Secondary Routes of Exposure

to Biocides

Rolf Halden, PhD, PE

Johns Hopkins University

Center for Water and Health

Bloomberg School of Public Health

Baltimore, MD

Presented to the Food and Drug Administration (FDA) Nonprescription Drugs Advisory Committee, Silver Spring, MD, on October 20, 2005

Overview

• Background

• Primary exposures

• Secondary exposures

– Biocides in aquatic environments

– Biocides in terrestrial environments

• Biocides in food, drinking water, human milk, blood, and urine

• Summary

Properties of Important Environmental Contaminants

• Toxic

• Large quantities

• Environmentally persistent

• Exposure routes exist

• Difficult to detect

Accordingly, Polychlorinated Biocides May Be Problematic

Triclocarban (TCC)

HN

O

HN

ClCl

Cl

Triclosan (TCS)

Cl

OH

O

Cl

Cl

Property Triclosan Triclocarban

Year Introduced 1964 1957

Formula C12H9Cl3O2 C13H9Cl3N2O

Molecular Weight 289.55 315.59

Water Solubility (mg/L at 25ºC) 1.97 – 4.6 0.65 – 1.55

Log KOW (at 25ºC, pH 7) 4.8 4.9

For each molecule in water, we expect to find ~100,000 in fat

Triclocarban:A chemical running under the radar

Number of Publications (ISI Web of Science)

0

25

50

75

100

1980 1985 1990 1995 2000 2005

Triclosan

Triclocarban

Pu

blic

ati

on

s p

er

year

Known / Potential Environmental and Human Health Risks of Triclosan

Triclosan

Degradates(including chloroform)

Cross-resistance to Antibiotics

Endocrine Disruption?

Acts as Carcinogen,Mutagen orTeratogen

(No, at least not directly)

Bioaccumulation

PersistentEnvironmentalContaminant

Impurities

Known / Potential Environmental and Human Health Risks of Triclocarban

Triclocarban

Cross-resistance to Antibiotics

?

Endocrine Disruption?

Acts as Carcinogen,Mutagen orTeratogen

? (Plausible Connection)

Bioaccumulation?

PersistentEnvironmentalContaminant

Impurities

?

H2N Cl

Degradates

NH2

Cl

Cl

H2N Cl

Biocides Are Persistent Environmental Pollutants

Estimated using quantitative structure activity relationship (QSAR) analysis

1

60120

540

0.75

0.1

1

10

100

1000

10000

Air Water Soil Sediment

Est

imat

ed H

alf-

life

(d

ays)

Triclosan

Triclocarban

Halden and Paull, 2005, ES&T 39(6):1420-1426

Overview

• Background

• Primary exposures

• Secondary exposures

– Biocides in aquatic environments

– Biocides in terrestrial environments

• Biocides in food, drinking water, human milk, blood, and urine

• Summary

Ingestion

Absorption(Inhalation)

Primary Human exposure

Sources of Biocides:

Personal care products

Plastics

Textiles

Laundry detergents

Others

Co-exposureManufacturingbyproducts

Routes of Primary Exposure

Wastewater WWTP Sludge

Effluent

Water resources

Air

Drinking water

Sediment

SoilIngestion

Absorption(Inhalation)

Secondary

Food (Plants and Animals)

BioconcentrationBioaccumulationBiomagnification

Human exposure

Co-exposure Degradates & Metabolites

Routes of Secondary Exposure

Disposal

Overview

• Background

• Primary exposures

• Secondary exposures

– Biocides in aquatic environments

– Biocides in terrestrial environments

• Biocides in food, drinking water, human milk, blood, and urine

• Summary

Triclocarban: 48 Years of Usage Before the First Publication on Its Environmental Fate

TCC Contamination in Baltimore Streams

Halden and Paull, 2005, Environ. Sci. Technol., 39(6):1420-1426

Co-Occurrence of TCC and TCS in MD Streams

TC

C [

ng/L

]

TCS [ng/L]

R2 = 0.9882

MeasureTCS

CalculateTCC

Halden and Paull, 2005, Environ. Sci. Technol., 39(6):1420-1426

Prediction: TCC Contamination Nationwide

Model Predicts Nationwide Contamination

Halden and Paull, 2005, Environ. Sci. Technol., 39(6):1420-1426

Predictions for 85 Streams Across the U.S.

Halden and Paull, 2005, Environ. Sci. Technol., 39(6):1420-1426

Toward an Inventory of Biocides inU.S. Water Resources Nationwide

Jochen Heidler: Initial Data from the U.S.

a

a a aa a

a

aa

a

River samples taken upstream and downstream of WWTPs in 9 states across the U.S.

••

••• ••••

Sapkota, Heidler, and Halden(In Review)

Preliminary Results

Model Experimental Upstream Downstream

Number of samples 85 18 18

Detection Frequency 60% 56% 100%

Mean [ng/L] 213 12±15 84 ±109

Predicted Nationwide Contamination Was Confirmed Experimentally

Sapkota, Heidler, and Halden(In Review)

However, concentrations are low, in the ng/L range!

Overview

• Background

• Primary exposures

• Secondary exposures

– Biocides in aquatic environments

– Biocides in terrestrial environments

• Biocides in food, drinking water, human milk, blood, and urine

• Summary

Typical U.S. Wastewater Treatment Plant (WWTP)

• Activated sludge

WWTP

• 680 ML/d

(180 MGD)

• Population served:

1.3 Million

Heidler and Halden, 2004

Schematic Overview of Studied Activated Sludge Wastewater Treatment Plant (WWTP)

Influent MechanicalScreens

PrimaryClarifiers

Activated SludgeTreatment

Secondary Clarifiers

SandFilters

Effluent

PrimarySludge

Chlorine

AnaerobicDigesters

SludgeThickeners

Air

Dewatered digested sludge

Solid Waste

SecondarySludge

Sampling Locations

Heidler and Halden, 2004

WWTP: Less Than 1 ppb in Effluent

1

10

100

1000

10000

100000

Influent Effluent Digested Sludge

TCS

TCC

pp

b

< 1 ppb

Acc

um

ula

tio

nHeidler and Halden (In Preparation)

Heidler and Halden (2004 Preliminary Estimate)

But Substantial Accumulation in Sludge

1

10

100

1000

10000

100000

Influent Effluent Digested Sludge

TCS

TCC

pp

b

< 1 ppb

Acc

um

ula

tio

n

Heidler and Halden (2004 Preliminary Estimate)

Fate of Biocides During Conventional Activated Sludge Wastewater Treatment

TCS

Mass in effluent

Massdegraded

TCC

Mass in sludge

45%

1%

54%

3%

54%43%

Heidler and Halden (2004 Preliminary Estimate)

(Data shown are based on a conservative 2004 estimate; revised estimates have been submitted for publication )

Estimated Mass & Use of Sludge in the U.S.

Land Application63%

Landfills17%

Other1%

Incineration19%

Biosolids Applied to Land, National Research Council of the National Academies, 2002

Sludge: A Potential Resource: 12.5 Billion dry lb/yr

After successful removal from wastewater, the majority of captured compounds is re-introduced into the environment

Biocides: Transfer from Water to Ag Soils

• Plant removes but does NOT degrade biocides effectively

• Biocides are transferred into municipal sludge

• Concentration ratio sludge/effluent: ~100,000

• >150,000 lbs/yr of TCS and >175,000 lbs/yr of TCC are applied on

agricultural land in sludge used as fertilizer

• Neither biocide is approved/tested for use in agriculture

Heidler and Halden (2004 Preliminary Estimate)

Overview

• Background

• Primary exposures

• Secondary exposures

– Biocides in aquatic environments

– Biocides in terrestrial environments

• Biocides in food, drinking water, human milk, blood, and urine

• Summary

Are People Getting Unintentionally Exposed and What Are the Risks/Outcomes?

Rare Infant Deaths From Laundry Disinfectants

AJPH 60(5):901 (1970)

1967: Rare Deaths Due to Improper Use of Laundry Agents

• 1967, Booth Memorial Hospital, St. Louis, MO• Infants: sweating, fever, difficulty breathing• 2 deaths, multiple illnesses• 2 drums of Loxene found in laundry closet

– 22.9% chlorophenols

– 4% triclocarban

• Analysis of blood showed phenol poisoning

AJPH 60(5):901 (1970)

Methemoglobinemia in Infants: U.S.

Pediatrics, February 1963

Committee on Drugs

“...clinical judgment would dictate avoiding... even the most innocent-appearing substances in the nursery ...until data on toxicity are available...”(verbiage from final paragraph)

Pediatrics, December 1971

Human Exposure toEnvironmentally Persistent Biocides

• Triclosan in drinking water resources (Multiple reports)

• Triclocarban in fruit juice (Sapkota et al. unpublished)

• Triclosan in fish (Multiple reports)

• Triclosan in breast milk (1 Report published; 1 in preparation)

• Triclosan/Triclocarban in human blood (WWF; Sapkota et al. unpublished)

• Triclosan in human urine (CDC, 2005)

In Summary: The Biocides TCS and/or TCC...

– persist in the environment

– are produced faster than they degrade (unsustainable usage)

– contaminate sludge, a potentially valuable resource

– contaminate the food supply

– bioaccumulate in biota (e.g., fish)

– are detectable in human blood, milk and urine (general population)

– contaminate soils and aquatic sediments; consequences unknown

These known/potential risks need to be weight against potential benefits

Acknowledgments

• Daniel Paull, Jochen Heidler, Amir Sapkota, David Colquhoun, Rey de Castro

• Guy Hollyday (Baltimore Sanitary Sewer Oversight Coalition)

• John Martin and Nick Frankos from the Department of Public Works, City of

Baltimore

Triclocarban research was made possible by the

– NIEHS grant P30ES03819 (Pilot Project)

– JHU Faculty Innovation Award

– CRF of Maryland

– JHU Center for a Livable Future

– JHU Faculty Research Initiative

Selected References

1. Kolpin et al., Environ. Sci. Technol., 36:1202, 2002

2. Halden and Paull, Environ. Sci. Technol., 38(18):4849, 2004

3. Halden and Paull, Environ. Sci. Technol., 39(6):1420, 2005

4. Okumura, Nishikawa, Anal. Chim. Acta, 325:175, 1996

5. Latch, J. Photochem. Photobiol., 158:63, 2003

6. Gledhill, Water Research, 9:649, 1975

7. Clark et al., Int. J. Environ. Anal. Chem., 45:169, 1991

8. Bester, Water Research, 37:3891, 2003

9. Federle et al., Environ. Toxicol. Chem., 21:1330, 2002

10. McAvoy et al., Environ. Toxicol. Chem., 21:1323, 2002

11. Heidler and Halden, ACS National Meeting, Washington, DC, 2004.

TCC in River Sediments

Source: Wastewater Treatment Plant

TCC in Human Urine

• 30 Anonymous Adult Volunteers Lacking Occupational Exposures

• 24 Had Detectable Levels of Triclosan

• Mean 127 ng/mL = µg/L = ppb

• 5th to 95th Percentile: <LOD to 702 ng/mL

Ye et al. 2005 Anal. Chem. 77:5407-5413; Data from the CDC in Atlanta, GA

Ecological Risk Posed by 3,4-Dichloroaniline

Versteeg et al. 1999; Environ. Tox. Chem. 18(6):1329