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Short-Term Pulmonary Response to Inhaled JP-8 Jet Fuel Aerosol in Mice
Raymond F. Robledo
Department of Pathology, University of Vermont, Burlington, Vermont
R. Scott Young
Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona
R. Clark Lantz
Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona
Mark L. Witten
Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona
B6.A.D. (Ahrd/Nat s) mice were utilized to investigate the short-term pulmonary response to JP-8 jet fuel (JP-8) aerosol inhalation. Mice were nose-only exposed to atmospheres of 0 to 118 mg/m3 for 1 h/d over a period of 7 days to further test the hypothesis that JP-8 concentrations below the permissible exposure level (PEL) of 350 mg/m3 will induce lung injury. At 24 to 30 hours after the final exposure, pulmonary function and respiratory permeability were measured on anesthetized mice and then randomly assigned for bronchoalveolar lavage or histopathology. Bronchoalveolar lavage fluid (BALF) was analyzed for total protein, lactic dehydrogenase (LDH), N-acetyl-β-D-glucosaminidase (NAG), and cytology. Respiratory permeability increases were observed following doses of 48 and 118 mg/m3 and were supported by concomitant BALF increases in total protein and LDH. Conversely, NAG and alveolar macrophage levels decreased following the same exposure concentrations. Morphological lung injury was characterized by the targeting of bronchiolar epithelium and consisted of perivascular edema, Clara cell vacuolization, and necrosis. Alveolar injury included sporadic pulmonary edema, intra-alveolar hemorrhage, and alterations in type II epithelial cells. These results indicate that repeated inhalation of aerosolized JP-8 induces physiological, biochemical, cellular, and morphological lung injury. This study also provides evidence for the reevaluation of the 350 mg/m3 PEL for more volatile petroleum distillates with regard to respirable aerosols.
Key Words: Lung injury • petroleum hydrocarbons • permissable exposure level (PEL) • 99mTc-labeled diethylenetriaminepentaacetic acid ( 99mTc-DTPA) • bronchoalveolar lavage fluid (BALF) • morphology
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Toxicologic Pathology, Vol. 28, No. 5,
656-663 (2000)
DOI: 10.1177/019262330002800504
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