Sumas Mountain chrysotile induces greater lung fibrosis in Fischer344 rats than Libby amphibole, El Dorado tremolite, and Ontario ferroactinolite

Our plain-English summary of Sumas Mountain chrysotile induces greater lung fibrosis in Fischer344 rats than Libby amphibole, El Dorado tremolite, and Ontario ferroactinolite, by J.M. Cyphert, A. Nyska, R.K. Mahoney, et al (Toxicological Sciences, 2012).

The study

• Authors: J.M. Cyphert, A. Nyska, R.K. Mahoney, M.C. Schladweiler, U.P. Kodavanti, S.H. Gavett
• Journal: Toxicological Sciences
• Published: 2012;130(2):405-15
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The physical properties of different types of asbestos may strongly affect health outcomes in exposed individuals. This study was designed to provide understanding of the comparative toxicity of naturally occurring asbestos (NOA) fibers including Libby amphibole (LA), Sumas Mountain chrysotile (SM), El Dorado tremolite (ED), and Ontario ferroactinolite (ON) cleavage fragments. Rat-respirable fractions (PM₂.₅) were prepared by water elutriation. Surface area was greater for SM (64.1 m²/g) than all other samples (range: 14.1-16.2 m²/g), whereas mean lengths and aspect ratios (ARs) for LA and SM were comparable and greater than ED and ON. Samples were delivered via a single intratracheal (IT) instillation at doses of 0.5 and 1.5mg/rat. One day post-IT instillation, low-dose NOA exposure resulted in a 3- to 4-fold increase in bronchoalveolar lavage fluid (BALF) cellularity compared with dispersion media (DM) controls, whereas high-dose exposure had a more severe effect on lung inflammation which varied by source. Although inducing less neutrophilic inflammation than ON and ED, exposure to either LA or SM resulted in a greater degree of acute lung injury. Three months post-IT instillation, most BALF parameters had returned to control levels, whereas the development of fibrosis persisted and was greatest in SM-exposed rats (SM > LA > ON > ED). These data demonstrate that fiber length and higher AR are directly correlated with the severity of fibrosis and that, in the rat, exposure to SM is more fibrogenic than LA which suggests that there may be cause for concern for people at risk of being exposed to NOA from the Sumas Mountain landslide.

In plain English

This was an animal experiment comparing four samples of naturally occurring asbestos: Libby amphibole (LA) from Montana, chrysotile from the Sumas Mountain landslide in Washington (SM), tremolite collected near El Dorado Hills, California (ED), and ferroactinolite cleavage fragments from Ontario (ON). The finest, rat-respirable fraction of each sample was placed once directly into the windpipe of male Fischer 344 rats, at 0.5 or 1.5 mg per rat. Control rats received only the suspending liquid. There were 144 rats in all, 8 per group, examined 1 day or 3 months after dosing. One day after dosing, all samples increased lung inflammation. At the high dose, cell counts were 9-fold above controls with ON and ED, 7-fold with SM and 4-fold with LA. Markers of lung damage were highest with LA and SM. At 3 months, fibrosis (lung scarring) ranked SM first, then LA, then ON. ED-exposed rats did not develop fibrosis. The authors concluded that in rats SM was more fibrogenic than LA, which suggested possible cause for concern for people exposed to material from the landslide. They cautioned that their single ED sample may not represent El Dorado Hills.

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: a single intratracheal instillation in rats, with lungs examined 1 day and 3 months later
• Who was studied: 144 healthy male Fischer 344 rats, 6 to 8 weeks old, in nine groups of 8 (control plus two doses of each of four samples) at each of two time points (1 day and 3 months)
• Exposure: Rat-respirable (PM2.5) fractions, separated by water elutriation, of four samples: Libby amphibole (Rainy Creek Complex near Libby, Montana); Sumas Mountain chrysotile (Swift Creek below the Sumas Mountain landslide, Washington); El Dorado tremolite (Flagstaff Hill along Folsom Lake, near El Dorado Hills, California); and Ontario ferroactinolite cleavage fragments (Marmora Mine, Ontario). Doses were 0.5 or 1.5 mg per rat. Controls received dispersion media (0.0 mg per rat).
• Main results:
  • The Sumas Mountain chrysotile sample had a surface area of 64.1 square meters per gram. The other three samples ranged from 14.1 to 16.2 square meters per gram.
  • Particles per milligram were about 1331 × 10^7 for El Dorado tremolite, 463 × 10^7 for Ontario ferroactinolite, 86 × 10^7 for Libby amphibole and 19 × 10^7 for Sumas Mountain chrysotile. In the article's text the 10^7 appears as '107' because the superscript was lost.
  • In the Sumas Mountain chrysotile sample, about 60% of particles were fibers (length-to-width ratio of at least 5:1). In the El Dorado tremolite sample, only 9% were fibers.
  • One day after dosing, the low dose of every sample raised the cell count in lung washing fluid 3- to 4-fold compared with controls.
  • One day after the high dose, total cells in lung washing fluid compared with controls were 9-fold higher for Ontario ferroactinolite and El Dorado tremolite, 4-fold higher for Libby amphibole and 7-fold higher for Sumas Mountain chrysotile.
  • One day after dosing, high-dose Sumas Mountain chrysotile raised markers of epithelial permeability and lung damage 21-fold compared with controls and 4-fold compared with high-dose Libby amphibole.
  • At 3 months, total cells in lung washing fluid had returned to control levels in most groups. They stayed slightly but significantly raised (1.5-fold) in the high-dose Libby amphibole, Ontario ferroactinolite and El Dorado tremolite groups.
  • At 3 months, Sumas Mountain chrysotile caused more pulmonary fibrosis than Libby amphibole at the same mass dose, even though the chrysotile sample had more than 4-fold fewer particles per milligram.
  • At 3 months, high-dose Ontario ferroactinolite was associated with minimal (grade 1) fibrosis.
  • At 3 months, collagen build-up increased with dose in every group except El Dorado tremolite, whose rats did not develop fibrosis.
  • Early markers of lung injury and inflammation did not necessarily predict how severe the lung disease was at 3 months.
• The authors' conclusion: The authors concluded that, in the rat, Sumas Mountain chrysotile was more fibrogenic than Libby amphibole. They said this suggests there may be cause for concern for people at risk of exposure to naturally occurring asbestos from the Sumas Mountain landslide. They reported that average particle length and length-to-width ratio seemed to correlate with fibrosis, with the order SM > LA > ON > ED.
• Limitations the authors state:
  • The El Dorado tremolite was a single sample, collected about 3 to 5 miles from the El Dorado Hills community center. It may not represent the amphiboles found within El Dorado Hills.
  • Biopersistence (how long fibers stay in the lung) was not directly measured.
  • Possible clumps of chrysotile fibers were seen in the lung tissue. The authors said these may have influenced the pathology 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.

• Libby vermiculite mine, Montana

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Fibrosis, Libby amphiboles, Tremolite, Ferro-actinolite, naturally occurring asbestos (NOA), Cleavage Fragment, Respirable Fraction.

Related studies

• Persistent effects of Libby amphibole and amosite asbestos following subchronic inhalation in rats — S.H. Gavett, C.U. Parkinson, et al. (2016)
• Pulmonary inflammatory and fibrotic responses in Fischer 344 rats after intratracheal instillation exposure to Libby amphibole — D.J. Padilla-Carlin, M.C. Schladweiler, et al. (2011)
• Comparative long-term toxicity of Libby amphibole and amosite asbestos in rats after single or multiple intratracheal exposures — J.M. Cyphert, D.J. Carlin, et al. (2015)
• Long-term toxicity of naturally occurring asbestos in male Fischer 344 rats — J.M. Cyphert, M.A. McGee, et al. (2016)
• Long-term response of rats to single intratracheal exposure of Libby amphibole or amosite — J.M. Cyphert, D.J. Padilla-Carlin, et al. (2012)
• Forsterite exposure causes less oxidative DNA damage and lung injury than chrysotile exposure in rats — A. Takata, H. Yamauchi, et al. (2009)

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