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  • 學位論文

乙二醇單甲基醚之代謝研究

METABOLISM STUDIES ON ETHYLENE GLYCOL MONOMETHYL ETHER

指導教授 : 陳繼明
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摘要


乙二醇單甲基醚 ( Ethylene glycol monomethyl ether, EGME ) 為一溶解性良好,無色、無嗅味、無刺激性及低揮發性之良好溶劑,是工業界運用極廣的溶劑。其可經由腸胃道、呼吸道及皮膚滲透而進入人體;在體內主要代謝成2-甲氧基醋酸 ( Methoxyacetic acid, MAA ),會累積於體內各器官,造成明顯的傷害,已知的傷害有生殖、血液、神經毒性及致畸胎性等。而於動物實驗報告指出,2-甲氧基醋酸會於體內與glycine結合形成其共軛代謝物,此外乙二醇單甲基醚也會形成 ?-glucuronate或sulfate之共軛代謝物。本研究分析乙二醇單甲基醚於人體之二級代謝途徑,及其於血液中之分布與血漿蛋白結合情形。 本實驗以現場暴露勞工之尿液與血液檢體分析其可能的共軛代謝物,以酸水解方式水解可能之2-甲氧基醋酸共軛代謝物後,再以氣相層析質譜儀分析水解前後2-甲氧基醋酸濃度差,求得2-甲氧基醋酸共軛代謝物含量。以 ?-glucuronidase 及sulfatase水解可能之乙二醇單甲基醚共軛代謝物後,再以氣相層析質譜儀分析水解前後乙二醇單甲基醚濃度差,求得共軛乙二醇單甲基醚 ?-glucuronidate 及sulfate 之共軛代謝物含量。 經由生物偵測分析現場十二位暴露勞工尿液檢體,顯示2-甲氧基醋酸共軛代謝物之含量佔尿液所排泄出2-甲氧基醋酸總量濃度之10.51 % 至 39.00 %,其平均值為24.88 ? 8.97 % ( Mean ? SD)。因檢體中乙二醇單甲基醚濃度遠低於2-甲氧基醋酸,在十二位暴露勞工尿液檢體中,僅一人測得其乙二醇單甲基醚sulfate共軛代謝物含量佔尿液所排泄出乙二醇單甲基醚總量濃度之31.25 %。而於血漿中並未測得乙二醇單甲基醚或2-甲氧基醋酸之共軛代謝物,原因推測為腎小管對此型共軛代謝物無再吸收作用,所以無法從血漿中測得其存在。 另外經本實驗亦發現人體乙二醇單甲基醚及2-甲氧基醋酸於血液中主要分布於血漿,而非血球中。且乙二醇單甲基醚及2-甲氧基醋酸也不會與血漿蛋白進行結合。

並列摘要


Ethylene glycol monomethyl ether ( EGME ) has high solvent power to many hydrophilic and hydrophobic organic compounds and it has been widely used in industry as organic solvent. EGME was found to be absorbed into human bady significantly through gastrointestinal tract, respiratory tract and skin. Methoxyacetic acid ( MAA ), the toxic metabolite of EGME, has been reported to cause encephalopathy, hematological toxicity, infertility and teratogenesis. In the present study, we like to explore the possible phase II metabolic pathway of EGME in human. Upon hydrochloric acid hydrolysis of urine and plasma samples from the workers exposed to EGME, the amount of MAA conjugates was determined by gas chromatography-mass spectrometry. After incubation with ?-glucuronidase and sulfatase, the EGME concentrations were also analyzed by gas chromatography-mass spectrometry to determine the amount of EGME conjugates in urine and plasma. The distribution of EGME in blood cells and the percentage of plasma protein binding of EGME were also studied. The urine samples of twelve workers exposed to EGME indicated that the percentage of conjugated forms in total MAA varied from 10.51 % to 39.00 % with the average value of 24.88 ? 8.97 % ( Mean ? SD ). Due to greater lower concentration of EGME than that of MAA in urine from exposed workers, we only able to detect EGME and its sulfate conjugate from the urine of the one exposed worker. The percentage of EGME sulfate conjugate excreted from urine was 31.25 % of the total EGME excreted from urine. Unfortunately, in the present study, neither EGME conjugates nor MAA conjugates were found in the plasma of the exposed workers. In the study, we found that EGME and MAA were only distributed into plasma rather than in blood cells. Both EGME and MAA did not bind to human plasma proteins at all.

參考文獻


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