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| 研究生： |
雲遠德 Yun, Yuan-Der |
|---|---|
| 論文名稱： |
二甲基甲醯胺、丁酮暨甲苯混合暴露之職業環境對生物偵測之影響 Biological monitoring of occupational exposure to the mixture of N,N-dimethylformamide, methyl ethyl ketone, and toluene |
| 指導教授： |
張火炎
Chang, Ho-Yuan |
| 學位類別： |
碩士 Master |
| 系所名稱： |
醫學院 - 環境醫學研究所 Department of Environmental and Occupational Health |
| 論文出版年： | 2004 |
| 畢業學年度： | 92 |
| 語文別： | 中文 |
| 論文頁數： | 84 |
| 中文關鍵詞： | 共同暴露 、生物暴露指標 、累積 、傳統動力學 、丁酮 、曲線下面積 、二甲基甲醯胺 、甲苯 、單甲基甲醯胺 、生物偵測 |
| 外文關鍵詞： | MRT, conventional kinetics, half-life, co-exposure, accumulation, methyl ethyl ketone (MEK), toluene (TOL), AUC, biological monitoring, N-methylformamide (NMF), N-dimethylformamide (DMF), biological exposure index, PBPK, N |
| 相關次數： | 點閱：165 下載：6 |
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在一般的環境或職場中，人類暴露到化學物質通常為混合物暴露，隨著化學物質的組成與強度不同，混合物暴露可能會導致其毒性降低或是增加。在職場環境中極易同時暴露到二甲基甲醯胺 (DMF)、丁酮 (MEK) 與甲苯 (TOL)，本研究主要目的是探討共同暴露丁酮與甲苯不同濃度時，對於DMF暴露生物指標即尿中DMF (U-DMF ) 與尿中NMF (U-NMF) 的影響，及探討DMF混合暴露下對MKE生物偵測的影響。研究上採二階段現場採樣策略，第一階段對於選定之一家合成皮工廠所有可能暴露DMF的勞工 (n=65) 進行個人空氣樣本採樣，依據DMF與共同暴露 (MEK/TOL) 濃度高低選取其中20位勞工分成四組，進行第二階段採樣包括連續二日及連續五日的實測，環境偵測包括個人空氣DMF, MEK與TOL及皮膚DMF暴露濃度測定，而生物偵測則收集勞工上、下班尿液樣本以及二日下班後至少連續36小時尿液樣本以分析U-DMF、U-NMF、U-AMCC與U-MEK濃度。連續二日的結果發現，高DMF暴露組的U-DMF濃度無論共同暴露高低均一致較低DMF暴露組的U-DMF濃度顯著為高 (p＜0.05)，此與四組DMF空氣暴露濃度趨勢呈現一致；然而在U-NMF方面則顯示不同的結果，DMF與混合暴露皆為高暴露組其U-NMF與U-AMCC較高DMF暴露但低共同暴露組的U-NMF顯著為低。由代謝指標比 (metabolic index, MI) 在四組分布情況可發現，高濃度共同暴露會在DMF高暴露時，對DMF生化轉換成NMF與AMCC產生顯著之抑制作用 (p＜0.05)；再進一步以簡單線性迴歸可得知，高DMF暴露 (＞7.8 ppm) 時增加一個自然指數單位的MEK及TOL分別對MI降低為原來的0.78與0.63倍。在連續五日的實測部分，本研究發現高混合暴露下每日上班前U-NMF會隨著暴露天數的增加而顯著累積在體內，在暴露DMF相同濃度下，當日產生NMF的濃度會是前一天NMF濃度的1.40倍，而在低混合暴露組則無U-NMF之逐日累積情形；動力學方面，發現高混合暴露的勞工其U-NMF的排出延滯時間較低混合暴露勞工之U-NMF為長，而且在半衰期、曲線下面積 (AUC) 及平均滯留時間 (MRT) 亦表現較長，顯示高混合暴露致使DMF代謝成NMF所需時間較長，且NMF留下在體內也較久。MEK之生物指標物 (U-MEK) 方面，經由高低DMF暴露濃度分組後的A-MEK與下班前U-MEK之簡單迴歸分析，發現U-MEK未受DMF暴露濃度高低而有顯著影響；然而在動力學表現上，卻顯示高混合暴露下U-MEK的半衰期及終止暴露後的濃度均較低混合暴露組為長或高。因此混合暴露仍可能對U-MEK產生影響，唯本研究動力學樣本數過少，未能在此議題下定明確的結論，未來應收集較多動力學樣本數方能給予更正確的答案；PBPK模式由於採樣參數可能有人種差異、暴露實態及樣本數過少的問題，其模擬曲線與動力學實測值部分差異，尤其是終止暴露後之最高濃度值更為明顯，未來應以台灣人 (黃種人) 之參數來進行模擬方能得到較佳的PBPK模式。本研究的結論是當有高混合暴露 (MEK/TOL) 時對DMF職業暴露之生物偵測可能於高濃度DMF (GM=7.8 ppm) 下，會有下列情況產生，1. 尿中NMF與AMCC會受到抑制，2. 隨著暴露天數增加上班前NMF會有逐日累積情形，3. NMF排出延滯時間增長，且半衰期、AUC及MRT也較長。另一方面，下班前U-MEK未受DMF混合暴露高低之影響，但於連續36小時尿液之傳統動力學方面則顯示高混合暴露下U-MEK的半衰期及終止暴露後的濃度均較低混合暴露組為長或高。因此混合暴露仍可能對U-MEK產生影響，但此結論需進一步研究方可確定。因為DMF暴露的職業現場之MEK/TOL共同暴露是十分普遍，我們建議未來在相關職場進行生物偵測時，需同時考量混合暴露的濃度及勞工已暴露DMF天數，以對生物暴露指標進行適當調整，以免對現場作業員工的DMF之暴露產生低估。
The exposure of the humans to the chemical mixtures is the general rule in the general environment as well as in most occupational settings. Lower toxicity or higher toxicity from mixtures than the expected depends on their constituents and potencies. It is very likely that the workers could be exposed to N,N-dimethylformamide (DMF), methyl ethyl ketone (MEK), and toluene (TOL) in the occupational environments simultaneously. This study was aimed to investigate the effects of the different co-exposure levels of MEK and toluene and different DMF on different biomarkers of DMF exposure metabolism-free form (U-DMF) and biotransformation-required forms (U-NMF, and U-AMCC), and the effects of co-exposure to DMF on urinary MEK biomarker, respectively. Twenty workers were selected from a two-stage field investigation strategy and were classified into four subgroups based on their DMF exposure and co-exposure levels. Breathing-zone air concentrations of DMF, MEK and TOL as well as dermal DMF exposure were determined for two consecutive and another five consecutive working days. The concentrations of U-DMF, U-NMF, U-AMCC and U-MEK in pre- and post-shift as well as during at least 36-hour period since the end of the exposure for each individual were analyzed. For post-shift urine measurements, we found U-DMF concentrations in high DMF subgroups were significantly higher than those in low DMF subgroups (p＜0.05). On the other hand, U-NMF and U-AMCC concentrations in high-DMF-high-coexposure subgroup were significantly lower than those in high-DMF-high-coexposure subgroup but no significant differences between two low DMF subgroups. Metabolic index (MI) showed the biotransformation from DMF to NMF, but not from NMF to AMCC, was significantly suppressed at high co-exposure (p＜0.001). We also found a significant daily accumulation of pre-shift U-NMF across five consecutive working days for those who have high co-exposure to high MEK/TOL and the day-to-day increase of U-NMF at pre-shift was approximate 1.4-fold given the occupational exposure to DMF at the same level. The lag time of excretory U-NMF for high MEK/TOL co-exposure group was significantly longer that for low co-exposure group in conventional kinetics study. The estimates of half-life, area under curve (AUC), and mean residence time (MRT) also showed the same tendency as found for lag time. For the biological monitoring of MEK part, the regression equations of A-MEK to post-shift U-MEK showed no significant differences between high and low DMF co-exposure groups. On the other hand, the estimates of the half-life and maximum concentration of post-shift U-MEK for high DMF co-exposure groups were greater than those for low DMF co-exposure groups in kinetics study. Owing to the insufficient sample sizes, this finding warranted a further study. The discrepancy between conventional kinetics approach and physiologically-based pharmacokinetics (PBPK) approach could result from the differences in races and exposure scenarios as well as insufficient sample size. We concluded that co-exposure to high MEK/TOL could result in 1. the suppression of U-NMF and U-AMCC at high DMF exposure; 2. the accumulation of U-NMF at daily pre-shift urines; 3). the increases of the lag time, half-life, MRT, and AUC for U-NMF. Difference. For the biological monitoring of MEK part, no significant effects of co-exposure to DMF on post-shift U-MEK. Some effects might exist in the estimates of the kinetic parameters and this warranted a further study to confirm. Due to the ubiquity of co-existence of MEK, TOL and DMF in occupational settings, biological monitoring for the above-mentioned chemicals should be carefully evaluated while the co-exposure is substantial and a more comprehensive longitudinal health evaluation program should be performed for those workers.
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行政院勞工委員會勞工安全衛生研究所 “作業環境勞工化學性暴露調查計畫(一)”，IOSH87 -A101：10. 民國八十七年
周瑞淑、石東生、黃文玉、沈晏如、戰洪、陳繼明 “丁酮暴露生物偵測技術研究”， 勞工安全衛生研究季刊目錄，六卷三期 民國87年9月
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校內：立即公開校外：2004-07-13公開