Interpretation of the carcinogenicity of amosite asbestos and ferroactinolite on the basis of retained fiber dose and characteristics in vivo

Our plain-English summary of Interpretation of the carcinogenicity of amosite asbestos and ferroactinolite on the basis of retained fiber dose and characteristics in vivo, by P.M. Cook, L.D. Palekar, D.L. Coffin (Toxicology Letters, 1982).

The study

• Authors: P.M. Cook, L.D. Palekar, D.L. Coffin
• Journal: Toxicology Letters
• Published: 1982;13(3-4):151-8
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Rats were exposed to amosite asbestos and ferroactinolite fibers by intrapleural inoculation and intratracheal instillation. The ferroactinolite sample was found to be more carcinogenic in both exposures than the amosite sample on the basis of total fiber dose or fiber dose expressed for any size category of hypothetical greatest carcinogenic potency. Quantitative transmission electron microscope analysis of low-temperature ashed whole lung samples collected at different times following intratracheal instillation of fibers demonstrated that concentrations and sizes of fibers retained in rat lungs were greatly influenced by the relative ability of each mineral to undergo longitudinal splitting as a consequence of dissolution in vivo. Ferroactinolite fibers rapidly split to produce many thin fibers so that the number of ferroactinolite fibers retained in the lung 2 years after intratracheal instillation was four times greater than the number of fibers originally instilled. The number of short, thin ferroactinolite fibers retained (10-fold more than amosite) after in vivo splitting best explains the greater lung carcinogenicity of ferroactinolite compared to amosite.

In plain English

This rat study asked why a ferroactinolite sample, an amphibole mineral, had been more carcinogenic than amosite asbestos, relative to fiber numbers given, in the authors' companion study. There, after injection into the chest cavity, amosite caused 50% more pleural tumors, but 600% more amosite fibers were given. Male Fischer-344 rats received 12 weekly intratracheal instillations totalling 6 mg ferroactinolite or 3 mg amosite. Pairs of rats were killed at up to 24 months, and their lung fibers were counted and measured by electron microscope. Ferroactinolite fibers split lengthwise as they partly dissolved in the lung. After two years the lungs held 1.91 × 10^9 ferroactinolite fibers, four times the 0.49 × 10^9 given. Amosite fell from 1.71 × 10^9 to 0.43 × 10^9. After one year, long, thin fibers of the two minerals were about equal in number, but short, thin ferroactinolite fibers were 10 times more numerous. The authors concluded that the number of very thin fibers of all lengths appeared a better determinant of carcinogenicity than the number of long fibers. They noted that the best time to measure retained dose is unknown and that relative carcinogenicity in humans may differ.

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: electron microscope measurement of fibers retained in rat lungs at different times after intratracheal instillation. The tumor results being explained come from a companion study (Coffin et al.).
• Who was studied: Male Fischer-344 rats, killed in pairs at 1, 4, 12 and 24 months after the last instillation. Further rats were killed 1 day after a single 0.5 mg ferroactinolite or 0.25 mg amosite instillation, or immediately after a single 5 mg instillation of either mineral. The total number of rats is not stated.
• Exposure: Ferroactinolite (an amphibole mineral) and amosite asbestos, given by intratracheal instillation: 12 weekly doses of 0.5 mg ferroactinolite (6 mg total) or 0.25 mg amosite (3 mg total).
• Main results:
  • From the companion study (reference 14), as cited here: after intrapleural inoculation, amosite produced 50% more pleural tumors than ferroactinolite. However, 600% more amosite fibers than ferroactinolite fibers were inoculated.
  • Ferroactinolite fibers in the lungs 2 years after instillation numbered 1.91 × 10^9, versus 0.49 × 10^9 instilled. This four-fold increase was unexpected.
  • Amosite fibers fell from an initial dose of 1.71 × 10^9 to 0.43 × 10^9 retained after 2 years.
  • After 2 years there was a 17-fold increase in the number of ferroactinolite fibers 0.1 micrometre wide or less. The authors attribute this to fibers splitting lengthwise, not to preferential clearance of thicker fibers.
  • Both minerals appeared to split lengthwise in the lung through dissolution. Ferroactinolite split faster and produced thinner, more numerous fibers.
  • Long, thin fibers (at least 8 micrometres long and no more than 0.25 micrometre wide, Stanton's criterion) one year after instillation: ferroactinolite 24.6 × 10^6, amosite 18.6 × 10^6. Ferroactinolite had essentially none of these fibers when instilled.
  • At 4 months and at 2 years, the number of amosite fibers meeting Stanton's criterion slightly exceeded the number of ferroactinolite fibers.
  • One year after instillation there were 10 times more short, thin ferroactinolite fibers (5 micrometres long or less, 0.1 micrometre wide or less) than short, thin amosite fibers in the lungs.
  • The authors calculated what Stanton's criterion would predict if dose were measured as long, thin fibers in the exposure samples, assuming a linear, no-threshold dose response. On that basis amosite would be predicted to cause 92 times more tumors in the intrapleural study and 46 times more in the intratracheal study, which conflicts with the observed results.
• The authors' conclusion: The authors concluded that their data suggest the number of very thin fibers of all lengths present in tissue is a better determinant of fiber carcinogenicity than the number of long fibers.
• Limitations the authors state:
  • The best point in time at which to measure the accumulated fiber dose that most indicates a mineral's carcinogenicity is unknown.
  • Because the time from exposure to disease is much longer in humans than in rodents, the relative carcinogenicity of mineral fibers may differ in humans.
  • Evidence of fiber splitting in the pleural cavity after intrapleural inoculation came only from qualitative electron microscope examination.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Actinolite, Amosite.

Medical terms in this study, explained in our Lexicon: Amosite, Ferro-actinolite, Carcinogenic.

Related studies

• Correlation of in vitro and in vivo methods by means of mass dose and fiber distribution for amosite and fibrous ferroactinolite — D.L. Coffin, L.D. Palekar, et al. (1983)
• Tumorigenesis by a ferroactinolite mineral — D.L. Coffin, L.D. Palekar, et al. (1982)
• Rapporteur's Report Session 4: grunerite asbestos (amosite) and tremolite-ferroactinolite asbestos: risk of environmental mesothelioma — J.F. Gamble (2008)
• Sumas Mountain chrysotile induces greater lung fibrosis in Fischer344 rats than Libby amphibole, El Dorado tremolite, and Ontario ferroactinolite — J.M. Cyphert, A. Nyska, et al. (2012)
• Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the syrian golden hamster. Part I. Results of a subchronic study and dose selection for a chronic study — T.W. Hesterberg, C. Axten, et al. (1999)
• In vivo studies on genotoxicity and cogenotoxicity of ingested UICC anthophyllite asbestos — C. Varga, G. Horváth, et al. (1996)

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