Abstract
BackgroundAn 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.MethodsPrimary 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.ResultsThe 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.ConclusionsOn 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.
Highlights
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
We further evaluate the effect of particle number, surface area, particle size distribution and reactive oxygen species production on the IL-8 response in an attempt to understand what physicochemical properties are critical to the toxicity of these asbestiform fibers
The sample masses shown differ, visible differences in particle size distribution (PSD) and morphology are apparent among the samples; the presence of blocky particles in conjunction with very thin fibers in the LA2000 sample (Figure 1A) as compared to the presence of some very long fibers in the other amphibole samples the RTI amosite sample (Figure 1C)
Summary
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. We conduct a comparative particle toxicity analysis of LA compared with standard reference asbestiform amphibole samples. If any, toxicological and risk assessment information exists for these non-regulated forms of asbestiform minerals, especially when they are present as a complex mixture. One component of the Libby Action Plan (LAP) involves a comparative toxicity assessment both in vitro in cultured cells and in vivo in animals in which LA is compared to standard reference amphibole samples that have extensive toxicological and risk assessment information available. The current study reports on the findings of the in vitro comparative toxicity analysis of Libby amphibole against two different reference samples of amosite, which will complement the rat inhalation and instillation studies conducted on these same LA samples as part of the LAP
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