Document ID: EPA-HQ-OPP-2007-0513-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-05-07T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

  AND TOXIC SUBSTANCES

MEMORANDUM

DATE:		April 17, 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. 

 PC Code: 054901.   DP Barcode: 373535

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 Preliminary 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, July 2007  

Triclosan: Occupational and Residential Exposure Assessment.  From
Timothy Leighton, Exposure/Risk Assessor, to Tim McMahon,  Ph.D., July
2007.

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.

Environmental Fate Science Chapter for the Triclosan  Reregistration
Eligibility Decision Doocument. From Srinivas Gowda, Microbiologist/
Chemist,  to  Mark Hartman, Branch Chief,  July 2007.  

 Ecological Hazard and Environmental Risk Assessment Chapter. From
Genevieve Angle, Biologist, July 2007. 

  

Epidemiology Assessment based on Incident Reports.  From J. Chen, Ph.D.
Toxicologist, to Tim McMahon, Ph.D. Toxicologist, July 2007.TABLE OF
CONTENTS

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

2.0 PHYSICAL/CHEMICAL PROPERTIES
--------------------------------------------------------------------13
3.0 HAZARD CHARACTERIZATION
------------------------------------------------------------------------
-   14 

3.1   Hazard Profile
------------------------------------------------------------------------
--------14

3.2  Dose-Response Assessment 
----------------------------------------------------------------15

3.3  FQPA
Considerations----------------------------------------------------------
---------------17

3.4  Endocrine Disruption
------------------------------------------------------------------------
-17

4.0  EXPOSURE ASSESSMENT AND  CHARACTERIZATION
------------------------------------------18

 

 

5.0	AGGREGATE RISK ASSESSMENT AND RISK CHARACTERIZATION
------------------18

5.1   NHANES Data for Triclosan----------------
-----------------------------------------------------19

5.1.1  NHANES Data and Dose Conversion--------
-------------------------------------------19

5.1.2  Pharmacokinetics of
Triclosan-------------------------------------------------------------21

5.1.3 
Uncertainties-----------------------------------------------------------
-----------------------22

5.2  Aggregate
Risks-------------------------------------------------------------------
-------------------22

6.0	Cumulative
Risk--------------------------------------------------------------------
---------------------------27

7.0      OCCUPATIONAL EXPOSURE
------------------------------------------------------------------------
----28

7.1  Occupational Postapplication Exposure
---------------------------------------------------30

7.2   Data Limitations/uncertainties
--------------------------------------------------------------30

ENVIRONMENTAL RISK
------------------------------------------------------------------------
------------31

8.1 Ecological
Hazard------------------------------------------------------------------
-----------31

8.2 Environmental fate and
transport------------------------------------------------------------37

8.3 Environmental exposure and
Risk-----------------------------------------------------------38

8.4 Endangered
Species-----------------------------------------------------------------
-----------40

Incident Report Assessment
------------------------------------------------------------------------
------------42

9.1  OPP Incident Data
System------------------------------------------------------------------
-42

9.2   Poison Control
Center------------------------------------------------------------------
------42

9.3  California Data
1982-2003---------------------------------------------------------------
----42

9.4   National Telecommunication Pesticide
Network----------------------------------------42

9.5  Hazardous Substances Data Bank
----------------------------------------------------------42

   
References--------------------------------------------------------------
------------------------------------------43

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 using population-based biological monitoring
data to assess the co-occurrence of uses to develop an aggregate
exposure assessment.  

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. 

On July 25, 2007, the Health Effects Division’s Carcinogenicity
Assessment Review Committee met to discuss the carcinogenicity
classification for triclosan and additional data submitted conducted
with triclosan in support of a mode of action involving peroxisome
proliferation as a causative factor in the positive tumorigenic results
observed in the mouse carcinogenicity study.  In accordance with the EPA
Final Guidelines for Carcinogen Risk Assessment (March 29, 2005), the
CARC classified triclosan as “Not Likely to be Carcinogenic to
Humans”.  This decision is based on the weight-of-evidence that
supports activation of peroxisome proliferator-activated receptor alpha
(PPARά) 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. 

FQPA Considerations

There are no food use tolerances for triclosan. Therefore, a formal FQPA
analysis is not needed for this chemical. However, in light of
residential exposures to triclosan, the ADTC did note that there was no
evidence for neurotoxicity of triclosan in the submitted toxicology
database. The data provided no indication of increased sensitivity of
rats or rabbits to in utero and post-natal exposure to triclosan.  Two
prenatal developmental toxicity studies, one in rats and one in rabbits,
failed to show 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. 

Exposure and Risk

Based on a review of EPA product labels, triclosan is the active
ingredient in products used in paints, textiles (mattresses and
clothing) and plastic toys,  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 aggregate assessment accounts for non-EPA
regulated uses of triclosan. Non-EPA uses include FDA uses such as
toothpaste, hand soaps, and deodorants. 

Although individual EPA-regulated uses have been assessed using standard
Agency methodology, the NHANES biological monitoring data is available
for assessing aggregate exposure and risk. Therefore, the supporting
human exposure chapter for the triclosan RED characterized exposures
from individual EPA-regulated uses but was not needed for the aggregate
risk assessment. EPA views the NHANES data as more representative of
aggregate exposures than determining probability of co-occurrence of

EPA and FDA-regulated uses. 

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).

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 results of the NHANES
data indicate that 74.6% of the samples had detectable levels of total
(free plus conjugated) triclosan.  Tables and  provide the mean and 99th
percentiles, respectively, of the (1) spot urine concentration to dose
conversion (in units of ug/kg); (2) the pharmacokinetic 54% corrected
daily dose; and (3) the MOEs for the three conversion methods. 
Aggregate exposures and risks are presented for several age groups (all
ages combined, ages 6-11, 12-19, 20-59, >=60, Mexican-American, White
non-Hispanic, and Black non –Hispanic). 

Based on the results at the mean and 99th percentile, the aggregate
risks to triclosan from all uses (EPA and FDA) do not trigger a risk of
concern.  The mean MOEs range from 4,700 to 19,000.  The MOEs at the
99th percentile range from 260 to 1,500.  In fact, applying the lowest
(most conservative) percent excreted from the results of the
pharmacokinetic data (i.e., 24 percent) to the most conservative dose
conversion method (i.e., 24-hour urine void extrapolation assuming the
upper percentile of daily urine volumes), the MOE is 120.

Occupational Exposure

 Triclosan 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
product.  

For intermediate-term dermal risks, the MOEs were above the target MOE
of 100, and therefore, not of concern except for commercial painters and
material preservative use for paper.  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 of 1000   except for the brush
application for paints.  The inhalation MOE for commercial use of an
airless sprayer for paints is is 54, for liquid pour and liquid pump
during paint manufacturing 330 and 290, respectively, and for pulp and
paper the metering pump is 28.

 Based on the low vapor pressure of triclosan and application methods,
inhalation post-application exposure 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
(MRID 420279-08).  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
(MRID 430226-08).  One major transformation product was identified, DCP
(2,4-dichlorophenol), which was a maximum of 93.8-96.6% of the applied
triclosan at 240 minutes post-treatment.

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 40
ng/L and the maximum concentration detected was 280 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).

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 to develop risk quotients (RQs) and
compare them to levels of concern (LOCs) for triclosan.  LOCs were not
exceeded for fish or 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. 

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 2-1a 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 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.  On July
25, 2007, the Health Effects Division Carcinogenicity Assessment Review
Committee met and classified triclosan as “not likely to be
carcinogenic to humans (HED TXR # 0054799). A summary of the selected
endpoints is shown in  table 2 below. 

 

Exposure

Scenario	Dose Used in Risk Assessment, UF 	Special FQPA SF* and Level of
Concern for Risk Assessment	Study and Toxicological Effects

Acute Dietary

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

UF = 100

aRfD = 0.03 mg/kg/day	FQPA SF = 1x	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

UF = 100

cRfD = 0.03 mg/kg/day	FQPA SF = 1x	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

	 MOE = 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)

  	

MOE = 100	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

UF = 100

	FQPA SF = 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

UF = 100

	FQPA SF = 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.

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)	Not likely to be carcinogenic to humans (Health Effects
Division Carcinogenicity Assessment Review Committee, July 2007).

UF = uncertainty factor, DB UF = data base uncertainty factor, FQPA SF =
special FQPA safety 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 

 

FQPA Considerations

 There are no food use tolerances for triclosan. Therefore, a formal 
FQPA analysis is not needed for this chemical. However, in light of
residential exposures to triclosan, the ADTC did note that there was no
evidence for neurotoxicity of triclosan in the submitted toxicology
database. The data provided no indication of increased sensitivity of
rats or rabbits to in utero and post-natal exposure to triclosan.  Two
prenatal developmental toxicity studies, one in rats and one in rabbits,
failed to show 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. 

 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).

When the appropriate screening and/or testing protocols being considered
under the Agency’s EDSP have been developed, triclosan may be
subjected to additional screening and/or testing to better characterize
effects related to endocrine disruption.

 

 EXPOSURE ASSESSMENT AND CHARACTERIZATION

Based on a review of EPA product labels, triclosan is the active
ingredient in products used in paints, textiles (mattresses and
clothing) and plastic toys,  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 aggregate assessment accounts for non-EPA
regulated uses of triclosan.  Non-EPA uses include FDA uses such as
toothpaste, hand soaps, and deodorants. 

Although individual EPA-regulated uses have been assessed using standard
Agency methodology, the NHANES biological monitoring data are available
for assessing aggregate exposure and risk. Therefore, the supporting
human exposure chapter for the triclosan RED characterized exposures
from individual EPA-regulated uses but was not needed for the aggregate
risk assessment.  EPA views the NHANES data as more representative of
aggregate exposures than determining probability of co-occurrence of

EPA and FDA-regulated uses.  Specific discussion of the individual
EPA-regulated uses have been assessed using standard Agency methodology
and are presented in the Occupational and Residential Exposure chapter.

	5.0 AGGREGATE RISK ASSESSMENT 

 In order for a pesticide registration to continue, it must be shown
that the use does not result in “unreasonable adverse effects on the
environment”.   Even though no pesticide tolerances have been
established for triclosan, 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 expected to be 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.

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.  Nonetheless, uncertainties in
the biological monitoring data also need to be addressed. Converting
spot urine concentrations to estimated 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

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
(1) the relatively large data set obtained from NHANES; (2) assumptions
used by Cohen (2008) for the dose conversion; (3) the characterization
of the dose at the lowest (most conservative) urinary excretion; (4) the
short urinary excretion half life 11 hours; and (5) the inclusion 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.  

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.  The
urinary excretion half life for triclosan is reported in the text of the
study (not taken from the graph) as 11 hours.

The urinary excretion of triclosan presented in Sandborgh-Englund (2006)
is highly variable (ranging from 24 to 83 percent).  The median value
reported of 54% urinary excretion has been used by EPA in the dose
estimates.  Additionally, to further characterize the uncertainty in the
urinary excretion, risks are also discussed using the full range of
urinary excretion values.  

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.  In order to determine
how sensitive the estimated dose was to urinary excretion volume, one of
the dose conversion methods (Geigy 1981 95% urine volume upper bound
estimate) is used to estimate a 24 hour urinary excretion 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.  However, the unique
aspects of triclosan -- short half life in urine and widespread daily
use of triclosan products – lend themselves to represent long-term
measurements of exposure from a nationally representative population
sample such as NHANES. 

5.2	Acute, Short-term, Intermediate-term, and Chronic Aggregate Risks 
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

The three basic conversion methods used in this risk characterization
are (1) Mage et al (2007) with an obesity correction factor; (2) Schafer
et al (2004) using actual body weights from subjects; and (3) Geigy
(1981) values for both a mean and 95th percentile of daily urine
excretion volume.  Based on the results at the mean and 99th percentile
of the dose, the aggregate risks to triclosan from all uses (EPA and
FDA) do not trigger a risk 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 1,500.  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 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 5.1.  Acute, Short, Intermediate-, and Long-term Aggregate Risks
for Triclosan (Mean)

Groups	Method:

Mage (2007) Obese Correct-based Dose 

[Creatinine Correction]	Method: 

Schafer (2004) Actual BW-based Dose

[Urinary Volume Correction]	

Method:  Geigy 1981 [Urinary Volume Correction]

	Mean Urine Volume-based

Dose	95% Urine Volume-based

Dose

	ug/kg/d	mg/kg/d	MOE	ug/kg	mg/kg/d	MOE	ug/kg	mg/kg/d	MOE	ug/kg/d	mg/kg/d
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 (Mage 2007
is based on creatinine excretion correction and both Schafer (2004) and
Geigy 1981 are based on urine volume excretion corrections).  

Groups (demographics) are based on the available data in NHANES.

Doses in units of ug/kg/day are based on the spot urine conversions to
daily dose without being corrected for the pharmacokinetics of
triclosan.

Doses in units of mg/kg/day = [dose (ug/kg/day) x 0.001 mg/ug unit
conversion] / 0.54 (representing the median urinary excretion of
triclosan of 54%).

Geigy (1981) 95% urine volume is the upper percentile of daily urine
volume.



Table 5.2.  Acute, Short, Intermediate-, and Long-term Aggregate Risks
for Triclosan (99th Percentile)

	Groups	Method:

Mage (2007) Obese Correct-based Dose

[Creatinine Correction]	Method: 

Schafer (2004) Actual BW-based Dose

[Urinary Volume Correction]	Method:  Geigy 1981 [Urinary Volume
Correction]

	Mean Urine Volume-based

Dose	95% Urine Volume-based

Dose

	ug/kg/d	mg/kg/d	MOE	ug/kg/d	mg/kg/d	MOE	ug/kg/d	mg/kg/d	MOE	ug/kg/d
mg/kg/d	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

See Cohen (2008) for details of the dose conversion methods (Mage 2007
is based on creatinine excretion correction and both Schafer (2004) and
Geigy 1981 are based on urine volume excretion corrections).  

Groups (demographics) are based on the available data in NHANES.

Doses in units of ug/kg/day are based on the spot urine conversions to
daily dose without being corrected for the pharmacokinetics of
triclosan.

Doses in units of mg/kg/day = [dose (ug/kg/day) x 0.001 mg/ug unit
conversion] / 0.54 (representing the median urinary excretion of
triclosan of 54%).

Geigy (1981) 95% urine volume is the upper percentile of daily urine
volume.

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.

AD did not perform a cumulative risk assessment as part of this RED for
triclosan because AD has not yet initiated a review to determine if
there are any other chemical substances that have a mechanism of
toxicity common with that of triclosan.

On this basis, the Registrant must submit, upon EPA’s request and
according to a schedule determined by the Agency, such information as
the Agency directs to be submitted in order to evaluate issues related
to whether triclosan shares a common mechanism of toxicity with any
other substance.  If AD identifies other substances that share a common
mechanism of toxicity with triclosan, AD will perform aggregate exposure
assessments on each chemical, and will begin to conduct a cumulative
risk assessment. 

The Health Effects Division, Office of Pesticide Programs, has recently
developed a framework proposed for conducting cumulative risk
assessments on substances that have a common mechanism of toxicity. 
This guidance was issued for public comment on January 16, 2002 (67 FR
2210-2214) and is available from the OPP Website at: 
http://www.epa.gov/pesticides/trac/science/cumulative_guidance.pdf.  In
the guidance, it is stated that a cumulative risk assessment of
substances that cause a common toxic effect by a common mechanism will
not be conducted until an aggregate exposure assessment of each
substance has been completed.

Before undertaking a cumulative risk assessment, AD will follow
procedures for identifying chemicals that have a common mechanism of
toxicity as set forth in the ( Guidance for Identifying Pesticide
Chemicals and Other Substances that Have a Common Mechanism of Toxicity
(64 FR 5795-5796, February 5, 1999).

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 6.2.  Short- and Intermediate-Term Inhalation 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
0.115	1.8	28	22

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.  

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 40 ng/L and the maximum concentration detected was 280
ng/L (Klopin et al., 2002).

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 (280 ng/L or 0.00028 mg/L) to the highest
toxicity found in aquatic plants (0.0012 mg/L), an RQ of 0.23 is
obtained.  This is less than the LOC and therefore the potential for
acute risk to aquatic plants from triclosan is not high.

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

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An AD Memo by Tim McMahon  to Jess Rowland, Executive Secretary for
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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)  

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

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.

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.

USEPA.  2000.  Residential SOPs.  EPA Office of Pesticide Programs,
Human Health Effects Division. Dated April 5, 2000.

USEPA.  2001.  HED Science Advisory Council for Exposure. Policy Update,
November 12. 
Rec浯敭摮摥删癥獩潩獮琠⁯桴⁥瑓湡慤摲传数慲楴杮倠
潲散畤敲⁳匨偏⥳映牯删獥摩湥楴污䔠灸獯牵⁥獁敳獳
敭瑮‬敆牢慵祲㈠ⰲ㈠〰⸱ഠ

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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 /

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.  

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.  

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.

 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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