The Walter Reed Institute of Army Research developed the antimalarial drug mefloquine then collaborated with Hoffman-La Roche to produce the drug under its brand name "Lariam," after Food and Drug Administration (FDA) approved licensure in 1989. For over twenty years, the Army used this pill as its "drug of choice" for soldiers deployed to endemic regions until 2009, and in 2013 the Food and Drug Administration warned that the drug's neurotoxic effects could be lasting, if not permanent. The sociopolitical exigence of developing a new biochemical antimalarial drug rushed the development and licensure processes, and the modern craving for certainty in the New Drug Application (NDA) process led to a biomedical disaster-- economically, politically, and interpersonally. In this paper, I present the factors contributing to uncertainty and heightened exigence in the development of what I call "mef-Lariam" in a nod to Latourian hybridization. By tracing the history of the drug's development process, I argue that definitional stasis around the NDA genre's terms safe and effective undergird a dangerous ontological orientation to medicine that privileges an ethic of expediency. Finally, I argue that actor-network theory can help medical rhetors apply a more ethical, multiple view of medical research that could prevent the future licensure of toxic pharmaceuticals.

Abstract: Pharmaceuticals and their metabolites, collectively known as pharmaceutically active compounds (PhACs), have been detected in surface water, groundwater, and drinking water, in a number of countries, since the mid-1990s. Pharmaceuticals can be used in human or veterinary medicine; human pharmaceuticals in the environment are the subject of this dissertation. Human pharmaceuticals enter the environment via wastewater treatment plants, after being consumed and excreted by humans, and through improper disposal, to toilets and garbage, among other routes of entry. Some PhACs have been found to have detrimental effects on aquatic organisms at low concentrations, such as the feminization of fish after exposure to low levels of 17-ethinylestradiol, the active ingredient in the birth control pill. Others are suspected of having effects on non-target species, but the impacts of long-term exposure to mixtures of PhACs generally remain poorly understood. Nevertheless, the precautionary principle suggests that management action to mitigate the environmental impacts of PhACs should be considered and possibly implemented. The purpose of this dissertation is to provide an analysis of precautionary management strategies to mitigate the environment impacts of human PhACs. Four underlying objectives are set. The first is to review the extant scientific understanding of human PhACs in the environment, so that this knowledge can be applied to the analysis of management strategies. The sources, transport, fate, and occurrence of PhACs are discussed, and several classes of PhACs of particular concern are highlighted. The effects of PhACs on humans and aquatic organisms are explored, in addition to the gaps in scientific understanding of PhACs in aquatic environments. Finally, a rough ranking of priority PhACs is conducted; the PhACs of greatest concern are found to be carbamazepine, clofibric acid, ifosfamid, 17a-ethinylestradiol, oxytetracycline, ciprofloxacin, and diclofenac. The second objective is to investigate how planning and management principles and theories can be applied to the problem of PhACs in the environment. The precautionary principle and the theory of adaptive planning are identified as essential tools in this regard. The application of the precautionary principle and adaptive planning to pharmaceuticals in the environment are discussed, and a management framework is developed. The third objective is to determine how human PhACs in the environment can be managed at a local scale, using a case study in the Region of Waterloo. Pharmaceuticals released from two wastewater treatment plans are found entering the local environment at concentrations similar to those in other cities internationally. Social surveys indicate that residents desire management action to prevent environmental contamination by pharmaceuticals, but at a limited cost. The surveys also indicate that many residents dispose of pharmaceuticals improperly; education to encourage proper drug disposal is therefore recommended as one of several management strategies. The other two recommended management strategies target the wastewater treatment plants. In Foxboro, where the wastewater treatment plant is functioning less than optimally, optimization without technological upgrades is suggested. In Kitchener, where the plant is functioning within ministerial guidelines, ozonation is suggested as a means of improving pharmaceutical removal without exceeding residents’ willingness to pay. The fourth and final objective is to assess how human pharmaceuticals can be managed at a broad scale, such as at the national scale. Stakeholder interviews are conducted with the purpose of gaining a deeper understanding of possible management strategies. A policy analysis is conducted to determine which combinations of management strategies are likely to optimally address the problem of PhACs in the environment, and some policy packages are recommended for implementation by governments – in particular, multiple levels of government in Canada. This dissertation is among the first research efforts to investigate the management of pharmaceuticals in the environment. Few efforts to date have combined natural scientific research, social scientific research, and an understanding of planning and management theories, to explore policy and management options for this issue. It is hoped that this research will provide assistance to various governments grappling with pharmaceuticals in the environment. Furthermore, the research provides insight into how environmental problems surrounded by high levels of scientific uncertainty can be managed. The framework for precautionary decision making developed in this study can provide guidance to planners, managers and policy makers faced with the problem of uncertain environmental risk.

Over the last decade, endocrine disrupting compounds (EDCs) and pharmaceutically active compounds (PhACs) have been detected in drinking water at very low levels, mostly ng/L concentrations, suggesting that these compounds resisted removal through water treatment processes. Concerns have been raised regarding the effectiveness of common drinking water treatment technologies to remove these emerging contaminants. Adsorption processes were suggested to play an important role in the removal of PhACs and EDCs, based on the assumption that these compounds are similar to other conventional micropollutants such as pesticides in both physicochemical properties and concentration levels present in water. However, this remains to be demonstrated since the availability of adsorption data for PhACs and EDCs is extremely limited and their environmental concentrations are typically much lower than the ones for pesticides. The primary objective of this research was to evaluate in detail the removal of representative EDCs and PhACs at environmentally relevant concentrations by granular activated carbon (GAC) adsorption. In the first stage of this study, EDCs (15) were screened separately from the PhACs (86) with two different sets of assessment criteria due to the different nature and the availability of information for these two groups of compounds. As a result, 6 EDCs and 12 PhACs were selected for further evaluation. Subsequently, a multi-residue analytical method based on gas chromatography/mass spectrometry (GC/MS) was developed for the simultaneous determination of the selected PhACs and EDCs. Two key analytical steps - solid phase extraction and derivatization - were systematically optimized using full factorial design and a central composite design, respectively. The statistical experimental design in combination with the concept of the total desirability was demonstrated to be an effective tool for developing a multi-residue analytical method. The application of the developed method to Grand River water, a local raw water source, and finished drinking water from this source indicated that PhACs such as naproxen, carbamazepine, salicylic acid, ibuprofen, and gemfibrozil, and EDCs such as estrone (E1) and nonylphenol mono-ethoxy carboxylate (NP1EC) were the most common contaminants. Based on these results, the quality of the analytical data, and the physicochemical properties relevant to the adsorption on activated carbon, two PhACs (naproxen, carbamazepine) and one EDC (nonylphenol (NP)) were finally chosen for the adsorption studies. Adsorptions of the selected target compounds were evaluated on two types of activated carbon (coal-based Calgon Filtrasorb® 400 (F400) and coconut shell-based PICACTIF TE (PICA) by first investigating their isotherms at environmentally relevant concentrations (equilibrium liquid phase concentration ranging from 10 to 1000 ng/L). The single-solute isotherm data determined for both carbons showed that the relative adsorbabilities of the three target compounds were not in agreement with expectations based on their log Kow values. Overall, in this low concentration range, carbamazepine was most easily removed, and NP was least adsorbable. The adsorption of naproxen was negatively influenced by its dissociation in water. Comparison of single-solute isotherms on F400 carbon for the target compounds to those for other selected conventional micropollutants showed that naproxen and carbamazepine have generally comparable isotherms to 2-methylisoborneol (MIB) and geosmin. The isotherm tests in a post-sedimentation (PS) water from a full-scale plant demonstrated that the presence of background natural organic matter (NOM) significantly reduced the adsorption of all three target compounds, among which.NP was the least impacted compound. Based on the quantification of the direct competition using the ideal adsorbed solution theory (IAST) in combination with the equivalent background compound (EBC) approach, the minimum carbon usage rates (CURs) for removing 90% of the target compounds in PS water were calculated at two environmentally relevant concentrations (50 and 500 ng/L). This work confirmed that the percentage removal of the trace level target compound at a given carbon dosage was independent of the initial target compound concentration. Isotherm experiments were conducted for the target compound on GACs preloaded with PS water for various time intervals (up to 16 weeks) at the Mannheim Water Treatment Plant (Region of Waterloo, ON, Canada). The results indicated that the adsorption of all target compounds were subject to significant negative impacts from preloading of NOM, albeit to different extents. Among the three target compounds, reduction in adsorption capacity for naproxen was most severe, followed by carbamazepine and then NP. The three target compounds followed quite different patterns of decrease in adsorption capacity with increasing preloading time, thus revealing different competitive mechanisms at work for the different compounds. For naproxen, the change in heterogeneity of the carbons due to preloading suggests that some pre-adsorbed NOM could not be replaced by naproxen. However, both direct competitive and pore blockage mechanisms could successfully explain the adsorption performance of naproxen and carbamazepine. The removal of NP even at prolonged preloading times could be explained by absorption or partitioning in the NOM matrix on the surface of, or inside the carbons. The kinetic parameters for each target compound-virgin carbon pair were determined using the short fixed bed (SFB) approach based on the pore and surface diffusion model (PSDM). The SFB results and sensitivity analyses indicated that, under the very low influent concentration conditions, film diffusion (indexed as βL) exerts a much greater effect on breakthrough profiles than internal diffusion. The SFB tests on preloaded GACs showed that mass transport of all the target compounds decreased with increasing preloading time. Similar to the impact of preloading on adsorption capacity, naproxen was subject to the most deteriorative effect, followed by carbamazepine and then NP. In addition, potential mechanisms for the decay of the film diffusion coefficient with increased preloading time were discussed based on scanning electron microscope (SEM) images of virgin and preloaded GAC. Electrostatic interactions between the NOM/bio film formed on the preloaded carbon and dissociated naproxen may have contributed to the enhanced reduction in its film diffusion. Sensitivity analyses and subsequent calculations of the Biot numbers confirmed that film diffusion was also the predominant mechanism controlling the mass transport on preloaded carbon, in particular for naproxen. This suggests that the early breakthrough prediction of the target compounds at their environmentally relevant concentrations could be further simplified by only considering film diffusion and adsorptive capacity. Kinetic and isotherm parameters were used as input for modeling using time-variable PSDM. It was found that the varying trends for Freundlich KF and 1/n, and βL could be generally depicted by a corresponding empirical model. Pilot scale treatability tests were performed for the target compounds which subsequently validated the time-variable PSDM results thus demonstrating its effectiveness and robustness to model GAC adsorber performance for PhAC and EDC removal at environmentally relevant concentrations. The time-variable approach was further improved by adjusting for NOM surface loading differences between the preloading and the pilot columns, which successfully compensated for the prediction errors at the early phase. The validated NOM surface loading associated time variable PSDM was used to predict performances of hypothetical F400 and PICA full-scale adsorbers. Both adsorbers were expected to provide satisfactory performance in achieving 90% removals for the neutral target compounds (carbamazepine and NP). Naproxen was predicted to break through fast since both, capacity and kinetic parameters decay quickly due to carbon fouling by NOM and the physicochemical properties of this compound. Initial recommendations on the choice of adsorption process (GAC vs. PAC) for removing EDCs and PhACs can be made based on the comparison of carbon usage rates (CUR) which were calculated for a GAC adsorber using the validated improved PSDM and for PAC using the minimum applied dosages predicted by the IAST-EBC model.

Syftet var att beskriva vilka omvårdnadsproblem som kan uppstå i samband med polyfarmacihos äldre personer. Litteraturstudien gjordes med beskrivande design. Datainsamling viadatabaserna PubMed och Cinahl. Resultatet baserades på 12 kvantitativa artiklar. Resultatetvisade att det fanns samband mellan polyfarmaci och flera specifika omvårdnadsproblembland äldre personer. Det omvårdnadsproblem som förekom mest bland de artiklar somstuderades var fall och frakturer. Det framkom att antalet använda läkemedel kundeidentifieras som en riskfaktor för fall och fraktur, men även att läkemedelstyp kunde påverka.Resultatet visade också att yrsel och balanssvårigheter kunde ha ett samband medpolyfarmaci. Andra omvårdnadsproblem som kunde kopplas samman med polyfarmaci varförsämrad nutritionsstatus, så som viktnedgång och undernäring. Det fanns också en kopplingmellan gastrointestinala problem och användandet av många läkemedel. Slutsatsen var att detfanns samband mellan polyfarmaci och flera omvårdnadsproblem bland äldre personer. Totaltfyra kategorier av omvårdnadsproblem identifierades utifrån de studerade artiklarna: fall ochfraktur, försämrad nutritionsstatus och malnutrition, mag- och tarmproblematik samt yrseloch balanssvårigheter. / The aim was to describe the nursing problems that may arise in connection withpolypharmacy in the elderly. The literature review was done with descriptive design. Datacollection through PubMed and Cinahl. The result was based on 12 quantitative articles. Theresults showed that there was a correlation between polypharmacy and several specificnursing problems among older people. The nursing problems that occurred most among thestudied articles were falls and fractures. It was revealed that the number of used medicinescould be identified as a risk factor for falls and fractures, but also drug type could influence.The results also showed that dizziness and balance problems could be associated withpolypharmacy. Other nursing problems that could connect with polypharmacy was impairednutritional status, such as weight loss and malnutrition. There were also a connection betweengastrointestinal problems and usage of many drugs. The conclusion was that a correlationbetween polypharmacy and several nursing problems among older people were found. A totalof four categories of nursing problems were identified in the studied articles: falls andfractures, impaired nutritional status and malnutrition, gastrointestinal problems, dizzinessand balance problems.

Abstract: Pharmaceuticals and their metabolites, collectively known as pharmaceutically active compounds (PhACs), have been detected in surface water, groundwater, and drinking water, in a number of countries, since the mid-1990s. Pharmaceuticals can be used in human or veterinary medicine; human pharmaceuticals in the environment are the subject of this dissertation. Human pharmaceuticals enter the environment via wastewater treatment plants, after being consumed and excreted by humans, and through improper disposal, to toilets and garbage, among other routes of entry. Some PhACs have been found to have detrimental effects on aquatic organisms at low concentrations, such as the feminization of fish after exposure to low levels of 17-ethinylestradiol, the active ingredient in the birth control pill. Others are suspected of having effects on non-target species, but the impacts of long-term exposure to mixtures of PhACs generally remain poorly understood. Nevertheless, the precautionary principle suggests that management action to mitigate the environmental impacts of PhACs should be considered and possibly implemented. The purpose of this dissertation is to provide an analysis of precautionary management strategies to mitigate the environment impacts of human PhACs. Four underlying objectives are set. The first is to review the extant scientific understanding of human PhACs in the environment, so that this knowledge can be applied to the analysis of management strategies. The sources, transport, fate, and occurrence of PhACs are discussed, and several classes of PhACs of particular concern are highlighted. The effects of PhACs on humans and aquatic organisms are explored, in addition to the gaps in scientific understanding of PhACs in aquatic environments. Finally, a rough ranking of priority PhACs is conducted; the PhACs of greatest concern are found to be carbamazepine, clofibric acid, ifosfamid, 17a-ethinylestradiol, oxytetracycline, ciprofloxacin, and diclofenac. The second objective is to investigate how planning and management principles and theories can be applied to the problem of PhACs in the environment. The precautionary principle and the theory of adaptive planning are identified as essential tools in this regard. The application of the precautionary principle and adaptive planning to pharmaceuticals in the environment are discussed, and a management framework is developed. The third objective is to determine how human PhACs in the environment can be managed at a local scale, using a case study in the Region of Waterloo. Pharmaceuticals released from two wastewater treatment plans are found entering the local environment at concentrations similar to those in other cities internationally. Social surveys indicate that residents desire management action to prevent environmental contamination by pharmaceuticals, but at a limited cost. The surveys also indicate that many residents dispose of pharmaceuticals improperly; education to encourage proper drug disposal is therefore recommended as one of several management strategies. The other two recommended management strategies target the wastewater treatment plants. In Foxboro, where the wastewater treatment plant is functioning less than optimally, optimization without technological upgrades is suggested. In Kitchener, where the plant is functioning within ministerial guidelines, ozonation is suggested as a means of improving pharmaceutical removal without exceeding residents’ willingness to pay. The fourth and final objective is to assess how human pharmaceuticals can be managed at a broad scale, such as at the national scale. Stakeholder interviews are conducted with the purpose of gaining a deeper understanding of possible management strategies. A policy analysis is conducted to determine which combinations of management strategies are likely to optimally address the problem of PhACs in the environment, and some policy packages are recommended for implementation by governments – in particular, multiple levels of government in Canada. This dissertation is among the first research efforts to investigate the management of pharmaceuticals in the environment. Few efforts to date have combined natural scientific research, social scientific research, and an understanding of planning and management theories, to explore policy and management options for this issue. It is hoped that this research will provide assistance to various governments grappling with pharmaceuticals in the environment. Furthermore, the research provides insight into how environmental problems surrounded by high levels of scientific uncertainty can be managed. The framework for precautionary decision making developed in this study can provide guidance to planners, managers and policy makers faced with the problem of uncertain environmental risk.

Over the last decade, endocrine disrupting compounds (EDCs) and pharmaceutically active compounds (PhACs) have been detected in drinking water at very low levels, mostly ng/L concentrations, suggesting that these compounds resisted removal through water treatment processes. Concerns have been raised regarding the effectiveness of common drinking water treatment technologies to remove these emerging contaminants. Adsorption processes were suggested to play an important role in the removal of PhACs and EDCs, based on the assumption that these compounds are similar to other conventional micropollutants such as pesticides in both physicochemical properties and concentration levels present in water. However, this remains to be demonstrated since the availability of adsorption data for PhACs and EDCs is extremely limited and their environmental concentrations are typically much lower than the ones for pesticides. The primary objective of this research was to evaluate in detail the removal of representative EDCs and PhACs at environmentally relevant concentrations by granular activated carbon (GAC) adsorption. In the first stage of this study, EDCs (15) were screened separately from the PhACs (86) with two different sets of assessment criteria due to the different nature and the availability of information for these two groups of compounds. As a result, 6 EDCs and 12 PhACs were selected for further evaluation. Subsequently, a multi-residue analytical method based on gas chromatography/mass spectrometry (GC/MS) was developed for the simultaneous determination of the selected PhACs and EDCs. Two key analytical steps - solid phase extraction and derivatization - were systematically optimized using full factorial design and a central composite design, respectively. The statistical experimental design in combination with the concept of the total desirability was demonstrated to be an effective tool for developing a multi-residue analytical method. The application of the developed method to Grand River water, a local raw water source, and finished drinking water from this source indicated that PhACs such as naproxen, carbamazepine, salicylic acid, ibuprofen, and gemfibrozil, and EDCs such as estrone (E1) and nonylphenol mono-ethoxy carboxylate (NP1EC) were the most common contaminants. Based on these results, the quality of the analytical data, and the physicochemical properties relevant to the adsorption on activated carbon, two PhACs (naproxen, carbamazepine) and one EDC (nonylphenol (NP)) were finally chosen for the adsorption studies. Adsorptions of the selected target compounds were evaluated on two types of activated carbon (coal-based Calgon Filtrasorb® 400 (F400) and coconut shell-based PICACTIF TE (PICA) by first investigating their isotherms at environmentally relevant concentrations (equilibrium liquid phase concentration ranging from 10 to 1000 ng/L). The single-solute isotherm data determined for both carbons showed that the relative adsorbabilities of the three target compounds were not in agreement with expectations based on their log Kow values. Overall, in this low concentration range, carbamazepine was most easily removed, and NP was least adsorbable. The adsorption of naproxen was negatively influenced by its dissociation in water. Comparison of single-solute isotherms on F400 carbon for the target compounds to those for other selected conventional micropollutants showed that naproxen and carbamazepine have generally comparable isotherms to 2-methylisoborneol (MIB) and geosmin. The isotherm tests in a post-sedimentation (PS) water from a full-scale plant demonstrated that the presence of background natural organic matter (NOM) significantly reduced the adsorption of all three target compounds, among which.NP was the least impacted compound. Based on the quantification of the direct competition using the ideal adsorbed solution theory (IAST) in combination with the equivalent background compound (EBC) approach, the minimum carbon usage rates (CURs) for removing 90% of the target compounds in PS water were calculated at two environmentally relevant concentrations (50 and 500 ng/L). This work confirmed that the percentage removal of the trace level target compound at a given carbon dosage was independent of the initial target compound concentration. Isotherm experiments were conducted for the target compound on GACs preloaded with PS water for various time intervals (up to 16 weeks) at the Mannheim Water Treatment Plant (Region of Waterloo, ON, Canada). The results indicated that the adsorption of all target compounds were subject to significant negative impacts from preloading of NOM, albeit to different extents. Among the three target compounds, reduction in adsorption capacity for naproxen was most severe, followed by carbamazepine and then NP. The three target compounds followed quite different patterns of decrease in adsorption capacity with increasing preloading time, thus revealing different competitive mechanisms at work for the different compounds. For naproxen, the change in heterogeneity of the carbons due to preloading suggests that some pre-adsorbed NOM could not be replaced by naproxen. However, both direct competitive and pore blockage mechanisms could successfully explain the adsorption performance of naproxen and carbamazepine. The removal of NP even at prolonged preloading times could be explained by absorption or partitioning in the NOM matrix on the surface of, or inside the carbons. The kinetic parameters for each target compound-virgin carbon pair were determined using the short fixed bed (SFB) approach based on the pore and surface diffusion model (PSDM). The SFB results and sensitivity analyses indicated that, under the very low influent concentration conditions, film diffusion (indexed as βL) exerts a much greater effect on breakthrough profiles than internal diffusion. The SFB tests on preloaded GACs showed that mass transport of all the target compounds decreased with increasing preloading time. Similar to the impact of preloading on adsorption capacity, naproxen was subject to the most deteriorative effect, followed by carbamazepine and then NP. In addition, potential mechanisms for the decay of the film diffusion coefficient with increased preloading time were discussed based on scanning electron microscope (SEM) images of virgin and preloaded GAC. Electrostatic interactions between the NOM/bio film formed on the preloaded carbon and dissociated naproxen may have contributed to the enhanced reduction in its film diffusion. Sensitivity analyses and subsequent calculations of the Biot numbers confirmed that film diffusion was also the predominant mechanism controlling the mass transport on preloaded carbon, in particular for naproxen. This suggests that the early breakthrough prediction of the target compounds at their environmentally relevant concentrations could be further simplified by only considering film diffusion and adsorptive capacity. Kinetic and isotherm parameters were used as input for modeling using time-variable PSDM. It was found that the varying trends for Freundlich KF and 1/n, and βL could be generally depicted by a corresponding empirical model. Pilot scale treatability tests were performed for the target compounds which subsequently validated the time-variable PSDM results thus demonstrating its effectiveness and robustness to model GAC adsorber performance for PhAC and EDC removal at environmentally relevant concentrations. The time-variable approach was further improved by adjusting for NOM surface loading differences between the preloading and the pilot columns, which successfully compensated for the prediction errors at the early phase. The validated NOM surface loading associated time variable PSDM was used to predict performances of hypothetical F400 and PICA full-scale adsorbers. Both adsorbers were expected to provide satisfactory performance in achieving 90% removals for the neutral target compounds (carbamazepine and NP). Naproxen was predicted to break through fast since both, capacity and kinetic parameters decay quickly due to carbon fouling by NOM and the physicochemical properties of this compound. Initial recommendations on the choice of adsorption process (GAC vs. PAC) for removing EDCs and PhACs can be made based on the comparison of carbon usage rates (CUR) which were calculated for a GAC adsorber using the validated improved PSDM and for PAC using the minimum applied dosages predicted by the IAST-EBC model.

The presence of pharmacologically active and persistent compounds in drinking water sources is an environmental and public health concern. Sources of pharmaceuticals in the aquatic environment include wastewater treatment plant effluents and veterinary use. Antibiotics are of special concern because of their role in the spread of bacterial resistance. Conventional drinking water treatment processes are often ineffective for removing trace organic contaminants. Ozonation processes have demonstrated the ability to remove pharmaceutical compounds from drinking water supplies. During the ozonation of drinking water, the primary oxidants are ozone and hydroxyl radicals formed during the decomposition of ozone. Both oxidants contribute to the removal of pharmaceutical compounds; however, the relative rates of destruction by these two oxidants depends on the treatment operating conditions, the background water chemistry and the structure and reactivity of the target compound. This study investigated the relative impact of natural water characteristics, such as pH, the carbonate system, and natural organic matter, on the removal of the fluoroquinolone antibiotic ciprofloxacin by ozonation processes. Rate constants for k"O3, Cip obtained at pH 7 were approximately one order of magnitude higher than at pH 5 because ciprofloxacin changes from a positively charged cation to a neutral species over this pH range. The results showed that there was very little variation of the rate constants for ciprofloxacin oxidation by O₃ or hydroxyl radicals regardless of the carbonate concentration or the presence of the two organic matters studied in this research. Typical values for k"O3, Cip and k"HO°, Cip obtained at pH 7 ranged between 1.49x10⁴ and 1.64x10⁴ M⁻¹s⁻¹ and 1.29x10¹⁰ to 1.80x10¹⁰ M⁻¹s⁻¹, respectively. However, the presence of carbonate and other hydroxyl radical scavengers did have an impact on O₃ and hydroxyl radical exposure. The relative impact of these two oxidants changed depending on the pH of the system and the presence of carbonate and natural organic matter. / text

Pharmaceuticals and personal care products (PPCPs) are detected routinely in raw and treated municipal wastewater. Conventional wastewater treatment processes are not effective in removing PPCP; therefore, treated wastewater discharges are one of the main entry points for PPCPs into the aquatic environment, and eventually into drinking water supplies. The use of laccase-catalyzed oxidation for removing low concentrations of PPCPs from municipal wastewater after primary treatment is investigated. Oxybenzone was selected as a representative PPCP. Like many other PPCPs, oxybenzone is not recognized directly by the laccase enzyme. Therefore, mediators were used to expand the oxidative range of laccase, and the efficacy of this laccase-mediator system in primary effluent was evaluated. Eight potential mediators were investigated. The greatest oxybenzone removal efficiencies were observed when 2,2’-azino-bis(3-ethylbenzthiazoline-6sulphonic acid) (ABTS), a synthetic mediator, and acetosyringone (ACE), a natural mediator, were present. An environmentally relevant concentration of oxybenzone (10 µg/L) in primary effluent was removed below the detection limit after two hours of treatment with ABTS, and 95% was removed after two hours of treatment with ACE. Several mediator/oxybenzone molar ratios were evaluated at two different initial oxybenzone concentrations. Higher mediator/oxybenzone molar ratios were required at the lower (environmentally relevant) oxybenzone concentrations, and ACE required higher molar ratios than ABTS to achieve comparable oxybenzone removal. The oxidation mechanisms and kinetics of the ACE mediator was evaluated. A better understanding of the mediator oxidation process would lead to a better design of the laccase-mediator system. An alternative laccase-mediator treatment configuration, which allows the enzyme and mediator to react prior to coming in contact with the target PPCP, was investigated. This treatment configuration shows promise for further development since it might reduce laccase and mediator requirements. Oxidation byproducts generated by the laccase-mediator system were characterized and compared to those generated during ozonation. Enzymatic treatment generated byproducts with higher mass to charge (m/z) ratios, likely due to oxidative coupling reactions. The results of this study suggest that, with further development, a laccase-mediator system has the potential to extend the treatment range of laccase to PPCPs not directly recognized by the enzyme, even in a primary effluent matrix. / text

Anthropogenically-derived substances, including pharmaceuticals and personal care products, endocrine-disrupting chemicals, and pesticides, are increasingly being detected in drinking water supplies and wastewater effluents. Concerns over the presence of these compounds in water supplies include their ability to impart toxicological activity, their capacity to spread antibiotic resistance, and their potential to affect cell-signaling processes. For these reasons, water treatment processes geared towards removal of these trace organic contaminants are vital. In this work, ozone was used to treat four pharmaceutical contaminants: ciprofloxacin, cyclophosphamide, erythromycin, and ifosfamide. Ciprofloxacin and erythromycin are antibiotic/antimicrobial compounds, and cyclophosphamide and ifosfamide are chemotherapy agents. Ozone effectively transformed all four pharmaceuticals, even in the presence of background natural organic matter, which exerts a considerable ozone demand. The apparent rate constants for the reaction of the pharmaceuticals with ozone at pH 7 were determined: 3.03 M-1s-1 for cyclophosphamide; 7.38 M-1s-1 for ifosfamide; 1.57×104 M-1s-1 for ciprofloxacin; and 7.18×104 M-1s-1 for erythromycin. Cyclophosphamide and ifosfamide, which do not react quickly with ozone, exhibited high rate constants (2.7×109 M-1s-1) for transformation by hydroxyl radicals, which are formed through ozone decomposition. Nevertheless, complete removal of cyclophosphamide and ifosfamide was achievable using a novel continuous aqueous ozone addition reactor and an ozone-based advanced oxidation process (peroxone). In ozone-based processes, pharmaceuticals are systematically transformed via complex oxidative pathways towards CO2, H2O, and the oxidized forms of other elements. Intermediate oxidation products containing oxygen atoms or hydroxyl groups substituted into the chemical structure of the parent pharmaceutical were identified using liquid chromatography-mass spectrometry (LC-MS). Given the structural similarity of intermediate oxidation products to the parent pharmaceuticals, an antimicrobial activity assay was employed to monitor the removal of pharmacological activity associated with ciprofloxacin, erythromycin, and their respective intermediate oxidation products throughout treatment. For solutions containing ciprofloxacin or erythromycin, ozone was able to completely eliminate the corresponding antimicrobial activity. Ciprofloxacin intermediate oxidation products were pharmacologically active; however, erythromycin’s intermediate products did not contribute to the residual antimicrobial activity. These results suggest that the design of conventional and advanced ozone-based processes must incorporate ozone demand from background organic matter and account for destruction of pharmacologically active intermediates. / text

The ubiquitous presence and chronic effect of pharmaceuticals is one of the emerging issues in environmental field. As a result of incomplete removal by sewage treatment plants, pharmaceuticals are released into the environment and drinking water sources. On the other hand, conventional drinking water treatment processes such as coagulation, filtration and sedimentation are reported to be ineffective at removing pharmaceuticals. Therefore, the potential presence of pharmaceuticals in finished drinking water poses a threat on public health. Antibiotics, as an important group of pharmaceuticals, are given special concerns because the potential development of bacteria-resistance. Ozonation and advanced oxidation processes are demonstrated to be quite effective at removing pharmaceuticals. The oxidation of pharmaceuticals is caused by ozone itself and hydroxyl radicals that are generated from ozone decomposition. Whether ozone or hydroxyl radicals are the primary oxidant depends on the specific pharmaceutical of interest and the background water matrix. In this research, erythromycin, a macrolide antibiotic, was chosen as the target compound because of its high detection frequency in the environment and its regulation status. The objective of this research was to investigate the removal performance of erythromycin by ozonation from the standpoint of kinetics. The effects of pH, carbonate and phosphate buffers, and initial ozone dose on ozonation of erythromycin were also studied. The second-order rate constant for the reaction between deprotonated erythromycin and ozone was determined to be 4.44x10⁹ M⁻¹·s⁻¹ while protonated erythromycin did not react with ozone. Ozone was determined to be the primary oxidant for erythromycin removal by ozonation. pH was found to have great positive impact on the degradation of erythromycin by ozonation due to the deprotonation of erythromycin at high pH. Carbonate and phosphate buffers were found to have negligible effects on the degradation of erythromycin by ozonation. Initial ozone dose showed a positive impact on the total erythromycin removal rate by ozonation. / text