The Acute Toxicity of Inhaled Beryllium Metal in Rats

The Acute Toxicity of Inhaled Beryllium Metal in Rats. HALEY,P. J., FINCH, G. L., HOOVER, M. D., AND CUDDIHY, R. G. (1990).Fundam. Appl. Toxicol. 15, 767–778. We exposed rats onceby nose only for 50 min to a mean concentration of 800 µg/m³of beryllium metal (initial lung burden, 625 µg) to characterizethe acute toxic effects within the lung. Histological changeswithin the lung and enzyme changes within bronchoalveolar lavage(BAL) fluid were evaluated at 3, 7, 10, 14, 31, 59, 115, and171 days postexposure (dpe). Beryllium metal-exposed rats developedacute, necrotizing, hemorrhagic, exudative pneumonitis and intraalveolarfibrosis that peaked at 14 dpe. By 31 dpe, inflammatory lesionswere replaced by minimal interstitial and intraalveolar fibrosis.Necrotizing inflammation was observed again at 59 dpe whichprogressed to chronic-active inflammation by 115 dpe. This inflammationworsened progressively, as did alveolar macrophage and epithelialhyperplasia, becoming severe at 171 dpe. Low numbers of diffuselydistributed lymphocytes were also present but they were notassociated with granulomas as is observed in beryllium-induceddisease in man. Throughout the experiment, total numbers ofcells were elevated within the BAL samples due primarily toincreased numbers of neutrophils. Lymphocytes were not elevatedin BAL samples collected from beryllium-exposed rats at anytime after exposure. Lactate dehydrogenase (LDH), ß-glucuronidase,and protein levels were elevated in BAL fluid from 3 through14 dpe but returned to near normal levels by 31 dpe. LDH increasedonce again at 59 dpe and remained elevated at 171 dpe. ß-Glucuronidaseand protein levels were slightly, but not significantly, elevatedfrom 31 through 171 dpe. Results indicate that inhalation ofberyllium metal by rats results in severe, acute chemical pneumonitisthat is followed by a quiescent period of minimal inflammationand mild fibrosis. Progressive, chronic-active, fibrosing pneumonitisis observed later. Chronic beryllium lung disease of man isan immunologically mediated granulomatous lung disease, whereasberyllium-induced lung lesions in rats appear to be due to directchemical toxicity and foreign-body-type reactions.