- 學位論文
頭孢子類抗生素與混合藥物於環境水體中自然光轉化機制研究
Phototransformation of Cephalosporin Antibiotics and Pharmaceutical Mixtures in Aqueous Environment
摘要
過去十幾年來，文獻證實許多常用藥物無法完全被污水處理廠去除並在全世界環境水體中被檢測出。然而藥物的自然光解機制與宿命尚未完全被了解，因此本研究的目標為探討頭孢子菌類抗生素及其他常見藥物在環境水體中的光化學宿命，定義主要的光反應機制、光轉化產物與初步毒性檢測。 頭孢子類抗生素在環境表面水體宿命中，自然光反應是一個重要的降解途徑，其中cefazolin (CFZ)與cephapirin (CFP)主要是進行直接光解(去離子水、pH=7)，半衰期分別為0.7與3.9小時。另外，cephalexin (CFX)與cephradine (CFD)主要是進行間接光解，並且與cefotaxime (CTX)在碳酸氫根離子與硝酸根離子同時存在的系統下([NO3−-N]=2.7 mg/L、[HCO3−]=2 mM、pH=7)會有快速的間接光解速率，其半衰期分別為4.5、5.3、1.3小時，相對於直接光解半衰期分別為33.6、31.9、6.9小時。硝酸根離子、碳酸氫根離子與溶解性有機物，此三水質因子可以良好模擬頭孢子類抗生素在景美溪水的自然光解，其相關性常數可達到0.8-1.0數值。本研究首度發現水中碳酸氫根離子之重要性，同時於硝酸根離子存在下，經由光照產生的碳酸根自由基可以大幅度地促進CFX與CFD的自然光解，決定了景美溪間接光解之66-80%降解比例。頭孢子類抗生素之光降解反應無礦化現象，全部進行轉化作用並定義出4-9個副產物。從生成與反應時間的關係，發現這些副產物具有光穩定性，且初步檢測出光副產物對Vibrio fischeri產生急毒性。 自然光降解是殘留藥物在環境表面水體中重要的自然淨化反應，然而殘留藥物是以混合物的形式存在於環境中，因此本研究為首例探討混合藥物於不同環境水體(醫院排放水、污水處理廠放流水、製藥廠排放水、河川等)中的自然光降解與轉化作用。挑選出具代表性的27種常見的殘留藥物(包含抗生素、非類固醇消炎止痛藥、降血脂血壓藥、抑制胃酸藥、管制藥物以及抗癌藥物)可以進行自然光降解並有顯著的污染來源。於混合藥物系統中，其他藥物的存在對於目標藥物而言是扮演溶解性有機物(DOMs)的角色。對於主要進行間接光解的目標藥物，DOMs會增加其光降解速度，以光感物質的特性產生具反應能力之物質(例如3DOM*、1O2、eaq−等)促進目標藥物的降解。對於主要進行直接光解的目標藥物，DOMs會減緩其光降解速度，其可能原因為遮蔽光照來源。進一步發現混合藥物經由光降解反應，主要是進行光轉化作用(11-23%礦化)，其副產物亦呈現急毒性反應。光轉化毒性根據初始濃度(0.1–4 μM)的差異會有所不同，但其毒性增加的趨勢皆相同。 藥物的光降解宿命是自然“淨化”作用嗎?雖然污染物本身可以快速地被自然光降解，但需要關注的是光轉化後所產生的副產物對於環境水體生態的影響。許多殘留藥物經由自然光的照射，會產生各式各樣的副產物，而這些副產物同時存在於環境水體中所形成的混合作用值得在未來的研究中持續地被深入探討並評估其造成之生態風險。
並列摘要
Pharmaceuticals undergo natural attenuation when they are not completely removed from wastewaters and are subsequently discharged to environmental water. Many pharmaceuticals were previously known to undergo sunlight photodegradation in surface waters. However, there is limited information on the mechanism and phototransformation of pharmaceutical residues. The objective of this study was to understand the photochemical behaviors of cephalosporin antibiotics in natural waters, to define photo-byproduct and to investigate their associated photo-toxicity. Further, numerous pharmaceuticals are simultaneously present in the environment (rather than a single compound itself). Therefore, the effect of solar phototransformation on pharmaceutical mixtures was also investigated in environmental water matrices. Photodegradation may be the most important elimination process for cephalosporin antibiotics in surface water. Cefazolin (CFZ) and cephapirin (CFP) underwent mainly direct photolysis (t1/2 = 0.7, 3.9 h) while cephalexin (CFX) and cephradine (CFD) were mainly transformed by indirect photolysis, during which process a bicarbonate-enhanced nitrate system contributed most to the loss rate of CFX, CFD and cefotaxime (CTX) (t1/2 = 4.5, 5.3 and 1.3 h, respectively). Laboratory data suggested that bicarbonate enhanced the phototransformation of CFD and CFX in nitrate system. When mixed together, NO3–, HCO3– and dissolved organic matters (DOMs) solution successfully reproduced the photolysis behavior in the Jingmei River, and these three were the strongest determinants in the photo-fate of cephalosporins. TOC and byproducts were investigated and identified. Transformation only (no mineralization) of all cephalosporins was observed through direct photolysis. This work identified 4-9 byproducts for each cephalosporins and found that byproducts were even less photolabile and more toxic (via the Microtox test). CFZ exhibited the strongest acute toxicity after just a few hours, which may be largely attributed to its 5-methyl-1,3,4-thiadiazole-2-thiol moiety. This study, for the first time, investigated the photo behavior of the mixture of 27-pharmaceuticals, and identified that the mixture also undergo phototransformation rather than mineralization. Results demonstrated that pharmaceutical mixtures could possibly act as DOMs for each other and affect the photolysis rates. When direct photolysis is the main photolytic pathway, the presence of other pharmaceutical residues will reduce the photolysis rates. Hospital effluents have thousands of pharmaceutical residues and these pharmaceuticals could act as DOMs, which produce transient excited species and could react with compounds that undergo mainly photosensitizing reactions, and enhance the photolysis rates. Although less toxicity was observed with lower initial target concentrations of the pharmaceutical mixture (0.1–4 μM each), the photo-toxicity was still demonstrated to gradually increase over the irradiation period. The increased toxicity from irradiated pharmaceutical mixtures challenges the validity of our current understanding of sunlight photolysis. The implications of this work suggest that our knowledge of the occurrence, natural attenuation, ecotoxicity, and human health risks of pharmaceuticals is far from complete; photolysis is not necessarily a purification process. Although phototransformation is often rapid, transformation byproducts of this continuous low-level release of pharmaceuticals could be even more toxic and resistant to further degradation, which has been overlooked by existing natural fate studies and risk assessment models.