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The main objective of this thesis was to develop statistical and analytical methods for untargeted analyses of complex environmental matrices like soil and sediment. Untargeted analyses are notoriously difficult to perform in matrices like soil and sediment because of the complexity of organic matter composition within these matrices. This thesis aimed to (1) Develop and compare extraction methods for untargeted analyses of soil and sediment while also developing data handling and quality control protocols; (2) Investigate novel applications of untargeted analyses for environmental classification and monitoring; and (3) Investigate the experimental factors that can influence the organic matter composition of untargeted extractions. CHAPTER TWO is a literature review of metabolomics protocols, and these protocols were incorporated into a proposed workflow for performing untargeted analysis in oil, soil, and sediment. This thesis contains the first application of untargeted analysis to freshwater lake sediment organic matter (i.e. sedimentomics) in CHAPTER THREE, and this has implications for discovering new biomarkers for paleolimnology (APPENDIX ONE). I demonstrated successful extraction methods for both sedimentomics and soil metabolomics studies in CHAPTER THREE and CHAPTER FIVE, respectively, using the proposed workflow from CHAPTER TWO. I also applied sedimentomics to the classification of lake sediments using machine learning and geostatistics based on sediment organic matter compositions in CHAPTER FOUR; this was a novel application of sedimentomics that could have implications for ecosystem classifications and advance our knowledge of organic matter cycling in lake sediments. Lastly, in CHAPTER FIVE I determined microbial activity, extraction method, and soil type can all influence the composition of soil organic matter extracts in soil metabolomics experiments. I also developed novel quality controls and quantitative methods that can help control these influences in CHAPTER FIVE and APPENDIX THREE. APPENDIX TWO was written in collaboration with multiple researchers and is a review of all “omics” types of analyses that can be performed on soil or sediment, and how methods like the untargeted analysis of soil and sediment organic matter can be linked with metagenomics, metatranscriptomics, and metaproteomics for a comprehensive metaphenomics analysis of soil and sediment ecosystems. In CHAPTER SIX the conclusions and implications for each chapter and overall for this thesis are detailed and I describe future directions for the field. In the end the overall conclusions of this thesis were: 1) Quality controls are necessary for sedimentomics and soil metabolomics studies, 2) Sedimentomics is a valid technique to highlight changes in sediment organic matter, 3) Soil metabolomics and sedimentomics yield more information about carbon cycling than traditional measurements, and 4) Soil metabolomics organic matter extractions are more variable and require more quality controls.

<p>Prirodna organska materija zemlji&scaron;ta/sedimenata predstavlja glavnu oblast<br />za sorpciju hidrofobnih organskih jedinjenja, a njene osobine utiču na stepen<br />retencije i konsekventnu (bio)dostupnost organskih jedinjenja. Da bi se procenio<br />ekotoksikolo&scaron;ki rizik zagađenih zemlji&scaron;ta/sedimenata po okolinu, dizajnirala<br />odgovarajuća strategija remedijacije ili predvidela sudbina i transport organskih<br />polutanata u zagađenim zonama, neophodno je razumevanje mehanizma sorpcije i<br />desorpcije na nivou mehanizma uspostavljenih veza. U radu je izvr&scaron;eno ispitivanje<br />sorpcije i desorpcije odabranih hidrofobnih organskih polutanata, pentahlorbenzena<br />i lindana, na sekvencijalno ekstrahovanim huminskim kiselinama i huminima iz<br />jednog uzorka sedimenta u cilju pronalaženja veze između strukturnih<br />karakteristika izolovanih huminskih kiselina i humina i sorpcionih i desorpcionih<br />parametara. Afinitet za sorpciju, nelinearnost izotermi i prividna sorpciono-desorpciona histereza korelirani su&nbsp; sa osobinama sorbenata dobijenim iz<br />elementarne i FTIR spektroskopske analize. Predloženo je da je mehanizam<br />sorpcije na huminskim kiselinama rezultat odigravanja raspodele i specifične<br />adsorpcije, pri čemu se pri nižim koncentracijama pentahlorbenzena i lindana prvo<br />popune sorpciona mesta u kondenzovanoj aromatičnoj oblasti, a tek potom pri<br />vi&scaron;im koncentracijama sorpciona mesta u amorfnim alifatičnim oblastima.<br />Sveukupno vi&scaron;i koeficijenti nelinearnosti dobijeni za sorpciju pentahlorbenzena na huminskim kiselinama u odnosu na nelinearnost sorpcionih izotermi lindana, ukazuju na to da u ukupnoj sorpciji pentahlorbenzena veći značaj ima mehanizam raspodele i sme&scaron;tanje molekula pentahlorbenzena u hidrofobne &scaron;upljine huminskih kiselina, u odnosu na specifičnu adsorpciju. Ovi zaključci su potvrđeni rezultatima spektroskopskih istraživanja interakcija&nbsp; odabranih organskih jedinjenja i N-metilformamida. Predloženi mehanizam sorpcije ne može objasniti sorpciju pentahlorbenzena i lindana na uzorcima humina, većje pretpostavljeno da nelinearna sorpcija za uzorke humina može biti rezultat ostvarivanja povr&scaron;inskih interakcija, a visoki afinitet za sorpciju rezultat je raspodele organskih jedinjenja u amorfnim alifatičnim oblastima koje pružaju odlično okruženje za sorpciju.</p><p>U cilju daljeg proučavanja mehanizma sorpcije, izvr&scaron;eno je ispitivanje kinetike<br />desorpcije tri odabrana hidrofobna organskajedinjenja, pentahlorbenzena, lindana i<br />pentahloranilina, posredstvom&nbsp; čvrstog adsorbenta, XAD-4 makroporozne<br />jonoizmenjivačke smole. Na osnovu rezultata dobijenih za uzorak sedimenta i<br />frakciju &lt; 125 &micro;m za dva ravnotežna vremena (15 i 90 dana) i za sva odabrana<br />organska jedinjenja može se zaključiti da se za procenu potencijalne (bio)dostupne<br />frakcije organskih jedinjenja može koristiti jednostavna desorpcija u prisustvu<br />XAD-4 makroporozne jonoizmenjivačke smole i to na dva načina: (1) ekstrakcijom<br />sedimenta tokom 24 časa, kada frakcija koja se desorbuje odgovara frakciji<br />jedinjenja koja se nalazi u brzo-desorbujućem domenu organske materije, ili (2)<br />ekstrakcijom tokom 6 časova, kada frakcija koja se desorbuje odgovara polovini<br />one frakcije jedinjenja koja se nalazi u brzo-desorbujućem domenu organske<br />materije.</p> / <p>Natural organic matter of soil/sediment make the main region for&nbsp;sorption of hydrophobic organic compounds, ant its properties influence the degree&nbsp;of retention and, consequently, (bio)availability of organic compounds. In order to&nbsp;assess the ecotoxicological risks of contaminated soils/sediments to the&nbsp;environment and design the appropriate remediation strategy or predict the fate and&nbsp;transport of organic pollutants in contaminated zones, it is necessary to understand&nbsp;the mechanisms of sorption/desorption at the level of the mechanism of established&nbsp;bonds. Study of the sorption and desorption of selected hydrophobic organic&nbsp;pollutants, pentachlorobenzene and lindane, on sequentially extracted humic acids&nbsp;and humins from a single sediment sample with the aim of finding the relationship&nbsp;between the structural characteristics of the isolated humic acids and humin and&nbsp;sorption and desorption parameters. Sorption affinity, nonlinearity of isotherms,&nbsp;and apparent sorption-desorption hysteresis were correlated to the sorbent&nbsp;characteristics obtained from elemental analysis and FTIR spectroscopic data. The&nbsp;proposed sorption mechanism on humic acids assumes that at low concentrations&nbsp;of pentachlorobenzene and lindane the sorption sites in the condensed aromatic&nbsp;region are occupied first, and then, at their higher concentrations, the sorption sites&nbsp;in the amorphous and aliphatic regions. Generally higher nonlinearity coefficient obtained for the sorption of pentachlorobenzene on &nbsp;umic acids compared with the nonlinearity of sorption isotherms for lindane, indicate that in the overall sorption of pentachlorobenzene of higher significance is the &nbsp;echanism of distribution and insertion of pentachlorobenzene molecule into hydrophobic dips of humic acids, compared to specific adsorption. These conclusions were confirmed with the results of spectroscopic investigation of &nbsp;intermolecular interaction of chosen organic compounds and N-methylformamide.Since suggested sorption mechanism could not explain sorption of &nbsp;pentachlorobenzene and lindane onto humin samples, it is supposed that the nonlinearity can be a result of surface interactions, while the high sorption affinity is result of distribution of organic compounds in the amorphous aliphatic regions that offer an excellent environment for sorption.</p><p>With the aim of further insight into the sorption mechanism, investigation of&nbsp;desorption kinetics of three chosen hydrophobic organic compounds,&nbsp;pentachlorobenzene, lindane and pentachloroaniline, in the presence of &nbsp;soild&nbsp;adsorbent XAD-4 macroporous ion-exchange resin was performed. On the basis of&nbsp;the results obtained for sediment sample and fraction &lt; 125 &micro;m at two equilibrium&nbsp;times (15 and 90 days) and for all selected organic compounds, it can be concluded&nbsp;that the assessment of the potential (bio)avialable fraction of organic compounds&nbsp;may be obtained by using simple method of desorption in the presence of XAD-4&nbsp;macroporous ion-exchange resin, performed in two ways: (1) by sediment&nbsp;<br />extraction during 24 hours, when the desorbing fraction corresponds to the fraction&nbsp;of &nbsp;he compound that is found in the fast-desorbing domain of organic matter, or&nbsp;(2) by 6-hour extraction, when the desorbing fraction corresponds to one half of the&nbsp;fraction appearing in the fast-desorbing domain of the organic matter.</p>

Os locais de estudo estão situados no PETAR – Parque Estadual Turístico do Alto Ribeira e PEI – Parque Estadual Intervales, na região do sudeste do Brasil. A área é caracterizada pela presença de vegetação nativa de Floresta Atlântica e dois lagos naturais conhecidos por Lagoa Grande E Lagoa Vermelha, onde foram coletados três testemunhos sedimentares. Análises químicas (C, N, mineralogia), isotópicas (12C, 13C e 14C) e biológicas (palinologia) foram usadas nesse estudo para entender a história da paleovegetação da região durante o Pleistoceno tardio e o Holoceno, assim como suas relações com as mudanças climáticas. Amostras de solo foram coletadas a partir de trincheiras e tradagens em dez locais sob vegetação de floresta natural no PETAR e no PEI. Os dados isotópicos (&#948;13C) da matéria orgânica do solo em dois pontos do PETAR mostraram valores de &#948;13C mais enriquecidos ( -17,1%0 e -20,1%0) nas camadas mais profundas, indicando a presença de uma vegetação menos densa que a atual, com uma provável mistura de plantas C3, e C4, no período de ~30.000 a 16.000 anos AP, sugerindo a presença de um clima mais seco. De ~16.000 anos AP até o presente um empobrecimento isotópico significativo (até -28,3 %0) foi observado em todos os locais, indicativo de expansão da floresta, provavelmente associada à presença de um clima mais úmido que no período anterior. Os dados isotópicos (&#948;13C) dos solos de PEI indicam a presença de vegetação de floresta desde ~14.000 anos AP, exceto em um local (SAI) onde valores de &#948;13C mais enriquecidos (-21,8 %0) foram observados, relacionados provavelmente à mistura de plantas C3 e C4 e/ou à presença de uma vegetação de floresta menos densa em ~14.000 anos AP. A partir dos resultados da matéria orgânica sedimentar do testemunho da Lagoa Grande foi verificado que as condições ambientais foram relativamente estáveis durante os últimos 1000 anos, caracterizados pela presença de plantas C3, e fitoplâncton, sugerindo condições climáticas úmidas e que o lago provavelmente não se apresentou seco durante o último milênio. Condições ambientais para a Lagoa Vermelha também foram relativamente estáveis durante os últimos 4500 anos, caracterizadas pela presença significativa de plantas C3 na matéria orgânica sedimentar indicando condições climáticas úmidas. Mudanças na composição da vegetação foram registradas pela palinologia durante o período de ~1400 a 1100 anos AP, relacionadas a presença de um provável clima frio que o atual. / The study sites are in the PETAR - Parque Estadual Turístico do Alto Ribeira and PEI - Parque Estadual Intervales, in the southeastern region of Brazil. The area is characterized by the presence of the native vegetation of Atlantic forest and two natural lakes called LAgoa Grande and Lagoa Vermelha, where three sediment cores were collected. Chemical (C, N and mineralogy), isotope (12C, 13C and 14C), and biological (pollen analyses) tools were used in the study to understand the palaeovegetation history of the region during the late Pleistocene and Holocene and its relation to climate changes. Soils samples were collected from trenches and by drilling at five locations under natural forest vegetation in the PETAR and PEI study sites.The isotope data (&#948;13C)collected in soil at two locations in the PETAR area showed much more enriched &#948;13C values ( -17,1%0 and -20,1%0)in the deeper horizons, indicating the presence of a less dense vegetation than the present modern day, with a probable mixture of C3 and C4 plants, in the period of ~30.000 to ~16.000 years BP. This pattern suggested the presence of a drier climate. From ~16.000 years BP to the present, a significant isotopic depletion (up to -28,3 %0)was observed in all sites indicating an expansion of the forest, probable associated to the presence of a more humid climate than the previous period. The isotope results (&#948;13C) collected at the PEI soils indicated the presence of forest vegetation since ~14.000 years BP, except in one location (SAI), where more enriched &#948;13C values (-21,8 %0) were observed probable related to mixture of C3 e C4 plants, and/or a presence of a less dense forest vegetation around ~14.000 years BP. From the results of the sediment organic matter compositions of LAgoa Grande, it was verified that the environmental conditions were relatively stable during the last 1000 years, characterized by the presence of C3 plants and phytoplankton, suggesting humid climaticconditions and the lake probable wasn't dry during the last millennium. Environmental conditions for the Lagoa Vermelha were also relatively stable during the last 4500 years, characterized by the significant presence of C3 plants in the sediment organic matter indicating humid climatic conditions. The changes in vegetation composition recorded by palynology during the period of ~1400 to 1100 years BP can be related to existence of a probable colder climate than today.

Os locais de estudo estão situados no PETAR – Parque Estadual Turístico do Alto Ribeira e PEI – Parque Estadual Intervales, na região do sudeste do Brasil. A área é caracterizada pela presença de vegetação nativa de Floresta Atlântica e dois lagos naturais conhecidos por Lagoa Grande E Lagoa Vermelha, onde foram coletados três testemunhos sedimentares. Análises químicas (C, N, mineralogia), isotópicas (12C, 13C e 14C) e biológicas (palinologia) foram usadas nesse estudo para entender a história da paleovegetação da região durante o Pleistoceno tardio e o Holoceno, assim como suas relações com as mudanças climáticas. Amostras de solo foram coletadas a partir de trincheiras e tradagens em dez locais sob vegetação de floresta natural no PETAR e no PEI. Os dados isotópicos (&#948;13C) da matéria orgânica do solo em dois pontos do PETAR mostraram valores de &#948;13C mais enriquecidos ( -17,1%0 e -20,1%0) nas camadas mais profundas, indicando a presença de uma vegetação menos densa que a atual, com uma provável mistura de plantas C3, e C4, no período de ~30.000 a 16.000 anos AP, sugerindo a presença de um clima mais seco. De ~16.000 anos AP até o presente um empobrecimento isotópico significativo (até -28,3 %0) foi observado em todos os locais, indicativo de expansão da floresta, provavelmente associada à presença de um clima mais úmido que no período anterior. Os dados isotópicos (&#948;13C) dos solos de PEI indicam a presença de vegetação de floresta desde ~14.000 anos AP, exceto em um local (SAI) onde valores de &#948;13C mais enriquecidos (-21,8 %0) foram observados, relacionados provavelmente à mistura de plantas C3 e C4 e/ou à presença de uma vegetação de floresta menos densa em ~14.000 anos AP. A partir dos resultados da matéria orgânica sedimentar do testemunho da Lagoa Grande foi verificado que as condições ambientais foram relativamente estáveis durante os últimos 1000 anos, caracterizados pela presença de plantas C3, e fitoplâncton, sugerindo condições climáticas úmidas e que o lago provavelmente não se apresentou seco durante o último milênio. Condições ambientais para a Lagoa Vermelha também foram relativamente estáveis durante os últimos 4500 anos, caracterizadas pela presença significativa de plantas C3 na matéria orgânica sedimentar indicando condições climáticas úmidas. Mudanças na composição da vegetação foram registradas pela palinologia durante o período de ~1400 a 1100 anos AP, relacionadas a presença de um provável clima frio que o atual. / The study sites are in the PETAR - Parque Estadual Turístico do Alto Ribeira and PEI - Parque Estadual Intervales, in the southeastern region of Brazil. The area is characterized by the presence of the native vegetation of Atlantic forest and two natural lakes called LAgoa Grande and Lagoa Vermelha, where three sediment cores were collected. Chemical (C, N and mineralogy), isotope (12C, 13C and 14C), and biological (pollen analyses) tools were used in the study to understand the palaeovegetation history of the region during the late Pleistocene and Holocene and its relation to climate changes. Soils samples were collected from trenches and by drilling at five locations under natural forest vegetation in the PETAR and PEI study sites.The isotope data (&#948;13C)collected in soil at two locations in the PETAR area showed much more enriched &#948;13C values ( -17,1%0 and -20,1%0)in the deeper horizons, indicating the presence of a less dense vegetation than the present modern day, with a probable mixture of C3 and C4 plants, in the period of ~30.000 to ~16.000 years BP. This pattern suggested the presence of a drier climate. From ~16.000 years BP to the present, a significant isotopic depletion (up to -28,3 %0)was observed in all sites indicating an expansion of the forest, probable associated to the presence of a more humid climate than the previous period. The isotope results (&#948;13C) collected at the PEI soils indicated the presence of forest vegetation since ~14.000 years BP, except in one location (SAI), where more enriched &#948;13C values (-21,8 %0) were observed probable related to mixture of C3 e C4 plants, and/or a presence of a less dense forest vegetation around ~14.000 years BP. From the results of the sediment organic matter compositions of LAgoa Grande, it was verified that the environmental conditions were relatively stable during the last 1000 years, characterized by the presence of C3 plants and phytoplankton, suggesting humid climaticconditions and the lake probable wasn't dry during the last millennium. Environmental conditions for the Lagoa Vermelha were also relatively stable during the last 4500 years, characterized by the significant presence of C3 plants in the sediment organic matter indicating humid climatic conditions. The changes in vegetation composition recorded by palynology during the period of ~1400 to 1100 years BP can be related to existence of a probable colder climate than today.

The discovery of antibiotics is considered as one of the most significant scientific achievements of the 20th century – lives of millions of people and animals have been saved. Thenceforth, substantial amounts of administered antibiotics and their metabo-lites have been excreted into waste stream via urine and faeces. In this dissertation, primary focus is the qualitative balance of 14 antibiotics and one metabolite in urban water management and in urban waters, respectively. In particular, antibiotics pre-scribed to human beings are drained in the urban sewer system and finally enter the environment: (i) Continuously via the effluent of the wastewater treatment plant after a partially effective removal or degradation or (ii) Intermittent via combined sewer overflow structures due to capacity limitations of the urban drainage system. The fate and the potential effects and risks of these substances on ecosystems and hu-man health are of major concern – their direct toxic effect to all trophic levels as well as the global spread of antibiotic resistance genes are challenging. Hence, an assessment of microbial community activity due to antibiotic exposure is presented. In particular, systematic work has been carried out to study the presence and character-istics of 14 antibiotics in urban waters. In detail, investigations were conducted to gain scientific knowledge with respect to adsorption, desorption, abiotic, biotic and photolyt-ic degradation as well as activity-inhibition of microorganism communities in sewage and of natural freshwater biofilm communities, respectively, due to inevitable urban drainage overflows. In order to provide information to assist potential management strategies, which miti-gate surface water pollution and minimize the adverse impacts of antibiotics on activity of microorganism communities, the following specific topics were addressed: ⑴ The occurrence of 14 antibiotics and one metabolite were determined in sewag-es at three sampling sites in the city of Dresden, Germany. ⑵ The adsorption affinities of 14 antibiotics and one metabolite to size dependent sewer sediments were determined in experimental investigations, three sam-pling campaigns and subsequently an antibiotic-specific adsorption coefficient, normalized to organic content, was quantified. ⑶ The desorption affinity and -dynamics of 14 antibiotics and one metabolite were quantified in size dependent sewer sediments in experimental investigation and with statistical analysis. ⑷ The abiotic, biotic and photolytic degradation affinity of 14 antibiotics and one metabolite were quantified based on batch experiments with three different sewages at 7°C and 22°C, with artificial irradiation and different dilution ratios of the sewage at 30°C and subsequently a model framework decrypted ranges of abiotic, biotic and photolytic degradation coefficients. ⑸ The occurrence of three antibiotics, namely ciprofloxacin, clarithromycin and doxycycline was determined in sewage sampled during dry weather conditions in a small catchment of Dresden, which spills intermittently combined sewage (a mixture of sewage and storm water) to an adjacent brook in the case of capacity limitations of the urban drainage system during periods of intense rainfall and subsequently the three antibiotics were determined in the adjacent brook water. ⑹ Then, the activity-inhibition of microorganism community in sewage of this small catchment was quantified due to an exposition with three different antibiotics and three different antibiotic concentrations. ⑺ Last but not least, the activity-inhibition of natural freshwater biofilm communities in the adjacent brook was quantified via exposure to three antibiotics, which were individually dosed in three different concentrations, and also in mixture. ⑻ Finally, a two-dimensional hierarchical cluster analysis with dendrogram and heat map based on before mentioned activity inhibition of natural freshwater biofilm communities were conducted to identify hot spots of antibiotic tolerant and resistant bacterial subpopulations due to inevitable urban drainage system overflows.:List of Figures IV List of Tables VIII Symbols and Abbreviations XII List of Publications on the Ph.D. topic XIX 1 General Introduction 2 1.1 Background 2 1.2 Aims and Objectives 3 1.3 Innovation and Contribution to the Knowledge 4 1.4 Outline of this Thesis 4 1.5 References 6 2 Adsorption and Desorption Affinity of 14 Antibiotics and One Metabolite for particulate components in urban drainage systems 10 2.1 Introduction 11 2.2 Materials and Methods 12 2.2.1 Study area 12 2.2.2 Sewer sediment and sewage sample collection 12 2.2.3 Sediment fractionation 13 2.2.4 Antibiotic determination in sewage and sediment 13 2.3 Results and Discussion 18 2.3.1 Antibiotics in composite sewage samples 18 2.3.2 Antibiotics adsorbed to sewer sediments 19 2.3.3 Organic-bound antibiotic load as a linear function of liquid concentration 20 2.3.4 Adsorption dynamics and adsorption coefficient determined by bath experiments 20 2.3.5 Mineral composition of sewer sediment SED#1B 23 2.3.6 Initial characteristics of sediment SED#1B 23 2.3.7 Desorption dynamics and desorption coefficient of SED#1B 24 2.4 Conclusions 25 2.5 References 26 3 Abiotic, Biotic and Photolytic Degradation Coefficients of 14 Antibiotics and One Metabolite 32 3.1 Introduction 34 3.2 Materials and Methods 35 3.2.1 Study area and sample collection 35 3.2.2 Experimental set up 35 3.2.3 Modelling framework 38 3.2.4 Procedure of model calibration 40 3.3 Results and Discussion 43 3.3.1 Primary metabolic parameter 43 3.3.2 Secondary metabolic parameter 44 3.4 Conclusions 50 3.5 References 50 4 Activity-Inhibition of Microorganisms due to an Exposition with different Antibiotics and Concentrations 56 4.1 Assessing Antibiotic Resistance of Microorganisms in Sanitary Sewage 56 4.1.1 Introduction 57 4.1.2 Material and Methods 58 4.1.2.1 Sampling Site and Antibiotic Agents 58 4.1.2.2 Analyzing Antibiotics 60 4.1.2.3 Respiration Rate 60 4.1.3 Results and Discussion 60 4.1.3.1 Concentration Range of Antibiotics and Typical Sewage Parameters 60 4.1.3.2 Oxygen Uptake Rate 62 4.1.4 Summary and Conclusions 63 4.1.5 References 64 4.2 Hot Spots of Antibiotic Tolerant and Resistant Bacterial Subpopulations in Natural Freshwater Biofilm Communities due to Inevitable Urban Drainage System Overflows 66 4.2.1 Introduction 68 4.2.2 Material and Methods 69 4.2.3 Results and Discussion 72 4.2.4 Conclusions 76 4.2.5 References 76 5 Summery and General Coclusions 82 5.1 Adsorption and Desorption Affinity 82 5.2 Abiotic, Biotic and Photolytic Degradation 83 5.3 Activity-Inhibition of Microorganism Communities due to Antibiotic Exposure 84 5.4 Enhancement of the Stockholm County Council (2014) assessment of antibiotics 84 5.5 References 87 6 Proposed Directions of Future Research 90 7 Appendixes 94 7.1 Chapters 94 7.2 Figures 95 7.3 Tables 115 7.4 References 139