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Identification and Confirmation of the Environmental Risks of Emerging Pollutants in Surface Waters and Sediments

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Identification and Confirmation of the Environmental Risks of Emerging Pollutants in Surface Waters and Sediments Identification and confirmation of the environmental risks of emerging pollutants in surface waters and sediments Von der Fakultät für Mathematik, Informatik und Naturwissenschaften der RWTH Aachen University zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigte Dissertation Vorgelegt von Shangbo Zhou, Master of engineering aus Gansu, China Berichter: Univ.-Prof. Dr. rer. nat. Henner Hollert Univ.-Prof. Dr. rer. nat. Andreas Schäffer Tag der mündlichen Prüfung: 24.09.2019 Diese Dissertation ist auf den Internetseiten der Universitätsbibliothek online verfügbar. Your teacher can open the door but you must enter by yourself. – Chinese verb Abstract Although the occurrence, the fate and the toxicology of emerging pollutants in the aquatic environment have been widely studied, there is still a lack in the correlation of the levels of pollutants with the possible adverse effects in wildlife. The shortcomings of traditional methods for risk assessment have been observed, and the contributions of the identified compounds to the observed risks are rarely confirmed. Therefore, the main purpose of this thesis was to develop reasonable methods for risk identification of single compounds and mixtures, and to identify and confirm environmental risks caused by non-specific and mechanism-specific toxicity in aquatic systems. In this thesis, optimized methods for risk identification of single compounds and mixtures were developed. For screening-level risk assessment of single compounds, an optimized risk quotient that considers not only toxicological data but also the frequency with which the detected concentrations exceeded predicted no-effect concentrations was used to screen candidate priority pollutants in European surface waters. Results showed that 45 of the 477 analyzed compounds indicated potential risks for European surface waters. For risk assessment of environmental samples, a risk quotient that considers the ratio of the BEQ to the environmental quality standard (EQS) and the frequency of BEQ exceeding EQS was recommended. Results showed that the highest risk of the anti-androgenic activities was presented at the site directly influenced by the effluents of wastewater treatment plants. To confirm the risk of selected pharmaceuticals, the three antimicrobials clarithromycin, triclosan and sulfamethoxazole, the two anti-inflammatories ibuprofen and diclofenac, the anticonvulsant carbamazepine, the lipid-lowering agent bezafibrate, and the stimulant caffeine were used to study their delayed toxicity using the zebrafish larvae behavioral test. Delayed hatch was observed for exposure to triclosan (1 μg/l) and ibuprofen (100 μg/l) in the early stages of development. In the early stages of development after hatching, the larval locomotor behavior following embryonic exposure to 0.1 μg/l triclosan and 1 μg/l caffeine was altered. Furthermore, for a mixture of the respective highest environmental concentrations of the 8 pharmaceuticals changes in larval behavior were observed. Mechanism-specific bioassays and chemical analyses were performed to identify and confirm endocrine disturbance activities (e.g., anti-androgenic activity) in surface waters and aryl hydrocarbon receptor (AhR)-mediated activities in sediments. Spatial I and temporal variations of anti-androgenic activities and environmental risks were observed. High cytotoxicity and anti-androgenic activities were observed in surface waters that were directly influenced by the effluents of wastewater treatment plants. Although sediment samples from the upper Danube River were considered less contaminated, high AhR-mediated activities were observed. Furthermore, by combining bioassays, fractionation, chemical analysis and confirmation to an effect-directed analysis (EDA), fractions with adverse effects were screened and effects further associated to specific pollutants and mixtures. The comparison between measured bioanalytical equivalents (BEQs) of sediment samples and BEQs of synthetic mixtures revealed that the US EPA priority PAHs seem to account only to a minor extent for the AhR-mediated activities of the sediment samples, while non-priority substances in medium-polar and polar fractions were high inducers. In this thesis, induced EROD and endocrine disturbance activities were expressed as BEQs of the respective reference standards. In order to properly use the BEQs and confirm the contributions of chemically analyzed compounds to bioassay-derived BEQs, the factors causing the variations of BEQs and relative potencies (REPs) were mathematically analyzed. The effects of the effect levels, slopes and the maximum response of the concentration-response curves of the samples and reference compounds on REP and BEQ variations were confirmed. Although bioassay-derived BEQs (Bio-BEQs) and chemically estimated BEQs (Chem-BEQs) vary with the selected effect level, the explanation of Bio-BEQs by Chem-BEQs of certain compounds at the same effect level will be theoretically stable. II Zusammenfassung Obwohl das Vorkommen, der Verbleib und die Toxikologie sogenannter ―Emerging Pollutants‖ in der aquatischen Umwelt bereits weitgehend untersucht worden sind, mangelt es immer noch an der Korrelation der Schadstoffgehalte mit den möglichen negativen Auswirkungen auf die Tierwelt. Zudem konnten bereits die Defizite traditioneller Methoden der Risikobewertung beobachtet werden, und die Beiträge der identifizierten Verbindungen zu den beobachteten Risiken werden selten bestätigt. Folglich war es das Hauptanliegen dieser Arbeit eine angemessene Methode zur Risikenidentifizierung von Einzelsubstanzen und Substanzgemischen zu entwickeln, sowie die Risiken für die Umwelt zu identifizieren und bestätigen, die durch nicht-spezifische und Mechanismus-spezifische Toxizität in aquatischen Systemen verursacht werden. In dieser Dissertation wurden optimierte Methoden zur Risikoidentifizierung einzelner Verbindungen und Gemische entwickelt. Für die Risikobewertung einzelner Verbindungen auf Screening-Ebene wurde ein optimierter Risikoquotient verwendet, um prioritäre Schadstoffe in Europäischen Oberflächengewässern zu screenen, der nicht nur toxikologische Daten berücksichtigt, sondern auch die Häufigkeit, mit der die ermittelten Konzentrationen die prognostizierten Grenzwerte überschritten werden. Die Ergebnisse zeigten, dass 45 der 477 untersuchten Verbindungen ein potenzielles Risiko für europäische Oberflächengewässer darstellten. Für die Umweltrisikobewertung von Umweltproben wurde ein Risikoquotient empfohlen, der das Verhältnis der BEQ zum Umweltqualitätsstandard (Environmental Quality Standard, EQS) und die Häufigkeit von BEQ-Überschreitungen berücksichtigt. Die Ergebnisse zeigten, dass das höchste Risiko für antiandrogene Aktivitäten am Standort vorlag, welcher direkt von den Abwässern von Kläranlagen beeinflusst wurde. Um das Risiko ausgewählter Arzneimittel zu bestätigen, wurden die drei antimikrobiellen Wirkstoffe Clarithromycin, Triclosan und Sulfamethoxazol, die beiden Entzündungshemmer Ibuprofen und Diclofenac, das Antikonvulsivum Carbamazepin, das Lipidsenkungsmittel Bezafibrat und das Stimulans Coffein mittels eines Verhaltenstests mit Zebrabärblingslarven auf ihre verzögerten Toxizität untersucht. Bei der Exposition gegenüber Triclosan (1 μg/l) und Ibuprofen (100 μg/l) wurde in den frühen Entwicklungsstadien eine verzögerte Schlupfphase beobachtet. In den frühen Stadien der Entwicklung nach dem Schlüpfen war das Verhalten der Larvenlokomotorik III nach Belastung mit 0,1 μg/l Triclosan und 1 μg/l Koffein verändert. Weiterhin wurden bei einer Mischung der jeweils höchsten Umweltkonzentrationen der acht Arzneimittel Veränderungen im Larvenverhalten beobachtet. Mechanismusspezifische Bioassays und chemische Analysen wurden durchgeführt, um endokrine Störungsaktivitäten (z. B. antiandrogene Aktivität) in Oberflächengewässern und Aryl-Hydrocarbon-Rezeptor (AhR) vermittelte Aktivitäten in Sedimenten zu identifizieren und zu bestätigen. Es wurden räumliche und zeitliche Variationen der antiandrogenen Aktivitäten und Umweltrisiken beobachtet. In Oberflächengewässern, die direkt von den Abwässern von Kläranlagen beeinflusst wurden, wurde eine hohe Zytotoxizität und antiandrogene Aktivität beobachtet. Obwohl Sedimentproben aus der oberen Donau als weniger kontaminiert angesehen wurden, wurden Aktivitäten mit hoher AhR-vermittelter Aktivität beobachtet. Weiterhin konnte durch die Kombination von Bioassays, Fraktionierung, chemischer Analyse und Bestätigung zu einer Effekt derigierten Analyse (EDA) Fraktionen mit negativen Auswirkungen gescreent und Effekte mit spezifischen Schadstoffen und Gemischen in Verbindung gebracht. Der Vergleich zwischen gemessenen bioanalytischen Äquivalenten (Bioanalytical equivalents, BEQs) von Sedimentproben und BEQs von synthetischen Gemischen ergab, dass die prioritären PAKs der US-amerikanischen EPA nur in geringem Maße für die AhR-vermittelten Aktivitäten der Sedimentproben verantwortlich zu sein scheinen, während nicht-prioritäre Substanzen in mittel-polaren und polaren Fraktionen hohe Induzierer waren. In dieser Arbeit wurden induzierte EROD- und endokrine Störungsaktivitäten als BEQs der jeweiligen Referenzstandards ausgedrückt. Um die BEQs angemessen zu verwenden und die Beiträge chemisch analysierter Verbindungen zu von Bioassays abgeleiteten BEQs zu bestätigen, wurden die Faktoren, die die Variationen der BEQs und relativen Potenzen (REPs) verursachen, mathematisch analysiert. Die Auswirkungen der Effektniveaus, Steigungen und
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