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

DECLARATION OF PARTIAL COPYRIGHT LICENCE

The author, whose copyright is declared on the title page of this work, has granted to Simon Fraser University the right to lend this thesis, project or extended essay to users of the Simon Fraser University Library, and to make partial or single copies only for such users or in response to a request from the library of any other university, or other educational institution, on its own behalf or for one of its users.

The author has further granted permission to Simon Fraser University to keep or make a digital copy for use in its circulating collection, and, without changing the content, to translate the thesislproject or extended essays, if technically possible, to any medium or format for the purpose of preservation of the digital work.

The author has further agreed that permission for multiple copying of this work for scholarly purposes may be granted by either the author or the Dean of Graduate Studies.

It is understood that copying or publication of this work for financial gain shall not be allowed without the author's written permission.

Permission for public performance, or limited permission for private scholarly use, of any multimedia materials forming part of this work, may have been granted by the author. This information may be found on the separately catalogued multimedia material and in the signed Partial Copyright Licence.

The original Partial Copyright Licence attesting to these terms, and signed by this author, may be found in the original bound copy of this work, retained in the Simon Fraser University Archive.

Simon Fraser University Library Burnaby, BC, Canada

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.

This page intentionally blank.

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.

9.0 REFERENCES

Aherne GW, Hardcastle A, Nield AH. 1990. Cytotoxic drugs and the aquatic environment - estimation of bleomycin in river water samples. Journal of Pharmacy and Pharmacology 42:74 1-742.

Ayscough NJ, Fawell J, Franklin G, Young W. 2000. Review of human pharmaceuticals in the environment. R&D Technical Report P390. UK Environment Agency, Rio House, Bristol.

Baronti C, Curini R, D'ascenzo G, Corcia AD, Gentili A, Samperi R. 2000. Monitoring natural and synthetic estrogens at activated sludge sewage treatment plants and in a receiving water. Environmental Science and Technology 345059-5066.

Becker AB, Simons KJ, Gillespie CA, Simons FE. 1984. The bronchodilator effects and pharmacokinetics of caffeine in asthma. New England Journal Of Medicine 31 0:743-746.

Beers MH. 2004.The Merck Manual of Medical Information. 2nd ed. Pocket Books. New York, NY, USA.

Belfioid AC, Van der Horst A, Vetaak AD, Schafer AJ, Rijs GBJ, Wegener J, Cofino AJ. 1999. Analysis and occurrence of estrogenic hormones and their glucoronides is surface water and waste water in The Netherlands. The Science of the Total Environment 225:lOl-l08.

Boxall ABA, Oakes D, Ripley P, Watts CD. 2000. Chemosphere 40:775-78 1.

Boyd RG, Reemtsma H, Grirnm DA, Mitra S. 2003. Pharmaceuticals and personal care products (PPCPs) in surface water and treated waters of Louisiana, USA and Ontario, Canada. The Science of The Total Environment 3 1 1 : 135-1 49.

Brain RA, Johnson DJ, Richards, SM, Sanderson H, Sibley PK, Solomon KR. 2004. Effects of 25 pharmaceutical compounds to Lemna gibba using a seven-day static-renewal test. Environmental Toxicology and Chemistry 23:371-382.

British Columbia Ministry of Environment, Lands and Parks (BCMELP). 1998. Guidance and checklist for tier 1 ecological risk assessment of contaminated sites in British Columbia. Draft. British Columbia, Canada.

Brooks BW, Turner PK, Stanley JK, Weston JJ, Glidewell EG, Foran CM, Slattery M, LaPoint TW, Huggett D. 2003. Waterborne and sediment toxicity of fluoxetine to select organisms. Chemosphere 52: 135- 142.

Canadian Council of Ministers of the Environment (CCME). 1996. A Framework for Ecological Risk Assessment: General Guidance. The National Contaminated Sits Remediation Program.

Canadian Environmental Protection Act (CEPA). 1999.

Cleuvers M. 2003. Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects. Toxicology Letters 142: 1 85- 1 94.

Cleuvers M. 2004. Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen and acetylsalicylic acid. Ecotoxicology and Environmental Safety 59:309-115.

Daughton CG, Ternes TA. 1999. Pharmaceuticals and personal care products: agents for subtle change? Environmental Health Perspectives 107:907-938.

Daughton CG. 2001. Pollution fiom personal actions, activities, and behaviours: Pharmaceuticals and personal care products in the environment, multidimensional science issues relevant to regulatory considerations. Environmental Chemistry Branch, Environmental Sciences Division, National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Las Vegas, Nevada, USA.

Derksen JG, Rijs GB, Jongbloed RH. 2004. Diffuse pollution of surface water by pharmaceutical products. Water Science and Technology 49: 2 13-22 1.

Dom PB. 1996. An industrial perspective on whole effluent toxicity testing. In Groth DR, Dickson KL, Reed-Judkins LH, eds, Whole Efluent Toxicity Testing: An Evaluation of Methods and Prediction of Receiving System Impacts. SETAC, Pensacola, Fl., USA, pp 34-47.

Ellis CN, Millikan LE, Smith EB, Chalker DM, Swinyer LJ, Katz IH, Berger RS, Mills OH Jr, Baker M, Verschoore M, Loesche C. 1998. Comparison of adapalene 0.1 % solution and tretinoin 0.025% gel in the topical treatment of acne vulgaris. British Journal ofDermatoIogy 139:41-47.

Environment Canada, 1994. A fiamework for ecological risk assessment of contaminated sites in Canada. Environment Canada, Hull, Quebec.

Erickson RJ, Ankley GT, DeFoe DL, Kosian PA, Makynen EA. 1999. Additive toxicity of binary mixtures of phototoxic polycyclic aromatic hydrocarbons to the oligochaete Lumbriculus variegatus. Toxicology and Applied Pharmacology l54:97-lO5.

European Agency for the Evaluation of Medicinal Products (EMEA). 2003. Note for guidance on environmental risk assessment of medical products for human use. EMEA CPMP/SWP/4447/00.Draft I. London, UK.

European Agency for the Evaluation of Medicinal Products (EMEA). 2005. Note for guidance on environmental risk assessment of medical products for human use. EMEA CPMP/SWP/4447/00.Draft 11. London, UK.

FmC M, Ferrer I, Ginebreda A, Figueras M, Olivella L, Tirapu L, Vilanova M, Barcel6 D. 2001. Determination of drugs in surface water and waste water samples by liquid chromatography - mass spectrometry: methods and preliminary results including toxicity studies with Vibrio3sheri. Journal of Chromatography A 938:187-197.

Fawell JK, Sheahan D, James HA, Hurst M, and Scott S. 2001. Oestrogens and oestrogenic activity in raw and treated water in Severn Trent water. Water Research 3 5 : 1240- 1244.

Ferrari B, Mons R, Vollat B, Fraysse B, PaxCus N. 2004. Environmental risk assessment of six human pharmaceuticals: Are the current environmental risk assessment procedures sufficient for the protection of the aquatic environment? Environmental Toxicology and Chemistry 25: 1 344- 1 3 54.

Ferrari B, PaxCus N, Giudice RL, Pollio A, Garric J. 2003. Ecotoxicological impact of pharmaceuticals found in treated waste water s: study of carbamazepine, clofibric acid, and diclofenac. Ecotoxicology and Environmental Safety 55:359-370.

Fong PP, Huminski PT, D'urso LM. 1998. Induction and potentiation of parturition in fingernail clams (Sphaerium striatinum) by selective serotonin re-uptake inhibitors (SSRIs). Journal of Experimental Zoology 280:260-264.

Fong PP. 1998. Zebra Mussel Spawning is induced in low concentrations of putative serotonin reuptake inhibitors. Biological Bulletin 194: 143-1 49.

Fredholm BB, Battig K, Holmh J, Nehlig A, Zvartau EE. 1998. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacological Reviews 5 1 :83- 133.

Giger W. 1999. Identifying future drinking water contaminants. Water and Science and Technology Board, Board on Environmental Studies and Toxicology, Commission of Geosciences, Environment, and Resources, National Research Council, National Academy Press, Washington DC. pp 1 1 1-1 19.

Halling-Sarrensen B, Holton Liitzhoft HC, Andersen HR, Ingerslev F. 2000. Environmental risk assessment of antibiotics: Comparison of mecillinam, trimethorprirn and ciprofloxacin. Journal of Antimicrobial Chemotherapy 4653- 58.

Halling-Snrrensen B, Nors-Nielsen S, Lansky PF, Ingerslev F, Holten-Liitzhoft, Jorgensen SE. 1998. Occurrence, fate, and effects of pharmaceutical substances in the environment: A review. Chemosphere 36:3 57-393.

Hansen BG, VanHaelst AG, VanLeeuwen K, VanderZandt P. 1999. Priority Setting for existing chemicals: European Union risk ranking method. Environmental Toxicology and Chemistry 18:772-779.

Health Canada, 2004. Federal Contaminated Site Risk Assessment in Canada. Part I: Guidance on human health preliminary quantitative risk assessment (PQRA). Health Canada, Ottawa, Ontario.

Herberer T, Verstraeten IM, Meyer MT, Mechlinski A, Reddersen K. 2001. Occurrence and fate of pharmaceuticals during bank filtration: Preliminary results fiom investigation in Germany and the United States. Water Resources Update 120:4- 17.

Herberer T. 2002. Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: A review of recent research data. Toxicology Letters 13 15- 17.

Hilton MJ, Thomas KV, Ashton D. 2003. Targeted monitoring programme for pharmaceuticals in the aquatic environment. R&D Technical Report P6- 0 12/06/TR. Environmental Agency, Bristol, UK.

Huang C, Sedalk DL. 2001. Analysis of estrogenic hormones in municipal wastewater effluent and surface water using enzyme-linked immunosorbent assay and gas chromatography/tandem mass spectrometry. Environmental Science and Technology 20: 133-1 39.

Hugget DB, Brooks BW, Peterson B, Foran CM, Schlenk D. 2002. Toxicity of select beta adrenergic receptor-blocking pharmaceuticals @-blockers) on aquatic organisms. Archives of Environmental Contamination and Toxicology 43:229-235.

Jones OAH, Voulvoulis N, Lest JN. 2002. Aquatic environmental assessment of the top 25 English prescription pharmaceuticals. Water Research 36501 3-5022.

Jorgensen SE, Halling-Sorensen B. 2000. Drugs in the environment. Chemosphere 40:691-699.

Kanda R, Griffin P James HA, Fothergill J. 2003. Pharmaceutical and personal care products in sewage treatment works. Journal of Environmental Monitoring 5:823- 830.

Koplin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT. 2002. Pharmaceuticals, hormones, and other organic waste water contaminants in US streams 1999-2000: A national reconnaissance. Environmental Science and Technology 36 1202-121 1.

Lai KM, Scrimshaw MD, Lester JN. 2002. The effects of natural and synthetic steroid estrogens in relation to their environmental occurrence. Critical Reviews in Toxicology 32:113-132.

Lkge R, Hutchinson TYH, Croudace CP, Siegmund F, Schweinfurth H, Hampe P, Panter P, Sumpter JP. 200 1. Effects of the synthetic estrogen 17-a-ethinylestradiol on the life-cycle of the fathead minnow (Pimephales promelas) Environmental Toxicology and Chemistry 20: 121 6-1227.

Luckenbach T, and Epel D, 2005. Nitromusk and polycyclic musk compounds as long- term inhibitors of cellular xenobiotic defence systems mediated by multidrug transporters. Environmental Health Perspectives 1 13 : 17-24.

McBride M, Wycoff J. 2002. Emerging liabilities from pharmaceuticals and personal care products. Environmental Claims Journal 14: 175-1 86.

Mecalfe CD, Metcalf TL, Kiparissis Y, Koeing BG, Khan C, Hughs RJ, Croley TR, March RE, Potter T. 2001. Estrogenic potency of chemicals detected in sewage treatment plant effluents as determined by in vivo assays with Japanese medaka (Oryzias latipes). Environmental Toxicology and Chemistry 20:297-308.

Metcalfe CD, Koenig BG, Bennie DT, Servos M, Ternes TA, Hirsch R. 2003a. Occurrence of neutral and acidic drugs in the effluents of Canadian sewage treatment plants. Environmental Toxicology and Chemistry 22:2872-2880.

Metcalfe CD, Miao X, Koenig BG, Struger J. 2003b. Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada. Environmental Toxicology and Chemistry 22:288 1-2889.

0llers S, Singer HP, Fhsler P, Miiller SR. 2001. Simultaneous quantification of neutral and acidic pharmaceuticals and pesticides at the low-ng/L level in surface and waste water. Journal of Chromatography A 91 1:225-234.

Olsen EA, Katz HI, Levine N, Shupack J, Billys MM, Prawer S, Gold J, Stiller M, Lufi-ano L, Thorne EG. 1993. Tretinoin emollient cream: a new therapy for photodarnaged skin. Journal of the American Academy of Dermatology 2:283- 284.

Petrovic M, Sol6 M, L6pez De Alda MJ, Barcel6 D. 2002. Endocrine disruptors in sewage treatment plants, receiving river waters, and sediments: Interaction of chemical analysis and biological effects on feral carp. Environmental Toxicology and Chemistry 2 1 :2 146-21 56.

Reinert KH, Bartell SM, and Biddinger GR, (editors)1998. Ecological risk assessment decision-support system: a conceptual design. Proceedings fi-om Society of Environmental Toxicology and Chemistry Ecological Risk Assessment Modelling Workshop; 1994 Aug 23-28; Pellston MI: Pensacola FL: Society of Environmental Toxicology and Chemistry.

Russom CL, Bradbury SP, Broderius SJ, Hammermeister DE, Dnunmond RA. 1997. Predicting modes of toxic action from chemical structure: acute toxicity in the fathead minnow (Pimephales promelas). Environmental Toxicology and Chemistry 16: 948-967.

Rybacki JJ. 2002. The essential guide to prescr@tion drugs. HarperCollins Publishers Inc., New York, NY, USA.

Sanderson H, Johnson DJ, Wilson CJ, Brain RA, Solomon KR. 2003. Probabilistic hazard assessment of environmentally occurring pharmaceuticals toxicity to fish Daphnis and algae by ECOSAR screening. Toxicology Letters 144:383-395.

Sanderson H, Johnson DJ, Reitsma T, Brain RA, Wilson J, Solomon KR. 2004. Ranking and prioritization of environmental risks of pharmaceuticals in surface waters. Regulatory Toxicology and Pharmacology 39: 158-1 83.

Scholz S, Gutzeit HO. 2000. 17-a-ethinylestradiol affects reproduction, sexual differentiation and aromatase gene expression of the medaka (Oryzias latipes) Aquatic Toxicology 50:363-373.

Seiler JP. 2002. Pharmacodynarnic activity of drugs and ecotoxicology: Can the two be connected? Toxicology Letters 1 3 1 : 1 05- 1 1 5.

Servos MR, Bennie DT, Starodub ME, Orr JC. 2002. Pharmaceuticals and personal care products in the environment: A summary of published literature. Report Number 02-309. National Water Research Institute, Environment Canada, Burlington Ontario, Canada.

Snyder SA, Westerhoff P, Yoon Y, Sedlak DL. 2003. Pharmaceuticals, personal care products, and endocrine disruptors in water: Implications for the water industry. Environmental Engineering Science 20:449-469.

Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart J. 1998. Cadiovascular drugs: Mechanism of action of fibrates on lipid and lipoprotein metabolism Circulation 98:2088-2093.

Stan H, Herberer T. 1997. Pharmaceuticals in the aquatic environment. Water Analysis 25~20-23.

Steger-Hartmann T, Kurnmerer K, Hartmann A. 1997. Biological degredation of cyclophosphamide and its occurrence in sewage water. Ecotoxicology and Environmental Safety 36: 174-1 79.

Steger-Hartmann T, Liinge R, Schweinfurth H. 1998. Environmental risk assessment for the widely used iodinated x-ray contrast agent iopromide (ultravist). Ecotoxicology and Environmental Safety 42:274-28 1.

Straub JO. 2002. Environmental risk assessment for new human pharmaceuticals in the European Union according to the draft guidelineldiscussion paper of January 200 1. Toxicology Letters 13 1 : 137- 143.

Stuer-Lauridsen F, Birkved M, Hansen LP, Holten-Liitzhoft HC, Halling-Smensen B. 2000. Environmental risk assessment of human pharmaceuticals in Denmark after normal therapeutic use. Chemosphere 40:783-793.

Suter GW, Efi-oyrnson RA, Sample BE, Jones DS. 2000. Ecological risk assessment for contaminated sites. Lewis Publishers, Boca Raton, Florida, USA.

Suter GW. 1993. Ecological Risk Assessment. Lewis Publishers. Ann Arbour, Michigan, USA.

Ternes TA, Bonerz M, Schmidt T. 2001. Determination of neutral pharmaceuticals in waste water and rivers by liquid chromatography -electrospray tandem mass spectrometry. Journal of Chromatography 938: 1 75-1 85.

Ternes TA, Hirsch R. 2000. Occurrence and behaviour of x-ray contrast media in sewage facilities and the aquatic environment. Environmental Science and Technology 34:2741-2748.

Ternes TA. 1998. Occurrence of drugs in German sewage treatment plants and rivers. Water Research 32:3245-3260.

Thompson HM. 1996. Interactions between pesticides; a review of reported effects and their implications for wildlife risk assessment. EcotoxicoEogy 559-81.

US Environmental Protection Agency (US EPA). 1989. Risk assessment guidance for superfimd. Volume I: Human Health Evaluation Manual (Part A); Interim Final. Office of Emergency and Remedial Response, Washington, D.C. EPAt54011- 891002.

US EPA. 199 1. Technical Guidance Manual. EPA Region 3 guidance on handling chemical concentration data near the detection limit in risk assessments. Interim Final.

US EPA. 1997. Ecological risk assessment guidance for s u p e h d : Process for designing and conducting ecological risk assessments. Interim Final. 540-R-97-006.

US EPA. 1998. Guidelines for ecological risk assessment. 630lR-951002F Federal Register 63(93):26846-26924.

US EPA. 2001. Risk assessment guidance for superfund. Volume 3 Part A: Process for Conducting Probabilistic Risk Assessment (RAGS 3A) Chapter 4. Draft.

US EPA. 2002. Guidance on cumulative risk assessment of pesticide compounds that have a common mechanism of toxicity. 20460. Office of Pesticide Programs, US. Environmental Protection Agency, Washington, DC, USA.

US Food and Drug Administration (US FDA). 1995. Guidance for Industry for the Submission of an Environmental Assessment in Human Drug Application and Supplements. Centre for Drug Evaluation and Research, Washington.

US FDA. 1998. Guidance for Industry. Environmental assessment of human drug and biologics applications. Revision 1. US Department of Health and Human Services, Food and Drug Administration. CMC6.

US FDA. 2001. Guidance for Industry. Environmental impact assessments for veterinary medicinal products. Phase I. Final Guidance. US Department of Health and Human Services, Food and Drug Administration. VICH GL6.

VanWezel AP, Jager T. 2002. Comparison of two screening level risk assessment approaches for six disinfectants and pharmaceuticals. Chemosphere 47: 1 1 13- 1 128.

Vilukselab M, Stahlc BU, Birnbaumd LS, Schramme KW, Kettrupe A, and Rozmanc KK. 1998. Subchronic/chronic toxicity of a mixture of four chlorinated dibenzo- p-dioxins in rats. Toxicology and Applied Pharmacology 15 1 57-69.

Webb SF. 2001. A data-based perspective on the environmental risk assessment of human pharmaceuticals - Collation of available ecotoxicity data. In: Kiimrnerer K, ed, Pharmaceuticals in the Environment. Sources, Fate, Effects and Risks. 1 st ed, Springer Verlag, Berlin, pp 175-200.

Weinbroum AA, Flaishon R, Sorkine P, Szold 0, Rudick V. 1997. A risk-benefit assessment of flumazenil in the management of benzodiazepine overdose. Drug Safety 17:181-196.

Xiao X, McCalley DV, McEvoy J. 2001. Analysis of estrogens in river water and effluents using solid-phase extraction and gas chromatography-negative chemical ionisation mass spectrometry of the pentafluorobenzoyl derivatives. Journal of Chromatography A 923: 195-204.

Zillioux EJ, Johnson IC, Kiparissis Y, Metcalfe CD, Wheat JV, Ward SG, Liu H. 2001. The sheepshead minnow as an in vivo model for endocrine disruption in marine teleosts: A partial life-cycle test with 1 7-a-ethinylestradiol. Environmental Toxicology and Chemistry 20: 1968-1 978.

APPENDICES

APPENDIX A: LITERATURE DATA

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

Che

mic

al N

ame

I Mea

sure

d E

nvir

onm

enta

l Occ

urre

nce

I M

atr

ii

(con

trace

ptiv

e)

Hor

mon

e - o

vula

tion

inhi

bito

r (c

ontr

acep

tive)

H

orm

one

-ovu

latio

n in

hibi

tor

(con

trace

ptiv

e)

Hor

mon

e - o

vula

tion

inhi

bito

r (c

ontra

cept

ive)

H

orm

one

- ovu

latio

n in

hibi

tor

Hor

mon

e -e

stro

gen

met

abol

ite

Hor

mon

e - o

vula

tion

inhi

bito

r (c

ontr

acep

tive)

H

orm

one

-ovu

latio

n in

hibi

tor

&on

trace

ptiv

e)

Hor

mon

e -o

vula

tion

inhi

bito

r Ic

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

ontra

cept

ive)

H

orm

one

-ovu

latio

n in

hibi

tor

(con

trace

ptiv

e)

Hor

mon

e - o

vula

tion

inhi

bito

r (c

ontr

acep

tive)

H

orm

one

-ovu

latio

n in

hibi

tor

Icon

trac

eptiv

e)

Hor

mon

e -o

vula

tion

inhi

bito

r

Hor

mon

e -r

epro

duct

ion

16 a

lpha

hyd

roxy

este

rone

17 a

lpha

eth

inyl

estra

diol

17 a

lpha

eth

inyl

estr

adio

l

17 a

lpha

eth

inyl

estra

diol

17 a

lpha

eth

inyl

estr

adio

l

17 a

lpha

elh

inyl

estr

adio

l

17 a

lpha

eth

inyl

estra

diol

17 a

lpha

eth

myl

estra

diol

17 a

lpha

eth

inyl

estr

adio

l

17 a

lpha

eth

inyl

estra

diol

IH

or

rn

on

kl

7

beta

est

radi

ol

bg

/L

I I

I 0.

35 -

3.3

ng/L

0.

0033

W

WTP

Effl

uent

- Ita

ly

/Bar

onti

a*

17 a

lpha

elh

inyl

estr

adio

l

17 a

lpha

eth

inyl

estr

adio

l

17 a

lpha

eth

inyl

estra

diol

17 a

lpha

eth

inyl

estra

diol

17 a

lpha

eth

inyl

estr

adio

l

17 a

lpha

est

radi

ol

17 a

lpha

est

radi

ol

17 a

lpha

est

radi

ol

I I

I I

I I

Hor

mon

e - r

epro

duct

ion

- nat

ural

11

7 be

ta e

stra

diol

I

lmax

12

nalL

10

.012

IM

P E

fllue

nt -

I IB

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

uaqdou!w

e~aov

-!we lep!o~ais-uou/so!sa61euv

pue16ua isea

wn

os

(~IV

SN

) kole

ww

eu

u!

(EO

OZ

) le la u

oll!~

- lu

an

~3

d

m

SZ

O'O

116u ffi >

xew

ua

qd

ou

~w

e~

ao

v q

ue

tep!o~a1s-uou/so!sa6leuv (sale~

AxoulaA

~od ~

ouaud~A

uouT

(8661) le la s

aw

al

- iua

n~

)3 a6

e~

as

80'0

i16d 08

0'0

xew

loualAxaro(q>p

le!qoJa!w!luv

Au

ew

~a

g - s

we

a~

ls

lisd

( 1

00

~) le la

sa

uw

pue w

a~

!~

~

9'0

SZ

O'O

> paw

i i16d EFO

xew

auuAd!)ue ou~

we-p

ko~

eww

e~u

~!1u

e/3!sa6leuv

Au

eu

af)

116d ( LO

OZ

) le la s

au

al

- wn

w3

dm

~

E'O

OS

O'O

> paw

I i16d sco xew

auuA

d!)ue ou!we-p

ko1ew

we~u

~!1ue/o

!sa6leuy

Au

eu

a~

(zooz) ~e la

u!~

do

nl

vsn - sw

ea

~is

l a

ua

ra~

s!q~

am

u-6

~

~ol!q!qu! uogelnno - auouuoH

I

I I

I

( LOO

Z) le la

oe!x C

nn - lua

n~

3

dm

P

LOO

'O

i16u P'L - F

1 lo!P

e~lsa elaq L L

lwnleu - u

o!~

on

po

lda

~

- au

ou

uo

~

I uapam

g( I

I I

(0002) le la u

os

wo

r W

I- iua

nu

3 d

m

LOO

'O

(rooz) ~

!WJ

!IQ

ylepas pue 6u

en

~

- ~a

lem

aoepng 8000'0

11

6~

8'0- ifiu

SO

'O

(~E

OO

Z)

le la a

wta

w

(~E

OO

Z)

le )a w3

ww

(~E

OO

Z)

le la w

e31aw

(WO

OZ

) le la a

ww

w

(~E

OO

Z)

le la a

~w

aw

(e

lep

parls!lqndun) am

3

(zooz) le la

u!~

do

n

(EO

OZ

) le la U

OW

H

(EO

OZ

) le la u

oll!~

- lu

aw

dm

~ 9E'O

116 9

t.0 u

ea

u

lolo

ua

lv 'a

~!su

au

ad

Aq

!lue

) ~ay

mlq

-ela

g

6rup Jeln3seno!ple3 I (ew

o3nel6!)ue L

K'O

1

16

~

00

' ~P

Z

- WE

lo

lou

aiy

'a~

!sua

ua

dfq

!lue

) ~ay

~o

lq-e

lag

A

ueuuaF)

dm

~

01 we

!w

~

ale

m

aw

ns

vsn - sw

ea

~ls

~

sea

ttlno

s sd

m~

jo w

ea

~lsu

mo

a

~s

ea

wo

s

sd

m~

40

we

a~

lsdn

JOSPU

!M lS

M

- 1u

an

u3

dm

~

Ja

w alu

!l - lu

an

w

uol6u!una -

lua

w

rlsn

wo

wa

w

- iua

nw

dm

~

an

no

au

e~

- 1

ua

n~

13

~

LM

M

Aueuuag

iawa

6EZ'O

SO

O'O

10.0

61

0'0

WO

'O

ZZ

O'O

6~

0'0

1awa

716u 6cz xew

116u 0 paw

1 y

6u

0 xew

opp

ha

ws

) i16u 01

>

(iaw

a) 1

16

~ oz >

ifid 6

10

'0 ueaw

11

6d

w0

'0 ueaw

i16d ZZ

O'O

uea

w

116d 6L0'0 xew

wln

qlv

a1ozexoqiawej1ns-1A

1a3y

alo

zexo

ua

we

4ln

elA

1a

3~

UR

elseNolv

u!le

~se

NO

lv

u!1

else

~o

ly

uw

lse

~o

iv

u!~

e~

se

~o

lv

u!le

lse

~o

lv

~!I~

W~

I~W

JV

(3

!1o

!q!w

T

a~

oze

xou

aw

ej~

ns

- al!~

oq

e~

ayy

(?!~

o!q

!lue

) a

~o

zexo

~g

aw

ej~

ns

- al!lo

qe

)a~

~o

leln

6a

~

p!d

!l

~o

ieln

6a

~

p!d

g

~o

leln

6a

~

ptd

g

~o

leln

6a

~

p!d

g

~o

leln

fia~

p

!dg

Joleln6a1 p!d

q

6rup-e3 1

(ew

o3

ne

l6!lu

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

qq

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

qq

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)

. .

.-

eay leaem

-

eu6ew e!u

ydea

auop!(ozem j

ueo

zop

~d-!lu

eneyay~eq

!~~~v -

-.

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

/lale

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%

W

olle

nber

ger e

t ai

(200

oJ

2. 10

00

40

Wol

lenb

erge

r et a

i j2

00

0) -

Hal

ling-

Sor

ense

n (2

000)

I-

I (~

u!IJ

~~

uY

) ( LO

OZ

) VdJsn

O

E L

OE

314PZ

sseq ped!)s

sygexes euomoyy

au!pAm

)aflxo w

13

A3

en

al - w

orqnuv --

1 I

(€161) SV

LH

I S

.Z9/ 0

~3

14

96

(ae

~e

l) sseq pad!ls

s11!1exes auoluoyy

au!13Am

laflxo ~

~!llA

lerla

l - 3llo!qnuv

I I

I I

ZOL -

WM

u! p

eu

od

atll

(q~

66

1) le 1%

e!a11e3 c

t (1ooz)l

I dw

uqs rO!e)

snle

yda

rn~

da

qq

qu!w

qs!quue 'iuexe(a8 0

E3

1w

zi

1 /

l3H,W

Wua:dJ]

1 T

wU

eq

ew

OE

33 4tZ

eay ~

ale

m

eu6eur eruydea 1

3~

a

uyp

eu

e~

dJ0

qu!w

qs!q!lue --

'lue

xqe

y G

weueqdau,

=y!wqs!q!lue

'luexelet(

3!u!wqs!s!q!lue 'lu

ew

ay

OS

31 UPZ

dwyqs euyq

13

~

auypeuaudro l!u!w

qs!qnue 'lusxelau

u! pauodat( ( 1002)

qq

aM

u! peuoda8

(9661) t(3m

-va

j

(9661) 83fJ3-VO

d

-8z. 88 -

OE?? O

E33

eay ~a

lem

eay ~a

lsm

eu6ew q

uq

de

a

eu6ew q

uq

de

a

131-1 uarlasuepuo

alo

zwd

aw

g

wa

wa

nu

v

~a

qn

-nu

\(

I l l

C

?. p C i * a *

E c 2 1 f ; ; i ? p . g $ $

n s e $ ! : a i f E m E 'e i s - m m i

( 1002) le la

~O

Q~

PU

V

L (0

53

1 4

8~

) 3

30

~

!!ldneu. podado3 esuol w

pe3y e

uw

als

afh

d

pn

leu

- uq

np

old

w - auouuok

-

(~0

02

) S

~J

~T

~T

p

.~

le la

e3

a~

~)e

llea

~

PO

Z'O

~L

C

Z314P

Z

dluuqs h!e

~

snleydeaouweyl

~U

W!U

P~

J~

p!w

awo3!uw

, - ho

~e

ww

wu

!-!~u

\l .-

(CO

O~

) snm

jj5A1es

le la

e3

a~

~)e

llaa

Z'ZS

L 0

53

1 UPZ

J~

~R

OJ

S

~U

O!I/~

~J

~

au

oq

up

wd

p

ya

s0

3y

o~

- ho]eluw

eyu!-gub 7

00

~)

(uo!leq!qolum

!) le

la e

3~

3e

llaa

000 1

OE

33 48P

eay ~a

jem

eu6ew

wu

yde

a

auos!upald p

!cu

a~

so

~o

s

- ho

~e

lulu

q)u

~g

ub

7EO

zT fu

og

eq

~w

~lu

!) le

la e

3w

wlla

a

00 1 3

30

N 4PZ

eay la~

em

eu6ew

ep

qd

ea

e

uo

qu

pa

ld

p!o

lalso

vo3

- ho

]elu

wq

u!-n

ub

7

ra

oz

T

sn

lo

ji

le la

e3a0e11aa 61.21

-

OE

31 UE

_ l

aw

snuo!yae~

g a

uq

os!u

pw

d

p!we1so3!uo3 - ho~

ewuteyu!-!tub

(~O

OZ

) sn~

n@$

qq

w u! p

eu

od

w

(~

66

~)

le

la e

!w3

0

53

1 l(P

Z dw

uqs h!e) snleyda3oldaqg

Wa

M u! pauoday

hP

66

L) le

le e!elle3

OE

33 4PZ eay ~

a~

em

eu6ew

ep

yde

a

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

05

33

eay ~alenr

I

05

31

q96 sseq pad!qs

0s33 eay ale^

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

Spe

cies

na

mel

Ani

mal

E

nd

po

int

Type

@

'NIL

)

xedi

cted

dat

a - A

lgae

al

gae

EC

50

0.63

3 S

ande

rson

et a

l(2

00

4)

I 3a

phni

a m

agna

w

ater

flea

3aph

nia

mag

na

wat

er fl

ea

-

3nco

rhvn

chus

mvk

iss

rain

bow

trou

t -

820

FD

A-C

DE

R (1

996)

R

epor

ted

in W

ebb

-

398

I::,:: FDA-CDER

(199

6)

Rep

orte

d in

Web

b

hepa

tocy

tes

(cyt

otox

icity

) --

Onc

orhy

nchu

s myk

iss

rain

bow

trou

t LC

50

FD

A-C

DE

R (1

996)

R

epor

ted

in W

ebb

(200

1 )

pred

icte

d da

ta - D

aphn

ia

1- wat

er fl

ea

EC

50

(lum

ines

cenc

e

spaw

ning

)

FD

A-C

DE

R (1

996)

R

epor

ted

in W

ebb

Bac

khau

s an

d G

rimm

e (1

999)

I I

I

--

5.4

And

erso

n et

al(

20

01

)

Dap

hnia

mag

na

wat

er fl

ea

EC

50

0.55

F

DA

-CD

ER

(1 99

6)

Rep

orte

d in

Web

b

Sph

aeriu

m st

riatin

um

finge

rnai

l cla

m

4h

LO

EC

,

0.00

31 8

I I

[l

ia

~

lum

ines

cent

bac

teria

24h

EC

50

Bac

khau

s an

d G

rimm

e (lu

min

esce

nce

(1 99

9)

inhi

bitio

n)

24h

LC50

0.

25

Mac

ri et

al(

19

88

) l-

Vib

rio fi

sche

ri lu

min

esce

nt b

acte

ria l

IE

;k

-;

~~

24

h E

C50

an

d o

rin

me

I

(lum

ines

cenc

e

Dap

hnia

mag

na

wat

er fl

ea

-1R

epor

ted

in W

ebb

(200

1 1

0933 VPZ

eay ~q

en

eu8ew

eruydea alefins run!^!^

lua

ssa~

da

pn

uy

a3

uw

6e

~)

0933

ee

lv - e

pp

pe

~y

pe

~d

la

a~

a6

~0

~0

~a

1

- 13npOJd ale3 leuoslad

(POOZ)

le la U

O~

J~

PU

~S

ae6le

ae61v - qe

p pal3!paJd

lop!luedol e

!pw

1se~luo3 Ael-x

(POOZ)

ie la u

os~

ap

ue

s 019'~

0933 eay lalem

eiuqdea - q

ep

pal3!pa~d

up

e~

au

op

ul ~

o~

ew~

ueyu

!-~u

ela!sa~leu

v

(POOZ)

P la

uo

s~a

pu

es

0001'8 ae6le

ae6lv - qe

p pel?!pa~

d ~

P!U

J~P

JJI 3nseldoaugw

. i

(POOZ)

le la U

O~

J~

PU

~S

(POOZ)

le la U

O~

J~

PU

~S

---

(~00~)

le la U

O~

J~

PU

~S

LIE

L61'0

0'20' I

(1

IW

uo

!$wu

e3uo

3

E33

0533

--

0933

$u!odpuq

ae

6p

eay 1a:su

ae6le

ed

Al

leui!u

vlemeu

u

ou

ruro

3

ae6lv - qe

p p

alq

pa

~d

e!uqdea - qe

p pal3!pa~

d

ae6ly - qe

p p

qq

pa

~d

seped

g

ap

!ze!w

o~

op

po

~p

A~

ap

!ue

wa

q!l~

I!ZO

Jq@U

a~

~n

a~

n!a

3naqe!pguv

Joleln6aJ p!d

!~

(e la

se

l u! pauodaw

( rooz: qqaM

u! pauodatl

(1001:

( 1 ooz: qqaM

u! pauodal!

(2002) ~e la

~6

6n

~

00 7

09

31

48

~

(986 1) (~

no

b~

eq

aq

!tuem

seuqs!~)( pue ~

46

nH

ZE'O

~

U!~

J~

!MS

) 3

30

N

eay Jalem I

eay ~a

lem

eu6elu e

yyde

a

I

(966 1) 83

a3

-va

dI

09331

cay J

~~

~M

~

eu6ew e

!uu

de

j 3!4a4lsau]

, s;i

l

ue~omp!w

i

(~

66

1) U

asuaJos -6

u!lle

~ pue A

yzuel . -

09

33

4ZL a

e6

p u

aa

~6

sue61nn ellem

ly3 alozep!uo~

ayy W

O!clnU

V

--

6~

p

Jelnx.eAo!pJe:,

1 (a~

!suauadAqgue)

(ZO

OZ

) le la !ysM

ole!za (~IE

J wa

ll) 33

01

eay ~

ale

m

eu6elu ep

qd

ea

lo

lo~

do

lafl

JW

wq

-ww

--

OE 1 E

33

eay ~

al

e~

eu6elu e

yy

de

a

U!II!~

~W

~W

W

o!W

JV

(4!1

!qw

~!)

3naqe!p!lue O

E33 48P

eay ~a

lem

eu6elu eruydea

u!u~ol)ayy

- 3!uae3A16~

adAqnuy

-

EL'Z

ysn3A

elueu sn ya

nle

s I

aae~o!w

aw

I I

(966 1) t13

03

-va

j €96 <

O

E33

eay ~a

lem

eu6elu eluydeg

(1lW

A

Ll

uo

~e

~ju

em

o3

1u!odpu3

~elu!u

v/elueu

sep

eds

uo

wlu

o3

PLO'O

E

33

4PZ

(uO!I!~!U

U!

a3ua3sau!wn~]

ZZO'O

0933 4PZ

C

eay ~a

len

t eudew

eruydec

eay Jqen

I- eu6ew

eruydea

Tab

le A

.5:

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--*"

APPENDIX A: REFERENCES

Aherne GW, Hardcastle A, Nield AH. 1990. Cytotoxic drugs and the aquatic environment - estimation of bleomycin in river water samples. Journal of Pharmacy and Pharmacology 42:741-742.

Andersen HR, Andersen A, Arnold SF, Autmp H, Barfoed M, Beresford NA, Bjerregaard P, Christiansen LB, Gissel B, Hummel R, Jorgensen EB, Korsgaard B, Le Guevel R, Leffers H, McLachlan J, Moller A, Nielsen JO, Olea N, Oles- Karasko A, Pakdel F. 2001. Comparison of short-term estrogenicity tests for identification of hormone-disrupting chemicals. Environmental Health Perspectives Supplements 1 07: 8 9- 1 08.

Backhaus T, Froehner K, Altenburger R, Grirnrne LH. 1997. Toxicity testing with Vibrio fisheri: a comparison between the long tenn (24h) and the short term (30 min) bioassay. Chemosphere 35:2925-2938.

Backhaus T, Grimme LH. 1999. The toxicity of antibiotic agents to the luminescent bacterium Vibriofisheri. .Chemosphere 38:3291-3301.

Backhaus T, Scholze M, Grimrne LH. 2000. The single substance and mixture toxicity of quinolones to the bioluminescent bacterium Vibriojiseri. Aquatic Toxicology 49:49-61.

Baldwin WS, Milam DL, LeBlanc GA. 1995. Physiological and biochemical perturbation in Daphnia magna following exposure to the model environmental estrogen diethylstilbestrol. Environmental Toxicology and Chemistry 1 4:945-952.

Baronti C, Curini R, D'ascenzo G, Corcia AD, Gentili A, Samperi R. 2000. Monitoring natural and synthetic estrogens at activated sludge sewage treatment plants and in a receiving water. Environmental Science and Technology 345059-5066.

Belfioid AC, Van der Horst A, Vetaak AD, Schafer AJ, Rijs GBJ, Wegener J, C o h o AJ. 1999. Analysis and occurrence of estrogenic hormones and their glucoronides in surface water and waste water in The Netherlands. The Science of the Total Environment 225: 101 - 108.

Boyd GR, Grimm DA. 2001. Occurrence of pharmaceutical contaminants and screening of treatment alternatives for southeastern Louisiana. Annals of the Nau York Academy of Sciences 948:80-89.

Boyd RG, Reemtsma H, Grirnrn DA, Mitra S. 2003. Pharmaceuticals and personal care products (PPCPs) in surface water and treated waters of Louisiana, USA and Ontario, Canada. The Science of The Total Environment 3 1 1 : 13 5- 149.

Brain RA, Johnson DJ, Richards, SM, Sanderson H, Sibley PK, Solomon KR. 2004. Effects of 25 pharmaceutical compounds to Lemna gibba using a seven-day static-renewal test. Environmental Toxicology and Chemistry 23:371-382.

Brambilla G, Civitareale C, Migliore L. 1994. Experimental toxicity and analysis of bacitracin, flumequine and sulphadimethoxine in terrestrial and aquatic organisms as a predictive model for ecosystem damage. Analytical Chemistry 13: 1 14-1 18.

Brooks BW, Turner PK, Stanley JK, Weston JJ, Glidewell EG, Foran CM, Slattery M, LaPoint TW, Huggett D. 2003. Waterborne and sediment toxicity of fluoxetine to select organisms. Chemosphere 52: 135-142.

Buser HR, Miiller MD, Theobald N. 1998b. Occurrence of the pharmaceutical drug clofibric acid and the herbicide mecoprop in various Swiss lakes and in the North Sea. Environmental Science and Technology 32: 1 88- 192.

Buser HR, Poiger T, Muller MD. 1998a. Occurrence and fate of the pharmaceutical drug diclofenac in surface waters: Rapid photodegradation in a lake. Environmental Science and Technology 32:3449-3456.

Buser HR, Poiger T, Miiller MD. 1999. Occurrmce and environmental behaviour of the chiral pharmaceutical drug ibuprofen in surface waters and wastewater. Environmental Science and Technology 33 :2529-253 5.

Calamari D, Zuccato E, Castiglioni S, Bagnati R, Fanelli R. 2003. Strategic survey of therapeutic drugs in the rivers Po and Lambro in northern Italy. Environmental Science and Technology 37: 1241-1248.

Cleuvers M. 2003. Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects. Toxicology Letters 142: 1 85- 194.

Cleuvers M. 2004. Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen and acetylsalicylic acid. Ecotoxicology and Environmental Safe@ 59:309-115.

Coats JR, Metcalfe RL, Lu PY, Brown DD, Williams JF, Hansen LG. 1976. Model ecosystem evaluation of the environmental impacts of the veterinary drugs phenothiazine, sulfamethazine, clopidol, and diethylstilbestrol. Environmental Health Perspectives 1 8: 167- 179.

DellaGreca M, Fiorentino A, Iesce R, Isidori M, NardelIi A, Previtera L, Temussi F. 2003. Identification of phototransformation products of predisone by sunlight: Toxicity of the drug and its derivatives on aquatic organisms. Environmental Toxicology and Chemistry 22534-539.

DellaGreca M, Fiorentino A, Isidori M, Lavorgana M, Previtera L, Rubino M, Temussi F. 2004. Toxicity of prednisolone, dexamethasone and their photochemical derivatives on aquatic organisms. Chemosphere 54:629-637.

Desbrow C, Routledge EJ, Brighty GC, Sumpter JP, Waldock M. 1998. Identificaiton of estrogenic chemicals in STW effluent. 1 Chemical fractionation and in virto biological screening. Environmental Science and Technology 32: 1549- 1558.

Drewes JE, Heberer T, Reddersen K. 2002. Fate of pharmaceuticals during indirect potable reuse. Water Science and Technology 46:73 -80.

Dzialowski EM, Brooks BW, Turner PK, Hugget DB. 2002. Influence of beta-adrenergic blockers on Daphnia magna heart rate and respiration. Annual Meeting of the

' Society of Environmental Toxicology and Chemistry.

FarrC M, Ferrer I, Ginebreda A, Figueras M, Olivella L, Tirapu L, Vilanova M, Barceld D. 2001. Determination of drugs in surface water and waste water samples by liquid chromatography - mass spectrometry: methods and preliminary results including toxicity studies with Vibrio jsheri. Journal of Chromatography A 938:187-197.

Fawell JK, Sheahan D, James HA, Hunt M, and Scott S. 2001. Oestrogens and oestrogenic activity in raw and treated water in Seven? Trent water. Water Research 35 : 1240- 1244.

Ferrari B, Mons R, Vollat B, Fraysse B, Paxkus N. 2004. Environmental risk assessment of six human pharmaceuticals: Are the current environmental risk assessment procedures sufficient for the protection of the aquatic environment? Environmental Toxicology and Chemistry 25: 1344-1 354.

Ferrari B, PaxCus N, Giudice RL, Pollio A, Garric J. 2003. Ecotoxicological impact of pharmaceuticals found in treated waste water: study of carbarnazepine, clofibric acid, and diclofenac. Ecotoxicology and Environmental Safety 55:359-370.

Fong PP, Huminski PT, D'urso LM. 1998. Induction and potentiation of parturition in fingernail clams (Sphaerium striatinurn) by selective serotonin re-uptake inhibitors (SSRIs). Journal o f ~ e r i m e n t a l Zoology 280:260-264.

Fong PP. 1998. Zebra Mussel Spawning is induced in low concentrations of putative serotonin reuptake inhibitors. BioIogicaI Bulletin 194: 143- 149.

Golet EM, Alder AC, Giger W. 2002. Environmental exposure and risk assessment of fluoroquinolone antibacterial agents in wastewater and river water of the Glatt Valley watershed, Switzerland. Environmental Science and Technology 36:3645- 3651.

Goto T, Hiromi J. 2003. Toxicity of 17a-ethynlestradiol and norethindrone, constituents of an oral contraceptive pill to the swimming and reproduction of cladoceran Daphnia magna, with special reference to their synergetic effect. Marine Pollution Bulletin 47: 139-1 42.

GVRD unpublished data

Halling-S~rensen B, Nors-Nielsen S, Lansky PF, Ingerslev F, Holten-Liitzhofi, Jorgensen SE. 1998. Occurrence, fate, and effects of pharmaceutical substances in the environment: A review. Chemosphere 36:357-393.

Halling-Smensen B. 2000. Alagal toxicity of antibacterial agents used in intensive farming. Chemosphere 40:73 1-739.

Halling-Smensen B, Holton Liitzhofi HC, Andersen HR, Ingerslev F. 2000. Environmental risk assessment of antibiotics: Comparison of mecillinam, trimethorprim and ciprofloxacin. Journal of Antimicrobial Chemotherapy 46:53- 58.

Harrass MC, Kindig AC, Taub FB. 1985. Responses of the blue-green and green algae to streptomycin in unialgal and paired culture. Aquatic Toxicology 6: 1-1 1.

Herberer S, Gramer S, Stan HJ. Occurrence and distribution of organic contaminants in the aquatic system in Berlin. Part 111: Determination of synthetic musks in Berlin surface water applying solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS). Acta Hydrochimica et Hydrobiologica 29: 150-1 56.

Herberer T, Verstraeten IM, Meyer MT, Mechlinski A, Reddersen K. 2001. Occurrence and fate of pharmaceuticals during bank filtration: Preliminary results fiom investigation in Germany and the United States. Water Resources Update 120:4- 17.

Herberer T, Reddersen K, Mechllnski A. 2002. From municipal sewage to drinking water: Fate and removal of pharmaceutical residues in the aquatic environment in urban areas. Water Science and Technology 46:8 1-88.

Herberer T. 2002. Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: A review of recent research data. Toxicology Letters 13 1:s- 17.

Herrmann K. 1993. Effects of the anticonwlsant drug valproic acid and related substances on the early development of the zebrafish (Brcahio rerio). Toxicology in Vitro 7:41-54.

Hilton MJ, Thomas KV, Ashton D. 2003. Targeted monitoring programme for pharmaceuticals in the aquatic environment. R&D Technical Report P6- 012/06/TR. Environmental Agency, Bristol, UK.

Hirsch R, Ternes T, Herberer K, Kratz K. 1999. Occurrence of antibiotics in the aquatic environment. Science of the Total Environment 225: 109-1 18.

Holten-LiitzhPrfi HC, ~alling-S'mens& B, Jsrgensen SE. 1999. Algal toxicity of antibacterial agents applied in Danish fish farming. Archives of Environmental Contamination 'and Toxicology 36: 1-6.

Huang C, and Sedalk DL. 2001. Analysis of estrogenic hormones in municipal wastewater effluent and surface water using enzyme-linked imrnunosorbent assay and gas chromatographyltandem mass spectrometry. Environmental Science and Technology 20: 133-139.

Hugget DB, Brooks BW, Peterson B, Foran CM, Schlenk D. 2002. Toxicity of select beta-adrenergic receptor-blocking pharmaceuticals @-blockers) on aquatic organisms. Archives of Environmental Contamination and Toxicology 43:229- 235.

Hugget DB, Khan IA, Foran CM, Schlenk D. 2003a. Determination of beta-adrenergic receptor blocking pharmaceuticals in United States wastewater effluent. Environmental Pollution 12 1 : 199-205.

Hugget DB, Foran CM, Brooks BW, Westin J, Peterson B, March KE, LaPoint TW, Schlenk D. 2003b. Comparison of in vitro and in vivo bioassays for estrogenicity in effluent fiom North American municipal wastewater effluent. Toxicological Sciences 72:77-83.

Johnson AC, Belfioid A, DiCorcia A. 2000. Estimating steroid oestrogen inputs into activated sludge treatment works and observations on their removal from the effluent. The Science of the Total Environment 256:163-173.

Jones OAH, Voulvoulis N, Lest JN. 2002. Aquatic environmental assessment of the top 25 English prescription pharmaceuticals. Water Research 36501 3-5022.

Joon Kang I, Yokota H, Oshima Y, Tsuruda Y, Yamaguchi T, Maeda M, Imada N, Tadokoro H, Honjo T. 2002. Effect of 17P-estradiol on the reproduction of Japanese medaka (Oryzias latipes) Chemosphere 47:71-80.

Jorgensen SE, Halling-Sorensen B. 2000. Drugs in the environment. Chemosphere 4O:69 1-699.

Jos A, Repetto G, Rios JC, Hazen MJ, Molero ML, delPeso A, Salguero M, Fernbdez- Freire P, Pkres-Martin JM, Cameb A. Ecotoxicological evaluation of carbamazepine using six different model systems with eighteen endpoints. Toxicology in Vitro 1 7525-532.

Kanda R, Griffin P James HA, Fothergill J. 2003. Pharmaceutical and personal care '

products in sewage treatment works. Journal of Environmental oni it or in^ 5:823- 830.

Koplin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT. 2002. Pharmaceuticals, hormones, and other organic waste water contaminants in US streams 1 999-2000: A national reconnaissance. Environmental Science and Technology 36 1202- 12 1 1.

Kiihn R, Pattard M, Pernak KD, Winter A. 1989. Results of the harmll effects of selected water pollutants (anilines, phenols, aliphatic compounds) to Daphnia magna. Water Research 23:495-499.

Kiimmerer K, Al-Ahmad A, Mersch-Sundermann V. 2000. Biodegradability of some antibiotics, elimination of the genotoxicity and affection of wastewater bacteria in a simple test. Chemosphere 40:701-710.

Kiimmerer K, Steger-Hartmann T, Meyer M. 1997. Biodegradability of the anti-turnour agent ifosfamide and its occurrence in hospital Effluents and communal sewage. Water Research 3 1 :2705-2710.

Lai KM, Scrimshaw MD, Lester JN. 2002. The effects of natural and synthetic steroid estrogens in relation to their environmental occwence. Critical Reviews in Toxicology 32: 1 1 3- 1 32.

L h g e R, Hutchinson TYH, Croudace CP, Siegmund F, Schweinfhth H, Harnpe P, Panter P, Sumpter J P . 2001. Effects of the synthetic estrogen 17-a-ethinylestradiol on the life-cycle of the fathead minnow (Pimephales promelas) Environmental Toxicology and Chemistry 20: 12 16-1 227.

Lanzky PF, Halling-Snrrensen B. 1997. The toxic effect of the antibiotic metronidazole on aquatic organisms. Chemosphere 35:2553-256 1.

Larsson DGJ, Adolfsson-Erici M, Parkkonen J, Pettersson M, Berg AH, Olsson PE, Forlin L. 1999. Ethinylestradiol - an undesired fish contraceptive? Aquatic Toxicology 45:91-97.

Laville N, kt-Aissa S, Gomez E, Casellas, C, Porcher JM. 2004. Effects of human phamaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes. Toxicology 196:41-55.

Macri A, Sbardella E. 1984. Toxicological evaluation of nitrofhzone and hazolidone on Selenastrum capricornutum, Daphnia magna and Musca domestica.

' Ecotoxicology and Environmental Safety 8:101-105.

Macri A, Stazi V, Di Delupis DG. 1988. Acute toxicity of Furazolidone on Artemia salina, Daphnia magna, and Culex pipiens molestus larvae. Ecotoxicology and Environmental Safety 16:90-94.

Mecalfe CD, Metcalf TL, Kiparissis Y, Koeing BG, Khan C, Hugh RJ, Croley TR, March RE, Potter T. 2001. Estrogenic potency of chemicals detected in sewage treatment plant efluents as determined by in vivo assays with Japanese medaka (Oryzias latipes). Environmental Toxicology and Chemistry 20:297-308.

Metcalfe CD, Koenig BG, Bennie DT, Servos M, Ternes TA, Hirsch R. 2003a. Occurrence of neutral and acidic drugs in the effluents of Canadian sewage treatment plants. Environmental Toxicology and Chemistry 22:2872-2880.

Metcalfe CD, Miao X, Koenig BG, Struger J. 2003b. Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada. Environmental Toxicology and Chemistry 22:288 1-2889.

Meyer MT, Bumgamer JE, Vams, JL, Daughtridge JV, Thurman EM, Hostetler A. 2000. Use of radioimmunoassay as a screen for antibiotics in confined animal feeding operations and confirmation by liquid chromatography / mass spectrometry. The Science of the Total Environment. 248: 18 1-1 87.

Migliore L, Brambilla G, Civitareale C, Di Delupis DG. 1997. Toxicity of several important agricultural antibiotics to Artemia. Water Research 3 1 : 1 80 1 - 1806.

Migliore L, Brambilla G, Grassitellis A, Di Delupis DG. 1993. Toxicity and bioaccumulation of sulphamethoxine in Artemia (Crustacea, Anostraca). International Journal of Salt Lake Research 2: 14 1 - 152.

Migliore L, Cozzolino S, Fiori M. 2000. Phytotoxicity to and uptake of flumequine used in intensive aquaculture on the aquatic week, Lythrum salicaria L. Chemosphere 40:741-750.

Mulroy A. 2001. Antibiotic contamination of surface water and groundwater may be promoting the development of drug resistant pathogens. KE&T 32-36.

0llers S, Singer HP, Fksler P, Miiller SR. 2001. Simultaneous quantification of neutral and acidic pharmaceuticals and pesticides at the low-ng/l level in surface and waste water. Journal of Chromatography A 9 1 1 :225-234.

Orvos DR, Versteeg DJ, Inauen J, Capdevielle M, Rothenstein A, Cunningham V. 2002. Aquatic toxicity of triclosan. Environmental Toxicology and Chemistry 2 1 : 13 3 8- 1349.

Paxkus N. 1996. Organic pollutants in the effluents of large wastewater treatment plants in Sweden. Water Research 30: 1 1 15-1 122.

Peterson SM, Batley GE, Scamrnell MS. 1993. Tetracycline in Antifouling Paints. Marine Pollution Bulletin 26:96-100.

Petrovic M, Solk M, Upez De Alda MJ, Barcel6 D. 2002. Endocrine disrupters in sewage treatment plants, receiving river waters, and sediments: Interaction of chemical analysis and biological effects on feral carp. Environmental Toxicology and Chemistry 2 1 :2146-2156.

Pomati F, Netting AG, Calamari D, Neilan BA. 2004. Effects of erythromycin, tetracycline and ibuprofen on the growth of Synechocystis sp. and Lemma minor. Aquatic Toxicology 67:3 87-396.

Putschew A, Wischnack S, Jekel M. 2000. Occurrence of triiodinated x-ray contrast agents in the aquatic environment. The Science of the Total Environment 255:129- 134.

Sanderson H, Johnson DJ, Reitsma T, Brain RA, Wilson J, Solomon KR. 2004. Ranking and prioritization of environmental risks of pharmaceuticals in surface waters. Regulatory Toxicology and Pharmacology 39: 1 5 8- 1 83.

Scholz S, Gutzeit HO. 2000. 17-a-ethinylestradiol affects reproduction, sexual differentiation and aromatase gene expression of the medaka (Oryzias latipes) Aquatic Toxicology 50:363-373.

Seiler RL, Zaugg SD, Thomas JM, Howcroft DL. 1999. Caffeine and Pharmaceuticals as indicators of waste water contamination in wells. Ground Water 37:405-410.

Seiler JP. 2002. Pharmacodynamic activity of drugs and ecotoxicology: Can the two be connected? TonicoIogy Letters 13 1 : 1 05- 1 1 5.

Servos MR, Bennie DT, Starodub ME, Orr JC. 2002. Pharmaceuticals and personal care products in the environment: A summary of published literature. Report Number 02-309. National Water Research Institute, Environment Canada, Burlington Ontario, Canada.

Snyd-er SA, Westerhoff P, ~ o o n Y, Sedlak DL. 2003. Pharmaceuticals, personal care products, and endocrine disruptors in water: Implications for the water industry. Environmental' Engineering Science 20:449-469.

Staels B, Dallongeville J, Auwm J, Schoonjans K, Leitersdorf E, Fruchart J. 1998. Cardiovascular drugs: Mechanism of action of fibrates on lipid and lipoprotein metabolism Circulation 98:2088-2093.

Stan H, Herberer T. 1997. Pharmaceuticals in the aquatic environment. Water Analysis 25 :2O-23.

Steger-Hartmann T, Kumrnerer K, Hartmann A. 1997. Biological degredation of cyclophosphamide and its occurrence in sewage water. Ecotoxicology and Environmental Safety 36: 1 74- 1 79.

Steger-Hartmann T, Lhge R, Schweinfhth H. 1999. Environmental risk assessment for the widely used iodinated x-ray contrast agent iopromide (ultravist). Ecotoxicology and Environmental Safety 42:274-28 1.

Stumpf M, Ternes TA, Wilken RD, Rodrigues SV, Baumann W. 1999. Polar drug residues in sewage and natural waters in the state of Rio de Janeiro, Brazil. The Science of the Total Environment 225: 135- 141. z

Tabak HH, Bloombuff R, Bunch RL. 1981. Steroid honnones as water pollutants: 11 Studies on the persistence and stability of natural urinary and synthetic ovulation- inhibiting hormones and treated wastewaters. DeveIopments in Industrial Microbiology 1 1 :367-76.

Tas JW, Balk F, Ford RA, van de Plassche EJ. 1997. Environmental risk assessment of musk ketone and musk xylene in the Netherlands in accordance with the EU- TGD. Chemosphere 35:2973-3002.

Ternes TA, Bonerz M, Schmidt T. 200 1. Determination of neutral pharmaceuticals in waste water and rivers by liquid chromatography -electrospray tandem mass spectrometry. JournaI of Chromatography 938: 175-1 85.

Ternes TA, Hirsch R. 2000. Occurrence and behaviour of x-ray contrast media in sewage facilities and the aquatic environment. Environmental Science and TechnoIogy 34:2741-2748.

Ternes TA, Kreckel P, Mueller J. 1999. Behaviour and occurrence of estrogens in municipal seawage treatment plants - 11. Aerobic batch experiments with activated sludge. The Science of the TotaI Environment. 225:91-99.

Ternes TA, Stiiber J, Herrrnann N, McDowell D, Reid A, Kampmann M, Teiser B. 2003. Ozonation: a tool for removal of pharmaceuticals, contrast media and musk fragrances for wastewater Water Research 37:1976-1982.

Ternes TA. 1998. Occurrence of drugs in German sewage treatment plants and rivers. Water Research 3 2:3245-3260.

Tooby TE, Hursey PA, Alabaster JS. 1975. The acute toxicity of 102 pesticides and miscellaneous substances to fish. Chemistry and Industty 6523-526.

VanWezel AP, Jager T. 2002. Comparison of two screening level risk assessment approaches for six disinfectants and pharmaceuticals. Chemosphere 47: 1 1 13- 1128.

Wang WH, Lay JP Lay. 1989. Fate and effects of salicylic acid compounds in freshwater systems. EcotoxicoIogy and EnvironmentaI Safety 17:308-3 16.

Watts MW, Pascoe D, Carroll K. 2001. Survival and precopulatory behaviour of GammaruspuIex (L.) exposed to two xenoestrogens. Water Research 35:2347- 2352.

Webb SF. 2001. A data-based perspective on the environmental risk assessment of human pharmaceuticals - Collation of available ecotoxicity data. In: Kiimmerer K, ed, Pharmaceuticals in the Environment. Sources, Fate, Effects and Risks. 1 st ed, Springer Verlag, Berlin, pp 175-200.

Weigel S, Bester K, H i i m e h s H. 2001. New method for rapid solid-phase extraction of large-volume water samples and its application to non-target screening of North Sea water for organic contaminants by gas chromatography-mass spectrometry. Journal of Chromatography A 9 1 2: 1 5 1 - 1 6 1.

Weigel S, Kuhlmann J, Hiirnefiss H. 2002. Drugs and personal care products as ubiquitous pollutants: occmence and distribution of clofibric acid, caffeine and DEET in the North Sea. Z?ze Science of the Total Environment 295: 13 1 - 141.

Winkler M, Lawrence JR, Neu TR. 2001. Selective degradation of ibuprofen and clofibric acid in two model river biofilm systems. Water Research 35:3 197-3205.

Wollenberger L, Halling-Sorensen B, Kusk KO. 2000. Acute and chronic toxicity of ' veterinary antibiotics to Daphnia magna. Chemosphere 40:723-730.

Xiao X, McCalley DV, McEvoy J. 200 1. Analysis of estrogens in river water and effluents using solid-phase extraction and gas chromatography-negative chemical ionisation mass spectrometry of the pentafluorobenzoyl derivatives. Journal of Chromatography A 923 : 195-204.

Zillioux EJ, Johnson IC, Kiparissis Y, Metcalfe CD, Wheat JV, Ward SG, Liu H. 2001. The sheepshead minnow as an in vivo model for endocrine disruption in marine teleosts: A partial life-cycle test with 17-a-ethinylestradiol. Environmental Toxicology and Chemistry 20: 1968-1 978.

Zou E, Fingermann M. 1997. Synthetic estrogenic agents do not interfere with sex differentiation but do inhibit molting of the cladoceran Daphnia magna. Bulletin of Environmental Contamination and Toxicology 58596-602.

APPENDIX B: RISK CHARACTERIZATION DATA

Table B.1: Summary of acute hazard quotient calculations and ranked PPCPs

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

Table B.9: Summary of the exposure concentrations and toxicity reference values used in cumulative frequency distributions for tetracycline