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© 1998 Oxford University Press
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Dose-Response Relationships between Inhaled Beryllium Metal and Lung Toxicity in C3H Mice
Inhalation Toxicology Laboratory, Lovelace Biomedical and Environmental Research Institute, Inc., Lovelace Respiratory Research Institute P.O. Box 5890, Albuquerque, New Mexico 87185
Received August 28, 1997; accepted November 30, 1997
Inhaled beryllium (Be) can induce a range of adverse pulmonary responses in animals and humans including acute pneumonitis, chronic granulomatous lung disease, and cancer. To facilitate comparisons with our previous data describing Be toxicity in rats, we evaluated the toxic effects of inhaled Be metal in mice. Groups of 34 strain C3H/HeJ mice were acutely exposed by the nose-only route to aerosolized Be metal to achieve measured initial lung burdens of 0, 1.7, 2.6, 12, or 34 µg. All mice received aerosolized 85Sr-labeled fused aluminosilicate particles (85Sr-FAPs) immediately before their Be exposure so that the influence of Be on lung retention of these poorly soluble tracer particles could be externally quantitated. Groups of mice were euthanized at 8, 15, 40, 90, 210, and 350 days after exposure for evaluation of histopathological changes and for cyto-logjc and biochemical indicators of lung damage measured in bron-choalveolar lavage fluid. Clearance of 85Sr-FAP tracer particles through 196 days after exposure was delayed in mice receiving the 12 and 34 µg Be lung burdens, but not the 1.7 or 2.6 µg lung burdens. Increased total cell numbers, increased percentage of neutrophils, and elevated levels of total protein and the activities of ß-glucuron-idase and lactate dehydrogenase in bronchoalveolar lavage fluid were observed in the two highest Be lung burden groups compared with controls. Lung lesions included particle-containing macrophages, granulomatous pneumonia, lymphocytic interstitial aggregates, and mononuclear interstitial infiltrates. These lesions were occasionally seen in mice receiving the 2.6 µg lung burden, were present in most of the mice receiving 12 or 34 µg lung burdens, and were generally increased in severity with time and lung burden. Thus, we have demonstrated that a single, acute inhalation exposure to Be metal can chronically retard particle clearance and induce lung damage in mice. The initial lung burdens used caused responses ranging from no apparent effects to significant Be-induced responses. A comparison of these data with our previous data from rats indicates that the mass of Be metal required to induce lung damage in mice is similar to that needed for rats. When expressed on a lung weight-normalized basis, mice appeared to be more resistant to the toxic effects of inhaled Be than rats.
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