title: Progression of lung inflammation and damage in rats after cessation of silica inhalation.
abstract: Human epidemiologic studies have found that silicosis may develop or progress even after occupational exposure has ended, suggesting that there is a threshold lung burden above which silica-induced pulmonary disease progresses without further exposure. We previously described the time course of rat pulmonary responses to silica inhalation as biphasic, the initial phase characterized by increased but controlled pulmonary inflammation and damage. However, after a threshold lung burden was exceeded, rapid progression of silica-induced pulmonary disease occurred. To test the hypothesis that there is a threshold lung burden above which silica-induced pulmonary disease progresses without further exposure we initiated a study to investigate the relationship between silica exposure, the initiation and progression of silica-induced pulmonary disease, and recovery. Rats were exposed to silica (15 mg/m(3), 6 h/day) for either 20, 40, or 60 days. A portion of the rats from each exposure were maintained without further exposure for 36 days to examine recovery. The major findings of this study are: (1) silica-exposed rats were not in pulmonary overload, and lung silica burden decreased with recovery; (2) pulmonary inflammation, damage and lipidosis increased with recovery for rats exposed to silica for 40 and 60 days, but not 20 days; (3) histopathology revealed changes in silica-induced alveolitis, epithelial hypertrophy and hyperplasia, and alveolar lipoproteinosis consistent with bronchoalveolar lavage (BAL) endpoints; and (4) pulmonary fibrosis developed even when exposure was stopped prior to its initial development.
authors.affiliation: National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Morgantown, West Virginia 26505, USA. DPorter@cdc.gov
authors.forename: Dale W
authors.initials: DW
authors.lastname: Porter
authors.forename: Ann F
authors.initials: AF
authors.lastname: Hubbs
authors.forename: Robert
authors.initials: R
authors.lastname: Mercer
authors.forename: Victor A
authors.initials: VA
authors.lastname: Robinson
authors.forename: Dawn
authors.initials: D
authors.lastname: Ramsey
authors.forename: Jeff
authors.initials: J
authors.lastname: McLaurin
authors.forename: Amir
authors.initials: A
authors.lastname: Khan
authors.forename: Lori
authors.initials: L
authors.lastname: Battelli
authors.forename: Kurt
authors.initials: K
authors.lastname: Brumbaugh
authors.forename: Alexander
authors.initials: A
authors.lastname: Teass
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018450:Disease Progression; D005355:Fibrosis; D019570:Inhalation Exposure; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008198:Lymph Nodes / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010743:Phospholipids / Q000032:analysis; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012709:Serum Albumin / Q000032:analysis; D012822:Silicon Dioxide / Q000032:analysis / Q000633:toxicity*
chemical_list: D010743:Phospholipids; D012709:Serum Albumin; D012822:Silicon Dioxide; D007770:L-Lactate Dehydrogenase