Dosimetry of beryllium in cultured canine pulmonary alveolar macrophages

Abstract

This study was designed to determine the dosimetry within macrophages of beryllium compounds administered at sublethal doses. Information on the dosimetry of beryllium within macrophages is required to guide further efforts to isolate and characterize beryllium-containing haptens. Inhalation of beryllium aerosols can cause chronic berylliosis, a progressive, granulomatous fibrosis of the lung. Studies in laboratory animals indicate that alveolar macrophages take up beryllium compounds and participate in a hypersensitivity immune response to beryllium-containing antigen. Beagle dog macrophage cultures were incubated with 7BeSO4 in solution or with suspensions of 7BeO particles that had been calcined at 500 or 1000 degrees C. Beryllium-7 was measured in fractions collected from cultures after successive centrifugation and filtration steps at 2, 6, 20, and 48 h after addition. An insignificant percentage of BeSO4 was taken up by the cells and did not cause cytotoxicity. Maximum BeO uptake occurred within 6 h, was 60 +/- 6% of added BeO, and was independent of BeO calcination temperature or specific surface area. Approximately 22% of 500 degrees C BeO dissolved within 48 h after addition to cell culture, concurrent with 39% cell killing. Dissolved beryllium remained associated with cells until a cytotoxic concentration was reached (2.2 x 10(-5) M, 15 nmol Be/10(6) cells), when the beryllium was released into the medium. There was no significant dissolution of the 1000 degrees C BeO within 48 h, and no significant cell killing. The results indicate that beryllium dissolved from phagocytized BeO was more cytotoxic than soluble beryllium added extracellularly. The data support an interactive mechanism in which phagocytized BeO particles were dissolved, and dissolved beryllium remained associated with the macrophage until a cytotoxic concentration accumulated, whereupon the beryllium was released to the medium and not appreciably taken up by viable cells.

Technology Development, Evaluation, and Application (TDEA) FY 1999 Progress Report, Environment, Safety, and Health (ESH) Division

“…Inside the phagocytes, particles are found initially within phagosomes and later in phagolysosomes (Figure 1). The phagolysosomes are the likely sites where dissolved beryllium (Eidson et al 1991, Kreyling 1992) and where the hapten involved in CBD immunopathology is formed.…”

Beryllium exposure: dermal and immunological considerations

“…Beryllium particles (metal, oxides, alloys, and others) are relatively insoluble and may be retained in the body for years, a condition which is sufficient for the formation and growth of granulomas (Stefaniak et al 2003). In vitro studies of the dissolution of beryllium from particles using an extracellular simulant lung fluid (Finch et al 1988), canine alveolar macrophages (Eidson et al 1991), a phagolysosomal simulant fluid , and a murine macrophage cell line model indicate that beryllium may become bioavailable following exposure.…”

An Official American Thoracic Society Statement: Diagnosis and Management of Beryllium Sensitivity and Chronic Beryllium Disease

“…What is clear from the existing evidence is that a permissible exposure limit of 2 mg/m 3 does not prevent BeS and CBD (25,33,34,46,51,55,56). Because a clear relationship between airborne beryllium level and risk of BeS and CBD has not been established, other routes (e.g., dermal) and/or factors may be important in determining sensitization to beryllium (51,54,(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72). As an example, solubility and size of the beryllium particles likely affect risk of BeS and CBD (62,63,(65)(66)(67)(68)73).…”

“…As an example, solubility and size of the beryllium particles likely affect risk of BeS and CBD (62,63,(65)(66)(67)(68)73). Exposure to poorly soluble materials such as beryllium oxide or oxidecoated metal appears to be associated with risk of CBD (37,47,(66)(67)(68); beryllium in these forms persists in the body for years (69)(70)(71)(72). Very small (i.e., <2.5 mm) particles penetrate to the deep lung and are associated with increased risk of CBD (55,73).…”