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Detecting Human Pharmaceutical Pollutants in Malaysian Aquatic Environment:

A new challenge for water quality management

Chapter · January 2011

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Detecting Human Pharmaceutical Pollutants in Malaysian Aquatic
Environment: A new challenge for water quality management
Najat Al-Odaini, Mohammed Pauzi Zakaria , Mohammed Ismail Yaziz and Salmijah Surif

Abstract. Emerging pollutants that are not included in the legislation such as pharmaceuticals and personal care
products become new aquatic pollutants. The main source of these pollutants is sewage treatment plants effluent.
Widespread pharmaceuticals pollution of lakes, streams, and groundwater has been reported in Europe and some
other parts of the world. However, the level of human pharmaceuticals and synthetic hormones in the Malaysian
aquatic environment is not known. The first investigation to study the occurrence of 23 human pharmaceuticals and
synthetic hormones that cover the top twenty prescribed and OTC drugs in Malaysia was conducted in the Langat
River and selected STPs along the river. Results show that the river is polluted by human pharmaceuticals and
STPs do not totally remove these pollutants. A few tap water samples were also tested and some of these pollutants
were detected. The occurrence of these pollutants in water samples is a new and critical challenge for water quality
management in Malaysia.

Keywords: water pollution, human pharmaceuticals, synthetic hormones, Langat River

1 Introduction

High quality surface water is critical for maintaining healthy ecosystems and ensuring safe drinking water.
The continued exponential growth in human population has created a corresponding increase in the demand
for the Earth’s limited supply of freshwater. Thus, protecting the integrity of our water resources is one of
the most essential environmental issues of the 21st century. Therefore, obtaining an adequate supply of
clean water has likely always been a challenge for much of humanity, yet is often compromised by point
and non-point contamination sources. Water pollution is a major problem in the global context. It has been
suggested that it is the leading worldwide cause of deaths and diseases and that it accounts for the deaths of
more than 14,000 people daily[1]. There are many sources of pollution in our waters. In addition to point
sources such as sewage and industrial waste, a great deal of water pollution comes from non-point sources
such as agricultural runoff, and storm water drainage. Common water pollutants include pesticides, lead,
arsenic, polychlorinated biphenyls (PCBs) and poly aromatic hydrocarbons (PAHs), to name few, are
known as “conventional priority pollutants”. These chemicals referred to as persistent organic pollutants
(POPs) which have been under study for the last few decades. Today, these compounds are less relevant for
many first world countries because emissions have been substantially reduced through the adoption of
appropriate legal measures and the elimination of many of the dominant pollution sources[2].
Only recently, the attention of the scientific community has started to shift to a new group of pollutants
which are known as “emerging pollutants” that is not included in the legislation (non-priority pollutants)
such as pharmaceuticals and personal care products which becomes a new environmental problem of
interest [3]. “Emerging pollutants” can be defined as those pollutants that are entering into or being
generated in the environment in appreciable amounts”, that have “a modicum of persistence,” and “exhibit
deleterious effects on organisms”. One of the interesting characteristics of many of the chemicals that
might cause this type of pollution is that they do not need to be persistent in the environment to cause
negative effects. This is because their high transformation and removal rates can be offset by their
continuous introduction into the environment; often through sewage treatment works [4].

2 Why pharmaceuticals are aquatic micropollutants?

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Pharmaceuticals are a large class of chemicals, as of January 2003, more than 140,000 bioactive
compounds were in various phases of drug research and development [5]. Pharmaceuticals and synthetic
hormones comprise a very diverse spectrum of "non-conventional", unregulated pollutants – a spectrum
that is continually expanding as new chemical entities are discovered and brought to market are only one of
many other chemical groups that have been largely ignored. When applying pharmaceuticals to humans,
many of their constituents are excreted unchanged through urine and faeces or as metabolites via municipal
sewage system [2]. Until recently pharmaceuticals have been exposed to the environment with very little
attention this is because they are not regulated as environmental pollutants. A large number of
pharmaceuticals are polar and predominantly water soluble and neither volatile nor biodegradable, thus
escaping sedimentation and biological treatment in STPs. Given the greater water solubility of
pharmaceutical pollutants in general compared with conventional pollutants, the major ultimate
environmental distribution compartment is probably the aquatic environment [6].
The reason why these medical substances are of environmental concern can be deduced from their
specific biological effects not only on patients but also on aquatic biota. Most often, they have low
biodegradability, and can accumulate to detectable levels and biologically active amounts [7] and can act as
persistent pollutants because of their continuous release to the environment through STPs [8]. As opposed
to many other hydrophilic or water-soluble pollutants currently under investigation, pharmaceuticals
especially synthetic hormones have obvious potential as endocrine disrupters[9] and can illicit changes of
physiological functions of biological systems [10, 11].

3 Sources, transport pathways and fate of human pharmaceuticals pollutants

into environment

Sources of pharmaceuticals and synthetic hormones into the environment can be classified into major and
minor sources. Major source include raw or treated sewage effluents of hosing and hospitals following
consumption and excretion of pharmaceuticals by humans or/and the disposal of unused medication via the
toilet. Minor sources include production residues [12], improper disposal of expired medicines and unused
drugs, landfills leachates and accidental spill during manufacturing and distribution. The sources, transport
pathways and fate of human pharmaceuticals to aquatic environment are illustrated in Fig.1. STPs of
housing and hospitals are considered the most significant entry route of emerging contaminants because
most of current STPs are not designed to treat these types of substances [8]. Therefore, the major source of
pharmaceuticals into the aquatic environment is the release from STPs. This is because after normal
application of medicines by patients, a large proportion of medication or their metabolites are eliminated
from the body mainly through the renal system (urine), biliary system (feces), or a combination of both.
Elimination rates vary depending on the individual, drug, and dosage. Examples include the β-blocker
nadolol, which is not metabolized at all by the body and the antibiotic amoxicillin, of which 80– 90% is
excreted unchanged [13]. After elimination of unmetabolized form and/or active metabolites of medicine
via urine or feces, they travel to wastewater which may or may not be treated. During sewage treatment,
most of these compounds are not quantitatively removed; they may escape degradation in waste treatment
plants and remain in the effluents that get into the surface and groundwater.

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Fig.1. Sources, transport pathways and fate of human pharmaceuticals to aquatic environment.
Adapted from[13]

In survey conducted in UK, it was demonstrated that disposal of unused or expired pharmaceuticals, either
by household waste or via the sink or toilet may be a prominent route that requires greater attention [14].
However, some still believe that flushing unused medicines down the toilet appears to be of minor
importance, while patient excretion following therapy is widely considered to be the primary pathway to
the environment. Even posthumously, the drugs administered in the closing phases of our lives likely leach
into cemeteries and groundwater [4].
STPs play a crucial role in the separation of pharmaceuticals into two exposure pathways associated
with the aquatic and the solid phase and the subsequent introduction into the environment. Partitioning
between phases depends in part on the degree of polarity of the particular pharmaceutical. Sludge material
and consequently terrestrial environments are likely to be the destination for less polar or nonpolar
pharmaceuticals, because many organic compounds, particularly hydrophobic compounds, are sorbed onto
sludge where they are concentrated (by several orders of magnitude) compared with the sewage from which
the sludge was derived. On the other hand, the polar pharmaceuticals are expected to remain primarily in
the aqueous phase. A large number of pharmaceuticals (or their metabolites) are highly water-soluble and
neither volatile nor biodegradable, thus escaping sedimentation and biological treatment in STPs; these
compounds unaffected by sewage treatment remain in the water effluent and as a result represent the bulk
of the load into aquatic environments [15, 16].
Although many pharmaceuticals are excreted mainly as metabolites (mostly conjugated to polar
molecules), these conjugates can easily be cleaved during sewage treatment and the original
pharmaceuticals will then be released into the aquatic environment mostly by effluents from municipal
STPs. Study on the natural hormone 17β-estradiol and the synthetic steroid hormone of the contraceptive
pill 17α-ethinylestradiol prove that metabolites are likely cleaved during sewage treatment to yield the
nonmetabolized pharmaceuticals and hence may increase the relevant environmental concentrations [17,
18].Other possibilities fates are that pharmaceuticals can be completely degraded by microbial
transformation during biological treatment, mineralized or partially degraded to produce breakdown
products. In addition, pharmaceuticals with low solubility can bypass STPs due to colloid-facilitated

3
transport during periods of high effluent turbidity. Overflow due to technical problems, floods, or high
influent loads may also cause substances with low solubility to shortcut the STPs [19, 6, 16].
Fate of pharmaceutical pollutants to groundwater could be as a result of the application of digested
sludge from municipal STPs on agricultural fields. Another sources to groundwater are irrigation with
treated wastewater or leaching into the groundwater aquifers from the contaminated surface water because
they are not significantly adsorbed in the subsoil as a result of polar structure of most pharmaceutical
compounds [20];[21]. Additionally, transport of hormones via bank filtration from contaminated surface
water into ground water, as well as the infiltration of waste waters directly from leakage in drains is also
possible [17].The controlled application of sludge to soils presents clear benefits, since it results in the
recycling of organic matter and nutrients. However the application of sludge directly adds undesirable
substances to the soil and leads to corresponding negative effects. Other disposal options for the sewage
sludge are landfill, incineration and dumping at sea. The most popular for solid waste disposal is landfill.
However, many of the disposal sites are open dumps without protective barriers or leachate-collection
systems, which involve risk to the quality of groundwater nearby [19].
In arid areas, as more treated wastewater is used for irrigation rather than directly discharged into
surface waters, runoff from agricultural fields will become an increasingly important source of
contaminants traditionally associated with STPs effluent. Whereas wastewater reuse may reduce overall
impacts to surface waters, irrigation with treated effluent does not eliminate the introduction of
pharmaceutical pollutants into aquatic ecosystems. Although some reductions in contaminant load may be
achieved by irrigation with treated effluent, this practice serves to shift the point of contaminant
introduction from the treatment plant outfall to the edge of irrigated fields. In addition to potential impacts
to surface waters, contaminants may also leach into groundwater after they are applied to cultivated fields.
The potential exists for contaminants present in treated wastewater to leach into groundwater supplies used
as drinking water sources or to enter aquatic ecosystems through irrigation runoff [22].

4 Ecotoxicity of human pharmaceuticals and impact on aquatic environment

4.1 Impact on aquatic environment

Pharmaceuticals released into the aquatic environment are of concern because of contamination of raw,
treated and recycled water used for drinking, irrigation and recreation; and potential to accelerate
widespread bacterial resistance to antibiotics and negative effect on important ecosystem bacteria (through
death or inhibition). Unlike many other pollutants to the aquatic environment, antibiotics have a direct
biological action on microbes, and in many cases are continually emitted to the environment thereby acting
as persistent pollutants even if some have high degradation rates[11]. Although pharmaceuticals are
designed to target humans or animal, aquatic organisms exhibiting the same enzyme receptors could also
experience those pharmaco-dynamic effects [13]. Also at risk are aquatic ecosystems, which are largely
controlled by, and dependent upon, microbial organisms for a suite of crucial processes (e.g.,
denitrification), associations (e.g., nitrogen fixation) and services (e.g., organic breakdown), all of which
can potentially be hindered by antibiotic substances. Similar effects are possible in sewage treatment
facilities that have adopted bacteria within their structure to perform wastewater treatment functions [11].
Pharmaceuticals in the environment are impairing aquatic life forms, sometimes profoundly, and are
producing changes that threaten the sustainability of the ecosphere on which our chemocentric civilization
depends. There is increasing evidence that some of these compounds are persistent in the environment,
impacting nontarget organisms in various ways including changes in sex ratios of higher organisms (Pascoe
et al., 2003).Pharmaceuticals are deliberately designed to affect biochemical and physiological functions by
either to be highly active and interact with receptors in humans and or to be toxic for many infectious
organisms, including bacteria, fungi, and parasites. However, many lower animals have receptor systems
similar to humans. Furthermore, many groups of organisms that negatively affect human and animal health,
and are therefore targeted by pharmaceuticals, play crucial roles in the functioning of ecosystems. Thus,
pharmaceuticals are often found to cause adverse ecological effects on aquatic and terrestrial organisms.
These effects are often not highlighted by the standard studies aimed at securing human safety. As human
medicines are almost continuously released to the environment, aquatic organisms in particular, and also

4
wildlife, are becoming exposed over their entire lifecycle. This is usually much longer than the durations of
exposures employed in standard safety testing [23].

4.2 Potential Health Risk of Pharmaceuticals

Impacts caused by pharmaceuticals on human health is of concern especially in areas that practice indirect
water reuse, where sewage effluent is released to streams and rivers that are in turn used as a source of raw
water for the production of potable supplies for communities living downstream. Therefore there is a risk
that humans might be exposed to drugs through potable water drawn from contaminated supplies. Since
there is currently no regulatory requirement for the monitoring of pharmaceuticals in drinking water,
human pharmaceuticals have occasionally been detected in drinking water. Antibiotics and resistant
bacteria are entering our local waterways and have potential to influence biotic processes so there is a risk
associated with the transfer of resistant genes from harmless bacteria to pathogenic bacteria and on to
humans interacting with the aquatic environment [11]. Some studies have also identified sensitization, or
the development of an allergenic response to antibiotics, as being of concern. However, bacteria with
antibiotic resistance genes have been found in biofilms inoculated with drinking water bacteria in Germany
[2]. This indicates possible gene transfer, perhaps from surface and/or wastewater, to the drinking water
distribution network. This certainly could also be a cause for concern as regards human health if it were a
widespread occurrence. The extensive use of antibiotics throughout the world, may raise the possibility,
that the tons of the antibiotics consumed either as therapeutics in humans and animals, or growth promoters
mixed to animal fodder, might have a different effect on the mankind, not only promoting antibiotic
resistance, but influencing human growth and possible obesity as well [24].
Another facet to this problem is that of the synergistic effects of mixtures of compounds. Although
concentrations of individual substances might be low, it is unknown what effects, if any, exposure to
repeated doses of a mixture of sub-therapeutic amounts of drugs and other chemicals could have on human
health .Minor side effects to medications given at prescription doses are common but are usually
outweighed by the health benefits of the medication. This would not be the case with unintended, routine
exposure to the drugs or mixture of drugs that could, potentially, be found in drinking water. If drugs are
present in drinking water, then potential health concerns will need to focus on individual,
synergistic/antagonistic and possible mixture effects over an extended period of time [2].

5 Global concern of pharmaceuticals pollution

Over the past decade, European chemists have been documenting widespread pharmaceuticals
contamination of their lakes, streams, and groundwater. As such, in recent years, the occurrence and fate of
pharmaceutical residues in the environment has become a subject of public interest and awakened great
concern among scientist in the last few years worldwide. A great body of literature has focused largely on
establishing the occurrence and sources of pharmaceuticals in the environment –primarily in the aquatic
domain (as a result of sewage discharge to receiving waters, which is the main route for pharmaceuticals
used in human medicine). Many studied have been carried out in different parts of the world in different
aquatic environmental matrices (tap water, drinking water, ground water wells, river and streams, sea
water, STP effluent, lake, and storm water canal). The detected compounds include Analgesics, Anti-
asthmatic agent, Antibacterial, disinfectant, Antibiotics, Anti-cancer drug, Antidepressant, Antiepileptic
drug (anticonvulsant), Antifungal, Antihypertensive agent, Gastrointestinal, lipid regulating agent,
hormone’s, and Stimulant [25-27, 20, 28-34].

5
6 Malaysian Scenario

Data about the pharmaceuticals pollution in Malaysian aquatic environment is missing. Therefore, in
response to the growing body of evidence in the research literature of the ubiquitous nature of this
emerging issue, the Center of Excellence of the Environmental Forensics of the faculty of the
environmental study (UPM) developed analytical method for simultaneously analyzing a group of 23
compounds from 8 therapeutic classes including the top twenty prescribed and over the counter drugs
(OTC) (Table 1) and conducted initial surveillance to determine what drug residues are present in
Malaysian waters and at what concentrations. The initial surveillance was conducted in Langat Basin
whereby the surface water, STPs effluents samples and few tap water samples were collected.
Sungai Langat is one of the four major river systems in Selangor. It has a catchment area of 2350
square kilometers and is about 180 kilometer long. The river has three main tributaries namely Sungai
Semenyih, Sungai Beranang and Sungai Labu. It is reported that the most significant source of organic
pollution in the Langat basin is STPs untreated sewage (organic pollution and pathogens), wastes from
animal husbandry (organic pollution, metals & pathogens) and industrial waste (organic& inorganic
pollution). Pollution to the river system caused by STPs is considered the second source of pollution after
the industrial source and followed by pig farms. Langat River receives STPs effluents form more than 520
STPs located in the basin and raw sewage. Along the Langat basin, here are eight water treatment plants
(WTPs) down stream of STPs except two WTP located upstream of river and any sewage source. With
exception of WTPs located upstream of Langat River, all the remaining WTPs are under significant
pollution threat to the raw water intake for the plants. All raw river water used to feed these plants is
classified as class ІІІ which is the worst class to be used as raw water for drinking water.

Table 1. Average concentration (ng/L) of detected pharmaceutical in Study area

Pharmaceutical River Samples STPs Effluents Tap Water

Metformina 55 4080 Nd
Atenolola 39 771 Nd
Metoprolola 62 854 39
Salbutamola 1 12 Nd
Perindoprila 3 19 Nd
Gliclazidea 4 55 Nd
Gibenclamidea 1 44 0.3
Loratadine 3 14 1
Diclofenaca 105 32 Nd
Mefenamic acida 37 147 Nd
chlorothiazidea 23 136 4.5
Amlodipinea 1 3 Nd
Nifidipinea 3 Nd Nd
Furosemidea 109 545 Nd
Lovastatina Nd 187 Nd
Simvastatina Nd Nd Nd
Chlorphernaminea Nd Nd Nd
Paracetamolb 38 405 3.4
Salicylic acidb 71 110 Nd
Cyproteroneb 27 103 Nd
Northindroneb Nd 7135 Nd
Norgestrelb 67 Nd 30
Ethinylestradiolb Nd 77 130
a Prescribed
drug
b Over
the counter drug
ND not detected

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 Surface water samples were collected before the water intake point of five WTPs in Langat basin and
from river downstream. Analysis results showed pharmaceutical pollutants are present in each sample
except the samples collected from river upstream that do not receive any sewage effluents (Table 1).
Pharmaceutical pollutants were also detected in all the STPs effluents samples collected from five different
STPs distributed in the basin. This confirm that the STPs act as the main point source of these pollutants to
the river and the current treatment technologies used are not able to totally remove these pollutants. Few
pharmaceutical pollutants were also detected in Tap water samples showing that these pollutants can not be
removed by the WTPs and therefore can reach the tap water (Table 1). These findings are in good
agreement with the other investigations carried out in the other parts of the world showing that
pharmaceutical pollution is threatening challenge to healthy aquatic environment and safe drinking water.

6 Controlling pharmaceuticals pollution

As a result of early detection of these pollutants in north America and Europe and based on the results of
the studies, several approaches have been used towards solving the problem starting from education of the
proper way of disposal to applying the advanced treatment technology in STPs and finally go beyond that
by conducting environmental impact assessment for the currently in use and new pharmaceuticals. Among
the several strategies of controlling pharmaceutical pollution, it was found that the most effective way to
control the fate of these pollutants in the environment is by applying environmental risk assessment on the
pharmaceuticals themselves to ensure that the drug cannot pose any potential risk if released to the
environment. Recently, on the basis of increasing pressure from environmental protection groups and
growing public awareness and concerns about the possible impact of human pharmaceuticals on the
environment, the EU has designed a draft document outlining a step-wise, phased procedure for the
environmental risk assessment (ERA) of such substances. This draft has been designed to encompass ERAs
for both new and renewed medicinal products, that is, the incorporation of new indications or an increase in
use of the product. The draft document requires that “an application for the marketing authorisation for a
medicinal product for human use shall be accompanied by an environmental risk assessment” and that “the
applicant indicate any potential risks exhibited by the medicinal product for the environment,” and relates
“to those risks to the environment arising from use, storage, and disposal of the medicinal product”
(O’Brien and Dietrich, 2004).
Pollution prevention (source reduction, minimization or elimination) is another approach of controlling
pharmaceutical pollution which embodies many advantages compared with waste treatment or
environmental remediation. This prevention is known as stewardship solution- the green pharmacy- which
benefits not just the environment but additionally unrelated benefits could automatically accrue, including
lessening medication expense for the consumer and improving overall patient health and consumer safety.
This key feature of the stewardship program or “cradle-to-cradle” program can be applied under a host of
monikers such as design for environment, industrial ecology, life cycle planning/design/assessment,
product stewership,extended product responsibility(including not just the producer but also the entire use-
chain including the consumer) product take back programs (where unused/unneeded product travel back up
through the distribution chain-“ reverse distribution” and many others. Another suggestion is substitutes for
antimicrobials. It is believed that the minimization of antibiotic usage can be attained by number of means,
including use of non-drug alternatives or use of synergists, live phage therapy, enzyme therapy and
vaccines. Nutritional measures are another area that highlights one of many possible examples of “natural”
alternative to medication includes the possibly unnecessary use of certain medications for trating the
symptoms that can be frequently controlled simply by proven nutritional measures [5].
Locally, authors suggest the implementing of “prevention is better than the cure” approach by educate
nation the proper disposal ways of unused or expired drugs. Proper consumption of water resources can
lead to less sewage therefore costly advanced technology can be implemented with less energy
consumption. Another approach could be locating the WTPs upstream of STPs or at least locating the
intake pumps of these WTPs at river upstream.

7
Acknowledgments. Authors would like to thank Public health laboratory, veterinary
department, Ministry of Agriculture Malaysia for providing the instrumental analysis.

References

1. Wikipedia. Available from: http://en.wikipedia.org/wiki/Water_pollution.

2. Jones, Lester, and Voulvoulis (2005) Pharmaceuticals: a threat to drinking water?
Trends in Biotechnology 23:163-167.
3. Richardson, Lam, and Martin (2005) Emerging chemicals of concern:
Pharmaceuticals and personal care products (PPCPs) in Asia, with particular
reference to Southern China. Marine Pollution Bulletin 50:913-920.
4. Khetan and Collins (2007) Human Pharmaceuticals in the Aquatic Environment:
A Challenge to Green Chemistry. Chemical Reviews 107:2319-2364.
5. Daughton (2003) Cradle-to-cradle stewardship of drugs for minimizing their
environmental disposition while promoting human health. I. Rational for and
avenues toward a green pharmacy Environmental Health Perspectives 111 757-
774
6. Bendz, Paxeus, Ginn, and Loge (2005) Occurrence and fate of pharmaceutically
active compounds in the environment, a case study: Hoje River in Sweden.
Journal of Hazardous Materials 122:195-204.
7. Halling-Sorensen, Nors Nielsen, Lanzky, Ingerslev, Holten Lutzhoft, and
Jorgensen (1998) Occurrence, fate and effects of pharmaceutical substances in the
environment- A review. Chemosphere 36:357-393.
8. Petrovic, Gonzalez, and Barceló (2003) Analysis and removal of emerging
contaminants in wastewater and drinking water Trends in Analytical Chemistry,
22.
9. Christensen (1998) Pharmaceuticals in the Environment--A Human Risk?
Regulatory Toxicology and Pharmacology 28:212-221.
10. Rodgers-Gray, Jobling, Morris, Kelly, Kirby, Janbakhsh, Harries, Waldock,
Sumpter, and Tyler (2000) Long-Term Temporal Changes in the Estrogenic
Composition of Treated Sewage Effluent and Its Biological Effects on Fish.
Environ. Sci. Technol. 34:1521-1528.
11. Costanzo, Murby, and Bates (2005) Ecosystem response to antibiotics entering
the aquatic environment. Marine Pollution Bulletin 51:218-223.
12. Cui, Ji, and Ren (2006) Determination of Steroid Estrogens in Wastewater
Treatment Plant of A Controceptives Producing Factory. Environmental
Monitoring and Assessment 121:407-417.
13. Bound and Voulvoulis (2004) Pharmaceuticals in the aquatic environment--a
comparison of risk assessment strategies. Chemosphere 56:1143-1155.
14. Bound, Kitsou, and Voulvoulis (2006) Household disposal of pharmaceuticals
and perception of risk to the environment. Environmental Toxicology and
Pharmacology 21:301-307.
15. Dietrich, Webb, and Petry (2002) Hot spot pollutants: pharmaceuticals in the
environment. Toxicology Letters 131:1-3.

8
16. Emmanuel, Perrodin, Keck, Blanchard, and Vermande (2005) Ecotoxicological
risk assessment of hospital wastewater: a proposed framework for raw effluents
discharging into urban sewer network. Journal of Hazardous Materials 117:1-11.
17. Ternes, Stumpf, Mueller, Haberer, Wilken, and Servos (1999) Behavior and
occurrence of estrogens in municipal sewage treatment plants -- I. Investigations
in Germany, Canada and Brazil. The Science of The Total Environment 225:81-
90.
18. Heberer (2002) Tracking persistent pharmaceutical residues from municipal
sewage to drinking water. Journal of Hydrology 266:175-189.
19. Diaz-Cruz, Lopez de Alda, and Barcelo (2003) Environmental behavior and
analysis of veterinary and human drugs in soils, sediments and sludge. TrAC
Trends in Analytical Chemistry 22:340-351.
20. Koutsouba, Heberer, Fuhrmann, Schmidt-Baumler, Tsipi, and Hiskia (2003)
Determination of polar pharmaceuticals in sewage water of Greece by gas
chromatography-mass spectrometry. Chemosphere 51:69-75.
21. Pedersen, Soliman, and Suffet (2005) Human Pharmaceuticals, Hormones, and
Personal Care Product Ingredients in Runoff from Agricultural Fields Irrigated
with Treated Wastewater. Journal of Agricultural and Food Chemistry 53:1625-
1632.
22. Pedersen, Soliman, and Suffet, Human Pharmaceuticals, Hormones, and Personal
Care Product Ingredients in Runoff from Agricultural Fields Irrigated with
Treated Wastewater. 2005. p. 1625-1632.
23. Khetan and Collins, Human Pharmaceuticals in the Aquatic Environment: A
Challenge to Green Chemistry. 2007. p. 2319-2364.
24. Ternak (2005) Antibiotics may act as growth/obesity promoters in humans as an
inadvertent result of antibiotic pollution? Medical Hypotheses
64:14-16
25. Ternes (1998) Occurrence of drugs in German sewage treatment plants and rivers.
Water Research 32:3245-3260.
26. Sacher, Lange, Brauch, and Blankenhorn (2001) Pharmaceuticals in
groundwaters: Analytical methods and results of a monitoring program in Baden-
Wurttemberg, Germany. Journal of Chromatography A 938:199-210.
27. Weigel, Kuhlmann, and Huhnerfuss (2002) Drugs and personal care products as
ubiquitous pollutants: occurrence and distribution of clofibric acid, caffeine and
DEET in the North Sea. The Science of The Total Environment 295:131-141.
28. Wiegel, Aulinger, Brockmeyer, Harms, Loffler, Reincke, Schmidt, Stachel, von
Tumpling, and Wanke (2004) Pharmaceuticals in the river Elbe and its tributaries.
Chemosphere 57:107-126.
29. Vieno, Tuhkanen, and Kronberg (2005) Seasonal Variation in the Occurrence of
Pharmaceuticals in Effluents from a Sewage Treatment Plant and in the Recipient
Water. Environmental Science & Technology 39:8220-8226.
30. Zuccato, Castiglioni, and Fanelli (2005) Identification of the pharmaceuticals for
human use contaminating the Italian aquatic environment. Journal of Hazardous
Materials 122:205-209.

9
 31. Roberts and Thomas (2006) The occurrence of selected pharmaceuticals in
wastewater effluent and surface waters of the lower Tyne catchment. Science of
The Total Environment 356:143-153.
32. Trenholm, Vanderford, Holady, Rexing, and Snyder (2006) Broad range analysis
of endocrine disruptors and pharmaceuticals using gas chromatography and liquid
chromatography tandem mass spectrometry. Chemosphere 65:1990-1998.
33. Ying-Hsuan, Chia-Yang, and Gen-Shuh (2007) Analysis of steroid estrogens in
water using liquid chromatography/tandem mass spectrometry with chemical
derivatizations. Rapid Communications in Mass Spectrometry 21:1973-1983.
34. Zhang and Zhou (2007) Simultaneous determination of various pharmaceutical
compounds in water by solid-phase extraction-liquid chromatography-tandem
mass spectrometry. Journal of Chromatography A 1154:205-213.

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