![](media/image1.png){width="0.8402777777777778in"
height="0.8486111111111111in"}**UNITED STATES ENVIRONMENTAL PROTECTION
AGENCY**

WASHINGTON, D.C. 20460

> OFFICE OF

PREVENTION, PESTICIDES

> AND TOXIC SUBSTANCES

[MEMORANDUM]{.underline}

DATE: April 17, 2008

**SUBJECT**: Number range
CHAPTER**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

8.  **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

9.  **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

10. **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/cm^2^) 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/m^3^ 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 C~max~
to 1/8C~max~ 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/cm^2^ by using the
surface area of the applied gauze (2 x 3 cm or 6 cm^2^)) 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/m^3^ (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 99^th^
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 99^th^ 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 99^th^ 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
K**~oc~** 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-m^3^/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 (K~ow~ 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.

Number range CHAPTERFrom 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: C~12~H~7~C~l3~0~2~

Chemical Structure:

![](media/image2.png){width="2.0833333333333335in"
height="0.9722222222222222in"}

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 10^3^ kg/m^3^ at  |
|                                           | 22˚C                     |
+-------------------------------------------+--------------------------+
| Dissociation Constant                     | pK~a~=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 (        | 4.8 at 25˚C              |
| LogK~OW~)                                 |                          |
+-------------------------------------------+--------------------------+
| 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).

+--------+-------------------+-------------+-----------------+--------+
| **Ta   |                   |             |                 |        |
| ble 1. |                   |             |                 |        |
| Acute  |                   |             |                 |        |
| To     |                   |             |                 |        |
| xicity |                   |             |                 |        |
| P      |                   |             |                 |        |
| rofile |                   |             |                 |        |
| for    |                   |             |                 |        |
| Tricl  |                   |             |                 |        |
| osan** |                   |             |                 |        |
+========+===================+=============+=================+========+
| **Gui  | **Study Type/**   | **MRID      | **Results**     | **To   |
| deline |                   | Number/**   |                 | xicity |
| Nu     | **Test substance  |             |                 | Cate   |
| mber** | (% a.i.)**        | *           |                 | gory** |
|        |                   | *Citation** |                 |        |
+--------+-------------------+-------------+-----------------+--------+
| 87     | Acute Oral- Rat   | 43206901    | LD~50~: \>5000  | IV     |
| 0.1100 | Triclosan (99.7%  |             | mg/kg           |        |
|        | a.i.)             |             |                 |        |
| (      |                   |             |                 |        |
| §81-1) |                   |             |                 |        |
+--------+-------------------+-------------+-----------------+--------+
| 87     | Acute Dermal-     | 94044       | LD~50~: \>9300  | IV     |
| 0.1200 | Rabbit            |             | mg/kg           |        |
|        |                   |             |                 |        |
| (      | Triclosan (97%    |             |                 |        |
| §81-2) | a.i.)             |             |                 |        |
+--------+-------------------+-------------+-----------------+--------+
| 87     | Acute Inhalation- | 42306902,   | LC~50~: \>0.15  | II     |
| 0.1300 | Rat               | 43310501    | mg/L            |        |
|        |                   |             |                 |        |
| (      | Triclosan (100.5% |             |                 |        |
| §81-3) | a.i.)             |             |                 |        |
+--------+-------------------+-------------+-----------------+--------+
| 87     | Primary Eye       | 94045       | moderately      | II     |
| 0.2400 | Irritation-       |             | irritating      |        |
|        | Rabbit            |             |                 |        |
| (      |                   |             |                 |        |
| §81-4) | Triclosan (97%    |             |                 |        |
|        | a.i.)             |             |                 |        |
+--------+-------------------+-------------+-----------------+--------+
| 87     | Primary Dermal    | 42306903    | PII: 3.5 at 72  | III    |
| 0.2500 | Irritation-       |             | hours           |        |
|        | Rabbit            |             |                 |        |
| (      |                   |             |                 |        |
| §81-5) | Triclosan (%      |             |                 |        |
|        | a.i.not provided) |             |                 |        |
+--------+-------------------+-------------+-----------------+--------+
| 87     | Dermal            | 43206502    | Not a           | NA     |
| 0.2600 | Sensitization-    |             | Sensitizer      |        |
|        | Guinea Pig        |             |                 |        |
| (      | Triclosan (99.7%  |             |                 |        |
| §81-6) | a.i.)             |             |                 |        |
+--------+-------------------+-------------+-----------------+--------+

####  

2.  **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.

+-------------+-------------+---------------+-------------------------+
| *           | **Dose Used | **Special     | **Study and             |
| *Exposure** | in Risk     | FQPA SF\* and | Toxicological Effects** |
|             | Assessment, | Level of      |                         |
| *           | UF**        | Concern for   |                         |
| *Scenario** |             | Risk          |                         |
|             |             | Assessment**  |                         |
+=============+=============+===============+=========================+
| **Acute     | NOAEL = 30  | FQPA SF = 1x  | Chronic Toxicity study  |
| Dietary**   | mg/kg       |               | in Baboons              |
|             |             |               |                         |
| **(gen.     | UF = 100    |               | MRID 133230             |
| pop.)**     |             |               |                         |
|             | **aRfD** =  |               |                         |
|             | 0.03        |               |                         |
|             | mg/kg/day   |               |                         |
+-------------+-------------+---------------+-------------------------+
| **Acute     | No          |               |                         |
| Dietary**   | appropriate |               |                         |
|             | endpoint    |               |                         |
| **(females  | identified  |               |                         |
| 13+)**      | in the      |               |                         |
|             | database    |               |                         |
+-------------+-------------+---------------+-------------------------+
| **Chronic   | NOAEL = 30  | FQPA SF = 1x  | Chronic Toxicity study  |
| Dietary**   | mg/kg       |               | in Baboons              |
|             |             |               |                         |
| **(all      | UF = 100    |               | MRID 133230             |
| pop         |             |               |                         |
| ulations)** | **cRfD** =  |               | LOAEL = 100 mg/kg/day,  |
|             | 0.03        |               | based on clinical signs |
|             | mg/kg/day   |               | of toxicity             |
+-------------+-------------+---------------+-------------------------+
| **          | NOAEL = 30  | MOE = 100     | Chronic Toxicity study  |
| Short-Term/ | mg/kg       |               | in Baboons              |
| Interm      |             |               |                         |
| ediate-Term |             |               | MRID 133230             |
| Incidental  |             |               |                         |
| Oral (1-30  |             |               | LOAEL = 100 mg/kg/day,  |
| days; 30    |             |               | based on clinical signs |
| days- 6     |             |               | of toxicity             |
| months)**   |             |               |                         |
+-------------+-------------+---------------+-------------------------+
| **Dermal    | NOAEL = 0.6 | MOE = 100     | 14-day dermal toxicity  |
| (sh         | mg/animal   |               | study in the mouse      |
| ort-term)** | (100        |               |                         |
|             | µg/cm^2^)   |               | MRID 44389708           |
|             |             |               |                         |
|             |             |               | LOAEL = 1.5 mg/kg/day,  |
|             |             |               | based on                |
|             |             |               | treatment-related       |
|             |             |               | dermal irritation at    |
|             |             |               | the treatment site and  |
|             |             |               | on increased liver      |
|             |             |               | weights                 |
+-------------+-------------+---------------+-------------------------+
| **Dermal    | NOAEL = 40  | FQPA SF = 1x  | 90-day Dermal Toxicity  |
| (i          | mg/kg       |               | in Rats                 |
| ntermediate |             | MOE = 100     |                         |
| term)**     | UF = 100    |               | MRID 43328001           |
|             |             |               |                         |
|             |             |               | LOAEL = 80 mg/kg/day,   |
|             |             |               | based on increased      |
|             |             |               | incidence occult blood  |
|             |             |               | in the urine.           |
+-------------+-------------+---------------+-------------------------+
| **Dermal    | NOAEL = 40  | FQPA SF = 1x  | 90-day Dermal Toxicity  |
| (l          | mg/kg       |               | in Rats                 |
| ong-term)** |             | MOE = 100     |                         |
|             | UF = 100    |               | MRID 43328001           |
|             |             |               |                         |
|             |             |               | LOAEL = 80 mg/kg/day,   |
|             |             |               | based on increased      |
|             |             |               | incidence occult blood  |
|             |             |               | in the urine.           |
+-------------+-------------+---------------+-------------------------+
|             |             |               |                         |
+-------------+-------------+---------------+-------------------------+
|             |             |               |                         |
+-------------+-------------+---------------+-------------------------+
| *           | NOAEL = 50  | MOE = 1000    | 21-Day Inhalation       |
| *Inhalation | mg/m3 or    |               | Toxicity study in the   |
| (all        | 3.21        |               | rat                     |
| d           | mg/kg/day   |               |                         |
| urations)** |             |               | MRID 0087996            |
|             | Where       |               |                         |
|             | mg/kg/day = |               | LOAEL = 0.115 mg/L,     |
|             | ((0.0087    |               | based on increased      |
|             | m3/hr \*    |               | total leukocyte count   |
|             | mg/m3 \* 2  |               | and increased serum     |
|             | hr/day)     |               | alkaline phosphatase    |
|             | /0.271 b.w. |               |                         |
+-------------+-------------+---------------+-------------------------+
| **Cancer    | Not likely  |               |                         |
| (oral)**    | to be       |               |                         |
|             | c           |               |                         |
|             | arcinogenic |               |                         |
|             | to humans   |               |                         |
|             | (Health     |               |                         |
|             | Effects     |               |                         |
|             | Division    |               |                         |
|             | Carc        |               |                         |
|             | inogenicity |               |                         |
|             | 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

3.  **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.

4.  **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.

4.  **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]{.underline}**

The following information has been excerpted from Cohen (2008). The
National Health and Nutrition Surveys (NHANES) are a series of US
national surveys of the health and nutrition status of the
non-institutionalized civilian population conducted by the Centers for
Disease Control and Prevention. As part of the 2003-2004 NHANES, urinary
concentrations (μg/L) of triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl
ether) were measured on a random sample of 2,517 participants of ages 6
and over. These measurements represent concentrations in spot urine
samples. The corresponding human dose (mg/kg/day) was not measured or
estimated by NHANES. The NHANES urinary metabolite concentration data
collection efforts were not designed to directly determine the dose and
CDC has not reported dose estimates for triclosan based on NHANES
measurement data. The NHANES 2003-2004 data were obtained from the
NHANES website:
[www.cdc.gov/nchs/nhanes.htm](http://www.cdc.gov/nchs/nhanes.htm)

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

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

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

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

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

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

**5.1.2 [Pharmacokinetics of Triclosan]{.underline}**

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.

![](media/image3.wmf){width="4.251388888888889in"
height="2.5104166666666665in"}

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

**5.1.3 [Uncertainties Associated with the Dose
Conversion]{.underline}**

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**

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
99^th^ 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;

```{=html}
<!-- -->
```
-   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 95^th^ percentile of daily urine
excretion volume. Based on the results at the mean and 99^th^ 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 99^th^ 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
95^th^ 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 style="width:100%;">
<colgroup>
<col style="width: 16%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 6%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="13"><strong>Table 5.1. Acute, Short, Intermediate-, and
Long-term Aggregate Risks for Triclosan (Mean)</strong></td>
</tr>
<tr class="even">
<td rowspan="2"><strong>Groups</strong></td>
<td colspan="3" rowspan="2"><p>Method:</p>
<p>Mage (2007) Obese Correct-based Dose</p>
<p><em>[Creatinine Correction]</em></p></td>
<td colspan="3" rowspan="2"><p>Method:</p>
<p>Schafer (2004) Actual BW-based Dose</p>
<p><em>[Urinary Volume Correction]</em></p></td>
<td colspan="6">Method: Geigy 1981 <em>[Urinary Volume
Correction]</em></td>
</tr>
<tr class="odd">
<td colspan="3"><p>Mean Urine Volume-based</p>
<p>Dose</p></td>
<td colspan="3"><p>95% Urine Volume-based</p>
<p>Dose</p></td>
</tr>
<tr class="even">
<td></td>
<td>ug/kg/d</td>
<td>mg/kg/d</td>
<td>MOE</td>
<td>ug/kg</td>
<td>mg/kg/d</td>
<td>MOE</td>
<td>ug/kg</td>
<td>mg/kg/d</td>
<td>MOE</td>
<td>ug/kg/d</td>
<td>mg/kg/d</td>
<td>MOE</td>
</tr>
<tr class="odd">
<td>All</td>
<td>1.373</td>
<td>0.0025</td>
<td>11801</td>
<td>1.5700</td>
<td>0.0029</td>
<td>10318</td>
<td>1.551</td>
<td>0.0029</td>
<td>10442</td>
<td>2.413</td>
<td>0.0045</td>
<td>6714</td>
</tr>
<tr class="even">
<td>6-11</td>
<td>0.872</td>
<td>0.0016</td>
<td>18582</td>
<td>1.0511</td>
<td>0.0019</td>
<td>15412</td>
<td>0.901</td>
<td>0.0017</td>
<td>17986</td>
<td>1.304</td>
<td>0.0024</td>
<td>12426</td>
</tr>
<tr class="odd">
<td>12-19</td>
<td>1.431</td>
<td>0.0027</td>
<td>11318</td>
<td>1.7404</td>
<td>0.0032</td>
<td>9308</td>
<td>2.189</td>
<td>0.0041</td>
<td>7400</td>
<td>3.361</td>
<td>0.0062</td>
<td>4820</td>
</tr>
<tr class="even">
<td>20-59</td>
<td>1.543</td>
<td>0.0029</td>
<td>10501</td>
<td>1.7187</td>
<td>0.0032</td>
<td>9426</td>
<td>1.635</td>
<td>0.0030</td>
<td>9911</td>
<td>2.562</td>
<td>0.0047</td>
<td>6322</td>
</tr>
<tr class="odd">
<td>&gt;= 60</td>
<td>1.013</td>
<td>0.0019</td>
<td>15996</td>
<td>1.2108</td>
<td>0.0022</td>
<td>13380</td>
<td>1.152</td>
<td>0.0021</td>
<td>14065</td>
<td>1.806</td>
<td>0.0033</td>
<td>8972</td>
</tr>
<tr class="even">
<td>Male</td>
<td>1.684</td>
<td>0.0031</td>
<td>9618</td>
<td>2.0316</td>
<td>0.0038</td>
<td>7974</td>
<td>1.963</td>
<td>0.0036</td>
<td>8254</td>
<td>2.997</td>
<td>0.0056</td>
<td>5405</td>
</tr>
<tr class="odd">
<td>Female</td>
<td>1.076</td>
<td>0.0020</td>
<td>15062</td>
<td>1.1306</td>
<td>0.0021</td>
<td>14329</td>
<td>1.160</td>
<td>0.0021</td>
<td>13969</td>
<td>1.857</td>
<td>0.0034</td>
<td>8726</td>
</tr>
<tr class="even">
<td>Mexican-American</td>
<td>1.863</td>
<td>0.0035</td>
<td>8694</td>
<td>2.2781</td>
<td>0.0042</td>
<td>7111</td>
<td>2.220</td>
<td>0.0041</td>
<td>7297</td>
<td>3.455</td>
<td>0.0064</td>
<td>4689</td>
</tr>
<tr class="odd">
<td>White, Non-Hispanic</td>
<td>1.355</td>
<td>0.0025</td>
<td>11956</td>
<td>1.4850</td>
<td>0.0028</td>
<td>10909</td>
<td>1.477</td>
<td>0.0027</td>
<td>10969</td>
<td>2.303</td>
<td>0.0043</td>
<td>7035</td>
</tr>
<tr class="even">
<td>Black, Non-Hispanic</td>
<td>1.082</td>
<td>0.0020</td>
<td>14967</td>
<td>1.5665</td>
<td>0.0029</td>
<td>10342</td>
<td>1.512</td>
<td>0.0028</td>
<td>10714</td>
<td>2.327</td>
<td>0.0043</td>
<td>6962</td>
</tr>
<tr class="odd">
<td colspan="13">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).</td>
</tr>
<tr class="even">
<td colspan="13"><p>Groups (demographics) are based on the available
data in NHANES.</p>
<p>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.</p>
<p>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%).</p>
<p>Geigy (1981) 95% urine volume is the upper percentile of daily urine
volume.</p></td>
</tr>
</tbody>
</table>

<table>
<colgroup>
<col style="width: 16%" />
<col style="width: 7%" />
<col style="width: 8%" />
<col style="width: 5%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 5%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 5%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 2%" />
<col style="width: 1%" />
<col style="width: 0%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="13"><strong>Table 5.2. Acute, Short, Intermediate-, and
Long-term Aggregate Risks for Triclosan (99th Percentile)</strong></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td rowspan="2"><strong>Groups</strong></td>
<td colspan="3" rowspan="2"><p>Method:</p>
<p>Mage (2007) Obese Correct-based Dose</p>
<p><em>[Creatinine Correction]</em></p></td>
<td colspan="3" rowspan="2"><p>Method:</p>
<p>Schafer (2004) Actual BW-based Dose</p>
<p><em>[Urinary Volume Correction]</em></p></td>
<td colspan="8">Method: Geigy 1981 <em>[Urinary Volume
Correction]</em></td>
</tr>
<tr class="odd">
<td colspan="3"><p>Mean Urine Volume-based</p>
<p>Dose</p></td>
<td colspan="5"><p>95% Urine Volume-based</p>
<p>Dose</p></td>
</tr>
<tr class="even">
<td></td>
<td>ug/kg/d</td>
<td>mg/kg/d</td>
<td>MOE</td>
<td>ug/kg/d</td>
<td>mg/kg/d</td>
<td>MOE</td>
<td>ug/kg/d</td>
<td>mg/kg/d</td>
<td>MOE</td>
<td>ug/kg/d</td>
<td>mg/kg/d</td>
<td colspan="3">MOE</td>
</tr>
<tr class="odd">
<td>All</td>
<td>15.51</td>
<td>0.029</td>
<td>1044</td>
<td>23.59</td>
<td>0.044</td>
<td>687</td>
<td>23.56</td>
<td>0.0436</td>
<td>688</td>
<td>38.06</td>
<td>0.070</td>
<td colspan="3">426</td>
</tr>
<tr class="even">
<td>6-11</td>
<td>10.85</td>
<td>0.020</td>
<td>1493</td>
<td>24.62</td>
<td>0.046</td>
<td>658</td>
<td>9.70</td>
<td>0.0180</td>
<td>1670</td>
<td>14.17</td>
<td>0.026</td>
<td colspan="3">1143</td>
</tr>
<tr class="odd">
<td>12-19</td>
<td>16.63</td>
<td>0.031</td>
<td>974</td>
<td>25.46</td>
<td>0.047</td>
<td>636</td>
<td>28.77</td>
<td>0.0533</td>
<td>563</td>
<td>46.48</td>
<td>0.086</td>
<td colspan="3">349</td>
</tr>
<tr class="even">
<td>20-59</td>
<td>19.08</td>
<td>0.035</td>
<td>849</td>
<td>29.07</td>
<td>0.054</td>
<td>557</td>
<td>29.87</td>
<td>0.0553</td>
<td>542</td>
<td>48.25</td>
<td>0.089</td>
<td colspan="3">336</td>
</tr>
<tr class="odd">
<td>&gt;= 60</td>
<td>14.42</td>
<td>0.027</td>
<td>1123</td>
<td>17.15</td>
<td>0.032</td>
<td>945</td>
<td>14.78</td>
<td>0.0274</td>
<td>1096</td>
<td>22.70</td>
<td>0.042</td>
<td colspan="3">714</td>
</tr>
<tr class="even">
<td>Male</td>
<td>18.96</td>
<td>0.035</td>
<td>855</td>
<td>35.15</td>
<td>0.065</td>
<td>461</td>
<td>35.20</td>
<td>0.0652</td>
<td>460</td>
<td>54.07</td>
<td>0.100</td>
<td colspan="3">300</td>
</tr>
<tr class="odd">
<td>Female</td>
<td>14.74</td>
<td>0.027</td>
<td>1099</td>
<td>17.77</td>
<td>0.033</td>
<td>912</td>
<td>17.62</td>
<td>0.0326</td>
<td>920</td>
<td>28.47</td>
<td>0.053</td>
<td colspan="3">569</td>
</tr>
<tr class="even">
<td>Mexican-American</td>
<td>20.56</td>
<td>0.038</td>
<td>788</td>
<td>42.37</td>
<td>0.078</td>
<td>382</td>
<td>40.64</td>
<td>0.0753</td>
<td>399</td>
<td>62.42</td>
<td>0.116</td>
<td colspan="3">260</td>
</tr>
<tr class="odd">
<td>White, Non-Hispanic</td>
<td>14.98</td>
<td>0.028</td>
<td>1081</td>
<td>16.30</td>
<td>0.030</td>
<td>994</td>
<td>18.97</td>
<td>0.0351</td>
<td>854</td>
<td>29.13</td>
<td>0.054</td>
<td colspan="3">556</td>
</tr>
<tr class="even">
<td>Black, Non-Hispanic</td>
<td>13.72</td>
<td>0.025</td>
<td>1181</td>
<td>26.12</td>
<td>0.048</td>
<td>620</td>
<td>28.25</td>
<td>0.0523</td>
<td>573</td>
<td>45.64</td>
<td>0.085</td>
<td colspan="3">355</td>
</tr>
<tr class="odd">
<td colspan="15">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).</td>
</tr>
<tr class="even">
<td colspan="15"><p>Groups (demographics) are based on the available
data in NHANES.</p>
<p>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.</p>
<p>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%).</p>
<p>Geigy (1981) 95% urine volume is the upper percentile of daily urine
volume.</p></td>
</tr>
</tbody>
</table>

**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 *A* *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]{.underline} 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.        |             |            |          |                  |
| Rep         |             |            |          |                  |
| resentative |             |            |          |                  |
| Exposure    |             |            |          |                  |
| Scenarios   |             |            |          |                  |
| Associated  |             |            |          |                  |
| with        |             |            |          |                  |
| O           |             |            |          |                  |
| ccupational |             |            |          |                  |
| Exposures   |             |            |          |                  |
| to          |             |            |          |                  |
| Triclosan** |             |            |          |                  |
+=============+=============+============+==========+==================+
| Rep         | Method of   | Exposure   | Example  | Application Rate |
| resentative | Application | Scenario   | Regi     |                  |
| Use         |             |            | stration |                  |
|             |             |            | \#       |                  |
+-------------+-------------+------------+----------+------------------+
| **Co        |             |            |          |                  |
| mmercial/In |             |            |          |                  |
| dustrial/In |             |            |          |                  |
| stitutional |             |            |          |                  |
| Premises    |             |            |          |                  |
| (Use        |             |            |          |                  |
| Category    |             |            |          |                  |
| III)**      |             |            |          |                  |
+-------------+-------------+------------+----------+------------------+
| HVAC coil   | Airless     | ST/IT      | 82523-1  | 6.1E-4 lb ai/10  |
| a           | sprayer     | Handler:   |          | ft^2^            |
| pplications |             |            |          |                  |
|             |             | Inhalation |          | (0.85 pints/10   |
|             |             |            |          | ft^2^ x 1 gal/8  |
|             |             |            |          | pts x 8.34       |
|             |             |            |          | lb/gal x 0.69%   |
|             |             |            |          | ai)              |
+-------------+-------------+------------+----------+------------------+
| Painting    | Paint       | ST/IT      | 42182-1  | 0.1 lb ai/gallon |
|             | brush,      | Handler:   |          |                  |
| (commercial |             |            |          | \[up to 1%       |
| painters)   | Airless     | Inhalation |          | product x 99% ai |
|             | sprayer     |            |          | x 10 lb/gal      |
|             |             |            |          | paint density =  |
|             |             |            |          | 0.099 lb         |
|             |             |            |          | ai/gallon of     |
|             |             |            |          | paint\]          |
+-------------+-------------+------------+----------+------------------+
| **Material  |             |            |          |                  |
| Pr          |             |            |          |                  |
| eservatives |             |            |          |                  |
| (Use        |             |            |          |                  |
| Category    |             |            |          |                  |
| VII)**      |             |            |          |                  |
+-------------+-------------+------------+----------+------------------+
| Paint       | Liquid      | ST/IT      | 42182-1  | 0.1 lb ai/gallon |
|             | pour,       | Handler:   |          |                  |
|             |             | inhalation |          | \[up to 1%       |
|             | Powder      |            |          | product x 99% ai |
|             |             |            |          | x 10 lb/gal      |
|             |             |            |          | paint density =  |
|             |             |            |          | 0.099 lb         |
|             |             |            |          | ai/gallon of     |
|             |             |            |          | paint\]          |
+-------------+-------------+------------+----------+------------------+
| **Number    |             |            |          |                  |
| range       |             |            |          |                  |
| CHAPTE      |             |            |          |                  |
| RIndustrial |             |            |          |                  |
| processes   |             |            |          |                  |
| and water   |             |            |          |                  |
| systems     |             |            |          |                  |
| (Use        |             |            |          |                  |
| Category    |             |            |          |                  |
| VIII)**     |             |            |          |                  |
+-------------+-------------+------------+----------+------------------+
| Pulp and    | Metered     | ST/IT      | 70404-5  | 2% ai by weight  |
| Paper       | pump        | Handler:   |          | of paper product |
|             |             | Inhalation |          |                  |
|             |             |            |          | (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>
<colgroup>
<col style="width: 13%" />
<col style="width: 14%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 8%" />
<col style="width: 8%" />
<col style="width: 8%" />
<col style="width: 6%" />
</colgroup>
<thead>
<tr class="header">
<th colspan="10"><strong>Table 6.2. Short- and Intermediate-Term
Inhalation Risks Associated with Occupational Handlers</strong></th>
</tr>
<tr class="odd">
<th rowspan="2">Exposure Scenario</th>
<th rowspan="2">Method of Application</th>
<th colspan="2"><p>Unit Exposure</p>
<p>(mg/lb a.i.)</p></th>
<th rowspan="2">Application Rate</th>
<th rowspan="2">Quantity Handled/ Treated per day</th>
<th colspan="2">Daily Dose (mg/kg/day)<sup>a</sup></th>
<th colspan="2"><p>MOE<sup>b</sup></p>
<p>(Target MOE = 100)</p></th>
</tr>
<tr class="header">
<th>Inhalation</th>
<th>Dermal</th>
<th>Inhalation</th>
<th>Dermal</th>
<th>Inhalation</th>
<th>Dermal</th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td colspan="10"><strong>Number range CHAPTERCommercial, Institutional
and Industrial Premises and Equipment (Use Site Category III
)</strong></td>
</tr>
<tr class="even">
<td>HVAC</td>
<td>Airless sprayer</td>
<td>0.83</td>
<td>38</td>
<td>6.1E-4 lb ai/10ft<sup>2</sup></td>
<td>Large building 1000 ft<sup>2</sup></td>
<td>0.00072</td>
<td>0.033</td>
<td>4,500</td>
<td>1,200</td>
</tr>
<tr class="odd">
<td rowspan="2">Painting (commercial)</td>
<td>Paint brush</td>
<td>0.26</td>
<td>180</td>
<td rowspan="2">0.1 lb ai/gal</td>
<td>5 gallons</td>
<td>0.002</td>
<td>1.3</td>
<td>1,600</td>
<td>31</td>
</tr>
<tr class="even">
<td>Airless sprayer</td>
<td>0.83</td>
<td>38</td>
<td>50 gallons</td>
<td>0.059</td>
<td>2.7</td>
<td>54</td>
<td>1</td>
</tr>
<tr class="odd">
<td colspan="10"><strong>Material Preservatives (Use Site Category
VII)</strong></td>
</tr>
<tr class="even">
<td rowspan="2">Paint (manufacturing process)</td>
<td>Liquid pour</td>
<td>0.00346</td>
<td>0.135 (gloves)</td>
<td rowspan="2">0.99% ai</td>
<td>20,000 lbs</td>
<td>0.0098</td>
<td>0.38</td>
<td>330</td>
<td>110</td>
</tr>
<tr class="odd">
<td>Liquid pump</td>
<td>0.000403</td>
<td>0.00629 (gloves)</td>
<td>200,000 lbs</td>
<td>0.011</td>
<td>0.18</td>
<td>290</td>
<td>220</td>
</tr>
<tr class="even">
<td colspan="10"><strong>Industrial Processes and Water Systems (Use
Site Category VIII)</strong></td>
</tr>
<tr class="odd">
<td>Pulp and Paper</td>
<td>Metering pump</td>
<td>0.000403</td>
<td>0.00629 (gloves)</td>
<td>2% ai</td>
<td>500 tons</td>
<td>0.115</td>
<td>1.8</td>
<td>28</td>
<td>22</td>
</tr>
</tbody>
</table>

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.

1.  **Occupational Post-application Exposures**

Occupational post-application dermal and inhalation exposures are
assumed to be negligible.

**7.2 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.

```{=html}
<!-- -->
```
-   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:

+-----------+---------+-----------+--------+--------------+----------+
| **        | **Chem  | **E       | **To   | **Satisfies  | **Ref    |
| Species** | ical,** | ndpoint** | xicity | G            | erence** |
|           |         |           | Cate   | uidelines/** |          |
|           | **%     | **        | gory** |              | **(MRID  |
|           | Active  | (mg/kg)** |        | **Comments** | No.)**   |
|           | Ingre   |           |        |              |          |
|           | dient** |           |        |              |          |
|           |         |           |        |              |          |
|           | **(     |           |        |              |          |
|           | a.i.)** |           |        |              |          |
|           |         |           |        |              |          |
|           | **T     |           |        |              |          |
|           | ested** |           |        |              |          |
+-----------+---------+-----------+--------+--------------+----------+
| Mallard   | Tr      | LD~50~ =  | Rela   | Yes (core)   | 4        |
| duck      | iclosan | \>2150    | tively |              | 30226-03 |
|           | 99.7%   |           | no     | \- 14-day    |          |
| (*Anas    |         | NOAEL =   | ntoxic | test         |          |
| platyr    |         | 2150      |        | duration     |          |
| hynchos*) |         |           |        |              |          |
|           |         |           |        | \- 19 weeks  |          |
|           |         |           |        | of age       |          |
+-----------+---------+-----------+--------+--------------+----------+
| Bobwhite  | Tr      | LD~50~ =  | Sl     | Yes (core)   | 4        |
| quail     | iclosan | 825       | ightly |              | 30226-02 |
|           | 99.7%   |           | toxic  | \- 14-day    |          |
| (*Colinus |         | NOAEL =   |        | test         |          |
| virg      |         | \<147     |        | duration     |          |
| inianus*) |         |           |        |              |          |
|           |         |           |        | \- 21 weeks  |          |
|           |         |           |        | of age       |          |
+-----------+---------+-----------+--------+--------------+----------+
| Bobwhite  | Tr      | LD~50~ =  | Rela   | Yes (core    | 4        |
| quail     | iclosan | \>2000    | tively | for a        | 10089-10 |
|           | 3.89%   |           | no     | formulated   |          |
| (*Colinus |         | NOAEL =   | ntoxic | product)     |          |
| virg      |         | N.R.      |        |              |          |
| inianus*) |         |           |        |              |          |
+-----------+---------+-----------+--------+--------------+----------+

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:

+-----------+----------+----------+---------+---------------+--------+
| **        | **Che    | **En     | **T     | **Satisfies   | *      |
| Species** | mical,** | dpoint** | oxicity | Guidelines/** | *Refer |
|           |          |          | Cat     |               | ence** |
|           | **%      | *        | egory** | **Comments**  |        |
|           | Active   | *(ppm)** |         |               | *      |
|           | Ingr     |          |         |               | *(MRID |
|           | edient** |          |         |               | No.)** |
|           |          |          |         |               |        |
|           | **       |          |         |               |        |
|           | (a.i.)** |          |         |               |        |
|           |          |          |         |               |        |
|           | **       |          |         |               |        |
|           | Tested** |          |         |               |        |
+-----------+----------+----------+---------+---------------+--------+
| Bobwhite  | T        | LC~50~   | Rel     | Yes (core)    | 430    |
| quail     | riclosan | (diet) = | atively |               | 226-04 |
|           | 99.7%    | \>5000   | n       | \- 8-day test |        |
| (*Colinus |          |          | ontoxic | duration      |        |
| virg      |          | NOAEC =  |         |               |        |
| inianus)* |          | 1250     |         | \- 13 days of |        |
|           |          |          |         | age           |        |
+-----------+----------+----------+---------+---------------+--------+
| Bobwhite  | T        | LC~50~   | Rel     | Yes (core for | 410    |
| quail     | riclosan | (diet) = | atively | formulated    | 089-11 |
|           |          | \>5000   | n       | product)      |        |
| (*Colinus | 3.89%    |          | ontoxic |               |        |
| virg      |          | NOAEC =  |         | \- 8-day test |        |
| inianus)* |          | N.R.     |         | duration      |        |
|           |          |          |         |               |        |
|           |          |          |         | \- 7-10 days  |        |
|           |          |          |         | of age        |        |
+-----------+----------+----------+---------+---------------+--------+

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:

+------------+---------+----------+--------+----------------+---------+
| *          | **Chem  | **En     | **To   | **Satisfies    | **Refe  |
| *Species** | ical,** | dpoint** | xicity | Guidelines/**  | rence** |
|            |         |          | Cate   |                |         |
|            | **%     | **       | gory** | **Comments**   | **(MRID |
|            | Active  | (mg/L)** |        |                | No.)**  |
|            | Ingre   |          |        |                |         |
|            | dient** |          |        |                |         |
|            |         |          |        |                |         |
|            | **(     |          |        |                |         |
|            | a.i.)** |          |        |                |         |
|            |         |          |        |                |         |
|            | **T     |          |        |                |         |
|            | ested** |          |        |                |         |
+============+=========+==========+========+================+=========+
| Rainbow    | Tr      | LC~50~ = | Highly | Yes (core)     | 43      |
| Trout      | iclosan | 0.288    | toxic  |                | 9693-01 |
| (*On       |         |          |        | \- 96-hr test  |         |
| corhynchus | 99.3%   | NOAEC =  |        | duration       |         |
| mykiss)*   |         | 0.100    |        |                |         |
|            |         |          |        | \- static test |         |
|            |         |          |        | system         |         |
+------------+---------+----------+--------+----------------+---------+
| Fathead    | Tr      | LC~50~ = | Highly | No             | 43      |
| minnow     | iclosan | 0.26     | toxic  | (supplemental) | 0460-01 |
|            |         |          |        |                |         |
| (*         | 99.7%   | LOEC =   |        | \- 96-hr test  |         |
| Pimephales |         | 0.18     |        | duration       |         |
| promelas*) |         |          |        |                |         |
|            |         | NOAEC =  |        | \- static test |         |
|            |         | 0.10     |        | system         |         |
|            |         |          |        |                |         |
|            |         |          |        | \- nominal     |         |
|            |         |          |        | concentrations |         |
|            |         |          |        | not verified   |         |
+------------+---------+----------+--------+----------------+---------+
| Bluegill   | Tr      | LC50 =   | Sl     | Yes (core for  | 41      |
| sunfish    | iclosan | 37.2     | ightly | formulated     | 0089-13 |
| (*Lepomis  | 3.89%   |          | toxic  | product)       |         |
| mac        |         | NOAEC =  |        |                |         |
| rochirus)* |         | N.R.     |        | \- 96-hr test  |         |
|            |         |          |        | duration       |         |
|            |         |          |        |                |         |
|            |         |          |        | \- static test |         |
|            |         |          |        | system         |         |
+------------+---------+----------+--------+----------------+---------+
| Rainbow    | Tr      | LC~50~ = | Sl     | Yes (core for  | 41      |
| Trout      | iclosan | 23.4     | ightly | formulated     | 0089-12 |
| (*On       | 3.89%   |          | toxic  | product)       |         |
| corhynchus |         | NOAEC =  |        |                |         |
| mykiss)*   |         | N.R.     |        | \- 96-hr test  |         |
|            |         |          |        | duration       |         |
|            |         |          |        |                |         |
|            |         |          |        | \- static test |         |
|            |         |          |        | system         |         |
+------------+---------+----------+--------+----------------+---------+

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:

+------------+----------+-----------+--------+--------------+--------+
| *          | **Che    | **E       | **To   | **Satisfies  | *      |
| *Species** | mical,** | ndpoint** | xicity | G            | *Refer |
|            |          |           | Cate   | uidelines/** | ence** |
|            | **%      | *         | gory** |              |        |
|            | Active   | *(mg/L)** |        | **Comments** | *      |
|            | Ingr     |           |        |              | *(MRID |
|            | edient** |           |        |              | No.)** |
|            |          |           |        |              |        |
|            | **       |           |        |              |        |
|            | (a.i.)** |           |        |              |        |
|            |          |           |        |              |        |
|            | **       |           |        |              |        |
|            | Tested** |           |        |              |        |
+============+==========+===========+========+==============+========+
| Waterflea  | T        | EC~50~ =  | Highly | No           | 430    |
| (*Daphnia  | riclosan | 0.39      | toxic  | (s           | 460-02 |
| magna)*    |          |           |        | upplemental) |        |
|            | 99.7%    | NOAEC =   |        |              |        |
|            |          | 0.10      |        | \- 48-hr     |        |
|            |          | (a.i.)    |        | test         |        |
|            |          |           |        | duration     |        |
|            |          |           |        |              |        |
|            |          |           |        | \- static    |        |
|            |          |           |        | test system  |        |
|            |          |           |        |              |        |
|            |          |           |        | \- nominal   |        |
|            |          |           |        | co           |        |
|            |          |           |        | ncentrations |        |
|            |          |           |        | not verified |        |
+------------+----------+-----------+--------+--------------+--------+
| Waterflea  | T        | LC~50~ =  | Highly | No           | 410    |
| (*Daphnia  | riclosan | 0.42      | toxic  | (s           | 089-14 |
| magna)*    |          |           |        | upplemental) |        |
|            | 3.89%    | NOAEC =   |        |              |        |
|            |          | N.R.      |        | \- 48-hr     |        |
|            |          |           |        | test         |        |
|            |          |           |        | duration     |        |
|            |          |           |        |              |        |
|            |          |           |        | \- static    |        |
|            |          |           |        | test system  |        |
|            |          |           |        |              |        |
|            |          |           |        | \- lack of   |        |
|            |          |           |        | pH and DO    |        |
|            |          |           |        | measurements |        |
|            |          |           |        | and          |        |
|            |          |           |        | formulated   |        |
|            |          |           |        | product used |        |
+------------+----------+-----------+--------+--------------+--------+
| Waterflea  |          |           |        |              | 423    |
| (*Daphnia  |          |           |        |              | 221-02 |
| magna)*    |          |           |        |              |        |
+------------+----------+-----------+--------+--------------+--------+

The results of these studies indicate that triclosan is highly toxic to
freshwater invertebrates. These studies **[do not]{.underline}** 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**    | **Ch      | **         | **Satisfies   | **Re      |
|                | emical,** | Endpoint** | Guidelines/** | ference** |
|                |           |            |               |           |
|                | **%       | **(mg/L)** | **Comments**  | **(MRID   |
|                | Active    |            |               | No.)**    |
|                | Ing       |            |               |           |
|                | redient** |            |               |           |
|                |           |            |               |           |
|                | *         |            |               |           |
|                | *(a.i.)** |            |               |           |
|                |           |            |               |           |
|                | *         |            |               |           |
|                | *Tested** |            |               |           |
+================+===========+============+===============+===========+
| Waterflea      | Triclosan | LOEC =     | No            | 437407-01 |
|                |           | \<0.1388   | (             |           |
| (*Daphnia      | \% purity |            | supplemental) |           |
| magna*)        | unknown   | NOAEC =    |               |           |
|                |           | N.R.       | \- 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  |           |
+----------------+-----------+------------+---------------+-----------+

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).

C.  **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:

+-----------+------------+-------------+------------------+----------+
| **        | **C        | *           | **Satisfies      | **Ref    |
| Species** | hemical,** | *Endpoint** | Guidelines/**    | erence** |
|           |            |             |                  |          |
|           | **% Active | **(mg/L)**  | **Comments**     | **(MRID  |
|           | In         |             |                  | No.)**   |
|           | gredient** |             |                  |          |
|           |            |             |                  |          |
|           | **(a.i.)** |             |                  |          |
|           |            |             |                  |          |
|           | **Tested** |             |                  |          |
+===========+============+=============+==================+==========+
| Marine    | Triclosan  | EC~50~ =    | Yes (core)       | 4        |
| Diatom    |            | \>0.066     |                  | 44228-01 |
| (*Sk      | 99.5%      |             | \- 96-hour test  |          |
| eletonema |            | NOEC =      | duration         |          |
| c         |            | 0.0126      |                  |          |
| ostatum*) |            |             | \- static test   |          |
|           |            |             | system           |          |
+-----------+------------+-------------+------------------+----------+
| F         | Triclosan  | EC~50~ =    | Yes (core)       | 4        |
| reshwater |            | 0.016       |                  | 44228-01 |
| Diatom    | 99.5%      |             | \- 96-hour test  |          |
| (         |            | NOEC =      | duration         |          |
| *Navicula |            | 0.005       |                  |          |
| pell      |            |             | \- static test   |          |
| iculosa*) |            |             | system           |          |
+-----------+------------+-------------+------------------+----------+
| Bluegreen | Triclosan  | EC~50~ =    | Yes (core)       | 4        |
| Cyan      |            | 0.0012      |                  | 44228-01 |
| obacteria | 99.5%      |             | \- 96-hour test  |          |
| (         |            | NOEC = N.R. | duration         |          |
| *Anabaena |            |             |                  |          |
| flo       |            |             | \- static test   |          |
| s-aquae*) |            |             | system           |          |
+-----------+------------+-------------+------------------+----------+
| Duckweed  | Triclosan  | EC~50~ =    | Yes (core)       | 4        |
| (*Lemna   |            | \>0.0625    |                  | 44228-01 |
| gibba*)   | 99.5%      |             | \- 7-day test    |          |
|           |            | NOEC =      | duration         |          |
|           |            | 0.0125      |                  |          |
|           |            |             | \- static test   |          |
|           |            |             | system           |          |
+-----------+------------+-------------+------------------+----------+

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.

2.  **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
K**~oc~** 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-m^3^/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 (K~ow~ 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.

Number range CHAPTEROf 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).

3.  **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) LC~50~ (fish and birds), (2) LD~50~ (birds
and mammals), (3) EC~50~ (aquatic plants and aquatic invertebrates) and
(4) EC~25~ (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               EEC^1^/LC50 or LD50/sqft^2^ or        0.5
                           LD50/day^3^                           

  Acute Restricted Use     EEC/LC50 or LD50/sqft or LD50/day (or 0.2
                           LD50 \< 50 mg/kg)                     

  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/ft^2^]{.underline} ^3^ [mg of toxicant consumed/day]{.underline}

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

  -----------------------------------------------------------------------
  **Risk Presumptions for Aquatic Animals**

  -----------------------------------------------------------------------

  ------------------------------- ------------------------------ --------
  Risk Presumption                RQ                             LOC

  Acute Risk                      EEC^1^/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/MATC^2^ or NOAEC           1
  ------------------------------- ------------------------------ --------

^1^ EEC = (ppm or ppb) in water

^2^ MATC = maximum allowable toxicant concentration

  ------------------------------- ------------------------------ --------
  **Risk Presumptions for                                        
  Plants**                                                       

  Risk Presumption                RQ                             LOC
  ------------------------------- ------------------------------ --------

+------------------------------+------------------------------+--------+
| ## Terrestr                  |                              |        |
| ial and Semi-Aquatic Plants  |                              |        |
+------------------------------+------------------------------+--------+
| Acute Risk                   | EEC/EC25                     | 1      |
+------------------------------+------------------------------+--------+
| Acute Endangered Species     | EEC/EC05 or NOAEC            | 1      |
+------------------------------+------------------------------+--------+

+------------------------------+------------------------------+--------+
| ## Aquatic Plants            |                              |        |
+------------------------------+------------------------------+--------+
| Acute Risk                   | EEC^1^/EC50                  | 1      |
+------------------------------+------------------------------+--------+
| Acute Endangered Species     | EEC/EC05 or NOAEC            | 1      |
+------------------------------+------------------------------+--------+

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 LC~50~ 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 EC~50~ 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.

2.  **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.[^1] 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.**

9.  **INCIDENT REPORT ASSESSMENT**

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

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

2)  Poison Control Centers

3)  California Department of Pesticide Regulations

4)  National Pesticide Telecommunications Network (NTPT)

5)  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

4.  **National Pesticide Telecommunications Network (NPTN)**

There were no reported incidents from examination of this database

5.  **Hazardous Substances Data Bank (HSDB)**

There were no reported incidents from examination of this database**.**

**10.0 References**

**Ecotox** Number range CHAPTER**REFERENCES**

41008910\. Terrell, Y. 1985. Acute Oral Toxicity Study of Issue Plus II;
ID No. 88-472; Prepared by American Standards Biosciences Corp. for
Diversey Wyandotte Corporation, Wyandotte, Michigan.

41008911\. Terrell, Y. 1988. Avian Dietary Quaily (Litmus Test) of Issue
Plus in Bobwhite Quail; Project No. 88-471; Prepared by American
Standard Biosciences Corp. for Diversey Wyandotte Corporation,
Wyandotte, Michigan.

41008912\. Terrell, Y. 1988. The Acute Toxicity Bioassay of Issue Plus
on Rainbow Trout; Project No. 88-474; Prepared by American Standard
Biosciences Corp. for Diversey Wyandotte Corporation, Wyandotte,
Michigan.

41008913\. Terrell, Y. 1988. The Acute Toxicity Bioassay of Issue Plus
on Bluegill Sunfish; Project No. 88-473; Prepared by American Standard
Biosciences Corp. for Diversey Wyandotte Corporation, Wyandotte,
Michigan.

41008914\. Terrell, Y. 1988. Acute Toxicity of Issue Plus on *Daphnia
magna*; Project No. 88-475; Prepared by American Standard Biosciences
Corp. for Diversey Wyandotte Corporation, Wyandotte, Michigan.

42322101\. Boettcher, J. 1990. Report on the Acute Toxicity (96h) of FAT
80, 023/Q to Zebrafish. Test No. G 069 04. Prepared by Ciba-Geigy, Ltd.,
D&C Product Ecotoxicology, Basel, Switzerland. Submitted by Ciba-Giegy
Corporation, Greensboro, North Carolina.

42322102\. Wuethrich, V. 1990. 48-Hour Acute Toxicity of FAT 80, 023/Q
to *Daphnia magna* (OECD-Immobilization Test). Project No. 262923.
Prepared by RCC Umweltchemie AG, Itingen, Switzerland. Submitted by
Ciba-Giegy Corporation, Greensboro, North Carolina.

43022602\. Pedersen, C.A. and B.R. Helsten. 1993. Triclosan (IRGASAN
DP300^^): 14-Day Acute Oral LD~50~ Study in Bobwhite Quail. Study
performed by Bio-Life Associates, Ltd., Neillsville, Wisconsin.
Laboratory Project No. 102-024-03. Submitted by CIBA-GEIGY Corporation,
Greensboro, North Carolina.

43022603\. Pedersen, C.A. and B.R. Helsten. 1993. Triclosan (IRGASAN
DP300^^): 14-Day Acute Oral LD~50~ Study in Mallard Ducks. Study
performed by Bio-Life Associates, Ltd., Neillsville, Wisconsin.
Laboratory Project No. 102-023-04. Submitted by CIBA-GEIGY Corporation,
Greensboro, North Carolina.

43022604\. Pedersen, C.A. and B.R. Helsten. 1993. Triclosan (IRGASAN
DP300^^): 8-Day Acute Dietary LC~50~ Study in Bobwhite Quail. Study
performed by Bio-Life Associates, Ltd., Neillsville, Wisconsin.
Laboratory Project No. 102-022-01. Submitted by CIBA-GEIGY Corporation,
Greensboro, North Carolina.

43046001\. Bowman, J.H. 1990. Acute Toxicity of D1063.01 (Triclosan:
Irgasan DP300) to Fathead Minnow (*Pimephales promelas*). Laboratory
Project ID No. 38655. Prepared by Analytical Bio-Chemistry Laboratories,
Inc, Columbia, Missouri. Submitted jointly by Proctor and Gamble Company
and Ciba-Geigy Corp.

43046002\. Forbis, A.D. and J.G. Muckerman. 1990. Acute Toxicity of
D1063.01 (Triclosan: Irgasan DP300) to *Daphnia magna*. Laboratory
Project ID No. 38656. Prepared by Analytical Bio-Chemistry Laboratories,
Inc, Columbia, Missouri. Submitted jointly by Proctor and Gamble Company
and Ciba-Geigy Corp.

43740701\. Wuethrich, V. 1990. Influence of FAT 80023/Q (Irgasan DP300)
on Reproduction of *Daphnia magna*. Project No. 262934. Prepared by RCC
Umweltchemie AG, Itingen, Switzerland. Submitted by Ciba-Giegy AG,
Basel, Switzerland.

43969301\. Sword, M.C. 1996. Static Acute Toxicity of Triclosan to
Rainbow Trout. Study performed by ABC Laboratories, Inc., Columbia,
Missouri. Laboratory Report No. 42997. Sponsored by CIBA Chemical
Division, Greensboro, North Carolina.

44422801\. Staveley, J.P. and T.L. Williams. 1997. Effects of Triclosan
on the Growth and Reproduction of Aquatic Plants. Study performed by
Carolina Ecotox, Inc., Durham, North Carolina. Laboratory Report ID:
21-02-1. Sponsored by Ciba-Geigy Corporation, Greensboro, North
Carolina.

Federle, T.W., Kaiser, S.K., and Nuck, B.A. 2002. Fate and Effects of
Triclosan in Activated Sludge. Environmental Toxicology and
Chemistry/SETAC. 21(7): 1330-7.

Kanda, R., Griffin, P., and James, H.A., *et al*. 2003. Pharmaceutical
and Personal Care Products in Sewage Treatment Works. Journal of
Environmental Monitoring. 5(5): 823-30.

Klopin, D.W., Furlong, E.T., Meyer, M.T., *et al*. 2002.
Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in
U.S. Streams, 1999-2000: A National Reconnaissance. Environmental
Science and Technology. 36(6): 1202-11.

McAvoy, D.C., Schatowitz, B., Martin, J., *et al*. 2002. Measurement Of
Triclosan In Wastewater Treatment Systems. Environmental Toxicology and
Chemistry. 21 (7): 1323-9.

**Dietary REFERENCES**

FDA, 2003, A Guidance For Industry: Preparations of food Contact
Notifications and Food Additive Petitions for Food Contact Substances,
Chemistry Recommendations. Final Guidance, April 2003.
[http://www.cfsan.fda.gov](http://www.cfsan.fda.gov/)

FDA, 2003. Sanitizing Solutions: Chemistry Guidance for Food Additive
Petitions, January 2003.
[Http://www.cfsan.fda.gov](http://www.cfsan.fda.gov/)

An AD Memo by Tim McMahon to Jess Rowland, Executive Secretary for
Agency's HIARC Committee, 1998.

Calculations reported by Bob Quick in an AD Memo by Bob Quick to Bob
Brennis,

1998\.

**Environmental Fate REFERENCES**

420279-08 Pointurier, R. 1990. Irgasan^®^ DP 300 -- Report on Hydrolysis
as a Function of pH. Unpublished study performed and submitted by
Ciba-Geigy Ltd., Basel, Switzerland.

430226-08 Spare, W. 1993. Aqueous Photolysis of Triclosan. Agrisearch
Project No.: 12208. Unpublished study performed by Agrisearch Inc.,
Frederick, MD; and submitted by Ciba-Geigy Corporation, Greensboro, NC.

\-\-\-\-\-\-\-\-\-\-\-\-\-- The Estimation Programs Interface (EPI)
Suite. Windows based suite of physical/chemical properties and
environmental estimation models developed by the US EPA's Office of
Prevention, Pesticides and Toxic substances (OPPTS) and Syracuse
Research Institute (SRC). Physical properties of Triclosan. EPI Suite
Summary (v3.12).
<http://www.epa.gov/opptintr/exposure/docs/EPISuitedl.htm>

\-\-\-\-\-\-\-\-\-\-\-\-- Hazard Substances Data Bank (HSDB). A Database
of the National Library of Medicine's TOXNET System. Triclosan:
Environmental Fate and Exposure.
[http://toxnet.nlm.nih.gov](../Triclosan%20Fate%20Chapter%20for%20RED.updated%2012-21-06.doc)

Agüera, A., Fernandez-Alba, A.R., Luis, P., et al. 2003. Evaluation Of
Triclosan And Biphenylol In Marine Sediments And Urban Wastewaters By
Pressurized Liquid Extraction And Solid Phase Extraction Followed By Gas
Chromatography Mass Spectrometry And Liquid Chromatography Mass
Spectrometry. Analytica Chimica Acta 480: 193-205.

Anderson, P.D., D\'Aco, V.J., Shanahan, P., et al. 2004. Screening
Analysis of Human Pharmaceutical Compounds in U.S. Surface Waters.
Environmental Science and Technology. 38(3): 838-49.

Bendz, D., Paxeus, N.A., Ginn, .R., et al. 2005. Occurrence And Fate Of
Pharmaceutically Active Compounds In The Environment, A Case Study: Hoje
River In Sweden. Journal of Hazardous Materials. 122: 195-204.

Bester, K. 2003. Triclosan In A Sewage Treatment Process\--Balances And
Monitoring Data. Water Research. 37 (16): 3891-6.

Bester, K. 2005. Fate of Triclosan and Triclosan-Methyl in Sewage
Treatment Plants and Surface Waters. Archives of Environmental
Contamination and Toxicology. 49 (1): 9-17.

Boyd, G.R., Palmeri, J.M., Zhang, S., et al. 2004. Pharmaceuticals And
Personal Care Products (PPCPs) And Endocrine Disrupting Chemicals (EDCs)
In Stormwater Canals And Bayou St. John In New Orleans, Louisiana, USA.
Science of the Total Environment. 333 : 137-48.

Boyd, G.R., Reemtsma, H., Grimm, D.A., et al. 2003. Pharmaceuticals And
Personal Care Products (PPCPs) In Surface And Treated Waters Of
Louisiana, USA And Ontario, Canada. Science of the Total Environment
(Netherlands). 311 (1-3): 135-49.

Federle, T.W., Kaiser, S.K., and Nuck, B.A. 2002. Fate and Effects of
Triclosan in Activated Sludge. Environmental Toxicology and
Chemistry/SETAC. 21(7): 1330-7.

Federle, T.W. and E.L. Schwab. 2003. Triclosan Biodegradation in
Wastewater Treatment Plant Effluent Diluted in Various River Wastes.
Abstr. Gen. Meet Am Soc. Microbiol 103. p. 0-017.

Gatidou, G., Thomaidis, N.S., Stasinakis, A.S., et al. 2007.
Simultaneous Determination Of The Endocrine Disrupting Compounds
Nonylphenol, Nonylphenol Ethoxylates, Triclosan And Bisphenol A In
Wastewater And Sewage Sludge By Gas Chromatography-Mass Spectrometry.
Journal of Chromatography A. 1138: 32-41.

Gomez, M.J., Martinez Bueno, M.J., Lacorte, S., et al. 2007. Pilot
Survey Monitoring Pharmaceuticals And Related Compounds In A Sewage
Treatment Plant Located On The Mediterranean Coast. Chemosphere. 66 (6):
993-1002.

Hua, W., Bennett, E.R., Letcher, R.J. 2005. Triclosan In Waste And
Surface Waters From The Upper Detroit River By Liquid
Chromatography-Electrospray-Tandem Quadrupole Mass Spectrometry.
Environment International. 31: 621-30.

Kanda, R., Griffin, P., and James, H.A., et al. 2003. Pharmaceutical and
Personal Care Products in Sewage Treatment Works. Journal of
Environmental Monitoring. 5(5): 823-30.

Kolpin, D.W., Furlong, E.T., Meyer, M.T., et al. 2002. Pharmaceuticals,
Hormones, and Other Organic Wastewater Contaminants in U.S. Streams,
1999-2000: A National Reconnaissance. Environmental Science and
Technology. 36(6): 1202-11.

Lee, H., and Peart, T.E. 2002. Organic Contaminants in Canadian
Municipal Sewage Sludge. Part I. Toxic or Endocrine-disrupting Phenolic
Compounds. Water Quality Research Journal of Canada. 37(4): 681-696.

Lee, H., Sarafin, K., and Peart, T.E., et al. 2003. Acidic
Pharmaceuticals in Sewage: Methodology, Stability Test, Occurrence, and
Removal from Ontario Samples. Water Quality Research Journal of Canada.
38(4): 667-682.

Lee, H., Peart, T.E., and Svoboda, M.L. 2005. Determination of
Endocrine-Disrupting Phenols, Acidic Pharmaceuticals, and Personal-care
Products in Sewage by Solid-phase Extraction and Gas Chromatography-Mass
Spectrometry. Journal of Chromatography. 1094(1-2): 122-9.

Lindstrom, A., Buerge, I.J., Poiger, T., et al. 2002. Occurrence and
environmental behavior of the bactericide triclosan and its methyl
derivative in surface waters and in wastewater. Environmental Science
Technology. 36: 2322-2329. Comment in Environmental Science
Technolology. 36 (11): 228A-230A.

Loraine, G.A., Pettigrove, M.E. 2006. Seasonal Variations In
Concentrations Of Pharmaceuticals And Personal Care Products In Drinking
Water And Reclaimed Wastewater In Southern California. Environmental
Science and Technology. 40(3): 687-95.

McAvoy, D.C., Schatowitz, B., Martin, J., et al. 2002. Measurement Of
Triclosan In Wastewater Treatment Systems. Environmental Toxicology and
Chemistry. 21 (7): 1323-9.

Mezcua, M., Gomez, M.J., Ferrer, I., et al. 2004. Evidence of
2,7/2,8-Dibenzodichloro-*p*-dioxin As A Photodegradation Product Of
Triclosan In Water And Wastewater Samples. Analytica Chimica Acta. 524
(1-2): 241-247.

Morales, S., Canosa, P., and Rodriguez, I., et al. 2005. Microwave
Assisted Extraction Followed by Gas Chromatography with Tandem Mass
Spectrometry for the Determination of Triclosan and Two Related
Chlorophenols in Sludge and Sediments. Journal of Chromatography. 1082:
128-35.

Nakada, N., Toshikatsu, T., and Hiroyuki, S., et al. 2006.
Pharmaceutical Chemicals and Endocrine Disrupters in Municipal
Wastewater in Tokyo and their Removal during Activated Sludge Treatment.
Water Research. 40(17): 3297-303.

Paxeus, N., and Gryaab, K. 2004. Removal Of Selected Non-Steroidal
Anti-Inflammatory Drugs (NSAIDs), Gemfibrozil, Carbamazepine,
Beta-Blockers, Trimethoprim And Triclosan In Conventional Wastewater
Treatment Plants In Five EU Countries And Their Discharge To The Aquatic
Environment. Water Science and Technology. 50 (5): 253-60.

Sabaliunas, D., Webb, S.F., Hauk, A., et al. 2003. Environmental Fate Of
Triclosan In The River Aire Basin, UK. Water Research (England). 37:
3145-54.

Samsoe-Petersen L.,Winther-Nielsen M., Madsen T. Fate and Effects of
Triclosan.

Environment Project No. 861. Copenhagen: Danish Environmental Protection

Agency; 2003.

Shiraishi, H., Otsuki, A., and Fuwa, K. 1985. Identification Of
Extractable Organic Chemicals In Sewage Effluent By Gas
Chromatography/Mass Spectrometry. Biomedical Mass Spectrometry. 12 (2):
86-94.

Singer, H., Muller, S., Tixier, C., et al. 2002. Triclosan: Occurrence
And Fate Of A Widely Used Biocide In The Aquatic Environment: Field
Measurements In Wastewater Treatment Plants, Surface Waters, And Lake
Sediments. Environmental Science and Technology. 36(23): 4998-5004.

Thomas, P.M., and Foster, G.D. 2004. Determination of Nonsteroidal
Anti-inflammatory Drugs, Caffeine, and Triclosan in Wastewater by Gas
Chromatography-Mass Spectrometry.2004. Journal of Environmental Science
and Health. Part A, Toxic/Hazardous Substances & Environmental
Engineering. 39(8): 1969-78.

Thomas, P.M., and Foster, G.D. 2005. Tracking Acidic Pharmaceuticals,
Caffeine, And Triclosan Through The Wastewater Treatment Process.
Environmental Toxicology and Chemistry. 24 (1): 25-30.

Thompson, A., Griffin, P., and Stuetz, R., et al. 2005. The Fate and
Removal of Triclosan during Wastewater Treatment. Water Environment
Research. 77(1):63-67.

Waltman, E.L., Venables, B.J., and Waller, W.T. 2006. Triclosan In A
North Texas Wastewater Treatment Plant And The Influent And Effluent Of
An Experimental Constructed Wetland. Environmental Toxicology and
Chemistry. 25 (2): 367-72.

Wind, T., Werner, U., Jacob, M., et al. 2004. Environmental
Concentrations Of Boron, LAS, EDTA, NTA and Triclosan Simulated with
GREAT-ER in the river Itter. Chemosphere (England). 54: 1135-44.

Ying, G. and Kookana, R.S. 2007. Triclosan In Wastewaters And Biosolids
From Australian Wastewater Treatment Plants. Environmental
International. 33 (2): 199-205.

**Toxicology REFERENCES**

MRID 34335: Stierlin, H. (1968) "Percutaneous Absorption of GP 41 353 in
the Rat and the Rabbit." (Unpublished study; prepared by J.R. Geigy, AG,
submitted by Ciba-Geigy Corp., Greens- boro, N.C.; CDL:000506-M)

MRID 43429: Stenger, E.G.; Scharer, (1963) "Local Effects on Rabbit\'s
Eye." (Unpublished study; prepared by J.R. Geigy, AG, Switzerland,
submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:108210-J)

MRID 96102: Burther, B.R.; Gordon, D.E. (1973) "Report to Ciba-Geigy
Corporation: 90-day Subacute Oral Toxicity Study with Irgasan DP-300 in
Beagle Dogs: IBT No. C1435." (Unpublished study; prepared by Industrial
Bio-Test Laboratories, Inc., submitted by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:008400-C)

MRID 100178/130187: Schoenig, G. (1967) "Report to Geigy Chemical
Company: Acute Dermal Toxicity Study on CH 3565: IBT No. A5460."
(Unpublished study; prepared by Industrial Bio-Test Laboratories, Inc.,
submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:000503-D)

MRID 133545: Goldsmith, L. (1983) 90-Day Oral Toxicity Study in Rats
with Fat 80'023/H: LBI Project No. 22188. Final Report. (Unpublished
study received Dec. 23, 1983 under 100-502; submitted by Ciba-Geigy
Corp.)

MRID 251773: Drake, J.C. & Buxtorf, A. (1976) 1 Year Oral Toxicity Study
in Baboons with Compound FAT 80 023/A. Geigy Pharmaceuticals, Toxicology
Department.

MRID 40623701: Morseth, S.L. (1988) "Two-Generation Reproduction Study
in Rats with FAT 80'02390" Hazleton Laboratories America, Inc.

MRID 42027906: Study 1 - Yau, E.T. and Green, J.D. (1986) Fat 80'023 2
Year Oral Administration to Rats; Study 2 -- Parkes, D.G. (1986)
Determination of Fat 80'023 in Blood and Tissue Samples Taken During a
Two-Year Chronic Oral Toxicity/Oncogenicity Study in Albino Rats
(24-month Final Report). Ciba-Geigy Corporation.

# MRID 42306902, 43310501: Duchosal F. and Ph. Thevenaz (1990) "4-Hour Acute Inhalation Toxicity Study with FAT 80'023/Q in Rats" Ciba-Geigy Ltd. 

MRID 42306903: Sachsse, K.; Ullman, L. (1975) Skin Irritation in the
Rabbits after Single Application of FAT 80'023/A. Unpublished Study
Conducted by Ciba Geigy Ltd., Basel Switzerland. Project No. Siss 4719.
Submitted to EPA by Chemical Division of Ciba Geigy Corp. (9/11/75).

MRID 43022605**:** Trutter, Janet A. (1993) "13-Week Subchronic Oral
Toxicity Study of Triclosan in CD-1® Mice." Hazleton Washington, Inc.

# MRID 43206501: Wnorowski, Gary. (1994) "Acute Toxicity Limit Test for Triclosan (Irgasan® DP 300) Product Safety Labs.

MRID 43206502: Wnorowski, G. (1994) Dermal Sensitization Test-Buehler
Method for Triclosan (Irgasan® DP 300) Lot No. 5.2.0211.0. Product
Safety Labs; Study No. 2635. Submitted to EPA by Ciba-Geigy Corp.
Unpublished.

MRID 43328001: Trimmer, Gary W. (1994) "90-Day Subchronic Dermal
Toxicity Study in the Rat with Satellite Group with Irgasan DP300
(MRD-92-399)" Exxon Biomedical Sciences, Inc.

MRID 43533301: Jones, E., Wilson, L.A. (1988) "Ames Metabolic Activation
Test to Address the Potential Mutagenic Effect of Triclosan (Irgasan DP
300)" Huntingdon Research Center, Ltd. Cambridgeshire, England.

MRID 43740801: Heidemann, A. (1990) "Chromosome Aberration Assay in
Chinese Hamster V79 Cells In Vitro with FAT 80'023/Q (Irgasan® DP 300);
Cytotest Cell Research GMBH & Co. KG, Federal Republic of Germany; Study
No. 179100. Unpublished.

MRID 43740802: Volkner, W. (1991) "Chromosome Aberration Assay in Bone
Marrow Cells of the Rat with FAT 80'023/Q (Irgasan® DP300); Cytotest
Cell Research GMBH & Co. KG, Federal Republic of Germany; Study No.
218305. Unpublished.

MRID 43817502, 43817503: Denning, H.J., Sliwa, S., and Willson, G.A.
(1992) "Triclosan: Effects on Pregnancy and Post-Natal Development in
Rats: Volume 1, Volume 2 and Appendices 1-17" Unilever Research,
Colworth/ Welwyn Lab.

# MRID 43820401, 43022607: Schroeder, R.E. et al. (1992) "A Segment II Teratology Study in Rabbits with Irgacare MP" Bio/dynamics Inc. 

MRID 44389701: Eldrige, S. (1993) Cell Proliferation in Rodent Liver:
(Triclosan): Final Report: Lab Project Number: 142. Unpublished study
prepared by Pathology Associates, Inc. 14 p.

MRID 44389702: Molitor, E., Persohn, E., Thomas, H. "The Effect of FAT
80'023/Q (Irgasan DP 300) on Selected Biochemical Liver Parameters
Following Subchronic Dietary Administration to Male and Female Mice.
Ciba-Geigy Limited, Switzerland, Report CB 91/18, May 22, 1992.

MRID 44389703: Molitor, E.; Persohn, E. (1993) The Effects of FAT
80'023/Q (Irgasan DP 300) on Selected Biochemical and Morphological
Liver Parameters Following Dietary Administration to Male Rats: Lab
Project Number: CB 92/28. Unpublished study prepared by Ciba-Geigy Ltd.
70p.

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

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

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

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

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

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

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

MRID 45307501, 45307502: Van Dijk, Dr. A. (1994) "^14^C- 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) "^14^C- 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

Number range CHAPTERFreeman, 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.

Number range CHAPTERUSEPA. 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. Recommended Revisions to the Standard Operating Procedures
(SOPs) for Residential Exposure Assessment, February 22, 2001.

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 [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.

[^1]: The Agency is making this statement because triclosan and
    triclosan transformation products are being detected in various
    environmental components (see triclosan environmental fate chapter).