Thesis (MTech (Chemistry))--Cape Peninsula University of Technology, 2017. / Pharmaceuticals have found extensive application in human health management. They are released into the environment through urine, excreta and inappropriate disposal methods. Residues of pharmaceutical products have been reported to show toxic consequences in some freshwater and marine organisms. Antibiotics are one of the most important groups of common human pharmaceuticals widely in use as prescribed and non-prescribed drugs. Antibiotics and their metabolites have been quantitated in water and found in trace levels. But even at such low concentrations they can maintain high biological activities with potential adverse effects on humans and animals. Unfortunately, many pharmaceutical compounds are resistant to breakdown in the environment, hence they have tendency for environmental magnification, since they are designed to be biologically active. Therefore, there is need to evaluate their environmental levels and their possible abatement methods using simple, cheap and low cost techniques, in order to avert their potential toxic consequences. In this research, a cost effective, robust, selective and rugged method for the analysis of antibiotics in water samples using liquid chromatography was developed, and used for monitoring levels of the selected antibiotics in Diep River. Also, an effective remediation procedure for these contaminants in water was developed using activated carbon produced from grape slurry waste.

Guan, Lijie. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 139-161). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Table of contents --- p.vii / List of Figures --- p.X / List of Tables --- p.xiii / Abbreviations --- p.xiv / Chapter 1. --- INTRODUCTION --- p.1 / Chapter 1.1 --- Source and Fate of Pharmaceuticals in the Environment --- p.1 / Chapter 1.2 --- Occurrence of Pharmaceuticals --- p.2 / Chapter 1.2.1 --- Wastewater --- p.2 / Chapter 1.2.2 --- Sewage sludge and soil --- p.5 / Chapter 1.2.3 --- "Surface water, ground water and seawater" --- p.6 / Chapter 1.2.4 --- Drinking water --- p.9 / Chapter 1.3 --- Effects on the Environment --- p.11 / Chapter 1.3.1 --- Antibiotic resistance --- p.11 / Chapter 1.3.2 --- Ecotoxicity on the aquatic organisms --- p.14 / Chapter 1.4 --- Removal in the Environment --- p.19 / Chapter 1.4.1 --- Adsorption --- p.20 / Chapter 1.4.2 --- Photodegradation and hydrolysis --- p.22 / Chapter 1.4.3 --- Biodegradation --- p.23 / Chapter 1.5 --- Analytical Method of Pharmaceuticals in Environmental Samples --- p.25 / Chapter 1.5.1 --- Solid-phase extraction --- p.25 / Chapter 1.5.2 --- Liquid chromatography mass spectrometry --- p.30 / Chapter 1.6 --- Objectives and Outline of Thesis --- p.33 / Chapter 2 --- OCCURRENCE AND FATE OF SELECTED PHARMCEUTICALS IN STPS --- p.35 / Chapter 2.1 --- Introduction --- p.35 / Chapter 2.2 --- Materials and Methods --- p.36 / Chapter 2.2.1 --- Choice of pharmaceuticals for study --- p.36 / Chapter 2.2.2 --- Description of sewage treatment plants (STPs) --- p.41 / Chapter 2.2.3 --- Experimental approach --- p.49 / Chapter 2.3 --- Results and Discussion --- p.55 / Chapter 2.3.1 --- Occurrence of azithromycin --- p.55 / Chapter 2.3.2 --- Fate of azithromycin --- p.59 / Chapter 2.3.3 --- Occurrence of erythromycin --- p.63 / Chapter 2.3.4 --- Fate of erythromycin --- p.67 / Chapter 2.3.5 --- Occurrence of roxithromycin --- p.70 / Chapter 2.3.6 --- Fate of roxithromycin --- p.74 / Chapter 2.3.7 --- Occurrence of atenolol --- p.75 / Chapter 2.3.8 --- Fate of atenolol --- p.79 / Chapter 2.3.9 --- Occurrence of simvastatin --- p.81 / Chapter 2.3.10 --- Fate of simvastatin --- p.84 / Chapter 2.3.11 --- Fate of pharmaceuticals during different treatment process --- p.85 / Chapter 2.3.12 --- Contribution of industrial (manufacturing) plants to STPs --- p.87 / Chapter 2.3.13 --- Seasonal variation --- p.87 / Chapter 2.4 --- Summary --- p.90 / Chapter 3 --- EFFECTS OF PHARMACEUTICALS ON ACTIVATED SLUDGE BACTERIA --- p.91 / Chapter 3.1 --- Introduction --- p.91 / Chapter 3.2 --- Materials and Methods --- p.92 / Chapter 3.2.1 --- Growth inhibition test --- p.92 / Chapter 3.2.2 --- Nitrification inhibition test --- p.94 / Chapter 3.3 --- Results and Discussion --- p.96 / Chapter 3.3.1 --- Growth inhibition of activated sludge bacteria --- p.96 / Chapter 3.3.2 --- Inhibition of nitrifying bacteria --- p.102 / Chapter 4 --- BIODEGRADATION PATHWAYS OF FOUR PHARMACEUTICALS --- p.106 / Chapter 4.1 --- Introduction --- p.106 / Chapter 4.2 --- Materials and Methods --- p.107 / Chapter 4.2.1 --- Test procedures --- p.107 / Chapter 4.2.2 --- Detection method --- p.108 / Chapter 4.3 --- Results and Discussion --- p.109 / Chapter 4.3.1 --- Degradation of atenolol --- p.109 / Chapter 4.3.2 --- Degradation of azithromycin --- p.117 / Chapter 4.3.3 --- Degradation of erythromycin --- p.129 / Chapter 4.3.4 --- Degradation of roxithromycin --- p.133 / Chapter 4.4 --- Summary --- p.134 / Chapter 5 --- GENERAL CONCLUSIONS --- p.136 / References --- p.139

Thesis (Ph.D.)--Civil and Environmental Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Huang, Ching-Hua; Committee Member: Kim, Jaehong; Committee Member: Pavlostathis, Spyros; Committee Member: Stack, Andrew; Committee Member: Yiacoumi, Sotira

The primary objective of this work was to determine the tissue-specific bioconcentration factors (BCFs) of the selected pharmaceuticals: norethindrone (NET), ibuprofen (IBU), verapamil (VER), clozapine (CLZ) and fenofibrate (FFB) in two freshwater fishes: fathead minnow and channel catfish. BCF tests on fathead followed the standard OECD 42-day test while a 14-day abridged test design was used in catfish exposures. Additional objectives included a) comparing the measured BCFs to the US EPA's BCFWIN model predicted values, b) comparing the BCF results from the standard and reduced tests, and c) prediction of chronic risk of the pharmaceuticals in fish using the human therapeutic plasma concentrations. Each test included uptake and depuration phases to measure tissue-specific kinetic BCFs. The results indicated that all the pharmaceuticals, except IBU, have the potential for accumulation in fish. Estimated BCFs for NET, VER and FFB may not be significant in view of the current regulatory trigger level (BCF ≥ 2000); however, CLZ's BCF in the liver had approached the criterion level. Significant differences were noticed in the tissue-specific uptake levels of the pharmaceuticals with the following general trend: (liver/kidney) > (gill/brain) > (heart/muscle) > plasma. IBU uptake was highest in the plasma. When compared to the measured BCFs, predicted values for NET, IBU, VER and FFB were slightly overestimated but did not differ largely. However, the measured BCF of CLZ in the liver was approximately two-orders of magnitude higher than the predicted level. The tissue-BCFs for the two species were not widely different indicating the potential usefulness of the reduced BCF test. Comparison of fish and human plasma levels indicated that NET, CLZ and VER have the potential to cause chronic effects in fish.

Recent studies have demonstrated the omnipresence of antibacterial agents in the aquatic environment due to high usage and widespread applications of these compounds in medicine and agriculture, raising concerns over proliferation of antibiotic-resistant bacteria and other adverse health effects. Tetracyclines (TCs) are among the most widely used antibiotics and their fate and transformation in the soil-water environment are not yet well understood. Based on TCs' strong tendency to interact with metals, their environmental fate and transport are expected to be greatly influenced by metal species commonly present in waters and soils and thus the focus of this study. The study results show that TCs are highly susceptible to oxidative transformation mediated by dissolved Mn(II) and Cu(II) ions and manganese dioxide under environmentally relevant conditions. The oxidative transformation can occur via different TC structural moieties and reaction pathways when different metal species are involved, leading to complicated product formation patterns. It was also found that Al oxide surfaces can promote the acid-catalyzed isomeration and dehydration of TCs. To better evaluate the surface reactions of Mn oxide with TCs and other compounds, a new kinetic model was successfully developed to describe the complex reaction kinetics based on the experimental results with TCs and three other classes of antibacterial agents. Overall, this work significantly advances the fundamental understanding of the reaction mechanisms of TC compounds and provides the knowledge basis for better risk assessment of these compounds in the environment.

There is relatively little known about the fate of human pharmaceuticals once they are released into the aquatic environment and what adverse impacts these compounds have on exposed aquatic organisms. Both of these factors are essential in defining the potential risk pharmaceuticals pose in the aquatic environment. For this project up to 14 human therapeutic agents were selected as representative compounds to assess both their fate and effects within model aquatic systems. Considering sediments often serve as a repository for aquatic contaminants, the interaction of the selected pharmaceuticals with sediment was assessed. The sorption of the selected pharmaceuticals was found to be highly variable. Furthermore, the solution pH and ionic strength, due to Ca2+, were found to exert a large degree of influence on the extent of sorption observed. These solution parameters, among others, may therefore make it difficult to predict the fate of pharmaceuticals, in terms of their association with sediments, using standardised assessment methods alone. There is an extensive pool of knowledge on pharmaceuticals, in terms of their pharmacological profile, so their distribution within the human body (using the volume of distribution or VD) was compared with their distribution within a sediment / water system (using the partition coefficient or Kd). The correlation between the VD and Kd indicated this relationship provided a reasonable basis for estimating the distribution of drugs within the test sediment / water systems. This finding suggests that further exploration of the use of pharmacological data in understanding the potential fate of pharmaceuticals in aquatic systems is warranted. The extent of the pharmaceuticals respective desorption values was also found to be highly variable within a standard test system. Further analysis on the desorption of carbamazepine, an anti-epileptic drug, was undertaken using an isotopic dilution technique. Observations from the isotopic dilution study indicated that both contact time with sediment and the quality of organic carbon could play an important role in the potential for sediments to irreversibly sorb carbamazepine present in aquatic systems. The desorption hysteresis observed for the other pharmaceuticals also indicates considerable effort is still required to address the issue of whether sediments can be a means of reducing exposure of pharmaceuticals to aquatic organisms (a “sink”) or a means of increasing exposure to sediment-dependent organisms (a “source”). The necessity for further work on investigating the role that sorption with sediments may play in the fate and effects of human pharmaceuticals was highlighted by a series of ecotoxicological assays in both sediment and solution-only systems. Sediment-dwelling freshwater midges, Chironomus tepperi, were exposed to carbamazepine in both short- and long-term assays. Wet weight was found to be significantly reduced during short-term assays, while the development of C. tepperi larvae was found to be significantly inhibited when exposed to spiked sediment, over a longer exposure period. For these assays, the aqueous phase may have been a more important route of exposure of carbamazepine for the midges. This study has indicated that sediments are likely to play an important role in the fate of pharmaceuticals and, subsequently, their effects. However, considerably more effort is required to assess the role sediments have and how this knowledge can be linked with current regulatory ecological risk assessments. / http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1298389 / Thesis (Ph.D.) -- University of Adelaide, School of Earth and Environmental Sciences, 2007

There is relatively little known about the fate of human pharmaceuticals once they are released into the aquatic environment and what adverse impacts these compounds have on exposed aquatic organisms. Both of these factors are essential in defining the potential risk pharmaceuticals pose in the aquatic environment. For this project up to 14 human therapeutic agents were selected as representative compounds to assess both their fate and effects within model aquatic systems. Considering sediments often serve as a repository for aquatic contaminants, the interaction of the selected pharmaceuticals with sediment was assessed. The sorption of the selected pharmaceuticals was found to be highly variable. Furthermore, the solution pH and ionic strength, due to Ca2+, were found to exert a large degree of influence on the extent of sorption observed. These solution parameters, among others, may therefore make it difficult to predict the fate of pharmaceuticals, in terms of their association with sediments, using standardised assessment methods alone. There is an extensive pool of knowledge on pharmaceuticals, in terms of their pharmacological profile, so their distribution within the human body (using the volume of distribution or VD) was compared with their distribution within a sediment / water system (using the partition coefficient or Kd). The correlation between the VD and Kd indicated this relationship provided a reasonable basis for estimating the distribution of drugs within the test sediment / water systems. This finding suggests that further exploration of the use of pharmacological data in understanding the potential fate of pharmaceuticals in aquatic systems is warranted. The extent of the pharmaceuticals respective desorption values was also found to be highly variable within a standard test system. Further analysis on the desorption of carbamazepine, an anti-epileptic drug, was undertaken using an isotopic dilution technique. Observations from the isotopic dilution study indicated that both contact time with sediment and the quality of organic carbon could play an important role in the potential for sediments to irreversibly sorb carbamazepine present in aquatic systems. The desorption hysteresis observed for the other pharmaceuticals also indicates considerable effort is still required to address the issue of whether sediments can be a means of reducing exposure of pharmaceuticals to aquatic organisms (a “sink”) or a means of increasing exposure to sediment-dependent organisms (a “source”). The necessity for further work on investigating the role that sorption with sediments may play in the fate and effects of human pharmaceuticals was highlighted by a series of ecotoxicological assays in both sediment and solution-only systems. Sediment-dwelling freshwater midges, Chironomus tepperi, were exposed to carbamazepine in both short- and long-term assays. Wet weight was found to be significantly reduced during short-term assays, while the development of C. tepperi larvae was found to be significantly inhibited when exposed to spiked sediment, over a longer exposure period. For these assays, the aqueous phase may have been a more important route of exposure of carbamazepine for the midges. This study has indicated that sediments are likely to play an important role in the fate of pharmaceuticals and, subsequently, their effects. However, considerably more effort is required to assess the role sediments have and how this knowledge can be linked with current regulatory ecological risk assessments. / http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1298389 / Thesis (Ph.D.) -- University of Adelaide, School of Earth and Environmental Sciences, 2007

There is relatively little known about the fate of human pharmaceuticals once they are released into the aquatic environment and what adverse impacts these compounds have on exposed aquatic organisms. Both of these factors are essential in defining the potential risk pharmaceuticals pose in the aquatic environment. For this project up to 14 human therapeutic agents were selected as representative compounds to assess both their fate and effects within model aquatic systems. Considering sediments often serve as a repository for aquatic contaminants, the interaction of the selected pharmaceuticals with sediment was assessed. The sorption of the selected pharmaceuticals was found to be highly variable. Furthermore, the solution pH and ionic strength, due to Ca2+, were found to exert a large degree of influence on the extent of sorption observed. These solution parameters, among others, may therefore make it difficult to predict the fate of pharmaceuticals, in terms of their association with sediments, using standardised assessment methods alone. There is an extensive pool of knowledge on pharmaceuticals, in terms of their pharmacological profile, so their distribution within the human body (using the volume of distribution or VD) was compared with their distribution within a sediment / water system (using the partition coefficient or Kd). The correlation between the VD and Kd indicated this relationship provided a reasonable basis for estimating the distribution of drugs within the test sediment / water systems. This finding suggests that further exploration of the use of pharmacological data in understanding the potential fate of pharmaceuticals in aquatic systems is warranted. The extent of the pharmaceuticals respective desorption values was also found to be highly variable within a standard test system. Further analysis on the desorption of carbamazepine, an anti-epileptic drug, was undertaken using an isotopic dilution technique. Observations from the isotopic dilution study indicated that both contact time with sediment and the quality of organic carbon could play an important role in the potential for sediments to irreversibly sorb carbamazepine present in aquatic systems. The desorption hysteresis observed for the other pharmaceuticals also indicates considerable effort is still required to address the issue of whether sediments can be a means of reducing exposure of pharmaceuticals to aquatic organisms (a “sink”) or a means of increasing exposure to sediment-dependent organisms (a “source”). The necessity for further work on investigating the role that sorption with sediments may play in the fate and effects of human pharmaceuticals was highlighted by a series of ecotoxicological assays in both sediment and solution-only systems. Sediment-dwelling freshwater midges, Chironomus tepperi, were exposed to carbamazepine in both short- and long-term assays. Wet weight was found to be significantly reduced during short-term assays, while the development of C. tepperi larvae was found to be significantly inhibited when exposed to spiked sediment, over a longer exposure period. For these assays, the aqueous phase may have been a more important route of exposure of carbamazepine for the midges. This study has indicated that sediments are likely to play an important role in the fate of pharmaceuticals and, subsequently, their effects. However, considerably more effort is required to assess the role sediments have and how this knowledge can be linked with current regulatory ecological risk assessments. / http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1298389 / Thesis (Ph.D.) -- University of Adelaide, School of Earth and Environmental Sciences, 2007

Municipal treated wastewater entering rivers contain biologically active pharmaceuticals capable of inducing effects in aquatic life. Phytoremediation of three of these pharmaceuticals and an herbicide was investigated using Sandbar willow (Salix exigua) and Arabidopsis thaliana. Both plants were effective at removing compounds from solution, with removal of 86% of the synthetic estrogen, 17α-ethynylestradiol, 65% of the anti-hypertensive, diltiazem, 60% of the anti-convulsant, diazepam (Valium®), and 51% of the herbicide atrazine, in 24 hours. Distribution of compounds within roots and shoots, in soluble and bound forms, differed among compounds. Uptake and distribution of pharmaceuticals within the study plants confirmed pharmaceutical behaviour can be predicted based on a physiochemical property, their octanol-water partitioning coefficients. An effective method for detection of 17α-ethynylestradiol within surface water using solid phase extraction and gas chromatography-mass spectrometry was developed. Previously unreported breakdown of 17α-ethynylestradiol into another common estrogen, estrone, during preparative steps and gas chromatography was resolved. / xv, 216 leaves ; 29 cm.

Triclosan (TCS) and triclocarban (TCC) are antimicrobials found in U.S. surface waters. This dissertation assessed the effects of TCS and TCC on early development and investigated their potential to bioaccumulate using Xenopus laevis as a model. The effects of TCS on metamorphosis were also investigated. For 0-week tadpoles, LC50 values for TCS and TCC were 0.87 mg/L and 4.22 mg/L, respectively, and both compounds caused a significant stunting of growth. For 4-week tadpoles, the LC50 values for TCS and TCC were 0.22 mg/L and 0.066 mg/L; and for 8-week tadpoles, the LC50 values were 0.46 mg/L and 0.13 mg/L. Both compounds accumulated in Xenopus. For TCS, wet weight bioaccumulation factors (BAFs) for 0-, 4- and 8-week old tadpoles were 23.6x, 1350x and 143x, respectively. Lipid weight BAFs were 83.5x, 19792x and 8548x. For TCC, wet weight BAFs for 0-, 4- and 8-week old tadpoles were 23.4x, 1156x and 1310x. Lipid weight BAFs were 101x, 8639x and 20942x. For the time-to-metamorphosis study, TCS showed an increase in weight and snout-vent length in all treatments. Exposed tadpoles metamorphosed approximately 10 days sooner than control tadpoles. For the hind limb study, although there was no difference in weight, snout-vent length, or hind limb length, the highest treatment was more developed compared to the control. There were no differences in tail resorption rates between the treatments and controls. At relevant concentrations, neither TCS nor TCC were lethal to Xenopus prior to metamorphosis. Exposure to relatively high doses of both compounds resulted in stunted growth, which would most likely not be evident at lower concentrations. TCS and TCC accumulated in Xenopus, indicating that the compound has the potential to bioaccumulate through trophic levels. Although TCS may increase the rate of metamorphosis in terms of developmental stage, it did not disrupt thyroid function and metamorphosis in regards to limb development and tail resorption.