Pharmaceuticals in the Environment –A Review of PhRMA Initiatives
Mary E. Buzby
Director, Environmental Technology
Merck & Co., Inc.1
Pharmaceutical Research and Manufacturers of America2
1. Introduction
When patients consume pharmaceuticals, there may be some active
pharmaceutical ingredient (API) that is not completely metabolised and is
excreted by the patient. These small quantities of material are then transported
to wastewater treatment systems where most of them are removed but some aredischarged to receiving streams.
Recently, as a result of advances in analytical techniques, it has become
possible to show that pharmaceuticals can be measured in wastewater, surface
water (rivers and streams) and drinking water at low concentrations. There issubstantial public concern about the possibility of health or environmental effects,
compounded by debate about the effects of endocrine modulating chemicals andworries about resistance to antibiotics.
There is ongoing scientific work to establish the extent of the issues. PhRMA
has been actively involved in industry efforts to develop models that can then be
used to identify potential environmental exposures from pharmaceutical products
entering the environment through patient use.

When used with appropriate

effects information, these exposure assessments may be used to assess
potential risk to human health and the environment from trace levels ofpharmaceuticals in drinking and surface waters. In addition, PhRMA has beenproactively involved in efforts to develop: the science needed to understand andmanage the technical aspects; the methodologies to better define theenvironmental fate characteristics of pharmaceuticals and the appropriate
end-points for impacts on aquatic life and ecosystems; and the strategies
needed to appropriately manage the issue. However, the state-of-the-art forthis issue is developing rapidly, and considerable additional work needs to bedone to ensure that this issue is understood, managed, and properly
1

2

WS2W14, Two Merck Drive, Whitehouse Station, NJ 08807
From work by Virginia Cunningham, Glaxo Smith Kline- 165 -

communicated to internal and external stakeholders, including employees,
contractors, suppliers, customers, investors, governmental agencies, NGOs,
and the public.
2. Background
The widespread detection of pharmaceuticals in environmental samples as a result of
improved analytical capabilities and focused field surveys has led to concern over the
potential risks associated with releases of pharmaceuticals into the environment. This
concern has been driven by surface water sampling programs in the US, Europe andelsewhere that have all shown the presence of many different classes ofpharmaceuticals. The high polarity and low volatility of most pharmaceuticals meansthat they are likely to be transported to and by the water compartment. The research
published to date describes the sampling and analysis of surface water, groundwater,
drinking water, and sewage treatment plant (STP) effluent, and the detection ofpharmaceutical active ingredients and their degradation products, usually atconcentrations much less than 1 µg/L. The pharmaceuticals reported in surface water
include hormones (e.g., synthetic and natural estrogens), antibiotics, blood lipid
regulators, non-steroid analgesics and anti-inflammatory agents, beta-blockers,
antiepileptics, antineoplastics, tranquilizers, and diagnostic contrast media. Althoughsome pharmaceuticals are unlikely to be a risk to the aquatic environment because of
low concentrations combined with low toxicity, other pharmaceuticals such as naturaland synthetic sex hormones may pose potentially significant risks.
Attention has focused on pharmaceuticals used in both veterinary and human medicine;
however the environmental exposure scenarios are quite different for these modes ofentry.

A comprehensive discussion of the issue of veterinary medicines in theenvironment, which may be introduced to the environment through a variety of direct andindirect, point and diffuse sources, is provided in Boxall et al.. In contrast, exposure ofaquatic wildlife to human pharmaceuticals is most likely to occur from sewage treatment
plant (STP) point source discharges and this exposure may therefore be at continuous,
low concentrations. Despite this, most published aquatic toxicity data and risk
assessments for pharmaceuticals are based on short-term acute studies. Concerns overthe possible environmental effects of low level continuous aquatic exposure to humanpharmaceuticals have led to significant revisions in European new drug regulatory
submission requirements, where chronic aquatic toxicity tests have been adopted in themost recent environmental risk assessment guidance document for humanpharmaceuticals produced by the European Medicines Agency in support of Directive
2001/83/EC.

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3.

Occurrence in the Environment
In the late 1980s, new, highly sensitive analytical methods for organic chemicals withpolar and nonpolar properties were developed. These new analytical methods could
detect and quantitate organic chemicals, including pharmaceuticals, at concentrations
ranging from 1-100 nanograms/litre (ng/L). Some pharmaceutical chemicals can now
be identified and quantified at sub-ng/L concentrations, i.e., down to 100 parts per
quadrillion (to 0.1 ng/L).
Efforts to improve the sensitivity of analytical methods for trace analytes in water willcontinue. As an example of the sensitivity of analytical methods for trace organics inwater, the currently approved analytical method for 2,3,7,8-tetrachloro-p-dioxin can
detect this chemical at less than 1 picogram/litre (pg/L) - 1000 times lower than 1 ng/L,nearly approaching the molecular level. As the sensitivity of analytical methods
increases, it is likely that additional chemicals will be identified in ambient waters andthat chemicals already found may prove to be more widespread.

4.

Behavior in the Environment
Aquatic transport and transformation processes in the environment include sorption,
ionization,

volatilization,hydrolysis,oxidation-reduction,transformation-degradation and precipitation-dissolution.

photolysis,

biological

These processes occur

continuously in the environment and influence the presence and bioavailability ofpharmaceuticals in aquatic ecosystems.

Response of drugs to any of these pathways

for partitioning, degradation or change in the environment could reduce theirconcentrations in the environment or remove them entirely and thereby reduce theirpotential to impact human health and aquatic life.

Pharmaceutical compounds that aremarketed in large quantities and are soluble or slightly soluble yet resistant todegradation through biological or chemical processes have the greatest potential toreach steady-state levels in the environment and be detected in surface and groundwaters and potable water supplies.

5.

Understanding the Risk to Human Health - Modeling as One Approach
The potential risk to human health associated with low levels of pharmaceuticals in theenvironment is a function of exposure and hazard.

One way to assess this risk is tocreate a model to predict human exposure and evaluate the hazard present.

However,models are merely predictive and are only as good as the input data and assumptions- 167 -

used.

Models can be constructed, using the principles discussed above, to estimate

the human health risk associated with pharmaceuticals in the environment.
Screening models can be used to evaluate large numbers of compounds, employing
conservative assumptions and readily available data, in order to identify thosecompounds with the greatest potential risk.
26 APIs has been published.

A PhRMA-sponsored risk assessment for

Other assessments have been published as well.

Detailed deterministic or probabilistic models can then be used to provide moredefinitive risk estimates for those compounds, and/or classes of compounds, identified
in the screening analysis.

Deterministic models are used to simulate site-specificconditions in a particular area, while probabilistic models are used to estimate thepercentage of the population exposed to various levels of risk.
A.

HazardThere is no universally accepted methodology to measure the human health hazard
associated with low levels of pharmaceuticals in the environment.

One approach

could be to use the therapeutic dose with a safety factor of 1000. Another approach is touse EPA's Reference Dose (RfD) methodology. The RfD is the amount of a chemicalthat a person, including sensitive subgroups, can be exposed to on a daily basis withoutcausing adverse health effects over a lifetime. The RfD is derived from the no observed
adverse effect level (NOAEL) by consistent application of generally order-of-magnitudeuncertainty factors.
One methodology developed and reported by pharmaceutical industry scientists is amodel to establish human health predicted no effects levels (PNECs). Typically during
the research and development of pharmaceuticals, a risk/benefit analysis is used byregulatory authorities to evaluate the safety of pharmaceuticals for the patient population.
A certain amount of risk, e.g., side effects, is recognized as acceptable to receive thetherapeutic benefits. This contrasts with the case where no benefit is presumed to bereceived by the exposed individual, such as the incidental exposure to pharmaceuticals
through drinking water or fish consumption. The potentially exposed population ispresumed to include healthy adults as well as susceptible sub-populations (e.g., children,
the elderly, and infirm) in which the pharmacologic effect is considered undesirable.
The database for a compound normally contains several toxic endpoints from which a
point of departure should be determined to calculate the most restrictive reference value(or allowable daily intake - ADI). The point of departure for determining an ADI for
chemicals is often either the highest dose resulting in no observed effects (no observed
effect level or NOEL) or in no observed adverse effects (no observed adverse effectlevel or NOAEL) for a given toxic endpoint. For many APIs, however, a point of departure- 168 -

is the lowest dose resulting in an observable effect (lowest observed effect level or
LOEL) or in an observable adverse effect (lowest observed adverse effect level or
LOAEL). For an API, the therapeutic effect usually occurs at a dose considerably below
those expected to result in toxicity.
B.

Exposure

Human exposure to environmental concentrations of pharmaceuticals is believed to be
primarily through ingestion of drinking water and, for compounds that bioaccumulate,
through ingestion of meat or fish.
The concentration of drug substances in drinking water depends on the following
factors:•

the quantity of drug substance consumed by a given population;•

the extent to which the drug is metabolised in the body;•available dilution in public sewer systems and in receiving waters;•

removal and partitioning in STPs and receiving waters; and,•degree of removal by drinking water treatment technologies.

Drug sales data available from IMS Health can provide the total mass of individual drug
substances across all product lines.

Since IMS data are not readily available except

through commercial license agreements, many published studies use prescription sales
data to characterize drug sales.

However, it is difficult to estimate the mass of drugs

sold from prescription data, because of the many different drug products and since thenumber of scripts typically does not include drugs dispensed in hospitals or nursing
homes.

Furthermore, there are several reasons why drug sales data may not translate

into accurate drug use data: (1) drugs may be discarded in toilets or household trash (asmall amount); (2) average sales data may not reflect geographic or seasonal variability
in consumption; and, (3) only a portion of the drug substance may be delivered to thebody, e.g., transdermal dosage forms.
After ingestion, human drugs undergo Phase I metabolism, which includes oxidation,
reduction or hydrolysis; followed by Phase II metabolism, which involves conjugation(e.g., addition of glucuronic acid, sulphate, acetic acid or amino acid).

Dependingupon the drug, these processes can yield various proportions of unchanged drug
substance, active or inactive metabolites, or conjugates.

There is evidence that

conjugates can be converted back to the parent drug or metabolite through bacterialhydrolysis in a STP.

The reduction in pharmacological activity following metabolism- 169 -

can range from zero to essentially 100 percent depending on the drug.
Drug substances excreted into the public sewer are diluted by the available wastewaterflow.

The average total STP influent flow in the US is 121.4 billion liters per day, which

is used to estimate the expected introductory concentration for FDA. Regional andseasonal variability in STP flow is expected as a result of differences in water
consumption per capita, industrial water use, weather conditions, etc.

STP effluent isfurther diluted by the receiving water – a factor of 1:10 is often used to account for
dilution in the environment.

As described in Section 2, a number of degradation andpartitioning mechanisms can act on drug substances in both an STP and theenvironment.
Conservative estimates of environmental concentrations of a drug substance can becalculated from the total mass of drug substance sold and the available dilution from
STP and receiving water flow as described above.

These estimates can be refined byconsidering metabolism and the various STP and environmental degradation andpartitioning mechanisms.
C. Characterizing Risk
The estimation of potential impact of human pharmaceuticals to human health fromenvironmental exposures typically uses two concepts: the predicted environmental
concentration (PEC) and the predicted no effect concentration (PNEC).

The PECelement is based on the physical, chemical and biological fate properties of themolecule, as well as hydrological information on STP effluent flows and surface waterflows.

The PNEC element estimates concentrations at which potential effects onhuman health might occur.

In general, if the PEC is less than the PNEC (PEC/PNEC <1) the risk is deemed acceptable.

This approach to environmental risk assessment iscalled the risk characterization ratio method.
7.

Modeling as One Approach Understanding the Risk to the Environment
As with the risk to human health, the potential risk to the environment presented by thepresence of pharmaceuticals is a function of hazard and exposure.
A.

Potential for and Evaluation of Acute Hazards

Pharmaceutical companies sometimes conduct acute toxicity studies to support
environmental assessments that are filed with NDA and MAA applications or to support- 170 -

internal programs.

Acute toxicity to aquatic receptors is usually assessed byevaluation of several common species including typically a fish (usually fatheadminnows, bluegills or rainbow trout), an invertebrate (usually a daphnid such as
Daphnia magna) and an algal species.

These acute toxicity studies last up to 96 hours.

The endpoints measured may include growth and/or growth rate (algae), immobilisation(Daphnia), and morbidity and/or mortality (fish) and are often expressed as aconcentration that elicits an effect in a specified percentage of the test group.

For

substances that may be expected to partition into soils or sediments, studies interrestrial species, such as earthworms, may be conducted.
Generally speaking, there is little potential for an acute environmental hazard to exist
from the presence of pharmaceuticals that find their way into the environment throughuse by humans because the levels are so low.

As for the potential for an acuteenvironmental hazard to be presented from pharmaceutical manufacturing, there areregulatory and industry practices in place that minimise the risk. Environmental
agencies have in place permitting programs that control acutely toxic manufacturing
discharges.
B. Potential for and Evaluation of Chronic Hazards
There are several methods that are currently approved by regulatory agencies for the
conduct of chronic aquatic toxicity studies.

The most commonly used are the Daphnia

21-day toxicity study and the prolonged toxicity study in fish.

Currently, such studies

are conducted relatively infrequently due to the relatively low introduction
concentrations of drug substances into the environment, the tendency for many drugs
to be metabolized to relatively more water-soluble and less active metabolites, andbecause they are primarily produced by batch vs. continuous manufacturing operations.
There is however, considerable interest in the development of improved methods foraquatic toxicity assessments of chronic effects.

In addition, the EMEA Guidelines forenvironmental risk assessments for new pharmaceuticals now requires a base set ofchronic ecotoxicity studies in lieu of the previously required acute studies.
C.

Characterizing Risk

The estimation of potential impact of human pharmaceuticals to aquatic life mirrors theprocedure used for human health risk characterization: the predicted environmental
concentration (PEC) and the predicted no effect concentration (PNEC).

Here, thePNEC element estimates concentrations at which potential effects on aquatic life might- 171 -

occur.

In general, if the PEC is less than the PNEC (PEC/PNEC < 1) the risk isdeemed acceptable.

This approach to environmental risk assessment is called therisk characterization ratio method.

C. Links
EMEA Guideline on the environmental risk assessment of medicinal products forhuman use; The European Agency for the Evaluation of Medicinal Products, London,
England, June 2006 Doc. Ref. EMEA/CHMP/SWP/4447/00
http://www.emea.eu.int/pdfs/human/swp/444700en.pdf
FDA-CDER. Guidance for industry - environmental assessment of human drugs andbiologics applications, FDA Center for Drug Evaluation and Research, Rockville, MD,
USA (CMC6 Revision 1), 1998, http://www.fda.gov/cder/guidance/index.html)
The Swedish Association of the Pharmaceutical Industry (LIF) (http://www.fass.se)
Pharmaceuticals and Personal Care Products (PPCPs) as Environmental Pollutants
http://www.epa.gov/esd/chemistry/pharma/
Monograph, Toward a Green Pharmacy (US EPA)
http://www.epa.gov/esd/chemistry/pharma/images/green1.pdf
Antibiotic Resistance (US FDA)
http://www.fda.gov/oc/opacom/hottopics/anti_resist.html
Endocrine Disruption (WHO)http://www.who.int/pcs/emerg_site/edc/global_edc_TOC.htm
US PhRMA Position on Pharmaceuticals in the Environment
http://www.phrma.org/mediaroom/press/releases///13.03.2002.366.cfm
PhRMA PhATE Model:Screening Analysis of Human Pharmaceuticals in US Surface
Watershttp://pubs.acs.org/cgi-bin/article.cgi/esthag/2004/38/i03/pdf/es034430b.pdf
Human pharmaceuticals in US surface waters: A human health risk assessment
http://dx.doi.org/ doi:10.1016/j.yrtph.2005.05.005- 172 -

Effects of Human Pharmaceuticals on Aquatic Life: Next Steps
http://pubs.acs.org/subscribe/journals/esthag/40/i11/pdf/060106viewpoint_cunningham.pdf

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assessment of human pharmaceuticals II — aquatic risk characterisation. In: K.
Kümmerer, Editor, Pharmaceuticals in the Environment: Sources, Fate, Effects andRisks (Second Edition), Springer, Berlin, Germany (2004), pp. 345–361.
Webb, 2004. S.F. Webb, A data-based perspective on the environmental risk
assessment of human pharmaceuticals I — collation of available ecotoxicity data.
In: K. Kümmerer, Editor, Pharmaceuticals in the Environment: Sources, Fate,
Effects and Risks (Second Edition), Springer, Berlin, Germany (2004), pp.
317–343.
Webb, et al. 2003. Indirect human exposure to pharmaceuticals via drinking water,
Toxicology Letters, 142, 157-167.
Williams 2005. Williams, R.T., Ed. Science for Assessing the Impacts of Human
Pharmaceuticals on Aquatic Ecosystems; SETAC Press, Pensacola, FL 2005
Zuccato et al. 2004. E. Zuccato, S. Castiglioni, R. Fanelli, R. Bagnati, G. Reitano and
D. Calamari, Risks related to the discharge of pharmaceuticals in the environment:- 178 -

further research is needed. In: K. Kümmerer, Editor, Pharmaceuticals in theEnvironment: Sources, Fate, Effects and Risks (Second Edition), Springer, Berlin,
Germany (2004), pp. 431–437.

Zuccato et al. 2004. E. Zuccato, S. Castiglioni, R. Fanelli, R. Bagnati and D. Calamari,Pharmaceuticals in the environment: changes in the presence and concentrationsof pharmaceuticals for human use in Italy. In: K. Kümmerer, Editor,
Pharmaceuticals in the Environment: Sources, Fate, Effects and Risks (Second
Edition), Springer, Berlin, Germany (2004), pp. 45–53.

- 179 -

IssuePharmaceuticals in the Environment– A Review of PhRMA Initiatives• Pharmaceutical products are being detected in
the environment• Concern has been expressed that human healthand aquatic life impacts might result fromenvironmental exposure to pharmaceuticalcompounds

Mary E. Buzby, Ph.D.
Merck & Co., Inc.
Pharmaceutical Research and Manufacturers of America
Prepared for
4th Japan – U.S. Governmental Conference on Drinking Water Quality
Management and Wastewater Control

PhRMA Perspective

Benefits of a Science Based Approach to PIE• A science-based approach:• Provide confidence to the industry, communities andgovernments that safety of pharmaceuticals in theenvironment is well understood− is required to understand and address concerns
resulting from presence of pharmaceutical compounds
in the environment• Identify any issues requiring further investigation
regarding existence and significance of potential impacts− will identify gaps in existing knowledge that require
further investigation regarding the potential for impacts

Characteristics of Pharmaceuticals

Characteristics of Pharmaceuticals• Pharmaceuticals are often ionic, which influences theirenvironmental fate.

• Pharmaceuticals enter the environment continuously.
• Sources are geographically diffuse and may be
influenced by regional use patterns.

• Ionic, hydrophilic behavior is not typical of chemicals
usually evaluated for environmental fate and effects.

• Compounds in the environment may be parent,
metabolites or conjugates.

– Many environmental models developed for non-ionicchemicals are not applicable to ionic, multifunctional
compounds; their use• Compounds may be present in mixtures with otherpharmaceuticals, organic and inorganic pollutants, etc.

• may lead to incorrect interpretations of test results• Science challenges exist, e.g., testing methods,
mixtures, chronic eco-toxicity endpoints• may lead to improper classifications

Pharmaceuticals in the Environment

A Science-based Approach: A step-wise progression• Understand the potential for exposure• Assess potential impacts to man• Assess potential impacts to environmental

SewageTreatment Plant

species
Drinking Water
Treatment Plant

Patient Use is the Primary Pathway Human
Pharmaceutical Compounds Enter the Environment- 180 -

The PhATE Model™

PhATE™ Model Development (2001)

Needs:• Watershed (drainage basin of receiving waterbody)– a geographic area in which water, sediments anddissolved materials drain to a common outlet• Evaluate potential distribution of pharmaceuticalcompounds in the environment• Assess the significance of reported concentrations tohumans and aquatic life

• Approach allows better understanding of the
cumulative impact of human activities

Action:• Many regions moving toward watershed based
water quality management• Develop tool to estimate concentrations ofpharmaceutical compounds in the environment

PhATE™ Model Development (2001)• Model predicts concentrations of pharmaceuticals in
the environment due to patient use• Model was developed by PhRMA PIE Task Force and
AMEC Earth and Environmental• Third party reviewers:• Dr. Josh Cohen, Harvard School of Public Health• Dr. Steve Chapra, Tufts University

Watershed Evaluation
(C1)
(C2)

POTW

DWS
(C3)

(C4)
(C5)

DWS
(C6)

POTW

Example PhATE™ Output: carbamazepine

Determination of Concentration Profiles

10,000.0

1,000.0

DWS

C1

CBZ Concentration, ng/L

Concentration

POTW = publicly owned wastewater
treatment plant
DWS = Drinking water system intake

DWS
C2
DWS
DWS

Low Flow PECs
from Ph ATE

FDA PEC (using
10:1 dilution)
100.0

10.0

MECs in the U.S.

C3v
1.0

C4
POTW

POTW

Mean Flow PECs
from Ph ATE

POTW
0.1

Distance Along River

0%

10%

20%

30%

40%

50%

60%

Cumulative Probability- 181 -

70%

80%

90%

100%

Model-related publications•

A Science-based Approach: A step-wise progression

USGS Paper:–Kolpin, et al., Pharmaceuticals, Hormones, & Other Wastewater Contaminants in
U.S. Streams, 1999-2000: A National Reconnaissance, Environ. Sci. Technol.. 2002,
36, 1202-1211.

•• Understand the potential for exposure

PhATE™ Papers:• Assess potential impacts to man–Cunningham, V.L. The PhATE™ Model: Estimating the Distribution of
Pharmaceuticals in the Environment, Southwest Hydrology, November/December 2003,
20-21• Assess potential impacts to environmental–Anderson, P.D.; D’Aco, V.J.; Shanahan, P.; Chapra, S.C.; Buzby, M.E.; Cunningham, V.L.;
DuPlessie, B.M.; Hayes, E.P.; Mastrocco, F.J.; Parke, N.J.; Rader, J.C.; Samuelian, J.H.;
Schwab, B.W. Screening analysis of human pharmaceutical compounds in U.S.
surface waters. Environ. Sci. Technol. 2004, 38, 838-849.

species–Cunningham, V. L.; Constable, D. J.; Hannah, R. E. Environmental Risk Assessment of
Paroxetine, Environ. Sci. Technol. 2004, 38, 3351-3359.
– Cunningham, V.L.; Buzby, M.; Hutchinson, T.; Mastrocco, F.; Parke, N.; Roden, N. Effectsof Human Pharmaceuticals on Aquatic Life: Next Steps,
Environ. Sci. Technol. 2006, 40, 3456 - 3462

Human Health Screening Analysis

Human Health Screening Analysis• Analysis included 26 USGS human health pharmaceuticals
–
–
–
–
–
–
–
–
–
–
–

• Identified measured environmental concentrations
for compounds reported in published articles (MEC)

Non-steroidal analgesics, non-steroidal anti-inflammatory
Opiate analgesic
Bronchodilator
H2 receptor antagonists
Antimicrobial, antibiotics, antibacterial
Calcium blocker, ACE inhibitor, anti-hypertensives
Serotonin uptake inhibitors, anti-depressive
Hypoglycemic
Anti-coagulant
Cardiac glycoside
Anti-hyperlipidemic• Used PhATE™ in screening mode to predict
concentrations in environment

PEC• Developed predicted no effect concentrations(PNEC)– Considered drinking water and fish consumption exposure
pathways
PNEC• Compounds studied excluded hormones which are being evaluatedseparately due to the complexity of that evaluation• Evaluated MEC/PNEC and PEC/PNEC ratios

Human Risk Assessment

Other Human Health Publications• Christensen, F.M. (1998) Pharmaceuticals in the environment –A Human Risk?, Reg. Toxicol. & Pharmacol., 28, 212-221.

Conclusion:• Schulman, et al., (2002) A human health risk assessment ofpharmaceuticals in the aquatic environment, Human &Ecological Risk Assessment, 8 (4), pp. 657-680.

“Results of this human health assessment indicatethat no appreciable human health risk exists fromthe presence of these trace residues in surface
water and drinking water.”• Mons, M.N., (2003) Pharmaceuticals and drinking water supply
in the Netherlands, Kiwa N.V. Water Research.

Schwab, B. W., et al. Human pharmaceuticals in US surface waters: A humanhealth risk assessment, Reg. Tox. Pharmacol. 2005, 42, 296-312• Webb, et al., (2003) Indirect human exposure topharmaceuticals via drinking water, Toxicology Letters, 142,
157-167.
All concluded that environmental exposure to human pharmaceuticals
poses little human health risk.

Aquatic Life Data Base - PhACT™

A Science-based Approach: A step-wise progression• Includes English language, peer-reviewed literature– chronic and acute effects to aquatic organisms• Understand the potential for exposure– fate and transport and treatment removal• Bibliographic information entered for 1028 articles• Assess potential impacts to man– 610 chronic and acute effects• Assess potential impacts to environmental– 618 fate and transport / treatment• Status

species– data from 583 articles have been entered– data from remaining 445 articles will be entered by 2007
– data from 30-40 new articles entered each quarter- 182 -

Low Flow PEC without loss
Mean Flow PEC without loss
Low Flow PEC with loss

Other PhRMA PIE Publications

Ibuprofen

Mean Flow PEC with loss
Max Kolpin
Max Other Investigators
Benchmarks

1000000000•

Till (2005) The detection of pharmaceutical compounds in surface water is amatter of significant interest to the pharmaceutical industry. Sci. Tot. Environ. In
press.

•

Till (2005) Pharmaceutical data do not elude researchers. Environ. Sci. Technol.
(Oct 1 2005, p 292a)

100000000

Concentration (ng/L)

10000000
1000000•

Carbamazepine risk assessment (SETAC presentations, Nov. 2005, May 2006)

100000•Cunningham et al. Human Health and Environmental Risk Assessment of
Carbamazepine in Surface Waters of North America and Europe, submitted forreview

10000
1000
100
10
1
0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

•

Analgesics case study (SETAC poster, Nov, 2005); manuscript in preparation•

Do pharmaceuticals in surface waters pose a risk to human health? In
submission process•

Environmental risk assessment of EE2 in EU and US - manuscripts in preparation•

Landfill Disposal of Medicines as a Potential Surface Water Pathway – WEF
presentation, August 2007, manuscript in preparation

Triangles represent acute benchmarks.
Squares represent chronic benchmarks.
NBR = Not biologically relevantContributors

Summary• Pharmaceutical Research and Manufacturers of America• The industry is committed to assessing the significance ofpharmaceuticals in the environment using science- based
approaches.

• Aquatic Life Working Group• Human Health Working Group• The human risk assessment concluded that, for the compounds
investigated to date, no appreciable risk to human health exists.

• Environmental Assessment Working Group• The industry is evaluating published data on aquatic life impacts
and formulating an approach to assess the potential for impacts
to ecosystems.

• Vince D’Aco, Quantum Management Group, Inc.

• Unused Medicines Working Group• Paul Anderson and Beth DuPlessie, AMEC

• The industry is committed to collaborating with other stakeholders• Lial Tischler, Tischler & Kocurek- 183 -