Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure

Our plain-English summary of Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure, by D.M. Bernstein, R.A. Rogers, R. Sepulveda, et al (Inhalation Toxicology, 2011).

The study

• Authors: D.M. Bernstein, R.A. Rogers, R. Sepulveda, K. Donaldson, D. Schuler, S. Gaering, P. Kunzendorf, J. Chevalier, S.E. Holm
• Journal: Inhalation Toxicology
• Published: 2011;23(7):372-91
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The marked difference in biopersistence and pathological response between chrysotile and amphibole asbestos has been well documented. This study is unique in that it has examined a commercial chrysotile product that was used as a joint compound. The pathological response was quantified in the lung and translocation of fibers to and pathological response in the pleural cavity determined. This paper presents the final results from the study. Rats were exposed by inhalation 6 h/day for 5 days to a well-defined fiber aerosol. Subgroups were examined through 1 year. The translocation to and pathological response in the pleura was examined by scanning electron microscopy and confocal microscopy (CM) using noninvasive methods. The number and size of fibers was quantified using transmission electron microscopy and CM. This is the first study to use such techniques to characterize fiber translocation to and the response of the pleural cavity. Amosite fibers were found to remain partly or fully imbedded in the interstitial space through 1 year and quickly produced granulomas (0 days) and interstitial fibrosis (28 days). Amosite fibers were observed penetrating the visceral pleural wall and were found on the parietal pleural within 7 days postexposure with a concomitant inflammatory response seen by 14 days. Pleural fibrin deposition, fibrosis, and adhesions were observed, similar to that reported in humans in response to amphibole asbestos. No cellular or inflammatory response was observed in the lung or the pleural cavity in response to the chrysotile and sanded particles (CSP) exposure. These results provide confirmation of the important differences between CSP and amphibole asbestos.

In plain English

This rat experiment compared inhaled sanded, recreated chrysotile joint compound plus added 7RF3 chrysotile (CSP) with amosite asbestos. Groups of 93 male rats inhaled CSP or amosite 6 hours daily for 5 days; 56 controls breathed filtered air; subgroups were followed through 365 days. The CSP aerosol held 6543 fibers/cm3 (295 longer than 20 microns), the amosite aerosol 953 (201). For CSP, the mean number of lung fibers longer than 20 microns fell from 0.31 million per lung at day 0 to 0 at 90 days (half-time 4.5 days), though single fibers appeared in one animal's sample later. For amosite it went from 2.74 million to 1.39 million per lung at 365 days (weighted half-time over 1000 days). No fibers were seen at the visceral pleural surface of CSP or control rats at 181 to 365 days. On the diaphragm, where fiber examination was qualitative, one CSP rat showed two possible short fibers at 30 days; no CSP pleural lesions or inflammation appeared. Amosite rats had thicker visceral pleura (about 5 versus about 2 microns, p less than 0.01), pleural defects, fibrin and adhesions. Georgia-Pacific funded the work.

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 inhalation toxicology experiment in rats, with microscopy of lung and pleura through 1 year after exposure
• Who was studied: Male weanling (8-10 week old) HanRcc:WIST(SPF) rats; 93 per exposed group (CSP and amosite) and 56 air controls; studies conducted at RCC/Harlan Laboratories, Füllinsdorf/Basel, Switzerland
• Exposure: Nose-only inhalation, 6 h/day for 5 days, of chrysotile joint-compound sanded particulate plus added JM 7RF3 chrysotile (CSP, 2.64 mg/m3, 6543 total fibers/cm3, 295 longer than 20 microns/cm3) or amosite asbestos (6.39 mg/m3, 953 total fibers/cm3, 201 longer than 20 microns/cm3)
• Main results:
  • In CSP-exposed rats, the mean number of lung fibers longer than 20 microns fell from 0.31 million per lung at day 0 to 0 at 90 days
  • After 90 days, single fibers longer than 20 microns were still observed in CSP-exposed rats: one fiber of 21 microns at 181 days and one of 25 microns at 275 and 365 days, each on the filter aliquot from one animal
  • In amosite-exposed rats, lung fibers longer than 20 microns fell from 2.74 million per lung at day 0 to 1.98 million at 7 days and 1.4 million (Table 4: 1.39 million) at 365 days
  • Clearance half-times in CSP-exposed animals: 4.5 days for fibers longer than 20 microns, 12.8 days for 5-20 microns, 27.8 days for under 5 microns
  • In amosite-exposed animals, fibers longer than 20 microns had a weighted clearance half-time greater than 1000 days (fitted to a double exponential), and the shorter length fractions also had weighted half-times over 1000 days
  • Visceral pleural wall thickness was about 2 microns in air controls and nearly identical in CSP-exposed rats, and about 5 microns in amosite-exposed rats, statistically significant at all time points from 181 to 365 days
  • No pleural defects in air control or CSP groups at any time point; amosite-exposed rats had 40 pleural defects per field of view at 181 days to over 15 at 365 days
  • No fibers were found at the visceral pleural surface in air control or CSP rats at 181, 275 or 365 days; amosite rats averaged 16 fibers at 181 days, 10 at 272 days and 4 at 365 days per 0.01 mm2
  • On the diaphragm (parietal pleura), examined 0 to 90 days with a fiber examination the authors considered qualitative, there was an indication of two possible shorter fibers in one CSP-exposed rat at 30 days, with no associated cellular or inflammatory response
  • CSP-exposed animals showed no parietal pleura lesions at any time point; amosite fibers were seen on the diaphragm within 7 days, with an inflammatory response and a fibrin matrix by 14 days
  • Lung histopathology (reported in detail in the earlier interim publication of this study) showed no pulmonary inflammation beyond a macrophage response with CSP, whereas amosite produced inflammation from day 0 and interstitial fibrosis of Wagner Grade 4 by 28 days
• The authors' conclusion: The authors concluded that amosite fibers persisted in the interstitium, produced granulomas and interstitial fibrosis, reached the parietal pleura within 7 days with inflammation by 14 days, and caused pleural fibrin deposition, fibrosis and adhesions, while no cellular or inflammatory response occurred with CSP, confirming differences between CSP and amphibole asbestos
• Limitations the authors state:
  • Confocal signal interference, probably from protein coatings on the parietal pleural surface, meant the diaphragm fiber examination was only qualitative
  • Lung digestion precluded determining whether the recovered fibers were associated with cells, particularly macrophages
  • The estimated total visceral pleural fiber burden relied on the assumption of uniform fiber distribution over the pleural surface
  • Counting free cells adherent to the parietal pleural surface did not yield a measurable observation, so only presence or absence of cell accumulations was reported

Mines named here

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

• Jeffrey mine, Asbestos, Quebec

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: Pleura, Chrysotile, Amosite, biopersistence, Amphibole Asbestos, Joint Compound, Translocation, Pleural Cavity.

Related studies

• The pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite asbestos following short-term inhalation exposure: interim results — D.M. Bernstein, R.A. Rogers, et al. (2010)
• Evaluation of the fate and pathological response in the lung and pleura of brake dust alone and in combination with added chrysotile compared to crocidolite asbestos following short-term inhalation exposure — D.M. Bernstein, R.A. Rogers, et al. (2015)
• Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 2: Histopathological examination, Confocal microscopy and collagen quantification of the lung and pleural cavity — D.M. Bernstein, B. Toth, et al. (2020)
• Evaluation of the exposure, dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 1: Experimental design, aerosol exposure, lung burdens and BAL — D.M. Bernstein, B. Toth, et al. (2020)
• Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to chrysotile or crocidolite asbestos in a 28-day quantitative inhalation toxicology study — D.M. Bernstein, B. Toth, et al. (2018)
• Final results from a 90-day quantitative inhalation toxicology study evaluating the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos: Histopathological examination, confocal microscopy and collagen quantification of the lung and pleural cavity — D.M. Bernstein, B. Toth, et al. (2021)

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