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 Triclosan (TCS)

OH Cl O Cl

Triclocarban (TCC)

H N H N O Cl Cl Cl Property Year Introduced Formula Molecular Weight Water Solubility (mg/L at 25ºC) Log K OW (at 25ºC, pH 7) Triclosan 1964 C 12 H 9 Cl 3 O 2 289.55

1.97 – 4.6

4.8

Triclocarban 1957 C 13 H 9 Cl 3 N 2 O 315.59

0.65 – 1.55

4.9

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

Triclocarban: A chemical running under the radar Number of Publications (ISI Web of Science) 100 75 50 T riclosan T riclocarban 25 0 1980 1985 1990 1995 2000 2005

Known / Potential Environmental and Human Health Risks of Triclosan

Degradates (including chloroform)  Persistent Environmental Contaminant  Cross-resistance to Antibiotics  Impurities

Triclosan

 Bioaccumulation  Acts as Carcinogen, Mutagen or Teratogen

(No, at least not directly)

Endocrine Disruption ?

Known / Potential Environmental and Human Health Risks of Triclocarban

Cl Cl Degradates H 2 N NH 2  Cl Persistent Environmental Contaminant  Cross-resistance to Antibiotics  ?

H 2 N Impurities Cl ? 

Triclocarban

Acts as Carcinogen, Mutagen or Teratogen ? 

(Plausible Connection)

Bioaccumulation ?  Endocrine Disruption ?

Biocides Are Persistent Environmental Pollutants 10000 1000 100 Triclosan Triclocarban 60 120 540 10 1 1 0.75

0.1

Air Water Soil Sediment

Estimated using quantitative structure activity relationship (QSAR) analysis

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

Routes of Primary Exposure

Primary Human exposure

Sources of Biocides: Personal care products

Plastics Textiles Laundry detergents Others

Ingestion

Absorption

(Inhalation)

Manufacturing byproducts Co-exposure

Routes of Secondary Exposure

Human exposure

Disposal

Secondary

Wastewater WWTP

Ingestion

Absorption (Inhalation)

Air Effluent

Sludge Soil

Drinking water Water resources

Sediment

Co-exposure

Food

(Plants and Animals)

Bioconcentration Bioaccumulation Biomagnification

Degradates & Metabolites

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

10 6 10 5

Calculate TCC

10 4 10 3 10 2 10 1 10 0 10 0 10 1

Measure TCS

10 2 10 3 10 4 TCS [ng/L]

Triclosan [ng/L]

10 5 10 6 R 2 = 0.9882

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 in U.S. Water Resources Nationwide

a

Jochen Heidler: Initial Data from the U.S.

a

• • • •

a a

• •••

a

•

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

Sapkota, Heidler, and Halden (In Review)

Predicted Nationwide Contamination Was Confirmed Experimentally Preliminary Results

Number of samples

Model

85

Experimental

Upstream Downstream 18 18 Detection Frequency 60% Mean [ng/L] 213

56%

12±15

100%

84 ±109

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

Sapkota, Heidler, and Halden (In Review)

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 Mechanical Screens Solid Waste Primary Clarifiers Primary Sludge Activated Sludge Treatment Secondary Clarifiers Chlorine Sand Filters Air Secondary Sludge Sludge Thickeners Effluent Sampling Locations Anaerobic Digesters Dewatered digested sludge

Heidler and Halden, 2004

WWTP: Less Than 1 ppb in Effluent

100000

TCS TCC

10000 1000 100 10

< 1 ppb

1

Influent Effluent Digested Sludge

Heidler and Halden (In Preparation) Heidler and Halden (2004 Preliminary Estimate)

But Substantial Accumulation in Sludge

100000 10000 1000 100 10 1

TCS TCC Influent < 1 ppb Effluent Digested Sludge

Heidler and Halden (2004 Preliminary Estimate)

Fate of Biocides During Conventional Activated Sludge Wastewater Treatment

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

TCS TCC 45% 54% 1% Mass degraded 43% 54% Mass in effluent 3% Mass in sludge

Heidler and Halden (2004 Preliminary Estimate)

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

Sludge: A Potential Resource:

12.5 Billion dry lb/yr

Incineration 19% Other 1% Landfills 17% Land Application 63%

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

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

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 to Environmentally 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.

2.

3.

4.

5.

Kolpin et al., Environ. Sci. Technol., 36:1202, 2002 Halden and Paull, Environ. Sci. Technol., 38(18):4849, 2004 Halden and Paull, Environ. Sci. Technol., 39(6):1420, 2005 Okumura, Nishikawa, Anal. Chim. Acta, 325:175, 1996 Latch, J. Photochem. Photobiol., 158:63, 2003 6.

7.

8.

9.

Gledhill, Water Research, 9:649, 1975 Clark et al., Int. J. Environ. Anal. Chem., 45:169, 1991 Bester, Water Research, 37:3891, 2003 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:

Ecological Risk Posed by 3,4-Dichloroaniline

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