The acute toxicity of inhaled beryllium metal in rats.
We exposed rats once by nose only for 50 min to a mean concentration of 800 micrograms/m3 of beryllium metal (initial lung burden, 625 micrograms) to characterize the acute toxic effects within the lung. Histological changes within the lung and enzyme changes within bronchoalveolar lavage (BAL) fluid were evaluated at 3, 7, 10, 14, 31, 59, 115, and 171 days postexposure (dpe). Beryllium metal-exposed rats developed acute, necrotizing, hemorrhagic, exudative pneumonitis and intraalveolar fibrosis that peaked at 14 dpe. By 31 dpe, inflammatory lesions were replaced by minimal interstitial and intraalveolar fibrosis. Necrotizing inflammation was observed again at 59 dpe which progressed to chronic-active inflammation by 115 dpe. This inflammation worsened progressively, as did alveolar macrophage and epithelial hyperplasia, becoming severe at 171 dpe. Low numbers of diffusely distributed lymphocytes were also present but they were not associated with granulomas as is observed in beryllium-induced disease in man. Throughout the experiment, total numbers of cells were elevated within the BAL samples due primarily to increased numbers of neutrophils. Lymphocytes were not elevated in BAL samples collected from beryllium-exposed rats at any time after exposure. Lactate dehydrogenase (LDH), beta-glucuronidase, and protein levels were elevated in BAL fluid from 3 through 14 dpe but returned to near normal levels by 31 dpe. LDH increased once again at 59 dpe and remained elevated at 171 dpe. beta-Glucuronidase and protein levels were slightly, but not significantly, elevated from 31 through 171 dpe. Results indicate that inhalation of beryllium metal by rats results in severe, acute chemical pneumonitis that is followed by a quiescent period of minimal inflammation and mild fibrosis. Progressive, chronic-active, fibrosing pneumonitis is observed later. Chronic beryllium lung disease of man is an immunologically mediated granulomatous lung disease, whereas beryllium-induced lung lesions in rats appear to be due to direct chemical toxicity and foreign-body-type reactions.
Haley
P J
PJ
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Finch
G L
GL
Hoover
M D
MD
Cuddihy
R G
RG
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001608:Beryllium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000201:enzymology; D005966:Glucuronidase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D000336:Aerosols; D007770:L-Lactate Dehydrogenase; D005966:Glucuronidase; D001608:Beryllium