Responses of Rat Lungs to Low Lung Burdens of Inhaled Beryllium Metal

Abstract

The linkage between acute and chronic toxic responses to inhaled beryllium (Be) is not well understood. This study described (1) the lowest lung burdens of Be that would induce acute pulmonary toxicity, (2) the progression of acute to chronic toxic responses, and (3) the effects of Be exposure on lung clearance. We simultaneously exposed groups of male F344/N rats by single, brief, nose-only inhalation to a mixed aerosol consisting of Be metal and radioactive tracer particles. Lung burdens of Be achieved were 0.32, 1. B, 10, and 100 μg; control rats received the tracer particles alone. The purpose of the tracer particle exposure was to compare lung clearance of these particles between groups. Groups of rats were sacrificed at 8, 16, 40, 90, 210, and 365 days after exposure for histopathologic examination and for bronchoalveolar lavage. No lesions were observed in controls or in animals receiving lung burdens of 0.32 μg Be. At the 1.8 μg lung burden of Be, only late-occurring, minimal chronic inflammation and alveolar epithelial hyperplasia was observed. Lung burdens of 10 and 100 μg Be induced minimal to mild acute and chronic inflammation, alveolar epithelial hyperplasia, and early-occurring fibrosis. The total numbers of cells, incidence of neutrophils, levels of total protein, and activities of the enzymes lactate dehydrogenase and β-glucuronidase were generally elevated in lavage fluids from groups of rats that also had histologic alterations. for the two highest lung burdens (10 and 100 μg), Be significantly decreased the early- and late-phase clearance of the tracer particles through 365 days after exposure compared to controls. At the lowest lung burden (0.32 μg), although effects on lung clearance were marginal, the more rapid phase of clearance had relatively less material that cleared slightly slower than for controls. Thus, a reduced ability of the lungs to clear the tracer particles was among the most sensitive indications of lung toxic responses to inhaled Be. This study serves to further define dose-response relationships in the rat between lung burdens of Be metal and retarded lung clearance and pulmonary pathological responses.