The biopersistence of brazilian chrysotile asbestos following inhalation

Our plain-English summary of The biopersistence of brazilian chrysotile asbestos following inhalation, by D.M. Bernstein, R. Rogers, P. Smith (Inhalation Toxicology, 2004).

The study

• Authors: D.M. Bernstein, R. Rogers, P. Smith
• Journal: Inhalation Toxicology
• Published: 2004;16(11-12):745-61
• Cited by: 39 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

With the initial understanding of the relationship of asbestos to disease, little information was available on whether the two different groups of minerals that are called asbestos were of similar or different potency in causing disease. Asbestos was often described as a durable fiber that if inhaled would remain in the lung and cause disease. It has been only more recently, with the development of a standardized protocol for evaluating the biopersistence of mineral fibers in the lung, that the clearance kinetics of the serpentine chrysotile have been shown to be dramatically different from those of amphibole asbestos, with chrysotile clearing rapidly from the lung. In addition, recent epidemiology studies also differentiate chrysotile from amphibole asbestos. The biopersistence studies mentioned have indicated that chrysotile from Canada and California clear rapidly from the lung once inhaled. However, variations in chrysotile mineralogy have been reported depending upon the region. This is most likely associated with variations in the forces which created the chrysotile fibers centuries ago. In the present study, the dynamics and rate of clearance of chrysotile from the Cana Brava mine in central Brazil was evaluated in a comparable inhalation biopersistence study in the rat. For synthetic vitreous fibers, the biopersistence of the fibers longer than 20 microm has been found to be directly related to their potential to cause disease. This study was designed to determine lung clearance (biopersistence) and translocation and distribution within the lung. As the long fibers have been shown to have the greatest potential for pathogenicity, the chrysotile samples were specifically chosen to have more than 450 fibers/cm(3) longer than 20 microm in length present in the exposure aerosol. For the fiber clearance study (lung digestions), at 1 day, 2 days, 7 days, 2 wk, 1 mo, 3 mo, 6 mo, and 12 mo following a 5-day (6 h/day) inhalation exposure, the lungs from groups of animals were digested by low-temperature plasma ashing and subsequently analyzed by transmission electron microscopy (at the GSA Corp.) for total chrysotile fiber number in the lungs and chrysotile fiber size (length and diameter) distribution in the lungs. This lung digestion procedure digests the entire lung with no possibility of identifying where in the lung the fibers are located. A fiber distribution study (with confocal microscopy) was included in order to identify where in the lung the fibers were located. At 2 days, 2 wk, 3 mo, 6 mo, and 12 mo postexposure, the lungs from groups of animals were analyzed by confocal microscopy to determine the anatomic fate, orientation, and distribution of the retained chrysotile fibrils deposited on airways and those fibers translocated to the broncho-associated lymphoid tissue (BALT) subjacent to bronchioles in rat lungs. While the translocation of fibers to the BALT and lymphatic tissue is considered important as in cases of human's with asbestos-related disease, there has been no report in the literature of pathological changes in the BALT and lymphatic tissue stemming from asbestos. Thus, if the fibers are removed to these tissues, they are effectively neutralized in the lung. Chrysotile was found to be rapidly removed from the lung. Fibers longer than 20 microm were cleared with a half-time of 1.3 days, most likely by dissolution and breakage into shorter fibers. Shorter fibers were also rapidly cleared from the lung with fibers 5-20 microm clearing even more rapidly (T1/2 = 2.4 days) than those < 5 microm in length (T1/2 weighted = 23. days). Breaking of the longer fibers would be expected to increase the short fiber pool and therefore could account for this difference in clearance rates. The short fibers were never found clumped together but appeared as separate, fine fibrils, occasionally unwound at one end. Short free fibers appeared in the corners of alveolar septa, and fibers or their fragments were found within alveolar macrophages. The same was true of fibers in lymphatics, as they appeared free or within phagocytic lymphocytes. These results support the evidence presented by McDonald and McDonald (1997) that the chrysotile fibers are rapidly cleared from the lung in marked contrast to amphibole fibers which persist.

In plain English

This animal experiment measured how long chrysotile asbestos from the Cana Brava mine in central Brazil stays in rat lungs after it is breathed in. Male Fischer 344 rats breathed the fibers through the nose for 6 hours a day on 5 consecutive days. The air contained a mean of 465 fibers longer than 20 µm per cm3. Fibers longer than 20 µm were cleared with a half-time of 1.3 days. Fibers 5 to 20 µm long had a half-time of 2.4 days, and fibers shorter than 5 µm had a weighted half-time of 23 days. At 182 days, one long fiber was found in one rat. Fibers seen on the epithelial surface (lining) of the lung at 12 months were not associated with macrophages or other cellular response. The authors concluded that the results support evidence that chrysotile clears rapidly from the lung, unlike amphibole fibers, which this study did not test. They noted that the very high exposure might have produced a different response than lower exposures would.

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: inhalation biopersistence study in rats
• Who was studied: Groups of 56 male Fischer 344 rats, 4 to 8 weeks old. The exposure phase took place at Research and Consulting Company Ltd., Füllinsdorf, Switzerland. The article does not state study dates.
• Exposure: Brazilian chrysotile (commercial grade CA300 from the Cana Brava mine), inhaled through the nose for 6 hours a day for 5 consecutive days. The target was 450 fibers longer than 20 µm per cm3.
• Main results:
  • The exposure air actually contained 465 fibers longer than 20 µm per cm3, 2098 WHO fibers per cm3 and 9226 total fibers per cm3.
  • Chrysotile fibers longer than 20 µm were cleared from the rat lung with a half-time of 1.3 days. The authors attributed this most likely to dissolution and breakage into shorter fibers.
  • Fibers 5 to 20 µm long had a clearance half-time of 2.4 days. Fibers shorter than 5 µm had a weighted half-time of 23 days.
  • At 182 days after exposure, one fiber longer than 20 µm was found in one rat. At 365 days, 1, 3 or 4 long fibers were found out of 250 fibers evaluated per sample.
  • Extrapolated to the whole lung, these counts corresponded to 900 fibers longer than 20 µm per lung at 182 days and 13,500 per lung at 365 days.
  • At 2 days after exposure, fibers seen under the confocal microscope appeared as separate, fine fibrils and were not clumped together.
  • At 12 months, fibers on the epithelial surface of the lung were not associated with macrophages or other cellular response.
• The authors' conclusion: The authors concluded that the results further support evidence that chrysotile fibers are rapidly cleared from the lung, in marked contrast to amphibole fibers, which persist. The amphibole comparison rests on other studies; this study exposed rats only to chrysotile.
• Limitations the authors state:
  • The authors stated that the very high total exposure may have produced a response very different from what would be expected at lower exposure concentrations.
  • No confocal microscope examination was done at 1 day after exposure, because clearance was not expected to be so rapid.
  • The lung digestion method cannot show where in the lung the fibers were located.
  • The chrysotile used in the study came from a different commercial batch than the sample used in the pre-study trial, so the exposure results differ from the trial results.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Cana Brava mine, Uruaçu, Goiás

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: biopersistence, Chrysotile, Mineral Fiber, Serpentine Group, Amphibole Asbestos, Epidemiology, Mineralogy, Cana Brava Mine.

Related studies

• Comparison of Calidria chrysotile asbestos to pure tremolite: final results of the inhalation biopersistence and histopathology examination following short-term exposure — D.M. Bernstein, J. Chevalier, et al. (2005)
• The biopersistence of Canadian chrysotile asbestos following inhalation: final results through 1 year after cessation of exposure — D. Bernstein, R. Rogers, et al. (2005)
• The biopersistence of Canadian chrysotile asbestos following inhalation — D.M. Bernstein, R. Rogers, et al. (2003)
• The toxicological response of Brazilian chrysotile asbestos: a multidose subchronic 90-day inhalation toxicology study with 92-day recovery to assess cellular and pathological response — D.M. Bernstein, R. Rogers, et al. (2006)
• Comparison of Calidria chrysotile asbestos to pure tremolite: inhalation biopersistence and histopathology following short-term exposure — D.M. Bernstein, J. Chevalier, et al. (2003)
• A biopersistence study following exposure to chrysotile asbestos alone or in combination with fine particles — D.M. Bernstein, K. Donaldson, et al. (2008)

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