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![Page 1: Secondary Routes of Exposure to Biocides Rolf Halden, PhD, PE Johns Hopkins University Center for Water and Health Bloomberg School of Public Health Baltimore,](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d175503460f949ed7f1/html5/thumbnails/1.jpg)
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
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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
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Properties of Important Environmental Contaminants
• Toxic
• Large quantities
• Environmentally persistent
• Exposure routes exist
• Difficult to detect
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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
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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
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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
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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
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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
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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
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Ingestion
Absorption(Inhalation)
Primary Human exposure
Sources of Biocides:
Personal care products
Plastics
Textiles
Laundry detergents
Others
Co-exposureManufacturingbyproducts
Routes of Primary Exposure
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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
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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
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Triclocarban: 48 Years of Usage Before the First Publication on Its Environmental Fate
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TCC Contamination in Baltimore Streams
Halden and Paull, 2005, Environ. Sci. Technol., 39(6):1420-1426
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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
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Prediction: TCC Contamination Nationwide
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Model Predicts Nationwide Contamination
Halden and Paull, 2005, Environ. Sci. Technol., 39(6):1420-1426
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Predictions for 85 Streams Across the U.S.
Halden and Paull, 2005, Environ. Sci. Technol., 39(6):1420-1426
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Toward an Inventory of Biocides inU.S. Water Resources Nationwide
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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)
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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!
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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
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Typical U.S. Wastewater Treatment Plant (WWTP)
• Activated sludge
WWTP
• 680 ML/d
(180 MGD)
• Population served:
1.3 Million
Heidler and Halden, 2004
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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
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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)
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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)
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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 )
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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
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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)
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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
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Are People Getting Unintentionally Exposed and What Are the Risks/Outcomes?
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Rare Infant Deaths From Laundry Disinfectants
AJPH 60(5):901 (1970)
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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)
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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
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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)
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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
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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
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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.
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TCC in River Sediments
Source: Wastewater Treatment Plant
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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
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Ecological Risk Posed by 3,4-Dichloroaniline
Versteeg et al. 1999; Environ. Tox. Chem. 18(6):1329