Chemical Characterization and Toxicologic Evaluation of Airborne Mixtures: Inhalation Toxicology of Diesel Fuel Obscurant Aerosol in Spargue-Dawley Rats. Final Report, Phase 2, Repeated Exposures

摘要

A series of repeated exposures of rats to aerosolized diesel fuel was performed to help establish indices of potential toxicity resulting from aerosol exposure and the relative importance of duration of exposures, the frequence of exposures, and aerosol concentration in the induction of observed lesions. Body weight and food consumption were recorded on a weekly basis. Assays were performed on selected animals within 1-2 days after the last exposure or after 2 weeks without exposure. Endpoints included number and phagocytic activity of pulmonary free cells, pulmonary function tests, neurotoxicity assays, clinical chemistry, organ weights, and histopathology. Data were analyzed by analysis of variance. After exposure, the primary target organ was the lungs. Focal accumulations of pulmonary free cells were observed in the lung parenchyma, associated with thickening and hypercellularity of alveolar walls. The number of lavaged pulmonary free cells correlated well with histologic observations, remaining elevated after two weeks without exposure. Lung volumes were altered by exposure, including increased FRC, decreased TLC, and decreased VC. Carbon monoxide diffusing capacity was decreased in several exposed groups also. None of the more systemic changes observed were considered to be of biologic significance, even though the exposure conditions were considered to result in a maximum tolerated dose. Frequency of exposure was the dominant variable over the range of parameters used in this study, 3 exposures/wk being more deleterious than 1/week. Variation in duration of exposure appeared to have very little effect and a dose-response was often not apparent with differences in concentration. 12 references, 13 figures, 18 tables. (ERA citation 09:034482)