COMPARATIVE PULMONARY TOXICITY OF BERYLLIUM METAL AND BERYLLIUM-OXIDEIN CYNOMOLGUS MONKEYS

Inhalation of beryllium (Be) may result in an immune-mediated, chronic granulomatous pulmonary disorder known as chronic beryllium disease ( CBD). The physicochemical form of Be may affect the incidence and seve rity of CBD. We exposed cynomolgus monkeys, by bronchoscopic, intrabro nchiolar instillation, to either beryllium oxide (BeO; heat-treated at 500 degrees C) or Be metal at concentrations selected to achieve equi molar concentrations of available Be2+ ions dissolving from the partic les. Monkeys underwent bronchoalveolar lavage of the right and left di aphragmatic lobes at 14, 30, 60, 90, and 120 days post exposure (dpe). Monkeys were sacrificed at 80 and 180 dpe for evaluation of histopath ological pulmonary changes. Numbers of lymphocytes from lung lobes of Be metal-exposed, but not BeO-exposed, monkeys were increased at 14, 3 0 and 90 dpe. Lung lymphocytes were increased for BeO exposed monkeys only at 60 dpe. In vitro, Be-specific, lung lymphocyte proliferation o ccurred at 14, 60, and 90 dpe for lymphocytes from Be metal-exposed lu ng lobes only. At no time were values from BeO-exposed lung lobes diff erent from values from control lobes. Lung lesions in Be metal-exposed monkeys were characterized by focally intense, interstitial fibrosis, marked Type II cell hyperplasia, and variable lymphocyte infiltration . Some Be-metal-exposed monkeys had discrete immune granulomas consist ing of tightly organized lymphocytic cuffs surrounding nodular aggrega tes of epithelioid macrophages. Lesions were rarely present in BeO-exp osed monkeys and were much less severe. These data suggest that Be met al produces more severe pulmonary lesions than does BeO and that these lesions are accompanied by Be-specific immune responses.