Pharmaceuticals and Personal CareProducts in U.S. Water Resources

Rolf Halden, PhD, PESpecialty Area Coordinator for Water Resources and Environmental Engineering

Department of Civil, Environmental and Sustainable Engineering, Arizona State University

Presented at: Interstate Technology & Regulatory Council (ITRC) Fall MeetingOctober 21, 2008, Phoenix, AZ

Outline

PPCPs

Sources

Status Quo

Tox Data

Summary

• 1 Acronym, 2 distinct issues

PPCPs

Image: Beyond Pesticides

http://www.diamond.ac.uk/

U.S. Animal ProductionBroilers 8,788,281,000Turkeys 254,455,000Hogs 103,584,000Cattle 32,734,000Sheep 2,844,000Calves 847,000

Total 9,182,745,000

USDA

http://photogallery.nrcs.usda.gov/Detail.asp

http://photogallery.nrcs.usda.gov/Detail.asp

Industrial Farm Animal Production (IFAP)New business model brings new challenges

• 70-80% of antibiotic usage• 55% of soil and sediment erosion• 37% of U.S. pesticide usage• 30% of N and P loading to drinking water resources

http://photogallery.nrcs.usda.gov/Detail.asphttp://photogallery.nrcs.usda.gov/Detail.asp

USGS Stream Monitoring Network

Source: USGS 2002

(1999-2000)

Target Chemicals (95 total)22 Antibiotics

14 Prescription drugs

5 Nonprescription drugs

15 Hormones and sterols

39 Household and industrial compounds

Source: USGS 2002

22 Veterinary and Human Antibiotics

• 4 Tetracyclines (Doxycycline)

• 4 Fluoroquinolones (Ciprofloxacin)

• 3 Macrolides (Erythromycin-H2O*)

• 7 Sulfonamides (Sulfamethazine)

• Others (Lincomycin, Trimethoprim Carbadox, Virginiamycin)

*metabolite

Source: USGS 2002

• Pharmaceuticals detected in ~80% of streams

• 75 of 95 pharmaceuticals detected

• Concentrations generally low

~5% hits > 1µg/L

~25% of sampling sites > 6 µg/L total compounds

75% > 1 compound => Mixtures

35% > 10 compounds

Few standards/guidelines exceeded, as few exist

USGS Results, 2002

Source: USGS 2002

Looking back:Pharmaceuticals in freshwater: NOT

a new problem! CH3H3C

COOHOCl

1976 Detected in WWTP effluent

1991 Detected in drinking water, Berlin, FRG

1995 River Elbe, FRG (27-157 ng/L)

1998 Detected in various Swiss lakes (1-9 ng/L)

1998 Detected in the North Sea, FRG (1-2 ng/L)

Buser et al. 1998, ES&T 32:188-192

Clofibric Acid

• phenoxyalkanoic acid

• 2-[4-chlorophenoxy]-2-methylpropionic acid

• blood lipid regulator (ethyl ester; clofibrate)

• 1-2 g/day therapeutic dosage

• structural isomer: herbicide mecoprop, MCPP

CH3H3C

COOHOCl

CH3H

COOHOCl

CH3

MCPP

• New, more sensitive analytical tools (e.g., MS-MS)

• Drugs typically are polar compounds

- native (underivatized) drugs & metabolites areinvisible to GC-MS

• LC-MS ==> polar, thermo-labile compounds

Why is the problem identifiednow?

HN

O

HN

ClCl

Cl

Triclocarban (TCC)

1957

1964

Cl

OH

O

Cl

Cl

Triclosan (TCS)

Triclocarban (TCC)

HN

O

HN

ClCl

Cl

Triclosan (TCS)

Cl

OH

O

Cl

Cl

4.94.8Log KOW (at 25ºC, pH 7)

TriclocarbanTriclosanProperty

Persistent Biocides as Surrogates for Multiple Issues• Personal care products

• Pharmaceuticals

• Pesticides

• Endocrine disruptors

• Persistent halogenated aromatic compounds

• Promoter of antimicrobial resistance

• Modulator of microbial communities

• Pollutant of aquatic & terrestrial environment

• Others

Heidler and Halden 2008 (In Revision)

Update of info from ES&T 39(6):1420-6 (2005)

PPCPs in the Environment: An Emerging Issue

Environmental and Human Health Concerns

Triclosan

Cross-resistance to Antibiotics

Endocrine Disruption

Bioaccumulation

PersistentEnvironmentalContaminant

Acts as Carcinogen,Mutagen orTeratogen

Impurities

O

O

Cl

ClCl

Cl

Degradates(including chloroform)

O

O

ClCl

TCS - A Case Study of Non-Green Chemistry (In Preparation)

Triclocarban

Cross-resistance to Antibiotics

?

Endocrine Disruption

Acts as Carcinogen,Mutagen orTeratogen

(Indirectly through metabolites) ?

Bioaccumulation?

PersistentEnvironmentalContaminant

Impurities

?

H2N Cl

Degradates

NH2

Cl

Cl

H2N Cl

Environmental and Human Health Concerns

TCC - A Case Study of Non-Green Chemistry (In Preparation)

Triclocarban: Case Study of an Emerging Contaminant

[M-H]-m/z 313315317

m/z 313315317

100

0

HPLC

Rel

ativ

e In

tens

ity (%

)So

lven

t (%

) 100

0

25

75

Time (min)

[M+60-H]-

(CH3COOH Adduct)

100

0 302010

m/z 373375377

15 2550

O

O-

HN

O

HN

ClCl

Cl

HN

O

HN

ClCl

Cl

Introduction of an LC-ESI-MS Method in 2004

ES&T 38(18):4849-4855 (2004)

Triclocarban in Maryland Streams

ES&T 38(18):4849-4855 (2004)

Co-Occurrence of Triclocarban and Triclosan

Triclosan [ng/L]

100 101 102 103 104 105 106

Tric

locarb

an

[ng/L

]

100

101

102

103

104

105

106

TCC

[ng/

L]

TCS [ng/L]

R2 = 0.9882

MeasureTCS

CalculateTCC

ES&T 39(6):1420-6 (2005)

• Activated sludge WWTP

• 600 ML/D (180 MGD)

• Population served: 1.3 M

Wastewater Treatment Plants are PrincipalSources of Antimicrobials in the U.S.

Environment

ES&T 40:3634-9 (2006)

Influent MechanicalScreens

PrimaryClarifiers

Activated SludgeTreatment

Secondary Clarifiers

SandFilters

Effluent

PrimarySludge

Chlorine

AnaerobicDigesters

SludgeThickeners

Air

Dewatered sludge

SecondarySludge

Sampling Locations

ES&T 40:3634-9 (2006)

Schematic Overview of Local Activated Sludge WastewaterTreatment Plant (WWTP)

Accumulation of TCC in Digested Sludge During Wastewater Treatment

0.1

1

10

100

1000

10000

100000

Influent Effluent Digested Sludge

ppb

Acc

umul

atio

n

Rem

oval

ES&T 40:3634-9 (2006)

Fate of Triclocarban During Activated Sludge Treatment

Mass in effluentMass in sludgeMass transformed/lost

21 ± 30%795 g/d

3 ± 1%127 g/d

76 ± 30%2815 g/d

ES&T 40:3634-9 (2006)

HN

O

HN

Cl Cl

Cl

Triclocarban (TCC)

2 ± 1%55 g/d

48 ± 19%1540 g/d

50 ± 19%1640 g/d

Mass in effluentMass in sludgeMass transformed/lost

Chemosphere 66(2):362-9 (2007)

Fate of Triclosan in Activated Sludge WWTP

O

Cl

Cl

Cl

OH

Triclosan (TCS)

Meta-analysis of Published Mass Balances

• 13 Peer-reviewed mass balance papers

• 19 Organic wastewater contaminants

• Approach: regression analysis

ES&T 42(17):6324-6332 (2008)

InfluentFinal

effluent

Primary

effluent

Activated

sludge

3

97

3

62

TSS removal in

primary clarifiers

= 36%

35 59

(log Koc= 6)

TSS removal in

final clarifiers

= 90%

100

0

19

8381

017

(log Koc= 2)

0

100

0

74

26

13

0

78

(log Koc= 4)

9

74

17

4

87

0

65

3

3

A

B

C

The Role of Partitioning & Sorption

ES&T 42(17):6324-6332 (2008)

Meta-Analysis ofMass Balances

Sludge

Effluent

Lost

ES&T 42(17):6324-6332 (2008)

Biosolids: An Emerging Research Area

Halden, unpublished

The ASU National Biosolids Repository

What Happens to Compounds That PassThrough the Plant?

ES&T 40:3634-9 (2006)

Environmental Persistence: Predicted & Measured

Estimated using quantitative structure activity relationship (QSAR) analysis

1

60120

540

0.75

0.1

1

10

100

1000

10000

Air Water Soil Sediment

Estim

ated

Hal

f-life

(day

s)

TriclosanTriclocarban

ES&T 39(6):1420-6 (2005)

Some PPCPs Persist in the Environment

TCS and/or TCC...

• are consistently found at ppm levels in biosolids from around the world(Bester 2003; Morales, Canosa et al. 2005; Heidler, Sapkota et al. 2006; Kinney, Furlong et al. 2006; Chuand Metcalfe 2007; Ying and Kookana 2007; Heidler and Halden 2008a,b).

• persist in anaerobic soils (Ying, Yu et al. 2007).

• persist and bioaccumulate in algae and earthworms (Coogan, Edziyie et al. 2007;Kinney, Furlong et al. 2008).

• persist in sediments for decades (Miller et al. 2008; in revision)

ES&T 2008, 42:4570-76Environmental Persistence: Empirical Evidence

ES&T 2008, 42:4570-76

Occurrence of Antimicrobialsin Estuarine Sediments

ES&T 2008, 42:4570-76

Young et al. 2008. ES&T 42(9):3335-3340Chalew and Halden 2008 (In Press)

Antimicrobials in Surface WaterCan Serve as Indicators ofMicrobial Contamination

log CFU/100 mL

• Microbes tolerate low levels of antimicrobials in surface waters

• TCS/TCC in surface waters can indicate presence of pathogens

• In contrast, more susceptible receptors (algae, crustacea) may

experience lifetime exposure to toxic TCS/TCC levels

Nationwide Data of PPCPs in Biosolids

• 110 Wastewater treatment facilities

• 30+ U.S. States

• 70+ PPCPs examined

McClellan and Halden (In internal review)

Present study73 PPCPs total

38 PPCPs

Kolpin et al.(2002) Total of 95 organic wastewater compounds

By taking care of2 chemicals, wecould take care of66% of the PPCPproblem

McClellan and Halden 2008 (In internal review)

TCC+TCS

Breakup of 73 PPCPs by Total Mass in Biosolids

Endocrine Disruption: A Risk Driver

UC Davis news release

Triclosan: Endocrine Disruption in Human Cells

Antimicrobials: Endocrine Disruption in Frogs

Cell assay: concentrations of as low as 30 ng/Lalter thyroid hormone receptor mRNA expression

http://www.vettorpisani.net/

Antimicrobials: Adverse Effects in Mussels

http://www.ealing.gov.uk/

Antimicrobials: Endocrine Disruption in Rats

Triclosan in U.S. Breast MilkTriclosan detectable in 97%of U.S. breast milk samplesanalyzed

Summary of Nationwide Data• TCC &TCS occur nationwide* in:

– raw sewage (1.86 – 26.8 µg/L for TCS; 0.4 – 50 µg/L for TCC)– sewage treatment plant effluent (0.027 – 2.7 µg/L for TCS; 0.1 – 6 µg/L for TCC)– surface waters (<2.3 µg/L for TCS; typically <0.25 µg/L; up to 6.75 µg/L of TCC in sewage

impacted streams)– biosolids (90 – 32,900 µg/kg for TCS; 3,050 – 51,000 µg/kg for TCC)– sediments (up to 53,000 µg/kg for TCS; up to 24,000 µg/kg for TCC)

• TCC & TCS are persistent, particularly under anaerobic conditions– can persist for decades in aquatic sediments

• PPCPs in the environment: dilution is not the solution

– ppb WWTP Influent => ppt WWTP Effluent => ppm Biosolids, Sediments, Earthworms, House Dust

* Chalew and Halden 2008 (In Press)

• PPCPs is an issue that won’t go away by itself; action is needed

• Endocrine disrupting properties are drivers of human health risks

• Emergence of drug-resistant pathogens is another major concern

• Environmental effects of PPCP mixtures are mostly unexplored

Summary & Conclusions

• Agriculture– discontinue use of antibiotics for growth promotion

– end the use of human drugs in animals (food animal production and veterinary medicine)

• Education (protect source water and increase acceptance that water is always “reused”)– the toilet is not a garbage bin

• promote drug take-back & disposal programs

• “wastewater” is a misnomer; used water is raw drinking water (“fortified drinking water”; “post-consumer drinking water”...)

– the sink is not a garbage bin or compost pile• remove persistent biocides and other unnecessary organohalogens from consumer products

• limit use of electrical garbage disposals for disposal of food waste

– avoid future problems• keep problematic compounds like organohalogens out of the water cycle

• Industry (organohalogens are persistent pollutants that should be replaced where possible– where feasible, phase-out/remove/replace organic compounds carrying -F; -Cl, -Br, -I substituents

• Policy (eliminating the root cause will saves $$ and has biggest impact most quickly)– consider a universal tax on halogen-carbon bonds* as an incentive for sustainable chemistry

– discontinue the unnecessary use of persistent biocides• >60% of the PPCP mass in biosolids are persistent biocides

• TCS/TCC have no proven benefits (compared to “regular” soaps) but pose numerous potential risks

• TCS/TCC alone represent several hundred thousand lbs/year of organohalogens that enter agriculture through sludge disposed on land

Opportunities/Possible Actions

*Graham & Halden, 2009 (Under Consideration at Chemical Reviews)

Acknowledgements

Contributors

• Kristin McClellan, MS

• Randhir Deo, PhD

• Daniel Paull, B.S.

• Jochen Heidler, PhD

• Amir Sapkota, PhD

• Todd Miller, PhD

• Thayer Young, MS

• Amelia DeLaquil, BS

• Talia Chalew, MS

• Steven Chillrud, PhD

• Richard Bopp, PhD

• Jerry Ritchie, PhD

Funding/Support

• US EPA

• NIEHS

• CDC

• JHU-CLF

• Gifts

Technical Assistance

• US EPA

• City of Baltimore

• John Martin, PhD and Nick Frankos

• WEF Collaborators

• Groundwater Foundation