Inflammatory Effects of Respirable Quartz Collected in Workplaces versus Standard DQ12 Quartz: Particle Surface Correlates

Abstract

In 1997, the IARC (International Agency for Research on Cancer) reevaluated its quartz classification from a class 2 carcinogen, to that of a class 1, stating sufficient evidence for carcinogenicity in both humans and experimental animals. However, tumor development did not occur across all occupational settings. It is probable that this is due to the considerable differences in toxicity between workplace quartz in comparison to quartz used in experimental studies. We therefore hypothesized that workplace quartz samples differ in toxicity from standard experimental quartz samples at equal mass. To test this hypothesis we compared 2 workplace quartz samples (RH1 and OM) with standard experimental quartz (DQ12) in several assays commonly used in particle toxicology. The sizes of the quartz samples were as closely matched as possible. The endpoints of this study were inflammation in the rat lung following intratracheal instillation (1000 microg or 250 microg for 3 or 14 days), release of soluble iron, cytotoxicity to cells in culture, and surface reactivity as assessed by hemolysis and ESR. The workplace samples did not cause inflammation at any dose or time point. DQ12 quartz caused marked inflammatory responses, as measured by an increased number of neutrophils in the lungs of instilled animals for both time points and doses. Protein in the bronchoalveolar lavage also increased in animals exposed to DQ12 but not the workplace samples. In vitro, DQ12 had the greatest hemolytic activity but only RH1 released substantial amounts of soluble iron. The increased inflammogenicity of DQ12 was not wholly explained by a greater surface area, by diameter, or by releasable iron. The hemolytic activity of DQ12, while not being informative in terms of understanding the mechanism of carcinogenicity, was the best in vitro predictor for in vivo activity. Therefore the surface reactivity of DQ12 appears to drive its inflammogenicity.

Repeated exposure to carbon nanotube-based aerosols does not affect the functional properties of a 3D human epithelial airway model

“…As with acute exposures , the repeated exposure strategy was validated by repeatedly aerosolizing DQ12 crystalline quartz as a positive inflammatory control. Results showed that DQ12 introduced a statistically significant increase in the secretion of the (pro)-inflammatory proteins IL-1b and TNF-a after both repeated exposure scenarios and consequently a biological relevant increase in IL-8, which clearly indicates that (pro-)inflammatory response can be triggered in the system by classical materials known for their inflammatory properties, such as DQ12 (Clouter et al, 2001). These findings further confirm the sensitivity of the in vitro system.…”

“…Additionally, crystalline Dörentruper Quartz (DQ12; 5 mm; Robock, 1973) at a concentration of 0.1 mg/ml ) was used as a positive (pro-)inflammatory ''particle control'', since it is known to induce severe pulmonary inflammation (Clouter et al, 2001;Monteiller et al, 2007).…”

Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than Healthy Cells

“…45 Indeed, DQ12-exposed animals have been observed to express severe inflammatory effects following either 14d or 90d of exposure, respectively. 46,47 Therefore, the ability of DQ12 to trigger (pro-)inflammatory reactions at both the gene and protein level highlights the effectiveness of the employed in vitro chronic strategy. Notably, the highest cytokine expression in DQ12-exposed cells was observed at w3 followed by a decrease over the last week, indicating a possible cell threshold or recovery from the repetitive challenge with DQ12.…”

Variation of airborne quartz in air of Beijing during the Asia-Pacific Economic Cooperation Economic Leaders' Meeting

“…For example, it has been suggested that the presence of highly reactive radicals on the surfaces of fractured silica that may be present in certain workplaces make the fractured silica highly cytotoxic (Castranova et al, 1996;Clouter et al, 2001). Dobias et al (2006) suggested that quartz dust is genotoxic and is an important contributor to the genotoxicity of complex mixtures of fibrogenic respirable airborne particles in ambient air in certain workplaces.…”