臺灣博碩士論文加值系統

N,N-dimethylformamide（DMF）為文獻上報導為容易經由皮膚吸收之物質之一，但大多研究都以人體自願者為研究對象，缺乏實際值場之推估；而多數採樣方法皆僅考慮呼吸暴露途徑而忽略皮膚暴露途徑，且過去DMF之重複性暴露是否會產生累積之研究並未有定論；因此，本研究之目的：1.建立DMF呼吸與皮膚之職業暴露暨其尿中生物暴露指標之相關性2.作業員工皮膚障壁功能與DMF皮膚吸收之相關 3.探討每日連續暴露下，DMF之代謝物是否有累積之情形，並討論累積情形與空氣暴露、皮膚暴露之關聯。本研究由職業暴露DMF之四家工廠員工進行環境與生物偵測，研究對象共75名，其中D廠之研究對象(24人)連續進行6天之暴露測定及尿液收集，其他3廠皆為一日之暴露測定。
本研究結果發現：1.不同製程之DMF工廠員工空氣中、手部皮膚之暴露濃度有顯著差異，其中以合成皮製造業暴露濃度為最高。2. DMF之手部、手前臂之暴露在銅箔基板業及亞克力纖維業較不嚴重，但於合成皮製造業則較為嚴重且以手部為主。3.本研究發現尿中生物指標（U-NMF與U-DMF）與員工之空氣DMF暴露與手部DMF暴露有顯著相關，且調整空氣中DMF暴露後，手部DMF之暴露濃度對尿中生物指標值仍有顯著影響。4.本研究無法證實經皮水分散失（TEWL）與尿中DMF生物指標之關聯，經皮水分散失指標值在職業現場應用於皮膚吸收之領域，仍有待進一步研究探討。5.本研究發現在平均員工空氣中DMF暴露值為3.94 ppm下，手部皮膚平均暴露值為0.71 μg/cm2時，員工尿中DMF生物指標值隨暴露天數有顯著之累積情形，以累積斜率進行統計分析後發現此累積情形主要與呼吸暴露有關與皮膚暴露無關。6.本研究發現尿中生物指標U-NMF與U-DMF在評估空氣DMF、皮膚DMF之關係時皆有相同的發現，因此本研究認為尿中DMF值亦可作為DMF職業暴露之生物指標。

N,N-dimethylformamide (DMF) has been considered as one of most readily skin-absorbed chemicals in literature. The previous researches regarding skin absorption of DMF were, however, conducted in a well-controlled condition in the laboratory using human volunteers. The skin absorption estimation of DMF exposure in actual occupational environment is still lacking. Moreover, the findings in the accumulation for repeatedly exposure to DMF in previous studies were inconsistent and, consequently, still inconclusive. Therefore, the aims of this study were: 1) to investigate the relations of urinary DMF biomarkers to the DMF exposures via inhalation and skin in the occupational settings; 2) to explore the association between skin barrier function and dermal absorption; 3) to determine the accumulation after day-after-day exposure to DMF, and the contribution of skin exposure and that of inhalation exposure to the accumulation. Seventy-five employees in four DMF-related factories were recruited in this study and one-day measurements on air, skin and urine were conducted. Among all subjects, 24 subjects from one of the synthetic leather factories were monitored for air, skin and urine items for six consecutive days.

We found that 1. Significant differences of DMF concentrations in air and skin were found among different manufacturing processes. Among them, synthetic leather industry was found with the highest DMF exposure. 2. Contrasting to unremarkable skin exposure in hands and forearms in the manufacturing processes of copper-laminate circuit board and synthetic acrylic fiber, the skin exposures in synthetic leather industry were considerably significant. 3. The urinary biomarkers of DMF exposure in this study were significantly associated with both the exposure via inhalation and that via skin. The contribution of skin exposure in hand to urinary biomarkers remained significant even after adjusting the contribution of inhalation exposure. 4. This study was unable to determine the role of trans-epidermal water loss (TEWL) in DMF skin exposure. Further study to explore the application of TEWL in the research of skin absorption in the occupational environment is needed. 5. Significant day-to-day accumulation after a-week-long exposure was affirmed in this study with the average airborne exposure of 3.94 ppm and hands' skin exposure of 0.71 mg/cm2. The accumluation coefficient was statisitically associtaed with respiratory exposure, not with skin exposure. 6. Based on the same findings by using U-DMF and U-NMF gleaned from biological monitoring part and accumulation part for DMF exposure in this study, we concluded that U-DMF measurements can be considered as a supplementary biomarker of DMF exposure.

目 錄
中文摘要 1
ABSTRACT 2
圖目錄 5
表目錄 6
第一章 序論 8
1-1 研究背景 8
1-2 研究目的 11
第二章 文獻探討 12
2-1 DMF物化特性及使用 12
2-2 DMF之代謝與健康效應 12
2-3 DMF之生物偵測 13
2-4 DMF 尿中代謝物累積之探討 15
2-5 DMF皮膚吸收研究之探討 16
2-6 皮膚採樣方法之探討 17
2-7 TRANSEPIDERMAL WATER LOSS（TEWL）之應用 18
2-8 研究限制 19
第三章 材料與方法 20
3-1 研究對象之選取 20
3-2 採樣策略與方法 22
3-3 問卷設計 25
3-4 化學試劑 25
3-5 儀器及設備 25
3-6 分析方法 26
3-7 實驗室分析之品保品管 29
3-8 統計分析方法 34
第四章 結果與討論 35
4-1 研究對象個人暴露濃度比較 35
4-2 TEWL量測值 38
4-3 尿中DMF與NMF濃度值 38
4-4 尿中生物指標與暴露之相關性 41
4-5 尿中生物指標累積性探討 43
第五章 結論與建議 45
參考文獻 46

圖目錄

圖1 研究架構圖………………………………………………….…49
圖2 DMF在人體內之代謝途徑……………………..…………….50
圖3 皮膚貼布採樣位置圖………………………………………….51
圖4 3M 3500正面及剖面圖………………………………………52
圖5 pre-shift尿中NMF每日濃度值……………………………..53
圖6 pre-shift尿中DMF每日濃度值……………………………..53
圖7 空氣樣本分析圖（於3M 3500）…………………………...54
圖8 DMF尿中生物指標分析圖（尿液樣本中）………………..55

表1. 被動式採樣器（3M 3500）不同濃度回收率測試結果…...56
表2. 尿液回收率試驗結果…………………………….…………57
表3. 以裸鼠進行皮膚貼膚回收率測試結果…………..……….58
表4. 皮膚回收率總和表……………………….………….…….58
表5. 研究對象基本資料………………………….…….……….59
表6. 四廠空氣中DMF濃度值……………………….…….……..60
表7. 四廠研究對象手部及手臂皮膚暴露濃度………………….61
表8. 四廠研究對象TEWL值的分布……………….….…………62
表9. 四廠研究對象NMF尿中濃度值的分布…….……….……..63
表10. 四廠研究對象DMF尿中濃度值的分布…….….…………64
表11. 以簡單迴歸探討生物偵測與DMF暴露的關係….…………65
表12. 複迴歸各自變項之相關矩陣……………………………..66
表13. 以複迴歸探討生物偵測與DMF暴露（空氣中 DMF、手部、手臂）的關係……………………………………………………………………..……….….…67
表14. 以複迴歸探討生物偵測與DMF暴露（空氣中 DMF、皮膚平均暴露）的關係……………………………………………………..……………………… ……67
表15. 以邏輯式簡單迴歸 (simple logistic regression)進行尿中NMF、DMF濃度
值是否大於偵測下限與各自變項的關係探討………………………….………..68
表16. 表15中達統計顯著意義者以邏輯式複迴歸 (Multiple logistic regression)進
行尿中NMF、DMF濃度值是否大於偵測下限與各自變項（空氣中、手部、
手前臂DMF濃度值是否大於偵測下限）的關探.…………………….……….69
表17. 以邏輯式複迴歸 (Multiple logistic regression)進行尿中NMF、DMF濃度值
是否大於偵測下限與各自變項（空氣中、手部、手前臂DMF濃度值是否大
於偵測下限）的關係探討………………………………………………………....70
表18. D廠連續六天空氣中DMF-TWA濃度值………………....71
表19. D廠連續6日手部及手臂暴露濃度值………….….……72
表20. D廠研究對象連續6日pre-shift與post-shift尿中NMF 濃度值…..…….….73
表21. D廠研究對象連續6日pre-shift與post-shift尿中DMF 濃度值..………….74
表22. 以簡單迴歸分析pre-shift尿中NMF暴露天數之相關…….75
表23. 以simple regression進行累積斜率與空氣中暴露值(Air)或手部(Hand)、
手臂(Forearm)、皮膚平均暴露(Whole)各變項之相關性…………………….…76

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陳俊璋，聚尿樹脂及合成皮製造工廠勞工二甲基甲醯胺暴露研究，中國醫藥學院碩士論文，民國89年。