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研究生: 陳柏均
Chen, Bo-Jyun
論文名稱: 污水廠中內分泌干擾活性及藥物之檢測和藥物氯化衍生物之活性變化
Endocrine disrupting activity and concentrations of pharmaceuticals in wastewater treatment plants and endocrine disrupting activity of pharmaceutical chlorinated derivatives
指導教授: 周佩欣
Chou, Pei-Hsin
學位類別: 碩士
Master
系所名稱: 工學院 - 環境工程學系
Department of Environmental Engineering
論文出版年: 2018
畢業學年度: 106
語文別: 中文
論文頁數: 122
中文關鍵詞: 藥物與個人保健用藥污水處理廠內分泌干擾活性報導基因生物試驗法氯化衍生物液相層析串聯式質譜儀風險商數
外文關鍵詞: Pharmaceuticals and personal care products, Endocrine disrupting activities, Wastewater treatment plants, Yeast-based reporter gene assays, Liquid chromatography tandem mass spectrometry, Chlorinated derivatives
相關次數: 點閱:101下載:6
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  • 隨著醫藥的普及,人們使用量與日俱增,而醫藥的濫用與隨意棄置,使之成為環境中之新興污染物。某些藥物具有可能影響生物內分泌系統之作用,進而影響環境生態,然而這些藥物通常無法透過污水處理流程而完全去除。在污水處理流程中的消毒程序同時也可能與藥物反應而生成氯化衍生物,無論是母物質或氯化衍生物,對於環境之影響須審慎評估。
    本研究選定南部地區四座民生污水處理廠與兩座醫院污水處理廠中不同處理單元進行樣本採集,利用報導基因酵母菌之生物試驗法與液相層析串聯式質譜儀,分析樣本中之內分泌干擾活性與六種環境中常見的個人保健用藥濃度,同時也鑑定藥物及其氯化衍生產物是否仍具有內分泌干擾活性。
    藥物之內分泌干擾活性試驗中,非類固醇類止痛藥具有干擾甲狀腺激素受體、糖皮質激素受體、鹽皮質激素受體之能力,而咖啡因與乙醯氨酚則不具有測試的內分泌干擾活性。此外,待克菲那 (Diclofenac)之氯化衍生物可能具有抗甲狀腺激素與抗糖皮質激素活性,那普洛辛 (Naproxen)之氯化衍生物則可能具有抗糖皮質激素活性。針對污水廠樣本中內分泌干擾活性之檢測,抗甲狀腺激素活性僅在三座污水處理廠中測得,而抗糖皮質激素活性與抗鹽皮質激素活性則在六座污水處理廠中皆有測得,且醫院污水處理廠進流水中之抗糖皮質激素與抗鹽皮質激素活性皆高於民生污水處理廠。
    以液相層析串聯式質譜儀檢測污水廠樣本中藥物濃度之結果顯示,藥物主要存在於水相中,進流水中乙醯氨酚 (Acetaminophen) (6.3~159.2 µg/L)與咖啡因 (Caffeine) (14.9~119.5 µg/L)具有相當高的濃度,而非類固醇類藥物各為可多普洛芬 (Ketoprofen) (20~305 ng/L)、待克菲那 (169~3818 ng/L)、異布洛芬 (Ibuprofen) (318~7040 ng/L)、那普洛辛 (195~6075 ng/L)。除了可多普洛芬,其餘藥物之最高濃度皆在醫院污水處理廠樣本中測得。比較藥物於污水廠中之去除率時,易生物降解之乙醯氨酚、咖啡因、異布洛芬、那普洛辛各為40-99%、36-99%、45-93%、-21-94%,而不易生物降解之待克菲那與可多普洛芬各為-179-50%、-674-100%。此外,將樣本中內分泌干擾物質之濃度轉換為內分泌干擾活性標準品當量濃度,並與生物試驗測得之活性比較,其結果顯示生物試驗所得之當量濃度遠高於由儀器分析濃度換算之活性,原因可能為環境樣本複雜而造成的協同作用或還有許多未被選定之內分泌干擾物質所致。
    比較污水廠各單元間拮抗活性之變化可得知,污水廠中內分泌干擾活性大多能透過生物處理程序得到有效的去除,而由藥物在出流水中殘餘濃度,計算風險商數後發現那普洛辛、異布洛芬及待克菲那皆為中度風險及高風險,對此需要更高級的處理流程才能完善的去除,達到保護環境之功用。

    The presence of pharmaceuticals and personal care products (PPCPs) in the environment has received a lot of attention in recent years. The waste streams from hospitals and wastewater treatment plants (WWTPs) have been identified as major contributors to environmental contamination with human-derived medications. Chlorination is a common disinfection process in sewage treatment. During the chlorination process, chlorinated derivatives of drugs may be produced, and there is a lack of sufficient toxicological information for these chlorination by-products.
    In this study, recombinant yeast bioassays and liquid chromatography–mass spectrometry (LC-MS/MS) were used to investigate the endocrine disrupting activities and concentrations of selected PPCPs, including naproxen, diclofenac, ketoprofen, ibuprofen, acetaminophen, caffeine in Taiwanese WWTPs. The endocrine disrupting activities of chlorinated derivatives were also examined. Our results showed that nonsteroidal anti-inflammatory drugs are potential endocrine disrupting chemicals, which elicited thyroid receptor hormone antagonistic activities, glucocorticoid receptor antagonistic activities and mineralocorticoid receptor antagonistic activities. Also, WWTP water samples showed thyroid hormone receptor antagonistic activities, glucocorticoid receptor antagonistic activities and mineralocorticoid receptor antagonistic activities. The concentrations of PPCPs were often detected at ng/L to µg/L levels. In addition, chlorinated derivatives of naproxen and diclofenac showed endocrine disrupting activities.

    摘要 I 目錄 VII 表目錄 XI 第一章 前言 1 1-1 研究動機及目的 1 第二章 文獻回顧 2 2-1 醫療用藥及其內分泌干擾活性 2 2-1-1 止痛藥及咖啡因 2 2-1-2 類(抗)雄激素活性 7 2-1-3 類(抗)雌激素活性 8 2-1-4 類(抗)甲狀腺激素活性 9 2-1-5 類(抗)糖皮質激素活性 11 2-1-6 類(抗)鹽皮質激素活性 12 2-1-7 醫療用藥氯化衍生物 14 2-2 生物試驗方法 17 2-2-1 活體內生物試驗法 17 2-2-2 活體外生物試驗法 17 2-3儀器分析方法 19 2-3-1 層析系統 19 2-3-2 偵測系統 19 2-4 檢測污水廠簡介 21 2-4-1 臺南AP水資源回收中心 21 2-4-2 高雄NZ污水處理廠 21 2-4-3 高雄FS污水處理廠 21 2-4-4 高雄ZC污水處理廠 22 2-4-5 臺南CH醫院污水處理廠 22 2-4-6 臺南TH醫院污水處理廠 22 第三章 實驗方法與步驟 23 3-1 實驗流程 23 3-2 樣本採集 24 3-3 實驗材料與設備 26 3-3-1 藥品及試劑 26 3-3-2 基因重組酵母菌試驗 28 3-3-3 實驗用設備 30 3-4 前處理步驟 32 3-4-1 水相樣本 32 3-4-2 懸浮固體相樣本 32 3-4-3 樣本稀釋序列 32 3-5 基因重組酵母菌生物試驗 33 3-5-1 類(抗)雄激素活性試驗 33 3-5-2 類(抗)雌激素活性試驗 33 3-5-3 類(抗)甲狀腺激素活性試驗 34 3-5-4 類(抗)糖皮質激素活性試驗 35 3-5-5 類(抗)鹽皮質激素活性試驗 36 3-5-6 活性計算與當量濃度換算 42 3-6 層析儀器分析 43 3-6-1 液相層析串聯式質譜儀 43 3-7 醫療用藥及個人保健用品之氯化衍生物 48 3-7-1 衍生物氯化合成方法 48 3-8 風險商數 49 3-8-1 風險商數之計算 49 第四章 結果與討論 51 4-1 藥物內分泌干擾活性 51 4-1-1 抗雄激素活性 51 4-1-2 抗雌激素活性 52 4-1-3 抗甲狀腺激素活性 53 4-1-4 抗糖皮質激素活性 54 4-1-5 抗鹽皮質激素活性 55 4-2 污水廠樣本之類(抗)甲狀腺激素活性 56 4-2-1 污水廠樣本之抗甲狀腺激素活性 56 4-2-2 水相樣本與懸浮固體相樣本中抗甲狀腺激素活性分布 58 4-2-3 污水廠樣本之類甲狀腺激素活性 59 4-3 污水廠樣本之類(抗)糖皮質激素活性 60 4-3-1 臺南AP水資源回收中心樣本之抗糖皮質激素活性 60 4-3-2 高雄NZ污水處理廠樣本之抗糖皮質激素活性 61 4-3-3 高雄FS污水處理廠樣本之抗糖皮質激素活性 62 4-3-4 高雄ZC污水處理廠樣本之抗糖皮質激素活性 63 4-3-5 臺南CH醫院污水處理廠樣本之抗糖皮質激素活性 64 4-3-6 臺南TH醫院污水處理廠樣本之抗糖皮質激素活性 66 4-3-7 水相樣本與懸浮固體相樣本中抗糖皮質激素活性分布 67 4-3-8 不同水處理單元之抗糖皮質激素活性綜合比較 68 4-3-9 污水廠樣本之類糖皮質激素活性 70 4-4 污水廠樣本之類(抗)鹽皮質激素活性 71 4-4-1 臺南AP水資源回收中心樣本之抗鹽皮質激素活性 71 4-4-2 高雄NZ污水處理廠樣本之抗鹽皮質激素活性 72 4-4-3 高雄FS污水處理廠樣本之抗鹽皮質激素活性 73 4-4-4 高雄ZC污水處理廠樣本之抗鹽皮質激素活性 74 4-4-5 臺南CH醫院污水處理廠樣本之抗鹽皮質激素活性 75 4-4-6 臺南TH醫院污水處理廠樣本之抗鹽皮質激素活性 76 4-4-7 水相樣本與懸浮固體相樣本中抗鹽皮質激素活性分布 77 4-4-8 不同水處理單元之抗鹽皮質激素活性綜合比較 78 4-5 藥物氯化衍生物之內分泌干擾活性 80 4-5-1 氯化Naproxen之內分泌干擾活性 80 4-5-2 氯化Diclofenac之內分泌干擾活性 83 4-5-3 氯化Acetaminophen之內分泌干擾活性 85 4-5-4 氯化Caffeine之內分泌干擾活性 87 4-6 LC-MS/MS儀器分析結果討論 90 4-6-1 污水廠中Naproxen濃度變化 90 4-6-2 污水廠中Diclofenac濃度變化 91 4-6-3 污水廠中Ketoprofen濃度變化 92 4-6-4 污水廠中Ibuprofen濃度變化 93 4-6-5 污水廠中Acetaminophen濃度變化 94 4-6-6 污水廠中Caffeine濃度變化 95 4-6-7 污水廠中藥物濃度綜合討論 96 4-6-8 各國污水處理廠藥物濃度及去除效率 97 4-6-9 風險商數 99 4-7 生物試驗與儀器分析結果比較 100 4-7-1 樣本之生物試驗與儀器分析相關性 100 第五章 結論 104 5-1 結論 104 5-2 建議 106 參考文獻 107 附錄 117

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