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Docket Number EPA-HQ-OPP-2014-0801

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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 Ross
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Table of Contents

Introduction...........................................................................................................................5

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

1.2 Case Overview ...............................................................................................................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 Incidents.......................................................................................................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 Risk 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 Toxicology 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 Preliminary Work Plan and Proposed Interim Registration 

Review Schedule for TBTO............................................................................................................ 6

Table 3 –Chemical Facts for TBTO................................................................................................ 7
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Introduction 

This document is the Environmental Protection Agency’s (EPA or “the agency”) combined 

Preliminary Work Plan (PWP) and Proposed Interim Registration Review Decision for 

tributyltin oxide, herein referred to as TBTO, and is being issued pursuant to 40 CFR Sections

155.50, 155.56 and 155.58. This document explains what EPA’s Office of Pesticide Programs 

knows about TBTO, noting that no additional data or further assessments are required, and 

provides an anticipated timeline for completing TBTO’s review. 

A registration review decision is the agency'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 require 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 registration 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 products were registered in the 1960’s. The Reregistration Eligibility Decision 

document (RED) for TBTO was issued in 2008. There are two registered TBTO products used

in antifouling systems in the U.S. These two applications are for (1) incorporation into rubber 

for the formation of sonar domes used in US Navy vessels and for (2) use in antifouling devices 

within oceanographic instruments deployed by government researchers to monitor global ocean 

conditions (i.e., conductivity sensors). All other uses have been cancelled. Documents 

associated with this registration review can be found in docket EPA-HQ-OPP-2014-801 at 

www.regulations.gov.

1.1 Statutory and Regulatory Authority

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. 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 labeling. 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 health 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 

marketplace 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 every 15 years to determine whether it 

continues to meet the FIFRA standard for registration. The regulations governing registration 
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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 registration review decision. 

1.2 Case Overview

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

number EPA-HQ-OPP-2014-0801. 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 Assessment 

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 

Application 

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 06-2015

Close Public Comment Period 08-2015

Issue Interim Decision 12-2015

Begin Post Decision Follow up 2016

Total (years) 1

*The anticipated schedule will be revised as necessary (e.g., need arising under the Endocrine Disruptor Screening Program with 

respect to the active ingredients in this case).
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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 

registrations, 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 C24H54OSn2

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 reviewer
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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 TBTO hull coatings became effective in September 2008. It remains legal to 

distribute, sell, and use TBTO 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 antifouling devices within 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 antifouling 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 the 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, there are no TBTO-specific human incidents reported in OPP’s Incident 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 oceanographic conditions.
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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).

Anticipated Data Needs

Although there was a DCI for confirmatory studies from the RED, the uses triggering the need 

for confirmatory data were voluntarily cancelled, and therefore, confirmatory 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 Assessment

The agency’s human health, risk assessment for TBTO which was conducted for the 2008 RED 

can be found in the public docket EPA-HQ-OPP-2008-0171 at www.regulations.gov. The 

agency does not anticipate updating the risk assessment for this registration review case.

3.1 Hazard Characterization and Risk

The toxicological database (Appendix A) is considered adequate for characterizing hazard and 

assessing risk from 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 residential uses and no residential exposure is expected. 

EPA Reg. No. 74487-1 is an anti-fouling device impregnated with TBTO. The antifouling device 

is used underwater within oceanographic instruments deployed by government researchers to 

monitor global ocean conditions. The amount of TBTO used in this antifouling device is minimal 

(< 0.1 ounces a.i.) and the 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 to 
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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 acoustically-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. 

Additionally, 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 glasses, faceshields and disposable protective clothing. 

Occupational 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 

Aggregate exposures are not anticipated 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 toxicity 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 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 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 

naval 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 TBTO as an outdoor wood preservative, which was the major use of the TBTOs 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 and 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 

2003). 
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4.1 Environmental Fate and Exposure

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

data show that TBTO is highly bioaccumulative, 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-HQ-OPP-2008-0171.

4.2 Ecological Risk Characterization

TBTO is highly 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 

instruments, exposure would occur only from the small amount of TBTO potentially leaching 

from these 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 exposed 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 sonar domes on vessels 

of 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 Endangered 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 endangered 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 numerous 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 loss, 

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 2008 RED for TBTO, EPA reviewed these 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 Program (EDSP). 
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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 endocrine 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 interact 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 the E, A, or T effect. 

Under FFDCA section 408(p), the agency 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 ingredients and nine inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 20131

2 and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed 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.32

Optional Label Changes

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

clarity.

Combined Preliminary Work Plan and Proposed Interim 

Registration Review Decision

In accordance with 40 CFR Sections 155.50, 155.56 and 155.58, the agency is issuing this 

combined Preliminary Work Plan and Proposed Interim Registration Review Decision 

document. Except for the EDSP component of the TBTO registration review case, the agency 

has made the following proposed decision that no 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 ESA for all listed species and designated critical 

habitat for such species.

Next Steps and Timeline

 2 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

3

http://www.epa.gov/endo/.
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A Federal Register Notice will announce the availability of this combined Preliminary Work 

Plan and Proposed Interim Registration Review Decision for TBTO and allow a 60-day 

comment period (see Table 2). If there are no significant comments or additional information 

submitted to the docket during the comment period that lead the agency to change its proposed 

decision, EPA may issue an interim decision. The final decision on the registration review for 

TBTO will occur after the ESA consultation and EDSP FFDCA section 408(p) determination 

have been made.
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Appendix A Toxicology 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

LD50 = 180 mg/kg (males)

LD50 = 150 mg/kg (females)

LD50 = 170 mg/kg (combined)

II

870.1100/ Acute oral toxicity 00085003, 92172004 LD50 = 123 mg/kg (females)

LD50 = 160 mg/kg (combined) II

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

Subchronic/Chronic 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 (equivalent to 3.8 

mg/kg bw/day in males; 4.9 mg/kg 

bw/day in females) based on mild 

hepatotoxicity and dermal irritation 

in the ear observed in male mice. 

Unacceptable/Non-guideline

Non-guideline

Range-finding 

Study in Dogs

MRID 41131001

Schweinfurth, H. (1987) 

Tributyltin oxide: 

Systemic toxicity study in 

Beagle dogs with daily 

oral (intragastric) 

administration over a total 

of 18-19 weeks. Schering 

AG, Berlin, Germany. 

Laboratory Project ID: 

TX 87.054, August 5, 

1987. Unpublished.

Beagle dogs 

Purity >96.1% a.i.

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

Weeks 1-5; 0, 0.2, 1.0, or 5.0 

mg/kg during Weeks 6-10; and 

0, 10, 1.0, or 5.0 mg/kg during 

Weeks 11-19.

Exposure to Tributyltin oxide 

caused elevated alkaline 

phosphatase and slight changes 

in serum protein composition 

at 1.0 mg/kg/day after 13-14 

weeks of exposure. While 

further biochemical changes 

and suspected effects on red 

and white blood cells were 

observed at 2.5 mg/kg/day 

after 5 weeks of exposure and 

at 5.0 mg/kg/day after 13-14

weeks of exposure, there was 

no evidence of organ 
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Guideline No.

and

Study Type

MRID No.

and

Citation

Dosing and Animal 

Information Results

toxicity. At 10 mg/kg/day, 

general toxic effects leading to 

weight loss and lymphotoxic 

effects, vacuolization of the 

liver cells and inhibition of 

follicle maturation in the 

ovaries (secondary effect) were 

observed. A dose of 10 

mg/kg/day was considered to 

be too toxic of a dose for the 1-

year oral dog study; therefore, 

dose levels of 0.2, 1.0, and 5.0 

mg/kg/day were recommended 

for the 1-year study.

Unacceptable/Non-guideline

Prenatal Developmental Toxicity

870.3700

Prenatal 

Developmental 

Toxicity Study 

MRID 00137158

Schroeder, R.; Hogan, G. 

(1981) A Teratology 

Study in Rats with 

Tributyltin Oxide: Project 

No. 80-2497A. Final rept. 

(Unpublished study 

received Jan 16, 1984 

under 5204-1; prepared 

by Bio/dynamics, Inc., 

submitted by M & T 

Chemicals Inc., Rahway, 

NJ; CDL:252178-A).

MRID 92172016

Schroeder, R. (1992) 

M&T Chemicals, Inc. 

Phase 3 Reformat of 

MRID 00137158. A 

Teratology Study in Rats 

with Tributyltin Oxide: 

Project No. 80-2497A. 

Prepared by 

Bio/dynamics, Inc. 83 p. 

Female pregnant CD®

(Sprague-Dawley derived) rats

Purity not reported

0, 5, 9, 18 mg/kg/day (via 

gastric intubation (gavage)

Maternal Toxicity

NOAEL = 5 mg/kg/day 

LOAEL = could not be identified 

due to the lack of data.

Developmental Toxicity

NOAEL is less than 5 mg/kg/day

LOAEL is equal to or less than 5 

mg/kg/day based on increased 

incidences of ossification variations. 

Acceptable/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

LOAEL = 2.5 mg/kg/day, based on 

increased incidence of abortion and 

decreased mean maternal body 

weight gain.

Developmental Toxicity

NOAEL = is equal to or greater than 

2.5 mg/kg/day

LOAEL= is greater than 2.5 

mg/kg/day (could not be established) 
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Guideline No.

and

Study Type

MRID No.

and

Citation

Dosing and Animal 

Information Results

Stevens, A. (1990) M&T 

Chemicals, Inc. Phase 3 

Summary of MRID 

40141901. A Teratology 

Study in Rabbits with 

TBTO: Project No. WILB0002. Prepared by Wil 

Research Laboratories, 

Inc. 7 p.

Acceptable/Guideline

Reproduction and Fertility Rates

870.3800

Reproduction and 

Fertility effects 

MRID 41693801

Schroeder, R.E. (1990) A 

two generation 

reproductions study in 

rats with bis (tri-nbutyltin) oxide. 

Bio/dynamics, Inc., East 

Millstone, NJ. 

Laboratory Project No.: 

88-3261, October 22, 

1990. Unpublished

Sprague Dawley rats

Purity 97.1%

0, 0.5, 5, or 50 ppm for two 

successive generations (diet)

Parental Toxicity

NOAEL = 5 ppm (equivalent to 

0.33/0.39 mg/kg/day in 

males/females).

LOAEL = 50 ppm (equivalent to 

mg/kg/day 3.47/3.93 in 

males/females) based on anogenital 

staining in the P dams; decreased 

body weights in the F1 males and 

females during pre-mating and 

continuing in the F1 males during the 

mating and post mating periods; and 

decreased absolute and relative 

thymus weights in the F1 males.

Reproductive Toxicity

NOAEL = 50 ppm (equivalent to 

3.47/3.93 mg/kg/day in 

males/females)

LOAEL = greater than 50 ppm (not 

established)

Offspring Toxicity

NOAEL = 5 ppm (equivalent to 

0.33/0.39 mg/kg/day in 

males/females).

LOAEL = 50 ppm (equivalent to 

3.47/3.93 mg/kg/day in 

males/females) based on decreased 

pup body weights in both generations

Acceptable/Guideline

Chronic Toxicity 

870.4100

Chronic Toxicity

MRID 42549801

Schuh, W. (1992) Bis (trin-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 

systemic toxicity (including 

mortality, clinical signs of toxicity, 

overall body weight losses, decreased 

body weights and food and water 
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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/day 

for low-, mid-, and high-dose 

males, respectively, and 0.9, 

4.8, and 9.2 mg/kg/day for low-

, mid-, and high-dose females, 

respectively) for 18 months

(diet)

LOAEL = 0.7 mg/kg/day (males)

LOAEL = 0.9 mg/kg/day (females),

based on decreased survivorship and 

increased body weight gain.

Acceptable/Guideline

Combined Chronic Toxicity/Carcinogenicity

870.4300

Combined chronic 

toxicity/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 

bw/day (diet)

NOAEL = 5 ppm (approximately 

equivalent to 0.25 mg/kg bw/day).

LOAEL = 50 ppm (approximately 

equivalent to 2.5 mg/kg bw/day)

based on increased mortality, 

systemic toxicity (ataxia, emaciation 

and decreased body weight/body 

weight gain in males and females) 

and organ toxicity (kidney, thyroid, 

adrenal glands, and pituitary. 

Acceptable/Guideline

Mutagenicity

870.5100

Bacterial Reverse 

Mutation Test

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/Guideline
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Guideline No.

and

Study Type

MRID No.

and

Citation

Dosing and Animal 

Information Results

or 0.15 μl/plate (with metabolic 

activation)

870.5375

In vitro

Chromosome 

Aberration Test 

(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. Unpublished 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

 870.5395 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-

14C] bis 

(tri-n-butyltin) oxide in 

mice. Environmental 

Management Laboratory, 

The University of Akron 

(Akron, Ohio).

Unpublished.

Female COBS albino mice

Purity not reported

0, 0.51, 3.75, or 18.5 ppm

Concentrations of 14C-TBTO 

were greatest in the kidneys, 

fat, liver, and spleen. 

Concentrations were found to 

be proportional to administered 

dose except in the kidney. 

Tissue accumulations were 

concentration dependent. The 

quantities absorbed were 

rapidly cleared when ingestion 

ceased. 

Acceptable/Non-guideline

870.7485

Metabolism and 

Pharmacokinetics

MRID 40253002

Humpel, M. (1986) 

Toxicokinetics of 113Snlabelled tributyltin oxide 

after intravenous (1 

mg/kg) and intragastric 

(25 mg/kg) administration 

to rats: bioavailability, 

excretion, and 

biotransformation. 

Schering AG, Berlin, 

Germany. Laboratory 

report numbers IC-Kl 3, 

KI 84 061, and KI 84 

062. January 23, 1986. Unpublished.

Female Wistar-Han (SPF) rats

Purity (>99%a.i)

1 mg/kg or 25 mg/kg

Absorption was very delayed after 

gavage administration, with a halflife of 9.5 hours. The intravenously 

administered 113Sn-labeled 

TBTO is rapidly distributed, 

with only 3% of the dose 

remaining in plasma volume 

after 5 minutes post 

administration. Based on the 

high volume of distribution 

and the binding to the cellular 

constituents of the blood, authors 

conclude that TBTO has a

pronounced affinity for tissues.

Acceptable/Non-guideline

Dermal Penetration

870.7600

Dermal 

Penetration

MRID 40050003

Hümel, M. (1985) Series 

85-2: Percutaneous 

absorption of tributyltin 

oxide (TBTO) through 

intact skin of baboon. 

Male baboon

Purity not reported

Dose volume 0.5 mL/25 cm2

skin

The total recovery of radioactively 

labeled 113Sn-Tributyltin oxide was 

less than 50%, perhaps due to the 

incomplete removal of unabsorbed 

TBTO on the skin surface as a result 

of extensive spreading from the site 
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19

Guideline No.

and

Study Type

MRID No.

and

Citation

Dosing and Animal 

Information Results

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%. 

Unacceptable/Non-guideline

Published Literature

Non Guideline

Literature Study

Vos et al., (1990) 

Immunotoxicity of bis

(tri-n-butyltin) oxide in 

the rat: Effects on 

thymus-dependent 

immunity and on 

nonspecific resistance 

following long-term 

exposure in young vs 

aged rats. Toxicol. Appl. 

Pharmacol. 105:144-155.

Wistar Rats

Purity: 95.3% active ingredient

Exposure to TBTO for up to 18 

months 

Dietary concentrations: 0.025, 

0.25 and 2.5 mg/kg-day.

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on 

immunotoxicity (depression of IgE 

titers and increase in T. spiralis 

larvae in muscle) following 4 months 

and 16.5 months of exposure to 

Tributyl Tin Oxide. (Review by 

EPA/IRIS, 1997).

Under the Reregistration Eligibility Decision for the Tributyltin Compounds: 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-occupation 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 sonar 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 anticipated to be required at this time. However, if new product 

registrations are submitted to the agency that are not supported by these existing TBTO data, additional 

toxicological data may be required.

Table A3 - Summary of Toxicological Endpoint Selection 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 chemicals do not indicate the potential for direct or indirect dietary exposures. 

Therefore, an acute dietary risk assessment is not required. 
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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)

BMD10 = 0.03 

mg/kg/day based on 

immunosupression 

(established by 

EPA/IRIS and used to 

estimate the oral RfD). 

Special Sensitivity = 10

UF = 100 (10x inter-species 

extrapolation, 10x intraspecies variation)

Chronic RfD (cRfD) = 

0.00003 mg/kg/day

Although the current use 

patterns for the tributyltincontaining chemicals do not 

indicate 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 the rat: Effects on 

thymus-dependent immunity and on 

nonspecific resistance following longterm exposure in young vs aged rats. 

Toxicol. Appl. Pharmacol. 105:144-155.

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on 

immunotoxicity (depression of IgE titers 

and increase in T. spiralis larvae in 

muscle) following 4 months and 16.5 

months of exposure to Tributyl Tin 

Oxide. (Review by EPA/IRIS, 1997). 

Non-Dietary Risk Assessments

Incidental Oral ShortTerm 

(1-30 days) and 

Intermediate-Term (1-

6 months) 

BMD10 = 0.03 

mg/kg/day based on 

immunosupression 

(established by 

EPA/IRIS and used to 

estimate the oral RfD). 

Special Sensitivity = 10

UF = 100 (10x inter-species 

extrapolation, 10x intraspecies variation)

Target MOE res. = 1000

Open Literature Study

Vos et al., (1990) Immunotoxicity of bis 

(tri-n-butyltin) oxide in the rat: Effects on 

thymus-dependent immunity and on 

nonspecific resistance following longterm exposure in young vs aged rats. 

Toxicol. Appl. Pharmacol. 105:144-155.

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on 

immunotoxicity (depression of IgE titers 

and increase in T. spiralis larvae in 

muscle) following 4 months and 16.5 

months of exposure to Tributyl Tin 

Oxide. (Review by EPA/IRIS, 1997). 

Dermal

(all durations)

BMD10 = 0.03 

mg/kg/day based on 

immunosupression 

(established by 

EPA/IRIS and used to 

estimate the oral RfD). 

Special Sensitivity = 10

UF = 100 (10x inter-species 

extrapolation, 10x intraspecies 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 longterm 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). 
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Exposure

Scenario

Dose Used in Risk 

Assessment

(mg/kg/day) 

Special Sensitivity*, UF, 

Target MOE, 

for Risk Assessment

Study and Toxicological Effects

Inhalation

(all durations)

BMD10 = 0.03 

mg/kg/day based on 

immunosupression 

(established by 

EPA/IRIS and used to 

estimate the oral RfD). 

Special Sensitivity = 10

UF = 100 (10x inter-species 

extrapolation, 10x intraspecies 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 longterm exposure in young vs aged rats. 

Toxicol. Appl. Pharmacol. 105:144-155.

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on 

immunotoxicity (depression of IgE titers 

and increase in T. spiralis larvae in 

muscle) following 4 months and 16.5 

months of exposure to Tributyl Tin 

Oxide. (Review by EPA/IRIS, 1997). 

Dermal Absorption Although there is no guideline dermal toxicity study (range-finding study only) and no acceptable 

dermal absorption study (75% recovery of 113Sn-tributyltin oxide), a 15% dermal absorption factor 

for tributyltin oxide has been used (EPA/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 tumors in 

Wistar rats, incidence variability in the treated groups and absence of a dose-effect relationship.

UF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, RfD = reference dose, MOE 

= margin of exposure, NA = Not Applicable

*The Special Sensitivity factor is applied to a selected dose if there is evidence of increased susceptibility to children from non-dietary exposures 

to pesticides. Several published literature 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. Therefore, application of this 

factor provides adequate protection to the most sensitive population, children.
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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 under 

5204-1; prepared by Bio/ dynamics, Inc., submitted by M & T Chemicals, Inc., 

Rahway, N.J.; CDL:246070-A).

00085004 Auletta, C.S., Hodge, P.S., Minczeski, N. et al. (1981). Acute Oral Toxicity Study 

in Rats: Project No. 6657-81. (Unpublished study received Oct 15, 1981 under 

5204-1; prepared by Bio/ dynamics, Inc., submitted by M & T Chemicals, Inc., 

Rahway, N.J.; CDL:246070-B).

00104789 Bruan, W., Rinehart, W. (1979). A Dermal Sensitization Study in Guinea Pigs: 

Compound TBTO: Project No. 5056-78. (Unpublished study received Mar 14, 

1979 under 5204-1; prepared by Bio/dynamics, Inc., submitted by M & T 

Chemicals, Inc., Rahway, NJ; CDL: 237804-A).

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

and excretion of [1-

14C] bis(tri-n-butyltin) oxide in mice. Environmental 

Management Laboratory, The University of Akron (Akron, Ohio). Unpublished.

00137158 Schroeder, R., Hogan, G. (1981). A Teratology Study in Rats with Tributyltin 

Oxide: Project No. 80-2497A. Final rept. (Unpublished study received Jan 16, 

1984 under 5204-1; prepared by Bio/dynamics, Inc., submitted by M & T 

Chemicals Inc., Rahway, NJ; CDL:252178-A).

40050003 Hümel, M. (1985). Series 85-2: Percutaneous absorption of tributyltin oxide 

(TBTO) through intact skin of baboon. Scherling AG, Berlin 65, Germany. 

Laboratory Project ID IC-KI 2, June 12, 1985. Unpublished.

40141901 Nemec, M. (1987). (Tributyltin Oxide) - A Teratology Study in Rabbits with 

TBTO: Laboratory Project ID: WIL-B0002. Unpublished study prepared by Wil 

Research Laboratories, Inc. 210 p.

40253002 Humpel, M. (1986). Toxicokinetics of 113Sn-labelled tributyltin oxide after 

intravenous (1 mg/kg) and intragastric (25 mg/kg) administration to rats: 

bioavailability, excretion, and biotransformation. Schering AG, Berlin, Germany. 

Laboratory report numbers IC-Kl 3, KI 84 061, and KI 84 062. January 23, 1986. 

Unpublished. 

40253005 Brunneman, A. (1986). Evaluation of the Clastogenic Potential in the Human 

Lymphocyte Test: ZK 21.955: Lab. Proj. ID IC 4/86. Un- published study 

prepared by Schering AG. 23 p.
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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. 

Laboratory Report No.: 658112 002, February 25, 1988. Unpublished.

41127001 Daly, I. (1989). A three month oral range-finding toxicity study in mice with bis 

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

Unpublished.

41131001 Schweinfurth, H. (1987). Tributyltin oxide: Systemic toxicity study in Beagle 

dogs with daily oral (intragastric) administration over a total of 18-19 weeks. 

Schering AG, Berlin, Germany. Laboratory Project ID: TX 87.054, August 5, 

1987. Unpublished.

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 Schroeder, R.E. (1990). A two generation reproductions study in rats with bis (trin-butyltin) oxide. Bio/dynamics, Inc., East Millstone, NJ. Laboratory Project 

No.: 88-3261, October 22, 1990. Unpublished.

42170001 Lang, R. (1986). Evaluation in the Ames Salmonella/Microsome Mutagenicity 

Test: ZK 21.955: Lab project Number: TX6106. Unpublished study prepared by 

Schering Ag. 29 p.

42265001 Daly, I. (1992). An eighteen month oncogenicity feeding study in mice with 

bis(tri-n-butyltin) oxide (TBTO). Bio/dynamic, Inc. Project No. 87-3131, March 

27, 1992. Unpublished.

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, 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).
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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 thymus 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).

Tributyltin 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 maleate (Case 2620). EPA 739-R08-005, 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 Ecological Criteria Division, 

Washington D.C. EPA 822-R-03-031. 138 pp.

EPA. 1997. Reregistration Eligibility Decision (RED) for the Tributyltin Compounds.