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暴露指标，这些模型和指标与生物利用度相关，因此与金属免疫介导的疾病风险有关。以铍为模型，这项拟议的研究将检验三个不溶颗粒的物理化学特征，即表面积、大小和化学形态预测溶解度的能力。了解铍颗粒的溶解性是很重要的，因为溶解的铍物种被认为是导致慢性铍病的免疫反应的外源输入。因此，了解不同化学形态的铍的细胞毒性与粒子的物理化学性质的关系将有助于阐明这些暴露参数，这些参数可以指示粒子的溶解度，从而表明形成铍抗原的能力。实验将使用可吸入的金属铍、氧化物和合金颗粒进行，这些颗粒可从市场上获得或从与引起CBD相关的制造工艺中取样。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为1-5天的暴露将使用静态无细胞溶解技术，该技术利用细胞内溶解环境的酸性模拟。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准确模拟，将研究铍铜合金，并将测试与导致CBD相关的工作场所采样暴露材料。

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.