Document ID: EPA-HQ-OPP-2009-0516-0031
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-10-02T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES  AND

TOXIC SUBSTANCES

Date: 03/30/2005

MEMORANDUM

SUBJECT:	Tributyltin maleate (TBTM): Non-Dietary Residential Exposure 
Considerations for Proposed Registration of  Ultra-Fresh® DM-50 as a
New Indoor Use Pattern for TBTM,

FROM:	Jeff Evans, Biologist

Chemistry and Exposure Branch

Health Effects Division (7509C)

TO:		Meta Bonner, Ph.D., Toxicologist

Registration Action Branch 3

Health Effects Division (7509C)

THRU:	David J. Miller., Acting Branch Chief

Chemistry and Exposure Branch

Health Effects Division (7509C)

PC Code (s).:		083118

DP Barcode:		314711

MRID:		45746801, 45746802

INGREDIENT PROFILE

Summary of Registered/Proposed Uses tc \l2 "Summary of
Registered/Proposed Uses 

Ultra-Fresh® DM-50 (EPA Reg. No. 10466-28) containing 25% ai
tri-n-butyltin maleate, is currently registered for use as a
bacteriostat and fungistat preservative finish for textiles (fabrics,
water-based emulsion/adhesives, and vinyl polymer materials) at
applications levels ranging from 0.08 to 0.4% (w/w).

The proposed new registration (File Symbol 10466-GO) is for dust mite
control in treated finished carpets and rug backings and fibers bearing
the label Ultra-Fresh® DM-50 Dust Mite Treated Carpeting.  Labeled
finished carpets and rugs backings and fibers are intended to contain 
0.075% tri-n-butyltin maleate (TBTM) [File Symbol 10466-??].   [NOTE: RD
has indicated the registrant will be required to propose a registration
of a separate manufacturing use product containing 0.075% tri-n-butyl
maleate].

Submitted Data

Thompson Research Associates has submitted data to support a Section 3
registration of a non-food use product intended to control dust mites
when incorporated into various materials (fibers, backing) and fabrics
during the carpet manufacturing process.  Some of the data submitted
were conducted in accordance with protocols submitted and reviewed by
the Agency in a memorandum dated 12, December, 2001. {K. O’Rourke to
George LaRocca, Ultra-Fresh DM-50 (tri-n-butyltin maleate [TBTM]):
Review of 2 Study Protocols for Product Integrity on Treated Carpet
Materials (D273967)}.  The two study protocols are as follows:

Transfer of TBTM by Abrasion from Carpet Samples Treated with
Ultra-Fresh DM-50, Experiment Number: RG-2001-01-001; and

Leaching of TBTM from a Nylon Carpet Sample Treated with Ultra-Fresh
DM-50 Using Acidic, Neutral and Alkaline Artificial Sweat,
RG-2000-01-004.

In the protocol review, it was suggested that the registrant provide the
 analytical methods for verification by the Agency and justification for
the types of carpet materials selected for use in the proposed carpet
residue studies.  Subsequent to the protocol review, Laird’s
Regulatory Consultants, Inc. submitted two fabric leaching studies on
behalf of Thompson Research Associates.   These studies are: 

Klein, D (2002) Leaching of TBTM from a Nylon Carpet Sample Treated with
Ultra-Fresh DM-50 Using Acidic, Neutral and Alkaline Artificial Sweat:
Final Report: Lab Project Number: RG-2000-01-004.  Unpublished study
prepared by Thompson research Associates [MRID 45746802].



Yau, L (1982) Exposure of Product on Carpet: (Ultra Fresh DM-50): Lab
Project Number: CM501:94.  Unpublished study prepared by Thompson
Research Associates.[MRID 45746801].

The first study, MRID 45746802, appears to be the study RG-2000-01-004
addressed in the aforementioned  protocol review.   The study
RG-2001-01-001, a potentially more useful for exposure assessments
(carpet wipes), was not  submitted.   The studies reported by Kline and
Yau.[MRID 45746801], analyze carpet samples (swatches) taken from
carpets treated with Ultra Fresh DM-50.   The Ultra Fresh DM-50
formulation intermediate used during the carpet manufacturing process
contains 25% TBTM.  

Both studies involve the immersion of carpet swatches in various
artificial sweat solutions and saline control solutions.   The pH of
human sweat varies from 4.5 to7.5. 
http://www.mercksource.com/pp/us/cns/cns_home.jsp.   The study designs
were intended to determine maximum levels of tributyltin maleate that
may leach from carpets treated with Ultra-Fresh® DM-50.  It should be
noted that the description of the carpet sample treatment concentrations
varies in the two studies.   It is recommended that these concentration
rates be verified by the registrant.

MRID 45746802  

In the study report authored by Klein, artificial sweat leaching
solutions were prepared in accordance with formulations described in the
American Association of Textile Colorists and Chemists (AATCC), Test
Method 15-1994 (Colorfastness to Prespiration).  In this study, saline
solutions, acid sweat (pH 3.6), neutral sweat (pH 7.0) and alkaline
sweat (pH 9.2) were prepared.  Swatch samples (2.5 cm2 x  2.5 cm2)
collected from a nylon carpet were immersed in the respective solutions.
 Concentrations of tributyltin maleate measured after 2 and 24 hours of
immersion are presented in Table 1.   The carpet samples were taken from
a commercial production facility during routine testing (0.03%
Ultra-Fresh® DM-50 (based on the total weight of the carpet (fibers,
latex, backing)). 

Table 1: Reported Parts per Million (µg/g)  Tributyltin Maleate/Nylon
Carpet Sample Treated with 0.03% Ultra-Fresh® DM-50 (Klein 2002)

Solution Type	

	2 Hours of Immersion

	24 Hours of Immersion

	µg/g	

	mean + SD	

	µg/g	

	mean + SD

Saline	

	5.5	

	5.2 + 0.4	

	6.9	

	7.2 + 0.2

	

	4.7

	7.3

	5.3

	7.3

	

Acidic Sweat

(pH 3.6)	

	4.1	

	3.3 + 1.1	

	3.9	

	3.8 + 0.1

	

	3.8

	3.7

	2.1

	3.9

	

Neutral Sweat

(pH 7.0)	

	1.4	

	2.2 + 1.1	

	4.6	

	5.3 + 0.8*

	

	3.5

	6.1

	1.7

	5.3

	

Alkaline Sweat

(pH 9.2)	

	4.8	

	4.7 + 2.6	

	10.9	

	10.6 + 0.6

	

	2.0

	9.9

	7.2

	11.1

	* Used in exposure assessment.

The calculations used to derive the parts per million tributyltin
maleate leached from the carpet samples presented in Table 1 and
reported in Klein are as follows:

µg Tributlytin Maleate/ gram of carpet at 2 hours =

ppm Tin2 hrs x 3.4131 x Solution Weight2 hours / Sample Weight

µg Tributlytin Maleate/ gram of carpet at 24 hours =

[(ppm Tin2 hrs x Solution Weight Removed 2 hours) + (ppm Tin24 hrs x
3.4131 x Solution Weight24 hours)] x 3.4131/ Sample Weight

The percent values presented in Table 2 and reported in Klein are
calculated as follows:

ppm tin presented in 0.03% Ultra-Fresh® DM-50 = 0.03 x 250000*/
100/3.4134 = 21.97

Percent Tributyltin Maleate leached at 2 hours = 

(ppm Tin2 hrs x Solution Weight2 hours)/ (21.97 x Sample Weight) x 100



Percent Tributyltin Maleate leached at 24 hours = 

[(ppm Tin2 hrs x Solution Weight Removed2 hours)+(ppm Tin24 hrs x
Solution Weight24 hours)] / (21.97 x Sample Weight) x 100

*25%

The value of 3.4131 is assumed to be a correction factor (ratio) for
estimating tributyltin maleate concentrations from measurements of tin. 
It should be noted that the standard operating procedures delineating
the analysis and calculations were not available in the package as
requested by the Agency.  Therefore the calculations and results are
presented in this memorandum as verbatim from the report submitted by
Laird’s Regulatory Associates.  Table 2 presents the percent
tributyltin maleate leached from the swatches.

Table 2: Percentage of Ultra-Fresh® DM-50 Leached from a Nylon Carpet
Sample Treated with 0.03% Ultra-Fresh® DM-50 (Klein 2002)

Solution Type	

	2 Hour

	24 Hour

	percent	

	mean + SD	

	percent	

	mean + SD

Saline

	

	7.3	

	6.6 + 0.5	

	9.2	

	9.5 + 0.3

	

	6.3

	9.7

	7.0

	9.7

	

Acidic Sweat

(pH 3.6)	

	5.5	

	4.4 + 1.5	

	5.2	

	5.1 + 0.2

	

	5.0

	4.9

	2.7

	5.2

	

Neutral Sweat

(pH 7.0)	

	1.9	

	2.9 + 1.5	

	6.2	

	7.1 + 1.0

	

	4.6

	8.1

	2.3

	7.1

	

Alkaline Sweat

(pH 9.2)	

	6.5	

	6.3 + 3.5	

	14.6	

	14.2 + 0.9

	

	2.7

	13.2

	9.6

	14.8

	

Klein asserts that the leaching results presented in Tables 1 and 2 are
based on extreme conditions and that exposure to treated carpets, under
normal use conditions, would result in contact measurements below the
detection limit of current analytical methodologies.  The highest
average amount leached from the carpet samples was 10.6 µg of
tributyltin maleate per gram of sample under alkaline conditions for a
period of 24 hours (14.2% Ultra-Fresh® DM-50).   Since the pH of human
sweat varies from 4.5 to7.5, the mean value from the neutral sweat
samples (5.3 µg) appears to be an appropriate value for use in the
assessment.  The samples however, were from a carpet treated at a lower
concentration than proposed for dust mites.  Artificial saliva
formulations are acidic (pH between 5.2 - 5.5).

In a similar study conducted in 1982, Yau addressed the leaching
potential of tributyltin maleate from carpets treated at higher rates -
similar to the proposed application rate.   Total tin measurements in
the treated carpet swatches were reported based on results using AATCC
extraction method 94 (identification of various finishing components).  
In this study, the carpet samples were treated at 0.1 and 0.2 percent
Ultra-Fresh® DM-50 (dry weight of face fibers) held in the respective
saline and acidic sweat liquors at a ratio of 20:1 for periods of 24 and
48 hours.  Analysis of the liquor samples (pH unspecified) indicated
zero ppm, tributyltin maleate (TBTM) had leached from the swatches.  The
swatches were 5 cm2 x 5 cm2.  Results of the analysis are presented in
Table 3.

Table 3: Removal of TBTM from treated Carpets (Yau 1982)

Carpet Samples (total amount in carpet)

	

Percent DM-50	

Contact Hours	

Saline (ppm)	

Sweat (ppm)

0.1	

0	

257	

257

	

24	

252	

254

	

48	

253	

252

0.2	

0	

515	

515

	

24	

511	

514

	

48	

517	

513

Liquor Samples

	

0.1	

24	

0	

0

	

48	

0	

0

0.2	

24	

0	

0

	

48	

0	

0

Yau also reported a separate leaching study in which 100% nylon swatch
samples (20 cm2 x 16 cm2) were immersed in similar saline and sweat
solutions as described in Klein, for periods of 2 and 5 hours.  The
fabric was treated with a 0.2% aqueous solution of Ultra Fresh 50®
followed by 15 minutes of drying at 90 C.  After treatment and drying,
the swatches were cut (12 separate pieces) and immersed in the
respective solutions.  There is no referenced AATCC method cited in this
report for extracting tributyltin maleate from the nylon swatches.  
Rather, the reports states that the method was done in accordance with
directions provided in an EPA letter dated April 5, 1982.  The results
of this third trial are presented in Table 4.   It is not clear in the
report whether the described nylon swatch treatment was performed in a
laboratory or in a manufacturing facility.

Table 4: Parts per Billion Tin (Sn) Leached from Nylon Swatches Immersed
in Solutions for 2 and 5 Hours.

Solution Type

First Reading	

Second Reading

Saline

	

Sample ID’s	

100N S 1 2	

200	

220

	

100N S 1 5 	

320	

305

	

100N S 2 2	

360	

345

	

100N S 2 5	

430	

420

	

100N S 3 2	

480	

465

	

100N S 3 5	

590	

590

Sweat 

pH 3.6	

	

	

100N 4 1 2	

130	

110

	

100N 4 1 5	

130	

140

	

100N 4 2 2	

120	

150

	

100N 4 2 5 	

160	

170

	

100N 4 3 2	

140	

126

	

100N 4 3 5 	

170	

165

Sweat 

pH 7.01

	

	

100N 7 1 2 	

70	

70

	

100N 7 1 5	

180	

185

	

100N 7 2 2 	

80	

75

	

100N 7 2 5 	

90	

95

	

100N 7 3 2	

30	

45

	

100N 7 3 5	

100	

100

Sweat

pH 9.2

	

	

100N 9 1 2	

113	

119

	

100N 9 1 5	

108	

112

	

100N 9 2 2 	

101	

100

	

100N 9 2 5	

104	

106

	

100N 9 3 2	

101	

99

	

100N 9 3 5	

107	

109

The author concludes that none of the samples indicated more than 8 ppm
of Ultra Fresh DM-50 (590 ppb x 3.41 (  25% = 8048 ppb).  

Postapplication Exposure

 The postapplication scenarios assessed in this memorandum are potential
incidental oral ingestion from mouthing hands that may contact the
impregnated carpet and potential dermal exposure.  Because tributyltin
maleate is bound to carpet materials, postapplication exposure via the
inhalation route is considered to be negligible.

The assessment utilized chemical-specific exposure data submitted by
Laird’s Regulatory Consultants, Inc. on behalf of Thompson Research
Associates (MRIDs 45746802 and 45746801).  The studies involve the
immersion of treated carpet swatches in alkaline, acidic and neutral
artificial sweat solutions and saline control solutions. The study
designs were intended to determine maximum levels of tributyltin maleate
that may leach from carpets treated with Ultra-Fresh® DM-50.  Overall,
it appears that the Klein data, provide a reliable screening level value
for use in a Tier 1 exposure/risk assessment.  To establish a flux rate
(FR), a 24 hour concentration was selected from Klein (2002) using the
average value of 5.3 ppm TBTM (µg/g) measured in swatches immersed in
neutral sweat (see Table 1).

This value was selected because it appears to be the most
representative of the range of pH values reported for human sweat (4.5 
to 7.5).  The swatches, measuring 2.5 cm x 2.5 cm (6.25 cm2) reportedly
weigh ~2 grams.  Therefore, the swatch contained 5.3 ppm TBTM (µg/g) or
0.848 µg/cm2 (5.3 µg/g  ( 6.25 cm2/g).  Thus, the value 8.48 mg/m2 can
be used as the flux rate (FR) in the following formula from HED’s
Residential SOP’s for assessing exposure to impregnated articles such
as mattresses:

PDR = FR * SA * ET * CF1

Where:

PDR	=	potential dose rate (mg/day)

FR	=	flux rate for pesticide of concern (mg/m2/day)

SA	=	body surface area (m2)

ET	=	exposure time (hours/day)

CF1	=	time unit conversion factor (day/24 hours)

In this assessment, a young child in direct contact with the carpet was
selected as a representative scenario.  The short and intermediate term
endpoint selected for this assessment is the BMD10 of 0.03 mg/gk/day. 
The dermal absorption value is 15%.  When using the flux rate SOP to
assess short- and intermediate-term exposures via the dermal and
non-dietary ingestion pathways, body surface areas (SA) are needed.  For
non-dietary ingestion via hand-to-mouth behavior, a surface area of 0.04
m2 has been selected to represent the palmar surface area of finger tips
of young children coming in contact with the carpet.   For short term
exposure durations, the residential SOPs suggest 20 contacts per hour
(90th percentile) with a surface area of 20 cm2 (400 cm2 = 0.04 m2). 
Since the endpoints for short term and intermediate term exposure were
the same, only short term durations were assessed.  Furthermore, in this
assessment the PDR in the above formula is adjusted to account for a
reduction in the amount of transfer of residues from fingers by 50
percent given the reduced extraction efficiency of saliva.

To assess dermal exposure of  young children in direct contact with the
carpet product, a surface area of 900 cm2 or 0.09 m2 representing half
the exposed area of a child wearing shorts and short sleeved shirt was
used.   This is based on EPA’s Exposure Factors Handbook recommending
a value of  25% of a child’s skin being exposed while wearing short
sleeved shirts, short pants and shoes.   The surface area of a 3 to 4
year old child is ~6000 cm2 or 0.6 m2.  In this assessment, an exposed
surface area of 30 percent was used in lieu of shoes being worn.  Given
the conservative nature of the assumed concentration coming in contact
with the skin, clothing penetration is not considered at this time. 
Both dermal and hand-to-mouth surface area values can be used with the
Antimicrobial Division’s SOP using a flux rate method for individuals
contacting impregnated materials. 

Exposure durations are for 2 hours as presented in the Antimicrobial
Division’s memorandum dated July 2, 2004. (D. Aviado to D. Edwards re:
Proposed Registration for AZOXYSTROBIN MOLD_RETARDANT 2.08 SC End-Use
Product as a New Indoor, Non-Agricultural Use Pattern for the
Azoxystrobin Active Ingredient: Non-Dietary Occupational/ Residential
Exposure Considerations).   HED typically uses 8 hours and 4 hours
contact time for exposure to residues collected by surface wipes for
carpets and hard surfaces respectively.  For this assessment, the 2 hour
duration used by AD appears to be a reasonable amount of time to be
spent on a carpet formulated with tributyltin maleate.  In particular,
given the extreme measurements of tributyltin maleate used in this
assessment which rely on immersion of carpet swatches in simulated sweat
for a 24 hour period.   Finally, a body weight of 15 kg was use used in
this assessment.  The results are presented in Table 5.

Table 5:  Screening Level Exposure Estimates.

	

FR: flux rate

(mg/m2/day)	

SA: body surface area (m2)	

ET: exposure time (hours)	

CF1: conversion factor (day/ hours)	

PDR (mg/day)	

Daily Dose (mg/kg/day)

	Short- and intermediate-term: hand-to-mouth exposure

	

8.48	

0.04	

2	

24	

0.014*	

0.0009

	Short- and intermediate-term: dermal exposure

	

8.48	

0.09 	

2	

24	

0.0095**	

0.0006

* Includes 50% extraction efficiency of saliva

** Includes a dermal absorption factor of 15%

These exposure estimates are likely to overestimate exposure,
considering the input values are from the extraction of swatches
immersed in sweat solutions for up to 24 hours.  These values represent
a steady state extraction process that may not be representative of
typical human intermittent contact with carpet surfaces but rather may
be indicative of the removal of TBTM by shampooing.   The registrant
suggests that the carpet may not be efficacious after 12 carpet shampoo
treatments.  

 The three studies submitted present confounding conclusions which may
be due to different carpet materials, treatment methods and
concentrations.   In the study conducted by Klein, residues were
extracted using standard sweat liquors.   In an older study reported by
Yau, no residues were detected in the sweat liquors.   This may be due
to different treatment rates or it may be a function of the types of
carpets sampled.  In the third study discussed in Yau, too few details
regarding the test material (100% nylon) were provided to make these
data useful in an exposure assessment.  In addition, 24 hour samples are
needed for estimation of exposure via the flux rate SOP used by the
Antimicrobials Division. In this study, a maxim of 5 hours duration was
selected..

 tc \l1 " A screening-level assessment was conducted for children’s
dermal and incidental oral exposure to TBTM impregnated carpet. Because
of the highly conservative nature of these single route exposure inputs,
children’s non-dietary ingestion and dermal exposures were not
combined. A separate assessment was not conducted for adults because the
child’s mouthing behaviors and surface to body weight parameters
represent the most highly exposed population. Exposure inputs obtained
from the carpet leaching study very likely overestimate the potential
for exposure.  After continuous 24 hour immersion in saline solution, a
mean of 7.1% of the TBTM was leached from treated carpet indicating that
TBTM, although potentially available in low amounts, is tightly bound to
the textile matrix.  Comparison of the benchmark dose (BMD10) of 0.03
mg/kg/day to the estimated exposure levels gives MOEs 33 and 50 for
short and intermediate term exposure for the hand-to-mouth and dermal
pathways respectively.   Two 10x safety factors addressing intra and
inter species variability were assigned for TBTM.   An additional
toxicology database uncertainty factor (10x) was also added.  

A benchmark dose (BMD) is a measure of exposure to a dose of a chemical
that relies on a modeled mathematical fit of all the dose response data
within a toxicology study.   Generally, the BMD is set in a range of 1
to 10% of a health effect.  The BMD 10 for TBTM is 0.03 mg/kg/day based
on  immunosuppression observed in an oral 18-month immunotoxicity study
in the rat. 

Table 5.  Summary of Daily Doses and MOEs for Residential Exposures to
TBTM

Exposure Scenario	

Daily Dose (mg/kg/day)	

MOE

(LOC=1000)

Short- and intermediate-term incidental oral	

0.0009	

33

Short- and intermediate term dermal	

0.0006	

50

Based on the data collected by Klein, the MOEs presented above indicate
that margins of exposure (MOE) do not meet or exceed 1000 indicating
that these estimates are estimates of concern.   It is suggested that
the registrant:

 clarify the carpet treatment rates used in the submitted studies; and

consider submitting the carpet wipe study discussed in the protocol
review (or consider other wipe sample studies in consultation with HED).



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