Pulmonary response to inhaled jet-propulsion fuel 8 aerosol in mice
AuthorRobledo, Raymond F., 1968-
KeywordsHealth Sciences, Toxicology.
AdvisorWitten, Mark L.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractStudies were initiated to characterize the acute and sub-chronic pulmonary responses to inhaled Jet-Propulsion Fuel 8 (JP-8) aerosol. At 24 to 30 hours following JP-8 exposure, physiological, biochemical, cellular, and morphological techniques were used to assay for lung injury. In addition, C57BL/6 and B6.A.D.(Ahyd mice were utilized in the acute study to determine if responsiveness to aryl hydrocarbon hydroxylase (AHH) induction modulates toxicity. JP-8 contains aromatic compounds that are known substrates for AHH. Acute lung injury was evident by increased respiratory permeability that was accompanied by alveolar macrophage infiltration and activation, following exposure to occupational permissible levels of JP-8. Morphological alterations were characterized by terminal bronchiolar lesions of vacuolization and necrosis. AHH responsiveness did not appear to influence the severity of JP-8 induced lung injury. Lung injury following sub-chronic inhalation was found to be progressive in nature. Repeated exposure induced alveolar hemorrhage and alveolar macrophage cytotoxicity. Morphological changes progressed to include epithelial denudation of bronchiolar airways and vacuolization of alveolar type II epithelial cells and adjacent endothelia. The pulmonary clearance of JP-8 following inhalation exposures was determined indirectly by analysis for tetradecane content within lung homogenates from exposed mice. Clearance of JP-8 following acute exposure was determined to have a half-life of 43 minutes and increased by 14 minutes following a toxic sub-chronic exposure. The relatively rapid pulmonary clearance of JP-8 following either acute or sub-chronic exposure implies that JP-8 induced lung injury was independent of pulmonary retention. Studies were also performed to determine if non-cytotoxic concentrations of JP-8 or tetradecane could decrease bronchial epithelial barrier function. Studies showed that one hour of exposure to JP-8 or tetradecane could significantly enhance paracellular permeability to mannitol in the BEAS-2B human bronchial epithelial cell line, at two hours after exposure. Bronchial epithelial permeability appeared to be more sensitive to tetradecane than JP-8. Subsequent recovery studies determined that JP-8 and tetradecane-induced decreases in barrier function reach a maximum at 12 hours and barrier function returns to control by 48 hours post-exposure. These results indicate that JP-8 induced lung injury may be initiated by changes in airway barrier function.
Degree ProgramGraduate College
Pharmacology and Toxicology