Correlation of in vitro and in vivo methods by means of mass dose and fiber distribution for amosite and fibrous ferroactinolite

Our plain-English summary of Correlation of in vitro and in vivo methods by means of mass dose and fiber distribution for amosite and fibrous ferroactinolite, by D.L. Coffin, L.D. Palekar, P.M. Cook (Environmental Health Perspectives, 1983).

The study

• Authors: D.L. Coffin, L.D. Palekar, P.M. Cook
• Journal: Environmental Health Perspectives
• Published: 1983;51:49-53
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Oncogenesis and in vitro data (reported elsewhere in detail) are compared on the basis of relative activity by mass and by dimensional fiber parameters. When tumor induction is compared to the number of fibers of various lengths and aspect ratios in the dose in rats to the degree of tumor induction, a degree of difference with the long thin fiber concept of tumorigenesis by mineral fibers is noted. Consistency is re-established, however, when cognizance is taken of the change in the length and aspect ratio that took place during residence in the lung. This change resulted in a severalfold excess for ferroactinolite of all fiber lengths with high aspect ratios, produced as a result of longitudinal splitting of the introduced fibers. The response by mass in the in vitro procedures did not mimic oncogenesis. When mass was so adjusted that there were an equal number of mineral fibers, aspect ratio greater than 3, for dose for the two minerals, agreement was closer in both the rabbit alveolar macrophage toxicity test and the clonal cytotoxicity assay in Chinese hamster ovary cells. When activity was related to the number of mineral fibers, the same aspect ratio computed to have been contained in the mass dose, agreement with the relative induction of lung tumors was closer. In all cases, erythrocyte lysis was more active in reflecting the number of mineral fibers.

In plain English

This paper compared rat tumor results and laboratory cell-test results, both reported in other papers, for two natural minerals: UICC amosite and fibrous ferroactinolite. Fischer 344 rats received the minerals either into the chest cavity (intrapleural) or into the windpipe (intratracheal). After intrapleural doses, mesotheliomas occurred in 33.6% of amosite-treated and 23% of ferroactinolite-treated rats. Both rates were significantly different from controls but not from each other. After intratracheal doses, pooled primary malignant lung tumors showed a low but statistically significant (p = 0.05) excess for ferroactinolite. Amosite contained far more long, thin fibers, so the similar mesothelioma rates seemed somewhat inconsistent with the idea that long thin fibers drive tumors. Fibers split lengthwise in the lung, much more so for ferroactinolite, and the authors speculated this may have contributed. Cell-test results compared by mass did not match the tumor results. The authors concluded that agreement was best when results were expressed per fiber with a length-to-width ratio greater than 3. They noted they had only a single data point for each mineral.

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: Comparative analysis of previously reported animal experiments (intrapleural and intratracheal dosing of rats) and in vitro cell assays
• Who was studied: Fischer 344 pathogen-free rats. Intrapleural groups: 135 ferroactinolite, 137 UICC amosite, 134 sham control, 219 untreated control. Intratracheal groups: 561 ferroactinolite, 139 UICC amosite, 212 sham control, 219 untreated control. In vitro tests used rabbit alveolar macrophages, Chinese hamster ovary cells and sheep red blood cells.
• Exposure: UICC amosite and fibrous ferroactinolite. Intrapleural dosing was one 20 mg dose. Intratracheal dosing was 12 doses of 0.50 mg ferroactinolite (6.0 mg total) or 12 doses of 0.25 mg amosite (3.0 mg total).
• Main results:
  • Intrapleural groups: mesotheliomas occurred in 46 of 137 amosite-treated rats (33.6%) and 31 of 135 ferroactinolite-treated rats (23%). Both were significantly different from controls but not from each other.
  • Intratracheal groups: pooled primary malignant lung tumors showed a low but statistically significant (p = 0.05) excess for ferroactinolite. Lung tumors occurred in 22 of 561 ferroactinolite rats (3.9%) and 1 of 139 amosite rats (0.71%).
  • The two minerals differed by nearly two orders of magnitude in the number of fibers longer than 8 µm and thinner than 0.25 µm, with amosite having more. Because pleural tumor induction was approximately equal, the authors described their data as somewhat inconsistent with the long-fiber concept.
  • Fibers split lengthwise during residence in the rat lung. This was much more pronounced for ferroactinolite, producing a large increase in its fiber numbers.
  • Against the Stanton et al. regression model of pleural tumors, the observed results were predicted closely for ferroactinolite, while amosite was overpredicted by a probability of 0.32.
  • In vitro dose response calculated by mass did not match the tumor results.
  • The macrophage (RAM) and hamster ovary cell (CHO) tests matched the pleural tumor results best when expressed per fiber with aspect ratio greater than 3.
  • Red blood cell lysis mimicked lung tumor induction, which the authors suggested may relate to short, very thin fibers.
  • When in vitro results were calculated per fiber longer than 8 µm and thinner than 0.25 µm, the response was strongly slanted toward ferroactinolite. The authors presumed this was an artifact.
• The authors' conclusion: The authors concluded that in vitro and in vivo results correlated best when the in vitro response was expressed per mineral fiber with aspect ratio greater than 3. They suggested that both tumor induction and in vitro response resulted from the mineral fibers.
• Limitations the authors state:
  • The authors said more dose-response data would be needed to verify that fiber splitting contributed. They noted the scatter in the comparison model and that they had only a single data point for each mineral.

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, Carcinogenesis, Aspect Ratio (Length-to-diameter ratio), Mineral Fiber, Fiber Length, Alveolar Macrophage.

Related studies

• Interpretation of the carcinogenicity of amosite asbestos and ferroactinolite on the basis of retained fiber dose and characteristics in vivo — P.M. Cook, L.D. Palekar, et al. (1982)
• 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)
• In vitro studies on the biologic effects of fibers: correlation with in vivo bioassays — B.T. Mossman (1990)
• Solubility of asbestos and man-made mineral fibers in vitro and in vivo: its significance in lung disease — A. Morgan, A. Holmes (1986)
• 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)

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