Page 1 of 34 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, DC 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

Draft

Triclosan

Residential Exposure & Illustrative Risk Assessment

Office of Pe sticide Programs

Antimicrobials Division U.S. Environmental Protection Agency

Date: May 4 , 20 11Page 2 of 34 Table of Contents

List of Tables

................................ ................................ ................................ ............................. 2 List of Figures

................................ ................................ ................................ ............................ 2

EXECUTIVE SUMMARY

................................ ................................ ................................ ....... 4

1.0 INTRODUCTION

................................ ................................ ................................ ........ 6

1.1 Purpose

................................ ................................ ................................ ............................. 6

1.2 Chemical Identification

................................ ................................ ................................ .... 6 1.3 Physical/Chemical Properties

................................ ................................ .......................... 6

2.0 USE INFORMATION

................................ ................................ ................................ .. 7

3.0 SUMMARY OF TOXICITY DATA

................................ ................................ ............ 7

4.0 RESIDENTIAL AGGREGATE EXPOSURE & RISK ASSESSMENT

..................... 7

4.1 Summary of Registered Uses

................................ ................................ ..................... 7

4.2 Residential Handler Exposures

................................ ................................ .................. 7

4 .3 Residential Post

- application Exposures

................................ ................................ ..... 8

4.3.1 NHANES Data for Triclosan

................................ ................................ ..................... 8

4.3.1.1 Pharmacokinetics of Triclosan

................................ ................................ ................ 10

4.3.1.2 Uncertainties Associated with the Dose Conversion

................................ .............. 11

4.3.2 Aggregate Risks Using NHANES

................................ ................................ ........... 12

4.3.2.1 Children (6 years) to Adults

................................ ................................ ..................... 12

4.3.2.2 Infants

................................ ................................ ................................ ...................... 26

5.0 REFERENCES

................................ ................................ ................................ ........... 33

List of Tables

Table 1.1

. Physical/Chemical Properties of Triclosan

................................ ........................ 6

Table 4.1

. Aggregate Exposure and Risk for Triclosan (2007

- 2008 NHANES)

.............. 18

Table 4.2

. Female

- Specific Aggregate Exposure and Risk for Triclosan Using Geigy (1981) Mean and 95th%tile Urinary Volumes (2007

- 2008 NHANES)

........................... 19

Table 4.3

. Incidental Oral Exposure and MOE for Infants Mouthing Triclosan

- Treated Objects such as Toys

................................ ................................ ................................ ......... 29

Table 4.4

. Short

- and Intermediate

- te rm (and Long

- term) Incidental Oral Post

- application Exposures and MOEs for Infant Hand

- to

- mouth from Contacting Triclosan

- contaminated

House Dust

................................ ................................ ................................ ........................ 31

Table 4.5

. Aggregate Exposure and Risks for Infants 6 to 12 Month Olds

...................... 32

List of Figures
Figure 1.1

. Molecular Structure of Triclosan

................................ ................................ ...... 6 Figure 4. 1. Triclosan Excretion i n Urine (taken from Sandborgh

- Englund (2006))

........ 11 Figure 4.2

. Geigy Mean Urine Volume Dose Estimation: Estimated Arithmetic Mean (95% Confidence Interval) Triclosan Dose, by Demographic Group a nd NHANES Survey Cycle

................................ ................................ ................................ ..................... 20 Figure 4.3. Geigy Upper Bound Urine Volume Dose Estimation: Estimated 95 th
Percentile (95% Confidence Interval) Triclosan Dose, by Demographic Group and

NHANES Surve y Cycle

................................ ................................ ................................ .... 21 Figure 4.4. Geigy Mean Urine Volume Dose Estimation: Estimated 95 th Percentile (95% Confidence Interval) Triclosan Dose, by Demographic Group and NHANES Survey Cycle

................................ ................................ ................................ ................................ . 22Page 3 of 34 Figure 4.5. Geigy Upper Bound Urine Volume Dose Estimation: Estimated 95 th
Percentile (95% Confidence Interval) Triclosan Dose, by Demographic Group and NHANES Survey Cycle

................................ ................................ ................................ .... 23 Figure 4.6. Geigy Mean Urine Volume Dose Estimation: Estimated 99 th Percentile (95% Confidence Interval) Triclosan Dose, by Demographic Group and NHANES Survey Cycle

................................ ................................ ................................ ................................ . 24 Figure 4.7. Geigy Upper Bound Urine Volume Dose Estimation: Estimated 99 th
Percentile (95% Confidence Interval) Triclosan Dose, by Demographic Group and NHANES Survey Cycle

................................ ................................ ................................ .... 25Page 4 of 34 EXECUTIVE SUMMARY

The recently released National Health and Nutrition Examination Surveys (NHANES) biological monitoring data on triclosan has been presented in this draft document to illustrate the new exposure information in context with the recently available toxicity data on triclos an that forms the basis of one of the case studies in the upcoming Science Advisory Panel (SAP) Integrated Approaches to Testing and Assessment Strategies: Use of New Computational and Molecular Tools. This draft document is not part of the SAP consultat ion. This draft assessment has been conducted to provide the general public with an update of the latest information on triclosan.

In 2008 EPA developed a Reregistration Eligibility Decision (RED) document for

triclosan

. The 2008 RED assessment addre sse d the potential risks result ing from the use s of EPA

- registered triclosan in occupational settings and general population risks from all

uses

. In part, the 2008 exposure and risk assessment was based on t he NHANES biological monitoring data from the 20 03

- 2004 survey

. Based on available data at that time, t he Agency concluded that total exposure to triclosan from all sources did not present risks of concern for human health. The Agency also acknowledged scientific literature suggesting potential endocri ne effects of triclosan and committed to examining

the endocrine interactions of triclosan further. In addition, as new data became available on human exposure, that data would also be considered as well in any update to the 2008

assessment. The EPA’s Reg istration Review of triclosan is scheduled to begin in 2013.

Since 2008, the Agency, in collaboration with the Office of Research and Development’s National Health and Environmental Effects Research Laboratory,

conducted additional re search investigations into the potential endocrine effects of

triclosan , with an interest in identifying adverse outcome pathways that would facilitate characterization of precursor events for human health risk assessment. These research efforts have involved investigation of triclosan’s effect on the estrogen, androgen, and thyroid hormone systems using in vitro and in vivo testing methodologies consistent with the Agency’s goal under the Endocrine Disruptor Screening Program (EDSP) to screen pesticides, commercial chemicals, and environmental contaminants for their potential to disrupt the endocrine system

. Research results on triclosan to date have identified precursor events involving the effect of triclosan on the thyroid hormone system that form the basis for the Agency’s proposal of an adverse outcome pathway for triclosan that will be presented to the FIFRA Scientific Advisory Panel in May of 2011. The case study document is available on the EPA’s public docket at regulations.gov using docket

number EPA

– HQ

– OPP

– 2011

– 0284.

Toxicity studies that form the basis of the oral endpoint used in this draft risk

assessment are:

**•** Zorrilla, LM, Gibson EK

, Jeffay SC

, Crofton KM

, Setzer WR

, Cooper RL

, Stoker

TE

. (2009) The effects of triclosan on puberty and thyroid hormones in male

Wistar rats. Toxi col. Sci. 107 (1): 56

- 64.

**•** Stoker, T.E., Gibson, E.K., Zorrilla, L.M. (2010) Triclosan exposure modulatesPage 5 of 34 estrogen

- dependent responses in the female Wistar rat. Toxicol. Sci. 177(1):45

- 53

.

In these studies, triclosan (99.5% pure) was administered by oral gavage commencing on postnatal day (PND) 21 in both sexes and continuing until PND 41 in the female and PND 53 in the male. Males were dosed with triclosan at 3, 30, 100, 200 or 300 mg/kg/day and the females were dosed with triclosan at 9.375, 37.5, 75 o r 150 mg/kg/day. These male and female pubertal screening protocols examined a variety of reproductive endpoints including an in life estimate of pubescence (vaginal opening in the female and preputial separation in the male) in addition to measurements o f serum thyroxine (T4), thyroid stimulating hormone (TSH) and thyroid histology. The lowest

dose effect observed in all three studies was a decrease in serum T4.

Using the serum T4 decrease as the endpoint, BMD modeling using EPA's Bench

Mark Dose Softwar e (BMDS) was performed to determine the benchmark dose estimate (BMD) and lower limit estimate (BMDL) using the T4 data from these studies . Initial statistical modeling demonstrated no significant difference between studies for the effects

of triclosan on T4. Therefore, benchmark dose modeling was conducted simultaneously for three data sets. The bench mark response (BMR) was set at both 10 and 20% using an unconstrained Hill estimate to fit the data. Using the 10% BMR, the BMD was 10.37 mg/kg and the B MDL was 3.47. Using the 20% BMR in the same model, the BMD was 19.05 mg/kg and the BMDL was 8.07 mg/kg . For a detailed discussion of the toxicological effects, bench mark dose, and uncertainty factor selection the reader is referred to the background inf ormation on the case study (triclosan) being provided for

the EPA’s Scien tific Advisory Panel (SAP) May 2011 meeting ( http://www.epa.gov/scipoly/sap/meetings/2011/052411meeting.html ).

The resulting draft aggregate risks presented herein include exposure s to both

EPA

- and FDA

- regulated uses. The results of the assessment indicate that the exposures

do not exceed the level

- of

- concern for effects on the thyroid hormone system based on the recent toxicity data used in the case study

.Page 6 of 34 1.0 I NTRODUCTION

1.1 Purpose

In this draft document, EPA’s Antimicrobials Division (AD) presents the results of its review of the potential human health effects of the aggregate residential exposure to triclosan (5

- chloro

- 2

- (2,4 dichlorophenoxy) phenol). Th is draft ass essment has been developed to communicate the updated general population monitoring levels of triclosan in urine from newly released NHANES data to illustrate these new data in a risk context.

1.2 Chemical Identification

Triclosa n ( 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 below in Figure 1.1 :

Figure 1.1 Molecular Stru cture of Triclosan

1. 3 Physical/Chemical Properties

Table 1 .1 shows physical/chemical characteristics that have been reported for

triclosan.

Table 1

. 1 Physical/Chemical Properties of Triclosan

Parameter Tri closan

Molecular Weight 290

Density 1.55E3 kg/m3 at 22  ̊ C

Boiling Point S olid

Water Solubility 12 ppm

Vapor Pressure 5.2E

- 6 mm Hg at 25  ̊CPage 7 of 34 2.0 USE INFORMATION

Triclosan is used as a bacteriostat, fungistat, mildewstat, and deodorizer. The products containing triclosan as the active ingredient (a.i) 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 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

in gredient in products used during manufacturing of textiles and fabrics , plastics, 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 general population monitoring data

.

3.0 SUMMARY OF TOXICITY DATA

Triclosan has been studied for its effects on the thyroid and estrogen hormone systems in experimental animals (Crofton et al., 2007; Zorilla et al., 2009; Stoker et al., 2010). These data indicate an effect on thyroxine levels in rats through a mec hanism involving induction of biotransformation enzymes resulting in increased clearance of thyroxine from serum, and a potentiating effect on the action of estrogen in the presence

of triclosan. The assessment herein is based on these recent data. For a detailed discussion of the toxicological effects, bench mark dose, and uncertainty factor selection the reader is referred to the case study (triclosan) being provided for the EPA’s

consultation with the Scien tific Advisory Panel ’s (SAP) Integrated Approa ches to Testing and Assessment Strategies: Use of New Computational and Molecular Tools May 2011 meeting http://www.epa.gov/scipoly/sap/meetings/2011/052411meeting.html ).

4.0 RESIDENTIAL AGGRE GATE EXPOSURE & RISK ASSESSMENT

4.1 Summary of Registered Uses

The re are no EPA registered product s containing triclosan that can be applied directly by the homeowner . Articles treated with triclosan as a bacteriostat in occupational settings (e.g., EPA Reg. No. 70404

- 5) may have the potential for post

application residential exposure. Triclosan

- treated articles that may routinely be used in

the residential market in clude, 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.

4.2 Residential Handler Exposures

The paint use was not eligible for re

- registration during the RED process.Page 8 of 34 Therefore, in the future there will be no residential h andler uses of triclosan products.

4. 3 Residential Post

- application Exposures

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 inc lude 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 applic ation assessment also includes an aggregate assessment of the F DA 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 Examination Surveys ( NHANES ) biological monitoring data are available for triclosan to assess aggregat e exposure and risk. For the 2008 RED, NHANES data were available for triclosan only for the 2003

- 2004 survey cycle . Subsequently, CDC has released the triclosan results for the 2005

- 2006 and 2007

- 2008 survey years. The review below presents a compariso n of the three NHANES

triclosan data sets.

EPA estimated triclosan exposure using nationally representative biomonitoring data available through NHANES. This approach was adopted by EPA because of the need to assess aggregate exposure that is expected from co

- use of different consumer products containing triclosan. T he NHANES monitoring data provides the most representative measure of aggregate exposures to daily use products

. In the case of triclosan, population

- based biological monitoring data are a vailable 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 the best predictor of aggregate exposure because not only are the data triclosan spec ific, they are also based on actual consumer use of the various triclosan products as they co

- occur in practice and

would ostensi b ly include drinking water exposures as well

.

Although the aggregate exposure/risk assessment presented herein using the

NHA NES data provides a holistic view of the exposure to 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. Ther efore, a separate estimate for children under 6 years old has been included. Finally, d ermal and

inhalation route

- specific assessments did not change since the 2008 RED and are

therefore not repeated herein

. The reader is referred to the 2008 RED for tho se

assessments.

4.3.1 NHANES Data for Triclosan

The National Health and Nutrition Examination Surveys (NHANES) are a seriesPage 9 of 34 of US national surveys of the health and nutrition status of the non

- institutionalized civilian population conducted by the Cente rs for Disease Control and Prevention. As part of NHANES, urinary concentrations (μg/L) of triclosan (2,4,4’

- trichloro

- 2’

- hydroxydiphenyl ether) were measured on a random sample of participants of ages 6 and

over as part of a complex multi

- stage, stratifi ed survey that is nationally representative

. These measurements represent concentrations in spot urine samples. The dose (mg/kg/day) corresponding to the urine concentration was not measured or estimated by

NHANES. The NHANES urinary metabolite concentr ation 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 data can be found on the

NHANES website: www.cdc.gov/nchs/nhanes.htm NHANES data for triclosan are now

available for the 2005

- 2006 and 2007

- 2008 surveys.

EPA evaluates health effects in terms of toxicity endpoints that represent an exposure level in mg or μg per kilogram body weigh t 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 calcula tion 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 o f 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 multiplyin g the triclosan concentration in the urine 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 were proposed in the

2008 RED 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 st andardizes 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, in 2008 the resul ts of both methods wer e presented. The dose

conversion methods used in the 2008 RED are summarized below:

**•** Mage et al. (2004, 2007) use the estimated daily creatinine excretion for specific individuals based on their anthropometric measurements and demog raphic characteristics (e.g, age, sex, race (Black, non

- Hispanic or not), height, weight, and obesity (based on the BMI)). The triclosan concentration is divided by the creatinine concentration in the urine, multiplied by the estimated daily creatinine

ex cretion 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 isPage 10 of 34 mult iplied 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 95 th %ile urine volumes from Geig y (1981) were used in this

method.

Detailed procedures and assumptions used in the 2008 RED assessment to convert spot urine concentrations into dose to assess the triclosan aggregate risks wer e provided by Cohen (2008). Cohen (2008) provided the dose co nversion from spot urine samples leaving the correction for the pharmacokinetics of triclosan to be done within th e risk

assessment for the 2008 RED

.

The results presented in the 2008 RED indicated that the 3 methods above were very similar and that the r esults of the Geigy (1981) method were the most conservative (i.e., producing the higher exposure estimates) . In this revised assessment, only the results using the Geigy (1981) method are presented.

Krishnan et al (2010) published an alternative to the methods described above in assessing triclosan by using a biomonitoring equivalent (BE) approach

. However, Krishnan et al (2010) were not able to include the current toxicological endpoint used

herein for their review of triclosan BEs because it was not a vailable at the time of publication. The BE for the BMDL20 of 8.07 mg/kg/day / 30x uncertainty factor is 5.8 mg/L (or 7.4 mg/g creatinine).

4.3.1.1 Pharmacokinetics of Triclosan

A correction factor to account for the disposition of triclosan, derive d from the data of Sandborgh

- Englund (2006) was applied to the biological (urine) monitoring data provided 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 tr iclosan 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 4. 1. Therefore, 54 percent excretion, corrected for baseline exposur es, was used by EPA in this assessment to convert the urine concentrations from NHANES to a dose using estimated 24 hour urine void volumes. The conversion is facilitated by the linear excretion kineticsPage 11 of 34 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) divided by the median value of the triclosan excretion in urine (i.e., 0.54 ).

Figure 4. 1. Triclosan Excretion in Urine (taken from Sandborgh

- Englund (2006))

4.3.1.2 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. The following uncertainties and data limitations are noted for the aggregate

assessment:

**•** For simplici ty (and lack of data)

, absorption, distribution, metabolism, and elimination ( ADME ) pharmacokinetic parameters are assumed to be similar for all individuals within the NHANES study and are constant within individuals over

time.

**•** Sandborgh

- Englund (2006) r eported urinary excretion over 4 days post dose.

F rom 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 excretio n 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. Krishnan (2010) indicates that ... “The pharmacokinetic data, specifically plasma clearance, obtained from ten volunteers (Sandorgh

- Englund et al., 2006) is considered to be fairly robust, given the additional support from the literature regarding steady

- state and inter

- individual variability.”Page 12 of 34 **•** NHANES urinary metabolite concentration data are not collected in a way amenable to directly determining 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. This is a bounding estimate that leads to an

overestimate of the estimated dose.

**•** Dose calculation is also difficult because there is no way to determine from the

NHANES data fro m 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. There is no longitudinal sampling for NHANES and no personal diaries to determine potential sour ces of exposure and by which route

. However, the unique aspects of triclosan

-- short half life in urine and widespread daily use of triclosan products

– lend themselves to represent a range of short

- and long

- term measurements of exposure from a nation ally representative population sample such as NHANES. The critical assumption for justifying the dose estimation approach and that it represents a range of exposure durations is that study participants within NHANES are likely to be at steady state with r espect to their elimination of triclosan in urine. This assumption is bolstered by the following:

o A high percentage (~82 percent) of the population has detectable levels of triclosan in their urine; given the short half

- life, this suggests that exposure

o ccurs frequently ; and

o Triclosan is found in a number of consumer products that individuals would conceivably contact multiple times per day (e.g., hand soap, toothpaste, treated textiles/plastics), it seems reasonable to assume individuals are at steady

- st ate condition.

Future refinements to using the NHANES data for assessing triclosan should focus on refining these parameters.

4.3.2 Aggregate Risks Using NHANES

4.3.2.1 Children (6 years) to Adults

T he NHANES results are believed to be representative of a range of short 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 among individuals for triclosan; and

becaus e the use of triclosan

- treated products by the NHANES population is unknown. 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

dat a set to use for predicting aggregate risks in a regulatory context

.Page 13 of 34 Demographic Subgroups:

The a ggregate assessment is presented for the age groups and subpopulations

listed below. While the point of departure (PoD) for triclosan is based on thyroid eff ects and would apply to women of childbearing age and young children (birth to age ~6), it is recognized that the triclosan RfD may be conservative and not relevant to other population subgroups.

**•** All age group s ;

**•** Ages 6

- 11;

**•** Ages 12

- 19

**•** Ages 20

- 59

**•** Ages >=6 0

**•** Male

**•** Females

**•** Mexican

- American

**•** White, non

- Hispanic

**•** Black, non

- Hispanic

A separate analysis of the NHANES data set for females is also included using the following subgroups:

**•** Confirmed non

- pregnant (females)

**•** Confirmed pregnant

**•** Females 13

- 49

**•** Females 6

- 12

**•** Females 50+

Uncertainties and Limitations in the Aggregate Assessment :

Many assumptions are used at each stage of the development of risk estimates

. These uncertainties must be acknowledged for transparency so the reader can understand the bounding natu re of the risk estimates. The uncertainties range from the selection of the hazard endpoint to the dose conversion to the reporting and interpretation of the risk estimates. Below is an acknowledgement of the identified uncertainties and limitations

that need to be considered in interpreting the presented exposures and risks:

**•** The uncertainties of the spot urine to dose conversion are discussed in Section 4.3.1.2 above. Taken together, these assumptions tend to influence the resulting

dose estimates to b e on the high end.

**•** The dose levels represent very conservative estimates (e.g., the 24

- hour urine

volume used to estimate dose for one of the two urine

- to

- dose conversion

methods presented is at the 95 th percentile) and it is unknown if actual individuals are exposed at the dose levels at the higher percentiles/confidence intervalsPage 14 of 34 presented. Because of smaller sample sizes, estimates for demographic subgroups are less reliable than estimates for all persons. The CDC National Exposure Report (CDC 2009) d oes not include percentile values above the 95th percentile. The estimates and confidence intervals for the 99th percentile reported herein may be less reliable than estimates and confidence intervals for the 90th and 95th percentiles. The 99th percentil es are reported to illustrate the conservative nature

of the assessment and the fact that a single dose cannot be ruled out to cause these toxicological effects

.

**•** Triclosan spot urine concentrations in NHANES are believed to represent steady

state exposur e based on the short half life, high frequency of detectable triclosan in urine, and because triclosan is used in daily use products ; however it is important to note that the steady

- state argument is most likely relevant at the central tendency of the repo rted NHANES data. The steady

- state assumption may be less likely at both extremes of the overall distribution of urinary triclosan levels in NHANES. At the upper end of the distribution it is unknown if the person’s behavior/activity lead s to higher expo sures on a daily basis or if the concentrations were influenced by a single event such as swallowing tooth paste prior to sampling. In the latter case, the use of the 95 th percentile urine volume in the dose conversion further exaggerates this flaw in dos e conversion (and overestimates the dose/risk)

. Krishnan et al (2010) provides a similar caveat:

“For short

- lived compounds such as triclosan, an exceedance of the corresponding BE value in a single urine sample may or may not reflect continuing elevated exposure. As demonstrated in the limited available datasets and based on the kinetics of urinary elimination, spot urinary concentrations may vary substantially both within and across days in an individual. Thus, occasional exceedances of the BE value i n individuals in cross

- sectional studies do not imply that adverse health effects are likely to occur...”

. The “BE” value is the biomonitoring equivalent that can be explained

, in

- short

, as the reference dose (RfD) expressed as a back

- calculation of the con centration in urine (e.g., mg/L)

. The reader is referred to Krishnan et al (2010), Hays et al (2007 and 2008), and LaKind et al (2008) for a more thorough explanation of the BE. It is important to note that at the time of the Krishnan et al (2010) public ation the toxicological endpoint in this assessment was not available to the authors ( BE has been calculated and presented above in Section 4.3.1)

.

**•** Although t he effects seen in the point of departure ( PoD ) for triclosan were not
measured after a single d ose (i.e., the study was designed as a repeat dose testing )

, this effect cannot be ruled out for a 1

- day dosing. However, a single dose would

not likely be expected to impact tissue function at environmental exposures due to the buffering of thyroid hormo ne concentrations by homeostatic mechanisms.

The PoD for this current assessment is considered protective of long

- term

exposures because the effects observed in a short

- term dosing study measuring thyroid hormone changes are expected to occur within the s hort

- term duration for a chemical such as triclosan which is rapidly excreted in the urine (11 hour urinary half life, Sandborgh

- Englund 2006)

.Page 15 of 34 **•** In general, i t is preferable to set a single RfD to cover the whole population, in particular for risk manageme nt purposes. It is important to ensure that any RfD established is adequate to protect children and the embryo/fetus from possible in utero effects. While the point of departure (PoD) for triclosan is based on thyroid effects and would apply to women of c hildbearing age and young children (birth to age ~6), it is recognized that the triclosan RfD may be conservative and not relevant to other population subgroups. Although the PoD for developmental thyroid effects was applied to other population subgroups in this illustrative risk assessment, those situations did not result in any exposures e xceed ing the level

of

- concern . In situations in which a developmental endpoint is used for the whole population and exceedances are found in subgroups for which the en dpoint is not relevant, it would be important to set a second value based on another non

developmental endpoint. Note: Female

- specific subpopulations (including pregnancy) are also provided herein.

Summary of Results from NHANES 2007

- 2008 :

The NHANES d ata show that the majority of the US population has detectable levels of total (free plus conjugated) triclosan. Detectable levels of triclosan were found

in 8 2 percent of the US population in the 2007

- 2008 survey.

Table 4.1 provide s the arithmetic mea n as well as the 95 th and 99 th percentiles of the (1) spot urine concentration to dose conversion prior to correcting for the 54% triclosan urinary excretion (in units of μ g/kg/day); (2) the pharmacokinetic 54% corrected daily dose converted to units of mg /kg/day; and (3) the margin of exposure ( MOE )

. Table 4.2 provides the same analysis for the female

- specific subpopulations. The Geigy (1981) dose conversion method s used in this risk characterization include risk estimates calculated using both the mean daily urinary excretion volume and the 95 th percentile daily urinary excretion volume. The use of the daily urinary excretion volumes is

necessary to extrapolate to a daily dose because the NHANES data represent only a single spot urine collection sample. The inclusion of the 95 th percentile urinary excretion volume provides an upper bound estimate as a conservative assumption.

Based on the results at the mean , 95 th

, and 99 th percentile s of the dose (using both

the mean and 95 th percentile daily urinary excretion volumes) , the estimated aggregate
risks from all triclosan uses (EPA and FDA) indicate that the dose levels do not exceed

the BMDL 20 using a target MOE of 30

. The MOEs for all of the age groups and subpopulations as well as the separate assessme nt for the female

- specific subgroups are summarized as follows:

**•** The mean MOEs range from 1

, 9 00 to 4

, 4 00 assuming the mean daily urinary

excretion volume and from 1

, 2 00 to 2

, 7 00 assuming the 95 th percentile

**•** The MOEs at the 9 5 th percentile of the dose range from 3 30 to 8 7 0 assuming the daily urinary excretion volume.

mean daily urinary excretion volume and from 2 3 0 to 5 40 assuming the 95 thPage 16 of 34 percentile

**•** The MOEs at the 99 th percentile of the dose range from 150 to 34 0 assuming t he daily urinary excretion volume.

mean daily urinary excretion volume and from 9 0 to 28 0 assuming the 95 th
percentile daily urinary excretion volume.

The assumptions provided herein leave room for further refinement of the

estimated dose levels and are not intended to be viewed as a pr ecedent for other

assessments. In summary , even with the considerable uncertainties in converting spot

urine concentration to dose and the uncertainties associated with the 99 th percentile for

this data set , the NHANES data as analyzed for triclosan chara cterizes the draft aggregate
risk assessment as a conservative bounding estimate that does not exceed the level

- of

concern (i.e., BMDL 20 of 8.07 mg/kg/day with an uncertainty factor of 30)

.

Comparisons of Aggregate Dose & Risk From NHANES ‘03

- ‘04, ’05

- ’ 06, ’07

- ‘08

USEPA (2010) provides an analysis of the NHANES urinary concentrations from sample survey years 2003

- 2004, 2005

- 2006, and 2007

- 2007 converted to dose. Detectable levels of triclosan were found in 74.6, 80.8, and 81.5 percent of the US popula tion in the 2003

- 2004, 2005

- 2006, and 2007

- 2008 surveys, respectively.

The comparisons of the results from the NHANES data sets are graphically depicted below in Figures 4.2 through 4.7 . The figures illustrate the following:

**•** Figure 4.2

– Arithmetic mean dose based on the mean daily urinary excretion volume;

**•** Figure 4.3

-- Arithmetic mean dose based on the 95 th % daily urinary excretion volume;

**•** Figure 4.4

– 95 th percentile dose based on the mean daily urinary excretion volume;

**•** Figure 4.5

– 95 th percentile dose based on the 95 th % daily urinary excretion volume;

**•** Figure 4.6

– 99 th percentile dose based on the mean daily urinary excretion volume; and

**•** Figure 4.7

-- 99 th percentile dose based on the 95 th % daily urinary excretion

volume

Each figure contains the following information:

**•** NHANES dose levels corrected for urinary excretion (i.e., 54% of triclosan is excreted in the urine) for survey years 2003

- 2004, 2005

- 2006, and 2007

- 2008;

**•** Results for the a ge and demographic groups provided in Section 4.3.2.1 above ;

**•** Error bars for the lower and upper 95 th % confidence intervals (CI);

**•** The l evel of concern or reference dose (RfD) is depicted as a solid horizontal line (i.e., BMDL 20 8 mg/kg/day / 30x uncertainty factor = 0.27 mg/kg/day); and

**•** The 95 th percent lower confi dence limit of the bench mark dose (i.e., BMDL 10 of 3.5 mg/kg/day ) is divided by the 30x uncertainty factor to represent the lowerPage 17 of 34 limit of the RfD (i.e., 3.5 mg/kg/day / 30x uncertainty factor = 0.12 mg/kg/day)

. This value is depicted as a dotted horizo ntal line in the figures

.

The results illustrated in the figures indicate that neither the means , 95 th

, nor the

99 th percentiles or their upper 95 th percent confidence intervals of the doses exceed the level of concern (i.e., RfD of 0.27 mg/kg/day) for any age or demographic group for any of the survey years.

The lower limit of the bench mark dose is not exceeded at the means , 95 th

, or 99 th
percentiles of the doses for any age or demographic group for any of the survey years. The upper confidence inter vals on the 99 th percentile using the mean daily urinary excretion volume for any age or demographic group for any of the survey years do not exceed the lower limit of the bench mark dose. However, the 2005

- 2006 NHANES data indicate that for two groups th e 95 th percent upper confidence interval on the 99 th
percentile using the mean daily urinary volume to estimate dose is at the lower limit of the bench mark dose (i.e., Figure 4.6 ). Finally, the lower limit of the bench mark dose is exceeded by several of the groups for various survey years (i.e., Figure 4.7 ). The dose levels in Figure 4.7 represent a very conservative estimate. The upper confidence limits

of the 99 th percentiles in Figure 4.7 are reported to illustrate the conservative nature of the

ass essment and that those bounding estimates have not exceeded the level

- of

- concern.Page 18 of 34 Table 4. 1 . Aggregate Exposure and Risk for Triclosan (2007

- 2008 NHANES)

Mean 95th Percentile 99th Percentile

Group Dose,

uncorrecte
d (μg/kg/d ay ) † Dose,

corrected (mg/kg/day) ‡ MOE

* Dose,

uncorrect
ed (ug/kg/da

y) † Dose,

corrected (mg/kg/da y) ‡ MO

E* Dose,

uncorrect
ed (ug/kg/da

y) † Dose,

corrected (mg/kg/da y) ‡ MO

E*

Dose Conversion Method: Geigy (1981) Using the Mean Urinary Volume

All 1.57 0.0029 2755 7.8 0.0144 554 23.9 0.044 180

6

- 11 1.35 0.0025 3206 7.4 0.0137 584 22.5 0.042 192

12

- 19 2.04 0.0038 2119 8.8 0.0163 491 29.1 0.054 148

20

- 59 1.58 0.0029 2731 8.0 0.0148 540 24.4 0.045 177

>= 60 1.30 0.0024 3314 6.8 0.0126 635 15.3 0.028 282

Male 1.57 0.0029 2750 7.8 0.0144 554 21.5 0.040 201

Female 1.56 0.0029 2761 7.5 0.0139 576 25.4 0.047 170

Mexican

American 1.85 0.0034 2336 10.1 0.0187 428 25.0 0.046 173
White, Non

Hispanic 1.40 0.0026 3080 7.3 0.0135 592 21.5 0.040 201
Black, Non

Hispanic 1.30 0.0024 3313 6.4 0.0119 675 21.2 0.039 203

Dose Conversion Method: Geigy (1981) Using the 95th Percentile Urinary Volume

All 2.44 0.0045 1772 12.0 0.0222 360 36.9 0.068 117

6

- 11 1.90 0.0035 2270 10.8 0.0200 400 32.8 0.061 132

12

- 19 3.13 0.0058 1382 13.3 0.0246 325 47.1 0.087 92

20

- 59 2.49 0.0046 1734 12.9 0.0239 335 37.5 0.069 115

>= 60 2.04 0.0038 2113 10.9 0.0202 396 24.8 0.046 174

Male 2.39 0.0044 1805 12.0 0.0222 360 33.0 0.061 131

Female 2.48 0.0046 1742 12.0 0.02 22 360 41.0 0.076 105

Mexican

American 2.84 0.0053 1519 15.5 0.0287 279 38.4 0.071 112
White, Non

Hispanic 2.19 0.0040 1976 11.1 0.0206 389 32.8 0.061 132
Black, Non

Hispanic 2.04 0.0038 2121 10.4 0.0193 415 32.6 0.060 132 † Dose, uncorrected (ug/kg/da y) = NHANES 2007

- 2008 data set of spot urine sampling converted to dose, but not corrected for urinary excretion of triclosan. ‡ Dose, Corrected (mg/kg/day) = (Dose, uncorrected (ug/kg/day) / 0.54 urinary excretion of unconjugated triclosan (i.e., 54%)) / 1000 ug/mg unit conversion
* MOE = BMDL20 (mg/kg/day) / Dose, Corrected (mg/kg/day); where BMDL20 is 8 mg/kg/day; Target MOE = 30.Page 19 of 34 Table 4.2 . Female

- Specific Aggregate Exposure and Risk for Triclosan Using Geigy (1981)

Mean and 95th%tile Urin ary Volumes (2007

- 2008 NHANES)

Group Mean 95th Percentile 99th Percentile

Dose, uncorrected Dose, corrected

MOE Dose, uncorrected Dose, corrected

MOE Dose, uncorrected Dose, corrected

MOE (ug/kg/day) (mg/kg/day) (ug/kg/day) (mg/kg/day) (ug/kg/day) ( mg/kg/day)

Dose Conversion Method: Geigy (1981) Using the Mean Urinary Volume
Confirmed Non Pregnant (20

- 44 Year Old Females) 1.8 0.00335 2386 9.6 0.0178 450 29.8 0.0551 145

Confirmed Pregnant (20

- 44 Year Old Females) 2.3 0.00429 1863 9.5 0.0176 454 9 .5 0.0176 454

13

- 49 Year Old Females 1.9 0.00348 2297 9.5 0.0176 454 29.8 0.0551 145

6

- 12 Year Old Females 1.8 0.00332 2409 13.2 0.0244 329 22.5 0.0416 192

50 and Above Year Old Females 1.0 0.00180 4432 5.0 0.0092 871 12.8 0.0237 337

Dose Conversion Me thod: Geigy (1981) Using the 95th Percentile Urinary Volume
Confirmed Non Pregnant (20

- 44 Year Old Females) 2.9 0.00542 1477 15.5 0.0287 279 48.1 0.0890 90

Confirmed Pregnant (20

- 44 Year Old Females) 3.7 0.00694 1153 15.4 0.0284 281 15.4 0.0284 281

13

- 49 Year Old Females 3.0 0.00558 1434 15.4 0.0284 281 48.1 0.0890 90

6

- 12 Year Old Females 2.5 0.00469 1707 19.2 0.0356 225 32.8 0.0608 132

50 and Above Year Old Females 1.6 0.00292 2743 8.0 0.0148 539 20.7 0.0383 209

† Dose, uncorrected (ug/kg/day) = NHANES 2007

- 2008 data set of spot urine sampling converted to dose, but not corrected for urinary excretion of triclosan. ‡ Dose, Corrected (mg/kg/day) = (Dose, uncorrected (ug/kg/day) / 0.54 urinary excretion of unconjugated triclosan (i.e., 54%)) / 100 0 ug/mg unit conversion

* MOE = BMDL20 (mg/kg/day) / Dose, Corrected (mg/kg/day); where BMDL20 is 8 mg/kg/day; Target MOE = 30.Page 20 of 34 Figure 4.2 . Geigy Mean Urine Volume Dose Estimation : Estimated Arithmetic Mean (95% Confidence Interval) Triclosan Dose, by

D emographic Group and NHANES Survey CyclePage 21 of 34 Figure 4.3 . Geigy Upper Bound Urine Volume Dose Estimation : Estimated 95 th Percentile (95% Confidence Interval) Triclosan Dose, by Demographic Group and NHANES Survey CyclePage 22 of 34 Figure 4.4 . Geigy Mean Urine V olume Dose Estimation : Estimated 95 th Percentile (95% Confidence Interval) Triclosan Dose, by Demographic Group and NHANES Survey CyclePage 23 of 34 Figure 4 .5 . Geigy Upper Bound Urine Volume Dose Estimation : Estimated 95 th Percentile (95% Confidence Interval) Tric losan Dose, by Demographic Group and NHANES Survey CyclePage 24 of 34 Figure 4.6 . Geigy Mean Urine Volume Dose Estimation : Estimated 99 th Percentile (95% Confidence Interval) Triclosan Dose, by Demographic Group and NHANES Survey CyclePage 25 of 34 Figure 4.7 . Geigy Upper Bo und Urine Volume Dose Estimation: Estimated 99 th Percentile (95% Confidence Interval) Triclosan Dose, by Demographic Group and NHANES Survey CyclePage 26 of 34 4.3.2.2 Infants

While NHANES data are measured exposures that represent the real world co

occurrence of tr iclosan

- treated products for those age groups which were surveyed , it is necessary to use screening

- level deterministic assessments and to make assumptions of potential co

- occurrence of triclosan

- treated products for children younger than 6 years old

.

T he 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 anatom y 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 spec ific 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 from this EPA reference to represent behavioral activiti es of children younger than 6 years old (i.e., this age group is not sampled by NHANES) that are potentially exposed to

triclosan

- treated products.

I nfants in the 6 to 12 month old age group has been selected for this assessment to represent the high end of exposure activities of children less th a n six years old to triclosan

treated products. This age group is considered the high end of exposure based on the

characteristics of behavioral development discussed in Table 2 presented in USEPA (2005)

and the l ikelihood of these activities co

- occurring. USEPA (2005

– Table 2 ) indicates that this age group includes behaviors where... “Food consumption expands. Children’s floor mobility increases (surface contact). Children are increasingly likely to mouth nonfoo d items. Development of personal dust clouds.” These types of behaviors 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

likel ihood of mouth ing nonfood items, and “development of personal dust clouds” as a characteristic relevant to inhalation exposure. Note: The dust inhalatio n assessment is not part of the updated aggregate assessment, and therefore, not reproduced herein from the 2008 RED. The nursing exposure pathway has been updated to include the birth to <1 month old age group.

The younger age groups recommended by USEP A (2005

– Table 4 ) such as birth to <1 month, 1 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

– Table 2 ” ). The older age groups recommended by USEPA (2005

– Table 4 ) include 1 to <2 years, 2 to <3 years, 3 to <6 years old. These age groups reflect the cessation of nursing

and a reduction in h and

- to

- mouth activities. The activities in the older age groups 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 activitie s 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:Page 27 of 34 **•** Nursing (i.e., triclosan

- contaminated breast milk);

**•** Object

- to

- mouth exposures (e.g., mouthing of plastic items s uch 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 gro up that are captured

– and likely 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 impregna ted 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, co unter and table tops).

Infant

- specific Exposure Pathways

Nursing

Triclosan has been detected in urine in a substantial portion of the population. Therefore, mothers that are exposed to triclosan also have the potential to expose their nursing infants to triclosan

- contain ing 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 mi lk 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 (200 8 ) Child

- specific Exposure Factors Handbook recommends nursing ingestion rates. The mean breast milk intake from birth to < 1 month old is 510 mL/day and

for a 6 to 12 month old is 620 mL/day (upper percentile s are estimated as the mean plus two standard deviations yielding value s of 950 and 10 00 m L /day , respectively ).

An infant’s estimated daily dose of triclosan

- contamina ted 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 =

BW BM (concentration) x CF1 x CF2 x SP x BM (intake)

where:Page 28 of 34 PD D = 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 = Convers ion 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).

**•** Th e breast milk intake rates from birth to <1 month old and 6 to <12 month old are means of 510 and 620 mL/day, respectively (upper percentiles of 950 and 1000 mL/day, respectively)

. (USEPA 200 8 )

.

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

**•** The body weight s for birth to <1 month is 4.8 kg and for a 6 to <11 month old is 9.2 kg (USEPA 200 8 ).

The daily dose s of triclosan resulting from nuring for an infant in the birth to <1 month

old and 6 to 12 months old age groups using the mean milk intake rates are estimated to be

0.0047 and 0.00 30 mg/kg/day , respectively . The corresponding MOE s are 1700 and 27 00

, respectively (i.e., BMDL20 of 8 mg/kg/day / daily dose). The target MOE of 3 0 indicates no

risks of concern.

Object

- to

- mouth

Plastics and polymer s 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.

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 =

BW SR x SE x SA

where:

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

SR = surface residue (mg/cm 2 );

SE = saliva extraction efficiency (unitless fraction)

SA = surface area of toy mouthed (cm 2 /day)

BW = body weight of an infant (kg).

And

SR = % a.i x W x CF x FPage 29 of 34 where:

SR = surface residue (mg a.i./cm 2 )

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

W = weight of toy (g/cm 2 )

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

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

Assumptions

**•** The maximum surface area for mouthing an object is taken from the SHEDs Technical Manual’s Appendix G. The maximum surface area is 50 cm 2

( http://www.epa.gov/heasd/products/sheds_multimedia/files/SHEDS_Residentialv4_Techman
ual_06

- 16

- 2010.Final.pdf )

**•** C hemical specific leaching data are not available, and therefore, the amount of active ingredient at the surface of the plastic object which is assumed to be available for mouthing is based on the following assumptions

o The plastic objec t such as a toy is manufactured from ABS or polystyrene plastic; and

o No more than 0.5% of the additive is available on the surface of the plastic object each day

.

**•** The weight of a 50 cm 2 toy is 5 g, which is based on data showing that a polyethylene highc hair sample with a surface area of 12.7 cm 2 weighs 1.3072 g (i.e., 0.1 g/cm 2 ).

**•** 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 femal e body weights rounded to a whole number) (USEPA 2002).

Table 4.3 shows the calculations of the incidental oral exposure and MOE for infants mouthing triclosan

- treated plastic objects such as toys. The MOE of 1

, 2 0 0 is above the target

MOE of 3 0 and is n ot of concern.

Table 4.3 . Incidental Oral Exposure and MOE for Infa nts Mouthing Triclosan

Treated Objects such as Toys

Duration % a.i. Plastic Weight

(g) Fraction of

triclosan

available on

plastic

surface Surface

area mouthed

(cm 2 ) Residue on

Surface of

plastic (mg/cm 2 ) Saliva

extraction efficiency Exposure a (mg/kg/day) MOE
(Target MOE is

30 ) b

ST 0.5% 5 0.5% 50 0.0025 50% 0.0 0 69 1

, 2 0 0

(a ) Potential exposures are expressed as mg/kg/day; equations used to estimate exposure are presented above.
( b) MOE = BMDL20 /exposure estimate [Where: BMDL20 = 8 mg/kg/day]. Target MOE = 3 0.Page 30 of 34 Hand

- to

- mout h Ingestion of House Dust

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 crawling on floors with triclosan

contaminated dust. H and

- to

- mouth activities are being assessed for an infant that may ingest

dust that adheres to their hands that is unique to this age group as another potential pathway for aggregate exposure

.

The amount of house dust ingested by children or the amount of dust that could

adhere to a child’s hand wa s not available for the 2008 triclosan RED

. Therefore

, in 20 08 the

triclosan assessment was based on soil adherence factors. Ozkaynak ( in press ) reports modeled estimates for dust ingestion rates for children 3 to <6 years old. This new publication models the dust ingestion from hand

- to

- mouth activities and repor ts a mean of 20 mg of dust ingested per day (p95 = 74 mg/day and p100 = 649 mg/day)

. Th e revised

trilcosan assessment herein has been updated to use the available information in Ozkaynak ( in press ) to estimate exposure to children from the hand

- to

- mouth d ust ingestion pathway. Note: Ozakaynak ( in press ) “...examined 3 to <6 year

- old children only based on high frequency of mouthing behaviors for this age group and availability of more adequate exposure factor and input data for the SHEDS model than for som e of the other age groups. ” Although this age group is older than t h e infant age group (6 to 12 month) selected for triclosan, the estimates for the 3 to <6 were selected by Ozkaynak ( in press ) as a high end estimate and is used herein as part of the boun ding estimate for the 6 to 12 month old age

group . If the need arises to refine the risks generated for this pathway, the ingestion rate by various age groups could be further modeled

.

Canosa et al (2007) provides triclosan dust concentrations from 10 pr ivate 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 th a n 60 um were collected.

To calculate incidental ingestion exposure to triclosan due to hand

- to

- mouth ingestion of dust, the following equation is used:

PDD = Dust (conc) x IGR x CF1 x CF2

BW

where:

PDD = P otential daily dose (mg/kg/day); Dust (conc) = Indoor dust concentration (ng triclosan /g house dust );

IGR = Dust ingestion rate ( mg of dust /day);

CF1 = Unit conversion factor (0.000001 mg triclosan in dust /ng

triclosan in dust );

CF2 = Unit conversi on factor (0.001 g hous e dust /mg house dust ); and

BW = Body weight (9 kg)Page 31 of 34 Assumptions

**•** Ozkaynak ( in press ) reports modeled estimates of ingestion rate s of dust from hand

to

- mouth activities for the 3 to <6 year old age group

-- mean of 20 mg/day, p 95 of 74 mg/day, and p100 of 649 mg/day ;

**•** 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 triclosan /g of house dust 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 protec tive of the long

- term duration ) and the oral MOEs are shown in Table

4.4 . The oral MOEs are well above the target MOE of 3 0. It is important to note that these results are intended to be used as a bounding estimate to illustrate that the dust ingestion

p athway

– at any combination of currently available dust concentration and dust ingestion

rates

– does not trigger a risk. It is unknown if any individuals exist at the point on the distribution estimated by combining the maximum dust concentrations from a sample size

taken in Spain with the maximum potential dust ingestion rate.

Table 4.4 . 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 Triclosan Dust

Residue a (ng

triclosan /g dust ) Dust Ingestion Rate b
(mg/day) Daily Dose c (mg/kg/day) Oral MOE d

Maximum dust concentration 2200 20 (mean) 4.8E

- 6 1.7E+6

74 (p95) 1.8E

- 5 4.4E+5

649 (p100) 1.6E

- 4 5.0E+4

Mean d ust concentration 702 20 (mean) !.5E

- 6 5.2E+6

74 (p95) 5.8E

- 6 1.4E+6

649 (p100) 5.1E

- 5 1.6E+5

a Dust residue: maximum concentration of 2200 ng triclosan /g house dust and average of 702 ng triclosan /g of

house dust (Canosa et al 2007).

b Dust in gestion rate from hand

- to

- mouth : Ozkaynak ( in press ) Table II.

c Daily Dose (mg/kg/day) = [(Dust residue, ng/g)*( ingestion rate of house dust )*(conversion factor 0.000001 mg/ng)*( conversion factor 0.001 g/mg)]/(body weight, 9 kg)]

d MOE = BMDL20 (mg/ kg/day) / daily dose(mg/kg/day) [Where BMDL20 = 8 mg/kg/day]. Target MOE = 3 0.

Infant Aggregate

Aggregate risks for children less th a n 6 years old have also been considered separately

from the results of the NHANES

- based biological monitoring assessmen t. Table 4.5 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 (i.e., MOE) estimated f or the 6

- 11 year old 2007

- 2008 NHANES age group is used in conjunction with infant

- specific exposure activities. The 6

- 11Page 32 of 34 year old age group represents exposures to all of the potential EPA

- registered uses such as textiles and fabrics; plastic products; a s well as FDA

- regulated soaps and toothpaste. Clearly, including e xposures 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 a ggregate 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 estimate with the infant

- specific bounding risks . The aggregate MOE

, from the measured mean exposure estimates converted from the 6

- 11 year old urine

concentrations in NHANES mathematically combined with the screening

- level deterministic

estimates for nursing, object

- to

- mouth, and hand

- to

- mouth

, is 61 0

.

Table 4.5 . Aggregate Exposure and Risk s for Infants 6 to 12 Month Old s

Scenario Risk (MOE) Representative Pathway

Mean Bounding

2007

- 2008 NHANES

6

- 11 year olds 2,300 NA Exposures inclusive of all triclosan

treated products that co

- occur in the

real world for 6

- 11 year olds (excludes infan t

- specific activities) Nursing NA 2700 6 to 12 month old infants nursing (contaminated breast milk) from mothers exposed to triclosan

- treated

products that co

- occur in the real

world Object

- to

- mouth NA 1200 Wide range of triclosan

- treated products such a s toys that may be mouthed by infants

Hand

- to

- mouth NA 5.2E+6 Infants mouthing hands that have been contaminated by triclosan

residues in house dust at the mean

triclosan house dust concentration and mean house dust ingestion rate (rate is for 3 to <6 yea r old age group) Aggregate a
(Total MOE) 610 b
(mean + bounding) Total exposure of a 6

- 11 year old plus

infant

- specific activity exposures
(a) Aggregate ( Total MOE ) = 1/((1/MOE NHANES ) + (1/MOE Nursing ) + (1/MOE Object ) + (1/MOE HTM )) (b) Mean Aggregate = Su m of the mean NHANES MOEs plus the bounding MOE estimates from nursing, object

- to

- mouth, and hand

- to

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