We investigated the modifying effects of preexisting, bleomycin-induced pulmonary fibrosis on the deposition, retention, and biological effects of inhaled 239PuO2 in the rat. Among rats exposed to similar airborne concentrations of 239PuO2, initial lung burdens of 239Pu per kilogram body mass were similar whether or not pulmonary fibrosis was present. However, clearance of 239Pu from the lungs was significantly decreased in the rats with preexisting pulmonary fibrosis. The incidence of lung lesions (epithelial hyperplasia, diffuse macrophage increases and aggregation, and loose and dense connective tissue) was significantly greater among rats with preexisting pulmonary fibrosis than among the exposed controls. Rats with preexisting fibrosis had shorter life spans than 239PuO2-exposed control rats. When groups of rats with similar alpha doses to the lungs were compared, the incidences of neoplastic lesions in the lung, the times to death of rats with lung neoplasms, and the risk of lung tumors per unit of alpha dose to the lungs in rats with or without pulmonary fibrosis were similar. The results of this study suggest that humans with uncomplicated pulmonary fibrosis may not be more sensitive to the carcinogenic effects of inhaled 239PuO2 than are individuals with normal lungs, assuming that the total alpha doses to the lungs are similar.
A study was conducted in rats to determine solubility and subsequent metabolism of an inhaled aerosol of curium treated at high temperatures. Young adult Fischer-344 rats received a single inhalation exposure to one of three monodisperse aerosols of 244Cm2O3 (0.70, 1.3, or 2.6 micron activity median aerodynamic diameter) heat-treated at 1150 degrees C. Animals were maintained individually in metabolism cages for excreta collection and serially sacrificed in groups of two male and two female rats from 2 to 33 days after inhalation exposure. Additionally an injection study with curium citrate was done to define the systemic behavior of Cm in this rat model. The in vivo solubility was inversely related to the aerosol particle size. The relationship of the results of this study to results from other experimental inhalation studies with curium oxide aerosols is discussed, as is the relevance to bioassay interpretation and risk assessment in man.
Whole-body retention and distribution of 239Pu in selected tissues of Beagle dogs were determined after a series of two or four inhalation exposures to 239PuO2. Exposures were made at half-year intervals with alveolar depositions of about 150 nCi per exposure. Data are reported on dogs followed for one and two years after the first exposure. The plutonium was found to be extremely insoluble; 2-3% of the amount deposited in the alveolar region translocated to tracheobronchial lymph nodes and less than 0.1% translocated to other tissues. The whole-body retention, when compared to retention of 239Pu following a single exposure, supported the hypothesis that each exposure was retained independently with the same retention characteristics. This is in agreement with results reported by other investigators for one human repeatedly exposed by inhalation to low levels of aerosols containing plutonium-uranium fuels.
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