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

Toxicol Sci. 2012 Dec;130(2):405-15. doi: 10.1093/toxsci/kfs249. Epub 2012 Aug 17.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Asbestos, Amphibole / chemistry
  • Asbestos, Amphibole / toxicity*
  • Asbestos, Serpentine / chemistry
  • Asbestos, Serpentine / toxicity*
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Dose-Response Relationship, Drug
  • Inflammation Mediators / metabolism
  • Inhalation Exposure
  • Lung / drug effects*
  • Lung / immunology
  • Lung / pathology
  • Particle Size
  • Pulmonary Fibrosis / chemically induced*
  • Pulmonary Fibrosis / immunology
  • Pulmonary Fibrosis / pathology
  • Rats
  • Rats, Inbred F344
  • Risk Assessment
  • Severity of Illness Index
  • Time Factors

Substances

  • Asbestos, Amphibole
  • Asbestos, Serpentine
  • Inflammation Mediators
  • ferroactinolite
  • tremolite