臺灣博碩士論文加值系統

在職場暴露中，作業勞工的化學物質暴露濃度常受工作性質、工作量、工作廠所通風換氣，以及有無配戴防護具所影響而有很大的變異，導致職業暴露流行病學研究，探討暴露與疾病的相關時，易產生高估或低估的現象。過去針對二甲基甲醯胺（N,N-dimethylformamide, DMF）的相關性研究，皆利用短期(單日或單週)的量測資料，探討DMF暴露勞工之生物指標及健康影響。然而真實職業環境中化學物質的暴露濃度常有極大變異，單日或短期的量測結果並無法有效代表長期暴露以及評估其內在劑量與健康的相關性。本研究主要目的為藉由連續監測DMF作業勞工的10週暴露濃度及尿中生物指標之量測資料，以了解DMF作業勞工長期暴露濃度及尿中各種DMF代謝物濃度及分布情形，以及暴露濃度的變化對尿中生物指標的影響，並藉由探討長期監測之DMF暴露勞工其空氣中濃度與DMF尿中生物指標之相關性來評估短期量測資料之適用性。本研究亦探討混合暴露對DMF暴露勞工尿中代謝物濃度之影響，以及探討尿中DMF代謝物AMCC之累積情形。研究結果顯示，勞工10週空氣中平均暴露濃度GM�bGSD (n=450) 分別為7.54�b2.21 ppm (DMF)、17.7�b6.42 ppm (MEK)、7.08�b4.90 ppm (TOL)，量測資料中有31%勞工其作業環境空氣中DMF濃度高於PEL (10 ppm)，同時約28% (14/47)混料作業勞工之作業環境空氣中TOL暴露濃度高於PEL(100ppm)，DMF暴露濃度以乾式底部塗佈勞工最高，混料作業勞工最低，MEK暴露濃度以乾式底部塗佈勞工最高，濕式塗佈勞工最低，TOL暴露濃度以混料作業勞工為最高，濕式塗佈為最低，在不同勞工之間及不同工作天之間暴露濃度皆有很大的差異且變化趨勢也不相同。高達70%量測資料尿中DMF代謝物U-DMF皆低於偵測下限，且下班前尿液中U-NMF濃度皆高於上班前，而U-AMCC則是上班前尿液中濃度高於下班前尿液中濃度，濃度變異情形則是隨著代謝物半衰期的增加而有下降的趨勢其中以U-AMCC為最低，但不同勞工及工作天濃度變異依然很高。而下班前U-NMF濃度與空氣中DMF暴露濃度有良好的相關性(r=0.54)，利用TWA-DMF濃度對應下班前U-NMF濃度為19.2mg/L；以各週暴露濃度與當週之下班前尿液中U-NMF濃度進行相關性分析則顯示差異很大(r=0.32-0.73)，然而利用勞工10週平均空氣中暴露濃度與下班後U-NMF平均濃度，相關卻呈現高度相關(r=0.95)，而各週最後一天工作天下班前U-AMCC濃度與當週暴露濃度亦有良好的相關性(r=0.63)。數據顯示混合暴露MEK及TOL會抑制上班前或下班前尿液中U-NMF及U-AMCC濃度，且抑制情形皆不相同，顯示抑制機制並非單一路徑，其中間機制尚需做進一步的探討。尿中AMCC濃度在連續10週暴露下，會有顯著的累積產生，此可作為長期暴露濃度與疾病相關性研究的重要指標之一。整體而言，DMF作業勞工暴露濃度及尿中代謝物濃度皆有很大的變異及變化趨勢，在探討暴露濃度與疾病之間的相關性研究時，建議要以長期的量測資料為依據，如此才可以較為準確的評估勞工實際的暴露情形，甚至於推估到對其健康之影響

In most occupational exposure settings, the variation of the workers exposure to chemicals usually affected by job title, quantity of output, the use of ventilation system,and respirator wearing. It may bias the relationship between the exposure and health outcomes in occupational epidemiology studies. In the past, most N,N-dimethylformamide (DMF) researches applied short-term measurements (one-day or one-week) to represent the exposure levels and to assess the association between biomarker and health outcomes for DMF exposed workers . However, the exposure profiles of workers varied considerably with different occupational exposure settings. One-day or short-term measurements were insufficient to evaluate the relationship between external exposure and internal dose or health risk. The objectives of this study are 1) to evaluate the long-term profiles of external exposure and their relevant biomarkers during 10 weeks for DMF exposed workers; 2) to investigate the intra-individual and inter-individual variability of the measurements from daily air, and urinary biomarkers; 3) to investigate the effects of the different exposure scenario on different biomarkers (U-DMF, U-NMF, and U-AMCC); 4) to evaluate the accumulation of urinary biomarker U-AMCC and the effects of co-exposure of toluene(TOL) and methyl ethyl ketone(MEK) to the metabolism of DMF. We found the geometric mean and geometric standard deviation (GM�bGSD)) of airborne DMF, MEK, TOL concentrations were 7.54�b2.21 ppm, 17.7�b6.42 ppm, 7.08�b4.90 ppm (n=450), respectively during 10 weeks. The DMF exposure levels in 31% workers were higher than permissible exposure level (10 ppm ), but only the workers in mixing process had higher exposure levels of TOL than permissible exposure level (100 ppm). The highest exposure level of DMF was found in dry Bottom Coating process, and the lowest was found in Mixing process; the highest MEK levels was found in Dry bottom Coating process, but the lowest exposure levels was Wet Coating process, and the highest TOL levels was found in Mixing process, lowest in Dry Coating process, too. Moreover, the individual exposure profiles showed significantly day-by-day variations among workers (inter-individual and intra-individual variability, P<0.05). The U-DMF of 70% samples were lower than the MDL. Furthermore, the concentration of biomarker of NMF in the post-shift urine samples was higher than that of the pre-shift urine samples, but the opposite results showed in the concentration of the biomarker of AMCC. Higher inter-&intra-individual variation was also found in the urinary biomarker and the variation of urinary DMF concentration was decreased with the increase of the half-life of biomarker, the lowest variation was found in U-AMCC. In addition, a significant association was found between daily exposure levels and post-shift urinary U-NMF (r=0.54). Furthermore the post-shift U-NMF corresponded to 8 hour time-weighted average DMF was 19.2 mg/L in ten weeks data. Higher variation was found between exposure levels in the different weeks and post-shift urinary U-NMF (r=0.32-0.73). However, the highest correlation was found between average exposures levels and average post-shift urinary U-NMF of ten weeks (r=0.95).Finally a high association was found between the weekly exposure levels and the post-shift urinary U-AMCC in final work-day during one week (r=0.63). The co-exposure to MEK and TOL showed no coincidence with the biomarkers of U-NMF and U-AMCC in pre-&post-shift urine samples. Further studies were needed to evaluate the mechanism of effects. The results showed that long term occupational DMF exposure might result in significant accumulation of DMF in human body. In conclusion, higher inter-and intra- variability of exposure levels and urinary biomarkers of DMF occupational exposed workers were observed. In further studies, long-term monitoring is needed to assess the relationship between exposure levels and health outcomes.

摘 要 II
Abstract IV
致 謝 VI
目 錄 VIII
表目錄 XI
圖目錄 XIII
附 錄 XVI
第一章 緒 論 1
1.1 研究背景及動機 1
1.2 研究目的 3
第二章 文獻回顧 4
2.1 職場暴露評估 4
2.1.1職場濃度分布及變異來源 4
2.1.2 勞工暴露濃度變異評估 4
2.2 長期暴露影響之指標評估 5
2.3 合成皮革製程簡介 6
2.4 DMF之基本資料 7
2.4.1 DMF之物化特性 7
2.4.2 DMF之應用及使用情形 7
2.4.3 DMF之代謝 7
2.4.4 DMF之健康效應 8
2.4.5 DMF之生物指標 8
2.4.6 DMF尿中代謝物累積之探討 9
2.4.7 DMF混合暴露MEK/TOL對尿中代謝物之影響 10
第三章 材料與方法 12
3.1 研究架構 12
3.2 使用材料及儀器設備 12
3.2.1 採樣材料 12
3.2.2 使用藥品 12
3.2.3 其他實驗器材 13
3.2.4分析儀器 13
3.3 研究對象之選取 14
3.4 環境監測-空氣樣本暴露量測 14
3.4.1 空氣樣本之前處理 14
3.4.2 空氣樣本分析之儀器參數及分析條件 15
3.5 生物監測-尿液樣本測定 15
3.5.1 尿液生物指標U-DMF,U-NMF測定之前處理 15
3.5.2 尿液生物指標U-DMF,U-NMF測定之儀器參數及分析條件 15
3.5.3 尿液生物指標U-AMCC測定之前處理 16
3.5.4 尿液生物指標U-AMCC測定之儀器參數及分析條件 16
3.6 採樣及分析之品保品管 17
3.6.1 空氣樣本採樣、前處理及分析之品保、品管 17
3.6.2 尿液樣本前處理及分析之品保、品管 18
3.7 資料分析 18
第四章 結果與討論 19
4.1 樣本分析之品保品管控制 19
4.2 研究對象基本人口學特徵及工作性質描述 19
4.3 研究對象10週環境監測濃度及分布 20
4.3.1空氣樣本DMF濃度分布及變異 20
4.3.2空氣樣本MEK濃度分布及變異 21
4.3.3空氣樣本TOL 濃度分佈及變異 21
4.3.4環境監測濃度變異影響因子探討 22
4.4研究對象10週DMF代謝物濃度及分布 22
4.4.1 DMF代謝物U-DMF濃度分布及變異 22
4.4.2 U-NMF濃度分布及變異性 23
4.4.3 U-AMCC濃度分布及變異性 24
4.4.4 DMF代謝物濃度變異性之影響因子探討 25
4.5環境暴露濃度與生物指標之相關性探討 25
4.5.1環境暴露濃度(A-DMF)與DMF代謝物濃度(U-DMF, U-NMF)之相關性 25
4.5.2環境暴露濃度(A-DMF)與DMF代謝物濃度(U-AMCC)之相關性 27
4.6 混合暴露MEK/TOL對生物指標之影響 28
4.7 DMF代謝物AMCC累積之探討 30
第五章 結論與建議 31
5.1 結論 31
5.2 建議 31
參考文獻 33

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