Cytoxicity and Solubility of Beryllium Particles

这项研究的长期目标是开发更具保护性的工业卫生模型和接触指标，这些模型和指标与金属的生物利用度和免疫介导疾病的风险有关。以铍为模型，提出的研究将检验三种不溶性颗粒的物理化学特性、表面积、大小和化学形式来预测溶解度的能力。了解铍粒子的溶解度是很重要的，因为溶解的铍被假设是导致慢性铍病的免疫反应的外源性输入。因此，了解各种化学形式的铍的细胞毒性作为粒子物理化学性质的函数，将有助于阐明指示粒子溶解度的暴露参数，从而形成铍抗原的能力。实验将使用可呼吸的铍金属、氧化物和合金颗粒进行，这些颗粒可以在商业上获得，或者从与CBD相关的制造过程中取样。增加表面积、大小和化学形式剂量对溶解度的影响将被确定。将在1至5天的暴露中使用静态细胞外溶解技术，该技术利用细胞内溶解环境的酸性模拟物。与已发表的文献相比，这项工作是新颖的，因为这些实验是细胞内溶解环境的精确模拟，将研究铍铜合金，并将测试与导致CBD相关的工作场所取样暴露材料。

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.