In vitro determinants of asbestos fiber toxicity: effect on the relative toxicity of Libby amphibole in primary human airway epithelial cells.

BACKGROUND: An abnormally high incidence of lung disease has been observed in the residents of Libby, Montana, which has been attributed to occupational and environmental exposure to fibrous amphiboles originating from a nearby contaminated vermiculite mine. The composition of Libby amphibole (LA) is complex and minimal toxicity data are available. In this study, we conduct a comparative particle toxicity analysis of LA compared with standard reference asbestiform amphibole samples. METHODS: Primary human airway epithelial cells (HAEC) were exposed to two different LA samples as well as standard amphibole reference samples. Analysis of the samples included a complete particle size distribution analysis, calculation of surface area by electron microscopy and by gas adsorption and quantification of surface-conjugated iron and hydroxyl radical production by the fibers. Interleukin-8 mRNA levels were quantified by qRT-PCR to measure relative pro-inflammatory response induced in HAEC in response to amphibole fiber exposure. The relative contribution of key physicochemical determinants on the observed pro-inflammatory response were also evaluated. RESULTS: The RTI amosite reference sample contained the longest fibers and demonstrated the greatest potency at increasing IL-8 transcript levels when evaluated on an equal mass basis. The two LA samples and the UICC amosite reference sample consisted of similar particle numbers per milligram as well as similar particle size distributions and induced comparable levels of IL-8 mRNA. A strong correlation was observed between the elongated particle (aspect ratio ≥3:1) dose metrics of length and external surface area. Expression of the IL-8 data with respect to either of these metrics eliminated the differential response between the RTI amosite sample and the other samples that was observed when HAEC were exposed on an equal mass basis. CONCLUSIONS: On an equal mass basis, LA is as potent as the UICC amosite reference sample at inducing a pro-inflammatory response in HAEC but is less potent than the RTI amosite sample. The results of this study show that the particle length and particle surface area are highly correlated metrics that contribute significantly to the toxicological potential of these amphibole samples with respect to the inflammogenic response induced in airway epithelial cells.

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

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.