Fate of Pharmaceuticals in the Environment and in Water Treatment Systems - Chapter 15 docx

Despite recent investigations documenting the occurrence of pharmaceuticals in the environment, important information on their fate and long-term effects is still lacking.13 15.2 FATE OF

Pharmaceuticals in

Biological Wastewater

Treatment Plants

Sungpyo Kim, A Scott Weber,

Angela Batt, and Diana S Aga

15.1 INTRODUCTION

Providing sufficiently clean water to the public has become a challenging issue worldwide as the quality of water sources increasingly deteriorates.1 As a conse-quence, treated wastewater has attracted attention as an alternative water resource, provided appropriate treatment can be applied.2Therefore, the removal of micro-contaminants, such as pharmaceuticals and personal-care products, in wastewater is critical because many of these compounds survive conventional treatment.3In gen-eral, these compounds are present at parts per billion (ppb) levels or less in wastewa-ter.4,5Although these concentrations are much lower than the levels of traditionally known organic pollutants (such as the persistent organic pollutants DDT, PCBs, and the like) the potential long-term effects of these compounds to humans and wildlife cannot be neglected For example, several studies have shown that even parts per tril-lion (ppt) levels of ethinyl estradiol (the active ingredients of birth control pills) and natural estrogens can disrupt the hormone system of aquatic species.6,7In addition, low levels of antibiotics from the effluents of wastewater treatment plants (WWTPs) can promote antibiotic resistance in microorganisms that are exposed constantly to these compounds.8–10

Contents

15.1 Introduction 349

15.2 Fate of Pharmaceuticals in Biological Wastewater Treatment Process 350

15.3 Pharmaceutical Removal Mechanisms 350

15.3.1 Biodegradation and Biotransformations 351

15.3.2 Sorption 352

15.4 Influence of Wastewater Treatment Plant (WWTP) Operating Conditions 354

15.5 Final Remarks 358

References 358

ronment via a number of pathways but primarily from discharges of wastewater treat-ment plants or land application of sewage sludge and animal manure Most active ingredients in pharmaceuticals are transformed only partially in the body and thus are excreted as a mixture of metabolites and bioactive forms into sewage systems Although WWTPs remove some pharmaceuticals during treatment,4,11,12 removal efficiencies vary from plant to plant Despite recent investigations documenting the occurrence of pharmaceuticals in the environment, important information on their fate and long-term effects is still lacking.13

15.2 FATE OF PHARMACEUTICALS IN BIOLOGICAL

WASTEWATER TREATMENT PROCESS

Some antibiotics and other pharmaceutical compounds in wastewater can be reduced

or eliminated in biological wastewater treatment systems using the activated sludge process, which is the most commonly used wastewater treatment process in the world Wastewater treatment process generally consists of a primary, secondary, and sometimes an advanced treatment stage, with different biological, physical, and chemical processes available for each stage of treatment A schematic diagram of a typical WWTP that employs the activated sludges for secondary treatment is shown

inFigure 15.1 The primary treatment stage generally utilizes physical treatment, such as screens and a gravity settling process, typically referred to as sedimenta-tion, to remove the solid contents in wastewater Secondary treatment, which typi-cally relies on microorganisms to biodegrade organic matter and/or other nutrients, can differ substantially In some wastewater treatment facilities, the effluent also is disinfected before it is released into the environment, typically by chlorination or ultraviolet (UV) radiation In addition, advanced waste treatment processes can be applied to remove nitrogen, phosphorus, and other pollutants or particles.14

Recent reports demonstrate that conventional WWTPs are not capable of remov-ing pharmaceutical contaminants under typical operatremov-ing conditions, which results

in a discharge of these compounds into surface waters.5,15–26Accordingly, WWTPs are important point sources for antibiotic contamination of surface waters.4,27–30

15.3 PHARMACEUTICAL REMOVAL MECHANISMS

Several laboratory studies have been conducted to assess the efficiencies of vari-ous treatment technologies in removing antibiotics and other pharmaceuticals from

A: Primary Treatment — Screen Bar and First Settlement

B: Secondary Treatment — Activated Sludge and Second Settlement

C: Advanced Treatment — Chlorination

FIGURE 15.1 A schematic diagram of biological wastewater treatment process.

wastewater.31–33The primary pollutant removal mechanisms in conventional biologi-cal wastewater treatment processes are biodegradation and sorption by microorgan-isms Therefore, it is reasonable to assume that the key component in biological WWTPs responsible for the removal of pharmaceutical pollutants is the aeration basin containing the microorganisms (activated sludge) Biodegradation and sorption also could take place in other unit processes, such as primary settling, but removal efficiencies at this stage are difficult to control.14Other removal mechanisms such as volatilization (due to aeration) or photodegradation (due to sunlight) are either negli-gible or nonexistent.34Disinfection processes, such as chlorination or UV treatment, which are intended to remove pathogens, not only reduce drug-resistant bacteria but may also contribute in the elimination of some pharmaceuticals in wastewater However, not all WWTPs include a disinfection step, many facilities only disinfect treated effluents seasonally, and several studies reported that disinfection does not effectively remove a wide range of antibiotics.18,35Accordingly, in this chapter we will limit our discussion on the pharmaceutical removal by biodegradation and sorp-tion However,Chapters 10,11, and12in this book examine the efficiencies of vari-ous disinfection processes in the removal of pharmaceuticals in drinking water

15.3.1 B IODEGRADATION AND B IOTRANSFORMATIONS

During biological degradation in WWTPs, pharmaceutical contaminants could undergo (1) mineralization; (2) transformation to more hydrophobic compounds, which partition onto the solid portion of the activated sludge; and (3) transformation

to more hydrophilic compounds, which remain in the liquid phase and are eventually discharged into surface waters.13,36

Despite the wide consortium of microorganisms present in the activated sludge,

it is unlikely that pharmaceuticals present as microcontaminants in wastewater can

be effectively removed by biodegradation alone First, the relatively low concentra-tion of pharmaceuticals relative to other pollutants in wastewater may be insufficient

to induce enzymes that are capable of degrading pharmaceuticals.3Second, many of these compounds are bioactive, which can inhibit growth or metabolism of microor-ganisms Thus, it is unlikely that pharmaceuticals will be favorable energy or carbon sources for microorganisms Third, the degree of biodegradation will depend on the nature of each compound and on the operating conditions employed in WWTPs Joss et al.34provided a comprehensive and intensive study investigating the bio-degradation of pharmaceuticals, hormones, and personal-care products in municipal wastewater treatment Target compounds included antibiotics, antidepressants, anti-epileptics, antiphlogistics, contrast agents, estrogens, lipid regulators, nootropics, and fragrances Among them, only 4 (ibuprofen, paracetamol, 17C-estradiol, and estrone) of the 35 compounds studied were degraded by more than 90%, while 17 compounds (including macrolides and sulfonamides) were removed by less than 50% during biological wastewater treatment The biodegradation of sulfonamides31,33and trimethoprim33has been evaluated in batch reactors, and they were found to be non-readily biodegradable and have the potential to persist in the aquatic environments Many biodegradation studies only report the disappearance of the parent com-pounds but do not elucidate the formation of metabolites, which also may be persistent

and may have similar ecotoxicological effects Recent studies that attempted to identify the byproducts of biodegradation in wastewater indicated that metabolites

of many pharmaceuticals are not very different from their parent compounds For example, Ingerslev and Halling-Sørensen31reported biodegradation of several sul-fonamide antibiotics in activated sludge, based on their disappearance over time, but quantities and identities of transformation product were not reported In another study, the reported metabolites37of the antibiotic trimethoprim in activated sludge have structures that are only slightly modified compared to the parent compound (Figure15.2) Whether these metabolites still exhibit the antibacterial activity of the parent compound or not remains to be tested The lack of sensitive analytical tools able to detect low concentrations of unknown compounds in complex matrices has unfortunately limited the identification of pharmaceutical metabolites formed dur-ing biodegradation in WWTPs This is a critical research need because risk assess-ments based only on the presence of parent compounds in wastewater could lead to underestimation of their risks to the aquatic environment

15.3.2 S ORPTION

It is important to note that the main removal mechanism of some recalcitrant phar-maceuticals in biological WWTPs is sorption on activated sludge, rather than bio-degradation Sorption in WWTPs is more likely an adsorption process, which is the physical adherence onto activated sludge or bonding of ions and molecules onto

O N

N

N 2

NH2 OCH3

H3CO

N

NH2

NH2 OCH3

H3CO

H3CO

CH3

N

NH

NH2

NH2 OCH3

H3CO

H3CO

OH

N

NH2

NH2 OCH3

H3CO

H3CO

Trimethoprim

Trimethoprim Metabolites

FIGURE 15.2 Trimethoprim and its biodegradation metabolites.

the surface of microorganisms or microbial flocs For example, ciprofloxacin and tetracycline are removed mainly by sorption to sludge.38,39A study was conducted

by Kim et al.39to examine the relative importance of biodegradation and sorption

in the removal of tetracycline in activated sludge The similarity in the concentra-tion profiles shown in Figure15.3 obtained from two types of bioreactors, one of which was amended with 0.1% sodium azide to suppress microbial activity, reveals that tetracycline concentration decreases over time even in the “activity-inhibited” control conditions This suggests that the decrease in concentration was not due to biodegradation In fact, chemical analysis of the aqueous phases from these bioreac-tors showed no biodegradation products being formed From this biodegradability test, the strong similarity between inhibited (spiked with tetracycline + 0.1% NaN3) and noninhibited biomass (spiked with tetracycline only), and the lack of tetracy-cline metabolites, suggests that sorption is the primary mechanism for tetracytetracy-cline removal in activated sludge

The sorption isotherm of tetracycline on activated sludge was determined and

is presented inFigure15.4.39The calculated Kadswas 8400 ± 500 mL/g (standard error of slope) This adsorption coefficient in activated sludge is approximately three times that reported for the more polar oxytetracycline (3020 mL/g) and much higher

than that of ciprofloxacin (Kd= 416.9 mL/g),40which was found to be 95% associated with the sludge or biosolids.38Therefore, it is reasonable to assume that tetracycline

is mostly adsorbed in the activated sludge

A study was conducted to compare the sorption kinetics of four selected antibi-otics in activated sludge To inhibit microbial activity, sodium azide was added into the mixed liquor Also, caffeine was spiked into the test system to serve as indicator

of residual biological activity (Caffeine is known to be readily biodegradable and has no measurable sorption to sludge.) The experiment was conducted using 3600 mg/L of mixed liquor suspended solid (MLSS) obtained from a local municipal

250

Spiked Spiked (+0.1% NaN3) 200

150

100

50

0

Time (d)

15

FIGURE 15.3 Removal of tetracycline under batch-activated sludge conditions with active

and “activity-inhibited” biomass (Reactor spiked with 200 μg/L.)

WWTP While more than 80% of ciprofloxacin and tetracycline were removed in the dissolved phase after a 5-h equilibration, only less than 20% of the more hydro-philic sulfamethoxazole and trimethoprim were removed (Figure 15.5) Removal of caffeine was not observed, indicating that the biological activity of the sludge was inhibited by the addition of azide It can be inferred from these results that sorption

is an important removal mechanism for both ciprofloxacin and tetracycline but not for sulfamethoxazole and trimethoprim Sorption of antibiotics on activated sludge that is eventually land applied poses a special concern because these antibiotics may remain biologically active and thus have the potential to influence selection of anti-biotic-resistant bacteria in the terrestrial environment

15.4 INFLUENCE OF WASTEWATER TREATMENT

PLANT (WWTP) OPERATING CONDITIONS

The performance efficiency of a biological WWTP depends highly on the operating conditions and design and may be affected by disturbances, such as high concentra-tions of pharmaceuticals or potentially toxic chemicals in influent wastewater Usu-ally the flow rate and pollutant concentrations of wastewater are time dependent and hard to control For example, the antibiotic concentrations in a composite sample and

in grab samples were compared in two different WWTPs (Amherst, New York, and Holland, New York) The populations served by Amherst and Holland WWTPs are 115,000 and 1,750, respectively Grab and composite samples were obtained twice during the day (8A.M and 4P.M.) Both grab and composite samples were analyzed for four selected antibiotics (ciprofloxacin, sulfamethoxazole, tetracycline, trim-ethoprim).Figure 15.6shows the difference in concentration (% variation) for each antibiotic in the grab samples relative to the concentrations obtained in composite

0.4

Kdes = 22600 ± 2,200

R2 = 0.850

Kads = 8400 ± 500

R2 = 0.943 0.3

0.2

0.1

0.0

0.0 1.0 × 10–5 2.0 × 10–5 3.0 × 10–5

Concentration of Tetracycline in Solution (mg/mL)

4.0 × 10–5 5.0 × 10–5 6.0 × 10–5

FIGURE 15.4 Adsorptionanddesorptionisothermsfortetracyclineonactivatedsludge.Kads:

samples There is high variability in the antibiotic concentrations during the two sampling times in the smaller WWTP (Holland), showing up to 70% difference in concentrations between the grab samples and the composite samples Joss et al.41also reported higher pharmaceutical loads in daytime composite samples (8:00 to 16:00)

as compared with other sampling times This trend is similar to the characteristics of conventional pollutant indicators such as suspended solid (SS) or biological oxygen demand (BOD).14This observation suggests that these conventional parameters may

be good indicators for predicting the load of antibiotics in WWTPs

Some degree of biological WWTP removal efficiency can be controlled by oper-ating parameters such as solid retention time (SRT) and hydraulic retention time (HRT) Several studies reported that biological wastewater treatment processes with higher solids retention time (SRT) (>10 days) tend to have better removal efficiencies for pharmaceutical compounds compared to lower SRT processes.35,42,43This obser-vation implies that there is an enhanced biodegradation ability or different sorption capacity for microcontaminants in sludge with a higher SRT

Kim et al.39 reported the influence of HRT and SRT on the removal of tetra-cycline in the activated sludge processes, using a sequencing batch reactor (SBR) spiked with 250 μg/L of tetracycline Three different operating conditions were applied during the study (Phase 1—HRT: 24 h, SRT: 10 d; Phase 2—HRT: 7.4 h, SRT: 10 d; Phase 3—HRT: 7.4 h, SRT: 3 d) The removal efficiency of tetracycline in Phase 3 (78.4 ± 7.1%) was significantly lower than that observed in Phase 1 (86.4 ± 8.7%) and Phase 2 (85.1 ± 5.4%) at the 95% confidence level The reduction of SRT

in Phase 3 while maintaining a constant HRT decreased tetracycline sorption, result-ing in decreased removal To date, there is little evidence in the literature to suggest biodegradation as a likely removal mechanism for tetracycline Because of the high sorption of tetracycline in sludge, the influence of SRT on the sorption behavior of
















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 "

!



FIGURE 15.5 Antibiotic removal by adsorption in activated sludge (Caffeine was used as

marker for residual biological activity.)

pharmaceuticals is of interest, as sorption characteristics of the biomass may change with SRT Several researchers have observed increased biomass hydrophobicity at higher SRTs.44,45In fact, recent work by Harper and Yi46has shown that bioreactor configuration can have a significant influence on biomass hydrophobicity and parti-cle size, which can affect the bioavailability and fate of pharmaceuticals in WWTPs because of their impact on particle floc characteristics Even though tetracycline has

a low n-octanol/water partition coefficient, at certain pH values, hydrophobic inter-actions still play a role for the sorption of tetracycline on soil or clay.47

Batt et al.48explored the occurrence of ciprofloxacin, sulfamethoxazole, tetracy-cline, and trimethoprim antibiotics in four full-scale WWTPs The WWTPs chosen utilized a variety of secondary removal processes, such as a two-stage activated sludge process with nitrification, extended aeration, rotating biological contactors, and pure oxygen activated sludge In all four WWTPs, the highest reduction in anti-biotic concentrations was observed after the secondary treatment processes, which

is where the majority of the organic matter is eliminated and therefore is the most important processes for antibiotic removal The extended aeration combined with

80 60 40 20 0 –20

–40

–60

Amherst Influent

8- AM 4- PM

–80

–100

Trimethoprim Tetracycline Ciprofloxacin Sulfamethoxazole

80 60 40 20 0

Holland Influent

8- AM 4- PM

100

–20

–40

–60

–80

–100

Trimethoprim Tetracycline Ciprofloxacin Sulfamethoxazole

FIGURE 15.6 Variation of antibiotic concentrations during the day (Error bars correspond

to one standard deviation.)

ferrous chloride precipitation utilized at the East Aurora, New York, plant proved to

be the most effective of the WWTP designs examined in terms of the overall removal

of the four antibiotics Extended aeration operates with the longest HRT among all the processes investigated (28 to 31 hours as opposed to 1 to 4 hours) Higher over-all removal was observed at the Amherst, New York, plant than the remaining two (Holland, New York, and Lackawana, New York), with the second-stage activated sludge process at the Amherst operating with the longest SRT of the investigated WWTPs

The enhanced nitrification activity under long SRT has been suggested to play an important role in the increased removal of micropollutants, such as pharmaceuticals,

in WWTPs.33,37,43It was noted that ammonia oxidizing bacteria (AOB) can come-tabolize various polyhalogenated ethanes49and monocyclic aromatic compounds.50

It also has been reported that trimethoprim antibiotic can be removed more effec-tively in nitrifying activated sludge (high SRT) compared with that in conventional activated sludge (short SRT).33,37,51 Batt et al.51 investigated the fate of iopromide and trimethoprim under lab-scale nitrifying activated sludge A significantly higher biodegradation of both iopromide and trimethoprim was observed in the bioreac-tor where the activity of nitrifying bacteria was not inhibited (Batch-1), relative to the bioreactor where nitrification was inhibited by addition of allylthiourea (Batch-2)(Figure 15.7) These results provide strong evidence that nitrifying bacteria play

a key role in enhancing the biodegradation of pharmaceuticals in WWTPs.33,37 It appears that prolonging SRT to achieve stable nitrification in the activated sludge has an added benefit of increasing the removal efficiencies of microcontaminants

A similar observation relating SRT and percent removal was reported recently for

100

90

80

70

60

50

40

30

20

10

0

Batch-1

Reactor Type

Batch-2

Iopromide Trimethoprim

FIGURE 15.7 Iopromide and trimethoprim removal in nitrifying activated sludge: without

amonia oxidizing material (AOB) inhibition (Batch-1), and with AOB inhibition (Batch-2) (Error bars correspond to one standard deviation.)

ing SRTs.43

It is clear from the existing knowledge that attention is needed on optimizing WWTP operation to achieve maximum removal efficiencies of pharmaceuticals in waste-water It is known that current WTTP designs do not eliminate many micropollut-ants completely While various treatment processes in drinking water production (such as activated carbon, ozonation, and membrane technologies) are effective in reducing concentration of micropollutant,32these technologies are not easily afford-able at many municipal WWTP facilities Therefore, prolonging SRT in WWTPs may be a simple solution to reduce the concentrations of pharmaceuticals in treated wastewater

Knowledge of the identities of metabolites, particularly those that are similar

in structures to the parent pharmaceuticals and are persistent in the environment,

is critical For a complete risk assessment of pharmaceuticals in the environment,

it will be necessary to consider persistent transformation products in the equation because these compounds may pose their own ecological risks To date, ecotoxicity data on metabolites and mixtures of pharmaceuticals are scarce

In a study that aimed at removing organic contaminants from an industrial wastewater treatment, it was found that despite the complete removal of the only known toxic contaminant (diethanolamine) in the wastewater, the toxicity of the bio-logically treated effluents was higher than what was calculated based on the removal efficiency of the total organic carbon.52This implies that the majority of the observed effects after biological treatment must be due to the formation of metabolites, which were not identified in the study In another study example, the photodegradation product of the diuretic drug furosemide was found to be more mutagenic than its parent compound,53further demonstrating the importance of considering byproducts

in toxicity testing and risk assessment

Based on a more realistic ecological and human health risk assessment, current water quality standards can be updated to set acceptable levels of micropollutants that determine how “clean” water should be before it can be discharged into the environment This is particularly critical for recycled wastewater that will be used

as a potable water resource Reduction of pharmaceutical contaminants at the source (effluent of WWTP) is obviously needed if recycled water is to become a significant part of our domestic water supply

REFERENCES

1 Saeijs, H.L and Van Berkel, M.J., Global water crisis: the major issue of the 21st

cen-tury, a growing and explosive problem, Eur Water Poll.Cont., 5, 26, 1995.

2 Papaiacovou, I., Case study—Wastewater reuse in limassol as an alternative water

source, Desalination, 138, 55, 2001.

3 Sedlak, D.L., Gray, J.L., and Pinkston, K.E., Understanding microcontaminants in

recycled water, Environ Sci Technol., 34, 509A, 2000.

The. .. removing organic contaminants from an industrial wastewater treatment, it was found that despite the complete removal of the only known toxic contaminant (diethanolamine) in the wastewater, the. .. efficiencies of pharmaceuticals in waste -water It is known that current WTTP designs not eliminate many micropollut-ants completely While various treatment processes in drinking water production