PHARMACEUTICALS IN THE ENVIRONMENT—GLOBAL OCCURRENCES
AND PERSPECTIVES
TIM AUS
DER
BEEK,*y FRANK-ANDREAS WEBER,y AXEL BERGMANN,y SILKE HICKMANN,z INA EBERT,z ARNE HEIN,z
and ANETTE KÜSTERz
yIWW Water Centre, Department of Water Resources Management, M€
ulheim an der Ruhr, Germany
zSection IV 2.2 Pharmaceuticals, Washing and Cleaning Agents, Umweltbundesamt (German Federal Environment Agency), Dessau, Germany
(Submitted 27 February 2015; Returned for Revision 3 July 2015; Accepted 11 December 2015)
Abstract: Pharmaceuticals are known to occur widely in the environment of industrialized countries. In developing countries, more
monitoring results have recently become available, but a concise picture of measured environmental concentrations (MECs) is still
elusive. Through a comprehensive literature review of 1016 original publications and 150 review articles, the authors collected MECs for
human and veterinary pharmaceutical substances reported worldwide in surface water, groundwater, tap/drinking water, manure, soil,
and other environmental matrices in a comprehensive database. Due to the heterogeneity of the data sources, a simplified data quality
assessment was conducted. The database reveals that pharmaceuticals or their transformation products have been detected in the
environment of 71 countries covering all continents. These countries were then grouped into the 5 regions recognized by the United
Nations (UN). In total, 631 different pharmaceutical substances were found at MECs above the detection limit of the respective analytical
methods employed, revealing distinct regional patterns. Sixteen substances were detected in each of the 5 UN regions. For example, the
anti-inflammatory drug diclofenac has been detected in environmental matrices in 50 countries, and concentrations found in several
locations exceeded predicted no-effect concentrations. Urban wastewater seems to be the dominant emission pathway for
pharmaceuticals globally, although emissions from industrial production, hospitals, agriculture, and aquaculture are important locally.
The authors conclude that pharmaceuticals are a global challenge calling for multistakeholder approaches to prevent, reduce, and manage
their entry into and presence in the environment, such as those being discussed under the Strategic Approach to International Chemicals
Management, a UN Environment Program. Environ Toxicol Chem 2016;35:823–835. # 2015 SETAC
Keywords: Pharmaceutical
Measured environmental concentration
Emerging pollutant
Pharmaceutical consumption
Global measured environmental concentration database
global issue. The aim was to provide an up-to-date review of the
current state of knowledge on the global relevance and prevailing
concentrations of pharmaceuticals in the environment.
Even though there are approximately 150 review articles
about the occurrence of pharmaceuticals in the environment
(see Supplemental Data, S1), these articles usually do not
include a global-scale assessment. Instead, most of these review
articles are limited to specific countries, such as China [13] or
Sweden [14], and/or to specific water bodies, such as the
Spanish Llobregat River [15] or the North American Great
Lakes [16]. Other review articles focus on specific therapeutic
groups, such as psychoactive drugs [17] or cytostatics [18],
or on specific substances, such as the antibiotic tetracycline
[19]. Further review articles have been published that report
measured environmental concentrations of pharmaceuticals in
the context of target populations [20], sampling matrices or
methods [21–24], emission sources [25–27], or transformation
products [28].
Very few articles provide even a semiglobal review, and
often the focus is only on peer-reviewed publications in
international journals [29–31]. Other quality data sources, such
as reports by governments, water body management and
monitoring authorities, and university researchers, and other
publications, especially in developing and emerging countries,
are frequently excluded. For example, university theses from
developing and emerging countries such as South Africa and
Brazil were a major data source for the present study because
peer-reviewed publication of monitoring campaign data is
relatively uncommon as a result of language barriers, publication costs, and limited time frames for graduation procedures.
INTRODUCTION
The practice of modern medicine cannot be imagined
without pharmaceuticals. A growing world population, increasing investment in the health-care sector, advances in research
and development, pervasive global market availability, and
aging societies in industrialized countries have led to a
significant increase in the consumption of pharmaceuticals in
the last few decades [1]. Simultaneously, laboratory instrumentation and analytical methods have advanced, enabling the
detection of some pharmaceutical substances in the aquatic and
terrestrial environment down to the range of micrograms per
liter or even picograms per liter [2]. This advance in technology
might partially explain the increase in scientific publications
pertaining to the occurrence of pharmaceuticals in the
environment since the late 1990s [3]. In parallel with these
monitoring studies, ecotoxicological effects that pharmaceutical
substances can exert on nontarget organisms at environmentally
relevant concentrations have been demonstrated in a growing
number of laboratory [4–7], field-scale [8–10], and ecosystemscale [11] studies.
The present study was initiated after this issue was
nominated to the Strategic Approach to International Chemicals
Management [12], with the goal of assessing whether the
occurrence of pharmaceuticals in the environment is truly a
This article includes online-only Supplemental Data.
* Address correspondence to t.ausderbeek@iww-online.de
Published online 14 December 2015 in Wiley Online Library
(wileyonlinelibrary.com).
DOI: 10.1002/etc.3339
823
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Environmental Toxicology and Chemistry, Vol. 35, No. 4, pp. 823–835, 2016
# 2015 SETAC
Printed in the USA
Environ Toxicol Chem 35, 2016
Because of the focus on industrialized countries, thus far no
concise picture of the global relevance of the environmental
presence of pharmaceutical substances has been provided. For
example, Hughes et al. [31] reviewed literature for 41 countries
and claimed “little work outside North America, Europe, and
China, and no work within Africa.”
The present study thus aimed to provide a comprehensive
review of measured environmental concentrations for both
human and veterinary pharmaceutical substances on a global
scale. Published measured environmental concentrations
(MECs) in sewage, surface water, groundwater, tap/drinking
water, sediment, manure, soil, and other environmental matrices
were compiled in a global database and analyzed with respect
to regional patterns. The MECs were also used to assess the
potential ecotoxicological risks to nontarget organisms based
on predicted no-effect concentrations (PNECs), derived from
ecotoxicity studies. The database was analyzed with respect to
regional patterns, current trends, and the relevance of different
emission pathways and can be used as a basis for developing
targeted global strategies of action. In addition, data on annual
pharmaceutical consumption were compiled from publicly
available publications to assess regional differences and aid in
the design of more effective monitoring strategies that address
existing data gaps.
MATERIALS AND METHODS
Defining relevant pharmaceuticals
Within the present study, pharmaceuticals have been defined
as substances that are primarily being used for therapeutic,
preventive, and diagnostic purposes. Recreational drugs, such as
cocaine and caffeine, have been excluded from the present
analysis. Other substances, such as homeopathics, minerals,
proteins, and immunologic substances, also were not included.
If not otherwise indicated, the terms “pharmaceuticals” and
“pharmaceutical substances” refer only to the actual active
pharmaceutical ingredients.
Bibliographic database
A systematic literature review was conducted up to and
including October 2013 using multiple search strategies. First,
peer-reviewed publications were identified using scientific
search engines including Web of Science and Science Direct
and by consulting original publications cited in review articles.
Second, non–peer-reviewed articles, books, university research,
and governmental reports in different languages were identified
using Internet search engines and library catalogues. Third,
existing databases available within the European Commission,
such as KNAPPE [32], FATE-SEES [33], and POSEIDON [34],
and international networks such as NORMAN, as well as a
database previously compiled by Bergmann et al. [35] on
behalf of the German Environment Protection Agency were
consulted for the present study. FInally, 41 stakeholders from
local governments, universities, and others institutions were
contacted to gather additional regional information, mainly in
Africa, Asia, and Latin America. The complete bibliography
of publications and databases that were included is listed in
Supplemental Data, S2.
All publications identified as relevant were categorized in a
bibliographic database (Endnote©; Thomson Reuters) according to the country where the data were collected. If a publication
included data for more than 1 country, the literature citation
was assigned to each of the countries. Although most of the
publications were written in the English language, publications
T. aus der Beek et al.
in Chinese, Dutch, French, German, Portuguese, Russian,
Slovenian, Spanish, and Swedish were also included.
MEC database
Data from all sources were transferred to the new MEC
database, which was implemented in Microsoft Access©. Each
database entry comprises 32 fields, including the name of
the pharmaceutical substance, its Chemical Abstracts Service
number, the environmental matrix the substance was measured
in, geographical location, sampling period, number of measurements, measured concentration in original and standardized
units, detection limit of the analytical method employed,
pollution source (if stated in the publication), literature citation,
publication language and type, and a data quality flag.
The environmental matrices in which MECs of pharmaceutical substances were reported included surface water; bank
filtrate; groundwater; well water; tap/drinking water; sewage
and wastewater-treatment plant (WWTP) influent, effluent, and
sludge; manure; soil; sediments; suspended particulate matter;
and other environmental matrices organized into multiple
subcategories (Supplemental Data, S3). No differentiation was
made between tap water and drinking water because many
publications made no clear distinction between tap water that
is suitable as a source of drinking water and nonpotable tap
water.
The geographical sampling locations (including geographical name, region, and country) were categorized according
to the United Nations (UN) regional groups (Africa Group,
Asia-Pacific Group, Eastern Europe Group, group of Latin
American and Caribbean States, and Western Europe and
Others Group, which also includes North America, Australia,
and New Zealand). An example of a typical database entry is
given in Supplemental Data, S4.
Most publication reports aggregate MEC data into a
descriptor value rather than reporting single observations.
Aggregated data were entered in a single database entry stating
the data descriptor used (average, median, 90th percentile,
minimum or maximum of a monitoring campaign) and the
number of underlying measurements. Because the statistical
distribution of the aggregated data is rarely known, only
database entries reporting single or average values were
considered in deriving weighted national average concentrations. National maximum concentrations were assigned the
highest concentrations reported for a specific environmental
matrix in each country.
A quality flag associated with each database entry identifies
the overall validity, reliability, and analytical standards (if
available) applied in each publication. In comparison with
governmental and project reports, peer-reviewed publications
were considered to be verified sources of higher quality because
their results and methods have already been reviewed. The
quality assessment of non–peer-reviewed reports and publications, which include university theses, was more difficult
to evaluate. Even though some of the methods and results
published in these theses and reports are difficult to verify,
the majority of publications received a good quality flag. It is
important to consider that, because of the heterogeneity of the
more than 1000 data sources used in the present study it was
not possible to conduct a standardized quality assessment. The
quality assessment was based on a subjective impression of
the plausibility of the methods used and the resulting data in the
context of comparable MECs. This needs to be kept in mind
when making assumptions based on an analysis of these MEC
database entries.
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824
Environ Toxicol Chem 35, 2016
825
Consumption database
Environmental matrices analyzed
Consumption or prescription quantities for human and
veterinary pharmaceuticals were compiled from the publicly
available literature using the search strategy outlined above.
Data sold by commercial international health-care data service
providers (e.g., IMS Health) were not included because of
high service charges. Generally, data service providers focus on
industrialized and emerging countries, with little information
available for developing countries. Only sources that reported
country-wide consumption in units such as kilograms per year
were included. Some publications report a defined daily dose
or other doses per patient, which could not be converted to
country-wide consumption figures without additional information. The database fields specify the name of the pharmaceutical,
the yearly amount consumed, the reference period, country,
and UN region, as well as the literature citation and data
quality flag. Another field identifies the underlying data
source because often no national sum of total consumption is
reported but rather a sectoral value only, such as consumption
in hospitals, by outpatients, or for veterinary purposes. The
relevant literature reporting consumption data is included
in the bibliography listed in Supplemental Data, S5. An
example of a typical consumption database entry is given in
Supplemental Data, S6.
Pharmaceutical substances were found in a variety of
environmental matrices (Supplemental Data, S3). Most measurements have been reported for surface waters (47% of all
database entries), the majority from river and stream samples,
followed by lakes and oceans. Groundwater and drinkingwater samples comprise 8% of the total database entries,
with the majority of the available measurements referring to
groundwater and very few to untreated well water, bank filtrate,
or tap/drinking water. Wastewater MECs, which make up
40% of all database entries, are dominated by measurements in
the WWTP effluent, followed by WWTP influent, untreated
hospital sewage, WWTP sludge, and untreated urban sewage.
By comparison, very few MECs were found for veterinary
pharmaceuticals in manure, dung, or soil (3% of all database
entries); and the occurrence of pharmaceuticals adsorbed to
suspended particulate matter and contamination of sediments
was hardly studied (2% of all database entries).
RESULTS
MEC database
Our literature review identified 1016 original publications
reporting unique MEC data for human and/or veterinary
pharmaceutical substances worldwide. In addition, 147 review
articles were assessed. Measured environmental concentrations
from these sources were entered into a database, resulting in
123 761 entries. Most entries represent a summary statistic of
multiple measurements. Therefore, the total number of
underlying MECs in the database is much higher than the
actual number of database entries. Because the number of
samples that each data point represents is missing for some
aggregated data and some database entries refer to different
statistical parameters of the same monitoring data (e.g., average,
median, maximum, minimum), the total number of underlying
measurements of the database cannot be exactly specified. Thus,
in the present study, we refer to the number of database entries
as an indicator of monitoring intensity. Most database entries
were generated from data published in peer-reviewed journal
articles, followed by existing databases (such as NORMAN).
By comparison, fewer database entries were generated from
governmental reports, books, and university theses.
The sampling period was reported in the source material for
approximately 88% of all database entries. Only 1281 database
entries were included that predate 2001; and the oldest
reference, published in 1987, refers to antibiotics used on pig
farms [36]. The number of database entries increases markedly
from approximately 2000 in the year 2001 to more than 24 000
in the year 2010. This may be the result of technological
advances, such as advanced gas chromatography–mass spectrometry and high-performance liquid chromatography–mass
spectrometry [24], but could also be the result of an increased
scientific, governmental, and public awareness of pharmaceuticals as emerging pollutants. After 2010, the number of
database entries drops to 8200 in 2011, to 1300 in 2012, and
finally to 224 by October 2013, when our literature review
ended.
Country survey reporting pharmaceutical substances in the
environment
According to the database, there are 71 countries worldwide
in which at least 1 pharmaceutical substance was reported in the
literature at concentrations exceeding the detection limit of
the analytical method employed. The 71 countries in which
pharmaceutical substances have been detected in the environment include countries from all 5 UN regional groups.
Despite the global coverage, pronounced regional patterns in
the intensity of environmental monitoring efforts prevail. For
Western Europe and Others Group countries, approximately
96 000 database entries were found in 730 publications so
that roughly 3 out of 4 database entries originate from this
geographical group. The majority of MECs are from Germany
(16 343 from 221 publications), followed by the United
States (9515 from 143 publications) and Spain (13 092 from
83 publications). For Malta, Iceland, Greenland, and the
Faroe Islands, only a single publication each was found. For
the entire African continent, in contrast, only 23 publications
were available, resulting in 1159 database entries with regional
representation mainly from South Africa, Nigeria, and Kenya.
Pharmaceutical substances detected
The most commonly analyzed pharmaceuticals belong to
the therapeutic groups of antibiotics, analgesics, and estrogens
(Figure 1). Regional monitoring priorities and preferences are
readily apparent, for example, antibiotics in the Asia-Pacific
Group, estrogens in Africa, analgesics in the Eastern Europe
Group, and a range of different pharmaceutical groups in
the Western Europe and Others Group. It must be noted in
this context, as discussed in the Country survey reporting
pharmaceutical substances in the environment section, that all
regions are subject to different numbers of database entries,
such that nearly 100 times as many database entries are available
for the Western Europe and Others Group compared with
Africa.
Globally, environmental water samples were analyzed for
713 different pharmaceuticals and related compounds. As a
result, 631 were found to be present above the detection limits of
the analytical method employed in the publication. This total
includes the detection of 127 transformation products (out of
142 analyzed). Further analysis showed that in most UN
regions very similar substances were found to those in the
Western Europe and Others Group countries (Western Europe
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Pharmaceuticals in the global environment
Environ Toxicol Chem 35, 2016
T. aus der Beek et al.
Figure 1. Regional patterns of pharmaceutical therapeutic groups analyzed in each United Nations region. MEC ¼ measured environmental concentration;
EEG ¼ Eastern Europe Group; GRULAC ¼ Latin American and Caribbean States; WEOG, Western Europe and Others Group.
and Others Group: samples were analyzed for 646 substances,
and 574 substances were found; Asia: samples were analyzed
for 313 substances, and 249 substances were found; Eastern
Europe Group: samples were analyzed for 205 substances,
and 126 substances were found; Latin American and Caribbean
States: samples were analyzed for 84 substances, and 55
substances were found; Africa: samples were analyzed for
59 substances, and 40 substances were found). However, some
regional differences are notable, especially in Asia and Africa
where some antibiotics, veterinary growth stimulants [37], and
antiviral substances [38] were detected (Figure 2) that have
never been detected in Western Europe and Others Group
countries.
Residues of 16 pharmaceutical substances were detected in
the surface, drinking, and groundwater of all the UN regions
(Table 1). In addition, the antibiotic tetracycline was detected
in WWTP effluents in all UN regions. Diclofenac, which is
a widely used analgesic for both human and veterinary
application, is the most frequently detected pharmaceutical in
environmental samples globally. In total, it has been found
in surface water, groundwater, and/or tap/drinking water in
50 countries. In all UN regions it belongs to the 5 most
often detected pharmaceuticals in the environment. Another 4
pharmaceutical substances have been found in the environment
nearly as often as diclofenac: carbamazepine (antiepileptic),
sulfamethoxazole (antibiotic), ibuprofen, and naproxen (both
Figure 2. Regional patterns of the number of pharmaceutical substances
detected in each United Nations regional group (of number of substances
analyzed) and intersection with pharmaceutical substances measured in
Western Europe and Others Group countries. EEG ¼ Eastern Europe;
GRULAC ¼ Latin America and Caribbean States; WEOG ¼ Western
Europe and Others Group.
analgesics). Other therapeutic groups that have been detected
in the environment include estrogens, such as estrone and
ethinylestradiol, as well as the metabolite of the lipid-lowering
drug clofibric acid. The list of pharmaceutical substances found
in all 5 UN regional groups is constrained by the low number of
measurements in Africa and Latin American and Caribbean
States. If the number of measurements in these 2 UN regions
continues to increase, it is to be expected that the number of
globally detected pharmaceuticals will also increase.
For pharmaceuticals listed in Table 1, an analysis of regional
average and maximum concentrations for each UN region as
well as on a global range is presented in Table 2. Please note that
the entries in Table 2 only include MECs that have been
provided as single data points or averages. Other data formats,
such as medians or percentiles, could not be used for the
calculation of average concentrations because of missing
information about the underlying data distribution. Table 2
shows that the global average and maximum concentrations are
dominated by Western countries (Western Europe and Others
Group) because most sampling programs have been conducted
in this UN region. In addition, MECs from several Asian
countries provide relatively good data coverage for several
pharmaceuticals. Out of the 16 globally found pharmaceutical
substances, the maximum concentrations can be found in
Western Europe and Others Group (n ¼ 8), Asia (n ¼ 5), and
Latin American and Caribbean States (n ¼ 3). In Asia, the
highest maximum concentrations were found for antibiotics in
surface waters close to pharmaceutical production sites (e.g.,
6.5 mg/L of ciprofloxacin in India). Average concentrations
of diclofenac, naproxen, estradiol, clofibric acid, and estriol
were present in amounts that are in the same order of magnitude
among the 5 UN regions. For carbamazepine, sulfamethoxazole,
ibuprofen, trimethoprim, and paracetamol Africa features the
highest average concentrations. This indicates that pharmaceuticals in the environment are not just a problem of industrialized
countries. However, the limited number of samples from Africa
needs to be considered as well. The antibiotics norfloxacin,
oflofloxacin, and ciprofloxacin have been measured in the
highest average concentrations in Asian surface waters. This
might be explained by the large number of samples targeted at
detecting antibiotics (Figures 1) and by multiple publications
that have analyzed samples from surface waters near
pharmaceutical production facilities. The highest average
concentrations of the hormones estrone, estradiol, and ethinylestradiol were found in South American surface waters. This
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Environ Toxicol Chem 35, 2016
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Table 1. Number of countries in each United Nations group in which positive detection of pharmaceutical substances in surface waters, groundwater, and/or tap
or drinking water has been reporteda
Pharmaceutical substance
Diclofenac
Carbamazepine
Ibuprofen
Sulfamethoxazole
Naproxen
Estrone
Estradiol
Ethinylestradiol
Trimethoprim
Paracetamol
Clofibric acid
Ciprofloxacin
Ofloxacin
Estriol
Norfloxacin
Acetylsalicylic acid
Therapeutic group
Africa
Asia-Pacific
EEG
GRULAC
WEOG
Global
Analgesics
Antiepileptics
Analgesics
Antibiotics
Analgesics
Estrogens
Estrogens
Estrogens
Antibiotics
Analgesics
Lipid-lowering drugs
Antibiotics
Antibiotics
Estrogens
Antibiotics
Analgesics
3
3
3
5
2
1
2
1
2
1
1
1
1
1
1
1
8
6
8
9
8
10
9
8
9
6
3
5
4
1
4
4
13
13
10
10
10
6
4
3
3
4
5
1
1
2
1
1
3
2
2
2
2
2
2
2
2
3
2
2
1
1
2
2
23
24
24
21
23
16
17
17
13
15
12
11
9
10
7
7
50
48
47
47
45
35
34
31
29
29
23
20
16
15
15
15
a
These 16 substances are the only ones that have been found in each region.
EEG ¼ eastern Europe; GRULAC ¼ Latin America and Caribbean; WEOG ¼ western Europe and others.
might be explained by the fact that estrogens are the most
frequently analyzed therapeutic group in South America
(Figure 1). Further details on global average and maximum
concentrations for more than 600 pharmaceutical substances
and the environmental matrices in which they were found are
included in Supplemental Data, S10.
Pharmaceutical substances in the aquatic environment
In each UN regional group at least 38 different pharmaceutical substances were found in surface water, groundwater, or
tap/drinking water. More than 100 different pharmaceutical
substances have been found in several European countries and
the United States in the aquatic environment (surface waters,
groundwater, and/or tap/drinking water) in concentrations
greater than the detection limit (Figure 3). More than 30
different pharmaceutical substances were found in Western
Europe and Others Group, Eastern Europe Group, Asia-Pacific,
and Latin American and Caribbean States countries. In most
regions of the Asia-Pacific Group, Africa Group, and Eastern
Europe Group, 30 different pharmaceutical substances or fewer
have been detected.
Pharmaceutical substances in tap/drinking water
In general, only limited data are available for tap/drinking
water. This especially applies to developing and emerging
countries (Figure 4). The majority of detections come from
Western Europe and Others Group countries such as Spain and
Germany, where more than 30 different pharmaceuticals have
been detected. Between 11 and 30 pharmaceutical substances
have been found in tap/drinking water in Canada, China, France,
Sweden, and the United States. Traces of pharmaceutical
substances have also been detected in bottled water in
France [39]. These results are not in accordance with a recent
report [40], which describes considerably fewer data on
pharmaceuticals in drinking water.
Pharmaceutical substances in sewage and WWTPs
In total, 559 different pharmaceuticals have been detected
globally in WWTP influent, effluent, and sludge. The number
of pharmaceuticals detected in wastewater matrices in each
country is illustrated in Supplemental Data, S7. High numbers
of pharmaceuticals detected in a region usually correlate with
a high number of measurements, for example, in Canada and
China. In general, a close relationship can be assumed between
occurrences in WWTP effluent and surface waters because most
WWTP effluent is discharged directly into surface waters such
as rivers and lakes.
Pharmaceutical substances in manure and soil
As shown in Supplemental Data, S3, only 3% of all database
entries refer to measurements of pharmaceuticals in manure
and soil. This is also depicted in Supplemental Data, S8,
which features a global map that includes the number of
pharmaceuticals detected in manure and/or soil in each
country. Between 30 and 100 pharmaceutical substances have
been found in manure and soil in Europe, North America,
and China. In many other regions, little research on this
topic has been published and, therefore, few data sets are
available. However, studies conducted in Brazil, Australia,
Turkey, South Korea, and Malaysia reported between 4 and 10
different substances.
Measured environmental concentrations: Case studies
A comprehensive analysis of national maximum and
weighted average concentrations of all 631 pharmaceuticals
for each environmental matrix, including the total number of
measurements, can be found in Supplemental Data, S10. As
described in the Materials and Methods section, only measurements which were reported as single values or average values
accompanied by the underlying numbers of measurements
were included (see also Table 2). The complete database will
be publicly available on the website of the German Federal
Environment Agency (see the Data availability section).
Case studies of frequently detected pharmaceutical substances,
diclofenac and 17a-ethinylestradiol (EE2), are presented below
in Example 1: Diclofenac in surface waters and Example 2:
17a-Ethinylestradiol in surface waters.
Example 1: Diclofenac in surface waters. Because diclofenac
is the most often detected pharmaceutical in the environment,
a more detailed analysis of its global occurrence was conducted.
National weighted average concentrations and national maximum concentrations in surface waters are illustrated in Figure 5
and Figure 6. The concentration value was weighted by the
number of measurements for each database entry within a
country (detailed values given in Supplemental Data, S9).
Maximum concentrations of >1 mg/L often occur downstream of
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Pharmaceuticals in the global environment
0.239 (130)
0.0 (10)
0.0 (121)
0.001 (95)
0.017 (9)
0.347 (79)
No data
1.175 (50)
0.005 (95)
0.74 (112)
0.0007 (94)
0.001 (95)
0.335 (86)
0.0002 (21)
0.0006 (95)
2.07 (112)
6.0
0.0
36.8
0.11
0.19
5.0
No data
5.9
0.48
37.0
0.03
0.74
0.34
0.03
1.74
20.96
0.020 (6301)
0.188 (24776)
0.097 (6264)
0.068 (7789)
0.057 (2666)
0.004 (1632)
0.005 (183)
0.005 (1238)
0.022 (2598)
0.046 (629)
0.023 (2796)
0.008 (343)
0.123 (451)
0.002 (536)
0.009 (274)
0.002 (107)
18.74
8.05
303.0
29.0
12.3
1.25
0.012
0.28
10.0
230.0
7.91
13.6
8.77
0.48
1.15
0.36
0.032 (7017)
0.187 (25115)
0.108 (6950)
0.095 (8599)
0.050 (3229)
0.016 (2228)
0.003 (297)
0.043 (1530)
0.037 (3060)
0.161 (937)
0.022 (2947)
18.99 (672)
0.278 (760)
0.009 (790)
3.457 (628)
0.922 (254)
18.74
8.05
303.0
29.0
32.0
5.0
0.012
5.9
13.6
230.0
7.91
6500
17.7
0.48
520.0
20.96
T. aus der Beek et al.
a
Values in parentheses describe the number of samples.
EEG ¼ eastern Europe; GRULAC ¼ Latin America and Caribbean; WEOG ¼ western Europe and others.
0.111 (420)
0.131 (302)
0.183 (529)
0.033 (139)
0.023 (403)
0.001 (262)
0.0005 (20)
0.002 (57)
0.012 (22)
0.028 (68)
0.009 (48)
0.002 (22)
0.0003 (11)
0.002 (131)
0.004 (15)
0.062 (29)
Diclofenac
Carbamazepine
Ibuprofen
Sulfamethoxazole
Naproxen
Estrone
Estradiol
Ethinylestradiol
Trimethoprim
Paracetamol
Clofibric acid
Ciprofloxacin
Ofloxacin
Estriol
Norfloxacin
Acetylsalicylic acid
0.273 (14)
0.868 (14)
3.181 (13)
2.53 (58)
0.012 (12)
0.004 (96)
0.0001 (46)
0.0 (32)
0.985 (12)
5.667 (6)
0.007 (6)
0.017 (6)
0.012 (6)
0.0 (34)
0.076 (6)
0.043 (6)
1.52
4.5
21.0
21.0
0.07
0.02
0.002
0.0
5.5
16.0
0.04
0.034
0.036
0.0
0.15
0.13
0.090 (152)
0.026 (18)
0.059 (23)
0.258 (518)
0.008 (139)
0.012 (159)
0.0003 (48)
0.008 (159)
0.128 (333)
0.023 (132)
0.003 (3)
61.94 (206)
0.617 (206)
0.008 (66)
9.11 (238)
No data
4.4
0.04
20.5
14.3
32.0
0.32
0.007
0.028
13.6
9.17
0.248
6500
17.7
0.074
520.0
7.5
4.2
7.6
11.7
0.3
0.85
0.07
0.003
0.08
0.174
0.61
0.42
0.031
0.004
0.08
0.057
0.73
Average
Maximum
Average
Maximum
Average
Maximum
Average
Maximum
Average
Maximum
Average
Pharmaceutical substance
WEOG
GRULAC
EEG
Asia-Pacific
Africa
Table 2. Average and maximum concentrations of the 16 pharmaceuticals found in each United Nations region for all surface water compartments (in micrograms per liter)a
Global
Maximum
Environ Toxicol Chem 35, 2016
sewage-treatment plants in densely populated areas. Weighted
average concentrations of >0.1 mg/L were found in at least 1
country of each UN region. Interestingly, no diclofenac
concentrations were available for Canadian and Australian
surface waters because reported concentrations for these 2
countries focused on maximum values and on measurements in
wastewater rather than surface waters.
For example, average diclofenac concentrations of some
countries, such as Germany (0.164 mg/L), are based on a large
number of measurements (Germany: 4137), whereas other
countries where MECs are in the same concentration range,
such as Malaysia (0.117 mg/L), only feature a few observations
(Malaysia: 2). Therefore, a direct comparison of countries is not
appropriate, and the map provided (Figures 5 and 6) should only
be treated as a visual indicator of global occurrence of
pharmaceutical substances.
Example 2: 17a-Ethinylestradiol in surface waters. A
second pharmaceutical substance that was found in each of
the UN regions is the estrogenic hormone EE2, which is used
as a contraceptive pill by 8.9% of all women globally [41].
Figure 7 illustrates the maximum EE2 concentrations found in
the surface waters of each country globally. Most measurements
have been made in Europe and North America, but Southeast
Asian countries also provided several data sets. Maximum
concentrations were in the range of 0.001 mg/L to 0.040 mg/L,
with more than half of the countries reporting maximum
concentrations >0.001 mg/L.
The lowest detectable concentration of several pharmaceuticals is an analytical challenge, and some reported MECs raise
questions about data quality. For example, the highest MECs
reported for EE2 in surface waters globally seem unrealistically
high. These include 5.9 mg/L found in a Brazilian river (K.S.
Machado, 2010, Master’s thesis, Universidade Federal do
Parana, Curitiba, Parana, Brazil), 0.28 mg/L in a Spanish river
[42], and several reports with concentrations >0.1 mg/L from
the United States, Germany, and Switzerland. These database
entries were flagged as questionable but were not removed
if analytical shortcomings were not apparent, because the
presence of local point sources, such as pharmaceutical factories,
could not be excluded.
Emission pathways
In addition to environmental concentrations, emission
pathways for pharmaceuticals entering the environment were
entered in the MEC database if specified in a publication.
However, information about the most likely emission sources
was available for only 13% of the database entries. This might
partially be a result of the large number of samples taken from
surface waters (Supplemental Data, S3), where the dominant
emission pathway upstream is often unknown.
Considering the database entries with a reported emission
source, urban wastewater is the dominant emission pathway.
The second most frequently listed emission sources is hospitals.
A multitude of different pharmaceuticals, often at high concentrations [27], can be found in the sewage effluent of health-care
facilities. Most hospitals do not have on-site sewage-treatment
plants and are connected directly to urban sewage systems. The
third most often listed emission source for pharmaceuticals is
commercial animal husbandry. Veterinary pharmaceuticals are
often administered to livestock to treat or prevent diseases.
Veterinary drugs and their metabolites excreted in the animals’
urine and feces can reach surface waters and groundwater in
runoff after precipitation events. Some pharmaceuticals, such
as the antibiotic sulfamethoxazole, are used in both veterinary
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828
Environ Toxicol Chem 35, 2016
Figure 3. Country survey on the number of pharmaceutical substances detected in surface waters, groundwater, or tap/drinking water.
Figure 4. Country survey on the number of pharmaceutical substances detected in tap water and/or drinking water.
Figure 5. Weighted-average diclofenac concentrations in surface water calculated from reported monitoring data for each country.
829
15528618, 2016, 4, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/etc.3339 by Wyoming State Library, Wiley Online Library on [22/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Pharmaceuticals in the global environment
Environ Toxicol Chem 35, 2016
T. aus der Beek et al.
Figure 6. Maximum diclofenac concentrations reported in surface waters in each country.
Figure 7. Maximum 17a-ethinylestradiol concentrations measured in surface waters in each country.
and human medicine. It is therefore not possible to make
conclusions about their origin from their presence in water
samples. Other important emission sources that can cause
localized increases of pharmaceutical concentrations in environmental matrices are pharmaceutical manufactures, aquaculture facilities, and wastewater used to irrigate field crops.
Pharmaceutical production in particular can cause high
concentrations in the range of milligrams per liter in rivers
adjacent to production facilities, especially in developing and
emerging countries [25,43]. Several high concentrations in the
MEC database are correlated with pharmaceutical production
facilities in these countries. For example, Dolar et al. [44]
reported a maximum concentration of 27.68 mg/L for trimethoprim in the sewage effluent of a Croatian production facility.
Regional patterns prevail when considering the database
entries with known emission sources. In Asia, for example,
more data on pharmaceutical concentrations originating from
aquaculture (i.e., fish and shrimp farming facilities) and
agriculture have been published, whereas more data on hospital
sewage effluent were available for Western Europe and Others
Group countries. An order of magnitude greater number of
database entries are available for Western Europe and Others
Group countries, and any regional patterns may be biased by
the number of underlying data points as well as potential data
quality issues.
Linking consumption of pharmaceuticals to MECs
In total, 69 publications have been identified that provide
consumption data for at least 1 pharmaceutical and country.
From these publications approximately 4500 entries were
transferred to the database. In many publications, however,
only partial consumption/sales are reported, which is frequently
specific to a particular sector, such as outpatient clinics,
hospitals, prescription quantities, veterinary use, and pharmacy
sales. When analyzing the data, therefore, it needs to be kept in
mind that not all of the database entries refer to total national
consumption values. The database provides consumption data
for only 257 different pharmaceuticals, whereas the MEC
database is nearly 3 times as large. The consumption data are
also not equally distributed in space and time. In Africa,
156 database entries are available for 2 countries (Kenya
and Morocco), whereas 81 entries are available for Asia.
Unfortunately, no consumption data were available for China,
which is the largest provider of Asian MEC data. Within the
Eastern Europe Group, 186 data points can be found, for a total
of 8 countries. Interestingly, Latin American and Caribbean
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830
States offers a far better database, with 619 entries for 10
countries. The Western Europe and Others Group has the largest
share of the consumption database, with nearly 3500 data points
for 18 countries.
The temporal range of the consumption database includes all
years between 1984 and 2012, whereas the majority of entries
are listed for the last decade. The most often reported
pharmaceutical substance is amoxicillin (142 entries), followed
by trimethoprim (123), erythromycin (103), ciprofloxacin (92),
vancomycin (91), clarithromycin (79), and azithromycin (76).
This ranking also shows that the therapeutic medication groups
within the consumption database do not follow a normal
distribution because each of the 10 most often reported
pharmaceutical agents belongs to the antibiotic group.
Antibiotic consumption has been more often reported (more
than 3000 database entries) and analyzed than all of the other
therapeutic groups together. The largest values within the
database have been reported for paracetamol (acetaminophen)
for the United States (5790 tons in 2002) and France (3303 tons
in 2005) as well as for chlortetracycline in South Korea (2763
tons in 2005 for veterinary purposes). The smallest value was
reported for pirlimycin in The Netherlands (0.3 g in 2009 for
veterinary purposes).
Example: Diclofenac consumption
National diclofenac consumption data were only available
for certain Western Europe and Others Group countries and
Poland (Figure 8). If consumption data for diclofenac are
compared with national weighted average MECs (Figure 5), it
becomes apparent that the analysis has to be limited to European
countries because that is the only region for which data for both
environmental occurrence and consumption data are available.
Furthermore, except for diclofenac, only a few other pharmaceutical agents feature an overlap of occurrences in the
environment with consumption data for more than 10 countries.
Thus, as long as no more consumption data are made publicly
available, especially outside the Western Europe and Others
Group, it will be difficult to predict environmental concentrations of pharmaceuticals from consumption data on a national
scale. Generally, the direct linkage of environmental occurrence
and consumption of a pharmaceutical substance is extremely
complex because a variety of factors, such as sorption, type of
wastewater treatment, environmental conditions, half-life, and
disposal schemes, need to be considered.
Environ Toxicol Chem 35, 2016
831
DISCUSSION
Global occurrence of pharmaceuticals
The present literature review has demonstrated that
pharmaceutical substances occur globally in the environment,
in industrialized, developing, and emerging countries covering
all 5 UN regional groups. More monitoring results in developing
and emerging countries have become available in recent years,
including analyses conducted by ourselves (e.g., K’Oreje
et al. [38], Shimizu et al. [45], and Weber et al. [46]). We
thus oppose the conclusion of others stating that there would be
little evidence for pharmaceutical pollution outside North
America, Europe, and China [31]. Part of this discrepancy in
recent review articles can be attributed to a global bias in
methodology, which misses relevant evidence from developing
and emerging countries by restricting literature reviews to
high-ranking English-language journals.
Nevertheless, the MEC database has demonstrated that there
is an order of magnitude more data available for Western Europe
and Others Group countries than for other UN regional groups.
More monitoring programs are thus needed globally to fully
assess the occurrence and environmental concentrations to
cover developing and emerging countries. Next to surface water
samples, pharmaceuticals in groundwater, tap/drinking water,
and soil are underrepresented in these regions. Also, veterinary
pharmaceutical substances in the environment are often being
neglected, which highlights the need for more specific
monitoring of these substances, especially in regions with
high agricultural outputs.
A major conclusion of the present literature review,
however, is that the more often pharmaceuticals are being
measured in a country, the more often they are being detected.
The smaller spectrum of different pharmaceuticals detected
in Africa and Latin American and Caribbean States is
thus likely not caused by lower pollution levels but a result
of the lack of environmental laboratories equipped and
funded to monitor pharmaceuticals in environmental matrices.
The required instrumental equipment, such as gas or liquid
chromatographs coupled to tandem mass spectrometers, is
expensive both to acquire and to maintain; thus, nearly all
water samples that were included for Africa in the database
(with the exception of South Africa) were analyzed in
industrialized countries [38]. Therefore, international cooperation and knowledge transfer is a prerequisite to clarify the
Figure 8. Country survey on publicly available data on diclofenac consumption per capita.
15528618, 2016, 4, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/etc.3339 by Wyoming State Library, Wiley Online Library on [22/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Pharmaceuticals in the global environment
Environ Toxicol Chem 35, 2016
pattern of environmental concentrations of pharmaceuticals in
developing countries.
The underrepresentation of some Asian, African, and South
American countries in the MEC database is troublesome for a
number of reasons. Some of these countries belong to the most
densely populated regions of the world, with the potential
to exhibit high pharmaceutical concentrations in watershed
receiving effluent due to high consumption in megacities and
low dilution of the discharged sewage. The pharmaceutical
manufacturing sector has gradually shifted to countries with
lower production costs, which could lead to increased emissions
from manufacturing in these countries [43]. In addition, key
differences between the low-income, middle-income, and highincome countries such as demographics, prescription practices,
sewer connectivity, design of WWTPs, reuse of waste and
wastewater, and disposal schemes of pharmaceuticals affect the
environmental occurrence of pharmaceutical substances [47].
Whereas in developed countries human pharmaceuticals are
expected to be mostly discharged as point source due to
high sewer connectivity, the diffuse pollution may be of greater
concern in many low-income or middle-income countries
because of leaks from sewer and septic systems and the
disposal of raw sewage or septage [47]. Also, the uptake of
pharmaceutical substances in plants is an important topic,
especially in (semi) arid countries, where often the effluent
of WWTPs is being used for irrigation purposes, such as in
Israel [48].
In addition, all average and maximum MECs in the present
study (Supplemental Data, S10) need to be interpreted carefully,
because data quality may vary among the different data sources.
Potential ecotoxicological effects
One striking result of the MEC database revealed that the
concentrations of several pharmaceutical substances in the
aquatic ecosystems are within the range known to cause acute or
chronic toxicity. Although similar conclusions have been drawn
in other publications [31,35,49,50], the global perspective of
the established database adds a new dimension to this issue.
Exposure to the nonsteroidal anti-inflammatory drug diclofenac led to the near-extinction of vultures on the Indian
subcontinent, caused by the birds’ feeding on the carcasses of
cattle treated with the drug [11]. In aquatic systems, diclofenac is
suspected of causing damage to the inner organs in rainbow
trout [4]. The weighted-average concentrations reported in
surface waters exceed the PNEC of 0.1 mg/L [51] in 12 countries
worldwide, indicating an unacceptable risk in terms of
regulatory environmental risk assessment. Hence, at least
temporal adverse ecotoxicological effects on local fish
populations can be suspected at the examined locations,
particularly at hot spots downstream of urban sewage discharge
in densely populated areas.
At concentrations of 5 ng/L to 6 ng/L EE2 has been
demonstrated to cause population collapse of fathead minnow
(Pimephales promelas) as a result of feminization of male fish in
a Canadian whole-lake experiment [8]. The feminization of
fish from estrogenic pollution of water bodies has already been
reported for several countries worldwide [52]. According to
the MEC database, the maximum EE2 concentrations reported
in surface waters exceed the PNEC of 0.01 ng/L [53] in
28 countries worldwide, also raising the possibility of at least
temporal adverse ecotoxicological effects on local fish population at hot spots.
Despite these 2 examples, it must be noted that for most of
the 631 different pharmaceutical substances detected in the
T. aus der Beek et al.
environment, ecotoxicologically derived no-effect concentrations have not yet been established [3,35,50], preventing a
comprehensive environmental risk assessment. In the EU, an
environmental risk assessment is mandatory for newly marketed
drugs [54,55], but many commonly used drugs were introduced
before this regulation came into force and thus have not been
assessed [56].
Moreover, the present literature review suggests that in many
locations several pharmaceuticals occur simultaneously in
environmental matrices, demanding new methods to assess
the ecotoxicological effects of long-term exposure to low
concentrations of mixtures of pharmaceuticals with potential
additive, synergistic, or antagonistic modes of action. This is
also relevant with respect to the potential presence of other
chemical and nonchemical stressors [3].
Monitoring programs and data distribution
Most entries in the MEC database represent a limited
number of grab samples at individual sampling sites with
relatively scarce long-term monitoring data. Therefore,
comprehensive data sets resolving potential seasonal or
annual fluctuations are scarce. Within each country, monitoring is often focused on a limited number of sampling sites; the
criteria for their selection remain unclear in many publications. Therefore, it must be doubted that the reported
MECs provide a representative picture of the environmental
concentrations, in terms of either average or maximum
concentrations. A possible explanation for the lack of robust
sampling strategies can be the relatively high proportion of
studies published in analytical chemistry journals focusing
on method development rather than representative sampling
strategies [31]. Furthermore, scientific sampling programs
often focus on hot spots such as WWTP influent and effluent
and surface waters downstream from these sites, which can
cause biased data. On the other hand, governmental sampling
campaigns are often located near river gauging stations, which
are not necessarily close to a hot spot. Generally, as a result
of the heterogeneity of the data and data quality, it is not
possible to generate quantitative conclusions about the data
distribution and any bias potential.
Although reliable analytical methods have been established
in laboratories worldwide, there is currently no internationally
standardized analytical protocol for pharmaceuticals in different
environmental matrices. However, there are some national
protocols, such as those from the US Environmental Protection
Agency, that are sometimes applied in other countries as well.
Different limits of detection may result in a bias that
technologically advanced countries may report more positive
detections than other countries, in which the pharmaceuticals
occurring at the same concentration range are below the
detection limits of the analytical method available.
Another bias may be caused by a regional focus on
monitoring specific therapeutic groups. Regional patterns in
the most often measured therapeutic group (Figure 1) could
falsely be misinterpreted as implying that, for example,
estrogens are the largest pharmaceutical problem in the African
environment because they are being more often reported than
other therapeutic groups. Indeed, estrogens seem to be more
often measured than other groups because 2 South African
research groups have focused on developing methods for their
detection. This pattern might be further enhanced because of
the so-called Matthew effect [57], which states that those
substances that have already been detected by 1 research group
will be further investigated by other research groups.
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832
In addition, it can be assumed that more than 3000 different
pharmaceutical agents exist [58], in addition to numerous often
unknown transformation products. The present study has
shown that, so far, analytical procedures have been developed
for only 713 substances and their transformation products. This
means that >75% of all pharmaceutical agents cannot be, or
have so far not been, measured in the environment. However,
it needs to be mentioned that the most often used and topselling substances as well as substances with known ecotoxic
properties are included in the analytical methods already
developed. Nevertheless, many transformation products are still
unknown, and methods to detect them should be a matter of
further research. These substances need to be characterized in
the laboratory before their fate in the environment can be
investigated.
Future application of the MEC database
Despite investing considerable efforts in compiling a global
MEC database, the present literature review and database
compilation may not be complete and may have missed relevant
publications. Moreover, the database has to be continually
enhanced and updated to incorporate the latest monitoring
results. We envision a web interface in which additional data
can be entered in the required format for incorporation into the
MEC database but compliance and quality insurance will be
ensured through a responsible project team.
Furthermore, we envision enhancing the MEC database by
conducting analyses on a river basin–scale approach, in addition
to national assessments. We also suggest coupling the MEC
database to modeling approaches for regional pharmaceutical
consumption patterns and emission pathways into the environment. This will urgently require more knowledge about
pharmaceutical prescription, usage, and disposal volumes.
CONCLUSIONS
The present study has incorporated data on environmental
pharmaceutical concentrations of more than a 1000 publications, which were then transferred into a global MEC database
with more than 123 000 entries. Our key findings are as
follows. First, pharmaceuticals are detected in environmental
samples globally and not just in industrialized countries. It can
be concluded that “pharmaceuticals in the environment” is a
topic of global concern: pharmaceuticals were detected in
71 countries covering all 5 UN regional groups; 631 out of
713 pharmaceuticals and transformation products measured
were positively detected in the environment (see Supplemental
Data, S10, for average and maximum values of all pharmaceuticals for multiple environmental matrices), and residues of
16 pharmaceutical substances were detected in the surface,
drinking, and groundwater of all the UN regions. Although there
is an order of magnitude more data available in Western Europe
and Others Group countries, MECs have become increasingly
available in emerging and developing countries, revealing the
global scale of the occurrence of pharmaceutical residues in
the environment. Second, in a number of countries, certain
pharmaceuticals are detected at concentrations above the PNEC
in surface waters, suggesting that adverse ecotoxicological
effects might be possible at hot spots downstream of urban
sewage discharge in densely populated areas. Third, there is
only a partial overlap of the pharmaceutical substances detected
globally: different pharmaceutical groups have been the focus
of monitoring campaigns in different UN regions, such as
antibiotics in Asia and estrogens in Africa. Fourth, urban
Environ Toxicol Chem 35, 2016
833
wastewater discharge is the dominant emission pathway, but
discharges from manufacturing, hospitals, animal husbandry,
and aquaculture facilities are important locally. Finally, the
publicly available data on national pharmaceutical consumption
is currently not sufficiently detailed for a comprehensive
regional analysis of environmentally relevant pharmaceuticals.
Given the undisputed benefits pharmaceuticals confer
in modern medicine, potential strategies to mitigate their
environmental impact must be directed to prevent, reduce, and
manage pharmaceuticals without compromising their effectiveness, availability, or affordability, especially in countries in
which access to health care is still limited. The decision of the
fourth session of the International Conference on Chemicals
Management that the topic “environmentally persistent pharmaceutical pollutants” is an emerging policy issue under
Strategic Approach to International Chemicals Management
can initiate a multisectoral, multistakeholder approach that
is needed to globally address pharmaceutical occurrence in
the environment with a life-cycle approach [59]. Suitable
work areas and associated activities spanning risk reduction,
knowledge and information, governance, capacity-building,
and technical cooperation, as well as illegal international traffic
have currently been discussed as potential targets for a global
plan of action [12]. The initial focus of cooperative action
will be to build awareness and understanding on the issue and
to share information relevant to fill knowledge gaps [59].
Strategic Approach to International Chemicals Management
will be an appropriate forum to initiate activities, especially
in developing/emerging countries or countries with clearly
identified knowledge gaps.
Supplemental Data—The Supplemental Data are available on the Wiley
Online Library at DOI: 10.1002/etc.3339.
Acknowledgment—The present study was initiated and funded by the
German Federal Environmental Agency (UBA) under Environmental
Research Plan No. 3712 65 408. We thank all scientists and agencies who
supported the study by sending data and providing additional information
on request. We thank J. Rose, J. Koch-Jugl, and H.-C. Stolzenberg
of Section IV 1.1 International Chemicals Management at UBA and
C. Schl€
uter for their support and valuable discussions, as well as S. Vinjarapu
and S. Xu for their assistance in translating publications and transferring
data into the database. We very much appreciate the comments of S. Kullik
and 2 anonymous reviewers. Further information about the global measured
environmental concentration database is available on our webpage (www.
phamaceuticals-in-the-environment.org).
Data availability—The database will soon be available online on the
homepage of the German Federal Environmental Agency (www.uba.de).
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Pharmaceuticals in the global environment