本研究之目為評估不同粒徑石英粉塵之質量濃度、表面積濃度、和個數濃度和肺部上皮細胞增生和免疫發炎反應之關係，並探討適用於不同粒徑石英微粒之最合適暴露評估指標。本研究利用液相沉積裝置（Liquid sedimentation device）將石英粉塵分為三粒徑分布，並以掃描式電子顯微鏡（Scanning electron microscopy；SEM）和穿透式電子顯微鏡（Transmission electron microscopy；TEM）分析石英粉塵之實際粒徑，結果發現三粒徑分布粒數中數粒徑（CMD）依序為0.98 μm、2.61 μm、和8.79 μm，且GSD均小於1.62。各測試微粒粒徑分布的石英含量範圍介於97.5 %及118.0 %，SD均介於 0.04和0.32之間。石英粉塵中總金屬含量為0.84 %，SD均介於 0.0032和0.79之間。本研究以MTT細胞增生分析評估石英粉塵促進肺部上皮細胞A549增生反應，而肺部免疫發炎反應則使用RAW264.7細胞株之細胞激素TNF-alpha和TGF-beta，分別作為急性和促纖維化之發炎指標。前述之指標均使用ELISA進行分析。當細胞暴露於不同粒徑之石英微粒後，發現粒徑愈小引起之上皮細胞增生情形和急性發炎反應愈嚴重，但就致TGF-beta的生成而言，2.61 μm之微粒則較其他粒徑嚴重之。前述結果說明不同粒徑之石英在造成肺部疾病上佔有不同角色。本研究進一步評估CMD分別為0.98 μm、2.61 μm、和8.79 μm之石英粉塵於不同暴露指標下其生物劑量反應關係。就上皮細胞增生而言，以質量濃度為暴露指標時之EC50分別為26.5、26.7、和25.7；表面積濃度為暴露指標時之EC50分別為5.11、1.60、和0.46 cm2；個數濃度為暴露指標時之EC50則分別為39.5×10^6、0.72×10^6、和0.014×10^6#。就急性發炎反應而言，以質量濃度為暴露指標時之EC50分別為67.4、66.2、和60.6 μg；表面積濃度為暴露指標時之EC50分別為52.1、15.9、和4.33 cm2；個數濃度為暴露指標時之EC50則分別為則分別為172×10^6、2.69×10^6、和0.056×10^6#。就促纖維化反應而言，以質量濃度為暴露指標時之EC50分別為23.9、26.3、和30.8 μg；表面積濃度為暴露指標時之EC50分別為24.4、6.30、和2.20 cm2；個數濃度為暴露指標時之EC50則分別為143×10^6、2.84×10^6、和0.065×10^6#。本研究並經由全部粒徑之劑量反應關係探討適用於石英微粒之最合適暴露評估指標，質量濃度、表面積濃度、和個數濃度暴露指標與上皮細胞增生之相關性（R2）分別為0.999、0.905、和0.205；與急性發炎反應之相關性（R2）分別為0.998、0.812、和0.526；與促纖維化反應之相關性（R2）分別為0.992、0.887、和0.491。綜合前述，本研究發現評估不同粒徑結晶型二氧化矽健康危害之最合適暴露指標為質量濃度。

The objectives of this study are to assess the relationships between mass, surface area, and number concentrations for quartz of different particle sizes and lung epithelia cell proliferation and inflammatory response, and to determine the most suitable exposure metric for quartz exposures. The quartz dusts were separated into three particle sizes using a liquid sedimentation system, and the separated quartz dust samples were analyzed using SEM (Scanning electron microscope) and TEM (Transmission electron microscopy) to determine their true particle size distributions. By count median diameters (CMD), three particle size distributions of quartz were found, 0.98 μm, 2.61 μm, and 8.79 μm, and the corresponding GSDs were consistently less than 1.62. All three tested particles had 97.5-118.0 % (SD= 0.04-0.32) of quartz contents, and total metal content less than 0.84 %, (SD= 0.0032-0.79). This study applied MTT cell proliferation assay to determine the proliferation index of pulmonary A549 cells and ELISA measurement of TNF-alpha and TGF-beta production of RAW264.7 cell as the index of acute and fibrogenic response. All of the above indices were assayed using ELISA. While cells were treated with quartz powders of different particle sizes, and the results show that the smaller quartz particle in size, caused the stronger cell proliferation and inflammatory response, and quartz with particle size 2.61 μm was found with the highest fibrogenic response than that of other particle sizes. The above results suggest that quartz of different particle sizes might play the different roles in causing diseases. This study further evaluated the biological-based dose-response relationship for quartz of different particle sizes while testing against difference exposure metrics. For assaying cell proliferation of CMD 0.98 μm, 2.61 μm and 8.79 μm of quartz dusts, EC50 would be 26.5, 26.7 and 25.7 ug, respectively, using mass concentration as exposure metric. EC50 would be 5.11, 1.60 and 0.46 cm2, respectively, using surface area concentration as exposure metric. EC50 would be 39.5×10^6, 0.72×10^6 and 0.014×10^6#, respectively, using surface area concentration as exposure metric. As obtained from the acute inflammation results, the use of mass concentration would result in EC50 of 67.2, 66.2, and 60.6 μg, respectively; the use of surface area concentration would result in EC50 of 52.1, 15.9, and 4.33 cm2, respectively; the use of number concentration would result in EC50 of 172×10^6, 26.9×10^6, and 0.056×10^6#, respectively. Based on the fibrogenic response results, the mass concentration would result in EC50 of 23.9, 26.3, and 30.8 μg, respectively; the surface area concentration would result in EC50 of 24.4, 6.30, and 2.20 cm2, respectively; the number concentration would result in EC50 of 143×10^6, 2.84×10^6, and 0.065×10^6#, respectively. This study further applied exposure dose-cummulative response to determine the most suitable exposure metric for assessing quartz exposures. The R2 for the mass concentration, surface area concentration, and number concentration in relation to cell proliferation were 0.999, 0.905, and 0.205, respectively; they were 0.998, 0.812, and 0.526, respectively, in realtion to acute inflammation; they were 0.992, 0.887, and 0.491, respectively, in relation to fibrogenic response. The above results clearly suggest that the mass concentration is the most suitable exposure metric to assess the health-risks associated with crystalline silica exposures.

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