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

Our plain-English summary 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: interim results, by D.M. Bernstein, R.A. Rogers, R. Sepulveda, et al (Inhalation Toxicology, 2010).

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: 2010;22(11):937-62
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The pathological response and translocation of a commercial chrysotile product similar to that which was used through the mid-1970s in a joint compound intended for sealing the interface between adjacent wall boards was evaluated in comparison to amosite asbestos. This study was unique in that it presents a combined real-world exposure and was the first study to investigate whether there were differences between chrysotile and amosite asbestos fibers in time course, size distribution, and pathological response in the pleural cavity. Rats were exposed by inhalation 6 h/day for 5 days to either sanded joint compound consisting of both chrysotile fibers and sanded joint compound particles (CSP) or amosite asbestos. Subgroups were examined through 1-year postexposure. No pathological response was observed at any time point in the CSP-exposure group. The long chrysotile fibers (L > 20 microm) cleared rapidly (T(1/2) of 4.5 days) and were not observed in the pleural cavity. In contrast, a rapid inflammatory response occurred in the lung following exposure to amosite resulting in Wagner grade 4 interstitial fibrosis within 28 days. Long amosite fibers had a T(1/2) > 1000 days and were observed in the pleural cavity within 7 days postexposure. By 90 days the long amosite fibers were associated with a marked inflammatory response on the parietal pleural. This study provides support that CSP following inhalation would not initiate an inflammatory response in the lung, and that the chrysotile fibers present do not migrate to, or cause an inflammatory response in the pleural cavity, the site of mesothelioma formation.

In plain English

This rat inhalation experiment reported interim results comparing a re-created chrysotile joint compound with amosite asbestos. Male rats breathed filtered air (56 rats), sanded joint compound with extra 7RF3 chrysotile added (CSP; 93 rats), or amosite (93 rats), 6 hours a day for 5 days. Lung results ran to 90 days. Pleural results to 181 days were described as initial, with the rest reserved for a later paper. Chrysotile fibers longer than 20 µm cleared from the lung with a half-time of 4.5 days. Long amosite fibers had a half-time greater than 1000 days. Chrysotile fibers were found in CSP lungs, but tissue examination showed no exposure-related changes or inflammation, and the Wagner score (1 means normal) stayed at 1, as in controls. Amosite lungs reached Wagner score 4, interstitial fibrosis, by day 28. Amosite fibers appeared on the diaphragm surface by 7 days, with extensive inflammatory proliferation by 90 days. CSP diaphragms did not differ from controls. The authors concluded that the sanded joint compound would not initiate lung inflammation and that its chrysotile fibers do not migrate to the pleural cavity. 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 experiment in rats (short-term exposure, follow-up planned to 1 year); this article gives interim results, with initial pleural results
• Who was studied: Male rats: 93 per exposed group (CSP and amosite) and 56 air controls; small subgroups were examined at each time point (for example, 3 animals per group for lung histopathology and 5 for the diaphragm). Exposures were done at RCC Ltd (now Harlan Laboratories Ltd.), Switzerland.
• Exposure: Nose-only inhalation, 6 h/day for 5 days, of one of three atmospheres. (1) Filtered air. (2) CSP: sanded re-created joint compound, with commercial 7RF3 chrysotile added because sanding produced few fibers longer than 20 µm; mean 295 fibers longer than 20 µm per cm3, 1496 WHO fibers/cm3, 2.64 mg/m3. (3) Amosite asbestos: mean 201 fibers longer than 20 µm per cm3, 584 WHO fibers/cm3, 6.39 mg/m3.
• Main results:
  • Immediately after exposure, the CSP rats had a mean of 0.31 million fibers longer than 20 µm per lung, compared with 2.74 million in the amosite-exposed rats.
  • CSP group: chrysotile fibers longer than 20 µm cleared from the lung with a half-time of 4.5 days and were not observed in the pleural cavity.
  • CSP group: chrysotile fibers were still present in the lung at 90 days. None was longer than 20 µm, and 91% were shorter than 5 µm.
  • Amosite group: fibers longer than 20 µm deposited in the deep lung persisted, with a half-time greater than 1000 days.
  • Fibers 5 to 20 µm long cleared with a half-time of 13 days in the CSP group and longer than 1000 days in the amosite group.
  • Fibers shorter than 5 µm cleared with a half-time of 26 days for chrysotile (CSP group) and 90 days for amosite.
  • No exposure-related lung histopathology, including any sign of inflammation, was seen at any time point in the air control or CSP groups, and the Wagner score was 1 in both. Macrophage aggregation in one CSP rat at 90 days was judged by the pathologist not to be exposure-related.
  • Amosite group: macrophage aggregation and microgranuloma were present from day 0 (Wagner score 2 through day 14). By day 28 the score was 4, indicating interstitial fibrosis, and this persisted through day 90.
  • Diaphragm (parietal pleura), amosite group: amosite fibers were seen on the surface at 7 days after exposure.
  • Diaphragm, amosite group at 90 days: extensive inflammatory proliferation with numerous activated inflammatory cells.
  • Diaphragms from the CSP group did not differ from those of the air control group.
  • Pleural space at 181 days: no inflammatory cells in the CSP-exposed animal shown; a small aggregate of activated pleural macrophages in the amosite-exposed animal shown.
• The authors' conclusion: The authors concluded that the study supports the view that the sanded joint compound would not initiate an inflammatory response in the lung after inhalation, and that the chrysotile fibers present do not migrate to the pleural cavity, the site of mesothelioma formation.
• Limitations the authors state:
  • The pleural results are initial; the remaining results were to be presented in a later paper.
  • The chest-wall (pleural space) examination was not yet complete; so far it gave only a qualitative indication of fiber movement to the pleura and of pathological response.
  • Some lungs used for confocal microscopy were not fully inflated, which the authors say affected only the lung-volume estimate, not the fiber counts.

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, Translocation, Joint Compound, Pleural Cavity, Interstitial Fibrosis, Mesothelioma.

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• 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 deposition, translocation and pathological response of brake dust with and without added chrysotile in comparison to crocidolite asbestos following short-term inhalation: interim results — D.M. Bernstein, R. Rogers, et al. (2014)
• 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)

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