Significance of particle parameters in the evaluation of exposure-dose-response relationships of inhaled particles.

作者：Günter Oberdörster · 发表于：PubMed · 年份：1996 · 被引用次数：227 · 研究领域：Inhalation and Respiratory Drug Delivery、Air Quality and Health Impacts

Chronic rat inhalation studies have shown that a number of different particle types can induce significant adverse effects, including impaired lung clearance, chronic pulmonary inflammation, pulmonary fibrosis, and lung tumors. These effects occurred when highly insoluble particles of low solubility and low cytotoxicity were inhaled in long-term studies. Inhaled concentrations ranged from a few milligrams per cubic meter up to 250 mg/m3. This wide range of inhaled concentrations may indicate that the particulate compounds have differed largely in their toxicity. This view appears to be supported by the fact that cytotoxic crystalline SiO2 shows very similar effects after much lower inhaled concentrations. However, although administered doses are customarily expressed in units of mass, this may not be the appropriate dose-metric for a correlation with observed effects. For example, effects on alveolar macrophage (AM) mediated clearance of particles could best be correlated with the volumetric lung burden of different particle types, suggesting that the particle volume phagocytized by AM is an appropriate dose parameter for this endpoint. On the other hand, the inflammatory response induced by a number of different particle types could best be correlated with the surface area of the particles retained in the alveolar space. In addition, total surface area of retained particles was the best dose parameter (or a correlation when the endpoint was lung tumors. In all of these studi...