| Summary: | The concern for pharmaceutically active compounds (PhACs) as contaminants in the environment and the need to assess their environmental risk have greatly increased since the early nineties. Among PhACs, antibiotics and antiviral drugs are of important concern due to their role in growing antibiotic and antiviral drugs resistance among pathogenic bacteria and influenza viruses, respectively. Besides resistance issue, the compounds may upset sensitive ecosystems as they are designed to be highly bioactive. Clinically-important antibiotics are virtually ubiquitous contaminants in sewage water and surface water. Notably, recent emergence of novel influenza and use of anti-influenza drugs (specially Tamiflu®) during seasonal influenza、 influenza epidemics and for future pandemic are of emerging concern. Every year seasonal influenza epidemic causes tens of millions of respiratory illnesses and 250, 000 to 500, 000 deaths worldwide. WHO (World Health Organization) recommend the use of antiviral drug Tamiflu® during pandemic, as they are easy to use. Currently only Japan uses over eighty percent of Tamiflu® prescribed globally during common seasonal influenza. It is a fact that a huge amount of antiviral drugs and antibiotics ( for post infection cure of respiratory illness) will be used during an influenza pandemic and will arrive to sewage treatment plants (STPs).Unfortunately, these compounds behaviors are mostly unknown in both conventional and advanced STPs. The exposure of antiviral drug in the wild fowl gut and its implications for hastening the generation of antiviral-resistance in avian influenza viruses are also an emerging issue. The major objective of this thesis work was to investigate the occurrence of antibiotics and antiviral drugs in sewage treatment plants and their fate in different sewage treatment plants. The specific objectives were as follows: (a) to established appropriate analytical method for the selected antibiotics and antiviral drugs in sewage treatment plants, (b) to investigate the occurrence and removal of antibiotics and antiviral drugs in sewage treatment plants differ in technology and operation conditions; and (c) to predicts environmental concentration of the target compounds during a pandemics and appraisal of appropriate technology to reduce the risk associated with widespread use under pandemic conditions. In this study we selected twenty antibiotics: one beta-lactam: ampicillin; four macrolides: azithromycin, clarithromycin and roxithromycin; five quinolones: ciprofloxacin, enrofloxacin, levofloxacin, nalidixic acid and norfloxacin; two tetracycline: tetracycline and oxytetracycline; five sulfonamides: sulfadimethoxine, sulfadimizine, sulfamerazine, sulfam- ethoxazole and sulfamonomethoxine; and four others: lincomycin, novobiocin, salinomycin and trimethoprim. Oseltamivir Carboxylate (OC), the active metabolite of oseltamivir phosphate (Tamiflu®) and amantadine (AMN) were selected as antiviral drugs. This dissertation consists of nine chapters: Chapter I describe the background and objective of the study and chapter II represent a brief literature review. In Chapter III, analytical methods for selected antibiotics and antiviral drugs (for the first time) in water and wastewater were described. In Chapter IV, the occurrences and fate of antibiotics in sewage treatment plants were investigated in Japan and China. Clarithromycin was detected in the highest concentration in influent (1129 to 4820 ng/L), followed by azithromycin (160 to 1347 ng/L), levofloxacin (255 to 587 ng/L) and norfloxacin ( 155 to 486 ng/L) and sulfamethoxazole (159 to 176ng/L) in Japan. Ozonation as tertiary treatment of secondary effluent for wastewater reclamation provided significant elimination of antibiotics. Fifty present of the selected antibiotics were removed over eighty percent during ozonation. There was no elimination of antibiotics in dissolve phase during ultra filtration. From Chapter IV a hypothesis was drawn on antibiotics removal and its relation with longer sludge retention time (SRT) in STPs and in Chapter V the role of nitrifier in antibiotics removal was evaluated to verify the hypothesis established from Chapter IV. Nitrifying activated sludge (NAS) can biodegrade the tested antibiotics with different biodegradation rate between 2.74 to 9.95 L/gSS/d. Sulfamethoxazole and sulfamerazine degraded faster than trimethoprim, clarithromycin and enrofloxacin. In Chapter VI, occurrence of antiviral drugs in sewage water discharge and in river water in Japan was conducted during seasonal influenza epidemic and their fate in different sewage treatment facilities were evaluated in Chapter VII. This is the fist findings of antiviral (anti-influenza) drugs in the environment in the world and for the first time the removal mechanism in STPs was elucidated. Finally, it was observed that only primary and secondary treatment processes in STPs were not sufficient to remove these compounds significantly. Overall OC and AMN removal in STP with ozonation as tertiary treatment was 90% and 96% respectively. In ozonation batch experiment, Chapter VIII, ( feed ozone gas concentration 4.0mg/L, ozone gas flow rate 0.23L/min to maintain ozone feed rate of 0.6 mg/L/min), it was observed that AMN and OC concentration decreased linearly with time in all the experiments conducted and it can be, therefore, said that the degradation reactions follow pseudo first-order reaction. The k'O3 (pseudo first-order rate constant for O3) of AMN was 0.596/min (0.00993/sec), and OC was 0.524 /min (0.008725/sec) and over 99% removal within 10min. Chapter VIII described the predicted OC and antibiotics concentration in STPs influent, secondary effluent, after advance tertiary treatment (ozonation) and receiving water during a pandemic with three expected infection scenario ( according to US CDC FluAid model 2.0) in Kyoto city. Both antiviral drugs and antibiotics pose an environmental risk associated to there widespread use during a future pandemic. Ozonation as tertiary treatment can provide a technological solution to reduce the ecotoxicological effect of antibiotics and antiviral drugs uses during a pandemic. In a full scale STP, the antiviral drugs (OC and AMN) reduction were over 90% from secondary effluent after ozonation during seasonal influenza outbreak in Kyoto city in 2008/2009. Finally, (1) analytical methods for commonly used antibiotics and antiviral drugs in water sample was developed with an excellent precision and accuracies, (2) both antibiotics and antiviral drugs were detected in environmental sample, and their behavior in STPs were elucidated. Antivirals in this study were the first time findings in sewage water. This study will provide a surrogate for planning a pandemic preparedness action plan for sewage treatment pants for ecotoxicological risk management. === Kyoto University (京都大学) === 0048 === 新制・課程博士 === 博士(工学) === 甲第14931号 === 工博第3158号 === 新制||工||1474(附属図書館) === 27369 === UT51-2009-M845 === 京都大学大学院工学研究科都市環境工学専攻 === (主査)教授 田中 宏明, 教授 伊藤 禎彦, 教授 藤井 滋穂 === 学位規則第4条第1項該当
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