Secondary Routes of Exposure to Biocides

1
Secondary Routes of Exposureto 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
2
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

3
Properties of Important Environmental Contaminants

• Toxic
• Large quantities
• Environmentally persistent
• Exposure routes exist
• Difficult to detect

4
Accordingly, Polychlorinated Biocides May Be
Problematic
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
5
TriclocarbanA chemical running under the radar

Publications per year
6
Known / Potential Environmental and Human Health
Risks of Triclosan
Persistent Environmental Contaminant ?
Cross-resistance to Antibiotics ?
Triclosan
Bioaccumulation ?
Acts as Carcinogen, Mutagen or Teratogen (No, at
least not directly)
Endocrine Disruption ?
7
Known / Potential Environmental and Human Health
Risks of Triclocarban
Persistent Environmental Contaminant ?
Cross-resistance to Antibiotics ??
Triclocarban
Bioaccumulation ? ?
Acts as Carcinogen, Mutagen or Teratogen ?
? (Plausible Connection)
Endocrine Disruption ?
8
Biocides Are Persistent Environmental Pollutants
Estimated using quantitative structure activity
relationship (QSAR) analysis
Halden and Paull, 2005, EST 39(6)1420-1426
9
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

10
Routes of Primary Exposure
Primary
Human exposure
Ingestion Absorption (Inhalation)
Sources of Biocides Personal care
products Plastics Textiles Laundry
detergents Others
Manufacturing byproducts
Co-exposure
11
Routes of Secondary Exposure
Disposal
Secondary
Human exposure
Wastewater
Sludge
WWTP
Ingestion Absorption (Inhalation)
Effluent
Air
Soil
Water resources
Drinking water
Sediment
Food (Plants and Animals) Bioconcentration Bioacc
umulation Biomagnification
Co-exposure
Degradates Metabolites
12
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

13
Triclocarban 48 Years of Usage Before the First
Publication on Its Environmental Fate
14
Isotope Dilution Liquid Chromatography
Electrospray Ionization Mass Spectrometry
Relative Intensity ()
Halden and Paull, Environ. Sci. Technol.,
38(18)4849-4855 (2004)
15
TCC Contamination in Baltimore Streams
Halden and Paull, 2005, Environ. Sci. Technol.,
39(6)1420-1426
16
Co-Occurrence of TCC and TCS in MD Streams
Calculate TCC
R2 0.9882
Measure TCS
Halden and Paull, 2005, Environ. Sci. Technol.,
39(6)1420-1426
17
Prediction TCC Contamination Nationwide
18
Model Predicts Nationwide Contamination
Halden and Paull, 2005, Environ. Sci. Technol.,
39(6)1420-1426
19
Predictions for 85 Streams Across the U.S.
Halden and Paull, 2005, Environ. Sci. Technol.,
39(6)1420-1426
20
Toward an Inventory of Biocides inU.S. Water
Resources Nationwide
21
Jochen Heidler Initial Data from the U.S.









River samples taken upstream and downstream of
WWTPs in 9 states across the U.S.
Sapkota, Heidler, and Halden (In Review)
22
Preliminary Results
Predicted Nationwide Contamination Was Confirmed
Experimentally
Model Experimental Upstream
Downstream Number of samples
85 18 18 Detection Frequency
60 56 100 Mean ng/L 213 1215 84
109
However, concentrations are low, in the ng/L
range!
Sapkota, Heidler, and Halden (In Review)
23
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

24
Typical U.S. Wastewater Treatment Plant (WWTP)

• Activated sludge WWTP
• 680 ML/d
• (180 MGD)
• Population served
• 1.3 Million

Heidler and Halden, 2004
25
Schematic Overview of Studied Activated Sludge
Wastewater Treatment Plant (WWTP)
Primary
Activated Sludge Treatment
Secondary
Sand
Chlorine
Influent
Clarifiers
Clarifiers
Filters
Effluent
Air
Primary
Secondary
Sludge
Sludge
Solid Waste
Sludge Thickeners
Anaerobic
Digesters
Sampling Locations
Dewatered digested sludge
Heidler and Halden, 2004
26
WWTP Less Than 1 ppb in Effluent
ppb
Accumulation
lt 1 ppb
Influent
Effluent
Digested Sludge
Heidler and Halden (In Preparation)
Heidler and Halden (2004 Preliminary Estimate)
27
But Substantial Accumulation in Sludge
ppb
Accumulation
lt 1 ppb
Influent
Effluent
Digested Sludge
Heidler and Halden (2004 Preliminary Estimate)
28
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
Mass in effluent
Mass in sludge
Mass degraded
Heidler and Halden (2004 Preliminary Estimate)
29
Estimated Mass Use of Sludge in the U.S.
Sludge A Potential Resource 12.5 Billion dry
lb/yr
Incineration 19
Other 1
Land Application 63
Landfills 17
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
30
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
• gt150,000 lbs/yr of TCS and gt175,000 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)
31
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

32
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)
35
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... (verbi
age from final paragraph)
Pediatrics, December 1971
36
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)

37
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

38
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

39
Selected References

1. Kolpin et al., Environ. Sci. Technol., 361202,
   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, 325175,
   1996
5. Latch, J. Photochem. Photobiol., 15863, 2003
6. Gledhill, Water Research, 9649, 1975
7. Clark et al., Int. J. Environ. Anal. Chem.,
   45169, 1991
8. Bester, Water Research, 373891, 2003
9. Federle et al., Environ. Toxicol. Chem., 211330,
   2002
10. McAvoy et al., Environ. Toxicol. Chem., 211323,
    2002
11. Heidler and Halden, ACS National Meeting,
    Washington, DC, 2004.

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Heidler and Halden (unpublished)
43
TCC in River Sediments
Source Wastewater Treatment Plant
44
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 ltLOD to 702 ng/mL

Ye et al. 2005 Anal. Chem. 775407-5413 Data
from the CDC in Atlanta, GA
45
Ecological Risk Posed by 3,4-Dichloroaniline
Versteeg et al. 1999 Environ. Tox. Chem.
18(6)1329