pharmaceutical compounds and ecosystem …udel.edu/~inamdar/nps2007/marshall2012.pdfpharmaceutical...

Pharmaceutical Compoundsand Ecosystem Function:

An Emerging Research Challengefor Aquatic Ecologists

Emma J. Rosi-Marshall1* and Todd V. Royer2

1Cary Institute of Ecosystem Studies, 2801 Sharon Turnpike, Millbrook, New York 12545, USA; 2School of Public & Environmental

Affairs, Indiana University-Bloomington, 1315 East Tenth Street, Bloomington, Indiana 47405, USA

ABSTRACT

The number of anthropogenic compounds that

occur in aquatic ecosystems today is in the thou-

sands, many at trace concentrations. One group of

compounds that has captured the interest of both

the scientific community and the general public

is pharmaceutical and personal care products

(PPCPs), for example, hormones, chemotherapy

drugs, antihistamines, stimulants, antimicrobials

and various cosmetic additives. Toxicology of some

PPCPs is currently understood, but their effect on

ecological structure and function of aquatic eco-

systems is largely unknown. We review sources

and fates of these compounds in aquatic ecosystems

and discuss how methods developed to study

aquatic ecosystem ecology can contribute to our

understanding of the influence of PPCPs on aquatic

ecosystems. We argue that aquatic ecology has a

well-developed tool kit for measuring the trans-

formation, fate, and transport of solutes using as-

says and experiments and that these methods could

be employed to investigate how PPCPs impact

ecological function. We discuss the details of these

approaches and conclude that application of exist-

ing ecological methods to the study of this issue

could substantially improve our understanding of

the effect of these compounds in aquatic ecosys-

tems.

Key words: methods; ecotoxicology; biogeo-

chemical processes; large-scale experiments;

nutrient spiraling; aquatic ecosystems.

INTRODUCTION

Pharmaceutical and personal care compounds,

such as fragrances, stimulants, analgesics, antibi-

otics, antihistamines, and hormones, are com-

monly found in surface waters that receive inputs

of livestock waste or municipal wastewater dis-

charges (for example, Kolpin and others 2002; Kim

and others 2007; Focazio and others 2008; Fick and

others 2009). There are approximately 4000 phar-

maceuticals on the market (Monteiro and Boxall

2010) and most of these compounds were devel-

oped for human or veterinary pharmaceutical uses

and, as such, are designed to be biologically active.

Although common in aquatic ecosystems, phar-

maceutical and personal care products (PPCPs)

typically occur at very low concentrations (ng/l to

lg/l) and the ability to measure environmental

Received 23 November 2011; accepted 21 April 2012

Author Contributions: EJRM and TVR conceived the ideas together

and EJRM led the writing of the paper with substantial contributions by

TVR.

*Corresponding author; e-mail: [email protected]

EcosystemsDOI: 10.1007/s10021-012-9553-z

� 2012 Springer Science+Business Media, LLC

concentrations of many PPCPs has been well

developed (Kolpin and others 2002 and subsequent

citations). The widespread input of PPCPs to surface

waters throughout the world and the potential

biological activity of PPCPs suggest that under-

standing how these compounds influence aquatic

ecosystem function is an important research

direction for aquatic ecosystem science. A recent

survey of policymakers and scientists placed the

question ‘‘what are the aggregate effects on eco-

systems of current-use and emerging toxicants?’’

on a list of the top 40 environmental concerns

(Fleishman and others 2011).

Currently, research on PPCPs covers two major

topics, (1) describing the occurrence and concentra-

tion of various PPCPs, or (2) single-species examina-

tions of the effect of PPCPs on mortality, growth, or

reproduction. Notably absent from the literature is an

ecosystem-based approach for assessing the effect of

PPCPs in the aquatic environment. As a result, we

know very little about how these compounds, alone

or in combination, might affect ecosystem function

(Likens 2004). A major tenet of ecosystem ecology is

to ‘‘develop an understanding of nature and to pro-

vide approaches and guide solutions to environ-

mental problems’’ (Likens 1998). Research on the

interactions between PPCPs and functional properties

of aquatic ecosystems has the potential to provide

information on a contemporary environmental

problem, as well as advance understanding of how

various ecosystem functions respond to anthropo-

genic stresses.

Recent reviews have called for food web and

ecosystem-scale research in the areas of pesticides

and nanomaterials (Relyea and Hoverman 2006;

Bernhardt and others 2010, respectively). There are

important differences between PPCPs and both

pesticides and nanomaterials. Many of the most

widely used herbicides and insecticides are applied

in support of crop production and are applied only

at specific times during the growing season, or in

response to observed pest outbreaks. Conversely,

PPCPs tend to enter the aquatic environment con-

tinuously, in rural, suburban, and urban settings.

In contrast to nanoparticles that are thought to not

be widely released into the environment to date

(Bernhardt and others 2010), PPCPs are manufac-

tured and used throughout the world and have

been widely released into the environment. Most

of these compounds are not regulated in the envi-

ronment as pollutants and new PPCPs are contin-

ually being developed. Recent reviews provide

detailed information about the concentration, fate,

and state of knowledge of PPCPs in the environ-

ment (Monteiro and Boxall 2010; Fatta-Kassinos

and others 2011). Here, we provide a brief over-

view of the sources of PPCPs to aquatic ecosystems,

review recent literature on the ecological effects of

PPCPs, and present an initial research agenda

regarding how PPCPs may influence functional

properties in aquatic ecosystems. Recently, there

has been a call for research programs that explore

the environmental consequences of contaminants

of emerging concern (Novak and others 2011) and

we argue that such research should include the

influence of PPCPs on aquatic ecosystem function.

The purpose of this review is to highlight research

opportunities regarding PPCPs and to describe how

methods developed in aquatic ecosystem ecology

could be applied to the question of how ecosystem

function is affected by the widespread occurrence

of PPCPs in surface waters. As occurred with other

wide-scale environmental problems, such as acid

rain, DDT, and stratospheric ozone depletion,

understanding the ecosystem-level consequences

of PPCPs may help to guide future science-based

regulatory decisions.

PATHWAYS OF PPCPS TO AQUATIC

ECOSYSTEMS

The range of compounds that are encompassed by

the term PPCPs is large and includes nearly any

compound designed for human or animal health or

personal care. These compounds vary widely in

chemical structure, biological activity, and poten-

tial ecological effects. In addition, a number of

pharmaceutical compounds enter the environment

largely unchanged in chemical structure (Kolpin

and others 2002). There are multiple pathways by

which PPCPs enter aquatic ecosystems and as a

consequence many aquatic ecosystems contain

measurable concentrations of PPCPs.

A commonly recognized pathway is effluent

from wastewater treatment plants (WWTP).

WWTPs are designed to remove solids and reduce

the biological oxygen demand of the effluent and

have been effective at removing both solids and

nutrients; however, removal of PPCPs is the not the

current focus of WWTP design. Rates of PPCP re-

moval vary in relation to the chemical properties of

the individual PPCPs and the size, age, and opera-

tion of the WWTP (Monteiro and Boxall 2010).

Removal by activated sludge can range from less

than 40% for some compounds (for example, car-

bamazepine and ibuprofen) to greater than 87%

for others (for example, caffeine and salicylic acid)

(Monteiro and Boxall 2010). The type of treatment

process employed can result in additional variabil-

E. J. Rosi-Marshall and others

ity in removal rates by compound (Monteiro and

Boxall 2010), but it is important to note that in

many regions of the world adequate wastewater

treatment lags behind population growth (Von

Sperling and others 2001) and as a consequence

untreated sewage is discharged directly to surface

waters. Demographic and socio-economic factors of

the population contributing to the waste stream

can result in seasonal variability in the types and

amounts of PPCPs in the receiving water. For

example, the concentrations of cold- or flu-associ-

ated medications increase in surface waters during

winter months (Vieno and others 2005; Ghosh and

others 2010).

One avenue of PPCP removal from wastewater is

sorption to solid wastes within the wastewater

treatment process (Horsing and others 2011). There

are a number of common disposal techniques for

biosolids generated during wastewater treatment,

including incineration, land application of dewa-

tered solids for fertilizer, and layering of biosolids in

landfills. The latter two methods may result in the

movement of PPCPs to aquatic ecosystems. The

extent to which these pathways lead to PPCPs

entering aquatic ecosystems will depend on the

sorption strength of the compounds to the bioso-

lids, proximity of the land application site to a

water body, and the extent to which the PPCPs are

degraded on the land surface (Lapen and others

2008; Edwards and others 2009; Larsbo and others

2009; Sabourin and others 2009). Municipal solid

wastes also contain PPCPs (Musson and Townsend

2009) and may be a source of PPCPs to aquatic

ecosystems via landfill leakage (Barnes and others

2004).

Leakage from underground sewage infrastruc-

ture is another pathway by which PPCPs enter

waterways (Figure 1). In many urban areas, com-

bined sewer overflows (CSOs) are used to convey

stormwater runoff and this results in the discharge

of a combination of raw sewage (with its load of

PPCPs) and stormwater to stream ecosystems (Pa-

iller and others 2009; Weyrauch and others 2010).

CSOs bypass potential degradation in WWTPs and

deliver PPCPs directly to aquatic ecosystems

(Weyrauch and others 2010). Septic systems are

not specifically designed to remove PPCPs and as a

consequence septic tank effluent can contain

PPCPs, which then enter the environment (Carrara

and others 2008; Conn and others 2010; Katz and

others 2010). However, as septic effluent flows

through the soil horizons below septic systems the

removal of some PPCPs can be 90% or more (Conn

and others 2010). The extent to which septic sys-

Figure 1. Aquatic ecosystems are tightly linked to the surrounding watershed (A, B) and in many areas human sewage

can enter streams via leaking infrastructure (C). What occurs in the drainage influences aquatic ecosystems. For example,

the type of products people use adjacent to these ecosystems and the methods by which they handle their wastes may

influence the ecosystem. Photo credits: Rosi-Marshall (A), Google Earth (B), and BES LTER Photo (C).

Aquatic Ecology and PPCPs

tems represent a significant source of PPCPs to

surface waters depends on factors such as soil

characteristics, density of septic systems, and the

depth of the groundwater (Conn and others 2010).

Pharmaceutical manufacturing facilities are a

significant source of PPCPs to aquatic ecosystems

(Phillips and others 2010; Larsson and others 2007;

Fick and others 2009). For example, New York

streams receiving effluent from WWTPs that trea-

ted wastewater from pharmaceutical manufactur-

ing facilities had concentrations of PPCPs ten to a

thousand times greater than streams receiving

water from WWTPs with no pharmaceutical man-

ufacturing facilities in the catchment (Phillips and

others 2010). In India, a concentration of fluoro-

quinolone antibiotics above 30 mg/l was detected

in a river downstream of a WWTP which received

wastewater from 90 pharmaceutical manufacturing

companies (Larsson and others 2007). In contrast,

in surface waters receiving typical municipal dis-

charges fluoroquinolone antibiotic concentrations

range from less than 0.02–0.25 lg/l (Monteiro and

Boxall 2010).

Large animal feeding operations represent an

agricultural source of PPCPs to aquatic ecosystems

(Burkholder and others 2007). Waste from large

animal feeding operations is stored in lagoons or

applied to fields and these storage and disposal

methods can result in PPCPs entering surface wa-

ters. Antibiotics commonly used in swine produc-

tion, for example, lincomycin and spectinomycin,

were detected in swine manure at concentrations

similar to the doses administered to the livestock.

Although some initial breakdown occurred, after

6 months the antibiotic concentrations in the

manure were largely unchanged suggesting that

manure applied to fields would be a source of

PPCPs (Kuchta and Cessna 2009). Indeed, swine

waste applied to Canadian prairies resulted in the

detection of the antibiotic lincomycin in surface

soils (46.3–117 lg/kg), in snowmelt entering

nearby wetlands (0.82 ± 0.11 lg/l), and in

groundwater basins receiving land applications of

swine waste (<0.005–0.036 lg/l) (Kuchta and

Cessna 2009; Kuchta and others 2009). Poultry

manure can contain antibiotics, for example, sal-

inomycin, and although recent research demon-

strates that this antibiotic can be broken down by

composting the litter (Ramaswamy and others

2010), other methods of disposal may lead to PPCPs

entering waterways. The extent to which the live-

stock industry is a source of PPCPs is in need of

continued research, but it is clear that PPCPs can be

an issue in rural streams that lack inputs of WWTP

effluent.

The pathways for PPCP input to aquatic ecosys-

tems are spatially and temporally dynamic, which

complicates studies of PPCP fate and transport. To

overcome this, passive samplers have been devel-

oped for measuring organic contaminants such as

PPCPs (MacLeod and others 2007; Bartelt-Hunt

and others 2011). Degradation and sorption of

PPCPs are widely variable among compounds

(Monteiro and Boxall 2010) and PPCPs are con-

sidered ‘‘pseudo-persistent’’ because the input of

these compounds tends to be constant. Finally, the

concentrations of PPCPs in waste streams prior to

entering aquatic ecosystems (for example, in sew-

age infrastructure) have been the subject of a great

deal of research over the last decade. A critique of

these studies pointed out the lack of recognition of

the variable flow regimes due to precipitation or

the dynamics of water use in these systems and the

general failure of researchers to incorporate this

variability into sampling schemes (Ort and others

2010). Incorporating temporal dynamics into

aquatic ecosystem solute budgets has been essential

because it has long been recognized that short-term

events can dominate solute fluxes (Meyer and

Likens 1979).

Typically, PPCPs occur in mixtures when de-

tected in surface waters and understanding the ef-

fects of these mixtures in combination with other

stressors will be necessary for a complete under-

standing of the ecosystem-scale effects of PPCPs.

For example, the effect of five pharmaceutical

compounds on algal communities differed when

applied singularly versus as a mixture (Backhaus

and others 2011). Specific methods for addressing

mixtures in toxicology are proposed in Olmstead

and LeBlanc (2005) and Backhaus and Faust

(2012), among others.

The extent to which compounds remain biologi-

cally active in nature is not fully understood and at

times breakdown products of PPCP compounds can

be biologically active, but may target different bio-

logical pathways. The complex behavior and break-

down of PPCPs in nature poses difficulties, but

simultaneously provides research directions on the

interesting pathways and fate of these compounds.

Arguably, the reason nitrogen is well studied in

ecosystem science is the variable biogeochemical

transformations of N in the environment and

research investigating these transformations has

taught us a great deal about ecosystem ecology and

nutrient cycling. Understanding the interactions

among stressors, including PPCPs, has been a chal-

lenge for ecology and will continue long into the

future. For this reason, research that encom-

passes multiple scales of inquiry (from laboratory


experiments, to ecosystem-level manipulations and

modeling) are needed for assessing the effects of

these many stressors (Carpenter 1998; Beketov and

Liess 2012). Here, we argue that considering PPCPs,

alone and in combination, with other ecological

stressors, will provide for a more complete under-

standing of aquatic ecosystems in the twenty-first

century. In addition, improving our understanding

of the fate and transport of PPCPs represents an

opportunity for collaboration among hydrologists,

environmental chemists and engineers, and aquatic

ecologists.

KNOWN ECOLOGICAL EFFECTS ON AQUATIC

ORGANISMS AND ECOSYSTEMS

The extent to which PPCPs affect aquatic organisms

has not been extensively studied, however, a

number of studies indicate that effects could be

diverse and potentially wide ranging. Extensive

literature reviews of research on the toxicology of

PPCPs provide a springboard for hypothesis gener-

ation about the influence of these compounds on

ecosystem functions (for example, Halling-Soren-

sen and others 1998; Crane and others 2006;

Corcoran and others 2010). Here, we provide some

examples of ecological effects of PPCPs that suggest

potential ecosystem-level consequences. First, it is

important to note that there are a variety of modes

of action associated with PPCPs and these com-

pounds could influence a diverse array of organ-

isms, possibly in complex ways. For example,

antibiotics were shown to influence the decom-

poser communities that develop on leaves by

favoring fungi over bacteria (Bundschuh and oth-

ers 2009). As a consequence of reduced bacteria

and increased fungi, a laboratory feeding experi-

ment demonstrated that leaves that had been ex-

posed to antibiotics were preferentially consumed

by shredders compared to leaves not exposed to

antibiotics (Bundschuh and others 2009). If PPCPs

cause indirect effects and interactions among tro-

phic levels, the result could be cascading effects

that are not predicted by single-species laboratory

tests, as shown in many ecological studies (Car-

penter 1996; Schindler 1998).

PPCPs can influence processes and organisms

different from the mode of action of a compound

designed for use in humans or other mammals,

although concentrations may not be high enough

to cause toxicological effects (for example, Brun

and others 2006). Studies of evolutionarily con-

served targets across species can provide insights

into likely effects of classes of drugs on aquatic

organisms (Gunnarsson and others 2008) and

provide a foundation for hypothesis development

about possible effects of drugs on aquatic organ-

isms. For example, histamines are used as neuro-

transmitters by invertebrates and as a consequence

common antihistamines can inhibit neurotrans-

mission in a suite of aquatic invertebrates (Has-

hemzadeh-Gargari and Freschi 1992). Therefore,

antihistamines detected in surface waters may

influence the physiology of aquatic invertebrates

and may cause sublethal effects that require long-

term chronic exposure experiments to detect. This

effect is predictable when considering invertebrate

neurophysiology but may not be widely recognized

by ecologists. Berninger and others (2011) dem-

onstrate that the antihistamine diphenhydramine

can result in mortality of Daphnia in laboratory

toxicology experiments. In addition, Hoppe and

others (2012) explored the sublethal effects of the

antihistamine cimetidine on aquatic invertebrates

and demonstrated that known physiological effects

of antihistamines can result in long-term popula-

tion-level effects at concentrations detected in

surface waters. An additional example is the effects

of the anti-seizure drug carbamazepine on inver-

tebrates. Carbamazepine is prescribed to reduce

seizures and has more recently been prescribed for

attention deficit and hyperactivity disorders, bipo-

lar disorders, and to reduce symptoms associated

with alcoholism. Carbamazepine can influence

brain and liver function in rainbow trout (Li and

others 2010) and can also disrupt pupation of

midge larvae in sediments (Oetken and others

2005). Finally, laboratory studies demonstrated

that the anti-depressant norfluoxetine induced

spawning in bivalves (Fong and Molnar 2008). It is

clear that some PPCPs can affect aquatic organisms,

but the effects need to be explicitly examined at

concentrations detected in surface waters.

PPCPs have also been demonstrated to influence

the species composition of organisms in mesocosms

and laboratory assays. Research examining aquatic

invertebrate and diatom community composition

in a Spanish river demonstrated that invertebrate

community composition was correlated with con-

centrations of anti-inflammatories and beta-block-

ers (Munoz and others 2009). The common

antimicrobial compound triclosan, found in anti-

bacterial soaps, can influence the biomass and

community structure of both attached and sus-

pended algal communities (Wilson and others

2003; Proia and others 2011). Although the

mechanism of triclosan toxicity to algae has not

been identified (Proia and others 2011), some

studies have suggested that algae may be more


sensitive to triclosan than bacteria (Tararazako and

others 2004).

Finally, PPCPs can bioaccumulate in freshwater

compartments including algal biofilms (Writer and

others 2011), sediments (Schultz and others 2010),

invertebrates (Kinney and others 2008) and fishes

(Ramirez and others 2007, 2009; Schultz and oth-

ers 2010; Lajeunesse and others 2011). In addition,

biomarkers have been widely used as indicators of

environmental exposure to PPCPs, especially

endocrine disrupting compounds (Kidd and others

2007; Vajda and others 2008; Barber and others

2011). Because of the potential to bioaccumulate,

assessing concentrations of PPCPs in tissues and the

use of biomarkers may provide insights into PPCP

movement through aquatic food webs.

Because PPCPs have the potential to affect

aquatic organisms, the influence of PPCPs may

extend to ecological processes and ecosystem

function. It has been predicted that PPCPs may

influence biogeochemical cycling of important

elements through disruption of algal and bacterial

communities (Likens 2004). Other ecosystem

functions that are mediated by bacteria, fungi, and

invertebrate consumers could be influenced by

PPCPs, such as organic matter decomposition

(Bundschuh and others 2009), nutrient transfor-

mations (Bunch and Bernot 2011), and inverte-

brate population dynamics (Hoppe and others

2012). Quantifying the potential for PPCPs to

influence ecosystem function will require process-

oriented and ecosystem-scale studies that build on

toxicological studies.

PPCPS AS A RESEARCH OPPORTUNITY

FOR AQUATIC ECOSYSTEM ECOLOGISTS

We propose that interesting questions regarding

PPCPs and aquatic ecosystem function are largely

unaddressed and provide a challenge for aquatic

ecology. The following list of questions is not

exhaustive, but rather a sampling of the types of

research that may garner the interest of aquatic

ecologists and simultaneously improve under-

standing of PPCPs in the environment.

1. Do PPCPs influence critical biogeochemical

pathways, especially with regard to carbon,

nitrogen, and phosphorus cycling? Managing

carbon and nutrients in human-dominated

ecosystems is of critical importance. However,

we do not fully understand how PPCPs may

interact with important biogeochemical pro-

cesses such as denitrification, N fixation, or the

activity of C-, N-, and P-acquiring enzymes.

2. Do PPCPs influence processes such as metabo-

lism or nutrient cycling at the ecosystem scale?

Aquatic ecosystem ecologists have made great

strides measuring ecosystem-level processes

such as metabolism, decomposition, and carbon

dynamics. In addition, recent meta-analyses

have linked these whole-system measurements

to higher trophic levels (for example, Marcarelli

and others 2011) and aquatic ecosystems are

important for carbon cycling on a global scale

(Cole and others 2007). However, it is not

known whether PPCPs affect these processes

and possibly impact higher trophic levels or

influence our ability to understand relationships

among these processes and higher trophic levels.

3. How do PPCPs influence growth rates, mortal-

ity, food web interactions, populations, com-

munity structure, and secondary production?

Although a handful of experiments demonstrate

the capacity for certain PPCPs to influence these

aspects of communities and ecosystems, our

understanding of the community/food web level

consequences of PPCPs, alone or in combina-

tion, is currently limited.

4. How variable are aquatic ecosystems in their

ability to attenuate PPCP compounds and what

ecological characteristics influence attenuation

across ecosystems? Recent research has mea-

sured the movement of a few PPCPs in a stream

ecosystem (Kunkel and Radke 2011) and dem-

onstrated that downstream attenuation varied

among the PPCPs examined. Similarly, PPCPs in

artificial wetlands are known to have variable

persistence (Walters and others 2010). It is likely

that attenuation/retention dynamics may be

influenced by the characteristics of ecosystems,

which has been well-demonstrated for nitrogen

(Peterson and others 2001; Mulholland and

others 2009). Understanding the movement,

attenuation, and breakdown of PPCPs upon

entering aquatic ecosystems could advance our

understanding of persistence, risk, and potential

consequences of these compounds in nature.

In the sections below, we outline specific methods

that are routinely used in studies of aquatic bio-

geochemistry, metabolism, organic matter pro-

cessing, and ecosystem-level effects that provide a

template for addressing the above questions (Fig-

ure 2).

CHAMBER APPROACHES

Most important biogeochemical processes are

mediated by microorganisms, and PPCPs that dis-


rupt microbial activities could directly or indirectly

affect rates of biogeochemical transformations. The

importance of these biogeochemical processes is

evidenced by the myriad approaches and methods

that have been developed for studying an array of

processes in aquatic ecosystems. For example, lab-

oratory assays are frequently used to determine the

bioavailability of dissolved organic carbon (for

example, Lutz and others 2011), denitrification

potential (for example, Findlay and others 2011),

nitrification rates (for example, Starry and others

2005), greenhouse gas production (Beaulieu and

others 2011), extracellular enzyme activity (for

example, Hill and others 2010) and effects of con-

taminants (Giller and others 1998). Many of the

methods are readily adaptable for use in investiga-

tions of how PPCPs might affect the biogeochemistry,

enzyme activity, and microbial community struc-

ture of aquatic systems.

Additions of various PPCPs, alone or in combi-

nation could be included with laboratory assays as

experimental treatments or samples collected in

regions with known PPCP concentrations could be

used. A range of concentrations and mixtures could

allow for identification of thresholds for influenc-

ing various biogeochemical processes, community

structure, and enzyme activity. Samples collected

upstream and downstream of a known source of

PPCPs, such as a WWTP or waste lagoon, could be

used, as could field campaigns that collect sedi-

ments from systems that span a range of PPCP

concentrations. Nitrogen and carbon cycling are

strongly influenced by microbial processes and

therefore may be particularly susceptible to PPCPs

that disrupt microbial activity or community

structure. Indeed, a recent study of streams in the

central US suggested that N cycling could be af-

fected by nicotine, caffeine, and acetaminophen

based on results from laboratory studies (Bunch

and Bernot 2011). When combined with in situ

manipulative studies, laboratory assays of biogeo-

chemical processes, microbial community structure

and activity could be a powerful tool for investi-

gating the effect of persistent, low-level concen-

trations of PPCPs on biogeochemical cycles in

aquatic ecosystems. In addition, understanding the

links between microbial community structure and

function remains an important research frontier

(Findlay 2010) and exploring disruption of struc-

ture and functional relationships that may result

from PPCP exposure may provide insights into this

area of ecosystem science.

PUSH-PULL EXPERIMENTS

The use of push-pull experiments, either in situ or

with intact cores, has led to numerous advances in

our understanding of subsurface biogeochemical

transformations and in situ reaction rates (for

example, denitrification, nitrification, DNRA, sul-

fate reduction) (Istok and others 2001; Burgin

and Hamilton 2008). Push-pull methods involve

injecting a solute of interest and a conservative

tracer into a saturated subsurface area, incubating

for a certain time period and ‘‘pulling’’ the mixed

ground water/injectate out of the subsurface. This

method allows explorations of transformation rates

and sorption processes in situ or in a core and may

provide an effective means for measuring either the

fate or transformations of PPCPs or the influence of

PPCPs on biogeochemical transformations of

interest. We are not aware of any push-pull studies

to date that have examined the fate or transfor-

mation of PPCPs, although this approach has been

used to study the effects of other contaminants,

such as landfill leachate (Harris and others 2005).

These methods hold promise for exploring the

influence of PPCPs on ecosystem function.

Figure 2. There are

various scales and

approaches that can be

applied to the issue of

pharmaceutical and

personal care products in

aquatic ecosystem and

their effects.


SOLUTE DIFFUSING SUBSTRATES

Nutrient limitation in lakes and streams has long

been a subject of study by aquatic ecologists. An

excellent method for assessing nutrient limitation

of biofilms is the use of nutrient diffusing substrates

(Fairchild and others 1985; Tank and Dodds 2003;

Hoellein and others 2010). This method uses a

nutrient-enriched agar contained within a porous

substrate through which water and dissolved

nutrients can pass, for example, terracotta pots,

fritted glass substrates, or cellulose sponges. These

substrates with nutrient-amended agar are placed

in an aquatic ecosystem and low concentrations of

solutes diffuse out of the agar and expose the

developing biofilm community to an elevated

concentration of these nutrients. The response of

the biofilm to the nutrient addition can then be

measured as, for example, chlorophyll a content,

primary production, community composition, or

microbial respiration. Although this method has

been widely used to explore the extent of nutrient

limitation in aquatic ecosystems, differences among

diffusing substrate design can influence conclu-

sions and methodological approaches should con-

tinue to be critically examined (Capps and others

2011).

This method may also be useful for measuring

the effects of water-soluble PPCPs, alone or in

combination, on aquatic biofilms. PPCP compounds

can be added to the agar individually or as mixtures

to assess the effect of the PPCPs on biofilm structure

and function. This method is relatively inexpensive

and can be used to study a wide variety of com-

pounds and ecosystem endpoints (for example,

algal production, composition, respiration). In

addition, this method requires very small additions

of PPCPs, but provides an excellent means for

detecting potentially sensitive processes or taxa to

PPCP exposure. For example, one could compare

the relative effects of multiple compounds on an

endpoint of interest and repeat the experiment

numerous times for very little cost. Similar to work

that has been done exploring nutrient limitation,

the amount of PPCPs diffusing out of the agar and

influencing biofilms may be difficult to measure.

We suggest that this method may be most useful for

identifying sensitive taxa and ecological processes,

for example, primary production or respiration.

Collaboration with toxicologists and environmental

chemists may be a fruitful way to explore exposure

pathways and compound interactions that occur

with this method. In general, this method has been

used very creatively in assessing nutrient limitation

in aquatic ecology and holds promise as a tool for

detecting the effects of PPCP on taxa or ecological

processes in situ.

NUTRIENT AND PARTICLE FATE

AND TRANSPORT IN STREAMS AND RIVERS

The methods that were developed to study solute

and particle fate and transport in streams, such as

nutrient spiraling, have been employed in a large

number of ecological studies (see Ensign and Doyle

2006; Tank and others 2008). Nutrient spiraling is a

concept developed to describe how nutrients cycle

in streams, but because these cycles are ‘‘stretched’’

by the downstream movement of water this is

conceptualized as spiraling (Webster and Patten

1979; Newbold and others 1981). This concept has

been a foundation of stream and river ecology and

provides a suite of tools that allow for the detailed

study of how low concentrations of nutrients are

retained or transported in stream and river eco-

systems (Tank and others 2006). Typically, trace

amounts of nutrient or isotopically labeled nutri-

ents are added to a stream in conjunction with a

conservative tracer and a series of measurements

downstream of the injection point are made to

estimate the rate of nutrient uptake, with the

conservative tracer correcting for any water losses

or gains that may occur in a study reach. Fine

particle spiraling methods are similar, but require a

labeled or traceable particle analog (Miller and

Georgian 1992; Cushing and others 1993). These

methods allow one to quantify the downstream

transport, retention, and resuspension of fine par-

ticles in streams and rivers (Cushing and others

1993; Thomas and others 2001; Newbold and oth-

ers 2005; Rosi-Marshall and others 2007).

Both of these methods can be readily applied to

the study of dissolved PPCP transport and attenu-

ation (Kunkel and Radke 2011), or PPCPs sorbed to

fine particles. To adapt these methods to PPCPs one

simply injects the PPCP of interest rather than a

nutrient. Because PPCPs can be detected at ng/l

concentrations, the amounts of PPCPs that would

need to be added to measure the uptake of these

compounds are extremely low (Kunkel and Radke

2011). Studies have also used the nutrients enter-

ing aquatic ecosystems via WWTPs as the source of

nutrients and applied a spiraling-based approach

along a downstream reach (Marti and others 2004;

Gibson and Meyer 2007). These methods could be

applied to PPCPs in which the compounds entering

a river from any source are measured in conjunc-

tion with a conservative tracer (added separately or

as a component of the WWTP effluent) to examine


downstream transport of a PPCP in a river system.

Indeed, a recent study released low concentrations

of five PPCPs to a stream in Sweden and the

breakthrough curves of PPCPs were used to explore

the mass loss and half-lives of PPCPs (Kunkel and

Radke 2011). This study demonstrated that ibu-

profen and clofibric acid were attenuated along a

16-km reach of the river. More research along

these lines, especially in conjunction with envi-

ronmental variables, for example, whole-stream

metabolism and whole-stream nutrient uptake

measurements, would add insight into the capacity

of streams to attenuate PPCP concentrations and

the processes responsible for the attenuation.

A number of PPCPs are also known to readily

adsorb to fine particles (either organic or inorganic)

(Writer and others 2011) and there are well-devel-

oped methods for measuring fine particle transport in

stream ecosystems (Cushing and others 1993; Miller

and Georgian 1992; Rosi-Marshall and others 2007).

For example, dyed corn pollen (78 lm in diameter

and readily available) can be added to streams in

conjunction witha conservative tracer tomeasure the

downstream distance fine particles travel in a given

stream reach (Miller and Georgian 1992; Rosi-

Marshall and others 2007). Measuring fine particle

transport below sources of PPCPs would facilitate

predictions about the downstream distances PPCPs

travel when associated with particles. This method

would not require an addition of PPCPs, but would

simply require studying the movement of fine parti-

cles in a system. Developing an empirically based

understanding of fine particle transport and retention

below a site of PPCP input could lead to predictions

about where PPCPs might accumulate within the

riverbed. For example, in a river system with high

rates of fine particle retention below a PPCP source,

one would predict that the concentrations of these

compounds may be relatively high in the sediments

and that degradation rates will be a strong driver in

the longevity of these compounds. In contrast, in a

river system with low retention of fine particles, one

would predict that the compounds associated with

fine particles are readily transported downstream and

this river may be a source of particles with sorbed

PPCPs to downstream ecosystems.

MESOCOSMS AND WHOLE-SYSTEM

MANIPULATIONS

Mesocosms are often used in aquatic ecology to

address a variety of topics, such as competition,

structure–function relationships, nutrient enrich-

ment, and have been used to explore the ecological

effects from pollution (for example, Relyea 2006).

In addition, research using mesocosms has dem-

onstrated discrepancies between acute laboratory

toxicity tests and community-level responses

observed in mesocosms that incorporate species

interactions, and differences in exposure resulting

from physiochemical transformations of the con-

taminant of study (Hayasaka and others 2012). A

number of papers have used mesocosms to study

the effects of PPCPs on important ecological phe-

nomena (Wilson and others 2004; Quinlan and

others 2011; Hoppe and others 2012). Mesocosms

have the benefit of being relatively easy to replicate

and large numbers of them can be used to examine

various concentrations of compounds and com-

pound mixtures, on species composition, species

interactions, and ecosystem function. In addition,

stable and radioisotopic versions of PPCPs are

commercially available and labeled compounds

may open up a suite of interesting research ave-

nues and could be used to trace the fate of these

compounds in mesocosm-based research.

Whole-system manipulations have been con-

ducted to address important ecological questions in

aquatic ecosystems. Large-scale manipulations such

as watershed forest removal (Likens and others

1970) or whole-lake nutrient additions (Schindler

1974) have advanced the field of ecology and could

be employed in the study of PPCP influence on

aquatic ecosystems. Although typically not ame-

nable to replication, large-scale ecological experi-

ments provide a holistic and integrative approach

to ecosystem ecology that cannot be achieved with

laboratory or even mesocosm-based studies (Car-

penter 1990). In addition, a number of statistical

approaches have been applied to large-scale

manipulation experiments to overcome the lack of

replication including before-after control-inter-

vention analysis (BACI) (Stewart-Oaten and others

1986; Underwood 1992), randomized intervention

analysis (Carpenter and others 1989), and boot-

strapped estimation techniques (Cross and others

2011). To fully understand the complex influence

that PPCPs may have on aquatic ecosystems, large-

scale manipulations may be necessary. In addition,

population/ecosystem-level responses, such as re-

duced rates of primary or secondary production,

and indirect effects, for example, trophic interac-

tions, may require long-term experiments. For

example, Kidd and others (2007) added low doses

of ethinyl estradiol-2 (EE2), the active ingredient in

birth control pills, to a lake in the Experimental

Lakes Area and found that concentrations compa-

rable to those observed in ecosystems receiving

municipals wastes caused a crash in the fathead


minnow population after the second year of con-

tinuous EE2 additions. Populations even remained

low for 2 years after EE2 additions ended. Methods

described in the sections above may provide insight

into which compounds would be best suited to

large-scale addition experiments. For example, if

the effects on important processes in chambers and

mesocosms suggest that compounds influence

multiple aspects of an ecosystem and that effects

may interact in non-predictable ways, a large-scale

experiment may be warranted. In urban areas with

infrastructure leakage problems that release PPCPs

to aquatic ecosystems, there may be an opportunity

to explore how removal of these compounds (as a

result of infrastructure improvements) alters an

ecosystem. We argue that ecosystem manipulations

with PPCPs will provide the most compelling

datasets for predicting the myriad responses in

ecosystem function that could result from the

widespread occurrence of PPCPs in aquatic systems

throughout the world.

CONCLUSIONS

Application of methods developed to answer a suite

of questions can be merged with traditional toxi-

cology and fate and transport studies to advance

our understanding of emerging environmental is-

sues. Studies that expand the methods of one field

can provide insight into larger issues that span

multiple disciplines, for example, ecology and

ecotoxicology (Walters and others 2008; Riva-

Murray and others 2011). We argue that there is an

important opportunity for aquatic ecology to con-

tribute to addressing the question of how PPCPs

affect aquatic systems, and that doing so requires

only modest modification of the existing tool kit.

The issue of PPCPs also provides opportunities for

cross-disciplinary, collaborative research that likely

will provide insights beyond those possible from a

single disciplinary perspective.

Surface waters are subject to the release of hu-

man wastes, including the compounds used in daily

life, are a source for municipal drinking water

supplies, harbor biodiversity and provide important

ecosystem services. As such, understanding the

influence of PPCPs on aquatic organisms and

ecosystem function is essential to develop a com-

prehensive understanding of the potential conse-

quences of these compounds in the environment.

These compounds are currently entering aquatic

ecosystems via multiple pathways, yet our under-

standing of the ecosystem-level consequences is

limited. We conclude that our understanding of

PPCPs in aquatic ecosystems will be enhanced by

the active participation of ecosystem ecologists in

this research direction.

ACKNOWLEDGMENTS

The authors would like to thank Peter Groffman,

Heather Bechtold, Daniel Schindler and 3 anony-

mous reviewers for their suggestions on earlier

drafts of this manuscript. Thank you to the scien-

tific staff at the Cary Institute for discussions about

the direction of this manuscript.

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