Cytoxicity and Solubility of Beryllium Particles

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The long-term goal of this research is to develop more protective industrial hygiene models and metrics of exposure that are related to bioavailability and therefore risk of immune mediated disease from metals. Using beryllium as a model, the proposed research will examine the ability of three insoluble particle physicochemical characteristics, surface area, size, and chemical form to predict solubility. An understanding of beryllium particle solubility is important because the dissolved beryllium species is hypothesized to be the exogenous input to the immune reaction resulting in chronic beryllium disease. Thus, knowledge of cytotoxicity for various chemical forms of beryllium as a function of particle physicochemical properties will help to elucidate those exposure parameters that are indicative of particle solubility, and therefore capacity to form beryllium antigen. Experiments will be performed using respirable beryllium metal, oxide, and alloy particles that are commercially available or were sampled from manufacturing processes associated with causing CBD. The effects of increasing surface area, size, and chemical form doses on solubility will be determined will be assayed for 1 to 5 day exposures using a static acellular dissolution technique that utilizes an acidic simulant of the intracellular dissolution environment. This work is novel compared to the published literature in that these experiments an accurate simulant of the intracellular dissolution environment, will investigate beryllium copper alloys, and will test workplace sampled exposure materials associated with causing CBD.