UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC 20460

			OFFICE OF  PREVENTION, PESTICIDES,  AND TOXIC SUBSTANCES

Triclosan

Occupational and Residential Exposure Assessment

Office of Pesticide Programs

Antimicrobials Division

U.S. Environmental Protection Agency

Date: September 11, 2008

TABLE OF CONTENTS

1.0  TOC \o "1-3" \h \z \u
INTRODUCTION............................................................
........................................................7

  HYPERLINK \l "_Toc208339547"  1.1	Purpose	  PAGEREF _Toc208339547 \h
6

  HYPERLINK \l "_Toc208339548"  1.2	Criteria for Conducting Exposure
Assessments	  PAGEREF _Toc208339548 \h  6

  HYPERLINK \l "_Toc208339549"  1.3	Chemical Identification	  PAGEREF
_Toc208339549 \h  7

  HYPERLINK \l "_Toc208339551"  1.4	Physical/Chemical Properties
PAGEREF _Toc208339551 \h  8

  HYPERLINK \l "_Toc208339552"  2.0	 USE
INFORMATION……………………………………………………
…………………..  PAGEREF _Toc208339552 \h  8

  HYPERLINK \l "_Toc208339553"  2.1	 Formulation Types and Percent
Active Ingredient	  PAGEREF _Toc208339553 \h  8

  HYPERLINK \l "_Toc208339554"  2.2	 Summary of Use Pattern and
Formulations............................................................
.............  PAGEREF _Toc208339554 \h  8

  HYPERLINK \l "_Toc208339555"  3.0	SUMMARY OF TOXICITY
DATA……………………………………………………….....
 PAGEREF _Toc208339555 \h  9

  HYPERLINK \l "_Toc208339556"  3.1	Acute Toxicity	    PAGEREF
_Toc208339556 \h  9

  HYPERLINK \l "_Toc208339557"  3.2	Summary of Toxicity Endpoints
PAGEREF _Toc208339557 \h  10

  HYPERLINK \l "_Toc208339558"  3.3	Other Toxicological Considerations
PAGEREF _Toc208339558 \h  12

  HYPERLINK \l "_Toc208339559"  4.0 	  RESIDENTIAL EXPOSURE
ASSESSMENT…………………………………………… 14

  HYPERLINK \l "_Toc208339560"  4.1	Summary of Registered Uses	  PAGEREF
_Toc208339560 \h  1  4

  HYPERLINK \l "_Toc208339561"  4.2	Residential Handler Exposures
PAGEREF _Toc208339561 \h  1  4

4.3          HYPERLINK \l "_Toc208339562"  Residential
Post-applicationExposure…………………………………………
………….16

4.3.1    National Health and Nutrition Surveys (NHANES) Data for
Triclosan…………………..17

<IP_ADDRESS>  Pharmacokinetics of
Triclosan……………………………………………………...
18

<IP_ADDRESS>  Uncertainties Associated with the Dose
Conversion…………………………...…..19

  HYPERLINK \l "_Toc208339563"  4.3.2	Aggregate Risks	 20

<IP_ADDRESS>  Children (6 years) to
Adults………………………………………………………...
20 <IP_ADDRESS>
Infants………………………………………………………
…………………….....24

  HYPERLINK \l "_Toc208339564"  4.3.3	Dermal
Irritation……………………………………………………
………………… … .25

    4.3.4    Dermal
Systemic………………………………………………………
…………………...31

  HYPERLINK \l "_Toc208339576"  5.0	OCCUPATIONAL EXPOSURE ASSESSMENT
PAGEREF _Toc208339576 \h  31

  HYPERLINK \l "_Toc208339577"  5.1 	Occupational Handler Exposures
PAGEREF _Toc208339577 \h  31

  HYPERLINK \l "_Toc208339578"  5.2  	Occupational Post-application
Exposures	  PAGEREF _Toc208339578 \h  34

  HYPERLINK \l "_Toc208339579"  5.3	Data Limitations/Uncertainties
PAGEREF _Toc208339579 \h  34

  HYPERLINK \l "_Toc208339580"  6.0	REFERENCES	  PAGEREF _Toc208339580
\h  35

  HYPERLINK \l "_Toc208339581"  APPENDIX A: Summary of CMA and PHED Data
 40

EXECUTIVE SUMMARY

	This document is the Occupational and Residential Exposure Chapter of
the Reregistration Eligibility Decision (RED) document for triclosan. It
addresses the potential risks to humans that result from the use of
triclosan in occupational and residential settings. The National Health
and Nutrition Surveys (NHANES) biological monitoring data are available
for assessing aggregate exposure and risk.  EPA views the NHANES data as
the most reliable and representative assessment of aggregate exposures
to determine probability of co-occurrence of EPA- and FDA-regulated
uses.  Although the aggregate exposure/risk assessment using the NHANES
data provides an encompassing review of triclosan-treated products, it
does not include exposures to children under the age of 6 years old.
Children under the age of 6 years exhibit unique activities that do not
occur at older ages.  Therefore, a separate estimate for children under
the age of 6 years old that exhibit behaviors representative of high-end
exposures to triclosan-treated products have been included.

	Triclosan is used as a bacteriostat, fungistat, mildewstat, 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%.  The EPA registered products are used in
commercial/ institutional/industrial, residential and public access, and
material preservatives.  The residential use includes a direct
application to HVAC coils (limited to commercial applicators).
Additionally, triclosan is registered to be used as a material
preservative in such products as paints (in-can preservative), polymers
and plastics (e.g., toys, tooth brushes, etc), and textiles and fabrics
(e.g., footwear, clothing, etc).  There are many other FDA uses of
triclosan (e.g., hand soaps, toothpaste) that are not under EPA’s
regulatory jurisdiction.  These exposures have been considered in this
chapter as well as in the aggregate assessment within the risk
assessment chapter for triclosan.  The general population biological
monitoring data from NHANES does not allow for the separation of
exposures attributed to EPA- versus FDA-regulated uses.

itation was observed at 0.6 mg/kg/day equivalent to 100 μg/cm2.  The
dermal study was based on a 99% ai formulation.  However, all of the
residential uses of triclosan are diluted.  Therefore, the short-term
dermal irritation observed for the 99% ai formulation does not reflect
the dilute use patterns.  The intermediate- and long-term dermal
endpoint was determined from the 90-day dermal rat study.  The
route-specific dermal NOAEL from this study is 40 mg/kg/day based on
increased incidence occult blood in the urine.  Because the
toxicological endpoints selected for inhalation, dermal, and oral routes
of exposure are not female-specific, a body weight of 70 kilograms is
used in the assessment.  EPA’s level of concern (LOC) for occupational
and residential triclosan dermal and oral routes of exposures is 100
(i.e., a margin of exposure (MOE) less than 100 exceeds the level of
concern). The level of concern is based on 10x for interspecies
extrapolation and 10x for intraspecies variation.  The LOC for the
inhalation route of exposure is 1000 based on10x for interspecies
extrapolation, 10x for intraspecies variation, and a 10x for the use of
a LOAEL.

 	This occupational and residential assessment was based on examination
of product labels describing their uses.  It has been determined that
exposure to residential handlers is restricted to the registered end use
product that is for paint containing triclosan as an in-can
preservative.  Occupational handlers may be exposed in the manufacturing
of other products (e.g., plastics, textiles) and during commercial HVAC
coil applications and commercial painters.  Post-application exposures
are likely to occur in residential settings from contacting treated
articles such as textiles and fabrics and plastic products such as toys.
 Additionally, infants can be exposed via nursing and breathing and/or
contacting triclosan-contaminated dust.

To assess the handler risks, EPA used surrogate unit exposure data from
the Chemical Manufacturers Association (CMA) antimicrobial exposure
study and the Pesticide Handlers Exposure Database (PHED).  Post
application/bystander exposures were assessed using the NHANES
biological monitoring data from the general population for ages 6+ years
old as well as bounding estimates for infants using EPA’s standard
assumptions (e.g., Health Effects Division’s (HED) Standard Operating
Procedures (SOPs) for Residential Exposure Assessment).  The aggregate
for children under 6 years old is based on the 6 to 12 month old age
category.  The infant aggregate includes the results of the 6-11 year
old age group from NHANES combined with bounding estimates of
infant-specific activities such as nursing, object-to-mouth, and
hand-to-mouth.

Residential Handler Risk Summary

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

		For the residential handler inhalation assessment, the inhalation
risks were calculated by comparing the daily inhalation dose to the
short-term inhalation endpoint.  The inhalation MOE of 4,000 is above
the target MOE of 1000 for the paint brush scenario. However, for the
airless sprayer scenario the inhalation MOE of 180 is below the target
MOE, and therefore, is of concern.  Mitigation options include reducing
the application rate in paint or removing the use.

Residential Post Application/Bystander Risk Summary

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

	For infants 6 to 12 months old, the mean NHANES 6-11 year old MOEs
combined with bounding estimates for infant-specific activities for
nursing, object-to-mouth, and hand-to-mouth exposures indicate an
aggregate MOE of 390.  At the 99th percentile NHANES distribution
combined with the infant-specific activities indicate a MOE of 290.
These MOEs are above the target MOE of 100.  Clearly, including
exposures to the FDA-regulated soaps and toothpaste for 6-11 year olds
is a conservative assessment of exposure from these products to 6 to 12
month olds.  Future refinements to the infant aggregate should focus on
this portion of the total exposure.

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

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

Occupational Handler Risk Summary

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

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

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

Occupational Post Application/Bystander Risk Summary

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

1.0	 INTRODUCTION tc \l1 "1.0	 INTRODUCTION

		1.1	Purpose  tc \l2 "1.1	Purpose

		In this document, EPA’s Antimicrobials Division (AD) presents the
results of its review of the potential human health effects of
occupational and residential exposure to triclosan (5-chloro-2-(2,4
dichlorophenoxy) phenol). This information is for use in EPA's
development of the triclosan Reregistration Eligibility Decision (RED)
document.

		1.2	Criteria for Conducting Exposure Assessments tc \l2 "1.2	Criteria
for Conducting Exposure Assessments

		An occupational and/or residential exposure assessment is required for
an active ingredient if (1) certain toxicological criteria are triggered
and (2) there is potential exposure to handlers (mixers, loaders,
applicators, etc.) during use or to persons entering treated sites after
application is complete.  For triclosan, both criteria are met.
Toxicological endpoints were selected for short-, intermediate-, and
long-term dermal, inhalation, and oral exposures to triclosan.  There is
the potential for exposure in a variety of occupational and residential
settings.  Therefore, risk assessments are required for occupational and
residential handlers as well as for occupational and residential post
application exposures that can occur as a result of triclosan use.

In this document, handler scenarios were assessed by using unit exposure
data to estimate occupational and residential handlers’ exposures.
Unit exposures are estimates of the amount of exposure to an active
ingredient a handler receives while performing various handler tasks and
are expressed in terms of micrograms or milligrams (1 mg = 1,000 µg) of
active ingredient per pounds of active ingredient handled.  A series of
unit exposures have been developed that are unique for each scenario
typically considered in assessments (i.e., there are different unit
exposures for different types of application equipment, job functions,
and levels of protection).  The unit exposure concept has been
established in the scientific literature and also through various
exposure monitoring guidelines published by the USEPA and international
organizations such as Health Canada and OECD (Organization for Economic
Cooperation and Development).

Using surrogate unit exposure data, maximum application rates from
labels, and EPA estimates of daily amount handled, exposures and risks
to handlers were assessed.  The exposure/risks were calculated using the
following equations:

Daily Exposure: Inhalation and dermal handler exposures are estimated
for each applicable handler task with the application rate, quantity
treated/handled in a day, and the applicable inhalation unit exposure
using the following formula:

Daily Inhalation or dermal Exposure:	E = UE x AR x AT			(Eq. 1)

Where:

E	=	Amount (mg ai/day) that is available for inhalation and dermal
exposure;

UE	=	Unit exposure value (mg ai/lb ai) derived from August 1998 PHED
data or from 1992 CMA data;

AR	=	Maximum application rate based on a logical unit treatment, such as
acres (A), square feet (sq. ft.), gallons (gal), or cubic feet (cu. ft).
Maximum values are generally used (lb ai/sq ft, lb ai/gal, lb ai/cu ft);
and

AT 	=	Normalized application area based on a logical unit treatment such
as square feet  (sq ft/day), gallons (gal/day), or pounds of
articles/products to be treated for material preservatives.

Daily Dose: The inhalation dose is calculated by normalizing the daily
exposure by body weight and adjusting, if necessary (not needed for
triclosan because of the availability of a dermal route-specific study),
with an appropriate dermal absorption factor.  Daily dose was calculated
using the following formula:

Daily Dose:	ADD = E x ABS							(Eq. 2)

			   BW

Where:

ADD 		= 	Average daily dose or the absorbed dose received from exposure
to a chemical in a given scenario (mg active ingredient/kg body
weight/day);

E 		=	Amount (mg ai/day) that is available for inhalation or dermal
exposure;

ABS 		= 	A measure of the amount of chemical that crosses a biological
boundary; and

BW		= 	Body weight determined to represent the population of interest in
a risk assessment (kg).

Margins of Exposure:  Non-cancer inhalation risks for each applicable
handler scenario are calculated using a Margin of Exposure (MOE).  This
is the ratio of the daily inhalation dose or dermal dose to the
toxicological endpoint of concern.

Margins of Exposure:			MOE = NOAEL or LOAEL			(Eq. 3)

							ADD

Where:

MOE 			= 	Margin of exposure, value used to represent risk or how close
a chemical exposure is to being a concern (unitless);

NOAEL or LOAEL	= 	Systemic toxicity level where no observed adverse
effects (NOAEL) or where the lowest observed adverse effects (LOAEL)
occurred in the study (mg ai/kg body weight/day); and

ADD 			= 	Average daily inhalation or dermal dose in a given scenario
(mg ai/kg body weight/day).

Chemical Identification

		Triclosan (5-Chloro-2-(2,4-dichlorophenoxy)phenol) was first
registered with the EPA on June 19, 1969.  Triclosan is a diphenyl ether
derivative.  The CAS number is 3380-34-5 and the molecular structure is
provided in Figure 1.

  HYPERLINK "http://en.wikipedia.org/wiki/Image:Triclosan.png" \o
"Triclosan"    INCLUDEPICTURE
"http://upload.wikimedia.org/wikipedia/commons/thumb/f/fc/Triclosan.png/
200px-Triclosan.png" \* MERGEFORMATINET

 				Figure 1.  Molecular Structure of Triclosan

		1.4	Physical/Chemical Properties tc \l2 "1.4	Physical/Chemical
Properties

		Table 1.2 shows physical/chemical characteristics that have been
reported for triclosan.

Table 1.2.  Physical/Chemical Properties of Triclosan

Parameter

Triclosan

Molecular Weight	290

˚C

Boiling Point	Solid

Water Solubility	12 ppm

Vapor Pressure	5.2E-6 mm Hg at 25 ˚C

2.0	 USE INFORMATION tc \l1 "2.0	 USE INFORMATION

		2.1	 Formulation Types and Percent Active Ingredient tc \l2 "2.1
Formulation Types and Percent Active Ingredient

≥99%.

		2.2	 Summary of Use Pattern and Formulations

	The Agency determines potential exposures to handlers of the product by
identifying exposure scenarios from the various application methods that
are plausible, given the label uses.  Based on a review of product
labels, triclosan is the active ingredient in products used in the
following Use Site Categories:

(III)   SEQ CHAPTER \h \r 1 Commercial, institutional and industrial
premises and equipment,

(IV)   SEQ CHAPTER \h \r 1 Residential and public access premises, and

(VII)   SEQ CHAPTER \h \r 1 Material preservatives,

	Specific uses within these use categories are identified in Table 2.1.
Examples of EPA registered uses for triclosan include application during
manufacturing of textiles and fabrics, plastics, paints, etc.
Additionally, FDA uses of triclosan include products such as hand soaps,
deodorants, and toothpaste.  Although the FDA uses are out of the scope
of EPA’s jurisdiction, exposures to these products are included in the
overall aggregate assessment and cannot be separately presented using
the NHANES data.

Table 2.1 illustrates the uses of triclosan.  These scenarios were
selected to be representative of the vast majority of uses and are
believed to provide high-end degrees of dermal, inhalation, or
incidental ingestion exposure.  The representative scenarios assessed in
this document are shown in Table 4.1 (residential) and Table 6.1
(occupational).

Table 2.1. Potential Use Scenarios Based on Product Labels for
Triclosan.

Use Site Category

Example Use Sites

Scenarios

Use Site Category

III

Commercial/ Institutional/Industrial

Conveyor belts, fire hoses, dye bath vats, ice making equipment, HVAC
coils

Application to HVAC coils

Painting (commercial painters)

Use Site Category IV

Residential and Public Access Premises

Treated articles

Painting

Exposure to treated articles (e.g., clothing, mattress, plastic toys)

Use Site Category VII

Material Preservatives

Used in the production of various household, institutional and
industrial items

adhesives

paints (latex)

textiles (cotton, wool, nylon, rayon, linen, fiber filling, mattress
ticking)

polymers and plastics

3.0	SUMMARY OF TOXICITY DATA tc \l1 "3.0	SUMMARY OF TOXICITY CONCERNS
RELATING TO EXPOSURE

	3.1	Acute Toxicity

 tc \l2 "3.1	Acute Toxicity

The acute toxicity data for triclosan are summarized below in Table 3.1
(USEPA, 2007).

Table 3.1.  Acute Toxicity Profile for Triclosan

Guideline Number	Study Type/

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

Citation	Results	Toxicity Category

870.1100

(§81-1)	Acute Oral- Rat Triclosan (99.7% a.i.)	43206501	LD50: >5000
mg/kg	IV

870.1200

(§81-2)	Acute Dermal- Rabbit

Triclosan (97% a.i.)	42306902

Phase III summary 92084037	LD50: >9300 mg/kg	IV

870.1300

(§81-3)	Acute Inhalation- Rat

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

870.2400

(§81-4)	Primary Eye Irritation- Rabbit

Triclosan (97% a.i.)	 Phase III summary 92084040	 PIS: 92/110 (24
hours), 82/110 (72 hours)	II

870.2500

(§81-5)	Primary Dermal Irritation- Rabbit

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

870.2600

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

	3.2	Summary of Toxicity Endpoints tc \l2 "3.2	Summary of Toxicity
Concerns Relating to Exposures

	Table 3.2 summarizes the toxicological endpoints for Triclosan (USEPA,
2007).

Table 3.2.  Summary of Toxicological Dose and Endpoint Selection for
Triclosan.

Exposure

Scenario	Dose Used in Risk Assessment	Hazard-based Uncertainty Factors
Study and Toxicological Effects

Acute Dietary

(gen. pop.)	NOAEL = 30 mg/kg	Inter-species extrapolation = 10x;

Intra-species variation = 10x;

 Data Base (special sensitivity) = 1x;

Target MOE = 100x	Chronic Toxicity study in Baboons

MRID 257773.  Effects of clinical signs of toxicity include vomiting,
failure to eat, and diarrhea.

Acute Dietary

(females 13+)	Endpoint not identified in the database

Chronic Dietary

(all populations)	NOAEL = 30 mg/kg

	Inter-species extrapolation = 10x;

Intra-species variation = 10x;

Data Base (special sensitivity) = 1x;

Target MOE = 100x	Chronic Toxicity study in Baboons

MRID 257773.  Effects of clinical signs of toxicity include vomiting,
failure to eat, and diarrhea.

Short-Term/ Intermediate-Term Incidental Oral (1-30 days; 30 days- 6
months)	NOAEL = 30 mg/kg	Inter-species extrapolation = 10x;

Intra-species variation = 10x;

Data Base (special sensitivity) = 1x;

Target MOE = 100x	Chronic Toxicity study in Baboons

MRID 257773

Effects of clinical signs of toxicity include vomiting, failure to eat,
and diarrhea.

Dermal

(short-term)	NOAEL = 0.6 mg/animal @ 99.3% active ingredient (100
µg/cm2)	Inter-species extrapolation = 3x;

Intra-species variation = 3x;

 Data Base (special sensitivity) = 1x;

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

MRID 44389708

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

Dermal (intermediate term)	NOAEL = 40 mg/kg

	Inter-species extrapolation = 10x;

Intra-species variation = 10x;

 Data Base (special sensitivity) = 1x;

Target MOE = 100x	90-day dermal toxicity study in rats. MRID 43328001.
LOAEL = 80 mg/kg/day, based on increased incidence occult blood in the
urine.

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

	Inter-species extrapolation = 10x;

Intra-species variation = 10x;

Data based (lack of chronic dermal study) = 3x;

Data Base (special sensitivity) = 1x;

Target MOE = 300x	90-day dermal toxicity study in rats. MRID 43328001.
LOAEL = 80 mg/kg/day, based on increased incidence occult blood in the
urine.

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

UF = 1000

Where mg/kg/day = ((0.0087 m3/hr * mg/m3 * 2 hr/day) /0.271 b.w.
Inter-species extrapolation = 10x;

Intra-species variation = 10x;

Lack of NOAEL = 10;

 Data Base (special sensitivity) = 1x;

Target MOE = 1000x	21-Day Inhalation Toxicity study in the rat.  MRID
0087996.  Effects seen in males at LOAEL include increased total
leucocyte count and increased serum alkaline phosphatase.

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

UF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL
= lowest observed adverse effect level, MOE = margin of exposure

	3.3	Other Toxicological Considerations

	There are no existing tolerances or tolerance exemptions for Triclosan
under 40 CFR 180, and there are no food additive clearances from the
Food and Drug Administration.  However, there are expected exposures of
infants and children to triclosan.  Therefore, the data on
developmental, reproductive, and neurotoxic effects of triclosan were
examined for any susceptibility issues. There is no indication of
developmental or reproductive effects in offspring of rats or rabbits to
in utero and post-natal exposure to triclosan.

	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."  There is some evidence
that triclosan disrupts thyroid hormone homeostasis and interacts with
the androgen and estrogen receptors. The available evidence is
summarized in the risk assessment chapter.

	Further research is needed on the effect of triclosan on thyroid
homeostasis and relevance of any perturbations in homeostasis of thyroid
hormone levels for human risk.  It is not readily apparent from the
available toxicology database for triclosan that the effects observed
are the direct result of perturbations of thyroid homeostasis. The
Agency, however, is aware that research is ongoing on endocrine effects
of triclosan, and this further research may require future modification
to the existing assessment for triclosan.

4.0	RESIDENTIAL EXPOSURE ASSESSMENT  tc \l1 "4.0	RESIDENTIAL EXPOSURE
ASSESSMENT

	4.1	Summary of Registered Uses tc \l2 "4.1	Summary of Registered Uses

	There are no EPA registered products containing triclosan that can be
applied directly by the homeowner.  There is a homeowner application of
triclosan when it is used as an in-can preservative for latex paint
(e.g., EPA Reg. No. 42182-1).  Articles treated with triclosan as a
bacteriostat in occupational settings (e.g., EPA Reg. No. 70404-5) may
also have the potential for post-application residential exposure.
Triclosan-treated articles that may routinely be used in the residential
market include, but are not limited to, material preservative uses in
mattresses, clothing, bibs, tooth brush bristles, plastic toys, garbage
bags, paper, playground equipment, sponges, furniture, footwear, etc.
Additionally, triclosan can be used to control/prevent/inhibit the
growth of fungi/mildew/mold/bacteria on coils in residential heating,
ventilating, and air conditioning (HVAC) systems (e.g., EPA Reg. No.
82523-1).  HVAC coil applications of triclosan are restricted to service
contractors only.  There are no homeowner applications to HVAC coils.
The aerosols from spraying the coils are expected to create minimal
inhalation exposure throughout the house.

	Table 4.1 presents the maximum application rate associated with the
representative uses and the EPA Registration number for the
corresponding product label(s).  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.

Table 4.1. Representative Uses Associated with Residential Exposure to
Triclosan.

Representative Use	Application Method	Example Registration Number
Application Rate

Paint (Latex)	Brush and airless sprayer	42182-1	0.1 lb ai/gallon

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

Textiles

	NAa	70404-5	Round to 2% ai in finished textiles and mattresses.

(Rates range up to the finished product containing  2%  formulated
product by weight.  Triclosan product contains 99% ai. )

Plastic

	NAa	42182-1	0.5% ai

(0.1% to 0.5% product x 99% ai)

Note: labels need to clarify that toys are limited to 0.5%

(a ) The handlers scenarios were not assessed because the products can
only be applied occupationally.

	4.2	Residential Handler Exposures tc \l2 "4.4	Residential Exposure/Risk
Pathway

	Handler exposures are assessed for the in-can preservative use in
paint.  Dermal exposures for the short-term duration were not assessed
because no systemic dermal toxicity was observed.  Dermal irritation was
observed in the toxicity study using a test substance containing 99
percent active ingredient (ai).  Residential uses are at or below 1 to 2
percent ai are not expected to cause irritation.  The lack of incident
data also support this assumption.

	The scenarios were assessed using PHED data along with the equations in
Section 1.2, “Criteria for Conducting Risk Assessment.”  A summary
of the PHED data are presented in Appendix A.

Unit Exposure Values: Unit exposure values were taken from the PHED data
presented in HED’s Residential SOPs (USEPA, 1997).

For the airless sprayer scenario, the PHED inhalation unit exposure
value for a residential handler applying a pesticide using an airless
sprayer was used.  The unit exposure value (0.83 mg/lb ai) represents a
handler using an airless sprayer to stain the exterior of a house.

For the brush/roller scenario, the PHED inhalation unit exposure value
for a residential handler is based on applying a fungicide in paint to
bathroom walls using a paint brush.  The unit exposure value is 0.28
mg/lb ai.

Quantity handled/treated: The quantities handled/treated were estimated
based on information from various sources, including EPA estimates.

For the brush/roller in paint applications, it is assumed that 20 lbs
(approximately 2 gallons) of treated paint will be used.  This is based
on the 90th percentile value of 8 gallons of latex paint used per year
divided by the mean frequency of 4 painting events/year.

For the airless sprayer in paint applications, it is assumed that 150
lbs           (approximately 15 gallons) of treated paint will be used.
This is based on the coverage of 200 ft2/gallon and a house size of 40 x
30 x 20 ft (surface area of 2,800 ft2).

Duration of Exposure: The duration of exposure for most handler
homeowner uses is believed to be best represented by the short-term
duration (1 to 30 days).  The reason that short-term duration was chosen
to be assessed is because painting is episodic in nature, not daily.  In
addition, homeowners are assumed to use different products with varying
activities, not exclusively triclosan treated products (e.g., in-can
paint preservative).

Results

	The resulting short-term inhalation exposures and MOEs for the painting
scenarios are presented in Table 4.2.  The calculated inhalation MOEs
are above the target MOE of 1000 for the paint brush but below the
target MOE for the airless sprayer (i.e., MOE = 180).  Therefore, the
risk exceeds EPA’s level of concern for painting.  Personal protective
equipment (PPE) such as respirators is not a viable mitigation option
for residential paint uses for an in-can preservative.

Table 4.2 Triclosan Short-Term Residential Handler Inhalation Exposures
and MOEs

Exposure Scenario

Application Method	Application Method	Application Ratea	Quantity
Handled/ Treated per dayb

Unit Exposure

(mg/lb a.i.)	Daily Dose (mg/kg/day) c	MOE d

(Target MOE = 1000)

Painting	Paint brush	0.1 lb ai/gal	2 gallons	0.28	0.0008	4,000

	Airless sprayer

15 gallons	0.83	0.018	180

a	Application rates are the maximum application rates determined from
EPA registered labels for triclosan.

b	Amount handled per day values are estimates or label instructions.

c	Daily dose (mg/kg/day) = [unit exposure (mg/lb a.i.) x application
rate (% a.i. weight or lb ai/gal) x quantity treated (lb/day or gal/day)
x absorption factor (1.0 for inhalation)]/ Body weight (70 kg for
inhalation).

d	MOE = LOAEL / Daily Dose.  [Where short-term inhalation LOAEL = 50
mg/m3 or a dose of 3.21 mg/kg/day]. Target MOE = 1000.

	4.3	Residential Post-application Exposures tc \l3 "4.4.2
Postapplication Exposure

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

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

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

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

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

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

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

daily creatinine excretion in μg/day specific to the individual being
considered, 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 raw data were available
in NHANES, actual (measured) body weights of subjects were used instead
of average body weights as described by Schafer et al. (2004).

The EPA Office of Research and Development (ORD) does not currently
recommend any single 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 (as opposed to L/day
above) for a demographic group; the triclosan urinary concentration is
multiplied by the estimated daily urine excretion in L/kg-day.  Two
variations of this approach are used.  Both mean and the 95th%ile urine
volumes 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 triclosan 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 within this risk assessment.

<IP_ADDRESS>	Pharmacokinetics of Triclosan

A correction factor to account for the disposition of triclosan, derived
from the data of Sandborgh-Englund (2006) was applied to the biological
(urine) monitoring data provided by Cohen (2008) and used in this
assessment.  Sandborgh-Englund (2006) dosed 10 subjects (5M/5F) ranging
from 26 to 42 years of age with a single oral dose of 4 mg of triclosan
in mouthwash solution.  Pre-exposure monitoring to establish baseline
exposure levels was also determined.  Results indicate that urinary
excretion among individuals is variable for triclosan.  Urinary
excretion ranged from 24 to 83 percent (median of 54 percent) of the
administered dose of triclosan in urine in 4 days.  The data also
indicate that the majority of urinary excretion occurred within 24 hours
as illustrated in Figure 1.  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 correction used to
estimate the total triclosan dose (i.e., corrected for triclosan
excretion) equals the urinary concentration derived dose (mg/kg/day) for
the 3 basic conversion methods divided by the median value of the
triclosan excretion in urine (i.e., 0.54).

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

<IP_ADDRESS>	Uncertainties Associated with the Dose Conversion

	Several uncertainties exist in the aggregate assessment for triclosan
that arise from using the biological monitoring using spot urine samples
from NHANES.  Therefore, EPA used conservative assumptions to err on the
side of overestimating the potential dose.  Conservatisms used in the
assessment include:  (1) assumptions used by Cohen (2008) for the dose
conversion (e.g., 95th percentile of urinary volume assumed for all
individuals); (2) the characterization of the risks if one were to
assume the pharmacokinetics of triclosan at the lowest (most
conservative) urinary excretion (urinary excretion ranged from 24 to 83
percent with a median of 54 percent); and (3) the inclusion of these
conservative assumptions even at the upper percentile of exposure.
Future refinements to using the NHANES data for the triclosan risk
assessment should focus on refining these parameters.  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.

Aggregate Risks

	<IP_ADDRESS>	Children (6 years) to Adults

 tc "6.1	Acute and Chronic Aggregate Risks " \l 2

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

All exposure durations were assessed using the selected oral NOAEL of 30
mg/kg/day with a target MOE of 100.  The oral endpoint was selected to
represent the various oral exposure scenarios that are expected from
antimicrobial exposure to triclosan. The calculated MOEs are
representative of all exposure durations.  The NHANES data show that
74.6% of the samples had detectable levels of total (free plus
conjugated) triclosan.  Tables 4.3 and 4.4 provide – for each of the
three basic concentration to dose conversion methods -- the mean and
99th percentiles, respectively, of the (1) spot urine concentration to
dose conversion prior to correcting for the 54% triclosan urinary
excretion (in units of ug/kg/day); (2) the pharmacokinetic 54% corrected
daily dose converted to units of mg/kg/day; and (3) the MOEs.  Aggregate
exposures and risks are presented for the following age groups and
subpopulations:

All age groups;

Ages 6-11;

Ages 12-19

Ages 20-59

Ages >=60

Male

Females

Mexican-American

White, non-Hispanic

Black, non-Hispanic

The three basic conversion methods used in this risk characterization
are (1) Mage et al (2007) with an obesity correction factor; (2) Schafer
et al (2004) using actual body weights from subjects; and (3) Geigy
(1981) values for both a mean and 95th percentile of daily urine
excretion volume.  Based on the results at the mean and 99th percentile
of the dose, the aggregate risks to triclosan from all uses (EPA and
FDA) do not trigger a risk of concern.  The mean MOEs range from 4,700
to 19,000.  The MOEs at the 99th percentile of the dose range from 260
to 1,500.  In fact, applying the lowest (most conservative) percent
urinary excretion from the results of the pharmacokinetic data (i.e., 24
percent) to the most conservative dose conversion method (i.e.,
Geigy’s 95th percentile of daily urine volumes), the MOE is 120.  In
conclusion, even with the considerable uncertainties in converting spot
urine concentration to dose, the NHANES data as analyzed for triclosan
sufficiently characterizes the aggregate risks as meeting the definition
of not resulting in unreasonable adverse effects.

Table 4.3.  Acute, Short, Intermediate-, and Long-term Aggregate Risks
for Triclosan (Mean)

Groups	Method:

Mage (2007) Obese Correct-based Dose

[Creatinine Correction]	Method:

Schafer (2004) Actual BW-based Dose

[Urinary Volume Correction]

Method:  Geigy 1981 [Urinary Volume Correction]

	Mean Urine Volume-based

Dose	95% Urine Volume-based

Dose

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Table 4.4.  Acute, Short, Intermediate-, and Long-term Aggregate Risks
for Triclosan (99th Percentile)

	Groups	Method:

Mage (2007) Obese Correct-based Dose

[Creatinine Correction]	Method:

Schafer (2004) Actual BW-based Dose

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

	Mean Urine Volume-based

Dose	95% Urine Volume-based

Dose

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

<IP_ADDRESS>	Infants

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

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

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

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

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

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

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

Inhalation of triclosan-contaminated dust.

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

Brushing teeth with triclosan-treated tooth paste;

Washing hands with triclosan-treated antibacterial soap;

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

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

Infant-specific Exposure Pathways

Nursing

	As indicated by the NHANES biological monitoring data set, a
substantial portion of the population has triclosan excreted in the
urine.  Therefore, mothers expose nursing infants to
triclosan-contaminated breast milk.  Dayan (2007) reports a breast milk
concentration of 35.8 ug of triclosan per kilogram whole breast milk.
Limited information is available in this study on the actual results of
the breast milk sampling.  The breast milk was obtained
“…anonymously after collection by the Mothers Milk Banks for routine
purposes” from 62 mothers from California and Texas.  The breast milk
concentration ranged from two non detect samples up to 2100 ug/kg lipid
(as opposed to whole milk).  Dayan (2007) does not report individual
data points but summarizes the data as “…the mean of the
concentrations in the 5 samples with the highest levels… 1742 ug/kg
lipid, corresponding to 35.8 ug/kg whole breast milk.”  Using the same
ratio by Dayan (2007) of lipids to whole milk, the maximum level
reported, 2100 ug/kg lipid, corresponds to 43.2 ug/kg whole breast milk.

	USEPA’s (2002) Child-specific Exposure Factors Handbook recommends
nursing ingestion rates.  The mean breast milk intake for a 1 to 6 month
old is 742 ml/day (upper percentile is estimated as the mean plus two
standard deviations yielding a value of 1033 ml/day).  The mean breast
milk intake for a 12 month old is 688 ml/day (upper percentile is 980
ml/day).

	An infant’s estimated daily dose of triclosan-contaminated breast
milk is the product of the breast milk concentration multiplied by the
daily intake volume.  The following equation is used to determine the
daily dose.

PDD =  BM (concentration) x CF1 x CF2 x SP x BM (intake)

	      			BW

where:

PDD			= 	potential daily dose (mg/kg/day);

BM (concentration) 	= 	Breast milk conc. (ug/kg whole breast milk);

BM (intake)		=	Breast milk intake (ml/day)

SP			=	Specific gravity of breast milk (1.03).

CF1			=	Conversion factor of 0.001 mg/ug.

CF2			=	Conversion factor of 0.001 kg/ml.

BW 			= 	body weight of an infant (kg).

Assumptions

As a bounding estimate, the maximum breast milk concentration in whole
breast milk from 62 mothers reported by Dayan (2007) is assumed (i.e.,
43.2 ug/kg whole breast milk).

As a bounding estimate, the upper percentile (i.e., mean plus two
standard deviations) of breast milk intake is assumed for a 1 to 6 month
old to represent the 6 to 12 month old infant (i.e., 1033 ml/day).

Specific gravity of breast milk 1.03 (KellyMom.com).

The body weight of a 6 to 11 month old infant is 9 kg (average of the
male and female body weights rounded to a whole number) (USEPA 2002).

The daily dose for an infant 6 to 12 months old is estimated to be 0.005
mg/kg/day.  The MOE is 6000 (i.e., chronic NOAEL of 30 mg/kg/day / daily
dose 0.005 mg/kg/day).  The target MOE of 100 indicates no risks of
concern.

Object-to-mouth

	Plastics and polymers used in toys can be treated with triclosan during
the manufacturing process.  Therefore, children’s post application
incidental oral exposures to treated toys may occur.  Regardless of the
fact that not all plastic toys are treated with triclosan and the toys
that are treated will not be used everyday, the oral endpoint selected
for triclosan is based on a long-ter toxicity study and was selected for
the short-, intermediate-, and long-term durations.

	There is potential for incidental ingestion of triclosan residues when
children play with and mouth plastic objects such as toys treated with
triclosan.  To determine incidental oral exposure of children mouthing
objects such as triclosan-treated plastic used to manufacture toys, the
following equations were used:

PDD = SR x SE x SA

	      BW

where:

PDD	= 	potential daily dose (mg/kg/day);

SR 	= 	surface residue (mg/cm2);

SE	=	saliva extraction efficiency (unitless fraction)

SA	=	surface area of toy mouthed (cm2/day)

BW 	= 	body weight of an infant (kg).

And

SR = % a.i x W x CF x F

	         SA

where:

SR	=	surface residue (mg a.i./cm2)

% a.i.	=	fraction active ingredient in toy by total weight (unitless)

W	=	weight of toy (g/cm2)

CF	=	conversion factor (1,000 mg/g)

F	=	fraction additive available at the surface of the toy (unitless)

SA	=	surface area (cm2)

Assumptions

It is assumed that 500 cm2 is a representative surface area of plastic
that is mouthed.

Since chemical specific leaching data were not available, the actual
amount of active ingredient at the surface of the plastic object which
is available for mouthing is based on the following assumptions

The plastic object such as a toy is manufactured from ABS or polystyrene
plastic; and

No more than 0.5% of the additive is available on the surface of the
plastic object for each mouthing event.  To put this value into
perspective, this is equivalent to one-half of the total amount of
triclosan in plastic products being excreted to the surface in 140 days.

The weight of a 500 cm2 toy is 50 g, which is based on data showing that
a polyethylene highchair sample with a surface area of 12.7 cm2 weighs
1.3072 g (i.e., 0.1 g/cm2).

The triclosan registered antimicrobial product contains 99% a.i. by
weight and is used to treat plastic at a rate of 0.5% product by weight
of the plastic material; thus, the % a.i. in treated plastic is
calculated as 0.99 ai weight fraction x 0.5% = 0.5% ai in the treated
plastic.

The saliva extraction efficiency is assumed to be 50% (EPA 2001).

The body weight of a 6 to 11 month old infant is 9 kg (average of the
male and female body weights rounded to a whole number) (USEPA 2002).

	Table 4.5 shows the calculations of the incidental oral exposure and
MOE for infants mouthing triclosan-treated plastic objects such as toys.
 The MOE of 430 is above the target MOE of 100 and is not of concern.

Table 4.5.  Incidental Oral Exposure and MOE for Infants Mouthing
Triclosan-treated  Objects such as Toys

Duration	% a.i.	Plastic Weight (g)	Fraction of triclosan available on
plastic surface

	Surface area mouthed (cm2)	Residue on Surface of plastic (mg/cm2)
Saliva extraction efficiency

	Exposure a

(mg/kg/day)	MOE

(Target MOE is 100) b

ST	0.5%	50	0.5%	500	0.0025	50%	0.069	430

(a )  Potential exposures are expressed as mg/kg/day; equations used to
estimate exposure are presented above.

(b)  MOE = NOAEL/exposure estimate [Where: short-, intermediate-, and
long-term oral NOAEL = 30 mg/kg/day].  Target MOE = 100.

Hand-to-mouth

	Children in the 6 to 12 month old age group exhibit hand-to-mouth
activities that may lead to triclosan exposure that would not be
accounted for in the NHANES 6-11 year old subpopulation.  Residues on
hands may result from touching triclosan-impregnated products or
crawling on floors with triclosan-contaminated dust.  An assessment is
already provided for directly mouthing treated items.  Therefore,
hand-to-mouth activities is being assessed for an infant that may ingest
dust that adheres to their hands as another potential pathway for
aggregate exposure.

	Canosa et al (2007) provides triclosan dust concentrations from 10
private homes in Spain.  Triclosan concentrations in dust averaged 702
ng/g in the homes (range of 240 to 2,200 ng/g).  The indoor dust samples
were collected using a vacuum cleaner with paper dust bags.  The
fraction of dust with particle sizes less then 60 um were collected.

	The amount of house dust that could adhere to a child’s hand is not
available.  To estimate the amount of dust that could adhere to an
infant’s hand, soil adherence factors for hands from USEPA (2002) are
used.  The difference between the adherences of soil versus house dust
is unknown.   Therefore, the high end of soil adherence is used.  USEPA
(2002) provides in it’s Table 8-8 a range of soil adherence factors
from 0.0063 mg/cm2 up to 0.15 mg/cm2.   The maximum value of 0.15 mg/cm2
represents 1 to 6.5 year olds in a daycare facility playing indoors and
outdoors (on bare earth).

	To calculate incidental ingestion exposure to these chemicals due to
hand-to-mouth transfer, the methodologies established in the Standard
Operating Procedures (SOPs) for Residential Exposure Assessments (USEPA
2000 and, 2001) were used.  Exposures were calculated for children
contacting triclosan-contaminated house dust in residential homes and/or
commercial day care centers using the following equations for
hand-to-mouth transfer of pesticide residues:

PDD = Dust (conc) x AF x SA x EF x ET x SE x CF1 x CF2

                                         BW

where:

PDD		=		Potential daily dose (mg/kg/day);

Dust (conc)	=		Indoor dust concentration (ng/g);

AF		=		Adherence factor for soil as surrogate for house dust (mg/cm2);

SA		=		Surface area of the hands that contact both the treated area, and
the individuals mouth (cm2/event);

FQ		=		Frequency of hand-to-mouth events (events/hr);

SE		=		Saliva extraction efficiency (unitless fraction);

ET		=		Exposure Time (4 hrs/day);

CF1		=		Unit conversion factor (0.000001 mg/ng);

CF2		=		Unit conversion factor (0.001 g/mg); and

BW		=		Body weight (9 kg)

Assumptions

Based on USEPA/OPP/HED’s Residential SOP, it was assumed that the
surface area used for each hand-to-mouth event is 20 cm2.  For
short-term exposures, it is assumed that there were 20 events per hour
(90th percentile) and for intermediate-term exposure; it was assumed
that there were 9.5 event/hour (mean value).

The maximum soil adherence factor of 0.15 mg/cm2 represents 1 to 6.5
year olds in a daycare facility playing indoors and outdoors (on bare
earth).

The exposure time is 4 hours a day (USEPA, 2000 and 2001).

The saliva extraction efficiency is 50% (USEPA, 2000 and 2001).

The body weight of a 6 to 11 month old infant is 9 kg (average of the
male and female body weights rounded to a whole number) (USEPA 2002).

Canosa et al.( 2007) provides triclosan dust concentrations from 10
private homes in Spain.  Triclosan concentrations in dust averaged 702
ng/g in the homes (range of 240 to 2,200 ng/g).

Results

	The calculation of the short- and intermediate-term oral doses
(toxicological endpoint selected is also protective of the long-term
duration) and the oral MOEs are shown in Table 4.6.  The oral MOEs are
above the target MOE of 100.

Table 4.6.  Short- and Intermediate-term (and Long-term) Incidental Oral
Post-application Exposures and MOEs for Infant Hand-to-mouth from
Contacting Triclosan-contaminated House Dust

Exposure Scenario

Dust Residuea (ng/g)

Soil Adherence Factor (mg/cm2)

Surface area mouthed (cm2/event)

Exposure Frequency (events/hr)

Saliva Extraction Factor

Exp. Time (hrs/day)

Daily Doseb (mg/kg/day)

Oral MOEc

Dust (ST)	2200	0.15

20

20

50%

4

	2.9E-5

1E+6

Dust (IT & LT)	702

9.5

4.4E-6

6.7E+6

a 	Dust residue:  ST maximum concentration of 2200 ng/g and long-term
average of 702 ng/g (Canosa et al 2007).

b 	Daily Dose  (mg/kg/day) = [(Dust residue, ng/g)*(adherence factor,
0.15 mg/cm2)*(exposure time, 4 hrs/day)*(surface area of hands, 20
cm2/event)*(frequency of hand-to-mouth activity, 20 events/hr, and 9.5
event for intermediate term)*(extraction by saliva, 0.5)*(conversion
factor 0.000001 mg/ng)*( conversion factor 0.001 g/mg)]/(body weight, 9
kg)]

c 	MOE = NOAEL (mg/kg/day) / daily dose(mg/kg/day) [Where short-,
intermediate-, and long-term oral NOAEL = 30 mg/kg/day].  Target MOE =
100.

Dust Inhalation

Characteristics of children in the 6 to 12 month age group include
behaviors described in USEPA (2002) as “development of personal dust
clouds”.   In other words, infants are in close proximity to
carpet/floor dust.   Canosa et al (2007) provides triclosan dust
concentrations from 10 private homes in Spain.  Triclosan concentrations
in dust averaged 702 ng/g in the homes (range of 240 to 2,200 ng/g).
The indoor dust samples were collected using a vacuum cleaner with paper
dust bags.  The fraction of dust with particle sizes less then 60 um
were collected.

Typical amounts of dust inhaled in indoor environments are not available
to estimate the inhalation exposure to triclosan-contaminated dust.
Therefore, a range of dust standards are used to represent the high end
of breathing dust.  Three estimates are provided to develop an overly
conservative estimate for up to a long-term duration.  EPA’s ambient
air quality standard for dust exposure is 0.15 mg/m3; the ACGIH-TLV
level is 10 mg/m3; and the OSHA PEL for dust is 15 mg/m3.

The resulting route-specific inhalation MOEs are in the millions (Table
4.7).  Based on this conservative approach, inhalation to
triclosan-contaminated dust is considered to be negligible.

Table 4.7.  Inhalation Risks to Infants Breathing Triclosan-contaminated
House Dust.

Exposure Standard	Dust Exposure Level

(mg/m3)	Triclosan Concentration in DustA	Triclosan Exposure LevelB

(ng/m3)	Inhalation MOEC (Target MOE = 1000)

EPA Ambient Air Quality Standard - PM10	0.15	0.702 ng/mg	0.11
450,000,000

ACGIH-TLV – Inhalable Fraction	10

7.0	70,000,000

OSHA PEL – Total Dust	15

11 	45,000,000

A. (702 ng/gm)/(1000 mg/gm) = 0.702 ng/mg

B. Trichlosan Exposure (ng/m3) = Dust Exposure (mg/m3) * Trichlosan
Concentration in Dust (0.702 ng/mg)

C. Inhalation MOE = [Inhalation LOAEL (50 mg/m3) * 1,000,000 ng/mg] /
[Trichlosan Exposure (ng/m3)]

Infant Aggregate

	Aggregate risks for children less then 6 years old have also been
considered separately from the results of the NHANES biological
monitoring assessment.  Table 4.8 presents the aggregate risks for the 6
to 12 month old age group.  The aggregate risks presented represent the
high-end of exposure that may co-occur from the various EPA and
FDA-regulated triclosan products.  The risk results of the 6-11 year old
NHANES age group are used in conjunction with infant-specific exposure
activities.  The 6-11 year old age group represents exposures to all of
the potential EPA-registered uses such as textiles and fabrics; plastic
products; as well as FDA-regulated soaps and toothpaste.  Clearly,
including exposures to the FDA-regulated soaps and toothpaste for 6-11
year olds is a conservative assessment of exposure from these products
to 6 to 12 month olds.  Future refinements to the infant aggregate
should focus on this portion of the total exposure.

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

Table 4.8.  Aggregate Exposure and Risks for Infants 6 to 12 Months.

Scenario	Risk (MOE)	Representative Products

	Mean	99th%	Bounding

	NHANES

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

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

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

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

Aggregate a

(Total MOE)	390b

(mean + bounding)	290c

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

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

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

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

Dermal Irritation

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

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

Dermal Systemic

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

Exposure Calculations

Potential doses are calculated as follows:

PDD = D x WF1 x TF. x SA

		BW

where:

PDD		= 	potential daily dose (mg/kg/day);

D		=	Textile density (mg/cm2);

WF1 		= 	weight fraction of ai product in textile (%);

TF		= 	Transfer factor from clothing to skin (%);

SA		= 	Surface area of body contacting treated clothing (cm2/day); and

BW		=	body weight (kg).

Assumptions

WF1:  The product is applied at rates as high as 2% of weight of
textile; the highest application rate of 2% product corresponds with the
highest percent triclosan formulation (i.e., 99 percent active
ingredient, EPA Reg. No. 70404-5).

SA:  The median surface area of clothing contacting skin for a
3-year-old toddler is 5,670 cm2 (total body surface area minus the head)
(USEPA, 1997).  For adults, the median surface area is 16,900 cm2 (total
body surface area minus the head) (USEPA, 1997).  Note:  The Phase I
comments suggested that triclosan in textiles is primarily limited to
sports wear.  However, no refinements to the assessment have been made
to represent short pants and short-sleeved shirts because it is not a
label restriction and some sports wear may be long pants and
long-sleeved shirts (e.g., sweat pants and sweat shirts).  Phase I
comments also suggested that the surface area should be adjusted for
inside surface area of clothing contacting skin (i.e., 50% adjustment).
However, adjustments were not made to the assessment because the
transfer of triclosan residues may come from both dermal contact with
the suggested inside surface of clothing as well as sweat-soaked
clothing which would appear to include the full fabric.  Adjustments
were also suggested for the fact that clothing is only worn 12 hours per
day and triclosan represents less than 100% market share.  These
adjustments were not made for this screening-level single textile use
because insufficient information on residue transfer to a person’s
skin over time is not available and risks are determined for those
individuals wearing the treated clothing articles (i.e., not a
population adjusted risk assessment).  However, the aggregate assessment
using the NHANES biological monitoring data for triclosan is based on
real world exposures and is believed to be the best data available to
regulate the uses.

D:  The textile density is 10 mg/cm2 based on the density of mixed
cotton and synthetics (HERA 2003).  It is assumed that the mixed
cotton/synthetic is used to cover the body for both adults and toddlers,
minus the head surface area.

TF:  Potential doses were calculated using residue transfer factor of
0.55% from a leaching study developed by Sanitized, Inc, dated December
4, 2007.  The leaching study provided results for cotton (0.55%
leached), wool (0.06% leached), and two poly-based fabrics (0.00% for PA
and 0.34% for PES).  The cotton fabric leached the highest amount over a
48 hour period at 20 degrees C.  The study used an acidic sweat solution
at a pH of 5.5 and the ISO 105/E04 method to extract the triclosan from
the various treated fabrics.

BW:  Toddlers (3 years old) are assumed to weigh 15 kg. This is the mean
of the median values for male and female toddlers (USEPA, 1997).  For
adults, a body weight of 70 kg has been assumed. (USEPA, 1997).

Results

	The calculations of the intermediate-term dermal doses and MOEs for
adults and toddlers wearing treated clothing are shown in Table 4.9.
The dermal MOEs for adults and toddlers are equal to or above the target
MOE of 100.

Table 4.9:  Dermal Intermediate-term Post-application Exposures and MOEs
for Toddlers and Adults Contacting Treated Textiles and Fabrics.

Exposure Scenario	Density of clothing (mg/cm2)	Percent triclosan in
product (%)	Percent of product applied (%)	Percent residue transferred
from clothing to skin (%)

	Surface Area (cm2)	Daily dosea

(mg a.i./ kg/day)	Dermal MOEc (Target MOE=100)b

Toddler	10	99%	2%	0.55%	5670	0.41	98

Adult	10	99%	2%	0.55%	16900	0.26	150

a.	Daily Dose (mg/kg/day) =  [(Density of fabric 10 mg/cm2) * (surface
area of body covered, cm2) * 1 outfit/day  * (percent a.i. in product,
%) / 100 * (percent of product applied, %) / 100 * (percent residue
transferred from clothing to skin, %/100) * (dermal absorption factor,
1)] / (body weight, 15 and 70 kg).

b. 	Dermal MOE = NOAEL (mg/kg/day) / Daily Dose [Where intermediate-term
dermal NOAEL = 40 mg/kg/day].  Target MOE = 100.

5.0	OCCUPATIONAL EXPOSURE ASSESSMENT tc \l1 "6.0	OCCUPATIONAL EXPOSURE
AND RISK

	The exposure scenarios assessed in this document for the representative
uses selected by EPA are shown in Table 5.1. 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.

	Potential occupational handler exposure for triclosan can occur in
three use sites:   commercial/institutional/industrial premises and
equipment, material preservatives, and industrial processes and water
systems.

Table 5.1.  Representative Exposure Scenarios Associated with
Occupational Exposures to Triclosan

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

Commercial/Industrial/Institutional Premises (Use Category III)

HVAC coil applications	Airless sprayer	ST/IT Handler:

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

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

Painting

(commercial painters)	Paint brush,

Airless sprayer	ST/IT Handler:

Inhalation	42182-1	0.1 lb ai/gallon

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

Material Preservatives (Use Category VII)

Paint

	Liquid pour,

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

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

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

Pulp and Paper

	Metered pump

	ST/IT Handler: Inhalation

	70404-5

	2% ai by weight of paper product

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

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

	5.1 	Occupational Handler Exposures

	The occupational handler scenarios included in Table 5.1 were assessed
to determine inhalation and dermal exposures.  The general assumptions
and equations that were used to calculate occupational handler
inhalation risks are provided in Section 1.2, Criteria for Conducting
the Risk Assessment. The majority of the scenarios were assessed using
CMA data and Equations 1-3 as outlined in Section 1.2.  However, for the
occupational scenarios in which CMA data were insufficient, other data
and methods were applied.

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.  The systemic dermal assessment is based on a dermal
route-specific endpoint, and therefore, dermal absorption adjustments
are not necessary.  The intermediate- and long-term dermal endpoints are
identical (but require different target MOEs to account for the
long-term duration).

Unit Exposure Values (UE):  Inhalation and dermal unit exposure values
were taken from the proprietary Chemical Manufacturers Association (CMA)
antimicrobial exposure study (USEPA, 1999b: DP Barcode D247642) or from
the Pesticide Handler Exposure Database (USEPA, 1998).

The For the liquid pour scenarios, the unit exposure depends on the
material being treated. The following CMA unit exposures were available
and used for the assessment of the risk associated with the treatment of
the specified materials.

Paint manufacturing: CMA preservative data.  The dermal unit exposure is
0.135 mg/lb ai (gloved).  The inhalation unit exposure is 0.00346 mg/lb
a.i.  These unit exposure values are based on 2 replicates where the
test subjects were wearing a single layer of clothing and chemical
resistant gloves.   SEQ CHAPTER \h \r 1 Although these unit exposures
are based on minimal replicates, the exposure values are similar to the
ones found in PHED for a similar scenario.

The For the liquid pump scenario, the unit exposure depends on the
material being treated. The following CMA unit exposures were available
and used for the assessment of the risk associated with the treatment of
the specified materials.

Paint and pulp & paper:  CMA preservative pump data.  The dermal UE is
0.00629 mg/lb ai(with gloves) and the inhalation UE is 0.000403 mg/lb
ai.  The values are based on two replicates where the test subjects were
wearing a single layer of clothing and chemical resistant gloves.

For airless sprayer scenarios, the occupational PHED inhalation and
dermal unit exposure values for airless sprayer application (PHED
scenario 23) were used. The inhalation exposure value is 0.83 mg/lb ai.
The dermal unit exposure is 38 mg/lb ai for ungloved replicates. PPE are
not considered for material preservatives in paint because the paint is
considered a treated article and as such there is no pesticide label on
the paint container to communicate PPE.

For roller/brush scenarios, the occupational PHED dermal and inhalation
unit exposure values for paintbrush applications (PHED scenario 22) were
used (single layer of clothing).  The inhalation exposure value is 0.28
mg/lb a.i. The dermal unit exposure is 180 mg/lb ai for no glove
replicates.  PPE are not considered for material preservatives in paint
because the paint is considered a treated article and as such there is
no pesticide label on the paint container to communicate PPE.

Quantity handled/treated: The quantity handled/treated values were
estimated based on information from various sources.  The following
assumptions were made:

For the liquid pour scenarios, the quantity of the chemical that is
handled depends on the material that is being treated.  The following
values were used for the different materials:

Paint:  20,000 lbs (approximately 2,000 gallons, weight based on a
density 10 lb a.i./gal) (standard AD assumption).

For the liquid/metering pump scenarios the quantity that is handled
depends on the material that is being treated.  The following values
were used for the different materials:

Pulp and Paper:  500 tons/day.

Paint:  200,000 lbs (approximately 20,000 gallons, weight based on a
density of 10 lb a.i./gal) (standard AD assumption).

For the roller/brush painting scenario, it was assumed that 50 lbs
(approximately 5 gallons of paint with a density of 10 lb/gal) of
treated paint are used (standard AD assumption).

For the airless sprayer in the painting scenario, it was assumed that
500 lbs (approximately 50 gallons of paint with a density of 10 lb/gal)
of treated paint are used. (standard AD assumption).

For the airless sprayer in the HVAC coil scenario, it was assumed 1,000
ft2 of coil surface area is treated.

Duration of Exposure: The MOEs were calculated for the short- and
intermediate-term durations for occupational handlers using the
appropriate endpoints in Table 3.2.

Exposure Calculations and Results

	The resulting inhalation and dermal exposures and MOEs for the
representative occupational handler scenarios are presented in Table
5.2. The calculated dermal MOEs were above the target MOE of 100 for all
scenarios, except for the commercial painters (both by brush and airless
sprayer) and the pulp & paper use.  The inhalation MOEs are below the
target MOE of 1000 for the airless sprayer (paint), the paint
manufacturing, and the pulp and paper.

Table 5.2.  Short- and Intermediate-Term Inhalation and
Intermediate-Term Dermal Risks Associated with Occupational Handlers

Exposure Scenario

Method of Application

Unit Exposure

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

Daily Dose (mg/kg/day)a

MOEb

(Target MOEs = 1000 inhalation, 100 dermal)

Inhalation 	Dermal

	Inhalation

	Dermal

	Inhalation

	Dermal

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

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

Painting

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

	Airless sprayer	0.83	38

50 gallons	0.059	2.7	54	1

Material Preservatives (Use Site Category VII)

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

	Liquid pump	0.000403	0.00629 (gloves)

200,000 lbs	0.011	0.18	290	220

Industrial Processes and Water Systems (Use Site Category VIII)

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

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

	b	MOE = LOAEL or 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 = 1000 for inhalation and 100 for dermal.

		5.2  	Occupational Post-application Exposures

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

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

	There are several data limitations and uncertainties associated with
the occupational handler and post application exposure assessments.
These 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) (See Appendix A for summaries of
these data sources).   Since the CMA data are of poor quality, the
Agency requires that confirmatory data be submitted to support the
occupational scenarios assessed in this document.

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

6.0	REFERENCES tc \l1 "7.0	REFERENCES

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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

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

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

APPENDIX A: Summary of CMA and PHED Data

 tc \l1 "APPENDIX A: Summary of CMA data and PHED Chemical
Manufacturers Association (CMA) Data:

In response to an EPA Data Call-In Notice, a study was undertaken by the
Institute of Agricultural Medicine and Occupational Health of The
University of Iowa under contract to the Chemical Manufacturers
Association.  In order to meet the requirements of Subdivision U of the
Pesticide Assessment Guidelines (superseded by  Series 875.1000-875.1600
of the Pesticide Assessment Guidelines), handler exposure data are
required from the chemical manufacturer specifically registering the
antimicrobial pesticide.   The applicator exposure study must comply
with the assessment guidelines for Applicator Exposure Monitoring in
Subdivision U and the Occupational and Residential Exposure Test
Guidelines in Series 875.  For this purpose, CMA submitted a study on 28
February, 1990, entitled "Antimicrobial Exposure Assessment Study
(amended on December 8, 1992)" which was conducted by William Popendorf,
et al.  It was evaluated and accepted by Occupational and Residential
Exposure Branch (OREB) of Health Effect Division (HED), Office of
Pesticides Program (OPP) of EPA in 1990.  The purpose of this CMA study
was to characterize exposure to antimicrobial chemicals in order to
support pesticide reregistrations (CMA, 1992).  The unit exposures
presented in the most recent EPA evaluation of the CMA database (USEPA,
1999b) were used in this assessment.

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e job functions of mixer/loader/applicator were defined based on common
application methods used for antimicrobial pesticides.  A few of the
deficiencies in the CMA data are noted below:

The inhalation concentrations were typically below the detection limits,
so the unit exposures for the inhalation exposure route could not be
accurately calculated.

QA/QC problems including lack of either/or field fortification,
laboratory recoveries, and storage stability information.

Data have an insufficient amount of replicates.

The Pesticide Handlers Exposure Database (PHED):

The Pesticide Handlers Exposure Database (PHED) has been developed by a
Task Force consisting of representatives from Health Canada, the U.S.
Environmental Protection Agency (EPA), and the American Crop Protection
Association (ACPA).  PHED provides generic pesticide worker (i.e.,
mixer/loader and applicator) exposure estimates.  The dermal and
inhalation exposure estimates generated by PHED are based on actual
field monitoring data, which are reported generically (i.e., chemical
specific names not reported) in PHED.  It has been the Agency’ policy
to use surrogate or generic exposure data for pesticide applicators in
certain circumstances because it is believed that the physical
parameters (e.g., packaging type) or application technique (e.g.,
aerosol can), not the chemical properties of the pesticide, attribute to
exposure levels. [Note: Vapor pressures for the chemicals in PHED are in
the range of E-5 to E-7 mm Hg.]  Chemical specific properties are
accounted for by correcting the exposure data for study specific field
and laboratory recovery values as specified by the PHED grading
criteria.

PHED handler exposure data are generally provided on a normalized basis
for use in exposure assessments.  The most common method for normalizing
exposure is by pounds of active ingredient (ai) handled per replicate
(i.e., exposure in mg per replicate is divided by the amount of ai
handled in that particular replicate).  These unit exposures are
expressed as mg/lb ai handled.  This normalization method presumes that
dermal and inhalation exposures are linear based on the amount of active
ingredient handled.

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