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年度	110	專案性質	實驗性質
專案類別	研究專案	研究主題	自訂
申請機構	國立臺灣大學	申請系所	生物環境系統工程學系
專案主持人	廖秀娟	職等/職稱	教授
專案中文名稱	提升臺灣地下水質永續管理：以地下水中藥物和個人保健用品污染之潛在環境風險為例
中文關鍵字	地下水,永續管理,藥物,個人保健用品,環境風險
專案英文名稱	-
英文關鍵字	-
執行金額	790,000元
執行期間	2021/1/1 至 2021/12/31
計畫中文摘要	藥物與個人衛生保健用品 (pharmaceuticals and personal care products, PPCPs) 因其廣泛使用及環境流布，被視為新興污染物質之一，且可能隨廢水排放進而污染環境水體。臺灣目前許多水體曾被檢測出多種PPCPs之存在，而地下水中亦被檢測出ppb (μg/L) 等級的PPCPs污染物。由於地下水為臺灣重要用水來源之一，地下水潛在污染問題影響層面廣泛，因此需要針對地下水永續利用及管理地下水資源制定具體規範或策略。然而，因PPCPs環境污染具複雜性及多樣性，目前仍缺乏充足的科學依據協助判定監測與管理環境中PPCPs的潛在風險極危害，尤其針對慢性及多種PPCPs共暴露之毒性評估。因此，為達成地下水資源之永續利用，本研究計畫針對臺灣地下水中污染較為嚴重之兩種不同PPCPs－雌激素藥物ethinylestradiol (EE2) 及抗生素sulfamethoxazole (SMX)，利用環境生物秀麗隱桿線蟲 (Caenorhabditis elegans) 評估其對生長與繁殖之影響，期建立慢性及共暴露實驗方法及毒性資料。期望本計畫所建立之成果，可作為未來制定相關法規與指引之參考依據，並增進現行地下水資源利用與永續管理。 本研究計畫期末報告，參考嘉義地區及新竹地區的地下水成分，配置相應的人工地下水 (AGW)：嘉義地區 (AGW-A) 及新竹地區 (AGW-B)，依計畫內容已完成C. elegans分別長期暴露EE2及SMX及兩者共暴露之生長及繁殖毒性試驗，並以dynamic energy budget毒理評估模式 (DEBtox model) 進一步評估EE2及SMX的潛在環境風險。 針對EE2的研究結果顯示，於AGW-A及AGW-B中暴露4天後，EE2皆顯著抑制C. elegans生長，最低有害濃度 (LOAEL) 均為10 mg/L。此外，C. elegans於兩種AGW暴露EE2均顯著造成繁殖毒性，毒性效應符合劑量—反應關係。進一步利用DEBtox model評估EE2之潛在環境風險，結果顯示於AGW-A及AGW-B中，C. elegans暴露EE2之毒性作用機制皆為增加生長及繁殖成本。另外，針對SMX的研究結果顯示，C. elegans暴露於SMX於AGW-A及AGW-B中均未顯著抑制生長。在繁殖試驗中，C. elegans於AGW-A暴露0.001 mg/L SMX即顯著造成繁殖毒性，於AGW-B暴露SMX則在1000 mg/L才顯著抑制繁殖。另由DEBtox model得知，SMX於AGW-A的毒物作用機制為增加繁殖成本，於AGW-B的毒物作用機制則增加生長及繁殖成本。EE2及SMX共暴露時，於兩種AGW中，C. elegans共暴露EE2及SMX時，均會導致生長與繁殖毒性增強，且可能以協同作用造成毒性效應增強。由DEBtox model擬合實驗數據發現，於AGW-A的毒物作用機制為增加生長及繁殖成本，於AGW-B的毒物作用機制則為增加繁殖成本。 綜上所述，C. elegans長期個別暴露EE2、SMX或共暴露時，在兩種不同AGW均顯示繁殖毒性較為敏感，且AGW成分會影響EE2及SMX之毒性效應。此外，EE2及SMX可能透過干擾C. elegans之能量分配，導致生長及繁殖毒性。本研究進一步以模式擬合之無效應濃度 (NEC) 計算風險商數 (RQ) 以探討EE2及SMX的個別環境風險，結果顯示不同地下水環境中之EE2及SMX均會造成高環境風險。此外，於不同地下水環境中，EE2及SMX共同存在時，會導致協同作用的高環境風險，且可能透過相似毒物作用途徑干擾能量分配，造成個體及族群之生態環境風險。 本計畫期末報告進度符合預期執行內容，期望本研究計畫成果，未來有助於推動以能量分配概念評估PPCPs之環境風險評估，以期未來可協助管理地下水資源與永續利用。
計畫英文摘要	Pharmaceuticals and personal care products (PPCPs) are regarded as emerging contaminants due to their large usage, environmental release, and possible water pollution through wastewater discharge. In Taiwan, the concentrations of PPCPs in several water bodies including groundwater have been detected in a range of ppb (μg/L) level. Considering groundwater is one of the major water resources in Taiwan, the potential environmental pollution in groundwater is a crucial factor for sustainable management of groundwater. However, because of the complexity and diversity, PPCPs pollution still lacks sufficiently scientific evidence for an appropriate environmental risk management, especially for long-term and co-exposure toxic effects of PPCPs. Herein, this research project aims to investigate two PPCPs, pharmaceutical estrogen ethinylestradiol (EE2) and antibiotic sulfamethoxazole (SMX), that were found to be relatively high in Taiwan’s groundwater. The long-term and co-exposure toxicity of these two PPCPs would be assessed by using the environmental organism Caenorhabditis elegans. Results from this project could provide scientific information for future PPCPs regulation in groundwater which could improve sustainable management of groundwater resources in Taiwan. In this final report, we constructed artificial groundwater (AGW) based on the reported data in Chiayi (AGW-A) and Hsinchu (AGW-B). We have respectively evaluated the long-term toxicity of EE2 and SMX on growth and reproduction of C. elegans, as well as the co-exposure of EE2 and SMX. In addition, the potential environmental risk in artificial groundwaters (AGW-A and AGW-B) was assessed using dynamic energy budget (DEBtox) model. For EE2, the results showed that EE2 significantly impaired growth of C. elegans in both AGW-A and AGW-B, and the lowest observed adverse effect level (LOAEL) for growth inhibition in AGW-A and AGW-B was both 10 mg/L at day 4. In addition, exposure to EE2 dose-dependently inhibited the reproduction of C. elegans in both AGWs. Moreover, DEBtox modeling suggested that the mode of action of EE2 was an increased cost of growth and reproduction in both AGWs. For SMX, the results showed that exposure to SMX did not significantly affect growth of C. elegans in both AGWs. In contrast, SMX significantly inhibited reproduction of C. elegans in AGW-A at 0.001 mg/L. The reproductive toxicity of SMX in AGW-B was observed at 1000 mg/L. Furthermore, DEBtox modeling suggested that the mode of action in AGW-A was an increased cost of reproduction, and that in AGW-B was an increased cost of growth and reproduction. For combined toxicity, C. elegans co-exposure to EE2 and SMX resulted in an increased toxicity on growth and reproduction in both AGWs and both toxicants might have synergistic effects. Moreover, DEBtox modeling suggested that the mode of action in AGW-A was an increased cost of growth and reproduction, and that in AGW-B was an increased cost of reproduction. Taken together, the results from this study showed that reproduction was a more sensitive endpoint for long-term toxicity of EE2 or SMX in both AGWs, and the constitutes of AGW might influence the toxicity of EE2 and SMX. In addition, both EE2 and SMX adversely affected growth and reproduction associated with energy allocation in C. elegans. Moreover, we assessed environment risks of EE2 and SMX as indicated by risk quotient (RQ) values based on model derived no effect concentration (NEC). The result showed that EE2 or SMX posed high risk in different groundwaters. In addition, co-exposure of EE2 and SMX even pose high risk with synergistic effect. This suggests that the combined toxicity of EE2 and SMX adversely affects growth and reproduction via similar pathways of disrupting energy allocation in C. elegans, and poses high ecological risk of individuals and population. In summary, in this final report we have fulfilled the progress as proposed in the grant proposal. We anticipated that results from this research would provide scientific data and make contribution to environment risk of PPCPs from the energy budget point of view, and provide valuable information for management and sustainable utilization of groundwater in Taiwan.