U.S. Department of the InteriorU.S. Department of the InteriorU.S. Geological SurveyU.S. Geological Survey

Pharmaceuticals in the Environment: Pharmaceuticals in the Environment: What we know and need to knowWhat we know and need to know

2009 Symposium on Pharmaceuticals in the Home and Environment2009 Symposium on Pharmaceuticals in the Home and EnvironmentNorthport, MaineNorthport, MaineOctober 18-19, 2009October 18-19, 2009

Herb BuxtonHerb BuxtonUSGS Toxic Substances Hydrology ProgramUSGS Toxic Substances Hydrology Program

2

Chemicals of Emerging Environmental Chemicals of Emerging Environmental Concern: EConcern: Emerging Contaminantsmerging Contaminants

Not Just Pharmaceuticals!Not Just Pharmaceuticals!

Chemicals that: Chemicals that:

• interactinteract in their affect on organisms, & in their affect on organisms, &

• co-occur co-occur in the environment.in the environment.

3

Modes of Action with Modes of Action with Chemical InteractionsChemical Interactions

• Endocrine Disruption (biogenic Endocrine Disruption (biogenic hormones, synthetic hormones, hormones, synthetic hormones, hormone mimics & blockers)hormone mimics & blockers)

• Antimicrobial Resistance (synthetic Antimicrobial Resistance (synthetic antimicrobials, natural antimicrobials, antimicrobials, natural antimicrobials, metals, pesticides?)metals, pesticides?)

4

Emerging ContaminantsEmerging Contaminants

• DetergentsDetergents• AntioxidantsAntioxidants• Fire retardantsFire retardants• DisinfectantsDisinfectants• FumigantsFumigants• FragrancesFragrances• Pesticides/ Pesticides/

RepellantsRepellants

• Industrial Chem’s, HPVsIndustrial Chem’s, HPVs• Some Metals Some Metals • Biogenic HormonesBiogenic Hormones• PhytoestrogensPhytoestrogens• Natural antimicrobialsNatural antimicrobials• Natural pesticidesNatural pesticides• Degradates/ Degradates/

MetabolitesMetabolites

• Human & Veterinary PharmaceuticalsHuman & Veterinary Pharmaceuticals

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Framing Research QuestionsFraming Research Questions• Are Pharm’s entering our environment? Are Pharm’s entering our environment?

• What are the source pathways, their chemical What are the source pathways, their chemical signatures/loads? signatures/loads?

• Are there sensitive environmental settings? Are there sensitive environmental settings?

• Do Pharm’s have adverse ecological health Do Pharm’s have adverse ecological health effects? effects?

• Do Pharm’s persist to finished drinking water Do Pharm’s persist to finished drinking water and are they a human health risk? and are they a human health risk?

• How can we minimize their entry to the How can we minimize their entry to the environment or remove them?environment or remove them?

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Are Emerging Contaminants Are Emerging Contaminants entering our natural entering our natural environment?environment?

7

High densityHigh density of population of population and animal production.and animal production.

Present in water at Present in water at sub-ppb concentrationssub-ppb concentrations

Present in complex Present in complex mixturesmixtures..

Greater levels in streams Greater levels in streams than wellsthan wells

National Surveys of National Surveys of “Susceptible” Waters“Susceptible” Waters

Kolpin, et al., 2002; Barnes et al., 2008Kolpin, et al., 2002; Barnes et al., 2008

0

20

40

60

80

100

Pe

rce

nt D

ete

cte

d

Surface (139) Ground (47)

Pre. d

rugs

Det

erge

nts

8

0%

20%

40%

60%

80%

Sul

fam

etho

xazo

le

Cod

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Cot

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Trim

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Dilt

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Per

cent

Det

ecte

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Water (30) Sediment (36)

Don’t just look in stream waters!Don’t just look in stream waters!

Furlong, et al., 2003Furlong, et al., 2003

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Measurement CapabilitiesMeasurement Capabilities• Clofibric Acid (Buser 1998)Clofibric Acid (Buser 1998)• 32 drugs in German WWTPs 32 drugs in German WWTPs (Ternes 1998)(Ternes 1998)• 45 drugs in US Rivers (Kolpin et al. 2002)45 drugs in US Rivers (Kolpin et al. 2002)

• amphetamines amphetamines • antibioticsantibiotics • antidepressants (SSRIs)antidepressants (SSRIs)• antiphlogistics antiphlogistics • antivirals antivirals • barbituratesbarbiturates• beta-blockers beta-blockers

• Ca channel blockerCa channel blocker• contraceptives contraceptives • cytostaticscytostatics• fibrates fibrates • glucocorticoids glucocorticoids • muscle relaxantsmuscle relaxants• opioidsopioids

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What are the source pathways What are the source pathways to the environment and their to the environment and their chemical signatures/loads?chemical signatures/loads?

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• WW Treatment PlantsWW Treatment Plants

• Domestic Septic Systems Domestic Septic Systems

• Land ApplicationLand Application

• Industrial/Commercial DischargesIndustrial/Commercial Discharges

• LandfillsLandfills

• Water ReuseWater Reuse

Human Source Pathways?Human Source Pathways?

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• GrazingGrazing

• AFOs/CAFOsAFOs/CAFOs

• Waste lagoons Waste lagoons

• Land application Land application

• ProcessingProcessing

• AquacultureAquaculture

• PetsPets

Animal Source Pathways?Animal Source Pathways?

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WWTP Discharges to StreamsWWTP Discharges to Streams

• Complex chemical mixtures. Complex chemical mixtures.

• Multiple upstream WWTP Multiple upstream WWTP discharges.discharges.

• Significant % WW in some Significant % WW in some streams (arid or urbanized streams (arid or urbanized watersheds).watersheds).

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Carbon Norm. Concentration (Carbon Norm. Concentration (g/kg,10-40% C)g/kg,10-40% C) RangeRange MedianMedian

CarbemazepineCarbemazepine 15-1,200 15-1,200 68 68DiphenhydramineDiphenhydramine 32-22,00032-22,000 340 340FluoxetineFluoxetine 100-4,700100-4,700 370 370TriclosanTriclosan 1,170-32,900 1,170-32,900 10,200 10,200

Kinney et al., 2006Kinney et al., 2006

• Biosolids from 9 sitesBiosolids from 9 sites

• 53 (of 87) ECs detected53 (of 87) ECs detected

• 30 to 45 in each biosolid30 to 45 in each biosolid

• 25 in all samples25 in all samples

ECs in Biosolids Destined for Land AppECs in Biosolids Destined for Land App

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Septic SystemsSeptic Systems

ECs found in septic wastewaters ECs found in septic wastewaters and adjacent groundwater and adjacent groundwater (Swartz (Swartz et al., 2006; Carrara et al., 2008)et al., 2006; Carrara et al., 2008)

Higher levels in commercial than Higher levels in commercial than domestic septics (domestic septics (restaurants, restaurants,

convenience stores, retail centers, schools, convenience stores, retail centers, schools,

veterinary hospitalsveterinary hospitals) ) (Conn et al., 2006)(Conn et al., 2006)

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Conc. Animal Feeding OperationsConc. Animal Feeding Operations

Manure (kg/day) Human 1.5 Cow 30 Hog 4 Sheep 1.5 Chicken 0.14

• Large facilities Large facilities

• Prophylactic dosesProphylactic doses

• Antibiotics, growth promoters, Antibiotics, growth promoters, estrus modulators, … estrus modulators, …

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Antibiotics in 46 Antibiotics in 46 Swine AFOsSwine AFOs

Det

ectio

ns (

%)

Antibiotics in Swine Antibiotics in Swine LagoonsLagoons

Meyer et al., 2003Meyer et al., 2003

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Are there sensitive Are there sensitive environmental settings?environmental settings?

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Hospital Effluents (Antibiotics)Hospital Effluents (Antibiotics)

3 Hospitals in Southeast Queensland, 3 Hospitals in Southeast Queensland, Australia Australia

16 of the 27 16 of the 27 antibioticsantibiotics detected.detected.

Watkinson et al., 2009Watkinson et al., 2009

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Pharm. Manufacturing FacilitiesPharm. Manufacturing Facilities

Larsson et al., 2007Larsson et al., 2007

WWTP near Hyderabad IndiaWWTP near Hyderabad India

• Receives effluent Receives effluent from 90 bulk drug from 90 bulk drug manufacturers.manufacturers.

• Samples on Samples on consecutive days.consecutive days.

Active IngredientActive Ingredient Drug TypeDrug Type Range (Range (g/L)g/L)

CiprofloxacinCiprofloxacin antibioticantibiotic 28,000-31,00028,000-31,000

LosartanLosartan angiotensin II receptor antagonistangiotensin II receptor antagonist 2,400-2,5002,400-2,500

CetrizineCetrizine HH11-receptor antagonist-receptor antagonist 1,300-1,4001,300-1,400

MetoprololMetoprolol BB11-andrenoreceptor antagonist-andrenoreceptor antagonist 800-950800-950

EnrofloxacinEnrofloxacin AntibioticAntibiotic 780-900780-900

CitalopramCitalopram SSRISSRI 770-840770-840

NorfloxacinNorfloxacin antibioticantibiotic 390-420390-420

LomefloxacinLomefloxacin antibioticantibiotic 150-300150-300

EnoxacinEnoxacin antibioticantibiotic 150-300150-300

Ofloxacin Ofloxacin antibioticantibiotic 150-160150-160

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Hydrologic EventsHydrologic Events

Cedar Rapids, IA

Spring FlushSpring Flush

21 herbicides, 27 degradates, 21 herbicides, 27 degradates, 36 antibiotics36 antibiotics in 51 Midwest in 51 Midwest StreamsStreams

Midwest Floods, Spring ‘08Midwest Floods, Spring ‘08

Scribner et al., 2003Scribner et al., 2003

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Animal Waste Lagoon FailureAnimal Waste Lagoon Failure

Aug 24, 2009 Sept 8, 2009

Sept 14, 2009 Sept 21, 2009

Midwest Headwaters StreamMidwest Headwaters Stream

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Do EC’s have adverse Do EC’s have adverse ecological health effects?ecological health effects?

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EC Uptake in OrganismsEC Uptake in Organisms

Plant TissuePlant Tissue

• OxytetracyclineOxytetracycline in in alfalfaalfalfa (Kong et al., 2007).(Kong et al., 2007).

• Oxytetracycline, flumequine Oxytetracycline, flumequine & oxolinic acid& oxolinic acid in in bryophytesbryophytes (Delepee et al., 2004).(Delepee et al., 2004).

• Trimethoprim inTrimethoprim in carrots & carrots & lettucelettuce (Boxall et al., 2006). (Boxall et al., 2006).

• SulfamethazineSulfamethazine in in corn, corn, lettuce, potatoeslettuce, potatoes (Dolliver, (Dolliver, et al., 2007).et al., 2007).

Animal TissueAnimal Tissue

• FluoxetineFluoxetine in in bluegill, catfish, bluegill, catfish, carp, crappiecarp, crappie (Brooks et al., (Brooks et al., 2005).2005).

• GemfibrozilGemfibrozil in in goldfishgoldfish (Mimeault (Mimeault et al, 2005).et al, 2005).

• Triclosan & Methyl-triclosanTriclosan & Methyl-triclosan in in carpcarp (Leiker et al., 2008). (Leiker et al., 2008).

• Trimethoprim & TriclosanTrimethoprim & Triclosan in in earthwormsearthworms (Kinney et al., 2008 (Kinney et al., 2008).).

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• AntibioticsAntibiotics: Reduced soil microbial activity at env. concentrations (Costanzo et : Reduced soil microbial activity at env. concentrations (Costanzo et al., 2005; Thiele-Bruhn and Beck, 2005).al., 2005; Thiele-Bruhn and Beck, 2005).

• Diclofenac (NSAID):Diclofenac (NSAID): Consumption of diclofenac-treated meat caused renal Consumption of diclofenac-treated meat caused renal failure in failure in vulturesvultures (Oaks et al., 2004). (Oaks et al., 2004).

• Ciprofloxacin, triclosan, Tergitol NP 10Ciprofloxacin, triclosan, Tergitol NP 10: shifts in algal community structure : shifts in algal community structure (Wilson et al., 2003) .(Wilson et al., 2003) .

• Drug Mixtures 13Drug Mixtures 13: Inhibited growth of human embryonic cells at environmental : Inhibited growth of human embryonic cells at environmental levels (Pomati et al., 2006, 2008). levels (Pomati et al., 2006, 2008).

• FluoxetineFluoxetine: Affected reproduction in freshwater molluscs -- water-sediment : Affected reproduction in freshwater molluscs -- water-sediment exchange (Sanchez-Arguello et al., 2009).exchange (Sanchez-Arguello et al., 2009).

• AntidepressantsAntidepressants: (: (environmental levels)environmental levels) Affected predator avoidance behavior Affected predator avoidance behavior of larval fathead minnow (of larval fathead minnow (McGee et al. 2009).McGee et al. 2009).

• 4-nonylphenol4-nonylphenol: (: (environmental exposuresenvironmental exposures) Impaired reproductive potential of ) Impaired reproductive potential of male fathead minnows. (male fathead minnows. (Schoenfuss et al., 2008).Schoenfuss et al., 2008).

• AlkylphenolethoxylatesAlkylphenolethoxylates: (: (environmental mixtures)environmental mixtures) Reduced reproductive Reduced reproductive competence in male fathead minnows (competence in male fathead minnows (Bistodeau et al., 2006).Bistodeau et al., 2006).

• Sewage SludgeSewage Sludge: Affected bone homeostasis in sheep (Lind et al., 2009).: Affected bone homeostasis in sheep (Lind et al., 2009).

Ecological EffectsEcological Effects

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Boulder Creek, COBoulder Creek, CO

Endocrine Disruption: A Case StudyEndocrine Disruption: A Case Study

Vajda et al., 2008Vajda et al., 2008

<0.8

2.11.4

2.9

1.2

17b-Estradiol in stream water, in ng/L

Boulder WWTP

Low-head Dam

27

Estrogenicity of Boulder Effluent & Estrogenicity of Boulder Effluent & Boulder CreekBoulder Creek

Vajda et al., 2008Vajda et al., 2008

Spring 2005

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Endocrine Effects in Endocrine Effects in Boulder Ck (Boulder Ck (White SuckerWhite Sucker))

Vajda et al., 2008Vajda et al., 2008

0%10%20%30%40%50%60%70%80%90%

100%

Upstream Downstream

18-Jun-04

Se

x, i

n P

erc

en

t

Female Male

Intersex 0% 19%Intersex 0% 19%

Cellular AbnormalitiesCellular Abnormalities

malemale

femalefemale

IntersexIntersex

Blood VitellogeninBlood Vitellogenin

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Do EC’s persist to finished Do EC’s persist to finished drinking water and are they a drinking water and are they a human health risk?human health risk?

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Natural Dilution and DegradationNatural Dilution and Degradation

DW Sources (Streams) 49Susceptible Streams 139

P

erce

nt D

etec

tion

National Source Water SurveyNational Source Water Survey

Focazio et al., 2008Focazio et al., 2008

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Benotti et al., 2008Benotti et al., 2008

ECs in Finished Drinking Water ECs in Finished Drinking Water

Conducted by Conducted by Southern Nevada Southern Nevada Water AuthorityWater Authority

Supported by AWWA Supported by AWWA Research Fnd. & Research Fnd. & WateReuse Fnd. WateReuse Fnd.

Pharm’sPCPs

42

19

18 182.1 470

93510

3

0.82 1000.33 1.2 25

15 Max. (ppt)

*11 of 20 Pharm’s not detected*11 of 20 Pharm’s not detected

Det

ecti

on

s

18 DW Facilities

32

Human Health Risk?Human Health Risk?

• Chronic low-level exposure.Chronic low-level exposure.

• Exposure to chemical mixtures.Exposure to chemical mixtures.

• Sensitive subpopulations.Sensitive subpopulations.

• Can we prioritize chemicals Can we prioritize chemicals systematically for effects studies?systematically for effects studies?

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How can we minimize their How can we minimize their entry to the environment or entry to the environment or remove them?remove them?

34

Phillips et al., 2008Phillips et al., 2008

WWTPs Ability To WWTPs Ability To Reduce ECsReduce ECs

A B C DPlant

activated sludge

trickling filter

35

Removal in Treatment, NJ FacilityRemoval in Treatment, NJ Facility

Stackelberg et al., 2004 & 2007Stackelberg et al., 2004 & 2007

Raw WaterRaw Water

Per

cen

t D

etec

tio

n

HHCB

AHTN

Levels Generally Reduced by Levels Generally Reduced by Treatment with GAC FiltersTreatment with GAC Filters

Finished WaterFinished Water

P

erce

nt

Det

ecti

on

HHCB

Pharmaceutical/AntibioticFlame retardant/PlasticizerFragrancePesticidePlant/Animal steroidDetergent metabolitePAHsOthers

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Thank you!Thank you!

And thanks to the many And thanks to the many researchers who provided the researchers who provided the information presented.information presented.

For more info on USGS EC research:For more info on USGS EC research: http://toxics.usgs.gov http://toxics.usgs.gov