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

349
15
Remov al of
Pharmaceuticals in
Biological Wastewater
Treatment Plants
Sungpyo Kim, A. Scott Weber,
Angela Batt, and Diana S. Aga
15.1 INTRODUCTION
Providingsufcientlycleanwatertothepublichasbecomeachallengingissue
worldwide as the quality of water sources increasingly deteriorates.
1
Asaconse-
quence, treated wastewater has attracted attention as an alternative water resource,
provided appropriate treatment can be applied.
2
Therefore, the removal of micro-
contaminants,suchaspharmaceuticalsandpersonal-careproducts,inwastewateris
critical because many of these compounds survive conventional treatment.
3
In gen-
eral, these compounds are present at parts per billion (ppb) levels or less in wastewa-
ter.
4,5
Although 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)levelsofethinylestradiol(theactiveingredientsofbirthcontrolpills)and
natural estrogens can disrupt the hormone system of aquatic species.
6,7

In addition,
low levels of antibiotics from the efuents 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 Inuence of Wastewater Treatment Plant (WWTP)
Operating Conditions 354
15.5 Final Remarks 358
References 358
© 2008 by Taylor & Francis Group, LLC
350 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems
Residues of human and veterinary pharmaceuticals are introduced into the envi-
ronmentviaanumberofpathwaysbutprimarilyfromdischargesofwastewatertreat-
ment plants or land application of sewage sludge and animal manure. Most active
ingredientsinpharmaceuticalsaretransformedonlypartiallyinthebodyandthus
areexcretedasamixtureofmetabolitesandbioactiveformsintosewagesystems.
AlthoughWWTPsremovesomepharmaceuticalsduringtreatment,
4,11,12
removal
efcienciesvaryfromplanttoplant.Despiterecentinvestigationsdocumentingthe
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.Wastewatertreatmentprocessgenerallyconsistsofaprimary,secondary,
andsometimesanadvancedtreatmentstage,withdifferentbiological,physical,and
chemicalprocessesavailableforeachstageoftreatment.Aschematicdiagramofa
typical WWTP that employs the activated sludges for secondary treatment is shown
in Figure1 5.1. The primary treatment stage generally utilizes physical treatment,
such as screens and a gravity settling process, typically referred to as sedimenta-
tion,toremovethesolidcontentsinwastewater.Secondarytreatment,whichtypi-
cally relies on microorganisms to biodegrade organic matter and/or other nutrients,
can differ substantially. In some wastewater treatment facilities, the efuent also is
disinfectedbeforeitisreleasedintotheenvironment,typicallybychlorinationor
ultraviolet(UV)radiation.Inaddition,advancedwastetreatmentprocessescanbe
appliedtoremovenitrogen,phosphorus,andotherpollutantsorparticles.
14
RecentreportsdemonstratethatconventionalWWTPsarenotcapableofremov-
ing pharmaceutical contaminants under typical operating conditions, which results
in a discharge of these compounds into surface waters.
5,15–26
Accordingly, WWTPs
areimportantpointsourcesforantibioticcontaminationofsurfacewaters.
4,27–30
15.3 PHARMACEUTICAL REMOVAL MECHANISMS
Several laboratory studies have been conducted to assess the efciencies of vari-
ous treatment technologies in removing antibiotics and other pharmaceuticals from
ABC
A: Primary Treatment — Screen Bar and First Settlement
B: Secondary Treatment — Activated Sludge and Second Settlement

C: Advanced Treatment — Chlorination
FIGURE 15.1 Aschematicdiagramofbiologicalwastewatertreatmentprocess.
© 2008 by Taylor & Francis Group, LLC
Removal of Pharmaceuticals in Biological Wastewater Treatment Plants 351
wastewater.
31–33
The primary pollutant removal mechanisms in conventional biologi-
cal wastewater treatment processes are biodegradation and sorption by microorgan-
is
ms.Therefore,itisreasonabletoassumethatthekeycomponentinbiological
WWTPsresponsiblefortheremovalofpharmaceuticalpollutantsistheaeration
basin containing the microorganisms (activated sludge). Biodegradation and sorption
alsocouldtakeplaceinotherunitprocesses,suchasprimarysettling,butremoval
efciencies at this stage are difcult to control.
14
Other removal mechanisms such as
volatilization(duetoaeration)orphotodegradation(duetosunlight)areeithernegli-
gi
ble or nonexistent.
34
Disinfection 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,notallWWTPsincludeadisinfectionstep,manyfacilitiesonlydisinfect
treated efuents seasonally, and several studies reported that disinfection does not
effectively remove a wide range of antibiotics.
18,35
Accordingly, in this chapter we
will limit our discussion on the pharmaceutical removal by biodegradation and sorp-
ti

on. However, Chapters 10, 11, and 12 int
his book examine the efciencies of vari-
ous disinfection processes in the removal of pharmaceuticals in drinking water.
15.3.1 BIODEGRADATION AND BIOTRANSFORMATIONS
DuringbiologicaldegradationinWWTPs,pharmaceuticalcontaminantscould
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
-
ti
on of pharmaceuticals relative to other pollutants in wastewater may be insufcient
to induce enzymes that are capable of degrading pharmaceuticals.
3
Second,manyof
these compounds are bioactive, which can inhibitgrowthormetabolismofmicroor-
ga
nisms. Thus, it is unlikely that pharmaceuticals will be favorable energy or carbon
sources for microorganisms. Third, the degree of biodegradation will depend on the
natureofeachcompoundandontheoperatingconditionsemployedinWWTPs.
Joss et al.
34
provided a comprehensive and intensive study investigating the bio-
degradationofpharmaceuticals,hormones,andpersonal-careproductsinmunicipal
wastewater treatment. Target compounds included antibiotics, antidepressants, anti
-

ep
ileptics, antiphlogistics, contrast agents, estrogens, lipid regulators, nootropics,
andfragrances.Amongthem,only4(ibuprofen,paracetamol,17
C-estradiol, a
nd
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 sulfonamides
31,33
and
trimethoprim
33
has been evaluated in batch reactors, and they were found to be non-
readilybiodegradableandhavethepotentialtopersistintheaquaticenvironments.
Many biodegradation studies only report the disappearance of the parent com
-
po
undsbutdonotelucidatetheformationofmetabolites,whichalsomaybepersistent
© 2008 by Taylor & Francis Group, LLC
352 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems
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-Sørensen
31
reported 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 metabolites
37

of the antibiotic trimethoprim in activated sludge
have structures that are only slightly modied compared to the parent compound
(Figure 15.2). 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 identication of pharmaceutical metabolites formed dur-
ingbiodegradationinWWTPs.Thisisacriticalresearchneedbecauseriskassess-
ments based only on the presence of parent compounds in wastewater could lead to
underestimationoftheirriskstotheaquaticenvironment.
15.3.2 SORPTION
Itisimportanttonotethatthemainremovalmechanismofsomerecalcitrantphar-
maceuticals in biological WWTPs is sorption on activated sludge, rather than bio-
degradation.SorptioninWWTPsismorelikelyanadsorptionprocess,whichis
the physical adherence onto activated sludge or bonding of ions and molecules onto
O
N
N
N
NH
2
NH
2
OCH
3
H
3
CO
H
3
CO

OH
N
N
NH
2
NH
2
OCH
3
H
3
CO
H
3
CO
CH
3
N
NH
NH
2
NH
2
OCH
3
H
3
CO
H
3

CO
OH
N
NH
2
NH
2
OCH
3
H
3
CO
H
3
CO
Trimethoprim
Trimethoprim Metabolites
FIGURE 15.2 Trimethoprim and its biodegradation metabolites.
© 2008 by Taylor & Francis Group, LLC
Removal of Pharmaceuticals in Biological Wastewater Treatment Plants 353
the surface of microorganisms or microbial ocs. For example, ciprooxacin and
tetracycline are removed mainly by sorption to sludge.
38,39
Astudywasconducted
byKimetal.
39
to examine the relative importance of biodegradation and sorption
in the removal of tetracycline in activated sludge. The similarity in the concentra-
tion proles shown inFigure 15.3obtainedfromtwotypesofbioreactors,oneof
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-
torsshowednobiodegradationproductsbeingformed.Fromthisbiodegradability
test,thestrongsimilaritybetweeninhibited(spikedwithtetracycline+0.1%NaN
3
)
andnoninhibitedbiomass(spikedwithtetracyclineonly),andthelackoftetracy-
cline metabolites, suggests that sorption is the primary mechanism for tetracycline
removal in activated sludge.
The sorption isotherm of tetracycline on activated sludge was determined and
is presented in Figure 15.4.
39
The calculated K
ads
was8400±500mL/g(standard
error of slope). This adsorption coefcient in activated sludge is approximately three
times that reported for the more polar oxytetracycline (3020 mL/g) and much higher
than that of ciprooxacin (K
d
=416.9mL/g),
40
whichwasfoundtobe95%associated
with the sludge or biosolids.
38
Therefore, 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-
oticsinactivatedsludge.Toinhibitmicrobialactivity,sodiumazidewasaddedinto
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
hasnomeasurablesorptiontosludge.)Theexperimentwasconductedusing3600
mg/Lofmixedliquorsuspendedsolid(MLSS)obtainedfromalocalmunicipal
250
Spiked
Spiked (+0.1% NaN
3
)
200
Concentration (µg/L)
150
100
50
0
0510
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.)
© 2008 by Taylor & Francis Group, LLC
354 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems
WWTP. While more than 80% of ciprooxacin and tetracycline were removed in
thedissolvedphaseaftera5-hequilibration,onlylessthan20%ofthemorehydro-
phi
lic sulfamethoxazole and trimethoprim were removed (Figure 15.5). Removal o
f
caffeine was not observed, indicating that the biological activity of the sludge was
inhibitedbytheadditionofazide.Itcanbeinferredfromtheseresultsthatsorption
is an important removal mechanism for both ciprooxacin 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 inuence selection of anti
-
bi
otic-resistant bacteria in the terrestrial environment.
15.4 INFLUENCE OF WASTEWATER TREATMENT
PLANT (WWTP) OPERATING CONDITIONS
The performance efciency of a biological WWTP depends highly on the operating
conditionsanddesignandmaybeaffectedbydisturbances,suchashighconcentra-
ti
ons of pharmaceuticals or potentially toxic chemicals in inuent wastewater. Usu-
al
ly the ow 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,NewYork).ThepopulationsservedbyAmherstandHollandWWTPsare
115,000and1,750,respectively.Grabandcompositesampleswereobtainedtwice
during the day (8
A.M.and4P.M.).Bothgrabandcompositesampleswereanalyzed
for four selected antibiotics (ciprooxacin, sulfamethoxazole, tetracycline, trim-
et
hoprim). Figure 15.6 shows t
he difference in concentration (% variation) for each
antibiotic in the grab samples relative to the concentrations obtained in composite
Amount of Tetracycline Sorbed/
Mass of Sorbent (mg/g)
0.5
0.4
K
des

= 22600 ± 2,200
R
2
= 0.850
K
ads
= 8400 ± 500
R
2
= 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 Adsorption and desorption isotherms for tetracycline on activated sludge.K
ads
:sorp-

tion coefcient, K
des
: desorption coefcient. (Error bars correspond to one standard deviation.)
© 2008 by Taylor & Francis Group, LLC
Removal of Pharmaceuticals in Biological Wastewater Treatment Plants 355
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.
41
also
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
conventionalpollutantindicatorssuchassuspendedsolid(SS)orbiologicaloxygen
demand (BOD).
14
This observation suggests that these conventional parameters may
be good indicators for predicting the load of antibiotics in WWTPs.
Some degree of biological WWTP removal efciency can be controlled by oper
-
ati
ng parameters such as solid retention time (SRT) and hydraulic retention time
(HRT). Several studies reported that biological wastewater treatment processes with
highersolidsretentiontime(SRT)(>10days)tendtohavebetterremovalefciencies
for pharmaceutical compounds compared to lower SRT processes.
35,42,43
This obser-
vation implies that there is an enhanced biodegradation ability or different sorption
capacityformicrocontaminantsinsludgewithahigherSRT.
Kimetal.
39

reported the inuence of HRT and SRT on the removal of tetra-
cyclineintheactivatedsludgeprocesses,usingasequencingbatchreactor(SBR)
spikedwith250μg/Loftetracycline.Threedifferentoperatingconditionswere
appliedduringthestudy(Phase1—HRT:24h,SRT:10d;Phase2—HRT:7.4h,
SRT: 10 d; Phase 3—HRT: 7.4 h, SRT: 3 d). The removal efciency of tetracycline in
Phase3(78.4±7.1%)wassignicantlylowerthanthatobservedinPhase1(86.4±
8.7%)andPhase2(85.1±5.4%)atthe95%condencelevel.ThereductionofSRT
inPhase3whilemaintainingaconstantHRTdecreasedtetracyclinesorption,result
-
in
gindecreasedremoval.Todate,thereislittleevidenceintheliteraturetosuggest
biodegradationasalikelyremovalmechanismfortetracycline.Becauseofthehigh
sorption of tetracycline in sludge, the inuence of SRT on the sorption behavior of










#
$ 
 "
!

 
FIGURE 15.5 Antibiotic removal by adsorption in activated sludge. (Caffeine was used as

marker for residual biological activity.)
© 2008 by Taylor & Francis Group, LLC
356 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems
pharmaceuticals is of interest, as sorption characteristics of the biomass may change
withSRT.Severalresearchershaveobservedincreasedbiomasshydrophobicityat
higher SRTs.
44,45
Infact,recentworkbyHarperandYi
46
has shown that bioreactor
conguration can have a signicant inuence on biomass hydrophobicity and parti-
cl
esize,whichcanaffectthebioavailabilityandfateofpharmaceuticalsinWWTPs
because of their impact on particle oc characteristics. Even though tetracycline has
a low n-octanol/water partition coefcient, at certain pH values, hydrophobic inter
-
act
ionsstillplayaroleforthesorptionoftetracyclineonsoilorclay.
47
Batt et al.
48
explored the occurrence of ciprooxacin, 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 nitrication, extended aeration, rotating biological contactors,
andpureoxygenactivatedsludge.InallfourWWTPs,thehighestreductioninanti
-
bi
otic 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
100
80
60
40
20
0
–20
Concentration Variation (%)
–40
–60
Amherst
Influent
8-
AM 4-PM
–80
–100
Trimethoprim
Tetracycline
Ciprofloxacin
Sulfamethoxazole
80
60
40
20
0
Concentration Variation (%)
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.)
© 2008 by Taylor & Francis Group, LLC
Removal of Pharmaceuticals in Biological Wastewater Treatment Plants 357
ferrous chloride precipitation utilized at the East Aurora, New York, plant proved to
bethemosteffectiveoftheWWTPdesignsexaminedintermsoftheoverallremoval
ofthefourantibiotics.ExtendedaerationoperateswiththelongestHRTamongall
theprocessesinvestigated(28to31hoursasopposedto1to4hours).Higherover
-
al
l removal was observed at the Amherst, New York, plant than the remaining two
(Holland,NewYork,andLackawana,NewYork),withthesecond-stageactivated
sludge process at the Amherst operating with the longest SRT of the investigated
WWTPs.
The
enhanced nitrication activity under long SRT has been suggested to play an
important role in the increased removal of micropollutants, such as pharmaceuticals,
in WWTPs.
33,37,43

It was noted that ammonia oxidizing bacteria (AOB) can come-
tabolize various polyhalogenated ethanes
49
andmonocyclicaromaticcompounds.
50
It also has been reported that trimethoprim antibiotic can be removed more effec-
ti
vely 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 signicantly higher
biodegradation of both iopromide and trimethoprim was observed in the bioreac-
to
r where the activity of nitrifying bacteria was not inhibited (Batch-1), relative to
the bioreactor where nitrication was inhibited by addition of allylthiourea (Batch-
2)
(Figure15.7).The
se results provide strong evidence that nitrifying bacteria play
a key role in enhancing the biodegradation of pharmaceuticals in WWTPs.
33,37
It
appearsthatprolongingSRTtoachievestablenitricationintheactivatedsludge
has an added benet of increasing the removal efciencies of microcontaminants.
A similar observation relating SRT and percent removal was reported recently for
100
Removal Percentage (%)
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.)
© 2008 by Taylor & Francis Group, LLC
358 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems
other pharmaceuticals and personal-care products in full-scale WWTPs with vary-
ing SRTs.
43
15.5 FINAL REMARKS
It is clear from the existing knowledge that attention is needed on optimizing WWTP
operation to achieve maximum removal efciencies of pharmaceuticals in waste-
wat
er.ItisknownthatcurrentWTTPdesignsdonoteliminatemanymicropollut-
an
tscompletely.Whilevarioustreatmentprocessesindrinkingwaterproduction
(such as activated carbon, ozonation, and membrane technologies) are effective in

reducing concentration of micropollutant,
32
these technologies are not easily afford-
able at many municipal WWTP facilities. Therefore, prolonging SRT in WWTPs
maybeasimplesolutiontoreducetheconcentrationsofpharmaceuticalsintreated
wastewater.
Knowledge of the identities of metabolites, particularly those that are similar
in structures to the parent pharmaceuticals and are persistent in the environment,
iscritical.Foracompleteriskassessmentofpharmaceuticalsintheenvironment,
itwillbenecessarytoconsiderpersistenttransformationproductsintheequation
becausethesecompoundsmayposetheirownecologicalrisks.Todate,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
-
lo
gically treated efuents was higher than what was calculated based on the removal
efciency of the total organic carbon.
52
This implies that the majority of the observed
effectsafterbiologicaltreatmentmustbeduetotheformationofmetabolites,which
werenotidentiedinthestudy.Inanotherstudyexample,thephotodegradation
product of the diuretic drug furosemide was found to be more mutagenic than its
parent compound,
53
further demonstrating the importance of considering byproducts
in toxicity testing and risk assessment.
Basedonamorerealisticecologicalandhumanhealthriskassessment,current
water quality standards can be updated to set acceptable levels of micropollutants

thatdeterminehow“clean”watershouldbebeforeitcanbedischargedintothe
environment. This is particularly critical for recycled wastewater that will be used
asapotablewaterresource.Reductionofpharmaceuticalcontaminantsatthesource
(efuent of WWTP) is obviously needed if recycled water is to become a signicant
part of our domestic water supply.
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