, needle-like fibrous tremolite from Ala di Stura, Italy. The fifth was a friable, powdery tremolite from Carr Brae, Dornie, Scotland. The sixth was prismatic-crystal tremolite from Shinness, Scotland. Each rat received a single 10 mg dose suspended in 2.0 ml of saline.
• Main results:
  • The three asbestiform tremolites produced mesotheliomas in almost all rats: California 36 of 36, Swansea 35 of 36, Korean 32 of 33. The timing of tumor deaths differed significantly between them. Median survival of tumor-bearing rats was 301, 365 and 428 days respectively.
  • The Italian tremolite produced peritoneal mesotheliomas in 24 of 36 rats (67%), with a longer median survival time than the three asbestiform samples.
  • The Dornie tremolite produced mesotheliomas in 4 of 33 rats and the Shinness tremolite in 2 of 36 rats. These were too few to calculate median survival times.
  • In the statistical model, the California tremolite was estimated to be about 2.3 times as hazardous as the Korean tremolite.
  • The Italian sample produced tumors in nearly 70% of rats, but its dose contained only about one-third as many fibers longer than 8 micrometers as the Dornie sample, which produced mesotheliomas in 12%.
  • Of the fiber-size measures tested, the number of fibers longer than 8 micrometers and thinner than 0.25 micrometers fitted the tumor results best (chi-square 41.03). Even this fit was not good, and tumor production did not relate entirely to fibers of any one size range.
• The authors' conclusion: The authors concluded that different physical forms of tremolite produce dusts with very different carcinogenic potential. They also concluded that carcinogenicity does not depend simply on the number of elongated particles injected, and that methods are needed to distinguish carcinogenic tremolite fibers from relatively innocuous tremolite dusts.
• Limitations the authors state:
  • The authors said the 10 mg dose was an overdose for the asbestiform tremolites, which may have blurred the link between long, thin fibers and mesothelioma. They said a dose-response study would be needed to clarify this.
  • The authors said the intraperitoneal injection test is extremely sensitive. With a 10 mg dose, a dust producing tumors in fewer than 10% of animals is usually considered unlikely to show carcinogenicity when inhaled.
  • Observers tried to separate smooth, parallel-sided fibers from other elongated particles during counting. They could not do this reproducibly, and the attempt was abandoned.
  • Full quantitative chemical analyses of the fibers were not carried out.
  • Of the three asbestiform reference samples, only one had a known exact place of origin.

Topics

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

Medical terms in this study, explained in our Lexicon: Tremolite, Asbestiform, Mesothelioma, Aspect Ratio (Length-to-diameter ratio), Respirable Fiber, Carcinogenic.

Related studies

• Inhalation studies on the effects of tremolite and brucite dust in rats — J.M. Davis, J. Addison, et al. (1985)
• Health effects of tremolite. Now and in the future — B.W. Case (1991)
• Biological effects of tremolite — J.C. Wagner, M. Chamberlain, et al. (1982)
• Chrysotile, tremolite, and malignant mesothelioma in man — A. Churg (1988)
• Mesothelioma in Cyprus: the role of tremolite — K. McConnochie, L. Simonato, et al. (1987)
• 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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