Pj. Haley et al., COMPARATIVE PULMONARY TOXICITY OF BERYLLIUM METAL AND BERYLLIUM-OXIDEIN CYNOMOLGUS MONKEYS, Immunopharmacology and immunotoxicology, 16(4), 1994, pp. 627-644
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.