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ECOLOGICAL RISK ASSESSMENT OF PHARMACEUTICALS AND PERSONAL CARE
PRODUCTS IN SURFACE WATER
Kelli Bergh B.Sc., University of Victoria, 2000
PROJECT SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF
MASTER OF ENVIRONMENTAL TOXICOLOGY
In the Department
of Biological Sciences
0 Kelli Bergh 2005
SIMON FRASER UNIVERSITY
Summer 2005
All rights reserved. This work may not be reproduced in whole or in part, by photocopy
or other means, without permission of the author.
Name:
APPROVAL
Kelli Bergh
Degree: Master of Environmental Toxicology
Title of Project:
Ecological risk assessment of pharmaceuticals and personal care products in surface water
Examining Committee:
Chair: Dr. N. Haunerland, Professor
Dr. F. Law, Professor, Senior Supervisor Department of Biological Sciences, S.F.U.
Dr. C. Kennedy, Associate Professor Department of Biological Sciences, S.F.U.
Dr. R. Nicholson, Associate Professor Department of Biological Sciences, S .F.U. Public Examiner
Date Approved
+@' SIMON FRASER @ "NlvEMdibrary &-&2
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ABSTRACT
More than 200 pharmaceuticals and personal care products (PPCPs) have been found in
samples of waste water treatment plant effluent and receiving waters throughout the
world. Deterministic and probabilistic risk characterization methods were used to rank
these PPCPs with regards to their potential risk to aquatic receptors. 14 PPCPs were
ranked medium to very high priority, and included the following classes: analgesics,
antibiotics, cardiovascular drugs, musks, and hormones. The chemical ranked highest was
the synthetic hormone 1 7-a-ethinylestradiol. Despite these findings, some uncertainty
exists in the ranking, due to data gaps for aquatic toxicity reference values. Thus, future
research in this area should focus on aquatic toxicity studies. The findings of this
assessment can be used in future studies by focusing on chemicals identified as high
priority and placing fewer resources toward those chemicals that appear to be of little
environmental concern with regards to the protection of aquatic life.
ACKNOWLEDGEMENTS
I would like to acknowledge Dr.Law and DrKennedy, my committee. I greatly
appreciate their advice and guidance throughout the completion of my MET project.
I would like to acknowledge Dr.Albert van Roodselaar of the Greater Vancouver
Regional District (GVRD) for fimding my project, and for his in-site into the many
challenges faced by the GVRD regarding wastewater treatment plant effluent discharge.
I would like to acknowledge Farida Bishay of the GVRD. I deeply appreciate her input
and encouragement.
I would like to thank Rick Guiton for his patience and support for the last two years. I
would also like to acknowledge him for taking the time to review the draft of my thesis.
I would also like to thank Rick Lee and Srinivas Sura for their help, advice and all the
laughs throughout the completion of both my MET project and course work.
TABLE OF CONTENTS
.. ............................................................................................................................ Approval n ... ............................................................................................................................. Abstract lu
.......................................................................................................... Acknowledgements iv
............................................................................................................... Table of Contents v .. ............................................................................................................. List of Acronyms vu ... List of Figures ................................................................................................................. VIU
List of Tables .................................................................................................................... ix .............................................................................................................. List of Appendices x
................................................................................................................ 1.0 Introduction 1 1 . 1 Background .................................................................................................................. 1
....................................................................................................... 1.2 Regulatory Context 5 ...................................................................... 1.3 Description of Risk Assessment Process 7
..................................................................................................................... 1.4 Objectives 9 ................................................................................................................... 1.5 Approach -10
............................................................................................... 2.0 Problem Formulation 12 .............................................................................................................. 2.1 Introduction 1 2
............................................................................... 2.2 Chemicals of Potential Concern 1 2 .................................................................................... 2.3 Chemical Exposure Pathways 1 3 ................................................................................. 2.4 Receptors of Potential Concern 1 4
.............................................................................................. 2.5 Assessment Endpoints 1 4 2.6 Conceptual Model ...................................................................................................... 15
3.0 Exposure Assessment ............................................................................................... 17 3.1 Introduction ............................................................................................................... 17 3.2 Methods ...................................................................................................................... 17
............................................................................................ 3.2.1 Literature Search 1 7 ............................................................ 3.2.2 Selection of Exposure Concentrations 18
............................................................................................. 3.3 Results and Discussion -20 . . .................................................................................................. 4.0 Toxlclty Assessment 30
............................................................................................................... 4.1 Introduction -30 ...................................................................................................................... 4.2 Methods 30
........................................................................................... 4.2.1 Literature Search 3 1 ................................................ 4.2.2 Selection of DRC Toxicity Reference Values -32
.............................. 4.2.3 Predicted No Observable Adverse Effect Concentrations 32 4.3 Results ........................................................................................................................ 33
................................................................................................................... 4.4 Discussion 41 4.4.1 Chemicals Not Included in Exposure Assessment .......................................... 42
5.0 Deterministic Risk Characterization ...................................................................... 45 ............................................................................................................... Introduction -45
..................................................................................................................... Methods -45 ....................................................................................................................... Results -4'7
.................................................................................. 5.3.1 Acute Hazard Quotients 47 ............................................................................... 5.3.2 Chronic Hazard Quotients 53
Discussion ................................................................................................................... 55 .................................................................. 5.4.1 Prioritization of Individual PPCPs 55
....................................................................... 6.0 Probabilistic Risk Characterization 57 ................................................................................................................ 6.1 Introduction 57
...................................................................................................................... 6.2 Methods 58 6.3 Results ........................................................................................................................ 59 6.4 Discussion ................................................................................................................... 64
............................................................................. 6.4.1 17-a-ethinylestradiol (EE2) 65
7.0 Uncertainty Analysis ................................................................................................ 66 ...................................................................................... 7.1.1 Exposure Assessment 67 ...................................................................................... 7.1.2 Toxicity Assessment -69
7.1.3 Risk Characterization ...................................................................................... 73
8.0 Summary and Conclusions ...................................................................................... 75
................................................................................................................. 9.0 References 78
Appendices ........................................................................................................................ 87
LIST OF ACRONYMS DRC
EC
EDC
EEC
EIC EU
EMEA
GVRD
HQ LC LOEC
LWMP
MDL
MWALP
mg/L
ng/L PEC
POP PPCP
PNEC PNOAEC
PRC
QSAR ROPC
SLRA
COPC SSD
TRV
WWTP
UF
pg/L US EPA
US FDA
Deterministic Risk Characterization
Effective Concentration
Endocrine Disrupting Chemical
Environmental Exposure Concentrations
Expected Introduction Concentration
European Union
European Agency for the Evaluation of Medicinal Products
Greater Vancouver Regional District
Hazard Quotient
Lethal Concentration Lowest Observable Effects Concentration
Liquid Waste Management Plan
Method Detection Limit
Ministry of Water Land and Air Protection Milligrams per Litre (parts per million)
Nanograms per Litre (parts per trillion) Predicted Environmental Concentration
Persistent Organic Pollutant Pharmaceutical and Personal Care Product
Predicted No Effects Concentration Predicted No Observable Adverse Effects Concentration
Probabilistic Risk Characterization
Quantitative Structure-Activity Relationship
Receptor of Potential Concern Screening Level Risk Assessment
Chemical of Potential Concern Species Sensitivity Distribution
Toxicity Reference Value
Waste Water Treatment Plant
Uncertainty Factor
Micrograms per Litre (parts per billion)
United States Environmental Protection Agency
United States Food and Drug Administration
vii
LIST OF FIGURES
Figure 1.1 : Components required for assessment of ecological risk (BCMELP, 1998) ............................................................................................................... 8
Figure 2.1 : Conceptual model for the screening level ecological risk assessment of pharmaceuticals and personal care products in surface waters
...................................................... (modified from Derkenson et al., 2004). 16
Figure 6.1 : The cumulative frequency distributions of exposure concentrations (represented by a) and toxicity reference values (represented by ) for 1 7-a-ethinylestradiol (A), carbmazapine (B), ciprofloxacin (C), and musk xylene (D). ................................................................................... 62
Figure 6.2: The cumulative frequency distributions of exposure concentrations (represented by a) and toxicity reference values (represented by ) for propanolol (A), sulfamethoxazole (B), and tetracycline (C). ................. 63
LIST OF TABLES
Table 3.1 : Summary of the selected environmental exposure concentrations of pharmaceuticals and personal care products. ............................................. ..2 1
Table 4.1 : Assessment factors recommended to derive predicted no observable adverse effects concentrations.. .................................................................. ..33
Table 4.2: Summary of derived predicted no observable adverse effect concentrations (PNOAECs) for pharmaceuticals and personal care products (PPCPs), based on acute (<96 hour exposure) endpoints. ............. 34
Table 4.3: Summary of derived predicted no observable adverse effect concentrations (PNOAECs) for pharmaceuticals and personal care products (PPCPs), based on chronic (>96 hour exposure) endpoints. ......... 39
Table 5.1 : Categories of prioritization for detailed aquatic ecological risk assessment of pharmaceutical and personal care products in surface water. ............................................................................................................ 46
Table 5.2: Acute hazard quotient prioritization of pharmaceuticals and personal care products in surface water based on predicted no observable adverse effects concentrations. HQ values in bold and italicised are derived fiom predicted toxicity value .......................................................... 49
Table 5.3: Chronic hazard quotient prioritisation of pharmaceuticals and personal care products in surface water, based on predicted no observable adverse effects concentrations. .................................................................... -54
Table 6.1 : Summary of the rationale and selection of pharmaceuticals and personal care products for the probabilistic risk characterization. N/A = not analysed. ...................................................................................... 60
LIST OF APPENDICES
APPENDIX A: LITERATURE DATA
................................... Table A . 1 : Summary of Environmental Concentrations 89
.......... Table A.2. Summary of Selected Environmental Exposure Concentrations 121
Table A.3. Summary of Acute Effects Data ............................................... 130
Table A.4. Summary of Chronic Effects Data ............................................. 163
Table A.5. Summary of Selected Acute Toxicity Values ................................ 176
............................. Table A.6. Summary of Selected Chronic Toxicity Values 189
Table A.7. References ....................................................................... -193
APPENDIX B: RISK CHARACTERIZATION DATA
Table B . 1:
Table B.2:
Table B.3:
Table B.4:
Table B.5:
Table B.6:
Table B.7:
Table B.8:
Table B.9:
Summary of acute hazard quotient calculations and ranked PPCPs ...... 205
Summary of chronic hazard quotient calculations and ranked PPCPs ... 207
Summary of the exposure concentrations and toxicity reference values used in cumulative frequency distributions for 17-a-ethinylestradiol ..... 208
Summary of the exposure concentrations and toxicity reference value used in cumulative frequency distributions for carbmazapine ............. 209
Summary of the exposure concentrations and toxicity reference values used in cumulative frequency distributions for ciprofloxacin ............. 210
Summary of the exposure concentrations and toxicity reference values used in cumulative frequency distributions for musk xylene .............. 2
Summary of the exposure concentrations and toxicity reference values ................ used in cumulative frequency distributions for propanolol 2
Summary of the exposure concentrations and toxicity reference values used in cumulative frequency distributions for sulfarnethoxazole ........ 213
Summary of the exposure concentrations and toxicity reference values ................ used in cumulative frequency distributions for tetracycline 214
1.0 INTRODUCTION
1 . Background
Pharmaceuticals and personal care products (PPCPs) comprise all drugs available by
prescription or over-the-counter and other consumer chemicals such as fragrances, soaps,
detergents, emollients, preservatives, disinfectants, sunscreen agents, and insect
repellents (Daughton and Ternes, 1999). In Canada, these chemicals are produced and
used in quantities that exceed hundreds of metric tomes annually (Metcalfe et al., 2003a).
In British Columbia the top prescribed drugs in 2002 were in the range of 500,000
prescriptions (personal communication with Dr. Wright of the University of British
Columbia, June 2005). The parent compounds and/or the metabolites of these PPCPs are
excreted or are discarded into domestic waste waters and eventually make their way to
municipal waste water treatment plants (WWTPs). For many PPCPs, the WWTPs are
ineffective for complete removal, thus they are discharged in the WWTP effluent (Griger,
1999) into the receiving environment.
A number of surveys of PPCPs in WWTP influent and effluent samples have shown
concentrations in the range of ng/L to pg/L. Steger-Hartrnann et al. (1997), found
concentrations of cyclophosphamide (an antineoplastic) up to 15 ng/L fiom hospital
effluent in Germany. Ternes (1998), measured the occurrence of 32 drug residues in
WWTP influent and effluent in Germany. This survey included a number of different
pharmaceutical classes: antiphlogistics (anti-inflammatories), lipid regulators, psychiatric
drugs, antiepileptic drugs, beta-adrenergic receptor blocking compounds (P-blockers),
and B2-syrnpathomimetics (bronchodilators). Over 80% of the drugs analysed were
found in WWTP effluent, in concentrations up to 6.3 pg/L (carbmazapine, an
antiepileptic). Since Ternes' (1998) study was published, concentrations of PPCPs have
been measured in WWTP influent and effluent around the world. For example, 0llers et
al. (2001) analysed six different drugs in two WWTPs in Switzerland and found
concentrations up to 3.5 pg/L naproxen (an analgesiclanti-inflammatory). Other drugs
analysed in this study were in the concentration range of 5 to 1500 ngL. Petrovic et al.
(2002) measured 8 hormone compounds in WWTP influent and effluent in Spain and
found, on average, 9.4 ngL of Estriol in the effluent. In 2002, the Greater Vancouver
Regional District (GVRD) analysed 52 PPCPs in influent and effluent fiom five WWTPs
in the Vancouver region. Of the 52 PPCPs analysed 29 were found in one or more of the
WWTP effluents, in concentrations ranging fiom 0.007 yg/L (roxithromycin-antibiotic)
to 5.8 yg/L (ibuprofen) (GVRD, unpublished data). As such, WWTPs are acting as point
sources of PPCPs in receiving waters (Stan and Herberer, 1997).
Subsequently numerous surveys of PPCPs in receiving environments adjacent to the
WWTP effluent discharges, have also been completed (Belfioid et al., 1999; Ternes and
Hirsch, 2000; F a d et al., 2001; Fawell et al., 2001; Huang and Sedalk, 2001; Xiao et al.,
2001; Boyd et al., 2003; Hilton et al 2003; Metcalfe et al., 2003b). These studies
measured PPCPs in surface waters in the concentration range of ng/L to low yg/L. One of
the most extensive surface water surveys was completed by Koplin et al. in 2002. Koplin
et al. (2002) analysed the environmental occurrence of 95 organic waste water
contaminants in 139 streams across 30 states throughout the USA. Over half of the
chemicals analysed were PPCPs, these included: antibiotics, synthetic reproductive
hormone modulators, anti-asthmatics, analgesics, anti-diabetics, anti-hypertensives,
cardiac stimulants etc. Concentrations in surface waters ranged fiom below the analytical
method detection limits to 6.0 yg/L (caffeine). The most often detected pharmaceutical
classes were the antibiotics and hormones (Koplin et al., 2002). To date more than 200
PPCPs have been detected in surface waters throughout the world (Ayscough et al.,
2000).
The number of PPCPs measured in surface waters, has inspired a surge of scientific
studies looking at the potential adverse effects to aquatic organisms, fiom exposure to
these PPCPs. The most studied PPCPs thus far are synthetic hormones, such as 17-a-
ethinylestradiol (EE2), found in birth control pills. Environmental exposure to low
concentrations of hormones such as those being measured in the environment, have been
shown to elicit deleterious effects in aquatic species (Routledge et al., 1998; Baronti et
al., 2000). These deleterious effects include disruption of endocrine responses, alteration
of sexual development and reduction in reproductive success (Lai et al., 2002). Foran et
al. (2002) found 2 pg/L of EE2 inhibited reproduction in transgenerationally exposed
adult medaka (Oryias latipes). This study also found EE2 decreased the percentage of
fertilized eggs that produced viable embryos at concentrations > 2 pg/L (Foran et al.,
2002). It has been shown that fish are sensitive to synthetic hormones when exposure
occurs during critical periods in development. For example (Metcalfe et al., 2001; and
Scholtz and Guzeit, 2000) found developmental exposure of synthetic estrogens to
medaka produced testis-ova in some males and complete reversal in others.
Concentrations that caused these adverse effects were in the range of 1 pg/L. In addition,
full life-cycle exposure of the fathead minnow to 4 ng/L found 100% of the test subjects
to be female by histological examination of the gonads (Lhge et al., 2001). Zillioux et al.
(200 1) found that sheepshead minnow (Cyprinodon variegates) exposed to 200 ng/L EE2
for 59 days caused reduced hatching success in the progeny of the fish exposed.
Histological examination showed generalized edema, damage to gill epithelia, hepatic
toxicity, firbrosis of the testis and evidence of sex reversal, including testes-ova and
spermatagonia-like cells in ovaries (Zillioux et al., 2001). As little as 2 ng/L of EE2 has
been shown to induce vitellogenin (pre-curser to egg yolk proteins in non-mammalian
vertebrates) and inhibit testis growth in male rainbow trout (Jobling et al., 1996). These
effects are observed at concentrations similar to those being measured in the aquatic
environment, thus it is possible that synthetic hormones in the aquatic environmental may
be eliciting estrogenic responses.
Some of the other PPCPs that have been assessed with regards to their toxicity on aquatic
organisms include: antibiotics, P-blockers, and selective serotonin reuptake inhibitors.
Brain et al. (2004) assessed the phytotoxicity of 22 antibiotics (fiom 12 different classes)
on the aquatic plant Lemna gibba. A 7-day static renewal test was used to assess multiple
growth and biochemical endpoints. The most toxic antibiotics were fiom the
fluoroquinolone, sulfonamide and tetracycline classes. Where growth (wet mass and
frond number) was affected at exposure concentrations ranging from 38 to 114 pg/L
(Brain et al., 2004).
Hugget et al. (2002) exposed Hyalella azteca, Daphnia magna, Ceriodaphnia dubia and
Oryias latipes (Japanese medaka) to the J3-blockers: metaprolol, nadolol, and propanolol
to determine potential aquatic toxicity. The endpoints measured were lethality (48h),
growth and reproduction. Medaka reproduction was impaired when exposed, to 0.5 pg/L
of propanolol for four weeks. This effective concentration of propanolol is lower than
those measured in surface waters, which have been measured as high as 0.59 j&L.
The selective serotonin reuptake inhibitors (SSRIs): fluvoxetine (Luvox), fluoxetine
(Prozac), and paraoxetine (Paxil) are commonly prescribed drugs for the treatment of
depression in humans. Fong (1998) tested the efficacy of these drugs at inducing
spawning in zebra mussels. All three drugs induced spawning at concentrations lower
than the natural concentrations of serotonin that induce oocyte maturation and spawning.
The tests preformed were 4 hour exposure tests. Fluvoxamine was the most potent,
inducing spawning in the 3 pg/L range (Fong, 1998). Fong et al. (1998) also conducted
similar studies on fingernail clams and found similar results. More recently, Brooks et al.
(2003) evaluated the aquatic toxicity of fluoxetine. In this study average LCso (the
concentration required to kill 50% of the test organisms) values for Ceriodaphnia dubia,
Daphnia magna, and Pimephales promelas were 234 pg/L, 820 pg/L, and 705 pg/L
respectively.
These studies indicate that PPCPs in surface waters have the potential to cause adverse
aquatic ecological effects (Servos et al., 2002). However, a comprehensive risk
environmental assessment has not been conducted for the majority of PPCPs. In general,
the risk assessments conducted to date, have only assessed a handful of PPCPs using
empirical data (Daughton, 1999 and Webb, 2001), while others have conducted risk
assessments using predicted environmental concentrations (PEC) (Steger-Hartmann et al.,
1998; Halling-Snrrensen et al., 2000; Stuer-Lauridsen et al., 2000; Jones et al., 2002)
and/or predicted toxicity values, based on quantitative structure activity relationships
(QSARs) (Jones et al., 2002; Sanderson et al., 2003 and Sanderson et al., 2004). As such,
the implications of the presence of PPCPs in the aquatic environment remain largely
unknown, as few PPCPs have been investigated in enough detail to identifjl their
environmental effects (Brain et al., 2004). Thus the question that continuously arises is:
what impacts/risks, if any, do PPCPs at trace concentrations pose for aquatic ecosystems?
1.2 Regulatory Context
Despite the emerging concern for PPCPs in the environment, these chemicals are not
currently regulated to the same extent as PCBs, petroleum hydrocarbons, metals etc. For
example, there are no regulatory requirements for monitoring water quality, nor are there
water quality guidelines, criteria or regulations in Canada, USA, or Europe for PPCPs
currently in use. However, these countries have legislated or developed draft regulatory
requirements for the environmental risk assessment of new pharmaceuticals which are, or
will be required as part of the approval procedure of new medicinal substances (CEPA,
1999; FDA, 2001 and EMEA, 2005). An overview of Canadian and international (USA
and Europe) policies relevant to the requirement for environmental assessments and
aquatic ecological risk assessments of PPCPs is provided below.
Canada
In British Columbia (BC) the applicable regulatory agencies include both provincial and
federal government agencies. The provincial regulatory agency is the Ministry of Water
Land and Air Protection (MWALP) while the federal regulatory agencies include
Environment Canada, Health Canada and Fisheries and Oceans Canada. Currently there
is no provincial or federal legislation governing the discharge of PPCPs, however, under
the federal Canadian Environmental Protection Act (CEPA), new pharmaceuticals must
meet environmental assessment requirements under New Substances Notification (NSN)
(CEPA, 1999).
The guidance document for conducting risk assessments for regulated substances in BC
(BCMELP, 1998) is entitled "Protocol for contaminated sites, guidance and checklist for
tier 1 ecological risk assessment". And the applicable federal document is entitled "A
framework for ecological risk assessment of contaminated sites in Canada"
(Environment Canada, 1994).
USA
There are currently no US regulations for PPCPs in surface waters however, there have
been directives by the US Food and Drug Administration (FDA) since 1995 stipulating
that an environmental risk assessment should be part of the approval procedure of new
veterinary and human medicinal substances (US FDA, 1995). The most recent guidance
documents for this directive are entitled "Environmental Impact Assessments (EL4 's) for
Veterinary Medicinal Products W P ' s ) Phase 1 Final Guidance" (US FDA, 2001) and
"Guidance for Industry, Environmental Assessment of Human Drug and Biologics
Applications, Revision I" (US FDA, 1998). The latter document recommends that
environmental risk assessments of new drugs are required if the predicted concentration
when entering the environment is 1 pg/L or more (US FDA, 1998). It is noted that this
level was set to guard against acute effects (as opposed to chronic effects) and was set on
the basis of very limited toxicity information (McBride and Wyckoff, 2002).
There are a number of ecological risk assessment guidance documents in the USA. The
main ones consulted in conducting this assessment are entitled: "Guidelines for
Ecological Risk Assessment and Ecological Risk Assessment Guidance For Superfind:
Process for designing and conducting Ecological Risk Assessments (Interim Final) " (US
EPA, 1997), "Guidelines for Ecological Risk Assessment ' (US EPA, 1997), "Risk
Assessment Guidance for Superfund Volume 3 Part A: Process for Conducting
Probabilistic Risk Assessment" (US EPA, 2001).
Europe
Like Canada and the USA, there are currently no European regulations for PPCPs in
surface waters, however Europe has been very active in establishing more detailed
guidance for conducting risk assessments of new pharmaceutical products. The European
Agency for the Evaluation of Medicinal Products (EMEA) released 2 drafts of the
document entitled "Guidance on Environmental Risk Assessment of Medicinal Products
for Human use". The document was initially released for public review and comments in
July 2003 (EMEA, 2003), and a second draft was released for public review and
comments in January 2005 (EMEA, 2005). The objectives of the document state that an
application for marketing authorization of a medicinal product for human use shall be
accompanied by an environmental risk assessment. The document outlines a step-wise
staged procedure that must be carried out when assessing the potential risk of new
pharmaceuticals in the European Union (EU). The draft guidance has proposed a
threshold of 0.01 pg/L as a predicted environmental concentration (PEC), above which a
more detailed assessment would be required. It is noted that this threshold value is 100
times more stringent than the US FDA (1998) level for triggering a more detailed
investigation. It is also noted that similar to Canada and the US, the European guidance
document is only for new medicinal products not already on the market.
1.3 Description of Risk Assessment Process
Ecological risk assessment is described by the US Environmental Protection Agency
(EPA) as "a process that evaluates the likelihood that adverse ecological effects may
occur or are occurring as a result of exposure to one or more stressors" (US EPA, 1998).
Based on Figure 1.1, there are three components that must all be present in order for risk
to be considered, these include: 1) substance (stressor); 2) receptor exposure pathway;
and 3) biological and or ecological effects.
Figure 1.1: Components required for assessment of ecological risk (BCMELP, 1998).
Most risk assessment processes consist of the following phases: problem formulation,
exposure characterization, effects characterization, risk characterization, and an
uncertainty assessment.
The problem formulation lays the foundation for the risk assessment. It defines the plan
for conducting the exposure, effects and risk characterization phases. This generally
includes an integration of available information on sources, stressors (chemical or
physical), effects, and ecosystem and receptor characteristics (US EPA, 1998). From this
information two products are generated: assessment endpoints, which identify the
environmental values that are to be protected, and a conceptual model which describes
the predicted relationships between the stressors and receptors (US EPA, 1998).
The next two phases, exposure characterization and effects characterization, are based on
the products of the problem formulation. During exposure characterization, data are
evaluated to determine the concentration of the stressors (if chemical) that are likely to
occur in the environment (i.e. soil, groundwater, air); while the effects characterization
identifies the types of ecological effects that may occur from the stressors.
The next phase, risk characterization, integrates the results of exposure and effects
characterization phases, (US EPA, 1997) to determine the likelihood and or magnitude of
ecological effects. Risks can be estimated by one or more approaches; however, two
main approaches are generally used. The first approach (deterministic or hazard
quotient), which is the most common, involves characterizing ecological risk by
calculating the ratio between single point estimates of exposure and effects, with
conservative safety factors being applied to overcome any underlying uncertainties
(Brooks et al., 2003). The second approach (probabilistic) uses the variability in
exposure and effects estimates to identify the magnitude of overlap between the two.
The final phase (uncertainty assessment) assesses the uncertainty and limitations of
assumptions used each of the phases of the risk assessment. The final product is a risk
description in which the results of all phases of risk assessment are presented (US EPA,
1998).
1.4 Objectives
In order to obtain a better understanding of the impacts, if any, PPCPs have on aquatic
receptors; the relationship between environmental occurrence and toxicological effects
must be established. The difficulty in establishing such a relationship is that there are so
many PPCPs in use that could be potentially discharged into aquatic environments and
not enough resources to investigate them all, to the degree that would make detailed
environmental risk assessments feasible (Sanderson et al., 2003). Thus, a prioritisation
procedure is required for the environmental risk assessment of PPCPs, so that resources
can be directed to those PPCPs that appear to be of highest risk.
The objective of this project was to perform a screening level risk assessment (SLRA) in
order to rank PPCPs based on their relative risk. Also, to identify substances that may
pose the greatest potential risk to the aquatic environment. This will provide guidance to
researchers, government and municipalities on where to focus future efforts and resources
in assessing the potential impacts to aquatic life via the discharge of PPCPs to the
receiving environment through municipal waste water treatment plants.
1.5 Approach
The objectives of the study were met though a modification of the ecological risk
assessment framework, which has previously been developed for assessing the risk of
other contaminants in the environment such as metals, petroleum hydrocarbons,
pesticides etc (US EPA, 1997; US EPA, 1998 and BCMELP, 1998). Although Canada,
USA and Europe have legislated or have developed draft regulatory requirements for the
registration and environmental assessment of new pharmaceuticals, these countries
presently have no regulatory requirements for formal environmental risk assessments of
PPCPs that are currently in use. Since PPCPs already in use are not regulated in any
jurisdiction, this risk assessment was not conducted in accordance with any one particular
regulatory agency. Rather it was based on an amalgamation of the various Canadian, US
and European risk assessment guidance documents for regulated substances as well as
those draft guidance documents for new pharmaceuticals (US FDA, 1998; CEPA, 1999
and EMEA, 2003 and 3005). In addition, guidance was based on risk assessments
conducted by other scientists looking at the potential adverse effects of PPCPs on aquatic
environments (Hansen et al., 1998; Stuer-Lauridsen et al., 2000; Boxall et al., 2000;
vanWezel and Jager, 2002; Jones et al., 2002; Sanderson et al., 2003 and Ferrari et al.,
2004). Furthermore, no one particular regulatory guidance document was followed as this
assessment is not a site-specific assessment, thus it does not fall under one regulatory
jurisdiction. The objectives could be better met through the use of several guidance
documents and methodology used by other scientists. In this way the most scientific
approach could be used. For example, the US EPA has well developed protocols for
conducting ecological risk assessments however the EU's guidance on assessing new
pharmaceuticals is well developed.
This assessment is considered a screening level risk assessment (SLRA), which is defined
by the US EPA as a simplified risk assessment that is conducted with limited data (US
EPA, 1997). SLRAs are characterized by simple qualitative and or comparative methods,
and rely heavily on literature information and previously collected data (CCME, 1996).
In general, SLRAs are used to evaluate chemicals at a site to see if they can be eliminated
fiom further concern or if they need additional investigation. The approach used at the
screening level, is to use consistently biased assumptions. For example for the exposure
assessment; the selected population would be the group with the highest reasonable
exposure, the exposure would be assumed to be all year and occur over an entire home
range, and the selected chemical exposure concentrations would be the highest detected
chemical concentrations. These conservative assumptions are used so that in the risk
characterization phase, calculated risk is over estimated, thus ensuring that the chemicals
that might pose an ecological risk are evaluated further (US EPA, 1997). The rationale
behind this is that without this bias, a screening evaluation could not provide a defensible
conclusion that negligible ecological risk exists or that certain chemicals could be
eliminated fiom further consideration (US EPA, 1997). If the results of the SLRA
indicate potential ecological risks, the screening-level ERA is refined, and the chemicals
at the site are assessed based on less conservative assumptions. This provides a more
realistic assessment of actual site-specific scenarios. It is noted that in British Columbia
over 90% of the ecological risk assessments completed are Tier 1 ERAS (BCMELP,
1 998), which is considered equivalent to the US EPA's SLRA.
This SLRA consists of six major sections: problem formulation, aquatic ecological
exposure assessment, aquatic toxicological assessment, risk characterization
(deterministic and probabilistic), uncertainty analysis and summary and conclusions. In
general each section consists of the following subsections: introduction, methods, results
and discussion.
2.0 PROBLEM FORMULATION
2.1 Introduction
The problem formulation component of risk assessment provides the foundation for the
entire assessment (US EPA, 2001). The problem formulation is the stage of the risk
assessment where the objectives for the risk assessment are defined. The nature of the
problem is evaluated and a plan for analysing the data and characterizing the risk is
developed (US EPA, 1998). It is a critical phase of the risk assessment as it is the point at
which the chemicals of potential concern (COPCs), exposure pathways and ecological
receptors of potential concern (ROPCs) are identified. The COPCs are generally those
chemicals that may cause potential risk when exposed to an organism at a given
concentration. The exposure pathways are the routes that the COPCs take from a source
to a biological receptor (Suter et al., 2000). The receptors of potential concern are those
species to be protected in the SLRA. Also identified in the problem formulation are
assessment endpoints for the SLRA. Assessment endpoints are expressions of the
ecological resources that are to be protected and that are the focus of the SLRA. The end
product of this phase is a conceptual model that relates the nature of the potential
ecological disturbance to the ecological effects of concern (Reinert et al., 1994). The
h c t i o n of the conceptual model is to identifj and link the important components of the
scenario being assessed i.e. the potentially exposed receptors, and the COPCs that may
result in risk to those receptors.
2.2 Chemicals of Potential Concern
For the purposes of this SLRA, the chemicals of potential concern (COPCs) are
pharmaceuticals or personal care products reported in the literature as having been
analysed in municipal waste water effluent or surface waters (i.e. rivers, lakes, and
oceans). As such, the PPCPs considered in the SLRA comprise a wide range of chemical
classes and include: drugs (available by prescription or over-the-counter, diagnostic
agents [(i.e. X-ray contrast media)], and other consumer chemicals, such as fiagrances
(i.e. synthetic musks) and sunscreen agents (i.e. methylbenzylidene camphor). Daughton
(2001) also includes "nutraceuticals" (bioactive food supplements such as huperzine A)
and "excipients" (considered "inert" ingredients used in PPCP manufacturing and
formulation) in the category of PPCPs, however such chemicals were not included in this
assessment, as it would have substantially increased the magnitude of the project.
Furthermore, in selecting the COPCs, the parent compound of each PPCP was considered
the primary stressor of concern, although a few metabolites were also included where
considered appropriate. For example, for PPCPs where a metabolite has been measured,
or is considered the prevalent form of the chemical in surface water, both were
considered in the assessment.
2.3 Chemical Exposure Pathways
For an exposure pathway to be complete, a contaminant must travel fiom the source to
the ecological receptors and be taken up by the receptors via one or more exposure routes
i.e. entry of a contaminant fiom the environment into an organism through irrigation,
ingestion, or dermal absorption. The contaminant exposure pathway in this SLRA is the
discharge of PPCPs fiom WWTPs into receiving waters where aquatic biota are exposed.
It is noted that this assessment did not distinguish between the different types of
municipal treatment processes (i.e. primary, secondary and tertiary) as no one waste
water treatment process is completely effective in removing all PPCPs fiom the influent
(Ternes, 1998; Desbrow et al., 1998; Belfioid et al., 1999; Bartoni et al., 2000; Kanada,
2003; Metcalf et al., 2003 and personal communication VanRoodselaar, GVRD, 2004).
In addition, all types of receiving waters were included in the assessment, i.e. streams,
rivers, tributaries, lakes, and oceans.
In order for the SLRA to be conservative, exposure was characterized in terms of
concentration of contaminants in surface water. Thus, it was assumed that 100% of the
chemical concentration in the surface water was bioavailable. In addition, the exposure
duration was assumed to be constant, as PPCPs are introduced on a continual basis to the
aquatic environment via WWTPs. This essentially causes "pseudo-persistence" in the
environment because their removal or transformation (by biodegradation, hydrolysis,
photolysis, etc.) is continually countered by their replenishment (Daughton, 2001).
2.4 Receptors of Potential Concern
The objectives of the SLRA were to rank the PPCPs with respect to their potential risk to
aquatic organisms. As such, only aquatic receptors are of potential concern. In most site-
specific SLRAs, receptors of concern are selected based on those species that are
identified at the site as being directly exposed to the COPCs. However, since this
assessment was based on all receiving environments where PPCPs have been measured,
the receptors considered were all aquatic species for which there was toxicological data
available for a given PPCP.
2.5 Assessment Endpoints
Assessment endpoints are statements about the ecological values that the risk assessor
wishes to protect and are usually defined in terms of population, community, or
ecosystem properties (i.e. risks of population extinction and reduction in species richness)
(Suter, 1993). As assessment endpoints are difficult to measure, measurement endpoints
that are related to the assessment endpoints are used as an alternative (Reinert et al.,
1994). Measurement endpoints commonly include toxicity tests and field surveys. The
measurement endpoints selected for this SLRA were any adverse effects (toxicity
endpoints that have been measured through laboratory or field toxicological studies)
reported for aquatic receptors from exposure to the COPCs. This included acute and
chronic effective concentrations (ECSo), lethal concentrations (LC50), and lowest
observable effect concentrations (LOEC). These endpoints were used to establish the
screening ecotoxicity values.
2.6 Conceptual Model
The conceptual model (Figure 2.1) provides a visual basis of the relationship between the
PPCPs and receptors of potential concern (ROPCs) (aquatic life) that are considered in
the SLRA. Initially the pharmaceuticals and over the counter drugs are consumed by
people for therapeutic purposes. The unabsorbed •’i-action of the chemicals and their
respective metabolic by-products are then excreted through urine and feces and end up in
the municipal waste water. Likewise the personal care products, which are generally
applied externally (i.e. anti-bacterial body washes, cosmetics etc), are washed off and as
such also end up in the municipal waste water. Once in the municipal waste water system
the PPCPs reach the WWTP where, depending on the PPCP and efficiency of the
treatment plant, varying percentages of the initial influent concentrations pass through the
treatment plant unabated, and are discharged to the aquatic environment, at which point
aquatic receptors living in the receiving environment are exposed.
Figure 2.1: Conceptual model for the screening level ecological risk assessment of pharmaceuticals and personal care products in surface waters (modified from Derkenson et al., 2004).
Human use of PPCPs FATE
Discharge of non-consumed production PPCPs to sewer
Sewage treatment plant
POTENTIAL EFFECTS
aquatic life
EXPOSURE ASSESSMENT
3.1 Introduction
Exposure is the contact or co-occurrence of a COPC with a receptor (US EPA, 1998).
The exposure assessment is based on measures of exposure and of ecosystem and
receptor characteristics. These measures are used to analyse the COPC sources,
distribution in the environment, and the extent and pattern of contact or co-occurrence
with the selected ROPCs. The exposure assessment includes the following steps: (1)
characterize exposure setting, (2) identifj exposure pathways, and (3) quantifj exposure.
As the exposure setting and exposure pathways were already identified in the problem
formulation, the main objectives of this exposure assessment were to determine the extent
of exposure of PPCPs to aquatic receptors.
3.2 Methods
3.2.1 Literature Search
The objectives were met by conducting a scientific literature search and compiling a
database of reported surface water concentrations of PPCPs, resulting from municipal
waste water discharge. The literature search consisted of primarily published scientific
literature and or regulatory submissions. Initially, the objective of the literature search
was to focus on reported surface water concentrations of PPCPs in Canada and the US
however, during the search it was found that there was limited data from these two
countries. Therefore, the search was broadened to include data from any country. In
compiling the data, attempts were made to ensure that the original sources of the data
were consulted. Where original data could not be obtained, both the original reference
and the article in which it was reported were recorded in the database. For journal articles
that reported more than one surface water value for a given PPCP, the highest value was
entered into the database.
Although the objective of the literature search was to compile only reported
environmental concentrations of PPCPs (i.e. concentrations of PPCPs in receiving surface
waters), WWTP effluent data were included where studies reported them.
3.2.2 Selection of Exposure Concentrations
The approach of this SLRA was to use both deterministic and probabilistic risk
methodologies for ranking the COPCs. The deterministic risk characterization (DRC)
involves calculating the ratio between single point estimates of exposure and effects,
whereas the probabilistic risk characterization (PRC) incorporates the variability in
exposure and effects estimates to identify the magnitude of overlap between the two. It is
noted that the results of the deterministic risk characterization were used to identify the
COPCs to be included in the probabilistic risk characterization. Thus, the exposure
concentrations for the PRC were not selected until the DRC was completed. Therefore,
only the methodology and results for the selection of the deterministic exposure
concentrations are presented below, while the methodology and results for the selection
of exposure concentrations for the PRC are presented in Section 6.
Selection of Deterministic Ekposure Concentrations
Upon completion of the surface water concentration database, the exposure values to be
used in the deterministic risk evaluation were selected. In order for the DRC to be a
conservative estimate, the maximum surface water value for each PPCP was selected as
the environmental exposure concentration (EEC). It is noted that maximum values for a
given PPCP reported in Canadian or US surface water were preferentially selected over
other countries in an attempt to keep the focus of the assessment on Canada and the US.
If a PPCP had not been analysed in surface water in Canada or the US then the maximum
values reported from other countries were used.
For many of the PPCPs, no surface water data was found in the literature. However in a
number of these cases, concentrations in WWTP effluent has been reported. For these
PPCPs, the WWTP effluent value was used and a 10-fold dilution factor was applied in
an attempt to approximate a realistic EEC (Brooks et a., 2003). The use of the 10-fold
dilution factor was based on guidance given by the US FDA (1998). Such an approach
was considered appropriate as 77% of permitted effluent discharges in the US receive
greater than 10 fold dilution (Dorn, 1996). It is noted that surface water concentrations
fiom countries other than Canada and the US were preferentially selected over WWTP
effluent values fiom either Canada or the US. This was to avoid the use of the dilution
factor, thus eliminating uncertainty associated with approximating the EEC. For PPCPs
where the maximum surface water concentration or approximated EEC was below the
laboratory method detection limit (MDL), half of the MDL was selected as exposure
concentration, as recommended by the US EPA (1989). For studies where a PPCP
concentration was reported below the MDL and it was the only data point for the PPCP,
it was included in the database but was excluded fiom the risk characterization phase of
the assessment.
A discussed in Section 1.5 both the US FDA and the European Agency for the Evaluation
of Medicinal Products (EMEA) give cut off values for including new PPCPs in
environmental assessments. The EMEA states that if the predicted environmental
concentration (PEC) is <0.01 pg/L and no other environmental concerns are apparent, it
may be assumed that the medical product is unlikely to represent a risk for the
environment following its prescribed use, and that no further action for that chemical is
required (EMEA, 2003). In the US, if the expected introduction concentration (EIC) of a
particular drug or its active metabolite is <1 pg/L at the point of entry (i.e. as municipal
effluent) no further investigations are necessary unless the toxicity or other characteristic
of the compound warrants some environmental testing (US FDA, 1998 and US FDA,
2001). Despite these guidance documents, no such cut off values were used in this
assessment, because as pointed out by Daughton and Ternes (1999), these values do not
consider the actual mode of action of a particular PPCP, and rely on traditional
ecotoxicological bioassay response variables. As such, all PPCPs that have been
measured in surface water or WWTP effluent, regardless of the concentration, were
selected for M e r assessment.
3.3 Results and Discussion
In total, 164 PPCPs have been reported in surface water and or WWTP effluent. Table
3.1 presents a list of the PPCPs and their respective selected EECs. Of the 164 PPCPs, 5
were reported to be below the MDL but the values were not reported. Thus, a total of 159
PPCPs were carried forward to the DRC. Of the PPCPs carried forward, 34 had no
reported surface water values. However there were WWTP effluent data available for
these chemicals, as such the 10-fold dilution factor was applied these chemicals. Table
3.1 below presents a summary of the PPCPs and their respective selected EECs. The 34
chemicals where WWTP effluent data was used have been indicated by bold and italics
and the approximated EEC value reported.
The list of PPCPs in Table 3.1 have been categorized into 16 separate classes, below is a
brief description of each class included in this assessment. It is noted that some PPCPs
have serve more than one therapeutic purpose and thus could be included or more than
one of the following classes.
Analgesics, Anti-inflammatory Drugs and Antipyretics
Analgesics, anti-inflammatories, and antipyretics are drugs used to reduce pain,
inflammation, and fever respectively (Beers, 2004). Many drugs have analgesic, anti-
inflammatory and antipyretic properties, thus have been grouped into one pharmaceutical
class.
Antibacterials, Antibiotics and Antimicrobials
Antibacterials, antibiotics and antimicrobials are drugs used to prevent and treat
infections (Beers, 2004). They inhibit microbial activity with minimal adverse effects to
the human body or tissues. This class of pharmaceuticals includes both synthetic
chemicals (i.e. sul fonamides) and those derived fiom natural products (i.e. penicillins,
aminoglycosides, cephalosporins, tetracyclines and chloramphenicol) (Spencer et al.,
1986).
Antianxiety, Antidepressants and Antipsychotics
In general, these drugs are used to produce or intensify moods and emotions or to
alleviate distressing mental syndromes (Spencer et al., 1986).
Antianxiety drugs are used to alleviate anxiety, panic attacks and phobias associated with
psychoneurotic and psychosomatic conditions (Beers, 2004). It is noted that symptoms of
anxiety include muscle tension, restlessness, fatigue, insomnia, sexual dysfunction,
excessive perspirations, and gastrointestinal upsets (Spencer et al., 1986). These drugs
taken over long periods of time may cause tolerance and dependence.
Antidepressants are used to mitigate depression. Some antidepressants are more effective
than others depending on the type of depression (i.e. endogenous, reactive or neurotic).
(Spencer et al., 1986). For example tricyclic and heterocyclic drugs are effective in
endogenous depressive states but not very effective for those suffering fiom reactive
depression.
The antipsychotics agents are effective in modifLing psychotic symptoms. These drugs
are prescribed to persons (1) exhibiting thought disorder and severe agitation in acute and
chronic psychoses (2) identified as schizophrenic or manic-depressive and (3) show
psychotic behaviours due to hostility, withdrawal, and perceptual disturbances such as
delusions and hallucinations. Such drugs produce little or no psychological or physical
dependence; and also lower the seizure threshold in epileptic patients (Spencer et al.,
1986).
It is noted that many of the drugs listed as antianxiety, antidepressants and antipsychotics
may also be considered sedatives or hypnotics.
Antidiabetics
Antidiabetic drugs are medicines that help control blood sugar levels in people with
diabetes. For instance metformin hydrochloride (Table 3.1) is an antihyperglycemic
agent that improves glucose tolerance in patients with type 2 diabetes, by lowering both
basal and postprandial plasma glucose. Metformin hydrochloride decreases hepatic
glucose production, decreases intestinal absorption of glucose, and improves insulin
sensitivity by increasing peripheral glucose uptake and utilization (Rybacki, 2002). The
second antidiabetic drug on Table 3.1 is glibenclamide, this drug works by lowering
blood sugar levels by stimulating the production and release of insulin fiom the pancreas.
It also promotes the movement of sugar fiom the blood into the cells in the body that
need it (Rybacki, 2002).
Anti-epileptics are those drugs used in the treatment of seizure disorders. The basis of the
drug action is to prevent abnormal nerve activity by decreasing impulse discharges
(Beers, 2004). It is noted that most anti-epileptic drugs are also considered depressants.
Antineoplastics
Antineoplastics are drugs used in cancer treatment. These drugs are classified as
alkylating agents (cell cycle independent), anti-metabolites (cell cycle dependent, phase
S), natural products, hormones and miscellaneous agents (Spencer et al., 1986). The
objective of using antineoplastics is to cause the cancer to go into remission. It is noted
that antineoplastics do not cure cancer, as they do not kill every turnour cell. It is noted
that certain pharmaceuticals in Table 3.1 listed under antineoplastics are not actually
antineoplastics but are prescribed in combination with the antineoplastic. These drugs are
used to alleviate some of the adverse effects associated with the use of antineoplastics,
and include: nausea, vomiting, gastrointestinal discomfort, dermatitis, hepatotoxicity etc.
(Beers, 2004).
Antiseptics and Disinfectants
In general antiseptics and disinfectants are used topically on tissues such as the skin and
mucous membranes to reduce the infective capability of mircro-organisms (Spencer et
al., 1986). Some chemicals in this class are used to disinfect environmental surfaces and
inanimate objects. Such chemicals may be quite non-specific in their modes of action,
affecting both microbial and tissue cells. These agents are generally to toxic for use on or
in the body. Whereas antiseptics applied to the body are more selective in action and are
less corrosive to tissues (Spencer et al., 1986).
Anti-ulcer and Antacids
Anti-ulcer drugs, such as cimetidine and ranitidine hydrochloride (Table 3.1), are used to
reduce acidity of the stomach by inhibiting the release of gastric (hydrochloric) acid
(Spratto, 1988 and Rybacki, 2002). These drugs are primarily used in the treatment of
duodenal ulcers. Whereas antacids are alkaline salts or insoluble salts with buffering
properties that act to neutralizehuffer gastric acidity thus relieving pain and discomfort
from indigestion or peptic ulcers. In ulcer patients, anti-ulcer drugs and antacids are
given concomitantly.
Bronchodilators and Anti-asthma Drugs
In general, bronchodilators and anti-asthma drugs are prescribed to help open blocked
airways, thus improving pulmonary function (Beers, 2004).
It is noted that caffeine has been included in Table 3.1 in the category of anti-asthma
drugs as citrated caffeine is used to treat breathing problems in premature babies (Becker
et al., 1984). However there are many other medical uses for caffeine such as: a
stimulant used to help restore mental alertness when unusual tiredness or weakness or
drowsiness, in combination with ergotamine (for treatment of migraine and cluster
headaches) or with certain pain relievers, such as aspirin or aspirin and acetaminophen, in
combination with an antihistamine to overcome the drowsiness caused by the
antihistamine (Bertil et al., 1998).
Cardiovascular Drugs
Cardiovascular drugs can be sub categorized into those affecting the heart, blood vessels,
and coagulation (Beers, 2004). Most of the cardiovascular drugs on Table 3.1 are those
used in the treatment of abnormal heart rhythms which are characterized by high pulse
rates, ectopic stimuli, premature contractions, flutter and fibrillation (Beers, 2004). Such
drugs are called antiarrythmics.
Contrast Agents
Contrast agents are used in diagnostic radiographic procedures. They are opaque to x-
rays and cast shadows on x-ray film. These substances can be injected into the body and
are used to produce images that illustrate the distribution and flow of body fluids such as
blood, bile, and urine (Spencer et al., 1986). Oral preparations of such compounds are
used to produce images of the gastrointestinal tract (unabsorbable compounds) or are
concentrated in the billary or urinary tracts (absorbable compounds). It is noted that all of
the contrast agents in Table 3.1 are iodine compounds.
Diuretics
Diuretics are drugs that increase the production of urine by inducing the body to lose
fluid (Rybacki, 2002). Because the bodies fluid balance is affected significantly by the
sodium ion, losing fluid usually involves increasing the kidney's excretion of sodium,
this sodium loss is the primary mechanism by which many diuretics act (Spencer et al.,
1986). Such drugs are used to treat: heart disease, nephrosis, hepatic cirrhosis,
premenstrual syndrome, toxemia of pregnancy, hypertension, obesity, asthma and
epilepsy.
Hormones
In the body, hormones are chemicals synthesized to alter the rate of cellular processes
(Beers, 2004). The substances are extremely potent in small amounts and few body
process are unaffected by them (Spencer et al., 1986). Hormones effect digestion,
metabolism, energy production, mental processes, emotions, sexuality, reproduction and
growth (Beers, 2004). Generally, hormone drugs are classified as either steroids or
glycoproteins and are administered to persons with endocrine deficiency diseases to
replace missing or insufficient biochemicals (Spencer et al., 1986). They are also
prescribed as drugs to regulate metabolism in a way that is beneficial to the patient i.e.
oral contraception.
Lipid Regulators
Lipid regulating drugs control the lipid levels in the blood. Most of the lipid regulating
drugs on Table 3.1 are fibrates such as: bezafibrate, clofibrate, and fenofibrate. Fibrates
lower elevated senun lipids by decreasing the low-density lipoprotein (LDL) fiaction rich
in cholesterol and the very low-density lipoprotein (VLDL) fraction rich in triglycerides
(Staels et al., 1998). In addition, fibrates increase the high density lipoprotein (HDL)
cholesterol fiaction. Due to their major action on lipoprotein and hepatic triglyceride
lipase, the fibrates appear to produce a greater reduction on the VLDL than on the LDL
fiaction. Such drugs are used to reduce serum cholesterol, in patients whose cholesterol
elevation is due to the presence of IDL as a result of Types 111, IV, or V
hyperlipoproteinemia (Staels et al., 1998).
Metabolites
Metabolites are the breakdown products of parent pharmaceuticals for instance salicylic
acid and clofibric acid are metabolites of acetylsalicylic acid and clofibrate respectively.
Personal Care Products
Personal care products include compounds used to enhance beauty and include:
cosmetics, fragrances, deodorants, sun tan oils etc. The most frequently analysed personal
care products are the synthetic musks. These compounds are used as fiagrances and
fixatives in a number of products such as shampoos, bath additives, skin care products,
hair sprays, oral hygiene products, soaps, sun screens perfumes and aftershaves (Kanda et
al., 2003)
Table A.l in Appendix A presents the database of the PPCP surface water and WWTP
concentrations and includes the countries where the samples were collected. Like other
reviews of this nature Table A.l provides a "snapshot" of the degree of PPCP
contamination throughout the world, where concentrations range from sub-ng/l to pg/L.
Table A.2 in Appendix A presents the selected exposure concentrations for each PPCP
and the location (country) in which it was collected.
It is noted that, if the EMEA guidance was followed in this assessment, only 116 PPCPs
would have been included in DRC as only 1 16 PPCPs, of the 164 PPCPs identified, were
greater than or equal to the cut off value of into 0.01 pg/L (EMEA, 2003). Likewise if the
US FDA (1 998) guidance document was used then only 21 PPCPs would be included in
the DRC as only 21 PPCPs exceeded the EIC of 1 pg/L. Nevertheless, all of the PPCPs
and EECs presented in Table 3.1 were used in the DRC. A discussion of any
uncertainties associated with the exposure assessment is presented in Section 7.1.
4.0 TOXICITY ASSESSMENT
4.1 Introduction
The toxicity assessment of an SLRA involves the compilation and evaluation of
toxicological information on the COPCs, in order to evaluate the potential for the
chemicals to cause adverse effects to the receptors (US EPA, 1989). The evaluation of the
toxicological evaluation forms the basis for the derivation of toxicity reference values
(TRVs) or predicted no observable adverse effects concentrations (PNOAECs), which are
used to estimate the potential for adverse effects in an exposed population. With the use
of the TRVs andlor PNOAECs a link between adverse effects and the chemical agent is
made.
The EMEA (2005) guidance on environmental risk assessment of medicinal products for
human use suggests that the toxicity assessment consist of standard acute effective
concentration (EC5O) toxicity test sets on fish (endpoint not specified), daphnia
(immobilization and reproduction) and algae (growth inhibition). From these data the
PNOAEC should be derived (EMEA, 2005). The purpose of this analysis is to predict
the concentration of the substance for which adverse effects are not expected to occur in
the aquatic environment.
4.2 Methods
For this assessment a literature search of aquatic toxicological data for PPCPs was
conducted. Once the database was completed the toxicity reference values to be used in
the deterministic risk characterization were selected and PNOAECs were derived. It is
noted that the TRVs for the probabilistic risk characterization were not selected until
completion of the deterministic risk characterization, the methodology and results of
which are presented in Section 6.
4.2.1 Literature Search
The primary literature and data from various regulatory agencies were the basis of a
literature search for toxicological data. The endpoints reported in the literature that were
included in the database were generally acute and chronic effective concentrations
(EC50), lethal concentrations (LCSo), and lowest observable effect concentrations
(LOEC). For the purposes of this assessment any test where the exposure period was
conducted for 96 hours or less was considered acute exposure and any test conducted for
greater than 96 hours was considered chronic exposure. It is noted that in some instances
the duration of toxicity test was not reported, these values were included in the database
and professional judgment was used to determine whether to categorize them as acute or
chronic exposure. The inclusion of such data was primarily due to the lack of aquatic
toxicity for many of the PPCPs. In addition, during the literature search some of the
toxicity concentrations were reported as < or > a given concentration. For these data
points the actual value reported was included in the database. For instance if the toxicity
value was reported as > 100 mg/L then 100 mg/L was input into the database.
Upon completion of the literature search, it was found that many of the PPCPs with
environmental exposure concentrations had no corresponding aquatic toxicological data.
Where aquatic toxicological data for a given PPCP could be not obtained, predicted
toxicity values for those chemicals were used based on Sanderson et al. (2004). In this
study, Sanderson et al. (2004) derived predicted toxicity values for 2986 pharmaceuticals
through the use of Quantitative Structure-Activity Relationship (QSAR) modelling using
the US EPA Estimation Programs Interface for Microsoft Windows EPIWIN package.
The endpoints input into the toxicity assessment database from the Sanderson data
included acute ECso (where 50% of the organisms either die or in other ways adversely
impaired (Sanderson et al., 2003 and 2004)) values for algae and daphnia.
4.2.2 Selection of DRC Toxicity Reference Values
Once the database for aquatic toxicity was completed, the values to be used in the
deterministic risk characterization were selected. Selection of the toxicity reference
values (TRVs) was based primarily based on the EMEA guidance (2005) where the value
selected was the lowest of the ECSo, LC50, or LOEC fiom the most sensitive species in the
database. It is noted that where there were both empirical toxicity testing data and
predicted toxicity values available for a given chemical, the empirical toxicity test data
was preferentially selected regardless of which had the lower value. This methodology
was used for both acute and chronic endpoints (although no predicted values were
available for chronic endpoints).
4.2.3 Predicted No Observable Adverse Effect Concentrations
As per the EMEA guidance (2003 and 2005), the selected toxicity values were used to
derive the predicted no observable adverse effects concentration PNOAEC for each
PPCP. The PNOAEC represents the values for which adverse effects are not expected to
occur in the aquatic environment (US EPA, 1998 and EMEA, 2003). It is derived by the
use of an assessment factor, which is an expression of the degree of uncertainty in the
extrapolation fiom the toxicological data set to the "real environment". In general, more
extensive data and longer duration tests reduce the degree of uncertainty and
consequently the size of the assessment factor (EMEA, 2003). The EMEA (2003)
provides the following guidance to select an appropriate assessment factor.
4.4 Discussion
Data on the toxicity of the PPCPs generally came from laboratory studies where groups
of organisms generally daphnia, fish and algae and to a lesser extent crustaceans, bacteria
and aquatic plants were exposed to differing levels of the PPCP, with one or more
responses (endpoints) measured (i.e. survival, growth, reproduction etc). The species
were primarily selected because they were easy to test in the laboratory and are the
species which are recommended for laboratory toxicological tests (EMEA, 2003).
Likewise, the toxicological endpoints measured were mainly those of "classical"
toxicological studies with ECso, LCSo, and NOECs being reported. There were however,
numerous studies regarding pharmaceuticals classified as endocrine disruptors, which
generally fall under the broad class of hormones, that looked at non-classical endpoints
such as: vitellogenin levels, interaction with plasma sex steroid binding and other
possible target sites, cytotoxicity using the E-Screen and A-Screen bioassays, sex ratio,
reproductive behaviour etc. Most of these studies however, did not report their findings
as an ECSo or NOEC and as such were not included in the toxicity assessment as there
was no basis to compare the endpoints measured with the other more classical
toxicological endpoints. In addition, there were only a limited number of studies
conducted on antibiotic resistance in aquatic bacteria, and as such this endpoint was not
included in the risk assessment. Thus, the results of the toxicity assessment and the
determination of PNOAEC for each of the PPCPs are based on "classical" toxicological
endpoints, due to availability of data and ease of comparison to one another in the
rankinglrisk characterization. A more detailed discussion of the uncertainty of not
directly considering endpoints such as those being assessed for those chemicals that are
considered endocrine disrupters and bacterial resistance is provided in Section 7.1.2. The
uncertainties associated with the use of predicted toxicity values is also presented in
Section 7.1.2.
The results of the literature search are presented on Tables A.3 (acute data) and A.4
(chronic data) in Appendix A. In addition, the toxicity values selected to derive the acute
and chronic PNOAECs for the PPCPs are presented in Tables A S and A.6 in Appendix
A. It is noted that the predicted values obtained fiom Sanderson et a1 (2004) have been
included in Table A.4.
4.4.1 Chemicals Not Included in Exposure Assessment
The results of the aquatic toxicity literature search identified 7 additional classes of
pharmaceuticals with aquatic toxicity values that were not found to have been measured
in surface water. Thus, a discussion of these classes was not included in the exposure
assessment. As such, a brief description of the 7 additional pharmaceutical classes is
provided.
Anesthetics
Anesthetics are drugs that induce anesthesia (loss of sensation) by inhibiting nerve
excitation or conduction, such drugs fall under the broad class of pharmaceuticals known
as central nervous system depressants (Beers, 2004). Local anesthetics cause loss of
sensation only to the area to which it is applied. Whereas general anesthetics, usually
administered by inhalation or intravenous injection, affect the entire body by acting on
the brain to cause loss of consciousness.
Dermatological Drugs
Dermatological drugs are used to treat skin disorders and diseases. The dermatological
drug list on Table 4.2 is tretinoin. This drug is used to treat acne and photo-aging (Ellis et
al., 1998; Olsen et al., 1992).
Gastrointestinal Drugs
Gastrointestinal drugs are administered primarily for their effect on the gastrointestinal
tract (Beers, 2004) and include both prescription pharmaceuticals and over the counter
drugs. The anti-ulcer drugs and antacids are considered a subclass of gastrointestinal
drugs. The gastrointestinal drug listed on Table 4.2 is cisapride. It is a prescribed drug
used to reduce heartburn. Cisapride is a "prokinetic" agent that increases muscle
contractions of the lower esophagus and the lower esophagus sphincter. It is noted that is
infrequently prescribed (only to patients where no other medication is effective) as it has
been found to cause irregular heart arrhythmias (irregular heart rhythms) and death in
some patients (Rybacki, 2002).
Bone Modulating Drugs
These agents are used in a variety of metabolic bone disorders. Both bone-modulating
drugs listed on Table 4.2 are bisphosphonates. Biphosphonates work by binding very
tightly to bone, preventing the removal of calcium from the bone cells. This decreases
breakdown and turnover of bone in the body (Rybacki, 2002). The increased calcium
content leads to stronger bones. This is beneficial in osteoporosis or Paget's disease of
bone, where bone turnover can sometimes be speeded up causing the bones to become
weak and prone to breaking.
Anti-virals are used to vaccinate persons from contracting viruses such as rubella,
influenza, rabies etc. In addition anti-virals are prescribed to induce general viral
resistance (Spencer et al, 1986). For instance famciclovir (Table 4.2) is used to treat
herpes zoster (shingles) and genital herpes (Rybacki, 2002). It is noted that such drugs do
not cure herpes infections but can decrease pain and itching, help sores to heal, and
prevent new ones from forming.
Sedatives and Hypnotics
These drugs fall under the broad pharmaceutical class of central nervous system
depressants. Hypnosis and hypnotherapy are aften used to manage pain and treat physical
disorders that have a psychologic component (Beers, 2004). In general, hypnotics are
drugs that induce sleep and are prescribed to relieve insomnia and promote rest (Spencer
et al, 1986). Sedatives are low dose hypnotics that are used to produce a state
characterized by reduced excitation and increased relaxation. It is noted that in large
doses, hypnotics can induce general anesthesia (Spencer et al, 1986).
Other
Flumazenil is a medicine used to reverse the effects of benzodiazepines (Weinbroum et
al., 1997). Benzodiazepines (e.g. diazepam and temazeparn) are often used to induce
sedation prior to minor surgical procedures.
Nicotine
Nicotine is used in chewing gum, trans-dermal systems, inhaler, and nasal spray to help
wean cigarette smokers fiom the drug (Rybacki, 2002). It is also noted that nicotine is
excreted in the urine of smokers and therefore may be present in WWTP effluent due to
smoking rather than the use of it as a PPCP. However, no reports of nicotine in effluent
or receiving waters were found during the literature search for the exposure assessment.
5.0 DETERMINISTIC RISK CHARACTERIZATION
5.1 Introduction
The deterministic risk characterization approach incorporates single point estimates of
exposure and effects to calculate a hazard quotient. This approach is the most
conservative method of estimating risk as the assumptions made in the estimates of
exposure and effects are usually reflective of the worst-case scenario (US EPA, 1998).
For example, the highest exposure concentrations are compared with the lowest reported
toxicity values which have an uncertainty factor applied to them. Due to the
conservativeness of the deterministic approach risk is often overestimated (US EPA,
1998). However, it was the selected methodology as the calculated hazard quotients
could easily be ranked thus allowing for the prioritization of PPCPs. The point estimate
approach is the method recommended by the FDA (1998) and EMEA (2005) when
conducting environmental impact assessments of new PPCPs and has been used by
several scientists (Hansen et al., 1998; Stuer-Lauridsen et al., 2000; Boxall et al., 2000;
vanWezel and Jager, 2002; Jones et al., 2002; Sanderson et al., 2003 and Ferrari et al,,
2004) in assessing the potential risks of PPCPs to aquatic species.
5.2 Methods
To enable the PPCPs to be prioritised, hazard quotient (HQ) values were calculated by
dividing the selected environmental exposure concentration of each PPCP by their
respective acute and chronic PNOAECs (US EPA, 1998 and EMEA, 2005), as per
Equation # 1.
Equation #l. HQ = EEC
PNOAEC
5.3 Results
5.3.1 Acute Hazard Quotients
In total there were 159 PPCPs with environmental exposure concentrations (EECs) and
210 PPCPs with acute aquatic toxicity reference values (TRVs). However there were
only 11 1 PPCPs that had both environmental exposure concentrations and acute aquatic
toxicity values, as such hazard quotients were calculated for 11 1 PPCPs based acute
PNOAECs. A table of the calculations is presented in Appendix B (Table B.1), while the
following table (Table 5.1) summarizes the priority given to each of the PPCPs based on
the calculated HQs. The number of PPCPs prioritized as: very high, medium and low
were 1, 13, and 97 respectively.
5.3.2 Chronic Hazard Quotients
There were 31 PPCPs that had both environmental exposure concentrations and chronic
aquatic toxicity values, as such hazard quotients were calculated for a total of 31 PPCPs
based on their lowest chronic PNOAECs (Table 5.3). Of the 30 PPCPs, 2 were given a
very high priority, 5 given a high priority, 5 were given a medium priority and 19 were
ranked as low priority.
5.4 Discussion
5.4.1 Prioritization of Individual PPCPs
Regulatory guidance documents (US EPA, 1997 and EMEA, 2003) recommend that
those substances with HQs >1 should be further investigated. Of the 1 11 HQs calculated
based on acute PNOAECs, 14 PPCPs had HQs greater >1. In addition, 12 of the 31
PPCPs ranked based on chronic PNOAECs had hazard quotients >1. As per regulatory
guidance, these PPCPs should be investigated further with priority given to those
chemicals ranked as medium, high and very high.
A hazard quotient 4 indicates that the PPCPs alone are unlikely to cause adverse
ecological effects (US EPA, 1997) however, as Sanderson et al. (2004) point out, HQs
based on predicted toxicity values cannot be used to negate the need to conduct actual
toxicological studies of the PPCPs. Thus, those chemicals where predicted toxicity values
were used, even of their HQ was 4 , need actual toxicological data before they can be
considered unlikely to pose a risk to aquatic life. It is noted that 97 of the 11 1 PPCPs
ranked, based on their acute PNOAECs, had HQ values less than one, however 54 of
these were based on predicted toxicity values. Therefore of the 97 PPCPs with HQ values
lower than 1, 43 likely require no further action as per regulatory guidance, while 54 of
them will require actual field or laboratory aquatic toxicity studies to more adequately
assess their potential to impact aquatic life. Of the 31 PPCPs ranked based on their
chronic PNOAEC 19, had HQ values < 1 and thus require no fbrther action.
In addition, surface water should be analysed for those PPCPs that have HQs >1 where
the EEC was derived ffom WWTP effluent data. As the surface water concentration was
derived for these PPCPs, the uncertainty in the HQ would decrease if actual surface water
concentrations were measured.
The objective of ranking the PPCPs with regards to their priority for future research was
accomplished by using the deterministic risk characterization approach. Future work
should focus on those PPCPs with HQ values >1, with initial priority on those ranked as
very high and high as well as those chemicals where predicted toxicity values were used.
6.1 Introduction
A discussed previously, two approaches for risk characterization were used in this SLRA.
Initially, all PPCPs were assessed using the deterministic risk characterization methods to
rank the PPCPs fiom highest to lowest priority. Based on these results selected PPCPs
were re-evaluated for their inclusion in the PRC.
The rationale for using two approaches is that the deterministic approach, although it is
the most common, relatively easy to implement, and could provide a prioritization
scheme for PPCPs measured in the aquatic environment, it has inherent uncertainties in
the assumptions of the exposure and toxicity models, which could lead to either over or
under protective estimates of risk (US EPA, 2001). Furthermore, Solomon et al. (2001)
points out that the hazard quotient approach cannot be used to establish a level of risk as
the quotient is based on point estimates and the term risk implies an element of
likelihood, and likelihood is reported as probabilities, which cannot be established fiom
point estimates. However, the probabilistic risk characterization generally can yield risk
estimates with reported probabilities that allow for a more complete characterization of
the variability and uncertainty in the risk estimates (US EPA, 2001), as it incorporates the
distributions of the exposures and toxicity values. As such the goal of the PRC is to
supplement the DRC, by refining the original risk estimates for selected PPCPs.
The basis of the PRC is that data available fiom multiple experiments, such as those
obtained in the exposure and toxicity literature searches, can be used to generate multiple
point estimates that can be displayed as cumulative distributions functions (US EPA,
1998). Variability in exposure can be used to describe risks to moderately or highly
exposed members of a population being investigated, while variability in effects can be
used to describe risks to average or sensitive population members (US EPA, 1998). As
such, by considering variability in exposure and effects, many different scenarios can be
assessed and numerous risk estimates can be calculated, instead of just one fixed value.
By using the PRC approach, the assessment becomes more refined and the levels of
certainty increase as the results show the range of possible environmental impacts with
the scenarios that are most likely to occur being identified. Thus, the PRC can provide a
better basis for decision-making regarding potential impacts.
US EPA (1998) guidance points out that probabilistic estimates are particularly usefbl
when the risk assessment is not based on an exceedence of a pre-determined decision rule
such as a regulatory guideline, which is the case for this particular assessment.
The following sections describe the methods, results and discussion of the probabilistic
risk characterization.
6.2 Methods
The results of the deterministic risk characterization were used to select, the PPCPs to be
carried forward into the PRC. The selection criteria was as follows:
1. The PPCP had to have either an acute andlor chronic HQ value in excess of 1, and;
2. The HQ value in excess of 1 had to be based on actual toxicological data and not predicted values.
Once the preliminary list of PPCPs to be included in the PRC was complete, the exposure
assessment characterization and toxicity characterization for those PPCPs was re-
conducted. This was done because in the initial exposure and toxicity characterization
phases only the highest surface water concentration for each PPCP fiom each study was
recorded; likewise only the lowest toxicity value for a given endpoint was recorded fiom
each study. Thus, by re-conducting the exposure and toxicity assessments all of the
available data points were evaluated and included in the PRC. Upon completion of the
exposure and toxicity assessments, the PPCPs were then re-considered for inclusion the
PRC. The final criteria for a PPCP to be carried forward into the PRC was:
3. The PPCP had to have enough environmental exposure concentrations and toxicological data points to create exposure and toxicity distribution curves.
Once the PPCPs were selected, the distribution curves for the exposure concentrations
and the toxicity reference values (TRVs) were created, based on the US EPA guidance
(US EPA RAGS, 2001) and Solomon et al (2000). Initially the empirical values of the
exposure concentrations were plotted to create cumulative frequency curves of exposure
for each of the PPCPs being assessed. The TRVs for all species, including all endpoints,
were then plotted on the same axis as the exposure concentrations. The region of overlap
between the two curves was assessed and if present, the percentage of the TRVs that may
be affected at a given exposure concentration was determined.
6.3 Results
Based on the results of the deterministic risk characterization there were 14 PPCPs that
were initially considered for inclusion in the PRC, however based on the subsequent
exposure and toxicity assessments, of those 14 PPCPs, there was only sufficient data to
carry 7 PPCPs forward into the PRC. Table 6.1 presents a summary of the rationale for
those chemicals that were carried forward and those that were not. PPCPs in bold were
included in the PRC.
Surface water concentrations and TRVs for each PPCP that were used to conduct the
PRC are provided in Tables B.l through B.9 in Appendix A.
Figures 6.1 through 6.8 present the results of the PRC. Of the seven chemicals assessed,
only 17-a-ethinylestradiol had surface water concentrations in excess of the reported
toxicity reference values. In other words this was the only chemical with a region of
overlap between the plotted EEC and TRV cumulative frequency distributions (Figure
6.1). For this pharmaceutical approximately 90% of the surface water concentrations
would affect 30% of the toxicological endpoints.
Figure 6.2: The cumulative frequency distributions of exposure concentrations (represented by o) and toxicity reference values (represented by a) for propanolol (A), sulfamethoxazole (B), and tetracycline (C).
6.4 Discussion
The PRC showed no overlap of environmental exposure concentrations with TRVs for all
of the PPCPs assessed except 17-a-ethinylestradiol. Thus, concentrations in surface water
of carbmazapine, ciprofloxacin, musk xylene (nitro musk), propanolol, sulfamethoxazole,
and tetracycline were lower than any of the reported toxicity values for these chemicals.
The reason for their initial inclusion in the PRC was because they had elevated HQs from
the deterministic calculations, which included a 1000 uncertainty factor when calculating
the PNOAEC values. Alternatively, in the PRC used the distribution of empirical TRVs,
to account for intra and interspecies variability, endpoint variability etc. Thus, the PRC
indicates that those PPCPs that were ranked as a priority based on the HQ approach, do
not appear to pose significant risk based on the PRC approach. These results could also
be reflective of the limited amount of TRVs used in the PRC for each of these species.
Due to the relative lack of aquatic toxicity data, it is likely that the most sensitive species
or toxicological endpoints may not have been tested, thus the uncertainty factor applied in
the deterministic assessment is warranted and despite the results of the PRC these
chemicals should not be acquitted fiom future risk assessments or toxicological studies.
Although the PRC method provides the greatest information regarding potential risk and
has some advantages over the DRC (US EPA, 2001), the results highlight it's main
limitation, which is the amount of information required to construct the distribution
curves. For instance, in this assessment the general lack of TRVs limits characterization
of risk and thus incorporates uncertainty, as does the DRC. Despite this, the PRC did
yield a more complete characterization of the variability in the EECs and TRVs, for the
PPCPs assessed.
The regulatory guidance for developing the TRV curves is based on selecting one
endpoint (lethality, growth, reproduction etc), and then selecting an appropriate type of
point estimate (LCso, EC20 etc) from the exposure-response curve for each species. For
example, the TRV might and LCso or the EC20 for growth (US EPA, 2001). The general
requirement is that species sensitivity distribution (SSD) be composed of TRV endpoints
that are all of the same type, not a mixture, and no species being represented more than
once (US EPA, 2001). However, due to lack of toxicological endpoints and lack of
number of species tested for the PPCPs in the PRC, all relevant toxicological tests were
included in constructing the TRV cumulative distribution curves (as described in the
Section 6.2). Thus, overlap of the two curves for 17-a-ethinylestradiol is only
representative of the species and endpoints tested, based on the literature search, and is
not representative of a bbregulaf' species sensitivity distribution.
The main limitation of the PRC was that few PPCPs had substantial data available on the
distribution of exposure and TRVs for aquatic receptors, as such a detailed risk
assessment is not yet feasible for most of the PPCPs, and more basic data is required.
17-a-ethinylestradiol (EE2) is a synthetic compound used mainly as an oral
contraceptive. Over the past ten years considerable public attention and research has
focused on EE2. Based on the literature studies conducted for this assessment EE2
appears to the most studied PPCP thus far. This is most apparent in the probabilistic risk
characterization where EE2 had more exposure concentrations and TRVs than the other
PPCPs. The deterministic risk assessment ranked EE2 as low based on the acute
PNOEAC and medium based on the chronic PNOAEC. As such the overlap of the two
curves in the PRC is reflective of the chronic toxicological endpoints. Thus it is
anticipated, based on the research conducted thus far, that any ecological impact from
EE2 in the aquatic environment will be due to chronic exposure rather than acute
exposure.
7.0 UNCERTAINTY ANALYSIS
The process of evaluating ecological risks from exposure to environmental media
involves multiple steps. Inherent in each step of the process are uncertainties that
ultimately affect the final risk estimates. Uncertainties may exist in numerous areas,
including the collection of samples used to identifi contaminant concentrations,
laboratory analysis of samples, estimation of potential exposures and derivation of
toxicity reference values. These uncertainties may result in an over or under estimation of
risks. However, for this assessment where uncertainties existed, a conservative approach
was taken where appropriate so as to overestimate rather than under estimate potential
risks.
Some of the uncertainties have been mentioned the preceding report sections. Below is a
qualitative discussion of the significant sources of uncertainty in this assessment. Other
sources of uncertainty may exist other than those evaluated here; however, their impact
on the estimated risks are considered to be comparatively insignificant.
Note that as this was a preliminary SLRA, any uncertainties that have to do with
assumptions that are made during more detailed assessments such as: exposure duration,
uptake, bioavailability, chemical persistence, etc. that were not inherently part of this
assessment, were not included for discussion in this uncertainty analysis.
Many uncertainties are generic to the risk assessment process, while others are specific to
particular scenarios evaluated andlor categories of the assessment. Determination of the
uncertainty associated with the information fiom the literature and any extrapolations
used throughout the assessment are evaluated below and are presented in the same order
that the risk assessment was conducted.
7.1.1 Exposure Assessment
The basis of the exposure assessment was primarily a search of the primary literature,
where surface water concentrations reported in the literature were input into the database
and recorded as environmental exposure concentrations.
Analytical Methods
In recent years there has been a breakthrough in the sophistication of analytical
techniques capable of detecting PPCPs at concentrations in which they occur in the
environment. (Daughton, 2001) However, the variability in the numerous analytical
techniques used in the various studies (reported in the literature) adds some uncertainty to
the overall accuracy of the database created for this assessment. For instance Koplin et
al. (2002) used more than one analytical technique to detect individual PPCPs, thus the
reported environmental exposure concentrations were different, for a given PPCP, even
fiom the same sample, due to differences in the analytical techniques used. Although the
differences in the concentrations were negligible in Koplin's study, there was uncertainly
when comparing the concentrations reported fiom many studies, particularly where the
method detection limits (MDLs) vary by a factor of ten, or where the MDLs were not
reported at all.
Further uncertainty is likely introduced through the analytical methodology for detecting
most of the PPCPs, which involves filtering the samples with a 0.45 micron filter. This
method of filtering removes suspended solids, particulate matter and the colloidal
particulate fraction. Unless it can be confirmed that PPCPs are not associated with the
filtered material, or if they are, they partition to this material in insignificant amounts,
then potentially relevant amounts of PPCPs are being eliminated from the analysis.
Despite the increase in the number of analytical techniques capable of detecting PPCPs in
the environment, to date only a limited number of the large spectrum of commercial
PPCPs have been measured in the environment (Daughton and Temes, 1999). As such,
although this assessment provided an extensive review of the current status of PPCPs
reported in the environment, it is likely there are many other PPCPs in the environment at
similar concentrations but for which there are no analytical methods yet to detect them.
Thus, it is anticipated that as chemical analytical tools become even more refined and
available, this list of reported environmental exposure concentrations will likely increase.
Source of Exposure
The goal of this assessment was to rank and prioritise PPCPs occurring in the
environment due to the discharge from municipal WWTPs. Therefore, during the
literature search, data was only included in the assessment if the exposure concentration
was measured in the vicinity of WWTP discharge points. Literature that reported surface
water concentrations of PPCPs adjacent to landfills or agricultural areas but where no
WWTP was reported was not included in the database. However, in some studies surface
water concentrations were measured in areas where both WWTP effluent and agricultural
runoff occurred, while many other studies did not describe the surrounding area where
the samples were collected. Thus, some exposure concentrations may be representative of
agricultural areas adjacent to WWTPs, yet they were not reported. In such instances this
data was input into the database, however it is noted that there is some uncertainty
associated with the source of the PPCP exposure concentrations. Despite this uncertainty,
Griger, (1999) found that PPCPs in the environment are predominantly found in human
medicine and not in both human and animal medicine, therefore he assumed that the load
of municipal WWTP effluents in surface water highly influenced the concentrations
where both WWTP and agricultural activities coincide.
Dilution Factor for W P Efluent Data
The use of a 10-fold dilution factor is recommended by the US FDA (1998) when
estimating the concentrations of PPCPs from WWTP effluent into surface water, and was
subsequently used in this assessment to estimate environmental exposure concentrations
for PPCPs where only WWTP effluent values were reported. However there is some
uncertainty associated with using the dilution factor, as effluent discharges do not always
benefit from dilution (Brooks et al., 2003). For instance Herberer et al. (2001) reported
that during the summer months in some places of the Platt River in the United States, the
flow consists almost entirely of effluent fiom WWTPs. Thus, environmental exposure to
PPCPs from WWTP discharge in areas such as the Platt River would not dilute ten fold
and could present a greater risk to aquatic organisms. Despite the uncertainty using a ten-
fold dilution factor, most regulatory agencies accept the use of it.
7.1.2 Toxicity Assessment
The objectives of the toxicity assessment were to collect toxicological data on the array
of PPCPs measured in the aquatic environment. However as this was a SLRA, the
toxicity assessment did not include a detailed literature search for each particular PPCP.
Thus, there is some uncertainty that there may be more aquatic toxicological data in the
literature for certain PPCPs, and this data was not included in this assessment. Despite
this uncertainty, there was a general lack of aquatic toxicological data for most PPCPs.
For almost half of those PPCPs reported to occur in the environment there was no
ecotoxicological data found in the literature. Where there was aquatic toxicological data
available it was generally limited across: endpoints, test duration, genera etc. For
instance, most studies only looked at acute toxicity for one or two species with inhibition
of growth or reproduction as an endpoint. In addition most of the studies were laboratory
based and conducted at concentrations much higher than those concentrations reported in
surface waters. Even if the ecological relevance of species and test durations can be
discussed and improved, the results of such approaches should assist in future
considerations when developing a more adequate testing strategy for the ecotoxicological
effects of PPCPs (Ferrari et al., 2003). It would be more ecologically relevant to perform
life cycle tests based on chronic exposure with organisms representing different trophic
levels at concentrations similar to those measured in the environment. The absence of
ecotoxicological data and the general inadequacy of the ecological relevance of those
tests that were conducted resulted in relatively high uncertainty in the accuracy of
PNOAECs derived in this assessment.
Predicted Toxicity Values
Due the to the lack of aquatic toxicological data, QSARs obtained from Sanderson et al.
(2004) were used to predict the toxicities for almost half of the PPCPs measured in
surface water. In the past ten years QSARs have been developed as scientifically credible
models for predicting the toxicity of chemicals in the absence of experimental data
(Rossum et al., 1997) and have been recognised as important prioritisation tools for risk
assessment, (Sanderson et al., 2003). Although the accuracy of toxic potency predictions
from QSARs continues to improve, there remains uncertainty in the appropriate selection
of QSARs for predicting adverse effects (Rossum et al., 1997). This is true particularly
for PPCPs that have been developed to affect specific biological systems where their
exact modes of action on non-target organisms are not known and thus cannot be
accounted for in the SARs predictions. In such cases narcosis is the mode of action used.
Daughton and Ternes (1999) point out that if QSARs continue to be used to predict the
potency of PPCPs with regards to aquatic toxicity, there needs to be a procedure that
considers the modes of action of therapeutic drugs on aquatic organisms. Rossum et al.
(1997) suggests that errors in QSAR selections can result in 10 to 1000 fold errors in
toxicity potency estimates. Sanderson et al. (2003) reported that when comparing the
QSARs with actual measured effect concentrations the QSAR predictions were more
"sensitive" 80% of the time, hence there is uncertainty in the prioritisation list of this
assessment due in part to the use of predicted values rather than actual TRVs.
Uncertainty Factor
Due to the lack of extensive toxicological studies for most PPCPs and the use of QSARs,
the most conservative uncertainty factor (1000) was applied to all selected TRVs to get
the PNOAECs. However the uncertainty factor may have caused the rank of a particular
PPCP to be either over protective or under protective, as there is inherent uncertainty
when an uncertainty factor is applied.
Factors Not Considered in Toxicity Assessment
In considering that concentrations of PPCPs have the potential to cause adverse effects to
aquatic organisms, the type of effects studied must be considered closely (Jorgenson and
Halling Sorensen, 2000). In this assessment conventional endpoints were used to rank the
PPCPs for prioritisation, for future more detailed assessments. These endpoints were used
as they were the most readily available, however the endpoints considered might not be
as relevant as others when considering actual potential effects on aquatic life. Below is a
brief summary of other endpoints that should be considered when conducting more
detailed assessments. It is noted that because these factors were not considered in this
assessment there is uncertainty in the ranking, since adding endpoints such as bacteria
resistance or endocrine disruption into the TRVs would likely alter the outcome of this
SLRA.
Bacteria Resistance
Concern for the potential impact on the aquatic system fkom the presence of antibiotics
has prompted many studies (McKeon et al., 1995 and Miranda, 1998). Assessing the
potential impacts of antibiotics to aquatic receptors is different than assessing other
PPCPs because the bacteria in the environment are the target organisms that antibiotics
were created to destroy. Endpoints that are normally studied are genetic changes in the
bacteria that have caused them to become resistant to the antibiotics. It has been found
that antibiotic resistance is favoured by low-level concentrations of antibiotics (Jorgenson
and Halling Sorensen, 2000). Despite these findings such endpoints are not suitable for
comparison in this particular assessment, as the concentrations that cause bacteria
resistance are not easily converted into an ECso or LCs0. Thus, although the assessment of
the significance of antibiotic resistance in the environment must be considered, it does
not fall within the realm of this SLRA.
Endocrine Disruption
PPCPs that can disturb the normal h c t i o n of hormones that regulate development and
reproduction are considered endocrine disrupters. The effects of which have been
observed in the range of nano-grams per litre. However, as mentioned previously most of
the studies regarding PPCP endocrine disruption are not quantified as an EC5o or EClo
measurement endpoint and thus were excluded fiom this assessment. However, as the
effects of PPCP endocrine disruption are being observed at such low level concentrations
these endpoints should be considered in future more detailed risk assessments.
Mixture Toxicity
Although not the focus of this particular assessment, PPCPs do occur in surface waters as
mixtures, not single contaminants, and as such aquatic receptors may be exposed to many
PPCPs at once. Cleuvers (2003a and 2003b) showed additive effects from
pharmaceuticals that have similar modes of action. These adverse effects were observed
in Daphnia (immobility) and algae (growth rate inhibition), when exposed to a mixture of
the non-steroidal anti-inflammatory drugs: diclofenac, ibuprofen and acetylsalicylic acid
at their respective NOECs. Thus, on their own, these anti-inflammatory drugs did not
cause an effect when exposed individually at their respective NOECs but these
concentrations when exposed as a mixture did cause adverse effects. However additive
effects are not the only concern with exposure to mixtures of PPCPs. For instance
Luckenbach and Epel (2005) have shown that nitro-musks and polycyclic musks inhibit
the activity of multi-drug efflux transporters responsible for multi-xenobiotic resistance
(MXR) in gills of the marine mussel, Mytilus califomianus. The consequence of the
inhibition of efflux transporters is that normally excluded xenobiotics (such as PPCPs)
would now be able to enter the cell and potentially cause effects that would normally not
be observed. Given that aquatic receptors may be exposed to mixtures of PPCPs, site-
specific detailed risk assessments of PPCPs should consider the potential effects of
mixtures.
7.1.3 Risk Characterization
The certainty of risk estimates depends on the uncertainties inherent in each preceding
step of the risk assessment process, which has been described in some detail above. This
section assesses how those uncertainties may affect the outcome of the prioritization of
PPCPs in the deterministic risk characterization and the probabilistic risk
characterization.
Deterministic Risk Characterization
Generally, the assumptions used in the DRC were highly conservative, i.e. the use of the
highest reported environmental exposure concentrations with the lowest reported TRV.
However, there was some uncertainty associated with the DRC primarily due to the use
of: dilution factors for WWTP effluent data, predicted aquatic toxicity values and the
1000 uncertainty factor to derive the PNOAECs. Despite these uncertainties it is
anticipated that HQs for most of the PPCPs have been over estimated. However, based on
the data available and the assumptions made, the calculated HQs are only suitable for
relative risks to be identified and conclusions cannot be drawn about the actual potential
risk of individual PPCPs.
It is also noted that there is inherent uncertainty in the DRC approach as it assesses only
one scenario (i.e. the worst case), out of many. Normally the US EPA would recommend
calculating several point estimates over the range of exposure concentrations and TRVs
to get an idea of the range of risk, not just the high-end risk. However, as the DRC was
only used to prioritise the PPCPs based on a worst case scenario, this inherent uncertainty
is considered irrelevant, but should be considered in future more detailed assessments of
the chemicals listed as very high or high priority.
Probabilistic Risk Characterization I
The PRC compared the cumulative frequency distribution of exposure concentrations to'
the cumulative frequency distributions of the TRVs. As the actual values for these were
used, the uncertainties associated with DRC are not applicable in the PRC because:
dilution factors, uncertainty factors and predicted toxicity values were not used in the
PRC. Thus, the PRC has less uncertainty than the DRC, as the assumptions driving the
uncertainty in DRC are not included in the PRC. Furthermore, all of the scenarios based I
on the data in the literature, were considered in the PRC, whereas in the DRC uncertainty
is inherent with assessing only one scenario.
The primary uncertainty associated with the PRC was the lack of data in the exposure and
stressor-response curves. It is noted that, although there was uncertainty in the exposure
distributions, they were on the conservative side as most studies only reported the
maximum values in surface water, rather than including all the data. Other uncertainty in
the TRV curves may be due to under-conservatism, as most endpoints were growth,
reproduction, and death from acute exposure. A more conservative TRV curve would
include more sensitive endpoints such as: behavioural changes, genetic changes, or
energetic costs due to chronic exposure.
8.0 SUMMARY AND CONCLUSIONS
The use of pharmaceutical products is growing, the US pharmaceutical industry for
instance, in 2001 was growing twice as fast as the rest of the economy, and it showed no
sign of slowing down (Farr6 et al., 2001). This increasing use of PPCPs along with the
growing global population has resulted in widespread occurrence of PPCPs in surface
water around the world through the discharge of WWTP effluent. The presence of these
chemicals may result in impacts on non-target organisms in the WWTP receiving
environment. The assessment presented in this paper brought together the published
literature on the environmental occurrence and toxicity levels for non-target species, of
the large and diverse spectrum of PPCPs. Similar compilations of such data has been
done by Daughton, 1999; Webb, 2001 and Servos et al., 2001. However, this assessment
was more than a compilation of the literature on PPCP environmental occurrence and
aquatic toxicity. This work incorporated information fiom the literature and applied the
methodology already established for conducting risk assessment of contaminants, such as
metals, petroleum hydrocarbons, pesticides etc. in order to establish a prioritization list of
the PPCPs that have the most potential to impact aquatic life. Subsequent more detailed
assessments, including toxicological research or environmental monitoring efforts, can
apply the findings of this assessment to focus on those chemicals that are of highest
priority and place less resources toward those chemicals that appear to be of little
environmental concern, with regards to the protection of aquatic life.
Both deterministic and probabilistic risk methods were used to rank the PPCPs. The
deterministic approach derived HQs for the PPCPs, which were calculated by comparing
the highest environmental exposure concentrations to both acute and chronic derived
PNOAECs. The PPCPs were then ranked based on their respective HQ values and
categorized into four priority groups. Of the 11 1 PPCPs that were ranked based on their
acute PNOAECs; 1, 13, and 97 have been prioritized as very high, medium and low
respectively. At the same time 31 PPCPs were ranked based on chronic PNOAECs. Of
these 30 PPCPs, 2 were assigned very high priority, 5 assigned high priority, 5 were
assigned medium priority and 19 were assigned low priority. It is recommended that all
PPCPs in the category of medium or higher (i.e. with HQ values greater that 1) be
subjected to more detailed aquatic toxicological evaluations with priority being given
those PPCPs highest on the list. Furthermore for all PPCPs where QSAR predictions
were used to derive the PNOAECs, regardless of their HQ values, they should also
undergo aquatic toxicological evaluations in order to verify the QSARs used and/or the
reduce the uncertainty of this assessment.
The PRC was conducted on PPCPs whose HQ was greater than 1 and where there was
enough environmental exposure data and TRVs, to construct cumulative frequency
distribution curves. Only 7 PPCPs (carbmazapine, ciprofloxacin, musk xylene,
propanolol, sulfamethoxazole, tetracycline, and 17-alpha-ethinylestradiol (EE2)) met the
qualifications for inclusion in the PRC. For each of the chemicals assessed (except EE2)
there was no overlap between the two cumulative distribution curves indicating the risk
of these chemicals are likely not significant. However additional aquatic toxicological
data using more sensitive endpoints and chronic exposure would solidify the results of
this assessment. At the same time it is noted however, that priority for future research
should be given to the PPCPs ranked as high and very high that have even less aquatic
toxicological information than these 6 chemicals.
EE2 had environmental exposure concentrations that overlapped with the TRV values. It
is noted that EE2 was ranked as low in the acute HQ and only as medium in the chronic
HQ rankings indicating that chronic exposure to this chemical is more of a concern than
short-term exposure. EE2 appears to be the highest priority chemical in this assessment
based on both the DRC and PRC. It is expected part of this prioritization is reflective of
the fact that this chemical has been studied the most and thus has the most extensive list
of exposure concentrations and also has the most aquatic toxicological data including
chronic and sub-lethal endpoints. Regardless, both the results of the DRC and the PRC
indicate that EE2 could present a risk to aquatic receptors and thus should be assessed in
the form of a detailed sitespecific risk assessment.
With respect to the literature search, there is a substantial amount of published work that
has focussed primarily on the origin and occurrence of PPCPs, whereas it has only been
in recent years that there has been a growing amount of published literature regarding the
potential ecological impacts fiom exposure to these substances. It is likely that it was
only after a large number of PPCPs were identified in aquatic environments that concern
increased regarding the potential implications of the presence of these chemicals. Thus,
although more and more studies are being completed each year, there is still a general
lack of aquatic toxicological studies for PPCPs in the literature. This was apparent in the
DRC where predicted TRVs were used and in the PRC where the lack of TRVs for most
PPCPs only allowed for seven chemicals to be assessed. Thus, the establishment of a
more comprehensive aquatic toxicological data set for the PPCPs that have been
measured in surface waters is required and this SLRA has provided a specific list of
PPCPs that should be given priority with regards to filling such data gaps.
Although this particular risk assessment did not estimate the potential risk to aquatic life
fiom exposure of these chemicals, it provides a basis for scientists when selecting
specific PPCPs for more detailed assessment. Priority PPCPs should undergo a series of
toxicological tests to evaluate their potential to cause adverse effects. Such tests should
include sub-lethal endpoints using both acute and chronic (such as life cycle) exposures,
evaluated under natural conditions using concentrations relevant to those measured in the
aquatic environment. Because exposures to PPCPs may be of more chronic nature
because they are constantly being discharged to the environment, chronic toxicity
assessments should be a priority. Other endpoints such as antibiotic resistance,
endocrine disruption, genetic changes, mixture toxicities etc. should also be included in
fiture toxicological evaluations.
There has been a growing amount of interest and research on this topic since the late
1990's, however much more research is needed to determine whether aquatic exposures
are significant for PPCPs.
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Tab
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elfm
id e
t a1
1199
9)
I
max
0.0
05 p
g/L
LOQ
(< 0
.3)
- 1.7
ng/
L
max
7.5
ng/
L
max
4.3
ng/
L
mea
n <
0.2
ng/
L (B
MD
L) - 7
.0
nglL
<
0.3
ng/
L (B
MD
L)
0.05
- 2.
4 ng
/L
< 0
.05
(BM
DL)
- 0.0
7 ng
/L
< 1
ng/
L (B
MD
L)
BM
DL
- 0.
2 ng
/L
max
0.8
31 p
g/U
med
0.0
73
pg/L
m
ax 4
.05
ng/L
< 5
pgl
L (B
MD
L)
< 0
.2 n
g/L
(BM
DL)
< 0
.2 n
g/L
(BM
DL)
max
5 n
g/L
max
3 n
g/L
max
0.0
74 p
g/L
1 med
0.0
3
0.00
5
0.00
17
0.00
75
0.00
43
0.00
7
0.00
015
0.00
24
0.00
007
0.00
05
0.00
02
Hor
mon
e - r
epro
duct
~on
- nat
ural
Hor
mon
e -r
epro
duct
ion
-nat
ural
0.83
1
0.00
405
2.5
0.00
01
0.00
01
0.00
5
0.00
3
0.07
4
Sew
age
Effl
uent
- G
erm
any
WW
TP E
fflue
nt -
Italy
WW
TP E
fflue
nt -
Net
herla
nds
WW
TP E
fflue
nt -
Brit
ian
WW
TP E
fflue
nt -
Cal
iforn
ia
WW
TP E
fflue
nt -
New
Y
ork
WW
TP E
fflue
nt - I
taly
17 b
eta
estr
adio
l
17 b
eta
estr
adio
l
WP
E
fflue
nt -
Sw
eden
W
WT
P E
fflue
nt -
Spa
in
WP
E
fflue
nt -
UK
WW
TP E
fllue
nt -
Net
herla
nds
Sur
face
wat
er -
N
ethe
rland
s
Sur
face
wat
er -
UK
max
5.5
ng/
L
e0.1
ng/
L (B
MD
L)
Tem
es e
t al(1
999)
Bar
onti
el a
1 (2
000)
Bel
froid
el a
l (19
99)
Bel
froid
el a
l (19
99)
Des
bmw
el a
l(199
8)
Faw
ell e
l al(2
001)
Hua
ng a
nd S
edal
k
Stre
ams
- US
A
Sur
face
wat
er -
UK
Sur
face
wat
er -
N
ethe
rland
s S
tream
s -U
SA
John
son
et a
l(20
00)
0.00
55
0.00
005
Kop
lin e
l al(2
002)
Lars
son
et a
l (19
99)
Pet
rovi
c et
al (
2002
)
Xia
o e
l a1
(200
1)
Xia
o et
al (
2001
)
Bel
froid
et a
l (19
99)
Bel
fmid
et a
l (19
99)
Kop
lin e
t al (
2002
)
-
Net
herla
nds
Sur
face
wat
er -
Net
herla
nds
Sur
face
wat
er -
. .
Bel
froid
et a
l (1 9
99)
Boy
d e
l al(
2003
)
1seaqinos sd
m
(~IV
W) ko
iew
we
uu
! (E
OO
Z) le la
uo
lw
40 w
ea
~~
sd
n
SZO'O
7/6u tx
> xew
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-!we lep!o~ais-uou/so!sa61euv
pue16ua isea
wn
os
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6a
~
p!d
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leln
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e
Tabl
e A
.1:
Sum
mar
y of
Env
iron
men
tal C
on
cen
trat
ion
s
1 I
IRep
orte
d C
once
ntra
tion
Ipg/
L IE
Mu
en
t \S
urfa
ce w
ater
1
Che
mic
al C
lass
C
hem
ical
Nam
e
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Pes
ronl
car
e pr
oduc
t -su
n s
cree
n ag
ent
Bet
aalo
cker
(ant
ihyp
erte
nsiv
e,
antig
lauc
oma)
1 c
ardi
ovas
cula
r dru
g Li
pid
regu
lato
r
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lip
~d
regu
lato
r
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Mea
sure
d E
nviro
nmen
tal O
ccur
renc
e
Ato
rvas
tatin
Ato
rvas
tatin
Ato
rvas
tatin
Avo
benz
ene
Bet
axol
ol
Bez
afib
rate
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Bez
afib
rate
Bez
afib
rate
Bez
afib
rate
Bez
afib
rate
Bez
afib
rate
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Ant
isep
tic
Ref
eren
ce
Rep
orte
d In
M
atrix
mea
n 0.
010
pglL
mea
n 0.
015
pg/L
< 1
0 ng
lL (B
MD
L)
max
0.0
28 p
glL
max
0.1
9 pg
lL
0.79
- 5
7.15
ng/
L
Bez
afib
rate
Bez
afib
rate
Bez
afib
rate
Bez
afib
rate
Bez
afib
rate
Ant
isep
tic
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) I
card
iova
scul
ar d
rug
Ref
eren
ces
max
0.0
78 p
glL
170
pS/L
mea
n 0.
259
pg
/~
mea
n 0.
012
pS/L
mea
n 0.
082
pg/L
Bez
afib
rate
Bez
afib
rate
Bez
afib
rate
Bez
afib
rate
Bez
afib
rate
Bez
afib
rate
Bez
afib
rate
Bip
heny
l01
0.01
0.01
5
0.00
5
0.02
8
0.19
0.05
715
mea
n 0.
065
pg/L
< 1
0 ng
lL (B
MD
L)
mea
n 0.
010
pS/L
mea
n 0.
137
pglL
< 1
0 ng
/L (B
MD
L)
Bip
heny
l01
Bis
opro
lol
0.07
8
0.1
7
0.25
9
0.01
2
0.08
2
max
0.6
pg/
U m
ed 0
.2 p
g/L
max
0.2
00 p
g/U
med
0.0
52
yg
lL
c 1
0 ng
/L (B
MD
L)
< 1
0 ng
/L (B
MD
L)
med
1 p
g/L
max
4.6
pgl
L
max
3.1
pg/
L
max
2.6
pg/
L
WW
TP E
fflue
nt -
Ger
man
y
0.06
5
0.00
5
0.01
0.13
7
0.00
5
max
0.2
5 pg
lL
max
0.3
7 pg
lL
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Pet
erbo
roug
h W
WTF
' Effl
uent
- B
urlin
gton
W
WTP
Effl
uent
-
0.6 0.2
0.00
5
0.00
5
1 4.6
3.1
2.6
Sur
face
wat
er
adja
cent
to W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Sur
face
wat
er
adja
cent
to W
WTP
R
iver
s an
d st
ream
s -G
erm
any
Riv
ers
- Ita
ly
Littl
e R
iver
W
WTP
Effl
uent
- W
est W
inds
or
0.25
0.37
Met
calfe
et a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l(2
00
3b
)
Ter
nes
(199
8)
Ter
nes
(1 99
8)
Cal
amar
i et a
1 (2
00
3)
Sur
face
wat
er -
Ger
man
y
WW
TP E
fflue
nt -
Can
ada
WW
TP
Effl
uent
- B
razi
l W
WTP
Effl
uent
- G
erm
any
WW
TP
Effl
uent
-
GV
RD
(unp
ublis
hed
data
) H
erbe
rer e
l al(2
001)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
i (20
03b)
Met
calfe
el a
l (20
03b)
Sur
face
wat
er
adja
cent
lo W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Sur
face
wat
er
ad'a
cent
to W
WTP
S
drfa
ce w
ater
Ger
man
y
WW
TP
Effl
uent
- G
erm
any
. .
Met
calfe
el a
l (20
03b)
Met
caife
el a
1 (2
003b
)
Met
calfe
el a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l(200
3b) -
ad
jace
nt to
WW
TP
Sur
face
wat
er -
Det
roit
Riv
er
Sur
face
wat
er -
Ham
ilton
har
bour
S
urfa
ce w
ater
- E
aste
rn C
anad
a
Riv
ers
and
stre
ams
-Ger
man
y
. .
Met
calfe
el a
l (20
03a)
Met
calfe
et a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Stu
mpf
el a
l. (1
999)
Tem
es (
1998
)
Ter
nes
(1 99
8)
Ter
nes
el a
l (19
98)
Sur
face
wat
er -
Ger
man
y T
erne
s e
l al(1
998)
Ter
nes
(1 99
8)
Tab
le A
.1:
Su
mm
ary
of E
nvi
ron
men
tal C
on
cen
trat
ion
s
Che
mic
al C
lass
I 1
I 1 S
wed
en
I I
1 P
erso
nal c
are
prod
uct -
frag
ranc
e l~
isp
he
no
l 0.
1 ng
/L (B
MD
L)
10.0
0005
IM
P E
fflue
nt -
I 1 Bo
yd e
l al (
2003
)
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) I
card
iova
scul
ar d
rug
Dis
infe
ctan
t
1 I
I 1 U
SA
I
I I
An
tin
e~
~la
sti
~
lBle
omvc
in
lma
x 17
na
l~
10.0
17
I IS
urfa
ce w
ater
- I~
he
rne
et a
lil9
90
) I
I I
I I
I I
I
Che
mic
al N
ame
Bis
opro
lol
Bis
phen
ol
Mea
sure
d E
nviro
nmen
tal O
ccur
renc
e
Ant
ineo
plas
tic
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
Rep
orte
d C
once
ntra
tion
max
2.9
gl
L
490
ngIL
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
St~
mul
ant
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
Stim
ulan
t
Mat
rix
Ble
omyc
in
Caf
fein
e
Caf
fem
e
Caf
fein
e
Caf
fein
e
I I
I I
I I
I
pg/L
2.9
0.49
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Caf
fein
e
Stim
ulan
t
Ref
eren
ces
max
19
ng/L
rnax
4.3
98 p
glL
max
3.0
pgl
L
max
265
ngl
L
max
6.0
pg
lU m
ed 0
.081
pgI
L
Rep
orte
d In
Effl
uent
WW
TP E
fflue
nt -
mea
n 0.
022
pglL
mea
n 0.
022
pglL
mea
n 0.
028
pg/L
mea
n 0.
677
pg/L
mea
n 0.
014
pg/L
mea
n 0.
033
glL
mea
n 0.
017
pglL
mea
n 0.
046
pgIL
2 -
3.3
pglL
0.06
pgI
L
mea
n 0.
19 p
glL
max
1.9
pg
lU m
ed 0
.072
pgi
L
rnax
0.8
8 p
glU
med
0.5
3 pg
lL
mea
n 0.
22 p
g/L
2 ng
lL
Caf
fein
e
0.01
9
4.39
8
3 0.26
5
6
Sur
face
wat
er
Riv
en
and
st
ream
s -G
erm
any
0.02
2
0.02
2
0.02
8
0.67
7
0.01
4
0.03
3
0.01
7
0.04
6
3.3
0.08
0.19
1.9
0.88
0.22
0.00
2
2.0
- 16.
1 ng
/L
Ter
nes
(199
8)
Lars
son
el a
l (19
99)
WW
TP E
fflen
t - E
ngla
nd
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
Pet
erbo
roug
h W
WTP
Effl
uent
- B
u~lin
gton
W
WTP
Effl
uent
- Li
nle
Riv
er
WW
TP E
fflue
nt -
Wes
t Win
dsor
WW
TP E
fflue
nt -
Sw
eden
W
WTP
Effl
uent
- N
evad
a W
WTP
Effl
uent
- G
erm
any
WW
TP E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
Gen
nany
0.01
61
Eng
land
Sur
face
wat
er -
Ger
man
y S
tream
s -U
SA
. ,
Ahe
rne
el a
l (19
90)
GV
RD
(unp
ublis
hed
data
) H
eber
er a
nd R
edde
rsen
(2
001)
H
erbe
rer e
l al (
2002
)
Kop
lin e
l al(2
002)
Sur
face
wat
er
adja
cent
to W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Sur
face
wat
er
adja
cent
to W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Riv
en
and
st
ream
s -G
erm
any
Nor
th S
ea
Nor
th S
ea
Wei
gel e
l al (
2002
)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
el a
i (20
03b)
Mel
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Pax
eus
(199
6)
Sei
ler e
l al (
1999
)
Ter
nes
el a
l(200
1)
Ter
nes
el a
l(200
1)
Ter
nes
et a
l (20
01)
Ter
nes
el a
l (20
03)
Wei
gel e
l al (
2001
)
-
Tab
le A
.1:
Su
mm
ary
of E
nvi
ron
men
tal C
on
cen
trat
ion
s
I C
hem
ical
Cla
ss
I C
hem
ical
Nam
e I M
easu
red
Env
ironm
enta
l Occ
urre
nce
( M
atrix
I
Ref
eren
ces
I I
I Repor
ted
Con
cenb
alio
n ( pg
/L
1 EMue
nt
l~u
rfa
ce
wat
er
( I
I I
I I
I B
eta-
bloc
ker (
anth
yper
tens
ive,
an
tiang
al, a
ntar
ryth
mic
) /
antia
ngal
, ant
arry
thm
ic) /
pie
pil
ep
tic
I C
arba
maz
epin
e I m
ax 4
45 n
g/L
I 0.4
45
I WW
TP E
fflue
nt -
I
Dre
wes
el a
l(200
2)
I
11C
A
card
iova
scul
ar d
mg
Ant
ibio
tic
Ant
ibio
tic
Car
azol
ol
max
0.1
1 p
g/L
Ant
iepi
lept
ic
ICar
bam
azep
ine
10.8
7 pg
/L
10.8
7 ~
WW
P
Effl
uent
- I
1 Fer
ran
el a
l(200
3)
Car
bado
x
Car
bado
x
. .
max
0.1
2 pg
/L
0.1
1
< 0
.005
pg/
L (B
MD
L)
BM
DL . -
1
0.12
Riv
ers
and
stre
ams
- Ge
ma
ny
1 Swed
en
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Tem
es (
1 998
)
0.00
25
BM
DL
IGer
man
y A
ntie
pile
ptic
Ant
~ep
ilept
rc
ICar
bam
azep
ine
lmax
1.2
g/L
11
.2
lWW
T~
Eff
lue
nl-
(
IFer
rari
el a
l(200
4)
. .
WW
TP E
fflu
en
l-
Ger
man
y
. .
Car
bam
azep
ine
0.30
- 0.
50 p
g/L
Car
bam
azep
ine
Car
bam
azep
lne
Car
bam
azep
ine
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
An
tie
pile
~ti
c
Tem
es (1
998)
WW
TP E
fflue
nt -
Van
couv
er
Ant
iepi
lept
ic
]Cab
amaz
epin
e lm
ax 1
075
ng/L
11
.075
I
l~u
rfa
ce
w
ater
- IH
eber
er e
l al (
2002
) 1 G
erm
any
Ant
iepi
lept
ic
Ref
eren
ce
0.5
max
0.8
6 g/
L
max
5.0
gl
L
235
ng/L
.
.
Car
bam
azep
ine
Car
bam
azep
ine
Car
bam
azep
ine
Car
bam
azep
ine
Car
bam
azep
ine
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Str
eam
s -U
SA
Car
bam
azep
ine
Car
bam
azep
ine
GV
RD
(unp
ublis
hed
data
) K
oplin
et a
l (20
02)
WW
TP E
fflue
nt - I
taly
0.86
5 0.23
5
mea
n 0.
126
pg/L
mea
n 0.
064
pg/L
mea
n 0.
1 12
pg/
L
mea
n 0.
007
pg/L
mea
n 0.
002
ud
L
Car
bam
azep
ine
Car
bam
azep
ine
Car
bam
azep
ine
Car
bam
azep
ine
Fer
ran
et a1
(20
03)
. -
mea
n 0.
023
pg/L
mea
n 0.
080
vg/L
Fra
nce
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Ger
man
y
0.12
6
0.06
4
0.11
2
0.00
7
0.00
2
mea
n 0.
004
pg/L
max
2.3
vg
/Ll m
ed 0
.7 v
glL
max
0.6
50 p
glL
1 m
ed 0
.185
pg
IL
max
0.3
10 p
g/L
1 med
0.1
20
pglL
0.02
3
0.08
Sur
face
wat
er -
WW
TP E
fflue
nt -
Pet
erbo
roug
h W
WP
Effl
uent
- B
urlin
gton
W
WTP
Effl
uent
- Li
ttle
Riv
er
WW
TP E
fflue
nt -
Wes
t Win
dsor
0.00
4
2.3
0.65
0.31
GV
RD
(unp
ublis
hed
data
) H
eber
er a
nd R
edde
rse~
(2
001)
H
eber
er e
t al (
2001
)
adja
cent
lo W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Sur
face
wat
er
Ger
man
y
Sur
face
wat
er
. .
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
WW
TP E
fflue
nt -
Can
ada
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
adja
cent
to W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Sur
face
wat
er -
Det
roit
Riv
er
Sur
face
wat
er -
Ham
ilton
Har
bour
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
0%)
Met
calfe
el a
l (20
03b)
Met
calfe
et a
l (20
03b)
Tab
le A
.1:
Su
mm
ary
of E
nvi
ron
men
tal C
on
cen
trat
ion
s
I C
hem
ical
Cla
ss
I C
hem
ical
Me
I M
easu
red
Env
ironm
enta
l Occ
urre
nce
I M
atrix
l~n
tie
pile
pti
c I
ICar
bam
azep
ine
1 max
1 .I
vpl
L 11
.1
I 1 R
iver
s an
d [~
em
es
(1
998)
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepd
eptic
Car
bam
azep
ine
Car
bam
azep
ine
Car
bam
azep
lne
Car
bam
azep
lne
Cab
amaz
epin
e
. .
. .
]str
eam
s - ~
erm
an
~l
IGer
man
y 1
1 1
(Ger
man
y I
1 I
Ant
ibio
tic
1 Chl
oram
phen
icol
lm
ax 0
.06
pglL
1~
0.0
2
pg/L
10
.06
I 1 R
iver
s an
d I~
irs
ch
et
al (
1999
) I
Rep
orte
d C
once
ntra
tion
max
0.0
20 p
glL
1 med
0.0
20
pg
/L
35 -
60 n
glL
30 -
250
nglL
100
- 800
ng1
L
max
6.3
pgl
L
Ant
iepi
lept
ic
ICar
bam
azep
ine
lmea
n 2.
1 pg
1L
12.1
IM
P E
fflue
nt -
1 l~
em
es
et
al(
20
03
) 1
Ant
iepi
lept
ic
ICar
bam
azep
ine
12 n
g1L
Be
tad
ock
er
(ant
hype
rten
sive
. an
tiang
al, a
ntar
ryth
mic
) I
card
iova
scul
ar d
rug
An
tib
~o
t~c
I I
1 I
1 US
A
I I
Ant
isep
tic
lChl
omph
ene
I< 0.1
ngl
L (B
MD
L)
10.0
0005
IW
WT
P E
fflue
nt -
I IB
oyd
et a
l (20
03)
pg/L
0.02
0.06
0.25
0.8
6.3
0.00
2
Cel
ipm
lol
Chl
oram
phen
icol
I
1 Nort
h S
ea
1 ~eig
el et a
l (20
02)
1
I Id
rain
ages
-
Effl
uent
WW
TP
Effl
uent
- S
witz
erla
nd
WW
TP
Effl
uent
mea
n 0.
28 v
g/L
max
0.5
6 pg
lL I ~0
.02
vg/L
Ant
isep
tic
lChl
omph
ene
Ic 0
.1 n
glL
(BM
DL)
10
.000
05
1 IS
urfa
ce w
ater
- I B
oyd
et a
1 (2
003)
I
Ant
ibio
tic -
tetr
acyc
line
Ant
ibio
tic -
tetr
acyc
line
Ant
ibio
tic -
tetr
acyc
line
Ant
ibio
tic -
tetr
acyc
line
I I
I I
I I
I A
ntib
iotic
- flu
oroq
uino
lone
lC
ipro
tloxa
cin
1 BM
DL
- 26.
1 5 n
g1L
10.0
2615
1
l~iv
ers
-Ita
ly
]cal
amar
i et a
1 (2
003)
I
Su
rfa
ce w
ater
Sur
face
wat
er -
Eas
tem
Can
ada
Lake
s -
Sw
itzer
land
R
iver
s -
Sw
itzer
land
0.28
0.56
Chl
orot
etra
cycl
ine
Chl
omte
trac
yclin
e
I I
I I
I
Chl
omte
trac
yclin
e
Chl
omte
trac
yclin
e
lmax
0.5
8 p
gl~
' 1 0.0
74 p
gll'
10
.58
I~n
tib
ioti
c-m
acm
lide
C
larit
hmm
ycin
1.
24 - 2
0.30
ngl
L 0.
0203
R
ive
n -
Italy
C
alam
ari e
t al (
2003
)
Met
calfe
et a
i (20
03b)
-
Olle
rs e
t al (
2001
)
Olle
rs e
t al (
2001
)
Olle
rs e
t al (
2001
)
Tem
es (
1 998
)
WW
TP
Effl
uent
- G
erm
any
WW
TP
Effl
uent
-
0.00
5 pg
lL (B
MD
L)
0.05
pgl
L (B
MD
L)
Ant
ibio
tic -
fluor
oqui
nolo
ne
Ant
ibio
tic -
fluom
quin
olon
e
Ant
ibio
tic -
fluom
quin
olon
e
Ant
ibio
tic -
fluor
oqui
nolo
ne
--
c 0.
05 v
g/L
(BM
DL)
-
max
0.6
9 vg
/L I m
ed 0
.42
uglL
Str
eam
s -U
SA
Tem
es e
t al (
2003
)
Hirs
ch e
l a1
(199
9)
0.00
25
0.02
5
Kop
lin e
t al (
2002
)
Cip
roflo
xaci
n
Cip
mflo
xacm
Cip
roflo
xac~
n
Cip
roflo
xaci
n
I I
I I
I I
I
-
0.02
5
0.69
Ant
ibio
tic -
mac
rolid
e
US
A
WW
TP
Effl
uent
- V
anco
uver
W
WT
P E
fflue
nt-
mea
n 55
-108
ng1
L
62 -
106
nglL
max
0.2
13 p
g/L
max
0.0
3 p
g/U
med
0.0
2 pg
/L
GV
RD
(unp
ublis
hed
data
) H
irsch
et a
1 (1
999)
G
erm
any
Cla
rithr
omyc
in
0.1 0
8
0.10
6
0.21
3
0.03
Riv
ers
and
drai
nage
s -
Stre
ams
-US
A
c 0.
001
pg/L
(BM
DL)
Hirs
ch e
t al (
1999
)
Kop
lm e
i al (
2002
)
WW
TP
Ter
tialy
E
fflue
nt -S
witz
erla
nd
WW
TP
Effl
uent
- S
witz
erla
nd
WW
TP
Effl
uent
- V
anco
uver
0.00
05
Str
eam
s - U
SA
Gol
et e
t a1
(200
1)
Gol
et e
t al (
2002
)
GV
RD
(unp
ublis
hed
data
) K
oplin
et a
l (20
02)
WW
TP
Effl
uent
- V
anco
uver
G
VR
D (u
npub
lishe
d da
ta)
Tab
le A
.1:
Su
mm
ary
of E
nvi
ron
men
tal C
on
cen
trat
ion
s
I C
hem
ical
Nam
a I M
easu
red
Env
ironm
enta
l Occ
urre
nce
I I
I IR
epor
ted
Con
cent
ratio
n I&
L
IEftlu
ent
l~u
rfa
ce
wa
ter
I I
I I
I I
I I
I A
ntib
iotic
- m
acm
lide
lCla
rithm
myc
in
Ima
x 0.
24 p
g/L
/ med
<0.
02
10.2
4 IW
WT
P E
fflue
nt-
I I~
irs
ch
e
l al(
l99
9)
I
An
tibid
ic -
mac
rolid
e
Ant
ibio
tic - m
acm
lide
I T
emes
(1 9
98)
Bet
a ag
onis
t -82
-sym
path
omim
etic
(b
ronc
hodi
alat
or)
Bet
a ag
onis
t -B
2-sy
mpa
thom
imet
ic
(bro
ncho
dial
ator
) Li
pid
regu
lato
r
Li~
id
reou
lato
r
I T
emes
(19
98)
Cla
rithr
omyc
in
Cla
nthr
omyc
in
1
Her
bere
r (19
951
I ReD
orte
d in
Cle
nbut
erol
Cle
nbut
erol
Clo
fibra
te
Clo
fibra
te
. .
l~e
ko
s
et a1
H
erbe
rer (
1 995
) I ~
e~
ort
ed
in
ng/L
m
ax 0
.26
pg
/L/ m
ed <
0.02
pg
/L(B
MD
L)
mea
n 0.
21 p
g/L
max
0.0
8 pg
lL
max
0.0
50 p
g/L
max
220
ng/
L
max
175
0 ng
/L
0.26
0.21
. -
0.08
0.05
0.22
1.75
(200
0)
Ger
man
y
WW
TP
Effl
eunt
-
I
Lipi
d re
gula
tor
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Ger
man
y W
WT
P E
fflue
nt -
Ger
man
y
. .
l~e
rm
an
~
1 serv
os e
l al
Tem
es (
1 998
) C
lofib
rate
l~o
rth
S
ea
I I
I 1
I I
I M
etab
olite
- clo
fibra
te
l~lo
fib
ric
acid
1 m
ax 2
5 ng
/L
10.0
25
IWW
TP
Effl
uent
- I
1 Dre
wes
el a
l (20
02)
1
Riv
ers
and
drai
nage
s -
Riv
ers
and
stre
ams
- Ger
mar
S
urfa
ce w
ater
- E
umpe
S
urfa
ce w
ater
-
Lipi
d re
gula
tor
Cio
fibra
te
Clo
fibric
aci
d
Clo
fibnc
aci
d
Clo
fibnc
aci
d
Clo
fibric
aci
d .
.
I I
Hirs
ch e
t al (
1 999
)
Tem
es e
t al (
2003
)
< 0
.10
pg/L
(BM
DL)
Met
abol
ite -
clof
ibra
te
l~io
fib
ric
acid
I<
1 - 9
ng
/~
10.0
09
I ]s
urf
ace
wat
er -
I Bus
er e
l a1
(199
8b)
1 (l
ake
s in
Clo
fibra
te
0.05
< 0
.03
pg/L
(BM
DL)
med
< 0
.005
pgl
L (B
MD
L) -
0.01
pg/
L <
0.6
ng/
L (B
MD
L)
< 0
.6 n
g/L
(BM
DL)
1.2
- 7.8
ng/
L
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite -
clof
ibra
te
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
max
9.7
4 pg
/L
0.01
5
0.01
0.00
03
0.00
03
0.00
78
Clo
fibric
aci
d
Clo
fibric
ac~
d
I 1 Fr
ance
Clo
fibnc
aci
d
Clo
fibric
ac
~d
Clo
fibric
aci
d .
.
1 Fran
ce
9.74
WW
TP
Effl
uent
- U
SA
BM
DL
BM
DL
- 0.6
8 pg
lL
Met
abol
ite - c
lofib
rate
IC
lofib
ric a
cid
1 BM
DL
~B
MD
L
IMP
Effl
uent
- I
1 Fer
rari
el a
l (20
04)
1 .
.
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
BM
DL
- 5.7
7 ng
/L
Met
abol
ite - c
lofib
rate
IC
lofib
ric a
cid
lmax
0.0
21 p
g/L
10.0
21
IMP
Efflue
nt-
I IG
VR
D (u
npub
lishe
d I
WW
TP
Effl
uent
- U
SA
Riv
ers
and
stre
ams
- Ger
man
y S
urfa
ce w
ater
- U
SA
S
urfa
ce w
ater
-
US
A
Sur
face
wat
er -
BM
DL
0.68
I
Clo
fibric
aci
d
Clo
fibric
aci
d
Tem
es (
1998
)
Boy
d an
d G
rimm
(20
01)
Boy
d e
l al (
2003
)
Boy
d e
l al(2
003)
Bus
er e
l al(1
998b
)
0.00
577
WW
TP
Effl
uent
- S
wed
en
WW
TP E
fflue
nt -
0.46
pg/
L
Hig
nite
and
Aza
rnof
f (1
977)
US
A
WW
TP
Effl
uent
- G
erm
any
WVV
TP E
fflue
nt -
Italy
Fer
rari
el a
l (20
03)
Fer
ran
el a
l (20
04)
0.46
max
0.7
3 pg
/L
max
450
ng/
L
Rep
orte
d in
S
ervo
s e
l al
Riv
ers
- Ita
ly
Fer
rari
et a
l (20
03)
Fer
rari
el a
l (20
03)
BM
DL
~B
MD
L
Cal
aman
el a
l (20
03)
0.73
0.45
Van
couv
er
WW
TP
Effl
uent
- G
erm
any
Sur
face
wat
er -
data
) H
eber
er a
nd R
edde
rsen
(2
001)
H
eber
er e
l al (
2002
)
Tab
le A
.1:
Su
mm
ary
of
En
viro
nm
enta
l Co
nce
ntr
atio
ns
I C
hem
ical
Cla
ss
I C
hem
ical
Nam
e 1 M
easu
red
Env
iron
men
tal O
ccur
renc
e I
Ma
trii
I R
efer
ence
s
I I
/Rep
orte
d C
once
ntra
tion
Ilrgl
L \E
fflu
ent
I~u
rfa
ce
w
ater
I
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
1
l~e
rm
an
~
Clo
fibric
acl
d
Clo
fibric
aci
d
Met
abol
ite - c
lofib
rate
Met
abol
ite -
clof
ibra
te
Met
abol
ite - c
lofib
rate
Met
abol
ite -
clof
ibra
te
. .
Ipg
l~
- h5 I
I~a
mil
ton
Har
bour
I
I Clo
fibric
aci
d lm
ax 0
.015
pg/
L 1 m
ed 0
.015
!s
urfa
ce w
ater
-
I Met
calfe
el a
l (20
03b)
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rale
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
BM
DL
- 875
ng/
L
50 n
g/L
Clo
fibric
aci
d c
8.3
ng/L
(BM
DL)
Clo
fibric
acl
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
acl
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite -
clof
ibra
te
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
0.87
5
0.05
0.00
415
mea
n 0.
044
pg/L
mea
n 0.
002
pg/L
< 2
0 n
dL
(BM
DL)
. -
I I
1 I
I I
l~lo
fib
ric
acid
1 18
.6 n
g/L
10.0
186
1 1 ~
ort
h
Sea
- 1 ~
eig
el el a
l(200
2)
-.
.
< 2
0 ng
/L (B
MD
L)
< 1
0 ng
lL (B
MD
L)
mea
n 0.
001
pg/L
mea
n 0.
003
pg/L
< 1
0 ng
lL (B
MD
L)
0.05
pg/
L (B
MD
L)
max
0.1
75 p
giL
l med
0.0
59
pglL
m
ax 0
.101
uq
/L/ m
ed 0
.077
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d .
.
I
. .
WYV
TP E
fflue
nt -
UK
0.04
4
0.00
2
0.01
lm
of
ib
ra
te
I~
lofi
bri
c aci
d Im
ean
0.12
pg/
L 10
.12
IMP
Eff
luen
t-
Istr
eam
s I
- ~
erm
an
~l
l~e
me
s el a
l (20
03)
Ref
eren
ce
Kan
da e
l al (
2003
)
0.01
0.00
5
0.00
1
0.00
3
0.00
5
0.02
5
0.17
5
0.10
1
pg/L
5
- 10
ng/L
< 4
.5 (
BM
DL)
- 25
nglL
<4.5
(BM
DL)
- 60
ngi
L
max
1.6
pg/
L
max
0.5
5 ua
lL
Met
abol
ite - c
lofib
rate
C
lofib
ric a
cid
BM
DL
- 1.3
5 ng
/L
0.00
135
Nor
th S
ea
IWei
gei e
t al (
2002
)-
]Ger
man
y
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Sur
face
wat
er -
B
erlin
S
urfa
ce w
ater
-
WW
TP
Effl
uent
- P
eter
bom
ugh
WW
TP
Effl
uent
- B
urlin
gton
W
WTP
Effl
uent
-
. .
Her
bere
r el a
l (19
98)
Her
bere
r el a
l(200
1)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
et a
l 120
03b)
Li
ttle
Riv
er
WYV
TP E
fflue
nt -
Wes
t Win
dsor
WW
TP
Effl
uent
- C
anad
a
10
0.02
5
0.06
1.6
0.55
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibnc
aci
d
Sur
face
wat
er
adja
cent
to W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WYV
TP
Sur
face
wat
er
adja
cent
to W
YVTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Sur
face
wat
er -
D
etm
it R
iver
S
urfa
ce w
ater
-
WW
TP E
fflue
nt -
Sw
itzer
land
W
YVTP
Effl
uent
- G
erm
any
BM
DL
-val
ue n
ot re
porte
d
0.57
pg/
L
0.04
9 pg
/L
. .
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03a)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Eas
tern
Can
ada
Lake
s -
Sw
itzer
land
R
iver
s -
Sw
itzer
land
Riv
ers
and
BM
DL
0.57
0.04
9
Olle
rs e
l al(
2001
)
Olle
rs e
l al (
2001
)
Olle
rs e
t al (
2001
)
Tem
es (1
998)
Ter
nes
(1 99
81
WW
TP E
fflue
nt -
Sas
kato
on
Trib
utar
y S
urfa
ce w
ater
- S
outh
Sas
k R
iver
Sur
face
wat
er -
Ger
man
y
Win
kler
el a
l (20
01)
Win
kler
el a
l (20
01)
Win
kler
el a
l (20
01)
Tab
le A
.1:
Sum
mar
y o
f E
nvi
ron
men
tal C
once
ntra
tions
I C
hem
ical
Cl
w
I C
hem
ical
Nam
e I M
easu
red
Env
iron
men
tal O
ccum
ence
Ile
pM
ed
Con
cent
ratio
n bL
A
ntib
iotic
- pen
icill
in
Ant
ibio
tic -p
enic
illin
Ana
lges
ic
Met
abol
ite - n
icot
ine
Met
abol
ite -n
icot
ine
1 I
I M
etab
olite
- nic
otin
e l~
oti
nin
e
20 n
g/L
(BM
DL)
10
.01
Clo
xaci
llin
I 1 p
glL
I
Met
abol
ite - n
icot
ine
Clo
xaci
iiin
Cod
eine
Cot
inin
e
Cot
inin
e
Cot
inin
e F
< 0
.02
pglL
(BM
DL)
0.03
9 M
etab
olite
- nic
otin
e
0.01
< 0
.02
pglL
(BM
DL)
max
0.1
9 pg
lL I
me
d 0
.12
pgIL
max
0.9
67 p
glL
max
0.9
0 pg
lL I med
0.0
24
Met
abol
ite - n
icot
ine
Cot
inin
e m
ean
0.00
4 pg
lL
Met
abol
ite - n
icot
ine
Cot
inin
e m
ean
0.01
3 p
gR
0.
013
0.01
0.19
0.96
7
0.9
Cot
inin
e
I I
mea
n 0.
039
pglL
mea
n 0.
022
pgIL
0.
022
I I
I
1
Ant
ineo
plas
tic
Cyc
loph
osph
amid
e
Ant
ineo
plas
tic
Cyc
loph
osph
amid
e m
ean
0.00
4 pg
lL
0.00
4
Ant
ineo
plas
tic
Cyc
loph
osph
amid
e <
20
nglL
(BM
DL)
Ant
ineo
plas
tic
Cyc
loph
osph
amid
e m
ean
0.00
8 pg
lL
0.00
8
BM
DL
Ant
ineo
plas
tic
Ant
ineo
plas
tic
Ant
ineo
plas
tic
Cyc
loph
osph
amid
e
Cyc
loph
osph
arni
de
Cyc
loph
osph
amid
e
I I
BM
DL
Ant
ineo
plas
tic
Ant
ineo
plas
tic
max
0.0
03
0.01
9 -4
.48
6 p
glL
Cyc
loph
osph
amid
e <
10
nglL
(BM
DL)
0.00
3
0.01
9
Cyc
loph
osph
amid
e
0.00
5
Ant
ineo
plas
tic
Cyc
loph
osph
amid
e
Mat
rix
Ant
ineo
plas
tic
Ant
ineo
plas
tic
Ant
ineo
plas
t~c
Eff
luen
t
WW
TP E
fflue
nt -
Ger
man
y
< 2
0 ng
/L (B
MD
L)
< 1
0 n
glL
(BM
DL)
WW
TP E
fflue
nt -
Van
couv
er
0.01
0.00
5
Cyc
loph
osph
amid
e
Cyc
loph
osph
amid
e
Cyc
loph
osph
arni
de
WW
TP E
fflue
nt -
Pet
erbo
roug
h W
WTP
Effl
uent
- B
urlin
gton
W
WTP
Effl
uent
- Li
ttle
Riv
er
MP
E
fflue
nt -
Wes
t Win
dsor
MP
E
fflue
nt -
tanc
ouve
r io
spit
al E
fflue
nt
mea
n 0.
005
pglL
mea
n c 1
0 ng
lL
< 0
.1 p
glL
(BM
DL)
NW
P E
fflue
nt
NW
TP
Effl
uent
- 'e
terb
orou
gh
MP
E
fflue
nt -
3urli
ngto
n M
nrrP
Effl
uent
- M
e Riv
er
MP
E
fflue
nt -
Nes
t Win
dsor
0.00
5
0.00
5
0.05
N
WT
P E
fflue
nt -
:ana
da
Sur
face
wat
er
GV
RD
(un
publ
ishe
d
Hin
ch e
t ai (
1999
)
Riv
en
and
dr
aina
ges
- S
tream
s -U
SA
I 1
Met
calfe
et a
l (20
03b)
Hirs
ch e
t al (
1999
)
Kop
lin e
t al (
2002
)
I I
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Sur
face
wat
er
I Met
calfe
et a
l (20
03b)
I
GV
RD
(un
publ
ishe
d
Ste
eerH
artm
ann
et a
l
Ste
ger-
Har
tman
n et
al
Met
caife
et a
l (20
03b)
I
I M
etca
lfe e
t al (
2003
b)
I I
Met
calfe
et a
l (20
03b)
I
1
Met
calfe
el a
l (20
03b)
I
Sur
face
wat
er
l~e
tca
lfe
et a
l 120
03b)
I A
ldja
cent
to W
WTP
S
urfa
ce w
ater
~
djac
ent to
WW
TP
Sur
face
wat
er
. .
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Tabl
e A
.l:
Sum
mar
y of
Env
iron
men
tal C
once
ntra
tions
I C
hem
ical
Cla
ss
I C
hem
ical
Nam
e / M
easu
red
Env
ironm
enta
l Occ
urre
nce
Ant
ineo
plas
tic
I
I I
Ant
iang
inal
lD
ehyd
mni
fedi
pine
lm
ax 0
.03
yg1U
med
0.0
12
10.0
3
I I
I
Cyc
loph
osph
amid
e
0.00
5 A
ntin
eopl
astic
I ps
ycho
stim
ulan
t (a
mph
etam
inel
ike)
I an
tiepi
lept
ic
Rep
orte
d C
once
ntra
tion
max
0.0
20 y
g/L
Nar
cotic
ana
lges
ic I ps
ycho
stim
ulan
t (a
mph
etam
inel
ike)
1 ant
iepi
lept
ic
pg/L
0.02
Cyc
loph
osph
arn~
de
Dex
trop
ropo
xyph
endD
extm
am
phet
amin
e
I I
I
1-tras
t ag
ent
< 0
.01
yg1L
(B
MD
L)
yg1L
m
ax 5
85 n
glL I m
ed
Dex
trop
ropo
xyph
enel
Dex
tro
amph
etam
ine
Nar
cotic
ana
lges
ic 1
psyc
host
imul
ant
(am
phet
amin
elik
e) I an
tiepi
lept
ic
1 I
I X
-ray
con
tras
t age
nt
/me
d 0
.23
yglL
0.
23
max
< 2
0 ng
1L (
BM
DL)
0.
01
X-r
ay c
ontr
ast a
gent
I A
ntid
epre
ssan
Van
tipsy
chot
ic
Dia
zepa
m
iBM
DL
- 2
13
ng
b-
Dex
trop
ropo
xyph
ene/
Dex
tro
amph
etam
ine
I I
I A
ntid
epre
ssan
Van
tipsy
chot
ic
Dia
zepa
m
max
0.0
4 yg
/L
0.04
Dia
triz
oate
12
1 I
I A
ntid
epre
ssan
Van
tipsy
chot
ic
1 Diaz
epam
1
~0
.03
0 yg
/L (
BM
DL)
10
.015
Max
682
ngl
L 1
med
58
ng1L
2
I I
Ant
idep
ress
anV
antip
sych
otic
1 D
iaze
pam
1
~0
.05
pglL
(BM
DL)
0.68
2
I I
Ant
idep
ress
anV
antip
sych
otic
1 D
iaze
pam
lm
ax 0
.053
yg1
U m
ed c
0.05
(0
.053
Mat
rix
Ref
eren
ce
I I Re
port
ed lr
~m
ue
nt
I surfa
ce w
ater
I
I
I I
NVVT
P E
fflue
nt -
I H
ilton
et a
l (20
03)
Sou
thea
st E
ngla
nd
MP
E
fflue
nt -
3erm
any
Riv
ers
and
stre
ams
- G
erm
any
Stre
ams
- US
A
of
WW
TPs
Sou
thea
st
Eng
land
1 Engl
and
[Sur
face
wat
er -
/put
sche
w e
t at
1200
0)
1
Tem
es (
1998
)
Tem
es (
1 998
)
Kop
lin e
t al (
2002
)
Hilt
on e
l at (
2003
)
I I
I
IGer
man
y IS
urfa
ce w
ater
afte
r IP
utsc
hew
et a
l (20
00)
Dow
nstre
am o
f W
R Sou
thea
st
. .
1 bank
fillr
atio
n -
1 N
WT
P E
fflue
nt -
I l~
em
es
and
Hirs
ch
1
Hilt
on e
t al (
2003
)
%m
an
y 1
1:;;;;; i
Sur
face
wat
er -
Tem
es a
nd H
inch
G
erm
an
R~
ve
n
-Ita
ly
Cal
amar
i et a
l (20
03)
I I
I iff
luen
t fro
m
Tem
es (
1998
) ie
dim
enta
tion
tank
- ;e
rman
y R
iver
s an
d Te
mes
(1 9
98)
stre
ams
- G
erm
any
MP
E
fflue
nt -
Tem
es e
t al(2
001)
;e
man
y M
P
Effl
uent
- T
emes
el a
l(200
1)
;em
any
Riv
ers
and
Tem
es e
l a1
(200
1)
stre
ams
-Ger
man
y La
kes
and
rive
n -
Bus
er e
t al(1
998a
) S
witz
erla
nd
MP
E
fflue
nt-
Bus
eret
al (
l99
8a
) .
. S
witz
erla
nd
'WV
TP E
fflue
nt- U
SA I
I Drew
es e
l a1
(200
2)
I R
ive
n -S
pa
in
Fa
d et
al(
20
01
)
WP
E
fflue
nt -
Far
re e
t al(2
001)
i
ain
WP
E
fflue
nt -
Fer
ran
et a
l (20
03)
WP
E
fflue
nt - I
taly
F
erra
ri et
al (
2003
) I
I I
VW
TP E
fflue
nt -
Fer
rari
et a
l(200
3)
iwed
en
Tabl
e A
.l:
Sum
mar
y of
Env
iron
men
tal C
once
ntra
tions
-- I
Che
mic
al I
am
I M
easu
red
Env
ironm
enta
l Occ
urre
nce
I M
atrix
Ana
lges
icsl
non-
ster
oida
l ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
nste
mid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
non-
ster
oida
l anl
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
nste
roid
al an
ti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
non-
ster
oida
l ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
loes
icsl
nons
tem
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
n-st
emid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
non-
ster
oida
l ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
n-st
emid
ai a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
non-
ster
oida
l ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
non-
ster
oida
l ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
nste
roid
al an
ti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
non-
stem
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
nste
roid
al an
ti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsi
non-
slem
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
n-st
eroi
dal a
nli-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
nons
tem
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
nons
tero
idal
anti-
in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
nste
mid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
nons
tero
idal
anti-
in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
n-st
em~
dal an
ti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
nons
tem
idal
ant
i- in
flam
mat
ory (
NS
AID
) A
nalg
esic
slno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
Dic
lofe
nac
Dic
lofe
nac
Dic
iofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
iofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Rep
orte
d C
once
ntra
tion
max
0.4
1 pg
/L
max
0.2
5 pg
lL
max
0.4
24 p
g1L
<1 (B
MD
L) -
960
ng1L
50 p
g/L
max
103
0 ng
lL
max
234
9 na
/L I m
ed 4
24 n
a1L
max
< 2
0 ng
lL (B
MD
L)
max
568
ngl
L I med
0 n
glL
381
ng1L
51 -
484
nglL
mea
n 0.
359
glL
mea
n 0.
005
pglL
mea
n 0.
088
pglL
mea
n 0.
063
pglL
c 1
0 ng
lL (B
MD
L)
mea
n 0.
018
pglL
mea
n 0.
05 p
g/L
< 1
0 ng
1L (
BM
DL)
< 0.
25 p
glL
(BM
DL)
max
0.0
42 p
glL
1 m
ed 0
.026
pg
lL
max
0.1
94 p
glL
1 m
ed 0
.194
pg
1L
< 5
ngl
L (B
MD
L)
100-
700
ng/L
< 3
.6 (
BM
DL)
- 150
ngl
L
< 4
.5 n
gIL
(BM
DL)
- 10
ngl
L
lglL
0.41
0.25
0.42
4
0.96
0.05
1.03
2.34
9
0.01
0.56
8
0.38
1
0.48
4
0.35
9
0.00
5
0.08
8
0.06
3
0.00
5
0.01
8
0.05
0.00
5
0.12
5
0.04
2
0.19
4
0.00
25
0.7
0.15
0.01
Effl
uent
WW
TP E
fflue
nt -
Fra
nce
WW
TP E
fflue
nt -
Fra
nce
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Sou
thea
st E
ngla
nd
WW
TP E
fflue
nt -
Spa
in
WW
TP E
fflue
nt -
Pet
erbo
roug
h W
WTP
Effl
uent
- B
urlin
gton
W
WTP
Effl
uent
- Li
llle
Riv
er
WW
TP E
fflue
nt -
Wes
t Win
dsor
WW
TP E
fflue
nt -
Can
ada
WW
TP E
fflue
nt -
Sw
itzer
land
Sur
face
wat
er
Sur
face
wat
er -
Ger
man
y S
urfa
ce w
ater
- G
erm
any
Sur
face
wat
er -
Ger
man
y
Fer
rari
et a
l (20
04)
Fer
rari
el a
l(200
4)
GV
RD
(unp
ublis
hed
data
) H
erbe
rer e
l al (
1998
)
Her
bere
r el a
t (2
001)
Her
bere
r el a
l (20
02)
Hilt
on e
l al (
2003
)
Ups
tream
of
WW
TPs
Sou
thea
st
Dow
nstre
am o
f W
WTP
s S
outh
east
R~
vers
-Spa
in
Sur
face
wat
er
adja
cent
to W
WrP
S
urfa
ce w
ater
ad
jace
nt to
WW
rP
Sur
face
wat
er
adja
cent
lo W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Sur
face
wat
er -
Det
roit
Riv
er
Sur
face
wat
er -
Ham
ilton
har
bour
S
urfa
ce w
ater
-
Eas
tem
Can
ada
Sur
face
wat
er -
Sw
itzer
land
La
kes
- S
witz
erla
nd
. .
Hilt
on e
l al (
2003
)
Hill
on e
l al (
2003
)
Far
re e
l al(2
001)
Far
re e
l al (
2001
)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
el a
i (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
t (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
i (20
03b)
Met
calfe
el a
l (20
0%)
Met
calfe
el a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
el a
l (20
03b)
Olle
rs e
l al (
2001
)
Olle
rs e
l al (
2001
)
Olle
rs e
l al (
2001
)
Tabl
e A
.1:
Sum
mar
y of
Env
iron
men
tal C
once
ntra
tions
Che
mic
al C
lass
Ana
lges
icsl
nons
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
nste
roid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
non-
ster
oida
l ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
nste
roid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsh
on-s
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
nons
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
non-
ster
oida
l ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
n-st
emid
al a
ntl-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
non-
ster
oida
l ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
slno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icsl
non-
ster
oida
l ant
i- in
flam
mat
ory
(NS
AID
) A
ntib
iotic
-pe
nici
llin
Ant
ibio
tic -
pen
icill
m
Hor
mon
e -s
ynth
etic
for
m o
f est
roge
n
Che
mic
al N
ame
I I
I /S
pain
I
I
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
D~
clof
enac
Dic
lofe
nac
Dic
lofe
nac
Dic
lofe
nac
D~
clox
acill
in
Dic
loxa
cill~
n
Die
thyl
stilb
estr
ol
I M
etab
olite
- dig
oxin
(car
diac
dm
g)
Car
diac
dm
g I
I
Ref
eren
ces
20 -
150
ng1L
100
- 700
ng1
L
1000
ng1
L
90 n
g1L
max
500
ngl
L I m
ed 2
00 n
g1L
max
450
ng1
L I m
ed 2
0 ng
1L
< 5
0 (B
MD
L) -
1590
ng1
L
< 5
(B
MD
L) - 4
89 n
g/L
max
930
ng1
L I m
ed 1
30 n
glL
max
2.1
pg1
L
max
1.2
pg1
L
mea
n 1.
3 pg
lL
6.2
ng1L
< 0
.02
pg1L
(B
MD
L)
< 0
.02
pg1L
(B
MD
L)
< 0
.5 p
g1L
(BM
DL)
- 1.4
pg1
L
Dig
oxig
enin
Dig
oxin
B
MD
L 1
I
Mea
sure
d E
nvir
onm
enta
l Occ
urre
nce
BM
DL
BM
DL
Stre
ams
- US
A
Antih
ypert
ensi
ve -
calc
ium
cha
nnel
bl
ocke
r I ca
rdio
vacu
lar d
mg
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ant
ibio
tic -
tetr
acyc
lme
Ant
ibio
tic -
tetr
acyc
line
Ant
ibio
tic -
tetr
acyc
lme
Ant
ibio
tic -
tetr
acyc
line
Ref
eren
ce
Rep
orte
d In
Rep
orte
d C
once
ntra
tion
Mat
rix
0.15
0.7
1 0.09
0.5
0.45
1.59
0.48
9
0.93
2.1
1.2
1.3
0.00
62
0.01
0.01
1.4
BM
DL
Stre
ams
-US
A
Kop
lin e
t al(2
002)
I I
I I
I I
pg/L
E
fflu
ent
Kop
lin e
t al (
2002
)
Dilt
iaze
m
Dim
ethy
lam
inop
hena
zone
Dim
ethy
lam
inop
hena
zone
Dox
ycyc
line
Dox
ycyc
line
Dox
ycyc
line
Dox
ycyc
line
Sur
face
wat
er
WW
TP
Effl
uent
- S
witz
erla
nd
WW
TP E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
Ger
man
y
WW
TP
Effl
uent
- B
razi
l W
WTP
Effl
uent
- G
erm
any
WW
TP
Effl
uent
- G
erm
any
WW
TP
Effl
uent
- G
erm
any
WW
TP E
fflue
nt -
Ant
ihyp
erte
nsiv
e/ca
rd~o
vasc
ular
drug
max
0.0
49 p
g1L I m
ed 0
.021
N
IL
max
1 .O
vg/L
max
0.3
4 pg
1L
max
0.0
46 p
g/L
< 0
.05
pg/L
(BM
DL)
< 0
.05
pg/L
(BM
DL)
BM
DL
0.00
054
Riv
ers
- S
witz
erla
nd
Sur
face
wat
er -
Ger
man
y R
ve
n -B
razi
l
R~
vers
- Bra
zil
Riv
ers
-Ger
man
y
Riv
ers
and
stre
ams
- G
erm
any
Nor
th S
ea -
Est
uary
Rlv
ers
and
drai
nage
s -
Ena
lapr
il
Olle
rs e
t al (
2001
)
Olle
rs e
t al (
2001
)
Sta
n an
d H
erbe
rer
1199
7)'
Sta
n an
d H
erbe
rer
1199
7)'
Stu
mpf
et a
l (19
98)
Stu
mpf
et a
l (19
99)
Stu
mpf
el a
1 (1
996)
Stu
mpf
el a
l (19
96)
Stu
mpf
et a
l. (1
999)
Tem
es (1
998)
Tem
es (
1998
)
Tem
es e
t al (
2003
)
Wei
gel e
l al (
2002
)
Hin
ch e
l al (
1999
)
Hin
ch
et a
l (19
99)
Pet
mvi
c et
al (
2002
)
0.04
9
1 0.34
0.04
6
0.02
5
0.02
5
BM
DL
BM
DL
- 0.
54 n
g/L
Riv
ers
-Ita
ly
Cal
amar
i et a
l (20
03)
WW
TP
Effl
uent
- G
erm
any
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Ger
man
y
Stre
ams
- U
SA
Riv
ers
and
stre
ams
-Ger
man
y
Riv
ers
and
drai
nage
s -
Stre
ams
- US
A
Kop
lin e
t al (
2002
)
Tem
es (
1998
)
Tem
es (
1998
)
GV
RD
(unp
ublis
hed
data
) H
inch
et a
l(l9
99
)
Hin
ch e
t al (
1 999
)
Kop
lin e
t al (
2002
)
Tabl
e A
.1:
Sum
mar
y o
f E
nvir
onm
enta
l Co
nce
ntr
atio
ns
Che
mic
al C
lass
--
-
Anb
blot
lc - f
luor
oqu~
nolo
ne
Anb
blot
lc - f
luor
oqul
nolo
ne
Mea
sure
d E
mir
on
me
nta
l Occ
urre
nce
Che
mic
al N
ame
Hor
mon
e -e
stro
gen
repl
acem
ent
Hor
mon
e -e
stro
gen
repl
acem
ent
Ant
ibio
tic - m
acro
lide
Enr
oflo
xacl
n
Enr
oflo
xacl
n
Ant
ibio
tic - m
acro
lide
Ant
ibio
tic - m
acro
llde
Ant
iblo
tlc - m
acm
lide
Ant
ibio
tic - m
acro
lide
Ant
ibio
tic - m
acm
lide
Ant
ibio
tic - m
acm
lide
Ant
ibio
tic - m
acro
lide
Ant
ibio
tic - m
acm
lide
Hor
mon
e -r
epro
duct
ion
Mat
rix
Equ
ileni
n
Equ
ilin
Ery
thro
myc
in
Hor
mon
e -r
epro
duct
ion
Hor
mon
e - r
epro
duct
ion
Rep
orte
d C
once
ntra
tion
< 0
008
pg/
L (B
MD
L)
BM
DL
Ery
thro
myc
in
Ery
thro
myc
in
Ery
thro
myc
in
Ery
thro
myc
in
Ery
thro
myc
in
Ery
thro
myc
in
Ery
thro
myc
in - H
,O
Ery
thro
myc
in -
HA
Est
radi
ol (E
2)
I
I
I
I
I
I
I
I I p
g/L
I I
I I
I H
orm
one
- rep
mdu
ctlo
n 1 E
strio
l (E
3)
0.25
(B
MD
L) -2
1.5
ual
L 12
1.5
1 WW
TP E
fflue
nt -
I 1 P
etro
vic
et a
l (20
02)
1
Ref
eren
ces
max
0.2
78 p
glL
I med
0.1
4 pg
/L
max
0.1
47 p
g/L
/ med
0.1
47
pg/L
1.
4 - 1
5.90
ng/
L
Est
radi
ol (E
2)
Est
riol (
E3)
I
I
I
, I
I I
Ref
eren
ce In
WL
0 00
4
BM
DL
max
184
2 n
g/L
/ med
el0
ngl
L
max
57
ng/L
/ m
ed 4
0 ng
/L
max
102
2 n
g/L
/ med
el0
ngl
L
max
600
0 ng
/L /
med
250
0 ng
/L
max
170
0 ng
/L /
med
150
ng/
L
mea
n 0.
62 p
g/L
max
1.7
27 p
g/L
max
1.7
pg/
L /
med
1 .O
pg/L
< 1
ngl
L - 2
0 ng
lL
Hor
mon
e -r
epro
duct
ion
Hor
mon
e -r
epro
duct
ion
1 Estr
iol (
E3)
lm
ax 0
.051
pg
lL/m
ed
0.1
9 10
.19
Hor
mon
e -r
epro
duct
ion
1 Estr
iol (
E3)
lc
0.2
(BM
DL)
- 3.1
ng/
L 10
.003
1 1
ISur
face
wat
er -
UK
~X
~~
O
et a
l (20
01)
0.27
8
0.14
7
0.01
59
< 5
- 7.
6 pg
/L
1 -1
8n
gIL
Est
riol (
E3)
B
MD
L - 2
8 ng
/L
IStr
eam
s -U
SA
l~
o~
lin
et
al (
2002
) 1
. .
Eff
luen
t
WW
TP
Effl
uent
- V
anco
uver
1.84
2
0.05
7
1.02
2
6 1.7
0.62
1.72
7
1.7
0.02
Stre
ams
-US
A
Stre
ams
-US
A
Riv
ers
- Ita
ly
7.6
0.01
8
0.02
8
. .
. -
Hor
mon
e - n
atur
al
Hor
mon
e -n
atur
al
Hor
mon
e -n
atur
al
Hor
mon
e -n
atur
al
Hor
mon
e -n
atur
al
Suf
face
wat
er
Stre
ams
-US
A
Kop
lin e
t al (
2002
)
Kop
lin e
t al (
2002
)
Cal
amar
i et a
l (20
03)
SP
T E
fflue
nt -
Sou
thea
st E
ngla
nd
WW
TP
EM
uent
- G
erm
any
WW
TP
EM
uent
- G
erm
any
WW
TP
EM
uent
- V
anco
uver
WVV
TP E
fflue
nt -
New
Hor
mon
e -r
epro
duct
ion
GV
RD
(unp
ublis
hed
data
) K
oplln
et a
l (20
02)
Yor
k W
WT
P E
fflue
nt -
Spa
in
WW
TP
Effl
uent
- Ita
ly
WW
TP
Effl
uent
- Ita
ly
Isp
ain
Est
roge
n
Est
mne
(E
l)
Est
mne
(E
l)
Est
mne
(E
l)
Est
mne
(E
l)
Ups
tream
of
WW
TP
s S
outh
east
D
owns
tream
of
WW
TP
S S
outh
east
Sur
face
wat
er -
Riv
ers
and
Stre
ams
-US
A
Pet
rovi
c et
al (
2002
)
Bar
onti
et a
l (20
00)
John
son
et a
l(200
0)
. .
Est
riol (
E3)
Hilt
on e
t a1
(200
3)
Hilt
on e
t al (
2003
)
Hiit
on e
t al (
2003
)
Hirs
ch e
t al (
1999
)
Hirs
ch e
t al (
1999
)
Tem
es e
t al (
2003
)
GV
RD
(unp
ublis
hed
data
) K
oplin
et a
l (20
02)
Hug
get e
t a1
(200
3b)
0.05
4 - 0
.13
pg/L
max
47
nglL
med
< O
.Olp
g/L
(BM
DL)
- 0.
015
pg/L
<
0.4
ng/
L (B
MD
L)
< 0
.4 n
g/L
(BM
DL)
2 -4
ng/
L
0.13
0.04
7
0.01
5
0.00
02
0.00
02
0.00
4
Raw
sew
age
wat
er -
Tel
Avi
v, I
srae
l W
WT
P E
fllue
nt -
Net
herla
nds
WW
TP
Effl
uent
-
WW
TP
Effl
uent
- U
K
Xia
o et
al (
2001
)
Sur
face
wat
er -
U
SA
S
urfa
ce w
ater
- U
SA
Hal
lingS
oren
sen
et a
l. (1
998)
B
elfm
id e
t al (
1999
)
Boy
d an
d G
rimm
(200
1)
Boy
d et
a1
(200
3)
Boy
d et
al (
2003
)
Tab
le A
.1:
Su
mm
ary
of
En
viro
nm
enta
l Co
nce
ntr
atio
ns
I C
he
mic
al N
ame
I Me
asu
red
En
vlro
nm
en
taI O
ccu
rre
nce
I
Ma
trii
I
Re
fere
nce
s
IRe
po
rte
d C
on
cen
tra
tion
I
wL
IE
mu
en
t l~
uif
ac
e
wat
er
I H
orm
one
- nat
ural
Hor
mon
e - n
atur
al
Hor
mon
e -n
atu
ral
Hor
mon
e -n
atu
ral
Hor
mon
e - n
atur
al
Est
mne
(E
l)
Est
mne
(E
l)
Hor
mon
e -n
atu
ral
Hor
mon
e -n
atu
ral
Hor
mon
e -n
atu
ral
Hor
mon
e - n
atur
al
Hor
mon
e -n
atu
ral
Lip
id re
gula
tor
Lip
id r
egul
ator
Lip
id re
gula
tor
Lip
id re
gula
tor
Lip
id r
egul
ator
Lip
id re
gula
tor
Meta
bolit
e - f
enof
ibra
te
Meta
bolit
e - f
enof
ibra
te
Meta
bolit
e - f
enof
ibra
te
Met
abol
ite - f
enof
ibra
te
iep
ort
ed
in
Ser
vos
et a
l
Est
mne
(E
l)
Est
rone
(E
l)
Est
mn
e (E
l)
Meta
bolit
e - f
enof
ibra
te
Meta
bolit
e - f
enof
ibra
te
Ana
lges
ic/n
on-s
tem
idal
ant
i- in
flam
mato
ry (N
SA
ID)
Ana
lges
icln
on-s
tero
idal
anti-
in
flam
mat
ory
(NS
AID
) A
nalg
esi
clnon-s
tem
~dal an
ti-
infla
mm
ator
y (N
SA
ID)
Analg
esi
c/nonst
ero
idal a
nti-
in
flam
mato
ry (N
SA
ID)
Zepo
rted
in
Ser
vos
et a
l te
port
ed in
ie
rvo
s et
al
mea
n 1.
4 - 7
6 ng
/L
< 0
.3 (
BM
DL)
- 7.
1 n
glL
Est
mne
(El)
Est
rone
(E
l)
Est
mne
(E
l)
Est
mn
e (E
l)
Est
mne
(E
l)
Eto
fibra
te
Eto
fibra
te
Fen
ofib
rate
Fen
ofib
rate
Fen
ofib
rate
Fen
ofib
rate
Fen
ofib
ric a
cid
Fen
ofib
ric a
cid
Fen
ofib
ric a
cid
Feno
fib~
ic ac
id
< 1
ng
/L-4
2n
g/L
BM
DL
- 54
ng
lL
max
0.1
12 p
glL
lme
d 0
.027
Fen
ofib
ric a
cid
Fen
ofib
ric a
cid
Fen
opm
fen
Fen
opm
fen
Fen
opro
fen
Fen
opro
fen
0.07
6
0.00
71
pg
IL
max
5.8
ng
lL
< 2
.5 p
g/L
(BM
DL)
- 8.
1 p
glL
mea
n 0.
015
pg/L
6.4
- 2
9 n
glL
0.2-
17 n
glL
< 0
.1 p
gIL
(BM
DL)
< 0
.03
og/L
(B
MD
L)
c 1
0 ng
R (
BM
DL)
max
0.1
pg
lL
max
0.0
3 og
/L
< 0
.01
pgl
L (B
MD
L)
0.05
vgR
max
0.1
72 p
glL
max
0.8
ng
lL
max
1.2
pg
lL
0.04
2
0.05
4
0.11
2
max
0.2
8 p
glL
me
an
0.1
3 p
glL
max
35
ng/L
max
0.7
28 p
glL
me
an
0.4
05 p
glL
me
an
0.0
62 p
glL
WW
TP
Eff
lue
nt -
Brit
ian
0.00
58
8.1
0.01
5
0.02
9
0.01
7
0.05
0.01
5
0.00
5
0.1
0.03
0.00
5
0.05
0.1
72
0.00
08
1.2
WW
TP
Effl
uent
-Ne
w
Yor
k W
P
Effl
uent
- Ita
ly
0.28
0.13
0.03
5
0.72
8
0.40
5
0.06
2
Sur
face
wat
er -
UK
WW
TP
Eff
lue
nt -
Sw
eden
W
WT
P E
fflue
nt -
Spa
in
WW
TP
Effl
uent
- G
erm
any
WW
TP
Eff
lue
nt -
UK
WW
TP
Effl
uent
- G
erm
any
WW
TP
Eff
lue
nt -
U
SA
WW
TP
Effl
uent
- G
erm
any
WW
TP
Eff
lue
nt -
Bra
zil
WW
TP
Eff
lue
nt -
Des
brow
et a
l (19
98)
Faw
ell e
t al (
2001
)
Stre
ams
-US
A
Ger
man
y
WW
TP
Effl
uent
- G
erm
any
WW
TP
Effl
uent
- U
SA
W
WT
P E
fflue
nt -
Van
couv
er
WW
TP
Effl
uent
- P
eter
boro
ugh
WW
TP
Eff
lue
nt -
B
urlin
gton
Hug
get e
t al (
2003
b)
John
son
et a
l(20
00
)
Kop
lin e
t al (
2002
)
Sur
face
wat
er -
UK
Riv
en
and
st
ream
s -G
erm
an
y
Sur
face
wat
er -
.Ger
man
y
Riv
ers
and
stre
ams
- Ger
man
y S
urfa
ce w
ater
- G
erm
an
y S
urfa
ce w
ater
- G
erm
any
La
nso
n e
l al (
1999
)
Pet
rovi
c et
al (
2002
)
Tem
es e
t a1
(200
3)
Xia
o et
al(2
00
1)
Xia
o e
l al (
2001
)
Tem
es (
1998
)
Tem
es (1
998)
Dre
wes
et a
l (20
02)
Kol
bus
(199
5)
Tem
es (1
998)
Tem
es (1
998)
AW
WR
(19
95)
Stu
rnpf
et a
l (1 9
96)
Stu
rnpf
et a
l (19
99)
Tem
es (1
998)
Riv
ers
and
stre
ams
-Ge
rma
ny
Tem
es (
1998
)
Tem
es e
t al (
2003
)
Dre
wes
el a
l (20
02)-
GV
RD
(unp
ublis
hed
data
) M
etca
lfe e
t al (
2003
b)
Met
calfe
et a
l (20
03b)
Tab
le A
.1:
Su
mm
ary
of E
nvi
ron
men
tal C
on
cen
trat
ion
s
I C
hem
ical C
lass
I
Ch
em
ica
l Nam
e I M
ea
sure
d E
nvi
ron
me
nta
l Occ
urr
en
ce
I M
atr
ii
Analg
esi
clnonst
em
idal a
nti-
infla
mm
ator
y (N
SA
ID)
Analg
esi
clnonst
ero
idal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icln
on-s
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esi
dnon-s
tero
idal a
nti-
infla
mm
ator
y (N
SA
ID)
Analg
esi
c/nonst
em
idaI a
nti-
infla
mm
ator
y (N
SA
ID)
Analg
esi
clnonst
em
idal a
nti-
infla
mm
ator
y (N
SA
ID)
Analg
esi
clnonst
em
idal a
nti-
infla
mm
ator
y (N
SA
ID)
Analg
esi
clnonst
ero
idal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icln
on-s
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esi
clnonst
ero
idal a
nti-
1 I "
/I '
I I
I I
I A
ntid
epre
ssan
t (S
SR
I) IF
luoxe
tine
lm
ea
n 0
.050
pg/
L 10
.05
IMP
Effl
uent
- I
1 Met
calfe
el a
l (20
03b)
I
infla
mm
ator
y (N
SA
ID)
Ana
lges
icln
on-s
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
lnon
-ste
roid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Beta
ago
nist
-B
2sy
mpath
om
imetic
(b
ronc
hodi
alat
or)
Beta
ago
nist
-B2sy
mpath
om
imetic
(b
mnc
hodi
alat
or)
Ant
idep
ress
ant (
SS
RI)
Ant
idep
ress
ant (
SS
RI)
Ant
idep
ress
ant (
SS
RI)
Ant
idep
ress
ant (
SS
RI)
. .
1 .
. la
djac
ent t
o W
WTP
I A
ntid
epre
ssan
t (S
SR
I)
1 Flu
oxet
ine
10 n
g1L
(BM
DL)
10
.005
I~
urf
ac
e
wat
er
I Met
calfe
el a
l (20
03b)
I
Fen
opm
fen
Fen
opm
fen
Fen
opm
fen
Fen
opro
fen
Fen
opro
fen
Fen
opro
fen
Fen
opm
fen
Fen
opm
fen
Fen
opm
fen
Fen
opro
fen
I I
I 1
. .
ladl
acen
t to
WW
TP I
Fen
opro
fen
Fen
opm
fen
Fen
otem
l
Fen
otem
l
Flu
oxet
ine
Flu
oxet
ine
Flu
oxet
ine
Flu
oxet
ine
mea
n 0.
075
pg1L
< 2
0 ng
1L (
BM
DL)
c 1
0 ng
1L (
BM
DL)
mea
n 0.
142
pg1L
mea
n 0.
132
pg
lL
< 1
0 ng
lL (B
MD
L)
< 0
.05
pg1L
(B
MD
L)
<5
ng/
L (B
MD
L)
max
0.0
64 p
g1L I m
ed 0
.045
p
glL
m
ax 0
.059
vg1
L I m
ed 0
.059
~
glL
<
0.0
50 p
g1L
(BM
DL)
-= 0.
010
pg
lL
max
0.0
60 p
g1L
max
0.0
61 p
g1L
< 2
5.8
ng1L
(B
MD
L)
< 2
5.8
ng1L
(B
MD
L)
< 0
.009
pg1
L (B
MD
L)
max
0.0
12 p
g/L
s/ m
ed 0
.012
0.07
5
0.01
0.00
5
0.14
2
0.13
2
0.00
5
0.02
5
0.00
25
0.06
4
0.05
9
0.02
5
0.00
5
0.06
0.06
1
0.01
29
0.01
29
0.00
45
0.01
2
WW
TP E
fflue
nt -
Littl
e R
iver
W
WTP
Effl
uent
- W
est W
inds
or
WW
TP
Eff
lue
nt -
Can
ada
WW
TP E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
US
A
WW
TP E
ffluen
t -
Van
couv
er
Sur
face
wat
er
adja
cent
to W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Sul
face
wat
er
adja
cent
to W
WTP
S
ulfa
ce w
ater
ad
jace
nt to
WW
TP
Sur
face
wat
er -
Det
roit
Riv
er
Sur
face
wat
er -
H
amilt
on h
arbo
ur
Sur
face
wat
er -
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
1 (2
003b
)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03a)
Met
calfe
et a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
el a
l (20
03b)
E
aste
rn C
anad
a
Riv
ers
and
stre
ams
-Ge
rma
ny
Rw
ers
and
stre
ams
- Ger
man
y S
urfa
ce w
ater
- U
SA
Stre
ams
- US
A
Ter
nes
(199
8)
Ter
nes
(1 99
8)
Tem
es (
1998
)
Ter
nes
(199
8)
Boy
d e
l al (
2003
)
Boy
d e
l al (
2003
)
GV
RD
(unp
ublis
hed
data
) K
oplin
et a
l (20
02)
Tabl
e A
.1:
Sum
mar
y of
En
viro
nm
enta
l Co
nce
ntr
atio
ns
- -
Che
mic
al C
lass
(
Che
mic
al N
ame
I Mea
sure
d E
nviro
nmen
tal O
ccur
renc
e I
Ma
trii
I R
efer
ence
s 1 z
rzi;n
1 1
/Rep
orte
d C
once
ntra
tion
IWL
IE
fnue
nt
(~u
rfa
ce
w
ater
I
I I
I I
I I
I I
Per
sona
l car
e pr
oduc
t -fr
agra
nce
Per
sona
l car
e pr
oduc
t -fr
agra
nce
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Cal
amar
i et a
l (20
03)
Lipi
d re
gula
tor
Lipi
d re
gula
tor
- Lipi
d re
gula
tor
Lipi
d re
gula
tor
Diu
retic
Gal
axol
ide
HH
CB
(p
loyc
yclic
mus
k)
Gal
axol
ide
HH
CB
(p
loyc
yclic
mus
k)
Gem
fibro
zil
Gem
fibm
zil
Lipi
d re
gula
tor
Lip
~d
regu
lato
r
Lipi
d re
gula
tor
LiD
id r
equl
ator
0.06
72
Gem
fibm
zil
Gem
fibm
zil
Gem
fibm
zil
Gem
fibro
zil
. -
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d R
egul
ator
Lipi
d R
egul
ator
Lipi
d R
egul
ator
Lipi
d R
egul
ator
Met
abol
ite -a
cety
lsal
icyl
ic a
cid
Riv
en
- Ita
ly
Fur
osem
ide
mea
n 0.
73 p
g/L
max
125
00 n
g/L
max
123
5 ng
1L
max
155
0 ng
/L
Gem
fibm
zil
Gem
fibro
zil
Gem
fibm
zil
Gem
fibm
zil
Met
abol
ite -a
cety
lsal
icyl
ic a
cid
1.72
- 67.
20 n
g/L
max
120
0 ng
/L
max
0.4
97 p
g/L
max
35
ng/L
max
0.7
9 pg
lL 1
med
0.0
48
Gem
fibm
zil
Gem
fibm
zil
Gem
fibro
zil
Gem
fibro
zil
Gem
fibm
zil
Gem
fibm
zil
Gem
fibm
zil
Gem
fibm
zil
Gem
fibm
zil
Gem
fibro
zil
Gen
tisic
aci
d
0.73
12.5
1.23
5
1.55
p9IL
m
ean
1.49
3 pg
/L
mea
n 0.
005
pg/L
mea
n 0.
012
pg/L
mea
n 0.
043
pg/L
Gen
tisic
aci
d
Glib
encl
amid
e
1.2
0.49
7
0.03
5
0.79
< ~
~B
MD
L)
mea
n 0.
038
pglL
mea
n 0.
034
pg/L
mea
n 0.
002
pglL
max
1.3
pg/
L /
med
1.3
pg/
L
max
0.1
12 p
g/L
/me
d 0
.066
vg
/L --
max
0.0
67 p
g/L I m
ed 0
.012
pg
lL
< 5
ng/
L (B
MD
L)
max
0.8
4 pg
/L
max
0.5
1 pg
/L
max
0.5
9 pg
lL
WW
TP E
fflue
nt -
Ger
man
y
WW
TP
Effl
uent
- U
SA
1.49
3
0.00
5
0.01
2
0.04
3
max
1.2
pg/
L
< 0
.025
pgR
(BM
DL)
WW
TP
Effl
uent
- S
pain
W
WT
P E
fflue
nt -
Van
couv
er
0.00
5
0.03
8
0.03
4
0.00
2
1.3
0.11
2
0.06
7
0.00
25
0.84
0.51
0.59
Sur
face
wat
er -
G
erm
any
Riv
ers
-Spa
in
WW
TP
Effl
uent
- P
eter
boro
ugh
WW
TP
Effl
uent
- B
urlin
gton
W
WTP
Effl
uent
- Li
ttle
Riv
er
WW
TP E
fflue
nt -
1.2
0.01
25
Ter
nes
et a
l (20
03)
Ter
nes
et a
l (20
03)
Dre
wes
et a
l (20
02)
Far
rb e
t al (
2001
)
Sur
face
wat
er -
Ger
man
y S
tream
s -U
SA
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
et a
l (20
03b)
W
est W
inds
or
WP
E
fflue
nt -
Can
ada
WW
TP
Effl
uent
- G
erm
any
WW
TP
Effl
uent
-
Far
rb e
t al(2
001)
GV
RD
(unp
ublis
hed
data
) H
erbe
rer e
t al(2
002)
Kop
lin e
t al (
2202
)
Ger
man
y
WW
TP E
fflue
nt -
Sur
face
wat
er
adla
cent
to W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Sur
face
wat
er -
Det
mit
Riv
er
Sur
face
wat
er -
Ham
ilton
har
bour
S
urfa
ce w
ater
- E
aste
m C
anad
a
Riv
ers
and
stre
ams
-Ger
man
y
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l(200
3b)
Met
calfe
et a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
et a
l (20
03a)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Ter
nes
(199
8)
Ter
nes
(199
8)
Ter
nes
(199
8)
Riv
ers
and
stre
ams
-Ger
man
y T
erne
s (1
998)
Tem
es e
t a1
(200
1)
(CO
OZ
) le
la ?
w
( 1.002) le la a
ue
j
(ZO
OZ
) le la
u!~
do
n
(8661) le la
JaJa
vaH
(8661.) le la
JaJa
qaH
(8661) le la
J~
J~
W~
H
(elw
u!e
ds - s
aw
vsn - sw
ea
~is
is
ea
wo
s W
M
pa
wq
nd
un
) at
r~
3
( 1.002) le la a
w
( LO
OZ
) le la a
ue
j
(ZO
OZ
) le la s
a~
a~
a
(EO
OZ
) le
la u
ew
w
- JaleM a
3e
yng
A
ueuuag - Jalem
a9
eyn
g
(6661) le ia
~a
sn
a
(6661) le la
Jasng
(6661) le ia
~a
sn
g
(EO
OZ) le la
PAW
(EO
OZ
) le la pA
og
we
ds
-1uanwi1
we
ds - s
aw
Ale11 - sa
w
Au
eu
uw
- lu
an
wa
a6
e~
as
~
a~
no
3u
e~
ea
s UYO
N
pu
e~
aw
s
- =at+ pue sa
ym
vsn - ~
aie
m aw
ns
S'L
898'0 1
- wn
w3
dl
~~
u
ted
s - 1
ua
n~
13
dm
vsn - lu
an
yl3 d
l~
~
z' o
82'0
10
'0
pu
ev
aw
s
- iua
~w
i~
dl
~~
vsn
- iua
nw
3 d
l~
~
i16u 00s 1 - (ia
wa
) EP >
lfiu 8
98
i16
d O
Z'O
pau
I 116d 0' 1
xew
LSB
'S
S8
L'Z
WE
SBLO'O
11
6~
ooz - iaw
a
ifiu oez - (ia
wa
) s >
11
6~
01
LO
OO
'O
8LOO
'O
180'0
~~
1.0
0'0
SLC
OO
'O
ua
jad
nq
l
ua
pd
nq
l
ua
jad
nq
l
116d LSV
S xe
w
i16
u 0
00
SB
11
6~
O
OLZ xe
w
i16
u O
BEE xew
11
6~
- la
w8
-. .
-!lue
lep
!ola
~s-u
ou
l~!sa
6~
eu
y (~
IVS
N) ,W
eu
ue
uu
! -11ue 1
ep
!ola
is-uo
u~
~!sa
61
eu
v (
a~
vs
~)
m
eu
~e
uu
! -!lu
e ~
ep
!ola
ls-uo
up
!sa6
1e
uv
(~IV
SN
) hoie
uu
eu
u!
ua
pd
nq
ua
~o
~d
nq
l
uaj0Jdnql
haw
s) i16u Z'O
>
i16
u B
'L - Z'O >
i16u 1.8
~-
(iaw
a) 1
16
~ S'E
>
haw
s) i16u S
'E >
-. .
-!we
1ep!aais-uou13!sa61e&
(~IV
SN
) hoie
ww
wu
! -!w
e lep!o~
a1ouou13!sa6leuv (O
IVS
N) h
oie
uw
eu
u!
we
1ep
1o
~a
is-uo
u/3
!sa6
1e
uv
(~IV
SN
) ho
~e
wu
eu
u!
ua
jo~
dn
ql
ua
pd
nq
l
ua
pd
nq
l
ua)O~
dllql
IJajO~
dnql
-sue 1ep!ola1s-uou/3!sa6leuy (~
IVS
N) ho
leu
we
~u
! -!w
e le
p!a
a1
s-uo
u/~
!sa6
leu
v (a
IvsN) h
oie
uu
eu
u!
-gue lep!olals-uou/3!sa61euy
(~IV
SN
) fioie
u~
ue
uu
! -gue le
p!a
ais-u
ou
p!sa
61
eu
v (a
IvsN) h
ole
uu
eu
u!
-!we
lep!aais-uou/3!sa61euv (a
IvsN) fio
ieu
ue
uu
! uapxdnql
uapxdnql
ua
jold
nq
l
ua
jad
nq
l
ua)rwdnql
-!we
1e
p!a
als-u
ou
/3!sa
61
eu
v (~
IVS
N) ho
ieu
ue
uu
! -!lue le
p!a
a1
s-uo
up
!sa6
leu
v (~
IVS
N) ho
iew
ue
uu
! -!lue 1
ep
!o~
ais-u
ou
13
!~6
1e
uv
(~IV
SN
) hoie
uw
eu
u!
-!lue
lep
!aa
1s-u
ou
/3!sa
6le
uv
(~IV
SN
) ho
ieu
ww
! -gue le
p!a
als-u
ou
p!sa
Qe
uv
Tab
le A
.1:
Sum
mar
y o
f E
nvi
ron
men
tal C
on
cen
trat
ion
s
I C
hem
ical C
lass
1
Ch
em
ica
l Nam
e I M
ea
sure
d E
nvi
ron
me
nta
l Occ
urr
en
ce
I M
atr
ix
I R
efe
ren
ces
I I
I~Q
/L
IEffl
uent
I~
ufa
ce
rate
r I
I Repo
tte
d C
on
cen
tra
tion
Anala
esi
dnon-s
tero
idal a
nti-
lm
ea
0.1
67 u
alL
10
.167
IM
P E
fflue
nt -
I 1 M
etca
lfe e
l ai (
2003
b)
Ana
lges
icln
on-s
tero
idai
anti-
c 1
0 n
g/L
(BM
DL)
. .
Wes
t Win
dsor
S
urfa
ce w
ater
M
etca
lfe e
l al (
2003
b)
adja
cent
to W
WTP
S
urfa
ce w
ater
M
etca
lfe e
l al (
2003
b)
(ad
jace
nt to
WW
TP I
I~u
rfa
ce
w
ater
1 M
etca
lfe e
l al (
2003
b)
adja
cent
to W
WT
P
Sur
face
wat
er
Met
calfe
el a
l (20
03b)
ad
jace
nt to
WW
TP
WW
TP E
fflue
nt -
Met
caife
el a
l (20
03a)
Ham
ilton
har
bour
. .
jnfla
mm
ato
ry (N
SA
ID)
Sw
itzer
land
A
nalg
esic
lnon
-ste
roid
al a
nti-
Ib
upro
fen
< 3
.6 (
MD
L) -
80 n
glL
0.
08
Sur
face
wat
er -
Olle
rs e
l al (
2001
) in
flam
mat
ory
(NS
AID
) S
witz
erla
nd
Ana
lges
icIn
on-s
tem
idaI
anti-
Ib
upro
fen
5-1
5 ng
/L
0.01
5 La
kes
- O
llers
el a
l (20
01)
infla
mm
ator
y (N
SA
ID)
Sw
itzer
land
A
nalg
esi
c/nonst
ero
idal a
nti-
Ibup
rofe
n <
4.5
(B
MD
L) - 8
0 ng
/L
0.08
R
iver
s -
Olle
rs e
t al (
2001
) in
flam
mat
ory
(NS
AID
) S
witz
erla
nd
Ana
iges
icln
on-s
tero
idal
ant
i- Ib
upro
fen
14
0 n
g/L
0.14
S
urfa
ce w
ater
- S
tan
and
Her
bere
r in
flam
mat
ory
(NS
AID
) G
erm
any
(199
7) '
Ana
lges
ic/n
on-s
tero
idal
ant
!-
Ibup
rofe
n 3
35
0 n
glL
3.
35
Sew
age
Effl
uent
- S
tan
and
Her
bere
r in
flam
mat
ory
(NS
AID
) G
erm
any
(199
7)'
Analg
esi
dnon-s
tero
idal a
nti-
Ib
upro
fen
max
3.5
5 vg
lL
3.55
E
fflue
nt fr
om
Stu
mpf
et a
l (1 9
96)
infla
mm
ator
y (N
SA
ID)
sedi
men
tatio
n ta
nk -
A
nala
esi
dnon-s
tero
idal a
nti-
Ib
upro
fen
6 - 4
1 n
a/L
0.04
1 R
iver
wat
er fr
om
Stu
mpf
el a
l (19
96)
infl
ark
ato
ry (
NS
AID
) A
nalg
esi
clnonst
em
idal a
nti-
Ib
upro
fen
infla
mm
ator
y (N
SA
ID)
I
Anala
esi
dnon-s
tero
idal a
nti-
1 Ib
upro
fen
I I
lma
x 30
00 n
alL
I med
600
na
1~
13
I
I
ISew
aae
Effl
uent
- I
ISum
pf e
l a1
(199
6)
. .
infla
mm
ator
y (N
SA
ID)
~e
rma
ny
A
nalg
esi
dnon-s
tero
idal a
nti-
Ib
upro
fen
19
0 n
g/L
0.19
S
urf
ace
wat
er -
Sum
pf e
l al (
1999
) in
flam
mat
ory
(NS
AID
) B
razi
l A
nalg
esic
lnon
-ste
roid
al a
nti-
Ib
upro
fen
max
0.5
3 vg
lL
0.53
R
iver
s an
d T
emes
(1 9
98)
infla
mm
ato
ry (N
SA
ID)
stre
ams
- Ger
man
y A
nalg
esic
lnon
-ste
roid
al a
nti-
Ibup
rofe
n m
ax
3.4
pg
lL
3.4
WW
TP
Effl
uent
- T
emes
(199
8)
infla
mm
ator
y (N
SA
ID)
Ger
man
y A
nalg
esic
lnon
-ste
roid
al a
nti-
Ibup
rofe
n m
ea
n 0
.13
bg
lL
0.13
W
WT
P E
fflue
nt -
Tem
es e
l al (
2003
) in
flam
mato
ry (N
SA
ID)
Ger
man
y A
nalg
esi
dnon-s
tero
idal a
nti-
Ib
upro
fen
0.6
ng
L
0.00
06
Nor
th S
ea -
Wel
gel e
t ai (
2002
) in
flam
mat
ory
(NS
AID
) E
stua
ry
Ana
lges
icln
on-s
tero
idal
anti-
Ib
upro
fen
BM
DL
-va
lue
not
repo
rted
BM
DL
WW
TP E
fflue
nt -
Wm
kler
et a
1 (2
001)
in
flam
mato
ry (N
SA
ID)
Sas
kato
on
Re
fere
nce
R
ep
ort
ed
In
Tabl
e A
.1:
Sum
mar
y of
En
viro
nm
enta
l Co
nce
ntr
atio
ns
Ana
lges
icln
on-s
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
/non
-ste
mid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Ant
ineo
plas
tic --
Ant
ineo
plas
tic
Ant
ineo
plas
tic
Ant
ineo
plas
tic
Ana
lges
ic/a
ntiin
flarn
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
wy
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
~dan
tiinf
lam
mat
ory
Ana
lges
ic/a
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flarn
mat
ory
Ana
lges
ic/a
ntiin
flam
mat
ory
Ana
lges
ic/a
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
ic/a
ntiin
flam
mat
ory
X-r
ay c
ontr
ast m
edia
X-r
ay c
ontra
st m
edia
X-r
ay c
ontr
ast m
edia
X-r
ay c
ontr
ast m
edia
X-r
ay c
ontr
ast m
edia
X-r
ay c
ontr
ast m
edia
X-r
ay c
ontr
ast m
edia
X-r
ay c
ontr
ast m
edia
Ref
eren
ces
Che
mic
al C
lass
R
efer
ence
R
epor
ted
In
Mat
rix
Ibup
rofe
n
lbup
mfe
n
lfosf
amid
e
lfosf
amid
e
lfosf
amid
e
lfosf
amid
e
lndo
met
haci
n
lndo
met
haci
n
lndo
met
haci
n
lndo
mel
haci
n
lndo
met
haci
n
lndo
met
haci
n
lndo
met
haci
n
lndo
met
haci
n
lndo
met
haci
n
lndo
met
haci
n
lndo
met
haci
n
lndo
met
haci
n
lom
epm
l
lom
epm
l
lopa
mid
ol
lopa
mid
ol
lopm
mid
e
lopm
mid
e
lopm
mid
e
lopm
mid
e
Che
mic
al N
ame
Eff
lue
nt
Sur
face
wat
er
BM
DL
- val
ue n
ot re
porte
d
0.08
7 pg
/L
max
191
4 ng
/L I med
109
ng1
L
max
43
ng/L
/ m
ed 6
.5 n
glL
< 0
.1 v
g/L
(BM
DL)
< 0
.01
pg/L
(BM
DL)
max
0.1
86
pg/L
mea
n 0.
378
pg1L
mea
n 0.
01 p
g/L
mea
n 0.
021
pg/L
c 2
0 ng
/L (B
MD
L)
c 1
0 ng
/L (B
MD
L)
mea
n 0.
039
uglL
mea
n 0.
073
pg/L
c 1
0 ng
1L (
BM
DL)
max
0.6
0 vg
lL
max
0.2
0 pg
/L
mea
n 0.
10 p
g/L
max
3.8
pg/
L 1
med
0.3
7 pg
/L
max
0.8
9 pg
/L /
med
0.1
0 pg
/L
max
15
pg/L
/ m
ed 0
.66
pg1L
max
2.8
pg
/U m
ed 0
.49
pg/L
1.6
pg/L
< 0
.05
pg/L
(BM
DL)
max
11
pg1L
I m
ed 0
.75
pg/L
max
0.9
1 w
g/L
1 m
ed 0
.10
pg/L
Mea
sure
d E
nviro
nmen
tal O
ccur
renc
e
Rep
orte
d C
once
ntra
tion
BM
DL
-.
0.08
7
1.91
4
0.04
3
0.05
0.00
5
0.18
6
0.37
8
0.01
0.02
1
0.01
0.00
5
0.03
9
0.07
3
0.00
5
0.6
0.2
0.1
3.8
0.89
15
2.8
1.6
0.02
5
1 1
0.91
WL
Hos
pita
l Effl
uent
- G
erm
any
WW
TP E
fflue
nt -
Ger
man
y W
WTP
Effl
uent
- C
anad
a
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Pet
erbo
roug
h W
WTP
Eff
lue
nl-
B
urlin
gton
W
WTP
Effl
uent
- Li
ttle
Riv
er
WW
rP E
fflue
nt -
Wes
t Win
dsor
WW
TP E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
Ger
man
y W
WTP
Effl
uent
-
Ger
man
y
WW
TP E
fflue
nt -
Ger
man
y
WW
P E
fflue
nt -
Ger
man
y
Sur
face
wat
er -
Sou
th S
ask
Riv
er
Sur
face
wat
er -
Ger
man
y
Riv
ers
and
stre
ams
-Ger
man
y
Sur
face
wat
er
adja
cent
to W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Sur
face
wat
er
adja
cent
to W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Riv
ers
and
stre
ams
-Ger
man
y
Sur
face
wat
er -
Ger
man
y
Sur
face
wat
er -
G
erm
any
Sur
face
wat
er -
G
erm
any
Sur
face
wat
er a
fler
bank
filtr
atio
n -
Sur
face
wat
er -
Ger
man
y
Win
kier
et a
l (20
01)
Win
kier
et a
l (20
01)
Kum
mer
er e
t al(
l99
7)
Kum
mer
er e
t al (
1997
)
Met
calfe
et a
l (20
03a)
Tem
es (
1998
)
GV
RD
(unp
ublis
hed
data
) M
etca
lfe e
t al (
2003
b)
Met
calfe
el a
1 (2
003b
)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Tem
es (
1 998
)
Tem
es (
1998
)
Tem
es e
t al (
2003
)
Tem
es a
nd H
irsch
(2
000)
T
emes
and
Hirs
ch
(200
0)
Tem
es a
nd H
irsch
12
000)
T
emes
and
Hirs
ch
(200
0)
Put
sche
w e
t al(2
000)
Put
sche
w e
t al(2
000)
Tem
es a
nd H
irsch
(2
000)
T
emes
and
Hirs
ch
1200
0)
Tab
le A
.l:
Su
mm
ary
of
En
viro
nm
enta
l Co
nce
ntr
atio
ns
I C
hem
ical
Cla
ss
I C
hem
ical
Nam
e 1 M
easu
red
Env
iron
men
tal O
ccur
renc
e I
Mat
rix
X-r
ay c
ontr
ast m
ed
~a
X-r
ay c
ontr
ast m
edia
X-r
ay c
ontr
ast m
edia
I I
I 1 U
SA
~
nalg
esic
lant
iinfla
mm
ator
y 1 Ke
topr
ofen
m
ax 3
00 n
glL
0.3
I Riv
ers
-Sp
ain
X-r
ay c
ontr
ast m
edia
Ana
lges
idan
tiinf
lam
mat
ory
I I
I I
I A
nalg
esic
lanb
infla
mm
ator
y 1 K
etop
rofe
n lm
ax
871
ng/L
10
.871
IM
P E
fflue
nt -
I
loth
alam
ic a
cid
loth
alam
ic a
cid
loxi
thal
amic
aci
d
loxi
thal
amic
aci
d
Ket
opro
fen
rem
es a
nd H
irsch
rem
es a
nd H
irsch
20
00
rern
es a
nd H
irsch
Rep
orte
d C
once
ntra
tion
max
0.6
4 pg
lL 1
med
<0.
050
pg/L
(BM
DL)
m
ax 0
.19
pg
lLl m
ed -0
.02
pg/L
(BM
DL)
m
ax 0
.21
pg1L
I m
ed <
0.0
50
Ana
lges
idan
tiinf
lam
mat
ory
Ana
lges
icla
ntiin
flam
mal
ory
Ana
lges
icla
ntiin
flarn
mal
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
icla
nt~i
nfla
mm
ator
y
Ana
lges
idan
liinf
lam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
idan
tiinf
lam
mat
ory
Ana
lges
idan
tiinf
lam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
ic/a
ntiin
Ram
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
idan
tiinf
lam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
rem
es a
nd H
irsch
Irew
es e
t al (
2002
)
pg
l~
(~
~~
~)
m
ax 0
.08
pg/L
I m
ed <
O.O
3O
pg/L
(BM
DL)
m
ax 4
5 ng
/L
;VR
D
(unp
ublis
hed
ierb
erer
et a
1 (2
002)
pg/L
0.64
0.19
0.21
Ket
opm
fen
Ket
opro
fen
Ket
opro
fen
Ket
opro
fen
Ket
opro
fen
Ket
opm
fen
Ket
opro
fen
Ket
opm
fen
Ket
opm
fen
Ket
opro
fen
Ket
opm
fen
Ket
opm
fen
Ket
opm
fen
Ket
opm
fen
Ket
opm
fen
Ket
opm
fen
Ket
opm
fen
Ket
opro
fen
Ket
opm
fen
detc
alfe
et a
l (20
03b)
Eff
luen
t S
urfa
ce w
ater
WW
TP
Effl
uent
- G
erm
any
Sur
face
wat
er -
Ger
man
y W
WT
P E
fflue
nt -
0.08
0.04
5
Aet
calfe
et a
l (20
03b)
Ger
man
y S
urfa
ce w
ater
-
WW
TP E
fflue
nt -
< 0
.015
pg/
L (B
MD
L)
max
65
ng1L
max
0.0
17 p
g1Ll
med
0.0
12
pglL
m
ax 0
.047
pg1
L I m
ed 0
.031
y
glL
m
ax 0
.050
pg1
L I m
ed 0
.050
~
g1
L
< 2
0 ng
1L (
BM
DL)
mea
n 0.
013
pg1L
c 2
0 ng
/L (B
MD
L)
< 2
0 ng
/L (
BM
DL)
< 1
0 n
g/L
(BM
DL)
< 1
0 ng
1L (
BM
DL)
< 1
0 ng
1L (
BM
DL)
< 1
0 ng
1L (B
MD
L)
< 0
.05
ugIL
(BM
DL)
< 4
.5 n
g1L
(BM
DL)
< 4
.5 n
glL
(BM
DL)
c 4
.5 (B
MD
L) - 2
00 n
g1L
max
0.3
8 pg
/L
max
0.1
2 pg
/L
I de
tcal
fe e
t al (
2003
b)
detc
alfe
el a
1 (2
003b
)
0.00
75
0.06
5
0.01
7
0.04
7
0.05
0.01
0.01
3
0.01
0.01
0.00
5
0.00
5
0.00
5
0.00
5
0.02
5
0.00
225
0.00
225
0.00
225
0.38
0.12
I de
tcal
fe e
t al (
2003
b)
I
Aet
calfe
et a
l (20
03b)
Spa
in
WP
E
fflue
nt -
Van
couv
er
I A
etca
lfe e
t al (
2003
b)
WW
TP E
fflue
nt -
Pet
erbo
mug
h W
P
Effl
uent
- B
ullin
gton
W
WT
P E
fflue
nt -
Littl
e R
iver
W
WT
P E
fflue
nt -
Wes
t Win
dsor
WW
TP
Effl
uent
- C
anad
a
WW
rP E
fflue
nt -
Sw
itzer
land
W
WT
P E
ffluent-
Ger
man
y
letc
alfe
et a
l (20
03b)
Sur
face
wat
er -
G
erm
any
Sur
face
wat
er -
Det
roit
Riv
er
Sur
face
wat
er -
Ham
ilton
har
bour
S
urfa
ce w
ater
- E
aste
m C
anad
a
Sur
face
wat
er
adja
cent
lo W
WT
P
Sur
face
wat
er
adja
cent
to W
P
Sur
face
wat
er
adja
cent
to W
P
Sur
face
wat
er
.adj
acen
t to
WW
TP
Lake
s -
Sw
ltzer
iand
R
iver
s -
Sw
itzer
land
Riv
ers
and
stre
ams
- G
erm
any
I A
etca
lfe e
l ai (
2003
b)
I A
etca
lfe e
l al (
2003
b)
Aet
calfe
et a
l (20
03a)
Ner
s ==I=
et a
1 (2
001)
I 'e
rnes
(1 9
98)
I 'e
mes
(1 99
8)
Tab
le A
.l:
Su
mm
ary
of E
nvi
ron
men
tal C
on
cen
trat
ion
s
Che
mic
al C
lau
I
Che
mic
al N
ame
I Mea
sure
d E
nv
lro
nm
e~
l Occ
urre
nce
I M
atrix
R
efer
ence
I
Ref
eren
ces
I Repo
rted
lr
IRep
orte
d C
once
ntra
tion
Ib
Ana
lges
ic/a
ntiin
flam
mat
ory
1 Keto
prof
en
IBM
DL
(LO
Q 3
3 pg
lL)
10.0
0003
3 .-
Hor
mon
e I
I Le
vono
rges
trei
I I
I
I I
I
Ant
iphl
ogis
tidan
tiinf
lam
mat
ory
I~e
clo
fen
am
inic
acid
I<
10 n
g/L
(BM
DL)
10
.005
c 0
.20
pglL
(BM
DL)
- 4 p
g/L
I I
I 0.13
84
Ant
ibio
tic -
linco
sam
ine
Effl
uent
1 sur
face
wat
er
I I
0.73
A
ntib
iotic
- lin
cosa
min
e Li
ncom
ycin
I I
I
Linc
omyc
in
max
0.7
3 pg
/L I med
0.0
6 pg
/L
WW
TP E
fflue
nt -
Spa
in
5.54
- 13
8.40
ngl
L
Ant
iphl
ogis
ticla
ntiin
flam
mat
ory
WW
TP E
fflue
nt -
US
A
c 1
0 ng
/L (B
MD
L)
Mec
lofe
nam
inic
aci
d
Nor
th S
ea a
nd
Nor
th S
ea E
stua
ry
Riv
ers
-Ita
ly
Dre
wes
et a
l (20
02)
Dre
wes
et a
l (20
02)
0.00
5
Ant
iphl
ogis
tidan
tiinf
larn
mat
ory
Ant
iphl
ogis
ticla
ntiin
flam
mat
ory
Ant
iinfla
mm
ator
y
Ant
i-inf
lam
mat
ory
Ant
iinfla
mm
atol
y
Ant
iinfla
mm
ator
y
Hor
mon
e -o
vula
tion
inhi
bito
r
Hor
mon
e - s
ynth
etic
form
of e
stro
gen
Hor
mon
e - s
ynth
etic
form
of e
stro
gen
Hor
mon
e - s
ynth
etic
form
of e
stro
gen
Ant
idia
betic
Ant
ibio
tic -
peni
cilli
n
Ant
ibio
tic -p
enic
illin
Bet
adlo
cker
(ant
ihyp
erte
nsiv
e) I
card
iova
scul
ar d
rug
~e
tad
loc
ke
r (ant
ihyp
erte
nsiv
e) I
card
iova
scul
ar d
rug
Bet
adlo
cker
(ant
ihyp
erte
nsiv
e) 1
ca
rdio
vasc
ular
dru
g B
etad
lock
er (a
ntih
yper
tens
ive)
I
card
iova
scul
ar d
rug
Per
sona
l car
e pr
oduc
t -fr
agra
nce
Per
sona
l car
e pr
oduc
t - fra
gran
ce
Per
sona
l car
e pr
oduc
t -fr
agra
nce
Wei
gel e
t al (
2002
)
Pet
rovi
c et
al (
2002
)
Cal
amar
i et a
l (20
03)
Mec
lofe
nam
inic
aci
d
Mec
lofe
nam
inic
aci
d
Mef
enam
inic
aci
d
Mef
enam
inic
aci
d
Mef
enam
inic
aci
d
Mef
enam
inic
aci
d
Mes
trano
l
Mes
trano
l
Mes
trano
l
Mes
trano
l
Met
form
in h
ydro
chlo
ride
Met
haci
llm
Met
haci
llin
Met
opm
lol
Met
opro
lol
Met
opm
lol
Met
opm
lol
Mus
k am
bret
te (n
itro
mus
k)
Mus
k ke
tone
(ni
tro m
usk)
Mus
k ke
tone
(ni
tro m
usk)
c 0
.050
pgl
L (B
MD
L)
c 0
.010
pgl
L (B
MD
L)
max
20
nglL
max
144
0 ng
lL I med
133
ngl
L
max
<SO
ng/
L
max
366
ngl
L 1 m
ed 6
2 ng
/L
max
0.4
07 p
glL
1 med
0.0
74
pglL
c 0
.001
pgl
L (B
MD
L)
max
0.0
04 p
g/L
c 0
.000
5 pg
/L (
BM
DL)
max
0.1
5 p
glL
sIm
ed
0.1
1 ua
/La
c 0
.02
pg/L
(BM
DL)
c 0
.02
pg/L
(BM
DL)
max
1.2
pg/
L /
med
0.0
18 g
/L
max
2.2
pgl
L
max
2.2
pgl
L
mea
n 1.
7 pg
lL
max
c 1
0 ng
/L (
BM
DL)
c 0
.5 n
glL
(BM
DL)
550
ng/L
0.02
5
0.00
5
0.02
1.44
0.02
5
0.36
6
0.40
7
0.00
05
0.00
4
0.00
03
0.15
0.01
0.01
1.2
2.2
2.2
1.7
0.00
5
0.00
025
0.55
1 WW
TP E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
Sou
thea
st E
ngla
nd
WW
TP E
fflue
nt -
Can
ada
WP
E
fflue
nt -
Ger
man
y
WP
E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
US
A
WP
E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
Ger
man
y
Riv
ers
and
stre
ams
-Ger
man
y S
urfa
ce w
ater
- .G
erm
any
Ups
tream
of
WP
s Sou
thea
st
Dow
nstre
am o
f W
Ps
Sou
thea
st
Stre
ams
-US
A
Sur
face
wat
er -
Ger
man
y S
tream
s -U
SA
Riv
ers
and
drai
nage
s -
Riv
ers
and
stre
ams
- Ger
man
y
Sur
face
wat
er -
Ger
man
y R
iver
Wat
er -
Elb
e in
Ger
man
y
Tem
es (
1998
)
Tem
es (
1 998
)
Her
bere
r et a
l (20
02)
Hilt
on e
t al(2
003)
Hilt
on e
t al (
2003
)
Hilt
on e
t al (
2003
)
Kop
lin e
t al (
2002
)
Tem
es e
t al (
1 999
)
Tem
es e
t al (
1999
)
Tem
es e
t al (
1999
)
Kop
lin e
t al(2
002)
Hirs
ch e
t al (
1999
)
Hirs
ch e
t ai (
1999
)
Hug
get e
t al (
2003
a)
Tem
es (
1998
)
Tem
es (
1 998
)
Tem
es e
t al (
2003
)
Her
bere
r et a
l(19
99)
Gat
erm
ann
et a
l (19
98)
Ga
ten
an
n e
t al (
1998
)
Tab
le A
.1:
Su
mm
ary
of E
nvi
ron
men
tal C
on
cen
trat
ion
s
Ch
emic
al C
lass
I
Ch
emic
al M*
I Mea
sure
d E
nvi
ron
men
tal O
ccu
rren
ce
I M
ab
i
Tab
le A
.1:
Su
mm
ary
of
En
viro
nm
enta
l Co
nce
ntr
atio
ns
I C
hem
ical C
lass
I
Ch
em
ica
l Nam
e I M
ea
sure
d E
nvi
ron
me
nta
l Occ
urr
en
ce
I M
atr
ix
I R
efe
ren
ces
Re
fere
nce
R
ep
ort
ed
In
Ana
lges
icln
on-s
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
lnon
-ste
mid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icln
on-s
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esi
dnon-s
tem
idal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icln
on-s
tem
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esi
clnonst
em
idal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icln
on-s
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esi
clnonst
ero
idai a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icln
on-s
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
lnon
-ste
mid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icln
on-s
tem
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
lnon
-ste
mid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icln
on-s
tem
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
lnon
-ste
roid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
iges
icln
on-s
tem
idal
ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esic
/non
-ste
mid
al a
nti-
infla
mm
ator
y (N
SA
ID)
Analg
esi
clnonst
em
idal a
nti-
infla
mm
ator
y (N
SA
ID)
Analg
esi
clnonst
em
idal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icln
on-s
tero
idal
ant
i- in
flam
mat
ory
(NS
AID
) C
alci
um c
hann
el b
lock
er -
card
iova
scul
ar d
rug
Cal
cium
cha
nnel
blo
cker -
ca
rdio
vasc
ular
dru
g C
alci
um c
hann
el b
lock
er -
ca
rdio
vasc
ular
dru
g H
orm
one
-syn
thetic
form
of
prog
esto
gen
Hor
mon
e -s
ynth
etic
form
of
prog
esto
gen
Ant
ibio
tic -
fluor
oqui
nolo
ne
Antib
iotic
- flu
omqu
inol
one
Nap
mxe
n
Nap
mxe
n
Nap
roxe
n
Nap
mxe
n
Nap
mxe
n
Nap
mxe
n
Nap
roxe
n
Nap
mxe
n
Nap
mxe
n
Nap
roxe
n
Nap
mxe
n
Nap
roxe
n
Nap
mxe
n
Nap
mxe
n
Nap
roxe
n
Nap
roxe
n
Nap
roxe
n
Nap
mxe
n
Nap
mxe
n
Nife
dipi
ne
Nife
dipi
ne
Nife
dipi
ne
Nor
ethi
ndro
ne
Nor
ethi
ster
one
Nof
floxa
cin
Nof
floxa
cin
Re
po
rte
d C
on
cen
tra
tion
max
95
ng
lL
max
0.5
51 p
glL
1 m
ed 0
.270
pg
1L
max
0.1
39 p
glL
lme
d 0
.094
pg
/L
c 5
ng
lL (B
MD
L)
mea
n 0.
524
pglL
mea
n 0.
041
pg/L
mea
n 0.
021
pglL
mea
n 0.
168
pglL
c 1
0 n
glL
(BM
DL)
mea
n 0.
039
pg1L
mea
n 0.
073
@L
< 1
0 n
glL
(BM
DL)
max
33
pg
lL 1
med
12.
5 pg
1L
< 4
.5 (
BM
DL)
- 10
ng
lL
10 - 4
00 n
glL
100
- 350
0 ng
lL
max
0.5
2 p
glL
max
0.3
9 p
glL
mea
n 0.
10 p
g/L
< 0
.025
pg1
L (B
MD
L)
max
0.0
89 p
g/L I m
ed <
0.0
25
yg1L
(B
MD
L)
< 0
.01
pgIL
(BM
DL)
< 0
.2 p
g1L
(BM
DL)
- 17
.4 p
g1L
max
17
ng
lL
mea
n 48
- 12
0 ng
lL
36 -
73 n
glL
pg/L
0.09
5
0.55
1
0.13
9
0.00
25
0.52
4
0.04
1
0.02
1
0.16
8
0.00
5
0.03
9
0.07
3
0.00
5
33
0.01
0.4
3.5
0.52
0.39
0.1
0.01
25
0.08
9
0.00
5
17.4
0.01
7
0.12
0.07
3
Eff
lue
nt
WW
TP E
fflue
nt -
Pet
erbo
roug
h W
WTP
Effl
uent
- B
urlin
gton
W
WTP
Effl
uent
- L
ittle
Riv
er
WW
TP E
fflue
nt -
Wes
t Win
dsor
WW
TP E
fflue
nt -
Can
ada
WW
TP E
fflue
nt -
Sw
itzer
land
W
WTP
Effl
uent
- G
erm
any
WW
TP E
fflue
nt -
Ger
man
y W
WTP
Effl
uent
- G
erm
any
WW
TP E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
Spa
in
WW
TP E
fflue
nt -
Spa
in
WW
TP T
ertia
ry
Effl
uent
- Sw
itzer
land
W
WTP
Effl
uent
- S
witz
erla
nd
Su
rfa
ce w
ate
r
Sur
face
wat
er -
G
erm
any
Sur
face
wat
er -
D
etro
it R
iver
S
urfa
ce w
ater
-
Ham
ilton
har
bour
S
urfa
ce w
ater
- E
aste
rn C
anad
a
Sur
face
wat
er
adja
cent
to W
WTP
S
urfa
ce w
ater
ad
jace
nt to
MP
S
urfa
ce w
ater
ad
jace
nt to
MP
S
urfa
ce w
ater
ad
jace
nt to
MP
Lake
s -
Sw
itzer
land
R
iver
s -
Sw
itzer
land
Riv
en
and
st
ream
s - G
erm
any
Riv
en
and
st
ream
s -G
erm
an
y
Her
bere
r et a
l (20
02)
Met
calfe
et a
l (20
036)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
caife
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03a)
Olle
n e
t al (
2001
)
Olle
rs e
t al (
2001
)
Olle
rs e
t al (
2001
)
Ter
nes
(1 99
8)
Ter
nes
(1 99
8)
Ter
nes
et a
l (20
03)
Tem
es e
t al(2
00
1)
Tem
es e
t al(2
00
1)
Ter
nes
et a
l(20
01
)
Pet
mvi
c et
al (
2002
)
Pet
mvi
c et
al (
2002
)
Gol
et e
t al (
2001
)
Gol
et e
t al (
2002
)
Tabl
e A
.1:
Sum
mar
y of
Env
iron
men
tal C
once
ntra
tions
Che
mic
al C
lass
Ant
ibio
bc - f
luom
quln
olon
e
Ant
ibio
tic - f
luor
oqui
nolo
ne
Met
abol
ite - f
luox
etin
e
Met
abol
ite - f
luox
etin
e
Met
abol
ite - f
luox
etin
e
Met
abol
ite - f
luox
elm
e
Met
abol
ite - f
luox
etin
e
Met
abol
ite - f
luox
etin
e
Met
abol
ite - f
luox
etin
e
Met
abol
ite - f
luox
etin
e
Met
abol
ite - f
luox
etin
e
Ant
ibio
tic - f
luom
quin
olon
e
Met
abol
ite -a
cety
lsal
icyl
ic a
cid
Met
abol
ite - a
cety
lsal
~cy
lic ac
id
Ant
ibio
tic
Ant
ibio
tic -
mac
mlid
e
Pro
ton
pum
p in
hibi
tor -
ant
i- ul
cer
drug
P
roto
n pu
mp
inhi
bito
r -an
ti- u
lcer
dr
ug
Pro
ton
pum
p in
h~bi
tor - a
nti-
ulce
r dr
ug
Pro
ton
pum
p in
hibi
tor -
ant
i- ul
cer
drug
A
ntib
iotic
-pe
nici
llin
Ant
ibio
tic -
peni
cilli
n
Ant
i-anx
iety
- an
tidep
ress
ent
Ant
ibac
teria
l
Ant
iinfla
mm
ator
y
Ant
iinfla
mm
ator
y
Che
mic
al N
ame
Nof
floxa
cin
~o
fflo
xa
c~
n
Nor
fluox
etin
e
Nor
fluox
etin
e
Nor
fluox
etin
e
Nor
fluox
etin
e
Nor
fluox
etin
e
Nof
fluox
etin
e
Nor
fluox
etin
e
Nor
fluox
etin
e
Nor
fluox
etin
e
Oflo
xaci
n
OH
ydro
xyhi
ppur
ic a
cid
0-H
ydm
xyhi
ppur
ic a
cid
Ola
quid
ox
Ole
ando
myc
in
Om
epra
zole
Om
epra
zole
Om
epra
zole
Om
epra
zole
Oxa
cilli
n
Oxa
cilli
n
Oxa
zepa
m
Oxo
linic
Aci
d
Oxy
phen
buta
zone
Oxy
phen
buta
zone
Mea
sure
d E
nvir
onm
enta
l Occ
urre
nce
Rep
orte
d C
once
ntra
tion
max
0.0
5 pg
/L
maz
0.1
2 pg
/L 1
med
0.1
2 pg
/L
< 0
.009
pg/
L (B
MD
L)
< 2
0 ng
/L (B
MD
L)
< 2
0 ng
/L (B
MD
L)
< 2
0 n
g/~
(BM
DL
)
< 2
0 ng
/L (B
MD
L)
< 1
0 ng
lL (B
MD
L)
c 1
0 ng
/L (B
MD
L)
< 1
0 ng
/L (B
MD
L)
< 1
0 ng
/L (B
MD
L)
max
0.2
08 p
g/L
c 0
.2 v
g/L
(BM
DL)
< 0
.075
pg/
L (B
MD
L)
< O
.OG6
pg/
L (B
MD
L)
BM
DL
- 2.7
9 ng
/L
BM
DL
< 0-
MDL)
< 0
.025
pg/
L (B
MD
L)
< 0
.01
pg/L
(BM
DL)
< 0
.02
pg/L
(BM
DL)
< 0
.02
pg/L
(BM
DL)
max
70
nglL
max
0.0
2 pg
/L
< 0
.050
pg/
L (B
MD
L)
< 0
.050
pg/
L (B
MD
L)
Mat
rix
lglL
0.05
0.12
.
WW
TP E
fflue
nt -
Van
couv
er
WP
E
fflue
nt -
Pet
erbo
roug
h W
WrP
Effl
uent
- B
urlin
gton
W
WTP
Effl
uent
- Li
nle
Riv
er
WW
TP E
fflue
nt -
Wes
t Win
dsor
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Ger
man
y W
VVTP
Effl
uent
- G
erm
any
WW
TP E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Ger
man
y W
WTP
Effl
uent
- G
erm
any
0.00
45
0.01
0.01
0.01
0.01
0.00
5
0.00
5
0.00
5
0.00
5
0.20
8
0.1
0.03
75
0.00
3
0.00
279
BM
DL
0.01
25
0.01
25
0.00
5
0.01
0.01
0.07
0.02
0.02
5
0.02
5
Ref
eren
ces
GV
RD
(unp
ublis
hed
data
) K
oplin
et a
l (20
02)
Eff
luen
t
WW
TP E
fflue
nt -
Van
couv
er
Ref
eren
ce
Rep
orte
d In
Sur
face
wat
er
Stre
ams
- US
A
Sur
face
wat
er
adja
cent
to W
WTP
S
urfa
ce w
aler
ad
jace
nt to
WW
TP
Sur
face
wat
er
adja
cent
to W
WTP
S
urfa
ce w
ater
ad
jace
nt to
WW
TP
Riv
ers
and
stre
ams
- Ger
man
y
Riv
en -
Italy
Riv
ers
-Ita
ly
Riv
ers
and
stre
ams
- Ger
man
y
Riv
ers
and
drai
nage
s -
Suf
race
wa
ten
- G
erm
any
GV
RD
(unp
ublis
hed
data
) M
etca
lfe e
t al (
2003
b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
GV
RD
(unp
ublis
hed
data
) T
emes
(199
8)
Tern
es (
1 998
)
GV
RD
(unp
ublis
hed
data
) C
alam
ari e
t al (
2003
)
Cal
amar
i et a
l (20
03)
Tem
es e
t al (
2001
)
Tern
es e
l al (
2001
)
Tem
es e
t al (
2001
)
Hirs
ch e
t al (
1999
)
Hin
ch e
t al (
1999
)
Her
bere
r el a
1 (2
002)
GV
RD
(unp
ublis
hed
data
) T
erne
s et
a1
(200
1)
Tem
es e
t al(
2001
)
-
1 (6661) le la
wJ
~!H
I pue s
la~
!u
10'01 (
la
~a
)
116d 10.0 >I u
!~~
p!u
ad
- 3!lo!q!iuv I
I I
I I
I
(1001) AO
JI~
W
VS
~
-la
w
9S00'0
116u 9.9 X
ELU
U
!ll!?!Uad
I I
I I
I I
I
Tab
le A
.l:
Su
mm
ary
of E
nvi
ron
men
tal C
on
cen
trat
ion
s
I C
hem
ical
Nam
e I M
em
.~re
d Env
ironm
enta
l Occ
urre
nce
I M
atr
ix
1 ~
efe
re
nm
Non
ster
oida
l ant
iinfla
mm
ator
y dr
ug
(NS
AID
) N
onst
emid
al a
ntiin
flam
mat
ory
drug
(N
SA
ID)
Ant
ibio
tic -
fluor
oqui
nolo
ne
Per
sona
l car
e pr
oduc
t -fr
agra
nce
Per
sona
l car
e pr
oduc
t -fr
agra
nce
Per
sona
l car
e pr
oduc
t -fr
agra
nce
Ref
eren
ce
Per
sona
l car
e pr
oduc
t - fr
agra
nce
Per
sona
l car
e pr
oduc
t -fr
agra
nce
Per
sona
l car
e pr
oduc
t - fr
agra
nce
Per
sona
l car
e pr
oduc
t - fr
agra
nce
Per
sona
l car
e pr
oduc
t - fr
agra
nce
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Hor
mon
e - r
epro
duct
ion
-nat
ural
Hor
mon
e - r
epro
duct
ion
- nat
ural
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) /
card
iova
scul
ar d
rug
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) I
card
iova
scul
ar d
rug
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) 1
ca
rdio
vasc
ular
dru
g B
eta-
bloc
ker (
antih
yper
tens
ive)
1 ca
rdio
vasc
ular
dru
g B
eta-
bloc
ker (
antih
yper
tens
ive)
I
card
iova
scul
ar d
rug
Bet
a-bl
ocke
r (an
tihyp
efie
nsiv
e) /
card
iova
scul
ar d
rug
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) 1
ca
rdio
vasc
ular
dru
g B
eta-
bloc
ker (
antih
yper
tens
ive)
I
card
iova
scul
ar d
rug
Ana
lges
ic/a
ntiin
flam
mat
ory
Ana
lges
ic/a
ntiin
flam
mat
ory
Rep
orte
d In
Phe
nylb
utaz
one
Phe
nylb
utaz
one
Pip
emid
ic A
cid
Pol
ycyc
lic m
usks
AH
TN
Pol
ycyc
lic m
usks
AH
TN
Pol
ycyc
lic m
usks
AH
TN
Pol
ycyc
lic m
usks
AH
TN
Pol
ycyc
lic m
usks
HH
CB
Pol
ycyc
lic m
usks
HH
CB
Pol
ycyc
lic m
usks
HH
CB
Pol
ycyc
lic m
usks
HH
CB
Pnm
idon
e
Prim
idon
e
Prim
idon
e
Pm
gest
emne
Pro
gest
eron
e
Pm
pano
lol
Pm
pano
lol
Pm
pano
lol
Pm
pano
lol
Pm
pano
lol
Pm
pano
lol
Pm
pano
lol
Pm
pano
lol
Pm
pyph
enaz
one
Pm
pyph
enaz
one
Rep
orte
d C
on
cen
tra
tion
< 0
.050
pgl
L (B
MD
L)
< 0
.01
pg/L
(BM
DL)
< 0
.004
pgl
L (B
MD
L)
10
- 400
ng/
L
30 -
6780
ng
lL
0.89
- 2.
6 n
glL
p@/L
0.02
5
0.00
5
0.00
2
0.4
6.78
0.00
26
110
- 440
0 ng
1L
0.7
- 610
ng/
L
20 -
12,4
70 n
g/L
0.09
-4.
8 n
glL
170
- 600
0 n
glL
max
220
ngl
L
10
5 n
g1L
max
635
ngl
L
max
0.1
99 p
glU
me
d 0
.11
pg
lL
0.20
pg/
L (B
MD
L) -
1.1
pg/L
max
0.0
4 p
glL
max
284
ng
lLl m
ed 7
6 ng
lL
max
115
ngl
L / m
ed -4
0 ng
lL
max
215
ngl
L 1
med
29
nglL
max
1.9
0 p
glL
I med
0.0
37
pg/L
m
ax 0
.29
pg
lL
max
0.5
9 pg
lL
mea
n 0.
18 p
g/L
max
20
nglL
max
197
0 n
glL
Sew
age
Wat
er -
Eum
pe
Sew
age
Wat
er -
Eur
oee
WW
TP E
fflue
nt -
US
A
WW
TP
Effl
uent
- S
pain
W
WT
P E
fflue
nt -
Fra
nce
WW
TP
Effl
uent
- S
outh
east
Eng
land
WW
TP E
fflue
nt -
US
A
WW
TP E
fflue
nt -
Ger
man
y
WW
TP
Effl
uent
- G
erm
any
WW
TP
Effl
uent
- U
SA
4.4
0.61
12.4
7
0.00
48
6 0.22
0.10
5
0.63
5
0.19
9
1.9
0.04
0.28
4
0.11
5
0.21
5
1.9
0.29
0.59
0.18
0.02
1.97
Effl
uent
WW
TP E
fflue
nt -
Ger
man
y
WW
TP E
fflue
nt -
Van
couv
er
Riv
er w
ater
-
Eum
pe
Sur
face
wat
er -
Eum
pe
Sea
wat
er -
Eur
ope
Sur
face
wat
er -
Ger
man
y S
urfa
ce w
ater
- G
erm
any
Str
eam
s - U
SA
Ups
trea
m o
f W
WTP
s S
outh
east
D
owns
trea
m of
W
WTP
s S
outh
east
Riv
ers
and
stre
ams
-Ger
man
y
Sur
face
wat
er -
Ger
man
y
Sur
face
wat
er
R~
vers
and
stre
ams
-Ger
man
y
Riv
er w
ater
- E
urop
e S
urfa
ce w
ater
- E
umpe
S
ea w
ater
- E
urop
e
Rim
kus
(199
9)'
Rim
kus
(199
9)'
Rim
kus
(199
9)'
Rim
kus
(199
9)'
Rim
kus
(199
9)'
Dre
wes
et a
l (20
02)
Her
bere
r el a
l(2
00
1)
Her
bere
r et a
l (20
02)
Kop
lin e
l al (
2002
)
Pet
mvi
c e
l al (
2002
)
Fer
rari
el a
l (20
04)
Hilt
on e
l al (
2003
)
Hilt
on e
l al (
2003
)
Hilt
on e
l al (
2003
)
Hug
gel e
t a1
(200
3a)
Tem
es (
1998
)
Tem
es (
1998
)
Tem
es e
t al (
2003
)
Dre
wes
el a
l (20
02)
Her
bere
r el a
l (19
98,
2002
)
Tem
es e
l al(2
001)
Tem
es e
l al (
2001
)
GV
RD
(un
publ
ishe
d da
ta)
Rim
kus
(199
9)'
Rim
kus
(199
9)'
Rim
kus
(199
9)'
Tab
le A
.1:
Su
mm
ary
of
En
viro
nm
enta
l Co
nce
ntr
atio
ns
Che
mic
al C
lass
Ana
lges
ic/a
nbin
flam
mat
ory
Ana
lges
icla
nlIin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
Ana
lges
icla
ntiin
flam
mat
ory
I I
I I
I I
Che
mic
al N
ame
Pm
pyph
enaz
one
Pm
pyph
enaz
one
Pro
pyph
enaz
one
Pro
pyph
enaz
one
Pro
pyph
enaz
one
Cal
amar
i el a
l (20
03)
I I
I I
I I
Mea
sure
d E
nvir
onm
enta
l Occ
urre
nce
An
tiu
lce
r dru
g -a
ntac
id
An
tiu
lce
r dru
g -a
ntac
id
l~a
nti
din
e
Hyd
roch
lorid
e lm
ax 0
.01
pg
/Ln
/me
d 0.
01
10.0
1
Ant
ibio
tic -
mac
mlid
e
Ant
ibio
tic -
mac
mlid
e
I
I I
Ant
ibio
tic -
mac
mlid
e 1 R
oxith
rom
vcin
I m
ean
0.54
uql
L 10
.54
IWW
TP
Effl
uent
- I
l~e
me
s
et a
l (20
03)
Rep
orte
d C
once
ntra
tion
280
ng1L
mea
n 0.
18 p
g/L
max
0.4
8 p
glL
I med
0.0
95
pglL
m
ax 0
.10
pglL
I med
0.0
43
pglL
0.
6 ng
/L
BM
DL
- 38.
50 n
g/L
Ran
tidin
e H
ydro
chlo
ride
I~tr
ea
ms
- US
A
l~o
plm
e
l ai (
2002
)
Ant
ibio
tic -
mac
mlid
e
Ant
ibio
tic -
mac
mlid
e
Mat
rix
Rox
ilhro
myc
in
Rox
ilhm
myc
in
Ref
eren
ces
lglL
0.28
0.18
0.48
0.1
0.00
06
0.03
85
Rox
ithm
myc
in
Rox
ithro
myc
in
I
Rve
rs -
Italy
t~n
ll
max
0.0
07 p
glL
max
1 p
g/L I med
0.6
8 pg
lL
(bro
ncho
dial
ator
) I
I I
I I
I
I I
I
Met
abol
ite - a
cety
lsal
icyl
ic a
cid
lSal
lcyl
ic a
cid
lma
x 13
000
ngl
L 11
3 IW
WT
P E
fflue
nt -
I I~
arr
e
el a
l (20
01)
Effl
uent
WW
TP
Effl
uent
- G
erm
any
WW
TP E
fflue
nt -
Ger
man
y
max
0.5
6 pg
lL 1
<0.
02 p
glL
(BM
DL)
m
ax 0
.18
pglL
I med
0.0
5 pg
lL
IGer
man
y B
eta
aqon
ist -
B2s
vmpa
thom
imet
ic
l~a
lbu
tam
olla
lbu
tem
l 1 B
MD
L - 2
.48
nglL
(0
.002
48
1 l~
ive
rs - Ita
ly
l~a
lam
ari
et a
l (20
03)
. -
i I
(bro
ncho
dial
ator
) B
eta
agon
ist 4
2-sy
mpa
thom
imet
ic
(bro
ncho
dial
ator
) M
etab
olite
-ace
tyls
alic
ylic
aci
d
0.00
7
1
. .
Bet
a ag
onis
t B2s
ympa
thom
imet
ic
ISal
buta
mol
/alb
uter
oI
lma
x 0.
17 p
g/L
10.1
7 IM
P E
fflu
ent-
I
I~e
me
s (1 99
8)
Sur
face
wat
er
Sur
face
wat
er -
Ger
man
y
Riv
ers
and
stre
ams
-Ger
man
y N
orth
Sea
0.56
0.18
Sal
buta
mol
/alb
uter
ol
Sal
icyl
ic a
cid
Met
abol
ite -a
cety
lsal
icyl
ic a
cid
Met
abol
ite -
acet
vlsa
licvl
ic a
cid
Her
bere
r el a
l (20
01)
Tem
es e
t al (
2001
)
Tem
es e
t al(
2001
)
Tem
es e
l al (
2001
)
Wei
gel e
l al (
2001
)
WW
TP
Effl
uent
- V
anco
uver
W
WT
P E
fflue
nt -
. .
Met
abol
ite - a
cety
lsal
icyl
ic a
c~
d
Ant
ibio
tic
GV
RD
(unp
ublis
hed
data
) H
irsch
el a
l (19
99)
Ger
man
y
max
0.0
35 p
glL
max
880
0 ng
lL
Sal
icyl
ic a
cid
Sal
icyl
ic a
cid
I
I I
I I
I
Ref
eren
ce
Rep
orte
d Ir
Sal
icyl
ic a
cid
Sar
aflo
xaci
n
Ant
ibio
tic -
sulfo
nam
ide
Ant
ibio
tic -
sul
fona
mid
e
Ant
ibto
t~c -
sulfo
nam
ide
Ant
ibio
tic -
sulfo
nam
ide
Sur
face
wat
er -
Riv
ers
and
Stre
ams
-US
A
0.03
5
8.8
max
59.
6 pg
lL I med
3.6
pg/
L
max
4.1
ugl
L
Ant
ibac
teria
l
Hirs
ch e
l al (
1999
)
Kop
lin e
t al (
2002
)
. .
max
0.1
4 pg
lL
BM
DL
BM
DL
- 74.
20 n
g/L
Spi
ram
ycin
Sul
fabe
nzam
ide
Sul
face
tam
ide
Sul
fach
loro
pyrid
azin
e
Sul
fach
loro
pyrid
azin
e
Ger
man
y
59.6
4.1
0.14
BM
DL
0.07
42
< 0
.001
(B
MD
L)
max
0.1
51 p
g/L
<0.0
02 @
glL (
BM
DL)
BM
DL
Riv
ers
and
stre
ams
- Ger
man
y R
iver
s -S
pain
Spa
in
WW
TP E
fflue
nt -
Can
ada
Tem
es (
1 998
)
Far
re e
t al (
2001
)
WW
TP
Effl
uent
- G
erm
any
Riv
ers
- Ita
ly
0.00
5
0.15
1
0.00
1
BM
DL
Riv
ers
and
Cal
amar
i et a
l (20
03)
Met
calfe
el a
l 200
3
Tem
es (
1998
) st
ream
s -G
erm
any
Stre
ams
-US
A
WW
TP
Effl
uent
- V
anco
uver
W
WT
P E
fflue
nt -
Van
couv
er
WW
TP
Effl
uent
- V
anco
uver
Tem
es (
1 998
)
Kop
lin e
l al (
2002
)
Stre
ams
- U
SA
GV
RD
(unp
ublis
hed
data
) G
VR
D (u
npub
lishe
d da
ta)
GV
RD
(unp
ublis
hed
data
) K
oplin
el a
l (20
02)
Tab
le A
.1:
Su
mm
ary
of E
nvi
ron
men
tal C
on
cen
trat
ion
s
Che
mic
al C
lass
Ant
ibio
tic -
sulfo
nam
ide
Ant
ibio
tic -
suifo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
I
I I
I I
I I
Che
mic
al N
ame
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
I I
I I
I I
I A
ntib
iotic
- sul
fona
mid
e 1 S
ulfa
met
er
0.00
6 pg
/L (B
MD
L)
10.0
03
IM
P
Effl
uent
- I
~G
VR
D (unp
ublis
hed
I
Sul
fadi
azin
e
Sul
fadi
mel
hoxi
ne
Sul
fadi
met
hoxi
ne
.
Mea
sure
d E
nvir
onm
enta
l Occ
urre
nce
Sul
fagu
anid
in
Sul
fam
eraz
ine
l~a
nco
uve
r I
Idal
a)
I~n
tib
ioti
c - sul
fona
mid
e I
I 1
l~u
lfa
me
lhiz
ole
I c 0
.003
ug/
L (B
MD
L)
10.0
015
IWW
TP
Effl
uent
- I
d?
Rep
orte
d C
once
ntra
tion
max
0.0
19 p
g/L
< 0
.001
pg/
L (B
MD
L)
max
0.2
2 pg
/L /
med
0.2
2 pg
/L
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Anl
iblo
tic -
sulfo
nam
ide
Mat
rix
< 0
.008
pg/
L (B
MD
L)
< 0
.002
ugl
L (B
MD
L)
Sul
fam
eraz
ine
I I
I I
I I
I A
ntib
iotic
- sul
fona
mid
e lS
ulfa
met
hoxa
zole
1 m
ax 0
.09
pg/L
10
.09
IMP
Effl
uent
- ]
1 Fer
rari
el a
l (20
04)
1
&L
0.01
9
0.00
05
0.22
Sul
fam
etha
zine
Sul
fam
etha
zine
Sul
fam
etha
zine
Sul
fam
etha
zine
I ..
.
. L
l~a
nco
uve
r
Ref
eren
ces
0.00
4
0.00
1
Idat
a)
Rep
orte
d In
Eff
luen
t
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Van
couv
er
BM
DL
max
0.0
23 p
g/L
< 0
.2 p
g/L
(BM
DL)
< 0
.2 p
g/L
(BM
DL)
max
0.0
6 pg
/L /
med
0.0
6 pg
/L
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Stre
ams
- US
A
BM
DL
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic -
sulfo
nam
ide
Sur
face
wat
er
Stre
ams
-US
A
I GV
RD
(unp
ublis
hed
data
) ~
GV
RD
(unp
ublis
hed
Kop
lin e
t al (
2002
)
0.02
3
0.01
0.01
0.06
Ant
ibio
tic - s
ulfo
nam
ide
Sul
fam
etho
xazo
le
Sul
fam
etho
xazo
le
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic -
sulfo
nam
ide
1 I
lVan
couv
er
Idat
a)
GV
RD
(unp
ubl~
shed
da
ta)
GV
RD
(unp
ublis
hed
data
) K
oplin
el a
l (20
02)
Stre
ams
-US
A
Sul
fam
etho
xazo
le
Sul
fam
etho
xazo
le
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Van
couv
er
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflue
nt -
Ger
man
y
Sul
fam
elhi
zole
K
oplin
el a
i (20
02)
max
0.8
71 p
g/L
max
200
0 ng
/L I med
400
ngl
L
Sul
fam
etho
xazo
le
Sul
fam
etho
xv~
vrid
azin
e
max
0.1
3 pg
/L I m
ed 0
.13
pg/L
max
480
ng/
L 1
med
30
ng/L
max
190
0 ng
/L 1
med
150
ng/
L
.. .
Sul
fam
oxol
e
Sui
faph
enaz
ole
Riv
en
and
dr
aina
ges
- S
tream
s -U
SA
0.87
1
2
mea
n 0.
62 p
glL
< 0
.005
ud
L (B
MD
L)
data
) G
VR
D (u
npub
lishe
d da
ta)
Hin
ch e
t al (
1999
)
Hin
ch e
l al (
1999
)
Kop
lin e
l al(2
002)
0.48
1.9
.
< 0
.002
pg/
L (B
MD
L)
BM
DL
Fra
nce
WW
TP E
fflue
nt -
Van
couv
er
Sew
age
Effl
uent
-
0.62
0.00
25
GV
RD
(unp
ublis
hed
data
) H
inch
el a
l (19
99)
Ger
man
y
0.00
1
BM
DL
WW
TP E
fflue
nt -
Ger
man
y W
WTP
Effl
uent
-
Riv
en
and
dr
aina
ges
- G
erm
any
Stre
ams
-US
A
Tem
es e
t al (
2003
)
GV
RD
(un
~u
blis
he
d
Van
couv
er
WW
TP E
fflue
nt -
Van
couv
er
WW
TP E
fflu
enl-
Hin
ch e
l al (
1999
)
Kop
lin e
l al (
2002
)
. .
data
) G
VR
D (u
npub
lishe
d da
ta)
GV
RD
(unp
ublis
hed
-
hu
euu
ag
(gsnw
- Jalem a3epng
8'9 7/6u 0099 X
eU
3!113A10d) NlH
V aP
!leUol
a3ueJ6eJj - 13npwd aJe3 (eu
Ou
ad
Auew
Jag - sueaJis pue u
an
!~
900'0
(1aWs) lm
10'0. p!3y 3!u
!weu
ajlol
ho
leu
ue
~u
~g
ue
/3!s
a6
leu
y
Aueuuag
- lua
n~
3
dl
~~
SZO
'O
(law
@ 1
/6d
050'0
>
p!3y 3!u!w
euaj(o
l h
o1eu
ue~
u~
gu
e/3!sa61euy
l!zeJg - 1
ua
n~
3
dl
~~
9'1
1/6d 9' r x
eu
p!3v ?
!u!w
eua~
lol
ho
iewu
e~u
~g
ue/3!sa61eu
v
Tabl
e A
.1:
Sum
mar
y of
Env
iron
men
tal C
once
ntra
tions
Che
mic
al C
lass
Pe
no
na
l car
e pr
oduc
t -fr
agra
nce
Ant
isep
tic
Ant
isep
tic
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
tena
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibio
tic -
glyc
opep
tide
Che
mic
al N
ame
Ton
aiid
e A
HT
N (p
olyc
ilic
mus
k)
Tric
losa
n
Tric
losa
n
Trim
etho
prim
Trir
neth
oprim
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Ant
ibio
tic -
stre
ptog
ram
in
Trir
neth
oprim
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Van
com
ycin
Virg
inia
myc
in
Mea
sure
d E
nvir
onm
enta
l Occ
urre
nce
mea
n 0.
071
vg/L
mea
n 0.
084
vglL
mea
n 0.
194
vg/L
mea
n 0.
009
vg/L
< 1
0 ng
/L (B
MD
L)
mea
n 0.
043
pg/L
mea
n 0.
137
pg/L
< 1
0 n
g/L
(BM
DL)
mea
n 0.
34
g/L
max
3.8
ng/
L
Rep
orte
d C
once
ntra
tion
mea
n 0.
10 u
g/L
< 0
.2 n
g/L
(BM
DL)
0.24
- 2.
7 vg
/L
max
0.6
22 v
g/L
max
128
8 ng
lL /
med
70
ng/L
max
36
ng
/L/ m
ed <
10 n
g/L
max
42
ng
/L/ m
ed <
I0 n
g/L
max
660
ng/
L 1 m
ed 3
20 n
g/L
max
200
ng/
L / m
ed <
20 n
glL
max
710
ngl
L /
med
150
ng/
L
BM
DL
Cgl
L
0.1
0.00
01
. 2.
7
0.62
2
1.22
8
0.03
6
0.04
2
0.66
0.2
0.71
Mat
rix
0.07
1
0.08
4
0.19
4
0.00
9
0.00
5
0.04
3
0.13
7
0.00
5
0.34
0.00
38
Ref
eren
ces
Tem
es e
t a1
(200
3)
Boy
d et
al (
2003
)
Tem
es e
l ai (
2001
)
GV
RD
(unp
ublis
hed
data
) H
ilton
et a
l (20
03)
Hilt
on e
l al (
2003
)
Hilt
on e
t al (
2003
)
Hin
ch e
t al (
1999
)
Hirs
ch e
t a1
(199
9)
Kop
lin e
t at
(200
2)
Efflu
ent
WW
P E
fflue
nt -
Ger
man
y W
WT
P E
fflue
nt -
US
A
WW
TP
Effl
uent
- G
erm
any
WW
TP
Effl
uent
- V
anco
uver
W
WT
P E
fflue
nt -
Sou
thea
st E
ngla
nd
Sew
age
Effl
uent
- G
erm
any
BM
DL
Ref
eren
ce
Rep
orte
d In
Sur
face
wat
er
Ups
trea
m o
f W
PS
Sou
thea
st
Dow
nstre
am o
f W
WT
Ps
Sou
thea
st
Riv
en
and
dr
aina
ges
- S
tream
s -U
SA
WW
TP
Effl
uent
- P
eter
boro
ugh
WW
TP
Effl
uent
- B
urlin
gton
W
WT
P E
fflue
nt -
L~
tlle
Riv
er
WW
TP
Effl
uent
- W
est W
inds
or
WW
TP
Effl
uent
- G
erm
any
Str
eam
s -U
SA
Sur
face
wat
er
adja
cent
to W
P
Sur
face
wat
er
adja
cent
to W
P
Sur
face
wat
er
adja
cent
to W
P
Sur
face
wat
er
adja
cent
to W
P
Riv
er - U
SA
Kop
lin e
t al (
2002
)
Met
calfe
el a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
el a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Met
calfe
et a
l (20
03b)
Tem
es e
t al (
2003
)
Mul
roy
(200
1)
Tab
le A
.1:
Su
mm
ary
of E
nvi
ron
men
tal C
on
cen
trat
ion
s
Chem
ical C
lass
Report
ed C
once
ntr
atio
n
I I
I I
I I
I
Chem
ical N
am
e
Note
s:
WP
=
Was
te w
ate
rtre
atm
ent p
lant
LO
Q =
Lim
it of
qua
ntifi
catio
n B
MD
L =
Ble
lw m
etho
d dete
ctio
n li
mit
All
conc
enlra
tions
report
ed to
be B
MD
L have
been d
ivid
ed b
y 2
R~
mku
s 199
9' -
Ref
eren
ce s
umm
ary
pape
r, be
caus
e m
ost
of t
he a
ctua
l slu
dies
wer
e no
t in E
nglis
h
Sta
n a
nd H
erbe
rer (
1997
) - R
efer
ence
d su
mm
ary
pape
r bec
ause
mos
t of t
he a
ctua
l stu
dies
wer
e no
t in
Englis
h
Tam
oxife
n -n
ot
dete
cted
in U
K -
Hilt
on e
t al 2
003
Lofe
pram
ine
- not
det
ecte
d in
UK
- met
hods
not v
iabl
e fo
r de
lect
ion
- Hilt
on e
t al 2
003
Con
cent
ratio
n es
timat
ed b
ecau
se th
e re
cove
ry w
as <
60
%
Che
mic
als
test
ed b
efo
re a
nd a
fter d
rinki
ng w
ater
trea
tmen
t -ch
em
icals
det
ecte
d (C
lofib
ric a
cid
and
napr
oxen
) to
trea
tmen
t wer
e be
low
MD
L af
ter t
reat
men
t 'a
naly
tes
wer
e qu
antif
ied
afte
r dilu
tion o
f the
final
sa
mpl
e vo
lum
e b
y 1 :I
0
max
val
ues
used
whe
re n
o m
ax v
alue
repo
rted
then
med re
port
ed, B
MD
L th
en M
DL
used
, if M
DL
not r
epor
ted
then
MD
L in
sert
ed, b
lank
cel
ls-n
o oc
cure
nce
data
foun
d fo
r th
at c
hem
ical
lglL
Measu
red E
nvi
ronm
enta
l O
ccurr
ence
M
atr
ix
Refe
rence
Efflu
ent
Surf
ace
wate
r
Tab
le A
.3:
Su
mm
ary
of A
cute
Eff
ects
Dat
a
I Spe
cies
C
om
mo
n
Co
nce
ntr
atio
n
Nam
elA
nim
al T
ype
Endpoin
t I
Ch
em
ica
l Cla
ss
I I
I I
I I
l~cr
ifla
vin
e
1 Lepo
mis
lb
lueg
ill s
unfis
h 12
4h L
C50
11
8 lw
ilfo
rd (1
966)
l~
ep
olt
ed
in
Web
b
Ref
eren
ces
mac
roch
irus --
Ant
i-inf
ectiv
e m
acro
chiru
s
--
larv
ae)
Ant
i-inf
ectiv
e M
oron
e sa
xatil
is
Mor
one
saxa
tilis
Ref
eren
ce R
epor
tec
In
Ch
em
ica
l Nam
e
(*
El
p-
z
rI
ir
"f
0w67100 R
epol
ted
) ~
n Web
b
--
strip
ed b
ass
96h
LC50
H
ughs
(197
3)
Acu
te A
quat
ic T
oxi
city
--
24h
LC50
--
. A
crifl
avin
e 48
h LC
50
(200
1 _
Rep
olte
d in
We
bb
Rep
orte
d in
We
bb
~n
ti-i
nfe
ctiv
e
Ant
i-inf
ectiv
e A
crifl
avin
e S
alve
linus
la
ke tr
out
Wilf
ord
11 9
661
I agen
t (bi
phos
phon
ate)
A
ntib
acte
rial;
antia
meb
ic
Am
inos
idin
e +---
1 1 i f I f ; 1; ; I"' i" " I " " n 1" n 1 " n 1" ! n ! ! I n n !n n 1 ~; F 'i 3 3 ,i ,F IF IF F IF ~F 1s 1s is 1 1 i 1 ~ . s Is 1s I s I E I I . s .s . .C ,.s 1.E .E
S is I .E
,I 111 I 'C - - m u ) - s:ggg-go
W C C n n . f S . E . E J 3 J 3 o o n n
I I I I ' I
I (~
66
~)
le
la e
~~
!qlu
w)
E'O
E ,
eay ~a
#e
mI
eu6ew e!uqdeaI
I I
I
I
a~
u! ~
av
od
atl (~
66
1) le
la w
nsso
tl 0
53
3 qg6
mout~!lu pe
ew
ej
sela
wo
~d
Sepqdw!d
alq
ps
au
!luq
aq
dw
v yxw
ou
en
ue
~n
mg
s SN
~
(roo
z) W
JM u! p
avo
da
v (
~6
61
)
le la
e!alle3 O
LZ 0
53
3 4PZ
eay Jalem
eu6ew eruqdeo
alq
lns e
u!w
qa
qd
wv
qx
~o
ue
nu
qn
~!ls
S
N~
1'PE
O
S3111PZ dw
uqs auyq cups e!w
evy u
!smlle
g
leu
el3
eq
wv
OZL <
0
53
1
-
ae61e ae6le paypadsun
up
hw
olq
zv
leua)aeq!luv
OZ 1 O
E33
eay ~a
em
eu6ew
rquqdea U
!~~
UO
J~
I!W
leu
aly
nu
v
(a3ua3seu!cunl)
(1001) q
qa
~
u! pa
uo
da
tl ( 1 0
05
q
qa
~
u! pe
uo
da
tl (io
oz
q
uy
ixiiw
e~
O
E33 q
l
eey ~a
lem
eu6ew
--
qu
yde
a
alq
ps
eu
!dw
y I 3geuphtu :3!6~
au!loqqluv snm
y!3Ip3 0
53
1 W
Z
JeJ!lm
snu
3e
g
a~
eg
ns au!do~
)v a
!n1
m6
~
- pn
po
ld w
e3 leu
wa
d
qu
ue
iinlu
gu
e
05
31
I(PZ
dwuqs auuq
eu!ps q
wa
w
alegns au
!dw
v I 3gepphlu !3!bau!loq3guv
Grup Je
ln3
sen
qp
m
0001 <
eey Jap
m
eu6ew q
uyd
ea
u!u!loldy
1 (aseelold) ~q
q!q
u! aw
hzu3
pue sne
qyw
g
(q~
66
1) le la
eIalle3
(qt366 1) le la
e!
~3
LEL'O
199
95E
OS
~~(IPZ
05
31
WZ
-
05
93
WZ
eual3eq lue
3s
ww
dwuqs h
!ej
eey ele em
!JW
W O
!w!A
sn
ap
pso
qo
d
sn
~e
qd
am
lde
g~
eu6ew q
uyd
ea
auuasezv
alq
lns au!dol)y
e~
lns
w
dw
v
3gseldoauguy quye3snm
!lue I qe
up
hlu
!3!bau!1oq3!1uv quye3snw
!)ue 1 w
eupAw
!3!&au!lotpguy
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
I I
I I
Ant
iepi
lept
ic
Car
barn
azep
ine
Cho
rella
vul
garis
gr
een
alga
e 12
4h E
C5O
(gm*vl
)l
~l~Os
et a
1 (2
003)
Che
mic
al C
lass
AC
E I
nhib
itor l
car
diov
ascu
!ar d
mg
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ant
iepi
lept
ic
Ch
em
lca
l Nam
e
Cap
topr
il --
Car
bam
azep
ine
Car
bam
azep
ine
Car
bam
azep
ine
.
Car
barn
azep
ine
Ant
iepi
lept
ic
I
Car
bam
azep
ine
Cho
rella
vul
garis
men
eghi
nian
a
Acu
te A
quat
ic T
oxi
city
--
I C
arba
maz
epin
e D
aphn
ia m
agna
Ref
eren
ces
Cle
uver
s (2
004)
Far
rari
et a
l(200
3)
Far
rari
et a
l(2
00
3)
Far
rari
et a
l(200
3)
Far
rari
et a
l(2
00
3)
Spe
cies
Sce
nede
smus
su
bspi
catu
s V
ibrio
fisc
heri
Pse
udok
irchn
erie
lla
subc
apita
la
Bra
chio
nus
ca&
icvu
s .-
Cer
ioda
phni
a m
agna
c.m
.ma2
ap*l
~ap
hnia
m
agna
Ref
eren
ce R
epor
tec
In
--
Car
bam
azep
ine
Dap
hnia
mag
na
Co
mm
on
N
amel
Anl
mal
Typ
e
gree
n al
gae
lum
ines
cent
bac
teria
gree
n al
gae
mtif
er
wat
er fl
ea
I di
atom
,
96h
EC
50 (g
row
th)
diat
om
Endpoin
t
EC
50 (g
row
th)
30 r
nin
EC
50
Jlum
ines
cenc
e)
96h
EC
50 (g
mw
th)
48h
NO
EC
@
pmdu
ctio
nJ
48h
LC50
wat
er R
ea
48h
EC
50
48h
LC50
Con
cent
ratio
n (m
QlL
)
> 1
68
> 8
1
> 1
00
0.37
7
77.7
1 Jo
s et
a1
(200
3)
I
> 1
00
Cle
uver
s (2
004)
--
I --
112.
23
Jos
et a
1 (2
003)
I
Jos
et a
1 (2
003)
> 1
3.8
Far
rari
et a
1 (2
003)
--
Ant
iepi
lept
ic
Car
bam
azep
ine
l~n
tiip
ilep
tic
Car
bam
azep
ine
1 I
12 c
ell l
ine
Ihn
ctiin
s)
myk
iss
~n
ti~
ile
~ti
c
ICar
bam
azep
ine
Onc
why
nchu
s ra
inbo
w h
ut
- TR
G-
48h
EC
50 (c
ell
I -. Ant
iepi
lept
ic
. .
-
yki;-
2 ce
ll lin
e.
yi s) A
ntie
pile
ptic
C
arba
rnaz
epin
e P
seud
ok~
chne
riella
gr
een
alga
e 96
h N
OE
C (g
row
th
subc
apca
ts
Ant
iepi
lept
ii C
arba
maz
epin
e S
cene
desm
us
gree
n al
gae
EC
50 (g
row
th)
subs
ica
tus
Ant
iepi
lept
ic
Car
bam
azep
ine
Syn
echo
cocc
us
blue
-gre
en a
lgae
96
h E
C50
(gro
wth
) l/e
opol
ensi
s I
I ~
nti
e~
ile
~ti
c
ICar
tiam
azep
ine
l~~
ne
ch
oc
oc
cu
s
[blu
e-gr
een
alga
e 19
6h N
OE
C (g
mw
th
leop
olen
sis
Ant
iepi
lept
ic
Car
bam
azep
ine
Vib
rio fi
sche
ri bi
olum
ines
cenc
e)
I
I
153.
81
Lavi
lle e
t al (
2004
) I
I 11
7.19
Jo
s et
a1
(200
3)
I 1
Jos
et a
1 (2
003)
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
Ch
em
ica
l Cla
ss
Per
ista
ttic
stim
ulan
t 1 g
astr
oint
estin
al
5!!!9.---
An
tin
eo
pla
tii
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Lipi
d re
gula
tor
Met
abol
ite - c
lofib
rate
-
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Ch
em
ica
l Nam
e
Cis
aprid
e
Cla
drib
ine
Clo
fibra
te
Clo
fibra
te
Clo
fibra
te
Clo
flbric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
~e
tab
oli
itx
ofi
bra
te
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
r%
Met
abol
ite -
clof
ibra
te
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
-
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Met
abol
ite - c
lofib
rate
Spe
cies
Lepo
mis
-. mac
roch
ius
-
Dap
hnia
mag
na
Dap
hnia
mag
na
Uns
peci
fied
alga
e
bnco
rhyn
chus
m
yk&
V
ibrio
fisc
heri
~&
kdo
k~ch
ne
rie
lla
subc
apita
ta
Bra
chio
nus
caIy
c1or
us
Bra
chyd
anio
rerio
-~o
sL-
Bra
chyd
anio
reri
o
FD
A-C
DE
R (
1996
)
FD
AC
DE
R (
19
96
5- .
Kop
f (1 9
95)
Kop
f (1
995)
Ref
eren
ce R
epor
ted
In
Rep
olte
d in
Web
b 20
01)
kepo
rted
in W
ebb
(200
1)
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in W
ebb
Acu
te A
qu
atic
Co
mm
on
N
am
elA
nim
sl T
ype
blue
gill
sunf
ish
wat
er fl
ea
wat
er fl
ea
alga
e
rain
bow
trou
t - h
ep
ato
cy
t3~
lu
min
esce
nt b
acte
ria
gree
n al
gae
mtif
er
-
zebr
afis
h
zebr
afis
h
To
xici
ty
End
poin
t
LC50
EC
50
24h
EC
50
EC
~O
24h
EC
50
(cyt
og
xict
yj
30 m
in E
C50
(lu
min
esce
nce)
96
h E
C5O
(gr
owth
)
4Bh
NO
EC
(r
epro
duct
ion)
48
h LC
50
EC
50 (p
ulse
race
)
Far
rari
et a
l(2
00
3)
Far
rari
et a1
(20
03)
Far
rari
et a
l(2
00
3)
Hen
sche
l et a
l(1
99
7)
Cle
uver
s (2
004)
Far
rari
et a
l(200
3)
Cle
uver
s (2
004)
Hen
sche
l et a
l(1
99
7)
Fa
mri
et a
l(200
3)
Hen
sche
l et a
l(1
99
7)
Cle
uvem
(200
4)
Far
rari
et a
l(2
00
3)
Far
rari
et a
l(200
3)
La
vila
et a
1 (2
004,
Far
rari
et a
l(2
00
3)
Far
rari
et a
l(2
00
3)
Far
rari
et a
l(200
3)
Hen
sche
l et a
l(l9
97
)
Hen
sche
l et a
l(l9
97
)
Clo
fibric
aci
d
~lo
fib
ric
acid
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
Gfi
bri
c a
cid
Clo
fibric
aci
d
Cbf
ibric
aci
d
Clo
fibric
aci
d
Clo
fibric
aci
d
wat
er fl
ea
diat
om
diat
om
wat
er fl
ea
wat
er fl
ea
wat
er fl
ea
duck
wee
d
blue
gill s
unfis
h ce
lls
gree
n al
gae
gree
n al
gae
gree
n al
gae
blu
eg
ree
n a
lgae
blue
-gre
en a
lgae
Co
nce
ntr
atio
n
(~Q
IL)
2. 10
00
233
28.2
12
2 uM
91.2
94
-.
0.24
6
86
126
--
-
---
2001
)
--
(em
bryo
s)
Cer
ioda
phni
a m
agna
Cyc
lote
lla
me
ng
hin
ian
a
Cyc
lote
lla
men
eghi
nian
a D
aphn
ia m
agna
Dap
hnia
mag
na
Dap
hnia
mag
na
Lem
na g
ibba
Lapo
mis
m
acro
chuu
s P
seud
okrc
hner
iella
su
bcap
itata
S
cene
desm
us
subs
pica
tus
Sce
nede
smus
su
bspi
qa!u
s S
ynec
hoco
ccus
le
opol
ensi
s S
ynec
hoco
ccus
le
opde
nsis
48h
L~
O
96h
EC
50 (g
row
th)
96h
NO
EC
(gm
wth
)
EC
50
(imob
iliza
tion)
48
h E
C50
(im
mob
ility
) 48
h LC
50
EC
50 (g
row
th)
EC
50 (c
ell d
ensi
ty)
96h
NO
EC
(gro
wth
)
72h
EC
50 (g
mw
th
inh
ib3
E
C50
(gro
wth
)
96h
EC
50 (g
row
th)
96h
NO
EC
(gro
wth
)
* 200
19.2
4
> 1
00
108
72
> 2
00
12.5
14
75
89
115
4012
23.5
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
1 C
hem
ical
CIa
88
I C
hem
ical
Nam
e 1
Acu
te A
quat
ic T
oxic
lty
I Spe
cies
C
omm
on
I C
on
cen
tra
tion
N
amel
Ani
mal
Typ
e
myk
iss
Ant
i-inf
lam
mat
ory
- cor
ticos
tem
id
Dex
amet
hazo
ne
1- *- l~aphnia
mag
na
I Gter fle
a
Met
abol
ite - c
bfib
rate
Met
abol
ite - c
lofib
rate
Ant
ibac
teria
l
f~nt
i-inf
lam
mat
ory - c
ortic
oste
mid
be
xam
etha
zone
1 ~h
amno
ceph
alus
-I----
Nar
cotic
ana
lges
ic I ps
ycho
stim
ulan
t D
extm
pmpo
xyph
ene
Bra
chio
nus
rotif
er
(am
phet
amin
elik
e) I an
tiepi
lept
ic
HC
UD
extm
amph
etam
ine
caly
cifo
rus
(lum
ines
cenc
e)
lrnm
unos
uppr
essa
nt
Cyc
losp
orin
e D
aphn
ia m
agna
w
ater
flea
E
C50
20
Clo
fibric
aci
d
Cbf
ibric
aci
d
Cyc
lose
rine
Iy-p/T
loa-
(am
phet
amin
elik
e) I an
tiepi
lept
ic
HC
UD
extm
amph
etam
ine
Nar
cotic
ana
lges
ic I ps
ycho
stim
ulan
t D
extm
pmpo
xyph
ene
Dap
hnia
mag
na
wat
er fl
ea
amph
etam
inel
ike)
I an
ti-ep
ilept
ic
HC
UD
extm
amph
etam
ine
I(
-I
Tel
rahy
men
a p
~ri
fcu
mis
V
ihrio
fisc
heri
Vih
rio fi
sche
ri
I I
--
Dex
trop
mpo
xyph
ene
Str
epto
ceph
alus
fa
iry s
hrim
p (a
mph
etam
inel
ike)
I an
tiepi
lept
ic
HC
UD
extr
oam
phet
amin
e pr
obos
cide
us
Ant
idep
ress
anffa
ntip
sych
otic
I D
iaze
pam
A
rtem
ia s
alin
a
cilia
ted
pmto
zoan
lum
ines
cent
bac
teria
lum
ines
cent
bac
teria
rp
ra
ze
pa
m
Ant
idep
ress
anV
antip
sych
otic
~
~ra
ch
ion
us
cam
s A
ntid
epre
ssan
Van
tipsy
chot
ic
Dia
zepa
m
Dap
hnia
mag
na
wat
er fl
ea
I I
Ant
idep
ress
anV
antip
sych
otic
+D
iaze
pam
D
aphn
ia m
agna
w
ater
flea
48h
EC
50 (g
mw
th
inJhib
3on)
30
m E
C50
(lu
min
esen
ce)
24h
EC
50
IAnt
idep
ress
anU
antip
s ych
otk
I Dia
zepa
m
/ Daphn
ia m
agna
**h
EC
50
175
100
65.5
14.1
(who
le
mdu
ct)
4.2
(act
ive
k
I le
nsch
el e
t al(1
997)
---
Ant
idep
ress
anffa
ntip
sych
otic
Ana
lges
icln
on-s
tero
idal
ant
i- in
flam
mat
o~y (N
SA
ID)
lens
chel
I-P
et a
1 (1
997)
lack
haus
and
.)
Dia
zepa
m
Dic
lofe
nac
!rim
-re(
l999
) D
A-C
DE
R (1
996)
R
epor
ted
in W
ebb
*I)
DA
-CD
ER
(199
6)
Rep
orte
d in
Web
b 12
001)
Ie
llaG
reca
et a
l
?E
Lp
Ie
llaG
reca
et a
l 2004)-.
Iella
Gre
ca e
t al
2004
) :a
lleja
et a
1 (1
994b
) R
epor
ted
in ~
eb
r
(200
1 )
1 --
:alle
ja e
t al(
l99
4b
) R
epot
ted
in W
ebb
(200
1 )
~b
ep
&e
ph
alu
s pr
obos
c&u~
V
ibrio
Bch
eri
:alle
ja e
t al (
1994
b)
Rep
orte
d in
Web
b (2
00 1
)
-.
fairy
shr
imp
24h
LC50
10
3
lum
ines
cent
bac
teria
30
min
EC
50
11.4
5 (lu
min
esce
nce)
--
:alle
ja e
t a1
(199
4b)
i~e
po
rte
d in W
ebb
ialle
ja e
t al (
1g
94
b)
r in
we;
ialle
ja e
t al(1
993)
R
epor
ted
in S
tuer
- La
urid
sen
et a
l 20
00
-
ialle
ja e
t al(
19
93
) R
epor
ted
in S
tuer
- La
urid
sen
et a
l(2
00
0:
ilius
et a
1 (1
994)
R
epor
ted
in W
ebb
Tab
le A
.3:
Su
mm
ary
of A
cute
Eff
ects
Dat
a
1 C
hem
ical
Cla
ss
( C
hem
ical
Nam
e I
Acu
te A
quat
ic T
oxic
ity
subs
pica
tus
Ana
lges
idno
n-st
eroi
dal a
nti-
Dic
lofe
nac
Dic
lofe
nac
-
~
Ana
lges
idno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
icln
on-s
tero
idal
anti-
in
flam
mat
ory (
NS
AID
) A
nalg
esid
non-
ster
oida
l ant
i- in
flam
mat
ory
(NS
AID
) A
nalg
esid
non-
ster
oida
l ant
i- in
flam
mat
ory (
NS
AID
) ---
Ana
lges
idno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
idno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
-
Ana
lges
idno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
-.
Ana
lges
idno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
-- -
Ana
lges
icln
on-s
tero
idal
anti-
in
flam
mat
ory (
NS
AID
) - Ana
lges
idno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
idno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
-SA
ID)
Ana
lges
idno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
Ana
lges
idno
n-st
eroi
dal a
nti-
infla
mm
ator
y (N
SA
ID)
I infl
am
ma
t~~
(N
SA
ID]
Ana
laes
idno
n-st
eroi
dal a
nti-
l~ic
lofe
na
c lu
min
esce
nt b
ac
teri
al~
~5
0
(bio
lum
ines
cenc
e in
hibi
tion)
A
nalg
esic
lnon
-ste
roid
al an
ti-
infla
mm
alo~
y (NS
AID
) (b
iolu
min
esce
nce
Ana
lges
icln
on-s
tero
idal
anti-
D
iclo
fena
c P
seud
okLc
hner
ieIIa
gr
een
alga
e 96
h N
OE
C (g
row
th
infla
mm
ator
y IN
SA
ID)
subc
apita
ta
--
Ana
lges
idno
n-st
eroi
dal a
nti-
Dic
bfen
ac
Sce
nede
smus
gr
een
alga
e E
C50
(gro
wth
)
Dic
bfen
ac
Dic
lofe
nac
Dic
lofe
nac
Diil
ofen
ac
-
Dic
bfen
ac
Dic
lofe
nac
'
Dic
bfen
ac
Dic
lofe
nac
Dic
bfen
ac
Dic
lofe
nac
Diil
ofen
ac
- Dic
lofe
nac
Dic
loie
nac
I I
linhi
bitii
n)
1 ~a
ph
nia
mag
na
lwat
er fle
a 1
~~
50
Hor
mon
e - s
ynth
etic
form
of
Die
thyl
stilb
estro
l e@!!!ee!! H
orm
one
- syn
thet
rc fo
rm o
f ~
ieth
~ls
tilb
est
rol
estro
gen
-
Spe
cies
Pse
udok
~ch
nerie
lla
subc
apita
ta
Bra
chio
nus
caly
cif7
wus
C
erio
daph
nia
mag
na
Cyc
lote
lla
men
eghi
nian
a C
yclo
tella
m
eneg
hini
ana
Dap
hnia
mag
na
Dap
hnia
mag
na -
Dap
hnia
mag
na
Des
mod
esm
us
subs
pica
tus
Des
mod
esm
us
sub
gka
tus
..-.
Dap
hnia
mag
na
Lem
na g
ibba
Onc
why
nchu
s m
ykis
s
I I R
efer
ence
Rep
orte
i
Con
cent
ratio
n
Far
rari
et a
l(200
3)
Com
mon
N
amel
Ani
mal
Typ
e
gree
n al
gae
rotif
er
wat
er fl
ea
diat
om
diat
om
wat
er fl
ea
..
wat
er fl
ea
wat
er A
ea
.
gree
n al
gae
gree
n al
gae
wat
er fl
ea
duck
wee
d
rain
bow
trou
t - he
pato
cyle
s
---t F
arra
ri et
a1 (
2003
)
End
poin
t
96h
EC
50 (g
row
th)
..
48h
NO
EC
(r
epm
duct
ion)
-
48h
LC50
96h
EC
50 .-
96h
NO
EC
(gro
wth
48h
NO
EC
--
48h
EC
50
@!
~o
bil
ity
)~
48
h E
C50
(im
mob
il'iy
] N
OE
C
EC
50
48h
LC50
EC
50 (g
row
th)
24h
EC
50
(_cy
otox
iclty
)
- ... --
I 71
.9
Cle
uver
s (2
003a
)
1 I
6.04
2 La
ville
et a
l(200
4)
I I
10
Far
rari
et a
l(200
3)
--
13.7
F
ad
et a
l(200
1)
I 4
Coa
ts e
t a1
(197
6)
-
1.09
ki" an
d F
inge
rman
I
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
Ch
em
lca
l Cla
ss
Ch
em
lca
l Nam
e
Hor
mon
e -s
ynth
etic
form
of
Die
thyl
stilb
estr
ol
estr
ogen
H
orm
one
-syn
the
tic fo
rm o
f D
ieth
ylst
ilbes
trol
es
t=en
-
Hor
mon
e -s
ynth
etic
form
of
Die
thyl
stilb
estr
ol
estr
ogen
H
orm
one
- syn
thet
ic fo
rm o
f D
iithy
lstil
best
rol
.!strow
!! C
ardi
ovas
cula
r dru
g D
igox
in
I
Car
diov
ascu
lar d
rug
Dig
oxin
I
Ant
ihyp
erte
nsiv
e - c
alci
um c
hann
el
l~il
tia
ze
m
I A
ntib
acte
rial
Diri
thm
myc
in
I A
ntib
acte
rial
Diri
thm
myc
in
ha
rbo
nic
anh
vdra
se in
hibi
tor.
~
~o
ao
loa
mid
e
HC
L
I trea
tmen
t of g
$uco
ma
I C
arbo
nic
anhy
dras
e in
hib
iir,
l~o
no
loa
mid
e
HC
L
Ant
ibio
tic -
fluor
oqui
nolo
ne
En
mb
xaci
n
I A
ntib
iotic
- flu
omqu
inol
one
Enm
floxa
cin
Ant
ibio
tic - f
luor
oqui
nolo
ne
En
mfb
xaci
n
Ant
ibio
tic - m
ac
mli
e
Ery
thro
myc
in
l&tib
iotic
- m
acm
lide
I Ery
thro
myc
in
~G
ZX
GR
Y~
~ E
ryth
rom
ycin
I
Ant
ibio
tic - m
acm
lide
Ery
thro
myc
in ph
osph
ate
~b
.bio
tic-
ma
cmlid
e
I Ery
thm
myc
in p
hosp
hate
I E
ryth
mm
ycin
thio
cyan
ate
l~iu
reti
cn
hib
itio
n
of a
nion
ch
an
ne
ls
pi
ha
~~
m~
-
Cal
cium
regu
lato
r - m
etab
olic
bon
e E
tiim
nic
aci
d di
seas
e I ca
rdio
vasc
ular
dru
g I I
Acu
te A
qu
at
Sp
eci
es
Cul
ex p
ipen
s m
osqu
ito
Dap
hnia
mag
na
wat
er fl
ea
I I V
ibrio
fisc
heri
lum
ines
cent
ba
cte
~
I D
aphn
ia m
agna
w
ater
flea
fath
ead
min
now
I
Dap
hnia
mag
na
wat
er R
ea
Dap
hnia
mag
na
wat
er R
ea
7
Sal
velin
us
lake
trou
t
Sal
velin
us
lake
trou
t
Fis
h - s
ever
al
spec
ies -
Vib
io fi
sche
ri lu
min
esce
nt b
acte
l
Ref
eren
ces
Ref
eren
ce .- R
epor
tec
En
dp
oin
t C
on
cen
tra
tio
n
(msl
L)
48h
LC50
>
1
Coa
ts e
t al(
19
76
)
Coa
ts e
t al(
19
76
) I
- r
--
48h
LC50
1.
2 B
aldw
in e
t al(
19
95
)
Coa
ts e
t a1
(1976)Ip
24h
EC
50
Bac
khau
s an
d (lu
min
esce
nce
LC50
>
288
0 F
DA
-CD
ER
(199
6)
Rep
orte
d in
Web
b
24h
LC50
B
ayer
(199
7)
I 96
h LC
50
Bay
er (1
997)
--
I
Di D
elup
is e
t al(
19
92
)
Bac
khau
s an
d
(199
2)
(200
1)
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
Spe
cies
C
om
mo
n
Co
nce
ntr
atio
n
~N
am
elA
nlm
al Typ
e lEnd
point
I I
Ch
em
lca
l Cla
ss
Che
mlc
al N
ame
I I
I I
I I
I
IIII
%-Z
F
ch
a
caffi
sh
Cal
cium
reg
ulat
or - m
etab
olic
bon
e E
tidm
nic
acid
I 7
LC50
an
d F
ee
di
seas
e I ca
rdio
vasc
ular
dru
g
Cal
cium
regu
lato
r - m
etab
olic
bon
e di
seas
e I ca
rdio
vasc
ular
drug
Cal
cium
reg
ulat
or - m
etab
olic
bon
e di
seas
e I ca
rdio
vasc
ular
dru
g t
Acu
te A
qu
atic
To
xici
ty
dise
ase I ca
rdio
vasc
ular
dru
g
Etid
mnk
aci
d
Etid
mni
c ac
id
Cal
cium
regu
lato
r - met
abol
ic b
one
dise
ase I ca
rdio
vasc
ular
drug
Ref
eren
ces
Da
ihn
ia m
agna
~
I~
c~
o~
~~
~~
~~
G
ledh
ill a
nd F
eijte
l R
epor
ted
in W
ebb
Etid
mni
c ac
id
L~
~i
KF
ei
ji
i P
in-1
(2
001 )
Ref
eren
ce R
ep
ort
ed
4..
Lepo
mis
mac
roch
ius
-
Ant
ivira
l
Ant
ivira
l 1-
I ro
mel
as
Li~
id
Rea
ulat
or
l~e
no
fib
rate
~
~on
corh
mnc
hus
!rain
bow
tm
ut -
IGZ
C~
OL
~
l~a
vil
le
et a
l120
04) I@
-
Ani
t-ul
cer,
his
tam
ine
(H-2
) blo
cker
Ani
t-ul
cer,
his
tam
ine
(H-2
) blo
cker
blue
gill
sunf
ish
Fam
cicl
ovir
Fam
cicl
ovir
mag
na
FD
A-C
DE
R (1
996)
R
epor
ted
in W
ebb
Po
ol)
Le
pom
is m
acro
chiu
s bl
uegi
ll su
nfis
h F
DA
-CD
ER
(199
6)
Rep
orte
d in
Web
b
Fam
otid
ine
. F
amot
idin
e
. -
Adr
ener
gic
rece
ptor
inhi
bito
r
Adr
ener
gic
rece
ptor
inhi
bito
r
96h
LC50
Ant
ibac
teria
l
Ant
ibac
teria
l
EiP
hn
ia m
agna
lw-;i
.- Pim
epha
les
fath
ead
min
now
Fin
aste
ride
Fin
aste
ride
Flu
maq
uine
Flu
maq
uine
868
398
> 6
80
Flu
maq
uine
Flu
maq
uine
--
Ant
ibac
teria
l .- A
ntib
acte
rial
Ant
ibac
teria
l
Ant
ibac
teria
l
(nau
plii)
A
rtem
ia s
alin
a @
a* A
rtem
ia s
alin
a
Gle
dhill
and
Fei
jtel
(1 99
2)
myk
kiss
- he
pato
cyte
s
myk
iss
Art
emia
sal
ina
(nau
plii)
A
rtem
ia s
alin
a
Flu
maq
uine
Flu
maq
uine
Flu
maq
uine
Flu
maq
uine
Rep
orte
d in
Web
b (2
001 )
(cyt
otox
icily
) E
C50
LC50
Dap
hnia
mag
na
Onc
orhy
nchu
s
brin
e sh
rimp
brin
e sh
rimp
wat
er fl
ea
rain
bow
trou
t
brin
e sh
rimp
brin
e sh
rimp
(cau
plii)
A
rtem
ia s
alin
a @
aupl
ii)
Art
emia
sal
ina
(nau
plii)
Mic
rocy
stis
ae
rugi
nosa
R
hodo
mon
as s
alin
a
21
20
72h
LC50
24h
LC50
24h
LC50
48h
LC50
brin
e sh
rimp
brin
e sh
rimp
blu
eg
ree
n a
lgae
mar
ine
mic
mal
gae
. ,
FD
A-C
DE
R (1
996)
FD
A-C
DE
R (1
996)
96.4
477
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in W
ebb
476.
8
307.
7
Mig
lire
et a
l(1
99
7F
Bra
mbi
lla e
t al(
19
94
) I 1
48h
LC50
72h
LC50
EC
50 (g
mw
th)
EC
5O (
gmw
th)
Mig
lwre
et a
l(1
99
7)
Mig
liore
et a
l(199
7)
308
96.4
0.15
9
18
pool
)
Bra
mbi
lla e
t al(1
994)
--
Bra
mbi
lla e
t al(1
994)
Hol
ten
Lo
hh
ofl
et
7
(1 9
99)
Hol
ten
Lotz
hofl
et a
l (1
999)
. .
.-
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
I C
he
mic
al C
lass
I
Che
mlc
al N
ame
I A
cute
Aqu
atic
To
xici
ty
I R
efer
ence
s I R
efer
ence
Re
po
rte
d I
X-r
ay c
ontr
ast m
edia
I
I 1
I
I~
-r
a~
co
ntra
st m
edia
lo
pmm
ide
I D-Izebraf
ish
-196
h LC
50
lopm
mid
e
X-r
ay c
ontr
ast m
edia
lo
pmm
ide
I I
I lo
pmm
ide
Spe
cies
Dap
hnia
mag
na
Uns
peci
fied
fish
X-r
ay c
ontr
ast m
edia
X-r
ay c
ontr
ast m
edia
fish
48h
EC
50
Dap
hnia
mag
na
-. X-r
ay c
ontr
ast m
edia
X-r
ay c
ontr
ast m
edia
X-r
ay c
ontr
ast m
edia
Co
mm
on
N
amel
Anl
mal
Typ
e
wat
er fl
ea
wat
er fl
ea
EC
50
lopr
nm.d
e
lopm
mid
e
lopm
mid
e 72
h E
C50
(gm
wth
)
lopm
mid
e lu
m&
esce
nce)
lo
thab
mic
aci
d
1
I
Ant
ibac
teria
l F
nia
zid
D
aphn
ia m
agna
lw
ater
ha
End
poin
t
24h
EC
50
Ant
ibac
teria
l
Ant
ibac
teria
l
Ant
ibac
teria
l
Dap
hnia
mag
na
Pse
udom
onas
put
ida
lson
iazi
d
lson
iazi
d B
rach
ionu
s c
aly
cif
~~
us
ls
onia
zid
Ant
ibac
teM
l
Ana
lges
icla
nti-i
nfla
mm
ator
y
Ana
lges
icla
nti-i
nfla
mm
atol
y
Ana
lges
idan
ti-in
mm
mat
ory
--
Ant
i-uke
r
wat
er fl
ea
bact
eria
- ~
-
~-
lson
iazi
d S
trep
toce
phal
us
fairy
shl
lmp
24h
LC50
pr
obos
cide
us
Ket
opm
fen
Vib
rio fi
sche
ri lu
min
esce
nt b
ac
te
ri
a~
i
(bio
lum
ines
cenc
e in
hibi
iion)
K
etop
mfe
n V
ibrio
fisc
heri
lum
ines
cent
bac
teria
EC
50
(bio
lum
ines
cenc
e in
hibi
tion)
--
Ket
omla
c tm
met
ham
ine
Lepo
mis
bl
uegi
ll sun
fish
96h
LC50
m
acro
chuu
s la
nsop
razo
le
Dap
hnia
mag
na
wat
er fl
ea
EC
50
'
Ant
i-ulc
er
Ant
ibio
tic - l
inco
sam
ide
24h
EC
50
(imm
obili
zatio
n)
16h
EC
50 (g
row
th)
bnso
praz
ole
Linc
omyc
in
72h
LC50
I
I I
I A
ntib
iotic
- lin
cosa
mid
e
Ant
ibio
tic - l
inco
sam
ide
- ..
3045
C
alle
ja e
t a1
(199
4b)
Rep
orte
d in
Web
b
35
, Li
lius
et a
l(1
99
4)
:onc
entr
atio
n :m
glL)
1000
0
1000
0
> 10
16
F0
.l
0.1
.-
> 0.
1 ~
Linc
omyc
in
Dap
hnia
mag
na
wat
er fl
ea
48h
EC
50
Linc
omyc
in
Dap
hnia
mag
na
wat
er fl
ea
Pho
tota
ctic
be
havi
our
125.
5
Fa
d et
a1
(200
1)
~ig
lio
re
et a
l(1
99
7)
Rep
orte
d in
Hol
ten
Lutz
hofi
et a
l(1
99
9
Rep
orte
d in
Hol
ten
Lutz
hofl
et a
l(l9
99
)
@EL
p--
> 0.
1 S
tage
r-H
artm
ann
et a
l (1
999)
>
0.1
Sta
ger-
Har
tman
n et
al
(199
9)
0.1
Ste
ger-
Har
tman
n et
al
1199
9)
322
Cal
leja
et a
l(l9
94
b)
Rep
orte
d in
Web
b
Sch
wei
nfur
th e
t al
(*=a)
Sch
wei
nfur
th e
t al
11 99
6a)
FD
A-C
DE
R (
1996
)
Ste
ger-
Har
tman
n et
al
(1
99
9'
S
tege
r-H
artm
ann
et a
l 19
99
ktig
e:-H
artm
ann
et a
1
In
Rep
orte
d in
Web
b (2
001 )
R
epor
ted
in W
ebb
(200
1)
Rep
orte
d in
Web
b @
Ol)
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
I A
ntid
epre
ssan
t l~
ith
ium
sulfa
te
jme
mia
sa
ha
b
rin
e s
hrim
p 12
4h L
C50
I
I I
I IL
iiiu
m su
lfate
1 Br
achi
onus
lm
tifer
12
4h L
C50
I
Ant
idep
ress
ent
Lii
um
sulfa
te
Dap
hnia
mag
na
wat
er fl
ea
t 24
h E
C50
Ref
eren
ces
Di D
elup
is e
t al(1
992)
Che
mic
al C
lass
Ant
ibio
tic - l
inco
sam
ide
Ref
eren
ce R
epor
ted
In
Che
mic
al N
ame
Linc
omyc
in
Acu
te A
quaU
c T
oxi
city
kti
bio
tk - fl
uom
quin
olon
e I
I L
I I~
om
eflo
xaci
n
(Onc
orhy
nchu
s lfi
sh
1~
~5
0
Ant
idep
ress
ent
Ant
ibio
tic - f
luom
quin
olon
e
vacu
dalu
s Lo
mef
loxa
cin
Con
cent
ratio
n (m
gl~
)
379.
39
Spe
cies
Dap
hnia
mag
na
Ant
ibio
tic - fl
uoro
quin
olon
e --
Ant
ibio
tic - f
luom
quin
olon
e Lo
mef
mxa
cin
Vib
rio fi
sche
ri
Lith
ium
sul
fate
.-
Lom
eflo
xaci
n
bn
ti-i
n fe
ctiv
e I
I l~
orc
arb
ef
IDaP
hnia
mag
na
iwa
te~
ka
(
~~
50
Com
mon
N
arnd
Anl
mal
Typ
e
wat
er fl
ea
I 1
I V
asod
ilato
r / a
ntih
yper
tens
ive
Losa
rtan
D
aphn
ia m
agna
w
ater
flea
tE
C50
72h
LC50
Slre
ptoc
epha
lus
prob
osci
deus
. . .
Dap
hnia
mag
na
I
Ant
ibio
tic
Mec
illin
am
vi
ar
lw
at
er
fle
a 14
8h N
OE
C
fairy
shr
imp
wat
er fl
ea
Vas
odila
tor I an
tihyp
erte
nsiv
e
Vas
odila
tor I an
tihyp
erte
nsiv
e
Vas
odila
tor I an
tihyp
erte
nsiv
e
Vas
odila
tor I an
tihyp
erte
nsiv
e
Ant
ibio
tic - b
eta-
lacl
am
?GG
b%i
24h
LC50
EC
50
Losa
rtan
Losa
rtan
Losa
rtan
Losa
rtan
Mec
illin
am
Mec
illin
am
Ant
ibio
tic
Ant
ibio
tic
0.02
2 B
ackh
aus e
l a1
(200
0)
431 8
712
197
33.1
112
130
170
Onc
orhy
nchu
s m
ykis
s P
imep
hale
s p
rom
rns
Uns
peci
fied g
reen
a&
ae
Uns
pecf
md g
reen
al
gae
Act
ivat
ed s
luge
ba
cter
ia
Bra
chyd
anio
rerio
Mec
illin
am
Mec
illin
am
--
(20
01
1
58
Bac
khau
s el a
1 (2
000)
I
Cal
leja
et a
l(199
4b)
Cal
leja
el a
1 (1
994b
)
Lu
e
a (1
994)
-- Cal
leja
el a
1 (1
994b
)
Cal
leja
et a
l (19
94b)
FD
A-C
DE
R (1
996)
FD
A-C
DE
R (1
996)
> 9
63
--
331
> 92
9
>I0
00
245
949
I 62.1
> 1
00 e.:: >
300
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in W
ebb
2001
k
ep
kd
in ~
er
p
oo
l)
Rep
orte
d in
Web
b I2
!2o
r)
.--
~
Rep
orte
d in
Web
b o-____
Rep
orte
d in
Web
b (
2o
e1
Lp
-
Rep
orte
d in
Web
b
rain
bo
wx
t
fath
ead
min
now
alga
e
alga
e
bact
eria
zebr
afis
h
Mic
rocy
stis
ay
ugin
osa
Sel
enas
lrum
ca
pric
wnu
tum
FD
AC
DE
R (1
996)
FD
AC
DE
R (
1996
)
FD
A-C
DE
R (1
996)
FD
A-C
DE
R (1
996)
FD
A-C
DE
R (1
996)
FD
AC
DE
R (
1996
)
Hal
ling-
Sor
ense
n et a
l (2
000)
H
allin
g-S
oren
sen e
t al
!2%- Hal
ling-
Sor
ense
n et a
l (2
000)
H
allin
g-S
oren
sen e
t al
L2
wL
H
ailin
g-S
oren
sen e
l ai
(200
0)
LC50
LC50
MIC
MIC
EC
50
72
hG
E~
Rep
orte
d in
Web
b 20
01
ke
po
L in
ebb
(200
1)
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in W
ebb
(200
1 )
Rep
orte
d in
Web
b P
C-
- -
Rep
orte
d in
Web
b (2
001)
blue
gree
n al
gae
blue
gree
n al
gae
EC
50
NO
EC
Tabl
e A
.3:
Sum
mar
y of
Acu
te ~
ffe
is
Dat
a
Che
mlc
al C
lass
Ant
i-inf
ectiv
e
Ant
i-inf
ectiv
e ---
Ant
i-inf
ectiv
e
Ant
i-inf
ectiv
e -
Ant
i-inf
ectiv
e
Ant
i-inf
ectiv
e
Ant
i-inf
ectiv
e
Ant
i-inf
ectiv
e
-- Ant
iinfe
ctiv
e
Ant
i-inf
ectiv
e
Ant
i-inf
ectiv
e --
Ant
i-inf
ectiv
e
Ant
ihyp
ergl
ycae
mic
- ant
idia
betic
Ant
ihyp
ergl
ycae
mic
- ant
idia
betic
Ant
ihyp
ergi
ycae
mic
- an
tidia
betic
Ant
ihyp
ergl
ycae
mic
- ant
idia
betic
Ant
ibio
tic
AnU
neop
iast
ic, a
ntirh
eum
atic
Che
mic
al N
ame
Acu
te A
quat
ic T
oxic
ity
Ref
eren
ce
in Rep
orte
d
Mel
thbl
ate
Mel
thio
late
Mer
thio
late
Mer
thio
late
Mer
thio
late
Mel
thio
late
Mer
thio
late
Mer
thbl
ate
Mer
thiil
ate
Mer
thiil
ate
Mer
thio
hte
Mel
thio
late
~e
tfo
nin
Met
form
in
Me
tfo
nin
Met
form
in h
ydm
chlo
ride
Met
haci
llin
Met
hotre
xate
Spe
cles
Icta
luru
s pun
ctat
us
Ant
ineo
plas
tic, a
xrhe
umat
ic
Ant
ineo
plas
tic, a
ntirh
eum
atic
Ant
ineo
plas
tic, a
ntirh
eum
atic
Ant
ineo
plas
tic, a
ntirh
eum
atic
-. A
ntin
eopl
astic
, ant
irheu
rnat
ic
Met
hotre
xate
_
Met
hotre
xate
Met
hotre
xate
Met
hotre
xate
Met
hotre
xate
Com
mon
N
amel
Ani
mal
Typ
e
chan
nel c
atfis
h
m!
!*
~
Bra
chyd
anio
re&
Le
mC
ws)
D
aphn
ia m
agna
Lepo
mis
m
acro
chuu
s S
cene
desm
us
subs
pica
tus
~-
Tetra
hym
ena
pyrif
orm
is
.-
zebr
afis
h
wat
er fl
ea
blue
gill s
unfis
h ce
lls
gree
n al
gae
cilia
ted
pmto
zoan
. . 24
h LC
50
lcta
luru
s pun
ctat
us
Lepo
mis
m
acro
ch~
US
Le
pom
is
mac
roch
rus
Onc
orhy
nchu
s m
ykis
s O
ncor
hync
hus
myk
iss
Sal
mo
lrutta
Sal
mo
~u
tta
Sal
velin
us fo
ntin
alis
~a
ive
linu
s font
inal
is
Sal
velin
us
nam
aycu
sh
Sal
velin
us
na-u
sh
Dap
hnia
mag
na
Lem
na g
ibba
Sce
nede
smus
su
bspi
catu
s Le
pom
is
mac
roch
ius
Dap
hnia
mag
na
Bra
chyd
anio
reri
o
--
EC
50 (p
irlse
rate
)
EC
50
(imob
iilia
tion)
EC
5O (
cell
dens
ity)
72h
EC5O
(gm
wth
e
bti
on
) 48
h E
C50
(gm
wih
in
hibi
ion)
chan
nel c
atfis
h
blue
giil s
unfis
h
blue
gill s
unfis
h
rain
bow
hu
t
rain
bow
hu
t
bmw
n h
ut
bmw
n h
ut
bmok
tmut
bmok
tmut
lake
trou
t
lake
tmut
wat
er fl
ea
duck
wee
d --
gree
n al
gae
blue
gill s
unfis
h
wat
er fl
ea
zebr
afis
h
Hen
sche
l et a
l(19
97)
Hen
sche
l et a
l(l9
97
)
Hen
sche
l et a
i (19
97)
Hen
sche
l et a
l(199
7)
Hen
sche
l et a
l(l9
97
)
142
>I0
00
3 260
--
45
Con
cent
ratio
n (~
QIL
)
7.5
48h
LC50
24h
LC50
48h
LC50
24h
LC
~O
-
48h
LC50
--
24h
LC50
48h
LC50
24h
LC50
48h
LC50
24h
LC50
48h
LC50
-
Wilf
ord
(196
6)
Wilf
ord
(1 96
6)
-.
W
ilfor
d (1
966)
-
. --
Wilf
ord
(196
6)
Wilf
ord
(196
6)
Wilf
ord
(1 96
6)
5.65
i10
64.5
--
60.5
21.2
110
54
89.5
74.5
13
2.13
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in W
ebb
OL---
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in W
ebb
12
00
1L
-p
R
epor
ted
in W
ebb
(2001) -
Rep
orte
d in
Web
b (2
001)
Wili
ord
(1 96
6)
-
Rep
orte
d in
Web
b (?
001)
48h
EC
50
(hrn
hili
i)
EC
50 (g
mw
th)
EC
50 (g
mw
th)
LC50
EC
50
48h
LC50
Wilf
ord
(196
6)
Wilf
ord
(196
6)
-. -
Wilf
ord
(1 96
6)
Wilf
ord
(196
6)
Wilf
od
(196
6)
Cle
uven
(200
4)
Cle
uver
s (20
04)
Cle
uven
(200
4)
--
FD
AC
DE
R (1
996)
FDA
-CD
ER
(199
6)
=he1
a a1
(199
7)
64
110
> 3
20
> 9
82
130
85
Rep
orte
d in
Web
b (20!?!--
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in W
ebb
(20
01
)---
. R
epor
ted
in W
ebb
1200
1)
Rep
orte
d in
Web
b (2
001 1
--
---
~e
po
rle
d in W
ebb
(200
1)
Rep
orte
d in
Web
b 20
01)
(
1 W
QM
U! ~
41
od
a~
1 (9661) 8
30
3-~
01
] "LC
] 0
93
31
e
w ~
a)e
m[
eudew e
pq
de
q
ap
pq
au
~~
u~
~~
I
I I
I I
.- (~nnzfl
I
I (e
la ~
a&
aq
ua
~lo
~l
0001 <I
33
01
48
tl e
a~
J
~~
MI
eudew e
!y
de
ak
a
~o
ze
pu
wa
wl
I I
I I
sons I
..
. (
4~
~6
)
OS
33 ae6le u
aw
6
snw
sep
au
a3
~ ~
lolwdolayy
I (a~
!suauadAq!lue) ~a
y3q
q-m
ag
6rup le
In3
sen
o!p
m
0~
37
4
8~
qsY
eyepew
--
-
- .. .-
6rup ~q
n3
se
ng
pm
(
~0
16
)
09
33
paam
ysnp eqq!6 euw
a7
OS
31.489 podiqdw
e e3alze e
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A~
-ier'
le la
!ysmole!za
EI 3lloqelaw) 3
30
11
- eay la
lem
l eu6ew
ep
qd
ea
l lo
lcud
o~
aw
l I (aysuauadA
qgue) ~ayxq
q-m
ag
(zn
nz)l
I I
I I
I (e
la !ysm
ole!za eay ~
ale
m
eu6ew q
uyd
ea
lqcudw
ayy I (a
~!su
au
ad
~q
!iIe)
~a
y3q
q-e
lag
(Z
OO
Z)
le la
!qsmole!za
eay ~a
lem
eu6ew
e~
uyd
ea
(zooz) ru
p Jeln3seA
o!pm
le la
!ysmolelzg
"9 O
S31
eay ~a
lem
eu6ew
eyq
de
a
Bi
up
qn
3s
e~
qp
le
3
(1002) le
la la
66
n~
6'E
9 O
E4
8P
eay ~
ale
m
eu6ew e
yqd
ea
3
11
ao
urlu
fi R
ID J
~I
~~
S~
AO
ID
J~
~
(ZO
OZ
) le la la66n1i
8'8
0
53
1 489
eay Jalem
elqnp e!uqdepo!~a3 (qcudqayy
I (a~!suauadA
q!aue) laymlq
-wa
g
(a3uasau!wnf
(~6
61
) le
la l
aw
ua
~
OZZL
1x33 W
OE
eya
pe
q lua3sau!w
nl !Jaq3sy W
~!
A
a~
exw
ow
ayy
aRew
nawgue '3gsqdoeuguy
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
Ch
em
lca
l Cla
ss
Ant
ihyp
erte
nsiv
e I ca
rdio
vasc
ular
&!-
Ant
ihyp
erte
nsiv
e I ca
rdio
vasc
ular
!!
!!
;
Per
sona
l car
e pr
oduc
t - fra
gtan
ce
Per
sona
l car
e pm
duct
- fra
gran
ce
Per
sona
l car
e pr
oduc
t - fr
agra
nce
Per
sona
l car
e pm
duct
- frag
ranc
e
~e
ko
na
l care
- f
ragr
ance
Per
sona
l car
e pr
oduc
t - fta
gran
ce
.-
~n
al~
~a
nti
-in
fla
mm
ato
ly
Ch
em
ica
l Nam
e
Moe
xipr
il (M
oexi
prila
t - ac
tive
met
abol
ite)
Moe
xipr
il (M
oexi
prih
t - ac
tive
met
abol
iie
~u
sk
ke
tone
(n&
m
usk)
Mus
k ke
tone
(n
lm m
usk)
Mus
k ke
tone
(ni
tro
mus
k)
Mus
k xy
lene
(ni
tro
mus
k)
Mus
k xy
lene
(ni
tro
mus
k)
Mus
k xy
lene
(ni
tm m
usk)
.
Nap
mxe
n
Nap
mxe
n
Nap
mxe
n
Nap
mxe
n
=rial c
are
prod
uct - f
ragr
ance
Pe
rso
na
l car
e pm
duct
- fra
gran
ce
pe
rso
na
l car
e pm
duct
- frag
ranc
e
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) I
card
iova
scuh
r dr
ug
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) I
card
iova
scul
ar dr
ug
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) I
I
Ant
ibio
tic
Ana
lges
idan
tiinl
lam
mat
oly
Spe
cies
Dap
hnia
mag
na
Mus
k xy
lene
(ni
tro
mus
k)
Mus
k xy
lene
(ni
tm m
usk)
Mu
sk
xyl
ene
(nitr
o m
usk)
.
Nad
olol
Nad
olol
Nad
olol
Nad
olol
Na
liixi
c ac
id
Na
liixi
c ac
id
Na
liixi
c ac
id
Nap
mxe
n
kp
o Aed
in
Ta
r etx
(1
997)
R
epor
ted
in T
as e
t al
1997
k
ep
oie
d in
la
s e
ci
11
997)
--
Ref
eren
ces
FD
A-C
DE
R (
1996
)
Le
rmi+
---
mac
roch
uus
Onc
orhy
nchu
s m
ykis
s - un
spec
ified
fish
s
pc
ies
C
erio
daph
nia
dubi
a
Dap
hnia
mag
na
Hya
lella
azt
eca
Med
aka
Vib
rio li
sche
ri
ViM
o fi
sche
ri
Vib
rio fi
sche
ri
Dap
hnia
mag
na
Da
ph
niK
gn
a
Dap
hnia
mag
na
Des
mod
esm
us
subs
pica
tus
Ref
eren
ce R
ep
ort
ed
In
Rep
orte
d in
Web
b
op-
Acu
te A
qu
atic
Co
mm
on
N
am
elA
nim
al T
ype
wat
er fl
ea
48h
EC
50
@nm
obiIii)
.
48h
EC
50
Qni
nm_o
bility
) N
OE
C
~
'wat
er fl
ea
wat
er fl
ea
gree
n al
gae
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in T
as e
t al
LI
Ep
R
epor
ted
in T
as e
t al
1997
k
ep
oie
d in
Tas
eG
~
(199
7 R
ep
ori
d in
Tas
et 2
(199
7)
Rep
orte
d in
Tas
et a
l (1997)
Rep
orte
d in
Tas
et a
l 19
97
Dap
hnia
mag
na
ele e
ns bu
m ca
pric
ornu
tum
S
elen
sbum
ca
pric
wnu
tum
S
elen
stru
m
ca
p~
ic
~x
~m
D
aphn
ia m
agna
Dap
hnia
mag
na
Sel
ensb
um
ca
icor
nutu
m
biue
gill
sunf
ish
rain
bow
trou
t
fish
wat
er fl
ea
wat
er il
ea
amph
ipod
-
fish --
lum
ines
cent
bac
teria
lum
ines
cent
bac
teria
lum
ines
cent
bac
teria
wat
er fl
ea
To
xici
ty
166.
3
174
100
.-
--
Des
mod
esm
us
-su
bsp
iatu
s
wat
er fl
ea
blu
eg
ree
n a
lgae
blue
-gre
en a
lgae
blue
-gre
en a
lgae
wat
er fl
ea
wat
er fl
ea
blue
-gre
en a
lgae
End
poin
t
EC
50
-~
~le
uv
ers
(2
003a
)
Cle
uver
s (2
004)
~z
ve
rs
(2
003a
)
~p
gree
n al
gae
EC
50 (g
row
th)
625.
5 C
leuv
ers
(200
3a)
. .
Co
nce
ntr
atio
n
(mg
lL)
800
Ade
ma
and
La
ng
erw
erf
ll98
5b
) M
inis
try
of
Inte
rnat
iona
l Tra
de
Ade
ma
and
Lang
ey$f
1!98
5c)
Hug
get e
t al(2
002)
Hug
get e
t a1
(200
2)
Hug
get e
t a1
(200
2)
Hug
get e
t a1
(200
2)
Bac
khau
s et
a1
(199
7)
Bac
khau
s et
al(
l99
7 j
Bac
khau
s an
d G
rimm
e (1
999)
C
leuv
ers
(200
3a)
96h
LC50
-
96h
LC50
48h
LC50
48h
LC50
48h
LC50
48h
LC50
.- 48h
LC50
30m
EC
50
(lum
ines
cenc
e)
24h
EC
50
(ium
ines
ce_n
ce)
24
h E
C50
flu
min
esce
nce)
48
h N
OE
C
EC
50
72h
NO
EC
EC
5O (
biom
ass)
EC
50 (g
row
th ra
te) -
48h
EC
50
1.2
--
> 1
000
3.75
2 0
0
.
r 0
0
5;
00
r 0
0
> 1
1.6
(lim
l of
solu
bilit
y)
0.18
4
0.20
6
32
> 1
000
0.08
8
0.1
18
0.24
4
> 5
.6
-
FD
A-C
DE
R (1
996)
- Gri
ihn
er (
1995
a)
~%
hn
er
(199
%)
G1i
jtzne
r(l9
95a)
Hug
hs a
nd
Kris
hnas
wam
i (19
85)
Hug
hs a
nd
Kris
hnas
wam
i (19
85)
Pay
ne a
nd H
a11
(197
9)
- . - -
NO
EC
(sw
imm
ing
beha
viou
r 5d
NO
EC
)(nu
mbe
r of
cel
ls)
0.32
> 5
.6
-. -
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
16pe
cies
C
om
mo
n
Co
nce
ntr
atio
n I
INam
eIA
nim
al T
ype IEn
dpoint
I C
hem
ical
Cla
ss
Uap
mxe
n
Uap
mxe
n
Uap
mxe
n
Uap
mxe
n so
dium
Fa
d et
al(2
001)
%TI
I I
I I
I I
I
Che
mlc
al N
ame
I I
~~
~d
ri
~~
~~
et
a1 (
1992
) I
Rep
orle
d in
Web
b rm
ni i
Sce
nede
smus
su
bspi
ca1u
s V
ibrio
fisc
heri
Vib
rio ti
sch
ki
Dap
hnia
mag
na
> 3
20
I I
1 ..
r=2'
I~na
lges
idan
ti-in
flam
mat
ory
l~a
pm
xe
n
sodi
um
t96h
LC
50
1383
R
odng
uez
et a
l(1
99
2)
Rep
orte
d In
Web
b
Acu
te A
quat
ic T
oxi
clty
Cle
uver
s (2
004)
gr
een
alga
e
lum
ines
cent
bac
teria
- lu
min
esce
nt b
acte
ria
wat
er fl
ea
Ref
eren
ces
EC
50 (g
row
th)
EC
50
(bio
lum
ines
cenc
e in
hibi
tion)
--
EC
50
(bio
lum
ines
cenc
e in
N$
&n
) 24
h E
C50
Ana
lges
idan
tiinf
lam
mat
oiy
Ana
lges
idan
tiinf
lam
mat
ofy
l~h
olin
erg
ic ag
onis
t I IN
icot
ine
I~o
ldfi
sh
l~
old
fis
h
Ref
eren
ce ~
ep
or6
d
In
I L
1
Nap
mxe
n so
dium
Nap
mxe
n so
dium
Nef
azod
one
HC
L
Nko
tlne
Gu
mc
ha
nn
el b
lock
er -
l~if
ed
i~in
e
ai
&s
ci
ie
&E
C
60
Cho
liner
gic
agon
ist
Cho
liner
gic
agon
ist
Cho
liner
gic
agon
ist
Cho
liner
gic
agon
ist
antia
ngin
al a
gent
1 ca
rdio
vasc
ular
I
I
I I~
um
ine
sce
nce
) A
ntih
yper
tens
ive,
ant
iang
inal
l N
isol
dipi
ne
Dap
hnia
mag
ne
lwat
er fl
ea
1~
~5
0
Lepo
mis
m
acro
chtu
s O
ncw
hync
hus
my@
s_
Dap
hnia
mag
na
Dap
hnia
mag
na
card
iova
scul
ar d
ru
Ant
i-inf
ectiv
e (t
opic
al)
Nitr
ofur
azon
e
blue
gill s
un
Fh
96
h LC
50
. .
rain
bow
tmut
96
h LC
50
wat
er fl
ea
EC
50
wat
er fl
ea
Nic
otin
e
Nic
otin
e
Nic
otin
e
Nic
otin
e su
lfate
Ant
i-inf
ectiv
e (t
opic
al)
1 Nitm
fura
zone
I
~o
r~
ne
~a
mt
ri
pe
d
bass
t2
4h
LC
50
Ant
iinfe
ctiv
e (t
opic
al)
Ant
i-inf
ectiv
e (t
opic
al)
72h
LC50
(la
rvae
) A
nti-i
nfec
tive
(top
ical
) 96
h LC
50
Lepo
mis
m
acro
chlv
s O
ncor
hync
hus
myk
iss
Pim
epha
les
prom
elas
P
imep
hale
s
--
Hug
hes
(197
3)
blue
gill s
unfis
h
.
rain
bow
tmut
fath
ead
min
now
fath
ead
min
now
4 7 20
13.8
--
35
33
L I
I (lar
vae)
I
I I
II
.
LC50
LC50
LC50
96h
LC50
1200
1)
10
Hug
hes
(197
3)
FD
~C
DE
R
(199
6)
FD
A-C
DE
R (1
996)
FD
A-C
DE
R (
1996
)
Rus
som
et a
3199
7)
Bac
khau
sand
G
rimm
e (1
999)
F
DA
-CD
ER
(199
6)
(200
1 R
ePo$
in
Web
b
(20
01
)._
__
R
epor
ted
in W
ebb
(200
1)-
Rep
orte
d in
Web
b (2
001
Re
po
ied
in W
ebb
(2_0
0 1 )
Rep
orte
d in
Web
b
Tabl
e A
.3:
Su
mm
ary
of A
cute
Eff
ects
Dat
a
ISp
rln
IN
am
elA
nim
aI
Co
mm
on
T
ype IEn
dpoint
l~o
nc
mtn
tio
n
(mg
lL)
I I
I I
I I
I I
Ant
i-inf
ectiv
e (t
opic
al)
1 Nitr
ofur
azon
e l~
en
ae
us
se
lferu
s lw
hite
shr
imp
124h
LC
50
b5
l~
oh
ns
on
(197
6)
IRe
~o
lle
d in W
ebb
Ch
em
lca
l Cla
ss
..
.
be
ct
iv
e (top
ical
) -
1 Nitr
ofur
azon
e
I I
I I
I I
I
Ch
em
ica
l Nam
e A
cute
Aq
ua
tic T
oxi
city
1 I
Sel
enas
trum
1 bl
ue-g
reen
alg
ae
1~
~5
0
11.4
5
. ,
2001
) {M
acri
an
d S
bard
ella
I(
Ref
eren
ces
Ref
eren
ce R
ep
ort
ed
In
Hor
mon
e -s
ynth
etic
form
of
pmge
stog
en
Ant
ibio
tic -
fluom
quin
olon
e
Ant
ibio
tic - f
luor
oqui
nobn
e
Ant
ibio
tic - f
luom
quin
obne
Ant
ibio
tic - f
luom
quin
obne
Ant
ibio
tic - fl
uom
quin
obne
Gb
io~
c
- fluo
mqu
inok
me
Ant
ibio
tic - fl
uom
quin
obne
Ant
ibio
tic - f
luom
quin
olon
e
Ant
ibio
tic - f
luom
quin
olon
e
Ant
ibio
tic - f
luom
quin
obne
Ant
ibio
tic - f
luom
quin
olon
e
Ant
ibio
tic - f
luom
quin
olon
e
Ant
ibio
tic - f
luom
quin
olon
e
Ant
ibio
tic - f
luom
quin
obne
Ant
ibio
tic - f
luom
quin
oion
e
I~n
tib
imti
c - fluo
mqu
inok
me
Nor
ethi
ndm
ne
Nor
Aox
acin
Nor
Aox
acin
Nor
Aox
acin
~fl
ox
ac
in
OR
oxac
in
Oflo
xaci
n
Oflo
xaci
n
OR
oxac
in
Ant
ibio
tic - f
luor
oqui
nolo
ne
Ant
ibio
tic
Ant
ibio
tic
Ant
ibio
tic
--
OR
oxac
in
OR
oxac
in
OR
oxac
in
Otlo
xaci
n
Oflo
xaci
n
Oflo
xaci
n
OR
oxac
in
OR
oxac
in
capr
icor
nutu
m
Dap
hnia
mag
na
Sce
nede
smus
va
cuol
atgs
V
im
Lc
he
ri
Vib
ria L
ch
eri
-
- - - --
Vibr
ia fi
sche
ri
Pse
udok
irchn
erie
lla
subc
apita
la
Era
chio
nus
ca/y
cfio
rus
Cyc
lote
lla
men
eghi
nian
a C
erio
daph
nia
mag
na
OR
oxac
in
Ola
quin
dox
Ola
quin
dox
Ola
quin
dox
cycl
otei
ia
men
eghi
nian
a D
aphn
ia m
agna
Pse
udom
onas
put
&
Pse
udok
irchn
erie
lla
s"ka
e!!a
!a- --
Sce
nede
smus
va
cuol
atus
S
ynec
hoco
ccus
le
opde
nsis
S
ynec
hoco
ccus
le
opol
ensi
s V
ituio
fisc
heri
wat
er fl
ea
gree
n al
gae
lum
ines
cent
bac
teria
lum
ines
cent
bac
teria
.- --
. .
-.
lum
ines
cent
bac
teria
gree
n al
gae
mtif
er
diat
om
wat
er fl
ea
Vitu
io fi
sche
ri
Dap
hnia
mag
na
Dap
hnia
mag
na
Sel
enas
bum
ca
pric
ornu
tum
diat
om
wat
er fl
ea
- -
bact
eria
gree
n al
gae
gree
n al
gae
blue
-gre
en a
lgae
blue
-gre
en a
lgae
-. 48
h E
C50
(s
wim
min
g in
hibi
tion)
E
C50
24
h E
C50
(iu
min
esce
nce)
24
h E
C50
pu
min
esce
nce)
-- - - -
-
30
min
EC
50
Ilum
ines
cenc
e)
96
h E
C50
(gro
wth
)
48h
NO
EC
C
repr
oduc
tion)
9
6h
NO
EC
(gro
wth
)
48h
LC50
lum
ines
&t
bact
eria
. w
ater
flea
wat
er R
ea
.- .--
blue
-gre
en a
lgae
.-
96
h E
C50
(gro
wth
)
48h
LC50
- - -- - -
EC
50 (g
row
th
inhi
bitio
n)
96
h N
OE
C (
grow
th)
EC
50
96
h E
C50
(gro
wth
)
Q6h
NO
EC
(gr
owth
)
.
. 6.
41
69
.6
0.02
2
0.02
2
> 9
0
4.74
12.5
0.31
2
26.7
lum
ines
cent
bac
teria
l24h
EC
50
24h
EC
50
---- -
48hr
LO
EC
48h
LOE
C
72
h E
C50
0.09
06
76.5
8 --
- - - --
0.0
1
2.5
--
82.8
0.01
6
0.00
5
---
(1 98
4)
Got
o a
nd
Him
mi
(200
3)
Bac
khau
s e
t a1
(200
0)
Bac
khau
s e
t al(
20
00
)
Bac
khau
s an
d
_G@
!~I! (1
9%3
Far
rari
et a
l(2
00
3)
Far
rari
et a
i (20
03)
Far
rari
et a
1 (2
003)
Far
rari
et a
l(2
00
3)
Far
rari
et a
l(2
00
3)
Far
rari
et a
i (20
03)
Far
rari
et a
l(2
00
3)
- Kum
mer
er e
t al
j20
00
) F
an
ari
et a
1 (2
003)
Bac
khau
s e
t a1
(200
1)
--
Fa
na
ri e
t al(
20
03
)
--
Fa
na
ri e
t al(
20
03
)
0.01
4
0.01
4
10
00
-
-.
Bac
khau
s e
t a1
(200
0)
Bac
khau
s an
d G
rimm
e (1
99%
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olle
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oJ
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Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
I Spe
cies
Che
mlc
al C
lass
C
hem
lcal
Nam
e
I Com
mon
I
IK;;ntratio
n 1
Nam
elA
nim
al T
ype
Acu
te A
quat
lc T
oxic
lty
I card
iova
scul
ar d-
rug
I B
eta-
bloc
ker (
antih
yper
tens
ive)
I
l~m
pa
no
lol
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) I
card
iova
scul
ar d
rug
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) I
men
eghi
nia_
na
I D
aphn
ia m
agna
lw
ater
flea
&
h E
C50
Refe
rence
s
Dap
hnia
mag
na
wat
er fl
ea
Hug
get e
t a1
(200
2)
~a
ph
nia
mag
na
wat
er fl
ea
EC
50
2.7
Liliu
s et
al(
lG4
) R
epor
ted
in W
ebb
_ ~
20
01
)_
D
aphn
ia m
agna
w
ater
flea
48
h LC
50
2.75
~=i
et a
l(200
3)
Ref
eren
ce R
epor
ted
In
Pm
pano
lol
Pm
pano
lol
Dap
hnra
mag
na
wat
er fl
ea
LC50
1
6
~z
ialo
ws
k~
et
al
LOE
C (g
row
th)
0 44
D
zial
owsk
~ et a
l
t card
iova
scul
ar d
rug
I B
eta-
bloc
ker (
antih
yper
tens
ive)
I
l~m
~a
no
lol
mag
na
~~
~~
~~
~~
,l
l
Cer
ioda
phni
a m
agna
Cyc
lote
lla
card
iova
scul
ar dr
ug
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) I
Pm
pano
lol
cxar
gmya
scul
ar d
rug
1 I
I I ra
te)
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) I
l~m
pa
no
lol
1 l~
ya
lell
a azte
ca
lam
phip
od
148h
LC
50
wat
er fl
ea.
diat
om
48h
LC50
24
.3
Hug
get e
t al(2
002)
85 p
M
Lavi
lle e
t al(2
004)
--
96h
NO
EC
(gm
wth
) 5
Far
rari
et a
l(200
31
I 1-
I .
. c
ard
iov
as
~b
rd~
g
I subC
apita
ta
Bet
a-bl
ocke
r (an
tihyp
erte
nsiv
e) I
l~m
pa
no
lol
t
l~ce
ne
de
smu
s Ig
reen
alg
ae
1~
~5
0
(gro
wth
) 15
8
(200
4)
I
48h
LC50
96-h)
subs
pica
tus
Syn
echo
cocc
us
blue
-gre
en a
lgae
96
h E
C5O
(gm
wth
) 0.
668
Far
rari
et a
l(200
3)
-..
leop
dens
is
Syn
echo
cocc
us
blue
gree
n al
gae
96h
NO
EC
(gro
wth
) 0.3
5 F
arra
ri et
al(2
003)
le
opde
nsis
A
nti-m
alar
ial
Pyr
imet
ham
ine
Vi&m
fis
cher
i lu
min
esce
nt b
acte
ria 2
4h E
C60
25
B
ackh
aus a
nd
.- (lu
min
esce
nce)
A
nthe
lmin
thic
; ant
imal
aria
l Q
uina
crin
e lc
talu
rus p
unct
atus
ch
anne
l cat
fish
24h
LC50
19
6 W
ilfor
d (1
966)
R
e~
ort
ed
in W
ebb
1.51
0.24
4
1-Icha
nneI
catfi
sh
li8
h L
C50
Far
rari
et a
l(200
3)
Far
rari
et a
1 (2
003)
Ant
helm
inth
ic; a
ntim
alar
ial
Qui
nacr
ine
Lepo
mis
m
acro
chru
s Q
uina
crin
e Le
pom
is
mac
roch
uus
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
I Spe
cies
-
-
Che
mic
al C
lass
C
hem
ical
Nam
e
Com
mon
N
amel
Ani
mal
Typ
e
Acu
te A
quat
ic
bnth
elm
inth
ic; ~
ntim
ala
ria
l ~
~u
in
a~
ri
ne
l~
al
m~
m~
n
trout
Ant
helm
inth
ic;
antim
alar
ial
Ant
helm
inth
ic;
antim
alar
ial
Ant
helm
inth
ic;
antim
alar
ial
~u
ina
crin
e
-.
--
I ..ye.--- I-.
(~n
the
lmin
thic
; antim
alar
ial
l~u
ina
crin
e
Sa
lve
hu
s la
ke tr
out
Qui
nacr
ine
Qui
nacr
ine
Onc
hory
nchu
s m
ykis
s S
alm
o bu
lta
-
rain
bow
tmut
brow
n tm
ut
-- -
Qui
nacr
ine
Sal
velrn
us
lake
tmut
Qui
nacr
ine
HC
L
card
iac
depr
essa
nt
card
iac
depr
essa
nt
(ant
iary
thm
ic
Mus
cle
rela
xant
. car
diac
dep
ress
ant
(ant
iany
thm
ic)
Mus
cle
rela
xant
, car
diac
dep
ress
ant
(ant
iarf
ythm
ic)
card
iac
depr
essa
nt
bock
er(a
nty&
%en
sive
) I
IR-(*)
Pro
pano
lol
I I
I~
em
ia
salin
a lb
rine
shrim
p
Ant
imal
aria
l
An
tima
b~
ial
1
Bra
chio
nus
mtif
er
,
card
iova
scul
ar d
rug
caly
ci/fo
rus
-
Dap
hnia
mag
na
wat
er fl
ea
Qui
nidi
ne s
ulfa
te
Qui
nidi
ne s
ulfa
te
Qui
nidi
ne s
ulfa
te
Qui
nidi
ne s
uff
ite
Qui
nidi
ne s
ulfa
te
Qui
nine
bis
uff
ite
Qui
nine
HC
L
Qui
nine
sul
fate
--
Art
emia
sal
ina
Bra
chio
nus
_~ak
c!!~
rls-
Dap
hnia
mag
na
Dap
hnia
mag
na
Str
epto
ceph
alus
po
bosc
ideu
s P
enae
us s
etfe
rus
Ant
ipsy
chot
ic. C
NS
age
nt
.- Met
abol
ite - a
cety
lsal
icyl
ic a
cid
En
dp
oin
t I~
on
ce
ntr
atl
on
(m
glL
) 1
To
xicl
fy
brin
e sh
rimp
- mtif
er
wat
er fl
ea
wat
er fl
ea
fairy
shr
imp
whi
te s
hrim
p
Sev
eral
spe
cies
of
fish
(trou
t) P
enae
us s
elfe
rus
kh
whi
te s
hrim
p
Ris
perid
one
Sal
icyl
ic a
cid
I
I
I
Ref
eren
ces
48h
LC50
24h
LC50
48h
LC50
48h
LC50
--
24h
LC50
48h
LC50
--
24
h L
C50
24h
LC50
24h
LC50
EC
50
24h
EC
50
24h
LC50
24h
LC50
48h
LC50
24h
LC50
24h
LC50
-- 24
h LC
50
-.
.-
24h
EC
50
24h
LC50
EC
50
EC
50
LC50
24h
EC
50
Lepo
mis
I
Fu
nt
is
h
~~
c~
oC
~K
US
Dap
hnia
mag
na
wat
er fl
ea
Ref
eren
ce R
epor
te
In
122
300
230
-
230
25
21
-
7.7
247
8.7 -
60
60
-- 8.3
13.1
>lo
0
13.8
407 -
2.59
15.8
7
1.87
650
6 .-
6 > 14
40
Wilf
ord
(196
6)
.- W
ilfor
d (1
966)
wil
foii
96
6)
Wilf
ord
(196
6)
- W
ilfor
d(19
66)
-
Wilf
ord
(196
6)
John
son
(197
6)
Cal
leja
et a
1 (1
994b
)
Cal
leja
et a
l(l9
94
b)
Liliu
s et
al(1
994)
calle
ja e
t a1
(199
4.)
ca
lkja
a a1
(199
4.)
~oh
nson
-76)
wilf
ord
(196
6)
John
son
(197
6)
Cal
leja
et a
l (19
94b)
ppp
Cal
leja
et a
l(l9
94
b)
-~-----
Cal
leja
et a
1 (1
994b
)
~a
lle
ja et a
l(l9
94
b)
FD
AC
DE
R (1
996)
FD
A-C
DE
R (1
996)
FDA
CD
ER
(19
96)
Brin
gman
n an
d K
uhn
(1 98
2)
Rep
orte
d in
Web
b 20
01
ke
po
h in
we
br
(2
0!Y
p
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in W
ebb
(2001)p
-p
Rep
orte
d in
Web
b ~*
?!?!)
Rep
orte
d in
Web
b (2
001)
-
_
Rep
orte
d in
Web
b P
oo
l)
Rep
orte
d in
Web
b @o
orl-.p
Rep
orte
d in
Web
b (2
00_!l
-p
Rep
orte
d in
Web
b
2001
-- -
ke
po
Ld
in W
ebb
2001
ke
poA
ed in
we
bP
2_
'?1
kp
oL
in W
ebb
(2001)
Rep
orte
d In
Web
b (2
001)
R
epor
ted
in W
ebb
(200
1)
Rep
orte
d in
Web
b 1
2E
&
Rep
orte
d In
Web
b 12001)----
Rep
orte
d in
Web
b 20
01
kep
o Aed
in
Web
b (2
001 )
R
epor
ted
in W
ebb
(*O
!!-
Rep
orte
d in
Web
b 20
01
iep
o Ae
d in
Web
b (2
001
Rep
oAed
in w
~M
JO
Ol
)
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
Ch
em
ica
l Cla
ss
Met
abol
ite - a
cety
lsal
icyl
ic a
cid
Met
abol
ite - a
cety
lsal
icyl
ic a
cid
Met
abol
ite - a
cety
lsal
icyl
ic a
cid
Met
abol
ite - a
cety
lsal
icyl
ic a
cid
~e
tab
oli
te - a
cety
lsal
icyl
ic a
cid
Met
abol
ite - a
cety
lsal
icyl
ic a
cid
Met
abol
ite - a
cety
lsal
icyl
ic a
cid
Met
abol
ite - a
cety
lsal
cylii
c ac
id
Met
abol
ite - a
cety
lsal
icyl
ic a
cid
Ant
iast
hmat
ic
Ant
ibio
tic
Ant
ibio
tic
Ant
ibio
tic
Sed
ativ
e, h
ypno
tic
~n
tifl
atu
len
t
Ant
ibio
tic
Ant
ihyp
erte
nsiv
e
Ant
ihyp
erte
nsiv
e
Ant
i(ret
r0)v
iral
Ant
ibio
tic - a
min
ogly
cosi
de
Ant
ibio
tic - a
min
ogly
cosi
de
Ant
ibio
tic -
amin
ogly
cosi
de
Che
mic
al N
ame
Sal
icyl
ic a
cid
Sal
icyl
ic a
cid
Sal
icyl
ic a
cid
Sal
icyl
ic a
cid
salic
ylic
aci
d
Sal
icyl
ic a
cid
salic
ylic
aci
d
Sal
icyl
ic a
cid
Sal
icyl
ic a
cid
Sal
met
eml
Sar
aRox
acin
Sar
aflo
xaci
n
Sar
aflo
xaci
n
Se
cob
arb
iil,
sodi
um s
alt
Sim
ethi
cone
Spi
ram
ycin
Spi
rapr
il HC
L
Spi
rapr
il HC
L
Sta
vudi
ne
Str
epto
myc
in
Str
epto
myc
in
Str
epto
myc
in
Spe
cies
Bra
chyd
anio
rerio
(e
mn
ws)
-
Bra
chyd
anio
rerio
(e
mb
']!o
sL
Dap
hnia
mag
na
Dap
hnia
mag
na
Lepo
mis
m
a~
oc
h~
~
-
Sce
nede
smus
su
bspi
~&tu
s T
etra
hym
ena
PY@
?!K
V
ibrio
fisc
heri
Vib
rio L
ch
eri
Dap
hnia
mag
na
Mic
rocy
stis
ae
rugi
nosa
R
hodo
mon
as s
alin
a
Sel
enas
trum
ca
pri
cw~
utu
m
Pim
ephd
es
omel
as
Pd
~p
hn
ia mag
na
Sel
enas
eum
ca
pric
ornu
tum
D
aphn
ia m
agna
Lepo
mis
m
acr0
ch;v
us
Dap
hnia
mag
na
Ref
eren
ces
Hen
sche
l et a
i (19
97)
Hen
sche
l et a
l(199
7)
Wan
g an
d La
y (1
989)
~e
ns
ch
el et
ai (
1997
) .-
Hen
sche
l et a
i (1
99
7)
Hen
sche
l et a
l(l9
97
) -
Hen
sche
l et a
l(l9
97
)
Far
re e
t a1-1
)
~e
nx
he
iet al(1
997)
FD
AC
DE
R (1
996)
Hol
ten
Lutz
hoR
et a
l (1
999)
H
olte
n Lu
lzho
fi et
al
P?
9L
.
Hol
ten
Luhh
oR e
t al
(1 99
9)
Ros
sum
et a
1 (1
997)
Hob
bs (1
975)
Hal
ling-
Sor
ense
n (2
00
9
FD
A-C
DE
R (
1996
)
FD
A-C
DE
R (1
996)
FD
AC
DE
R (1
996)
Ref
eren
ce R
ep
ort
ed
In
-
Rep
orte
d in
Web
b (2
001 )
Rep
orte
d in
Web
b 20
01
kp
ok
d in w
et%
(2
001
)
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in W
ebb
(200
1)
Rep
orte
d in
Web
b
Acu
te A
qu
atic
To
xici
ty
1200
1)
-
Co
mm
on
N
amel
Ani
mal
Typ
e
zebr
afis
h.
zebr
afis
h
wat
er fl
ea
wat
er fl
ea
blue
giil s
unfis
h ce
lls
Sel
enas
trum
ca
pric
or~u
rwum
M
icro
cyst
is
aeru
gino
sa
Dap
hnia
mag
na
End
poin
t
48h
LC50
EC
50 (
puls
e ra
te)
24h
EC
50
EC
50
(imm
obili
zatio
n)
EC
50 (
cell
dens
ity)
-
blu
eg
ree
n a
lgae
blu
eg
ree
n a
lgae
wat
er fl
ea
,
Co
nce
ntr
atio
n
(mg
lL)
37
50
230
--
118
> 5
00
> 1
00
> 1
00
41.3
90
20
0.01
5
. .-
24
16
23.6
44.5
2.3
.- > 9
30
> 9
70
> 9
80
gree
n al
gae
cilia
ted
Pm
tozo
ai
lum
ines
cent
bac
teria
MIC
MIC
48h
EC
5O
-.
72h
EC
50 (g
row
th
inhi
bitio
n 48
h E
Cd
(gro
wth
in
hibi
tion)
E
C50
(b
iium
ine
sce
nce
in
hibi
tion
- Tox
Ale
rt
100)
.-
2.1 -
0.3
487
lum
ines
cent
bac
teria
wat
er fl
ea
blue
-gre
en a
lgae
-
mar
ine
mic
mai
gae
blu
eg
ree
n a
lgae
fath
ead
min
now
wat
er fl
ea
blue
-gre
en a
lgae
wat
er fl
ea
blue
gill s
unfis
h
wat
er fl
ea
Har
rass
et a
1 (1
985)
Har
rass
et a
1 (1
985)
~o
lle
nb
er6
et
al
(200
0)
..
30m
EC
50
jlum
Lne_
senc
e)
EC
50
EC
50
~
EC
50
EC
50
96h
EC
50
48h
TL5
0
72h
EC
50
- E
C50
,
LC50
EC
50
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
I C
hem
ical
Cla
m
Che
mic
al N
ame
Acu
te A
quat
lc T
oxlc
lty
,-
Reh
renc
e8
( Ref
eren
ce R
epor
te'
Ant
ibio
tic - a
min
ogly
cosi
de
Ant
ibio
tic - a
min
ogly
cosi
de
Ant
ibio
tic - a
min
ogly
cosi
de
Ant
ibio
tic - s
ulbn
amid
e
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ubna
mid
e
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
nam
ide
Stre
ptom
ycin
stre
ptom
ycin
Stre
ptom
ycin
Sul
fabe
nzam
ide
-
Sul
fach
lom
pyrid
azin
e
~u
ifa
ch
lom
~~
rid
&e
Sul
fadi
azin
e
Sul
fadi
azin
e
Sul
fadi
azin
e
Sul
fadi
azin
e
Sul
fadi
azin
e -
Sul
fadi
azin
e
Sui
fadi
azin
e
Sul
fadi
azin
e
Sul
fadi
rnet
hoxi
ne
Sul
fadi
met
hoxi
ne
Sui
fadi
met
hoxi
ne
Sul
fadi
met
hoxi
ne
Sul
fadi
met
hoxi
ne
Sul
fadi
met
hoxi
ne
Ant
ibio
tic - s
ulfo
nam
ide
Sui
fadi
met
hoxi
ne
Ant
ibio
tic - s
ulfo
nam
ide
Sul
fadi
met
hoxi
ne
Ant
ibio
tic - s
ulfo
nam
ide
Sul
fam
eraz
ine
Sev
eral
spe
cies
of
Spe
cies
Dap
hnia
mag
na
Sel
enas
bum
ca
picc
fnut
um
Vib
rio fis
cher
i
Sce
nede
smus
va
cuol
atus
D
aphn
ia m
agna
Uns
peci
fied
spec
ies -
zebr
afis
h M
icro
cyst
is
aeru
gino
sa
. -
Ckr
hinu
s m
rigal
a
~a
ph
nia
mag
na
Dap
hnia
mag
na
Dap
hnia
mag
na
Dap
hnia
mag
na
Rho
dom
onas
sal
ina
Sel
enas
bvm
ca
pric
y-ut
um
Arte
mia
sal
ina
(na3
plii)
A
rtem
ia s
alin
a (n
aupl
ii)
Arte
mia
sal
ina
(nau
pbi)
Arte
mia
sal
ine
(nau
plii)
A
rtem
ia s
alin
a na
uplii
) A
rtem
ia s
alin
a
brin
e sh
rimp
--
brin
e sh
rimp
fish
Com
mon
N
amel
Anl
ma1
Typ
e
wat
er R
ea
blue
-gre
en a
lgae
lum
ines
cent
bac
teria
gree
n al
gae
wat
er R
ea
zebr
afis
h
blu
Gre
en
alg
ae
carp
wat
er R
ea
wat
er fl
ea
wat
er R
ea
wat
er fl
ea
mar
ine
mic
roal
gae
blue
gree
n al
gae
brin
e sh
rimp
brin
e sh
rimp
brin
e sh
ri,mp
brin
e sh
rimp
brin
e sh
rimp
brin
e sh
rimp
End
poin
t
24h
EC
50
--
72h
ECSO
24h
EC
50
(lum
ines
cenc
e)
.- --
ln
hibi
ton
of
repm
duct
iin
48h
EC
50
96h
LC50
EC
50 (p
opul
atio
n)
EC
(g
row
)
48h
EC5O
24h
EC
50
(ph
ys
gy
) 48
h E
C50
Ip
hysi
oiog
y)
72h
EC
50
(phy
siol
ogy)
E
C50
EC
50
Rep
orte
d in
Web
b (2
001)
Mig
liore
et a
l(199
3)
Mig
liore
et a
l(199
3)
Wilb
rd (1
966)
72h
LC50
--
96h
LC50
48h
LC50
Con
cent
ratio
n (m
glL)
947
0.13
3
8.21
17.4
2-50
.
> 1
000
0.13
5
-
537
-. 19
.5 --
> 1
00
Wol
lenb
erge
r et a
l (2
000)
B
ackh
aus
and
G_r
imm
e (1
999)
B
ackh
aus
and
Grim
me
(199
9)
Mey
er e
t a1
(200
0)
~-
-
(1 99
9)
Bra
mbi
lla e
t a1
(199
4)
Bra
mbi
lla e
t a1
(199
4)
Bra
mbi
lla e
t a1
(1 99
4)
Bra
mbi
lla e
t a1
(199
4)
--
Mig
liore
et a
l(199
3)
Mig
liore
et a
l(199
3)
24h
LC50
48h
LC50
72h
LC50
96h
LC50
24h
LC50
.-
48h
LC50
Nov
artis
(199
9)
- Nov
artis
(1 99
9)
Hon
en L
utzh
oft e
t al
--
.-
--
--
221
-
112
88
--
57
403
7.8
1866
851
537
19.5
1866
851
Wol
lenb
erge
r et a
l (2
000)
U
SE
PA
(200
1)
US
EP
A (
2001
)
US
EP
A (2
001)
--
Hok
en L
utzh
oft e
t el
1199
9)
HoR
en L
utzh
oft e
t al
le la ~
a6
~e
qu
allo
~
OPE 3
30
~-W
P
eay ~a
~e
rn
eu6ew ep
qd
ea au
!pA
m]a~
- 3t1o!q!)uy --
(UO
!S!A!P
Ilea u! uo!pnpw)
(~6
61
) le la
uoslalad 9 L
05
33
~Z
L
wq
e!p
W~
I!J~
JS
O~
~
e!q
3s
q~
w
13A3w
1a1- wocqauv
(00027 u
as
ua
~o
~-6
u!lle
~
2.Z 0
53
3 ~
ZL
ae6le ua
a~
6a
nlq
w
nqseuales e
u!W
wa
) - q~o
!q!~u
w
Tab
le A
.3:
Su
mm
ary
of A
cute
Eff
ects
Dat
a
I C
hem
lcal C
lass
I
Chem
icalN
am
e
I A
cute
Aquatic
To
xici
ty
I R
efer
ence
s I Re
fere
nce
Report
ed
I..
Ant
ibio
tic -
tetr
acy
clin
e
Ant
ibio
tic -
tetr
acy
clin
e
Ant
ibio
tic -
tetr
acyc
line
Ant
ibio
tic - t
etra
cycl
ine
-
Ant
ibio
tic - t
etra
cycl
ine
Ant
ibio
tic -
tetr
acy
clin
e
Ant
ibio
tic -
tetr
acy
clin
e
Ant
ibio
tic - t
etra
cycl
ine
Bm
ncho
dila
tor
Bro
ncho
dila
tor
Bm
ncho
dila
tor
Bm
ncho
dila
tor
Bro
ncho
dila
tor
Ane
sthe
tic
Ant
ipsy
chot
ic, C
NS
agent I
ca
rdio
vasc
ular
dru
g A
ntip
sych
otic
. CN
S a
gent I
card
iova
scul
ar d
rug
Ant
ipsy
chot
ic, C
NS
age
nt I
card
iova
scul
ar d
rug
Ant
ipsy
chot
ic. C
NS
age
nt 1
c
ar
d@
~a
~~
lar
dr
ug
Ant
ipsy
chot
ic, C
NS
age
nt I
card
iova
scul
ar d
rug
-
Ant
ineo
plas
tic
[~n
tib
ioti
c
Tet
racy
clin
e
~%
mc~
clin
e
Tet
racy
clin
e
Tet
racy
clin
e -.
Tet
racy
clin
e .
Tet
racy
clin
e
Tet
racy
clin
e
Tet
racy
clin
e
The
ophy
lline
--
The
ophy
lline
The
ophy
lline
The
ophy
lline
The
ophy
lline
Thi
open
tol,
sodi
um s
ale
Thi
orid
azin
e
Thi
orid
azin
e
Thi
orid
azin
e
Thiir
idazi
ne
Thi
orid
azin
e
Thi
otep
a
lTim
ulin
Specl
es
Cra
ssos
bea
giga
s
Cul
ex
qu
inq
ue
fas
cia
tus
~
Cul
ex
quin
quef
asci
atus
C
ulex
q
uin
qu
eim
ktu
s -.--
Pho
toba
cter
ium
P
~O
SP
~~
%~
X~
~
Vib
rio li
scheri
--
Vib
rio li
scheri
%br
io
fmch
eri
Arte
mia
sal
ina
- Bra
chio
nus
caly
cifl~
yus
Dap
hnia
mag
na
Dep
hnia
ma
gn
a
Sbe
ploc
ephe
lus
prob
osci
deus
P
imep
hale
s
von!e
&s
Art
emia
sal
ina
Bra
chio
nus
caly
ciflw
us
Dap
hnia
mag
na
Dap
hnia
mag
na
Sbe
ptoc
epha
lus
prob
osci
deus
D
aphn
ia m
agna
IDap
hnia
mag
na
Com
mon
Narn
elA
nim
al T
ype
oyst
er
mo
sq
u6
'
mos
quito
mos
quito
mar
ine
bact
eria
lum
ines
cent
bac
teria
lum
ines
cent
bsc
teria
lum
ines
cent
bac
teria
brin
e sh
rimp
mtif
er
wat
er fl
ea
wat
er fl
ea
fairy
shr
imp
fath
ead
min
now
brin
e sh
rimp
mtif
er
wat
er fl
ea
wat
er fl
ea
fairy
shr
imp
wat
er fl
ea
lwate
r fle
a
End
poin
t
48h
LC50
4Bh
LC50
Effect
on
Rep
rodu
ctio
n LC
1 00
15m
in
Jum
ines
cenc
e)
24h
EC
50
(lum
ines
cenc
e)
30m
EC
50
(lum
ines
cenc
e)
24h
EC
50
(lum
ines
cenc
e)
24h
LC50
zh
LC50
EC
50
-. 24
h E
C50
24h
LC50
96h E
C50
24h
LC50
24h
LC50
24h E
C50
24h
E&
24h
LC50
24h
EC
50
)24h E
C50
Co
nce
ntr
atio
n
(m
d~
)
520-
579
127.
8
127.
8
300
38
0.02
51
19.6
0.02
41
8247
3926
155
. 48
3
425
26.2
14.5
0.3
0.69
4.56
0.3
3
546
181
US
EP
A (2
001)
US
EP
A (2
001) -~
U
SE
PA
(200
1)
US
EP
A (
2001
)
Pet
erso
n et a
l(1993)
Bac
khau
s an
d G
rimm
e (1
999)
B
ackh
aus
et a
l(l9
97
)
Bac
khau
s et
a1
(199
7)
Cal
leja
el a
1 (1
994b
)
Cal
leja
et a
l(l9
94
b)
Liliu
s et a
1 (1
994)
Cal
leja
el a
1 (1
994b
)
Cal
leja
et a
1 (1
994b
)
Rus
sum
et a
1 (1
997)
-
Cal
leja
el a
1 (1
994b
)
Cal
leja
et a
1 (1
994b
)
Liliu
s et
al(
lG4
)
Cal
leja
el a
1 (1
994b
)
Cal
leja
el a
1 (1
994b
)
FD
A-C
DE
R (1
996)
l~o
lle
nb
erg
er e
l al
--
--
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in W
ebb
(200
1)
Rep
orte
d in
Web
b (2
001)
R
epor
ted
in W
ebb
po
ol)
R
epor
ted
in W
ebb
(2001)
Rep
orte
d in
Web
b
~~G!EL-
Rep
orte
d in
Web
b (2
001
Re
po
ied
in ~
eb
r
(?
!?
!E
L
Rep
orte
d ~
n Web
b 12
001)
R
epor
ted
in W
ebb
(200
1)
Rep
orte
d in
Web
b (2
001
Re
p0
lW in
web
b-
i2%.--
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
I C
hem
lcal
Cla
ss
Ant
ibio
tic I
I Ant
ibio
tic
Bon
e m
odul
atin
g dr
ug - o
steo
pom
sir
Bon
e m
odul
atin
g dr
ug - o
steo
pom
si!
-.
Ana
lges
ic
1 Antis
eptic
Ant
isep
tic
Ant
isep
tic
I Ant
isep
tic
I Ant
ibio
tic - d
iam
inop
yrim
idin
e
Che
mlc
al N
ame
~ri
clo
sa
n
AP
IIhal
es
fath
ead
min
now
96
h LC
50
0.26
pr
omel
as
--
Tric
losa
n A
naba
ena
flos-
bl
uegr
een
alga
e 72
h E
C50
0
0009
7
Tia
mul
in
Tia
mul
in
rT;
et
(2Ei-i-Iyp
72h
EC
50
Orv
os e
t al(2
002)
bi
omas
s in
hibi
tion
72h
NO
EC
ILO
EC
0
.00
05
~0
01
2 O
rvos
el a
1 (2
002)
(b
iom
ass
inhi
bitio
n)
Acu
te A
quat
ic T
oxlc
lty
--
~T
~~
~~
~~
G~
~~
~~
zF
\~
~~
--
~
-. -
-. -
Tri
cbsa
n S
cene
desm
us
gree
n al
gae
72h
NO
ECIL
OEC
0.
0005
10.0
012
Orv
os e
t a1
(200
2)
I su
bspi
catu
s (b
iom
ass
inhi
bitio
n)
Tilu
dmna
te d
isod
ium
D
aphn
ia m
agna
w
ater
flea
4
8h
~c
50
32
0 S
anof
i (19
96)
Rep
orte
d in
Web
b (2
001)
T
iludm
nate
dis
odiu
m
Dap
hnia
mag
na
24h
EC
50
562
San
ofi (
1996
) R
epor
ted
in W
ebb
. -
L200
1)-._
_-
Tol
azol
ine
Pim
epha
les
fGe
ad
min
now
Q
6h E
C50
35
4 R
ossu
m e
t al(
l99
7)
Rep
orte
d in
Web
b --
prom
elas
..
~
-
(200
1)
Tm
mad
ol
Uns
peci
fied
fish
fish
LC50
13
0 FD
A-C
DE
R (1
996)
R
epor
ted
in W
ebb
.-
0
Tre
tinoi
n D
aphn
ia m
agna
w
ater
flea
E
C50
73
FD
A-C
DE
R (1
996)
R
epor
ted
in W
ebb
Tric
bsan
~
ap
hn
ia
ma
gn
al
GG
~a
48
h E
C50
Spe
cies
Sel
enas
trum
c
~~
nu
&m
D
aphn
ia m
agna
Tric
bsan
S
elen
astru
m
blue
gree
n al
gae
. 72h
EC
50
0.00
5 O
rvos
et a
l(20
02)
capf
kyut
um
[~ri
cbsa
n
Ske
leto
nem
a m
arin
e di
atom
72
h E
C50
>
0.06
6 O
rvos
et a
l(20
02)
c=um--
Trim
etho
prim
A
ctiv
ated
slu
dge
bact
eria
E
C50
17
.8
bact
eria
--
-
Trim
etho
prim
B
rach
ydan
io re
rio
zebr
afis
h 72h
NO
EC
>
100
&
lling
-~or
ense
n et
al
-
(200
0)
Trim
etho
prim
D
aphn
ia m
agna
w
ater
flea
48
h E
C50
12
3 H
allin
g-S
oren
sen
el a
l
Ref
eren
ces
Ref
eren
ce
I- R
epof
tec
Com
mon
N
amel
Ani
maI
Typ
e
blue
gree
n al
gae
wat
er fl
ea
72h
EC
50
48h
EC
50
Con
cent
ratio
n (m
glL)
0.16
5
40
Hal
ling-
Sor
ense
n (2
000)
W
olle
nber
ger e
t al
1200
0)
Tabl
e A
.3:
Sum
mar
y of
Acu
te E
ffec
ts D
ata
--
I C
hem
ical
Cla
ss
Ant
ibio
tic - d
iam
inop
yrim
idin
e I
p<tib
iotic
- di
amin
opyr
imid
ine
- mac
mlid
e
Cal
cium
chan
nel b
lock
er I
card
iova
scul
ar d
rug
Cal
cium
chan
nel b
lock
er I
card
iova
scul
ar d
rus
Cal
cium
chan
nel b
lock
er I
Che
mic
al N
ame
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Trim
etho
prim
Tyl
osin
Tyl
osin
Val
pmic
aci
d
Ver
alpa
mil
Ver
alpa
mil
Ver
alpa
mil
Ver
alpa
mil
Ver
apam
il
Ref
eren
ces
Hol
ten
Lubo
R e
t al
(1 99
9)
Hal
ling-
Sor
ense
n et a
l @
El
Hol
ten
Lubo
R e
t al
(1
99
9L
--
H
olte
n L
ub
ofl
et a
l LlE
%9
Hal
ling-
Sor
ense
n et a
l (2
!!?
-
Hal
ling-
Sor
ense
n (2
000)
W
olle
nber
ger e
t ai
12
EO
L._
._ .-
Hem
nann
(199
3)
Cal
leja
et a
l(l9
94
b)
ca
lkre
t a1
(199
4.)
Liliu
s et
al(1
994)
Cal
leja
et a
l(l9
94
b)
Cal
leja
et a
l(l9
94
b)
Co
nce
ntr
atio
n
(mw
)
112
112
16
130
110
1.38
680
- 0.1
mM
10.9
55.5
327
6.24
356
Spe
cies
Mic
rocy
stis
ae
rugi
nosa
M
icro
cyst
is
ae
ru
gin
~-
R
hodo
mon
as s
alin
a
Sel
enas
bum
ca
pric
ornu
tum
S
elen
astru
m
c=~n
ujum
S
elen
as!~
um
capr
icor
nutu
m
Dap
hnia
mag
na
Bra
chyd
anm
rw
ia (e
mbr
yos)
Bra
chio
nus
caly
citI
(~u
s D
aphn
ia m
agna
Dap
hnia
mag
na
Str
epto
ceph
alus
pr
obos
cide
us
Atte
mia
sal
ina
Ref
eren
ce R
epor
ted
In
-- Rep
orte
d in
Web
b (2
001
Rep
oAed
in W
ebb
(200
1)
Rep
orte
d in
Web
b
(2
00
1L
--
R
epor
ted
in W
ebb
(200
1)
Rep
orte
d in
eb
b
Acu
te A
quat
ic
Com
mon
N
amel
Anl
mal
Typ
e
blue
-gre
en a
lgae
blue
gree
n al
gae
mar
ine
mic
mal
gae
blue
-gre
en a
lgae
blue
gree
n al
gae
.
blue
gree
n al
gae
wat
er fl
ea
zebr
afis
h
mtif
er
wat
er fl
ea
wat
er fl
ea
-
fairy
shr
imp
brin
e sh
rimp
To
xicl
ty
End
poin
t
EC
50
EC
50
--
EC
50
EC
50
EC
50
72h
EC
50
48h
EC
50 --
LOA
EC
(em
bryo
de
velo
pmen
t m
alfo
rmat
ions
)
24h
LC50
24h
EC
50
24h
EC
50
24h
LC50
24h
LC50
Tab
le A
.3:
Su
mm
ary
of A
cute
Eff
ects
Dat
a
Che
mlc
al C
lass
P~
gu
la
nt
I W
arfa
rin
Che
mlc
al N
ame
I
I~
n~
co
ag
ul
an
t~
I
war
farin
Ant
icoa
gula
nt
IAn
tic
oa
gu
bn
t 1 W
arfa
rin
War
farin
Ant
icoa
gula
nt
Ant
icoa
gula
nt
I
Acu
te A
quat
lc T
oxlc
lty
I R
efer
ence
s I R
efer
ence
Rep
orte
d
Ant
icoa
gula
nt
War
farin
Not
es:
EC
50 =
Con
cent
ratio
n whe
re a
n ef
fect
isob
serv
ed in
50%
of t
he te
st o
rgan
ism
s E
C50
val
ues
in D
aphn
ia ti
pica
lly r
elat
e to
imm
obili
zatio
n E
C50
val
ues
in a
glae
rel
ate
to e
ffect
s up
on g
mw
th (b
iom
ass
or c
ell n
umbe
r)
LC50
= C
once
ntra
tion r
esul
ting
in 5
0% o
f tes
t org
anis
m le
thal
ity
LOE
C =
Low
est o
bser
vabl
e ef
fect
s co
ncen
tratio
n N
OE
C - N
o ob
serv
able
effe
cts
conc
entra
tion
MIC
- min
imum
inhi
bito
ry co
ncen
tratio
n T
L50
- Sta
tistic
ally
der
ived
ave
rage
tim
e in
terv
al d
urin
g w
hich
50%
of a
giv
enpo
pula
tion
may
be
expe
cted
to
die
follo
win
g ac
ute
adm
inis
tratio
n of
a c
hem
ical
or
phys
ical
age
nt (r
adia
tion)
at a
giv
en c
once
ntra
tion
unde
r ad
efin
ed s
et o
f con
ditio
ns
LC50
val
ues
rela
te to
leth
ality
all
orga
nism
s E
C50
val
ues
in D
aphn
ia ti
pica
lly r
elat
e to
imm
obili
atio
n - u
nles
s ot
herw
ise
stat
ed
EC
50 v
alue
s in
Agl
ae r
elat
e to
effe
cts
upon
gm
wth
(bio
mas
s or
cel
l num
ber)
- unl
ess
othe
rwis
e st
ated
Spe
cies
Arte
mia
sal
ina
Bra
chio
nus
caly
c~o
rus
-
Dap
hnia
mag
na -
Da
ph
nk
mag
na
Ras
bora
he
tero
mor
pha
--
Ras
bora
he
tero
mor
pha
Ras
bara
he
tero
mor
pha
-- . .-
Sbe
ptoc
epha
lus
prob
osci
deus
D
aphn
ia m
agna
Com
mon
N
amel
Ani
mal
Typ
e
brin
e sh
rimp
mtif
er
wat
er fl
ea
wat
er fl
ea
harle
quin
fish
harle
quin
fish
harle
quin
fish
fairy
shr
imp
wat
er fl
ea
End
poin
t
24h
LC50
-. -
24h
LC50
24h
EC
50
24h
EC
50
.-
96h
LC50
48h
LC50
24h
LC50
24h
LC50
EC
50
Con
cent
ratio
n O
WL
)
3638
444
89
475
- 12
14
17
342 --
> 1
790
~
~
Cal
leja
et a
l (l9
94
b)
Cal
leja
et a
l(l9
94
b) -
Liliu
s et
al(1
994)
Cal
leja
et a
l(l9
94
b)
Too
by e
t al(
l97
5)
Too
by e
t al(
l97
5)
Too
by e
t al(
1975
)
Cal
leja
et a
l(l9
94
b)
DF
C-C
DE
R (1
996)
--
Rep
orte
d in
Web
b (2
001 )
R
epor
ted
in W
ebb
@E
L
Rep
orte
d in
Web
b (2
301)
-
Rep
orte
d in
Web
b (2
001)
--
Rep
orte
d in
Web
b -
2001
L
ep
o Ae
d in
we
bg
-
Tab
le A
.4:
Sum
mar
y of
Chr
onic
Eff
ects
Dat
a
(con
trac
eptiv
e)
Horm
one - o
vula
tion
inhib
itor
(con
trac
eptiv
e)
Go
ne
- ovu
latio
n in
hibi
tor-
(c
ontr
acep
tive)
-
Hor
mon
e - o
vula
tion
inhi
bito
r (c
ontr
acep
tive)
H
orm
on
e -o
vula
tion in
hib
itor
(con
trace
p!i\r
e)
Hor
mon
e - o
vula
tion
inhib
itor
(con
trac
eptiv
e)
Hor
mon
e -o
vula
tion in
hibi
tor
(con
trac
eptiv
e)
Hor
mon
e - o
vula
tion
inhi
bito
r (c
ontr
acep
tive)
H
orm
on
e - o
vula
tion
inhib
itor
(con
trac
eptiv
e)
Hor
mon
e - o
vula
tion
inhi
bito
r (c
ontr
acep
tive)
H
orm
one
- ovu
latio
n in
hibi
tor
(con
trac
eptiv
e)
Hor
mon
e - o
vula
tion
inhi
bito
r (c
ontr
acep
tive)
Chem
ical C
lass
Hor
mon
e - o
vula
tion
inhi
bito
r
Hor
mon
e - o
vula
tion
inhi
bito
r
~H
~l
&i
on
in
hibi
tor
Chem
ical N
ame
17 a
lpha
eth
inyl
estra
diol
(con
trac
eptiv
e)
Hor
mon
e - o
vula
tion
inhi
bito
r co
ntra
cept
ive)
H
orm
one
- ovu
latio
n in
hibi
tor
[con
trac
eptiv
e)
Hor
mon
e - o
vula
tion
inhi
bito
r co
ntr
ara
tive
H
orm
one
- ovi
ati
on
in
hib
K
(con
trac
eptiv
e) I co
ntra
cept
ive)
Hor
mon
e - o
vula
tion
inhi
bito
r (c
ontr
acep
tive)
Hor
mon
e - o
vula
tion
inhi
bito
r (c
ontr
acep
tive)
Ch
ron
lc A
qu
atlc
To
xici
ty
Zili
ioux
et a
1 (2
001)
Refe
rence
s
And
erso
n et
a1
(200
1)
Spe
cies
Aca
rtia
tons
a
17 a
lpha
eth
~nyl
est
rad
iol ic
yp
no
do
n v
ar
ie
ga
tu
s~
~P
~m
in
i~
-
-fish
su
rviv
al)
T~
I~
il
li
ou
xi
i*
(2
~1
)r
~
I
Refe
rence
R
eport
ed I
n
-
I7 al
pha
ethi
nyle
stra
diol
C
ypfin
odon
va
riega
tus
jshe
epsh
ead
min
now
INOE
C (f
imis
of t
estis
) ~
0.0
000002 -ux
et a
1 (2
001)
1
I
Co
mm
on
N
amel
Ani
maI
Typ
a co
pepo
d na
uplii
17 a
lpha
eth
inyl
est
rad
Cyp
rin
od
on
var
iega
lus
:she
epsh
ead
min
now
iLO
EC
(fib
rosi
s o
f ~~
st
is
)~
0.
00
00
02
~~
~2
~~
~-
En
dp
oln
UD
ura
tion
I
(mglL
) 5d
EC
50 (l
arva
l 10
.088
I 17
alp
ha e
thin
yles
tradi
ol
Cyp
rinod
on
~~
~~
~~
-~
-~
0.
oo
oo
02
~~
il
li
ou
x
varie
galu
s sh
eeps
head
min
now
N
OE
C (t
estis
-ova
) et
a1
(2001 )
I I7
alp
ha e
thin
yles
tradi
ol l
Cyp
inod
on
varie
gatu
s is
heep
shea
d m
inm
INO
EC
(rep
ro&
ctio
n)
Fq
li
00
~
et a1
(20
01) I
I
I I
I
I
I - .
--
1 I
17 a
lpha
eth
inyl
estra
diol
C
yprin
odon
m
inno
w
LOE
C (r
epro
duct
ion)
0.
002
12illi
oux
et a
1 (
20
d~
r
varie
gahr
s sh
eeps
head
min
now
I I
I C
yprin
odon
var
iega
lus
shee
pshe
ad m
inno
w
NO
EC
(ha
tchi
ng s
ucce
ss)
0.00
002
\-
LOE
C (t
estis
-ova
)
1 I
I
1
.-
shee
pshe
ad m
inno
w
I I
I
17 a
lpha
eth
inyl
estr
adio
l D
aphn
M sp
p w
ater
flea
l~
chw
ein
furt
h et a
l 'k
eport
ed in
I I
17 a
lpha
eth
inyl
estra
diol
Ly
mna
ea s
tagn
alis
po
nd s
nail ---!
50-6
0d L
OE
C g
row
th
0.00
002
offs
prin
g)
-
17 a
lpha
eth
inyl
estra
diol
17 a
lpha
eth
inyl
estra
diol
Zill
iux e
t al(2001)
NO
EC
(hat
chin
g su
cces
s)
(199
6)
Dap
hnia
spp
Gam
mar
us p
ule
x
.17 a
lpha
eth
inyl
estra
diol
17 a
lpha
eth
inyl
estra
diol
I I
-
17 a
lpha
eth
inyl
estr
adio
l P
imep
hale
spfo
mel
as
fath
ead
min
now
- 28
d LO
EC
(mor
talit
y)
adul
t
0.00
2
Box
all e
t al
17 a
lpha
eth
inyl
estra
diol
17 a
lpha
eth
inyl
estra
diol
P
imep
hale
s pro
me
las
fath
ead
min
now
- 28
4 LO
EC
(mor
talit
y)
juve
nile
I
Zill
iux e
t al (
2001
)
wat
er fl
ea
amph
ipod
Onc
hory
nchu
s myk
iss
Onc
hory
nchu
s myk
iss
I m
inno
w -
28d
LOE
C (de
crea
sed
grow
th)
28-w
k pl
asm
a vi
tello
geni
n ra
inbo
w t
r7
lL
OE
c
rain
bow
trou
t 10
-d p
lasm
a vi
tello
geni
n
Pim
epha
les p
rom
ela
s
21d
NO
EC
(im
mo
bili
atio
n)
1Od
LC50
0.00
0001
25
0.00
0000
3 --
0.00
001
2 a
]000
1 fa
thea
d m
inno
w -
adul
t
> 0
.387
1.5
28d
LOE
C (i
nhib
ited
egg
prod
uctio
n)
r a0
01
Sch
wei
nfur
th e
t al
Rep
orte
d in
(1
996)
B
oxai
l et a
l
Bei
froid
and
Le
on
ard
~
(199
6)
She
ahan
et a
l(1994)
FWR
(1
992)
Sch
wei
nfur
th e
t al
(199
6)
Sch
wei
nfur
th e
t ai
1996
L
tts
'et
ai (
2001 )
--
Rep
orte
d in
W
ebb
(200
1)
Rep
orte
d in
W
ebb (2
001)
Rep
orte
d in
W
ebb
(2001)
Rep
orte
d in
B
oxal
l et a
l (2
004)
f20_
04Lp
R
epor
ted
in
Box
all e
t a12
004
Tabl
e A
.4:
Sum
mar
y of
Chr
onic
Eff
ects
Dat
a
~i
pd
re
gula
tor
Lip
id re
gula
tor
l~n
ti-in
flam
ato
ry -
IDex
amet
hazo
ne
ICer
ioda
phni
a du
bia
lwat
er fl
ea
17da
y E
C50
(re
prod
uctio
n)
10.0
5 ID
ella
Gre
ca e
t a1
(200
4) I
I M
etab
olite
- cb
fibra
te
IClo
fibric
a.c~
d F
arra
ri et
al(2004)
Far
rari
et a
l(2004)
Clo
fibra
te
Clo
fibra
te
Web
b-f2
001)
72h
NO
EC
(gr
owth
) t
I100
-(D
WG
reca
et a
1 1-
(200
4)
Web
b (2
001)
21
d E
C50
(rep
rodu
ctio
n)
0.10
6 R
epor
ted
in
---Iz;
; fle
a a
~p
lz
p~
~o
pf
(1
995)
--I-
Dap
hnia
mag
na
Web
b (2
001)
K
bpf (
1995
) R
epor
ted
in
Uns
peci
fed
alga
e
cort
icos
tero
ld
Ant
i-inf
iam
ator
y - co
rtic
ost
em
id
Ana
lges
icln
on-s
tero
idal
anti-
in
flam
mato
ly (N
SA
ID)
Ana
lges
icho
n-st
eroi
dal a
nti-
infl
am
ma
ry (
NS
AID
) H
orm
one
- syn
thet
ic fo
rm o
f es
trog
en
Hor
mon
e - s
ynth
etic
form
of
estr
ogen
-
(rep
rodu
ctio
n)
I I F
arra
ri et
al(2004) 1
-
- --
-- -
Bal
dwin
et a
1 (1
995)
fre
quen
cy)
--
Dex
amet
hazo
ne
Dic
lofe
nac
Dic
lofe
nac
Deth
ylst
ilbest
rol
--
Die
thyl
stilb
estr
ol
Pse
udok
rchn
erie
Na
subc
apita
ta
Cer
ioda
phni
a du
bia
Dan
io re
rio
-- --
Dap
hnia
mag
na
Dap
hnia
mag
na
gree
n al
gae
wat
er fl
ea
-
zebr
afis
h em
bryo
wat
er fl
ea
wat
er R
ea
Tab
le A
.4:
Sum
mar
y of
Chr
onic
Eff
ects
Dat
a
Chem
ical C
lass
Per
sona
l car
e pr
oduc
t - fr
agra
nce
Per
sona
l car
e pr
oduc
t - fr
agra
nce
A
nalp
sicl
anti-
infla
mat
ory
Ant
ibio
tic - a
mm
ogly
cosi
de
Ant
ibio
tic - a
min
ogly
cosi
de
Ant
ibio
tic -
arni
nogl
ycos
ide
-
Ant
ibio
tic - a
min
ogly
cosi
de
@$b
iotic
- a
min
ogly
cosi
de
Cho
liner
gic
agon
ist
Ant
ibio
tic - f
luor
oqui
nolo
ne
Ant
ibio
tic - R
uoro
quin
olon
e A
ntib
iotic
- flu
oroq
uino
lone
A
ntib
iotic
- flu
omqu
inol
one
An
bti
c - f
luor
oqui
nolo
ne
Ant
ibio
tic - f
luor
oqui
nolo
ne
Ant
ibio
tic - f
luor
oqui
nolo
ne
Antib
ollc
- flu
oroq
uino
lone
A
ntib
iotic
- fluoro
quin
~~
lone
Ant
ibio
tic - f
luor
oqui
nolo
ne
Ant
ibio
tic - f
lu~
roq
uin
~n
e
&tib
iotic
- fl
uom
quin
olon
e A
ntib
iotic
- flu
oroq
u&ol
one
-. Ant
ibio
tic - fl
uoro
quin
olon
e A
ntib
iotic
- flu
oroq
uino
lone
Chem
ical N
ame
Mus
k xy
lene
(ni
tro
mus
k)
~..
--
Mus
k xy
lene
(ni
tro m
usk)
Nag
mxe
n N
eom
ycin
N
eom
ycin
N
eom
ycin
N
eom
ycin
N
eom
ycin
N
icot
ine
NG
~a
cin
N
orflo
xaci
n N
offlo
xaci
n N
orflo
xaci
n N
orf
lfia_ci
n
N*ac
in N
_o
rRo
~ci
n
Nor
floxa
cin
No
fflo
~c
in
Nor
Rox
acin
N
ex
-a-c
in
Nor
floxa
cJn
Nor
Roy
aCin
N
offlo
xaci
n .N
orR
oxac
in
Spe
cies
Dap
hnia
mag
na
Sel
enst
rum
ca
pric
wnu
tum
Le
mna
gib
ba
Lem
na g
ibba
L
pn
ibb
a
Lem
na g
ibba
Le
mna
gib
ba
-.
Lem
na g
ibba
D
aphn
ia p
ulex
Le
z
jib
ba
Le
mna
gb
ba
Le
mna
gib
ba
Le
mn
ibb
a
--
Le
mn
ag
ibb
a
Lem
na g
ibba
Le
mna
gib
ba
Lem
n-@
ba
Refe
rence
s
Ade
ma
and
Lang
erw
erf
1198
5a)
-_
P
ayne
and
Ha1
1 (1 97
9)
Cle
uve
5 (2
004)
B
rain
~e!_
al(2004) -
.Bra
in e
t al1
2004
) B
rain
et a
i (20
04)
Bra
in e
t al(
20
04
j~
Bra
in e
l a1
(200
4)
FDA
-CD
ER
(1 9
96)
Bra
in e
l al(2004)
Bra
in e
l a1
(200
4)
--
Bra
in e
t al(2004)
-
Bra
in e
t al(2004)
Bra
in e
l a1
(200
4)
.
Bra
in e
l al (
2004
) B
rain
el a
l(2004)
Bra
in e
t a1
(200
4)
Refe
rence
R
eport
ed I
n .
Rep
orte
d in
Tas
et
a1
(199
7)
Rep
orte
d in
Tas
et a
1 (1
997)
--
--
-. -
Rep
orte
d in
W
ebb
(2001)
-. -
Lem
na g
ibba
Le
mna
gib
ba
Lem
na g
ibba
Le
mna
gib
ba
Lem
na g
ibba
Le
mna
gib
ba
Lem
na g
ibba
Ch
mn
lc A
qu
alc
To
xlcl
ty
Co
mm
on
N
am
elA
nlm
al T
ype
w
ater
flea
blue
-gre
en al
gae
duck
wee
d du
ckw
eed
duck
wee
d du
ckw
eed
En
dp
oin
UD
ura
tion
2ld
LC
50 --
5d N
OE
C n
uinb
er o
f cel
ls
EC
50 (g
row
th)
7d
LO
EC
Wet
wei
ght
7d L
OE
C F
rond
num
ber
7d L
OE
C C
hlor
ophy
il a
duck
wee
d du
ckw
eed
duck
wee
d du
ckw
eed.
du
ckw
eed
duck
wee
d _d
uckw
eed
(mflI
L)
0.68
--
> 5
.6
24.2
>
1
> 1
E
L-
7d E
C50
9rop
hyll
b 7d
EC
5O C
arot
enoi
ds
76 E
ClO
Wet
we
bh
t 7d
EC
lO F
rond
num
ber
7d E
C10
Chl
orop
hyll a
7
d E
ClO
Chl
orop
hyll b
7d
EC
10 C
arot
enoi
ds
1.
04
L
1.13
0.
245
0.20
6 0.
903
0.
04
2
0.96
6
>_1_
> 1
0.
07 --
I
1 -
1 1.
1 0.91
3 1.
146
1.07
2
duck
wee
d du
ckw
eed
wat
er fle
a
duck
wee
d '
duck
wee
d du
ckw
eed
duck
wee
d du
ckw
eed
duck
wee
d du
ckw
eed
duck
wee
d B
rain
st a
1 (2
004)
B
rain
el a
l(2004)
Bra
ina
t a1
(200
4) .
Bra
in e
t al(2
@4>
B
r@sa
l(2
00
4)
Bra
in e
l a1 (
2004
) B
rain
et a
l(2004)
7d L
OE
C C
hlo
mp
hflb
74
LO
EC
Ca
role
no
ds
LOE
C (l
engt
h)
7d
LO
EC
Wet
wei
ght
7d L
OE
C F
rond
num
ber
7d L
OE
C C
hlor
ophy
ll a
7d L
OE
C C
hlo
rom
ll b
7d L
OE
C C
arot
enoi
ds
7d E
C50
Wet
wei
ght
7d
EC
50 F
rond
num
ber
Id
EC
50 C
hlor
ophy
ll a
Tabl
e A
.4:
Sum
mar
y of
Chr
onic
Eff
ects
Dat
a
Ant
i-inf
lam
ator
y -
cort
icos
tero
id
Chem
ical C
lass
Ant
ibio
tic - f
luor
oqui
nolo
ne
Ant
ib_m
tic - f
luor
oqui
nolo
ne
Ant
ibio
tic - f
luor
oqui
nolo
ne
Ant
ibio
tic - f
luor
oqui
nolo
ne
Ant
ibio
tic - f
luor
oqui
nolo
ne
.-
Ant
ibio
tic - f
luor
oqui
nolo
ne
Ant
ibio
tic - fl
uoro
quin
olon
e O
floxa
* Le
mna
jib
ba
du
ckw
eed
76 L
OE
C C
arot
enoi
ds
1 B
rain
et a
1 (2
004)
Le
mna
gib
ba
duck
wee
d 7d
EC
50 W
-et w
eigh
t 0L
532
!-rain
et a
i (20
04)
Lem
na g
ibb?
. du
ckw
eed
7dE
KS
Frc
nd!!
&!e
~ U%
L
Bra
in e
t a1
1200
4)
Lem
na-g
ibbb
du
ckw
eed-
- 7d
EC
50 C
hlor
ophy
ll a
Bra
in e
t al(2004)
0.98
0 Le
mna
gib
ba
duck
wee
d 7d
EC
50 C
hlor
ophy
ll b
0.84
B
rain
et a
l (20
04)
&m
na
gibb
a d
!kw
ee
d_
_
7d E
C50
Car
oten
oids
1.
374
Bra
in e
t ai (
2004
) Le
mna
gib
ba
duck
wee
d 7d
EC
lO W
et w
eigh
t 0.
157
Bra
in e
t al(2004)
Lem
na g
i@a
duck
wee
d 7
d_
EG
@F
ron
d@
be
r 0.
121
Bra
in e
t al(2004)
Lem
na g
ibba
du
ckw
eed
7d E
ClO
Chl
orop
Jyll
a 0.
376
Bra
in e
t al (
2004
) Le
mna
gib
ba
duck
wee
d 7d
EC
lO C
hlor
ophy
ll b
0.34
7 B
rain
et a
1 (2
0041
Le
mna
gib
ba
duck
wee
d 7_
4EC
10 C
arot
enoi
ds
0.58
6 B
rain
et a
1 (2
004)
M
icro
cytis
aer
ugin
osa
blue
-gre
en a
lgae
7d
EC
50
5.1
~
Hai
ling-
Sor
ense
n (20
00)
-.
Ant
ibio
tic
Oxo
linic
aci
d D
aphn
ia m
agna
w
ater
fle
a 21
d N
OE
C
0.38
W
olle
nber
ger
et a
l
Chem
ical N
ame
Oflo
xacj
n O
fixaci
n
Oflo
xaci
n O
floxa
cin
Oflo
xaci
n O
floxa
cin
Ch
ron
ic A
qu
atic
To
xici
ty
Refe
rence
s
Far
rari
et a
L(20
04)
F~
ri
e
t al(2004)
Bra
in e
t a1
(200
4)
Bra
in e
t al(2004)
.Bra
-in1a
1_(2
004)
B
rain
et a
l(2
00
41
Refe
rence
R
eport
ed I
n
-~
CO
n;en
'r~io
n m
nlL
10
> 1
6 -.
0.3
1.
1 1
Sp
eci
es
Ce
rio
da
p*n
hu
bia
D
anio
r~
b
Lem
na g
ibba
Le
mna
gib
ba
Le
mrn
ibb
a
Lem
na g
ibba
Co
mm
on
N
ameI
Ani
mal
Typ
e
wat
er fl
ea
zebr
afis
h-em
bryo
du
ckw
eed
duck
wee
d du
ckw
eed
-
duck
wee
d
En
dp
oln
ffD
un
tlon
7d N
OE
~re
~o
du
cti
on
) 10
d N
OE
C (
mor
talit
y)
7d L
OE
C W
et w
eigh
t 7d
LO
EC
Fro
nd n
umbe
r 7d
LO
EC
Chl
orop
hyll a
76
LO
EC
Chl
orop
hyll b
Tabl
e A
.4:
Sum
mar
y of
Chr
onic
Eff
ects
Dat
a
Ref
eren
ce
Re
po
rle
d I
n
Ch
em
lca
l Cla
ss
Hor
mon
e - r
epro
duct
ion
- na
tura
l B
eta-
bloc
ker
(ant
ihyp
erte
nsiv
e) I
Bet
a-bl
ocke
r (a
ntih
yper
tens
ive)
I
-
Bet
a-bl
ocke
r (a
ntih
yper
tens
ive)
I
card
lova
scul
ar d
rug
Bet
a-bl
ocke
r (a
ntih
yper
tens
ive)
I
card
iova
scul
ar d
rug
I I
I I
Spi
ram
ycin
al
gae
7d E
C50
0.
005
Ikiling- o
r ens en
(200
4
Chr
onic
Aq
ua
tic T
oxi
clty
C
hem
ical
Nam
e R
efer
ence
s
Pro
gest
eron
e
. .
.- -
Pro
pano
lol
~ro
~a
no
lol
Pro
pano
lol
Pro
pano
lol
I 1
I I
I~n
ab
ae
na
cyIin
@ic
a [a
lgae
H
arra
ss e
t a1
(198
5 I~
na
ba
en
a flos-
aqua
e Ib
lue-
geen
alg
ae
135d
LO
EC
(g
roe
)
Pro
pano
lol
Ant
ibio
tic -
am
inog
lyco
side
S
trep
tom
ycin
Ant
ibio
tic -
amin
o I
cost
de
Stre
ptom
ycin
lA
nkis
trod
esm
us sp
[a
lgae
I gd
LOE
C (g
row
th)
/Ant
ibio
tic -
am
ino
;blS
tre
pto
m
ycin
l~
ph
an
izo
me
no
n nos-
]a
lgae
35
d LO
EC
(gro
wth
) 10
.86
And
erso
n et
al(
2001
)
Far
rari
et a
1 (2
004)
-
Far
rari
et a
1 (2
004)
Hug
get e
t a1
(200
2)
Hug
get e
t a1
(200
2)
--
Spe
cies
Aca
rtia
tons
a
Cer
ioda
phni
a du
bia
Dan
io re
rio
Cer
ioda
phni
a du
bia
Cer
ioda
phni
a du
bia
Dap
hnia
mag
na
Mic
rocy
iis a
erug
inos
a
Hug
get e
t a1
(200
2)
-
Hya
lella
azt
eca
Lem
na g
ibba
~e
mn
a
gibb
a-
Lem
na-g
~bb
a Le
mna
gib
ba
Lem
na g
ibba
Le
mna
gib
ba
Dap
hnia
mag
na
Hya
lella
azt
eca
wat
er h
a ~
~-
--
I~
~I
(2
0'3)
bl
uegr
een
alga
e 7d
EC
50
0.00
7 H
allin
g-S
oren
sen (
2000
)
I aq
_ae-
Co
mm
on
cope
pod
naup
iii
wat
er fl
ea
zebr
afis
h em
bryo
wat
er fl
ea
wat
er fl
ea
-
Ant
ib~
otic
- am
inog
lyco
side
am
ph
ipo
F
duck
wee
d
dxk
we
ed
amph
ipod
Stre
ptom
ycin
.-
En
dp
oin
tlDu
ratio
n
NO
EC
(5d
EC
50 la
val
deve
lopm
ent)
7d
NO
EC
(rep
rodu
ctio
n)
10d
NO
EC
(mor
talit
y)
-- 76 N
OE
C (r
epro
duct
ion)
74 L
OE
C (r
epro
duct
ion)
.--
-
IChl
amy d
omon
as
(.
u/
~~
(J
s~
Lo
EC
1
6%
kp
lmg
~5
*--
re
inar
dtii
Con
cent
ratio
n Im
glL
) 1 0.
009
2 0.1
25
0.25
27d
NO
EC
(re
prod
uctio
n)
27d
LOE
C (r
epro
duct
ion)
EC
50 (g
row
th)
--
- .. --
7d L
OE
C W
et w
eigh
t
0.00
1
0.1
114
> 1
,d
uckw
eed
d!
~k
.~
~d
~
duck
wee
d =w
eed
wat
er fl
ea
Hug
get e
t a1
(200
2)
Cle
uver
s (2
004)
Bra
in e
t al(2
004)
74
LO
EC
Fro
nd n
umbe
r 7d
LO
EC
Chl
orop
hyll a
7d
LO
EC
Chl
orop
hyll
b 7d
LO
EC
Car
oten
oids
21
4 N
OE
C (
repr
oduc
tion)
> 1
>
1
-
> 1
>
1
< 2
0
Bra
in e
t al(
2004
1 __-
Bra
in e
t la
ljOO
4)
Bra
in e
t a1
(200
4)
Bra
in e
t al (
2004
) W
ang
and
Lay
(198
9)
Tabl
e A.
4: S
umm
ary
of C
hron
ic E
ffec
ts D
ata
ti
io
ti
- uf
na
me
1S
K$j
&K
oxin
e A
ntib
iotic
- su
lfona
mid
e ~S
ulfa
dim
etho
xine
~
~d
dd
~~
~~
W~
IF
1~
,"
~t
(20,471
4 IL
emna
gib
ba
duck
wee
d 7d
LO
EC
Frd
nd n
umbe
r B
rain
et a
1 (2
004)
Tab
le A
.4:
Sum
mar
y of
Chr
onic
Eff
ects
Dat
a
Ch
emic
al C
lass
R
epo
rted
In
Ch
emic
al N
ame
Chr
onic
Aqu
atic
Tox
lclty
R
efer
ence
s R
efer
ence
palms es!rm
ewo sselun - (~
eq
wn
u
1193 JO ssew
o!q) ~0
~6
uodn slseue q
eieleJ ee16v u! sanlen 09
33
P
alms es!rm
elno sselun - uonez!l!qolulu! 01 elelel Alleqdg e
yqd
ea
u! sa
np
0533 sw
s!uef%o Ile h
!leu
iq o
i eie
pJ sanlen 0
53
1
aq Aew uqlelndod W
A!~
e lo
%O
S qqqm
6uunp lemeiu! ew
n e6
e~
en
e panyep file
qs
gq
~ -
UO
!lWlU
e3UO
3 sl3ege qqeNeS
q0 ON
- 33
0N
uoneauesuos siseya qqem
esqo isa
mo
l= 3
30
1
h!le
uiq
ws!ue6~
o isei lo
%O
S u! 6u!ilnsa~
uwe
Jiua
3u
og
= 13531 (~
eq
wn
u Ile3 JO
ssewqq) 4
wa
6 uodn sisege 01 eielw
eel6e u] sanlen 05
33
uo!leq!qow
w! 01 eielaj A
((es!d!i e!uqdea u! sanlen 05
33
S
UJS
!U~~JO
ise
i eui lo %
OS
u! pemesqo s! i3age ue w
aum u
we
1iu
a3
u~
=
0533 paie1nqe3 IO
U
= 3~
:Sa)ON
sp!o
ua
lo~
e3
330
1 P
L paam
ymp
eqq!6 euw
e-j u
!sqA
l e
mlo
~3
ew
- ~!J
O!~
RW
q IIW
~J
~IW
3
30
1 PL
paamym
p eqq!6
euwe-j
u!s
qG
~
ap~om
T5ijolijjLQ
e llh
do
~o
(~3
3
30
1 PL
-- --
paamy3W
egg@
euwe-j
u!solAl
ep!lo~3ew
- 3go!qnuv Ja
Wn
u P
uo
Jj 33
03
paam
ymp
u!so(hl ep!lo~
3ew - ~
nq
q!
~~
~
eg
g6
euwe-j
146!em lw
33
01
PL paam
ymp
eg
g6
euwe-j
u!s
wl
-_ ep
!lo~
xw
- 5ijo!q!luv
paamqm
p e
gg
6 euw
e-j w
ud
olg
aw
y~
I I
pe
e~
wn
p
egg@ euw
e-j w
udoulawu J
paamym
p e
qg
6 euw
e-j w
ud
oq
lew
y~
I
- 6n
ri 6u!ielnpow auog
(a)euoqdsoid!qj I
Tab
le A
.5:
Su
mm
ary
of
Sel
ecte
d A
cute
To
xici
ty V
alu
es
Acu
te A
quat
ic T
oxic
ity
Ch
emic
al C
lass
I
Ref
eren
ces
I R
efer
ence
R
epor
ted
In
Che
mic
al N
ame
-
~
Ant
ineo
plas
tic
Ant
ibac
teria
l
Bet
axol
ol (f
or b
etax
olol
pr
edic
ted
data
-A
lga
e
alga
e .
EC
50
1.24
0 (a
ntih
yper
tens
ive)
I
hydr
ochl
orid
e)
card
iova
scul
ar d
rug
--
Lipi
d R
egul
ator
B
ezaf
ibra
te
pred
icte
d da
ta - A
lgae
al
gae
EC
50
3.53
6 S
ande
rson
et a
1 (2
004)
I
I
I I
I .
,
Aza
serin
e
Azi
thro
myc
in
Bac
itrac
in
Me
mia
sal
ina
(nau
plii)
br
ine
shrim
p 21
.8
48h
LC50
I I
I A
CE
Inhi
bito
r I
ICap
topr
il I Lem
na g
ibba
ld
uckw
eed
lEC
5O (g
row
th)
[2
~l
~l
ek
er
s
(200
4)
Mig
liore
et a
l(1
99
7)
3.15
4 (a
ntih
yper
tens
ive)
I
card
iova
scul
ar d
rug
Stim
ulan
t EC
5Q
6.80
0
Spe
cies
Vib
rio b
che
ri
-
Dap
hnia
mag
na
San
deno
n et
a1
(200
4)
San
ders
on e
t a1
(200
4)
card
iova
scul
ar d
rug
lA
nt
ib
io
ti
cI
ta
*a
do
x
card
iova
scul
ar d
rug
Bet
a-bl
ocke
r C
araz
olol
pr
edic
ted
data
- Dap
hnia
w
ater
flea
(a
ntih
yper
tens
ive)
I
data
- Dap
hnia
w
ater
flea
Com
mon
na
mel
Ani
mal
Ty
pe
.ium
ines
cent
bac
teria
wat
er fl
ea
San
ders
on e
t a1
(200
4)
San
ders
on e
t a1
(200
4)
w-
End
poin
t
24h
EC
50
(lum
ines
cenc
e ~
-
inhi
bitio
n)
.-
EC
50
Car
bam
azep
ine
Bra
chio
nus
caly
ciflw
us
rotif
er
48h
NO
EC
0.
377
(rep
rodu
ctio
n)
Bet
a-bl
ocke
r C
elip
rolo
l (fo
r cel
ipro
lol
pred
icte
d da
ta - A
lgae
al
gae
EC
~O
1.
669
(ant
ihyp
erte
nsiv
e) I
hydr
ochl
orid
e)
Chl
oram
phen
icol
V
ibrio
fisc
heri
lum
ines
cent
bac
teria
24h
EC
50
0.06
Ant
i-ulc
er d
rug I
i Cim
etid
ine
Con
cent
ratio
n
0.15
1
120
Far
rari
et a
l(2
00
4)
--
San
ders
on e
t a1
(200
4)
Bac
khau
s et
a1
(199
7)
Ant
imal
aria
l, an
tiam
ebic
, an
tirhe
umat
ic
Ant
ibio
tic -
tetr
acyc
line
t
Bac
khau
s an
d G
rimm
e (1
999)
--
FD
A-C
DE
R (1
996)
Chl
oroq
uine
pho
spha
te
Chl
orot
etra
cycl
ine
Rep
orte
d in
Web
b 12
001)
Bra
chio
nus
caly
cifw
us
---
Sel
enas
trum
capr
icw
nutu
m
rotif
er
blue
-gre
en a
lgae
24.
LC50
I::
Cal
leja
et a
l(199
4b)-
?Re&e
d in Webb
72h
EC
50
Hal
ling-
Sor
ense
n (2
000)
Tab
le A
S:
Sum
mar
y of
Sel
ecte
d A
cu
te T
oxic
ity V
alu
es
I Co
mm
on
'
na
me
lAn
ima
l
I I
I
Per
ista
ltic s
timul
ant I
l~is
a~
rid
e
l~a
ph
nia
m
agna
1 w
ater
flea
Acu
te A
qu
ati
c T
ox
icit
y
Re
fere
nce
s C
he
mic
al C
las
s
Ant
ibio
tic - f
luor
oqui
nolo
ne
/Ant
ibio
tic - m
acro
lide
I lCla
rithr
omyc
in
Re
fere
nce
R
ep
ort
ed
In
C
he
mic
al N
am
e
Dap
hnia
mag
na I
Cip
roflo
xaci
n
wat
er fl
ea
+-
1 pr
edic
ted
data
- Alg
ae
I lalg
ae
Mic
rocy
stis
aer
ugin
osa
Bet
a ag
onis
t-82
- sy
mpa
thom
imet
ic
hydr
ochl
orid
e)
(bro
ncho
dial
ator
)
Lipi
d re
gula
tor
Clo
fibra
te
Uns
peci
fied
alga
e
Typ
e
blue
-gre
en a
lgae
I M
etab
olite
- clo
fibra
te
Clo
fibric
aci
d
I
I
L
I I
alga
e
I I
I
pred
icte
d da
ta -
Alg
ae
Ant
ibio
tic - p
enic
illin
pred
icte
d da
ta -
Dap
hnia
w
ater
flea
A
nalg
esic
Cyc
lose
rine
IAnb
-lnfla
mat
ow -
I 1
I
1 Dex
amet
hazo
ne
bra
chio
nu
s ca
lyci
floru
s 1 ro
tifer
Clo
xaci
llin
l- C
odei
ne h
ydro
chlo
ride
wat
er fl
ea
Cyc
loph
osph
amid
e
I I
I
I
cort
icos
tero
id
I I
bra
chio
nu
s ca
lvci
foru
s / ro
tifer
pred
icte
d da
ta - D
aphn
ia
Vib
rio fi
sche
ri
I(am
phet
amin
e1ik
e) 1 an
ti-
I I
I
--
lum
ines
cent
bac
teriz
wat
er fl
ea
epile
ptic
P
sych
iatr
ic d
rug
Dap
hnia
mag
na
Imm
unos
uppr
essa
nt
Dap
hnia
mag
na
t
Cyc
losp
orin
e
wat
er fl
ea I
rain
bow
trou
t -
infla
mm
ator
y (N
SA
ID)
1-
hepa
tocy
tes
En
dp
oin
t C
on
cen
tra
tio
n
1 C
50
I>
1000
!F
DA
-CD
ER
(199
6)
ike
po
rte
d in
Web
b
EC
50
1. -
I(2d
01)
San
ders
on e
t a1
(200
4)
EC
50
Kop
f (19
95)
Rep
orte
d in
eb
b-
-
(200
1)
48h
NO
EC
0.
246
, F
arra
ri et
al(
20
04
) :r
epro
duct
ion)
EC
50
23.4
S
ande
rson
et a
1 (2
004)
Rep
orte
d in
Box
all e
t a1
2004
I
--
I
I
I
I
San
ders
on e
t a1
(200
4)
0.00
5
EC
50
I
.- I
EC
50
8.16
8 S
ande
rson
et a
l(2
00
4) I
Hol
ten-
Lutz
hoft
and
Hal
ling-
S
oren
sen
(unp
ublis
hed)
Bac
khau
s and
Grim
me
[lum
ines
cenc
e (1
999)
in
hibi
tion)
0.04
0
FD
A-C
DE
R (1
996)
R
epor
ted
in W
ebb
gh
LC50
D
ella
Gre
ca e
t a1
(200
4)
San
ders
on e
l a1
(200
4)
Cal
leja
et a
1 (1
994b
) R
epor
led
in W
ebb
(200
1 )
24h
EC
50
[cyt
otox
icity
) 16,042
/~a@
!d~
enet
a1 (
2000
Lavi
lle e
t al(
20
04
)
(6661) let* ]uoqanl
uatlou u! pauodau 9'01:
09
33
48P
eau ~a
em
I-
Z.LZ 0
93
3 4PZ
eay ~a
lem
(L66 L) ue
u~
a6
u! j pue no2
eu6ew e
yq
de
a
lonsaqlns(hq)a!a 40 W
JO4 3R
allluhs - au
wJ
oH
(1002) q
qa
~
u! pavo
daa
(9661) ~3
~1
3-v
ad
0201 c
G
33
eay latern
eu6ew e!u
ydea
au!souep!a ~
e~
!~(o
na
~)n
uy
Tab
le A
S:
Su
mm
ary
of
Sel
ecte
d A
cute
To
xici
ty V
alu
es
Ch
emic
al C
lass
C
hem
ical
Nam
e
+
Lipi
d re
gula
tor
Eto
fibra
te
I
Ant
ivira
l I
Fam
cicl
ovir
I I
Ani
t-ul
cer
Far
notid
ine
PG
r
Fen
ofib
rate
I
Adr
ener
gic
rece
ptor
inhi
bito
r F
inas
terid
e I
1 A
ntib
iotic
- flu
oroq
uino
lone
F
lero
xaci
n
Flu
maq
uine
I
Ant
ineo
plas
tic
1 F
luor
oura
cil
I
Ant
idep
ress
ant
Flu
oxet
ine
HC
L
I A
ndro
gen
Flu
tam
ide
Cor
licos
tero
id a
ntia
smat
ic
Rut
icas
one
prop
iona
te
I F
luvo
xam
ine
I A
ntib
iotic
1 F
osfo
myc
in
Ant
ibac
teria
llant
i-pro
tozo
an
Fur
azol
idon
e I A
ntib
acte
rial
Fus
idic
aci
d
adju
nctiv
e G
abap
entin
--I
Acu
te A
quat
ic T
oxi
city
R
efer
ence
s R
efer
ence
R
epo
rted
In
Com
mon
C
once
ntra
tion
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Tab
le A
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Sum
mar
y o
f Se
lec
ted
Acu
te T
oxic
ity V
alu
es
Ant
ibio
tic - a
rnin
ogly
cosi
de
Ant
ibio
tic - s
ulfo
narn
ide
Ac
ute
Aq
ua
tic
To
xic
ity
R
efe
ren
ces
Ch
em
ica
l Cla
ss
Ant
ibio
tic - s
ulfo
narn
ide
Ch
em
ica
l Na
me
Ant
ibio
tic -
sulfo
narn
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
narn
ide
Ant
ibio
tic - s
ulfo
narn
ide
Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
narn
ide
Ant
ibio
tic - s
ulfo
narn
ide
~n
tib
ioti
c - sul
fona
mid
e
-- Ant
ibio
tic - s
ulfo
nam
ide
Ant
ibio
tic - s
ulfo
narn
ide
I Co
mm
on
n
am
elA
nim
al
-- Sul
fach
loro
pyrid
azin
e (l
wa
ler
Dap
hnia
mag
na
~C
I
Stre
ptom
ycin
Sce
nede
smus
vac
uola
tus
gree
n al
gae
Si
ii
ii
ie
~~
~~
l~
~
Sul
fadi
azin
e ae
rugi
nosa
bl
uegr
een
alga
e ---I
Sel
enas
trum
cap
ricor
nutu
m
TY
~e
blue
gree
n al
gae
pred
icte
d da
ta - D
aphn
ia
wat
er fl
ea
t
I
.-
Sul
fam
eraz
ine
spec
ies
of,
Sul
fadi
met
hoxi
ne
-- Sul
farn
ethi
zole
bp
redi
cted
dat
a - A
lgae
Arte
mia
sal
ina
(nau
plii)
br
ine
shrim
p I al
gae
Sul
farn
etho
xazo
le
I -
I S
ulfa
rnox
ole
lpre
dict
ed d
ata
- Alg
ae
1 algae
~G
ch
oc
oc
cu
s
leop
olen
sis
Sul
faqu
inox
alin
e
blue
-gre
en a
lgae
I S
ulfa
pyrid
ine
En
dp
oin
t C
on
cen
tra
tio
n
IbW
I
pred
icte
d da
ta - A
lgae
I I
72h
EC
50
0.13
3 B
ackh
aus a
nd G
rimm
e (1
999)
--
48h
~~
50
250
N
ovar
tis (1
999)
pred
icte
d da
ta - D
aphn
ia
. -- --
-
lnhi
bito
n -1
17.41~~~~~
of
et a1
(20
00)
repr
oduc
tion
wat
er fl
ea
96h
LC50
-
p9
.5
M
iglio
re e
t al(
1993
)
I San
ders
on e
t al(
2004
)
Far
rari
et a
l (20
04) I-
San
ders
on e
t a1
(200
4) F Re
po
rte
d I
n
Tab
le A
S:
Sum
mar
y o
f S
elec
ted
Acu
te T
oxic
ity V
alu
es
Che
mic
al C
lass
C
hem
ical
Nam
e
I
Ant
ibio
tic -
sulfo
nam
ide
Sul
fath
iazo
le
Ant
ibio
tic -
sulfo
nam
ide
Sul
fisom
idin
e
I
Ant
ibio
tic -
sulfo
nam
ide
Sul
fisox
azol
e
Ant
imig
rane
I~
um
atr
i~a
n
succ
inat
e
Est
roge
n an
tago
nist
sym
path
omim
etic
Bro
ncho
dila
tor
The
ophy
lline
I
Ane
sthe
tic
Thi
open
tol,
sodi
um s
ale
I I A
ntip
sych
otic
l~
hio
rid
azi
ne
Ant
ineo
plas
tic
Thi
otep
a
Bon
e m
odul
atin
g dr
ug -
l~ilu
dro
na
te diso
dium
~
ste
op
oro
sis a
gent
.-
I B
eta-
bloc
ker
l~im
olo
l mal
eate
:a
ntih
yper
tens
ive)
I
:ard
iova
scul
ar d
rug
4ntia
dren
ergi
c H
CL
Tol
azol
ine
.- 4nal
gesi
clan
ti-in
flam
mat
ory
Tol
fena
min
ic s
cid
t----
Acu
te A
quat
ic T
oxic
ity
Com
mon
S
peci
es
nam
elA
nim
al
~n
d~
oin
t '
Type
pr
edic
ted
data
- Dap
hnia
w
ater
flea
E
C50
lum
ines
cent
bac
teria
24h
NO
EC
I
Sev
eral
spe
cies
of f
ish
trou
t 48
h LC
50
Dap
hnia
mag
na
I
Aca
rtia
tons
a
pred
icte
d da
ta - D
aphn
ia
wat
er fl
ea
1-
r'
Vib
rio fi
sche
ri (lu
min
esce
nce)
Dap
hnia
mag
na
Pim
epha
les p
rom
elas
Bra
chio
nus
caly
ciflo
rus
rotif
er
24h
LC50
Dap
hnia
mag
na
li
ii
te
r fle
a I 12
4h E
C50
I S
elen
astr
um ca
pric
ornu
tum
b
lue
gre
en
alg
ae
72h
EC
50 -I
Dap
hnia
mag
na
I I
pred
icte
d da
ta - D
aphn
ia
Wat
er fl
ea
EC
50
Pim
epha
les p
rom
elas
pred
icte
d da
ta - A
lgae
al
gae
Ref
eren
ces
Ref
eren
ce
Rep
orte
d In
Con
cent
ratio
n
San
ders
on e
l al(
20
04
)
Bac
khau
s an
d G
rimm
e
Wilf
ord
(196
6)
F-R (1
996)
R
epor
ted
in W
ebb
(20
01
) A
nder
son
et a
l(2
00
1)
San
ders
on e
t al(
20
04
)
r6
r1
r
]02
41
-IP
B
ackh
aus
el a
l(l9
97
)
I 15
5 I~
iliu
s
el a
l(1
99
4)
IRe
~o
rle
d in W
ebb
1.3
Cal
leja
et a
l (19
94b)
R
epor
ted
in e
bb
- (2
00
1 )
546
FD
A-C
DE
R (1
996)
R
epor
ted
in W
ebb
--
(20
01
) 1.
165
Hal
ling-
Sor
ense
n (2
000)
320
San
ofi (
1 99
6)
Rep
orte
d in
Web
b (2
001 )
3.29
S
ande
rson
-I-
el a
1 (2
004)
San
ders
on e
t a1
(200
4)
I--*"
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Table B.1: Summary of acute hazard quotient calculations and ranked PPCPs
I I I (surface water ~PNOAEC I I Rank (chemical Class lchemical Name (~a lues (pglL) I(pg1~) l ~ c u t e HQ
IPsychiatric drug (anxiolytic; rnucle relaxant anti- I I I I
Table 8.2: Summary of chronic hazard quotient calculations and ranked PPCPs
Exposure /Concentration IPNOAEC IChmnic I
Rank 1 2
8 l~ersonal care product - fragrance ( ~ u s k xylene (nitro musk))0.18 10.06 13.21 I ~ u s k ketone (nitro I 1
3 4 5 6 7
Chemical Class Hormone - ovulation inhibitor (contraceptive) Lipid regulator Beta-blocker (antihypertensive) 1 cardiovascular drug Antiepileptic Antibiotic - sulfonarnide Antibacterial Antibiotic - tetracycline
Chemical Name 17 alpha ethinylestradiol Clofibrate
Propanolol Carbarnazepine Sulfarnethoxazole Spiramycin ChloEacycl ine
()lg/L) 0.83 1.75
0.59 0.65 1.90 0.07 0.69
(pglL) 0.00 0.01
HQ 4.16E+06 175.00
0.01 0.03 0.10 0.01 0.05
65.6 26.0 19.0 14.8 13.8
Table 8.4: Summary of the exposure concentrations and toxicity reference values used in cumulative frequency distributions for carbmazapine
r Envimnmenbl Exposun I Aquatic Toxicity
Table B.5: Summary of the exposure concentrations and toxicity reference values used in cumulative frequency distributions for ciprofloxacin
Environmental Exposure Aquatic Toxicity
Table B.6: Summary of the exposure concentrations and toxicity reference values used in cumulative frequency distributions for musk xylene
I I I 1
Table 6.8: Summary of the exposure concentrations and toxicity reference values used in cumulative frequency distributions for sulfamethoxazole
Environmental Exposure Aquatic Toxicity