![](media/image1.png){width="1.1in" height="1.0638888888888889in"}Number
range CHAPTER

**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

WASHINGTON, D.C. 20460

OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: April 2, 2008

[MEMORANDUM]{.underline}

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.

[1.0 EXECUTIVE SUMMARY 4](#executive-summary)

[**1.1** **Hazard Profile:** 4](#__RefHeading___Toc194462644)

[**1.2** **Toxicity Endpoints:** 6](#__RefHeading___Toc194462645)

[**1.3** **FQPA Safety Factor:** 7](#__RefHeading___Toc194462646)

[**1.4** **Dietary Exposure and Risk:** 7](#__RefHeading___Toc194462647)

[**1.5** **Water Exposure and Risk:** 7](#__RefHeading___Toc194462648)

[**1.6** **Residential (Non-Occupational) Exposure and Risk:**
8](#__RefHeading___Toc194462649)

[**1.8** **Occupational Exposure and Risk**
9](#__RefHeading___Toc194462650)

[**1.9** **Environmental Hazard and Risk:**
10](#__RefHeading___Toc194462651)

[2.0 PHYSICAL AND CHEMICAL PROPERTIES
11](#physical-and-chemical-properties)

[3.0 HAZARD CHARACTERIZATION 12](#hazard-characterization)

[3.1 Hazard Profile 12](#hazard-profile)

[3.2 Dose-Response Assessment 13](#dose-response-assessment)

[3.3 FQPA Considerations 16](#fqpa-considerations)

[**3.4** **Endocrine Disruption** 16](#__RefHeading___Toc194462657)

[4.0 INCIDENT REPORTS 17](#__RefHeading___Toc194462658)

[5.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION
18](#exposure-assessment-and-characterization)

[5.1 Dietary Exposure and Risk 18](#dietary-exposure-and-risk)

[5.2 Drinking Water Exposure and Risk for Active Ingredient Uses
19](#drinking-water-exposure-and-risk-for-active-ingredient-uses)

[5.3 Residential Exposure/Risk Pathway
19](#residential-exposurerisk-pathway)

[6.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION
21](#aggregate-risk-assessments-and-risk-characterization)

[7.0 CUMULATIVE EXPOSURE AND RISK 22](#cumulative-exposure-and-risk)

[8.0 OCCUPATIONAL EXPOSURE AND RISK 22](#occupational-exposure-and-risk)

[9.0. ENVIRONMENTAL FATE 24](#environmental-fate)

[10.0 ENVIRONMENTAL RISK 25](#environmental-risk)

[**10.1** **Summary of Ecological Toxicity Data Conclusions**
25](#__RefHeading___Toc194462668)

[**10.2** **Environmental Risk Assessment Criteria**
26](#__RefHeading___Toc194462669)

[**10.3** **Aquatic Risk Characterization**
27](#__RefHeading___Toc194462670)

[**10.4** **Endangered Species Considerations**
28](#__RefHeading___Toc194462671)

[11.0 DATA NEEDS AND LABELING 29](#__RefHeading___Toc194462672)

[12.0 REFERENCES 32](#__RefHeading___Toc194462673)

[Appendix A: Label Query/Summary for TBT-Containing Compounds
42](#__RefHeading___Toc194462674)

[Appendix B: Toxicity Profile for TBT Oxide, Maleate and Benzoate
44](#__RefHeading___Toc194462675)

[Appendix C: Residential and Occupational Uses Selected for Assessing
Risks to TBT-containing Products 50](#__RefHeading___Toc194462676)

# **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;

-   \(III\) Number range CHAPTERCommercial, institutional and industrial
    premises and equipment;

-   \(VII\) Number range CHAPTERMaterial preservatives;

-   \(VIII\) Industrial processes and water systems;

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

-   \(X\) Wood preservatives.

    []{#__RefHeading___Toc194462644 .anchor}**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   | **S  |                                               |
| Number**      | tudy |                                               |
|               | Ty   |                                               |
|               | pe** |                                               |
+---------------+------+-----------------------------------------------+
| **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   |      | Mutagenicity Test (1 Study)                   |
| 870.5915      |      |                                               |
+---------------+------+-----------------------------------------------+
| **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   |      | Battery of Mutagenicity Studies (3 studies;   |
| 870.5915      |      | 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      |      | Battery of Mutagenicity Studies (1 study from |
|               |      | "Other Mechanisms" category)                  |
| to            |      |                                               |
|               |      |                                               |
| 870.5915      |      |                                               |
+---------------+------+-----------------------------------------------+

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.

[]{#__RefHeading___Toc194462645 .anchor}**1.2 Toxicity Endpoints:**

[]{.mark}

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)]{.underline} (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):]{.underline} 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 BMD~10~ (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.

    []{#__RefHeading___Toc194462646 .anchor}**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 (BMD~10~ = 0.03 mg/kg/day)
selected for all residential exposure scenarios.

[]{#__RefHeading___Toc194462647 .anchor}**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.

    []{#__RefHeading___Toc194462648 .anchor}**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).

6.  []{#__RefHeading___Toc194462649 .anchor}**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.

.

[]{#__RefHeading___Toc194462650 .anchor}**1.8 Occupational Exposure and
Risk**

Number range CHAPTERBased 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.

```{=html}
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```
-   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

[]{.mark}

[]{#__RefHeading___Toc194462651 .anchor}**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     **Study Type**
  Number**        

  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 &         Honey/beeswax residues and acute toxicity of treated
  850.3030        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]{.underline} (endangered and threatened) freshwater and
estuarine/marine fish and invertebrates, but this is not the case for
the chronic risk LOC for [listed]{.underline} species. For [non-listed
species]{.underline}, 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]{.underline}: 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      **Tributyltin      **Tributyltin
                     Oxide**            Benzoate**         Maleate**

  PC Code            083001             083106             083118

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

  Chemical Formula   C~24~H~54~OSn~2~   C~19~H~32~O~2~Sn   C~16~H~30~O~4~Sn

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

  Density            1.17 g/L           NA                 NA

  Boiling Point      417.34^o^C         390.12^o^C         415.18^o^C

  Melting Point      131.93 ^o^C        128.33 ^o^C        153.42^o^C

  Vapor Pressure     7.8 x 10^-06^ mm   1.34 x 10^-06^ mm  1.74 x 10^-07^@
                     Hg @ 25 ^o^C       Hg @ 25 ^o^C       25^o^C

  Henry's Law        6.83 x 10^-05^ atm 2.83 x 10^-06^ atm 1.43 x 10^-07^atm
  Constant           m^3^/mol           m^3^/mol           m^3^/mol

  log Koc            7.57               5.10               2.99

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

  Half life in Water 2.49 hours (model  2.172 hrs (model   343.5 days (model
                     river)             river)             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;   NA                 NA
                     liquid                                
  ------------------ ------------------ ------------------ ------------------

NA: Not available

# 

# **3.0 HAZARD CHARACTERIZATION**

##  3.1 Hazard Profile 

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:]{.underline}**

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

[]{.mark}

+----------+---------------+------------+-------------------+----------+
| **Table  |               |            |                   |          |
| 4. Acute |               |            |                   |          |
| Toxicity |               |            |                   |          |
| Profile  |               |            |                   |          |
| for      |               |            |                   |          |
| T        |               |            |                   |          |
| echnical |               |            |                   |          |
| (95.0-   |               |            |                   |          |
| 97.5 %   |               |            |                   |          |
| a.i.)    |               |            |                   |          |
| Tri      |               |            |                   |          |
| butyltin |               |            |                   |          |
| Com      |               |            |                   |          |
| pounds** |               |            |                   |          |
+----------+---------------+------------+-------------------+----------+
| **G      | **Study       | **MRID     | **Results**       | **       |
| uideline | Type**        | Number**   |                   | Toxicity |
| Number** |               |            |                   | Ca       |
|          |               |            |                   | tegory** |
+----------+---------------+------------+-------------------+----------+
| **Tri    |               |            |                   |          |
| butyltin |               |            |                   |          |
| Oxide**  |               |            |                   |          |
+----------+---------------+------------+-------------------+----------+
| 870.1100 | Acute Oral -- | 00085004,  | LD~50~ =180 mg/kg | II       |
|          | Rat           |            | (males)           |          |
| (§ 81-1) |               | 92172013   |                   |          |
|          |               |            | LD~50~ =150 mg/kg |          |
|          |               |            | (females)         |          |
|          |               |            |                   |          |
|          |               |            | LD~50~ =170 mg/kg |          |
|          |               |            | (combined)        |          |
+----------+---------------+------------+-------------------+----------+
| 870.1100 | Acute Oral -- | 00085003,  | LD~50~ =193 mg/kg | II       |
|          | Rat           |            | (males)           |          |
| (§ 81-1) |               | 92172004   |                   |          |
|          |               |            | LD~50~ =123 mg/kg |          |
|          |               |            | (females)         |          |
|          |               |            |                   |          |
|          |               |            | LD~50~ =160 mg/kg |          |
|          |               |            | (combined)        |          |
+----------+---------------+------------+-------------------+----------+
| 870.2600 | Skin          | 00104789,  | Non sensitizer    | Not      |
|          | Sensitization | 92172014   |                   | ap       |
| (§ 81-6) | --Guinea pigs |            |                   | plicable |
+----------+---------------+------------+-------------------+----------+
| **Tri    |               |            |                   |          |
| butyltin |               |            |                   |          |
| M        |               |            |                   |          |
| aleate** |               |            |                   |          |
+----------+---------------+------------+-------------------+----------+
| 870.1100 | Acute Oral -- | 43851201   | LD~50~ = 224.7    | II       |
|          | Rat           |            | mg/kg             |          |
| (§ 81-1) |               |            |                   |          |
+----------+---------------+------------+-------------------+----------+
| 870.2600 | Skin          | 44142303   | Non sensitizer.   | Not      |
|          | Sensitization |            | Not sensitizing;  | ap       |
| (§ 81-6) | -- Guinea     |            | minimal           | plicable |
|          | pigs          |            | irritation in     |          |
|          |               |            | response to       |          |
|          |               |            | induction, but no |          |
|          |               |            | increase in       |          |
|          |               |            | response to       |          |
|          |               |            | challenge dose    |          |
+----------+---------------+------------+-------------------+----------+
| **Tri    |               |            |                   |          |
| butyltin |               |            |                   |          |
| Be       |               |            |                   |          |
| nzoate** |               |            |                   |          |
+----------+---------------+------------+-------------------+----------+
| 870.1100 | Acute Oral -- | 42415801   | LD~50~ =115 mg/kg | II       |
|          | rat           |            | (males)           |          |
| (§ 81-1) |               |            |                   |          |
|          | Purity        |            | LD~50~ =115 mg/kg |          |
|          |               |            | (females)         |          |
|          |               |            |                   |          |
|          |               |            | LD~50~ =115 mg/kg |          |
|          |               |            | (combined)        |          |
+----------+---------------+------------+-------------------+----------+
| 870.1200 | Acute Dermal  | 42415802   | LD~50~ \> 2000    | III      |
|          | -- rat        |            | mg/kg (combined)  |          |
| (§ 81-2) |               |            |                   |          |
|          | Purity        |            |                   |          |
+----------+---------------+------------+-------------------+----------+
| 870.2500 | Primary       | 42415803   | Severe Irritation | I        |
|          | Dermal        |            |                   |          |
| (§ 81-5) | Irritation -- |            |                   |          |
|          | rabbit        |            |                   |          |
|          |               |            |                   |          |
|          | Purity        |            |                   |          |
+----------+---------------+------------+-------------------+----------+

## 3.2 Dose-Response Assessment 

[]{.mark}

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

+-------------+--------------+----------------+-----------------------+
| **Table 5:  |              |                |                       |
| Summary of  |              |                |                       |
| Toxicology  |              |                |                       |
| Endpoint    |              |                |                       |
| Selection   |              |                |                       |
| for         |              |                |                       |
| Tributyltin |              |                |                       |
| Compounds** |              |                |                       |
+=============+==============+================+=======================+
| Number      | **Dose Used  | **Special      | **Study and           |
| range       | in Risk      | Sensitivity\*, | Toxicological         |
| CHAPTER*    | Assessment** | UF, Target     | Effects**             |
| *Exposure** |              | MOE,**         |                       |
|             | **(          |                |                       |
| *           | mg/kg/day)** | **for Risk     |                       |
| *Scenario** |              | Assessment**   |                       |
+-------------+--------------+----------------+-----------------------+
| **Dietary   |              |                |                       |
| Risk        |              |                |                       |
| As          |              |                |                       |
| sessments** |              |                |                       |
+-------------+--------------+----------------+-----------------------+
| **Acute     | No           |                |                       |
| Dietary**   | appropriate  |                |                       |
|             | endpoints    |                |                       |
| (females    | were         |                |                       |
| 13-49 and   | identified   |                |                       |
| general     | in the oral  |                |                       |
| population) | toxicity     |                |                       |
|             | studies that |                |                       |
|             | represent a  |                |                       |
|             | single dose  |                |                       |
|             | effect for   |                |                       |
|             | the general  |                |                       |
|             | population   |                |                       |
|             | and females  |                |                       |
|             | 13-49. In    |                |                       |
|             | addition,    |                |                       |
|             | the current  |                |                       |
|             | use patterns |                |                       |
|             | for the      |                |                       |
|             | tributylti   |                |                       |
|             | n-containing |                |                       |
|             | chemicals do |                |                       |
|             | not indicate |                |                       |
|             | the          |                |                       |
|             | potential    |                |                       |
|             | for direct   |                |                       |
|             | or indirect  |                |                       |
|             | dietary      |                |                       |
|             | exposures.   |                |                       |
|             | Therefore,   |                |                       |
|             | an acute     |                |                       |
|             | dietary risk |                |                       |
|             | assessment   |                |                       |
|             | has not been |                |                       |
|             | conducted.   |                |                       |
+-------------+--------------+----------------+-----------------------+
| **Chronic   | **BMD~10~**  | **Special      | **Open Literature     |
| Dietary**   | = 0.03       | Sensitivity**  | Study**               |
|             | mg/kg/day    | = 10           |                       |
| (all        | based on     |                | **Vos et al.**,       |
| p           | immu         | **UF** = 100   | (1990) Immunotoxicity |
| opulations) | nosupression | (10x           | of bis                |
|             | (established | inter-species  | (tri-n-butyltin)      |
|             | by EPA/IRIS  | extrapolation, | oxide in the rat:     |
|             | and used to  | 10x            | Effects on            |
|             | estimate the | intra-species  | thymus-dependent      |
|             | oral RfD).   | variation)     | immunity and on       |
|             |              |                | nonspecific           |
|             |              | **Chronic RfD  | resistance following  |
|             |              | (cRfD) =**     | long-term exposure in |
|             |              | 0.00003        | young vs. aged rats.  |
|             |              | mg/kg/day      | Toxicol. Appl.        |
|             |              |                | Pharmacol.            |
|             |              | Although the   | 105:144-155.          |
|             |              | database for   |                       |
|             |              | the            | **NOAEL** = 0.025     |
|             |              | tributyl       | mg/kg/day             |
|             |              | tin-containing |                       |
|             |              | chemicals does | **LOAEL** = 0.25      |
|             |              | not provide    | mg/kg/day based on    |
|             |              | information on | immunotoxicity        |
|             |              | which to base  | (depression of IgE    |
|             |              | an assessment  | titers and increase   |
|             |              | of chronic     | in T. spiralis larvae |
|             |              | dietary        | in muscle) following  |
|             |              | exposures,     | 4 months and 16.5     |
|             |              | this endpoint  | months of exposure to |
|             |              | is selected    | Tributyl Tin Oxide.   |
|             |              | for future     | (Review by EPA/IRIS,  |
|             |              | reference. A   | 1997).                |
|             |              | chronic        |                       |
|             |              | dietary risk   |                       |
|             |              | assessment has |                       |
|             |              | not been       |                       |
|             |              | conducted..    |                       |
+-------------+--------------+----------------+-----------------------+
| **          |              |                |                       |
| Non-Dietary |              |                |                       |
| Risk        |              |                |                       |
| As          |              |                |                       |
| sessments** |              |                |                       |
+-------------+--------------+----------------+-----------------------+
| *           | **BMD~10~**  | **Special      | **Open Literature     |
| *Incidental | = 0.03       | Sensitivity**  | Study**               |
| Oral**      | mg/kg/day    | = 10           |                       |
| Short-Term  | based on     |                | **Vos et al.**,       |
|             | immu         | **UF** = 100   | (1990) Immunotoxicity |
| (1-30 days) | nosupression | (10x           | of bis                |
| and         | (established | inter-species  | (tri-n-butyltin)      |
| Interm      | by EPA/IRIS  | extrapolation, | oxide in the rat:     |
| ediate-Term | and used to  | 10x            | Effects on            |
| (1- 6       | estimate the | intra-species  | thymus-dependent      |
| months)     | oral RfD).   | variation)     | immunity and on       |
|             |              |                | nonspecific           |
|             |              | **Target MOE   | resistance following  |
|             |              | res.** = 1000  | 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**  | **BMD~10~**  | **Special      | **Open Literature     |
|             | = 0.03       | Sensitivity**  | Study**               |
| (all        | mg/kg/day    | = 10           |                       |
| durations)  | based on     |                | **Vos et al.**,       |
|             | immu         | **UF** = 100   | (1990) Immunotoxicity |
|             | nosupression | (10x           | of bis                |
|             | (established | inter-species  | (tri-n-butyltin)      |
|             | by EPA/IRIS  | extrapolation, | oxide in the rat:     |
|             | and used to  | 10x            | Effects on            |
|             | estimate the | intra-species  | thymus-dependent      |
|             | oral RfD).   | variation)     | immunity and on       |
|             |              |                | nonspecific           |
|             |              | **Target MOE   | resistance following  |
|             |              | occ.** = 100   | long-term exposure in |
|             |              |                | young vs. aged rats.  |
|             |              | **Target MOE   | Toxicol. Appl.        |
|             |              | res.** = 1000  | 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).                |
+-------------+--------------+----------------+-----------------------+
| **I         | **BMD~10~**  | **Special      | **Open Literature     |
| nhalation** | = 0.03       | Sensitivity**  | Study**               |
|             | mg/kg/day    | = 10           |                       |
| (all        | based on     |                | **Vos et al.**,       |
| durations)  | immu         | **UF** = 100   | (1990) Immunotoxicity |
|             | nosupression | (10x           | of bis                |
|             | (established | inter-species  | (tri-n-butyltin)      |
|             | by EPA/IRIS  | extrapolation, | oxide in the rat:     |
|             | and used to  | 10x            | Effects on            |
|             | estimate the | intra-species  | thymus-dependent      |
|             | oral RfD).   | variation)     | immunity and on       |
|             |              |                | nonspecific           |
|             |              | **Target MOE   | resistance following  |
|             |              | occ.** = 100   | long-term exposure in |
|             |              |                | young vs. aged rats.  |
|             |              | **Target MOE   | Toxicol. Appl.        |
|             |              | res.** = 1000  | 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    | Although     |                |                       |
| A           | there is no  |                |                       |
| bsorption** | guideline    |                |                       |
|             | dermal       |                |                       |
|             | toxicity     |                |                       |
|             | study        |                |                       |
|             | (r           |                |                       |
|             | ange-finding |                |                       |
|             | study only)  |                |                       |
|             | and no       |                |                       |
|             | acceptable   |                |                       |
|             | dermal       |                |                       |
|             | absorption   |                |                       |
|             | study (75%   |                |                       |
|             | recovery of  |                |                       |
|             | ^113^Sn      |                |                       |
|             | -tributyltin |                |                       |
|             | oxide), a    |                |                       |
|             | 15% dermal   |                |                       |
|             | absorption   |                |                       |
|             | factor for   |                |                       |
|             | tributyltin  |                |                       |
|             | oxide has    |                |                       |
|             | been used    |                |                       |
|             | (EPA/HED)    |                |                       |
|             | for          |                |                       |
|             | ro           |                |                       |
|             | ute-to-route |                |                       |
|             | ex           |                |                       |
|             | trapolation. |                |                       |
+-------------+--------------+----------------+-----------------------+
| **Carcin    | EPA has      |                |                       |
| ogenicity** | assigned     |                |                       |
|             | tributyltin  |                |                       |
|             | oxide to     |                |                       |
|             | category D   |                |                       |
|             | (U.S., 1987) |                |                       |
|             | or to the    |                |                       |
|             | "cannot be   |                |                       |
|             | determined"  |                |                       |
|             | category for |                |                       |
|             | car          |                |                       |
|             | cinogenicity |                |                       |
|             | (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  |                |                       |
|             | r            |                |                       |
|             | elationship. |                |                       |
+-------------+--------------+----------------+-----------------------+

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

[]{.mark}

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).

[]{.mark}

[]{#__RefHeading___Toc194462657 .anchor}**3.4 Endocrine Disruption**

Number range CHAPTER 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.

[]{.mark}

[]{#__RefHeading___Toc194462658 .anchor}**4.0 INCIDENT REPORTS**

[]{.mark}

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

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

2.  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).

(1) **[OPP Incident Data System (IDS)]{.underline}** - 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.

(2) **[Poison Control Centers]{.underline}** - 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.

(3) Number range CHAPTER**[California Department of Pesticide Regulation
    (1982-2004)]{.underline}** - 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.

(4) **[National Pesticide Information Center (NPIC)]{.underline}** -
    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.

(5) **[Published Incident Reports]{.underline}** - 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)]{.underline}**

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]{.underline}**

Although the following incidents have been reported for exposure to
tributyltin oxide, the incidences occurred when used in combination with
other chemicals.

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.

1.  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.

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

3.  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]{.underline}**

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**

## 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 

***[Exposure Scenarios]{.underline}***

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.

[]{.mark}

***[Exposure Data and Assumptions for Handlers:]{.underline}***

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:]{.underline}***

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.

[]{.mark}

***[Risk Characterization: Handler and Post application]{.underline}***

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**

# 

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
[[http://www.epa.gov/pesticides/trac/science/aggregate.pdf]{.underline}](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]{.underline} 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** 

***[Exposure Scenarios]{.underline}***

The Agency has assessed the exposures and risks to occupational workers
that handle TBT containing products (memorandum from T. LeightonNumber
range CHAPTER). 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:]{.underline}***

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]{.underline} or [minimal]{.underline}. PPE
worn by the worker can protect from these residual exposures.

[Negligible exposure]{.underline} 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]{.underline}, 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]{.underline}
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:]{.underline}***

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**

[]{#__RefHeading___Toc194462668 .anchor}**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* I*nvertebrates: *** 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.

[]{#__RefHeading___Toc194462669 .anchor}**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                 **Terrestrial             **[Plants]{.underline}**
                       [Animals]{.underline}**   [Animals]{.underline}**   

  Acute:               0.5                       0.5                       1

  Acute, listed        0.05                      0.1                       1
  species:                                                                 

  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).

[]{#__RefHeading___Toc194462670 .anchor}**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[^1], 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.

[]{#__RefHeading___Toc194462671 .anchor}**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.

[]{#__RefHeading___Toc194462672 .anchor}**11.0 DATA NEEDS AND LABELING**

[Hazard Data Gaps:]{.underline} 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   | **S  |                                               |
| Number**      | tudy |                                               |
|               | Ty   |                                               |
|               | pe** |                                               |
+---------------+------+-----------------------------------------------+
| **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   |      | Mutagenicity Test (1 Study)                   |
| 870.5915      |      |                                               |
+---------------+------+-----------------------------------------------+
| **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   |      | Battery of Mutagenicity Studies (3 studies;   |
| 870.5915      |      | 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      |      | Battery of Mutagenicity Studies (1 study from |
|               |      | "Other Mechanisms" category)                  |
| to            |      |                                               |
|               |      |                                               |
| 870.5915      |      |                                               |
+---------------+------+-----------------------------------------------+

[Ecological Effects:]{.underline}

  --------------- -------------------------------------------------------
  **Table 8.      
  Ecological Data 
  Gaps for        
  Tributyltin     
  Compounds**     

  **Guideline     **Study Type**
  Number**        

  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 &         A study addressing honey/beeswax residues and acute
  850.3030        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]{.underline}: 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:]{.underline} There are no identified outstanding
product chemistry data requirements.

[]{.mark}

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

[Dietary Data Gaps:]{.underline} Additional data will improve our
understanding of [actual]{.underline} 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]{.underline}:**

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:]{.underline}**
> Labeling for appropriate engineering controls (closed delivery and
> loading systems) and PPE can reduce handler exposures.

**[Specific to products with wood preservative uses]{.underline}:**

> 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.

[]{#__RefHeading___Toc194462673 .anchor}**12.0 REFERENCES**

**[Occupational and Residential Exposure Assessment:]{.underline}**

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**[Environmental Fate Science Chapter]{.underline}**

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[]{.mark}

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[]{.mark}

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**[Toxicology Disciplinary Chapter]{.underline}**

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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).

[]{.mark}

[]{.mark}

[]{.mark}

[]{.mark}

[]{.mark}

[]{#__RefHeading___Toc194462674 .anchor}**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,                    | 2.25                                    |
|                            |                                         |
| -73839                     |                                         |
+----------------------------+-----------------------------------------+
| 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
  ---------------------------- ------------------------------------------

[]{#__RefHeading___Toc194462675 .anchor}**Appendix B: Toxicity Profile
for TBT Oxide, Maleate and Benzoate**

[]{.mark}

+-----------+---------------+-------------------+----------------------+
| **Table   |               |                   |                      |
| B-1.      |               |                   |                      |
| Toxicity  |               |                   |                      |
| Profile   |               |                   |                      |
| for       |               |                   |                      |
| Tr        |               |                   |                      |
| ibutyltin |               |                   |                      |
| Oxide,    |               |                   |                      |
| Tr        |               |                   |                      |
| ibutyltin |               |                   |                      |
| Maleate   |               |                   |                      |
| and       |               |                   |                      |
| Tr        |               |                   |                      |
| ibutyltin |               |                   |                      |
| B         |               |                   |                      |
| enzoate** |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| **        | **MRID No./** | **Dosing and      | **Results**          |
| Guideline |               | Animal            |                      |
| No./**    | **Citation**  | Information**     |                      |
|           |               |                   |                      |
| **Study   |               |                   |                      |
| Type**    |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| ***Rang   |               |                   |                      |
| e-finding |               |                   |                      |
| To        |               |                   |                      |
| xicity*** |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| Non-      | MRID 41127001 | CD-1^®^ mice      | **NOAEL** = **4      |
| guideline |               | (male and female) | ppm** (equivalent to |
|           | Daly, I.      |                   | 0.7 mg/kg bw/day in  |
| Rang      | (1989) A      | Purity 97.1 %     | males; 1.0 mg/kg     |
| e-finding | three month   | a.i.              | bw/day in females).  |
| Study in  | oral          |                   |                      |
| Mice      | range-finding | 0, 4, 20, 80, or  | **LOAEL** = **20     |
|           | toxicity      | 200 ppm           | ppm** (equivalent to |
|           | study in mice | (equivalent to    | 3.8 mg/kg bw/day in  |
|           | with bis      | 0.7, 3.8, 15.1,   | males; 4.9 mg/kg     |
|           | (tr           | or 36.9 mg/kg     | bw/day in females)   |
|           | i-n-butyltin) | bw/day in males;  | based on mild        |
|           | oxide (TBTO). | 1.0, 4.9, 17.9,   | hepatotoxicity and   |
|           | Bio/dynamics, | or 46.9 mg/kg     | dermal irritation in |
|           | Inc. (East    | bw/day in         | the ear observed in  |
|           | Millstone,    | females) for 13   | male mice. The       |
|           | New Jersey).  | weeks (diet).     |                      |
|           | Unpublished.  |                   | **Unaccept           |
|           |               |                   | able/Non-guideline** |
+-----------+---------------+-------------------+----------------------+
| Non-      | MRID 41131001 | Beagle dogs       | Exposure to          |
| guideline |               |                   | Tributyltin oxide    |
|           | Schweinfurth, | Purity \>96.1%    |                      |
| Rang      | H. (1987)     | a.i.              | caused elevated      |
| e-finding | Tributyltin   |                   | alkaline             |
| Study in  | oxide:        | 0, 0.1, 0.5, or   |                      |
| Dogs      | Systemic      | 2.5 mg/kg during  | phosphatase and      |
|           | toxicity      | Weeks 1-5; 0,     | slight changes       |
|           | study in      | 0.2, 1.0, or 5.0  |                      |
|           | Beagle dogs   | mg/kg during      | in serum protein     |
|           | with daily    | Weeks 6-10; and   | composition          |
|           | oral          | 0, 10, 1.0, or    |                      |
|           | (             | 5.0 mg/kg during  | at 1.0 mg/kg/day     |
|           | intragastric) | Weeks 11-19.      | after 13-14          |
|           | a             |                   |                      |
|           | dministration |                   | weeks of exposure.   |
|           | over a total  |                   | While                |
|           | of 18-19      |                   |                      |
|           | weeks.        |                   | further biochemical  |
|           | Schering AG,  |                   | changes              |
|           | Berlin,       |                   |                      |
|           | Germany.      |                   | and suspected        |
|           | Laboratory    |                   | effects on red       |
|           | Project ID:   |                   |                      |
|           | TX 87.054,    |                   | and white blood      |
|           | August 5,     |                   | cells were           |
|           | 1987.         |                   |                      |
|           | Unpublished.  |                   | 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.               |
|           |               |                   |                      |
|           |               |                   | **Unaccept           |
|           |               |                   | able/Non-guideline** |
+-----------+---------------+-------------------+----------------------+
| ***21-Day |               |                   |                      |
| Dermal    |               |                   |                      |
| To        |               |                   |                      |
| xicity*** |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| 870.3200  | MRID 43177201 | Dorsal skin of    | The maximum          |
|           |               | Crl:CD**^®^**BR   | tolerable dose for a |
| 21-Day    | Naas, Dennis  | rats              | subsequent 90-day    |
| Dermal    | J. (1990)     |                   | toxicity study was   |
| Toxicity  | Three week    | Purity not        | determined to be 250 |
| Study in  | dermal        | provided          | mg/kg/day.           |
| Rats      | range-finding |                   |                      |
|           | studies in    | 0, 250, 500,      | **Unaccept           |
|           | rats with     | 1000, or 2000     | able/Non-guideline** |
|           | Tributyltin   | mg/kg/day for 6   |                      |
|           | Benzoate. WIL | hours/day         |                      |
|           | Research      |                   |                      |
|           | Laboratories, |                   |                      |
|           | Inc.          |                   |                      |
|           | (Ashland,     |                   |                      |
|           | Ohio).        |                   |                      |
|           | Laboratory    |                   |                      |
|           | study number  |                   |                      |
|           | WIL-159010,   |                   |                      |
|           | December 18,  |                   |                      |
|           | 1990.         |                   |                      |
|           | Unpublished.  |                   |                      |
+-----------+---------------+-------------------+----------------------+
| **        |               |                   |                      |
| *Prenatal |               |                   |                      |
| Deve      |               |                   |                      |
| lopmental |               |                   |                      |
| To        |               |                   |                      |
| xicity*** |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| 870.3700  | MRID 00137158 | Female pregnant   | **Maternal           |
|           |               | CD^®^             | Toxicity**           |
| Prenatal  | Schroeder,    | (Sprague-Dawley   |                      |
| Deve      | R.; Hogan, G. | derived) rats     | **NOAEL =** 5        |
| lopmental | (1981) A      |                   | mg/kg/day            |
| Toxicity  | Teratology    | Purity not        |                      |
| Study     | Study in Rats | reported          | **LOAEL = could not  |
|           | with          |                   | be identified due to |
|           | Tributyltin   | 0, 5, 9, 18       | the lack of data.**  |
|           | Oxide:        | mg/kg/day (via    |                      |
|           | Project No.   | gastric           | **Developmental      |
|           | 80-2497A.     | intubation        | Toxicity**           |
|           | Final rept.   | (gavage)          |                      |
|           | (Unpublished  |                   | **NOAEL** is less    |
|           | study         |                   | than 5 mg/kg/day     |
|           | received Jan  |                   | **LOAEL** is equal   |
|           | 16, 1984      |                   | to or less than 5    |
|           | under 5204-1; |                   | mg/kg/day based on   |
|           | prepared by   |                   | increased incidences |
|           | Bio/dynamics, |                   | of ossification      |
|           | Inc.,         |                   | variations.          |
|           | submitted by  |                   |                      |
|           | M & T         |                   | **Unacce             |
|           | Chemicals     |                   | ptable/Upgradeable** |
|           | Inc., Rahway, |                   |                      |
|           | NJ;           |                   |                      |
|           | C             |                   |                      |
|           | DL: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.    |                   |                      |
+-----------+---------------+-------------------+----------------------+
| 870.3700  | MRID 40141901 | New Zealand White | **Maternal           |
|           |               | female rabbits    | Toxicity**           |
| Prenatal  | Nemec, M.     |                   |                      |
| Deve      | (1987)        | Purity \>95%      | **NOAEL =** 1.0      |
| lopmental | (Tributyltin  |                   | mg/kg/day            |
| Toxicity  | Oxide) - A    | 0, 0.2, 1.0, 2.5  |                      |
| Study     | Teratology    | mg/kg/day (oral   | **LOAEL =** 2.5      |
|           | Study in      | gavage)           | mg/kg/day, based on  |
|           | Rabbits with  |                   | increased incidence  |
|           | TBTO:         |                   | of abortion and      |
|           | Laboratory    |                   | decreased mean       |
|           | Project ID:   |                   | maternal body weight |
|           | WIL-B0002.    |                   | gain.                |
|           | Unpublished   |                   |                      |
|           | study         |                   | **Developmental      |
|           | prepared by   |                   | Toxicity**           |
|           | Wil Research  |                   |                      |
|           | Laboratories, |                   | **NOAEL =** is equal |
|           | Inc. 210 p.   |                   | to or greater than   |
|           |               |                   | 2.5 mg/kg/day        |
|           | MRID 92172006 |                   |                      |
|           |               |                   | **LOAEL=** is        |
|           | Stevens, A.   |                   | greater than 2.5     |
|           | (1990) M&T    |                   | mg/kg/day (could not |
|           | Chemicals,    |                   | be established)      |
|           | Inc. Phase 3  |                   |                      |
|           | Summary of    |                   | **Ac                 |
|           | MRID          |                   | ceptable/Guideline** |
|           | 40141901. A   |                   |                      |
|           | Teratology    |                   |                      |
|           | Study in      |                   |                      |
|           | Rabbits with  |                   |                      |
|           | TBTO: Project |                   |                      |
|           | No.           |                   |                      |
|           | WIL-B0002.    |                   |                      |
|           | Prepared by   |                   |                      |
|           | Wil Research  |                   |                      |
|           | Laboratories, |                   |                      |
|           | Inc. 7 p.     |                   |                      |
+-----------+---------------+-------------------+----------------------+
| 870.3700  | MRID 42903101 | Cr1: CD^®^ (SD)   | **Maternal           |
|           |               | BR VAF/Plus       | Toxicity**           |
| Prenatal  | Bryson, A.    | strain rats       |                      |
| Deve      | (1993)        |                   | **NOAEL =** 1.0      |
| lopmental | Tributyltin   | Purity 97.1% a.i. | mg/kg/day            |
| Toxicity  | Benzoate: A   |                   |                      |
| Study     | Study of the  | 0, 1.0, 4.5 and   | **LOAEL =** 4.5      |
|           | Effect on     | 20.0 mg/kg/day    | mg/kg/day based on   |
|           | Pregnancy of  | (intragastric     | increased incidences |
|           | the Rat: Lab  | intubation)       | of post-dose         |
|           | Project       |                   | salivation, wet      |
|           | Number:       |                   | coat, and impaired   |
|           | NDX/41: NDX   |                   | respiration.         |
|           | 41/921129.    |                   |                      |
|           | Unpublished   |                   | **Developmental      |
|           | study         |                   | Toxicity**           |
|           | prepared by   |                   |                      |
|           | Huntingdon    |                   | **NOAEL =** 1.0      |
|           | Research      |                   | mg/kg/day            |
|           | Centre Ltd.   |                   |                      |
|           | 106 p.        |                   | **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.      |
|           |               |                   |                      |
|           |               |                   | **Ac                 |
|           |               |                   | ceptable/Guideline** |
+-----------+---------------+-------------------+----------------------+
| ***Rep    |               |                   |                      |
| roduction |               |                   |                      |
| and       |               |                   |                      |
| Fertility |               |                   |                      |
| Rates***  |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| 870.3800  | MRID 41693801 | Sprague Dawley    | **Parental           |
|           |               | rats              | Toxicity**           |
| Rep       | Schroeder,    |                   |                      |
| roduction | R.E. (1990) A | Purity 97.1%      | **NOAEL** = 5 ppm    |
| and       | two           |                   | (equivalent to       |
| Fertility | generation    | 0, 0.5, 5, or 50  | 0.33/0.39 mg/kg/day  |
| effects   | reproductions | ppm for two       | in males/females).   |
|           | study in rats | successive        |                      |
|           | with bis      | generations       | **LOAEL =** 50 ppm   |
|           | (tri-         | (diet)            | (equivalent to       |
|           | *n*-butyltin) |                   | mg/kg/day 3.47/3.93  |
|           | oxide.        |                   | in males/females)    |
|           | Bio/dynamics, |                   | based on anogenital  |
|           | Inc., East    |                   | staining in the P    |
|           | Millstone,    |                   | dams; decreased body |
|           | NJ.           |                   | weights in the F1    |
|           | Laboratory    |                   | males and females    |
|           | Project No.:  |                   | during pre-mating    |
|           | 88-3261,      |                   | and continuing in    |
|           | October 22,   |                   | the F1 males during  |
|           | 1990.         |                   | the mating and post  |
|           | Unpublished   |                   | 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     |
|           |               |                   |                      |
|           |               |                   | **Ac                 |
|           |               |                   | ceptable/Guideline** |
+-----------+---------------+-------------------+----------------------+
| *         |               |                   |                      |
| **Chronic |               |                   |                      |
| To        |               |                   |                      |
| xicity*** |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| 870.4100  | MRID 42549801 | Beagle dogs       | Multiple microscopic |
|           |               |                   | finding indicative   |
| Chronic   | Schuh, W.     | Purity 95.9-97.1% | of immunotoxicity    |
| Toxicity  | (1992) Bis    | a.i.              | (detailed above)     |
|           | (tri-         |                   | were noted at 1.0    |
|           | *n*-butyltin) | 0, 0.2, 1.0, or   | mg/kg/day,           |
|           | oxide (TBTO;  | 5.0 mg/kg/day for | particularly in the  |
|           | ZK 21.955):   | 52 weeks (oral    | males. At 5.0        |
|           | 12-month      | gavage)           | mg/kg/day, increased |
|           | chronic oral  |                   | severity of          |
|           | toxicity      |                   | immunotoxicity and   |
|           | study in      |                   | indications of       |
|           | beagle dogs.  |                   | systemic toxicity    |
|           | Schering AG,  |                   | (including           |
|           | Berlin,       |                   | mortality, clinical  |
|           | Germany.      |                   | signs of toxicity,   |
|           | Laboratory    |                   | overall body weight  |
|           | Project ID:   |                   | losses, decreased    |
|           | Study Number  |                   | body weights and     |
|           | TX 85.330,    |                   | food and water       |
|           | September 4,  |                   | consumption,         |
|           | 1992.         |                   | increased blood      |
|           | Unpublished.  |                   | 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.            |
|           |               |                   |                      |
|           |               |                   | **Unac               |
|           |               |                   | ceptable/Guideline** |
|           |               |                   |                      |
|           |               |                   | **(not               |
|           |               |                   | upgradeable)**       |
+-----------+---------------+-------------------+----------------------+
| ***       |               |                   |                      |
| Carcinoge |               |                   |                      |
| nicity*** |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| 870.4200  | MRID 42265001 | CD-1 mice         | **LOAEL = 0.7        |
|           |               |                   | mg/kg/day (males)**  |
| Carcin    | Daly, I.      | Purity 97.1% pure |                      |
| ogenicity | (1992) An     |                   | **LOAEL = 0.9        |
|           | eighteen      | 0, 5, 25, or 50   | mg/kg/day            |
|           | month         | ppm (equivalent   | (females),** based   |
|           | oncogenicity  | to 0.7, 3.7, and  | on decreased         |
|           | feeding study | 7.7 mg/kg/day for | survivorship and     |
|           | in mice with  | low-, mid-, and   | increased body       |
|           | bis           | high-dose males,  | weight gain**.**     |
|           | (tr           | respectively, and |                      |
|           | i-n-butyltin) | 0.9, 4.8, and 9.2 | **Ac                 |
|           | oxide (TBTO). | mg/kg/day for     | ceptable/Guideline** |
|           | Bio/dynamic,  | low-, mid-, and   |                      |
|           | Inc. Project  | high-dose         |                      |
|           | No. 87-3131,  | females,          |                      |
|           | March 27,     | respectively) for |                      |
|           | 1992.         | 18 months (diet)  |                      |
|           | Unpublished   |                   |                      |
+-----------+---------------+-------------------+----------------------+
| **        |               |                   |                      |
| *Combined |               |                   |                      |
| Chronic   |               |                   |                      |
| Toxicity/ |               |                   |                      |
| Carcinoge |               |                   |                      |
| nicity*** |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| 870.4300  | MRID 40623201 | Wistar rats       | **NOAEL =** 5 ppm    |
|           |               |                   | (approximately       |
| Combined  | Wester, P.W.; | Purity 95.3% a.i. | equivalent to 0.25   |
| chronic   | Krajnc, E.I.; |                   | mg/kg bw/day).       |
| toxici    | et al. (1988) | 0, 0.5, 5, or 50  |                      |
| ty/Carcin | Bis           | ppm               | **LOAEL =** 50 ppm   |
| ogenicity | (tributyltin) | (approximately    | (approximately       |
|           | oxide -- Two  | equivalent to 0,  | equivalent to 2.5    |
|           | year feeding  | 0.025, 0.25, and  | mg/kg bw/day) based  |
|           | study in rats | 2.5 mg/kg bw/day  | on increased         |
|           | with bis      | (diet)            | mortality, systemic  |
|           | (tri-         |                   | toxicity (ataxia,    |
|           | *n*-butyltin) |                   | emaciation and       |
|           | oxide. RIVM,  |                   | decreased body       |
|           | Bilthoven,    |                   | weight/body weight   |
|           | The           |                   | gain in males and    |
|           | Netherlands.  |                   | females) and organ   |
|           | Laboratory    |                   | toxicity (kidney,    |
|           | Report No.:   |                   | thyroid, adrenal     |
|           | 658112 002,   |                   | glands, and          |
|           | February 25,  |                   | pituitary.           |
|           | 1988.         |                   |                      |
|           |               |                   | **Ac                 |
|           | Unpublished.  |                   | ceptable/Guideline** |
+-----------+---------------+-------------------+----------------------+
| ***M      |               |                   |                      |
| etabolism |               |                   |                      |
| and       |               |                   |                      |
| P         |               |                   |                      |
| harmacoki |               |                   |                      |
| netics*** |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| 870.7485  | MRID 01246480 | Female COBS       | Concentrations of    |
|           |               | albino mice       | ^14^C-TBTO           |
| M         | Evans, W., D. |                   |                      |
| etabolism | Smith, and N. | Purity not        | were greatest in the |
| and       | Cardarelli    | reported          | kidneys,             |
| Pharmac   | (date of      |                   |                      |
| okinetics | study not     | 0, 0.51, 3.75, or | fat, liver, and      |
|           | provided)     | 18.5 ppm          | spleen.              |
|           | Accumulation  |                   |                      |
|           | and excretion |                   | Concentrations were  |
|           | of            |                   | found to             |
|           | \[1-^14^C\]   |                   |                      |
|           | bis           |                   | be proportional to   |
|           | (tr           |                   | administered         |
|           | i-n-butyltin) |                   |                      |
|           | oxide in      |                   | dose except in the   |
|           | mice.         |                   | kidney.              |
|           | Environmental |                   |                      |
|           | Management    |                   | Tissue accumulations |
|           | Laboratory,   |                   | were                 |
|           | The           |                   |                      |
|           | University of |                   | concentration        |
|           | Akron (Akron, |                   | dependent. The       |
|           | Ohio).        |                   |                      |
|           | Unpublished.  |                   | quantities absorbed  |
|           |               |                   | were                 |
|           |               |                   |                      |
|           |               |                   | rapidly cleared when |
|           |               |                   | ingestion            |
|           |               |                   |                      |
|           |               |                   | ceased.              |
|           |               |                   |                      |
|           |               |                   | **Accept             |
|           |               |                   | able/Non-guideline** |
+-----------+---------------+-------------------+----------------------+
| 870.7485  | MRID 40253002 | Female Wistar-Han | Absorption was very  |
|           |               | (SPF) rats        | delayed after gavage |
| M         | Humpel, M.    |                   | administration, with |
| etabolism | (1986)        | Purity (\>99%a.i) | a half-life of 9.5   |
| and       | T             |                   | hours. The           |
| Pharmac   | oxicokinetics | 1 mg/kg or 25     | intravenously        |
| okinetics | of            | mg/kg             |                      |
|           | ^11           |                   | administered         |
|           | 3^Sn-labelled |                   | ^113^Sn-labeled      |
|           | tributyltin   |                   |                      |
|           | oxide after   |                   | TBTO is rapidly      |
|           | intravenous   |                   | distributed,         |
|           | (1 mg/kg) and |                   |                      |
|           | intragastric  |                   | with only 3% of the  |
|           | (25 mg/kg)    |                   | dose                 |
|           | a             |                   |                      |
|           | dministration |                   | remaining in plasma  |
|           | to rats:      |                   | volume               |
|           | bio           |                   |                      |
|           | availability, |                   | after 5 minutes post |
|           | excretion,    |                   |                      |
|           | and           |                   | administration.      |
|           | biotr         |                   | Based on the         |
|           | ansformation. |                   |                      |
|           | Schering AG,  |                   | high volume of       |
|           | Berlin,       |                   | distribution         |
|           | Germany.      |                   |                      |
|           | Laboratory    |                   | and the binding to   |
|           | report        |                   | the cellular         |
|           | numbers IC-Kl |                   |                      |
|           | 3, KI 84 061, |                   | constituents of the  |
|           | and KI 84     |                   | blood, authors       |
|           | 062. January  |                   |                      |
|           | 23, 1986.     |                   | conclude that TBTO   |
|           |               |                   | has a                |
|           | Unpublished.  |                   |                      |
|           |               |                   | pronounced affinity  |
|           |               |                   | for tissues.         |
|           |               |                   |                      |
|           |               |                   | **Accept             |
|           |               |                   | able/Non-guideline** |
+-----------+---------------+-------------------+----------------------+
| ***Dermal |               |                   |                      |
| Penet     |               |                   |                      |
| ration*** |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| 870.7600  | MRID 40050003 | Male baboon       | The total recovery   |
|           |               |                   | of radioactively     |
| Dermal    | Hümel, M.     | Purity not        | labeled              |
| Pe        | (1985) Series | reported          | ^113^Sn-Tributyltin  |
| netration | 85-2:         |                   | oxide was less than  |
|           | Percutaneous  | Dose volume 0.5   | 50%, perhaps due to  |
|           | absorption of | mL/25 cm^2^ skin  | the incomplete       |
|           | tributyltin   |                   | removal of           |
|           | oxide (TBTO)  |                   | unabsorbed TBTO on   |
|           | through       |                   | the skin surface as  |
|           | intact skin   |                   | a result of          |
|           | of baboon.    |                   | extensive spreading  |
|           | Scherling AG, |                   | from the site of     |
|           | Berlin 65,    |                   | application.         |
|           | Germany.      |                   | However, reviewer    |
|           | Laboratory    |                   | generated data       |
|           | Project ID    |                   | indicates that the   |
|           | IC-KI 2, June |                   | total recovery was   |
|           | 12, 1985.     |                   | approximately 75%.   |
|           | Unpublished   |                   |                      |
|           |               |                   | **Unaccept           |
|           |               |                   | able/Non-guideline** |
+-----------+---------------+-------------------+----------------------+
| **        |               |                   |                      |
| Published |               |                   |                      |
| Lit       |               |                   |                      |
| erature** |               |                   |                      |
+-----------+---------------+-------------------+----------------------+
| Non       | Vos et al.,   | Wistar Rats       | **NOAEL** = 0.025    |
| Guideline | (1990)        |                   | mg/kg/day            |
|           | I             | Purity: 95.3%     |                      |
| L         | mmunotoxicity | active ingredient | **LOAEL** = 0.25     |
| iterature | of            |                   | mg/kg/day based on   |
| Study     | bis(tri-n-b   | Exposure to TBTO  | immunotoxicity       |
|           | utyltin)oxide | for up to 18      | (depression of IgE   |
|           | in the rat:   | months            | titers and increase  |
|           | Effects on    |                   | in T. spiralis       |
|           | thy           | Dietary           | larvae in muscle)    |
|           | mus-dependent | concentrations:   | following 4 months   |
|           | immunity and  | 0.025, 0.25 and   | and 16.5 months of   |
|           | on            | 2.5 mg/kg-day.    | exposure to Tributyl |
|           | nonspecific   |                   | Tin Oxide. (Review   |
|           | resistance    |                   | by EPA/IRIS, 1997).  |
|           | following     |                   |                      |
|           | long-term     |                   |                      |
|           | exposure in   |                   |                      |
|           | young vs.     |                   |                      |
|           | aged rats.    |                   |                      |
|           | Toxicol.      |                   |                      |
|           | Appl.         |                   |                      |
|           | Pharmacol.    |                   |                      |
|           | 105:144-155.  |                   |                      |
+-----------+---------------+-------------------+----------------------+

[]{.mark}

[]{.mark}

[]{#__RefHeading___Toc194462676 .anchor}**Appendix C: Residential and
Occupational Uses Selected for Assessing Risks to TBT-containing
Products**

+-------------+-----------+--------------+-----------+----------------+
| **Table     |           |              |           |                |
| C-1.        |           |              |           |                |
| Rep         |           |              |           |                |
| resentative |           |              |           |                |
| Uses        |           |              |           |                |
| Associated  |           |              |           |                |
| with        |           |              |           |                |
| Residential |           |              |           |                |
| Exposure to |           |              |           |                |
| TBT.**      |           |              |           |                |
+=============+===========+==============+===========+================+
| Rep         | Ap        | Exposure     | Example   | Application    |
| resentative | plication | Scenario     | Reg       | Rate           |
| Use         | Method    |              | istration |                |
|             |           |              | Number    |                |
+-------------+-----------+--------------+-----------+----------------+
| Wood        | -   Brush | ST Handler:  | 1022-511  | 0.062 lb       |
| P           |     and   | adult dermal |           | ai/gallon      |
| reservative |           | and          | (577-539, |                |
|             |   airless | inhalation.  | 577-544,  | \[8.3 lbs per  |
|             |           |              | 1022-511, | gal density x  |
|             |   sprayer |              | 7313-6,   | 0.75% ai =     |
|             |           |              | 8177-71)  | 0.062 lb       |
|             | (Note:    |              |           | ai/gallon of   |
|             | dip not   |              |           | stain\]        |
|             | assessed  |              |           |                |
|             | se        |              |           |                |
|             | parately) |              |           |                |
+-------------+-----------+--------------+-----------+----------------+
| Textiles    | -   NA^a^ | ST Post-app: | 3090-123  | 0.05% ai or    |
| (a)         |           | wearing      |           | 500 ppm TBT    |
|             |           | treated      | (textile) |                |
| (exposures  |           | clothing,    |           | \[1% pesticide |
| to treated  |           | adult        | 10466-24  | product by     |
| articles    |           | dermal;      |           | weight of      |
| are         |           | child        | (         | material       |
| represented |           | incidental   | mattress) | treated x 5%   |
| by exposure |           | ingestion    |           | ai in          |
| to clothing |           | and dermal   |           | formulated     |
| and         |           |              |           | product =      |
| mattress)   |           | []{.mark}    |           | weight         |
|             |           |              |           | fraction of    |
|             |           | []{.mark}    |           | 0.0005 ai or   |
|             |           |              |           | 0.05% ai or    |
|             |           | []{.mark}    |           | 500 ppm\]      |
|             |           |              |           |                |
|             |           | []{.mark}    |           | 0.056% ai or   |
|             |           |              |           | 560 ppm TBT    |
|             |           | []{.mark}    |           |                |
|             |           |              |           | \[3.5%         |
|             |           | []{.mark}    |           | formulated     |
|             |           |              |           | product by     |
|             |           | ST           |           | weight of      |
|             |           | Post-appl:   |           | goods x 1.6%   |
|             |           | Sleeping on  |           | ai in          |
|             |           | treated      |           | formulated     |
|             |           | mattress;    |           | product =      |
|             |           | adult dermal |           | weight         |
|             |           | and child    |           | fraction of    |
|             |           | incidental   |           | 0.00056 ai or  |
|             |           | ingestion    |           | 0.056% ai or   |
|             |           | and dermal   |           | 560 ppm\]      |
+-------------+-----------+--------------+-----------+----------------+

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

+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| **Table     |   |             |   |            |   |          |   |                 |
| C-2.        |   |             |   |            |   |          |   |                 |
| Rep         |   |             |   |            |   |          |   |                 |
| resentative |   |             |   |            |   |          |   |                 |
| Exposure    |   |             |   |            |   |          |   |                 |
| Scenarios   |   |             |   |            |   |          |   |                 |
| Associated  |   |             |   |            |   |          |   |                 |
| with        |   |             |   |            |   |          |   |                 |
| O           |   |             |   |            |   |          |   |                 |
| ccupational |   |             |   |            |   |          |   |                 |
| Exposures   |   |             |   |            |   |          |   |                 |
| to TBT**    |   |             |   |            |   |          |   |                 |
+=============+===+=============+===+============+===+==========+===+=================+
| Rep         | M |             | E |            | E |          | A |                 |
| resentative | e |             | x |            | x |          | p |                 |
| Use         | t |             | p |            | a |          | p |                 |
|             | h |             | o |            | m |          | l |                 |
|             | o |             | s |            | p |          | i |                 |
|             | d |             | u |            | l |          | c |                 |
|             | o |             | r |            | e |          | a |                 |
|             | f |             | e |            | R |          | t |                 |
|             | A |             | S |            | e |          | i |                 |
|             | p |             | c |            | g |          | o |                 |
|             | p |             | e |            | i |          | n |                 |
|             | l |             | n |            | s |          | R |                 |
|             | i |             | a |            | t |          | a |                 |
|             | c |             | r |            | r |          | t |                 |
|             | a |             | i |            | a |          | e |                 |
|             | t |             | o |            | t |          |   |                 |
|             | i |             |   |            | i |          |   |                 |
|             | o |             |   |            | o |          |   |                 |
|             | n |             |   |            | n |          |   |                 |
|             |   |             |   |            | \ |          |   |                 |
|             |   |             |   |            | # |          |   |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| **A         |   |             |   |            |   |          |   |                 |
| gricultural |   |             |   |            |   |          |   |                 |
| Premises    |   |             |   |            |   |          |   |                 |
| and         |   |             |   |            |   |          |   |                 |
| Equipment   |   |             |   |            |   |          |   |                 |
| (Use        |   |             |   |            |   |          |   |                 |
| Category    |   |             |   |            |   |          |   |                 |
| I)**        |   |             |   |            |   |          |   |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| Agricul     |   | Brush, mop, |   | ST/IT      |   | 65020-12 |   | Liquid: 0.00033 |
| tural/farm/ |   | wipe,       |   | Handler:   |   |          |   | lb ai/gal       |
|             |   | spray, and  |   |            |   |          |   |                 |
| poultry     |   | fogger      |   | Inhalation |   |          |   | \[(0.5 oz       |
| structure   |   |             |   |            |   |          |   | formulated      |
| s/buildings |   |             |   | Dermal     |   |          |   | product x 1 %   |
| and         |   |             |   |            |   |          |   | ai x 8.34       |
| equipment   |   |             |   |            |   |          |   | lb/128 oz) / (1 |
|             |   |             |   |            |   |          |   | gal water) =    |
|             |   |             |   |            |   |          |   | 0.00033 lb      |
|             |   |             |   |            |   |          |   | ai/gal\]        |
|             |   |             |   |            |   |          |   |                 |
|             |   |             |   |            |   |          |   | Fogger: 1.3E-6  |
|             |   |             |   |            |   |          |   | lb ai/ft3       |
|             |   |             |   |            |   |          |   |                 |
|             |   |             |   |            |   |          |   | \[(1 gal        |
|             |   |             |   |            |   |          |   | formulated      |
|             |   |             |   |            |   |          |   | product x 8.34  |
|             |   |             |   |            |   |          |   | lb/gal density  |
|             |   |             |   |            |   |          |   | x 1 % ai) /     |
|             |   |             |   |            |   |          |   | (6000ft2 x 10   |
|             |   |             |   |            |   |          |   | ft ceiling) =   |
|             |   |             |   |            |   |          |   | 1.3E-6 lb       |
|             |   |             |   |            |   |          |   | ai/ft3\]        |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| **Co        |   |             |   |            |   |          |   |                 |
| mmercial/In |   |             |   |            |   |          |   |                 |
| dustrial/In |   |             |   |            |   |          |   |                 |
| stitutional |   |             |   |            |   |          |   |                 |
| Premises    |   |             |   |            |   |          |   |                 |
| (Use        |   |             |   |            |   |          |   |                 |
| Category    |   |             |   |            |   |          |   |                 |
| III)**      |   |             |   |            |   |          |   |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| (See wood   | N |             | N |            | N |          | N |                 |
| p           | A |             | A |            | A |          | A |                 |
| reservative |   |             |   |            |   |          |   |                 |
| category    |   |             |   |            |   |          |   |                 |
| for         |   |             |   |            |   |          |   |                 |
| commercial  |   |             |   |            |   |          |   |                 |
| painters    |   |             |   |            |   |          |   |                 |
| using       |   |             |   |            |   |          |   |                 |
| treated     |   |             |   |            |   |          |   |                 |
| stain)      |   |             |   |            |   |          |   |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| **Material  |   |             |   |            |   |          |   |                 |
| Pr          |   |             |   |            |   |          |   |                 |
| eservatives |   |             |   |            |   |          |   |                 |
| (Use        |   |             |   |            |   |          |   |                 |
| Category    |   |             |   |            |   |          |   |                 |
| VII)**      |   |             |   |            |   |          |   |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| Caulks,     | L |             | S |            | 5 |          | 0 |                 |
| sealants,   | i |             | T |            | 3 |          | . |                 |
| adhesives,  | q |             | / |            | 8 |          | 1 |                 |
| etc         | u |             | I |            | 3 |          | 4 |                 |
|             | i |             | T |            | - |          | 5 |                 |
|             | d |             | H |            | 4 |          | % |                 |
|             | p |             | a |            | 7 |          | a |                 |
|             | o |             | n |            |   |          | i |                 |
|             | u |             | d |            | ( |          |   |                 |
|             | r |             | l |            | 6 |          | \ |                 |
|             |   |             | e |            | 7 |          | [ |                 |
|             | M |             | r |            | 3 |          | 0 |                 |
|             | e |             | : |            | 6 |          | . |                 |
|             | t |             | I |            | 0 |          | 5 |                 |
|             | e |             | n |            | - |          | % |                 |
|             | r |             | h |            | 3 |          | f |                 |
|             | e |             | a |            | , |          | o |                 |
|             | d |             | l |            | 1 |          | r |                 |
|             | p |             | a |            | 5 |          | m |                 |
|             | u |             | t |            | 2 |          | u |                 |
|             | m |             | i |            | 9 |          | l |                 |
|             | p |             | o |            | - |          | a |                 |
|             |   |             | n |            | 3 |          | t |                 |
|             |   |             |   |            | 0 |          | e |                 |
|             |   |             | d |            | , |          | d |                 |
|             |   |             | e |            | a |          | p |                 |
|             |   |             | r |            | n |          | r |                 |
|             |   |             | m |            | d |          | o |                 |
|             |   |             | a |            | 1 |          | d |                 |
|             |   |             | l |            | 5 |          | u |                 |
|             |   |             |   |            | 2 |          | c |                 |
|             |   |             |   |            | 9 |          | t |                 |
|             |   |             |   |            | - |          | x |                 |
|             |   |             |   |            | 3 |          | 2 |                 |
|             |   |             |   |            | 5 |          | 9 |                 |
|             |   |             |   |            | ) |          | % |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
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|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | 5 |                 |
|             |   |             |   |            |   |          | % |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | r |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | 5 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | p |                 |
|             |   |             |   |            |   |          | p |                 |
|             |   |             |   |            |   |          | m |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | \ |                 |
|             |   |             |   |            |   |          | ] |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| MWF         | L |             | S |            | 5 |          | 0 |                 |
|             | i |             | T |            | 3 |          | . |                 |
|             | q |             | / |            | 8 |          | 1 |                 |
|             | u |             | I |            | 3 |          | 4 |                 |
|             | i |             | T |            | - |          | 5 |                 |
|             | d |             | / |            | 4 |          | % |                 |
|             | p |             | L |            | 7 |          | a |                 |
|             | o |             | T |            |   |          | i |                 |
|             | u |             | h |            |   |          | i |                 |
|             | r |             | a |            |   |          | n |                 |
|             |   |             | n |            |   |          | c |                 |
|             | M |             | d |            |   |          | u |                 |
|             | a |             | l |            |   |          | t |                 |
|             | c |             | e |            |   |          | t |                 |
|             | h |             | r |            |   |          | i |                 |
|             | i |             | / |            |   |          | n |                 |
|             | n |             | m |            |   |          | g |                 |
|             | i |             | a |            |   |          | o |                 |
|             | s |             | c |            |   |          | i |                 |
|             | t |             | h |            |   |          | l |                 |
|             |   |             | i |            |   |          |   |                 |
|             |   |             | n |            |   |          | \ |                 |
|             |   |             | i |            |   |          | [ |                 |
|             |   |             | s |            |   |          | 0 |                 |
|             |   |             | t |            |   |          | . |                 |
|             |   |             | : |            |   |          | 5 |                 |
|             |   |             |   |            |   |          | % |                 |
|             |   |             | D |            |   |          | f |                 |
|             |   |             | e |            |   |          | o |                 |
|             |   |             | r |            |   |          | r |                 |
|             |   |             | m |            |   |          | m |                 |
|             |   |             | a |            |   |          | u |                 |
|             |   |             | l |            |   |          | l |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             | I |            |   |          | t |                 |
|             |   |             | n |            |   |          | e |                 |
|             |   |             | h |            |   |          | d |                 |
|             |   |             | a |            |   |          | p |                 |
|             |   |             | l |            |   |          | r |                 |
|             |   |             | a |            |   |          | o |                 |
|             |   |             | t |            |   |          | d |                 |
|             |   |             | i |            |   |          | u |                 |
|             |   |             | o |            |   |          | c |                 |
|             |   |             | n |            |   |          | t |                 |
|             |   |             |   |            |   |          | x |                 |
|             |   |             |   |            |   |          | 2 |                 |
|             |   |             |   |            |   |          | 9 |                 |
|             |   |             |   |            |   |          | % |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | = |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | 5 |                 |
|             |   |             |   |            |   |          | % |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | r |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | 5 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | p |                 |
|             |   |             |   |            |   |          | p |                 |
|             |   |             |   |            |   |          | m |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | \ |                 |
|             |   |             |   |            |   |          | ] |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| **Number    |   |             |   |            |   |          |   |                 |
| range       |   |             |   |            |   |          |   |                 |
| CHAPTE      |   |             |   |            |   |          |   |                 |
| RIndustrial |   |             |   |            |   |          |   |                 |
| processes   |   |             |   |            |   |          |   |                 |
| and Water   |   |             |   |            |   |          |   |                 |
| Systems     |   |             |   |            |   |          |   |                 |
| (Use        |   |             |   |            |   |          |   |                 |
| Category    |   |             |   |            |   |          |   |                 |
| VIII)**     |   |             |   |            |   |          |   |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| Pulp and    | M |             | S |            | 4 |          | I |                 |
| Paper       | e |             | T |            | 7 |          | n |                 |
|             | t |             | / |            | 3 |          | i |                 |
|             | e |             | I |            | 7 |          | t |                 |
|             | r |             | T |            | 1 |          | i |                 |
|             | e |             | H |            | - |          | a |                 |
|             | d |             | a |            | 2 |          | l |                 |
|             | p |             | n |            | 9 |          | : |                 |
|             | u |             | d |            |   |          | 0 |                 |
|             | m |             | l |            |   |          | . |                 |
|             | p |             | e |            |   |          | 0 |                 |
|             |   |             | r |            |   |          | 1 |                 |
|             |   |             | : |            |   |          | 4 |                 |
|             |   |             | I |            |   |          | l |                 |
|             |   |             | n |            |   |          | b |                 |
|             |   |             | h |            |   |          | a |                 |
|             |   |             | a |            |   |          | i |                 |
|             |   |             | l |            |   |          | / |                 |
|             |   |             | a |            |   |          | t |                 |
|             |   |             | t |            |   |          | o |                 |
|             |   |             | i |            |   |          | n |                 |
|             |   |             | o |            |   |          |   |                 |
|             |   |             | n |            |   |          | C |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             | d |            |   |          | n |                 |
|             |   |             | e |            |   |          | t |                 |
|             |   |             | r |            |   |          | i |                 |
|             |   |             | m |            |   |          | n |                 |
|             |   |             | a |            |   |          | u |                 |
|             |   |             | l |            |   |          | o |                 |
|             |   |             |   |            |   |          | u |                 |
|             |   |             |   |            |   |          | s |                 |
|             |   |             |   |            |   |          | : |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 7 |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | b |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | / |                 |
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|             |   |             |   |            |   |          |   |                 |
|             |   |             |   |            |   |          | \ |                 |
|             |   |             |   |            |   |          | [ |                 |
|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | I |                 |
|             |   |             |   |            |   |          | n |                 |
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|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | : |                 |
|             |   |             |   |            |   |          | 9 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 6 |                 |
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|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | C |                 |
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|             |   |             |   |            |   |          | f |                 |
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|             |   |             |   |            |   |          | * |                 |
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|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 8 |                 |
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|             |   |             |   |            |   |          | z |                 |
|             |   |             |   |            |   |          | / |                 |
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|             |   |             |   |            |   |          | n |                 |
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|             |   |             |   |            |   |          | p |                 |
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|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          |   |                 |
|             |   |             |   |            |   |          | W |                 |
|             |   |             |   |            |   |          | h |                 |
|             |   |             |   |            |   |          | e |                 |
|             |   |             |   |            |   |          | r |                 |
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|             |   |             |   |            |   |          | 9 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 6 |                 |
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|             |   |             |   |            |   |          | z |                 |
|             |   |             |   |            |   |          | p |                 |
|             |   |             |   |            |   |          | r |                 |
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|             |   |             |   |            |   |          | u |                 |
|             |   |             |   |            |   |          | c |                 |
|             |   |             |   |            |   |          | t |                 |
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|             |   |             |   |            |   |          | 2 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 2 |                 |
|             |   |             |   |            |   |          | 5 |                 |
|             |   |             |   |            |   |          | % |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | x |                 |
|             |   |             |   |            |   |          | 8 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 3 |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | b |                 |
|             |   |             |   |            |   |          | / |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 2 |                 |
|             |   |             |   |            |   |          | 8 |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | z |                 |
|             |   |             |   |            |   |          | = |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | b |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | / |                 |
|             |   |             |   |            |   |          | t |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | n |                 |
|             |   |             |   |            |   |          | p |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | p |                 |
|             |   |             |   |            |   |          | e |                 |
|             |   |             |   |            |   |          | r |                 |
|             |   |             |   |            |   |          | \ |                 |
|             |   |             |   |            |   |          | ] |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| Re          | L |             | S |            | 5 |          | I |                 |
| circulating | i |             | T |            | 1 |          | n |                 |
| Cooling     | q |             | / |            | 8 |          | i |                 |
| Water       | u |             | I |            | 5 |          | t |                 |
|             | i |             | T |            | - |          | i |                 |
|             | d |             | H |            | 3 |          | a |                 |
|             | p |             | a |            | 9 |          | l |                 |
|             | o |             | n |            | 9 |          | : |                 |
|             | u |             | d |            |   |          | 0 |                 |
|             | r |             | l |            |   |          | . |                 |
|             |   |             | e |            |   |          | 0 |                 |
|             | M |             | r |            |   |          | 8 |                 |
|             | e |             | : |            |   |          | 9 |                 |
|             | t |             | I |            |   |          | l |                 |
|             | e |             | n |            |   |          | b |                 |
|             | r |             | h |            |   |          | a |                 |
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|             | m |             | i |            |   |          | 0 |                 |
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|             |   |             | r |            |   |          | C |                 |
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|             |   |             |   |            |   |          | 2 |                 |
|             |   |             |   |            |   |          | 8 |                 |
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|             |   |             |   |            |   |          | t |                 |
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|             |   |             |   |            |   |          | e |                 |
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|             |   |             |   |            |   |          | * |                 |
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|             |   |             |   |            |   |          | p |                 |
|             |   |             |   |            |   |          | r |                 |
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|             |   |             |   |            |   |          | c |                 |
|             |   |             |   |            |   |          | t |                 |
|             |   |             |   |            |   |          | x |                 |
|             |   |             |   |            |   |          | 8 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 3 |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | b |                 |
|             |   |             |   |            |   |          | / |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 2 |                 |
|             |   |             |   |            |   |          | 8 |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | z |                 |
|             |   |             |   |            |   |          | x |                 |
|             |   |             |   |            |   |          | 3 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | % |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | / |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | g |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | n |                 |
|             |   |             |   |            |   |          | s |                 |
|             |   |             |   |            |   |          | w |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | t |                 |
|             |   |             |   |            |   |          | e |                 |
|             |   |             |   |            |   |          | r |                 |
|             |   |             |   |            |   |          | \ |                 |
|             |   |             |   |            |   |          | ] |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| Oil fields  | L |             | S |            | 5 |          | I |                 |
| and         | i |             | T |            | 1 |          | n |                 |
| pe          | q |             | / |            | 8 |          | i |                 |
| trochemical | u |             | I |            | 5 |          | t |                 |
| water       | i |             | T |            | - |          | i |                 |
| injection   | d |             | H |            | 3 |          | a |                 |
| systems     | p |             | a |            | 9 |          | l |                 |
|             | o |             | n |            | 9 |          | : |                 |
|             | u |             | d |            |   |          | 0 |                 |
|             | r |             | l |            |   |          | . |                 |
|             |   |             | e |            |   |          | 0 |                 |
|             | M |             | r |            |   |          | 8 |                 |
|             | e |             | : |            |   |          | 9 |                 |
|             | t |             | I |            |   |          | l |                 |
|             | e |             | n |            |   |          | b |                 |
|             | r |             | h |            |   |          | a |                 |
|             | e |             | a |            |   |          | i |                 |
|             | d |             | l |            |   |          | / |                 |
|             | p |             | a |            |   |          | 1 |                 |
|             | u |             | t |            |   |          | 0 |                 |
|             | m |             | i |            |   |          | 0 |                 |
|             | p |             | o |            |   |          | 0 |                 |
|             |   |             | n |            |   |          | g |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             | d |            |   |          | l |                 |
|             |   |             | e |            |   |          |   |                 |
|             |   |             | r |            |   |          | C |                 |
|             |   |             | m |            |   |          | o |                 |
|             |   |             | a |            |   |          | n |                 |
|             |   |             | l |            |   |          | t |                 |
|             |   |             |   |            |   |          | i |                 |
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|             |   |             |   |            |   |          | : |                 |
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|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 2 |                 |
|             |   |             |   |            |   |          | 2 |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | b |                 |
|             |   |             |   |            |   |          | a |                 |
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|             |   |             |   |            |   |          | / |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | g |                 |
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|             |   |             |   |            |   |          | l |                 |
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|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | n |                 |
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|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | f |                 |
|             |   |             |   |            |   |          | w |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | t |                 |
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|             |   |             |   |            |   |          | r |                 |
|             |   |             |   |            |   |          |   |                 |
|             |   |             |   |            |   |          | \ |                 |
|             |   |             |   |            |   |          | [ |                 |
|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | I |                 |
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|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | : |                 |
|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | z |                 |
|             |   |             |   |            |   |          | p |                 |
|             |   |             |   |            |   |          | r |                 |
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|             |   |             |   |            |   |          | t |                 |
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|             |   |             |   |            |   |          | 8 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 3 |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | b |                 |
|             |   |             |   |            |   |          | / |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 2 |                 |
|             |   |             |   |            |   |          | 8 |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | z |                 |
|             |   |             |   |            |   |          | x |                 |
|             |   |             |   |            |   |          | 3 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | % |                 |
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|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | / |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | g |                 |
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|             |   |             |   |            |   |          | l |                 |
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|             |   |             |   |            |   |          | w |                 |
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|             |   |             |   |            |   |          | t |                 |
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|             |   |             |   |            |   |          | r |                 |
|             |   |             |   |            |   |          |   |                 |
|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | C |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | n |                 |
|             |   |             |   |            |   |          | t |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | n |                 |
|             |   |             |   |            |   |          | u |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | u |                 |
|             |   |             |   |            |   |          | s |                 |
|             |   |             |   |            |   |          | f |                 |
|             |   |             |   |            |   |          | e |                 |
|             |   |             |   |            |   |          | e |                 |
|             |   |             |   |            |   |          | d |                 |
|             |   |             |   |            |   |          | : |                 |
|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | * |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | z |                 |
|             |   |             |   |            |   |          | p |                 |
|             |   |             |   |            |   |          | r |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | d |                 |
|             |   |             |   |            |   |          | u |                 |
|             |   |             |   |            |   |          | c |                 |
|             |   |             |   |            |   |          | t |                 |
|             |   |             |   |            |   |          | x |                 |
|             |   |             |   |            |   |          | 8 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 3 |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | b |                 |
|             |   |             |   |            |   |          | / |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 2 |                 |
|             |   |             |   |            |   |          | 8 |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | z |                 |
|             |   |             |   |            |   |          | x |                 |
|             |   |             |   |            |   |          | 3 |                 |
|             |   |             |   |            |   |          | . |                 |
|             |   |             |   |            |   |          | 4 |                 |
|             |   |             |   |            |   |          | % |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | / |                 |
|             |   |             |   |            |   |          | 1 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | 0 |                 |
|             |   |             |   |            |   |          | g |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | n |                 |
|             |   |             |   |            |   |          | s |                 |
|             |   |             |   |            |   |          | w |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | t |                 |
|             |   |             |   |            |   |          | e |                 |
|             |   |             |   |            |   |          | r |                 |
|             |   |             |   |            |   |          | \ |                 |
|             |   |             |   |            |   |          | ] |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| **          |   |             |   |            |   |          |   |                 |
| Antifouling |   |             |   |            |   |          |   |                 |
| Coatings    |   |             |   |            |   |          |   |                 |
| (Use        |   |             |   |            |   |          |   |                 |
| Category    |   |             |   |            |   |          |   |                 |
| IX)**       |   |             |   |            |   |          |   |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| Sonar Domes | U |             | S |            | 1 |          | 5 |                 |
| & Hulls     | n |             | T |            | 2 |          | . |                 |
|             | k |             | / |            | 2 |          | 7 |                 |
|             | n |             | I |            | 5 |          | 8 |                 |
|             | o |             | T |            | - |          | % |                 |
|             | w |             | H |            | 1 |          | a |                 |
|             | n |             | a |            | 1 |          | i |                 |
|             |   |             | n |            |   |          | i |                 |
|             |   |             | d |            | 7 |          | n |                 |
|             |   |             | l |            | 4 |          | f |                 |
|             |   |             | e |            | 4 |          | o |                 |
|             |   |             | r |            | 8 |          | r |                 |
|             |   |             | : |            | 9 |          | m |                 |
|             |   |             |   |            | - |          | u |                 |
|             |   |             | I |            | 0 |          | l |                 |
|             |   |             | n |            | 1 |          | a |                 |
|             |   |             | h |            |   |          | t |                 |
|             |   |             | a |            |   |          | i |                 |
|             |   |             | l |            |   |          | o |                 |
|             |   |             | a |            |   |          | n |                 |
|             |   |             | t |            |   |          |   |                 |
|             |   |             | i |            |   |          | 5 |                 |
|             |   |             | o |            |   |          | 3 |                 |
|             |   |             | n |            |   |          | % |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             | D |            |   |          | i |                 |
|             |   |             | e |            |   |          | i |                 |
|             |   |             | r |            |   |          | n |                 |
|             |   |             | m |            |   |          | f |                 |
|             |   |             | a |            |   |          | o |                 |
|             |   |             | l |            |   |          | r |                 |
|             |   |             |   |            |   |          | m |                 |
|             |   |             | ( |            |   |          | u |                 |
|             |   |             | a |            |   |          | l |                 |
|             |   |             | s |            |   |          | a |                 |
|             |   |             | s |            |   |          | t |                 |
|             |   |             | u |            |   |          | i |                 |
|             |   |             | m |            |   |          | o |                 |
|             |   |             | e |            |   |          | n |                 |
|             |   |             | d |            |   |          |   |                 |
|             |   |             | ) |            |   |          |   |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| **Wood      |   |             |   |            |   |          |   |                 |
| Pr          |   |             |   |            |   |          |   |                 |
| eservatives |   |             |   |            |   |          |   |                 |
| (Use        |   |             |   |            |   |          |   |                 |
| Category    |   |             |   |            |   |          |   |                 |
| X)**        |   |             |   |            |   |          |   |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+
| Staining    | P |             | S |            | 1 |          | 0 |                 |
|             | a |             | T |            | 0 |          | . |                 |
| (commercial | i |             | / |            | 2 |          | 0 |                 |
| painters)   | n |             | I |            | 2 |          | 6 |                 |
|             | t |             | T |            | - |          | 2 |                 |
|             | b |             | H |            | 5 |          | l |                 |
|             | r |             | a |            | 1 |          | b |                 |
|             | u |             | n |            | 1 |          | a |                 |
|             | s |             | d |            |   |          | i |                 |
|             | h |             | l |            | ( |          | / |                 |
|             | , |             | e |            | 5 |          | g |                 |
|             |   |             | r |            | 7 |          | a |                 |
|             | A |             | : |            | 7 |          | l |                 |
|             | i |             |   |            | - |          | l |                 |
|             | r |             | I |            | 5 |          | o |                 |
|             | l |             | n |            | 3 |          | n |                 |
|             | e |             | h |            | 9 |          |   |                 |
|             | s |             | a |            | , |          | \ |                 |
|             | s |             | l |            | 5 |          | [ |                 |
|             | s |             | a |            | 7 |          | 8 |                 |
|             | p |             | t |            | 7 |          | . |                 |
|             | r |             | i |            | - |          | 3 |                 |
|             | a |             | o |            | 5 |          | l |                 |
|             | y |             | n |            | 4 |          | b |                 |
|             | e |             |   |            | 4 |          | s |                 |
|             | r |             | D |            | , |          | p |                 |
|             |   |             | e |            | 1 |          | e |                 |
|             |   |             | r |            | 0 |          | r |                 |
|             |   |             | m |            | 2 |          | g |                 |
|             |   |             | a |            | 2 |          | a |                 |
|             |   |             | l |            | - |          | l |                 |
|             |   |             |   |            | 5 |          | d |                 |
|             |   |             |   |            | 1 |          | e |                 |
|             |   |             |   |            | 1 |          | n |                 |
|             |   |             |   |            | , |          | s |                 |
|             |   |             |   |            | 7 |          | i |                 |
|             |   |             |   |            | 3 |          | t |                 |
|             |   |             |   |            | 1 |          | y |                 |
|             |   |             |   |            | 3 |          | x |                 |
|             |   |             |   |            | - |          | 0 |                 |
|             |   |             |   |            | 6 |          | . |                 |
|             |   |             |   |            | , |          | 7 |                 |
|             |   |             |   |            | 8 |          | 5 |                 |
|             |   |             |   |            | 1 |          | % |                 |
|             |   |             |   |            | 7 |          | a |                 |
|             |   |             |   |            | 7 |          | i |                 |
|             |   |             |   |            | - |          | = |                 |
|             |   |             |   |            | 7 |          | 0 |                 |
|             |   |             |   |            | 1 |          | . |                 |
|             |   |             |   |            | ) |          | 0 |                 |
|             |   |             |   |            |   |          | 6 |                 |
|             |   |             |   |            |   |          | 2 |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | b |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | / |                 |
|             |   |             |   |            |   |          | g |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | l |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | n |                 |
|             |   |             |   |            |   |          | o |                 |
|             |   |             |   |            |   |          | f |                 |
|             |   |             |   |            |   |          | s |                 |
|             |   |             |   |            |   |          | t |                 |
|             |   |             |   |            |   |          | a |                 |
|             |   |             |   |            |   |          | i |                 |
|             |   |             |   |            |   |          | n |                 |
|             |   |             |   |            |   |          | \ |                 |
|             |   |             |   |            |   |          | ] |                 |
+-------------+---+-------------+---+------------+---+----------+---+-----------------+

[^1]: *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.