Role of exposure parameters in toxicity of aerosolized diesel fuel in the rat

Sprague-Dawley rats were exposed to aerosolized diesel fuel (ADF) to determine the potential health effects in military troops during exposure to this visual obscurrant. Acute range finding studies were performed to estimate exposure conditions at which minimal (less than 1%) mortality would occur. This information was used in the design of a repeated exposure study to test the relative significance of the frequency of exposures, the duration of exposure, and aerosol concentration in any toxicity which might occur. Animals were exposed once or three times per week for a total of nine times to concentrations ranging from 1.3 mg ADFl-1 to 6 mg ADFl-1 and exposure durations of 2 or 6 h. Body weight and food consumption were recorded at weekly intervals during the exposure period and in animals that were retained for 2 weeks after the last exposure. Animals were used for a variety of endpoints, including neurotoxicological tests, pulmonary function tests, hematology, clinical chemistry, organ weights, and histopathology, either within 2 days of the last exposure or after the 2-week recovery period. Animals exposed to ADF showed an initial depression in body weight followed by a slower rate of growth than the sham exposed controls. No exposure related changes were observed in any of the neurotoxicology assays. The lung was the primary site of toxicity. Focal accumulations of pulmonary free cells were observed histologically, with thickening and hypercellularity of nearby alveolar walls. The number of lavaged pulmonary free cells increased similarly. Both pulmonary wet and dry weights increased. Lung volumes were altered by exposure, including increased FRC and decreased TLC. Carbon monoxide diffusing capacity was decreased. Histologic abnormalities were not observed in any other organs. Of the exposure parameters tested, the frequency of exposure appeared to be the most significant in relation to degree of toxicity.