2011-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/658150摘要：隨著奈米科技的發展，奈米材料可能引起的健康危害也開始引發關注，為了預防奈米微粒可能引起的健康危害，有必要進行奈米材料健康風險評估與管理。奈米科技還在發展中，健康風險評估不能等待流行病學的結果，所以必須仰賴動物實驗。呼吸道是重要的吸收途徑，也是重要的標的器官，但是目前大部分實驗都使用氣管灌注方式，雖然可以回答一些毒性及機制之問題，但是並非正常生理呼吸方式，所以本計畫將使用呼吸暴露方式進行急性及亞慢性動物實驗。先前大氣微粒毒性研究指出，微粒的健康效應多發生於易感族群，在奈米材料的製造、排放及其產品使用的過程中，健康及易感族群都可能接觸到奈米材料或物質，所以本計畫除了進行健康動物實驗，也將納入疾病動物模式，希望藉由毒性比較，可進一步瞭解奈米毒理機制，同時也可將易感族群列入風險評估的考量。奈米材料種類很多，奈米銀是目前使用最多的奈米材料，在未來兩年，我們將進行奈米銀微粒呼吸暴露研究，子計畫一將產生不同特性奈米銀微粒供本計畫進行實驗。我們將探討急性及亞慢性呼吸暴露奈米銀微粒後，各組織及體液的銀濃度，基因氧化傷害及發炎指標與病理變化等，並比較健康大鼠與氣喘及糖尿病疾病動物的呼吸道與心血管毒性。我們將以動物實驗劑量反應關係，估算benchmark concentration，推估人類安全劑量，然後與子計畫三職場暴露評估值比較。這些研究成果將可增進我們對奈米材料毒性及風險的瞭解，提供政府制訂奈米法規的參考。<br> Abstract: With the development of nanotechnology, the potential health effects of nanoparticles (NPs) have raised concerns. To prevent and control the potential hazards from using NPs, we need to conduct risk assessment and management for NPs. NPs have unique physicochemical characteristics, but the toxicity remains unclear. Respiratory tract is a major route of entry and target organ. However, most of studies were conducted with intratracheal instillation, which is not physiological. Thus, it is important to conduct an inhalation study for risk assessment. Previous studies showed that most health effects of ambient particles developed in the susceptible populations. Thus, we will also conduct inhalation studies in diseased animals. Silver NPs rank as most used nanomaterial in the market. In the next 2 years, we will investigate the systemic distribution of silver NPs and their acute and subchronic toxicities including cardiopulmonary function and oxidative DNA damage and pathological changes. The cardiopulmonary toxicities will also be compared between healthy and asthmatic or diabetic animals after acute and subchronic inhalation exposure. Subproject 1 will generate different type of silver NPs for our study. The dose-response relationship from inhalation studies will be used to calculate the benchmark concentration, which could be extrapolated to humans. The exposure assessment data at worksite together with toxicological data will be used for the risk assessment. Our study will enhance our knowledge in NPs toxicity and their associated risk. The results can also provide for the regulatory setting.發炎反應肺部呼吸道阻力氧化壓力腹膜發炎奈米銀微粒allergic inflammationairway hyperresponsivenessinductively coupled plasma-mass spectrometryoxidative stressperitoneal inflammationsilver nanoparticle