Comparison of Calidria chrysotile asbestos to pure tremolite: final results of the inhalation biopersistence and histopathology examination following short-term exposure

Our plain-English summary of Comparison of Calidria chrysotile asbestos to pure tremolite: final results of the inhalation biopersistence and histopathology examination following short-term exposure, by D.M. Bernstein, J. Chevalier, P. Smith (Inhalation Toxicology, 2005).

The study

• Authors: D.M. Bernstein, J. Chevalier, P. Smith
• Journal: Inhalation Toxicology
• Published: 2005;17(9):427-49
• Cited by: 53 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Calidria chrysotile asbestos, which is a serpentine mineral, has been shown to be considerably less biopersistent than the durable amphibole mineral tremolite asbestos, which persists once deposited in the lung. The initial results of this inhalation biopersistence study in rats that demonstrates this difference were reported in Bernstein et al. (2003). This article presents the full results through 1 yr after cessation of the 5-day exposure. This study was based upon the recommendations of the European Commission (EC) Interim Protocol for the Inhalation Biopersistence of synthetic mineral fibers (Bernstein & Riego-Sintes, 1999). In addition, the histopathological response in the lung was evaluated following exposure. In order to quantify the dynamics and rate by which these fibers are removed from the lung, the biopersistence of a sample of commercial-grade chrysotile from the Coalinga mine in New Idria, CA, of the type Calidria RG144 and that of a long-fiber tremolite were studied. 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 the histopathological response. As the long fibers have been shown to have the greatest potential for pathogenicity, the aerosol generation technique was designed to maximize the number of long respirable fibers. The chrysotile samples were specifically chosen to have 200 fibers/cm3 longer than 20 microm in length present in the exposure aerosol. These longer fibers were found to be largely composed of multiple shorter fibrils. The tremolite samples were chosen to have 100 fibers/cm3 longer than 20 microm in length present in the exposure aerosol. Calidria chrysotile has been found to be one of the most rapidly cleared mineral fibers from the lung. The fibers longer than 20 microm in length are cleared with a half-time of 7 h. By 2 days postexposure all long fibers have dissolved/disintegrated into shorter pieces. The fibers between 5 and 20 microm in length were cleared with a half-time of 7 days. This length range represents a transition zone between those fibers that can be fully phagocytosed and cleared as particles and the longer fibers that cannot be fully engulfed by the macrophage. The fibers/objects shorter than 5 microm in length were cleared with a half-time of 64 days, which is faster than that reported for insoluble nuisance dusts such as TiO2. By 12 months postexposure, 99.92% of all the remaining chrysotile was less than 5 microm in length. Following the 5 days of repeated exposure to more than 48,000 chrysotile fibers/cm3 (190 fibers L > 20 microm), histopathological examination revealed no evidence of any inflammatory reaction either after the cessation of the last exposure or at any time during the subsequent 12-mo period. This is in marked contrast to the amphibole tremolite, which was also investigated using the same inhalation biopersistence protocol. The long tremolite fibers, once deposited in the lung, remain over the rat's lifetime with essentially an infinite half-time. Even the shorter fibers, following early clearance, also remain with no dissolution or further removal. At 365 days postexposure, there was a mean lung burden was of 0.5 million fibers L > 20 microm and 7 million fibers 5-20 microm in length with a total mean lung burden of 19.6 million fibers. The tremolite exposed rats, even with exposure to 16 times fewer total fibers than chrysotile, showed a pronounced inflammatory response with the rapid development of granulomas as seen at day 1 postexposure, followed by the development of fibrosis characterized by collagen deposition within these granulomas and by 90 days even mild interstitial fibrosis. With the short exposure, this study was not designed specifically to evaluate pathological response; however, it is quite interesting that even so there was such a marked response with tremolite. These findings provide an important basis for substantiating both kinetically and pathologically the differences between chrysotile and the amphibole tremolite. As Calidria chrysotile has been certified to have no tremolite fiber, the results of the current study together with the results from toxicological and epidemiological studies indicate that this fiber is not associated with lung disease.

In plain English

Male Wistar rats breathed Calidria chrysotile (commercial chrysotile from the Coalinga mine, New Idria, California), tremolite, or filtered air for 6 hours a day for 5 days and were followed for up to 12 months. The chrysotile air held 48,343 fibers/cm3 of all sizes and the tremolite air 3128. Chrysotile fibers longer than 20 µm cleared from the lung with a half-time of 7 hours, and none were left by 2 days. Chrysotile fibers 5 to 20 µm long cleared with a half-time of 7 days. After early clearance in the first 24 hours, long tremolite fibers showed no statistically significant decrease through 365 days. At that point the total tremolite lung burden averaged 19.6 million fibers. The authors reported no exposure-related lung findings in chrysotile-exposed or control rats. Tremolite-exposed rats had granulomas by day 1, fibrosis in granulomas, and interstitial fibrosis in 1 animal at 90 days. The authors noted that, with the short exposure, the study was not designed specifically to evaluate pathological response. They concluded that, with other studies, the results indicate Calidria chrysotile is not associated with lung disease.

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 measuring lung clearance of fibers (biopersistence) and lung tissue changes (histopathology) after a 5-day exposure, with follow-up to 12 months
• Who was studied: Male Wistar rats, about 8 weeks old, in groups of 56 per exposure group plus a filtered-air control group, supplied by RCC Ltd, Füllinsdorf, Switzerland; subgroups were examined at time points from 0 days to 12 months after exposure (5 rats per group per time point for lung fiber counts; 3 to 5 per group for histopathology)
• Exposure: Nose-only inhalation, 6 hours/day for 5 days, of Calidria chrysotile type RG144 (target 200 fibers longer than 20 µm per cm3) or tremolite (target 100 fibers longer than 20 µm per cm3); measured mean total fibers of all sizes were 48,343 fibers/cm3 for chrysotile and 3128 fibers/cm3 for tremolite
• Main results:
  • Chrysotile fibers longer than 20 µm cleared with a half-time of 7 hours (0.31 days in Table 4); by 2 days after exposure no long chrysotile fibers remained
  • Chrysotile fibers 5 to 20 µm long cleared with a half-time of 7 days; by 365 days more than 99.9% had been eliminated
  • Chrysotile fibers/objects shorter than 5 µm cleared with a half-time of 64 days (tremolite: weighted half-time 151.5 days)
  • In tremolite-exposed rats, after early clearance in the first 24 hours, there was no statistically significant decrease in tremolite fiber concentration in the lung through 365 days
  • At 365 days, tremolite-exposed rats had a mean lung burden of 0.5 million fibers longer than 20 µm, 7 million fibers 5 to 20 µm long, and 19.6 million fibers in total
  • No exposure-related histopathological findings were seen in the chrysotile-exposed rats or the air-control rats
  • In tremolite-exposed rats, granulomas were already well formed 1 day after the end of the 5-day exposure
  • At 90 days in tremolite-exposed rats, fibrosis in granulomas had a mean severity of 2.8 (on a 1 to 5 scale), and interstitial fibrosis was seen in 1 animal (of 4 examined), persisting through 180 days
  • No pleural lesions were noted in the tremolite-exposed rats
  • Mean lung weights of chrysotile-exposed rats were not statistically different from air controls at any time point; tremolite lung weights were significantly greater than air controls at all compared time points and greater than the chrysotile group through 90 days
• The authors' conclusion: The authors concluded that, because Calidria chrysotile has been certified to have no tremolite fiber, the results of this study together with toxicological and epidemiological studies indicate that this fiber is not associated with lung disease
• Limitations the authors state:
  • Because the exposure was short, the study was not designed specifically to evaluate pathological response, although determining the histopathological response was one of the study's stated aims
  • Clearance coefficients for the long tremolite fibers could not be calculated because the clearance curve had no slope
  • The authors noted that the slower clearance of short tremolite fibers compared with short chrysotile fibers may have been influenced by two factors: continued breakage of chrysotile, and trapping of short fibers in tremolite-induced granulomas

Mines named here

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

• Santa Rita mine, Joaquin Ridge near Coalinga, California

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: Calidria, Chrysotile, Tremolite, biopersistence, Histopathology, Short-Term Exposure, Serpentine Group, Amphibole Group.

Related studies

• Comparison of Calidria chrysotile asbestos to pure tremolite: inhalation biopersistence and histopathology following short-term exposure — D.M. Bernstein, J. Chevalier, et al. (2003)
• The biopersistence of brazilian chrysotile asbestos following inhalation — D.M. Bernstein, R. Rogers, et al. (2004)
• 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)
• 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 — D.M. Bernstein, R.A. Rogers, et al. (2011)
• 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 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)

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