title: Comparison of low doses of aged and freshly fractured silica on pulmonary inflammation and damage in the rat.
abstract: Most previous studies of silica toxicity have used relatively high exposure doses of silica. In this study, male rats received by intratracheal instillation either vehicle, aged or freshly fractured silica at a dose of either 5 microg/rat once a week for 12 weeks (total dose=60 microg) or 20 microg/rat once a week for 12 weeks (total dose=240 microg). One week after the last exposure, bronchoalveolar lavage (BAL) was conducted and markers of pulmonary inflammation, alveolar macrophage (AM) activation and pulmonary damage were examined. For rats exposed to a total of 60 microg silica, both aged and freshly fractured silica increased polymorphonuclear leukocytes (PMN) yield and AM activation above control to a similar degree, but no evidence of pulmonary damage, as measured by BAL fluid lactate dehydrogenase activity or albumin concentration, was detected. For rats exposed to 240 microg silica, aged or freshly fractured silica increased PMN yield and AM activation above control. However, zymosan-stimulated and L-NAME sensitive AM chemiluminescence was greater for rats exposed to freshly fractured silica compared to aged silica. Exposure to 240 microg aged or freshly fractured silica also resulted in pulmonary damage, but the extent of this damage did not differ between the two types of silica. The results suggest that exposure of rats to silica levels far lower than those previously examined can cause pulmonary inflammation. In addition, exposure to freshly fractured silica causes greater generation of reactive oxygen species from AM, measured as AM chemiluminescence, in comparison to aged silica, but there is an apparent threshold below which this difference does not occur.
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, National Institutes of Health, 1095 Willowdale Road, M/S 2015, Morgantown, WV 26505, USA. dporter@cdc.gov
authors.forename: Dale W
authors.initials: DW
authors.lastname: Porter
authors.forename: Mark
authors.initials: M
authors.lastname: Barger
authors.forename: Victor A
authors.initials: VA
authors.lastname: Robinson
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Leonard
authors.forename: Douglas
authors.initials: D
authors.lastname: Landsittel
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology; D008297:Male; D009504:Neutrophils / Q000166:cytology; D011014:Pneumonia / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000633:toxicity*; D013047:Specific Pathogen-Free Organisms
chemical_list: D000418:Albumins; D012822:Silicon Dioxide; D007770:L-Lactate Dehydrogenase