Influence of physicochemical properties on dissolution of beryllium from respirable beryllium particles and powders associated with prevalence of chronic beryllium disease

Chronic beryllium disease (CBD) is a potentially fatal cell-mediated immune disease of the lung with no known cure that continues to be diagnosed among current and former beryllium workers. CBD is associated with exposure to beryllium-containing particles; however, at the cellular level a dissolved beryllium species is the hypothesized input to the immune reaction that drives development of CBD. Little is known about the physicochemical properties or dissolution behavior of respirable beryllium aerosols, suggesting that the relationship between exposure to beryllium and dose is not well understood. Research performed as part of this dissertation improves our understanding of how physicochemical properties of beryllium aerosols relate to solubility, and, potentially, development of CBD.; Dissolution (conversion from particle to a dissolved species) is a physicochemical process. Physicochemical properties of beryllium aerosols associated with elevated prevalence of CBD were characterized utilizing techniques such as aerodynamic size-separation and microscopy to understand size and morphology, x-ray diffraction to determine chemical composition, and surface area analysis to determine specific surface area (SSA). Lacking a model of the liquid environment of the pulmonary alveolar macrophage phagolyososome, the hypothesized site of beryllium dissolution, a dissolution model was refined and characterized. This model was used to determine the chemical dissolution rate constant (k) for each material, a constant unique to a given chemical form of beryllium.; Results indicated that physicochemical properties, and in turn, values of k, differed among the study materials. For the copper-beryllium particles studied, measured SSA for the entire sample did not govern beryllium dissolution. Additional studies of this material showed that dissolution did not vary with measured SSA of the entire sample as expected from dissolution theory. Using k determined for beryllium oxide, the effective beryllium oxide SSA was calculated for the copper-beryllium material using a technique developed as part of this dissertation. To account for measured dissolution the SSA of the beryllium oxide component of master alloy particles must be several orders of magnitude higher than the SSA determined for the total particle sample.; An understanding of beryllium particle dissolution is important because the rate of dissolved beryllium production may be the rate limiting step in the activation of the CBD immune response. Data collected indicate that k values with capacity to cause CBD may vary by an order of magnitude or more. Thus, an improved approach for regulating exposure might categorize chemical forms of beryllium according to solubility characteristics and SSA, with those materials producing dissolved beryllium at a rate sufficient for activation of the CBD immune response posing the highest risk.