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Recent studies have confirmed that the aquatic ecosystem is being polluted with an unknown cocktail of pharmaceuticals, their metabolites and/or their transformation products (TPs). Although individual pharmaceuticals are typically present at low concentrations, their continuous input into the aquatic ecosystem and their toxic and persistent presence are the major environmental concerns. Therefore, it is necessary to assess the environmental risk caused by these aquatic pollutants. Data on exposure are required for quantitative risk assessment of parent compounds and their transformation products (TPs) and/or metabolites. Such data are mostly missing, especially for TPs, because of the non-availability of TPs and very often metabolites for experimental testing. Therefore, the application of different in silico tools for qualitative risk assessment can be used. Also, the presence of these micro-pollutants (active pharmaceutical ingredients, APIs) in the aquatic cycle are increasingly seen as a challenge to the sustainable management of water resources worldwide due to ineffective effluent treatment and other measures for their input prevention. Given the poor prognosis for effluent treatment (‘end of the pipe’ approach) for input prevention of APIs in the environment, it is necessary to focus on the ‘beginning of the pipe’ strategy. The very beginning of the pipe is the molecules themselves. Therefore, novel approaches are needed like designing greener pharmaceuticals, i.e. better biodegradable ones in the aquatic environment after their release. Therefore, the present research work focused on two important topics a) assessment of the environmental risk associated with the presence of highly prescribed drugs and their TPs; b) demonstrating the feasibility of the ‘benign by design’ concept for designing biodegradable drug derivatives, which will have the better biodegradability in the environment after their release. The present thesis includes four research articles (1-4) which address these approaches. The first article is about the qualitative environmental risk assessment using the example of transformation products formed during photolysis (photo-TPs) of Diatrizoic acid (DIAT). Photolysis is the chemical reaction in which the compound is broken down by photons and often in combination with hydroxyl radicals. Photolysis is the most common abatement process of micro-pollutants in the environment. The qualitative risk assessment of DIAT and selected photo-TPs was performed by the PBT approach (i.e. Persistence, Bioaccumulation and Toxicity), using chemical analysis, experimental biodegradation test assays, QSAR models with several different toxicological endpoints and in silico read-across approaches. The second article addresses a tiered approach of implementing green and sustainable chemistry principles for theoretically designing better biodegradable and pharmacologically potent pharmaceuticals derivatives. Photodegradation process coupled with LC-MSn analysis, biodegradability testing and in silico tools such as quantitative structure-activity relationships (QSAR) analysis and molecular docking proved to be a very significant approach for the preliminary stages of designing chemical structures that would fit into the ´benign by design´ concept in the direction of green and sustainable pharmacy. Metoprolol (MTL) was used as an example. The third article was also the conceptual framework to get new drug derivatives that are biodegradable in order to tackle the global challenge of micro-pollutants in the aquatic cycle. This study increased the knowledge about the role of the attachment of certain functionalities to the parent drug molecule for its biodegradability whilst conserving drug-likeness. This approach was in the past a totally neglected issue within drug development. Atenolol (ATL), a selective β1 blocker, was selected as an example to incorporate the additional attribute such as biodegradability into its molecular structure while conserving its substructures responsible for β adrenergic receptor blocker activity. In fourth article, the concept of designing green biodegradable pharmaceuticals has been proven through expanded experimental analysis setting out from the experiences collected as described in article two and three. This study could be considered as a more extensive feasibility study of rational design of green drug derivatives. The non-selective β-blocker Propranolol (PPL) was used as an example. The risk assessment study (Article #1) contributes in enhancing the existing knowledge about the life cycle and behavior (fate) of pharmaceuticals with a special focus on photo-TPs which are generally formed during advanced effluent treatment and enter as such into the environment. Based on the obtained results, the application of the in silico tools for qualitative risk assessment analysis increased knowledge space about the environmental fate of TPs in case of their non-availability for experimental testing. The benign by design studies (Article #2-4) were based on the knowledge and experience collected during the work on DIAT. It demonstrated the feasibility of a novel approach of designing comparatively better degradable and pharmacological potent derivatives through the implementation of ´green chemistry´ principles. However, the present approach is in the juvenile stage and further knowledge has to be collected beforehand for the full implementation of this approach into drug development.
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been widely used since 1950 in various consumer products as well as in industrial applications owing to their unique properties, e.g. being hydrophobic and lipophobic at the same time. Nowadays, some of these persistent and man-made PFASs can ubiquitously be found in humans, wildlife and various environmental media. One prominent representative of concern, belonging to the subgroup of perfluorocarboxylates (PFCs) and their conjugate acids (PFCAs), is perfluorooctanoat (PFO) and its conjugate acid (PFOA). Because of its adverse effects on human health and its persistency in the environment industry has started to replace PFO(A) and related long chain chemicals (with seven and more fully fluorinated carbon atoms) with so-called short chain PFASs (less than seven fully fluorinated carbon atoms), including precursors of PFC(A)s. Also these short chain PFC(A)s are persistent and can already be found in humans, ground- and drinking water and in remote regions. However, knowledge gaps exist in understanding the partitioning and the resulting mobility of short chain PFC(A)s in the environment. This is due to the fact that partitioning data of PFC(A)s from standardised experiments can easily be biased by various artefacts, e.g. self-aggregation of the molecules. Therefore, the objectives of this thesis are (i) to quantify the partitioning of PFC(A)s into mobile environmental media, (ii) to show how results from non-standard tests can be used to assess substance properties of concern and (iii) to conclude on whether the environmental exposure to short chain PFC(A)s is of concern from a regulatory point of view. In the first part of this thesis, the environmental mobility of short chain C4-7-PFC(A)s was investigated by quantifying their partitioning under non-standardised semi-environmental conditions into mobile environmental media, focusing on water and air, and comparing it to long chain PFC(A)s. Results are: Partitioning between water and particles in the aeration tank, primary and secondary clarifier of a wastewater treatment plant (WWTP) showed no distinct differences for short chain PFC(A)s compared to their long chain homologues (Paper 1). In a water-saturated sandy sediment column short chain PFC(A)s were not retarded, whereas long chain homologues were retarded by sorption to the sediment (Paper 2). Atmospheric particle-gas partitioning showed a lower fraction sorbed to particles for short chain PFC(A)s compared to long chain ones in samples from a WWTP (Paper 3). Air-water concentration ratios based on samples from the tanks of a WWTP were found to be higher for short chain PFC(A)s compared to long chain PFC(A)s (Paper 1). Additionally, in a newly developed experimental set-up the water to air transfer was used to derive that the pKa of C4-11-PFCAs must be <1.6 instead of up to 3.8 as reported in the literature (Paper 4). Overall, in the investigated systems short chain PFC(A)s showed a higher mobility due to a more pronounced partitioning into mobile environmental media compared to long chain PFC(A)s. In the second part of the thesis it was shown how PFO(A) - owing to its persistent, bioaccumulative and toxic (PBT-)properties – was in the context of this thesis successfully assessed as a substance of very high concern according to the criteria of the European REACH Regulation (EC No 1907/2006) by using data from non-standard tests (Paper 5). In conclusion, based on the knowledge of the high environmental mobility of short chain PFC(A)s and taking into account the argumentation of the PBT-concern of PFO(A), environmental exposure to short chain PFC(A)s is of concern and existing knowledge is already sufficient to initiate measures to prevent emissions of short chain PFC(A)s and their precursors into the environment.
Fire plays an important role in the earth system by influencing ecosystems and climate, but climate in turn also influences fire. The system became more complex when humans started using fire as a tool. Understanding the interaction between humans, fire and climate is the major aim of paleofire research. Understanding changes in these three aspects in the past will help predicting future climate, fire and human interactions. The use of lake sediment cores as natural archives for reconstructing past fire activity by counting charcoal particles is well established. This present dissertation is dedicated to the evaluation and application of specific organic molecular markers for biomass burning: levoglucosan, mannosan and galactosan were used as proxies for reconstructing past fire activity in lake sediments thorough the entire Holocene. First, a new analytical method was developed using high-performance anion exchange chromatography combined with mass spectrometry to separate and detect these three monosaccharide anhydrides in lake sediments. The suitability of this analytical method was proven by comparing the levoglucosan, mannosan and galactosan results in selected lake sediment samples from Lake Kirkpatrick, New Zealand and by correlating the results with macroscopic charcoal. Furthermore, the method was successfully applied to a lake sediment core from Lake Petén Itzá, Guatemala to reconstruct regional Holocene fire history. The analyses of levoglucosan were combined with fecal sterols to reconstruct late Holocene human fire interactions at Lake Trasimeno, Italy, demonstrating low fire activity during the Roman period. This combination of studies proves that these molecular markers are valid fire proxies in sediments from multiple locations around the globe. Comparison of levoglucosan, mannosan and galactosan concentrations with macroscopic charcoal trends in Lake Kirkpatrick and Lake Petén Itzá, suggests that the molecular markers represent more regional fire history and low temperature fires in contrast to macroscopic charcoal, which is a local fire proxy. In addition, vegetation changes (Lake Kirkpatrick and Lake Petén Itzá) and charcoal morphotypes (Lake Petén Itzá) were compared to the levoglucosan/mannosan and levoglucosan/(mannosan+galactosan) ratios suggesting that these ratios may be a suitable tool to track burned fuel. Biodegradation tests demonstrate the potential degradation of levoglucosan, mannosan and galactosan if dissolved in water, but findings in ancient sediment samples suggest that particle-bound levoglucosan, mannosan and galactosan can be buried in sediments over millennial time scales. Although uncertainties still exist, the results of this research suggests that organic molecular markers are a suitable regional fire proxy and isomer ratios may help understand changes in burned vegetation.
Despite the great progress that has been made in the prophylaxis of oral diseases over the past decades, dental caries and periodontal diseases remain major challenges in the field of dentistry. Biofilm formation on dental hard tissues is strongly associated with the etiology of these oral diseases. Therefore, the process of bioadhesion and biofilm formation on tooth surfaces is of particular interest for dental research. The first stage of bioadhesion on dental surfaces is the formation of the pellicle layer. This mainly acellular film, composed largely of adsorbed proteins, glycoproteins, and lipids, is distinguished from the microbial biofilm (plaque). As the interface between teeth and the oral environment, the pellicle plays a key role in the maintenance of oral health and is of great physiological and pathophysiological importance. On the one hand, the pellicle shows protective properties for the underlying dental hard tissues. On the other hand, it also serves as the basis for dental plaque and therefore, for the development of oral diseases such as caries and periodontitis. Hydrophobic interactions, which are governed by lipophilic substances, are of high relevance for bacterial adherence. Therefore, pellicle lipids, which are a significant constituent of this biological structure, are an interesting target for dental research, as they could modulate oral surfaces, influence microbial interactions, and potentially impede bacterial adherence. Compared to the extensive work on the pellicle´s ultrastructure and protein/amino acid composition, little attention has been given to its lipid profile. Knowledge of the lipid composition of the pellicle may provide insight into several oral pathological states, including caries, dental erosion, and periodontal disease processes and could contribute to novel approaches in preventive dentistry. The principle aim of this thesis was the comprehensive characterization of the fatty acid (FA) profile of the in situ formed pellicle layer. This includes the influence of pellicle maturation on the FA profile as well as intra- and interindividual differences. Furthermore, investigations on the effect of rinses with edible oils on the pellicle´s FA composition were a focus of this work. For these purposes, an analytical method based on a combination of innovative specimen generation and convenient sample preparation with sensitive mass spectrometric analysis was successfully developed and comprehensively validated within this thesis. Pellicle samples were formed in situ on bovine enamel slabs mounted on individual upper jaw splints. After a comprehensive sample preparation, gas chromatography coupled with electron impact ionization mass spectrometry (GC-EI/MS) was used in order to characterize qualitatively and quantitatively a wide range of FA (C12-C24). The individual FA profiles of pellicle and saliva samples collected from ten research participants were investigated. The relative FA profiles of the pellicle samples gained from the different subjects were very similar, whereas the amount of FAs showed significant interindividual variability. Compared to the pellicle´s characteristic FA profile, higher proportions of unsaturated FAs were detected in the saliva samples, highlighting that FAs available in saliva are not adsorbed equivalently to the pellicle layer. This, in turn, shows that pellicle formation is a highly selective process that does not correlate directly with salivary composition. Additionally, pellicle samples collected after 3, 30, 60, 120, and 240 min of intraoral exposure were analyzed. It could be shown that pellicle maturation has only a minor impact on the FA composition. However, the FA content increased substantially with increasing oral exposure time. Modifying the pellicle´s lipid composition by using edible oils as a mouthwash could alter the physicochemical characteristics of the pellicle and strengthen its protective properties by delaying bacterial adhesion. Therefore, the impact of rinses with safflower oil on the pellicle´s FA composition was determined. The application of rinses with safflower oil resulted in an accumulation of its specific FAs in the pellicle, thus representing a possibility for modifying the pellicle´s lipid profile. The present work is the first to apply a validated method that combines in situ pellicle formation, sample preparation, and the comprehensive determination of FAs via a sensitive analytical method. The results provide valuable information regarding the pellicle´s FA composition which closes an existing knowledge gap in pellicle research. A broader knowledge of the lipid composition of the pellicle contributes to the understanding of oral bioadhesion processes and may help facilitate novel approaches in preventive dentistry.
In the discourse on pharmaceuticals in the environment, hardly any attention has been paid to anticancer drugs. Because of their none-selective modes of action, that is, because they affect both cancerous and healthy cells, these drugs are regarded as potentially carcinogenic, genotoxic, mutagenic, and teratogenic substances. It is, however, not known how and to what extent these substances affect organisms and the environment in the long run. For this reason, this dissertation evaluated, addressing several endpoints and using organisms from different trophic levels and in silico predictions, the fate (bio- and photo degradation) and ecotoxicity of these substances. Four anticancer drugs (cyclophosphamide (CP), 5-fluorouracil (5-FU), methotrexate (MTX), and imatinib (IM) were selected. None of these anticancer compounds can be classified as ´readily biodegradable,´ a classification that indicates that biodegradation will only play a minor role in the elimination of these compounds and that they cannot be removed by the conventional processes used in sewage treatment plants and will most likely remain in the water cycle. Despite the high degrees of mineralization achieved in advanced (photo)oxidation processes, it was not possible to fully mineralize the compounds, a result that indicates that transformation products were created during these reactions. The ecotoxicity assays performed with V. fischeri indicated that 5-FU was, of all the substances tested, likely to be the most toxic (very toxic), followed by MTX (toxic) and IM (toxic/harmful), whereas CP was nontoxic. MTX presented the highest phytoxicity activity in the Lactuca sativa assay, followed by 5-FU, IM, and CP. The results of the tests performed with A. cepa showed cytotoxic (5-FU, MTX, and CP) and genotoxic effects (5-FU, CP, and IM) and mutagenic activity (5-FU, MTX, CP, and IM) of the compounds. Photo transformation products (PTPs) of CP, MTX, and 5-FU were nontoxic towards V. fischeri. However, some PTPs formed during the photodegradation of 5-FU led to positive mutagenic and genotoxic alerts in several in silico models. Not one of the compounds examined in this dissertation is likely to be fully eliminated from the water cycle by (natural) photolysis and/or advanced oxidation. Moreover, some of the treatments resulted in the formation of stable intermediates that were even less biodegradable than parent compounds. This finding shows that it is not enough to focus on primary elimination because TPs are not necessarily better biodegradable than their respective parent compounds. As indicated by the genotoxic and mutagenic positive alerts presented by different in silico models, the PTPs observed here are likely to require, despite their lower toxicity in comparison to the parent compounds, screening after treatments.
Uranine (sodium fluorescein, UR) has been routinely used in hydrological research to monitor surface and subsurface water flow, transport and mixing processes since the end of nineteenth century. Based on such obtained data, further conclusions can be drawn on the spread and behavior of pollutants (partly on models). Use of UR for qualitative (visual) studies of underground contamination is common, however data available on its environmental behavior (e.g., conversion, degradation or formation and fate of the transformation products, TPs) are incomplete or not readily comparable. UR observations of biodegradation are still speculative. S-metolachlor (SM) is a popular worldwide chloroacetamide herbicide, which highly correspond to the global pesticide use. It is offered on the French market as an effective multicrop herbicide against annual grasses and certain broadleaf weeds under the trade name Mercantor Gold (MG). Photodegradation contributes to the fate of SM in the aquatic environment. TPs were already found in surface and groundwater. However, further fate and assessment of the TPs was not done. Moreover, adjuvants in MG´s formula can affect the solubility, biodegradation, photolysis and sorption properties of the active compound SM. TPs can have different properties (e.g. more mobile, toxic or present at higher concentrations) that enable them to reach the environmental compartments not affected by the parent compound (PC) itself. To assess the ecological impact of pesticides, tracers, and their respective TPs on water organisms, their behavior can be investigated in laboratory screening biodegradation tests. Yet, incomplete data was available on SM, MG and UR transformation or their photo- TPs´ fate in surface and water-sediment systems. The combination of photolysis with aerobic biodegradation in order to identify persistent photo-TPs could provide new insight into the environmental behavior of the selected compounds. Therefore, principle of this thesis was to 1) identify the impact of MG´s adjuvants on the biodegradation, photolysis (Xe lamp) and sorption compared to the SM alone, 2) examine the photolysis and biodegradability of UR 3) monitor the primary elimination (photolysis) of the PCs by HPLC (-UV, -FLD) and measure the degree of mineralization by means of nonpurgeable organic carbon (NPOC) 4) elucidate the photo-TPs of SM, MG and UR by using LCMS/ MS 5) analyze biodegradability of the photo-TPs in order to determine their fate and persistence in aquatic environment 6) conduct in silico toxicity predictions (pesticides) in human (carcinogenicity, genotoxicity and mutagenicity) and eco-toxicity (microtoxicity, bioconcentration factor and toxicity in rainbow trouts). SM, MG and UR were found not readily biodegradable in Closed Bottle test (CBT), Manometric Respiratory test (MRT) and in water-sediment test (WST). Chemical analysis of photolysis samples showed higher elimination of SM in MG compared to SM alone whereas UR displayed high primary elimination rate in general. The overall low degree of mineralization indicated that abundant photo-TPs were formed. Furthermore, the photo-TPs were found not biodegradable in performed biodegradation tests. Only small degradation rates for UR could be observed in the CBT and WST. Additionally, in the MRT and WST new bio-TPs were generated from the photo-TPs of SM and SM in MG. Obtained results suggest that the MG formulation did not significantly affect the biodegradation, however it influenced the diffusion of the active substance (SM) to sediment and potentially affected the photolysis efficiency, which might result in faster formation of photo-TPs in the environment. In silico predictions showed that for many endpoints, biotransformation might lead to an increased toxicity in humans and to water organisms compared with the parent compound SM. No indications were found for UR toxicity. Still, target-oriented investigations on long term impacts of photo-TPs from UR are warranted. The present work demonstrates that a combination of laboratory tests, analytical analysis and in silico tools result in valuable information regarding environmental fate of the TPs from selected compounds. Furthermore, it was shown that photo-TPs formed in the aquatic environment should be taken into account not only the parent compound and its decay.
Verbräuche von Arzneistoffen, die auf das menschliche Nervensystem wirken (Neurologika), unterliegen aufgrund der auf dem Markt befindlichen Arzneistoffvielfalt einem ständigen Wandel. Zudem waren die Haupteintragspfade für Neurologika in die aquatische Umwelt bisher nicht eindeutig geklärt. Haushalte (diffuser Eintrag) und Einrichtungen des Gesundheitswesens (punktueller Eintrag), wie psychiatrische Fachkliniken oder Pflegeheime, wurden als maßgebliche Eintragspfade diskutiert. Ziel dieser Arbeit war es deshalb, Arzneimittelverbräuche und damit verbundene Arzneistoffemissionen durch Haushalte und Einrichtungen des Gesundheitswesens mit Hilfe einer neu entwickelten Methode abzuschätzen. Bei dieser Methode wurde das jeweilige Ausmaß der Emissionen durch die Kalkulation von Abwasserkonzentrationen und den Vergleich von Verbrauchsmengen an Arzneistoffen bestimmt. Im Ergebnis konnte gezeigt werden, dass sich Arzneimittelverbrauchsmuster in psychiatrischen Fachkliniken und Pflegeheimen von denen in allgemeinen Krankenhäusern und Haushalten unterscheiden. Außerdem konnte mit dieser Methode deren jeweiliger Beitrag am gesamten Arzneistoffeintrag in das kommunale Abwasser eingeschätzt und in hohen Mengen in das Abwasser eingetragene Arzneistoffe identifiziert werden. Durch Haushalte wurde das hinsichtlich des Umweltverbleibs und -verhaltens wenig untersuchte Antiepileptikum Gabapentin in hohen Mengen in das Abwasser eingetragen. Die Bedeutung von Einrichtungen des Gesundheitswesens am Arzneimitteleintrag in das kommunale Abwasser konnte für alle untersuchten Einrichtungstypen im Vergleich zu Haushalten als gering eingestuft werden. Bestimmte einrichtungstypische Arzneistoffe, insbesondere Neurologika, können bei regionaler Betrachtung jedoch eine größere Rolle spielen. Insbesondere Quetiapin wurde in psychiatrischen Fachkliniken und Pflegeheimen als Substanz mit hohen Verbrauchsmengen und hohem Emissionspotential identifiziert. Ausgehend von diesen Erkenntnissen wurden Gabapentin und Quetiapin tiefergehend hinsichtlich ihres Verbleibs und ihres Verhaltens in der aquatischen Umwelt charakterisiert. Beide Arzneistoffe wurden bei verschiedenen Startkonzentrationen zur Simulation eines technischen Behandlungsverfahrens mit UV-Licht bestrahlt. Im weiteren Verlauf wurden Gabapentin und Quetiapin und die jeweilige Muttersubstanz im Gemisch mit gebildeten Phototransformationsprodukten hinsichtlich biologischer Abbaubarkeit im Closed Bottle Test und im Manometrischen Respirationstest nach OECD-Richtlinien und hinsichtlich toxischer Eigenschaften im Leuchtbakterientest und im Umu-Test beurteilt. Die Strukturaufklärung von Photo- und Biotransformationsprodukten erfolgte mittels hochauflösender Massenspektrometrie. Im Ergebnis konnten weder Gabapentin noch Quetiapin bei hohen Startkonzentrationen durch Photolyse über 128 min mineralisiert oder vollständig eliminiert werden. Identische Phototransformationsprodukte wurden bei unterschiedlichen Startkonzentrationen für die UVBehandlung gebildet. Die Arzneistoffe Gabapentin und Quetiapin waren nach OECD-Richtlinien im Closed Bottle Test nicht leicht biologisch abbaubar. Die photolytischen Gemische von Gabapentin sind nicht besser als Gabapentin selbst abbaubar und die Phototransformationsprodukte wurden im Closed Bottle Test ebenfalls nicht eliminiert. Auch das photolytische Gemisch von Quetiapin im Closed Bottle Test war nicht besser biologisch abbaubar als Quetiapin selbst. Die Phototransformationsprodukte von Quetiapin und Quetiapin selbst unterlagen beim Closed Bottle Test und im Manometrischen Respirationstest verschiedenen biologischen Transformationsprozessen und führten zur Bildung von verschiedenen Biotransformationprodukten. Das in biologischen Abbautests von Quetiapin maßgeblich gebildete Biotransformationprodukt BTP 398 konnte in diversen Flusswasserproben nachgewiesen werden. Dies lässt sich höchstwahrscheinlich damit erklären, dass BTP 398 unter anderem auch beim humanen Metabolismus gebildet wird. Die Langzeit-Leuchthemmung und die Zellvermehrungshemmung im Leuchtbakterientest stiegen im Verlauf der Photolyse von Gabapentin durch Bildung von Phototransformationsprodukten. Dies deutet auf eine erhöhte Toxizität der Phototransformationsprodukte im Vergleich zu Gabapentin hin. Bei Quetiapin war unter Photolyse keine Abnahme der schon vorhandenen Toxizität beim Leuchtbakterientest zu erkennen. Gabapentin, Quetiapin und deren Phototransformationsprodukte wiesen im Umu-Test keine Genotoxizität auf. …
After being administrated to humans or animals, pharmaceuticals may be metabolized by a variety of mechanisms and pathways within the body. Once these compounds and/or their metabolites are excreted, they may undergo degradation in the aquatic environment. Unfortunately, a rapid and complete mineralization cannot always be guaranteed, whereas relatively stable transformation products (TPs) may be formed. The largest part of older studies focused on investigation of the elimination kinetics of parent compounds without considering the amount and chemical structure of individual TPs. Only recently, there is an increasing trend to deliver such information. Nevertheless, since drugs are defined as significant environmental pollutants, it is not only important to elucidate their TPs, but also necessary to investigate whether these formed compounds preserve the same mode of action as the parent compound or are even more toxic. Thus, two main objectives of this thesis can be formulated. Firstly, to highlight the concern originated by metabolites and transformation products of pharmaceuticals that contaminate the environment. Hereby, the already-published knowledge on TPs within a certain selection of drugs is assessed to exemplify the number and quality of the existing information on their TPs. Secondly, to particularly investigate the fate of the antibiotic ciprofloxacin (CIP). This is done by (a) evaluating the suitability and sustainability of the photolytic decomposition as an advanced water treatment technique, (b) monitoring the course of genotoxicity of the irradiated mixtures using a battery of genotoxicity and cytoxicity in vitro assays, and (c) considering the potential genotoxicity for CIP´s individual TPs by the employment of in silico approaches using quantitative structure activity relationships (QSAR) models. This thesis based on the results and conclusions of five articles, which can be found in the appendix. A systematic literature review was conducted on the current state of knowledge on pharmaceuticals and its derivatives in the environment. Two groups, namely antibiotics and anticancer drugs, were considered more closely with respect to the availability of chemical structures for their TPs. Furthermore, the photodegradation of CIP as well as a preliminary toxicity assessment of its identified TPs were investigated in three research papers. An extensive review with a table at its core shows the existing data on 158 TPs, which already have an assigned registry number in chemical abstracts service (CAS-RN), was presented. In total, 294 TPs, identified with chemical structures in the literature, were found for 15 compounds out of the 21 that were selected as target compounds. Eleven TPs, created from CIP, were identified by high-performance liquid chromatography/high-resolution multiple-stage mass spectrometry. It was detected that the transformation of CIP mainly occurred through substitution of fluorine, defluorination, hydroxylation of the quinolone core and the breakdown of the piperazine ring. Some of the identified TPs of CIP were predicted as genotoxic by QSAR analysis, while the experimental testing for a few genotoxic and cytotoxic endpoints showed that the potential of the resultant mixtures could be primarily dependent on the concentration of residual CIP. In contrast, irradiation mixtures were neither mutagenic in the Ames Test nor genotoxic in the in vitro Micronucleus Test. It is possible that the effect of the TPs was masked by antagonistic mixture interactions and/or they were not formed at effectively concentrations. Nevertheless, all of the identified TPs of CIP still retained the core quinolone moiety, which is responsible for the biological activity. Thus, a more comprehensive assessment, encompassing more genotoxic endpoints, chemical analysis characterization and exposure analyses, needs to be conducted. Information available on TPs demonstrates that already slight changes in treatment conditions and processes result in the formation of different TPs. Nevertheless, most of the transformation products could neither be identified nor fully assessed regarding their toxicity. This, in turn, presents a major challenge for the identification and assessment of TPs. Hence, from a practical and sustainability point of view, limiting the input of pharmaceuticals into effluents as well as improving their (bio)degradability and elimination behavior, instead of only relying on advanced effluent treatments, is urgently needed. Solutions that focus on this