NERL Research Abstract
EPA's National Exposure Research Laboratory
GPRA Goal 8 - Sound Science
Significant Research Findings:
Pharmaceuticals & Personal Care Products in the
Environment: An Emerging Concern?
Purpose A particularly troublesome environmental pollution scenario is one resulting in continual
but unnoticed biochemical effects on organisms — effects that accumulate so slowly that
major change is not detectable until their cumulative level finally cascades to irreversible
change. One possible example fitting this scenario, starting with subtle, unnoticed effects
and culminating with outward change, could be manifested by the continual exposure of
aquatic organisms to the complex spectrum of pharmaceuticals that can persist in the
treated effluent from sewage facilities. During the last three decades, the impact of
chemical pollution has focused almost exclusively on the conventional "priority
pollutants," including those collectively referred to as "persistent, bioaccumulative, and
toxic" (PBT) pollutants or "persistent organic pollutants" (POPs) — the "dirty dozen" is
a notorious subset of these. This group of diverse chemicals (which mainly comprises
halogenated agricultural and industrial chemicals), however, is only one piece of a larger
puzzle. Another diverse group of chemicals receiving comparatively little attention as
potential enviromnental pollutants includes the pharmaceuticals and active ingredients in
personal care products (collectively termed PPCPs). These extremely bioactive
compounds can be continually introduced to the aquatic enviromnent as complex
mixtures via a number of routes — primarily via treated sewage effluents. Aquatic
pollution is particularly troublesome because aquatic organisms are captive to continual
life-cycle exposure.
PPCPs comprise all drugs (available by prescription or over-the-counter; including the
new genre of proteinaceous "biologies"), diagnostic agents (e.g.. X-ray contrast media),
"nutraceuticals" (bioactive food supplements such as huperzine A), and other consumer
chemicals, such as fragrances (e.g., musks) and sun-screen agents (e.g.,
methylbenzylidene camphor); the use of pharmaceuticals is only expected to increase,
especially with new, previously unforeseen uses, such as "chemoprevention" (to reduce
the chances of disease on slow its onset; e.g., tamoxifen for breast cancer; aspirin for
colon cancer). While their immediate biological actions on non-target species (especially
in the aquatic habitat) might be imperceptible, they nonetheless could lead to adverse
impacts — as a result of subtle effects, from low, ppb-ppt concentrations (ng-ng/L),
whose continual expression over long periods of time could lead to cumulative, insidious
changes that would otherwise be attributed to "natural" change or adaptation.
Research Approach To advance the state-of-the-science and catalyze collaboration, a comprehensive
assessment was undertaken of the world's literature with the intent of synthesizing the
first critical review of all the aspects of this emerging pollution issue — including
sources, enviromnental occurrence, transport, effects, risk assessment, and mitigation. All
published occurrence and effects data (albeit very limited and uneven in scope) were
compiled, and recommendations were made in each of the distinct areas of the risk
paradigm with respect to further research or mitigative measures. The major goal of this
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work is to catalyze more research in this area — especially in the U.S.
A primary goal of the U.S. EPA's Office of Research and Development is to identify and
foster investigation of "hidden" or potential environmental issues/concerns before they
become critical ecological or human health problems. Our critical review article
{Pharmaceuticals and Personal Care Products in the Environment: Agents of Subtle
Change?) represents the first attempt to bring together the published literature on the
environmental occurrence, and effects to non-target species, of the large and diverse
spectrum of PPCPs. One of the intentions of this first-ever review is to catalyze a
discussion in the scientific community and to further a national research effort on the
issue. As such, the outcome of this review is hoped to be one of stimulating new research
both from outside (e.g., via STAR grants program) and from within the EPA. We will be
able to gage our success in this endeavor by measuring an eventual increase in
publications from the U.S. (where little has been published to date) on PPCPs and
possibly an increase in directed proposals on PPCPs from STAR and unsolicited research
proposals submitted via STAR. It is hoped that this issue can alter the Agency's
historically persistent focus on conventional pesticides and toxics, to redirect the energies
of many environmental chemists away from an exclusive focus on the traditional priority
pollutants (and traditional toxicological endpoints), and to raise the general awareness
among the environmental community as to the complexity of performing true,
comprehensive risk assessments.
Nearly all of the world's published work on PPCPs in the environment has been led from
Europe. The NERL-Las Vegas Environmental Chemistry Branch's (ECB) planned
research on PPCPs will focus on a 2001 Eco APM under GPRA's Sound Science -
Emerging Issues, and as such will represent the first concerted attempt in the U.S. to
foster research into PPCPs in our environment. The first step of this effort has been
completed — a critical review of the world's literature on occurrence, transport, fate, and
effects of PPCPs (excluding antibiotics and steroids) in the aquatic environment. This
comprehensive critical review has been accepted for publication by Environmental
Health Perspectives (EHP) and will appear in the December 1999 Supplement of EHP.
The authors are Christian Daughton (ECB) and Thomas Ternes (Germany), the latter
being a world's authority on the analysis/occurrence of PPCPs in the environment. The
first ever symposium session on Pharmaceuticals in the Environment at a national
American Chemical Society meeting is also being planned and organized for March 2000
in San Francisco - by Daughton, Ternes, and Jones-Lepp.
Laboratory research at ECB is only beginning. A number of potential collaborators have
been identified, including experts from other countries (e.g., Dr. Thomas Ternes), U.S.
university faculty members (e.g., various participants in EPA's NAFEO program and
other U.S. universities), and other ORD labs (NHEERL-Gulf Breeze).
Major Findings While the available scientific literature is limited, after critical examination, the
following picture emerges. Sewage and solid waste are the primary sources of PPCPs in
the environment. These bioactive compounds are continually introduced to the
environment (primarily via surface and ground waters) from human and animal use
largely through sewage treatment works (STWs) and wet-weather runoff. Bioactive
metabolites (including some that can be converted back to their parent chemical forms)
are also excreted. Disposal via municipal refuse serves as another route of introduction to
the environment. While aspirin and caffeine have long been known to occur in sewage,
only since the 1980's have other PPCPs been identified in surface and ground waters —
even drinking water. The low concentrations of individual PPCPs (possibly exceeding
the catabolic enzyme affinities of sewage microbiota), coupled with their metabolic
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"novelty" to microorganisms, leads to incomplete removal from STWs; in general,
removal efficiencies from STWs tend to average roughly 60% for PPCPs, but span the
spectrum from complete to nonexistent. Introduction of many PPCPs to individual STWs
is in the range of multi-kg/day (depending on the population served by the STW).
Excluding the antibiotics and steroids, over 50 distinct PPCPs or metabolites (from more
than 10 broad classes of therapeutic agents or personal care products) have been
identified in sewage treatment effluent or in environmental samples (mainly surface and
ground waters); representative classes include analgesics/anti-inflammatories,
antineoplastics, antiseptics, betablockers (antihypertensives), (^-sympathomimetics
(bronchodilators), lipid regulators and bioactive metabolites, musks (synthetic nitro and
polycyclics; also reduced metabolites of nitro musks), anti-psychotics, sun screen agents,
and X-ray contrast media. Concentrations generally range from the low ppt- to ppb-levels
(ng/L to ng/L). Most of these compounds, however, have no associated aquatic toxicity
data. Some PPCPs (such as antidepressants) that do have associated aquatic effects data
have yet to be surveyed in environmental samples. Still others have great potential for
profound aquatic effects but have neither the aquatic toxicological database nor any
occurrence data (e.g., psychoactive agents and narcotics). Furthermore, no
representatives from a diverse class of xenobiotics called "chemosensitizers", which
disrupt the active extracellular transport of toxicants, have been the targets of any
surveys.
Many PPCPs and their metabolites are ubiquitous and display persistence in, and
bioaccumulation (e.g., musks) from, surface waters on par with that of the widely
recognized organochlorine POPs (e.g., DDT, PCBs, dioxins). From the limited studies,
concentrations in natural surface waters (including oceans) have been found to range
from ppt (ng/L) to ppb (ng/L). Some PPCPs are extremely persistent and introduced to
the environment in very high quantities (e.g., musks and polyiodinated X-ray contrast
media). Others act as if they were persistent, simply because their continual infusion to
the aquatic environment serves to sustain perpetual life-cycle exposures for aquatic
organisms. Effects on aquatic organisms can be extremely subtle and go undetected.
Subtle, unnoticed effects could accumulate over time until any additional incremental
burden imposed by exposure to one additional stressor (whether it be a toxic PPCP or
any other xenobiotic) could trigger sudden collapse or alteration of a biochemical
function or physiologic behavior. "Abnormal" behavior can masquerade as seemingly
normal deviation within a natural statistical variation. Change can occur so slowly that it
appears to result from natural events - with no reason to presume artificial causation.
Connections of cause and effect are difficult to draw, in part because of the ambiguous
and subjective nature of the effects, but especially when they are convoluted as
aggregations of numerous, unrelated interactions.
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Research Collaboration See: Research Approach (above)
Publications
(Peer-reviewed)
Daughton1, Christian G. and Ternes2, Thomas A. "Pharmaceuticals and Personal Care Products in the Environment:
Agents of Subtle Change?" Environmental Health Perspectives Supplement (accepted for publication; target date:
December 1999)1
'Environmental Chemistry Branch, Environmental Sciences Division
U.S. Environmental Protection Agency, ORD/NERL
944 East Harmon Ave., Las Vegas, Nevada 89119
daughton.christian@epamail.epa.gov
702-798-2207; fax 702-798-2142
2ESWE-Institute for Water Research and Water Technology
Sohnlcinstraffc 158
D-65201 Wiesbaden-Schierstein
Thomas.Ternes@stadtwerke-Wiesbaden.de
49 611 780 4343; fax 49 611 780 4375
f the full publication will also appear on EHP's web site for subscribers:
http://ehpnetl.niehs.nih.gov/docs/publications.html
Future Plans The Environmental Chemistry Branch (NERL-Las Vegas) will begin in-house research
on the environmental occurrence of PPCPs in the U.S. in FYOO. This effort will be led by
ECB principal investigators with collaboration from internal U.S. EPA students, NRC
postdoctoral fellows, and visiting scientists. External collaborators are also interested.
Collaboration with a water district is being pursued.
The first ever symposium session on Pharmaceuticals in the Environment at a national
American Chemical Society (ACS) meeting is being planned and organized for March
2000 in San Francisco - by Daughton (ECB), Ternes (Germany), and Jones-Lepp (ECB).
Interest in this meeting by potential contributors has proved to be keen. Plans are to also
produce an ACS Symposium Series book from this meeting. This would be the first book
from the U.S. to cover this topic.
For further information regarding this emerging research issue, contact Dr. Christian
Daughton (702-798-2207; daughton.christian@epamail.epa.gov). Other ORD contacts
(for additional PPCP research, outside of ECB, not covered by the critical review)
include: Dr. Joseph Bumgarner (919-541-5001) and Dr. Ronald Landy (410-305-2757).
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