Beryllium Carcinogenesis. I. Inhalation Exposure of Rats to Beryllium Sulfate Aerosol

One hundred fifty rats (with equal number of controls) were exposed to the inhalation of beryllium sulfate aerosol at a mean atmospheric concentration of 34.25 µg of Be/cu m, and sacrificed in monthly groups during 72 weeks of exposure. Average lung weight towards the end of exposure was 4.25 times normal. Histopathologic examination disclosed 2 gradually developing pathologic processes: ( a ) an inflammatory response chiefly characterized by marked accumulation of histiocytic elements forming clusters of macrophages in the alveolar spaces; and ( b ) a proliferative response, progressing from early epithelial hyperplasia of the alveolar surfaces, through metaplasia and anaplasia, to lung cancer. The first tumors were found after 9 months of exposure, the incidence rapidly rising, and reaching 100% at 13 months ( vs. 0% in controls). All tumors appeared to be alveolar adenocarcinomas, in some instances with focal intermixture of other types. Out of 56 tumors studied, 3 reached a very large size comparatively early. Females appeared to be more vulnerable to the exposure than males in terms of attritional mortality and body weight loss.