title: 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.
authors.affiliation: School of Life Sciences, Napier University, 10 Colinton Road, Edinburgh EH10 5DT, Scotland. a.clouter@napier.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Clouter
authors.forename: D
authors.initials: D
authors.lastname: Brown
authors.forename: D
authors.initials: D
authors.lastname: Höhr
authors.forename: P
authors.initials: P
authors.lastname: Borm
authors.forename: K
authors.initials: K
authors.lastname: Donaldson
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D002460:Cell Line; D004391:Dust; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D009504:Neutrophils; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D011506:Proteins / Q000032:analysis; D011791:Quartz / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
chemical_list: D000395:Air Pollutants, Occupational; D004391:Dust; D011506:Proteins; D011791:Quartz