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Emerging Topics in Ecotoxicology
Principles, Approaches and Perspectives
Volume 4
Series Editor
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L.R. Shugart and Associates, Oak Ridge, TN, USA

Bryan W. Brooks

Duane B. Huggett
Editors
Human Pharmaceuticals
in the Environment
Current and Future Perspectives
Editors
Bryan W. Brooks
Baylor University
Waco, Texas, USA
Duane B. Huggett
University of North Texas
Denton, Texas, USA
ISSN 1868-1344 ISSN 1868-1352 (electronic)
ISBN 978-1-4614-3419-1 ISBN 978-1-4614-3473-3 (eBook)
DOI 10.1007/978-1-4614-3473-3
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 201293197
© Springer Science+Business Media, LLC 2012
All rights reserved. This work may not be translated or copied in whole or in part without the written

Human Health Risk Assessment for Pharmaceuticals in the
Environment: Existing Practice, Uncertainty, and Future Directions 167
E. Spencer Williams and Bryan W. Brooks
Contents
vi
Contents
Wastewater and Drinking Water Treatment Technologies 225
Daniel Gerrity and Shane Snyder
Pharmaceutical Take Back Programs 257
Kati I. Stoddard and Duane B. Huggett
Appendix A. Take Back Program Case Studies 287
Index 297
vii
Jason P. Berninger Department of Environmental Science , Center for Reservoir
and Aquatic Systems Research, Institute of Biomedical Studies, Baylor University ,
Waco , TX 76798 , USA
Of fi ce of Research and Development, National Health and Environmental Effects
Research Laboratory , U.S. Environmental Protection Agency , Duluth , MN 55804 , USA
Alistair B. A. Boxall Environment Department , University of York , Heslington ,
York YO10 5DD , UK
Richard A. Brain Ecological Risk Assessment , Syngenta Crop Protection LLC ,
Greensboro , NC 27409 , USA
Bryan W. Brooks Department of Environmental Science , Center for Reservoir
and Aquatic Systems Research, Institute of Biomedical Studies, Baylor University ,
Waco , TX 76798 , USA
Jon F. Ericson P fi zer Global Research and Development, Worldwide PDM,
Environmental Sciences , MS: 8118A-2026 , Groton , CT 06340 , USA
Florence Fulk National Exposure Research Laboratory, Ecological Exposure
Research Division , US Environmental Protection Agency, Of fi ce of Research and
Development , Cincinnati , OH 45268 , USA

Emily A. McVey Of fi ce of Pharmaceutical Science, Center for Drug Evaluation
and Research, U.S. Food and Drug Administration , Silver Spring , MD 20993 ,
USA
WIL Research, 5203DL ’s-Hertogenbosch, The Netherlands
Alejandro J. Ramirez Mass Spectrometry Center, Mass Spectrometry Core
Facility, Baylor University, Baylor Sciences Building , Waco , TX 76798 , USA
Shane Snyder Chemical and Environmental Engineering , University of Arizona ,
Tucson , AZ 85721 , USA
Jürg Oliver Straub F.Hoffmann-La Roche Ltd, Group SHE , LSM 49/2.033 ,
Basle CH-4070 , Switzerland
Kati I. Stoddard Department of Biological Sciences , University of North Texas ,
Denton , TX 76203 , USA
E. Spencer Williams Department of Environmental Science, Institute of
Biomedical Studies , Center for Reservoir and Aquatic Systems Research, Baylor
University , Waco , TX 76798-7266 , USA
1
B.W. Brooks and D.B. Huggett (eds.), Human Pharmaceuticals in the Environment:
Current and Future Perspectives, Emerging Topics in Ecotoxicology 4,
DOI 10.1007/978-1-4614-3473-3_1, © Springer Science+Business Media, LLC 2012
Background
Human interaction with the environment remains one of the most pervasive facets
of modern society. Whereas the anthropocene is characterized by rapid popula-
tion growth, unprecedented global trade and digital communications, energy
security, natural resource scarcities, climatic changes and environmental quality,
emerging diseases and public health, biodiversity and habitat modi fi cations are
routinely touted by the popular press as they canvas global political agendas and
scholarly endeavors. With a concentration of human populations in urban areas
B. W. Brooks (*)
Department of Environmental Science, Center for Reservoir and Aquatic Systems Research ,
Institute of Biomedical Studies, Baylor University , One Bear Place , #97266 ,

2, 3 ] . Male fi sh
becoming female [ 4, 5 ] ? Drugs found in drinking water [ 6, 7 ] . India’s drug
problem [ 8 ] . Chances are you have seen these headlines or read related reports.
Pharmaceuticals and trace levels of other contaminants (e.g., antibacterial agents,
fl ame retardants, per fl uorinated surfactants, harmful algal toxins) are increasingly
reported in freshwater and coastal ecosystems. In the developed world, many of
these chemicals are released at very low levels (e.g., parts per trillion) from waste-
water ef fl uent discharges to surface and groundwaters. But why were citizens so
engaged by stories about fi sh on Prozac [ 3 ] and drugs in drinking water [ 7 ] ?
Because pharmacotherapy is now entrenched in everyday life, a realization that
common drugs were found in the water we drink or the fi sh we eat likely produces
a boomerang effect, where our daily reliance on well-accepted therapies was con-
cretely linked in a new way with their potential consequences to the natural world.
On an increasingly urban planet, pharmaceutical residues and traces of other
contaminants of emerging concern represent signals of the rapidly urbanizing
water cycle and harbingers of the “New Normal.”
Over the past 2 decades the implications of endocrine disruption and modula-
tion have permeated public consciousness, scienti fi c inquiry, regulatory frame-
works, and management decisions in the environmental and biomedical sciences.
Publication of Colburn, Dumanoski, and Myers’ “Our Stolen Future [ 9 ] ,” which
is often referred to as the second coming of Rachel Carson’s “Silent Spring [ 10 ] , ”
stimulated the public, scienti fi c, and regulatory attention given to endocrine dis-
ruptors and ultimately in fl uenced the environmental studies of human pharma-
ceuticals [ 11 ] . For example, human reproductive developmental perturbations
elicited by the estrogenic human pharmaceutical diethylstilbestrol and feminiza-
tion of male fi sh exposed to municipal ef fl uent discharges represent examples of
causal relationships among endocrine active substances and biologically important
adverse outcomes [ 12 ] .
In the late 1990s, research in the area of endocrine disruption was taking off,
particularly to identify constituents of ef fl uents or other environmental matrices that

special issue of Environmental Toxicology and Chemistry entitled “Pharmaceuticals
and Personal Care Products in the Environment” in 2009. Following an editorial by
Brooks et al. [ 20 ] entitled “Pharmaceuticals and Personal Care Products: Research
Needs for the Next Decade,” an international workshop entitled “Effects of
Pharmaceuticals and Personal Care Products in the Environment: What are the Big
Questions?” was held by Health Canada/SETAC in April 2011 [ 21 ] . In 2012, the
SETAC Pharmaceutical Advisory Group is planning another Pellston conference on
antimicrobial resistance, which represents a major threat to global public health.
Though the information in this timely area continues to rapidly expand, it appears
Year
1998 2000 2002 2004 2006 2008 2010
Relative Cumulative Frequency of Citations
0.0
0.2
0.4
0.6
0.8
1.0
Cumulative Frequency of Citations
0
500
1000
1500
2000
2500
Fig. 1 Representative increase in peer-reviewed publications related to pharmaceuticals in the
environmental through 2010, summarized by the cumulative and relative cumulative citation
frequency of early review papers by Halling-Sorensen et al. [
15 ] , Ternes [ 16 ] , and Daughton and
Ternes [

[
68 ] , anti-in fl ammatory drugs [ 69 ] ,
recent advances [
70 ]
Solids
a
LC–MS/MS [ 71 ] , tetracycline antibiotics [ 72 ]
Water, solids Analytical methods [
73 ] , LC–MS/MS
methods [
74 ]
Conventional and/or
contaminants of
emerging concern,
including
pharmaceuticals
Water Analytical methods [
75, 76 ]
Water, solids LC–MS in environmental analysis [
77 ]
Various environmental
matrices
Analytical methods [
78, 79 ] , methods
applied to fate [
80 ] , environmental mass
spectrometry [
81 ] , recent advances [ 82 ]
Pharmaceuticals
and/or degradation

Perspectives on Human Pharmaceuticals in the Environment
Gas chromatography–mass spectrometry (GC–MS) was the primary analytical
tool used to assess the environmental occurrence of PPCPs in initial studies (Table 1 ).
The popularity of GC–MS in early work was due to its widespread availability and
historical use in contract service laboratories for historical industrial chemical
contaminants. The availability of electron-impact spectral libraries was initially
important, as they increased con fi dence in analyte identi fi cation. Further, the dis-
tinctive nonpolar operating range of GC–MS was consistent with analysis of most
personal care products (PCPs). In contrast, the use of GC–MS for analysis of phar-
maceuticals, which are relatively polar compared to most PCPs, typically requires
derivatization prior to analysis. For example, Brooks et al. [
3 ] employed GC–MS
with derivatization for initial identi fi cation of the antidepressants sertraline and
fl uoxetine in fi sh tissue. However, derivatization reactions are often unpredictable
for complex samples and can limit the quality of quantitative data. Consequently,
liquid chromatography–mass spectrometry (LC–MS) has become the technique of
choice for analyzing pharmaceuticals in environmental samples.
Numerous studies have demonstrated the distinct advantages of LC–MS for
analysis of pharmaceuticals (Table 1 ). LC–MS enables identi fi cation and
quanti fi cation without derivatization and typically results in lower detection limits
(below 1 ng/L and 1 ng/g for liquid and solid samples, respectively) and better
precision than comparable GC–MS methodologies. In environmental applications,
LC is typically combined with tandem MS (or MS/MS) to promote enhanced
selectivity and sensitivity for target analytes. In a routine MS/MS analysis, a
molecular ion is selected and subsequently fragmented to produce one or more
distinctive product ions that enable both qualitative and quantitative monitoring.
Recently introduced ultraperformance liquid chromatography (UPLC) provides a
novel approach to chromatographic separation. UPLC differs from regular LC by
the implementation of chromatographic columns with smaller particle diameters
(i.e., sub-2- m m particles), which generates elevated back pressures and narrower

ronment, environmental analyses typically include rigorous quality assurance and
quality control (QA/QC) metrics to con fi rm reliability of analytical data. Initial
method validation provides essential performance parameters, such as method
recoveries, precision, and limits of detection (LODs). Recurring analysis of quality
control (QC) samples (e.g., method blanks, matrix spikes, laboratory control sam-
ples) is important to verify performance of the method over time, and to assess
potential matrix effects. Considering the unpredictable nature of matrix interference
in LC–MS analysis and the lack of effective strategies to deal with this dif fi culty, it
has become imperative to use QA/QC data to document and qualify analytical
results for human pharmaceuticals in environmental matrices. This is particularly
important when reporting concentrations at or near the limit of detection for a given
analytical method.
In this volume, an overview of global environmental regulatory activities rele-
vant to human pharmaceuticals is provided in Chaps.
2 and 3 . In Chap. 4 , Boxall
and Ericson examine important considerations for understanding the environmental
fate of therapeutics. Below we provide some perspectives on bioaccumulation and
effects of human pharmaceuticals in the environment.
Environmental Bioaccumulation and Effects
Though the potential for uptake of veterinary medicines by animals reared in aqua-
culture were understood for some time (see [ 24, 25 ] ), Boxall et al.’s [ 26 ] study of
the uptake of veterinary medicines from soils to plants highlighted the importance
of considering potential accumulation of human medicines in terrestrial organisms
because biosolids and ef fl uents from wastewater treatment plants can be applied
to agricultural fi elds. Such observations are particularly relevant for antibiotics.
In fact, developing an understanding of the in fl uences of human antibiotics and
antimicrobial agents on antibiotic resistance was recently identi fi ed as critical areas
of research need for environmental science and public health [ 21 ] .
In aquatic systems, Larsson et al. [ 27 ] likely provided the fi rst report of bioac-
cumulation of a human pharmaceutical, 17 a -ethinylestradiol, in bile of fi sh exposed

cological data compared to other industrial contaminants. To illustrate available
data, Table 2 provides a summary of common characteristics for hundreds of phar-
maceuticals. During the design of therapeutics, careful consideration is given to
target-speci fi c biomolecules (e.g., receptors, enzymes) and pathways to elicit
bene fi cial outcomes. Because side effects are not desirable and large margins of
safety (relationship between therapeutic and toxic doses) are ideal, pharmaceutical
development often results in therapeutics with relative well-understood mecha-
nisms/modes of actions (MOAs) and very low acute toxicity in mammals. For
example, a recent study predicted that less than 8% of all pharmaceuticals are
expected to be classi fi ed as highly acutely toxic to rodent models [ 41 ] . Similarly,
Berninger and Brooks [ 41 ] predicted that less than 6% of all pharmaceuticals are
acutely toxicity to fi sh below 1 mg/L.
As noted previously, concentrations of individual human pharmaceuticals in
surface water of developed countries rarely exceed parts per billion levels; thus,
limited acute toxicity is expected in surface waters of the developed world.
Unfortunately, most studies to date have only examined acute toxicity in standard
aquatic organisms [ 42 ] . However, chronic adverse responses resulting from thera-
peutic MOAs are more likely to be observed in the environment [ 41 ] , particularly
in systems with instream fl ows dominated by continuous release of ef fl uent dis-
charges [ 43 ] leading to longer effective exposure durations [ 11 ] . Early investigators
8
B.W. Brooks et al.
Table 2 A summary of the minimum and maximum values and 10th, 50th, and 90th centiles of common properties associated with pharmaceuticals
MW log P LD
50
C
max
AT R C l T
½
V

half-life of elimination (hour); V
d
apparent volume of distribution (L/kg); AqET is the aqueous effect threshold (mg/L) where
fi sh plasma BCF/ C
max
= aquatic exposure concentration at the point in which C
max
= fi sh plasma concentration and fi sh plasma BCF × exposure concentra-
tion = fi sh plasma concentration [
29 ]
9
Perspectives on Human Pharmaceuticals in the Environment
recognized the importance of leveraging mammalian pharmacological safety data
to help understand various pharmaceutical effects in the environment, because
many MOAs of human therapeutics appear to be evolutionarily conserved, particularly
in vertebrates [
14, 44– 46 ] .
In 2003, Huggett et al. [ 47 ] proposed a screening approach to identify pharma-
ceuticals in water that may result in fi sh plasma levels (or internal doses) ³ human
therapeutic levels (e.g., C
max
). Huggett’s plasma model was based on three core
assumptions: (1) Evolutionary conservation of structure and function of drug targets
among mammals and fi sh species; (2) Internal fi sh doses approaching mammalian
C
max
levels would result in similar therapeutic outcomes; and (3) A gill uptake model
[ 48 ] for predicting rainbow trout plasma concentrations following waterborne expo-
sure to nonionizable chemicals [ 48 ] . Subsequently, several recent studies have
employed the Huggett et al. plasma model approach [ 49– 51 ] or conceptually similar

90th centiles of probabilistic pharmaceutical distributions (PPD) of molecular
weight, logP, acute LD
50
, C
max
, acute to therapeutic ratio margin of safety analog
(LD
50
/ C
max
; see [ 41 ] ), clearance rate, half-life of elimination, apparent volume of
distribution ( V
d
), and the aqueous effect threshold (AqET; see [ 52 ] ) based on data
from hundreds of pharmaceuticals. PPD approaches can be used to predict the
10
B.W. Brooks et al.
likelihood of encountering another therapeutic with attributes of interest. To illus-
trate the utility of PPD analyses, Fig. 2 depicts a PPD for V
d
. Brie fl y, V
d
data were
ranked and converted to probability percentages then plotted against respective
probability ranks on a log-probability scale; centiles were determined by regression
(see [ 30 ] for a complete description of methods). Using this approach, we predict
that 10% or less of all pharmaceuticals would have V
d
values of 0.15 L/kg. In Fig. 3 ,
we extend the PPD assessment to predict the likelihood of encountering a pharma-

10
3
10
4
Percent Rank
0.01
0.1
1
10
30
50
70
90
99
99.9
99.99
Fig. 2 Probabilistic pharmaceutical distribution of apparent volume of distribution (L/kg) for 944
pharmaceuticals. Reference lines relate to the 10th, 50th and 90th centiles (Table
2 ), which corre-
spond to 0.15, 1.03, and 6.96 L/kg, respectively. For example, apparent volume of distribution is
predicted by this model to be at or above 6.96 L/kg for 10% of all pharmaceuticals

11
Perspectives on Human Pharmaceuticals in the Environment
contaminants in treated wastewater ef fl uents, a number of treatment approaches,
including appropriately designed and maintained constructed wetlands [ 56 ] , appear
viable for supporting risk management of indirect and direct potable water reuse.
In this volume, Chaps. 9 and 10 examine timely issues related to environmental risk
management. In Chap. 9 , Gerrity and Snyder examine the available information
related to the ef fi cacy of various wastewater and drinking water treatment technolo-

10
3
10
5
10
7
10
9
Percent Rank
0.01
0.1
1
10
30
50
70
90
99
99.9
99.99
Fig. 3 Probabilistic pharmaceutical distribution of aqueous effect threshold (AqET; mg/L) for 831
pharmaceuticals. Reference lines relate to the 10th, 50th, and 90th centiles (Table
2 ), which cor-
respond to 29 ng/L, 44.6 m g/L, and 66.4 mg/L, respectively. For example, an aquatic concentration
leading to a plasma concentration in fi sh above the mammalian C
max
value is predicted by the
AqET model to be at or below 29 ng/L for 10% of all pharmaceuticals

12

7. Benotti MJ, Trenholm RA, Vanderford BJ, Holady JC, Stanford BD, Snyder SA (2009)
Pharmaceuticals and endocrine disrupting compounds in U.S. drinking water. Environ Sci
Technol 43:597–603
8. India’s drug problem.
http://www.nature.com/news/2009/090204/full/457640a.html
9. Colburn T, Dumanoski D, Myers JP (1996) Our stolen future. Dutton, Peguin Books, New York
10. Carson R (1962) Silent spring. Houghton Mif fl in Company, New York
11. Ankley GT, Brooks BW, Huggett DB, Sumpter JP (2007) Repeating history: pharmaceuticals
in the environment. Environ Sci Technol 41:8211–8217
12. Hotchkiss AK, Rider CV, Blystone CR, Wilson VS, Hartig PC, Ankley GT, Foster PM,
Gray CL, Gray LE (2008) Fifteen years after “Wingspread”—environmental endocrine dis-
rupters and human and wildlife health: where we are today and where we need to go. Toxicol
Sci 105:235–259
13. Desbrow C, Routledge E, Brighty G, Sumpter J, Waldock M (1998) Identi fi cation of estro-
genic chemicals in STW ef fl uent. 1. Chemical fractionation and in vitro biological screening.
Environ Sci Technol 32:1549–1558
14. Arcand-Hoy L, Nimrod AC, Benson WH (1998) Endocrine-modulating substances in the envi-
ronment: estrogenic effects of pharmaceutical products. Int J Toxicol 17:139–158
15. Halling-Sorensen B, Nielsen SN, Lanzky PF, Ingerslev F, Lutzhoft HCH, Jorgensen SE (1998)
Occurrence, fate and effects of pharmaceutical substances in the environment—a review.
Chemosphere 36:357–394
16. Ternes TA (1998) Occurrence of drugs in German sewage treatment plants and rivers. Water
Res 32:3245–3260
13
Perspectives on Human Pharmaceuticals in the Environment
17. Daughton CG, Ternes TA (1999) Pharmaceuticals and personal care products in the environ-
ment: agents of subtle change? Environ Health Perspect 107(suppl 6):907–938
18. Williams RT (ed) (2005) Human pharmaceuticals: assessing impacts on aquatic ecosystems.
SETAC Press, Pensacola, Florida
19. Crane M, Barrett K, Boxall A (eds) (2008) Veterinary medicines in the environment. SETAC

30. Zhang X, Oakes KD, Cui S, Bragg L, Servos MR, Pawliszyn J (2010) Tissue-speci fi c in vivo
bioconcentration of pharmaceuticals in rainbow trout (Oncorhynchus mykiss) using space-
resolved solid-phase microextraction. Environ Sci Technol 44:3417–3422
31. Paterson G, Metcalfe CD (2008) Uptake and depuration of the anti-depressant fl uoxetine by
the Japanese medaka (Oryzias latipes). Chemosphere 74:125–130
32. Nallani G, Paulos P, Vanables B, Constantine L, Huggett DB (2011) Bioconcentration of
Ibuprofen in Fathead minnow ( Pimephales promelas ) and Channel cat fi sh ( Ictalurus puncta-
tus ). Chemosphere 84:1371–1377
33. Nallani G, Paulos P, Vanables B, Constantine L, Huggett DB (2011) Tissue speci fi c uptake and
bioconcentration of the oral contraceptive, Norethindrone, in two freshwater fi shes. Arch
Environ Contam Toxicol 62(2):306–313
34. Smith EM, Chu S, Paterson G, Metcalfe CD, Wilson JY (2010) Cross-species comparison of
fl uoxetine metabolism with fi sh liver microsomes. Chemosphere 79:26–32
35. Gomez C, Constantine L, Moen M, Vaz A, Huggett DB (2010) The in fl uence of gill and liver
metabolism on the predicted bioconcentration in fi sh. Chemosphere 81:1189–1195
36. Gomez CF, Constantine L, Moen M, Vaz A, Wang W, Huggett DB (2011) Ibuprofen metabolism in the
liver and fi ll of rainbow trout, Oncorhynchus mykiss. Bull Environ Contam Toxicol 86:247–251
37. Schultz MM, Painter MM, Bartell SE, Logue A, Furlong ET, Werner SL, Shoenfuss HL (2011)
Selective uptake and biological consequences of environmentally relevant antidepressant phar-
maceutical exposures on male fathead minnows. Aquat Toxicol 104:38–47
14
B.W. Brooks et al.
38. Nakamura Y, Yamamoto H, Sekizawa J, Kondo T, Hirai N, Tatarako N (2008) The effects of
pH on fl uoxetine in Japanese medaka ( Oryzias latipes ): acute toxicity in fi sh larvae and bioac-
cumulation in juvenile fi sh. Chemosphere 70:865–873
39. Zhou SN, Oakes KD, Servos MR, Pawliszyn J (2008) Application of solid-phase microextrac-
tion for in vivo laboratory and fi eld sampling of pharmaceuticals in fi sh. Environ Sci Technol
42:6073–6079
40. Environmental Defense Fund (1997) Toxic ignorance: the continuing absence of basic health
testing for top-selling chemicals in the United States. Environmental Defense Fund, New York

52. Berninger JP, Du B, Connors KA, Eytcheson SA, Kolkmeier MA, Prosser KN, Valenti TW,
Chambliss CK, Brooks BW (2011) Effects of the antihistamine diphenhydramine to select
aquatic organisms. Environ Toxicol Chem 30:2065–2072
53. Valenti TV, Gould GG, Berninger JP, Connors KA, Keele NB, Prosser KN, Brooks BW (2012)
Human therapeutic plasma levels of the selective serotonin reuptake inhibitor (SSRI) sertraline
decrease serotonin reuptake transporter binding and shelter seeking behavior in adult male
fathead minnows. Environ Sci Technol 46:2427–2435
54. Valenti TW, Perez Hurtado P, Chambliss CK, Brooks BW (2009) Aquatic toxicity of sertraline
to Pimephales promelas at environmentally relevant surface water pH. Environ Toxicol Chem
28:2685–2694
55. Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR,
Nichols JW, Russom CL, Schmieder PK, Serrano JA, Tietge JE, Villeneuve DL (2010) Adverse
outcome pathways: a conceptual framework to support ecotoxicology research and risk assess-
ment. Environ Toxicol Chem 29:730–741
15
Perspectives on Human Pharmaceuticals in the Environment
56. Mokry L, Brooks BW, Chambliss CK, Knight R, Keller C, Sedlak DL (2011) Evaluate wetland
systems for treated wastewater performance to meet competing ef fl uent quality goals.
WateReuse Research Foundation, Alexandria, VA. 153 p
57. Garrison AW (2006) Probing the enantioselectivity of chiral pesticides. Environ Sci Technol
40:16–23
58. Stanley JK, Brooks BW (2009) Perspectives on ecological risk assessment of chiral com-
pounds. Integr Environ Assess Manag 5:364–373
59. Valenti TW, Taylor JT, Back JA, King RS, Brooks BW (2011) In fl uence of drought and total
phosphorus on diel pH in wadeable streams: implications for ecological risk assessment of
ionizable contaminants. Integr Environ Assess Manag 7:636–647
60. Brooks BW, Valenti TW, Cook-Lindsay BA, Forbes MG, Scott JT, Stanley JK, Doyle RD
(2011) In fl uence of Climate change on reservoir water quality assessment and management:
effects of reduced in fl ows on diel pH and site-speci fi c contaminant hazards. In: Linkov I,
Bridges TS (eds) Climate: global change and local adaptation. NATO science for peace and

72. Buchberger WW (2007) Novel analytical procedures for screening of drug residues in water,
waste water, sediment and sludge. Anal Chim Acta 593:129–139
73. Petrovic M, Hernando MD, Diaz-Cruz MS, Barcelo D (2005) Liquid chromatography–tandem
mass spectrometry for the analysis of pharmaceutical residues in environmental samples: a
review. J Chromatogr A 1067:1–14
74. Giger W (2009) Hydrophilic and amphiphilic water pollutants using advanced analytical
methods for classic and emerging contaminants. Anal Bioanal Chem 393:37–44
75. Richardson S (2009) Water analysis: emerging contaminants and current issues. Anal Chem
81:4645–4677
76. Barcelo D, Petrovic M (2007) Challenges and achievements of LC-MS in environmental
analysis: 25 years on. Trends Anal Chem 26:2–11
16
B.W. Brooks et al.
77. Hao C, Zhao X, Yang P (2007) GC-MS and HPLC-MS analysis of bioactive pharmaceuticals
and personal-care products in environmental matrices. Trends Anal Chem 26:569–580
78. Morley MC, Snow DD, Cecrle C, Denning P, Miller L (2006) Emerging chemicals and analyti-
cal methods. Water Environ Res 78:1017–1053
79. Kot-Wasik A, Debska J, Namiesnik J (2007) Analytical techniques in studies of the environ-
mental fate of pharmaceuticals and personal-care products. Trends Anal Chem 26:557–568
80. Richardson S (2008) Environmental mass spectrometry: emerging contaminants and current
issues. Anal Chem 80:4373–4402
81. Rubio S, Perez-Bendito D (2009) Recent advances in environmental analysis. Anal Chem 81:
4601–4622
82. Perez S, Barcelo D (2007) Application of advanced MS techniques to analysis of human and
microbial metabolites of pharmaceuticals in the aquatic environment. Trends Anal Chem 26:
494–514
83. Petrovic M, Barcelo D (2007) LC-MS for identifying photodegradation products of pharma-
ceuticals in the environment. Trends Anal Chem 26:486–493
84. Radjenovic J, Petrovic M, Barcelo D (2007) Advanced mass spectrometric methods applied to
the study of fate and removal of pharmaceuticals in wastewater treatment. Trends Anal Chem

96. Ramirez AJ, Mottaleb MA, Brooks BW, Chambliss CK (2007) Analysis of pharmaceuticals in
fi sh tissue using liquid chromatography—tandem mass spectrometry. Anal Chem 79:
3155–3163
17
B.W. Brooks and D.B. Huggett (eds.), Human Pharmaceuticals in the Environment:
Current and Future Perspectives, Emerging Topics in Ecotoxicology 4,
DOI 10.1007/978-1-4614-3473-3_2, © Springer Science+Business Media, LLC 2012
Introduction
An overview is given on environmental risk assessment for pharmaceuticals (ERA),
with a description of the current regulatory requirements for human pharmaceuti-
cals ERA in Europe and the USA as well as developments worldwide. In addition,
further developments on national levels concerning the environmental safety of
pharmaceuticals are presented. Also, a short comparison with international veteri-
nary pharmaceuticals guidelines and with biocides ERA is given.
As long as human population density is low and excreta are spread diffusely over
a large area, no signi fi cant levels of PAS or metabolites are expected in the environ-
ment. But when population density increases, when excreta collect in sewage and
the latter is discharged, after wastewater treatment or not, to receiving waters, mea-
surable to signi fi cant concentrations in surface waters may be reached. With strong
population growth in industrialised societies from the nineteenth century onward,
with sewage collection systems in the growing cities and with the increase in the
number of pharmaceutical companies and their biologically active products, a rise
in environmental concentrations of at least certain PAS followed during the past
century. A parallel development in analytical methods and power, expressed as
constantly decreasing limits of detection and quantitation, inevitably led to determi-
nations of PAS in environmental matrices.
J. O. Straub (*)
F.Hoffmann-La Roche Ltd, Group SHE ,
LSM 49/2.033 , Basle CH-4070, Switzerland
e-mail: [email protected]