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2Docket Number EPA

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3 TBTO Registration Review Team

Human Health & Environmental Effects Michelle Centra Nathan Mottl William Erickson Najm Shamim Siroos Mostaghimi

Health Effects Division Julie Van Alstine

Risk Management Sandra O’Neill /SanYvette Williams Terria Northern Rose Kyprianou

Office of General Counsel Philip RossDocket Number EPA

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### Table of Contents
Introduction

................................ ................................ ................................ ........................... 5 1.1 Statutory and Regulatory Authority

................................ ................................ ............... 5 1.2 Case Overvi ew

................................ ................................ ................................ ............... 6 1.3 Chemical Identification and Properties

................................ ................................ .......... 7 1.4 Use/Usage Information

................................ ................................ ................................ .. 8 1.4.1 Registrations

................................ ................................ ................................ .................... 8 1.5 Regulatory History

................................ ................................ ................................ ......... 8 1. 5.1 Recent/Pending Regulatory Actions

................................ ................................ .............. 8 1.5.2 Tolerance Information

................................ ................................ ................................ .... 8 1.6 Incidents

................................ ................................ ................................ ......................... 8 1.6.1 Human Health Incidents

................................ ................................ ................................ . 8 1.6.1 Ecological Incident s

................................ ................................ ................................ ....... 9 Anticipated Data Needs

................................ ................................ ................................ ........ 9 Human Health Assessment

................................ ................................ ................................ ... 9 3.1 Hazard Characterization and Risk

................................ ................................ .................. 9 3.2 Dietary Exposure Assessment

................................ ................................ ........................ 9 3.3 Occupational and Residential Exposure Assessment

................................ ..................... 9 3.4 Aggregate and Cumulative Exposure

................................ ................................ ........... 10 Environmental Risk Assessment

................................ ................................ ......................... 10 4.1 Environmental Fate and Exposure

................................ ................................ ............... 11 4.2 Ecological Ri sk Characterization

................................ ................................ ................. 11 4.3 Threatened and Endangered Species

................................ ................................ ............ 11 Endocrine Disruptor Screening Program (EDSP)

................................ ............................... 11 Optional Label Changes

................................ ................................ ................................ ...... 12 Combined Preliminary Work Plan and Proposed Interim Registration Review Decision

. 12 Next Steps and Timeline

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

Appendix A T oxicology Profile

................................ ................................ ............................. 14 Appendix B REFERENCES

................................ ................................ ................................ .. 22

List of Tables Table 1

– Summary of Anticipated Risk Assessments and Data Needs for Registration Review for TBTO

................................ ................................ ................................ ................................ ........ 6 Table 2

– Anticipated Combined Prelimina ry Work Plan and Proposed Interim Registration Review Schedule for TBTO

................................ ................................ ................................ ............ 6 Table 3

– Chemical Facts for TBTO

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## Introduction

This document is the Environmental Protection Agency’s (EPA or “ the a gency ” ) combined Preliminary Work Plan (PWP) and Proposed Interim Registration Review Decision for
t ributy ltin oxide , herein referred to as TBTO

, and is being issued pursuant to 40 CFR Sections 155.50, 155.5 6 and 155.58. This document explains what EPA’s Office of Pesticide Programs know s about TBTO

, noting that no additional data or further assessments are re quired, and provides an anticipated timeline for completing TBTO ’s review.

A registration review decision is the a gency's determination whether a pesticide meets, or does not meet, the standard for registration in the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The agency may issue, when it determines it to be appropriate, a proposed interim registration review decision before completing a registration review. Among other things, the proposed interim registration review decision may req uire new risk mitigation measures, impose interim risk mitigation measures, identify data or information required to complete the review, and include schedules for submitting the required data, conducting the new risk assessment and completing the registra tion review.

TBTO, formerly known as the Tributyltin (TBT)

- Containing Compounds, is registered for use as an antifouling coating. It is formulated as ready

- to

- use solutions. The first tributyltin (TBT)

- containing product s w ere registered in the 1960’s

. The Reregistration Eligibility Decision document (RED) for TBTO was issued in 200 8. There are t wo registered TBT O p roducts use d in anti fouling systems in the U.S. These two applications are for (1) incorporation into rubber for the formation of sonar do mes used in US Navy vessels and for (2) use in antifoul ing devices within oceanographic instruments deployed by government researchers to monitor global ocean conditions (i.e., conductivity sensors). All other uses have been cancelled. Documents associate d with this registration review can be found in docket EPA

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- 801 at www.regulations.gov

.


## 1.1 Statutory and Regulatory Authority

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review p rogram. All pesticides distributed or sold in the United States generally must be registered by the USEPA based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product label ing. The registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human he alth or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the agency periodically reevaluates pesticides to make sure that as change occurs, products in the market place can be used safely. Information on this program is provided at http://www2.epa.gov/pesticide

- reevaluation.

The agency is implementing the registration review program pursuant to Section 3(g) of the FIFRA and will review each registered pesticide ever y 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registrationDocket Number EPA

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6 review begin at 40 CFR 155.40. The agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the agency’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a regist ration review decision.



## 1.2 Case Overview

The docket for TBTO (case 2620 ) has been established at http://www.regulations.gov in docket number EPA

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- 080 1 . Documents associated with this registration review can be viewed in this docket. Tables 1 and 2 below summarize the issues relevant to this registration review case and the anticipated registration review schedule.

Table 1

– Summary of Anticipated Risk Assessments and Data Needs for Registration Review for TBTO

Risk Assessm ent Assessment Necessary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Anticipated as Needed

Dietary (food/ drinking water ) No N/A None None

Occupational & Residential Handler/Post Applica tion No N/A None None

Aggregate No N/A None None

Cumulative No N/A None None

Tolerance Review No N/A None None Ecological No N/A None None N/A = Not applicable

Table 2

– Anticipated Combined Preliminary Work Plan and Proposed Interim Registration Review Schedule for TBTO
Anticipated Activity Target Date* Completion Date Combined Preliminary Work Plan and Interim Registration Review Decision and Implementation Open 60

- Day Public Comment Period for Combined Preliminary Work Plan and Proposed Interim Decision 06

- 201 5

Close Public Comment Period 0 8

- 2015
Issue Interim Decision 12

- 2015 Begin Post Decision Follow up 201 6 Total (years) 1

* The anticipated schedule will be revised as necessary ( e.g ., need arising under t he Endocrine Disruptor Screening Program with respect to the active ingredients in this case).Docket Number EPA

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## 1.3 Chemical Identification and Properties
Table 3 presents the active ingredient to be assessed in case 2620: TBTO (PC Code 083001). The TBTO case was formerly known as the Tributyltin (TBT)

- Containing Compounds case. The agency completed a RED for the TBT

- Containing Compounds in 2008. At that time, the case consisted of three compounds: bis

- tributyltin oxide (PC code 083001, TBTO), tributyltin benzoate (PC Code 083106, TBTB), and tributyltin maleate (PC Code 083118, TBTM). There are no inert uses of TBT in pesticides. The agency also notes that stannane, tributyl(2

- methyl

- 1

-
oxo

- 2

- propenyl)oxy

- (PC Code 083120) is a TBT

- containing compound with no EPA registratio ns , and therefore it will not be included in this registration review or undergo further evaluation

. As such, this registration review case will assess registrations only for TBTO (PC Code 083001).

Table 3

– Chemical Facts for TBTO

Chemical Name TBTO Pesticide type Antifouling Coatings (Nonfood Use) Case 2620 Chemical Classification Organometallic
PC Code 083001
CAS Number 26

- 35

- 9 Molecular Formula C 24 H 54 OSn 2 Molecular Weight (grams/mole) 596.12

Molecular Structure

Year first registered 1960 Reregistration Eligibility Decision (RED) 2008

Dual use Antimicrobial use only

40 CFR Citation There are no registered food/feed uses and no established tolerances for TBTO Antimicrobials Division, Chemical Review Manager Sandra O ’Neill, oneill.sandra@epa.gov, (703) 347

- 0141

Antimicrobials Division, Product Manager Terria Northern

, northern. @epa. gov, PM reviewerDocket Number EPA

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## 1.4 Use/Usage Information

1.4.1 Registrations

There are two EPA

- registered products that contain TBTO as an active ingredient (a.i.) at concentrations of 5.78 percent and 53 percent a.i. TBTO . The EP is formulated as ready

- to

- use solutions.



## 1.5 Regulatory History

The first pesticides containing TBT compounds were registered in the 1960s, for use in antifouling paints. Adverse ecological effects associated with TBT antifouling paints captured global attention in the 1980s. In 2005, the agency processed the voluntary cancellation of the last TBT (now TBTO, PC code 083001) registration for ship hull antifouling use

. In 2008, EPA completed the Reregistration Eligibility Decision (RED) for tributyltin

, and Data Call Ins ( DCIs ) requiring confirmatory data were issued in September 2011

. An international treaty prohibiting the use of TBT O hull coatings became effective in September 2008. It remains legal to distribute, sell , and use TBT O antifouling systems in the U.S. for two applications for (1) incorporation into rubber for the formation of sonar domes used in US Navy vessels and for (2) use in antifoul ing devices wi thin oceanographic instruments deployed by government researchers to monitor global ocean conditions (i.e., conductivity sensors). The rubber application is considered to be critical for naval operations and releases a much smaller amount of TBTO into the aquatic environment than did the antifouling hull coatings. For the antifoul ing devices use, the total amount of TBTO present in the oceanographic instruments is small, and the use is considered to be critical by government research organizations such as t he National Oceanographic and Atmospheric Administration (NOAA)

.


## 1.5. 1 Recent/ Pending Regulatory Actions

There are no recent or pending regulatory actions for TBTO.



## 1.5.2 Tolerance Information

There are no U

. S

. tolerances or exemptions from tolerances for TBTO because there are no currently registered uses under FIFRA for this active ingredient that are associated with food or feed.



## 1.6 Incidents

1.6.1 Human Health Incidents
As of April, 2015, t here are no TBTO

- specific human incidents reported in OPP’s Incid ent Data System (IDS) that are associated with current registered uses of this antifouling agent when it is impregnated into rubber sheets for the formation of sonar domes in U.S. Navy vessels and incorporated into instruments for monitoring global oceanog raphic conditions.Docket Number EPA

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## 1.6.1 Ecological Incidents
There are no fish or wildlife poisoning incidents in OPP’s Incident Data System (IDS) involving TBTO as of March 2015. However, the agency is aware that numerous incidents occurred in aquatic ecosystems when the TBTs were widely used as antifoulant coatings on ship hulls (EPA 2008a,b).


## A nticipated D ata N eeds

Although there was a DCI for confirmatory studies from the RED, the uses triggering the need for confirmatory data were voluntarily cancelled

, and theref ore, confirma tory data were not generated. Based on the limited use pattern and low potential exposure, no new risk assessments are planned for TBTO and no additional data are anticipated to be required during registration review.


## Human Health Asses sment

The agency’s human health

, risk assessment for TBTO which w as conducted for th e 200 8 RED can be found in the public docket EPA

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. The agency does not anticipate updatin g the risk assessment for this re gistration review case.



## 3.1 Hazard Characterization and Risk
The toxicological database (Appendix A) i s considered adequate for character izing hazard and assessing risk fro m this use of TBTO (EPA 2008d) . No additional studies are anticipated to be needed for registration review.



## 3.2 Dietary Exposure Assessment

The two FIFRA

- registered uses of TBTO are not expected to result in direct or indirect dietary (food) or drinking water exposure. There are no FDA food use clearances for TBTO. Therefore, a dietary assessment is not required at this time.



## 3.3 Occupational and Residential Exposure Assessment
There are only two registered TBTO products (EPA Reg. No. 74487

- 1 and EPA Reg. No. 1225

- 11). These products are not labeled for residentia l uses and no residential exposure is expected

. EPA Reg. No. 74487

- 1 is an anti

- fouling device impregnated with TBTO. T he antifouling device is used underwater within oceanographic instruments deployed by government researchers to monitor global ocean co nditions. The amount of TBTO used in this antifouling device is minimal (< 0.1 ounces a.i. ) and t he label specifies that handlers must wear protective gloves when working with this device.

EPA Reg. 1225

- 11 is an impregnated TBTO rubber sheet that is used on the hulls of U.S. Navy ships and submarines for the sonar domes located on the hull . According to the label, the impregnated TBTO marine anti

- fouling rubber is designed with special acoustic properties toDocket Number EPA

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10 work well with sonar. Sonar domes of submarines are typically submerged under water on the hull of large ships and submarines. The product is a thin (<1/4 inch thick) TBTO impregnated neoprene rubber (NEOPRENE®) sheet that is used as an antifouling wrap for much of the exterior of the sonar dome. The a coustically

- designed rubber matrix minimizes the potential for handler and post application exposure to TBTO aerosols and the migration of TBTO residues for dermal contact during installation or cleaning when the ships or submarines are out of water. Addit ionally, dermal and inhalation handler exposures are also mitigated by the personal protective equipment (PPE) requirements on the product label which require that handlers use NIOSH/MSHA approved respirators, chemical resistant rubber gloves, safety glass es, face

shields and disposable protective clothing.

O ccupational handler and post application exposure to TBTO while wearing the required PPE is minimal

. 

## 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures

A ggregate exposure s are not anticip ated since there are no dietary or residential concerns.

3.4.2 Cumulative Exposures

With respect to cumulative exposure, 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 toxic ity finding as to TBTO and any other substances and TBTO does not appear to produce a toxic metabolite produced by other substances. For the purposes of this registration review, therefore, EPA has not assumed that TBTO has a common mechanism of toxicity w ith 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 http://www .epa.gov/pesticides/cumulative/

. 

## Environmental Risk Assessment

The agency has not previously conducted a risk assessment that supports a complete endangered species determination

. No risk assessment has previously been conducted for the use of TBTO on

na val sonar domes and oceanographic instruments deployed by government researchers . For the RED (EPA 2008a,b), the agency only assessed the potential environmental risks associated with use of the TBT O as a n outdoor wood preservative, which was the major us e of the TBT Os at that time. That assessment concluded that endangered aquatic invertebrates could be at acute risk from exposure to TBTO leached from wood and into the aquatic environment.

The available acute toxicity data for a variety of freshwater an d estuarine/marine species characterize TBTO as being very highly toxic to aquatic organisms (EPA 2008a,b ). The open literature also contains considerable information on the toxicity of TBTO to aquatic invertebrates, including reports of shell deformation in oysters and reproductive aberrations (imposex) in certain marine snails (EPA 200 3 ).Docket Number EPA

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## 4.1 Environmental Fate and Exposure
TBTO is persistent in water (MRID # 41557801) and binds strongly to soils and sediments

. F ate data show that TBTO is highly bioaccumul ative, and is not readily biodegradable. A fate assessment for TBTO was completed for the RED and can be found at www.regulations.gov in docket # EPA

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## 4.2 Ecological Risk Characterization

TBTO is hi ghly toxic to aquatic organisms (EPA, 2008a,b)

. However, because TBTO is currently used only on sonar domes ( TBTO is incorporated into the rubber dome) and marine instrume nts, exposure would occur only fr o m the small amount of TBTO potentially leaching fro m the se surfaces. Additionally, because these applications use only a small quantity of TBTO, risks from leachate from the rubber domes and instruments are likely to be minimal

. Nevertheless, a potential for some risk exists if aquatic organisms are expo sed to any TBTO that leaches out

. 

## 4.3 Threatened and Endangered Species
Although EPA has not previously conducted a risk assessment for TBTO to support a complete endangered species determination , the use of TBTO as an antifoulant on s onar d omes on vessels

o f the Armed Forces will be covered during DoD's and EPA's Uniform National Discharge Standards (UNDS) consultation process . The UNDS rulemaking process was divided into two batches. Sonar Dome discharge is included in the "Batch 2" discharges. The Endange red Species Act ( ESA ) consultation for "Batch 2" is projected to begin in 2016.

Because potential risk to endangered species will be evaluated by the UNDS consultation
process, EPA anticipates conducting no further analysis of potential risks to endangere d or threatened species under registration review

. After the UNDS consultation is complete, any recommendations will be implemented on TBTO pesticide labels. 

## Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews nume rous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive los s, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its 200 8 RED for TBTO , EPA reviewed thes e data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database . However, as required by FFDCA section 408(p), TBTO is subject to the endocrine screening part of the Endocrine Disruptor Screening P rogram (EDSP).Docket Number EPA

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12 EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such e ndocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to intera ct with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and establish a dose

- response relationship between the dose and t he E, A, or T effect.

U nder FFDCA section 408(p), the a gency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingred ients and nine inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013

1 2 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be const rued as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 3

2 

## Optional Label Changes

The agency invites comment on any label amendments that could be considered to improve label clarity. 

## Combined Preliminary Work Plan and Pr oposed Interim Registration Review Decision

In accordance with 40 CFR Sections 155.50, 155. 5 6 and 155.58, the a gency is issuing this

c ombined Preliminary Work Plan and Proposed Interim Registration Review Decision document. Except for the EDSP component of the TBTO registration review case, t he a gency has made the following proposed decision tha t n o additional data and no further risk assessments are required

. In addition, EPA will rely on the ESA consultation for the DoD ’ s and EPA’s UNDS to make a determination under the E SA for all listed species and designated cri tical habitat for such species. 

## Next Steps and Timeline

2 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

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- 2009

- 0477

- 0074 for the final second list of chemicals.

3 h ttp://www.epa.gov/endo/

.Docket Number EPA

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13 A Federal Register N otice will announce the availability of this combine d Preliminary Work Plan and Proposed Interim R egistration R eview D ecision for TBTO and allow a 60

- day comment period (see Table 2)

. If there are no significan t comments or additional information submitted to the docket during the comment period that lead the a gency to change its proposed decision, EPA may issue an interim decision. The final decision on the r egistration r eview for TBTO will occur after the ESA consultation an d EDSP FFDCA section 408(p) determination have been made

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# Appendix A T oxicology Profile

Acute Toxicity for Product Labeling

TGAI tributyltin oxide has a high order of acute toxicity via the oral route of exposure (Toxicity Category II) ; it is not a skin sensitizer.

Table A1

– Acute Toxicity Studies for TGAI Tributyltin Oxide

Guideline No./ Study Type MRID Number(s) Results Toxicity Category

870.1100/ Acute oral toxicity 00085004, 92172013 LD 50 = 180 mg/kg (males) LD 50 = 150 mg/kg (fema les) LD 50 = 170 mg/kg (combined) I I

870.1100/ Acute oral toxicity 00085003, 92172004 LD 50 = 123 mg/kg (females) LD 50 = 160 mg/kg (combined) II

870.2600/ Skin sensitization 00104789, 92172014 Buehler: Not a skin sensitizer Not applicable



## Subchronic/Chr onic Toxicity Studies

Table A2

- Subchronic, Chronic and Other Toxicity Profile for TGAI Tributyltin Oxide

Guideline No. and Study Type MRID No. and Citation Dosing and Animal Information Results

Range

- finding Toxicity
Non

- guideline Range

- finding Study in Mice MRID 41127001 Daly, I. (1989) A three month oral range

- finding toxicity study in mice with bis (tri

- n

- butyltin) oxide (TBTO). Bio/dynamics, Inc. (East Millstone, New Jersey). Unpublished. CD

- 1 ® mice (male and female)

Purity 97.1 % a.i.

0 , 4, 20 , 80, or 200 ppm (equivalent to 0.7, 3.8, 15.1, or 36.9 mg/kg bw/day in males; 1.0, 4.9, 17.9, or 46.9 mg/kg bw/day in females) for 13 weeks (diet). NOAEL = 4 ppm (equivalent to 0.7 mg/kg bw/day in males; 1.0 mg/kg bw/day in females). LOAEL = 20 ppm (equiv alent to 3.8 mg/kg bw/day in males; 4.9 mg/kg bw/day in females) based on mild hepatotoxicity and dermal irritation in the ear observed in male mice. Un acceptable /Non

- g uideline

Non

- guideline Range

- finding S tudy in Dogs MRID 41131001 Schweinfurth, H. (198 7) Tributyltin oxide: Systemic toxicity study in Beagle dogs with daily oral (intragastric) administration over a total of 18

- 19 weeks. Schering AG, Berlin, Germany. Laboratory Project ID: TX 87.054, August 5, 1987. Unpublished. Beagle dog s

Purity >96.1% a.i.

0, 0.1, 0.5, or 2.5 mg/kg during Weeks 1

- 5; 0, 0.2, 1.0, or 5.0 mg/kg during Weeks 6

- 10; and 0, 10, 1.0, or 5.0 mg/kg during Weeks 11

- 19. Exposure to Tributyltin oxide caused elevated alkaline phosphatase and slight changes in s erum protein composition at 1.0 mg/kg/day after 13

- 14 weeks of exposure. While further biochemical changes and suspected effects on red and white blood cells were observed at 2.5 mg/kg/day after 5 weeks of exposure and at 5.0 mg/kg/day after 13

- 14 weeks of exposure, there was no evidence of organDocket Number EPA

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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 e ffect) were observed. A dose of 10 mg/kg/day was considered to be too toxic of a dose for the 1

- year oral dog study; therefore, dose levels of 0.2, 1.0, and 5.0 mg/kg/day were recommended for the 1

- year study. Unacceptable/ Non

- guideline Prenatal D evelopmental Toxicity
870.3700 Prenatal Developmental Toxicity Study MRID 00137158 Schroeder, R.; Hogan, G. (1981) A Teratology Study in Rats with Tributyltin Oxide: Project No. 80

- 2497A. Final rept. (Unpublished study received Jan 16, 1984 under 5204

- 1 ; prepared by Bio/dynamics, Inc., submitted by M & T Chemicals Inc., Rahway, NJ; CDL:252178

- A).

MRID 92172016 Schroeder, R. (1992) M&T Chemicals, Inc. Phase 3 Reformat of MRID 00137158. A Teratology Study in Rats with Tributyltin Oxide: Project No. 80

- 249 7A. Prepared by Bio/dynamics, Inc. 83 p. Female pregnant CD ® (Sprague

- Dawley derived) rats

Purity not reported

0, 5, 9, 18 mg/kg/day (via gastric intubation (gavage) Maternal Toxicity NOAEL = 5 mg/kg/day LOAEL = could not be identified due to the lack of data.

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

870.3700 Prenatal Developmental Toxicity Study MRID 40141901 Nemec , M. (1987) (Tributyltin Oxide)

- A Teratology Study in Rabbits with TBTO: Laboratory Project ID: WIL

- B0002. Unpublished study prepared by Wil Research Laboratories, Inc. 210 p.

MRID 92172006 New Zealand White female rabbits

Purity >95%

0, 0.2, 1.0, 2.5 mg/kg/day ( oral gavage) Maternal Toxicity NOAEL = 1.0 mg/kg/day LOA EL = 2.5 mg/kg/day, based on increased incidence of abortion and decreased mean maternal body weight gain.

Developmental Toxicity NOAEL = is equal to or greater than 2.5 mg/kg/day LOAEL = is greater than 2.5 mg/kg/day (could not be established)Docket Number EPA

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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. Accept able/ Guideline

Reproduction and F ertility R ates 870.3800 Reproduction and

Fertility effects MRID 41693801 Schroeder, R.E. (1990) A two generation reproductions study in rats with bis (tri

- n

butyltin) oxide

. Bio/dynamics, Inc., East Millstone, NJ. Labo ratory Project No.: 88

- 3261, October 22, 1990. Unpublished Sprague Dawley rats

Purity 97.1%

0, 0.5, 5, or 50 ppm for two successive generations (diet) Parental Toxicity NOAEL = 5 ppm (equivalent to 0.33/0.39 mg/kg/day in males/females). LOAEL = 5 0 ppm (equivalent to mg/kg/day 3.47/3.93 in males/females) based on anogenital staining in the P dams; decreased body weights in the F1 males and females during pre

- mating and continuing in the F1 males during the mating and post mating periods; and decrea sed 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 m g/kg/day in males/females). LOAEL = 50 ppm (equivalent to 3.47/3.93 mg/kg/day in males/females) based on decreased pup body weights in both generations Acceptable/ Guideline Chronic Toxicity
870.4100 Chronic Toxicity MRID 42549801 Schuh, W. (1992) Bis ( tri

n

- butyltin) oxide (TBTO; ZK 21.955): 12

- month chronic oral toxicity study in beagle dogs. Schering AG, Berlin, Germany. Laboratory Project ID: Study Number TX Beagle dogs

Purity 95.9

- 97.1% a.i

.
0, 0.2, 1.0 , or 5.0 mg/kg/day for 52 weeks (oral gavage) Multiple microscopic finding indicative of immunotoxicity (detailed above) were noted at 1.0 mg/kg/day, particularly in the males. At 5.0 mg/kg/day, increased severity of immunotoxicity and indications of

s ystemic toxicity (including mortality, clinical signs of toxicity, overall body weight losses, decreased body weights and food and waterDocket Number EPA

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17 Guideline No. and Study Type MRID No. and Citation Dosing and Animal Information Results

85.330, September 4, 1992. Unpublished. consumption, increased blood sedimentation rate, decreased nucleated bone marrow cellularity, increased hepatic enzymes , increased liver weight, decreased spleen and thymus weights, and gross pathological findings in the liver, spleen, and thymus) were observed. Unacceptable/ Guideline (not upgradeable) Carcinogenicity
870.4200 Carcinogenicity MRID 42265001 Daly, I. (1992 ) An eighteen month oncogenicity feeding study in mice with bis (tri

- n

- butyltin) oxide (TBTO). Bio/dynamic, Inc. Project No. 87

- 3131, March 27, 1992. Unpublished CD

- 1 mice

Purity 97.1% pure

0, 5, 25, or 50 ppm (equivalent to 0.7, 3.7, and 7.7 mg/kg/da y for low

- , mid

- , and high

- dose males, respectively, and 0.9, 4.8, and 9.2 mg/kg/day for low

- , mid

- , and high

- dose females, respectively) for 18 months (diet) LOAEL = 0.7 mg/kg/day ( males ) LOAEL = 0.9 mg/kg/day ( females ), based on decreased survivorship a nd increased body weight gain

. Acceptable/ Guideline

Combined Chronic Toxicity/Carcinogenicity
870.4300 Combined chronic toxicity/Carcinoge nicity MRID 40623201 Wester, P.W.; Krajnc, E.I.; et al. (1988) Bis (tributyltin) oxide

– Two year feeding study in rats with bis (tri

- n

- butyltin) oxide. RIVM, Bilthoven, The Netherlands. Laboratory Report No.: 658112 002, February 25, 1988. Unpublished. Wistar rats

Purity 95.3% a.i.

0, 0.5, 5, or 50 ppm (approximately equivalent to 0, 0.025, 0.25, and 2.5 mg/kg b w/day (diet) NOAEL = 5 ppm (approximately equivalent to 0. 25 mg/kg bw/day)

. LOAEL = 50 ppm (approximately equivalent to 2.5 mg/kg bw/day) based on increased mortality, systemic toxicity (ataxia, emaciation and decreased body weight/body weight gain in male s and females) and organ toxicity (kidney, thyroid, adrenal glands, and pituitary. Acceptable/ Guideline
Mutagenicity
870.5100 Bacterial R everse

M utation T est MRID 42170001 Lang, R. (1986) Evaluation in the Ames Salmonella/Microsome Mutagenicity Test: ZK 21.955: Lab project Number: TX6106. Unpublished study prepared by Schering Ag. 29 p. Salmonella typhimurium TA 1535, TA 100, TA1537, TA 1538, and TA 98

Purity: 97.1 ± 3.4 % and 103 ± 5.6%

0.0001, 0.00025, 0.0005, 0.001, 0.0025, 0.005, 0.01, 0. 02 and 0.03 μl/plate (without metabolic activation)

0, 0.001, 0.0025, 0.005, 0.01, 0.02, 0.03, 0.04 and 0.05, 0.08 Negative

No evidence of mutagenic activity in the presence or absence of metabolic activation (S9 from rat liver) in strains of S. typhimurium. Acceptable/ GuidelineDocket Number EPA

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or 0.15 μl/plate (with metabolic activation) 870.5375 In vitro C hromosome A berration T est (Rat) MRID 40253005 Brunneman, A. (1986) Evaluation of the Clastogenic Potential in the Human Lymphocyte Test: ZK 21.955: Lab. Proj. ID IC 4/86. Un

published study prepared by Schering AG. 23 p. human lymphocyte

Purity 97.1 ± 3.4% and 103.0 ± 5.6% 0.0025, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, 0.5 and 1.0 μg/ml (without activation)

0.01, 0.025, 0.05, 0.1, 0.25, 0.5, 1.0, 2.5 and 5.0 μg/ml with metabolic activation Negative

There was no evidence of chromosome aberration induced when compared with the negative control. However, at higher concentrations reduction in the mitotic index was observed. Acceptable/Guideline

870.5385 or 870.5 395 Study not submitted

Metabolism and Pharmacokinetics
870.7485 Metabolism and Pharmacokinetics MRID 01246480 Evans, W., D. Smith, and N. Cardarelli (date of study not provided) Accumulation and excretion of [1

- 14 C] bis (tri

- n

- butyltin) oxide in mice. E nvironmental Management Laboratory, The University of Akron (Akron, Ohio). Unpublished. F emale COBS albino mice

Purity not reported

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

- TBTO were greatest in the kidneys, fat, liver, and spleen. Concentrati ons were found to be proportional to administered dose except in the kidney. Tissue accumulations were concentration dependent. The quantities absorbed were rapidly cleared when ingestion ceased. Acceptable/ Non

- guideline 870.7485 Metabolism and Ph armacokinetics MRID 40253002 Humpel, M. (1986) Toxicokinetics of 113 Sn

labelled tributyltin oxide after intravenous (1 mg/kg) and intragastric (25 mg/kg) administration to rats: bioavailability, excretion, and biotransformation. Schering AG, Berlin, Germ any. Laboratory report numbers IC

- Kl 3, KI 84 061, and KI 84 062. January 23, 1986. Unpublished

. F emale Wistar

- Han (SPF) rats

Purity (>99%a.i)

1 mg/kg or 25 mg/kg Absorption was very delayed after gavage administration, with a half

life of 9.5 hours

. The intravenously administered 113 Sn

- labeled TBTO is rapidly distributed, with only 3% of the dose remaining in plasma volume after 5 minutes post administration. Based on the high volume of distribution and the binding to the cellular constit uents of the blood, authors conclude that TBTO has a pronounced affinity for tissues. Acceptable / Non

- guideline

Dermal Penetration
870.7600

Dermal Penetration MRID 40050003 Hümel, M. (1985) Series 85

- 2: Percutaneous absorption of tributyltin oxide (TBTO ) through intact skin of baboon. Male baboon

Purity not reported

Dose volume 0.5 mL/25 cm 2 skin The total recovery of radioactively labeled 113 Sn

- Tributyltin oxid e was less than 50%, perhaps due to the incomplete removal of unabsorbed TBTO on the skin surface as a result of extensive spreading from the siteDocket Number EPA

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Scherling AG, Berlin 65, Germany. Laboratory Project ID IC

- KI 2, June 12, 1985. Unpublished of application. However, reviewer generated data indicates that the total recovery was approximately 75%. Un acceptable/ Non

- guideline Published Literature Non Guideline Literature Study Vos et al., (1990) Immunotoxicity of bis (tri

- n

- butyltin) oxide in the rat: Effects on thymus

- dependent immunity and on nonspecific resistance following long

- term exposure in yo ung vs aged rats. Toxicol. Appl. Pharmacol. 105:144

- 155. Wistar Rats

Purity: 95.3% active ingredient

E xposure to TBTO for up to 18 months

D ietary concentration s: 0.025, 0.25 and 2.5 mg/kg

- day. NOAEL = 0.025 mg/kg/day LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of IgE titers and increase in T. spiralis larvae in muscle) following 4 months and 16.5 months of exposure to Tributyl Tin Oxide. (Review by EPA/IRIS, 1997).

Under the Reregistration Eligibility Decision for the Tributyltin Co mpounds: Bis(tributyltin) oxide, Tributyltin benzoate, and Tributyltin maleate (Case 2620) (EPA 739

- R

- 08

- 005, June, 2008)

, toxicological endpoints were selected from the TBTO toxicity database for conducting risk assessments in occupational and non

- occupat ion settings (Table A3). These existing toxicological endpoints remain adequate for regulatory purposes and therefore, can be used to assess potential TBTO risk(s) to humans during incorporation of this active ingredient into rubber for the formation of s onar domes used in U.S. Navy vessels and when used in antifoulant devices within oceanographic instruments deployed by government researchers to monitor global ocean conditions (i.e., conductivity sensors). No additional toxicological data for TBTO are an ticipated to be required at this time. However, if new product registrations are submitted to the agency that are not support ed by these existing TBTO data, additional toxicological data may be required.

Table A3

- Summary of Toxicolog ical Endpoint Select ion for TGAI Tributyltin Oxide

Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Special Sensitivity*, UF, Target MOE, for Risk Assessment Study and Toxicological Effects

Dietary Risk Assessments

Acute Dietary (females 13

- 49 and general population) No appropriate endpoints were identified in the oral toxicity studies that represent a single dose effect for the general population and females 13

- 49. In addition, the current use patterns for the tributyltin

- containing chemic als do not indicate the potential for direct or indirect dietary exposures. Therefore, an acute dietary risk assessment is not required.Docket Number EPA

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20 Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Special Sensitivity*, UF, Target MOE, for Risk Assessment Study and Toxicological Effects

Chronic Dietary (all populations) BMD 10 = 0.03 mg/kg/day based on immunosupression (established by EPA/IRIS and used to estimate the oral RfD). Special Sensitivity = 10 UF = 100 (10x inter

- species extrapolation, 10x intra

species variation)

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

Although the current use patterns for the tributyltin

containing chemicals do not indi cate the potential for chronic dietary exposures, this endpoint is selected for future reference. A chronic dietary risk assessment is not required at this time. Open Literature Study

Vos et al. , (1990) Immunotoxicity of bis (tri

- n

- butyltin) oxide in th e rat: Effects on thymus

- dependent immunity and on nonspecific resistance following long

term exposure in young vs aged rats. Toxicol. Appl. Pharmacol. 105:144

- 155.

NOAEL = 0.025 mg/kg/day LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of I gE titers and increase in T. spiralis larvae in muscle) following 4 months and 16.5 months of exposure to Tributyl Tin Oxide. (Review by EPA/IRIS, 1997).

Non

- Dietary Risk Assessments Incidental Oral Short

Term (1

- 30 days) and Intermediate

- Term (1

- 6 months) BMD 10 = 0.03 mg/kg/day based on immunosupression (established by EPA/IRIS and used to estimate the oral RfD). Special Sensitivity = 10 UF = 100 (10x inter

- species extrapolation, 10x intra

species variation) Target MOE res. = 1000 Open Literatu re Study

Vos et al. , (1990) Immunotoxicity of bis (tri

- n

- butyltin) oxide in the rat: Effects on thymus

- dependent immunity and on nonspecific resistance following long

term exposure in young vs aged rats. Toxicol. Appl. Pharmacol. 105:144

- 155.

NOAEL = 0.025 mg/kg/day LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of IgE titers and increase in T. spiralis larvae in muscle) following 4 months and 16.5 months of exposure to Tributyl Tin Oxide. (Review by EPA/IRIS, 1997).

Dermal (all duration s) BMD 10 = 0.03 mg/kg/day based on immunosupression (established by EPA/IRIS and used to estimate the oral RfD). Special Sensitivity = 10 UF = 100 (10x inter

- species extrapolation, 10x intra

species variation) Target MOE occ. = 100 Target MOE res. = 1000 Open Literature Study

Vos et al. , (1990) Immunotoxicity of bis (tri

- n

- butyltin) oxide in the rat: Effects on thymus

- dependent immunity and on nonspecific resistance following long

term exposure in young vs aged rats. Toxicol. Appl. Pharmacol. 105:144

- 1 55.

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).Docket Number EPA

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21 Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Special Sensitivity*, UF, Target MOE, for Risk Assessment Study and Toxicological Effects

Inhala tion (all durations) BMD 10 = 0.03 mg/kg/day based on immunosupression (established by EPA/IRIS and used to estimate the oral RfD). Special Sensitivity = 10 UF = 100 (10x inter

- species extrapolation, 10x intra

species variation) Target MOE occ. = 100 Targ et MOE res. = 1000 Open Literature Study

Vos et al. , (1990) Immunotoxicity of bis (tri

- n

- butyltin) oxide in the rat: Effects on thymus

- dependent immunity and on nonspecific resistance following long

term exposure in young vs aged rats. Toxicol. Appl. Pha rmacol. 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/IRI S, 1997).
Dermal Absorption Although there is no guideline dermal toxicity study (range

- 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/ 2005 ) for route

- to

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

- effect relationship. UF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, RfD = refere nce dose, MOE = margin o f exposure, NA = Not Applicable

* The S pecial 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 studies 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. Th erefore, application of this factor provides adequate protect ion to the most sensitive population, children.Docket Number EPA

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22 

# Appendix B REFERENCES

MRID CITATION

00085003 Auletta, C.S., Hodge, P.S., Minczeski, N. et al. (1981)

. Acute Oral Toxicity Study in Rats: Project No. 6656

- 81. (Unpublished study received Oct 15, 1981 un der 5204

- 1; prepared by Bio/ dynamics, Inc., submitted by M & T Chemicals, Inc., Rahway, N.J.; CDL:246070

- A).

00085004 Auletta, C.S., Hodge, P.S., Minczeski, N. et al. (1981)

. Acute Oral Toxicity Study in Rats: Project No. 6657

- 81. (Unpublished study rec eived Oct 15, 1981 under 5204

- 1; prepared by Bio/ dynamics, Inc., submitted by M & T Chemicals, Inc., Rahway, N.J.; CDL:246070

- B).

00104789 Bruan, W., Rinehart, W. (1979)

. A Dermal Sensitization Study in Guinea Pigs: Compound TBTO: Project No. 5056

- 78. ( Unpublished study received Mar 14, 1979 under 5204

- 1; prepared by Bio/dynam ics, Inc., submitted by M & T Chemicals, Inc., Rahway, NJ; CDL: 237804

- A).

01246480 Evans, W., D. Smith, and N. Cardarelli (date of study not provided) Accumulation and excretion of [1

- 14 C] bis(tri

- n

- butyltin) oxide in mice. Environmental Management Laboratory, The University of Akron (Akron, Ohio). Unpublished.

00137158 Schroeder, R., Hogan, G. (1981)

. A Teratology Study in Rats with Tributyltin Oxide: Project No. 80

- 2497A. Fina l rept. (Unpublished study received Jan 16, 1984 under 5204

- 1; prepared by Bio/dynamics, Inc., submitted by M & T Chemicals Inc., Rahway, NJ; CDL:252178

- A).

40050003 Hümel, M. (1985)

. Series 85

- 2: Percutaneous absorption of tributyltin oxide (TBTO) throu gh intact skin of baboon. Scherling AG, Berlin 65, Germany. Laboratory Project ID IC

- KI 2, June 12, 1985. Unpublished.

40141901 Nemec, M. (1987)

. (Tributyltin Oxide)

- A Teratology Study in Rabbits with TBTO: Laboratory Project ID: WIL

- B0002. Unpublished study prepared by Wil Research Laboratories, Inc. 210 p.

40253002 Humpel, M. (1986)

. Toxicokinetics of 113 Sn

- labelled tributyltin oxide after intravenous (1 mg/kg) and intragastric (25 mg/kg) administration to rats: bioavailability, excretion, and biot ransformation. Schering AG, Berlin, Germany. Laboratory report numbers IC

- Kl 3, KI 84 061, and KI 84 062. January 23, 1986. Unpublished.

40253005 Brunneman, A. (1986)

. Evaluation of the Clastogenic Potential in the Human Lymphocyte Test: ZK 21.955: L ab. Proj. ID IC 4/86. Un

- published study prepared by Schering AG. 23 p.Docket Number EPA

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23 40623201 Wester, P.W., Krajnc, E.I. et al. (1988)

. Bis(tributyltin) oxide

– Two year feeding study in rats with bis(tri

- n

- butyltin) oxide. RIVM, Bilthoven, The Netherlands. Labora tory Report No.: 658112 002, February 25, 1988. Unpublished.

41127001 Daly, I. (1989)

. A three month oral range

- finding toxicity study in mice with bis (tri

- n

- butyltin) oxide (TBTO). Bio/dynamics, Inc. (East Millstone, New Jersey). Unpublished.

41131001 Schweinfurth, H. (1987)

. Tributyltin oxide: Systemic toxicity study in Beagle dogs with daily oral (intragastric) administration over a total of 18

- 19 weeks. Schering AG, Berlin, Germany. Laboratory Project ID: TX 87.054, August 5, 1987. Unpublished.

41557801 Pisigin, Rodolfo, PhD, Liu.Larry, PhD, Zavala, Pedro, PhD (1990). Hydrolysis of Bis (TBTO) in Water. Study Conducted at Laboratory of Environmental Science & Engineering, PO Box #1703, Gainsville, FL 32602

- 1703. Unpublished



### .

41693801 Schroede r, R.E. (1990)

. A two generation reproductions study in rats with bis (tri

n

- butyltin) oxide . Bio/dynamics, Inc., East Millstone, NJ. Laboratory Project No .: 88

- 3261, October 22, 1990. Unpublished.

42170001 Lang, R. (1986)

. Evaluation in the Ames Salm onella/Microsome Mutagenicity Test: ZK 21.955: Lab project Number: TX6106. Unpublished study prepared by Schering Ag. 29 p.

42265001 Daly, I. (1992)

. An eighteen month oncogenicity feeding study in mice with bis(tri

- n

- butyltin) oxide (TBTO). Bio/dynamic, Inc. Project No. 87

- 3131, March 27, 1992. Unpublished.

42549801 Schuh, W. (1992)

. Bis (tri

- n

- butyltin) oxide (TBTO; ZK 21.955): 12

- month chronic oral toxicity study in beagle dogs. Schering AG, Berlin, Germany. Laboratory Project ID: Study Number TX 85.330, September 4, 1992. Unpublished.

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, I nc. 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).Docket Number EPA

- HQ

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24 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

Vos

, J

. S

. , De Klerk

, A

. , Kranjc

, E

. I . et al. (1990). Immunotoxicity of bis (tri

- n

- butyltin) oxide in the rat. Effects on t hymus dependent immunity and on nonspecific resistance following long

- term exposure in young versus aged rats. Toxicology and Applied Pharmacology, 105:144

- 155.

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 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).


### Tributylti n Compounds

– Toxicology Chapter in Support of Issuance of the Reregistration Eligibility Decision (RED) 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, J. Bloom and D. Isbell, February 4, 2008).

EPA

. 2008a. Reregistration Eligibility Decision for the Tributyltin Compounds: Bis(tributyltin) oxide, Tributyltin benzoate, and Tributyltin ma leate (Case 2620). EPA 739

- R

08

- 005, June, 2008.

EPA

. 2008b. Ecological Hazards and Risk Assessment for Tributlytin Compounds . Prepared by W. Erickson, Risk Assessment and Science Support Branch, Antimicrobials Division, January 18, 2008

.
EPA. 2003. Ambient Aquatic Life Water Quality Criteria for Tributyltin (TBT)

– Final

. Office of Water

, Office of Science and Technology, Health and E cological C riteria D ivision, Washington D.C. EPA 822

- R

- 03

- 031 . 138 pp.

EPA

. 1997. Reregistration Eligibility Decis ion (RED) for the Tributyltin Compounds

.