1a Origins and Fate of PPCPs in the Environment

Pharmaceuticals and Personal Care Products U.S. Environmental Protection Agency

Office of Research and Development
National Exposure Research Laboratory
Environmental Sciences Division
Environmental Chemistry Branch
2 1b
worldwide.
3a
6 ♦ Seminal publications have helped to lay the foundation for current and future
5
Mun 3b
research and regulatory attention in the U.S. for "emerging" contaminants.
icip

♦ Pioneering efforts for a Green Pharmacy is fostering attention to the need for
al S
ew
Le
ac
Le
ak
ag
age
7
h e
ate
8
Aqu
4 consumer-level environmental stewardship programs for PPCPs (pollution
ifer
Gro
u
rechndwa
prevention).
arg ter

♦ More attention is being devoted to the use of PPCPs as "tracers" or "markers"

Leegend e

Regulated pollutants represent but a small Environmental Chemistry Branch

. . .
1 • Usage by individuals and pets:
Metabolic excretion (unmetabolized
parent drug, parent-drug conjugates, and
9
— tools for rapidly detecting trace levels of
portion of the total numbers of manmade bioactive metabolites); sweat and vomitus.
Excretion exacerbated by disease and slow-dissolving 292ecb0
2.Daugh
ton
sewage contamination of waters (a major issue The
10
and naturally occurring pollutants to which Chemical Universe Non-Chemical Universe
medications
• Disposal of unused/outdated medication to sewage systems especially with regard to septic systems, Green
Countless previously • Underground leakage from sewage system infrastructure Pharmacy
humans are continually exposed. unrecognized pollutants entry of chemicals to environment
(those non-chemical stressors acting at the [sub]cellular level)
100 2 • Release of treated/untreated hospital wastes to domestic sewage systems
7 • Disposal to landfills via domestic refuse,
medical wastes, and other hazardous wastes
"straight-piping," and POTW overflow
Physical Stress
are often present in waters. (stress protein response; 0
(weighted toward acutely toxic drugs and diagnostic agents, as opposed to long-term
medications); also disposal by pharmacies, physicians, humanitarian drug surplus
• Leaching from defective (poorly engineered) landfills and cemeteries
events).
PPCPs Anthropogenic hormonal modulation)
Our limited understanding of the universe ♦ Schools are using PPCPs Web Site materials
8 • Release to open waters from aquaculture (medicated feed and resulting excreta)
These ubiquitous "micro- Naturally Occurring Pathogens Temperature/
Humidity
3 • Release to private septic/leach fields
• Treated effluent from domestic sewage treatment plants discharged to surface waters or re-injected
• Future potential for release from molecular pharming (production of therapeutics in crops) to
of chemical exposure is partly a result of the contaminants" occur at Agriculture Important
Known
Chemicals Unknowns
(immune response;
apoptosis/necrosis) (heat balance; stress
protein response)
into aquifers (recharge)
• Overflow of untreated sewage from storm events and system failures directly to surface waters
9 • Release of drugs that serve double duty as pest control agents:
examples: 4-aminopyridine, experimental multiple sclerosis drug used as avicide;
teach principles of environmental science and
(pesticides) Factors:
limitations of analytical chemistry. minute concentrations of Food Combustion
concentration
(dosage, level),
Transport, Distribution & Fate 4 • Transfer of sewage solids ("biosolids") to land (e.g., soil amendment/fertilization)
warfarin, anticoagulant rat poison; azacholesterol, antilipidemics avian/rodent repro-
ductive inhibitors; certain antibiotics used for orchard pathogens; acetaminophen, proper use of the literature ("literature
• "Straight-piping" from homes (untreated sewage discharged directly to surface waters) analgesic brown tree snake control; caffeine, stimulant coqui frog control

M Exc
Matrix:
parts-per-billion (µg/L) and Household Products weathering, • Release from agriculture: spray drift from tree crops (e.g., antibiotics) forensics").

et re
&
transformation, Air Electromagnetic

ab tio
Chemicals chemical Radiation Noise
• Dung from medicated domestic animals (e.g., feed) - CAFOs (confined animal feeding operations) 10 Ultimate environmental fate:

oli n
below. 'species' Water • most PPCPs eventually transported from terrestrial domain to aqueous domain

sm
(ionizing damage; (hormonal modulation;
• Direct release to open waters via washing/bathing/swimming
Limitations and Complexity of Industrial
Industrial Soil diurnal cycles) chemical signal cascades)
5 • phototransformation (both direct and indirect reactions via UV light)
• physicochemical alteration, degradation, and ultimate mineralization
Wastes
Environmental Chemical Analysis Toxicology has yet to reveal Products Sediment 6 • Discharge of regulated/controlled industrial manufacturing waste streams
• Disposal/release from clandestine drug labs and illicit drug usage
• volatilization (mainly certain anesthetics, fragrances)

the human or environmental Exposure Pathways http://www.epa.gov/nerlesd1/chemistry/ppcp/greenpharmacy.htm

Anthropogenic pollutants Christian G. Daughton, U.S. EPA-Las Vegas February 2001 (revised July 2002) http://www.epa.gov/nerlesd1/chemistry/pharma/index.htm
Ingestion/enteral Respiratory: "Window of Vulnerability"
ty health significance of long- Important
Dermal
Pulmonary/Gills
Organism

ici
Timing: critical time for exposure;
spectrum of chemical classes, structures and conformations
x developmental/reproductive stage &
SAMPLE
water, air, extract
to term, simultaneous exposure Factors:
absorbed dose,
health status can determine current/ http://www.epa.gov/nerlesd1/chemistry/pharma/images/drawing.pdf
future susceptibility to effects

Extraction (if using chromatography)

to multitudes of chemical amount available
to receptors

♦ Pharmaceuticals and personal care products (PPCPs) comprise a diverse galaxy of

or Sample preparation/clean-up
EXTRACTABLES
Separation (physical or signal)
stressors
(subtle effects such as behavioral
NON-EXTRACTABLES
changes are the primary concern).
Parenteral
Past Exposure Trajectory
Routes of Exposure Interactions/Potentiation micro-pollutants that gain entry to the environment by way of their usage in human and
Additive, Synergistic, Antagonistic (can occur from
(Prior Exposure History): molecular
stressors
interactions between chemical and non-chemical
stressors and a vast, complex array of biological
veterinary medicine as well as agriculture. PPCPs and metabolites are excreted and washed
multidimensional time line; spatial/temporal function of countless variables,
including exposure duration, timing, and complex interplay of genetics,
nutrition, metabolic stress, activities, behaviors, and events Short-Term
receptors; resulting from similar and dissimilar
mechanisms of action)
into sewage and waterways. Expired/unwanted medications are also directly disposed to
Exposure toilets and trash.
12

♦ Pollution of water by PPCPs and many other previously unrecognized chemicals results
RESOLVED UN-RESOLVED biochemical
9 3
ectory
Long-term, continual, chronic exposure receptors re Traj
Detection
6
Exposu
Future primarily from the individually minuscule but significant combined impacts from
Dose-Response
ARTIFACT

oida al

s)
on
(acute,

rm l
l

ho xica
esi
sigm iti
The 4T's account for an organism's complete exposure time line (a trajectory described by its prior multi-dimensional exposure history)

trad

.g do
sequential, Changes: Overt and Subtle

(e ara
and the fact that a major objective of all organisms is to maintain homeostasis (in the face of continual perturbation by stressors).

consumerism.

.,
p
Toxicant: Toxic Totality: Emphasizes that Tolerance: Ability to resist Trajectory: Individually unique spatial/- intermittent,
NATIVE chemical (spanning the organisms can be exposed to change (susceptibility or temporal exposure route experienced episodic)
dose - concentration Effects on health or populations = reactions to exposure
February
♦ Sewage and drinking water treatment facilities are often not effective at removing PPCPs
large portion of naturally occurring
♦ Form interagency workgroup to address wide array of research needs regarding
COMPOUNDS spectrum of
proteinaceous toxins to
a multitude of different mem-
bers from the large universe
vulnerability to perturbing
homeostasis; homeostasis
by an organism (multidimensional
function of its activities and behaviors,
September Alteration/disruption to function/processes, morbidity
and anthropogenic chemicals of man-made synthetics; of toxicants (not just to can be maintained only as well as isolated/sustained exposure
1 2 3 4 5 6 7 Future 1 2 3 4 5 6 7 (including mutagenesis, carcinogenesis, teratogenesis),
Identification varied toxicity excluding radionuclides). individual toxicants in within the tolerance bounds events). Note that any exposure event 8 9 10 11 12 13 14 8 9 10 11 12 13 14 mortality, selective disadvantage, enhancement of
isolation from others). for an organism's (short-term, long-term) or exposure 15 16 17 18 19 20 21 Health State 15 16 17 18 19 20 21 function (selective advantage)

ty
biochemical defensive
repertoire).
phenomenon (e.g., "Window of
Vulnerability") may be applicable at any
Prior Phenotype
No effect = homeostasis (status quo) and other unregulated pollutants. PPCPs as pollutants and for making progress toward a Green Pharmacy: EPA,
ici
For more information regarding the many facets of exposure and stressors, see: time in an organism's exposure

TICs
unknowns
NEGLECTED ... IGNORED ...
OMITTED ... OVERLOOKED ...
to
x http://www.epa.gov/nerlesd1/chemistry/ppcp/stressors.htm
http://www.epa.gov/nerlesd1/chemistry/pharma/critical.htm
trajectory (past or future).
300odc02.daughton rev: 5 Feb 03 FDA, USGS, CDC, USDA, DEA, USFWS, NAS-IOM, health care industry.
"TARGET" RECOGNIZABLE ♦ Develop consistent nationwide guidance for disposal of unwanted PPCPs: collaboration among
ANALYTES ARTIFACT http://www.epa.gov/nerlesd1/chemistry/ppcp/stressors.htm
TICs = tentatively identified compounds
EPA's OSW, OPPT, Regions, and ORD. Water Reuse
♦ Innovate more effective approaches to risk
http://www.epa.gov/nerlesd1/chemistry/pharma/critical.htm
communication, especially for groundwater recharge
and water reuse. Communicating Risk
More Effectively
EPA's research role beginning in This work is complemented by: ♦ Design and implement a nationwide, universal early Rapidly growing importance of public acceptance of
the late 1990s is largely ♦ Publishing seminal articles in the peer-reviewed literature on the state of ♦ Catalyzing research worldwide by delineating research needs, promulgating warning water monitoring system for "emerging" wastewater reuse for human consumption (especially so-
called "toilet-to-tap" reuse programs) highlights the need
promulgated from its design and the science and future research needs. funding opportunities, and fostering collaborations. chemical pollutants (would serve double duty for for vastly improved approaches to risk communication.

maintenance of the world's only ♦ Championing the need for environmental stewardship programs ♦ Maintaining an in-house research program for improving the scope and sensitivity Homeland Security).
Points to need for scientists to better convey the significance of their
work to the public.
web site devoted to the many (pollution prevention) to minimize the introduction of PPCPs to the of chemical analysis approaches for problematic unregulated pollutants (including ♦ Develop holistic "systems-level" approaches for
Points to need for exploring more effective means for aligning the
scientific and social aspects of environment - The Green Pharmacy. PPCPs). toxicological assessment more amenable to the subtle long-troubling disconnect of disparate views of risks as held by scientists
versus the public: real hazard vs. risk perception.
PPCPs as pollutants. ♦ Presenting invited lectures at numerous international, national, regional, ♦ Devoting significant time to public outreach activities and education of the press. effects that come into play with ecological communities.
Receiving little attention is the more substantive role that could be
played by the cognitive sciences (social scientists and psychologists) in
http://www.epa.gov/nerlesd1/chemistry/pharma/ and academic scientific conferences and seminars. http://www.epa.gov/nerlesd1/chemistry/pharma/science-issues.htm#OneProposal
helping to bridge the widening risk communications gap.

203ecb03

this poster available at: http://www.epa.gov/nerlesd1/chemistry/pharma/images/forum.pdf