臺灣博碩士論文加值系統

在晶圓廠中，離子植入機台的定期維修保養作業過程是項潛在危害暴露的作業，當維修保養工程師定期拆卸使用固態砷或砷化氫為原料的離子植入機台，以進行不同程度的維修保養工作時，便有可能遭受到殘留在機台的元素態砷或含砷化合物暴露的危害。先前的作業環境研究結果顯示維修工程人員在離子植入機台維修工作期間，尿中砷濃度會有些微上升現象。
隨著尿中無機砷代謝產物物種分析技術日趨進步成熟，本研究以高效率液相層析儀連接氫化法原子吸收光譜儀（HPLC-HG-AAS），分析晶圓廠離子植入機台維修工程師尿中無機砷代謝物種濃度，瞭解各物種分布變化情形，以探討相關作業潛在砷暴露的可能性與暴露程度。
研究結果分析六個半導體晶圓製造廠，共計30名暴露組之離子植入機台維修保養之工程人員及12名非暴露組對照人員，一週中連續收集七天之早晨第一泡新鮮尿液樣本。結果顯示維修工程師之尿中無機砷代謝產物濃度分別為三價砷1.7±1.4 μg/L、五價砷1.4±1.1 μg/L、單甲基砷酸6.3±6.7 μg/L、二甲基砷酸20.2±14.1 μg/L，總無機砷代謝物濃度為29.8±17.0 μg/L；非暴露組人員之中無機砷代謝產物濃度分別為三價砷1.6±1.5 μg/L、五價砷1.0±1.0 μg/L、單甲基砷酸4.1±5.5 μg/L、二甲基砷酸21.3±13.1 μg/L，總無機砷代謝物濃度為28.1±17.5 μg/L。以肌酸酐濃度校正後維修工程師尿液中總無機砷代謝物濃度為21.5±10.0 μg/g creatinine；非暴露人員尿液中總無機砷代謝物經肌酸酐濃度校正後濃度為24.7±12.3 μg/g creatinine。
研究結果顯示維修工程師與非暴露人員間尿中無機砷代謝產物濃度差異並不大，顯示維修工程師目前受到砷暴露的危害似乎不大，但對於長期之慢性暴露而言，建議仍應做持續之監測，不應掉以輕心。但是在於維修工程師有無進行維修保養工作時及非暴露人員間之單甲基砷酸百分比、二甲基砷酸百分比略有呈現單甲基砷酸由高到低（22.6±16.4 ％、18.7±12.2 ％、13.9±9.5 ％）、二甲基砷酸百分比由低到高（66.0±15.5 ％、69.2±14.4 ％、76.6±10.0 ％）的差異，值得更進一步探討。此外，在低濃度的職業暴露下，體內無機砷代謝產物之來源有待進一步研究探討，以瞭解是否例如海產食物之來源會干擾分析結果。

In the wafer fabrication facility of semiconductor industry, the routine maintenance of ion implanter potentially exposes the engineers to hazard when the maintenance engineers disassemble the ion implanter for different types of maintenance, especially arsenic or arsenic compounds in it. A previous study has shown that the urinary inorganic arsenic metabolites levels of maintenance engineers slightly increased during the ion implanter maintenance days.
This study analyzed specific inorganic arsenic metabolites levels of the ion implanter maintenance engineers'' urine using HPLC-HG-AAS to study the potential arsenic exposure during a maintenance work.
Totally, 30 subjects of exposure group and 12 subjects of control group from 6 wafer fabrication facilities subject were recruited in this study. First morning-voided urine of each was sampled for 7 consecutive days. Results show the levels of urinary inorganic arsenic metabolites for maintenance engineers group were 1.7±1.4 μg/L, 1.4±1.1 μg/L, 6.3±6.7 μg/L, 20.2±14.1 μg/L, 29.8±17.0 μg/L for As3+, As5+, monomethylarsonic acid, dimethylarsinic acid and total inorganic arsenic, respectively. Meanwhile, these arsenic of non-exposure group were 1.6±1.5 μg/L, 1.0±1.0 μg/L, 4.1±5.5 μg/L, 21.3±13.1 μg/L and 28.1±17.5 μg/L, respectively. After adjusted for the creatinine level, the total urinary inorganic arsenic metabolites levels were 21.5±10.0 μg/g creatinine, 24.7±12.3 μg/g creatinine for the maintenance engineers group and non-exposure group, respectively. It was also indicated that only a little difference of urinary inorganic arsenic metabolites level between maintenance engineers group and non-exposure group. It seemed like the arsenic exposure of the maintenance engineers was limited. But, continuous exposure control and motoring are still recommended to prevent the chronic adverse health effect after long-term occupational exposure. But, among 3 comparing groups, i.e. the maintenance engineers with maintenance work, the maintenance engineers without maintenance work and the non-exposure group, the proportions of monomethylarsonic acid 22.6±16.4 ％, 18.7±12.2 ％ and 13.9±9.5 ％, respectively, and that for dimethylarsinic acid 66.0±15.5 ％, 69.2±14.4 ％, and 76.6±10.0 ％, respectively shows a indicating a interesting reverse rends. Further study is warranted to explore the mechanism of this phenomenon. Besides, at low dose of occupational arsenic exposure, the sources of urinary inorganic arsenic metabolites need to be more clearly defined to exclude the confounding source from seafood.

目 錄
摘 要i
Abstractiii
目 錄I
表 目 錄III
圖 目 錄IV
第一章 前 言1
第二章 文 獻 探 討4
2.1 離子植入機台維修工程師之砷暴露4
2.1.1 半導體晶圓製造的作業環境4
2.1.2 半導體製程作業的潛在危害4
2.1.3 離子植入機設備維修保養及砷暴露5
2.2 砷的物化特性7
2.3 砷的環境流佈7
2.3.1 自然污染源7
2.3.2 人為污染源8
2.4 砷的使用9
2.5 砷的暴露9
2.5.1 醫療用藥暴露9
2.5.2 環境暴露10
2.5.3 職業暴露10
2.6 砷的健康效應10
2.7 砷的物種12
2.8 砷在體內之甲基化代謝13
2.8.1 砷在哺乳類動物體內的甲基化代謝14
2.8.2 無機砷在體內進行甲基化的基礎架構14
2.8.3 可能影響甲基化反應的因素及作用16
2.8.3.1 三價砷酸對二甲基化反應的影響16
2.8.3.2 細胞質蛋白（cytosol protein）的影響16
2.8.3.3 雙硫醇（dithiol）的影響17
2.8.3.4 飲食對於砷的甲基化反應效率之影響17
2.8.4 海鮮攝取對尿液中砷物種分析的影響18
2.9 生物偵測指標18
第三章 材 料 與 方 法20
3.1 研究對象20
3.2 樣本收集22
3.3 樣本分析22
3.3.1 肌酸酐（Creatinine）濃度測定23
3.3.2 無機砷代謝產物物種分析23
3.3.2.1 前處理23
3.3.2.2 尿液中無機砷代謝物種的分離24
3.3.2.3 無機砷代謝物種的偵測24
3.3.2.4 儀器設備25
3.3.2.5 試藥及試劑26
3.4 分析法的品質控制與保證28
3.4.1 檢量線28
3.4.2 偵測極限28
3.4.3 準確度28
3.4.4 精密度28
3.5 砷物種標準品及尿液樣品分離結果29
3.6 問卷資料收集29
3.7 資料分析30
第四章 結 果31
第五章 討 論37
第六章 結 論 與 建 議42
附 錄69
參考文獻73

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