(Litvinov et al. 1975). The first neoplasms were observed after 16 months in rats exposed to beryllium fluoride at 0.4 mg/m3 and beryllium chloride at 0.2 mg/m3. Neoplasms also developed in the lungs of rats exposed at the lower concentrations, but not in the lungs of the control rats.
Litvinov et al. (1984) exposed female albino rats to beryllium oxide or beryllium chloride at 0.8, 4, 30, and 400 μg/m3 for 1 h/day, 5 days/week, for 4 months. Malignant lung neoplasms developed in a dose-related manner after exposure to either beryllium oxide or beryllium chloride, but none was found in the controls. The carcinogenicity of two beryllium ores, bertrandite and beryl, was evaluated in male squirrel monkeys (Saimiri sciurea), male Charles River-CD rats, male Greenacres Controlled Flora (GA) rats, and male Golden Syrian hamsters (Wagner et al. 1969). The rats and hamsters were exposed to bertrandite or beryl at 15 mg/m3 for 6 h/day, 5 days/week, for 17 months, and the monkeys were exposed for 23 months. Beryllium from bertrandite was present in the test atmospheres at 210 μg/m3 and from beryl at 620 μg/m3; the geometric means of the particles were 0.27 μm and 0.64 μm, respectively. In the beryl-exposed rats, squamous metaplasia or small epidermoid tumors were identified in the lungs of five of 11 rats killed after 12 months of exposure and 18 of 19 rats after 17 months of exposure. Eighteen of the rats had bronchiolar alveolar-cell tumors, nine had adenocarcinomas, seven had adenomas, and four had epidermoid tumors. Although granulomatous lesions were observed in the bertrandite-exposed rats, no neoplasms were identified in the rats exposed for 6, 12, or 17 months. Neither neoplasms nor granulomas developed in the control rats.
Atypical proliferations were observed in the lungs of hamsters 12 months after exposure to bertrandite or beryl. The lesions were reported to be larger and more adenomatous in the beryl group after 17 months. No pulmonary lesions occurred in the control hamsters. No tumors were observed in either the bertrandite- or beryl-treated monkeys.
The carcinogenicity of beryllium metal has also been investigated. In one study, male and female F344/N rats were received a single, nose-only exposure to a beryllium metal aerosol at 500 mg/m3 for 8 min, at 410 mg/m3 for 30 min, at 830 mg/m3 for 48 min, or at 980 mg/m3 for 39 min (Nickell-Brady et al. 1994). The latent period for development of neoplasms was about 14 months; tumor incidence was 64% over the lifetime of the rats. Most of the neoplasms were adenocarcinomas, although multiple tumor types were observed.
In another study of beryllium metals (Groth et al. 1980), lung adenomas and adenocarcinomas were observed in nine of 16 female Wistar rats that received a single intratracheal instillation of 2.5 mg of beryllium metal, nine of 26 rats treated with 2.5 mg of passivated beryllium metal, and four of 24 rats given 2.5 mg of beryllium-aluminum alloy. No neoplasms were observed in the lungs of the controls.
Pulmonary neoplasms developed in inbred albino rats that were given single intratracheal deposits of beryllium oxide (fired at high and low temperatures) at 0.036, 0.36, 3.6, or 18 mg/kg (Litvinov et al. 1983). The neoplasms were adenomas, adenocarcinomas, and squamous-cell carcinomas.
Wistar rats received intratracheal instillations of 1 mg of beryllium oxide (low-fired) once a week for 15 weeks (Ishinishi et al. 1980). An adenocarcinoma, a squamous-cell carcinoma, and four adenomas were observed in the lungs of 30 beryllium-treated rats and no neoplasms in the 16 controls.
Genotoxicity studies of beryllium have yielded conflicting results that appear to be somewhat compound dependent. The committee will critically evaluate the literature in its next report and consider how the information should be factored into the carcinogenic assessment of beryllium.
There is evidence from controlled studies that exposure to beryllium can cause lung cancer in both sexes of rats, and one study reported lung tumors in monkeys. Epidemiologic studies have reported increases in lung-cancer risk in two worker cohorts exposed to beryllium. Those studies were instrumental in forming the basis of the current cancer classifications by such agencies as the International Agency for Research on Cancer, the U.S. Environmental Protection Agency, and the National Toxicology Program. In its second report, the committee will focus on assessing the collective evidence in characterizing the carcinogenic potential of beryllium and estimating carcinogenic risks.