Document ID: EPA-HQ-OPP-2008-0171-0010
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-04-02T04:00Z

SEQ CHAPTER \h \r 1 							

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: April 2, 2008

MEMORANDUM

SUBJECT:	Revised Tributyltin – Containing Compounds (tributyltin
oxide, tributyltin benzoate and tributyltin maleate) Reregistration
Eligibility Decision Document (RED).  PC Codes: 083001, 083106, 083118.
Case No. 2620. D350668.

FROM:	Talia Lindheimer, Chemist/Risk Assessor

		Antimicrobials Division (AD) (7510P)

		And

		Jim Breithaupt, Agronomist

		Michelle Centra, Ph.D., Toxicologist 

		Jonathan Chen, Ph.D., Toxicologist 

William Erickson, Ph.D., Biologist

Timothy Leighton, Senior Scientist

Siroos Mostaghimi, Ph.D., Senior Scientist

Cassi Walls, Ph.D., Chemist

		

		Antimicrobials Division (AD) (7510P)

THRU:		Nader Elkassabany, Team Leader

		Norm Cook, Branch Chief

		Risk Assessment Science Support Branch (RASSB)

		Antimicrobials Division (AD) (7510P)

TO:		Jill Bloom, Chemical Review Manager, Special Review and
Reregistration Division

		Diane Isbell, Team Leader

		Regulatory Management Branch II

		Antimicrobials Division (7510P)     

        

Attached is the Preliminary Risk Assessment for the tributyltin –
containing compounds considered in this case.  The appropriate
disciplinary science chapters are also included as attachments and are
listed on the following page.  

Supporting chapters discussed in this Risk assessment and are included
as Appendices:

Revised Draft: Occupational and Residential Assessment.  March 26, 2008.
 T. Leighton. D350669.

Revised Product Chemistry Chapter for the Tributyltin – Containing
Compounds (tributyltin oxide, tributyltin benzoate and tributyltin
maleate) Re-registration Eligibility Decision Document (RED). March 19,
2008.  T. Lindheimer. D350673.

	

Ecological Hazards and Risk Assessment for Tributyltin Compounds. 
January 18, 2008.  W. Erickson. D347645.

Dietary and Drinking Water Exposure Chapter for Tributyltin-Containing
Compounds for the Reregsitration Eligibility Decision (RED) Document
(Case 2620).  January 14, 2008.  C. Walls.  D347970.

Tributyltin Compounds – Revised Toxicology Chapter in Support of
Issuance of the Reregistration Eligibility Decision (RED) for
Tributyltin Oxide, Tributyltin Maleate and Tributyltin Benzoate.  PC
Code(s):  083001, 083118, 083106.  CAS Registry Number(s): 56-35-9,
4027-18-3, 4342-36-3.  March 30, 2008.  M. Centra. D350670.

Environmental Fate Assessment of TBT for the RED.  January 29, 2008.  J.
Breithaupt. D350671.

Incident Reports Associated with Tributyltin (TBT) Containing Chemicals.
 January 29, 2008.  J. Chen.  D347979.

Estimated Environmental concentrations for Tributyltin Oxide (TBTO)
Leached from Wood into Soil and Water.  December 18, 2007.  S.
Mostaghimi.  D347647.

	

   TOC \o "1-3" \h \z \u  

  HYPERLINK \l "_Toc194462643"  1.0	EXECUTIVE SUMMARY	  PAGEREF
_Toc194462643 \h  4  

  HYPERLINK \l "_Toc194462644"  1.1	Hazard Profile:	  PAGEREF
_Toc194462644 \h  4  

  HYPERLINK \l "_Toc194462645"  1.2 	Toxicity Endpoints:	  PAGEREF
_Toc194462645 \h  6  

  HYPERLINK \l "_Toc194462646"  1.3	FQPA Safety Factor:	  PAGEREF
_Toc194462646 \h  7  

  HYPERLINK \l "_Toc194462647"  1.4	Dietary Exposure and Risk:	  PAGEREF
_Toc194462647 \h  7  

  HYPERLINK \l "_Toc194462648"  1.5	Water Exposure and Risk:	  PAGEREF
_Toc194462648 \h  7  

  HYPERLINK \l "_Toc194462649"  1.6	Residential (Non-Occupational)
Exposure and Risk:	  PAGEREF _Toc194462649 \h  8  

  HYPERLINK \l "_Toc194462650"  1.8	Occupational Exposure and Risk	 
PAGEREF _Toc194462650 \h  9  

  HYPERLINK \l "_Toc194462651"  1.9	 Environmental Hazard and Risk:	 
PAGEREF _Toc194462651 \h  10  

  HYPERLINK \l "_Toc194462652"  2.0	PHYSICAL AND CHEMICAL PROPERTIES	 
PAGEREF _Toc194462652 \h  11  

  HYPERLINK \l "_Toc194462653"  3.0	HAZARD CHARACTERIZATION	  PAGEREF
_Toc194462653 \h  12  

  HYPERLINK \l "_Toc194462654"  3.1 Hazard Profile	  PAGEREF
_Toc194462654 \h  12  

  HYPERLINK \l "_Toc194462655"  3.2 Dose-Response Assessment	  PAGEREF
_Toc194462655 \h  13  

  HYPERLINK \l "_Toc194462656"  3.3   FQPA Considerations	  PAGEREF
_Toc194462656 \h  16  

  HYPERLINK \l "_Toc194462657"  3.4	Endocrine Disruption	  PAGEREF
_Toc194462657 \h  16  

  HYPERLINK \l "_Toc194462658"  4.0	INCIDENT REPORTS	  PAGEREF
_Toc194462658 \h  17  

  HYPERLINK \l "_Toc194462659"  5.0	EXPOSURE ASSESSMENT AND
CHARACTERIZATION	  PAGEREF _Toc194462659 \h  18  

  HYPERLINK \l "_Toc194462660"  5.1	Dietary Exposure and Risk	  PAGEREF
_Toc194462660 \h  18  

  HYPERLINK \l "_Toc194462661"  5.2   Drinking Water Exposure and Risk
for Active Ingredient Uses	  PAGEREF _Toc194462661 \h  19  

  HYPERLINK \l "_Toc194462662"  5.3 	Residential Exposure/Risk Pathway	 
PAGEREF _Toc194462662 \h  19  

  HYPERLINK \l "_Toc194462663"  6.0 	AGGREGATE RISK ASSESSMENTS AND RISK
CHARACTERIZATION	  PAGEREF _Toc194462663 \h  21  

  HYPERLINK \l "_Toc194462664"  7.0	CUMULATIVE EXPOSURE AND RISK	 
PAGEREF _Toc194462664 \h  22  

  HYPERLINK \l "_Toc194462665"  8.0	OCCUPATIONAL EXPOSURE AND RISK	 
PAGEREF _Toc194462665 \h  22  

  HYPERLINK \l "_Toc194462666"  9.0.	ENVIRONMENTAL FATE	  PAGEREF
_Toc194462666 \h  24  

  HYPERLINK \l "_Toc194462667"  10.0 	ENVIRONMENTAL RISK	  PAGEREF
_Toc194462667 \h  25  

  HYPERLINK \l "_Toc194462668"  10.1	Summary of Ecological Toxicity Data
Conclusions	  PAGEREF _Toc194462668 \h  25  

  HYPERLINK \l "_Toc194462669"  10.2	Environmental Risk Assessment
Criteria	  PAGEREF _Toc194462669 \h  26  

  HYPERLINK \l "_Toc194462670"  10.3	Aquatic Risk Characterization	 
PAGEREF _Toc194462670 \h  27  

  HYPERLINK \l "_Toc194462671"  10.4	Endangered Species Considerations	 
PAGEREF _Toc194462671 \h  28  

  HYPERLINK \l "_Toc194462672"  11.0	DATA NEEDS AND LABELING	  PAGEREF
_Toc194462672 \h  29  

  HYPERLINK \l "_Toc194462673"  12.0	REFERENCES	  PAGEREF _Toc194462673
\h  32  

  HYPERLINK \l "_Toc194462674"  Appendix A: Label Query/Summary for
TBT-Containing Compounds	  PAGEREF _Toc194462674 \h  42  

  HYPERLINK \l "_Toc194462675"  Appendix B:  Toxicity Profile for TBT
Oxide, Maleate and Benzoate	  PAGEREF _Toc194462675 \h  44  

  HYPERLINK \l "_Toc194462676"  Appendix C:  Residential and
Occupational Uses Selected for Assessing Risks to TBT-containing
Products	  PAGEREF _Toc194462676 \h  50  

  

EXECUTIVE SUMMARY 

 tc "1.0 	EXECUTIVE SUMMARY" 

	Tributyltin containing compounds are intended to serve as
bacteriocides, microbiocides, fungicides, algaecides, slimicides, and
virucides.  The three chemicals that are being considered for purpose of
this re-registration eligibility document are: tributyltin oxide (PC
Code 083001), tributyltin benzoate (PC Code 083106), and tributyltin
maleate (PC Code 083118).   Examples of some of the primary uses of the
TBT-containing products include:  agricultural premises and equipment;
oilfield/petrochemical injection water systems; industrial
re-circulating water cooling systems; livestock operations and
hatcheries; material preservation (textiles, metalworking fluids, paper
mills, plastics, construction materials, mattress ticking, laundry
treatment, etc); sonar domes to prevent antifouling; and for
non-pressure treated wood preservation.  There are several labels that
the registrants have indicated that a voluntary cancellation is in
process.  All of the appropriate registration numbers to date affiliated
with this case are outlined in Appendix A.

	

	There are 33 registered end use products that contain tributyltin oxide
as the active ingredient with the percent active ranging from 0.30% to
53.0%.  The end-use products that are specific to this active ingredient
include ready-to-use soluble concentrates that are used primarily for
wood and material preservation.  Tributyltin benzoate (two registered
ready-to-use soluble concentrates) is used in materials preservatives
for various building and construction materials, and the percent actives
in the two labels are 15.0% and 45.5%.  Tributyltin maleate (one
product) is used to protect foam, sponges, carpet backing, and
polyolefin drip irrigation tubing and piping; the product is 25% active
ingredient.  

In summary, the following Use Site Categories (USCs) are appropriate to
this case: 

(I) Agricultural premises and equipment; 

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

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

(VIII) Industrial processes and water systems;

(IX) Antifouling coatings (only very limited uses remain); and 

(X) Wood preservatives.

	1.1	Hazard Profile:

Tin compounds, organic and inorganic (organotins), have been studied in
a variety of animals, but primarily in rodents following the oral route
of ingestion.  There are limited data on the effects of tins in humans
and any reports of industrial and individual accidental exposures have
been provided in the incidence report discussion.  

There is some evidence that many of the tributyltin compounds cause
similar toxic effects.  In 1990, the World Health Organization (WHO,
Environmental Health Criteria 119) reported that tributyltin compounds
are skin, eye and respiratory irritants.  Published literature for
tributyltin oxide identifies immunotoxicity as the chemical’s primary
toxicological action in laboratory mammals, and is also a reported
thymolytic agent.  Later reviews by EPA/IRIS (1997) and the WHO (1997)
identify a large body of information demonstrating the critical effect
of tributyltin oxide as depression of thymus-dependent immunological
responses.  Immunological effects are evident in short- and long-term
studies in rats and mice, where exposure to tributyltin oxide has been
linked to decreased immunoglobulin levels, decreased thymus weight,
various inflammation responses. 

Reproductive and developmental toxicity in rats due to tributyltin oxide
and/or tributyltin benzoate exposures has been noted to have occurred
along with maternal toxicity, which was generally characterized by
decreased body weight or body weight gains.  Available studies show
pre-weanling rat pups to be more sensitive to the immunologic effects of
tributyltin oxide than adult rats in their thymus-dependent immunity.  
Some organotin compounds are known to have neurotoxicity effects, and a
few studies that had been initiated to investigate other effects also
showed some minor toxicities of tributyltin on the nervous system
(reduced brain weight, decreased motor activity, lympho- and
hepatobiliary toxicity).  However, oral exposure to tributyltin oxide in
these studies did not cause severe neurological signs or result in
morphological or histopathological changes in brain tissue.  Based on
the evidence from available studies conducted with tributyltin oxide,
there is no suggestion that neurotoxicity is a likely critical or
co-critical effect. 

It is unclear if tributyltin oxide is a carcinogen in rats; however, it
is not a carcinogen in mice and does not appear to be genotoxic.  EPA
has assigned tributyltin oxide to category D (U.S., 1987) or to the
“cannot be determined” category for carcinogenicity (U.S. EPA, 1996)
based on high spontaneous incidences of tumors in Wistar rats, incidence
variability in the treated groups and absence of a dose-effect
relationship.  Therefore the significance of the increases in benign
pituitary tumors, pheichromocytomas and parathyroid tumors at the
highest tested doses in rats remains unclear.    

As discussed in the supporting toxicology chapter, the Antimicrobials
Division’s Toxicity Endpoint Selection Committee (ADTC) re-evaluated
the issue of bridging the available toxicity data for these three
organotins.  It has been determined that the oxide, maleate and benzoate
forms of tributyltin are considered toxicologically equivalent based on
similar structure and physical chemical properties (e.g., dissociation
constants).  However, to fully assess whether exposure to these
compounds will result in similar toxicities, Tier 1 toxicity testing is
needed for each chemical.  These tests include acute toxicity (oral,
dermal, inhalation, eye and dermal irritation and skin sensitization),
subchronic (oral) toxicity, prenatal developmental toxicity and the full
battery of mutagenicity tests.  The data gaps for tributyltin oxide,
tributyltin maleate and tributyltin benzoate are summarized in Table 1:

Table 1.  Generic Data Gaps for Tributyltin Compounds

Guideline Number	Study Type

Tributyltin Oxide (TBTO)

870.1200	Acute Dermal Toxicity

870.1300	Acute Inhalation Toxicity

870.2400	Primary Eye Irritation

870.2500	Primary Dermal Irritation

870.3250	90-Day (dermal) Subchronic - Rodents

870.5450 to 870.5915	Mutagenicity Test (1 Study)

Tributyltin Maleate (TBTM)

870.1200	Acute Dermal Toxicity

870.1300	Acute Inhalation Toxicity

870.2400	Primary Eye Irritation

870.2500	Primary Dermal Irritation

870.3250	90-Day (dermal) Subchronic -Rodents

870.3700	Prenatal Developmental Toxicity in Rats

870.5100 to 870.5915	Battery of Mutagenicity Studies (3 studies; one
from each category; “Gene Mutation,” “Cytogenitics” and “Other
Mechanisms”)

Tributyltin Benzoate (TBTB)

870.1300	Acute Inhalation Toxicity

870.2400	Primary Eye Irritation

870.2600	Skin Sensitization

870.3250	90-Day (dermal) Subchronic - Rats

870.5450

to

870.5915	Battery of Mutagenicity Studies (1 study from “Other
Mechanisms” category)

The acute toxicity databases for these three compounds are considered to
be incomplete.  Based on available data, it is conclusive that exposure
to TBTO and TBTM can result in severe oral and dermal toxicities
(Toxicity Category II) and are not considered to be dermal sensitizers. 
TBTB can potentially cause moderate (Toxicity Category III) to severe
(Toxicity Category II) toxicities respectively.  

	1.2 	Toxicity Endpoints:

	The toxicity endpoints used in this document to assess potential risks
are provided below although the cited data gaps will need to be filled
to allow refinement of the human health risk assessment. Please refer to
the supporting toxicology chapter for a complete in depth discussion of
the studies and conclusions that were considered in the selection of the
toxicological endpoints (M. Centra, February 2008). Additionally it is
important to note that a special sensitivity factor of 10 has been
applied in the selection of the non-dietary residential doses because
there is evidence of increased susceptibility to children.

Acute Reference Dose (aRfD) (Females 13 – 49) 

	No appropriate endpoints were identified in the oral toxicity studies
to represent a single dose effect for the general population and females
13-49.  In addition, the current use patterns for the
tributyltin-containing chemicals do not indicate the potential for
direct or indirect dietary exposures.  Therefore, an acute dietary risk
assessment is not required at this time.

Chronic Reference Dose (cRfD), Short- and Intermediate-term Incidental
Oral, Dermal (all durations) and Inhalation (all durations):  Open
Literature

Although the current use patterns do not indicate the potential for
chronic dietary exposure, the chronic RfD was selected for future
reference.  The endpoints were selected based on the immunotoxicity of
bis (tri-n-butyltin) oxide in the rat as reported in Vos et al. (1990). 
It showed effects on thymus dependent immune responses at a dose lower
than that at which any other toxic effects have been observed. This
study also establishes that weanling animals are more sensitive than
adults to the effects of TBTO.  For example, following subchronic
exposure, the LOAEL in weanling rats was 0.25 mg/kg body weight per day,
whereas the LOAEL in aged rats was 2.5 mg/kg body weight per day.  The
reported NOAEL = 0.025 mg/kg/day. 

The established toxicity endpoint is a BMD10 (bench mark dose) of 0.03
mg/kg/day (same between all routes of exposures and aforementioned
durations).  The target Margins of Exposures – MOEs, is scenario
specific for dietary, incidental oral, dermal and inhalation.  Specific
to the dermal assessment, a 15% dermal absorption factor has been used
for route-to-route extrapolation.

Chronic dietary exposures: uncertainty factor = 100 (10x inter-species
extrapolation, 10x intra-species variation); chronic RfD = 0.00003
mg/kg/day.

Incidental Oral (residential):  uncertainty factor = 100 (10x
inter-species extrapolation, 10x intra-species variation), Target MOE =
1,000 

Dermal and Inhalation (all durations): The uncertainty factor is
identified to be 100 (10x inter-species extrapolation, 10x intra-species
variation), and the Target MOEs are 1,000 and 100 for residential and
occupational exposures respectively.

	1.3	FQPA Safety Factor: 

	Some of the labeled uses for the tributyltin-containing chemicals have
the potential to result in direct or indirect food exposures, or other
residential exposures, which may impact children.  A special sensitivity
factor can be applied to a selected dose if there is evidence of
increased susceptibility to children from non-dietary exposures to
pesticides.  Based on the numerous published literature studies on the
immunotixicity of tributyltin oxide, the application of a sensitivity
factor would provide adequate protection to the most sensitive
population, children.  Therefore, a special children’s sensitivity
factor of 10x was applied to the dose/endpoint (BMD10 = 0.03 mg/kg/day)
selected for all residential exposure scenarios. 

1.4	Dietary Exposure and Risk: 

	A quantitative dietary assessment was not conducted for purposes of
this review.   However, the uses in animal housing facilities and in
hatcheries were considered due to TBT-containing compounds’ high
persistence and potential to bioaccumulate.  Please refer to the dietary
assessment for a comprehensive discussion of the qualitative assumptions
utilized (C. Walls January 2008).  While specific risks were unable to
be calculated at this time, the following recommendations have been
made.

Product labels for animal housing facilities are recommended to be
revised such to direct for surfaces to be rinsed before re-housing
animals to remove any potential residues.  This revision will need to be
supported with data regarding the effectiveness of water rinsing.  

Due to confirmation that eggs are not removed during hatchery treatment,
data examining and supporting that the pesticide does not penetrate the
shells would facilitate a quantitative assessment of the potential risks
associated with this use.

1.5	Water Exposure and Risk:

	Based on the use patterns, the potential for tributyltin containing
compounds to impact drinking water sources is assumed to be negligible
and therefore a quantitative drinking water assessment was not conducted
at this time.  Please refer to the supporting dietary and drinking water
chapter for a complete discussion (C. Walls January 2008).

	

Residential (Non-Occupational) Exposure and Risk:  

 It has been determined that there are residential products that contain
one of the three TBT compounds and are applied directly to a determined
surface (e.g., wood stain preservative), thus triggering the need for a
handler exposure assessment.  Additionally post-application exposures
resulting from the chemical’s use as a materials preservative (e.g.
treated clothing) were also quantitatively assessed.  The representative
scenarios that were assessed are believed to represent high-end dermal,
inhalation, and incidental oral exposures.  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 EPA’s standard assumptions (e.g., Health Effects
Division’s (HED) Standard Operating Procedures (SOPs) for Residential
Exposure Assessment).  

	All of the calculated margins of exposures (MOEs) in the residential
setting were below the target MOE of 1,000 (dermal, inhalation and
incidental oral) and therefore are of a concern.  For this reason a
total MOE, which accounts for dermal and inhalation exposures combined,
was not calculated.  These scenarios include:

The residential handler dermal and inhalation exposures that result from
staining wood with a paint brush and/or airless sprayer.

The residential post-application short- and intermediate-term dermal and
incidental oral risks for children and/or adults coming in contact with
or wearing treated textiles (mattress covers and clothing).

	It is important to note that during the error comment phase, two
leaching studies were provided to the Agency for Ultra-Fresh leaching
from mattress ticking onto pig skin.  The first study, (Thomson Research
Associates Report No. RG-2002-03-01), resulted in the transfer of TBTO
residues during the leaching.  A second study (Thomson Research
Associates Report No. RG-2004-03-01) was conducted with a less abrasive
monitoring technique and indicated no leaching of TBTO residues (LOD =
10 ppb).  EPA is currently reviewing the methodologies to determine the
appropriate sampling method.  Therefore, the results of this scenario
may change the risks for the dermal exposure scenarios, but not the
incidental oral.

	In addition, scenarios associated with residual active ingredient from
treated sponges could not be assessed qualitatively.  It is plausible
that both adults and children could encounter post-application residues
from tributyltin maleate-treated sponges used on household surfaces such
as kitchen counters.  Infants and children also may be incidentally
exposed via contact with floors cleaned with these sponges.  No FDA
clearance for tributyltin maleate exists to cover residues associated
with food-contact surfaces.  

 	1.7	Aggregate Exposure and Risk:

	In order for a pesticide registration to continue, it must be shown
“that there is reasonable certainty that no harm will result from
aggregate exposure to pesticide chemical residue, including all
anticipated dietary exposures and other exposures for which there are
reliable information.”  Aggregate exposure is the total exposure to a
single chemical (or its residues) that may occur from dietary (i.e.,
food and drinking water), residential, and other non-occupational
sources, and from all known or plausible exposure routes (oral, dermal,
and inhalation).  An aggregate assessment was not conducted at this time
because all of the quantitatively assessed scenarios that would have
been considered generate individual risks of concern, so the estimated
aggregate risk would also be of concern.

.

1.8	Occupational Exposure and Risk

	  SEQ CHAPTER \h \r 1 Based on examination of product labels, it has
been determined that exposure to handlers can occur in a variety of
occupational environments.  Occupational handlers may be exposed in the
manufacturing of other products (e.g., textiles), during the treatment
of water systems, hatcheries, farm premises, and commercial painting
with preserved paint, etc.).  In addition, post-application exposures
are likely to occur in occupational settings from reentry into treated
poultry/animal premises.  The representative scenarios selected by the
Agency were evaluated using maximum application rates as recommended on
the product labels for TBT-containing products.

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 EPA’s standard
assumptions (e.g., Health Effects Division’s (HED) Standard Operating
Procedures (SOPs) for Residential Exposure Assessment) as well as
Multi-Chamber Concentration and Exposure Model (MCCEM v1.2). 

It is important to note:

Based on the low application rate and the magnitude of the MOEs
generated when unit exposures were available to assess gloved scenarios,
chemical resistant gloves can be expected to afford substantial
reduction in exposures.  Data will be necessary for assessing the impact
of the gloves on exposure.  

Closed loading systems for the use of TBT compounds in industrial
processes and recirculating/cooling water and oilfields, along with
pants, long sleeved shirts, and chemical resistant gloves, will
substantially reduce occupational exposures.

Some of the calculated MOEs in the occupational setting were above the
target MOE of 100 (for both dermal and inhalation) except for the listed
scenarios.  However, as with the residential assessment, total MOEs
(inhalation and dermal) were not calculated because of the individual
risks of concern.

Applying the product in agricultural premises via a paintbrush type
method: dermal MOE = 47 (with gloves = 350).

Wiping in agricultural premises: dermal MOE  = 57.

Hand held spraying of the pesticide in agricultural premises: dermal MOE
= 22.

Preparing the fogging solution for agricultural premises: dermal MOE <1
and inhalation MOE  = 2.

Liquid pouring and liquid pumping of the product for the preservation of
construction materials: dermal MOEs = 36 and 2 respectively.

Liquid pour preservation of metalworking fluids, dermal MOE = 21 (with
gloves) and inhalation MOE = 68.

Preservation via liquid pouring for oilfield uses, dermal and inhalation
MOEs = 3.

Handler applying TBT preserved product via brushing to wood: dermal MOE
<1 and inhalation MOE  = 24.

Handler applying TBT preserved wood product via airless spraying: dermal
and inhalation MOEs both are  <1.

Machinist handling TBT preserved metalworking fluid: dermal MOE = 3 and
inhalation MOE = 36.

Person entering a hatchery after a 1 hour restricted interval has
passed: inhalation MOE = 17

	1.9		Environmental Hazard and Risk: 

	

	An ecological risk assessment is not currently required for the uses of
the TBT-containing compounds other than for the wood preservative
applications.  This is because the release and exposure levels are
expected to be low when those products are applied according to label
directions and use precautions.  As a result, the environmental hazard
and risk assessment was only conducted for TBTO.  Tributyltin benzoate
and tributyltin maleate, as previously mentioned are used as
preservatives in products that are considered to pose little or no
impact on the environment because of the specified use sites.  

	A propriety study was used for the purposes of modeling such that data
compensation will be necessary, and is identified as Rohm and Haas,
2006.  Environmental Risk Assessment of DCOIT for Wood Preservative
Applications.  Prepared by John P Carbone and Andrew H. Jacobson, Rohm
and Haas Company, Spring House, PA.  Company Report 06R-1006.  February
9, 2006.

	Regarding the environmental hazards and risks for TBTO there are
several data requirements that will need to be fulfilled for a complete
assessment.   These are reiterated in the data gaps section of this risk
assessment but are as follows (Table 2):

	

Table 2.  Ecological Data Gaps for Tributyltin Compounds

Guideline Number	Study Type

850.1735	Whole sediment: acute freshwater invertebrates

850.1740	Whole sediment: acute marine invertebrates

No Guideline	Whole sediment: chronic invertebrates

850.5400	Freshwater diatom; TGAI or EP

	Marine diatom; TGAI or EP

	Blue-green cyanobacteria; TGAI or EP

	Freshwater green alga; TGAI or EP

850.4400	Freshwater floating macrophyte duckweed; TGAI or EP

850.4225	Freshwater rooted macrophyte rice seedling emergence; EP

850.4250	Freshwater rooted macrophyte rice vegetative vigor; EP

171-4 & 850.3030	Honey/beeswax residues and acute toxicity of treated
wood residues to bees (see Confirmatory Data Required section of
assessment for more information; study can be waived by label statement
specified in Label Hazard Statements)

	TBTO poses potential problems in the aquatic environment because it is
extremely toxic to aquatic organisms.  Specific to such organisms, TBTO
has been linked to imposex (i.e., masculinization of females) shell
deformities and behavioral abnormalities.  Although most of this
information is related to the consequences of using TBTO preserved
antifouling paints (which has been cancelled), it is expected that the
environmental concentrations from wood preservative uses may pose a
similar concern.  TBTO has very high bioconcentration and
bioaccumulation factors, and it persists in sediments, which may result
in environmental transport from wood-preservative application sites to
water bodies.  As a result of the severe toxicity to aquatic organisms,
precautionary label (as identified in the Label Statement) will be
required.  The acute-risk level of concern (LOC) is equaled to or
exceeded for listed (endangered and threatened) freshwater and
estuarine/marine fish and invertebrates, but this is not the case for
the chronic risk LOC for listed species.  For non-listed species, the
acute-risk and chronic risks both are not exceeded.  Risks to aquatic
plants and organisms were not able to be completed at this time because
of the identified data gaps.

	Endangered Species Considerations:   Section 7 of the Endangered
Species Act, 16 U.S.C. Section 1536(a)(2), requires all federal agencies
to consult with the National Marine Fisheries Service (NMFS) for marine
and anadromous listed species, or the United States Fish and Wildlife
Services (FWS) for listed wildlife and freshwater organisms, if they are
proposing an "action" that may affect listed species or their designated
habitat.  Each federal agency is required under the Act to ensure that
any action authorized, funded, or carried out is not likely to
jeopardize the continued existence of a listed species or result in the
destruction or adverse modification of designated critical habitat.  To
jeopardize the continued existence of a listed species means "to engage
in an action that reasonably would be expected, directly or indirectly,
to reduce appreciably the likelihood of both the survival and recovery
of a listed species in the wild by reducing the reproduction, numbers,
or distribution of the species." 50 C.F.R. ( 402.02.

	For certain use categories, the Agency assumes there will be minimal
environmental exposure, and only a minimal toxicity data set is required
(Overview of the Ecological Risk Assessment Process in the Office of
Pesticide Programs U.S. Environmental Protection Agency - Endangered and
Threatened Species Effects Determinations, 1/23/04, Appendix A, Section
IIB, pg.81).  Chemicals in these categories therefore do not undergo a
full screening-level risk assessment, and are considered to fall under a
“No Effect” determination.  

2.0	PHYSICAL AND CHEMICAL PROPERTIES

	 

				Each chemical considered for this case is identified by an
individual CAS number such that product chemistry information is
provided separately.  The values presented in Table 3 have been obtained
from the best available data and the product chemistry chapter (memo
from T. Lindheimer, November 2007) provides a comprehensive discussion.

Table 3: Physical and Chemical Properties Reported for Tributyltin
Containing Compounds

Parameter	Tributyltin Oxide	Tributyltin Benzoate	Tributyltin Maleate

PC Code	083001	083106	083118

CAS #	56-35-9	4342-36-3	4027-18-3

Chemical Formula	C24H54OSn2	C19H32O2Sn	C16H30O4Sn

Molecular Weight	596.12 g/mol	411.18 g/mol	405.13 g/mol

Density	1.17 g/L	NA	NA

Boiling Point	417.34oC	390.12oC	415.18oC

Melting Point	131.93 oC	128.33 oC	153.42oC

Vapor Pressure	7.8 x 10-06 mm Hg @ 25 oC	1.34 x 10-06 mm Hg @ 25 oC	1.74
x 10-07@ 25oC

Henry’s Law Constant	6.83 x 10-05 atm m3/mol	2.83 x 10-06 atm m3/mol
1.43 x 10-07atm m3/mol

log Koc	7.57	5.10	2.99

Solubility in Water	0.0896 mg/L	0.257 mg/L	4.086  mg/L

Half life in Water	2.49 hours (model river)	2.172 hrs (model river)
343.5 days (model river)

Half Life in Air	0.125 days	0.241 days	2.5 hr

log Kow	3.84	4.69	3.79

Physical State	Slightly yellow; liquid	NA	NA

NA: Not available

3.0	HAZARD CHARACTERIZATION tc "

3.0	HAZARD CHARACTERIZATION" 

   3.1 Hazard Profile  tc "3.1 Hazard Profile " \l 2 

	A detailed Toxicology Assessment for the tributyltin containing
compounds is presented in the attached memorandum from M. Centra
(January 2008).  A summary of the key toxicological studies is presented
in Appendix B because of the large amount of toxicological information
on this compound.  A brief hazard assessment is presented below.

	Acute Toxicity: 

	Table 4 provides the Acute Toxicity that has been reported for TBT
containing compounds.

Table 4. Acute Toxicity Profile for Technical (95.0- 97.5 % a.i.)
Tributyltin Compounds

Guideline Number	Study Type	MRID Number	Results	Toxicity Category

Tributyltin Oxide

870.1100

(§ 81-1)	Acute Oral – Rat 

	00085004,

92172013	LD50 =180 mg/kg (males)

LD50 =150 mg/kg (females)

LD50 =170 mg/kg (combined)	II

870.1100

(§ 81-1)	Acute Oral – Rat

	00085003,

92172004	LD50 =193 mg/kg (males)

LD50 =123 mg/kg (females)

LD50 =160 mg/kg (combined)	II

870.2600

(§ 81-6)	Skin Sensitization –Guinea pigs

	00104789, 92172014	Non sensitizer	Not applicable

Tributyltin Maleate

870.1100

(§ 81-1)	Acute Oral – Rat 

	43851201	LD50 = 224.7 mg/kg	II

870.2600

(§ 81-6)	Skin Sensitization – Guinea pigs

	44142303	Non sensitizer. Not sensitizing; minimal irritation in
response to induction, but no increase in response to challenge dose	Not
applicable

Tributyltin Benzoate

870.1100

(§ 81-1)	Acute Oral – rat

Purity 

	42415801	LD50 =115 mg/kg (males)

LD50 =115 mg/kg (females)

LD50 =115 mg/kg (combined)	II

870.1200

(§ 81-2)	Acute Dermal – rat

Purity 

	42415802	LD50  > 2000 mg/kg (combined)	III

870.2500

(§ 81-5)	Primary Dermal Irritation – rabbit

Purity 

	42415803	Severe Irritation	I

3.2 Dose-Response Assessment  tc "3.3 Dose-Response Assessment " \l 2  

Table 5 summarizes the toxicological endpoints utilized for this risk
assessment (USEPA, 2008).

Table 5: Summary of Toxicology Endpoint Selection tc \l1 "     VIII.
SUMMARY OF TOXICOLOGY ENDPOINT SELECTION  for Tributyltin Compounds

  SEQ CHAPTER \h \r 1 Exposure

Scenario	Dose Used in Risk Assessment

(mg/kg/day) 	Special Sensitivity*, UF, Target MOE, 

for Risk Assessment	Study and Toxicological Effects

Dietary Risk Assessments

Acute Dietary

(females 13-49 and general population)	No appropriate endpoints were
identified in the oral toxicity studies that represent a single dose
effect for the general population and females 13-49.  In addition, the
current use patterns for the tributyltin-containing chemicals do not
indicate the potential for direct or indirect dietary exposures. 
Therefore, an acute dietary risk assessment has not been conducted. 

Chronic Dietary

(all populations)	BMD10 = 0.03 mg/kg/day based on immunosupression
(established by EPA/IRIS and used to estimate the oral RfD). 

	Special Sensitivity = 10

UF = 100 (10x inter-species extrapolation, 10x intra-species variation)

 

Chronic RfD (cRfD) =  0.00003 mg/kg/day

Although the database for  the tributyltin-containing chemicals does not
provide information on which to base an assessment of chronic dietary
exposures, this endpoint is selected for future reference.  A chronic
dietary risk assessment has not been conducted.. 	Open Literature Study

Vos et al., (1990) Immunotoxicity of bis (tri-n-butyltin) oxide in the
rat: Effects on thymus-dependent immunity and on nonspecific resistance
following long-term exposure in young vs. aged rats.  Toxicol. Appl.
Pharmacol.  105:144-155.

 

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of IgE titers
and increase in T. spiralis larvae in muscle) following 4 months and
16.5 months of exposure to Tributyl Tin Oxide.  (Review by EPA/IRIS,
1997). 

Non-Dietary Risk Assessments

Incidental Oral Short-Term 

(1-30 days) and Intermediate-Term  (1- 6 months) 

	BMD10 = 0.03 mg/kg/day based on immunosupression (established by
EPA/IRIS and used to estimate the oral RfD). 

	Special Sensitivity = 10

UF = 100 (10x inter-species extrapolation, 10x intra-species variation)

Target MOE res. = 1000	Open Literature Study

Vos et al., (1990) Immunotoxicity of bis (tri-n-butyltin) oxide in the
rat: Effects on thymus-dependent immunity and on nonspecific resistance
following long-term exposure in young vs. aged rats.  Toxicol. Appl.
Pharmacol.  105:144-155.

 

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of IgE titers
and increase in T. spiralis larvae in muscle) following 4 months and
16.5 months of exposure to Tributyl Tin Oxide.  (Review by EPA/IRIS,
1997). 

Dermal

(all durations)	BMD10 = 0.03 mg/kg/day based on immunosupression
(established by EPA/IRIS and used to estimate the oral RfD). 

	Special Sensitivity = 10

UF = 100 (10x inter-species extrapolation, 10x intra-species variation)

Target MOE occ. = 100

Target MOE res. = 1000	Open Literature Study

Vos et al., (1990) Immunotoxicity of bis (tri-n-butyltin) oxide in the
rat: Effects on thymus-dependent immunity and on nonspecific resistance
following long-term exposure in young vs. aged rats.  Toxicol. Appl.
Pharmacol.  105:144-155.

 

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of IgE titers
and increase in T. spiralis larvae in muscle) following 4 months and
16.5 months of exposure to Tributyl Tin Oxide.  (Review by EPA/IRIS,
1997). 

Inhalation

(all durations)	BMD10 = 0.03 mg/kg/day based on immunosupression
(established by EPA/IRIS and used to estimate the oral RfD). 

	Special Sensitivity = 10

UF = 100 (10x inter-species extrapolation, 10x intra-species variation)

Target MOE occ. = 100

Target MOE res. = 1000	Open Literature Study

Vos et al., (1990) Immunotoxicity of bis (tri-n-butyltin) oxide in the
rat: Effects on thymus-dependent immunity and on nonspecific resistance
following long-term exposure in young vs. aged rats.  Toxicol. Appl.
Pharmacol.  105:144-155.

 

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of IgE titers
and increase in T. spiralis larvae in muscle) following 4 months and
16.5 months of exposure to Tributyl Tin Oxide.  (Review by EPA/IRIS,
1997). 

Dermal Absorption	Although there is no guideline dermal toxicity study
(range-finding study only) and no acceptable dermal absorption study
(75% recovery of 113Sn-tributyltin oxide), a 15% dermal absorption
factor for tributyltin oxide has been used (EPA/HED) for route-to-route
extrapolation.   

Carcinogenicity	EPA has assigned tributyltin oxide to category D (U.S.,
1987) or to the “cannot be determined” category for carcinogenicity
(U.S. EPA, 1996) based on high spontaneous incidences of tumors in
Wistar rats, incidence variability in the treated groups and absence of
a dose-effect relationship.

UF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL
= lowest observed adverse effect level, RfD = reference dose, MOE =
margin of exposure, NA = Not Applicable

 

*The Special Sensitivity factor is applied to a selected dose if there
is evidence of increased susceptibility to children from non-dietary
exposures to pesticides.  Several published literature show that
tributyltin oxide causes depression of immune functions dependent on the
thymus, particularly in young animals.  This is a critical effect that
occurs at doses lower than those causing other toxicities.  Therefore,
application of this factor provides adequate protection to the most
sensitive population, children.

3.3   FQPA Considerations

	Under the Food Quality Protection Act (FQPA), P.L. 104-170, which was
promulgated in 1996 as an amendment to the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug and
Cosmetic Act (FFDCA), the Agency was directed to "ensure that there is a
reasonable certainty that no harm will result to infants and children"
from aggregate exposure to a pesticide chemical residue.  The law
further states that in the case of threshold effects, for purposes of
providing this reasonable certainty of no harm, "an additional tenfold
margin of safety for the pesticide chemical residue and other sources of
exposure shall be applied for infants and children to take into account
potential pre- and post-natal toxicity and completeness of the data with
respect to exposure and toxicity to infants and children. 
Notwithstanding such requirement for an additional margin of safety, the
Administrator may use a different margin of safety for the pesticide
residue only if, on the basis of reliable data, such margin will be safe
for infants and children."

	The labeled uses for the tributyltin-containing chemical active
ingredients could result in direct or indirect food exposures and
incidental exposures; therefore, potential for enhanced sensitivity of
infants and children from exposure to these chemicals was assessed as
required by the Food Quality Protection Act (FQPA).  The developmental
and prenatal database for TBT-containing chemicals which consists of
submitted studies is considered complete and adequate for regulatory
purposes.  Acceptable prenatal and postnatal data consist of one
developmental toxicity study in the rat conducted with TBTO, one
developmental toxicity study in the rat conducted with TBTB, and one
reproduction toxicity study in rats conducted with TBTO.  No evidence of
increased sensitivity was observed in fetuses or offspring in the
available studies.  Information from the open literature suggests that
children are more sensitive than adults to the immunotoxic effects of
TBT exposure, and that the application of a sensitivity factor can
provide protection for this most sensitive population, children.  The
FQPA special safety factor is 10 xs (retained).

	

3.4	Endocrine Disruption

	  SEQ CHAPTER \h \r 1  EPA is required under the 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 endocrine effects as the
Administrator may designate.”  Following recommendations of its
Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC),
EPA determined that there was a scientific basis for including, as part
of the program, the androgen and thyroid hormone systems, in addition to
the estrogen hormone system.  EPA also adopted EDSTAC’s recommendation
that EPA include evaluations of potential effects in wildlife.  For
pesticides, EPA will use FIFRA and, to the extent that effects in
wildlife may help determine whether a substance may have an effect in
humans, FFDCA authority to require the wildlife evaluations.  As the
science develops and resources allow, screening of additional hormone
systems may be added to the Endocrine Disruptor Screening Program
(EDSP).  When the appropriate screening and/or testing protocols being
considered under the EDSP have been developed, tributyltin oxide,
tributyltin maleate and tributyltin benzoate may be subject to
additional screening and/or testing to better characterize the known
effects related to endocrine disruption, reproductive anomalies in
marine invertebrates and thyroid effects in several other species.  

4.0	INCIDENT REPORTS

	Two approaches were used to generate the incident report for TBT
containing compounds.  

The potential health effects of TBT in humans, reported as incident
reports from different sources, and;

A literature search of health effects associated with TBT exposure,
including results of epidemiological studies.

The following databases have been consulted and are the results of the
reports are discussed in further detail within the supporting incidence
chapter (J. Chen, January 2008).

OPP Incident Data System (IDS) - The Incident Data System of The Office
of Pesticide Programs (OPP) of the Environmental Protection Agency (EPA)
contains reports of incidents from various sources, including
registrants, other federal and state health and environmental agencies
and individual consumers, submitted to OPP since 1992.  

Poison Control Centers - as the result of a data purchase by EPA, OPP
received Poison Control Center data covering the years 1993 through 1998
for all pesticides.  Most of the national Poison Control Centers (PCCs)
participate in a national data collection system, the Toxic Exposure
Surveillance System, which obtains data from about 65-70 centers at
hospitals and universities.  

  SEQ CHAPTER \h \r 1 California Department of Pesticide Regulation
(1982-2004) - California has collected uniform data on suspected
pesticide poisonings since 1982.  Physicians are required, by statute,
to report to their local health officer all occurrences of illness
suspected of being related to exposure to pesticides.  

National Pesticide Information Center (NPIC) - NPTN is a toll-free
information service supported by OPP.  A ranking of the top 200 active
ingredients for which telephone calls were received during calendar
years 1984-1991, inclusive, has been prepared.  

Published Incident Reports - Some incident reports associated with
octhilinone related human health hazard are published in the scientific
literature.

Incidents due to exposure to TBT (alone or in combination)

There are several incidents that have been reported in the California
Pesticide Surveillance Program Database (1982-1998) as definitely or
probably related to tributyltin compounds alone or in combination. As
summarized in the supporting chapter, the primary symptoms were
associated with eyes.  Nausea, dizziness, headache, and sore throat are
the primary systemic effects that have been reported.  The primary
dermal effects that have been reported are rash, burning sensation,
itching. None of the people were either hospitalized or lost days from
work. 

Summary of the Incident Reports due to Exposure to Tributyltin Oxide

Although the following incidents have been reported for exposure to
tributyltin oxide, the incidences occurred when used in combination with
other chemicals. tc \l2 "1.1 	OPPs Incident Data System (IDS) 

A total of 3 incidents were reported due to residential uses of
tributyltin oxide either for painting the wall or handling the wooden
joists that had been treated to control mildew.  Inhalation of
tributyltin oxide in combination with other chemicals was considered to
be the primary route of exposure. 

When a couple painted the interior of their sail boat with a chemical
containing tributyltin oxide; the husband suffered from muscle weakness,
muscle fasciculation, tremors and weakness in his shoulders, and was
diagnosed with Lou Gehrig’s disease; while the wife experienced muscle
fatigue and numbness in her extremities. 

The second incident occurred in apartments, where the residents
complained of offensive odors, eye irritations, and respiratory
distress. 

Building workers experienced poor coordination and unsteadiness 3 days
after handling treated wooden joists. The route of exposure could not be
determined from the information provided in the incident report.

A total of 11 incidents were reported from the use of tributyltin oxide,
in combination with other chemicals, in wood preservative stain. Dermal
exposure to wood preservative stain (indoor/outdoor/deck painting) led
to 9 incidents of rash, hives/welts, itching, blisters, color
alteration, ocular irritation, headache, nausea, and dizziness/vertigo.
Inhalation of the chemical vapors resulted in chest pain and one
incident of seizures.

Summary of the Incident Reports due to Exposure to Tributyltin Maleate

An incident in which a woman was exposed to pillows (dermal and ocular
routes) treated with Ultrafresh DM 50, containing tributyltin maleate,
reported development of a swollen mouth, cheeks, neck, lips and a
swollen throat (that inhibited her from talking), irritation of the eyes
and mouth, quivering of the jaws and lack of concentration. 

EXPOSURE ASSESSMENT AND CHARACTERIZATION tc "4.0	EXPOSURE ASSESSMENT AND
CHARACTERIZATION" 

5.1	Dietary Exposure and Risk

	For a complete discussion of the dietary exposures considered as well
as specific assumptions, please refer to the supporting dietary and
drinking water chapter (C. Walls, January 2008).  TBT compounds can be
used in following use sites where a potential for food contact may occur
(water cooling systems for pasteurization/canneries, paper mills, and
adhesives).  However, all of the TBT labels that have one of these use
sites contain specific “non-food contact” requirements or use
directions that minimize the indirect dietary exposure such that an
assessment was not warranted for these particular uses.

There is also the use of TBT-containing compounds in livestock
operations, in which the animals are removed prior to the treatment of
the facilities, and the feeding equipment is rinsed with water prior to
animal reuse.  It typically is assumed that this results in negligible
residues such that livestock premises were not considered for the
dietary assessment.  However, for TBT products used in animal housing
facilities, the Agency believes there may be a potential for human
dietary exposure.  This is a combined result of the way in which such
treatments are conducted and the particular fate characteristics of TBT.
 Specifically, 1) the product label does not require rinsing or removal
of TBT solution or fogging residue after treatment (except for feed
bowls not removed during treatment), 2) animal premises may be treated
frequently, and 3) TBT is environmentally persistent and
bioaccumulative.  

Based on the qualitative assessment of the aforementioned scenarios, the
product label is recommended to indicate that treated surfaces must be
rinsed before animals can be re-housed.  Data on the effectiveness of
rinsing in removing TBT residues from the treated premises, and residue
data in the associated food commodities will enable the Agency to
further refine the assessment of the animal premises use.

Historically, it has been assumed by the Antimicrobials Division that
incubating eggs do not absorb pesticide chemicals, but data are lacking
to support the assumption.  The hatchery use of TBTO (hatchery rooms,
incubators, and hatchers) may pose a greater likelihood of producing
residues in eggs, especially in consideration of the environmental fate
properties of this chemical.  The registrant has indicated that the
removal of eggs to avoid any residues during applications of the product
is not viable and that premises may be treated as frequently as once a
day.  A chemical like TBTO, with its large potential for persistence and
bioaccumulation, could pose an increased risk of residues in eggs
relative to other pesticides identified to be of lesser persistence and
bioaccumulative potential.  Data appropriate for use in examining the
assumption that this pesticide does not penetrate eggshells in
incubation would facilitate a quantitative assessment of dietary
exposures resulting from the use of TBTO in hatcheries.

5.2   Drinking Water Exposure and Risk for Active Ingredient Uses 

Based on the use patterns, the potential for TBT-containing products to
impact drinking water sources is assumed to be negligible and therefore
a quantitative drinking water assessment was not conducted at this time.
 

5.3 	Residential Exposure/Risk Pathway  tc "4.4 	Residential
Exposure/Risk Pathway " \l 2 

Exposure Scenarios

	Details of the residential exposure assessment can be found within the
companion memorandum that contains the comprehensive occupational and
residential exposure assessment (T. Leighton, January 2008).  A summary
of the residential assessment is presented below.

	For the purposes of this screening level assessment, the Agency
selected representative scenarios based on end-use product application
methods, rates, and use amounts.  These scenarios reflect high-end
exposure and risk estimates for all of the products represented. The
selected scenarios are summarized in Appendix C.

Exposure Data and Assumptions for Handlers:

	The short-term inhalation and dermal handler exposures were assessed
for non-pressure wood preservation (e.g., siding, shingles, fences,
decks, millwork, etc.) and risks associated with these uses are
considered to be representative of all other potential residential
handler exposures.  Only short-term exposure durations (1 to 30 days)
were estimated for handlers because it was assumed that a homeowner or
do-it-yourself individual would typically treat on an intermittent basis
(i.e., once or twice a year, which is a short-term duration). 
Additionally, in the case of the tributylins, the vapor pressure is low
and therefore the vapor phase was not necessary to evaluate.  Only
inhalation exposure to preservative aerosols was quantitatively
assessed.

	

Exposure Data and Assumptions for Post application:

	For the purposes of this portion of the assessment, post application
scenarios have been selected that encompass multiple products.  These
selected scenarios represent high end exposures and include: post
application dermal and/or incidental ingestion exposures to treated
articles such as clothing and mattress.  Post-application/bystander
inhalation exposures are expected to be minimal for most uses, except
for drift occurring during the airless spray painting.  The inhalation
bystander exposures to aerosols generated during painting are assumed to
be less then that of the applicator and therefore were not assessed
separately.  Additionally because of the vapor pressures of TBTO, TBTM
and TBTB being low, post application exposures to vapors are assumed to
be negligible. 

	It is important to note that during the error comment phase, two
leaching studies were provided to the Agency for Ultra-Fresh leaching
from mattress ticking onto pig skin.  The first study, (Thomson Research
Associates Report No. RG-2002-03-01), resulted in the transfer of TBTO
residues during the leaching.  A second study (Thomson Research
Associates Report No. RG-2004-03-01) was conducted with a less abrasive
monitoring technique and indicated no leaching of TBTO residues (LOD =
10 ppb).  EPA is currently reviewing the methodologies to determine the
appropriate sampling method.  Therefore, the results of this scenario
may change the risks for the dermal exposure scenarios, but not the
incidental oral.

Risk Characterization: Handler and Post application

	Data sources and methodologies utilized for both the handler and
postapplication residential risk assessment include: the HED Residential
Standard Operating Procedures (SOPs) (USEPA, 1997a), the USEPA Exposure
Factors Handbook (USEPA 1997b), Recommended Revisions to the Residential
SOPs (USEPA, 2001), and the Human and Environmental Risk Assessment
(HERA) Guidance Document (2003).  The specific input parameters and
assumptions are discussed in the supplementary exposure assessment (T.
Leighton January 2008).  A summary of the residential handler exposure
and risk estimates are below. The target MOEs for all durations and
routes of exposures is 1,000, and the body weight assumed for adults and
children were 70 kg and 15 kg respectively.

All of the risks assessed for the residential handler and post
application scenarios (summarized below) were well below the target MOE
of 1,000 and therefore are of a concern to the Agency.

Preserving wood via paint brushing (dermal and inhalation)

Preserving wood via airless spraying (dermal and inhalation)

Wearing treated clothing (dermal and incidental oral (child))

Using a treated mattress cover (dermal)

6.0 	AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION tc "5.0 
AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION" 

	In order for a pesticide registration to continue, it must be shown
that the use does not result in “unreasonable adverse effects on the
environment”.  Section 2 (bb) of FIFRA defines this term to include
“a human dietary risk from residues that result from a use of a
pesticide in or on any food inconsistent with standard under section
408...” of FFDCA.  As mandated by the FQPA amendments to FIFRA and the
Federal Food, Drug and Cosmetic Act (FFDCA), the Agency must consider
total potential aggregate exposure from food, drinking water and
residential sources of TBT. Aggregate exposure is the total exposure to
a single chemical (or its residues) that may occur from dietary (i.e.,
food and drinking water), residential, and other non-occupational
sources, and from plausible exposure routes (oral, dermal, and
inhalation).  Typically, aggregate risk assessments are conducted for
acute (1 day), short-term (1-30 days), intermediate-term (1-6 months)
and chronic (6 months to lifetime) exposures. 

		In performing aggregate exposure and risk assessments, the Office of
Pesticide Programs has published guidance outlining the necessary steps
to perform such assessments (General Principles for Performing Aggregate
Exposure and Risk Assessments, November 28, 2001; available at    
HYPERLINK "http://www.epa.gov/pesticides/trac/science/aggregate.pdf" 
http://www.epa.gov/pesticides/trac/science/aggregate.pdf   ).  Steps for
deciding whether to perform aggregate exposure and risk assessments are
listed, which include: identification of toxicological endpoints for
each exposure route and duration; identification of potential exposures
for each pathway (food, water, and/or residential);  reconciliation of
durations and pathways of exposure with durations and pathways of health
effects; determination of which possible residential exposure scenarios
are likely to occur together within a given time frame; determination of
magnitude and duration of exposure for all exposure combinations;
determination of the appropriate technique (deterministic or
probabilistic) for exposure assessment; and determination of the
appropriate risk metric to estimate aggregate risk.  

	The inhalation, dermal, and oral endpoints are based on the same
toxicological study/effects, and therefore, it would be appropriate to
estimate aggregate MOEs.  The residential uses that could potentially be
aggregated are the wood preservation (referred to as painting based on
the method of application) applications, textiles, and mattresses. 
There is the likelihood of co-occurrence for two of the uses but it
would be unlikely that all three uses would co-occur because of the
limited frequency.  Therefore, residential uses could be aggregated for
two of the three uses at a time.  However, at this time the risks are of
concern for each of the individual uses, and therefore, the aggregate
risks would be of a concern as well.

7.0	CUMULATIVE EXPOSURE AND RISK

		Another standard of section 408 of the FFDCA which must be considered
in making an unreasonable adverse effect determination is that the
Agency considers "available information” concerning the cumulative
effects of a particular pesticide's residues and "other substances that
have a common mechanism of toxicity.” 

		Unlike other pesticides for which EPA has followed a cumulative risk
approach based on a common mechanism of toxicity, EPA has not made a
common mechanism of toxicity finding as to octhilinone and any other
substances and octhilinone does not appear to produce a toxic metabolite
produced by other substances.  For the purposes of this tolerance
action, therefore, EPA has not assumed that octhilinone has a common
mechanism of toxicity with other substances.  For information regarding
EPA’s efforts to determine which chemicals have a common mechanism of
toxicity and to evaluate the cumulative effects of such chemicals, see
the policy statements released by EPA’s Office of Pesticide Programs
concerning common mechanism determinations and procedures for cumulating
effects from substances found to have a common mechanism on EPA’s
website at http://www.epa.gov/pesticides/cumulative/.

8.0	OCCUPATIONAL EXPOSURE AND RISK tc "7.0	OCCUPATIONAL EXPOSURE AND
RISK"  

Exposure Scenarios

		The Agency has assessed the exposures and risks to occupational
workers that handle TBT containing products (memorandum from T. Leighton
 SEQ CHAPTER \h \r 1 ).  This section summarizes the results of the
occupational exposure assessment.  The selected occupational scenarios
are summarized in Appendix C.

	Based on examination of product labels describing uses for the product,
it has been determined that exposure to handlers can occur in a variety
of occupational settings; agricultural premises and equipment;
commercial/institutional/industrial premises and equipment; material
preservatives; and industrial processes and water systems; and wood
preservatives.  The Agency has determined that there is potential for
dermal and inhalation worker exposure to TBT-containing compounds and
representative scenarios were selected for evaluation based on the use
sites and maximum application rates. There are expected post application
exposures with the exceptions of a machinist handling TBTO preserved
metalworking fluids as well as a person re-entering a hatchery upon
fogging. 

Exposure Data and Assumptions:

	Occupational handler exposures to TBT can occur during applications for
the preservation of materials and use in cooling water towers,
oilfields, and wood preservatives.  The “preservation of materials”
refers to the scenario of a worker adding the preservative to the
material being treated (paint, joint compound, adhesives, etc.) through
either liquid pour or liquid pump methods.  Liquid pour refers to
transferring the antimicrobial product from a small container to an open
vat.  Liquid pump refers to transferring the preservative by
connecting/disconnecting a chemical metering pump from a tote or by
gravity flow. 

	Use directions indicating that a biocide should be introduced into a
system via liquid pumping commonly are changing over to indicate that a
“metered pump” should be used in such operations.  The use of a
metered pump will reduce risk estimates for handlers performing the
tasks identified as “liquid” pump” in this assessment.  Closed
loading systems are engineering controls that are “…designed to
prevent human exposure and should not require human intervention to
eliminate exposure” (CDPR 2003).   Although closed loading and
delivery systems are designed to prevent or eliminate exposure, zero
exposure is difficult to obtain.  Analytical techniques can measure
residues at extremely low levels, and for practical purposes, at a
particular point these residues can be considered negligible or minimal.
 PPE worn by the worker can protect from these residual exposures.  

Negligible exposure can be considered to result from the use of systems
that are designed to drip less than 2 mL per coupling as in dry coupling
or metering pumps that are closed on both ends. The second category,
minimal exposure, has been established because some closed systems are
not entirely enclosed or have not been engineered to reduce drips to 2
mL, but for practical purposes effectively reduce exposure such that
risks are not of concern.  Minimal exposure can be considered to result
from closed systems that are designed to prevent or eliminate inhalation
and dermal exposure but are not engineered to a specification (e.g.,
volume expected to be discharged).  

 

For handling of the tributyltin-containing products via closed loading,
EPA expects that occupational exposures will be negligible or minimal
assuming that label-specified PPE (i.e., coveralls, long pants,
long-sleeved shirts, and chemical resistant gloves) and label-specified
closed delivery and loading systems such as dry coupling and closed
system metering pumps are consistently utilized.  Therefore, a
quantitative exposure and risk assessment is not warranted and the risks
can be considered not a concern.

	

Additional points relative to the occupational exposure assessment:

Regardless of the fact that gloves potentially can reduce the risks for
the majority of the occupational uses, gloves are not a viable
mitigation option for in-can preservative products such as joint
compound and adhesives.  This is because it is not feasible to label the
end-use product with the biocide information.

Due to their differences, exposures for a machinist working with
metalworking fluids or an individual re-entering a hatchery that has
been fogged are discussed in separate sections of the supporting
chapter.

	The parameters utilized for the occupational exposure assessment are
provided and discussed in more detail within the supporting exposure
chapter.  The dermal and inhalation unit exposure values were taken from
the proprietary CMA antimicrobial exposure study (EPA 1999: DP Barcode
D247642) or from the Pesticide Handler Exposure Database (EPA 1998). 
The quantity handled/treated values were estimated based on information
from various resources.  Exposures and MOEs were calculated for short-
and intermediate-term dermal and inhalation exposures using the
appropriate endpoints in Table 5.  

Risk Characterization:

	The MOEs in the occupational setting were above the target MOE of 100
for both dermal and inhalation except for the following scenarios
(without gloves or respiratory protection unless otherwise indicated):

Applying the product in agricultural premises via a paintbrush type
method: dermal MOE = 47 (with gloves = 350).

Wiping in agricultural premises after treatment: dermal MOE = 57.

Hand held spraying of the pesticide in agricultural premises: dermal MOE
= 22.

Preparing the fogging solution for agricultural premises: dermal MOE <1
and inhalation MOE  = 2.

Liquid pouring and liquid pumping of the product for the preservation of
construction materials: dermal MOE = 36 and 2 respectively.  

Liquid pour preservation of metalworking fluids, dermal MOE = 21 (with
gloves) and inhalation MOE = 68.

Preservation via liquid pouring for oilfield uses, dermal and inhalation
MOEs = 3.

Person entering a hatchery after the 1 hour restricted entry interval
has passed: inhalation MOE = 17 (2 hr REI MOE = 910).

	

	The risks associated with the following scenario cannot be mitigated
with the addition of PPE because the handler comes into contact with the
material after TBT has been added; he has no way of knowing that the
material contains TBT:

Handling treated metalworking fluids, dermal MOE = 3 and inhalation MOE
= 36.

Professionals applying wood preservatives that have been manufactured to
contain TBTO via painting with a brush, roller, or airless sprayer.  
For the brush, the dermal MOE = 24 and the inhalation MOE <1; for
airless spraying, both the dermal and inhalation MOEs <1.

9.0.	ENVIRONMENTAL FATE

	Detailed information on environmental fate is presented in the attached
environmental fate assessment (memo from J. Breithaupt, January 2008). 
A brief summary is provided below, and for purposes of this risk
assessment, environmental fate properties were reported for TBTO.  The
environmental fate properties for the other two active ingredients in
this case, TBTM and TBTB, were not reported because of the nature of the
use sites of these chemicals as previously discussed.  For a complete
presentation and discussion of the available resources that were
considered in developing the fate conclusions, please refer to the
supporting chapter.  

	TBTO is essentially stable to hydrolysis and photolysis in freshwater
and saltwater.  Based on its low vapor pressure it is not expected to
volatilize from water.  Biodegradation is considered to be the major
breakdown pathway of this chemical when it is present in either water or
sediments.  Half-lives are in the range of several days to weeks in
water and from several days to more than a year in sediments.  These
combined properties support the conclusion that TBTO has a high tendency
to bioconcentrate (e.g., concentrate in the tissues of species that may
ingest the chemical) and bioaccumulate (e.g., become transparent in the
food chain).  The octanol/water partition coefficient is very high, and
further supports the high tendency of TBTO to bioconcentrate 

10.0 	ENVIRONMENTAL RISK

 tc "9.0	ENVIRONMENTAL RISK" 

			10.1	Summary of Ecological Toxicity Data Conclusions

  	A detailed ecological hazard and environmental risk assessment for
TBTO is presented in supporting ecological risk assessment (memorandum
from W. Erickson, January 2008), and a summary of findings is presented
below.  An ecological risk assessment is warranted for the use of TBTO
wood preservative applications, because release and exposure levels are
expected to be low when the remaining TBT-containing products are
applied according to label directions and use precautions.  As
previously stated TBTO poses potential problems in the aquatic and
sedimentary environments, because it is extremely toxic to aquatic
organisms and has very high bioconcentration and bioaccumulation factors
(EPA 2003).  Environmental exposure levels from wood preservative
applications may be hazardous to organisms exposed to leachate and
runoff into surface waters; therefore an ecological assessment was
warranted. 

	Acute and Dietary Risks to Birds:  Three available acute-oral and
dietary studies indicate that technical-grade TBTO is moderately toxic
to birds if ingested and are considered acceptable.  Based on the study
results, an avian precautionary statement is not indicated for the TBT
product labels.  The guidelines for avian acute-oral toxicity (OPPTS
850.2100) and avian dietary toxicity OPPTS 850.2200) are satisfied.  

	Non-target Insects – Honeybees:  No guideline data are available for
TBTO.  For wood preservative uses, a study addressing honey/beeswax
residues and acute toxicity of treated wood residues to bees can be used
in the assessment of risks to bees; in lieu of these studies, product 
labels may bear a  statement prohibiting the use of TBT on wood used for
beehive construction.  

	Acute for Freshwater Fish:   Two acute toxicity studies with the TGAI
are required to establish the toxicity of TBTO compounds to freshwater
fish. The data characterize technical-grade TBTO as being very highly
toxic to freshwater fish.  A precautionary statement is triggered for
product labels.  The guideline for freshwater-fish acute toxicity (OPPTS
850.1075) is satisfied.

	Acute for Freshwater Invertebrates:  A study with the TGAI is required
to establish the acute toxicity of TBT to freshwater invertebrates.  The
preferred test species is the water flea, Daphnia magna.  Results from
two guideline studies categorize technical-grade TBTO as being very
highly acutely toxic to the water flea.  A precautionary statement is
triggered for product labels.  A study testing dibutylyin dichloride
categorizes this degradates as moderately toxic.  The guideline
requirement (OPPTS 850.1010) is satisfied.

	Estuarine and Marine Fish and Invertebrates, Acute: Acute toxicity of
the TGAI with estuarine/marine fish and invertebrates is required when
the end-use product is intended for direct application to the
marine/estuarine environment or the active ingredient is expected to
reach this environment in significant concentrations because of its use
and environmental fate characteristics.  The preferred fish test species
is sheepshead minnow (Cyprinodon variegatus).  Two guideline fish
toxicity studies are available.  The results of these studies indicate
that TBTO compounds are very highly toxic to estuarine/marine fish.  The
guideline for estuarine/marine-fish acute toxicity (OPPTS 850.1075) is
satisfied.  

	Chronic for Aquatic Organisms:  No guideline studies are available to
assess chronic risks of TBT-containing compounds to freshwater fish and
invertebrates.  However, EPA’s (2003) Ambient Aquatic Life Water
Quality Criteria for Tributyltin (TBT) – Final presents chronic
toxicity values for a 32-day early life-stage study with the fathead
minnow (Pimephales promelas) and for two 21-day life-cycle studies with
Daphnia magna.  NOEC values for adverse reproductive affects ranged from
0.1 to 0.19 µg ai/L across the three studies.   Two guideline studies
with the sheepshead minnow are available to assess the chronic toxicity
of TBTO to estuarine/marine fish. These studies fulfill the guideline
(850.1400) for a fish early life-stage (freshwater) study.  No valid
guideline studies are available for aquatic invertebrates.  

	Acute and Chronic Sediment Toxicity:  No guideline studies are
available.  Acute and chronic sediment toxicity data are indicated for
the TBTO wood preservative uses because of expected movement of active
ingredient into the aquatic environment and its expected deposition and
persistence in sediments as indicated by pertinent environmental fate
data (Kd >10 for acute and >50 for chronic, log Kow >3, Koc >1,000, soil
aerobic half-life = 127 days  in sediment).  

	Aquatic Plants:  No guideline studies have been submitted for TBT. 
Aquatic plant growth testing (850.5400) with the TGAI or TEP is required
for all pesticides that entail wood preservative uses.  The EPA (2003)
Ambient Aquatic Life Water Quality Criteria for Tributyltin (TBT) –
Final provides some information indicating that phytotoxicity of TBTO to
aquatic plants might be of concern.  

	10.2	Environmental Risk Assessment Criteria

	Risk assessment and characterization integrates exposure and toxicity
information to evaluate the potential for adverse ecological effects. 
Risk quotients (RQs) are determined for each taxa or ecological group by
comparing exposure estimates (Estimated Environmental Concentrations,
EECs) to the available acute and chronic ecotoxicity values, where:  

RQ = Exposure estimate (EEC) / Toxicity value

RQs are compared to OPP's levels of concern (LOCs).  Exceedance of an
LOC indicates a potential for acute or chronic adverse effects and
identifies a need for regulatory action to mitigate risk.  

Table 6:  LOCs for the Subgroups Assessed

Presumption	Aquatic Animals	Terrestrial Animals	Plants

Acute:	0.5	0.5	1

Acute, listed species:	0.05	0.1	1

Chronic:	1	1	n/a

	When available, toxicity measures or other appropriate information from
non-guideline studies or from the open literature also may be used to
characterize risk.  

	OPP generally uses computer simulation models to estimate exposure of
aquatic organisms to an active ingredient.  These models estimate EECs
in surface waters using product-label information (e.g., treatment site,
application rate, application method,) and available environmental-fate
data to determine how fast the pesticide breaks down and its expected
movement in the environment.  The models used in the risk assessment for
TBTO compound wood preservative uses are described in more detail in the
supporting Ecological Chapter (W. Erickson, January 2008).

	10.3	Aquatic Risk Characterization

	Estimated Environmental Concentrations for the leaching of TBTO from
treated wood into soil and surface waters were calculated for six uses,
including transmission poles, fence posts, fences, deck posts, decks,
and houses.  The methodology for this analysis is based on an
environmental risk assessment previously prepared by the Rohm and Haas
(2006) for 4,5-dichloro-2-n-octyl-3(2H)-isothiazolone (DCOIT).  Soil
concentrations and other input data are then used with EPA’s Express
model EXAMS-PRZM Exposure Simulation Shell (version 1.03.02) to estimate
concentrations in surface water.  Data compensation will need to be paid
for the use of Rohm and Haas’ study.  A complete assessment,
parameters, and model output are discussed in the supporting chapter.  

	Based on the values calculated for the ecological risks, acute risks to
listed fish and invertebrates are presumed to result from aquatic
exposure to TBTO.  This presumption of risk necessitates a more
comprehensive risk assessment for listed species, but this is not
included in the current assessment (see Endangered Species
Considerations section).  Although the Agency's calculated chronic LOC
is not exceeded for either fish or aquatic invertebrates, evidence
exists that chronic exposure may be a concern for some organisms.  EPA's
Office of Water considers TBT containing compounds to be a concern in
the aquatic environment due in part to its persistence and its link to
imposex and immuno-supression in snails and bivalves.  Through its
authority under the Clean Water Act, the Agency has developed ambient
water quality criteria for TBT containing compounds (EPA 2003).  EPA
does not regulate based on these criteria, but uses it to support that
TBTO concentrations may be detrimental to aquatic organisms.  This
potential will need to be examined in more detail when a more in-depth
risk assessment is conducted to address and mitigate risks to listed
species.

TBT also is expected to accrue in aquatic sediments, with half-lives
from several days to months or more (EPA 2003); thus, sediments may be a
long-term source of exposure of aquatic organisms.  The risks associated
with the presence of TBT in the sediment cannot be adequately assessed
without acute and chronic sediment-toxicity data.  There is evidence in
the open literature that certain sediment concentrations can trigger
severe effects in various aquatic organisms, and the particulars of the
various effects are discussed in more detail in the supporting
ecological hazard chapter.  The potential risks to aquatic plants cannot
be quantitatively assessed without the relevant toxicity data.  

	TBTO is reported to be toxic to honey bees (Apis mellifera) housed in
hives made from TBTO-treated wood (WHO 1999).  Guideline toxicity data
are not available to assess risk to honey bees at this time.  However,
if product labels prohibit use of treated wood in bee hives (see
Required Label Statements section), minimal exposure and risk would be
presumed. 

	10.4	Endangered Species Considerations

	Section 7 of the Endangered Species Act (ESA), 16 U.S.C. Section
1536(a)(2), requires that federal agencies consult with the National
Marine Fisheries Service (NMFS) for marine and anadromous listed
species, or with the United States Fish and Wildlife Services (FWS) for
listed wildlife and freshwater organisms, if proposing an "action" that
may affect listed species or their designated habitat.  Each federal
agency is required under the Act to insure that any action they
authorize, fund, or carry out is not likely to jeopardize the continued
existence of a listed species or result in the destruction or adverse
modification of designated critical habitat.  To jeopardize the
continued existence of a listed species is to "to engage in an action
that reasonably would be expected, directly or indirectly, to reduce
appreciably the likelihood of both the survival and recovery of a listed
species in the wild by reducing the reproduction, numbers, or
distribution of the species." 50 C.F.R. §402.02.

To comply with subsection (a)(2) of the ESA, EPA’s Office of Pesticide
Programs has established procedures to evaluate whether a proposed
registration action may directly or indirectly appreciably reduce the
likelihood of both the survival and recovery of a listed species in the
wild by reducing the reproduction, numbers, or distribution of any
listed species (U.S. EPA 2004).  If any of the Listed Species LOC
Criteria are exceeded for either direct or indirect effects in the
Agency’s screening-level risk assessment, the Agency identifies any
listed or candidate species that may occur spatially and temporally in
the footprint of the proposed use.  Further biological assessment is
undertaken to refine the risk.  The extent to which any species may be
at risk determines the need to develop a more comprehensive consultation
package as required by the ESA.

For TBT containing compound uses other than wood preservatives, the
Agency assumes there will be minimal environmental exposure, and only a
minimal toxicity data set is required (Overview of the Ecological Risk
Assessment Process in the Office of Pesticide Programs U.S.
Environmental Protection Agency - Endangered and Threatened Species
Effects Determinations, 1/23/04, Appendix A, Section IIB, p 81).  Uses
in these categories do not undergo a full screening-level risk
assessment and are considered to fall under a no effect determination.  

The assessment for wood treatment uses indicates that there is a
potential for TBTO exposure of listed freshwater and estuarine/marine
organisms, and possibly terrestrial birds and mammals, and a more
refined assessment is warranted for direct, indirect, and habitat
effects.  The refined assessment will involve clear delineation of the
action area associated with proposed use of TBTO and best available
information on the temporal and spatial co-location of listed species
with respect to the action area.  This analysis has not been conducted
for this assessment.  An endangered species effect determination will
not be made at this time.  The label statement required for wood
preservative products is expected to provide some mitigation until a
full endangered species assessment is conducted.

11.0	DATA NEEDS AND LABELING

Hazard Data Gaps: The following studies were identified as data gaps
following bridging of the tributyltin chemical toxicity databases:

Table 7.  Generic Data Gaps for Tributyltin Compounds

Guideline Number	Study Type

Tributyltin Oxide (TBTO)

870.1200	Acute Dermal Toxicity

870.1300	Acute Inhalation Toxicity

870.2400	Primary Eye Irritation

870.2500	Primary Dermal Irritation

870.3250	90-Day (dermal) Subchronic - Rodents

870.5450 to 870.5915	Mutagenicity Test (1 Study)

Tributyltin Maleate (TBTM)

870.1200	Acute Dermal Toxicity

870.1300	Acute Inhalation Toxicity

870.2400	Primary Eye Irritation

870.2500	Primary Dermal Irritation

870.3250	90-Day (dermal) Subchronic -Rodents

870.3700	Prenatal Developmental Toxicity in Rats

870.5100 to 870.5915	Battery of Mutagenicity Studies (3 studies; one
from each category; “Gene Mutation,” “Cytogenetics” and “Other
Mechanisms”)

Tributyltin Benzoate (TBTB)

870.1300	Acute Inhalation Toxicity

870.2400	Primary Eye Irritation

870.2600	Skin Sensitization

870.3250	90-Day (dermal) Subchronic - Rats

870.5450

to

870.5915	Battery of Mutagenicity Studies (1 study from “Other
Mechanisms” category)

Ecological Effects:  

Table 8.  Ecological Data Gaps for Tributyltin Compounds

Guideline Number	Study Type

850.1735	Whole sediment: acute freshwater invertebrates

850.1740	Whole sediment: acute marine invertebrates

No Guideline	Whole sediment: chronic invertebrates

850.5400	Freshwater diatom; TGAI or EP

	Marine diatom; TGAI or EP

	Blue-green cyanobacteria; TGAI or EP

	Freshwater green alga; TGAI or EP

850.4400	Freshwater floating macrophyte duckweed; TGAI or EP

850.4225	Freshwater rooted macrophyte rice seedling emergence; EP

850.4250	Freshwater rooted macrophyte rice vegetative vigor; EP

171-4 & 850.3030	A study addressing honey/beeswax residues and acute
toxicity of treated wood residues to bees is indicated if bee hives
might be constructed of treated wood or if any product is intended for
application to a bee hive.  The study is a combination of Guidelines
171-4 and 850.3030 (see information regarding residue data requirements
for uses in beehives in the residue chemistry section of 40 CFR part
158).  The toxicity portion of this study is conducted in lieu of a
honeybee contact LD50 test. The protocol for this study must be
consistent with OPPTS Guideline 850.3030.  The study may be waived if
wood preservative product labels are amended to prohibit their use on
wood used in hive construction.

Environmental Fate Data Gaps:  There is no guideline number affiliated
with this data gap; but leaching data from treated wood is necessary to
support the registration of wood preservation.

Product Chemistry:  There are no identified outstanding product
chemistry data requirements.

Residential/Occupational Data Gaps.  Data will be needed to determine
the level of protection afforded by PPE for occupational handlers.  

Dietary Data Gaps:  Additional data will improve our understanding of
actual exposures to animals housed in treated facilities.  Additionally,
data regarding the effectiveness of water as a rinsate for removing TBT
residues from the treated premises will be useful in refining the
assessment.  Lastly, residue data in the associated food commodities
will enable the Agency to further refine the assessment of the animal
premises use.  Data examining the assumption that TBT does not penetrate
eggshells in incubation would facilitate a quantitative assessment of
dietary exposures associated with the hatchery use.

	

Labeling:  

	All products:

	The following ENVIRONMENTAL HAZARDS statement is indicated for all
products:  

"This pesticide is toxic to fish and aquatic invertebrates. Do not
contaminate water when disposing of equipment washwaters.  Do not
discharge effluent containing this product into lakes, streams, ponds,
estuaries, oceans, or other waters unless in accordance with the
requirements of a National Pollutant Discharge Elimination System
(NPDES) permit and the permitting authorities are notified in writing
prior to discharge.  Do not discharge effluent containing this product
to sewer systems without previously notifying the local sewage treatment
plant authority.  For guidance contact your State Water Board or
Regional Office of the EPA."

For uses in which occupational risk estimates are of concern, labeling
for appropriate PPE is indicated.

For products used in the manufacture of materials including wood 
preservatives, and in water towers and oilfields:  Labeling for
appropriate engineering controls (closed delivery and loading systems)
and PPE can reduce handler exposures.

Specific to products with wood preservative uses:

If honeybee studies 850.3030 and 171-4 are to be waived, the following
label statement is indicated for wood preservative products:  

“This product must not be applied to wood used in the construction of
beehives.”

Products also must have a statement prohibiting use of TBT-treated wood
in the aquatic environment.

12.0	REFERENCES 

Occupational and Residential Exposure Assessment:

MCCEM V 1.2 The Multi-Chamber Concentration and Exposure Model (MCCEM)
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USEPA. 1992.  A Laboratory Method to Determine the Retention of Liquids
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USEPA. 1996.  Office of Research and Development, Descriptive Statistics
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USEPA.  1997.  Exposure Factors Handbook. Volume I-II.  Office of
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USEPA. 1998. PHED Surrogate Exposure Guide. Estimates of Worker Exposure
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Shelton, D., B. Urch, and S. M. Tarlo. 1992. Occupational asthma induced
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43997001	Williams, M. and Bradley, A., 1996. Aqueous Availability of
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Carbone, J. and Jacobson, A. 2006. Environmental risk assessment of
DCOIT for wood preservative applications. Report # 06R-1006. Rohm and
Haas Company. 9 February 2006.

EPA, 2007.  “TBT Oxide Fate Profile,” Power Point Presentation by
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2007.

EPA, 2006a.  “PE5 User’s Manual for PRZM EXAMS Modeling Shell,
Version 5.0.”   Environmental Fate and Effects Division. Office of
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EPA, 2006b.  “Draft, Antimicrobials Division’s (AD) Standard
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Assessments.”  Prepared by: Cassi Walls, Talia Milano, and Timothy
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Fent, K and Hunn, J, 1995. Organotins in freshwater harbors and rivers:
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EPA, 2007.  Revised Estimated Environmental Concentrations for AMICAL
Leached from Wood into Soil and Water using PE5 PRZM-EXAMS Model Shell. 
Memorandum from Siroos Mostaghimi to Norm Cook, U.S. Environmental
Protection Agency,, November 28, 2007

Krahn, P. and Strub R. 1990. Standard leaching test for antisapstain
chemicals: Regional Program Report 90-10. Environment Canada.
Conservation and Protection, Pacific and Yukon Region North Vancouver,
BC. 1990.

Maguire, RJ, Carey JH, Hale, EJ, 1983. Degradation of the tri-n-butylin
species in water. Journal of Agricultural and Food Chemistry. 31:
1060-5.

Maguire, RJ, Tkacz, RJ, 1985. Degradation of the tri-n-butylin species
in water and sediment from Toronto Harbor. Journal of Agricultural and
Food Chemistry. Vol. 33: 947-53.

Parker, Ronald. 2007. Office of Pesticide Programs. U.S. Environmental
Protection Agency. Personal communication with ICF. November.

Rohm and Haas, 2006.  Environmental Risk Assessment of DCOIT for Wood
Preservative Applications.  Prepared by John P Carbone and Andrew H.
Jacobson, Rohm and Haas Company, Spring House, PA.  Company Report
06R-1006.  February 9, 2006.

Versar, 2005. "ADBAC Antisapstain Modeling (TAF 1-4-10, CM-43),"
memorandum to Najm Shamim, U.S. EPA, from Ron Lee and Jignasha Patel,
Versar, Inc., December 5, 2005.

Environmental Fate Science Chapter 

41024501	Lee, R. (1988) Degradation of ?carbon 14|-Bis(Tri-n-Butyltin)
Oxide in Coastal Waters and Sediments Under Aerobic and Anaerobic
Conditions. Unpublished study prepared by Skidway Institute of
Oceanography. 24 p. 

41557801	Pisigan, R.; Liu, L.; Zavala, P. (1989) Hydrolysis of
Bis(Tributyl- tin) Oxide in Water: Lab Project Number: 3903019.
Unpublished study prepared by Environmental Science & Engineering, Inc.
54 p.

41557802	Liu, S.; Zavala, P.; Gensheimer, G. (1990) Photodegradation of
Bis- (Tributyltin) Oxide in Water: Lab Project Number: 3903021. Un-
published study prepared by Environmental Science & Engineering, Inc. 69
p. 

41668901	Stuerman, L.; Lochhaas, C.; Young, B. (1990) Uptake, Depuration
and Bioconcentration of (carbon 14)-Bis(tri-n-butyltin) Oxide by
Bluegill Sunfish (Lepomis macrochirus): Lab Project No. 38561.
Unpublished study prepared by Analytical Bio-Chemistry Labora- tories,
Inc. 453 p. 

41811501	Gendusa, T.; Brancato, M. (1990) Steady State Tissue
Concentrations of Tributyltin and its Degradation Intermediates in
Bluegill Sunfish (Lepomis macrochirus) Following Tributyltin Uptake and
Depuration: Lab Project Number: Final Report: ES-7387. Unpublished study
prepared by Texas A & M University, Parametrix, ABC Labs. 40 p. 

43737401	Schocken, M. (1995) Tributyltin Oxide--Determination of Soil
Metabolism Under Aerobic Conditions at 25 (degrees) C: Final Report: Lab
Project Number: 95-1-5658: 12442.0193.6155.760. Unpublished study
prepared by Springborn Labs, Inc. 69 p. 

43831801	Schocken, M. (1995) Tributyltin Oxide--Determination of
Anaerobic Aquatic Metabolism at 25 (degrees) C: Final Report: Lab
Project Number: 95-5-5879: 12442-0193-6158-755. Unpublished study
prepared by Springborn Labs, Inc. 78 p. 

43984201	Schocken, M. (1995) Tributyltin Oxide--Determination of Aerobic
Aquatic Metabolism at 25 (degrees) C: Final Report: Lab Project Number:
94-9-5462: 12442-0193-6157-750. Unpublished study prepared by Springborn
Labs, Inc. 72 p. 

43979701	Mao, J. (1995) Tributyltin Oxide--Determination of the
Adsorption and Desorption Properties: Final Report: Lab Project Number:
94-9-5476: 12442.0193.6154.710: 55-1807-05. Unpublished study prepared
by Springborn Labs, Inc. 82 p. 

45487301 	Simmons, R.; Kluck, M.; Bennett, J. et al. (2001) Annual
Report for the Long-Term National Monitoring Program for Tributyltin and
Its Primary Degradation Intermediates: Year 8, 1999-2000: Lab Project
Number: 55-1807-07 (8A). Unpublished study prepared by Parametrix, Inc.
3412 p. 

92172011	Ben-Dyke, B. (1990) M&t Chemicals, Inc. Phase 3 Summary of MRID
00140824. Bioaccumulation and Chronic Toxicity of Bis(tributyltin)
Oxide: Tests with a Saltwater Fish. Prepared by EG&G, Bionomics. 6 p. 

Toxicology Disciplinary Chapter 

00085003 	Auletta, C.S., Hodge, P.S., Minczeski, N. et al. (1981). Acute
Oral Toxicity Study in Rats: Project No. 6656-81. (Unpublished study
received Oct 15, 1981 under 5204-1; prepared by Bio/ dynamics, Inc.,
submitted by M & T Chemicals, Inc., Rahway, N.J.; CDL:246070-A).

00085004 	Auletta, C.S., Hodge, P.S., Minczeski, N. et al. (1981). Acute
Oral Toxicity Study in Rats: Project No. 6657-81. (Unpublished study
received Oct 15, 1981 under 5204-1; prepared by Bio/ dynamics, Inc.,
submitted by M & T Chemicals, Inc., Rahway, N.J.; CDL:246070-B).

00104789 	Bruan, W., Rinehart, W. (1979). A Dermal Sensitization Study
in Guinea Pigs: Compound TBTO: Project No. 5056-78. (Unpublished study
received Mar 14, 1979 under 5204-1; prepared by Bio/dynamics, Inc.,
submitted by M & T Chemicals, Inc., Rahway, NJ; CDL: 237804-A).

01246480 	Evans, W., D. Smith, and N. Cardarelli (date of study not
provided) Accumulation and excretion of [1-14C] bis(tri-n-butyltin)
oxide in mice. Environmental Management Laboratory, The University of
Akron (Akron, Ohio). Unpublished.

00137158 	Schroeder, R., Hogan, G. (1981). A Teratology Study in Rats
with Tributyltin Oxide: Project No. 80-2497A. Final rept. (Unpublished
study received Jan 16, 1984 under 5204-1; prepared by Bio/dynamics,
Inc., submitted by M & T Chemicals Inc., Rahway, NJ; CDL:252178-A).

40050003 	Hümel, M. (1985). Series 85-2: Percutaneous absorption of
tributyltin oxide (TBTO) through intact skin of baboon. Scherling AG,
Berlin 65, Germany. Laboratory Project ID IC-KI 2, June 12, 1985.
Unpublished.

40141901 	Nemec, M. (1987). (Tributyltin Oxide) - A Teratology Study in
Rabbits with TBTO: Laboratory Project ID: WIL-B0002. Unpublished study
prepared by Wil Research Laboratories, Inc. 210 p.

40253002 	Humpel, M. (1986). Toxicokinetics of 113Sn-labelled
tributyltin oxide after intravenous (1 mg/kg) and intragastric (25
mg/kg) administration to rats:  bioavailability, excretion, and
biotransformation.  Schering AG, Berlin, Germany.  Laboratory report
numbers IC-Kl 3, KI 84 061, and KI 84 062.  January 23, 1986.
Unpublished. 

40253005 	Brunneman, A. (1986). Evaluation of the Clastogenic Potential
in the Human Lymphocyte Test: ZK 21.955: Lab. Proj. ID IC 4/86. Un-
published study prepared by Schering AG. 23 p.

40623201 	Wester, P.W., Krajnc, E.I. et al. (1988). Bis(tributyltin)
oxide – Two year feeding study in rats with bis(tri-n-butyltin) oxide.
 RIVM, Bilthoven, The Netherlands.  Laboratory Report No.: 658112 002,
February 25, 1988. Unpublished.

41127001 	Daly, I. (1989). A three month oral range-finding toxicity
study in mice with bis (tri-n-butyltin) oxide (TBTO). Bio/dynamics, Inc.
(East Millstone, New Jersey). Unpublished.

41131001 	Schweinfurth, H. (1987). Tributyltin oxide: Systemic toxicity
study in Beagle dogs with daily oral (intragastric) administration over
a total of 18-19 weeks.  Schering AG, Berlin, Germany.  Laboratory
Project ID: TX 87.054, August 5, 1987. Unpublished.

41693801 	Schroeder, R.E. (1990). A two generation reproductions study
in rats with bis (tri-n-butyltin) oxide.  Bio/dynamics, Inc., East
Millstone, NJ.  Laboratory Project No.:  88-3261, October 22, 1990.
Unpublished.

42170001 	Lang, R. (1986). Evaluation in the Ames Salmonella/Microsome
Mutagenicity Test: ?ZK 21.955: Lab project Number: TX6106. Unpublished
study prepared by Schering Ag. 29 p.

42265001 	Daly, I. (1992). An eighteen month oncogenicity feeding study
in mice with bis(tri-n-butyltin) oxide (TBTO). Bio/dynamic, Inc. Project
No. 87-3131, March 27, 1992. Unpublished.

42412501 	Bakke, J. (1991). Evaluation of Cotin 310 in the CHO/HGPRT
Gene Mutation Assay: Final Report: Lab Project Number: LSC-2112-200:
2112-G200-91. Unpublished study prepared by SRI International. 22 p.

42412502 	O'Loughlin, K. (1991). Bone Marrow Erythrocyte Micronucleus
Assay of Cotin 310 in Swiss Webster Mice: Lab Project Number:
2112-C100-91. Unpublished study prepared by SRI International. 41 p.

42412503 	Bakke, J. (1990). Evaluation of the Potential of Cotin 310 to
Induce Unscheduled DNA Synthesis in the In vitro Hepatocyte DNA Repair
Assay Using the Male F-344 Rat: Final Report: Lab Project Number:
LSC-1482: 1482-VO1-90. Unpublished study prepared by SRI International.
21 p.

42412504  	Bakke, J. (1992). Evaluation of the Potential of Cotin 310 to
Induce Unscheduled DNA Synthesis in the In vitro Hepatocyte DNA Repair
Assay Using the Male F-344 Rat: Final Report, Amendment One: Lab Project
Number: LSC 1482: 1482-VO1-90. Unpublished study prepared by SRI
International. 7 p. (Supplemental copy to MRID 42412503).

42415801 	Allan, S. (1992). Acute Oral Toxicity to Rats of Tributyltin
Benzoate: Lab Project Number: 920351D/NDX 25/AC. Unpublished study
prepared by Huntingdon Research Centre, Ltd. 24 p.

42415802 	Allan, S. (1992). Acute Dermal Toxicity to Rats of Tributyltin
Benzoate: Lab Project Number: 920319D/NDX 26/AC. Unpublished study
prepared by Huntingdon Research Centre, Ltd. 20 p.

42415803 	Liggett, M. (1992). Skin Irritation to Rabbit of Tributyltin
Benzoate: Lab Project Number: 920395D/NDX 27/SE. Unpublished study
prepared by Huntingdon Research Centre, Ltd. 14 p.

	

42549801 	Schuh, W. (1992). Bis (tri-n-butyltin) oxide (TBTO; ZK
21.955):  12-month chronic oral toxicity study in beagle dogs.  Schering
AG, Berlin, Germany.  Laboratory Project ID:  Study Number TX 85.330,
September 4, 1992. Unpublished.

42903101 	Bryson, A. (1993). Tributyltin Benzoate: A Study of the Effect
on Pregnancy of the Rat: Lab Project Number: NDX/41: NDX 41/921129.
Unpublished study prepared by Huntingdon Research Centre Ltd. 106 p.

42966201 	Mahoney, D. (1992). Analysis of Tributyltin Benzoate: Product
Chemistry: Chemical Purity: Lab Project Number: 239-39. Unpublished
study prepared by Huls America Inc. 9 p.

42966201 	Mahoney, D. (1992). Analysis of Tributyltin Benzoate: Product
Chemistry: Chemical Purity: Lab Project Number: 239-39. Unpublished
study prepared by Huls America Inc. 9 p.

42966203 	Bakke, J. (1992). Evaluation of the Potential of Cotin 310 to
Induce Unscheduled DNA Synthesis in the In vitro Hepatocyte DNA Repair
Assay Using the Male F-344 Rat: Modification of Final Report Amendment
One: Lab Project Number: LSC-1482: 1482-V01-90. Unpublished study
prepared by SRI International. 7 p. (Duplicate copy of the MRID
42412504).

43177201 	Naas, Dennis J. (1990). Three week dermal range-finding study
in rats with Tributyltin Benzoate.  WIL Research Laboratories, Inc.
(Ashland, Ohio). Laboratory study number WIL-159010, December 18, 1990.
Unpublished.

43851201 	Pucaj, K. (1994). Acute Oral Toxicity Study of Tri-n-Butyl Tin
Maleate (TBT-M) in Rats: Lab Project Number: 86816. Unpublished study
prepared by Nucro-Technics, Inc. 79 p.

44142303 	Yau, L. (1996). Phase 4 Summary: Ultra-Fresh DM-50: Dermal
Sensitization: Tri-N-Butyltin Maleate: Laboratory Project Number: 28752:
206666: TRA/966-1. Unpublished study prepared by Nucro-Technics, Inc. 29
p.

92172004 	Stevens, A. (1990). M&T Chemicals, Inc. Phase 3 Summary of
MRID 00085003. Acute Oral Toxicity Report: Grignard Sourced TBTO:
Project No. 6656-81. Prepared by Bio/dynamics. 7 p. (Supplemental copy
to MRID 00085003).

92172006 	Stevens, A. (1990). M&T Chemicals, Inc. Phase 3 Summary of
MRID 40141901. A Teratology Study in Rabbits with TBTO: Project No.
WIL-B0002. Prepared by Wil Research Laboratories, Inc. 7 p.

92172013 	Stevens, A. (1990). M&T Chemicals, Inc. Phase 3 Summary of
MRID 00085004. Acute Oral Toxicity Study: Alkyl Aluminum Sourced TBTO:
Project No. 6657-81. Prepared by Bio/dynamics, Inc. 7 p. (Supplemental
copy to MRID 00085004).

92172014 	Stevens, A. (1990). M&T Chemicals, Inc. Phase 3 Summary of
MRID 00104789. A Dermal Sensitization Study in Guinea Pigs: Compound
TBTO: Project No. 5056-78. Prepared by Bio/dynamics. 6 p. (Supplemental
copy to MRID 00104789). 

92172016 	Schroeder, R. (1992). M&T Chemicals, Inc. Phase 3 Reformat of
MRID 00137158. A Teratology Study in Rats with Tributyltin Oxide:
Project No. 80-2497A. Prepared by Bio/dynamics, Inc. 83 p.

PUBLISHED LITERATURE

Agency for Toxic Substances and Disease Registry (ATSDR). (2003)
Toxicological profile for tin and compounds (Draft for Public Comment). 
Atlanta, GA: U.S. Department of Health and Human Services, Public Health
Service.

Baroncelli, S., Karrer, D., Turllazzi, P. G. (1990). Embryotoxic
evaluation of bis (tri-n-butylin) oxide (TBTO) in mice. Toxicology
letters, 50: 257-262.

Boyer, I.J. (1989). Toxicity of dibutyltin, tributyltin and other
organotin compounds to humans and to experimental animals. Toxicology
55:253-298.

Bressa, G., Hinton, R.H., Price, S.C., et al. (1991). Immunotoxicity of
tri-n-butyltin oxide (TBTO) and tri-n-butyltin chloride (TBTC) in the
rat. Journal of applied toxicology, 11: 397-402.

Buckiova, D., Dostal, M., Hofmannova, V. (1992) Embryotoxicity of
organotins [abstract]. Reproductive toxicology, 6:178–179.

Centers for Disease Control (CDC). (1991). Acute effect of indoor
exposure to paint containing bis(tributyltin) oxide-Wisconsin, 1991.
MMWR Morb Mortal Wkly Rep. 1991, May 3; 40(17):280-1. [MMWR. Morbidity
and mortality weekly report]

Crofton, K.M., Dean, K.F., Boneck, V.M., et al. (1989). Prenatal or post
natal exposure to bis(tri-n-butyltin) oxide in the rat: postnatal
evaluation of teratology and behavior. Toxicology and applied
pharmacology, 97:113-123.

Karrer, D., Baroncelli, S. and Turillazzi, P.G. (1995). Oral
bis(tri-n-butyltin) oxide in pregnant mice. II. Alterations in
hematological parameters. J. Toxicol. Environ. Health 46: 369-377.

Karrer, D., Baroncelli, S., Ciaralli, L. et al. (1992). Effect of
subchronic bis (tri-n-butyltin) oxide (TBTO) oral administration on
hematological parameters. Journal of toxicology and environmental
health, 46: 369-377.

Krajnc, E.I., Vos, J.G., Wester, PW, Loeber, J.G., van der, Heijden,
C.A., (1987) Toxicity of bis(tri-n-butyltin)oxide (TBTO) in rats.
Unpublished report submitted to the Office of Toxic Substances, US
Environmental Protection Agency, with cover letter dated 18 May 1987
(Document Control No. FYI-OTS-0687-0550 Sequence A).

Kranjc, E.I., Wester, P.W., Loeber, J.G. et al.(1984). Toxicity of bis
(tri-n-butyltin) oxide (TBTO) in rats. I. Short-term effects on general
parameters and on the endocrine and lymphoid systems. Toxicology and
applied pharmacology, 75: 363-386.

Luebke, R.W., Chen, D.H., Dietert, R. et al. (2006). Immunotoxicology
Workgroup. The comparative immunotoxicity of five selected compounds
following developmental or adult exposure. J Toxicol Environ Health B
Crit Rev. 2006 Jan-Feb; 9(1):1-26. [Journal of toxicology and
environmental health. Part B, Critical reviews]

Raffray, M., Cohen, G.M. (1991). Bis(tri- n-butyltin) oxide induces
programmed cell death (apoptosis) in immature rat thymocytes. Archives
of toxicology, 65: 135-139.

Raffray, M., Cohen, G.M. (1993) Thymocyte apoptosis as a mechanism for
tributyltin-induced thymic atrophy in vivo. Archives of toxicology,
67:231–236.

Simalowicz, R.J., Riddle, M.M., Rogers, R.R. et al.(1989).
Immunotoxicity of tributyltin oxide in rats exposed as adults of
pre-weanlings. Toxicology, 57: 97-111.

Snoeji, N.J., Penninks, A.H. and Seinen, W. (1987). Biological Activity
of Organotin compounds - An overview. Environ. Res. 44:335-353.

Schuh, W. (1992) One year chronic feeding study in beagle dogs.
Unpublished report prepared by Schering AG Laboratories for Elf Atochem
North America, Inc., Aceto Chemicals, and Schering Berlin Polymers (MRID
No. 425498).

Thompson, T.A., Lewis, J.M., Dejneka, N.S. et al. (1996) Induction of
apoptosis by organotin compounds in vitro: neuronal protection with
antisense oligonucleotides directed against stannin. Journal of
pharmacology and experimental therapeutics, 276:1201–1214.

Viviani, B., Ross, A.D., Chow, S.C., Nicotera, P. (1995) Organotin
compounds induce calcium overload and apoptosis in PC12 cells.
Neurotoxicology, 16:19–26.

Vos, J.S., De Klerk, A., Kranjc, E.I. et al. (1990). Immunotoxicity of
bis (tri-n-butyltin) oxide in the rat. Effects on thymus dependent
immunity and on nonspecific resistance following long-term exposure in
young versus aged rats. Toxicology and Applied Pharmacology,
105:144-155.

Wester, P.W., Kranjc, E.I., Van Leeuwen, F.X.R. et al. (1990). Chronic
toxicity and carcinogenicity of bis (tri- n-butyltin) oxide (TBTO) in
the rat. Food and Chemical toxicology, 28: 179-196.

WHO working group. (1990). Tributyltin compounds. Environmental Health
Criteria , 116. 273 p.

World Health Organization. Tributyltin oxide. Concise International
Chemical Assessment Document (CICAD) Vol:14 (1999) 24p.

SUPPORTING AGENCY DOCUMENTATION

IRIS (1997) Toxicological Review: Tributyltin oxide (CAS No. 56-35-9):
In support of summary information on the Integrated Risk Information
System (IRIS). U.S. Environmental Protection Agency, July 1997.

Tributyltin maleate (TBTM): Non-Dietary Residential Exposure/Risk
Considerations for Proposed Registration of Ultra-Fresh® DM-50 as a New
Indoor Use Pattern of TBTM.  PC Code: 083118.  DP Barcode D291315
(Memorandum: P. Deschamp to G. LaRocca and M. Swindell, March 31, 2005).

Tributyltin Compounds - Report of the Antimicrobials Division Toxicity
Endpoint Selection Committee (ADTC) for Tributyltin Oxide, Tributyltin
Maleate and Tributyltin Benzoate.  PC Code(s):  PC Code(s):  083001,
083106, 083118.  CAS Registry Number(s): 56-35-9, 4342-36-3, 14275-57-1
(Memorandum: M. Centra to T. Lindheimer and J. Bloom, February 4, 2008).



Appendix A: Label Query/Summary for TBT-Containing Compounds



TBTO Registrations as of January 2, 2008

Registration #	% TBT

577-539	0.34

577-544	0.30

748-246	registrant will request voluntary cancellation

748-248

	748-257

	1022-511	registrant has requested voluntary cancellation

1757-99	registrant will request voluntary cancellation

1225-11	5.78

1839-121	1.80

1839-122	1.80

2749-119	97.40

5204-1-2749	97.40

3090-123	5.00

5204-1	93.30

5383-47	29.00

6390-16	25.00

6390-17	registrant will request voluntary cancellation

7313-6	0.50

8177-71	0.30

8898-17	registrant will request voluntary cancellation

9339-12	5.05

9339-14	3.07

9386-18	2.25

-48130,

-73839	2.25

10324-100	0.50

10324-101	5.00

10466-24	1.06

10466-43	93.30

47371-29	2.25

47371-84	4.50

67360-3	5.0

71654-19	1.00

-1007

	74489-1	53.00

83451-6	3.40

TBT Benzoate and TBT Maleate as of January 2, 2008

Registration #	% TBT

1529-30	15.00

1529-35	45.50

10466-28	25.00



Appendix B:  Toxicity Profile for TBT Oxide, Maleate and Benzoate



Table B-1.  Toxicity Profile for Tributyltin Oxide, Tributyltin Maleate
and Tributyltin Benzoate

Guideline No./

Study Type	

MRID No./

Citation	

Dosing and Animal Information	

Results

Range-finding Toxicity 

Non-guideline

Range-finding Study in Mice	MRID 41127001

Daly, I. (1989) A three month oral range-finding toxicity study in mice
with bis (tri-n-butyltin) oxide (TBTO). Bio/dynamics, Inc. (East
Millstone, New Jersey). Unpublished.

	CD-1® mice (male and female)

Purity 97.1 % a.i.

0, 4, 20, 80, or 200 ppm (equivalent to 0.7, 3.8, 15.1, or 36.9 mg/kg
bw/day in males; 1.0, 4.9, 17.9, or 46.9 mg/kg bw/day in females) for 13
weeks (diet).	NOAEL = 4 ppm (equivalent to 0.7 mg/kg bw/day in males;
1.0 mg/kg bw/day in females).

LOAEL = 20 ppm (equivalent to 3.8 mg/kg bw/day in males; 4.9 mg/kg
bw/day in females) based on mild hepatotoxicity and dermal irritation in
the ear observed in male mice. The  

Unacceptable/Non-guideline

Non-guideline

Range-finding Study in Dogs	MRID 41131001

Schweinfurth, H. (1987) Tributyltin oxide: Systemic toxicity study in
Beagle dogs with daily oral (intragastric) administration over a total
of 18-19 weeks.  Schering AG, Berlin, Germany.  Laboratory Project ID:
TX 87.054, August 5, 1987. Unpublished.

	Beagle dogs 

Purity >96.1% a.i.

0, 0.1, 0.5, or 2.5 mg/kg during Weeks 1-5; 0, 0.2, 1.0, or 5.0 mg/kg
during Weeks 6-10; and 0, 10, 1.0, or 5.0 mg/kg during Weeks 11-19.

	Exposure to Tributyltin oxide 

caused elevated alkaline 

phosphatase and slight changes 

in serum protein composition 

at 1.0 mg/kg/day after 13-14 

weeks of exposure.  While 

further biochemical changes 

and suspected effects on red 

and white blood cells were 

observed at 2.5 mg/kg/day 

after 5 weeks of exposure and 

at 5.0 mg/kg/day after 13-14 

weeks of exposure, there was 

no evidence of organ 

toxicity.  At 10 mg/kg/day, 

general toxic effects leading to 

weight loss and lymphotoxic 

effects, vacuolization of the 

liver cells and inhibition of 

follicle maturation in the 

ovaries (secondary effect) were 

observed.  A dose of 10 

mg/kg/day was considered to 

be too toxic of a dose for the 1-

year oral dog study; therefore, 

dose levels of 0.2, 1.0, and 5.0 

mg/kg/day were recommended 

for the 1-year study.

Unacceptable/Non-guideline

21-Day Dermal Toxicity 

870.3200 

21-Day Dermal Toxicity Study in Rats	MRID 43177201

Naas, Dennis J. (1990) Three week dermal range-finding studies in rats
with Tributyltin Benzoate.  WIL Research Laboratories, Inc. (Ashland,
Ohio).  Laboratory study number WIL-159010, December 18, 1990.
Unpublished.	Dorsal skin of Crl:CD®BR rats

Purity not provided

0, 250, 500, 1000, or 2000 mg/kg/day for 6 hours/day

	The maximum tolerable dose for a subsequent 90-day toxicity study was
determined to be 250 mg/kg/day.

Unacceptable/Non-guideline

Prenatal Developmental Toxicity

870.3700 

Prenatal Developmental Toxicity Study 	MRID 00137158

Schroeder, R.; Hogan, G. (1981) A Teratology Study in Rats with
Tributyltin Oxide: Project No. 80-2497A. Final rept. (Unpublished study
received Jan 16, 1984 under 5204-1; prepared by Bio/dynamics, Inc.,
submitted by M & T Chemicals Inc., Rahway, NJ; CDL:252178-A).

MRID 92172016

Schroeder, R. (1992) M&T Chemicals, Inc. Phase 3 Reformat of MRID
00137158. A Teratology Study in Rats with Tributyltin Oxide: Project No.
80-2497A. Prepared by Bio/dynamics, Inc. 83 p.  	Female pregnant CD®
(Sprague-Dawley derived) rats

Purity not reported

0, 5, 9, 18 mg/kg/day (via gastric intubation (gavage)	Maternal Toxicity

NOAEL = 5 mg/kg/day 

LOAEL = could not be identified due to the lack of data.

Developmental Toxicity

NOAEL is less than 5 mg/kg/day LOAEL is equal to or less than 5
mg/kg/day based on increased incidences of ossification variations. 

Unacceptable/Upgradeable

870.3700 

Prenatal Developmental Toxicity Study	MRID 40141901

Nemec, M. (1987) (Tributyltin Oxide) - A Teratology Study in Rabbits
with TBTO: Laboratory Project ID: WIL-B0002. Unpublished study prepared
by Wil Research Laboratories, Inc. 210 p.

MRID 92172006

Stevens, A. (1990) M&T Chemicals, Inc. Phase 3 Summary of MRID 40141901.
A Teratology Study in Rabbits with TBTO: Project No. WIL-B0002. Prepared
by Wil Research Laboratories, Inc. 7 p.	New Zealand White female rabbits

Purity >95%

0, 0.2, 1.0, 2.5 mg/kg/day (oral gavage)	Maternal Toxicity

NOAEL = 1.0 mg/kg/day 

LOAEL = 2.5 mg/kg/day, based on increased incidence of abortion and
decreased mean maternal body weight gain.

Developmental Toxicity

NOAEL =  is equal to or greater than 2.5 mg/kg/day 

LOAEL=  is greater than 2.5 mg/kg/day (could not be established)  

Acceptable/Guideline

870.3700 

Prenatal Developmental Toxicity Study	MRID 42903101

Bryson, A. (1993) Tributyltin Benzoate: A Study of the Effect on
Pregnancy of the Rat: Lab Project Number: NDX/41: NDX 41/921129.
Unpublished study prepared by Huntingdon Research Centre Ltd. 106 p.

	Cr1: CD® (SD) BR VAF/Plus strain rats

Purity 97.1% a.i.

0, 1.0, 4.5 and 20.0 mg/kg/day (intragastric intubation)	Maternal
Toxicity

NOAEL = 1.0 mg/kg/day 

LOAEL = 4.5 mg/kg/day based on increased incidences of post-dose
salivation, wet coat, and impaired respiration. 

Developmental Toxicity 

NOAEL = 1.0 mg/kg/day 

LOAEL = 4.5 mg/kg/day, based on increased resorption, a dose related
increased in incidence of double outlet of right ventricle (and an
intraventricular septal defect) along with increased incidence of
extracervical ribs at this dosage.

Acceptable/Guideline

Reproduction and Fertility Rates

870.3800

Reproduction and Fertility effects 	MRID 41693801

Schroeder, R.E. (1990) A two generation reproductions study in rats with
bis (tri-n-butyltin) oxide.  Bio/dynamics, Inc., East Millstone, NJ. 
Laboratory Project No.:  88-3261, October 22, 1990.  Unpublished

	Sprague Dawley rats

Purity 97.1%

0, 0.5, 5, or 50 ppm for two successive generations (diet)	Parental
Toxicity

NOAEL = 5 ppm (equivalent to 0.33/0.39 mg/kg/day in males/females).

LOAEL = 50 ppm (equivalent to mg/kg/day 3.47/3.93 in males/females)
based on anogenital staining in the P dams; decreased body weights in
the F1 males and females during pre-mating and continuing in the F1
males during the mating and post mating periods; and decreased absolute
and relative thymus weights in the F1 males. 

Reproductive Toxicity

NOAEL = 50 ppm (equivalent to 3.47/3.93 mg/kg/day in males/females)

LOAEL = greater than 50 ppm (not established)

Offspring Toxicity

NOAEL = 5 ppm (equivalent to 0.33/0.39 mg/kg/day in males/females).

LOAEL = 50 ppm (equivalent to 3.47/3.93 mg/kg/day in males/females)
based on decreased pup body weights in both generations 

Acceptable/Guideline

Chronic Toxicity 

870.4100

Chronic Toxicity	MRID 42549801

Schuh, W. (1992) Bis (tri-n-butyltin) oxide (TBTO; ZK 21.955):  12-month
chronic oral toxicity study in beagle dogs.  Schering AG, Berlin,
Germany.  Laboratory Project ID:  Study Number TX 85.330, September 4,
1992. Unpublished.

	Beagle dogs

Purity 95.9-97.1% a.i.

0, 0.2, 1.0, or 5.0 mg/kg/day for 52 weeks (oral gavage)	Multiple
microscopic finding indicative of immunotoxicity (detailed above) were
noted at 1.0 mg/kg/day, particularly in the males.  At 5.0 mg/kg/day,
increased severity of immunotoxicity and indications of systemic
toxicity (including mortality, clinical signs of toxicity, overall body
weight losses, decreased body weights and food and water consumption,
increased blood sedimentation rate, decreased nucleated bone marrow
cellularity, increased hepatic enzymes, increased liver weight,
decreased spleen and thymus weights, and gross pathological findings in
the liver, spleen, and thymus) were observed.

Unacceptable/Guideline

(not upgradeable)

Carcinogenicity

870.4200

Carcinogenicity	MRID 42265001

Daly, I. (1992) An eighteen month oncogenicity feeding study in mice
with bis (tri-n-butyltin) oxide (TBTO). Bio/dynamic, Inc. Project No.
87-3131, March 27, 1992. Unpublished

	CD-1 mice 

Purity 97.1% pure

0, 5, 25, or 50 ppm (equivalent to 0.7, 3.7, and 7.7 mg/kg/day for low-,
mid-, and high-dose males, respectively, and 0.9, 4.8, and 9.2 mg/kg/day
for low-, mid-, and high-dose females, respectively) for 18 months
(diet)	LOAEL = 0.7 mg/kg/day (males) 

LOAEL = 0.9 mg/kg/day (females), based on decreased survivorship and
increased body weight gain.

Acceptable/Guideline

Combined Chronic Toxicity/Carcinogenicity

870.4300

Combined chronic toxicity/Carcinogenicity	MRID 40623201

Wester, P.W.; Krajnc, E.I.; et al. (1988) Bis (tributyltin) oxide –
Two year feeding study in rats with bis (tri-n-butyltin) oxide.  RIVM,
Bilthoven, The Netherlands.  Laboratory Report No.: 658112 002, February
25, 1988.  

Unpublished.	Wistar rats

Purity 95.3% a.i.

0, 0.5, 5, or 50 ppm (approximately equivalent to 0, 0.025, 0.25, and
2.5 mg/kg bw/day (diet)	NOAEL = 5 ppm (approximately equivalent to 0.25
mg/kg bw/day).

LOAEL = 50 ppm (approximately equivalent to 2.5 mg/kg bw/day) based on
increased mortality, systemic toxicity (ataxia, emaciation and decreased
body weight/body weight gain in males and females) and organ toxicity
(kidney, thyroid, adrenal glands, and pituitary. 

Acceptable/Guideline 

Metabolism and Pharmacokinetics

870.7485

Metabolism and Pharmacokinetics	MRID 01246480

Evans, W., D. Smith, and N. Cardarelli (date of study not provided)
Accumulation and excretion of [1-14C] bis (tri-n-butyltin) oxide in
mice. Environmental Management Laboratory, The University of Akron
(Akron, Ohio). Unpublished.	Female COBS albino mice

Purity not reported

0, 0.51, 3.75, or 18.5 ppm	Concentrations of 14C-TBTO 

were greatest in the kidneys, 

fat, liver, and spleen. 

Concentrations were found to 

be proportional to administered 

dose except in the kidney. 

Tissue accumulations were 

concentration dependent. The 

quantities absorbed were 

rapidly cleared when ingestion 

ceased. 

Acceptable/Non-guideline

870.7485

Metabolism and Pharmacokinetics	MRID 40253002

Humpel, M. (1986) Toxicokinetics of 113Sn-labelled tributyltin oxide
after intravenous (1 mg/kg) and intragastric (25 mg/kg) administration
to rats:  bioavailability, excretion, and biotransformation.  Schering
AG, Berlin, Germany.  Laboratory report numbers IC-Kl 3, KI 84 061, and
KI 84 062.  January 23, 1986.  

Unpublished. 	Female Wistar-Han (SPF) rats

Purity (>99%a.i)

1 mg/kg or 25 mg/kg	Absorption was very delayed after gavage
administration, with a half-life of 9.5 hours.  The intravenously 

administered 113Sn-labeled 

TBTO is rapidly distributed, 

with only 3% of the dose 

remaining in plasma volume 

after 5 minutes post 

administration.  Based on the 

high volume of distribution 

and the binding to the cellular 

constituents of the blood, authors 

conclude that TBTO has a

pronounced affinity for tissues.

Acceptable/Non-guideline

Dermal Penetration

870.7600 

Dermal Penetration	MRID 40050003

Hümel, M. (1985) Series 85-2: Percutaneous absorption of tributyltin
oxide (TBTO) through intact skin of baboon. Scherling AG, Berlin 65,
Germany. Laboratory Project ID IC-KI 2, June 12, 1985. Unpublished	Male
baboon

Purity not reported

Dose volume 0.5 mL/25 cm2 skin	The total recovery of radioactively
labeled 113Sn-Tributyltin oxide was less than 50%, perhaps due to the
incomplete removal of unabsorbed TBTO on the skin surface as a result of
extensive spreading from the site of application. However, reviewer
generated data indicates that the total recovery was approximately 75%. 

Unacceptable/Non-guideline

Published Literature

Non Guideline

Literature Study	Vos et al., (1990) Immunotoxicity of
bis(tri-n-butyltin)oxide in the rat: Effects on thymus-dependent
immunity and on nonspecific resistance following long-term exposure in
young vs. aged rats.  Toxicol. Appl. Pharmacol.  105:144-155.	Wistar
Rats

Purity: 95.3% active ingredient

Exposure to TBTO for up to 18 months 

Dietary concentrations:  0.025, 0.25 and 2.5 mg/kg-day.	NOAEL = 0.025
mg/kg/day

LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of IgE titers
and increase in T. spiralis larvae in muscle) following 4 months and
16.5 months of exposure to Tributyl Tin Oxide.  (Review by EPA/IRIS,
1997).

  TC \l3 "9.1.2	Subchronic, Chronic and Other Toxicity Tables 



Appendix C:  Residential and Occupational Uses Selected for Assessing
Risks to TBT-containing Products



Table C-1. Representative Uses Associated with Residential Exposure to
TBT.

Representative Use	Application Method	Exposure Scenario	Example
Registration Number	Application Rate

Wood Preservative	Brush and airless sprayer

(Note:  dip not assessed separately)	ST Handler:  adult dermal and
inhalation.	1022-511

(577-539, 577-544, 1022-511, 7313-6, 8177-71)	0.062 lb ai/gallon

[8.3 lbs per gal density x 0.75% ai   = 0.062 lb ai/gallon of stain]

Textiles (a)

(exposures to treated  articles are represented by exposure to clothing
and mattress)	NAa	ST Post-app: wearing treated clothing, adult dermal;
child incidental ingestion and dermal 

ST Post-appl: Sleeping on treated mattress; adult dermal and child
incidental ingestion and dermal	3090-123

(textile)

10466-24

(mattress)	0.05% ai or 500 ppm TBT

[1% pesticide product by weight of material treated x 5% ai in
formulated product = weight fraction of 0.0005 ai or 0.05% ai or 500
ppm]

0.056% ai or 560 ppm TBT

[3.5% formulated product by weight of goods x 1.6% ai in formulated
product = weight fraction of 0.00056 ai or 0.056% ai or 560 ppm]

 (a)    The handler scenarios for textiles were not assessed for
residents because the products can only be applied occupationally.



Table C-2.  Representative Exposure Scenarios Associated with
Occupational Exposures to TBT

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

Agricultural Premises and Equipment (Use Category I)

Agricultural/farm/

poultry structures/buildings and equipment	Brush, mop, wipe, spray, and
fogger	ST/IT Handler:

Inhalation

Dermal	65020-12	Liquid:  0.00033 lb ai/gal

[(0.5 oz formulated product x 1 % ai x 8.34 lb/128 oz) / (1 gal water) =
0.00033 lb ai/gal]

Fogger:  1.3E-6 lb ai/ft3

[(1 gal formulated product x 8.34 lb/gal density x 1 % ai) / (6000ft2 x
10 ft ceiling) = 1.3E-6 lb ai/ft3]

Commercial/Industrial/Institutional Premises (Use Category III)

(See wood preservative category for commercial painters using treated
stain)	NA	NA	NA	NA

Material Preservatives (Use Category VII)

Caulks, sealants, adhesives, etc	Liquid pour

Metered pump	ST/IT Handler: Inhalation

dermal

	5383-47

(67360-3, 1529-30, and 1529-35)	0.145% ai 

[0.5% formulated product x 29% ai = 0.145% ai or 1450 ppm ai]

MWF 	Liquid pour

Machinist	ST/IT/LT handler/machinist:

Dermal

Inhalation	5383-47	0.145% ai in cutting oil

[0.5% formulated product x 29% ai = 0.145% ai or 1450 ppm ai]

  SEQ CHAPTER \h \r 1 Industrial processes and Water Systems (Use
Category VIII)

Pulp and Paper 

 	Metered pump

	ST/IT Handler: Inhalation

dermal

	47371-29

	Initial:  0.014 lb ai/ton

Continuous:  0.007 lb ai/ton

[Initial:  9.6 oz/ton paper

Continuous feed: 4.8 oz/ton paper.  

Where 9.6 oz  product x 2.25% ai  x 8.34 lb/128 oz = 0.014 lb ai/ton
paper]

Recirculating Cooling Water	Liquid pour

Metered pump	ST/IT Handler: Inhalation

dermal	5185-399	Initial:  0.089 lb ai/1000 gal

Continuous:  0.022 lb ai/1000 gallons of water

[Initial:  40 oz  product x 8.34 lb/128 oz x 3.4% ai /1000 gallons water

Continuous feed: 10 oz  product x 8.34 lb/128 oz x 3.4% ai /1000 gallons
water]

Oil fields and petrochemical water injection systems	Liquid pour

Metered pump	ST/IT Handler: Inhalation

dermal	5185-399	Initial:  0.089 lb ai/1000 gal

Continuous:  0.022 lb ai/1000 gallons of water

[Initial:  40 oz  product x 8.34 lb/128 oz x 3.4% ai /1000 gallons water

Continuous feed: 10 oz  product x 8.34 lb/128 oz x 3.4% ai /1000 gallons
water]

Antifouling Coatings (Use Category IX)

Sonar Domes & Hulls	Unknown	ST/IT Handler:

Inhalation

Dermal

(assumed)	1225-11

74489-01	5.78 % ai in formulation

53% ai in formulation

Wood Preservatives (Use Category X)

Staining 

(commercial painters)	Paint brush,

Airless sprayer	ST/IT Handler:

Inhalation

Dermal	1022-511

(577-539, 577-544, 1022-511, 7313-6, 8177-71)	0.062 lb ai/gallon

[8.3 lbs per gal density x 0.75% ai   = 0.062 lb ai/gallon of stain]

 Overview of the Ecological Risk Assessment Process in the Office of
Pesticide Programs, U.S. Environmental Protection Agency: Endangered and
Threatened Species Effects Determinations.  Office of Prevention,
Pesticides and Toxic Substances Office of Pesticide Programs,
Washington, D.C., January 23, 2004. 

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