The biological effects of magnesium-leached chrysotile asbestos

Our plain-English summary of The biological effects of magnesium-leached chrysotile asbestos, by A. Morgan, P. Davies, J.C. Wagner, et al (British Journal of Experimental Pathology, 1977).

The study

• Authors: A. Morgan, P. Davies, J.C. Wagner, G. Berry, A. Holmes
• Journal: British Journal of Experimental Pathology
• Published: 1977;58(5):465-73
• Cited by: 89 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Chrysotile asbestos was leached in N hydrochloric acid for varying times to produce a range of magnesium-depleted samples. The protein adsorptive capacity, the haemolytic activity, and the capacity to cause selective release of acid hydrolases from macrophages were measured for the various samples in vitro. The carcinogenicity of the same materials was determined following intrapleural inoculation in rats. The adsorptive capacity for albumin decreased linearly with magnesium removal. The haemolytic activity also declined until about half the magnesium had been removed, after which there was little further change. The selective release of acid hydrolases from macrophages in culture increased up to the point at which half the magnesium had been removed but by 90% depletion had declined rapidly. The carcinogenicity of 50% -depleted chrysotile was similar to that of intact, but at 90% depletion the incidence of mesothelial tumours had fallen considerably. There was no evidence that the leached samples fragmented more than the unleached in vivo.

In plain English

This laboratory and animal study tested whether removing magnesium from chrysotile asbestos changes its biological effects. The authors soaked a standard UICC sample of Rhodesian chrysotile in hydrochloric acid for different times, removing up to 93 to 95% of its magnesium. In test-tube experiments, the fibers' ability to bind the blood protein albumin fell steadily as more magnesium was removed. Their ability to burst red blood cells fell until about half the magnesium was gone and then changed little. Their ability to make mouse macrophages (scavenger cells) release certain enzymes held up, and even rose, with up to 55% removed, but fell sharply at 93%. Rats received 20 mg of fiber injected into the chest (pleural) cavity, in groups of 32. Mesotheliomas developed in 12 rats given untreated fiber, 13 given 50%-leached fiber and 2 given 95%-leached fiber. The authors found that last difference statistically significant. Leached fibers did not appear to break up more in tissue. There was no untreated control group. The authors concluded that heavy magnesium removal markedly changed chrysotile's biological activity.

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 (rats given asbestos by injection into the pleural cavity) combined with laboratory (in vitro) tests on red blood cells and mouse macrophages
• Who was studied: Animal part: barrier-protected, Caesarean-derived Wistar rats bred at the MRC Pneumoconiosis Unit, 32 per treatment group (16 of each sex), three groups, aged 6 to 12 weeks at injection. One rat in the 95%-leached group died after 12 days and was excluded. Laboratory part: red blood cells from a single human donor, and peritoneal macrophages from outbred Swiss mice. Dates not stated.
• Exposure: UICC standard reference sample of Rhodesian chrysotile, either unleached or leached in N hydrochloric acid to remove magnesium. Laboratory tests used samples with up to 93% of magnesium removed. Rats received unleached, 50%-leached or 95%-leached chrysotile, 20 mg per rat injected into the right pleural cavity.
• Main results:
  • Albumin binding did not fall much when surface magnesium was removed, then declined progressively with further leaching. Fully leached chrysotile had little affinity for albumin.
  • Red blood cell bursting (haemolytic) activity, measured per weight of the original unleached fiber, fell to one third of its original value when 55% of the magnesium had been leached.
  • When corrected for the weight lost in leaching, haemolytic activity at 55% depletion was half that of unleached fiber, with no further change as more magnesium was removed.
  • In mouse macrophage cultures, the 55%-leached sample caused significantly greater selective release of all three enzymes measured, at both 9 and 24 hours, than the water-treated (unleached) sample.
  • The 93%-leached sample caused a highly significant decrease in enzyme release from macrophages compared with the water-treated (unleached) sample.
  • In rats, the 50%-leached sample produced one more mesothelioma than the unleached sample: 13 versus 12 rats, with mean survival of 738 versus 694 days.
  • After allowing for the longer survival in the 50%-leached group, its mesothelioma rate relative to unleached fiber was 0.95 by Pike's method and 0.92 by Cox's method (95% limits 0.42 to 2.13). The difference did not approach significance.
  • In the 95%-leached group, 2 rats developed mesotheliomas (mean survival 717 days). The relative mesothelioma rate was 0.15 by Pike's method and 0.17 by Cox's method (95% limits 0.03 to 0.68). Compared with the other two groups, the difference was reported as significant (P less than 0.01).
  • One mesothelioma in the 95%-leached group appeared early, 347 days after injection. All other mesotheliomas appeared after more than 500 days.
  • Electron microscopy of tissue from rats given leached and unleached chrysotile gave similar pictures. The authors found no evidence that leached fibers broke up more in the body than unleached fibers.
• The authors' conclusion: The authors concluded that leaching chrysotile with hydrochloric acid, removing a large proportion of its structural magnesium, produced marked changes in its biological activity both in the laboratory and in animals. They judged the laboratory and animal results to be compatible once the precision of the results is taken into account.
• Limitations the authors state:
  • There was no untreated control group in the animal experiment. The authors relied on their earlier experiments, in which controls developed no mesotheliomas.
  • The laboratory and animal results cannot be strictly compared because the two kinds of study lasted very different lengths of time.
  • The animal experiment, with 32 rats per group, was less precise than the laboratory tests.
  • Leached fiber received extra ultrasonic treatment before the macrophage tests. The increase in enzyme release might therefore reflect more exposed fiber surface rather than leaching itself.
  • The ultrasonic treatment did not fully separate the unleached fibers into their finest strands (fibrils).
  • No samples leached between 55% and 93% were tested, although maximum enzyme-release activity would be expected in that range.

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile, Macrophage.

Related studies

• Adsorption isotherms of albumin and ferritin on Rhodesian chrysotile: effects of magnesium depletion — F. Valerio, M. Veggi, et al. (1980)
• The lung biological activity of American attapulgite — R. Bégin, S. Massé, et al. (1987)
• Advanced bredigite-containing magnesium-matrix composites for biodegradable bone implant applications — S.N. Dezfuli, Z. Huan, et al. (2017)
• Forsterite exposure causes less oxidative DNA damage and lung injury than chrysotile exposure in rats — A. Takata, H. Yamauchi, et al. (2009)
• Acid leaching studies of chrysotile asbestos from mines in the Coalinga region of California and from Quebec and British Columbia — A. Morgan (1997)
• Mesotheliomas in rats following inoculation with acid-leached chrysotile asbestos and other mineral fibres — G. Monchaux, J. Bignon, et al. (1981)

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