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Objectives-To describe relative hazards in sectors of the beryllium industry, risk factors ofberyllium disease and sensitisation related to work process were sought in a beryllium manufacturing plant producing pure metal, oxide, alloys, and ceramics. Methods-All 646 active employees were interviewed; beryllium sensitisation was ascertained with the beryllium lymphocyte proliferation blood test on 627 employees; clinical evaluation and bronchoscopy were offered to people with abnormal test results; and industrial hygiene measurements related to work processes taken in 1984-93 were reviewed. Results-59 employees (9.4%) had abnormal blood tests, 47 of whom underwent bronchoscopy. 24 Beryllium exposure leads to cell mediated immunological sensitisation in a small percentage of workers exposed to beryllium aerosols, dusts, or fumes; of the sensitised workers, many have granulomatous lung disease.' Prevention of beryllium disease depends on knowledge of risk factors which can be modified. Although inborn genetic factors are associated with risk of disease in those exposed to beryllium,4 these cannot be changed in an existing workforce exposed to beryllium. In contrast, work related risk factors offer the opportunity to lower risk of beryllium disease and to understand the exposure characteristics associated with high disease rates. In our previous studies of plant workforces exposed to beryllium, we found risks of beryllium sensitisation or disease related to work processes in three plants representing single sectors of the beryllium industry. These include machining of beryllium metal,' grinding, dicing, and drilling of beryllia ceramics,' dry pressing, and research and development in a plant which manufactured beryllia ceramics historically.' We report here the results of epidemiological and exposure surveillance in a plant which encompasses most sectors of the beryllium industry in production of beryllium metal, alloys, and beryllium oxide from which ceramics were made historically. We sought to describe risks of beryllium disease related to work processes which could provide opportunities for future study of exposure variables conferring excess risk. Understanding of qualitative and quantitative exposure-response relations is critical to prevention of disease in the many sectors of the beryllium industry.The plant opened in 1953 to produce beryllium-copper alloy, which is cast and fabricated into tubes, wire, sheet, plates, and metal parts before shipment to other factories to become finished products. Beryllium metal operations were developed in about 1957 in buildings and under management which were largely separate from alloy operations. Beryllium metal is produced from beryllium hydroxide through a chemical process. The two component areas involved in beryllium metal production are the pebble plant, which contains fluoride and reduction furnaces, and vacuum melting.' As the crystalline structure of cast beryllium metal is unsuitable for many applications, the metal is partitioned into differing grade...

Lung granulomas are associated with numerous conditions, including inflammatory disorders, exposure to environmental pollutants, and infection. Osteopontin is a chemotactic cytokine produced by macrophages, and is implicated in extracellular matrix remodeling. Furthermore, osteopontin is up-regulated in granulomatous disease, and osteopontin null mice exhibit reduced granuloma formation. Animal models currently used to investigate chronic lung granulomatous inflammation bear a pathological resemblance, but lack the chronic nature of human granulomatous disease. Carbon nanoparticles are generated as byproducts of combustion. Interestingly, experimental exposures to carbon nanoparticles induce pulmonary granuloma-like lesions. However, the recruited cellular populations and extracellular matrix gene expression profiles within these lesions have not been explored. Because of the rapid resolution of granulomas in current animal models, the mechanisms responsible for persistence have been elusive. To overcome the limitations of previous models, we investigated whether a model using multiwall carbon nanoparticles would resemble chronic human lung granulomatous inflammation. We hypothesized that pulmonary exposure to multiwall carbon nanoparticles would induce granulomas, elicit a macrophage and T-cell response, and mimic other granulomatous disorders with an up-regulation of osteopontin. This model demonstrates: (1) granulomatous inflammation, with macrophage and T-cell infiltration; (2) resemblance to the chronicity of human granulomas, with persistence up to 90 days; and (3) a marked elevation of osteopontin, metalloproteinases, and cell adhesion molecules in granulomatous foci isolated by laser-capture microdissection and in alveolar macrophages from bronchoalveolar lavage. The establishment of such a model provides an important platform for mechanistic studies on the persistence of granuloma.