Document ID: EPA-HQ-OPP-2007-0513-0035
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-10-29T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

  AND TOXIC SUBSTANCES

MEMORANDUM

DATE:		September 15, 2008

SUBJECT:	   SEQ CHAPTER \h \r 1 5-Chloro-2-(2,4-dichlorophenoxy)phenol
(Triclosan): Risk Assessment for the Reregistration Eligibility Decision
(RED) Document.  Case No 2340. DP Barcode 343544.    PC Code: 054901.

FROM:	Tim McMahon, Ph.D., Senior Toxicologist

		Najm Shamim, Ph.D., Chemist

                        Srinivas Gowda, Microbiologist/Chemist

		Genevieve Angle, Biologist

		Timothy Leighton, Exposure/Risk Assessor

		Antimicrobials Division (7510C)

 			

              

TO:		Diane Isbell, Team Leader

		Heather Garvie, Chemical Review Manager 

		Regulatory Management Branch II

		Antimicrobials Division (7510C)     

        

Attached is the Risk Assessment for Triclosan for the purpose of issuing
a Reregistration Eligibility (RED) Decision.  The disciplinary science
chapters and other supporting documents for the Triclosan RED are also
included as attachments as follows:  

Toxicology Science Chapter for the Reregistration Eligibility Decision
Document, T. McMahon, August 2008  

Triclosan: Occupational and Residential Exposure Assessment.  From
Timothy Leighton, Environmental Scientist, September, 2008.

Triclosan:  Dietary Exposure Assessments for the Reregistration
Eligibility Decision Memorandum. From Najm Shamim, Ph.D. Chemist,  to
Tim McMahon, Ph.D. Toxicologist April, 2007.

Product Chemistry Chapter for the  Triclosan Reregistration Eligibility
Decision (RED) Document.  From Srinivas Gowda Microbiologist/Chemist, 
to  Mark Hartman, Branch Chief, July 2007.

Revised Environmental Fate Science Chapter for the Triclosan 
Reregistration Eligibility Decision (RED) Document. From Srinivas Gowda,
Microbiologist/ Chemist, September, 2008 

Revised Ecological Hazard and Environmental Risk Assessment Chapter for
the Triclosan  Reregistration Eligibility 

              Decision (RED) Doocument . From Richard C. Petrie,
Agronomist, September, 2008. 

  

TABLE OF CONTENTS  

1.0  EXECUTIVE
SUMMARY-----------------------------------------------------------------
---------------------- 4

2.0 PHYSICAL/CHEMICAL PROPERTIES
--------------------------------------------------------------------17
3.0 HAZARD CHARACTERIZATION
------------------------------------------------------------------------
-   18 

3.1   Hazard Profile
------------------------------------------------------------------------
--------18

3.2  Dose-Response Assessment 
----------------------------------------------------------------20

3.3  Susceptibility
Considerations----------------------------------------------------------
------20

3.4  Endocrine Disruption
------------------------------------------------------------------------
-20

4.0  EXPOSURE ASSESSMENT AND  CHARACTERIZATION
------------------------------------------25

 

5.0  AGGREGATE RISK ASSESSMENT AND RISK CHARACTERIZATION
-----------------------26

        5.1 National Health and Nutrition Surveys (NHANES) for Triclosan
--------------------------------26

5.1.1  NHANES Data and Dose Conversion--------
-------------------------------------------26

5.1.2 Pharmacokinetics of
Triclosan-------------------------------------------------------------28

5.1.3 Uncertainties Associated with the Dose
Conversion------------------------------------28

        5.2 Aggregate
Risks-------------------------------------------------------------------
----------------------------29

	5.2.1 Children (6yrs) to Adult
------------------------------------------------------------------------
------29

	5.2.2 
Infants-----------------------------------------------------------------
----------------------------------32

	5.2.3 Dermal
Irritation--------------------------------------------------------------
-------------------------35

	5.2.4 Dermal
Systemic----------------------------------------------------------------
-----------------------35

	

6.0	Cumulative
Risk--------------------------------------------------------------------
--------------------------37

7.0      OCCUPATIONAL EXPOSURE
------------------------------------------------------------------------
--38

7.1  Occupational Postapplication Exposure
--------------------------------------------------40

7.2   Data Limitations/uncertainties
------------------------------------------------------------40

ENVIRONMENTAL RISK
------------------------------------------------------------------------
------------41

8.1 Ecological
Hazard------------------------------------------------------------------
-----------41

8.2 Environmental fate and
transport------------------------------------------------------------47

8.3 Environmental exposure and
Risk-----------------------------------------------------------48

8.4 Endangered
Species-----------------------------------------------------------------
-----------52

Incident Report Assessment
------------------------------------------------------------------------
------------53

9.1  OPP Incident Data
System------------------------------------------------------------------
-53

9.2   Poison Control
Center------------------------------------------------------------------
------53

9.3  California Data
1982-2003---------------------------------------------------------------
----53

9.4   National Telecommunication Pesticide
Network----------------------------------------54

9.5  Hazardous Substances Data Bank
----------------------------------------------------------54

   
References--------------------------------------------------------------
------------------------------------------55

1.0 Executive Summary

Triclosan (2,4,4’ –trichloro-2’-hydroxydiphenyl ether) is a
chlorinated aromatic compound that has functional groups representative
of both phenols and ethers.  It is used as a synthetic broad-spectrum
antimicrobial agent in the form of a white to off-white powder.  It is
practically insoluble in water but is soluble in most organic solvents. 
 

Only a small portion of the uses of triclosan are regulated by the U.S.
EPA and therefore covered in this document.  

Triclosan is used as a bacteriostat, fungistat, mildewistat, and
deodorizer.  The EPA registered products containing triclosan as the
active ingredient (ai) are formulated as ready-to-use,
pelleted/tableted, emulsifiable concentrate, soluble concentrate, and
impregnated materials. Concentrations of triclosan in these products
range widely from 0.69% to >99%. Use sites for triclosan include
commercial, institutional and industrial premises and equipment,
residential and public access premises, and as a material preservative. 
As a material preservative, triclosan is used in adhesives, fabrics,
vinyl, latex, plastics, polyethylene, polyurethane, synthetic polymers,
styrene, floor wax emulsions, rope, textiles, caulking compounds,
sealants, coatings, polypropylene, rubber, inks, cellulosic materials,
slurries, films and latex paints.  The residential and public access
premises uses include: brooms, mulch, floors, shower curtains, awnings,
tents, mattresses, toothbrushes, toilet bowls, urinals, garbage cans,
refuse container liners, insulation, concrete mixtures, grouts, air
filter materials, upholstery fabrics, and rugs/carpets.  The commercial,
institutional and industrial premises and equipment uses include:
conveyor belts, fire hoses, dye bath vats and ice making equipment.

There are many other uses under the regulation of the US Food and Drug
Adminstration (FDA) (e.g., hand soaps, toothpaste, antiseptics for wound
care, and medical devices) that are not under EPA’s regulatory
jurisdiction, however, these exposures have been considered in the
aggregate risk assessment within the preliminary risk assessment chapter
for triclosan.  

Toxicology  

The toxicology database for triclosan is complete.  Some studies,
although cited with certain deficiencies, were considered adequate for
regulatory purposes, and thus no new toxicology studies are requested
for triclosan.  A complete toxicology profile for triclosan can be found
in the toxicology chapter .

Acute toxicity studies in experimental animals with technical grade
triclosan show that by the oral and dermal routes, triclosan is of low
acute toxicity (Toxicity Category IV;   MRIDs 43206501  and 94044;
44831105).  By the inhalation route of exposure, triclosan was assigned
Toxicity Category II for acute exposures and is thus of higher acute
toxicity by inhalation exposure than by oral or dermal exposures (MRID
42306902 and 43310501).  Triclosan produces moderate irritation to the
eyes (MRID 94045) and skin (MRID 42306903) with a Toxicity Category III
assigned for both for acute exposures.  Triclosan was not a dermal
sensitizer in guinea pigs using the Buehler method (MRID 43206502). 

Liver toxicity was noted after repeated oral dosing of triclosan to
rats, mice, and dogs. In the 90-day rat study, (MRID 43022605, 99.7%
a.i.; MRID 133545, % a.i. not stated), fatty metamorphosis and
cytomegaly, hypertrophic hepatocytes, vacuolization, inflammation, and
pigmentation of Kupffer cells were noted at a dose of 50 mg/kg/day.  In
the 28-day mouse study, liver cell necrosis and an increase in the
liver-body weight ratio were observed at doses of 135 and 158 mg/kg/day
for male and female mice respectively (MRID 44389707).  In a 90-day oral
toxicity study in dogs (MRID 96102), histopathologic examination of
tissues from dogs that were killed or died showed evidence of
hepatotoxicity resulting in obstructive jaundice at a dose of 25
mg/kg/day. 

Dermal irritation is noted after repeated dermal exposure to the
technical grade active ingredient (99% a.i.) in a 90-day dermal toxicity
study in rats (MRID 43328001) and in two 14-day dermal toxicity studies
in rats and mice (MRIDs  44389708 and  44389710). 

Data from the 90-day rat dermal toxicity study (MRID 43328001) showed
irritation at 10 mg/kg/day (500 µg/cm2) and a NOAEL for systemic
effects at 40 mg/kg/day.   

Systemic toxicity was also observed in the mouse study with a NOAEL of
0.6 mg/animal/day. 

Repeated exposure by the inhalation route to the assumed technical grade
of triclosan (MRID 0087996) resulted in inflammation of the respiratory
tract as well as changes in several serum enzymes.  Acute purulent
inflammation with focal ulceration of the mucous membrane in the nasal
cavity and in the trachea were also observed.  A LOAEL of 50 mg/m3 or
3.21 mg/kg/day was observed in male rats and no NOAEL was established in
males. 

Developmental toxicity testing of triclosan in rats and rabbits (MRIDs
43817502/43817503  and MRIDs 43820401/43022607) showed no evidence of
pre- or postnatal developmental toxicity  at any dose level in either
study up to and including 300 mg/kg/day.  Developmental LOAELs were
therefore not identified.  In 2-generation reproductive toxicity testing
of triclosan in rats showed effects in offspring (decreased viability
and weaning index) only at doses producing toxicity in parental animals
(decreased body weights) (MRID 40623701).  

Chronic toxicity testing of triclosan in baboons (MRID 133230) showed
signs of clinical toxicity (vomiting, diarrhea, failure to eat) at a
dose of 100 mg/kg/day with a NOAEL of 30 mg/kg/day.  In rats, chronic
toxicity testing (MRID 42027906;161332) showed decreases in erythrocyte
count, hemoglobin concentration, and hematocrit.  Serum alanine and
aspartate aminotransferase activities were increased in males at 168.0
mg/kg/day, and blood urea nitrogen was increased in females at 217.4
mg/kg/day. Hepatocellular hypertrophy was observed in males at 52.4
mg/kg/day and above.  Chronic toxicity testing of triclosan in hamsters
(MRID 44874001/44751101) showed increased mortality, decreased weight
gain, increased incidence of nephropathy, and histopathologic findings
of the stomach and testes of male hamsters at a dose of 250 mg/kg/day
with a NOAEL of 75 mg/kg/day. 

In carcinogenicity testing of triclosan in hamsters (MRID
44874001/44751101), there was no evidence of a carcinogenic effect.  In
carcinogenicity testing in rats (MRID 42027906; 161332), there was no
evidence of a carcinogenic effect.  In public documents available from
the FDA, administration of triclosan in the diet to mice at doses of 
10, 30, 100, and 200 mg/kg/day resulted in increases in the incidence of
liver tumors at 30 mg/kg/day and above. A systemic NOAEL of 10 mg/kg/day
was established from the data in this study, based on increased
incidence of liver neoplasms in male and female mice at 30 mg/kg/day. 

In several mutagenicity tests including Ames Salmonella assays (MRIDs
43533301 and 44389705), a mammalian cell gene mutation assay at the
thymidine kinase locus (MRID 44389704), a chromosome aberration assay
[Broker, et al. (1988)], an in vivo bone marrow cytogenetic assay (MRID
43740802), and an in vitro DNA synthesis assay [SanSebastian, 1993 ],
triclosan was negative for mutagenicity. However, in an in vitro
cytogenetic assay (MRID 43740801), there was a dose-related increase in
the yield of cells with abnormal chromosome morphology.  In the presence
of S9 activation, nonsignificant but concentration dependent increases
in cells bearing exchange figures were also seen.    

In a metabolism study in hamsters (MRID 45307501/45307502), urine was
the major route of elimination for triclosan radioactivity.  Peak plasma
and blood concentrations of triclosan-derived radioactivity occurred at
one hour post-dose.  Area Under the Curve (AUC) measurements indicated
that saturation may have been achieved at the high dose, as AUC was not
proportional to dose.  The major urinary metabolite detected after oral
administration was the glucuronide conjugate of triclosan.  The major
fecal metabolite was parent triclosan.  The plasma, kidney, and liver
eliminated triclosan equivalent rapidly.  Tissue metabolite analyses
showed that the glucuronide and sulfate conjugates of triclosan were the
major metabolites detected.  In a metabolism study in mice, (MRID
45307503), triclosan was eliminated primarily through the feces, via
biliary excretion.  Bioretention studies indicate that values from Cmax
to 1/8Cmax in the liver were higher than those in plasma following
repeated administration at both dose levels, indicating that the liver
is the target organ.  Primary excreted compounds in the urine following
single oral exposures included the unmetabolized parent compound and two
parent conjugates; fecal excretion was primarily that of the free parent
compound.  

In metabolism studies conducted in rats, dogs, and rabbits (MRID
149464), results  indicated that at least 70% of an oral dose of
triclosan is absorbed from the gastrointestinal tract and that biliary
secretion and subsequent fecal elimination is a major excretory route in
the rat and dog.  Urinary excretion appeared to be a major route of
elimination in the rabbit.  Tissue accumulation was minimal and
primarily associated with highly perfused tissues and organs with
excretory function.  Metabolite data in rats revealed glucuronide
conjugates and unchanged parent compound as biliary metabolites.  

Biochemical and cell proliferation studies submitted for triclosan
(MRIDs 44389702,  44389703, 44389706, 44389701) suggest that triclosan
acts as a peroxisome proliferator and that the hepatotoxic effect is
followed by cell regeneration. For chemicals producing increased cell
turnover through cytolethality, a threshold can be inferred below which
these effects would not occur. 

ά) as the mode of action for triclosan-induced hepatocarcinogenesis in
mice. The data did not support either mutagenesis or cytotoxicity
followed by regenerative proliferation as alternative modes of action. 
While the proposed mode of action for liver tumors in mice is
theoretically plausible in humans, hepatocarcinogenesis by this mode of
action is quantitatively implausible and unlikely to take place in
humans based on quantitative species differences in PPARά activation
and toxicokinetics.  The quantification of risk is not required.  

Dose-Response Assessment	

On March 10, 1998, the Health Effects Division’s Hazard Identification
Assessment Review Committee   reviewed the available toxicology data for
triclosan and selected endpoints for use as appropriate in
occupational/residential exposure risk assessments.  The potential for
increased susceptibility of infants and children from exposure to
triclosan was also evaluated.  On October 31, 2006, the
Antimicrobial’s Division Toxicity Endpoint Committee met to provide
additional endpoints for incidental oral and dermal exposures. 

For acute and chronic dietary exposure risk assessments,  a NOAEL value
of  30 mg/kg/day was selected, based on clinical signs of toxicity
(vomiting, diarrhea, failure to eat) at a dose of 100 mg/kg/day in a
chronic toxicity study in baboons (MRID 133230.      For dietary risk
assessments, an uncertainty factor of 100 is assigned (10x inter-species
extrapolation, 10x intra-species variation).  The hazard-based FQPA
safety factor is not applied in this case as there are no existing food
use tolerances for triclosan. The resulting acute and chronic Reference
Dose value is 0.30 mg/kg/day. 

For short-term and intermediate-term incidental oral risk assessments
(1-30 days and 30 days - 6 months), a NOAEL value of 30 mg/kg/day was
selected, based on clinical signs of toxicity (vomiting, diarrhea,
failure to eat) at a dose of 100 mg/kg/day in a chronic toxicity study
in baboons (MRID 133230). An uncertainty factor of 100 was assigned to
this endpoint (10x inter-species extrapolation, 10x intra-species
variation).   

For short-term dermal risk assessment (1-30 days), a NOAEL of 0.6
mg/animal (converted to concentration of 100 µg/cm2 by using the
surface area of the applied gauze (2 x 3 cm or 6 cm2)) was selected from
a 14-day dermal toxicity study in the mouse (MRID 44389708), based on
treatment-related dermal irritation at the treatment site and on
increased liver weights at 1.5 mg/animal.  It is to be noted that the
short-term dermal endpoint was derived from a study using the technical
grade (99%) test material. Residential uses of triclosan involve
exposure to diluted formulations (e.g., 0.5% ai for carpet shampoo
further diluted by water).  Therefore, the short-term dermal irritation
observed for the 99% ai formulation is not applicable for the dermal
risk assessment in this case.

For intermediate-term and long-term dermal risk assessments, the
endpoint was selected from a 90-day dermal toxicity study in rats with a
NOAEL value of 40 mg/kg/day, based on increased occult blood in the
urine observed at 80 mg/kg/day..   

For inhalation risk assessments, a LOAEL of 50 mg/m3 (3.21 mg/kg/day)

was selected from a 21-day inhalation toxicity study (MRID 0087996),
based on increased total leukocyte count and increased serum alkaline
phosphatase in male rats at  3.21 mg/kg/day.  While this study contained
deficiencies that resulted in it not meeting the guideline requirement
for a repeat dose inhalation toxicity study, the endpoint was chosen
from this study as it was the only data available. 

Susceptibility Considerations

There are no food use tolerances for triclosan but in light of
residential exposures to triclosan, including exposures of infants and
children, the data on developmental, reproductive, and neurotoxic
effects of triclosan were examined for any suscepitiblity issues. The
data provided no indication of developmental or reproductive effects in
offspring of rats or rabbits to in utero and post-natal exposure to
triclosan.  Three prenatal developmental toxicity studies in rats 
rabbits, and mice, showed no evidence of developmental toxicity in the
absence of maternal toxicity.  In the two-generation reproduction study
in rats, effects in the offspring were observed only at or above
treatment levels which resulted in evidence of parental toxicity. The
available data on triclosan for evaluation of neurotoxicity, including
the 14-day neurotoxicity study in rats, developmental and reproductive
toxicity studies in rats and rabbits, and subchronic and chronic data in
rats and mice showed no evidence of a neurotoxic effect of triclosan in
any of these studies.  

Dietary Exposure and Risk

Dietary exposure and risk were assessed for the indirect food uses of
triclosan involving pulp and paper use, ice-making equipment, adhesives,
cutting boards, conveyor belts, and counter top use.  As there were no
residue chemistry data submitted for triclosan,  methods developed by
the Food and Drug Administration were used to estimate migration of
residues.  A detailed explanation is found within the dietary risk
assessment chapter for triclosan. 

For the various indirect food uses of triclosan in this risk assessment,
none of the individual scenarios presented with risks of concern for
either adults or children.  

 

Drinking Water Exposure and Risk

The environmental fate assessment chapter for triclosan (DP barcode
335393) notes that triclosan was detected in both raw and finished
drinking water in Southern California at levels of 56 and 49 ng/L,
respectively (Loraine and Pettigrove, 2006). Using the assumption of 2L
consumption per day for adults, intake of triclosan is estimated at 98
ng/person/day or 1.4 ng/kg/day for a 70 kg adult.  Comparing this intake
value to the Reference dose for triclosan selected (0.3 mg/kg/day or
300,000 ng/kg/day), the intake of triclosan in drinking water using the
measured value from Loraine and Pettigrove does not present a risk of
concern.  However, additional monitoring data would be useful in
deriving a more accurate estimate that is not based on measurement at
one location only.  

 

Residential Handler Exposure and Risk

                                                                        
  

Residential handler dermal exposure scenarios are best represented by
the short-term duration (i.e. painting is intermittent in nature).  The
short-term dermal duration toxicological endpoint is based on dermal
irritation observed during the dosing of mice with a 99% ai product. 
The in-can paint preservation (1 % ai) is not considered to be as
irritating as the more concentrated test substance.  The short-term
dermal exposures are believed to exhibit minimal skin irritation.  This
is supported by the lack of incident data and a bounding estimate of
film thickness on the skin compared to the dermal irritation endpoint.  

For the residential handler inhalation assessment, the inhalation risks
were calculated by comparing the daily inhalation dose to the short-term
inhalation endpoint.  The inhalation MOE of 4000 is above the target MOE
of 1000 for the paint brush scenario. However, for the airless sprayer
scenario the inhalation MOE of 180 is below the target MOE, and
therefore, is of concern.  Mitigation options include reducing the
application rate in paint or removing the use.  

Residential Post-application Exposure and Risk

The residential post-application assessment is protective of long-term
exposure.  The results of the NHANES aggregate risks using the most
conservative methodology option assessed for those 6+ years old indicate
mean MOEs ranging from 4,700 to 19,000. At the 99th percentile the MOEs
range from 260 to 1,700.  These MOEs are above the target MOE of 100. 
The NHANES aggregate risks include exposure to both EPA- and
FDA-regulated uses.

	For infants 6 to 12 months old, the mean NHANES 6-11 year old MOEs
combined with bounding estimates for infant-specific activities for
nursing, object-to-mouth, and hand-to-mouth exposures indicate an
aggregate MOE of 390.  At the 99th percentile NHANES distribution
combined with the infant-specific activities indicate a MOE of 290. 
Clearly, including exposures to the FDA-regulated soaps and toothpaste
for 6-11 year olds is a conservative assessment of exposure from these
products to 6 to 12 month olds.  Future refinements to the infant
aggregate should focus on this portion of the total exposure.

	Based on the low vapor pressure of triclosan and the lack of aerosol
generation over time by the application methods (excluding bystanders in
the vicinity of airless spraying of paint which triggers risks of
concern), inhalation exposure is expected to be minimal.  This
expectation is confirmed by the MOEs estimated to be in the millions for
breathing triclosan-treated dust.

The dermal irritation potential of diluted uses of triclosan impregnated
into textiles/fabrics and plastics are also expected to be minimal. 
This expectation is supported by the low incidents of irritation as well
as the screening-level assessment provided herein.   The dermal systemic
effects were also investigated for children and adults contacting
treated articles.  The systemic dermal MOE using conservative
assumptions is at or above the target MOE for dermal effects.  

Aggregate Exposure and Risk

EPA has performed an assessment of the aggregate exposure to triclosan. 
Aggregate exposure is the total exposure to a single chemical (or its
residues) that may occur from dietary (i.e., food and drinking water),
residential, and other non-occupational sources including triclosan FDA
uses such as hand soaps and toothpaste, and from all known or plausible
exposure routes (oral, dermal, and inhalation).  An aggregate risk
assessment was conducted using the single selected toxicological
endpoint for acute dietary, short-term (1-30 days), intermediate-term
(1-6 months), and chronic (several months to lifetime) exposure
durations. Inhalation aggregate risks are minimal based on the low vapor
pressure of triclosan and uses such as tooth paste, hand soap,
impregnated textiles, etc that do not involve inhalation as the primary
route of exposure.  Further discussion of inhalation exposure can be
found in  the Occupational and Residential Exposure Assessment chapter
for triclosan.

In performing aggregate exposure and risk assessments, the Office of
Pesticide Programs has published guidance outlining the necessary steps
to perform such assessments (General Principles for Performing Aggregate
Exposure and Risk Assessments, November 28, 2001; available at
http://www.epa.gov/pesticides/trac/science/aggregate.pdf).  Steps for
deciding whether to perform aggregate exposure and risk assessments are
listed, which include: identification of toxicological endpoints for
each exposure route and duration; identification of potential exposures
for each pathway (food, water, and/or residential);  reconciliation of
durations and pathways of exposure with durations and pathways of health
effects; determination of which possible residential exposure scenarios
are likely to occur together within a given time frame; determination of
magnitude and duration of exposure for all exposure combinations;
determination of the appropriate technique (deterministic or
probabilistic) for exposure assessment; and determination of the
appropriate risk metric to estimate aggregate risk

	In the case of triclosan, population-based biological monitoring data
are available to assess the co-occurrence of uses to develop an
aggregate exposure assessment.  The population-based biological
monitoring data are believed to be a more accurate predictor of
aggregate exposure because not only are the data triclosan specific,
they are also based on actual consumer use of the various triclosan
products as they co-occur in practice.  Although the aggregate
exposure/risk assessment using the NHANES data provides an encompassing
review of all triclosan-treated products, it does not include exposures
to children under the age of 6 years old.  Children under the age of 6
years exhibit unique activities that do not occur at older ages. 
Therefore, a separate estimate for children under 6 years old has been
included.  

The results of the aggregate risk assessment at both the mean and 99th
percentile, respectively showed that the combined EPA and FDA uses do
not trigger risks of concern.  The MOEs at the mean dose range from
4,700 to 19,000.  The MOEs at the 99th percentile of the dose range from
260 to 1,700.  In fact, applying the lowest (most conservative) percent
urinary excretion from the results of the pharmacokinetic data (i.e., 24
percent) to the most conservative dose conversion method (i.e.,
Geigy’s 95th percentile of daily urine volumes), the MOE is 120.  In
conclusion, even with the reliance of conservative assumptions in
estimating risks to account for the considerable uncertainties in
converting spot urine concentration to dose, the NHANES data as analyzed
for triclosan sufficiently characterizes the aggregate risks as meeting
the definition of not resulting in unreasonable adverse effects.

Occupational Exposure

Occupational Handler Risk Summary

 The short-term dermal irritation exposures and risks were not estimated
for occupational handler exposures.  Instead, dermal irritation
exposures and risks will be mitigated using default personal protective
equipment requirements based on the toxicity of the end-use products. 
For occupational uses it is OPP practice to mitigate dermal irritation
by requiring the user to wear PPE (e.g., chemical resistant gloves and
clothing). Mitigating with PPE is only a viable option for
pesticide-labeled products (i.e., a label is needed to inform workers to
wear PPE).  Therefore, EPA can direct workers using pesticide-labeled
products (concentrated form) at the manufacturing setting to wear PPE to
mitigate dermal irritation.  Conversely, for in-can material
preservatives there is no pesticide label that goes with the preserved
product to inform the workers/painters that PPE is needed (i.e., there
is no pesticide label on a can of paint).  Thus PPE is not a viable
option to mitigate exposure to products preserved by triclosan such as
the in-can paint use.

For the intermediate-term dermal risks, the MOE were above the target
MOE of 100, and therefore, not of concern except for commercial painters
and material preservative use for paper which will require a closed
delivery system.  The intermediate-term MOEs for using a paint
brush/roller and an airless sprayer are 31 and 1, respectively. Because
triclosan is used as a material preservative in the paint, the use of
chemical resistant gloves on the label is impractical. 

	For the occupational handler inhalation exposure and risk assessment,
the MOEs were below the target MOE of 1000 for all scenarios except for
the brush application for paints.  The inhalation MOE for commercial use
of an airless sprayer for paints is 54, for liquid pour and liquid pump
during paint manufacturing 330 and 290, respectively.  For the pulp and
paper use a closed delivery system will be required.

Occupational Post Application/Bystander Risk Summary

	Based on the low vapor pressure of triclosan and the lack of aerosol
generation over time by the application methods, inhalation
post-application exposures are expected to be minimal.

Environmental Fate Assessment

 Triclosan is hydrolytically stable under abiotic and buffered
conditions over the pH 4-9 range based on data from a preliminary test
at 50°C.  Photolytically, triclosan degrades rapidly under continuous
irradiation from artificial light at 25°C in a pH 7 aqueous solution,
with a calculated aqueous photolytic half-life of 41 minutes.  One major
transformation product was identified, DCP (2,4-dichlorophenol), which
was present at a maximum of 93.8-96.6% of the applied dose at 240
minutes post-treatment.  Triclosan degrades rapidly in aerobic soils
maintained in darkness at 20 ( 2°C, with calculated half-lives of
2.9-3.8 days.  One major transformation product was identified, methyl
triclosan, at maximum averages of 13.5-24.0% of the applied dose at
14-28 days post-treatment.  In aerobic water-sediment systems maintained
in darkness at 20 ( 2°C, triclosan degraded with calculated nonlinear
half-lives of 1.3-1.4 days in the water, 53.7-60.3 days in the sediment,
and 39.8-55.9 days in the total system.  The major transformation
product, identified as methyl triclosan, was a maximum average of 4.8%
of the applied dose at 104 days post-treatment (sediment; sandy loam
system).  

The Agency has used its databases (EPI Suite) and open literature
(TOXNET) to conduct the environmental fate risk assessment.

In soil, triclosan is expected to be immobile based on an estimated Koc
of 9,200.  Triclosan is not expected to volatilize from soil (moist or
dry) or water surfaces based on an estimated Henry’s Law constant of
1.5 x 10-7 atm-m3/mole.  Triclosan partially exists in the dissociated
form in the environment based on a pKa of 7.9, and anions do not
generally adsorb more strongly to organic carbon and clay than their
neutral counterparts.  In aquatic environments, triclosan is expected to
adsorb to suspended solids and sediments and may bioaccumulate (Kow
4.76), posing a concern for aquatic organisms.  

There is also a low to moderate potential for bioconcentration in
aquatic organisms based on a BCF range of 2.7 to 90.

Hydrolysis is not expected to be an important environmental fate process
due to the stability of triclosan in the presence of strong acids and
bases.  However, triclosan is susceptible to degradation via aqueous
photolysis, with a half-life of <1 hour under abiotic conditions, and up
to 10 days in lake water.  An atmospheric half-life of 8 hours has also
been estimated based on the reaction of triclosan with photochemically
produced hydroxyl radicals.  Additionally, triclosan may be susceptible
to biodegradation based on the presence of methyl-triclosan following
wastewater treatment.  Although these data are limited, they indicate
triclosan is not likely to contaminate surface or ground waters due to
its immobility in soils, and susceptibility to photodegradation, and
potentially biodegradation, in soil and water.

  SEQ CHAPTER \h \r 1 From published literature studies on the
occurrence of triclosan in waste water treatment plants, treatment plant
efficiency, and open water measurements of triclosan, the majority
suggest that aerobic biodegradation is one of the major and most
efficient biodegradation pathways (70-80%) through which triclosan and
its by-products are removed from the aquatic environment with actual
efficiencies ranging from 53-99% (Kanda et al., 2003) in activated
sludge plants and trickle down filtration, ranging from 58-86% (McAvoy
et al., 2002).  Another pathway of removing triclosan from water in
wastewater treatment plants is through the sorption of triclosan and
associated by-products to particles and sludge (10-15%) because of the
chemical’s medium to high hydrophobicity (Agüera et al., 2003; Gomez
et al., 2007; Kanda et al., 2003; Lee and Peart, 2002; Bester, 2003 and
2005; Xia et al., 2005).  Benchtop fate testing of triclosan found that
1.5-4.5% was sorbed to activated sludge and 81-92% was biodegraded
(Federle et al., 2002). 

Activated sludge and/or sludge samples examined for triclosan residue in
Ohio showed a range of 0.5 to 15.6 μg/g (dry weight) with higher
concentrations of triclosan observed in anaerobic sludge as compared to
aerobic sludge (McAvoy et al., 2002). Other countries where sludge
samples were analyzed for triclosan are as follows: Canada found 370
ng/g (Lee and Peart, 2002); Germany found 1000-8000 ng/g (Bester, 2003
and 2005); Greece found 1,840 ng/g (Gatidou et al. 2007); Spain found
420-5400 ng/g (Morales et al., 2005); and 19 WWTP were analyzed in
Australia, which had a range of 90-16,790 ng/g dry weight and a median
of 2,320 mg/g (Ying and Kookana, 2007). 

Effluent concentrations from wastewater treatment plants in the US were
10-21 ng/L in Louisiana (Boyd et al., 2003); 63 ng/L in the upper
Detroit river (Hua et al., 2005); 72 ng/L in Arlington, Virginia (Thomas
and Foster, 2004); 110 ng/L in North Texas (Waltman et al., 2006); and
the highest was 200-2700 ng/L in Ohio (McAvoy et al., 2002). Effluent
concentrations from wastewater treatment plants in other countries were
measured to be 160 ng/L (Lee et al., 2003) or 50-360 ng/L in Canada (Lee
et al., 2005); 50 ng/L (Bester, 2003), 10-600 ng/L (Bester, 2005), or
180 ng/L (Wind et al., 2004) in Germany; 160 ng/L in Sweden (Bendz et
al., 2005); 430 ng/L (31.2 μg/g particulate matter), 1120 ng/L (16.1
μg/g particulate matter), or 230 ng/L (22.4 μg/g particulate matter)
in three different WWTP in Greece (Gatidou et al. 2007); 80-400 ng/L in
Spain (Gomez et al., 2007); 100-269,000 ng/L in Spain (Mezcua et al.,
2004); 0.15±0.08 mg/person in 5 European countries (Paxeus, 2004); 340
or 1100 ng/L, for trickle filtration and activated sludge treatment
plant in England (Sabaliunas et al., 2003); 42-213 ng/L in Switzerland
(Singer et al., 2002); and from 19 WWTP in Australia the range was
23-434 ng/L with a median concentration of 108 ng/L (Ying and Kookana,
2007). 

Triclosan was found in approximately 36 US streams (Klopin et al., 2002)
where effluent from activated sludge waste water treatment plants,
trickle down filtration, and sewage overflow are thought to contribute
to the occurrence of triclosan in open water. For this study, the U.S.
Geological Survey surveyed a network of 139 streams across 30 states
during 1999 and 2000.  The selection of sampling sites was biased toward
streams susceptible to contamination (i.e. downstream of intense
urbanization and livestock production). The median concentration was 140
ng/L and the maximum concentration detected was 2300 ng/L (Klopin et
al., 2002). In another study, storm water canal measurements over a 6
month period in Bayou St. John in Louisiana indicated that triclosan
ranged from below the detection level to 29 ng/L (Boyd et al., 2004).
Raw drinking water in Southern California was found to have 560 ng/L
triclosan and 490 ng/L triclosan in finished water (Loraine and
Pettigrove, 2006).  Other published data on surface water concentrations
of triclosan in the US indicated concentrations of 4 and 8 ng/L in the
upper Detroit river (Hua et al., 2005) and 56 ng/L in Arlington,
Virginia (Thomas and Foster, 2004). Published data on surface water
concentrations of triclosan in other countries indicated concentrations
of <3-10 ng/L in Germany (0.3-10 ng/L methyl-triclosan) (Bester, 2005);
19±1.4 ng/L in England (Sabaliunas et al., 2003); 11-98 ng/L in
Switzerland (Singer et al., 2002); 30 ng/L in Germany (Wind et al.,
2004); and in Australia 75 ng/L (Ying and Kookana, 2007).

From published literature on the aquatic toxicity of triclosan in
zebrafish, average bioconcentration factors (BCF) for triclosan
following a 5-week accumulation period were 4157 at 3 (g/L and 2532 at
30 (g/L (Orvos et al., 2002).  Following 2 weeks of depuration, average
BCF values decreased to 41 at 3 (g/L and 32 at 30 (g/L.  Depuration rate
constants were 0.142 and 0.141 per day at 3 (g/L and 30 (g/L,
respectively.  The predicted bioconcentration factor for triclosan was
calculated to be ca. 2500.  The lethal body burden was determined to
range from 0.7-3.4 mM/kg, indicating a narcosis mode of action.  These
data indicate that triclosan bioconcentrates in zebra fish, but
depuration occurs rapidly once triclosan exposure is removed. Relative
to bioaccumulation, there are no data presently available to determine
if this occurs.  However, some authors (Balmer, M.E. et. al., 2004;
DeLorenzo et al., 2008; Heidler, J. and Halden, R. U., 2007;
Samsoe-Petersen L. et. al., 2003) suggest that triclosan and methyl
triclosan may bioaccumulate in the environment.

Ecological/Environmental Risk Assessment

An ecological risk assessment is not typically conducted for the types
of uses registered for triclosan.  However, since triclosan has been
detected in natural waters, EPA has performed a qualitative
environmental risk assessment using monitoring levels of triclosan found
in waterways and toxicity values from published literature including
USGS montoring  data to develop risk quotients (RQs) and compare them to
levels of concern (LOCs) for triclosan.  LOCs were not exceeded for fish
but were exceeded for aquatic plants.  There were no acceptable acute
toxicity studies for freshwater invertebrates or estuarine and marine
organisms nor were there any acceptable chronic toxicity studies
available for aquatic organisms.  Therefore, risk to these species could
not be assessed and data gaps were identified. These data gaps are
listed specifically within the Ecological and Environmental Risk
Assessment Science Chapter (D343548, from Richard C. Petrie).  

Additionally, EPA performed consumer environmental modeling for
triclosan as discussed within the Appendix to the Revised Ecological
Hazard and Environmental Risk Assessment Chapter of the RED.  For this
screening level analysis the Down-the Drain (DTD) module of EFAST-2
(Exposure and Fate Assessment Screening Tool, Version 2.0) was used. 
The DTD module of E-FAST 2 is used to estimate exposure to aquatic
organisms from releases of a chemical to surface water from consumer
use.

A simplifying assumption used  is that all of the triclosan under
EPA’s jurisdiction is released to surface water as a result of
consumer uses. Results of the assessment of exposure and risk to aquatic
organisms from uses of triclosan under EPA’s jurisdiction  for acute
risk presumptions for aquatic animals, endangered species risk
presumptions for aquatic animals, and acute and endangered species risk
presumptions for aquatic plants showed that estimated concentrations of
triclosan in surface water did not exceed concentrations of concern for
acute risk presumptions for aquatic animals or endangered species risk
presumptions for aquatic animals. No exceedances were predicted for  the
concentration of concern for triclosan for endangered species risk
presumptions for aquatic vascular plants, but concentrations of
triclosan in surface water were predicted to exceed concentrations of
concern for acute risk presumptions for species that represent
non-vascular freshwater plants (i.e., algae).  Although this evaluation
is considered supplemental data, it indicates the need for additional
investigation of shifts in algal communities, reductions in biomass, and
effects on higher trophic levels (Wilson et al., 2003).

 

For industrial use scenarios, s discussed within the revised
environmental fate chapter, little is known about how much, if any,
triclosan is released from industrial sites (where triclosan is
incorporated into plastic and textile items) into effluents and the
environment (e.g., surface waters).  Considering this, the Agency is
requiring that the registrants perform environmental modeling and
monitoring to address this issue.  Until EPA receives these data we are
unable to calculate risk quotients specific to these industrial
scenarios.

Endangered Species

 To facilitate compliance with the requirements of the Endangered
Species Act subsection

(a)(2) the Environmental Protection Agency, Office of Pesticide Programs
has

established procedures to evaluate whether a proposed registration
action may directly or

indirectly reduce appreciably the likelihood of both the survival and
recovery of a listed

species in the wild by reducing the reproduction, numbers, or
distribution of any listed

species (U.S. EPA 2004).  After the Agency’s screening-level risk
assessment is

performed, if any of the Agency’s Listed Species LOC Criteria are
exceeded for either

direct or indirect effects, a determination is made to identify if any
listed or candidate

species may co-occur in the area of the proposed pesticide use.  If
determined that listed

or candidate species may be present in the proposed use areas, further
biological

assessment is undertaken.  The extent to which listed species may be at
risk then

determines the need for the development of a more comprehensive
consultation package

as required by the Endangered Species Act.

For certain use categories, the Agency assumes there will be minimal
environmental

exposure, and only a minimal toxicity data set is required (Overview of
the Ecological

Risk Assessment Process in the Office of Pesticide Programs U.S.
Environmental

Protection Agency - Endangered and Threatened Species Effects
Determinations,

1/23/04, Appendix A, Section IIB, pg.81).  Chemicals in these categories
therefore do not

undergo a full screening-level risk assessment.

Preliminary analysis indicates that there is a potential for triclosan
use to overlap with listed species and that a more refined assessment is
warranted, to include direct, indirect and habitat effects [the Agency
is making this statement because triclosan and triclosan transformation
products are being detected in various environmental components (see
triclosan environmental fate chapter)].

  

The more refined assessment should involve clear delineation of the
action area associated with proposed use of triclosan and best available
information on the temporal and spatial co-location of listed species
with respect to the action area.  This analysis has not been conducted
for this assessment.  An endangered species effect determination will
not be made at this time.  

Incident Reports

There are no reported incidents for triclosan from a search of the
available databases. 

 

2.0	PHYSICAL/CHEMICAL PROPERTIES AND CHARACTERIZATION

	Chemical Identity:

	Chemical Name:		triclosan

	Chemical Family:		diphenoxyether

	Common/Trade Name:	2,4,4’-Trichloro-2’-hydroxydiphenyl ether

					Phenol, 5-chloro-2-(2,4-dichlorophenoxy)-

					5-Chloro-2-(2,4-dichlorophenoxy)phenol

					Irgasan DP-300R

					Irgaguard B1000

					VIV-20

 	

	CAS Number:			3380-34-5

	Molecular Formula:		C12H7Cl302

	Chemical Structure:		

			

	

Table 2-1 Chemical Characteristics for Technical Grade Active Triclosan

Molecular Weight	289.541

Color	White crystals

Physical State	White crystalline powder

Specific Gravity	1.55 x 103 kg/m3 at 22˚C

Dissociation Constant	 pKa=8.14 at 20°C

pH	N/A

Stability	Stable at normal conditions

Melting Point	56.5  o  C

Boiling Point	N/A 

Water Solubility	0.012 g/l at 20˚C

Octanol-Water Partition constant ( LogKOW)	4.8 at 25˚C

Vapor Pressure	5.2E-6 mm Hg at 25˚C

2.2E-6 mm Hg at 20˚C

3.0	HAZARD CHARACTERIZATION

3.1	Hazard Profile

Acute Toxicity

Acute toxicity studies in experimental animals with technical grade
triclosan show that by the oral and dermal routes, triclosan is of low
acute toxicity (Toxicity Category IV;   MRID 43206501 and 94044 .  By
the inhalation route of exposure, triclosan was assigned Toxicity
Category II for acute exposures and is thus of higher acute toxicity by
inhalation exposure than by oral or dermal exposures (MRID 42306902 and
43310501).  Triclosan produces moderate irritation to the eyes (MRID
94045) and skin (MRID 42306903) with a Toxicity Category III assigned
for both for acute exposures.  Triclosan was not a dermal sensitizer in
guinea pigs using the Buehler method (MRID 43206502). 

Table 3-1.  Acute Toxicity Profile for Triclosan

Guideline Number	Study Type/

Test substance (% a.i.)	MRID Number/

Citation	Results	Toxicity Category

870.1100

(§81-1)	Acute Oral- Rat Triclosan (99.7% a.i.)	43206901	LD50: >5000
mg/kg	IV

870.1200

(§81-2)	Acute Dermal- Rabbit

Triclosan (97% a.i.)	94044 	LD50: >9300 mg/kg	IV

870.1300

(§81-3)	Acute Inhalation- Rat

Triclosan (100.5% a.i.)	42306902, 43310501	LC50: >0.15 mg/L	II

870.2400

(§81-4)	Primary Eye Irritation- Rabbit

Triclosan (97% a.i.)	 94045	moderately irritating	II

870.2500

(§81-5)	Primary Dermal Irritation- Rabbit

Triclosan (% a.i.not provided)	42306903	PII: 3.5 at 72 hours 	III

870.2600

(§81-6)	Dermal Sensitization- Guinea Pig          Triclosan (99.7%
a.i.)	43206502	Not a Sensitizer	NA

 

 

Dose-Response Assessment

On March 10, 1998 the Health Effects Division’s Hazard Identification
Assessment Review Committee   reviewed the available toxicology data for
triclosan and selected endpoints for use as appropriate in
occupational/residential exposure risk assessments.  The potential for
increased susceptibility of infants and children from exposure to
triclosan was also evaluated.  On October 31, 2006, the
Antimicrobial’s Division Toxicity Endpoint Committee met to provide
additional endpoints for incidental oral and dermal exposures.  A
summary of the selected endpoints is shown in the table below. 

 

Table 3-2.  Summary of Toxicity Endpoints Selected for Triclosan

Exposure

Scenario	Dose Used in Risk Assessment 	Uncertainty factors for Risk
Assessment	Study and Toxicological Effects

Acute Dietary

(gen. pop.)	NOAEL = 30 mg/kg

 

aRfD = 0.03 mg/kg/day	 Interspecies = 10x

Intraspecies = 10x

DBSS* = 1x

 

UF = 100	Chronic Toxicity study in Baboons

MRID 133230

Acute Dietary

(females 13+)	No appropriate endpoint identified in the database

Chronic Dietary

(all populations)	NOAEL = 30 mg/kg

 

cRfD = 0.03 mg/kg/day	 Interspecies = 10x

Intraspecies = 10x

DBSS* = 1x

 

UF = 100	Chronic Toxicity study in Baboons

MRID 133230

LOAEL = 100 mg/kg/day, based on clinical signs of toxicity

Short-Term/ Intermediate-Term Incidental Oral (1-30 days; 30 days- 6
months)	NOAEL = 30 mg/kg

	  Interspecies = 10x

Intraspecies = 10x

DBSS* = 1x

 

UF = 100	Chronic Toxicity study in Baboons

MRID 133230

LOAEL = 100 mg/kg/day, based on clinical signs of toxicity

Dermal (short-term)	NOAEL = 0.6 mg/animal (100 µg/cm2)

  	

 Interspecies = 3x

Intraspecies = 3x

DBSS* =1x

MOE  = 10	14-day dermal toxicity study in the mouse 

MRID 44389708

LOAEL = 1.5 mg/kg/day, based on treatment-related dermal irritation at
the treatment site and on increased liver weights

Dermal (intermediate term)	NOAEL = 40 mg/kg

 

	 Interspecies = 10x

Intraspecies = 10x

DBSS* =1x

MOE  = 100

 	90-day Dermal Toxicity in Rats

MRID 43328001

LOAEL = 80 mg/kg/day, based on increased incidence occult blood in the
urine.

Dermal (long-term)	NOAEL = 40 mg/kg

 

	 Interspecies = 10x

Intraspecies = 10x

DBSS* =3x (lack of chronic dermal study)

MOE  = 300

 	90-day Dermal Toxicity in Rats

MRID 43328001

LOAEL = 80 mg/kg/day, based on increased incidence occult blood in the
urine.

Inhalation (all durations)	NOAEL =  50 mg/m3 or 3.21 mg/kg/day

Where mg/kg/day = ((0.0087 m3/hr * mg/m3 * 2 hr/day) /0.271 b.w.  

 	

MOE = 1000	21-Day Inhalation Toxicity study in the rat

MRID 0087996

LOAEL = 0.115 mg/L, based on increased total leukocyte count and
increased serum alkaline phosphatase

Cancer (oral)	 In accordance with the EPA Final Guidelines for
Carcinogen Risk Assessment (March 29, 2005), the HED CARC classified
triclosan as “Not Likely to be Carcinogenic to Humans”.   

UF = uncertainty factor,   DBSS = database uncertainty [special
sensitivity] factor, NOAEL = no observed adverse effect level, LOAEL =
lowest observed adverse effect level, PAD = population adjusted dose (a
= acute, c = chronic), RfD = reference dose, MOE = margin of exposure 

 

Susceptibility Considerations

 There are no existing tolerances or tolerance exemptions for Triclosan
under 40 CFR 180, and there are no food additive clearances from the
Food and Drug Administration.  However, as there are expected exposures
of infants and children to this chemical as well as potential exposures
from indirect food uses, the data on developmental, reproductive, and
neurotoxic effects of triclosan were examined for any suscepitiblity
issues. The data provided no indication of developmental or reproductive
effects in offspring of rats or rabbits to in utero and post-natal
exposure to triclosan.  Three prenatal developmental toxicity studies in
rats  rabbits, and mice, showed no evidence of developmental toxicity in
the absence of maternal toxicity.  In the two-generation reproduction
study in rats, effects in the offspring were observed only at or above
treatment levels which resulted in evidence of parental toxicity. The
available data on triclosan for evaluation of neurotoxicity, including
the 14-day neurotoxicity study in rats, developmental and reproductive
toxicity studies in rats and rabbits, and subchronic and chronic data in
rats and mice showed no evidence of a neurotoxic effect of triclosan in
any of these studies.  Residual uncertainties regarding exposure to
infants and children have not been underestimated but instead
conservative assumptions have been used. 

 Endocrine Disruption

EPA is required under the Federal Food Drug and Cosmetic Act (FFDCA), as
amended by FQPA, to develop a screening program to determine whether
certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect
produced by a naturally occurring estrogen, or other such endocrine
effects as the Administrator may designate."  Following the
recommendations of its Endocrine Disruptor Screening and Testing
Advisory Committee (EDSTAC), EPA determined that there was scientific
basis for including, as part of the program, the androgen and thyroid
hormone systems, in addition to the estrogen hormone system.  EPA also
adopted EDSTAC’s recommendation that the Program include evaluations
of potential effects in wildlife.  For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effect in humans, FFDCA has authority to
require the wildlife evaluations.  As the science develops and resources
allow, screening of additional hormone systems may be added to the
Endocrine Disruptor Screening Program (EDSP).

 There is some evidence that triclosan disrupts thyroid hormone
homeostasis and interacts with the androgen and estrogen receptors. The
available evidence is summarized below. 

Anti-estrogenic/Androgenic Effects

The first studies reported were in medaka fry (Oryzias latipes) where
changes in fin length and trends in the sex ratio suggested that
triclosan could be weakly anti-estrogenic/ androgenic (Foran et al.,
2000). Flaherty and Dodson (2005) studied the aquatic toxicity of
several environmentally-detected pharmaceuticals by performing single
species laboratory toxicity tests with Daphnia magna, a freshwater
zooplankton. Acute exposure to triclosan (1,10, 100 µg/L) yielded no
significant effects on survivorship, morphology, ephippium production,
fecundity or sex ratio.  However, chronic exposure to 10 ug/L triclosan
significantly increased the sex ratio of the first brood only.  Daphnia
exposed to triclosan produced on average about 72% males, over double
that of the control counterparts who produced about 31% males in the
first brood.  

Gee et al. (2007) reported displacement of  3H-estradiol from the
estrogen receptor of human MCF7 breast cancer cells by triclosan  and
inhibition of the estrogen-responsive ERE-CAT reporter gene by triclosan
at 10-5 M in the presence of 10-10 M estradiol.  Triclosan was also
shown to have anti-androgenic activity in this study as shown by
displacement of 3H-testosterone from the rat androgen receptor, although
a 1000-fold molar excess of triclosan was needed to produce a 49%
displacement of testosterone. Using a mouse mammary tumor cell line with
a stably-transfected androgen reporter gene (LTR-CAT), induction of CAT
activity by testosterone was inhibited in the presence of triclosan at
10-5 M and above. The proliferative response of these mouse mammary
tumor cells to testosterone was also inhibited by triclosan. 

Ahn et al. (2008) examined the biological activity of triclosan in in
vitro, cell-based, and nuclear receptor-responsive bioassays for the
aryl hydrocarbon (Ah), estrogen (E), and androgen (A) receptors. As
reported in the study, triclosan at a concentration of 10 μM  induced
luciferase expression to 40% of that seen with 2,3,7,8-tetrachloro
dibenzo-p-dioxin (TCDD), but it inhibited the induction of luciferase
expression by TCDD by approximately 30%. These agonist/antagonist
results are consistent with TCS being a partial agonist of the Ah
receptor. In both the ER- and AR-responsive bioassays,  triclosan 
exhibited antagonistic activity in this study. 

Chen et al. (2007) examined the anti-androgenic potential of triclosan
using a cell-based stably transfected cell line lacking critical steroid
metabolizing enzymes. Triclosan alone exhibited no androgenic activity
at concentrations up to 10 µM, but transcriptional activity in the
presence of 0.125 nM testosterone was inhibited by 10 µM triclosan by
92%, and by 38.8% at 1.0 µM triclosan. 

Estrogenic Effects

	

Further work showed that triclosan had high toxicity on the early life
stages of medaka and that its metabolite could have weak estrogenic
properties with the ability to induce vitellogenin in male medaka
(Ishibashi et al., 2004).  When the medaka were exposed to triclosan at
20, 100 and 200 µg/L, there was a significant reduction the length of
female medakas relative to control. (Not in male).  A metabolite of
triclosan may be a weak estrogenic compound with the potential to induce
vitellogenin in male medaka but with no adverse effect on reproductive
success and offspring. (Ishibashi, et. al., 2004)

Tamura  et al. (2006) studied the androgen receptor (AR) activity of
listed chemicals, so called SPEED 98, by the ministry of the
Environment, Japan, and structurally related chemicals was characterized
using MDA-kb2 human breast cancer cells stably expressing an androgen
responsive luciferase reporter gene, MMTV-luc. Based on results
generated above suggesting that chemicals with diverse structures were
capable of disrupting the endocrine systems mediated by AR, a
comparative molecular field analysis (C0MFA) model was developed to
analyze the structural requirements necessary to disrupt AR function.
Triclosan had AR antagonist activity with an IC50 value of 7.5 µM,
which was as potent as linuron based on in vitro MDA-kb2 reporter gene
assay. 

In male South African clawed frogs (Xenopus laevis), intraperitoneal
injection of triclosan resulted in reduced plasma vitellogenin and
reduced testosterone levels, suggesting that at higher concentrations,
triclosan could possess oestrogen antagonist activity (Matsumura et al.,
2005).

Effects on Thyroid 

Veldhoen et al. (2006) investigated the effects of pre-treatment to
environmentally relevant concentrations of triclosan (nominal
concentrations of 0, 0.3, 3.0, and 30 µg/L) on the expression of
thyroid hormone receptor, basic transcription element binding protein,
and proliferating nuclear cell antigen in premetamorphic tadpoles given
injections of 1 x 10-11 mol/g body weight triiodothyronine (T3).  
Premetamorphosis represents a period in tadpole growth that occurs in
the absence of endogenous thyroid hormone, characterized by limited
development of the hindlmb buds.  Exposure to triclosan alone produced
no significant changes in hindlimb development or in expression of any
of the receptor transcripts. However, pre-treatment with triclosan
followed by T3 administration compared to treatment with triclosan alone
resulted in significant weight loss, accelerated hind-limb development,
elevated brain activity of genes linked with uncontrolled cell growth,
and decreased gene activity in the tail fin at level at concentrations
of triclosan as low as 0.15 µg/L.  These results suggest that changes
in thyroid hormone regulated gene expression in the North American
bullfrog at a sensitive life stage can occur following exposure to low
concentrations of triclosan and are coincident with an accelerated rate
of T3-induced development. Thus, triclosan does not mimic thyroid
hormone itself but instead accelerates processes associated with
exposure to thyroid hormone.   

Recent in vivo data from rats provides further evidence that triclosan
alters thyroid hormone homeostasis.  Crofton et al (2007) demonstrated
that short-term (4-day) oral exposure to triclosan decreased serum total
T4 concentrations and increased liver weights.  Using a benchmark
response of 20%, the benchmark dose (BMD) and lower bound (BMDL) for T4
were 69.7 and 35.6 mg/kg/day, respectively. This study discussed the
possibility of more than one mechanism involved in the decrease of T4
levels after oral exposure to triclosan, including activation of the
human pregnane X receptor (PXR; Jacobs et al., 2005) resulting in
increases in sulfonation or glucuronidation activity.

The effect of triclosan on thyroid has also been investigated using the
pubertal assay (US EPA, 2008). Weanling male  rats were dosed by oral
gavage for 30 days starting on postnatal day 23 with  0, 3, 30, 100, 200
or 300 mg/kg/day of triclosan,. Triclosan did not alter pubertal
development, reproductive tract development or gonadal histopathology. ,
T4 concentrations decreased by 47.4, 49.8, 80, and 81% at 30, 100, 200,
and 300 mg/kg respectively. Triiodothyronine (T3) was only significantly
decreased at 200 mg/kg, while thyroid stimulating hormone (TSH) levels
were unaffected at any dose level. Thyroid histology was also not
altered at 100 and 200 mg/kg. Histology at 300 mg/kg is currently under
examination. Mean liver weight of dosed male rats was increased
significantly at the 100 mg/kg dose and above, suggestive of hepatic
enzyme induction and increased clearance of thyroid hormone Using a BMR
of 20% and the BMD was calculated as 14.51 mg/kg with a benchmark dose
limit (BMDL) of 7.23.     

The mechanism of action for the decrease in T4 levels observed in
juvenile rats in this study was not investigated. Mean liver weight of
dosed male rats was increased significantly at the 100 mg/kg dose and
above, suggestive of hepatic enzyme induction and increased clearance of
thyroid hormone. However, the study noted no induction of liver
UDP-glucuronyl transferase at the 3 or 30 mg/kg dose levels. In a
shorter term study in which weanling female Long-Evans rats were exposed
by oral gavage for 4 consecutive days to triclosan at 0, 10, 30, 100,
300, or 1000 mg/kg (Crofton et al., 2007), significant decreases in
serum T4 concentrations were observed at 100 mg/kg and above in a
dose-related manner. This study discussed the possibility of more than
one mechanism involved in the decrease of T4 levels after oral exposure
to triclosan, including activation of the human pregnane X receptor
(PXR; Jacobs et al., 2005) resulting in increases in sulfonation or
glucuronidation activity. Further research is needed in this area. 

While there are some uncertainties with respect to the pharmacodynamics
of triclosan, the pharmacokinetics of triclosan, which has been studied
in several animal species and in humans, shows similar half-life of
elimination in experimental animal species studied  (rat, hamster,
mouse) in comparison to humans.  In addition, it is also known that the
rat is a more sensitive species than the human with respect to 
perturbations in thyroid homeostasis, based on the shorter half-life of
T4 in the rat (12-24 hours) compared to humans (5-9 days), and the lack
of the high affinity binding protein thyroxine binding globulin in rats
(Capen, 1996). 

Further research is needed on the effect of triclosan on thyroid
homeostasis and relevance of any perturbations in homeostasis of thyroid
hormone levels for human risk.  The BMDL value (7.23) for decreases in
T4 in the 30 day study in weanling rats represents the lower bound  for
a 20% decrease in T4, which is considered applicable to humans based on
the association of neurodevelopmental and cognitive deficits with this
percentage decrease in thyroid hormone (Haddow et al., 1998). It is not
readily apparent from the available toxicology database for triclosan
that the effects observed are the direct result of perturbations of
thyroid homeostasis. The Agency, however, is aware that research is
ongoing on endocrine effects of triclosan, and this further research may
require future modification to the existing assessment for triclosan. 

 

 EXPOSURE ASSESSMENT AND CHARACTERIZATION

Based on a review of EPA-registered product labels, triclosan is the
active ingredient in textiles and fabrics (e.g., mattresses and
clothing/bibs) and plastic products (e.g., toys, cutting boards, etc). 
Exposures also include those uses where there is the possibility of
indirect food migration, including paper/pulp use, use in ice-making
equipment, adhesives, cutting boards, and counter tops as well use in
conveyer belts.  In addition to EPA-regulated uses, the post application
assessment also includes an aggregate assessment of the FDA uses such as
toothpaste, hand soaps, and deodorants.   This assessment includes both
EPA- and FDA-registered uses because of the biological monitoring
methodology used to collect the samples from the general population does
not allow us to separate the contribution of individual products to
total exposure. 

The National Health and Nutrition Surveys (NHANES) biological monitoring
data are available for triclosan to assess aggregate exposure and risk. 
EPA views the NHANES monitoring data as most representative assessment
of aggregate exposures to daily use products.  In the case of triclosan,
population-based biological monitoring data are available to assess the
co-occurrence of uses to develop an aggregate exposure assessment for
ages 6 years and older.  The population-based biological monitoring data
are a more accurate predictor of aggregate exposure because not only are
the data triclosan specific, they are also based on actual consumer use
of the various triclosan products as they co-occur in practice.  

Although the aggregate exposure/risk assessment using the NHANES data
provides an encompassing review of all triclosan-treated products, it
does not include exposures to children under the age of 6 years old. 
Children under the age of 6 years exhibit unique activities that do not
occur at older ages.  Therefore, a separate estimate for children under
6 years old has been included.  Finally, dermal and inhalation
route-specific assessments are also summarized.

	5.0 AGGREGATE RISK ASSESSMENT 

In order for a pesticide registration to continue, it must be shown
“that there is reasonable certainty that no harm will result from
aggregate exposure to pesticide chemical residue, including all
anticipated dietary exposures and other exposures for which there are
reliable information.”   Aggregate exposure is the total exposure to a
single chemical (or its residues) that may occur from dietary (i.e.,
food and drinking water), residential, and other non-occupational
sources, and from all known or plausible exposure routes (oral, dermal,
and inhalation).  

In performing aggregate exposure and risk assessments, the Office of
Pesticide Programs has published guidance outlining the necessary steps
to perform such assessments (General Principles for Performing Aggregate
Exposure and Risk Assessments, November 28, 2001; available at
http://www.epa.gov/pesticides/trac/science/aggregate.pdf).  Steps for
deciding whether to perform aggregate exposure and risk assessments are
listed, which include: identification of toxicological endpoints for
each exposure route and duration; identification of potential exposures
for each pathway (food, water, and/or residential);  reconciliation of
durations and pathways of exposure with durations and pathways of health
effects; determination of which possible residential exposure scenarios
are likely to occur together within a given time frame; determination of
magnitude and duration of exposure for all exposure combinations;
determination of the appropriate technique (deterministic or
probabilistic) for exposure assessment; and determination of the
appropriate risk metric to estimate aggregate risk

In the case of triclosan, population-based biological monitoring data
are available to assess the co-occurrence of uses to develop an
aggregate exposure assessment.  The population-based biological
monitoring data are believed to be a more accurate predictor of
aggregate exposure because not only are the data triclosan specific,
they are also based on actual consumer use of the various triclosan
products as they naturally co-occur.  Nonetheless, uncertainties in the
biological monitoring data also need to be addressed. Converting spot
urine concentrations to dose is a difficult endeavor.  The
population-based biological monitoring data based on spot urine
concentrations used in this assessment were obtained from the National
Health and Nutrition Surveys (NHANES).

5.1	National Health and Nutrition Surveys (NHANES) Data for Triclosan

5.1.1	NHANES Data and Dose Conversion

 As part of the 2003-2004 NHANES, urinary concentrations (μg/L) of
triclosan (2,4,4’-trichloro-2’-hydroxydiphenyl ether) were measured
on a random sample of 2,517 participants of ages 6 and over.  These
measurements represent concentrations in spot urine samples.  The
corresponding human dose (mg/kg/day) was not measured or estimated by
NHANES.  The NHANES urinary metabolite concentration data collection
efforts were not designed to directly determine the dose and CDC has not
reported dose estimates for triclosan based on NHANES measurement data. 
The NHANES 2003-2004 data were obtained from the NHANES website:  
HYPERLINK "http://www.cdc.gov/nchs/nhanes.htm" 
www.cdc.gov/nchs/nhanes.htm   

EPA evaluates health effects in terms of toxicity endpoints that
represent an exposure level in mg or μg per kilogram body weight that
is not expected to be associated with adverse health effects. The
conversion of measured spot urine concentrations to daily doses can be
difficult because of variable dilution caused by wide fluctuations in
fluid intake and excretion.  Dose calculation is also difficult because
there is no way to determine from the NHANES data from what route of
exposure (i.e., oral, dermal, inhalation) and when (i.e., duration and
time interval prior to measurement) the exposure to triclosan occurred,
and because of uncertainty and variability in the absorption,
distribution, metabolism, and excretion (ADME) parameters.  If NHANES
collected total daily urine excretion for each participant, then that
participant’s dose could be more accurately estimated by multiplying
the triclosan concentration by the total daily urine volume and then
dividing by the body weight.  However, NHANES only collected spot urine
samples so that total urine volume was not measured.  

 In the absence of total urine volume data, various methods have been
proposed to estimate the dose from the measured spot urine
concentration.  The methods have been categorized into two main groups: 
one that uses measured pesticide concentrations in urine directly and
the other that standardizes urinary concentrations on the basis of
creatinine, a by-product of metabolism.  There is some debate on whether
creatinine is less variable than urinary output.  Therefore, at this
time, results of both methods are presented.  The dose conversion
methods are summarized below: 

Mage et al. (2004, 2007) use the estimated daily creatinine excretion
for a demographic group; the triclosan concentration is divided by the
creatinine concentration, multiplied by the daily creatinine excretion
in μg/day, and divided by the body weight. 

Schafer et al. (2004) use the estimated daily urine excretion in L/day
and the average body weight for a demographic group; the triclosan
concentration is multiplied by the daily urine excretion in L/day, and
divided by the average body weight.  Because the data were available in
NHANES, actual body weights of subjects were used instead of average
body weights as described by PANNA (2004).  

The EPA Office of Research and Development (ORD) does not currently
recommend an approach for converting spot urine concentration to a dose.
 However, the approach used by some ORD researchers is to use the
estimated daily urine excretion in L/kg-day for a demographic group; the
triclosan concentration is multiplied by the estimated daily urine
excretion in L/kg-day.  Urine volumes (mean and upper percentile) from
Geigy (1981) were used in this method.

Detailed procedures and assumptions used by EPA/OPP/AD to convert spot
urine concentrations into dose to assess the tricolsan aggregate risks
are provided by Cohen (2008).  Cohen (2008) provided the dose conversion
from spot urine samples leaving the correction for the pharmacokinetics
of triclosan to be done at a later date (see Section 6.1.2 below for
pharmacokinetic correction).

5.1.2	Pharmacokinetics of Triclosan  

A correction factor to account for the disposition of triclosan, derived
from the data of Sandborgh-Englund (2006) was applied to the biological
(urine) monitoring data provided by Cohen (2008) and used in this
assessment.  Sandborgh-Englund (2006) dosed 10 subjects (5M/5F) ranging
from 26 to 42 years of age with a single oral dose of 4 mg of triclosan
in mouthwash solution.  Pre-exposure monitoring to establish baseline
exposure levels was also determined.  Results indicate that urinary
excretion among individuals is variable for triclosan.  Urinary
excretion ranged from 24 to 83 percent (median of 54 percent) of the
administered dose of triclosan in urine in 4 days.  The data also
indicate that the majority of urinary excretion occurred within 24 hours
as illustrated in Figure 1.  The urinary excretion half life of
triclosan in this study was determined to be 11 hours.  Therefore, 54
percent excretion, corrected for baseline exposures, was used by EPA in
this assessment to convert the urine concentrations from NHANES to a
dose using estimated 24 hour urine void volumes as described by Cohen
(2008).  The conversion is facilitated by the linear excretion kinetics
observed for triclosan in this study.  Based on the above, the
pharmacokinetic equation used to calculate the triclosan dose is as
follows:  Triclosan dose (mg/kg/day) / 0.54.  

Figure 1.  Triclosan Excretion in Urine (taken from Sandborgh-Englund
(2006))

5.1.3	Uncertainties Associated with the Dose Conversion

	Several uncertainties exist in the aggregate assessment for triclosan
that arise from using the biological monitoring data from NHANES. 
However, these uncertainties are balanced (and perhaps even offset) by
the relatively large data set obtained from NHANES; assumptions used by
Cohen (2008) for the dose conversion; the characterization of the dose
at the lowest (most conservative) urinary excretion; the short urinary
excretion half life 11 hours; and use of the upper percentile of
exposure.  The following uncertainties and data limitations are noted
for the aggregate assessment:

It is assumed that the ADME parameters are the same across all
individuals within the NHANES study and are constant within individuals
over time.  The ADME assumptions are offset by the use of the lowest
urinary excretion value available in Sandborgh-Englund (2006) and by
characterization of the risks at the 99th percentile of exposure from
NHANES using the method which assumes the an upper percentile of daily
urine excretion for everyone in the sample.

Sandborgh-Englund (2006) reported urinary excretion over 4 days post
dose.  However, from the graphical presentation of the data (raw data
not reported) the profile of urinary excretion of triclosan indicates
that the results at 24 hours are similar to those at 4 days with a
urinary excretion half life of 11 hours.  

NHANES urinary metabolite concentration data are not collected in a way
to directly determine the dose, and CDC has not reported dose estimates
for triclosan based on NHANES measurement data.  

The conversion of measured spot urine concentrations to daily doses can
be difficult because of variable dilution caused by wide fluctuations in
fluid intake and excretion.  This is offset by one of the dose
conversion methods presented that assumed the upper percentile of daily
urine volume for all individuals in the NHANES data set.  

Dose calculation is also difficult because there is no way to determine
from the NHANES data from what route of exposure (i.e., oral, dermal,
inhalation) and when (i.e., duration and time interval prior to
measurement) the exposure to triclosan occurred.  This is offset by the
short half life of triclosan (11 hours in urine). 

 Aggregate Risks  

5.2.1	Children (6 years) to Adults tc "6.1	Acute and Chronic Aggregate
Risks " \l 2 

The NHANES results are believed to be representative of a range of acute
to chronic exposures to children and adults because of the relatively
short half-life of triclosan in urine (i.e., 11 hours) and the often
daily use of triclosan products such as hand soaps and tooth paste.  The
upper range of exposures is important because of the uncertainties in
converting the spot urine concentrations to a dose; because the
pharmacokinetic data appears to be highly variable for triclosan; and
because the use of triclosan by the NHANES population is unknown. 
Interpreting the NHANES data for triclosan as representing a range of
acute to chronic exposures is also supported by the fact that the 2,517
samples selected for analyses of triclosan were randomly selected from
the total NHANES random population of 9,643, and therefore, “…the
representative design of the survey was maintained” (Calafat et al
2007).  Given the uncertainties in aggregating screening-level single
use exposure estimates and assumptions on co-occurrence of uses, the
NHANES data are viewed to be a reasonable data set to use for predicting
aggregate risks.

All exposure durations were assessed using the selected oral NOAEL of 30
mg/kg/day with a target MOE of 100.  The oral endpoint was selected to
represent the various oral exposure scenarios that are expected from
antimicrobial exposure to triclosan. The calculated MOEs are
representative of all exposure durations.  The NHANES data show that
74.6% of the samples had detectable levels of total (free plus
conjugated) triclosan.  Tables 5.1 and 5.2 provide – for each of the
three basic concentration to dose conversion methods -- the mean and
99th percentiles, respectively, of the (1) spot urine concentration to
dose conversion prior to correcting for the 54% triclosan urinary
excretion (in units of ug/kg/day); (2) the pharmacokinetic 54% corrected
daily dose converted to units of mg/kg/day; and (3) the MOEs.  Aggregate
exposures and risks are presented for the following age groups and
subpopulations: 

All age groups;

Ages 6-11;

Ages 12-19

Ages 20-59

Ages >=60

Male

Females

Mexican-American

White, non-Hispanic

Black, non-Hispanic

Tables 5.1 and 5.2 report the results of the aggregate risks at both the
mean and 99th percentile, respectively.  These analyses of the combined
EPA and FDA uses do not trigger risks of concern.  The mean MOEs range
from 4,700 to 19,000.  The MOEs at the 99th percentile of the dose range
from 260 to 1,700.  In fact, applying the lowest (most conservative)
percent urinary excretion from the results of the pharmacokinetic data
(i.e., 24 percent) to the most conservative dose conversion method
(i.e., Geigy’s 95th percentile of daily urine volumes), the MOE is
120.  In conclusion, even with the reliance of conservative assumptions
in estimating risks to account for the considerable uncertainties in
converting spot urine concentration to dose, the NHANES data as analyzed
for triclosan sufficiently characterizes the aggregate risks as meeting
the definition of not resulting in unreasonable adverse effects.

Table 5-2a.  Acute, Short, Intermediate-, and Long-term Aggregate Risks
for Triclosan (Mean)

	Group	 

Mage (2007) Obese Correct 

 	 

Schafer (2004) Actual BW

 	 

Geigy 1981 Mean Urine Vol 

 	 

Geigy (1981) 95% Urine Vol

 

 	ug/kg	mg/kg/day	MOE	ug/kg	mg/kg/day	MOE	ug/kg	mg/kg/day	MOE	ug/kg
mg/kg/day	MOE

All	1.373	0.0025	11801	1.5700	0.0029	10318	1.551	0.0029	10442	2.413
0.0045	6714

6-11	0.872	0.0016	18582	1.0511	0.0019	15412	0.901	0.0017	17986	1.304
0.0024	12426

12-19	1.431	0.0027	11318	1.7404	0.0032	9308	2.189	0.0041	7400	3.361
0.0062	4820

20-59	1.543	0.0029	10501	1.7187	0.0032	9426	1.635	0.0030	9911	2.562
0.0047	6322

>= 60	1.013	0.0019	15996	1.2108	0.0022	13380	1.152	0.0021	14065	1.806
0.0033	8972

Male	1.684	0.0031	9618	2.0316	0.0038	7974	1.963	0.0036	8254	2.997	0.0056
5405

Female	1.076	0.0020	15062	1.1306	0.0021	14329	1.160	0.0021	13969	1.857
0.0034	8726

Mexican-American	1.863	0.0035	8694	2.2781	0.0042	7111	2.220	0.0041	7297
3.455	0.0064	4689

White, Non-Hispanic	1.355	0.0025	11956	1.4850	0.0028	10909	1.477	0.0027
10969	2.303	0.0043	7035

Black, Non-Hispanic	1.082	0.0020	14967	1.5665	0.0029	10342	1.512	0.0028
10714	2.327	0.0043	6962

See Cohen (2008) for details of the dose conversion methods.  Geigy
(1981) 95% urine vol is the upper percentile of daily urine volume.

Table 5-b.  Acute, Short, Intermediate-, and Long-term Aggregate Risks
for Triclosan (99th Percentile)

	Group	 

Mage (2007) Obese Correct 

 	 

Schafer (2004) Actual BW

 	 

Geigy 1981 Mean Urine Vol 

 	 

Geigy (1981) 95% Urine Vol 

 

 	ug/kg	mg/kg/day	MOE	ug/kg	mg/kg/day	MOE	ug/kg	mg/kg/day	MOE	ug/kg
mg/kg/day	MOE

All	15.51	0.029	1044	23.59	0.044	687	23.56	0.0436	688	38.06	0.070	426

6-11	10.85	0.020	1493	24.62	0.046	658	9.70	0.0180	1670	14.17	0.026	1143

12-19	16.63	0.031	974	25.46	0.047	636	28.77	0.0533	563	46.48	0.086	349

20-59	19.08	0.035	849	29.07	0.054	557	29.87	0.0553	542	48.25	0.089	336

>= 60	14.42	0.027	1123	17.15	0.032	945	14.78	0.0274	1096	22.70	0.042	714

Male	18.96	0.035	855	35.15	0.065	461	35.20	0.0652	460	54.07	0.100	300

Female	14.74	0.027	1099	17.77	0.033	912	17.62	0.0326	920	28.47	0.053	569

Mexican-American	20.56	0.038	788	42.37	0.078	382	40.64	0.0753	399	62.42
0.116	260

White, Non-Hispanic	14.98	0.028	1081	16.30	0.030	994	18.97	0.0351	854
29.13	0.054	556

Black, Non-Hispanic	13.72	0.025	1181	26.12	0.048	620	28.25	0.0523	573
45.64	0.085	355

5.2.2	Infants

While NHANES data are measured exposures that represent the real world
co-occurrence of triclosan-treated products, it is necessary to use
screening-level deterministic assessments as well as to make assumptions
of potential co-occurrence of triclosan-treated products for younger
children.  USEPA (2005), in an internally and externally scientific peer
reviewed document, provides the basis of the age group selection: 
“This document recommends a set of age groupings based on current
understanding of differences in lifestage behavior and anatomy and
physiology that can serve as a starting set for consideration by Agency
risk assessors and researchers.  In specific situations, it is
recognized that exposure factors data may not be available for many of
the recommended age groupings or that a specific age group may not need
to be the subject of a particular assessment, so flexibility and
professional judgment are essential in applying these generic age
groupings.”   One age group was selected to represent behavioral
activities of children younger than 6 years old that are exposed to
triclosan-treated products.

An assessment of infants in the 6 to 12 month old age group has been
selected to represent the high end of exposure activities of children
less then six years old to triclosan-treated products.  This age group
is considered the high end of exposure based on the characteristics
discussed in Table 2 presented in USEPA (2005) and the likelihood of
these activities co-occurring.  USEPA (2005) indicates that this age
group includes behaviors that would lend themselves to potentially
expose children to triclosan-treated products.  Characteristics of
children at this age that potentially exposes children to triclosan that
would not have been captured by the 6-11 year old age category in NHANES
include nursing, increasingly likely to mouth nonfood items, and
“development of personal dust clouds” as a characteristic relevant
to inhalation exposure.  

The younger age groups recommended by USEPA (2005) such as birth to 3
months and 3 to 6 months are less likely to be the high exposure groups
to triclosan because of less contact with treated objects (not to say
there is no contact, but the 6 to 12 month age group are “increasingly
likely to mouth nonfood items”).  The older age groups recommended by
USEPA (2005) include 12 to 24 months and 2 to less than 6 years old. 
These age groups reflect the cessation of nursing and a reduction in
hand-to-mouth activities.  The activities in the 12 to 24 month age
group as well as the 2 to 6 year age group reflect decreasing frequency
of mouthing of objects, nursing, etc and decreasing potential for
co-occurrence (e.g., nursing) in comparison to the 6 to 12 month old age
group.   

Infant-specific activities resulting in potential exposures that are not
accounted for by the 6-11 year old age group in NHANES that are likely
to co-occur include: 

Nursing (i.e., triclosan-contaminated breast milk);  

Object-to-mouth exposures (e.g., mouthing of plastic items such as toys,
combs & brushes, playground equipment); 

Hand-to-mouth exposure (e.g., residues in dust stuck to children’s
hands);  and

Inhalation of triclosan-contaminated dust.

Other potential exposure pathways for infants in the 6 to 12 month old
age group that are captured – and overestimated for the 6 to 12 month
olds -- by the NHANES age groups 6-11 years old include:

Brushing teeth with triclosan-treated tooth paste;

Washing hands with triclosan-treated antibacterial soap;

Exposure to impregnated fabrics and textiles such as
clothing/sportswear, blankets, mattresses, tooth brush bristles, etc.
that may be treated with triclosan;

Exposure to impregnated polymers and plastics such as food contact
surfaces (e.g., cutting boards, conveyor belts, counter and table tops).

	Table 5.3 presents the aggregate risks for the 6 to 12 month old age
group.  The aggregate risks presented represent the high-end of exposure
that may co-occur from the various EPA and FDA-regulated triclosan
products.  The risk results of the 6-11 year old NHANES age group are
used in conjunction with infant-specific exposure activities.  The 6-11
year old age group represents exposures to all of the potential
EPA-registered uses such as textiles and fabrics; plastic products; as
well as FDA-regulated soaps and toothpaste.  Clearly, including
exposures to the FDA-regulated soaps and toothpaste for 6-11 year olds
is a conservative assessment of exposure from these products to 6 to 12
month olds.  Future refinements to the infant aggregate should focus on
this portion of the total exposure. 

	The aggregate risks for infants 6 to 12 months old have been estimated
by combining the mean NHANES distribution with the infant-specific
bounding risks.  The aggregate MOE from the measured mean of the 6-11
year old NHANES subjects combined with the bounding risks from nursing,
object-to-mouth, and hand-to-mouth indicate a long-term MOE of 390.  The
99th percentile of the NHANES dose (when using the 95% urine volume to
estimate the 99th percentile dose) is combined with the infant-specific
bounding risks and indicates a long-term MOE of 290.

Table 5.3.  Aggregate Exposure and Risks for Infants 6 to 12 Months.

Scenario	Risk (MOE)	Representative Products

	Mean	99th%	Bounding

	NHANES 

6-11 year olds	12,000	1,100	NA	Exposures inclusive of all
triclosan-treated products that co-occur in the real world for 6-11 year
olds (excludes infant-specific activities)

Nursing	NA	NA	6,000	Infants nursing (contaminated breast milk) from
mothers exposed to triclosan-treated products that co-occur in the real
world

Object-to-mouth	NA	NA	430	Wide range of triclosan-treated products such
as toys that may be mouthed by infants

Hand-to-mouth	NA	NA	6.7E+6	Infants mouthing hands that have been
contaminated by triclosan residues in house dust

Aggregate a

(Total MOE)	390b

(mean + bounding)	290c

(99th + bounding)	NA	Total exposure of a 6-11 year old plus
infant-specific activity exposures

(a) Aggregate (Total MOE) = 1/((1/MOENHANES) + (1/MOENursing) +
(1/MOEObject) + (1/MOEHTM))

(b) Mean Aggregate = Sum of the mean NHANES MOEs plus the bounding MOE
estimates from nursing, object-to-mouth, and hand-to-mouth.

(c) 99th%tile Aggregate = Sum of the 99th%tile NHANES MOEs plus the
bounding MOE estimates from nursing, object-to-mouth, and hand-to-mouth.

5.2.3  Dermal Irritation

The potential for dermal irritation to occur from incidental dermal
exposures from products treated at low concentrations of triclosan are
expected to be minimal.  The lack of incident data for irritation
confirms this assumption.  

The localized dermal irritation effects tested at the concentrated
product (i.e., 99 percent triclosan) occurs at levels lower than the
NOAEL of 100 ug/cm2.  EPA applies a 10x uncertainty factor for risk
assessment purposes.  Plastic articles are treated at a use dilution of
0.5 percent triclosan.  Only a fraction of triclosan in impregnated
articles would be available on the surface.  Furthermore, only a
fraction of the triclosan on the surface would be transferred to a
localized skin area for irritation to occur.  For illustrative purposes,
the film thickness of a fluid on the hands is 1.75 mg/cm2, which was
extracted from the document entitled, “A Laboratory Method to
Determine the Retention of Liquids on the Surface of Hands” (Cinalli,
1992).  The film thickness is based on a machinist immersing both hands
in metalworking fluid and then partially cleaning hands with a rag. 
Clearly this is an exaggerated estimate of exposure compared to dermal
contact of triclosan-impregnated articles.  This type of a
screening-level approach indicates that 1.75 mg/cm2 x 1000 ug/mg unit
conversion x 0.005 triclosan application rate is 8.75 ug/cm2.  This
conservative estimate does not indicate a dermal irritation concern. 
Additional residue transfer assumptions for impregnated articles up to 2
percent could be determined for similar screening-level assessments but
are not warranted based on the above discussions.5.2.4   Dermal
Systemic

	There is the potential for dermal-specific route of exposure to adults
and children contacting impregnated textiles and fabrics such as
clothing items and mattresses.  The contribution of dermal exposure to
the aggregate exposure is represented in the NHANES data.  Nonetheless,
a post-application screening-level clothing assessment to represent
exposure to treated textiles and fabrics is provided.  The
route-specific dermal toxicological endpoint for the intermediate-term
exposure duration is used to represent all textile uses.  Long-term
duration was not assessed because transferable triclosan residues from
treated textiles and fabrics are not expected to be available
continuously at the levels used in this screening-level assessment.6.0 
	CUMULATIVE RISK

FQPA (1996) stipulates that when determining the safety of a pesticide
chemical, EPA shall base its assessment of the risk posed by the
chemical on, among other things, available information concerning the
cumulative effects to human health that may result from dietary,
residential, or other non-occupational exposure to other substances that
have a common mechanism of toxicity.  The reason for consideration of
other substances is due to the possibility that low-level exposures to
multiple chemical substances that cause a common toxic effect by a
common mechanism could lead to the same adverse health effect as would a
higher level of exposure to any of the other substances individually.  A
person exposed to a pesticide at a level that is considered safe may in
fact experience harm if that person is also exposed to other substances
that cause a common toxic effect by a mechanism common with that of the
subject pesticide, even if the individual exposure levels to the other
substances are also considered safe.

  A cumulative risk assessment for triclosan was not performed.  The
point has been raised in the public comment phase of the preliminary
risk assessment that the chemical triclocarban should be included in a
cumulative risk assessment for triclosan based on the co-occurrence of
these chemicals in the environment and the structural similarity of
these two chemicals. 

 Examination of the chemical structure of triclocarban shows that it is
in a different chemical class (hydroxyphenylurea) than triclosan
(hydroxyphenylether). Furthermore, there is not necessarily a
relationship between the mechanism of antimicrobial activity and
mechanism of toxicity in mammals. There is currently insufficient
evidence to suggest that these two chemicals share a common mechanism of
toxicity with respect to toxic effects in mammals and that a cumulative
assessment should be conducted. 

7.0	OCCUPATIONAL EXPOSURE AND RISK 

A complete explanation of the occupational exposure and risk assessment
can be found in the supporting disciplinary chapter entitled Triclosan:
Occupational and Residential Exposure Assessment Summary information is
provided in this section.

 

The exposure scenarios assessed for representative uses of triclosan
selected by EPA are shown in Table 7.1. The table also shows the maximum
application rate associated with the representative use and the
appropriate EPA Registration number for the product label.  It should be
noted that for the calculation of application rates in which 8.34 lb/gal
is noted, the product is assumed to have the density of water because no
product-specific density is available.   

The occupational handler scenarios included in Table 7.1 were assessed
to determine inhalation exposures.  The general assumptions and
equations that were used to calculate occupational handler inhalation
risks are provided in Section 1.2 of the Occupational and Residential
Exposure Chapter.  The majority of the scenarios were assessed using CMA
data and Equations 1-3.  However, for the occupational scenarios in
which CMA data were insufficient, other data and methods were applied. 

Triclosan dermal irritation exposures and risks were not estimated for
occupational handler exposures.  Instead, dermal irritation exposures
and risks will be mitigated using default personal protective equipment
requirements based on the toxicity of the end-use product.   



Table 7.1.  Representative Exposure Scenarios Associated with
Occupational Exposures to Triclosan

Representative Use	Method of Application	Exposure Scenario	Example
Registration #	Application Rate

Commercial/Industrial/Institutional Premises (Use Category III)

HVAC coil applications	Airless sprayer	ST/IT Handler:

Inhalation	82523-1	6.1E-4 lb ai/10 ft2

(0.85 pints/10 ft2 x 1 gal/8 pts x 8.34 lb/gal x 0.69% ai)

Painting 

(commercial painters)	Paint brush,

Airless sprayer	ST/IT Handler:

Inhalation	42182-1	0.1 lb ai/gallon

[up to 1% product x 99% ai x 10 lb/gal paint density = 0.099 lb
ai/gallon of paint]

Material Preservatives (Use Category VII)

Paint

	Liquid pour,

Powder	ST/IT Handler: inhalation	42182-1	0.1 lb ai/gallon

[up to 1% product x 99% ai x 10 lb/gal paint density = 0.099 lb
ai/gallon of paint]

  SEQ CHAPTER \h \r 1 Industrial processes and water systems (Use
Category VIII)

Pulp and Paper 

	Metered pump

	ST/IT Handler: Inhalation

	70404-5

	 2% ai by weight of paper product

(2% product by weight x 99% ai for paper mulch )

Note :  other labels for paper and paper board have lower rates,
42182-1 and 3090-165)

The resulting inhalation exposures and MOEs for the representative
occupational handler scenarios are presented in Table 6.2. The
calculated MOEs were above the target MOE of 100 for all scenarios,
except for the commercial painters (both by brush and airless sprayer).



Table 7.2.  Short- and Intermediate-Term Inhalation and
Intermediate-Term Dermal Risks Associated with Occupational Handlers

Exposure Scenario	

Method of Application

	

Unit Exposure

(mg/lb a.i.) 	Application Rate	Quantity Handled/ Treated per day	

Daily Dose (mg/kg/day)a	

MOEb 

(Target MOE = 100)

Inhalation 	Dermal 

	Inhalation 

	Dermal 

	Inhalation 

	Dermal 

  SEQ CHAPTER \h \r 1 Commercial, Institutional and Industrial Premises
and Equipment (Use Site Category III )

HVAC	Airless sprayer	0.83	38	6.1E-4 lb ai/10ft2	Large building 1000 ft2
0.00072	0.033	4,500	1,200

Painting (commercial)	Paint brush	0.26	180	0.1 lb ai/gal	5 gallons	0.002
1.3	1,600	31

	Airless sprayer	0.83	38

50 gallons	0.059	2.7	54	1

Material Preservatives (Use Site Category VII)

Paint (manufacturing process)	Liquid pour	0.00346	0.135 (gloves)	0.99%
ai	20,000 lbs	0.0098	0.38	330	110

	Liquid pump	0.000403	0.00629 (gloves)

200,000 lbs	0.011	0.18	290	220

Industrial Processes and Water Systems (Use Site Category VIII)

Pulp and Paper	Metering pump	0.000403	0.00629 (gloves)	2% ai	500 tons
Require closed loading systems to mitigate the exposure/risk

a	Daily dose (mg/kg/day) = [unit exposure (mg/lb a.i.) x absorption
factor (1 for inhalation and 1 for dermal) x application rate x quantity
treated / Body weight (70 kg).

	b	MOE = NOAEL  (mg/kg/day) / Daily Dose [Where inhalation LOAEL = 3.21
mg/kg/day for all inhalation exposure durations and the IT dermal NOAEL
is 40 mg/kg/day from a dermal route-specific study].  Target MOE = 100.

Occupational Post-application Exposures   

Occupational post-application dermal and inhalation exposures are
assumed to be negligible based on the use patterns.  

7.2	Data Limitations/Uncertainties tc \l2 "6.3	Data
Limitations/Uncertainties 

There are several data limitations and uncertainties associated with the
occupational handler and post application exposure assessments as noted
in the occupational and residential exposure chapter.  These are
reproduced here and include:

Surrogate dermal and inhalation unit exposure values were taken from the
proprietary Chemical Manufacturers Association (CMA) antimicrobial
exposure study (USEPA, 1999: DP Barcode D247642) or from the Pesticide
Handler Exposure Database (USEPA, 1998).   Since the CMA data are of
poor quality, the Agency requires that confirmatory data be submitted to
support the occupational scenarios assessed in this document.

The quantities handled/treated were estimated based on information from
various sources, including HED’s Standard Operating Procedures (SOPs)
for Residential Exposure Assessments (USEPA, 2000 and 2001), and
personal communication with experts.  The individuals contacted have
experience in these operations and their estimates are believed to be
the best available without undertaking a statistical survey of the uses.
 In certain cases, no standard values were available for some scenarios.
 Assumptions for these scenarios were based on AD estimates and could be
further refined from input from registrants.

8.0      ENVIRONMENTAL RISK  

8.1 Ecological Hazard

The toxicity endpoints presented below are based on the results of
ecotoxicity studies submitted to EPA to meet the Agency’s data
requirements for the uses of triclosan.

	A.	Toxicity to Terrestrial Animals

(1)	Birds, Acute 

The results of three acute oral toxicity studies, submitted for
triclosan, are provided in the following table:

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint

(mg/kg)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Mallard duck

(Anas platyrhynchos)	Triclosan 99.7%	LD50 = >2150

NOAEL = 2150

	Relatively nontoxic	Yes (core)

- 14-day test duration

- 19 weeks of age	430226-03

Bobwhite quail

(Colinus virginianus)	Triclosan 99.7%	LD50 = 825

NOAEL = <147	Slightly toxic	Yes (core)

- 14-day test duration

- 21 weeks of age	430226-02

Bobwhite quail

(Colinus virginianus)	Triclosan 3.89%	LD50 = >2000

NOAEL = N.R.

	Relatively nontoxic	Yes (core for a formulated product)

	410089-10

These three acceptable acute oral toxicity studies indicate that
triclosan is slightly toxic to relatively nontoxic to birds on an acute
oral basis. The guideline requirement OPPTS 850.2100/(71-1) is
satisfied.  

(2)	Birds, Subacute

This testing was required for triclosan.   The results of two subacute
dietary toxicity studies, submitted for triclosan, are provided in the
following table:

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint

(ppm)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Bobwhite quail

(Colinus virginianus)	Triclosan 99.7%	LC50 (diet) = >5000

NOAEC = 1250	Relatively nontoxic	Yes (core)

-	8-day test duration

-	13 days of age	430226-04

Bobwhite quail

(Colinus virginianus)	Triclosan 

3.89%	LC50 (diet) = >5000

NOAEC = N.R.	Relatively nontoxic	Yes (core for formulated product)

- 8-day test duration

- 7-10 days of age 	410089-11

The results of these two acceptable studies indicate that triclosan is
relatively nontoxic to

avian species through subacute dietary exposure. These studies fulfill
guideline requirement OPPTS 850.2100/ (71-2a – Bobwhite quail/71-2b
– Mallard duck). 

B.	Toxicity to Aquatic Animals

The Agency requested that aquatic toxicity studies be conducted with
triclosan since, under typical use conditions, it may be introduced into
the aquatic environment.

(1)	Freshwater Fish, Acute

In order to establish the acute toxicity of triclosan to freshwater
fish, the Agency requires freshwater fish toxicity studies using the
TGAI.  The preferred test species are rainbow trout (a coldwater fish)
and bluegill sunfish (a warm water fish).  The results of 5 freshwater
fish acute studies submitted for triclosan are presented in the
following table:

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint

(mg/L)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Rainbow Trout (Oncorhynchus mykiss)	Triclosan

99.3%	LC50 = 0.288

NOAEC = 0.100	Highly toxic	Yes (core)

-	96-hr test duration

-	static test system	439693-01

Fathead minnow

(Pimephales promelas)	Triclosan

99.7%	LC50 = 0.26

LOEC = 0.18

NOAEC = 0.10

	Highly toxic	No (supplemental)

-	96-hr test duration

-	static test system

-  nominal concentrations not verified	430460-01

Bluegill sunfish (Lepomis macrochirus)	Triclosan 3.89%	LC50 = 37.2 

NOAEC = N.R.	Slightly toxic	Yes (core for formulated product)

-  96-hr test duration

-  static test system	410089-13

Rainbow Trout (Oncorhynchus mykiss)	Triclosan 3.89%	LC50 = 23.4

NOAEC = N.R.	Slightly toxic	Yes (core for formulated product)

-	96-hr test duration

-	static test system	410089-12

Freshwater acute toxicity tests indicate that triclosan is highly toxic
to slightly toxic to fish on an acute basis.  These studies fulfill
guideline requirement OPPTS 850.1075 (72-1a&b).  Because acute toxicity
to fish is <1.0 mg/L, the environmental hazard section of triclosan
labels must state: “This pesticide is toxic to fish.”

(2)	Freshwater Invertebrates, Acute

The results of the two acute studies submitted for triclosan are
provided in the following table:

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint

(mg/L)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Waterflea (Daphnia magna)	Triclosan

99.7%	EC50 = 0.39 

NOAEC = 0.10 (a.i.)	Highly toxic	No (supplemental)

-	48-hr test duration

-	static test system

-  nominal concentrations not verified	430460-02

Waterflea (Daphnia magna)	Triclosan 

3.89%	LC50 = 0.42

NOAEC = N.R.	Highly toxic	No (supplemental)

-  48-hr test                duration

-  static test system

-  lack of pH and DO measurements and formulated product used	410089-14

Waterflea (Daphnia magna)

	423221-02

The results of these studies indicate that triclosan is highly toxic to
freshwater invertebrates.  These studies do not fulfill guideline
requirement OPPTS 850.1010 (72.2a).  Because the acute aquatic
invertebrate toxicity values are < 1.0 mg/L, the environmental hazard
section of triclosan labels must state:  “This pesticide is toxic to
aquatic invertebrates.”

(3)	Estuarine and Marine Organisms, Acute

Acute toxicity testing with estuarine and marine organisms using the
TGAI is required when the end-use product is intended for direct
application to the marine/estuarine environment or effluent containing
the active ingredient is expected to reach this environment.  The
preferred fish test species is the sheepshead minnow.  The preferred
invertebrate test species are mysid shrimp and eastern oysters.  At this
time this testing is not required for triclosan, but is dependent upon
the results of environmental fate data which may be required.  (See
triclosan environmental fate chapter and comments above on potential
data requirements).  No studies have been submitted to fulfill these
data requirements (OPPTS 850.1075/(72-3a), OPPTS 850.1035/(72-3c) and
OPPTS 850.1025/(72-3b)).

(4)	Aquatic Organisms, Chronic

Chronic toxicity testing (fish early life stage and aquatic invertebrate
life cycle) is required for pesticides when certain conditions of use
and environmental fate apply.  The preferred freshwater fish test
species is the fathead minnow.  The preferred freshwater invertebrate is
Daphnia magna.  At this time this testing is not required for triclosan,
but is dependent upon the results of environmental fate data which may
be required.  (See triclosan environmental fate chapter and comments
above on potential data requirements).

The results of one toxicity study submitted for triclosan is presented
in the following table:

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint

(mg/L)	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Waterflea 

(Daphnia magna)	Triclosan

% purity unknown	LOEC = <0.1388

NOAEC = N.R.

	No (supplemental)

-  21-day test             duration 

-  static renewal test     system

-  growth not measured as a chronic endpoint

-  % a.i. not given 

-  raw data missing

-  concentration analysis insufficient	437407-01

No fathead minnow study has been submitted. The study on the waterflea
does not fulfill the guideline requirement for a chronic aquatic
invertebrate study (OPPTS 850.1300).

Toxicity to Plants

Non-target plant phytotoxicity testing is required for pesticides when
certain conditions of use and environmental fate apply.  At this time
this testing is not required for triclosan, but is dependent upon the
results of environmental fate data which may be required.  (See
triclosan environmental fate chapter and comments above on potential
data requirements).  However, testing has been conducted with triclosan
on several aquatic plant species.  Testing is normally conducted with
one species of aquatic vascular plant (Lemna gibba) and four species of
algae:  (1) freshwater green alga, Selenastrum capricornutum, (2) marine
diatom, Skeletonema costatum, (3) freshwater diatom, Navicula
pelliculosa, and (4)  bluegreen cyanobacteria, Anabaena flos-aquae.  The
rooted aquatic macrophyte rice (Oryza sativa) is also tested in seedling
emergence and vegetative vigor tests.

Four studies that evaluate the toxicity of triclosan to freshwater
aquatic plants have been submitted. Results of these studies are
presented in the following table:

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint 

(mg/L)	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Marine Diatom (Skeletonema costatum)	Triclosan 

99.5%	EC50 = >0.066

NOEC = 0.0126	Yes (core)

-  96-hour test duration

-  static test system	444228-01

Freshwater Diatom (Navicula pelliculosa)	Triclosan 

99.5%	EC50 = 0.016

NOEC = 0.005	Yes (core)

-  96-hour test duration

-  static test system	444228-01

Bluegreen Cyanobacteria (Anabaena flos-aquae)	Triclosan 

99.5%	EC50 = 0.0012

NOEC = N.R.	Yes (core)

-  96-hour test duration

-  static test system	444228-01

Duckweed (Lemna gibba)	Triclosan 

99.5%	EC50 = >0.0625

NOEC = 0.0125	Yes (core)

-	7-day test duration

-	static test system	444228-01

The guideline requirement for an algal toxicity test (850.5400, 123-2)
is partially fulfilled.  One additional algal toxicity test under
850.5400 is outstanding: a test with the freshwater green alga,
Selenastrum capricornutum.  The other non-target aquatic plant toxicity
requirement, floating freshwater aquatic macrophyte duckweed (Lemna
gibba) – guideline 850.4400 - is satisfied.  Studies on the rooted
freshwater macrophyte rice (Oryza sativa) – 850.4225 and 850.4250 (2
tests on seedling emergence and vegetative vigor) -- have not been
submitted.

   Environmental fate and Transport

Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol] is a white
crystalline powder with low solubility in water (12 ppm).  Triclosan is
hydrolytically stable under abiotic and buffered conditions over the pH
4-9 range based on data from a preliminary test at 50°C. 
Photolytically, triclosan degrades rapidly under continuous irradiation
from artificial light at 25°C in a pH 7 aqueous solution, with a
calculated aqueous photolytic half-life of 41 minutes.  One major
transformation product has been identified, DCP (2,4-dichlorophenol),
which was a maximum of 93.8-96.6% of the applied triclosan at 240
minutes post-treatment.

In soil, triclosan is expected to be immobile based on an estimated Koc
of 9,200.  Triclosan is not expected to volatilize from soil (moist or
dry) or water surfaces based on an estimated Henry’s Law constant of
1.5 x 10-7 atm-m3/mole.  Triclosan exists partially in the dissociated
form in the environment based on a pKa of 7.9, and anions do not
generally adsorb more strongly to organic carbon and clay than their
neutral counterparts.  In aquatic environments, triclosan is expected to
adsorb to suspended solids and sediments and may bioaccumulate (Kow
4.76), posing a concern for aquatic organisms.  There is a low to
moderate potential for bioconcentration in aquatic organisms based on a
BCF range of 2.7 to 90.

Hydrolysis is not expected to be an important environmental fate process
due to the stability of triclosan in the presence of strong acids and
bases.  However, triclosan is susceptible to degradation via aqueous
photolysis, with a half-life of <1 hour under abiotic conditions, and up
to 10 days in lake water.  An atmospheric half-life of 8 hours has also
been estimated based on the reaction of triclosan with photochemically
produced hydroxyl radicals.  Additionally, triclosan may be susceptible
to biodegradation based on the presence of methyl-triclosan following
wastewater treatment.

  SEQ CHAPTER \h \r 1 Of the published literature studies on the
occurrence of triclosan in waste water treatment plants, treatment plant
efficiency, and open water measurements of triclosan, the majority
suggest that aerobic biodegradation is one of the major and most
efficient biodegradation pathways (70-80%) through which triclosan and
its by-products are removed from the aquatic environment, with actual
efficiencies ranging from 53-99% (Kanda et al., 2003) in activated
sludge plants, and trickle down filtration ranging from 58-86% (McAvoy
et al., 2002).  Another pathway of removing triclosan from water in
wastewater treatment plants is through the sorption of triclosan and
associated by-products to particles and sludge (10-15%) because of the
chemical’s medium to high hydrophobicity.  Benchtop fate testing of
triclosan found that 1.5-4.5% was sorbed to activated sludge and 81-92%
was biodegraded (Federle et al., 2002).

Environmental Exposure and Risk

The ecotoxicity test values (measurement endpoints) used in the acute
and chronic risk quotients are derived from required studies.  Examples
of ecotoxicity values derived from short-term laboratory studies that
assess acute effects are: (1) LC50 (fish and birds), (2) LD50 (birds and
mammals), (3) EC50 (aquatic plants and aquatic invertebrates) and (4)
EC25 (terrestrial plants).  Examples of toxicity test effect levels
derived from the results of long-term laboratory studies that assess
chronic effects are: (1) LOAEC (birds, fish, and aquatic invertebrates),
and (2) NOAEC (birds, fish and aquatic invertebrates). For birds and
mammals, the NOAEC generally is used as the ecotoxicity test value in
assessing chronic effects, although other values may be used when
justified. However, the NOAEC is used if the measurement endpoint is
production of offspring or survival.

Risk Presumptions for Terrestrial Animals

Risk Presumption	

RQ	

LOC

Birds and Wild Mammals

Acute Risk	

EEC1/LC50 or LD50/sqft2 or LD50/day3	

0.5

Acute Restricted Use	

EEC/LC50 or LD50/sqft or LD50/day (or LD50 < 50 mg/kg)	

0.2

Acute Endangered Species	

EEC/LC50 or LD50/sqft or LD50/day 	

0.1

Chronic Risk	

EEC/NOAEC	

1

 1  abbreviation for Estimated Environmental Concentration (ppm) on
avian/mammalian food items   

 2    mg/ft2             	3  mg of toxicant consumed/day

   LD50 * wt. of bird             	LD50 * wt. of bird  

Risk Presumptions for Aquatic Animals	 

Risk Presumption	

RQ 	

LOC

Acute Risk	

EEC1/LC50 or EC50	

0.5

Acute Restricted Use	

EEC/LC50 or EC50	

0.1

Acute Endangered Species	

EEC/LC50 or EC50	

0.05

Chronic Risk	

EEC/MATC2 or NOAEC	

1

 1  EEC = (ppm or ppb) in water

 2  MATC = maximum allowable toxicant concentration

Risk Presumptions for Plants	

	

Risk Presumption	

RQ	

LOC

Terrestrial and Semi-Aquatic Plants 

Acute Risk	

EEC/EC25	

1

Acute Endangered Species	

EEC/EC05 or NOAEC	

1

Aquatic Plants

Acute Risk	

EEC1/EC50	

1

Acute Endangered Species	

EEC/EC05 or NOAEC 	

1

EEC = (ppb/ppm) in water 

Triclosan was found in approximately 36 US streams (Klopin et al.,
2002), where effluent from activated sludge waste water treatment
plants, trickle down filtration, and sewage overflow are thought to
contribute to the occurrence of triclosan in open water. For this study,
the U.S. Geological Survey surveyed a network of 139 streams across 30
states during 1999 and 2000.  The selection of sampling sites was biased
toward streams susceptible to contamination (i.e. downstream of intense
urbanization and livestock production). The median concentration of
triclosan was 140 ng/L and the maximum concentration detected was 2300
ng/L (Klopin et al., 2002). Discharge into U.S. surface waters has
resulted in other researchers finding triclosan from the low ng/L levels
to a maximum of 2.3 µg/L (U.S. EPA, 2007).

From the toxicity tables in section I above, the highest toxicity in an
acceptable fish study was achieved in a study on the rainbow trout
(Oncorhynchus mykiss).  The LC50 value obtained in this study was 0.288
mg/L (MRID 439693-01).  There were no acceptable acute toxicity studies
for freshwater invertebrates or estuarine and marine organisms nor were
there any acceptable chronic toxicity studies available for aquatic
organisms.  Therefore, risk to these species cannot be assessed.  The
highest toxicity in an acceptable aquatic plant toxicity study was
achieved in a study on the bluegreen cyanobacteria (Anabaena
flos-aquae).  The EC50 value obtained in this study was 0.0012 mg/L and
no NOEC was reported (MRID 444228-01).   

For aquatic animals the LOC ranges from 0.05 for endangered species to 1
for chronic risks.  Comparing the maximum concentration of triclosan
found in US streams (280 ng/L or 0.00028 mg/L) to the highest toxicity
found in a fish acute study (0.288 mg/L), an RQ of 0.00097 is obtained. 
This is less than all LOCs for aquatic animals and therefore the
potential for triclosan to cause adverse effects on fish is not high.

 For aquatic plants the LOC is 1.  Comparing the maximum concentration
of triclosan found in US streams (2.3 µg/L or 0.0023 mg/L) to the
highest toxicity found in aquatic plants (0.0012 mg/L), an RQ of 1.92 is
obtained.  This is higher than the LOC and therefore the potential for
acute risk to aquatic plants from triclosan exists.  An evaluation of
the effects of triclosan on natural freshwater algae located above and
below a wastewater treatment plant indicates that a concentration of
0.00015 mg/L caused a significant reduction in Chlamydomonas sp. (RQ of
15.33).  This is considered supplemental data, but points to the need
for further research on shifts in algal communities, reductions in
biomass, and effects on higher trophic levels (Wilson et al., 2003).  A
meta-analysis of literature, plus exposure modeling were used to conduct
a probabilistic assessment of triclosan.  This analysis sheds light on
the difficulties associated with relating laboratory data to field
effects and concludes that additional studies may be needed to refine
scientific knowledge of metabolites and degradates, bioaccumulation
factors, endocrine-related effects, and community level impacts.  The
exposure models used in this study (GREAT-ER and PhATE) have not been
peer reviewed by the Agency (Capdevielle et al., 2008).  

The triclosan degradation product methyl triclosan was studied by the
National Oceanic and Atmospheric Administration’s (NOAA) Hollings
Marine Laboratory to assess it’s toxicity to the estuarine organisms
grass shrimp (Paleamonetes pugio), bioluminescent bacterium (Vibrio
fischeri), and the phytoplankton Dunaliella tertiolecta.  Methyl
triclosan is believed to be more persistent in the environment that its
parent and have a higher potential to bioaccumulate since it is more
lipophilic.  However, mechanisms of transformation (and subsequent
uptake) if by microbes in the gut or in the seawater, are unclear
(DeLorenzo et al, 2007).  Uncertainties exist as to the potential for
triclosan degradates to contribute to acute and/or chronic impacts on
aquatic organisms and ecosystems.

Risk Quotients – Based On Consumer Environmental Modeling

For a full discussion of the assumptions, approaches, and techniques
used in the Agency’s consumer environmental modeling effort for
triclosan, the reader is referred to the Appendix  of the Triclosan
Ecological Hazard and Environmental Risk Assessment Chapter entitled
“Estimates of Exposures and Risks To Aquatic Organisms From Releases
of Triclosan to Surface Water as a Result of Uses Under EPA’s
Jurisdiction” and the environmental fate chapter for triclosan.  These
documents discuss in detail how the Agency performed this modeling
effort.  The conclusions of this consumer environmental modeling are
summarized here.

	

Consumer Environmental Modeling Results:  As outlined in the Appendix,
the Agency performed screening level environmental modeling and
concluded that, if all of the triclosan produced annually for
antimicrobial uses is released to surface water as a result of consumer
uses, then:

Aquatic Animals:  Estimated concentrations of triclosan in surface water
do not exceed concentrations of concern for acute risk presumptions for
aquatic animals.  (See Appendix, Table 2.)

Aquatic Animals:  Estimated concentrations of triclosan in surface water
do not exceed concentrations of concern for endangered species risk
presumptions for aquatic animals.  (See Appendix, Table 3.)

Aquatic Vascular Plants:  Estimated concentrations of triclosan in
surface water do not exceed concentrations of concern for endangered
species risk presumptions for aquatic vascular plants (e.g., duckweed,
Lemna gibba).  (See Appendix, Table 4.)

Aquatic Non-Vascular Plants:  Estimated concentrations of triclosan in
surface water do exceed concentrations of concern for acute risk
presumptions for species that represent non-vascular freshwater plants
(i.e., algae).  The number of days of exceedance of the concentration of
concern is 1 day for blue-green algae, 5 days for green algae, and 57
days for Chlamydomonas sp.  (See Appendix, Table 4.)

Adjustments to Consumer Environmental Modeling Results:  As indicated
above, the Agency performed this environmental modeling in an effort to
estimate:

(1) Concentrations of triclosan in surface water [from antimicrobial
uses of triclosan (e.g., triclosan-treated plastic and textile items in
households) to which aquatic organisms may be exposed as a result of
potential releases of triclosan from these consumer uses; and

(2) Number of days per year that the concentration of triclosan in
surface water exceeds the concentration of concern for aquatic
organisms.

A critical assumption in this screening level, modeling analysis was
that all of the triclosan produced annually for antimicrobial uses is
released to surface water as a result of consumer uses.  That is, 100 %
of all triclosan produced annually is released into household wastewater
during washing and rinsing of products treated with triclosan as a
materials preservative or as a functional component.

However, in an effort to check this 100 % release value used above for
consumer scenarios, EPA reexamined available textile leaching data and
determined that the 100 % assumption (for release of triclosan into
household wastewater) is highly unlikely.  Specifically, available data
for textile leaching of triclosan indicate that triclosan leaches from a
variety of fabrics in the range of 0.00 % to 0.55 %. 

Endangered Species Consideration

Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2),
requires all federal agencies to consult with the National Marine
Fisheries Service (NMFS) for marine and anadromous listed species, or
the United States Fish and Wildlife Services (FWS) for listed wildlife
and freshwater organisms, if they are proposing an "action" that may
affect listed species or their designated habitat.  Each federal agency
is required under the Act to insure that any action they authorize,
fund, or carry out is not likely to jeopardize the continued existence
of a listed species or result in the destruction or adverse modification
of designated critical habitat.  To jeopardize the continued existence
of a listed species means "to engage in an action that reasonably would
be expected, directly or indirectly, to reduce appreciably the
likelihood of both the survival and recovery of a listed species in the
wild by reducing the reproduction, numbers, or distribution of the
species." 50 CFR. ( 402.02.

To facilitate compliance with the requirements of the Endangered Species
Act subsection (a)(2) the Environmental Protection Agency, Office of
Pesticide Programs has established procedures to evaluate whether a
proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed
species in the wild by reducing the reproduction, numbers, or
distribution of any listed species (U.S. EPA 2004).  After the
Agency’s screening-level risk assessment is performed, if any of the
Agency’s Listed Species LOC Criteria are exceeded for either direct or
indirect effects, a determination is made to identify if any listed or
candidate species may co-occur in the area of the proposed pesticide
use.  If determined that listed or candidate species may be present in
the proposed use areas, further biological assessment is undertaken. 
The extent to which listed species may be at risk then determines the
need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.

For certain use categories, the Agency assumes there will be minimal
environmental exposure, and only a minimal toxicity data set is required
(Overview of the Ecological Risk Assessment Process in the Office of
Pesticide Programs U.S. Environmental Protection Agency - Endangered and
Threatened Species Effects Determinations, 1/23/04, Appendix A, Section
IIB, pg.81).  Chemicals in these categories therefore do not undergo a
full screening-level risk assessment, and are considered to fall under a
no effect determination.   

A preliminary analysis indicates that there is a potential for triclosan
use to overlap with listed species and that a more refined assessment is
warranted, to include direct, indirect and habitat effects.  The more
refined assessment should involve clear delineation of the action area
associated with proposed use of triclosan and best available information
on the temporal and spatial co-location of listed species with respect
to the action area.  This analysis has not been conducted for this
assessment.  An endangered species effect determination will not be made
at this time.  

INCIDENT REPORT ASSESSMENT	

 The Following databases were consulted for poisoning incidence data on
OPP: 

Office of Pesticides Programs (OPP) Incident Data System (IDS)

Poison Control Centers

California Department of Pesticide Regulations

National Pesticide Telecommunications Network (NTPT)

Published Scientific Literature on Incidences

9.1	OPP’s Incident Data System (IDS)		

 There were no reported incidents from examination of this database. 

9.2	Poison Control Center	

 There were no reported incidents from examination of this database

9.3	California Data- 1982-through 2003.			

 There were no reported incidents from examination of this database

    National Pesticide Telecommunications Network (NPTN) 		

 

There were no reported incidents from examination of this database

Hazardous Substances Data Bank (HSDB) 

 

There were no reported incidents from examination of this database.

10.0  References

Ecotox   SEQ CHAPTER \h \r 1 REFERENCES

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An AD Memo by Tim McMahon  to Jess Rowland, Executive Secretary for
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Calculations reported by Bob Quick in an AD   Memo by Bob Quick to Bob
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Project Number: CB 92/28.  Unpublished study prepared by Ciba-Geigy Ltd.
70p.

MRID 44389704: Henderson, L.M., et al.  (1988) An Assessment of the
Mutagenic Potential of Triclosan Using the Mouse Lymphoma TK Locus
Assay.  Huntingdon Research Center Ltd., Huntingdon, Cambridgeshire,
PE18 6ES, England. Study No. ULR 216/88644. Unpublished.

MRID 44389705: Stankowski, L.F., Jr. et al. (1993) Amended Final Report,
Ames/Salmonella Plate Incorporation Assay on Test Article 39316 (CC
#14663-09).  Pharmakon USA, P.O. Box 609, Waverly, PA.  Laboratory Study
Report No. PH 301-CP-001-93.  Unpublished.

MRID 44389706: Thomas, Rer. Nat. H. (1994) The Effect of FAT 80’023/Q
and the Model Inducers Phenobarbitone, 3-Methylcholanthrene,
Pregnenolone 16 ∞ -carbonitrile and Nafenopin on Selected Biochemical
and Morphological Liver Parameters in the Syrian Hamster.  Study
conducted by Ciba-Geigy Limited.  Study number CB 93/40.  Unpublished.

MRID 44389707: Thevenaz, Dr. Phil.  (1987) Final Report: FAT 80023:
28-Day Toxicity Study in Mice (Administration in Feed) with Special
Reference to Histopathology.  Ciba-Geigy Ltd., Basle, Switzerland.
Unpublished.

MRID 44389708: Burns, J.M. (1997) 14-Day Repeated Dose Dermal Study of
Triclosan in CD-1 Mice.  Corning Hazleton Incorporated (CHV), 9200
Leesburg Pike, Vienna, Virginia.  Laboratory Study No. CHV 2763-100. 
April 29, 1997.  Unpublished. 

MRID 44389710: Burns, J.M. (1997) 14-Day Repeated Dose Dermal Study of
Triclosan in Rats.  Corning Hazleton Incorporated (CHV), 9200 Leesburg
Pike, Vienna, Virginia.  Laboratory Study No. CHV 6718-102. 
Unpublished.

MRID 44874001, 44751101: Chambers, P.R. (1999) “Potential Tumorigenic
and Chronic Toxicity Effects in Prolonged Dietary Administration to
Hamsters.”  Huntingdon Life Sciences Ltd., Huntingdon, England. CBG
756/972896.

MRID 45307501, 45307502:  Van Dijk, Dr. A. (1994) “14C- Triclosan:
Absorption, Distribution, Metabolism, and Elimination after
Single/Repeated Oral and Intravenous Administration to Hamsters.”  RCC
Umweltchemie AG.  RCC Project No. 351707.  

MRID 45307503:  Van Dijk, Dr. A. (1995) “14C- Triclosan: Absorption,
Distribution, Metabolism, and Elimination after Single/Repeated Oral and
Intravenous Administration to Mice.”  RCC Umweltchemie AG.  RCC
Project No. 337781.  

Tox Record No. 001955, 001956 (1968) 

Tox Record No. 001968 (1977)  

Allmyr, M.; McLachlan, MS; Sandborgh-Englund, G.; and Adolfsson-Erici,
M. 2006. Determination of Triclosan as Its Pentafluorobenzoyl Ester in
Human Plasma and Milk Using Electron Capture Negative Ionization Mass
Spectrometry.  Anal. Chem. 2006, 78, 6542-6546. 

Capen, C. Toxic Responses of the Endocrine System. In: Casarett and
Doull’s Toxicology: The Basic Science of Poisons, 5th ed., Curtis D.
Klaassen, Ph.D., editor. McGraw-Hill. 

Crofton, KM; Paul, KB; DeVito, PB; Hedgea, JH.  2007.  Short-term in
vivo exposure to the water contaminant triclosan: Evidence for
disruption of thyroxine.  Environmental Toxicology and Pharmacology 24:
194–197. 

Flaherty, C.M. and S.I. Dodson. (2005). Effects of pharmaceuticals on
Daphnia survival, growth, reproduction. MRID to be assigned.
Chemosphere. 61: 200-207.	 

Hanioka, N. et. al. (1996) effect of
2,4,4’-Trichloro-2’-hydroxyphenyl Ether on Cytochrome P450 Enzymes
in the Rat Liver. MRID to be added. Chemosphere. 34: 719-730.   

Hovander, L. et. al. (2001). Identification of Hydroxylation PCB
Metabolites and Other Phenolic Halogenated Pollutants in Human Blood
Plasma. MRID to be added. Environmental Contamination and Toxicology.
42: 105-117.  

Ishibashi, H.; Matsumura, N.; Hirano, M.; Matsuoka, M.; Shiratsuchi, H.;
Ishibashi, Y.; Takao, Y.; and Arizono, K. 2004. Effects of triclosan on
the early life stages and reproduction of medaka Oryzias latipes and
induction of hepatic vitellogenin. Aquatic Toxicology 67:167–179 

Matsumura, N.; Ishibashi, H.; Hirano, M.; Nagao, Watanabe N;
Shiratsuchi, H; Kai, T;  Nishimura, T.; Kashiwagi,  A.. and Arizono,  K.
2005. Effects of nonylphenol and triclosan on production of plasma
vitellogenin and testosterone in male South African clawed frogs
(Xenopus laevis).Biol. Pharm. Bull. 28: 1748–1751. 

Palenske, N.M., Dzialowski, E.M (2005). Effects of the Environmental
Contaminant Triclosan on the Physiology of Developing Xenopus Laevis
Tadpoles. Integrative and Comparative Biology. 45(6): 1175. Published. 

Tamura,H., Y. Ishimoto., T. Fujikawa et al. (2006). Use of Structural
basis for androgen receptor agonists and  Antagonists: Interaction of
SPEED 98-listed chemicals and  Related compounds with the androgen
receptor based on an In vitro reporter gene assay and 3D-QSAR. MRID to
be Assigned. Bioorganic & Medicinal Chemistry. 14:7160-7174.     

Veldhoen, N; Skirrow, RC; Osachoff, H.; Wigmore, H; Clapson, DJ;
Gunderson, MP; Aggelen, GV; Helbing, CC. (2006).  The bactericidal agent
triclosan modulates thyroid hormone-associated gene expression and
disrupts postembryonic anuran development.  Aquatic Toxicology 80:
217–227. 

U.S. EPA 2008). T. E. Stoker and W. Setzer. The Endocrine Disrupting
Effects of Triclosan, a common pharmaceutical and personal care product:
Alteration of the Thyroid Axis Following a Peri-juvenile Exposure in the
Male Wistar Rat. EPA/600/X-08/010. 

Broker, P.C., Gray, V.M., Howell, A.  (1988)  “Analysis of Metaphase
Chromosomes Obtained from CHO Cells Cultured in vitro and Treated with
Triclosan.” Huntingdon Research Center, Ltd. ULR 214/88731; Unilever
Test #: KC880171. Unpublished.

Eldrige, S. (1995) Cell Proliferation in Rodent Liver.  Study conducted
by Pathology Associates, Inc. Submitted to EPA (no MRID). Unpublished.

     

San Sebastian, J.R., Morgan, J.M. (1993) “Rat Hepatocyte Primary
Culture/DNA Repair Test on 39317” Pharmakon Research International,
Inc. Pharmakon Study #: PH311-CP-001-93.  Unpublished.  

See, Norman A.  (1996) Review and Evaluation of Pharmacology and
Toxicology Data Division of Dermatologic and Dental Drug Products
(HFD-540) Food and Drug Administration.

Human Exposure REFERENCES

Calafat AM, Ye X, Wong LY, Reidy JA, and Needham LL.  2007.  Urinary
Concentrations of Triclosan in the U.S. Population:  2003-2004. 
Environmental Health Perspectives.  Dated December 7, 2007.  Available
online at   HYPERLINK "http://dx.doi.org"  http://dx.doi.org /

Cauosa (2007).  Determination of Parabens and Triclosan in Indoor Dust
Using Matrix Solid-Phase Dispersion and Gas Chromatography with Tandem
Mass Spectrometry.  Anal. Chem. 2007, 79, 1675-1681.

Cohen J.  2008.  Computations of Human Triclosan Dose Based On NHANES
Urine Concentrations.  Memorandum from Dr. Jonathan Cohen, ICF
International to Tim Leighton, David Miller, Philip Villaneuva, USEPA,
dated March 6, 2008.  Contract EP-W-06-091, WA 0-02, TAF CM 19.  

Dayan AD.  2007.  Risk assessment of triclosan [Irgasan] in human breast
milk.  Food and Chemical Toxicology 45 (2007) 125-129.

DOE.  1997.  Energy Information Administration: Profile of Commercial
Buildings in 1995. 
http://www.eia.doe.gov/emeu/cbecs/char95/profile.html

  SEQ CHAPTER \h \r 1 Freeman, N , Jimenez M, Reed KJ,Gurunathan S,
Edwards RD, Roy A, Adgate JL, Pellizzari ED, Quackenboss J, Sexton K,
Lioy PJ, 2001.  Quantitative analysis of chilren’s microactivity
patterns:  The Minnesota Children’s Pesticide Exposure Study.  Journal
of Exposure Analysis and Environmental Epidemiology.  11(6): 501-509.

Geigy. 1981. Geigy Scientific Tables, Volume 1. Units of measurement,
body fluids, composition of the body, nutrition. Eighth edition. (Edited
by C. Lentner). CIBA-GEIGY.

Mage D.T., Allen R., Gondy G., Smith W., Barr D.B., Needham L.L. 2004.
Estimating Pesticide Dose from Pesticide Exposure Data by Creatinine
Correction in the Third National Health and Nutrition Examination Survey
(NHANES-III). J Exposure Anal Environ Epidemiol 14:457-465.

Mage D.T., Allen, R.H., Kodali, A. 2007. Creatinine corrections for
estimating children’s and adult’s pesticide intake doses in
equilibrium with urinary pesticide and creatinine concentrations. J
Exposure Sci Environ Epidemiol 1-9.  

Sandborgh-Englund G, Adolfsson-Erici M, Odham G, and Ekstrand J.  2006. 
Pharmacokinetics of Triclosan Following Oral Ingestion in Humans. 
Journal of Toxicology and Environmental Health, Part A, 69:1861-1873,
2006.

Schafer, K.S,, Reeves, M., Spitzer, S., Kegley, S. E. 2004. Chemical
Trespass: Pesticides in Our Bodies and Corporate Accountability. 
Pesticide Action Network North America. May 2004.

USEPA. 1996.  Office of Research and Development, Descriptive Statistics
Tables from a Detailed Analysis of the National Human Activity Pattern
(NHAPS) Data; EPA/600/R-96/148, July 1996.   Data Collection Period
October 1992 - September 1994 . 

USEPA.  1997.  Exposure Factors Handbook. Volume I-II.  Office of
Research and Development.  Washington, D.C.  EPA/600/P-95/002Fa. August
1997.

USEPA. 1998. PHED Surrogate Exposure Guide. Estimates of Worker Exposure
from the Pesticide Handler Exposure Database Version 1.1.   Washington,
DC:  U.S. Environmental Protection Agency.

  SEQ CHAPTER \h \r 1 USEPA. 1999.  Evaluation of Chemical Manufacturers
Association Antimicrobial Exposure Assessment Study (Amended on 8
December 1992).  Memorandum from Siroos Mostaghimi, PH.D., USEPA to
Julie Fairfax, USEPA. Dated November, 4 1999.  DP Barcode D247642.

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icide Programs, Human Health Effects Division. Dated April 5, 2000.

USEPA.  2001.  HED Science Advisory Council for Exposure. Policy Update,
November 12.  Recommended Revisions to the Standard Operating Procedures
(SOPs) for Residential Exposure Assessment, February 22, 2001.

USEPA.  2002. CHILD-SPECIFIC EXPOSURE FACTORS HANDBOOK (INTERIM REPORT).
USEPA EPA-600-P-00-002B. 01 Sep 2002. U.S. Environmental Protection
Agency, Office of Research and Development, National Center for
Environmental Assessment, Washington Office, Washington, DC, 448.

USEPA.  2005.  Guidance on Selecting Age Groups for Monitoring and
Assessing Childhood Exposures to Environmental Contaminants.  Risk
Assessment Forum, U.S. Environmental Protection Agency, November 2005. 
EPA/630/P-03/003F.

USEPA.  2007.  5-Chloro-2-(2,4-dichlorophenoxy)phenol (triclosan):
Toxicology Chapter for the Reregistration Eligibility Decision (RED)
document.

Product Chemistry References

42027901	LoMenzo, J. (1991) Irgasan DP 300: Product Identity and
Composition. Unpublished study prepared by Ciba-Geigy Corp.

42027902	Basingthwaite, J. (1983) Irgasan DP 300: Batch Analysis and
Analytical Methodology. Unpublished study prepared by Ciba-Geigy Ag.

42027904	Vogel, A. (1990) Irgasan 300 DP: Report on Melting
Point/Melting Range. Unpublished study prepared by Ciba-Geigy Ltd.

43022601	Morrissey, M. (1993) Stability Determination of Irgasan DP 300
in the Presence of Metal: Final Report: Lab Project Number: HWI
6117-246. Unpublished study prepared by Hazleton Wisconsin, Inc.

43277801	Morrissey, M. (1994) Stability Determination of Irgasan DP300
Exposed to Metal Ions: Final Report: Lab Project Number: HWI 6117-261.
Unpublished study prepared by Hazleton Wisconsin, Inc.

43277802	Schatowitz, B. (1990) Additional Data Required by the US EPA
for the Results of the Analysis of Irgasan DP300 for Dioxins/Furans: Lab
Project Number: 102290. Unpublished study prepared by Ciba-Geigy Ltd.

43533901	Schatowitz, B. (1995) Additional Data Required by the U.S. EPA
for the Product Analysis of Irgasan DP 300: Lab Project Number: 11995.
Unpublished study prepared by Ciba Research Services.

 As discussed in the revised triclosan environmental fate chapter, only
acute concentrations of concern were evaluated for aquatic organisms
since acceptable chronic aquatic data are not available.  However,
considering the low probability of triclosan being released into
household wastewater and surface waters, EPA also concludes that chronic
aquatic risks are unlikely from consumer uses of triclosan-treated
plastic and textile items.

  EPA assumes that leaching values for plastic are of the same magnitude
as for textile products.  Note that the Agency used the 0.55 % leaching
value in its evaluation for children who may mouth (incidental oral
ingestion) plastic items (e.g., toys).

 The Agency is making this statement because triclosan and triclosan
transformation products are being detected in various environmental
components (see triclosan environmental fate chapter).

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