Académique Documents
Professionnel Documents
Culture Documents
discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/256289366
CITATIONS READS
75 845
8 authors, including:
Some of the authors of this publication are also working on these related projects:
Towards Sustainable Environmental Quality: The Global Horizon Scanning Project View project
All content following this page was uploaded by Bowen Du on 25 May 2017.
The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document
and are linked to publications on ResearchGate, letting you access and read them immediately.
Science of the Total Environment 466467 (2014) 976984
H I G H L I G H T S
An analysis of efuents from wastewater systems receiving a common inuent was performed.
Seasonal differences of select pharmaceuticals were identied in inuent wastewater.
Removal of pharmaceuticals by an advanced aerobic onsite system compared to a centralized system
Various pharmaceuticals in efuents were predicted to present therapeutic hazards to sh.
a r t i c l e i n f o a b s t r a c t
Article history: A comparative understanding of efuent quality of decentralized on-site wastewater treatment systems, partic-
Received 3 July 2013 ularly for contaminants of emerging concern (CECs), remains less understood than efuent quality from central-
Received in revised form 31 July 2013 ized municipal wastewater treatment plants. Using a novel experimental facility with common inuent
Accepted 31 July 2013
wastewater, efuent water quality from a decentralized advanced aerobic treatment system (ATS) and a typical
Available online xxxx
septic treatment system (STS) coupled to a subsurface ow constructed wetland (WET) were compared to
Editor: D. Barcelo efuent from a centralized municipal treatment plant (MTP). The STS did not include soil treatment, which
may represent a system not functioning properly. Occurrence and discharge of a range of CECs were examined
Keywords: using isotope dilution liquid chromatographytandem mass spectrometry during fall and winter seasons. Con-
Efuent ventional parameters, including total suspended solids, carbonaceous biochemical oxygen demand and nutrients
Decentralized wastewater treatment were also evaluated from each treatment system. Water quality of these efuents was further examined using a
Pharmaceuticals therapeutic hazard modeling approach. Of 19 CECs targeted for study, the benzodiazepine pharmaceutical
Wastewater indicators diazepam was the only CEC not detected in all wastewater inuent and efuent samples over two sampling
Water quality
seasons. Diphenhydramine, codeine, diltiazem, atenolol, and diclofenac exhibited signicant (p b 0.05) seasonal
differences in wastewater inuent concentrations. Removal of CECs by these wastewater treatment systems was
generally not inuenced by season. However, signicant differences (p b 0.05) for a range of water quality indi-
cators were observed among the various treatment technologies. For example, removal of most CECs by ATS was
generally comparable to MTP. Lowest removal of most CECs was observed for STS; however, removal was
improved when coupling the STS to a WET. Across the treatment systems examined, the majority of pharmaceu-
ticals observed in on-site and municipal efuent discharges were predicted to potentially present therapeutic
hazards to sh.
2013 Elsevier B.V. All rights reserved.
1. Introduction
0048-9697/$ see front matter 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.scitotenv.2013.07.126
B. Du et al. / Science of the Total Environment 466467 (2014) 976984 977
1999; Halling-Srensen et al., 1998; Kolpin et al., 2002). Introduction of existed for wastewater inuent and centralized and decentralized
CECs to aquatic systems can contaminate surface and ground waters efuent discharges. Lastly, efuent water quality of each discharge
and thus present risks to human health and ecosystems (Brooks et al., was compared using a sh plasma model to estimate therapeutic
2009), particularly when pharmaceuticals and other CECs bioaccumulate hazards of pharmaceuticals.
in aquatic organisms (Daughton and Brooks, 2011). Clearly, a number of
research questions need to be answered to better understand human
and ecological risks of pharmaceuticals and personal care products in 2. Material and methods
the environment (Boxall et al., 2012).
Though centralized WWTPs have received much study in recent 2.1. Study site
years, comparatively less attention has been given to efuent quality
from onsite-wastewater treatment plants, which service over 20% of This study was performed at the Baylor Wastewater Research
the United States population (American Housing Survey, 2011). Insuf- Program (BWRP) site (Fig. 1), located at the Waco Metropolitan Area
cient removal, due to design, malfunction or lack of maintenance, has Regional Sewerage System (WMARSS; www.wmarss.com) in Waco,
resulted in this release of little treated or untreated wastewater contain- Texas, USA, adjacent to the National Sanitation Foundation's (NSF)
ing CECs to the environment from on-site wastewater treatment sys- international testing facility for on-site wastewater treatment systems.
tems (Conn et al., 2006; Garcia et al., 2013; Godfrey et al., 2007; Inuent from WMARSS, a traditional activated sludge municipal treat-
Hinkle et al., 2005; Stanford and Weinberg, 2010; Wilcox et al., 2009). ment plant (MTP) with a mean daily load of ~25 million gal per day
Historically, septic treatment systems have been commonly employed (MGD) and a design capacity of 40 MGD, is continuously diverted to
for on-site wastewater treatment, but it is estimated that at least 10 to the NSF and BWRP facilities, in which it is further partitioned to various
20% of septic systems malfunction annually (U.S.EPA., 2002, 2005). on-site wastewater treatment technologies for study (Fig. 1). In the
Subsequently, similar to the environmental exposures resulting from present study, we selected one advanced aerobic treatment systems
efuent discharge of municipal treatment plants, releases of untreated (ATS), a two-chambered 1500-gallon tank with no lter septic treat-
wastewater to groundwater and surface water can degrade water ment system (STS), and a subsurface ow constructed wetland (WET)
quality and result in impacts to surface waters in regions experiencing receiving efuent from STS as model systems for a comparative efuent
high groundwatersurface water exchange (U.S.FDA, 2009; Meredith- water quality evaluation to the MTP (Garcia et al., 2013). The ATS was a
Williams et al., 2012). Pharmaceuticals, estrogenic contaminants, and 1500-gallon multi-chambered system with an activated sludge process,
nonylphenols have been detected in groundwater of regions heavily a pretreatment tank, an aeration chamber and a nal clarier. It is criti-
relying on septic systems (Conn et al., 2006; Godfrey et al., 2007; cal to note that STS did not have traditional soil absorption draineld
Swartz et al., 2006). However, a comparative understanding of efuent following septic tank, which may represent an improperly functioning
quality of these decentralized systems, particularly for CECs, remains system (Garcia et al., 2013). In this study, a WET was employed to po-
less understood than those from centralized municipal wastewater tentially improve indicators of water quality from septic tank efuent.
treatment plants (Garcia et al., 2013). The WET was lled with media composed of siliceous and carbonate
Understanding the relevance of CEC exposures to the health of gravel, 2 to 4 cm in diameter, with an average porosity of 37.3%. Plants
aquatic organisms represents a major prerequisite to evaluate efuent selected in this study included cattail (Typha latifolia), bulrush (Scirpus
quality of wastewater treatment systems (Boxall et al., 2012; Brooks cubensis), pickerel weed (Pontederia cordata) and iris (Iris pseudacorus).
et al., 2009). Because therapeutic targets are evolutionarily conserved The majority of these plants were transplanted from the Lake Waco
in many aquatic organisms, mammalian pharmacology data can be Wetlands to the WET (Davila, 2006). All on-site treatment systems
leveraged to predict adverse effects (Ankley et al., 2007; Gunnarsson were dosed 480 gal/day municipal wastewater inuent following an
et al., 2008). In fact, such comparative pharmacology methods are criti- American National Standards Institute/standard of 40 design loading
cal to evaluate the aquatic risks of pharmaceuticals due to the linkage (NSF International, 2005).
between adverse effects and therapeutic activity (Berninger and Brooks,
2010; Connors et al., 2013).
In the present study, a comparative examination of centralized 2.2. Chemicals
and decentralized efuent quality was performed by applying a sh
plasma model approach to estimate the therapeutic hazards of efu- Target analytes were selected based on their previously monitored
ent discharge. This approach predicts internal doses of pharmaceuti- occurrences in wastewater, surface water, and aquatic organisms ex-
cals in sh based on water exposure concentrations, builds on an posed to efuent discharge (Du et al., 2012; Gheorghe et al., 2008;
initial concept proposed by Huggett et al (2003) and was recently Kolpin et al., 2002; Letzel et al., 2010; Loos et al., 2009; MacLeod and
demonstrated by our research team (Berninger et al., 2011; Valenti Wong, 2010; Radjenovi et al., 2009). Selection also required the avail-
et al., 2012) and others (Fick et al., 2010a; Fick et al., 2010b; ability of isotopically-labeled analogs for each study compound and the
Schreiber et al., 2011). Interpreting the internal doses of pharmaceu- capacity of the analytes to be concurrently extracted effectively. Methyl-
ticals in plasma of aquatic organisms (e.g., sh) is more critical for phenidate, methylphenidate-d9, benzoylecgonine, and benzoylecgonine-
pharmaceuticals than water or traditional body burden approaches d3 were obtained as certied analytical standards from Cerilliant (Round
because critical plasma levels are closely relevant to therapeutic ac- Rock, TX, USA). Erythromycin-13Cd3, celecoxib, celecoxib-d4, warfarin,
tivity and resulting ecological consequences (Brooks et al., 2009; warfarin-d5, and diclofenac-d4 were purchased from Toronto Research
Daughton and Brooks, 2011; Huggett et al., 2003). For example, a con- Chemicals (Toronto, Ontario, Canada). Sucralose, erythromycin, and
ceptually similar approach was applied by Fick et al. (2010a) to quantify diclofenac were obtained from Sigma-Aldrich (St. Louis, MO, USA).
pharmaceuticals in plasma of trout caged in several Swedish rivers Sucralose-d6 was purchased from Santa Cruz Biotechnology (Santa
inuenced by wastewater efuents. Because an ER 1 indicates that Cruz, CA, USA). All chemicals obtained for present study were with purity
the predicted FSSPC may be expected to trigger a pharmacological effect 97%. Vendors for the remaining standards and labeled analogs were
in sh, an ER = 1000 was suggested by Huggett et al (2003) as a safety provided in previous work (Du et al., 2012; Ramirez et al., 2007). HPLC
factor. grade methanol was obtained from Fisher Scientic (Fair Lawn, NJ,
The primary objective of present study was to compare occurrence, USA) and formic acid was purchased from VWR Scientic (Radnor, PA,
removal and discharge of selected CECs from municipal and on-site USA). A Thermo Barnstead Nanopure (Dubuque, IA, USA) Diamond UV
treatment systems receiving a common wastewater inuent. As a water purication system was used throughout the analysis to provide
secondary objective, we further examined whether seasonal patterns 18 M water.
978 B. Du et al. / Science of the Total Environment 466467 (2014) 976984
MTP
Discharge
ATS
Municipal
Influent A B C
Fig. 1. Schematic of Baylor Wastewater Research Program (BWRP) site. A. permanent tank; B. aeration chamber; C. nal clarier. MTP = municipal treatment plant; ATS = aerobic treat-
ment system; STS = septic treatment system; WET = wetland.
2.3. Sample collection and 0.2-m paper lters and a mixture of internal standards was added
to each sample (150 ml of inuent and STS efuent; 250 ml of efuents
Composite samples of efuent from four treatment systems and the from other systems); all samples contained 100 ng of each labeled
MTP inuent were collected in October 2011 and January 2012, labeled analog prior to extraction. Samples were loaded onto preconditioned
fall and winter, in accordance with one of our objectives to evaluate 6 ml/200 mg hydrophiliclipophilic-balanced (HLB) SPE cartridges
the inuence of season. The mean temperatures over the two sampling from Waters Corporation (Milford, MA, USA). The cartridges were air-
seasons were 18.3 C and 10.8 C, respectively. Heterogeneity caused by dried for 5 min and subsequently eluted with 5 mL methanol followed
a number of discrete wastewater discharge from various domestic or by 5 mL 10:90 (v/v) methanol-methyl tertiary butyl and resulting ex-
industrial activities may result in short-term variations of pollutant tracts were evaporated to dryness under a gentle nitrogen stream.
loadings, particularly for personal care products and pharmaceuticals Prior to analysis, samples were sonicated and ltered using Pall Acrodisc
in wastewater inuent (Ort et al., 2010; Teerlink et al., 2012). In the hydrophobic Teon Supor membrane syringe lters (13-mm diameter;
present study, in order to minimize the variation during sampling pe- 0.2-m pore size).
riods, 48-hour ow-weighted inuent and on-site composite efuent Wastewater samples were analyzed using isotope dilution liq-
samples and 24-hour ow-weighted MTP efuent were automatically uid chromatographytandem mass spectrometry (LCMS/MS) with
collected by using timers and peristaltic pumps to collect volumetrically electrospray ionization (ESI). Details pertaining to LCMS/MS analysis,
calibrated samples each hour. Sample collection from each treatment including the ionization mode (ESI+ or ESI) and precursor-to-
system accounted for each corresponding hydraulic retention times product ion transitions for most analytes, were previously described
(MTP: ~6 h; ATS, STS, and WET: ~48 h), which have not varied over (Du et al., 2012). The ionization mode and monitored transitions for
the last ten years (Davila, 2006; Garcia et al., 2013). Experimental sam- benzoylecgonine and internal standard benzoylecgonine-d3, which
pling included four samples each on weekends and weekdays during had not been reported previously by our group, were as follows:
each season to identify possible day of week inuences on CEC loading. ESI + benzoylecgonine 290 N 168 and benzoylecgonine-d3 293 N 171.
All wastewater inuent and efuent samples were collected in 4-L A second primary metabolite of cocaine, ecgonine methyl ester (EME),
amber glass bottles and kept dark and refrigerated at 4 C during was not examined in the present study. EME's exclusion was based on
composite collection period. Blank samples were collected by placing preliminary work (data not shown) that indicated that EME was poorly
sample bottles openly up to 2 h during composite collection and lled retained in the reversed-phase analytical column employed to separate
in laboratory with tap water. Samples were transported to laboratory the target analytes in the present study; a tendency for EME to elute
on ice and stored at 4 C prior to analysis. Conventional wastewater early is likely due to its high polarity. This observation was consistent
parameters, including total suspended solids (TSS) and carbonaceous with previous ndings (Gheorghe et al., 2008), which suggested that
biological oxygen demand (CBOD) were analyzed at the City of Waco hydrophilic interaction chromatography columns may be the desired
Water Utilities' WMARSS laboratory following standard methods. analytical column to analyze EME or compounds with high polarity.
Ammonia (NH3) was analyzed in the laboratory of Center for Reservoir Method detection limits (MDLs) were determined by extracting and
and Aquatic Systems Research (CRASR) at Baylor University. Solid phase analyzing reference samples (tap water) fortied with target analytes
extraction (SPE) was performed for all CEC samples within 48 h after at a concentration 10 times the reported MDL (Code of Federal
collection. Regulations, 1986). These values represent the lowest concentration of
analyte that may be reported with 99% condence that the concentra-
2.4. Sample preparation and analysis tion is different from zero. MDLs and instrumental limits of detection
(LODs) of target analytes are provided in Table 1. Observed MDLs
The sample extraction used in the present study generally followed a were higher (by a factor of 1.24.4) than the corresponding instrumen-
previously reported protocol (Vanderford and Snyder, 2006). Prior to tal LOD that was calculated using a response equivalent to a signal-to-
SPE, each sample was sequentially ltered through 10 m, 0.45 m, noise ratio of 3 for blank samples. A variety of laboratory control
B. Du et al. / Science of the Total Environment 466467 (2014) 976984 979
Table 1
Application classes, log scale of n-octanol water partition coefcient (logKow), human therapeutic dose (Cmax), matrix spike recovery % ranges, investigated method detection limits
(MDLs) and instrumental limit of detection (LOD) of target analytes.
Analytes Class logKowa Cmax (g/mL)b Matrix spike recovery % range MDL (ng/L) LOD (ng/L)
samples were used in the present study to evaluate data quality. which compared human therapeutic plasma concentrations (HTPC)
Continuing calibration verication (CCV) samples with 100 ng/mL of (e.g. Cmax) of pharmaceuticals to predictions of sh steady state plasma
all analytes were used to monitor instrument calibration with an ac- concentrations (FSSPC) (Huggett et al., 2003):
ceptability criterion of 20%. CCV samples were typically analyzed
after every 5 or 6 injections. Each analytical sample batch included effect ratio ER HTPC=Fss PC: 1
one blank (i.e., tap water spiked with isotopically-labeled internal stan-
dards only) and duplicate matrix spikes (i.e., replicate efuent sample Huggett et al.'s (2003) approach was based on empirical models by
randomly selected and fortied with target analytes at concentrations Fitzsimmons et al (2001) that can be used to predict gill uptake and
identical to the CCV sample). To evaluate the utility of isotope dilution resulting plasma levels of contaminants:
calibration to compensate matrix effects in wastewater, duplicate inu-
ent or efuent samples were fortied with target analytes and internal Fss PC Caqueous Pbw 2
standards. Subsequently, the fortied samples were extracted and
analyzed following the same protocol used for all samples. Matrix where Caqueous was the concentration of pharmaceuticals in an efuent
spike recoveries were calculated as the difference between observed discharge study and Pbw is the partition coefcient between water and
concentrations in spiked and unspiked samples divided by the fortied sh blood. In the present study, partition coefcient between water
concentration. This isotope dilution calibration approach resulted in all and sh blood for a particular pharmaceutical was predicted using the
matrix spike recoveries between 80% and 120%. Eq. 3:
0:73 logKow
2.5. Statistical analysis Pbw 10 0:16 0:84 3
Statistical analysis was performed using SigmaPlot by Systat Soft- where logKow represents n-octanol water partition coefcient and
ware (San Jose, CA, USA) for CECs. Two-way ANOVAs with Tukey test logKow of all pharmaceuticals are given in Table 1.
( = 0.05) was utilized to detect differences in CEC concentrations
among MTP, ATS, STS, and WET samples with sampling dates and sam- 3. Results and discussion
pling seasons as factors if data was normally distributed. Conversely, if
the data did not meet assumptions for ANOVA, the nonparametric 3.1. Conventional wastewater parameters
KruskalWallis test ( = 0.05) was used. Seasonal difference was test-
ed using the MannWhitney test ( = 0.05). Analytes that were not TSS, CBOD, and NH3 were observed in efuent discharges from
detected in the inuent and various efuents were set at half the MDL each treatment system. TSS and CBOD, but not NH3, were also monitored
value for the purpose of statistical analysis (Antweiler and Taylor, in municipal inuent samples. STS efuent exhibited signicantly higher
2008). TSS and CBOD levels (Table 2) than MTP, ATS, and WET efuents
(p b 0.05). Consistent with previous work (Garcia et al., 2013), STS peri-
2.6. Therapeutic hazards of efuent discharges odically failed to meet a CBOD criterion of 65 mg/L that was established
by the Texas Commission on Environmental Quality (TNRCC, 2002).
In the present study, comparative efuent quality was examined by However, efuents from MTP, ATS, and WET did not exceed the criteria
predicting whether pharmaceuticals in efuents would be expected to of TSS and CBOD during the sampling periods. Furthermore, all on-site
accumulate in sh plasma to levels exceeding mammalian therapeutic treatment systems exhibit signicantly higher NH3 levels than the
thresholds. Huggett et al. (2003) initially proposed a sh plasma model MTP (p b 0.05). Lower NH3 concentrations were observed in October
to identify whether various pharmaceuticals may present hazards to than January, possibly due to higher temperature, which results in
sh. This plasma model included an effect ratio (ER) (see Eq. 1 below), higher nitrication. As noted above, it is important to recognize that
980 B. Du et al. / Science of the Total Environment 466467 (2014) 976984
Table 2
Mean (SD) levels of total suspended solids (TSS), carbonaceous biochemical oxygen demand (CBOD), and NH3 of municipal inuent and treated efuent from municipal treatment plant
(MTP), aerobic treatment system (ATS), septic treatment system coupled with subsurface constructed wetland (STS + WET), and septic treatment system only (STS) in October 2011 and
January 2012, respectively.
Oct. 2011 Jan. 2012 Oct. 2011 Jan. 2012 Oct. 2011 Jan. 2012
efuents from on-site treatment tanks were collected directly without concentration in the fall, which potentially coincided with treatment
further soil absorption draineld and thus NH3 was not adequately of elevated seasonal allergies in Texas, USA. Late October pollen counts
nitried. Nutrient loadings from on-site wastewater treatment systems in Waco, Texas, USA during this study revealed that ragweed and other
to groundwater sources, inland and coastal water bodies may exhibit weed levels, which are sources of common allergens, were considered
risks to aquatic organisms (Brooks et al., 2008). Previous studies high and very high, respectively (Allergy and Asthma Center, 2011). In-
(Hinkle et al., 2005) reported further nitrication with various sand terestingly, ragweed and other weed pollen counts were undetected
lters, which may effectively reduce NH3 in efuent discharges. during late January and early February (Allergy and Asthma Center,
2011). Diphenhydramine was recently identied to elicit acute and
3.2. Occurrence patterns of CECs in inuent wastewater chronic toxicity to several aquatic organisms, including the fathead
minnow (Pimephales promelas) (Berninger et al., 2011). Clearly, season-
Of 19 CECs monitored in the present study, 18 were detected in al and site-specic hazards of pharmaceuticals in aquatic systems
municipal treatment plant inuents. Only diazepam was not detected require additional study (Boxall et al., 2012).
during either sampling season. Table 3 shows the mean concentrations Though no signicant difference (p N 0.05) was observed be-
of detected CECs in municipal treatment plant inuent samples collect- tween the two seasons for benzoylecgonine (a primary metabolite
ed for 4 consecutive weeks in both October 2011 and January 2012. The of cocaine), variation in weekday benzoylecgonine levels was evi-
majority of CECs did not exhibit signicant differences between the two dent. Benzoylecgonine concentrations in inuents collected on week-
seasons. However, some pharmaceutical concentrations in the waste- ends were signicantly higher (p b 0.05) than on weekdays. A similar
water inuent varied between seasons. Codeine and diltiazem, for weekday/weekend variability of benzoylecgonine was also observed
example, were signicantly greater (p b 0.05) in winter than in fall; by Kinyua and Anderson (2012); however, absolute concentration of
however, levels of methylphenidate, diphenhydramine, diclofenac, benzoylecgonine detected in wastewater at Lubbock, TX was much
and atenolol were observed to be signicantly greater (p b 0.05) in fall. higher than that detected in wastewater at Waco, TX. The difference
Pharmaceutical concentrations in municipal wastewater treatment of benzoylecgonine level in two cities suggested benzoylecgonine may
plant inuent are increasingly employed to explore temporal consump- exhibit special consumption patterns. Our observations highlight the
tion patterns in cities (Metcalfe et al., 2010). For example, diphenhydra- utility of employing environmental monitoring of wastewater as an ap-
mine, a rst generation antihistamine used in many common over-the- proach to better understand consumption patterns of drugs of abuse
counter or prescription formulations, had approximately 3-fold higher (Thomas et al., 2012; van Nuijs et al., 2011).
Table 3
Mean (SD) levels of detected contaminants of emerging concerns in municipal wastewater inuent on weekdays and weekends in October 2011 and January 2012, respectively.
3.3. Removal of CECs treatment step coupling with septic tank to further attenuate level of
nutrient, organic contaminants (Conn et al., 2010; Van Cuyk et al.,
Percent removals were calculated as the ratio of deviation between 2001) and pharmaceuticals in particular (Teerlink et al., 2012). Lowe
inuent concentrations and efuent concentrations divided by inuent et al. (2008) also evaluated purication efciencies for a couple of
concentrations. Percent removals for all wastewater treatment systems engineered treatment units (a textile lter unit and a membrane
during fall (October 2011) and winter (January 2012) were initially bioreactor coupling with septic tanks), demonstrating both engineered
examined to evaluate potential temporal inuences on the various treatment units result in better removal efciency for organic matter,
wastewater treatment capacities to remove target analytes in this TSS, nutrients, and bacteria relative to a septic tank only. Furthermore,
study. The mean temperature during a 4-week sampling period in here we employed a unique study design to directly compare the per-
October, 2011 was signicantly (p b 0.05) higher than the January, cent removal of CECs and pharmaceuticals in particular for WET relative
2012 study period. CEC removal efciencies were expected to be higher to MTP. Surface and subsurface ow constructed wetlands have been
in the warmer (7.5 C higher) sampling season because of potentially previously shown to remove selected pharmaceuticals (Hijosa-Valsero
higher biodegradation. Contrary to our expectations, however, no et al., 2010; Matamoros et al., 2005). The mechanisms to remove CECs
signicant difference was observed for removals of total concentrations using WET typically include a variety of different processes, such as bio-
of all detected compounds between the two sampling seasons. How- degradation, sorption, sedimentation, and vegetation uptake (Kadlec
ever, signicantly higher removal was observed in the fall for several and Knight, 1996; Matamoros et al., 2005). However, pathways to
CECs, including caffeine (p b 0.05), erythromycin (p b 0.05), gem- remove CECs were not differentiated in the current study. Thus, the pri-
brozil (p b 0.05) and sucralose (p b 0.05). Only removal of diltiazem mary pathways responsible for removal of classes of CECs by wetlands
(p b 0.05) was lower in the fall. Beyond the signicant seasonal remain an area of important research need (Brooks et al., 2011). As
difference observed for these compounds, we observed signicant shown in Table 4, WET offered similar or better removal efciencies
difference in percent removal of some pharmaceuticals across treat- for most CECs examined in the present study relative to MTP with few
ment types. For example, percent removal of caffeine exhibited exceptions (diclofenac, gembrozil, benzoylecgonine), indicating that
signicant difference between STS and STS + WET, STS and ATS, coupling WET with STS may represent an alternative to centralized
STS and MTP, and ATS and STS + WET. Additionally, we did not MTP for removing some CECs from wastewater. Furthermore, the re-
observe signicant differences in percent removal of sucralose across moval data showed that removal efciencies of the on-site wastewater
treatment types, which may be anticipated because sucralose ap- treatment systems studied were relatively lower than or comparable to
pears to be an ideal anthropogenic tracer (Soh et al., 2011). centralized MTP even with extended hydraulic retention times, imply-
The unique design of the BWRP site allowed for direct comparisons ing that upgraded or alternative treatment steps may improve removal
of CEC removal effectiveness between on-site and municipal systems efciency prior to efuent discharges from on-site treatment systems.
(Table 4). Removal of most CECs by ATS was generally comparable to Future studies are needed to examine treatment efcacy and economic
centralized MTP (Table 4). This work supports a previous suggestion tradeoffs when employing and maintaining subsurface constructed
that additional aerobic treatment beyond anaerobic septic treatment wetlands for treatment of efuent from septic tanks as examined in
systems may improve removal efciencies of some CECs likely due to the present study.
improved aerobic biotransformation (Carrara et al., 2008; Conn et al., Among the target CECs in the present study, carbamazepine
2006). Swartz et al (2006) also suggested that percent removal of (Andreozzi et al., 2003) and sucralose (Scheurer et al., 2009) were
many organic wastewater contaminants in the more aerobic portion previously shown to be recalcitrant to various wastewater treatment
of the plume is higher than the sub-aerobic or anaerobic portion processes. Together with caffeine, all three compounds have been
when observing vertical concentration patterns. In current study, the suggested as hydrologic tracers of wastewater (Clara et al., 2004;
lowest removals for most CECs among the studied systems were ob- Oppenheimer et al., 2011; Seiler et al., 1999). In urbanized watersheds,
served with the STS system; however, STS removal was signicantly incomplete removal of these compounds when employing on-site
(p b 0.05) improved when coupled with further treatment by a subsur- wastewater treatments resulted in a greater likelihood of groundwater
face ow constructed wetland (WET). and surface water contamination (Scheurer et al., 2009; Standley
Employment of subsurface constructed wetland to treatment waste- et al., 2008), ultimately contaminating source waters and nished
water efuent from septic tanks may particularly be relevant for areas drinking water (Mawhinney et al., 2011). In both sampling seasons of
that are not suitable for soil absorption draineld, which is a critical the present study, ubiquitously low removal efciencies were observed
Table 4
Mean (SD) percent removal of contaminants of emerging concerns for municipal treatment plant (MTP), aerobic treatment system (ATS), septic treatment system coupled with
subsurface constructed wetland (STS + WET), and septic treatment system only (STS) in October 2011 (mean temp. = 18.3 C) and January 2012 (mean temp. = 10.8 C), respectively.
MTP ATS STS + WET STS MTP ATS STS + WET STS
6 ha 48 h 48 h 48 h 6h 48 h 48 h 48 h
Acetaminophen 100 0.03 100 0.2 100 0.06 65 8 100 0.6 100 0.6 100 0.6 28 30
Codeine 83 20 90 7 99 0.2 33 10 86 30 83 10 100 0.04 42 10
Trimethoprim 88 10 86 3 93 10 20 7 71 40 46 10 100 0.01 12 10
Caffeine 100 0.06 99 0.7 100 0.2 52 40 98 3 89 10 100 0.5 40 20
Sulfamethoxazole 57 40 31 20 48 30 11 10 81 30 17 7 27 10 7.7 5
Diphenhydramine 69 40 60 10 87 40 10 10 68 40 20 30 99 2 3.1 9
Carbamazepine 6.3 7 7.8 5 6.5 3 5.9 3 2.9 3 6.0 6 17 10 7.4 6
Erythromycin 81 30 52 20 92 9 27 20 59 20 47 10 65 20 19 5
Diclofenac 82 20 56 10 43 20 18 8 87 20 34 10 32 10 9.3 4
Gembrozil 91 10 38 10 52 30 36 20 83 30 23 10 30 10 12 7
Atenolol 58 10 84 2 79 4 12 10 38 20 77 8 77 3 13 8
Sucralose 27 20 24 20 18 10 13 10 11 10 10 7 13 8 6.0 4
Diltiazem 96 4 92 7 88 8 47 20 99 1 98 1 98 1 76 10
Benzoylecgonine 98 1.6 86 6 47 20 15 10 89 5 78 10 49 20 18 20
a
Respective hydraulic retention times.
982 B. Du et al. / Science of the Total Environment 466467 (2014) 976984
for carbamazepine (b 20%) and sucralose (b30%) over all treatment diphenhydramine was as resistant as carbamazepine to biodegradation,
systems, but not for caffeine. Typically, ATS was able to remove more indicating that additional treatment processes (e.g., sorption to retained
than 90% of caffeine from wastewater, resulting in similar treatment organic matters) beyond biodegradation may help remove diphen-
performance to MTP (Table 4). Such observations for caffeine are con- hydramine in the wastewater treatment systems (Matamoros and
sistent with previous reports (Hinkle et al., 2005) of greater than Bayona, 2006). Further, given matrix differences between inuent
90% removal in septic tanks. In the present study, however, much and efuent samples, it is possible that uneven matrix effects prevented
less removal of caffeine was observed in STS system, which eventu- the detection of insensitive compounds in inuent samples. In this
ally beneted from maximal removal efciency for caffeine when study, we observed unparallel degree of ion suppression among inu-
coupled with the WET. This observation suggested that carbamaze- ent and efuent samples during LCMS/MS analysis, which may result
pine and sucralose are more recalcitrant during treatment and may in lower detection of CECs in inuent samples.
be more suitable than caffeine to serve as indicators of anthropo-
genic impact via municipal and on-site treatment systems (Soh
et al., 2011). 3.4. Therapeutic hazards of pharmaceuticals in efuent discharges
It is also important to note that elevated concentrations of selected
CECs were observed in efuent, whereas these concentrations were To date, little is known about potential ecological risks of most phar-
undetected or below the corresponding MDLs in the inuent. Similar maceuticals after their introduction in the aquatic environment (Ankley
observations have been previously reported. For example, conjugation et al., 2007; Boxall et al., 2012; Brooks et al., 2009). As noted previously,
of pharmaceuticals to glucoronides during phase II metabolism occurs an understanding of efuent water quality of on-site wastewater
for many drugs. Parent pharmaceuticals are obtained via cleavage of treatment systems is typically only examined using course measures
those conjugates by biotransformation during wastewater treatment, (e.g., TSS, CBOD). The occurrence of numerous pharmaceuticals and
which is reected in the presence, or even elevated concentrations other CECs, such as carbamazepine, sulfamethoxazole, trimethoprim,
seen in the released efuent (Heberer, 2002). In the present study codeine, acetaminophen, caffeine, in septic tank efuent and groundwa-
(Fig. 2 and Table 3), this trend was occasionally observed for methylphe- ter has been previously reported (Fram and Belitz, 2011; Godfrey et al.,
nidate, diphenhydramine, propranolol, warfarin, and celecoxib. Elevated 2007; Hinkle et al., 2005; Standley et al., 2008), indicating the capacity
concentration of propranolol was also detected in efuent relative to in- of selected CECs to percolate to unconned aquifers, or to eventually
uent elsewhere (Ashton et al., 2004). Propranolol is extensively metab- recharge to surface water that may serve as habitats for aquatic
olized in the liver and is excreted from human mainly as metabolites organisms.
(Martindale, 2002), which are introduced in wastewater inuent and Valenti et al (2012) recently provided an independent validation of a
subsequently deconjugated in the treatment process. Deconjugation of plasma modeling approach with the antidepressant sertraline, when pH
propranolol during wastewater treatment has not been fully understood inuences on logDow and bioavailability were considered. When plasma
previously. Conjugates of propranolol to glucoronides are probably levels exceeded therapeutic plasma concentrations in adult fathead
cleaved at ether group in molecular structure. Additionally, it was also minnows, the pharmacological target (serotonin reuptake transport)
interesting to observe that the concentration of diphenhydramine was for sertraline was signicantly affected, which also resulted in signi-
typically greater in STS efuent than common inuent. In contrast, cant behavioral modications (Valenti et al., 2012). Of the 15 pharma-
diphenhydramine was generally removed to a greater extent by MTP, ceuticals detected in both on-site and municipal efuent discharges,
ATS, and WET, potentially due to aerobic conditions. However, one ER values of close to half of pharmaceuticals were less than 1000 in
recent laboratory microcosm study (Wu et al., 2010) that examined deg- the ATS, STS, and MTP, but ER values of only 4 pharmaceuticals in
radation of pharmaceuticals in soil altered with biosolids suggested that fall and 3 pharmaceuticals in winter were less 1000 in the WET
(See Fig. 3). Additionally, diltiazem also had ER values consistently
lower than 10 for all systems in both seasons. More importantly, in
STS, diltiazem also had an ER value lower than 1, which implied releas-
1e+6 ing diltiazem in STS efuent may result in therapeutic hazard to sh.
Oct. 2011 Jan. 2012 Less pharmaceuticals have ER values lower than 1000 for STS + WET
Influent in both seasons, suggesting that coupling with a wetland may lower
1e+5 MTP ecological risk associated with efuent discharge from septic systems.
ATS
STS+WET These lower ER values (ER b 10 or 1) suggest that these pharmaceuti-
Concentrations (ng/L)
1e+4 STS cals and the efuents in which they were observed deserve additional
investigation. Within the investigated treatment systems, STS consis-
tently possessed the lowest water quality based on therapeutic hazards
1e+3
because the number of pharmaceuticals exceeding ER thresholds and
lowest ER of diltiazem were observed in STS efuent (See Fig. 3).
1e+2 Because ionization plays a critical role governing bioaccumulation of
ionizable organic compounds and subsequent toxicity to aquatic organ-
isms (Erickson et al., 2006; Berninger et al., 2011; Valenti et al., 2012),
1e+1 development of robust, empirically-based studies are needed to more
accurately describe site-specic efuent pH inuences on bioavailabili-
1e+0 ty and thus the therapeutic hazard modeling results presented here.
However, the approach employed in the present study represents a
Caffeine
Sucralose
Carbamazepine
Sulfamethoxazole
Trimethoprim
Erythromycin
Acetaminophen
Codeine
Gemfibrozil
Atenolol
Diltiazem
Propranolol
Benzoylecgonine
Diphenhydramine
Diclofenac
Celecoxib
Methylphenidate
Warfarin
novel attempt to assess CECs removal and thus comparative water qual-
ity of decentralized and centralized systems. It also highlights the need
for further studies of additional classes of pharmaceuticals and other
CECs in on-site wastewater efuents, particularly in regions impacted
Contaminants of emerging concern
by failing onsite systems and high groundwater exchange with surface
Fig. 2. Detected target contaminants of emerging concern in inuent and various efuent
water.
discharges by season. MTP = municipal treatment plant; ATS = aerobic treatment Supplementary data to this article can be found online at http://dx.
system; STS = septic treatment system; WET = wetland. doi.org/10.1016/j.scitotenv.2013.07.126.
B. Du et al. / Science of the Total Environment 466467 (2014) 976984 983
107 107
MTP ATS
106 106
105 Oct. 2011
Jan. 2012
105
Effect Ratio
Effect Ratio
104 104
103 103
102 102
101 101
100 100
10-1 10-1
Acetaminophen
Codeine
Trimethoprim
Methylphenidate
Sulfamethoxazole
Diphenhydramine
Propranolol
Carbamazepine
Erythromycin
Warfarin
Celecoxib
Diclofenac
Gemfibrozil
Atenolol
Diltiazem
Acetaminophen
Codeine
Trimethoprim
Methylphenidate
Sulfamethoxazole
Diphenhydramine
Propranolol
Carbamazepine
Erythromycin
Warfarin
Celecoxib
Diclofenac
Gemfibrozil
Atenolol
Diltiazem
107 107
STS+WET STS
106 106
105 105
Effect Ratio
Effect Ratio
104 104
103 103
102 102
101 101
100 100
10-1 10-1
Acetaminophen
Codeine
Trimethoprim
Methylphenidate
Sulfamethoxazole
Diphenhydramine
Propranolol
Carbamazepine
Erythromycin
Warfarin
Celecoxib
Diclofenac
Gemfibrozil
Atenolol
Diltiazem
Acetaminophen
Codeine
Trimethoprim
Methylphenidate
Sulfamethoxazole
Diphenhydramine
Propranolol
Carbamazepine
Erythromycin
Warfarin
Celecoxib
Diclofenac
Gemfibrozil
Atenolol
Diltiazem
Fig. 3. Effect ratios of detected pharmaceuticals in efuent discharges by season. Effect Ratio (ER) = 1000 (long dash), ER = 1 (short dash). MTP = municipal treatment plant; ATS =
aerobic treatment system; STS = septic treatment system; WET = wetland. Calculated ER values are provided in a Table in Supplementary information.
Acknowledgment Brooks BW, Chambliss CK, Sedlak DL, Knight RL. Evaluate wetland systems for treated
wastewater performance to meet competing efuent water quality goals. Water
reuse research foundation; 2011.
This work was funded in part by the Texas Commission on Envi- Carrara C, Ptacek CJ, Robertson WD, Blowes DW, Moncur MC, Sverko E, et al. Fate of
ronmental Quality and the City of Waco Water Utilities. We gratefully pharmaceutical and trace organic compounds in three septic system plumes, Ontario,
Canada. Environ Sci Technol 2008;42:280511.
acknowledge additional nancial support from the Department of Clara M, Strenn B, Kreuzinger N. Carbamazepine as a possible anthropogenic marker
Environmental Science and the Center for Reservoir & Aquatic Systems in the aquatic environment: investigations on the behaviour of carbamazepine in
Research at Baylor University. We also thank Christopher Rash for labo- wastewater treatment and during groundwater inltration. Water Res 2004;38:
94754.
ratory assistance.
Code of Federal Regulations. Denition and procedure for the determination of the
method detection limit. Title 40, section 136, appendix B; 1986.
References Conn KE, Barber LB, Brown GK, Siegrist RL. Occurrence and fate of organic contaminants
during onsite wastewater treatment. Environ Sci Technol 2006;40:735866.
Allergy & Asthma Center. www.aactx.com/pollencount/index.php, 2011. [Austin, TX, USA]. Conn KE, Siegrist RL, Barber LB, Meyer MT. Fate of trace organic compounds during
American Housing Survey Table 14 selected equipment and plumbing all housing vadose zone soil treatment in an onsite wastewater system. Environ Toxicol Chem
units. U.S.A. Bureau (Ed.), Current Housing Report Series. Washington, DC; 2011. 2010;29:28593.
Andreozzi R, Raffaele M, Nicklas P. Pharmaceuticals in STP efuents and their solar Connors KA, Du B, Fitzsimmons PN, Hoffman AD, Chambliss CK, Nichols JW, et al. Compar-
photodegradation in aquatic environment. Chemosphere 2003;50:131930. ative pharmaceutical metabolism by rainbow trout (Oncorhynchus mykiss) liver S9
Ankley GT, Brooks BW, Huggett DB, Sumpter JP. Repeating history: pharmaceuticals in the fractions. Environ Toxicol Chem 2013;32:1810-1818.
environment. Environ Sci Technol 2007;41:82117. Daughton C, Brooks B. Active pharmaceutical ingredients and aquatic organisms. In: WN
Antweiler RC, Taylor HE. Evaluation of statistical treatments of left-censored environmen- Beyer JM, editor. Environmental contaminants in biota. Boca Raton: CRC Press, Taylor
tal data using coincident uncensored data sets: I. Summary statistics. Environ Sci and Francis; 2011.
Technol 2008;42:37328. Daughton CG, Ternes TA. Pharmaceuticals and personal care products in the environment:
Ashton D, Hilton M, Thomas KV. Investigating the environmental transport of human agents of subtle change? Environ Health Perspect 1999;107:90738.
pharmaceuticals to streams in the United Kingdom. Sci Total Environ 2004;333: Davila P. The evaluation of a subsurface-ow constructed wetland for on-site wastewater
16784. treatment under the NSF/ANSI standard 40 protocol design loading. Department of
Berninger JP, Brooks BW. Leveraging mammalian pharmaceutical toxicology and pharma- Environmental Science. Waco, TX: Baylor University; 2006.
cology data to predict chronic sh responses to pharmaceuticals. Toxicol Lett Du B, Perez-Hurtado P, Brooks BW, Chambliss CK. Evaluation of an isotope dilution liquid
2010;193:6978. chromatography tandem mass spectrometry method for pharmaceuticals in sh.
Berninger JP, Du B, Connors KA, Eytcheson SA, Kolkmeier MA, Prosser KN, et al. Effects of J Chromatogr A 2012;1253:17783.
the antihistamine diphenhydramine on selected aquatic organisms. Environ Toxicol Erickson RJ, McKim JM, Lien GJ, Hoffman AD, Batterman SL. Uptake and elimination of
Chem 2011;30:206572. ionizable organic chemicals at sh gills: I. Model formulation, parameterization,
Boxall AB, Rudd MA, Brooks BW, Caldwell DJ, Choi K, Hickmann S, et al. Pharmaceuticals and behavior. Environ Toxicol Chem 2006;25:151221.
and personal care products in the environment: what are the big questions? Environ Fick J, Lindberg RH, Parkkonen J, Arvidsson B, Tysklind M, Larsson DGJ. Therapeutic
Health Perspect 2012;120:12219. levels of levonorgestrel detected in blood plasma of sh: results from screening
Brooks BW, Scott JT, Forbes MG, Valenti TW, Stanley JK, Doyle RD, et al. Reservoir zonation rainbow trout exposed to treated sewage efuents. Environ Sci Technol 2010a;44:
and water quality: science, management and regulations. Lakeline 2008;28:3943. 26616.
Brooks BW, Huggett DB, Boxall ABA. Pharmaceuticals and personal care products: Fick J, Lindberg RH, Tysklind M, Larsson DGJ. Predicted critical environmental concentra-
research needs for the next decade. Environ Toxicol Chem 2009;28:246972. tions for 500 pharmaceuticals. Regul Toxicol Pharmacol 2010b;58:51623.
984 B. Du et al. / Science of the Total Environment 466467 (2014) 976984
Fitzsimmons PN, Fernandez JD, Hoffman AD, Butterworth BC, Nichols JW. Branchial elim- Ort C, Lawrence MG, Reungoat J, Mueller JF. Sampling for PPCPs in wastewater systems:
ination of superhydrophobic organic compounds by rainbow trout (Oncorhynchus comparison of different sampling modes and optimization strategies. Environ Sci
mykiss). Aquat Toxicol 2001;55:2334. Technol 2010;44:628996.
Fram MS, Belitz K. Occurrence and concentrations of pharmaceutical compounds in Radjenovi J, Petrovi M, Barcel D. Fate and distribution of pharmaceuticals in wastewa-
groundwater used for public drinking-water supply in California. Sci Total Environ ter and sewage sludge of the conventional activated sludge (CAS) and advanced
2011;409:340917. membrane bioreactor (MBR) treatment. Water Res 2009;43:83141.
Garcia SN, Clubbs RL, Stanley JK, Scheffe B, Yelderman Jr JC, Brooks BW. Comparative Ramirez AJ, Mottaleb MA, Brooks BW, Chambliss CK. Analysis of pharmaceuticals in sh
analysis of efuent water quality from a municipal treatment plant and two on-site using liquid chromatographytandem mass spectrometry. Anal Chem 2007;79:
wastewater treatment systems. Chemosphere 2013;92:3844. 315563.
Gheorghe A, van Nuijs A, Pecceu B, Bervoets L, Jorens P, Blust R, et al. Analysis of cocaine Scheurer M, Brauch H-J, Lange F. Analysis and occurrence of seven articial sweeteners in
and its principal metabolites in waste and surface water using solid-phase extraction German waste water and surface water and in soil aquifer treatment (SAT). Anal
and liquid chromatographyion trap tandem mass spectrometry. Anal Bioanal Chem Bioanal Chem 2009;394:158594.
2008;391:130919. Schreiber R, Gndel U, Franz S, Kster A, Rechenberg B, Altenburger R. Using the sh
Godfrey E, Woessner WW, Benotti MJ. Pharmaceuticals in on-site sewage efuent and plasma model for comparative hazard identication for pharmaceuticals in the envi-
ground water, western Montana. Ground Water 2007;45:26371. ronment by extrapolation from human therapeutic data. Regul Toxicol Pharmacol
Gunnarsson L, Jauhiainen A, Kristiansson E, Nerman O, Larsson DGJ. Evolutionary conser- 2011;61:26175.
vation of human drug targets in organisms used for environmental risk assessments. Schulz M, Iwersen-Bergmann S, Andresen H, Schmoldt A. Therapeutic and toxic blood
Environ Sci Technol 2008;42:580713. concentrations of nearly 1,000 drugs and other xenobiotics. Crit Care 2012;16:14.
Halling-Srensen B, Nors Nielsen S, Lanzky PF, Ingerslev F, Holten Ltzhft HC, Jrgensen Seiler RL, Zaugg SD, Thomas JM, Howcroft DL. Caffeine and pharmaceuticals as indicators
SE. Occurrence, fate and effects of pharmaceutical substances in the environment a of waste water contamination in wells. Ground Water 1999;37:40510.
review. Chemosphere 1998;36:35793. Soh L, Connors KA, Brooks BW, Zimmerman J. Fate of sucralose through environmental
Heberer T. Occurrence, fate, and removal of pharmaceutical residues in the aquatic and water treatment processes and impact on plant indicator species. Environ Sci
environment: a review of recent research data. Toxicol Lett 2002;131:517. Technol 2011;45:13639.
Hijosa-Valsero M, Matamoros V, Martn-Villacorta J, Bcares E, Bayona JM. Assessment Standley LJ, Rudel RA, Swartz CH, Atteld KR, Christian J, Erickson M, et al.
of full-scale natural systems for the removal of PPCPs from wastewater in small Wastewater-contaminated groundwater as a source of endogenous hormones
communities. Water Res 2010;44:142939. and pharmaceuticals to surface water ecosystems. Environ Toxicol Chem 2008;27:
Hinkle SR, Weick Rj, Johnson JM, Cahill JD, Smith SG, Rich BJ. Organic wastewater 245768.
compounds, pharmaceuticals, and coliphage in ground water receiving discharge Stanford BD, Weinberg HS. Evaluation of on-site wastewater treatment technology to
from onsite wastewater treatment systems near La Pine, Oregon: occurrence and remove estrogens, nonylphenols, and estrogenic activity from wastewater. Environ
implications for transport. USGS Scientic Investigations Report 20055055. Reston, Sci Technol 2010;44:29943001.
Virginia: USGS; 2005. Swartz CH, Reddy S, Benotti MJ, Yin H, Barber LB, Brownawell BJ, et al. Steroid estrogens,
Huggett DB, Cook JC, Ericson JF, Williams RT. A theoretical model for utilizing mammalian nonylphenol ethoxylate metabolites, and other wastewater contaminants in ground-
pharmacology and safety data to prioritize potential impacts of human pharmaceuti- water affected by a residential septic system on Cape Cod, MA. Environ Sci Technol
cals to sh. Hum Ecol Risk Assess 2003;9:178999. 2006;40:4894902.
Kadlec RH, Knight RI. Treatment wetlands. Boca Raton, FL: CRC Press LLC; 1996. Teerlink J, Martnez-Hernndez V, Higgins CP, Drewes JE. Removal of trace organic
Kinyua J, Anderson TA. Temporal analysis of the cocaine metabolite benzoylecgonine in chemicals in onsite wastewater soil treatment units: a laboratory experiment.
wastewater to estimate community drug use. J Forensic Sci 2012;57:134953. Water Res 2012;46:517484.
Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, et al. Pharmaceu- Texas Natural Resources Conservation Commission Chapter 285 On-Site Sewage Facilities.
ticals, hormones, and other organic wastewater contaminants in US streams, 1999 in: Texas Administrative Code, ed. 30. Austin, TX, USA; 2002b.
2000: a national reconnaissance. Environ Sci Technol 2002;36:120211. Thomas KV, Bijlsma L, Castiglioni S, Covaci A, Emke E, Grabic R, et al. Comparing illicit drug
Letzel M, Weiss K, Schssler W, Sengl M. Occurrence and fate of the human pharma- use in 19 European cities through sewage analysis. Sci Total Environ 2012;432:4329.
ceutical metabolite ritalinic acid in the aquatic system. Chemosphere 2010;81: U.S.EPA. On-site wastewater treatment systems manualIn: Ofce of Water Ofce of
141622. Research and Development, editor. 2002. [Washington DC, USA].
Loos R, Gawlik BM, Boettcher K, Locoro G, Contini S, Bidoglio G. Sucralose screening U.S.EPA. Handbook for managing on-site and clustered (decentralized) wastewater treat-
in European surface waters using a solid-phase extraction-liquid chromatography ment systems: an introduction to management tools and information for implementing
triple quadrupole mass spectrometry method. J Chromatogr A 2009;1216:112631. EPA's management guidelinesIn: U.S.EPA, editor. 2005. [Washington, DC, USA].
Lowe K, Van Cuyk S, Siegrist R, Drewes J. Field evaluation of the performance of U.S.FDA. Maximum recommended therapeutic dose (MRTD) database. Silver Spring: MD:
engineered on-site wastewater treatment units. J Hydrol Eng 2008;13:73543. Ofce of Pharmaceutical Science; 2009.
MacLeod SL, Wong CS. Loadings, trends, comparisons, and fate of achiral and chiral phar- Valenti TW, Gould GG, Berninger JP, Connors KA, Keele NB, Prosser KN, et al. Human ther-
maceuticals in wastewaters from urban tertiary and rural aerated lagoon treatments. apeutic plasma levels of the selective serotonin reuptake inhibitor (SSRI) sertraline
Water Res 2010;44:53344. decrease serotonin reuptake transporter binding and shelter-seeking behavior in
Martindale. The complete drug reference. London, UK: Pharmaceutical Press Royal adult male fathead minnows. Environ Sci Technol 2012;46:242735.
Pharmaceutical Society; 2002. Van Cuyk S, Siegrist R, Logan A, Masson S, Fischer E, Figueroa L. Hydraulic and purication
Matamoros V, Bayona JM. Elimination of pharmaceuticals and personal care products in behaviors and their interactions during wastewater treatment in soil inltration
subsurface ow constructed wetlands. Environ Sci Technol 2006;40:58116. systems. Water Res 2001;35:95364.
Matamoros V, Garca J, Bayona JM. Behavior of selected pharmaceuticals in subsurface van Nuijs ALN, Castiglioni S, Tarcomnicu I, Postigo C, de Alda ML, Neels H, et al. Illicit drug
ow constructed wetlands: a pilot-scale study. Environ Sci Technol 2005;39:544954. consumption estimations derived from wastewater analysis: a critical review. Sci
Mawhinney DB, Young RB, Vanderford BJ, Borch T, Snyder SA. Articial sweetener sucra- Total Environ 2011;409:356477.
lose in U.S. drinking water systems. Environ Sci Technol 2011;45:871622. Vanderford BJ, Snyder SA. Analysis of pharmaceuticals in water by isotope dilution
Meredith-Williams M, Carter LJ, Fussell R, Raffaelli D, Ashauer R, Boxall AB. Uptake and liquid chromatography/tandem mass spectrometry. Environ Sci Technol 2006;40:
depuration of pharmaceuticals in aquatic invertebrates. Environ Pollut 2012;165: 731220.
2508. Wilcox JD, Bahr JM, Hedman CJ, Hemming JDC, Barman MAE, Bradbury KR. Removal of
Metcalfe C, Tindale K, Li H, Rodayan A, Yargeau V. Illicit drugs in Canadian organic wastewater contaminants in septic systems using advanced treatment
municipal wastewater and estimates of community drug use. Environ Pollut technologies all rights reserved. No part of this periodical may be reproduced or
2010;158:317985. transmitted in any form or by any means, electronic or mechanical, including
NSF International. NSF/ANSI residential wastewater treatment systems. 2005. [http:// photocopying, recording, or any information storage and retrieval system, without
www.nsf.org/Certied/Wastewater/Listings.asp?TradeName=&Standard=040]. permission in writing from the publisher. J Environ Qual 2009;38:14956.
Oppenheimer J, Eaton A, Badruzzaman M, Haghani AW, Jacangelo JG. Occurrence and Wu C, Spongberg A, Witter J, Fang M, Czajkowski K, Ames A. Dissipation and leaching
suitability of sucralose as an indicator compound of wastewater loading to surface potential of selected pharmaceutically active compounds in soils amended with
waters in urbanized regions. Water Res 2011;45:401927. biosolids. Arch Environ Contam Toxicol 2010;59:34351.