Fate of Pharmaceuticals in the Environment and in Water Treatment Systems - Chapter 10 docx

10.2 OCCURRENCE IN THE AQUATIC ENVIRONMENT The occurrence of different classes of PhACs, such as analgesics and antiinflam-matories, antibiotics, antiepileptics, beta-blockers, blood lip

Part III

Treatment of Pharmaceuticals in Drinking Water and Wastewater

1 0 Drugs in Drinking Water

Treatment Options

Howard S Weinberg,

Vanessa J Pereira, and Zhengqi Ye

10.1 INTRODUCTION

The high usage of drugs throughout the world, their partial metabolism after inges-tion, and inconsistencies in the way they are disposed make their presence in the aquatic environment inevitable Their sources in natural waters are not limited to excretion of parent compounds and their metabolites by individuals and pets but also include disposal of unused medications to sewage systems, underground leakage from sewage system infrastructures, release of treated or untreated hospital wastes, disposal by pharmacies and physicians, and humanitarian drug surplus to domestic sewage systems Transmission routes include release to private septic fields; treated effluent from domestic sewage treatment plants discharged to surface waters; over-flow of untreated sewage from storm events and system failures directly to surface waters; transfer of sewage solids to land; release from agriculture; dung from medi-cated domestic animals and confined animal feeding operations; direct release via washing, bathing, or swimming; discharges from industrial manufacturing and clandestine drug laboratories, as well as illicit drug usage; leaching from defective landfills; and release from aquaculture.1After release into the environment, most pharmaceutically active compounds (PhACs) are eventually transported to the aque-ous domain and are expected to be only partially degraded and transformed into other products by phototransformative, physicochemical, and biological degradation reactions The environmental fate of only a fraction of these compounds has been evaluated in laboratory studies, and only recently has their occurrence in drinking

Contents

10.1 Introduction 217

10.2 Occurrence in the Aquatic Environment 218

10.3 Drinking Water Treatment 218

10.3.1 Pretreatment 220

10.3.2 Filtration 220

10.3.3 Chlorine-Based Disinfection 221

10.3.4 Ozone and Advanced Oxidation Treatment 222

10.3.5 Ultraviolet (UV) and Advanced Oxidation Treatment 223

10.4 Conclusion 225

References 226

water been considered.2Their presence at low levels presents analytical challenges, and the environmental impact and public health effects of long-term, low-level expo-sure and combinatory effects of these compounds requires further study Particular concern should be raised over those compounds that resist wastewater and drinking water treatment Treatment processes that are expected to efficiently remove PhACs from water include adsorption using activated carbon, ozonation, ultraviolet (UV), and advanced oxidation processes The concentrations investigated in laboratory-controlled evaluations of treatment options are often higher than those expected in the aquatic environment This is a standard procedure in laboratory-scale studies for determination of rate constants and other fundamental process parameters minimiz-ing interference and analytical constraints, since workminimiz-ing at these levels allows the analyte reduction to be followed over at least an order of magnitude without involv-ing extensive extractions or preparation procedures

Although the lifetime ingestion of drinking water may result in consumer expo-sure to PhACs at an order of more or less than a single therapeuticdose, little is known about long-term, low-level exposure to humans or the potential synergisms that may arise from exposure to multiple compounds Consequently, it is prudent to consider the options available to prevent PhACs from reaching drinking water

10.2 OCCURRENCE IN THE AQUATIC ENVIRONMENT

The occurrence of different classes of PhACs, such as analgesics and antiinflam-matories, antibiotics, antiepileptics, beta-blockers, blood lipid regulators, contrast media, oral contraceptives, cytostatic, and bronchodilator drugs, has been reported

in sewage, surface, ground and drinking water.3,4,5–13Maximum occurrence levels for some of these compounds reported in different countries are presented inTable 10.1, which also presents estimates of quantities of PhACs sold for use in human medicine

in Germany in 1997, where scrip data are more widely accessible than in the United States, together with secondary wastewater treatment plant (WWTP) removal effi-ciencies obtained by collecting composite raw influent and final effluent samples over a period of 6 days.3The reported WWTP removal efficiencies were highly vari-able, and during other sampling events conducted at the same plant lower removal efficiencies were observed These results make clear the need to investigate further the fate and potential remediation options for those PhACs that were found to resist wastewater treatment and that were found in drinking water, such as clofibric acid, iopromide, carbamazepine, diclofenac, and ibuprofen

10.3 DRINKING WATER TREATMENT

A conventional surface water treatment process that consists of coagulation, floc-culation, sedimentation, filtration, and disinfection is often employed in drinking water treatment facilities Ozone and UV can be used as oxidants and disinfectants, but chlorine and chloramines are most often employed for final disinfection in the United States so that a persistent residual is maintained in the distribution system

Pharmaceuticals Sold in Germany, Wastewater Removal Efficiency in Germany, and Maximum Concentrations Reported by Several Authors in Different Countries (References Given in Parentheses)

Maximum Concentrations Reported Compound Therapeutic Class

PhACs Sold in Germany (Tons)

WWTP Removal Efficiency (%)

WWTP Effluent (µg/L)

Surface Water (µg/L)

Groundwater (µg/L)

Drinking Water (µg/L)

Acetaminophen Analgesics/

nonsteroidal antiinflammatories

>99 (3) 6.0 (6) 10 (7) Diclofenac 75 (3) 69 (3) 2.5 (6) 1.2 (6) 0.006 (3)

Ibuprofen 180 (3) 90 (3) 85 (4) 2.7 (4) 0.003 (3)

Ketoprofen 0.38 (6) 0.12 (6)

Naproxen 66 (3) 3.5 (11) 0.4 (11)

Oxytetracycline Antibiotics 0.34 (7)

Tetracycline 1.0 (5)

Ciprofloxacin 0.132 (10) 0.07 (9) 0.018 (9)

Carbamazepine Antiepileptic 80 (3) ~0 (3) 6.3 (6) 1.1 (6) 1.1 (4) 0.258 (12)

Metoprolol Beta-blockers 52 (3) 67 (3) 2.2 (6) 2.2 (6)

Clofibric acid Antilipemic 51 (3) 1.6 (13) 0.55 (13) 4.0 (4) 0.270 (4)

Iohexol Contrast media 7.0 (8) 0.5 (8)

Iopromide 130 (3) 20 (8) 4.0 (8) 0.086 (3)

17B-ethinylestradiol Oral contraceptives 0.050 (3) 0.003 (4) 0.831 (7)

Ifosfamide Cytostatic 2.9 (6)

Salbutamol Bronchodilator >90 (3) 0.035 (6)

10.3.1 P RETREATMENT

The potential for the removal of PhACs from drinking water by different treatment processes has been reviewed.14Neither coagulation, which is expected to remove only hydrophobic compounds associated with particulate or colloidal material with high organic carbon content, nor flocculation would be efficient tools for remov-ing most of these compounds from water This was confirmed in a bench-scale coagulation/flocculation/sedimentation study on antibiotic removal with alum and iron salts.15Under simulated drinking water treatment conditions with ng/L initial concentrations and 68 mg/L alum coagulant dose at pH 6 ~ 8, the removal rates

of sulfamethoxazole and trimethoprim were below 20%, while erythromycin-H2O could be removed by up to 33%.16 Erythromycin is much more hydrophobic than sulfamethoxazole and trimethoprim (log Kow = 3.06, 0.89, and 0.91, respectively) and is therefore more likely to partition onto solids and have higher removal rates Diclofenac, carbamazepine, bezafibrate, and clofibric acid were also poorly removed

by ferric chloride precipitation.17

10.3.2 F ILTRATION

Adsorption using activated carbon could play an important role in the removal of PhACs, but competition with more polar or larger compounds, including natural organic matter (NOM), has a major impact For example, even though the addition

of 10 to 20 mg/L of powdered activated carbon (PAC) efficiently removed seven antibiotics from distilled water (50 to greater than 99% removal), when the same experiment was conducted in river water the removal decreased by 10 to 20%.14 The percent removal of sulfonamides, trimethoprim, and carbadox in a filtered (0.45 µm) surface water sample with dissolved organic content of 10.7 mg/L ranged from

49 to 73% and 65 to 100% at PAC dosages of 10 and 20 mg/L, respectively.15 In another laboratory-controlled batch study at an initial antibiotic concentration of 30

to 150 ng/L, sulfamethoxazole, trimethoprim, and erythromycin-H2O were removed through PAC adsorption by 21%, 93%, and 65%, respectively, in a natural water of DOC 3.5 mg/L with 4 mg/L PAC dose and contact time of 4 h.16These findings show that even though the NOM in surface water may compete with the antibiotics for some of the adsorption sites on PAC, this process might still be somewhat effective

as a treatment tool

Membrane filtration processes are used for water treatment and various industrial applications when production and distribution of water with high chemical and micro-biological quality is required Processes such as reverse osmosis, nanofiltration, and ultrafiltration were found to efficiently remove many PhACs from water.18,19However,

a major disadvantage of using any of these filtration processes is that the removal of PhACs is accompanied by production of a rejection concentrate that will be much more concentrated than the feed water with respect to suspended and dissolved con-stituents and will consequently require additional treatment and disposal.20

Drugs in Drinking Water 221

10.3.3 C HLORINE -B ASED D ISINFECTION

Chlorine disinfectants, such as free chlorine and chloramines, are widely used in drinking water disinfection in the United States Free aqueous chlorine (HOCl/OCl–) can be formed by dissolving chlorine gas or hypochlorite into water, while chlora-mines can be formed by reaction of free chlorine with ammonia Free chlorine, as a strong oxidant, is reactive toward many organic pollutants and produces chlorination byproducts Chloramines, as relatively weaker oxidants, are expected to react much more slowly with organics.21

Aliphatic amines react rapidly with HOCl to produce N-chloramines, and direct

correlations were observed between degree of nucleophilicity of amines and reaction rate with chlorine.22N-chloro compounds with a hydrogen atom on the carbonB- to the amine could undergo elimination reactions to form an imide, which subsequently hydrolyzes, resulting in bond cleavage between the nitrogen and carbon atoms and removal of theB-carbon side-chain.23Aromatic amines tend to form ring-substituted

rather than N-chlorinated products Chlorination of phenol proceeds via a typical

electrophilic substitution pathway The phenolate anion has a higher electron den-sity and, hence, reacts quite rapidly with HOCl Among antibiotics, sulfonamides contain an aromatic amine group that is susceptible to free chlorine attack, while the aliphatic amine groups in the structures of fluoroquinolones, tetracyclines, and

macrolides are likely to react with free chlorine to form N-chloroamines that can

further decompose

The kinetics and mechanisms of sulfamethoxazole, trimethoprim, and three fluoroquinolone antibiotics (ciprofloxacin, enrofloxacin, and flumequine) in reaction with free chlorine and chloramines have been studied, albeit at a far lower disin-fectant-to-analyte ratio (~10) than would be typical with full-scale water treatment (~6000).24–26 All these antibiotics react rapidly with free chlorine and at slower rates with preformed chloramines, except for flumequine, lacking the characteristic piperizine ring in its structure, which exhibits no apparent reactivity toward chlorine

oxidants Sulfamethoxazole yields an N-chlorinated adduct, which rearranges to a

ring chlorination product or leads to rupture of the sulfonamide moiety to form the

major product N-chloro-p-benzoquinoneimine Reaction of trimethoprim appears to

occur primarily on the molecule’s trimethoxybenzyl moiety at pH <5, while at pH ≥5

an N-chlorinated intermediate is generated, which may react further or rearrange to

a number of stable substitution products Ciprofloxacin reacts very rapidly to form a chloramine intermediate that spontaneously decays in water by piperazine fragmen-tation Enrofloxacin reacts relatively slowly to form a chlorammonium intermedi-ate that can catalytically halogenintermedi-ate the parent in aqueous solution The incomplete oxidation of fluoroquinolones may not completely eliminate the biological effect of these compounds.26However, the substantial structural modification resulting from reaction of sulfamethoxazole with free chlorine may lead to a significant reduction

of that parent molecule’s antimicrobial activities.25Nevertheless, sulfonamides were demonstrated to be readily removed from drinking water at near neutral pH although barely affected by monochloramine.27 The antimicrobial activity of trimethoprim might not be significantly reduced via chlorination due to the formation of primarily

stable and multiple-substituted products.24The reaction kinetics of carbadox with chlorine are highly pH dependent, with the apparent second-order rate constants ranging from 51.8 to 3.15 × 104M–1 s-1 at pH 4 to 11.28Carbadox was completely removed to below detection levels by both free chlorine (0.1 mg/L) and monochlo-ramine (1 mg/L) within 1 min of contact time in both deionized and surface water.27 However, chlorination did not appear to remove the antibacterial activity of the par-ent compound, as the idpar-entified chlorination byproducts of carbadox retain their bio-logically active functional groups Although dechlorination agents were not used in many of these studies, they are employed when samples are collected for disinfection byproduct analysis, but only after they have been evaluated to determine if they do not affect the stability of the analytes the samples are being collected for Such an approach must also be used before field samples are collected for the analysis of PhACs

Chlorine dioxide (ClO2) is an alternative to chlorine for disinfection, and it is a highly selective oxidant for specific functional groups of organic compounds.29For example, sulfamethoxazole and roxithromycin were reactive to ClO2with second-order rate constants (pH 7, 20ºC) of 6.7 × 103M–1s–1and 2.2 × 102M–1s–1, respectively.30 Organic pollutants can associate with dissolved NOM in the aquatic phase via the same mechanism as their sorption to particulate natural organic matter For example, the sorption coefficient (Kd, DOM) values of tetracyclines on Aldrich humic acid were 2060 and 1430 L/Kg at pH 4.6 and 6.1, respectively,31which is comparable

to the Kdvalue of tetracycline Association of antibiotics with dissolved NOM may facilitate their transport in the aquatic environment along with the dissolved NOM

10.3.4 O ZONE AND A DVANCED O XIDATION T REATMENT

Ozone (O3), with its high standard oxidation potential, is expected to oxidize organic compounds more quickly than chlorine or chlorine dioxide Ozonation is used in drinking water treatment plants to achieve disinfection and oxidation for purposes such as color, taste and odor control, control of iron and manganese, destabilization

of colloidal material to aid flocculation, oxidation of disinfection byproduct (DBP) precursors, and elimination of organic compounds.32Ozone is a very selective oxi-dant that will react with double bonds, activated aromatic compounds, and deproton-ated amines, whereas hydroxyl (OH) radicals generdeproton-ated when ozone is employed in advanced oxidation mode react with most water constituents with nearly diffusion controlled rates.33Diclofenac was efficiently degraded in a semibatch reactor in dis-tilled and river water at an ozone dose of 1 mg/L but not ibuprofen or clofibric acid (Co= 2µg/L and reaction time = 10 min).34 On the other hand, greater than 70% removal of each in a pilot-scale plant was achieved using 2.5mg/L ozone.2These three compounds were effectively degraded by advanced oxidation processes (AOPs) using two O3to H2O2ratios (3.7:1.4 and 5.0:1.8 mg/mg).34

Batch experiments have also been conducted to determine the degradation rate constants of several pharmaceuticals (bezafibrate, carbamazepine, diazepam, diclofenac, 17B-ethinylestradiol, ibuprofen, sulfamethoxazole, and roxithromycin) with ozone and OH radicals.35 Carbamazepine, diclofenac, 17B-ethinylestradiol, sulfamethoxazole, and roxithromycin were completely degraded during ozonation,

Drugs in Drinking Water 223

and the rates obtained in pure water solutions could efficiently be applied to predict these compounds’ behavior in natural waters (bank filtrate, well, and lake waters) with different dissolved organic carbon content and alkalinity A rapid reaction of ozone with the double bond in carbamazepine has been reported36as has the for-mation of byproducts containing quinazoline-based functional groups that can be further oxidized by reaction with OH radicals Moreover, in a full-scale ozonation plant, removal of sulfamethoxazole and carbamazepine, at occurrence levels of 9.7 and 2.4 ng/L in the source water, to below detection limit (<1 ng/L) was observed.2 The actual mechanism of removal, however, remains unclear In a pilot-scale study, samples of coagulated/settled/filtered (dual media) water illustrated little change in the levels of carbamazepine in the plant’s source water However, when ozone was introduced prior to coagulation, 66 to 96% reduction was observed, although it could not be determined if this was the result of enhanced coagulation rather than ozone alone.37

10.3.5 U LTRAVIOLET (UV) AND A DVANCED O XIDATION T REATMENT

Even though few studies of degradation of PhACs by UV light treatment process exist, in combination with ozone or hydrogen peroxide this process may effectively transform the compounds UV radiation is widely used for drinking water disinfec-tion in Europe In the United States, this technology is currently gaining importance, since its use can reduce the chlorine dose applied for final disinfection, therefore, decreasing the levels of DBPs formed.38AOPs using UV in place of O3can also be used for DBP precursor removal and are attractive due to lower cost and lower poten-tial for producing alternative chemical byproducts

Degradation of organic compounds can also be obtained using direct photolysis and AOPs For a compound to be photolabile it needs to have the capacity to absorb light As a consequence of that light absorption, it will undergo transformation It can also undergo degradation by receiving energy from other excited species (sen-sitized photolysis) or by chemical reactions involving very reactive and short-lived species such as hydroxyl-radicals, peroxy-radicals, or singlet oxygen.39

UV radiation can be generated using low pressure (LP) lamps that emit mono-chromatic light at 254 nm or medium pressure (MP) lamps that emit a broadband ranging from 205 to above 500 nm.40MP lamps were found to achieve a more effec-tive degradation of bisphenol A, ethinyl estradiol, and estradiol as compared to direct photolysis using LP lamps.41

The kinetic degradation constant of carbamazepine and reaction intermediates formed using LP UV/H2O2have been studied.42Even though direct photolysis in the absence of H2O2leads to negligible degradation, an effective removal of carbamaze-pine can be obtained, and pathways were suggested to describe the degradation to acradine, a potentially mutagenic and carcinogenic byproduct

The effectiveness of ozonation and LP UV/H2O2processes were compared to test the degradation of paracetamol and diclofenac and identify the main byproducts formed.43,44 Both processes proved to be effective in inducing the degradation of both xenobiotics and achieved degrees of mineralization of approximately 30 and 40% for ozonation and HO photolysis, respectively

LP and MP ultraviolet systems were evaluated in batch-sale laboratory reac-tors45,46to investigate the UV photolysis and UV/H2O2oxidation of PhACs that were found to occur in the aquatic environment and belong to different therapeutic classes The chemicals investigated were carbamazepine (antiepileptic agent), clofibric acid (metabolite of the lipid regulator clofibrate), iohexol (x-ray contrast agent), cipro-floxacin (antibiotic), naproxen, and ketoprofen (both analgesics) Fundamental direct and indirect photolysis parameters obtained in laboratory-grade water were reported and used to model the UV photolysis and UV/H2O2oxidation of the pharmaceuticals

in a surface water using LP and MP lamps MP-UV photolysis and MP-UV/H2O2 oxidation modeling predicted the experimental results very well The LP-UV model predicted the experimental UV photolysis removals well but underestimated the LP-UV/H2O2oxidation results Overall, MP lamps proved to be more efficient at maxi-mizing the degradation of the selected group of compounds by both UV photolysis and UV/H2O2oxidation in the bench-scale experiments conducted The UV fluences required to achieve 50% removal of the selected pharmaceuticals from surface and laboratory-grade water ranged from 34 to 3466 mJ/cm2using MP-UV photolysis,

39 to 23105 mJ/cm2using LP-UV photolysis, 91 to 257 mJ/cm2using MP-UV/H2O2 oxidation, and 108 to 257 mJ/cm2using LP-UV/H2O2oxidation

It should be emphasized that the irradiance measurement in a batch reactor is much less complex than in a full-scale UV reactor with multiple light sources Future studies should validate these results in pilot and full-scale facilities and evaluate whether the use of high UV fluences and AOPs that could degrade a wide variety of organic compounds are economically feasible and competitive when compared to the use of other treatment processes (such as ozonation and membranes) The com-parison should take into consideration the possibility of byproduct formation during photolysis, ozonation, and AOPs as well as how to deal with the membrane rejection concentrate

Photocatalysis is an AOP that has proven to be efficient for application in water disinfection and degradation of pollutants It relies on the formation of strongly oxi-dative hydroxy radicals that inactivate microorganisms and degrade resilient organic micropollutants relatively nonselectively and may be carried out in the presence of

a semiconductor (heterogeneous photocatalysis) or in the presence of chemical oxi-dants such as iron and hydrogen peroxide (photo-Fenton)

Among the heterogeneous catalysts widely tested, titanium dioxide (TiO2) appears to be one of the most promising materials in promoting a good level of disinfection and efficient destruction of chemical compounds Its advantages include chemical inertness, photostability, absence of toxicity, and low cost, and it has there-fore been considered for a wide range of applications.47To be catalytically active, titanium dioxide requires irradiation with a source in a wavelength range lower than

390 nm that will induce the photoexcitation of an electron, since it has an energy band gap of about 3.2 eV

After finding that photocatalysis in controlled laboratory-scale experiments appeared to reduce persistent substances such as NOM, carbamazepine, clofibric acid, iomeprol, and iopromide (even if they are present in a complex matrix),48the process was evaluated in combination with microfiltration at the pilot scale to test the degradation of some of these compounds in a model solution without the presence

Drugs in Drinking Water 225

of NOM.49High photocatalytic degradation of carbamazepine and clofibric acid was accompanied by elimination of the model solution’s dissolved organic carbon show-ing that the xenobiotics were mineralized to some extent On the other hand, the photocatalytic degradation of iomeprol was accompanied by formation of degrada-tion products and intermediates The combinadegrada-tion of photocatalysis with cross-flow microfiltration allowed the efficient separation and reuse of the TiO2particles

Despite the lowlevels of PhACs expected in the environment, their constant infu-sion can cause them to become more persistent and, therefore, even if the half-lives

of these compounds are short, long-term exposure effects and combinatory effects need to be addressed The ecotoxicological potential of 10 prescription drugs has been evaluated, and even though for most of the substances toxicities were moder-ate, tests with combinations of various pharmaceuticals revealed stronger effects than expected from the effects measured individually.50The potential for indirect human exposure to pharmaceuticals from drinking water supplies was studied, and the margin between potential indirect daily exposure via drinking water and daily therapeutic dose was higher by at least three orders of magnitude or more.51Despite these findings, concerns are raised about long-term, low-level human exposure to pharmaceutical products, their metabolites, and degradation compounds via drink-ing water Research has also shown that the presence of antibiotics in the aquatic environment poses a potential threat to ecosystem function and human health.10,52 Minor side effects from prescribed drugs are common, and even though they are usually outweighed by the health benefits of the medication, they can possibly have adverse effects in routine unintended exposure

This chapter has attempted to consider what does and does not work in remediat-ing the presence of drugs in drinkremediat-ing water There is no question that subtherapeutic doses of these compounds are finding their way into the surface and groundwaters that ultimately become consumers’ drinking water and that, for now, the levels found in that finished drinking water are most often close to the analytical limits of detection Nevertheless, there are insufficient occurrence data for us to conclude that all conven-tional drinking water treatment plants are generating a finished product that is “drug free.” If the surface water source is impacted by an upstream wastewater discharge from a major population center, there is a strong likelihood that a small downstream conventional drinking water plant will receive elevated levels of pharmaceutically active compounds that will survive to some degree into the finished drinking water One study even suggests that subsequent chlorination of such water could generate an even more toxic end product so that a switch to chloramination, already favored for reducing disinfection byproduct formation, might be preferable Also, the introduc-tion of advanced treatments such as AOPs or photolysis that target reactive centers in the chemical contaminant offer some degree of remediation that, when coupled with adsorption, appear to offer a fair degree of protection to the consumer

Further studies should focus on evaluating the environmental and human impact

of these compounds to determine to what extent they should be removed from drink-ing water In addition, economic viability studies of usdrink-ing higher UV fluences than