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Bis(bromoacetoxy)-2-butene Registration Review Team

Human Health & Environmental Effects

Pat Jennings

James Breithaupt

David Bays

Tim Dole

Tim McMahon

Julie VanAlstine

Risk Management

Stephen Savage

Tina Pham

Rose Kyprianou

Terria Northern

Jacqueline Hardy

Office of General Counsel

Philip Ross
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TERMS, ABBREVIATIONS AND SYMBOLS

A.I. or a.i. active ingredient

aPAD acute population adjusted dose 

ASRI activated sludge respiration inhibition

atm-m3/mole atmospheric pressure-cubic meter per mole

BBAB bis(bromoacetoxy)-2-butene

°C degrees Celsius

CAS Chemical Abstracts Service 

CFR Code of Federal Regulations 

cPAD chronic population adjusted dose 

DCI data call-in

EC50 median (or 50 percent) effect concentration

ECOTOX ECOTOXicology

EDSP Endocrine Disruptor Screening Program 

E-FAST Exposure and Fate Assessment Screening Tool

EPI Suite Estimation Program Interface Suite

EPA Environmental Protection Agency

FDA Food and Drug Administration 

FFDCA Federal Food, Drug, and Cosmetic Act

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FQPA Food Quality Protection Act 

FWP Final Work Plan

g/mol grams per mole

GLN guideline number

IDS Incident Data System 

Koc organic carbon normalized soil-water partition coefficient

Kow octanol-water partition coefficient

LC50 median (or 50 percent) lethal concentration

LD50 median (or 50 percent) lethal dose

LOAEL lowest-observed-adverse-effect-level

Log Kow logarithm of the octanol-water partition coefficient

μg microgram

ml/g milliliter per gram

mg/kg milligram per kilogram

mg/kg/day milligram per kilogram per day 

mg/L milligram per liter

mm Hg millimeter of mercury

MOE margin of exposure 

MRID Master Record Identification Number

MRL maximum residue limit 

N/A not applicable 

nm nanometers

NOAEL no-observed-adverse-effect-level

OCSPP Office of Chemical Safety and Pollution Prevention

OECD Organization for Economic Co-operation and Development

OPP Office of Pesticide Programs

PC Code Pesticide Chemical Code

pH power of hydrogen or power of the concentration of the hydrogen ion

pKa power of the acid dissociation constant or negative base-10 logarithm of the acid 

dissociation constant of a solution
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ppb parts per billion 

ppm parts per million

FWP Final Work Plan

QSAR quantitative structure-activity relationship

RED Reregistration Eligibility Decision

SAR structure activity relationship

SF safety factor

TGAI technical grade active ingredient

TMDL total maximum daily loads

UF uncertainty factor

WWTPs wastewater treatment plants
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Table of Contents

1 Introduction............................................................................................................................. 7

1.1 Statutory and Regulatory Authority ................................................................................. 7

1.2 Updates to the Workplan.................................................................................................. 7

1.3 Case Overview ................................................................................................................. 8

1.4 Chemical Identification and Properties............................................................................ 9

1.5 Use/Usage Description................................................................................................... 11

1.5.1 Registrations ........................................................................................................... 11

1.5.2 Summary of Registered Uses.................................................................................. 11

1.5.3 Usage Information .................................................................................................. 12

1.6 Regulatory History ......................................................................................................... 12

1.6.1 Tolerance Information ............................................................................................ 12

1.7 Incidents......................................................................................................................... 12

1.7.1 Human Health ......................................................................................................... 12

1.7.2 Ecological ............................................................................................................... 13

2 Anticipated Data Needs ........................................................................................................ 13

3 Human Health Risk Assessment........................................................................................... 16

3.1 Existing Toxicological Endpoints.................................................................................. 16

3.2 Dietary Exposure............................................................................................................ 17

3.2.1 Food ........................................................................................................................ 17

3.2.2 Drinking Water ....................................................................................................... 17

3.3 Occupational and Residential Exposures....................................................................... 17

3.3.1 Occupational Handler Exposure ............................................................................. 18

3.3.2 Residential Handler Exposures............................................................................... 18

3.3.3 Residential Post-Application Exposures................................................................. 18

3.4 Aggregate and Cumulative Exposure............................................................................. 18

3.4.1 Aggregate Exposures.............................................................................................. 18

3.4.2 Cumulative Exposures............................................................................................ 18

4 Environmental Risk Assessment........................................................................................... 18

4.1 Environmental Fate Assessment .................................................................................... 19

4.2 Environmental Exposure Pathways................................................................................ 19

4.3 Ecological Effects Assessment....................................................................................... 20

4.3.1 Measures of Effect (Ecotoxicology Endpoints)...................................................... 20

4.4 Exposure Analysis Plan.................................................................................................. 21

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates ............................................ 21

4.5 Effects Analysis Plan ..................................................................................................... 22

5 Endocrine Disruptor Screening Program (EDSP)................................................................. 22

6 Label Changes....................................................................................................................... 23

7 Next Steps............................................................................................................................. 23

8 References............................................................................................................................. 24

Appendices

Appendix A Toxicology Profile............................................................................................... 26

Appendix B Environmental Fate ............................................................................................. 33

Appendix C Ecotoxicology Profile.......................................................................................... 39

Appendix D Down-the-Drain (DtD) Assessment.................................................................... 42
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Appendix E Chemical and Physical Properties of BBAB and its Degradation Products ....... 43

List of Tables

Table 1 – Summary of Anticipated Risk Assessments and Data Needs for Registration Review: 

BBAB.............................................................................................................................................. 8

Table 2 – Anticipated Registration Review Schedule .................................................................... 9

Table 3 – Chemical Identification of BBAB .................................................................................. 9

Table 4 – Chemical, Physical, and Environmental Fate Properties for Parent BBAB................. 10

Table 5 – Estimated Chemical, Physical, and Environmental Fate Properties of Hydrolytic 

Degradation Compounds of BBAB.............................................................................................. 10

Table 6 – Summary of BBAB Registered Uses............................................................................ 11

Table 7 – Studies Anticipated as Needed for the Registration Review of BBAB........................ 14

Table 8 – Existing Toxicological Endpoints for BBAB............................................................... 16
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1 Introduction

This document is the United States Environmental Protection Agency’s (USEPA, EPA or “the 

Agency”) Final Work Plan (FWP) for 1,4-bis-bromoacetoxy-2-butene, herein referred to as 

BBAB. The FWP document explains what EPA's Office of Pesticide Programs (OPP) knows 

about BBAB, highlighting anticipated data and assessment needs, identifying the types of 

information that would be especially useful to the Agency in conducting the review, and 

providing an anticipated timeline for completing BBAB review.

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it knows about BBAB and what types of new data or other 

information would be helpful for the Agency to receive as it moves toward a decision on BBAB.

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 

Federal Insecticide, Fungicide, and Rodenticide Act (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 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 Updates to the Workplan

Since the publication of the Preliminary Work Plan (PWP), the Agency has made the following 

updates:

• Updated Section 1.3, Case Overview.

• Updated Table 1 and Sections 1.5.2, 3.3.1, and 3.4 based on label changes submitted

since the publication of the PWP, specifying closed loading only. 

• Updated the timeline in Table 2, Anticipated Registration Review Schedule.
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• Revised Table 7, Studies Anticipated as Needed for the Registration Review to remove 

occupational exposure from open pour applications which are no longer needed, to clarify 

neurotoxicity requirements, and added footnote to work with stakeholders to determine 

the appropriate test substances.

• Revised Section 3.2.1 Food to update the aPAD and cPAD estimates.

• Updated Section 6, Optional Label Changes to closed loading application label change 

and reduction in DCI requirements.

• Deleted Table 9, “Occupational Handler Exposure Scenario for BBAB” from section 

3.3.1.

• Deleted the “Guidance for Commenters” Section.

• Updated Section 7 and Next Steps.

No public comments were received on the initial docket. Modifications were made to the 

anticipated data needs which did not change the registration review schedule of the BBAB PWP. 

This document makes final the work plan for the BBAB registration review process.

1.3 Case Overview

The docket for BBAB (case 3030) has been established at http://www.regulations.gov in docket 

number EPA-HQ-OPP-2014-0799. Documents associated with this registration review can be 

viewed in this docket. Tables 1-2 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: BBAB

Risk Assessment 

Assessment 

Necessary to 

Support 

Registration 

Review

Date of 

Most 

Recent 

Assessment

Type of 

Assessment 

Required 

(New/

Updated)

Data Anticipated as Needed

(See Table 7 for details)

Dietary (food) Yes 2000 Updated

Developmental Toxicity Study in Rabbits

Reproduction and Fertility Effects in Rats

Chronic Toxicity in Rats

Carcinogenicity in Rats

Acute Neurotoxicity 

Immunotoxicity

Dietary (drinking water) Yes 2000 New See above data needs for Dietary (food)

Occupational Handler No 

(See Section 3.3.1) 2000 None None1

Residential Handler No

(See Section 3.3.2) 2000 None None2

Residential Post 

Application

No

(See Section 3.3.3) 2000 None None2

Aggregate Yes 2000 New See above data needs for Dietary (food)

Cumulative No

(See Section 3.4.2) 2000 None None
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Risk Assessment 

Assessment 

Necessary to 

Support 

Registration 

Review

Date of 

Most 

Recent 

Assessment

Type of 

Assessment 

Required 

(New/

Updated)

Data Anticipated as Needed

(See Table 7 for details)

Tolerance Review No

(See Section 1.6.1) N/A N/A None

Ecological Yes 2000 Updated

Biodegradability in WWTP

Activated Sludge Respiration Inhibition 

Aerobic Aquatic Metabolism

Acute Estuarine/Marine Toxicity Test

Fish Early-Life Stage Test

Aquatic Invertebrate Life-Cycle Test

Aquatic Plant Growth (Algal) Test

Aquatic Plant Growth (Vascular Plant) Test

N/A = Not applicable

1 Application method was changed. BBAB is only applied in closed loading and delivery systems.

2 Residential use from 2000 assessment was cancelled. Currently, there are no registered residential uses for BBAB.

Table 2 – Anticipated Registration Review Schedule

Anticipated Activity Target Date* Completion Date

Phase 1: Opening the Docket

Open Docket and 60-Day Comment Period for Preliminary Work Plan 2015-03 2015-03-30

Close Public Comment Period 2015-05 2015-05-29

Phase 2: Case Development

Issue Final Work Plan 2015-09 2015-09

Issue Data Call-In (DCI) 2016-03

Receive Data to be Considered in Risk Assessment 2020-03

Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2021-09

Close Public Comment Period 2021-10

Phase 3: Registration Review Decision and Implementation

Open 60-Day Public Comment Period for Proposed Decision 2022-03

Close Public Comment Period 2022-05

Issue Final Decision 2022-09

Begin Post-Decision Follow-up 2022

Total (years) 7

*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).

1.4 Chemical Identification and Properties

Table 3 presents the active ingredient to be assessed in case 3030: BBAB (PC Code 035605). 

Table 3 – Chemical Identification of BBAB

Chemical Name 1,4-bis-bromoacetoxy-2-butene (BBAB)

Chemical Classification Halogenated alkane

PC Code 035605

CAS Number 20679-58-7

Smiles code BrCC(=O)OCC=CCOC(=O)CBr
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Molecular Formula C8H10Br2O4

Molecular Weight (grams/mole) 329.97

Molecular Structure

The product chemistry information for parent BBAB that is relevant to risk assessment is 

summarized in Table 4, and the details of the product chemistry and environmental fate 

information are discussed in Appendix E and B, respectively.

Table 4 – Chemical, Physical, and Environmental Fate Properties for Parent BBAB

Guideline 

No. Parameter

EPA Reg. No. 707-234:

1,4-bis-bromoacetoxy-2-

butene, 87 % AI

Reference (MRID)/Comments

830.7050 UV/Visible Absorption Not applicable Based on chemical structure, structure will 

not absorb light between 290 and 800 nm

830.7370 Dissociation constant (pKa) Not applicable No ionizable functional groups

830.7550 Octanol-water partition 

coefficient at 25 oC (Log Kow) 1.7 43376103

830.7840 Solubility in water (mg/L) 630 43376101

20 oC

830.7950 Vapor pressure (mmHg) 1.59 x 10-6 43376102

20 oC

None

Henry's law constant at 25 oC 

(atm-m3/mol)

CALCULATED

1.1 x 10-9 None

835.2120 Hydrolysis

Half-life = 8.3 days (pH 5)

Half-life = 7 hours (pH 7)

Half-life = 4 minutes = (pH 9)

44458401

atm-m3/mol = atmosphere cubic meter per mole; oC = degrees Celsius; mg/L = milligrams per liter; mmHg = 

millimeters of mercury;

Based on the hydrolytic half-life of 8 days at pH 5 and 7 hours at pH 7, persistence of BBAB in 

the environment would be expected to increase as pH values decrease. In the hydrolysis study of 

BBAB (MRID 44458401), three straight-chain hydrolytic degradation compounds were 

identified: (1) the parent compound minus a bromine molecule (BAAB); (2) the parent 

compound minus one bromoacetic acid group (BAHB); and (3) bromoacetic acid (BA). 

Estimated physical/chemical and environmental fate properties of these degradates are presented 

in Table 5. 

Table 5 – Estimated Chemical, Physical, and Environmental Fate Properties of Hydrolytic 

Degradation Compounds of BBAB1

Compound

Test Guideline (OCSPP No.) BAAB BAHB BA

 1 Except for hydrolysis half-lives (MRID 44458401), all values in this table are from EPI-WEB 4.11. 
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Chemical structure 

Smiles code BrCC(=O)OCC=CCOC(=O)C BrCC(=O)OCC=CCO BrCC(=O)O

Molecular formula C8H11BrO4 C6H9BrO3 C2H3BrO2

Molecular weight (grams/mol) 251.08 209.04 138.95

Octanol-water partition coefficient 

at 25 oC (Log Kow)

830.7550

1.52 0.51 0.41

Solubility in water (mg/L)

830.7840 1,185 46,640 1.75 x 106

Vapor pressure (mm Hg)

830.7950 2.2 x 10-2 6.31 x 10-4 1.2 x 10-1

Henry’s law constant at 25 oC 

(atm-m3/mol)

CALCULATED – No OCSPP No.

6.1 x 10-6 3.7 x 10-9 2.6 x 10-7

Hydrolysis

835.2120

At pH 5, stable but not present 

in significant amounts (<10 %)

Not detected (pH 7 and 9)

43 days (pH 5)

29 hours (pH 7)

16 minutes (pH 9)

Stable at pH 5, 7, 

and 9)

Additional product chemistry information on BBAB and its degradates is available in Appendix E.

1.5 Use/Usage Description

1.5.1 Registrations

There are two EPA-registered products that contain BBAB as an active ingredient (a.i.). The 

products include one manufacturing use product (MUP) and one end-use product (EUP). The 

MUP (EPA Reg. No. 1448-374) contains 95 percent a.i. in the form of a liquid. The EUP (EPA 

Reg. No. 1448-353) contains 80 percent a.i. in the form of a ready-to-use solution in drums

ranging from 55 to 330 gallons and permits application rates of 0.15-0.30 lbs of product 

(equivalent to 0.24 lb ai) per ton of paper produced.

1.5.2 Summary of Registered Uses

Table 6 presents a summary of the registered uses of BBAB that will be assessed in this 

registration review. BBAB can be applied by the following application methods: closed loading 

meter pump.

Table 6 – Summary of BBAB Registered Uses

Use Application Method Application Rate

Control of Microbial Slime in Pulp and Paper Mills Closed loading Meter pump 0.15-0.30 lb AI/ton paper

Br

O

O

O

O

CH3

Br

O

O

OH

Br

O

OH
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1.5.3 Usage Information

No usage information is available for BBAB in the Kline Biocides Report.

2

1.6 Regulatory History

The first product containing BBAB as an active ingredient was registered in the United States in 

1964. In 2000, EPA completed a preliminary risk assessment for BBAB.

3 Documents associated 

with the 2000 preliminary risk assessment will be made available on www.regulations.gov under 

the registration review docket for BBAB (See Section 1.2).

The Agency intends to issue a PDCI and complete product reregistration for all BBAB products.

Existing data gaps will be addressed during registration review. 

1.6.1 Tolerance Information

EPA has not established tolerances for residues of BBAB in or on raw agricultural commodities 

or processed food and feed products under the Federal Food, Drug, and Cosmetic Act (FFDCA) 

Section 408. There are also no tolerance exemptions for residues of BBAB under FFDCA 

Section 408. BBAB has been cleared as an indirect food additive by the US Food and Drug 

Administration (US FDA) under FFDCA Section 409 for use in the manufacture of paper and 

paperboard that contact food (21CFR176.300).

1.7 Incidents

1.7.1 Human Health 

Individual Incident Reports

Incidents that are rated as moderate (HC), major (HB) or fatality (HA) are reported as individual 

reports in the OPP Incident Data System (IDS). These reports include information regarding the 

causes of the incident and symptoms experienced. In the case of BBAB, two individual reports 

 2 Special Biocides 2004-2005. A Global Series of Regional Market Analysis. Volume II: United States, Kline & 

Company, 2006.

3 The 2000 preliminary risk assessment for BBAB includes the following documents:

• Executive Summary for the Reregistration Eligibility Decision (RED)

• Human Health Science Chapter (Revised)

• Addendum - Final Draft of Human Health Chapter (Revised Dietary)

• Human exposure RED chapter

• Toxicology Review for the Reregistration Eligibility Decision (RED) Document

• Risk Characterization for the Reregistration Eligibility Decision (RED) Document

• Final Draft of Dietary Exposure-Food (Residue Chemistry) Science Chapter

• Final Draft of Product Chemistry Science Chapter

• RED Ecological Effects Review and Risk Assessment

• Final Draft Environmental Fate Science Chapter

• Summary of Incident Data and Epidemiological Information for the Reregistration Eligibility Decision 
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are listed in the ID, as of January 13, 2015 for the time period from 1999 to 2014. These 

incidents are described below.

• A paper mill worker (millwright) had contact with residual product on papermill 

machinery and experienced dermal irritation and difficulty breathing. The dermal 

irritation was resolved with the use of a steroid treatment but the difficulty in breathing 

persisted and the worker later claimed to have “Moderate Restricted Lung Disease.” The 

consulting doctor indicated however, that he did not believe that the product could be the 

cause of this condition. This incident was rated as HB.

• A feed line developed a leak at the location of post-dilution with the city water supply. A 

worker in the facility had blistering on forearms and 2nd degree chemical burns. This 

incident was rated as HC.

Aggregate Incident Reports

Incidents that are rated as minor (HD) or that cannot be rated (HE) are reported in aggregate 

reports which are listings of the incidents for a manufacturer or distributer over a certain time 

period (often quarterly). Typically these reports only contain basic information such as the date, 

location and product involved and more detailed information such the cause of the incident or 

symptoms experienced are not included. In the case of BBAB, there are 28 aggregate incidents 

listed in the IDS, as of January 13, 2015 for the time period from 1999 to 2014. All of these 

incidents are classified as human minor (HD). There is no information regarding these incidents.

1.7.2 Ecological

No BBAB incidents have been reported in the Agency’s Ecological Incident Information System 

(EIIS) as of December 8, 2014.

2 Anticipated Data Needs

Table 7 presents a summary of the data anticipated as being needed to support this registration 

review. 
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Table 7 – Studies Anticipated as Needed for the Registration Review of BBAB

GLN Study Name Test 

Substance1

Time Frame 

(Measured in 

months from 

DCI Receipt)

Risk Assessment(s) 

Data Will Support

Use Site(s) 

Triggering 

Anticipated Data 

Requirement

Applicable 

Exposure 

Scenario

835.31102

835.32202

835.32402

835.32802

Biodegradability in WWTP

TGAI, BAHB 

and BA 

degradates

12 Environmental exposure Pulp and paper mills Ecological 

850.33002, 3 Activated Sludge Respiration Inhibition (ASRI)

TGAI, BAHB, 

and BA 

degradates

12 Environmental exposure Pulp and paper mills Ecological

835.43004 Aerobic aquatic metabolism TGAI 24 Environmental exposure Pulp and paper mills Ecological

850.1075 Acute estuarine fish toxicity TGAI 12 Environmental effects Pulp and paper mills Ecological

850.1300 Aquatic invertebrate life-cycle TGAI 24 Environmental effects Pulp and paper mills Ecological

850.1400 Fish early life-stage TGAI 24 Environmental effects Pulp and paper mills Ecological

850.45005 Aquatic plant growth (algal) Tier II (dose 

response) TGAI 12 Environmental effects Pulp and paper mills Ecological

850.45505 Aquatic plant growth (aquatic vascular plant) 

Tier II (dose response) TGAI 12 Environmental effects Pulp and paper mills Ecological

870.3700 Developmental Toxicity Study in Rabbits TGAI 24

Aggregate

Dietary Pulp and paper mills Food and Water

870.38006 Reproduction and fertility effects in rats TGAI 48

Aggregate

Dietary Pulp and paper mills Food and Water

870.41007 Chronic toxicity in rats TGAI 48 Aggregate

Dietary Pulp and paper mills Food and Water

870.42007 Carcinogenicity in rats TGAI 48 Aggregate

Dietary Pulp and paper mills Food and Water

870.62008 Neurotoxicity screening battery TGAI 24

Aggregate

Dietary Pulp and paper mills Food and Water

870.78009 Immunotoxicity TGAI 12

Aggregate

Dietary Pulp and paper mills Food and Water
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1. The Agency intends to work with stakeholders to determine the appropriate test substance, based on BBAB’s pH dependent degradation pattern. This may result in data being 

required on certain degradates or may eliminate the need for certain data..

2. For BBAB, BAHB, and bromoacetic acid, the results of the Activated Sludge Respiration Inhibition Test (ASRI) will determine which of these four biodegradation tests is/are

anticipated to be required. 

• If the ASRI test EC50 is less than or equal to 20 mg/L, then either the (i) Biodegradation in Activated Sludge Study or (ii) Simulation Test - Aerobic Sewage Treatment: A. 

Activated Sludge Units or (iii) the Porous Pot Test would be anticipated to be required. If the ASRI test EC50 is greater than 20 mg/L, then the registrant would be anticipated 

to be required to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test - Aerobic Sewage Treatment: A. Activated 

Sludge Units or c) the Porous Pot Test. 

• If the Ready Biodegradability study is conducted and passes, then no further testing would be anticipated to be required. If, however, the antimicrobial fails the Ready 

Biodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test - Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot 

study would be anticipated to be required.

3. EPA published draft guidance under guideline 850.6800 and has since published final guidance for this study under guideline 850.3300: 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0021. OECD Test Guideline 209 can also be used as guidance for this study, available online at 

http://www.oecd-ilibrary.org/content/book/9789264070080-en.

4. The anticipated Data Call-In Notice will provide that one study using parent BBAB may be conducted: aerobic aquatic metabolism studies measure parent compounds and 

degradates.

5. In a Federal Register Notice dated June 27, 2012, EPA split the Public Draft OPPTS 850.5400 test guideline into two test guidelines: OCSPP 850.4500 and OCSPP 850.4550. 

See “Final Test Guidelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-

0154-0028.

6. Results from a multi-generation (EPA guideline 870.3800) or an extended one-generation reproductive and fertility effects study using OECD Test Guideline 443 

(http://www.oecd-ilibrary.org/environment/test-no-443-extended-one-generation-reproductive-toxicity-study_9789264185371-en) will satisfy this anticipated requirement.

7. The use of BBAB in manufacture of pulp and paper is an indirect food use that triggers the need for chronic toxicity and carcinogenicity data (see 40 CFR §158.2230 footnotes 

20 and 21) based on the expectation that use is likely to result in repeated human exposure over a considerable portion of the human lifespan. The anticipated Data Call-In 

Notice will provide that a combined chronic toxicity/carcinogenicity study (870.4300) may be conducted to fulfill these data needs in lieu of conducting separate chronic

toxicity and carcinogenicity studies.

8. Acute (study due 12 months after receipt of DCI) and subchronic (study due 24 months after receipt of DCI) neurotoxicity studies are anticipated to be required. A protocol 

should be submitted to the agency for review prior to conducting the neurotoxicity studies.

9. All 90-day subchronic studies in the rodent can be designed to simultaneously fulfill the requirements of the 90-day immunotoxicity studies by adding separate groups of 

animals for testing of immunotoxicity parameters.
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3 Human Health Risk Assessment

The Agency anticipates the need to conduct a human health risk assessment for BBAB for the 

pulp and paper mill use of the chemical. The Agency expects to require additional toxicology 

data on BBAB (as noted in Table 7 of this document) to conduct this risk assessment for 

registration review. 

3.1 Existing Toxicological Endpoints

The Agency anticipates the need to revise the existing toxicological endpoints and uncertainty 

factors as part of registration review for BBAB. Table 8 shows the endpoints and uncertainty 

factors used in the 2000 preliminary human health risk assessment. The lack of a complete 

toxicology and exposure database for BBAB was noted in the 2000 assessment. All available 

information including existing toxicology studies, valid scientific literature, and studies that are 

required for registration review will be considered in establishing the endpoints to be used in the 

registration review risk assessment. A detailed description of the available toxicity studies is 

provided in Appendix A.

Table 8 – Existing Toxicological Endpoints for BBAB

Exposure Scenario

Dose Used in 

Risk 

Assessment 

Target Margin of 

Exposure (MOE), 

Uncertainty Factor (UF) 

Study and Toxicological Effects

Acute Dietary 5 mg/kg/day 

(NOAEL) UF =100a

Prenatal Developmental Toxicity Study – Rats (MRID 

44750901), based on increased incidence of salivation 

in maternal animals at a dose of 20 mg/kg/day

Chronic Dietary 4.5 mg/kg/day 

(LOAEL) UF = 3000b

Subchronic toxicity study – Rats (MRID 44757001), 

based on microscopic findings of hyperkeratosis and 

hyperplasia of the non-glandular mucosa of the 

stomach in both sexes and edema of the stomach in 

the female at a dose of 4.5 mg/kg/day

Short-, intermediatelong-term Dermal4.5 mg/kg/day 

(LOAEL) Target MOE = 300c Subchronic toxicity study – Rats (MRID 44757001)(See above for effects)

Short-term 

inhalation

5 mg/kg/day 

(NOAEL) Target MOE =100a Prenatal Developmental Toxicity Study – Rats (MRID 44750901) (See above for effects)

Intermediate- and 

long-term inhalation

4.5 mg/kg/day 

(LOAEL) Target MOE = 1000d Subchronic toxicity study – Rats (MRID 44757001)(See above for effects)

Dermal Absorption No study available; assumed 100% absorption a

10x interspecies scaling factor, 10x intra-species variation factor b

10x interspecies scaling factor, 10x intra-species variation factor, 3x for LOAEL/NOAEL extrapolation, 3x for use 

of subchronic study endpoint for chronic effects, 3x for lack of chronic toxicity data.

c

10x interspecies scaling factor, 10x intra-species variation factor, 3x for LOAEL/NOAEL extrapolation d

10x interspecies scaling factor, 10x intra-species variation factor, 3x for LOAEL/NOAEL extrapolaion, 3x for 

subchronic to chronic extrapolation. 
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3.2 Dietary Exposure

EPA anticipates the need to conduct an updated dietary exposure (food and water) assessment to 

support the existing uses of BBAB during registration review. This assessment should reflect 

updated SOPs, consumption data, and any changes to the toxicity endpoints. The use of BBAB to 

control slime in the manufacture of paper and paperboard that contact food is considered an 

indirect food use by the Agency. The Agency has concluded that there may be potential for

BBAB and degradates to contaminate drinking water sources; therefore, a drinking water dietary 

exposure assessment is anticipated to be conducted for registration review.

Dietary risk is characterized in terms of the Population Adjusted Dose (PAD) which reflects the 

reference dose (RfD), either acute or chronic, that has been adjusted to account for the FQPA 

Safety Factor (SF). This calculation is performed for each population subgroup for which an 

endpoint exists. A risk estimate that is less than 100% of the acute or chronic PAD is not of 

concern. Acute and chronic dietary risk for BBAB will be assessed by comparing dietary 

exposure estimates expressed in mg/kg/day to the acute Population Adjusted Dose (aPAD) and 

chronic Population Adjusted Dose (cPAD).

3.2.1 Food

The Agency anticipates the need to conduct a dietary (food) assessment for BBAB during 

registration review. A screening-level (food only) assessment was completed in support of this 

FWP using updated assumptions (20% of food consumed in the human diet may contact paper; 

100 pounds of slurry contains 1 pound of pulp by weight) and NHANES/WWEIA 2003-2008 

consumption data. Exposure estimates utilized <1% of the aPAD and 9% of the cPAD for the 

general U.S. population, and utilized <1% of the aPAD and 23% of the cPAD for children 1-2 

years old, the most highly-exposed population subgroup (aPAD=0.05 mg/kg/day; cPAD = 

0.0015 mg/kg/day).

3.2.2 Drinking Water

The Agency anticipates the need to conduct a drinking water assessment for BBAB and its 

degradates (BAHB and BA) during registration review. In 2000, drinking water exposure to 

BBAB was not assessed because drinking water exposure was not expected. However, it has

recently been determined that there is potential for human drinking water exposure to degradates 

of BBAB (BAHB and BA) (see Section 4.1). 

3.3 Occupational and Residential Exposures

EPA does not anticipate the need to conduct an updated occupational handler assessment for

BBAB during registration review. As the labels have been revised to specify that closed system 

loading and delivery systems be used for BBAB, occupational exposures are no longer 

anticipated during the closed system loading and delivery systems addition of BBAB into pulp 

and paper mill process tanks.
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3.3.1 Occupational Handler Exposure

The Agency does not anticipate the need to conduct an occupational handler exposure 

assessment because BBAB is only applied in closed loading and delivery systems. 

3.3.2 Residential Handler Exposures

The Agency does not anticipate the need to conduct a residential handler assessment because 

BBAB is used only in pulp and paper mills and is not registered for residential use. BBAB is not 

applied to residential areas nor is it used to preserve consumer products such as paint, household 

cleaning products, plastics, textiles that lead to residential exposure. The residential use that was 

considered in the 2000 assessment (paint) was cancelled.

3.3.3 Residential Post-Application Exposures

The Agency does not anticipate the need to conduct a residential post-application assessment as 

there are no registered residential uses of BBAB (See Section 3.3.2).

3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures 

EPA anticipates the need to conduct an aggregate assessment for BBAB. Upon a reevaluation 

and selection of toxicological endpoints, combined with the human health exposure assessments 

expected as a part of this registration review case, aggregate exposures will need to be assessed. 

This assessment will include dietary (food and water) exposures. Residential exposures, which 

are normally included in an aggregate assessment, are not anticipated for BBAB based on 

currently registered uses. 

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 BBAB and any other substances and BBAB 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 BBAB 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/.

4 Environmental Risk Assessment

The Agency has not previously conducted a risk assessment that supports a complete endangered 

species determination for BBAB. The ecological risk assessment planned during registration 

review will allow the Agency to determine potential acute and chronic risks to aquatic organisms 

exposed to BBAB transported from treatment sites into the aquatic environment. The risk 

assessment also will allow the Agency to determine whether each use of the BBAB has 'no 
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effect' or 'may affect' federally listed threatened or endangered species (listed species) or their 

designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a 

listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and 

Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate.

4.1 Environmental Fate Assessment

Through the results of a hydrolysis study of BBAB (MRID 44458401), three straight-chain 

hydrolytic degradation compounds were identified: (1) the parent compound minus a bromine 

molecule (BAAB); (2) the parent compound minus one bromoacetic acid group (BAHB); and (3) 

bromoacetic acid (BA). Estimated physical/chemical and environmental fate properties of these 

degradates are presented in Table 5. The experimentally-determined hydrolytic half-life of 

BBAB is 8.3 days at pH 5, 7 hours at pH 7, and 4 minutes at pH 9. Based on this information, 

BBAB may be persistent enough in surface water that aquatic organisms may be exposed

particularly at lower pHs.

Of the three hydrolytic degradates, BAHB and BA appear to have the potential to be persistent 

enough to be released to surface water downstream of WWTPs that receive pulp and paper mill 

discharges. Based on a hydrolytic half-life of 43 days at pH 5 and 29 hours at pH 7, BAHB was 

determined to be a significant degradate that could potentially be persistent enough to enter 

surface water following discharge from pulp and paper mill effluent. Bromoacetic acid was 

stable to hydrolysis at pH values of 5, 7 and 9. Consequently, there may be the potential for 

aquatic organisms downstream of wastewater treatment plants receiving pulp and paper mill 

effluent to be exposed to BBAB, BAHB, and BA.

No data on photodegradation in water for BBAB and its degradation compounds have been 

submitted. Data on photodegradation in water for BBAB and its degradates are not anticipated to 

be required since these chemicals do not absorb light in the 290-800 nm range (Lyman et al., 

1990).

BBAB and its degradation compounds are highly water soluble and are expected to have limited 

potential for sorption to soil and sediment (Table 4 and 5). Based on Henry’s Law constants of 

10-6 or less for BBAB and its degradates, these chemicals are unlikely to volatize from water into 

air (Table 4 and 5).

For BBAB, BAHB, and BA, the Agency anticipates requiring environmental fate data on aerobic 

aquatic metabolism, biodegradability during wastewater treatment, and activated sludge 

respiration inhibition to further refine information on the persistence of these chemicals in the 

environment. A more detailed discussion of the environmental fate of BBAB and its degradates 

is presented in Appendix B of this FWP.

4.2 Environmental Exposure Pathways

Based on the registered use of BBAB in pulp and paper mill systems as well as 

physical/chemical properties and environmental fate data for BBAB and its degradates, the 

Agency cannot rule out the possibility that aquatic organisms downstream of wastewater 

treatment facilities that receive pulp and paper mill discharges have the potential to be exposed 
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to BBAB and/or its degradates. The Agency has created conceptual models for potential routes 

of environmental exposure which are included in “Conceptual Models for Environmental 

Exposure Pathways of Antimicrobial Pesticides,” found in the docket at www.regulations.gov, 

EPA-HQ-OPP-2014-0638-0002. A conceptual model of pulp and paper mill systems can be 

found on page 26.

4.3 Ecological Effects Assessment

Based on the hydrolysis study (MRID 44458401), the primary residues that can reach surface 

water are parent BBAB and the degradates, BAHB and BA. The Agency anticipates requiring 

additional ecological effects studies based on this potential exposure from effluent to reduce the 

uncertainties in the risk assessment (See Table 7). Appendix C contains the previously-submitted 

toxicity data. The additional aquatic testing listed in Table 10 is anticipated to be required based 

on the persistence of BBAB and its degradates in the aquatic environment and the possibility of 

the exposure of nontarget organisms in water downstream from wastewater treatment plants that 

receive pulp and paper mill discharges. Since the degradates are formed within hours of the onset 

of testing, testing the parent compound (BBAB) would be sufficient to determine the toxicity of 

these degradates, since they will be formed during the duration of the aquatic tests. Therefore, no 

degradate ecotoxicity testing is expected to be necessary for BBAB.

4.3.1 Measures of Effect (Ecotoxicology Endpoints)

Ecotoxicity endpoint data are used as measures of effects to aquatic and terrestrial organisms. All 

available ecotoxicity endpoints in the Agency’s files from BBAB and its degradation products, 

studies submitted by registrants or other interested parties, federal laboratory data, or from the 

public literature are tabulated in Appendix C . The most sensitive values for each receptor group 

will be used for the risk assessment (Table 10). These selected endpoints and the missing 

endpoints from the indicated data gaps may be updated during the risk assessment phase based 

on any additional submitted data or data found in the public literature. 

Table 9 - Selected Ecological Effects Endpoints for Risk Assessment of BBAB

Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Reference

(MRID)

Birds Mallard duck Acute Oral LD50 = 196 mg/kg 43214201

Subacute Dietary LC50 = >5000 mg/kg 43214202

Mammals Acute NOAEL = 5 mg/kg/day 44750901

Freshwater fish and 

amphibians Rainbow trout

Acute LC50 = 0.025 mg/kg 43191001

Chronic Data anticipated to be 

required (fish early life stage) --

Freshwater 

invertebrates Waterflea

Acute EC50 = 0.14 mg/kg 43204501

Chronic

Data anticipated to be 

required (aquatic invertebrate 

life-cycle)

--

Freshwater benthic 

invertebrates -- Subchronic or Chronic Data not anticipated to be required: Not expected to be associated with sediment

Estuarine/marine fish Sheepshead minnow Acute Data anticipated to be 

required --

Estuarine/marine 

invertebrates

Eastern oyster (shell 

deposition/ embryo 

larval)

Acute Data anticipated to be 

required --
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Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Reference

(MRID)

Mysid Acute Data anticipated to be 

required --

Estuarine/marine 

benthic invertebrates -- Subchronic or Chronic Data not anticipated to be required: Not expected to be associated with sediment

Aquatic plant 

growth, algae

Non-listed Data anticipated to be 

required -- Listed

Aquatic plant 

growth, vascular 

plants

Non-listed Data anticipated to be 

required -- Listed

Terrestrial Plants

Vegetative Vigor Nonlisted Data not anticipated to be required: Not

expected to come into contact with 

terrestrial plants in the environment Vegetative Vigor 

Listed

4.4 Exposure Analysis Plan

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates

Based on available information, the Agency cannot rule out potential for exposure of aquatic 

organisms to BBAB, BAHB, and bromoacetic acid downstream of wastewater treatment plants 

that receive pulp and paper mill discharges at facilities that use BBAB to control slime 

formation. The Agency plans to use the General Population and Ecological Exposures from 

Industrial Releases module (hereinafter referred to as the Industrial Releases module) of E-FAST 

(Exposure and Fate Assessment Screening Tool) to determine the number of days of exceedance 

of BBAB, BAHB, and bromoacetic acid concentrations of concern for aquatic organisms to 

predict the potential for exposures and risks to aquatic organisms downstream of pulp and paper 

mills where BBAB is used to control slime formation.

The use of BBAB to control slime formation at pulp and paper mills is an industrial use. Since a 

screening tool to analyze exposures and ecological risk from industrial uses is not currently 

available, a screening-level down-the-drain analysis of these uses is not within the scope of this 

FWP (see Appendix D). To analyze potential exposures and ecological risks from this industrial 

use, the input data required to run the Industrial Releases module of E-FAST include:

- Percent removal of antimicrobial or degradate during wastewater treatment;

- Environmental releases of antimicrobial to surface water in kg/site/day;

- Annual number of days of release to surface water; 

- Standard Industrial Classification code to represent pulp and paper mills; and

- Concentrations of concern for aquatic animals and plants.

Any information on processes that would be expected to reduce concentrations of BBAB, 

BAHB, and bromoacetic acid released via pulp and mill discharges will be considered by the 

Agency to determine whether potential exposures of aquatic organisms to these chemicals can be 

mitigated.
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4.5 Effects Analysis Plan

Additional open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) 

database. The ECOTOX database will be searched during the risk assessment phase of BBAB

and the data reviewed following the Agency’s policy for reviewing public literature for use in

assessing risks from pesticides.

4 Open literature studies will be reviewed that potentially may 

provide data for missing endpoint values or provide values more sensitive than those available 

from studies submitted by registrants. ECOTOX was created and is maintained by the USEPA, 

Office of Research and Development, and the National Health and Environmental Effects 

Research Laboratory’s Mid-Continent Ecology Division.

5 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 most recent risk assessment for BBAB, 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), BBAB is subject to 

the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

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 9 inert ingredients. A second list of chemicals 

 4

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_reregistration_work

group/esa_evaluation_open_literature.htm
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identified for EDSP screening was published on June 14, 20135 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.6

6 Optional Label Changes

As noted in Section 3.3, all registrations and labels were clarified to require closed loading and 

delivery systems where appropriate. Dermal and inhalation exposure studies are no longer 

anticipated to be needed to evaluate occupational exposure. In addition the Agency invites any 

label amendments that could be considered to eliminate the anticipated need for EPA to require 

certain data, reduce the possibility that EPA’s planned risk assessments overestimate risk due to 

reliance on conservative assumptions, and/or improve label clarity.

A DCI will be developed requiring generation and submission of the data listed under the 

“Anticipated Data Needs” Section of this document. The Agency expects to issue the DCI by

September of 2016. 

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

chemicals. 6 http://www.epa.gov/endo/
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8 References 

Kline, 2005. Specialty Biocides North America 2004-2005, Volume II: United States, Kline and 

Company, Inc.

Lyman, W.J., W.F. Reehl, and D.H. Rosenblatt. 1990. Handbook of Chemical Property 

Estimation Methods. American Chemical Society. ISBN O-8412-1761-0

MRID 43191001. Bettencourt, Michael J. 1994. BBAB – Acute Toxicity to Rainbow Trout 

(Oncorhynchus mykiss) Under Flow-through Conditions. Guideline 72-1©. SLI Study 

#995.1193.6173.108. Submitted by Springborn Laboratories, to Buckman Laboratories 

International.

MRID 43204501 Putt, Arthur E. 1994. BB–B - Acute Toxicity to Daphnids (Daphnia magna)

Under Flow-through Conditions. Guideline 72-2. SLI Study #995.1193.6174.115. 

Submitted by Springborn Laboratories, to Buckman Laboratories International. 

MRID 43214201. BBAB: An Acute Oral Toxicity Study with the Mallard. Wildlife International 

LTD. Project No.: 210-121. FIFRA Guideline 71-1. 1994. Submitted to Buckman 

Laboratories International, Inc. 

MRID 43214202. BBAB: A Dietary LC50 Toxicity Study with the Mallard. Wildlife 

International LTD. Project No.: 210-120. FIFRA Guideline 71-1. 1994. Submitted to 

Buckman Laboratories International, Inc. 

MRID 43376101. Wells, D. (1994) BBAB–Determination of the Solubility on Water and 

Selected Solvents: Final Report: Lab Project Number: 94-3-5218: 995.0792.6156.700. 

Unpublished study prepared by Springborn Labs, Inc. 41 p.

MRID 43376102. Wells, D. (1994) BBAB–Determination of Vapor Pressure: Amended Final 

Report: Lab Project Number: 94-7-5355: 995.0792.158.740. Unpublished study prepared 

by Springborn Labs, Inc. 50 p.

MRID 43376103. Mao, J. (1994) BBAB–Determination of the n-Octanol/Water Partition 

Coefficient: Amended Final Report: Lab Project Number: 94-4-5244: 

995.0792.6157.705. Unpublished study prepared by Springborn Labs, Inc. 35 p.

MRID 44458401. Cohen, S. (1997) Hydrolysis of cis 1, 4-Bisbromoacetoxy-2-butene (BBAB) in 

Buffered Aqueous Solutions: Final Report: Lab Project Number: ME 9600202. 

Unpublished study prepared by Pittsburgh Environmental Research Lab., Inc. 97 p.

MRID 44750901. Cappon, G. (1999) A prenatal developmental toxicity study of BBAB in rats. 

WIL Research Laboratories, Inc., 1407 George Road, Ashland, OH. Laboratory Study 

No.: WIL-94052, January 14, 1999. Unpublished.

MRID 44757001. Rush, R. (1999). A 90-day oral (gavage) toxicity study in rats with a 28-day 

recovery phase. Springborn Laboratories, Inc. (SLI), Ohio Research Center, 640 North 
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Elizabeth Street, Spencerville, OH. SLI Study No. 3138.109, January 25, 1999. 

Unpublished.

U.S. Environmental Protection Agency (EPA). 2002. ECOTOX User Guide: ECOTOXicology 

Database System. Version 3.0. Available: http://www.epa.gov/ecotox/

U.S. Environmental Protection Agency. 2012. EPI-WEB 4.11. 

http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
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Appendix A Toxicology Profile

Acute Toxicity for Product Labeling 

As shown in Table A1, BBAB is moderately acutely toxic by the oral and dermal routes. No 

studies are available for acute inhalation, eye irritation, dermal irritation, and skin sensitization. 

Due to the corrosive properties of BBAB, this chemical is currently classified as toxicity 

category I for skin and eye irritation. It is assumed to be a positive dermal sensitizer in the 

absence of data. 

Table A1– Acute Toxicity Studies for BBAB

Guideline No./ Study 

Type 

MRID 

Number Results Toxicity Category

870.1100/ 

Acute oral toxicity 43181101 LD50 = 292 mg/kg(M); 163 mg/kg (F);

220mg/kg (combined) II

870.1200/ 

Acute dermal toxicity 43152401 LD50 > 2000mg/kg III

870.1300/ 

Acute inhalation toxicity N/A Data gap.1 unknown

870.2400/ 

Acute eye irritation N/A Data waived due to corrosive nature of the product. I

870.2500/ 

Acute dermal irritation N/A Data waived due to corrosive nature of the product. I

870.2600/ 

Skin sensitization N/A Data waived due to corrosive nature of the product. positive

1 This data is anticipated to be required during product reregistration.

Subchronic Toxicity 

There is one 90-day oral toxicity study available for BBAB.

In the 90 day oral toxicity study (MRID 44757001), 10 Sprague-Dawley Crl:CD®(SD)IGS BR 

rats/sex/group were administered BBAB (Lot No. KDD, Batch # 9, 93.1% a.i.) in Mazola® corn 

oil orally by gavage at doses of 0, 4.5, 22.5, or 39.1 mg/kg/day for a minimum of 90 consecutive 

days. An additional 10 animals/sex/group were incorporated into the control and high-dose 

groups for a recovery phase. For high-dose animals, the test article was initially administered at a 

dosage of 45 mg/kg/day on days 1-37, but was reduced to 35 mg/kg/day on days 38-91 due to 

dose-related toxicity, for a total time-weighted dose of 39.1 mg/kg/day. 

Treatment with BBAB resulted in significant toxicity in mid- and high-dose animals. In the highdose groups, 4/20 males and 3/20 females died or were euthanized moribund due to treatmentrelated toxicity. During the treatment period, clinical signs in mid- and high-dose animals 

included a dose-related increased incidence of salivation prior to and post dosing, and high-dose 

males and females additionally exhibited decreased activity (11/20 and 3/20, respectively) and a 

wobbly gait (8/20 and 3/20, respectively). High-dose females had decreased mean absolute body 
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weights at the end of treatment (day 90; 92% of controls; p<0.05). Reductions in mean body 

weight gains during treatment were biologically significant in high-dose males and females, with 

the greatest reduction occurring toward the end of treatment on days 57-90 (58% and 70% of 

controls, respectively, statistical analysis not conducted). Statistically significant decreases 

(p<0.05; 0.01) in food consumption in the high-dose males (82-93%) and females (80-90%) and 

mid-dose females (80-90%) may have been treatment-related. 

Treatment with BBAB also resulted in irritative/corrosive effects on the stomach. Mid- and highdose animals had mild anemia (possibly due to blood loss from the stomach) as indicated by 

generally statistically significant, dose-related decreases in erythrocytes, hemoglobin, and 

hematocrit. A regenerative response to the anemia in mid- and high-dose animals was evidenced 

by generally statistically significant increases in MCV and MCH, changes in red blood cell 

morphology that are consistent with immature erythrocytes (macrocytes, polychromasia, and 

anisocytosis), and minimal to moderate splenic extramedullary hematopoiesis observed during 

microscopic examination. 

High-dose animals additionally had enlarged spleens and increased absolute and relative spleen 

weights (94 and 107% vs. the controls for males, respectively; 146 and 163% vs. the controls for 

females, respectively). Eroded and thickened areas of the stomachs of mid-and high-dose 

animals were observed during gross necropsy, while microscopic examination revealed multiple 

findings in the nonglandular mucosa of the stomach including edema, hemorrhage, 

inflammation, hyperkeratosis, and hyperplasia. Ulcers (high-dose) and erosion (mid- and highdose) of the nonglandular epithelium were also sometimes present.

Low-dose males and females had a slightly increased incidence of minimal hyperkeratosis (3/10 

for both) and hyperplasia (2/10 and 4/10, respectively) of the nonglandular mucosa of the 

stomach (controls: 0/10 for both lesions). In the female, minimal edema of the stomach and 

minimal extramedullary hematopoiesis were seen in 1/10 animals compared to 0/10 in the 

control group for both lesions. 

Clinical chemistry analysis revealed statistically significantly elevated levels of serum chloride 

in mid- and high-dose males (+11% and +30%, respectively) and females (+9 and +15%, 

respectively). Microscopic evaluation of the liver revealed minimal to marked periportal 

hepatocyte vacuolation in 10/12 high-dose males, and minimal to mild vacuolation in 2/10 middose males: no other supporting markers of liver toxicity were present.

Following the 28-day recovery phase, body weight gain in high-dose males still trailed controls 

by 9%, but was increased by 35% in high-dose females. High-dose males still had elevated 

relative spleen weights (127%), but no changes were noted during gross or microscopic 

examination of the spleen. The only lesion still evident in the animals was periportal hepatocyte 

vacuolation in 5/8 high-dose males, but the severity was decreased to minimal to mild. All 

remaining indicators of toxicity observed during treatment were generally comparable to controls 

or were not biologically significant following the recovery phase.

The LOAEL is 4.5 mg/kg/day (lowest dose tested) in male and female rats and is based on 

microscopic findings of hyperkeratosis and hyperplasia of the non-glandular mucosa of the 

stomach in both sexes and edema of the stomach in the female. An NOAEL was not determined.
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This subchronic toxicity study is classified as Acceptable and satisfied the OPPTS 870.3100 

guideline. 

There are no 90-day dermal or inhalation studies for BBAB. A 90 day dermal and 90 day 

inhalation toxicity study are anticipated as being needed for registration review of BBAB to 

assess occupational hazard from dermal and inhalation exposures.

Developmental Toxicity 

There is an available range-finding developmental toxicity study and a guideline developmental 

toxicity study in rats for BBAB. 

In the dose range-finding rat developmental toxicity study (MRID 44739401), maternal toxicity 

occurred in dams treated with 50 mg/kg/day and higher. Gross clinical examination revealed 

increased salivation and decreased body weights, body weight gains, and food consumption. 

Internal examination revealed gastric irritation (reddened mucosa, thickening, distention, fluidfilled, and/or dark red areas) and enlarged adrenals. Treatment with 50 mg/kg/day resulted in 

post-implantation loss accompanied by increases in the number of resorptions/dam (both early 

and late resorptions), and decreases in the number of live fetuses/litter, mean fetal body weights, 

and gravid uterine weights. 

In the definitive developmental toxicity study (MRID 44750901), 25 bred Crl:CD®(SD)BR rats 

per group were administered BBAB (Lot/Batch No. K.D.D., 93.5% a.i.) in Mazola® corn oil 

orally by gavage at doses of 0, 5, 20, or 35 mg/kg/day on gestation days (GD) 6-19, inclusive. 

On GD 20, dams were sacrificed, subjected to gross necropsy, and all fetuses examined 

externally, viscerally, and skeletally for malformations/variations. 

One mid-dose female was found dead on GD 16 from gavage trauma. All other animals survived 

to scheduled necropsy. Maternal toxicity was manifested in the 20 and 35 mg/kg/day groups. 

During the treatment period of GD 6-20, dose-related, increased salivation prior to dosing 

correlated with observation of clear and tan matting around mouth at the time of dosing and 1-

hour post-dosing in both the mid- and high-dose groups. The treatment related increased 

salivation was considered to be associated with the corrosivity of BBAB. In addition, the 35 

mg/kg/day group also had statistically significant decreases in mean maternal absolute body 

weights, body weight gains, and food consumption. Mean absolute body weights were 

statistically significantly decreased (p<0.05; 0.01) starting on GD 12 and continuing to study 

termination on GD 20 (93% to 95% of controls). For the overall treatment period (GD 6-20), 

high-dose dams gained 20% less weight and consumed 9% less food than controls (p<0.01), and 

had final absolute and corrected body weights 7% and 8% less than controls, respectively 

(p<0.01). 

No treatment-related differences in body weights, body weight gains, or food consumption were 

noted in low- or mid-dose dams. No treatment-related effects were noted in any of the treatment 

groups during gross necropsy.

Therefore, the maternal toxicity LOAEL is 20 mg/kg/day based on an increased incidence 

of salivation, and the maternal toxicity NOAEL is 5 mg/kg/day.
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Mean fetal body weight was statistically significantly (p≤0.05) decreased in the high-dose group 

(3.5 g) as compared with controls (3.7 g). No dose- or treatment-related, statistically significant 

effects on pregnancy rates, number of corpora lutea, pre- or post-implantation losses, 

resorption/dam, fetuses/litter, or fetal sex ratios were observed in the treated groups as compared 

with the controls. No dams had complete litter resorption.

No treatment-related external, visceral, or skeletal malformations/variations were observed in 

any litter. Most treated and control litters contained fetuses with minor variations in skeletal 

ossification. 

Therefore, the developmental toxicity LOAEL is 35 mg/kg/day based on decreased mean 

fetal body weights, and the developmental toxicity NOAEL is 20 mg/kg/day.

This developmental toxicity study is classified as Acceptable/guideline and fulfills the OPPTS 

870.3700 Prenatal Developmental Toxicity Study Guideline.

There is no available developmental toxicity study in rabbits; this study is anticipated to be 

required to support the indirect food use of BBAB under registration review.

Reproductive Toxicity

There is no reproductive toxicity study available for BBAB. This study is anticipated to be 

required to support the indirect food use of BBAB under registration review. 

Chronic Toxicity 

There are no chronic toxicity data available for BBAB. For the indirect food use of BBAB in 

pulp and paper mills, a chronic toxicity study is expected to be required. The toxicology data 

requirements in the Antimicrobial Data Requirements rule (40 CFR 158.2230) require a chronic 

toxicity study when residue of the pesticide chemical in the diet from indirect food use is greater 

than 200 parts per billion (> 200ppb), or when residue is less than 200 parts per billion (< 200 

ppb) if the use of the pesticide is likely to result in repeated human exposure over a considerable 

portion of the human lifespan.

Carcinogenicity 

There are no carcinogenicity data available for BBAB. For the indirect food use of BBAB in 

pulp and paper mills, a carcinogenicity study is expected to be required. The toxicology data 

requirements in the Antimicrobial Data Requirements rule (40 CFR 158.2230) require a 

carcinogenicity study when residue of the pesticide chemical in the diet from indirect food use is 

greater than 200 parts per billion (> 200ppb), or when residue is less than 200 parts per billion 

(< 200 ppb) if the use of the pesticide is likely to result in significant human exposure over a 

considerable portion of the human lifespan (in terms of frequency, time, duration, and/or 

magnitude of exposure).
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Mutagenicity 

The database for BBAB mutagenicity is considered adequate based on EPA’s 1991 mutagenicity 

guidelines.

In an Ames test (MRID 43201001), BBAB was not mutagenic to Salmonella typhimurium tester 

strains TA98, TA100, TA1535, and TA1537 with or without the microsomal S9activation. In the 

mouse lymphoma assay (MRID 43202601), cultures of mouse lymphoma (L5178Y) cells were 

exposed to BBAB solutions for determination of potential to induce forward mutation at the 

thymidine kinase (TK+ to TK-) locus. Under S9 activation, a dose related increased frequency of 

mutant colonies occurred at a level of moderate toxicity. Without S-9 activation, however, 

BBAB was active in the presence of moderate to severe cytotoxicity. This effect was deemed 

“equivocal” because mutagenic activity is only obvious in the presence of excessive toxicity 

(<10% of total growth); however a possible clastogenic effect was suggested. In an in vivo ICR 

mouse bone marrow micronucleus test (MRID 43156301), BBAB was negative for micronucleus 

induction in mice. 

Other Toxicological Effects (Neurotoxicity/Immunotoxicity)

There are no submitted neurotoxicity data for BBAB. Signs of neurotoxicity are noted in the 

following studies:

1. In the subchronic toxicity study (MRID 44757001), 10 Sprague-Dawley 

Crl:CD®(SD)IGS BR rats/sex/group were administered BBAB (Lot No. KDD, Batch # 9, 

93.1% a.i.) in Mazola® corn oil orally by gavage at doses of 0, 4.5, 22.5, or 39.1 

mg/kg/day for a minimum of 90 consecutive days. Clinical signs observed in surviving 

22.5 and 39.1 mg/kg/day doses animals included a dose-related increase in salivation 

prior to and post dosing, and high-dose animals additionally had decreased activity and 

wobbly gait. The incidence rates and occurrence of decreased activity and wobbly gait 

were greater in males than females.

2. In the range-finding prenatal developmental study (MRID 44739401), eight bred 

Crl:CD®(SD)BR rats per group were administered BBAB (Lot/Batch No. K.D.D., 93.5% 

a.i.) in Mazola® corn oil orally by gavage at doses of 0, 25, 50, 75, 100, or 150 mg/kg/day 

on gestation days (GD) 6-19, inclusive. Numerous signs were observed in animals dosed 

with 50 mg/kg/day and higher. Potential neurotoxic signs included hypoactivity; head 

held low; drooping/closed eyelid; body dragging, rocking, lurching or swaying while 

walking; flattened body/extended limbs; prostration; and abnormal respiration. 

Additionally, one or more 50 mg/kg/day group dams occasionally exhibited circling, 

splayed hind limbs, walking on tiptoes, sporadic nasal clicks, hunched or unkempt 

appearance. 

As there were no formal neurotoxicity measurements made in the available studies, a

neurotoxicity screening battery in the rat (OCSPP 870.6200) is anticipated to be required. 
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There are no data on the immunotoxicity of BBAB. Data on immunotoxicity is anticipated to be 

required during registration review as immunotoxicity is a data requirement for all use patterns 

under the Antimicrobial Pesticide Data Requirements rule.
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Toxicology References

Cappon, G. (1999) A dose range-finding prenatal developmental toxicity study of BBAB in rats. 

WIL Research Laboratories, Inc., 1407 George Road, Ashland, OH. Laboratory Study No.: 

WIL-94051, January 14, 1999. MRID 44739401. Unpublished.

Cappon, G. (1999) A prenatal developmental toxicity study of BBAB in rats. WIL Research 

Laboratories, Inc., 1407 George Road, Ashland, OH. Laboratory Study No.: WIL-94052, 

January 14, 1999. MRID 44750901. Unpublished.

Douds, D.A. (1994) An Acute Toxicity Study in Rats with BBAB. Springborn Laboratories 

(SLS), Spencerville, OH. Laboratory Study No.: SLS 3138.99, March 22, 1994. MRID 

43181101. Unpublished

Douds, D.A. (1994) An Acute Dermal Toxicity Study in Rabbits with BBAB. Springborn 

Laboratories (SLS), Spencerville, OH. Laboratory Study No.: SLS 3138.100, February 28, 

1994. MRID 43152401. Unpublished

Putnan, D.C. And Young, R.R. (1994) Micronucleus Cytogenetic Assay in Mice. 

Microbiological Associates Inc. (MAI), Rockville, MD. Laboratory Study No.: (MAI) 

TE064.122. March 04, 1994. MRID 43156301. Unpublished.

Rush, R. (1999). A 90-day oral (gavage) toxicity study in rats with a 28-day recovery phase. 

Springborn Laboratories, Inc. (SLI), Ohio Research Center, 640 North Elizabeth Street, 

Spencerville, OH. SLI Study No. 3138.109, January 25, 1999. MRID 44757001. 

Unpublished.

San, R.C. and Clarke, J.J. (1994) L5178Y/TK+/- Mouse Lymphoma Mutagenesis Assay. 

Microbiological Associates Inc. (MAI), Rockville, MD. Laboratory Study No.: (MAI) 

TE064.702020, April 5, 1994. MRID 43202601. Unpublished.

San, R.C. and Klug, J.J. (1994) Salmonella Plate Incorporation Mutagenicity Assay (Ames Test) 

with a Confirmatory Assay. Microbiological Associates Inc. (MAI), Rockville, MD. 

Laboratory Study No.: (MAI) TE064.501014, April 6, 1994. MRID 43201001. Unpublished
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Appendix B Environmental Fate

Environmental Fate and Transport Properties of BBAB and its 

transformation products BA, BAHB, and BAAB

This environmental fate data addresses the persistence and mobility of the parent compound 1,4-

bis-bromoacetoxy-2-butene (BBAB) and the straight-chain hydrolytic degradation compounds 

bromoacetic acid (BA), parent compound minus one bromoacetic acid group (BAHB), and 

parent compound minus a bromine molecule (BAAB).

Based on the chemical and physical properties (Table 4) and a hydrolysis study of BBAB (MRID 

44458401), three straight-chain hydrolytic degradation compounds were identified: (1) the parent 

compound minus a bromine molecule (BAAB); (2) the parent compound minus one bromoacetic 

acid group (BAHB); and (3) bromoacetic acid (BA). Physical/chemical and environmental fate 

properties of these degradates are presented in Table 5. Of the three hydrolytic degradates, 

BAHB and BA appear to have the potential to be persistent enough to be released to surface 

water downstream of WWTPs that receive pulp and paper mill discharges. BAHB was 

determined to be a significant degradate that did demonstrate some breakdown at pH values of 5 

and 7, but bromoacetic acid did not demonstrate any degradation at pH values of 5, 7 and 9.

Consequently, there may be the potential for aquatic organisms downstream of wastewater 

treatment plants receiving pulp and paper mill effluent to be exposed to BBAB, BAHB, and BA.

BBAB and its degradation compounds are highly water soluble and are expected to have limited 

potential for sorption to soil and sediment (Table 4 and 5). Based on Henry’s Law constants of 

10-6 or less for BBAB and its degradates, these chemicals are unlikely to volatize from water into 

air (Table 4 and Table 5).

Parent BBAB and its degradation compounds, BAHB and BA, have the potential to be in 

papermill effluents based on formation in significant (>10 % of applied parent compound) 

amounts and stability in the hydrolysis study. Because additional environmental fate data on 

aerobic aquatic metabolism and fate in wastewater treatment plants (ASRI and biodegradation 

studies) have not been submitted, they are anticipated to be required to reduce the uncertainty for 

the risk assessment. 

Water and Sediment

Hydrolysis

BBAB degraded in buffered solutions with half-lives of 8.3 days at pH 5, 6.9 hours at pH 7, and 

4.2 minutes at pH 9. Three degradation compounds were formed in the study, including 

bromoacetic acid (BA), parent compound minus 1 bromoacetic acid group (BAHB), and parent 

compound minus a bromine molecule (BAAB). For all three pH values, BA increased until the 

end of the study12 and reached significant concentrations (>10 % of applied parent compound). 

 12 Study duration was 30 days at pH 5, 72 hours at pH 7, and 4 hours at pH 9
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At all pH values, BAHB reached significant concentrations and declined to 19-20, 5.5, and 0 % 

by the end of the study at pH 5, 7, and 9, respectively. The half-lives of the BAHB degradate 

were 43 days, 29 hours, and 16 minutes at pH 5, 7, and 9, respectively. BAAB reached 

significant concentrations at pH 5 and declined to 8-8.8 %, but was not detected at pH 7 and 9 

(MRID 44458401).13

Aqueous Photolysis

Data on photodegradation in water for BBAB and its degradates are not anticipated to be 

required since, based on the absence of double bonds, these chemicals do not absorb light in the 

290-800 nm range (Lyman et al., 1990).

Aerobic Aquatic Metabolism

Aerobic aquatic metabolism data on parent BBAB are anticipated to be required because BBAB 

and its degradates, BAHB and BA, have the potential to reach surface water from WWTP 

effluent. Since identification and formation and decline of major degradates of the parent 

chemical is a part of this study, a study on the parent compound alone will provide the 

information needed for risk assessment. Parent BBAB, and degradates, BAHB and BA, are

highly water soluble (Tables 4 and 5) and will preferentially partition to water in the presence of 

suspended solids.

Soil

Soil Leaching/Adsorption/Desorption Batch Equilibrium

Guideline mobility data are not anticipated to be required for BBAB and its degradation 

compounds. BAHB, BAHB, and BA have negligible sorption potential based on estimated Koc 

values of 1-66 L/kg (log Koc values of 0.1-1.8) from EPI-Suite 4.11. Based on these predicted 

Koc values, these chemicals would be classified as mobile to highly mobile in soil in the FAO 

system which designates Log Koc values of <1 as highly mobile and 1-2 as mobile.

14

Aerobic and Anaerobic Soil Metabolism

Due to high solubility and limited sorption potential, any residues of BBAB and its degradates 

are expected to be present in the water phase of wastewater and not biosolids. The primary 

potential pathway for release of BBAB to soil would be expected to be land application of 

biosolids. Based on log Kow values, limited potential for BBAB and its degradates to sorb to 

biosolids would be expected. Since release of BBAB and its degradates to soil media would be 

expected to be negligible, data on aerobic and anaerobic soil metabolism are not anticipated to be 

required.

 13 D251932, Robert Quick to Norm Cook, 2/28/2000. 14 http://www.fao.org/docrep/003/x2570e/x2570e06.htm
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Bioconcentration in Fish

Parent BBAB is not likely to bioconcentrate in fish based on the low measured log Kow value of 

1.7 (Table 4). The measured low log Kow is <3, which is the general Agency level of concern 

for bioconcentration.

15 Parent BBAB also has a high measured water solubility of 630 mg/l;

compounds that have a tendency to bioconcentrate generally have low water solubility values. 

The degradation compounds, BAAB, BAHB, and BA are also not expected to bioconcentrate in 

fish based on estimated log Kow and water solubility values from EPI-WEB 4.1.

16 The estimated 

log Kow values were 1.52 for BAAB, 0.51 for BAHB, 0.41 for BA. The estimated water 

solubility values from EPI-WEB 4.1 were 1185 mg/L for BAAB, 46,640 mg/L for BAHB, and 

1.75 million mg/L for BA.

Fate, Transport, and Effects in WWTP

Activated Sludge Respiration Inhibition

Data on activated sludge respiration inhibition (ASRI) are anticipated to be required since BBAB 

and its degradates are expected to be in pulp and paper mill wastewater.

Activated Sludge Sorption Isotherm

Data on activated sludge sorption isotherm (ASSI) are not required based on the low log Kow 

values of BBAB (1.7) and of the degradates (0.41-0.52). According to the Final 158W Rule,

17

ASSI data are not required if the log Kow is <3 (Test note 19 of Environmental Fate 

Requirements Table).

Biodegradation in WWTP

For parent BBAB and the degradates, BAHB and BA, data on activated sludge biodegradation 

are anticipated to be required because BA has the potential to be present in wastewater from pulp 

and paper mills.

Table B1. Status of BBAB Environmental Fate Studies

Test Guideline

(parent compound 

unless stated)

OCSPP 

Guideline 

No. 

Study result Significant 

Degradation 

Products18

Study status Reference (MRID) 

and Comments

Hydrolysis 835.2120 DT50 of 8.3 

days, 6.9 

hours, and 4.2 

minutes at pH 

5, 7, and 9

Bromoacetic acid 

(stable)

BAHB (parent 

compound minus a 

bromoacetic acid 

group)

Acceptable 44458401

25 oC

 15 Bioconcentration in fish 850.1730 tests guideline states that log Kow values of >3 indicate high potential for 

bioconcentration.

16 EPA, 2012

17 https://www.federalregister.gov/articles/2013/05/08/2013-10162/data-requirements-for-antimicrobial-pesticides 18 Significant degradation products formed at >10 % of applied parent compound
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BAHB half-lives of

43 days, 29 hours, 

and 16 minutes at 

pH 5, 7, and 9

BAAB detected at 

pH 5 only (stable) 

Photodegradation 

in water 

835.2240 No data Not applicable Not

anticipated to 

be required

BBAB is not 

expected to absorb 

light in the 290-800 

nm range

Aerobic soil 

metabolism

835.4100 No data Not applicable Not 

anticipated to

be required

Not required based on 

use pattern

Anaerobic soil 

metabolism

835.4200 No data Not applicable Not 

anticipated to 

be required

Not required based on 

use pattern

Aerobic aquatic 

metabolism

835.4300 No data Not applicable Anticipated 

to be required

Required because BA 

degradate can be 

present in surface 

water downstream of 

WWTPs

LeachingAdsorptionDesorption 

(unaged)

835.1230 Kocs (L/kg)

33-66 

(parent)

17-43

(BAAB)

5-10 (BAHB)

1-2 (BA)

No degradation

products measured

Not 

anticipated to 

be required 

based on lack 

of sorption 

and EPISuite 

predictions

EPI-Suite 4.11

Bioconcentration 

in Fish

850.1730 No data None Not 

anticipated to 

be required

Bioconcentration of 

BBAB and 

degradation 

compounds expected 

to be limited because 

of low log Kow and 

high water solubility

Activated sludge 

sorption isotherm 

(ASSI)

835.1110 No data None Not 

anticipated to 

be required

Low Kow <3, not 

required per 158W, 

final rule1

Environmental Fate 

Data Requirements 

table

Activated sludge 

respiration 

inhibition (ASRI)

850.3300

or OECD 

2092

No data None Anticipated 

to be required

BBAB, BAHB and 

BA have the potential 

to be present in pulp 
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and paper mill 

wastewater 

Ready 

biodegradability 

or one of three 

biodegradation in 

activated sludge 

simulation tests

835.31103

835.3220

835.3240

835.3280

No data None Anticipated 

to be required

BBAB, BAHB, and 

BA have potential to 

be present in pulp and 

paper mill wastewater

1 https://www.federalregister.gov/articles/2013/05/08/2013-10162/data-requirements-for-antimicrobial-pesticides 2 EPA published draft guidance under guideline 850.6800 and has since published final guidance for this study under 

guideline 850.3300: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0021. OECD 

Test Guideline 209 can also be used as guidance for this study, available online at http://www.oecdilibrary.org/content/book/9789264070080-en. 3 For BBAB, BAHB, and bromoacetic acid, the results of the Activated Sludge Respiration Inhibition Test (ASRI) 

will determine which of these four biodegradation tests is/are anticipated to be required. 

• If the ASRI test EC50 is less than or equal to 20 mg/L, then either the (i) Biodegradation in Activated 

Sludge Study or (ii) Simulation Test - Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the 

Porous Pot Test would be anticipated to be required. If the ASRI test EC50 is greater than 20 mg/L, then 

the registrant would be anticipated to be required to conduct either: (i) Ready Biodegradability or (ii) a) 

Biodegradation in Activated Sludge or b) Simulation Test - Aerobic Sewage Treatment: A. Activated 

Sludge Units or c) the Porous Pot Test. 

• If the Ready Biodegradability study is conducted and passes, then no further testing would be anticipated 

to be required. If, however, the antimicrobial fails the Ready Biodegradability study, then the a) 

Biodegradation in Activated Sludge or b) Simulation Test - Aerobic Sewage Treatment: A. Activated 

Sludge Units, or c) the Porous Pot study would be anticipated to be required.
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Environmental Fate References

Lyman, W.J., W.F. Reehl, and D.H. Rosenblatt. 1990. Handbook of Chemical Property 

Estimation Methods. American Chemical Society. ISBN O-8412-1761-0

MRID 44458401. Cohen, S. (1997) Hydrolysis of cis 1,4-Bisbromoacetoxy-2-butene (BBAB) in 

Buffered Aqueous Solutions: Final Report: Lab Project Number: ME 9600202. 

Unpublished study prepared by Pittsburgh Environmental Research Lab., Inc. 97 p.

Quick, Robert. February 28, 2000. Risk Assessment and Science Support Branch: Final Draft 

Environmental Fate Science Chapter of Science Chapter for 1,4-Bis(bromoacetoxy)-2-

butene. PC Code 035606, Case 3030, Barcode D251932.

U.S. Environmental Protection Agency. May 8, 2013. Data Requirements for Antimicrobial 

Pesticides; Final Rule. Docket identification number EPA-HQ-OPP-2008-0110.

https://www.federalregister.gov/articles/2013/05/08/2013-10162/data-requirements-forantimicrobial-pesticides

U.S. Environmental Protection Agency. 2012. EPI-WEB 4.11. 

http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
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Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Receptors

Birds

An acute oral toxicity study using the technical grade of the active ingredient (TGAI) is available

to establish the toxicity of 1,4-bis(bromoacetoxy)-2- butene to birds. The preferred test species is 

either mallard duck (a waterfowl) or bobwhite quail (an upland gamebird). Results of this test are 

tabulated below.

Table C1 - Avian Acute Oral Toxicity

Species % ai LD50 

(mg/kg)

Toxicity 

Category

MRID No.

Author/Year

Study 

Classification

Mallard duck

(Anas platyrhynchos) 82 196 moderately 

toxic

43214201

Wildlife International, LTD/1994 Core

1,4-bis(bromoacetoxy)-2-butene has an LD50 of 196 mg/kg and is categorized as moderately 

toxic to avian species on an acute oral basis. The guideline (71-1/850.2100) is fulfilled (MRID 

43214201). 

A subacute dietary study using the TGAI of 1,4-bis(bromoacetoxy)-2-butene is available to 

establish the toxicity to birds. The preferred test species are mallard duck and bobwhite quail. 

Results of this test are tabulated below.

Table C2 - Avian Subacute Dietary Toxicity

Species % ai 5-Day

LC50(ppm)

Toxicity 

Category

MRID No.

Author/Year

Study 

Classification

Mallard duck

(Anas platyrhynchos) 82 >5000 practically nontoxic

43214202

Wildlife International, LTD/1994 Core

1,4-bis(bromoacetoxy)-2-butene has an LC50 is >5000 ppm and is categorized as practically 

nontoxic to avian species on a subacute dietary basis. The guideline (71-2(b)/850.2200) is 

fulfilled (MRID 43214202). 

Mammals

Refer to the human toxicology chapter for details on the available mammalian toxicity studies.
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Toxicity to Aquatic Receptors

Freshwater Fish

Two freshwater fish toxicity studies using the TGAI are available to establish the toxicity of 1,4-

bis(bromoacetoxy)-2-butene to fish. The preferred test species are rainbow trout (a coldwater

fish) and bluegill sunfish (a warmwater fish). Results of these tests are tabulated below.

Table C3 - Freshwater Fish Acute Toxicity

Species/

Flow-through % ai LC50 

(ppm) Toxicity Category MRID No.

Author/Year

Study 

Classification

Rainbow trout

(Oncorhynchus mykiss) 82 0.025 Very Highly Toxic 43191001Bettencourt, MJ/1994 Core

Bluegill sunfish 

(Lepomis macrochirus) 82 0.057 Very Highly Toxic 43230101Bettencourt, MJ/1994 Core

1,4-bis(bromoacetoxy)-2-butene has an LC50 which falls in the range of 0.025-0.057 ppm, and is 

categorized as very highly toxic to freshwater fish on an acute basis. The guideline (72-

1/850.1750) is fulfilled (MRID#’s 43191001, 43230101).

Freshwater Invertebrates

A freshwater aquatic invertebrate toxicity test using the TGAI is available to establish the 

toxicity of 1,4-bis(bromoacetoxy)-2-butene to aquatic invertebrates. The preferred test species is 

Daphnia magna. Results of this test are tabulated below.

Table C4 - Freshwater Invertebrate Acute Toxicity

Species % ai EC50 (ppm) Toxicity Category MRID No.

Author/Year

Study 

Classification

Waterflea

(Daphnia magna)

82 0.14 Highly Toxic 43204501

Putt, AE/1994 Core

1,4-bis(bromoacetoxy)-2-butene is categorized as highly toxic to aquatic invertebrates on an 

acute basis with an EC50 of 0.14 ppm. The guideline (72-2/850.1010) is fulfilled (MRID 

43204501). 
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Ecotoxicology References

Bettencourt, Michael J. 1994. BBAB – Acute Toxicity to Bluegill Sunfish, (Lepomis

Macrochirus) Under Flow-through Conditions. Guideline 72-1(a). SLI Study 

#995.1193.6172.105. Submitted by Springborn Laboratories, to Buckman Laboratories 

International. MRID# 43230101

Bettencourt, Michael J. 1994. BBAB – Acute Toxicity to Rainbow Trout (Oncorhynchus mykiss) 

Under Flow-through Conditions. Guideline 72-1©. SLI Study #995.1193.6173.108. 

Submitted by Springborn Laboratories, to Buckman Laboratories International. MRID# 

43191001

Putt, Arthur E. 1994. BB–B - Acute Toxicity to Daphnids (Daphnia magna) Under Flow-through 

Conditions. Guideline 72-2. SLI Study #995.1193.6174.115. Submitted by Springborn 

Laboratories, to Buckman Laboratories International. MRID# 432045-01 

BBAB: An Acute Oral Toxicity Study with the Mallard. Wildlife International LTD. Project No.: 

210-121. FIFRA Guideline 71-1. 1994. Submitted to Buckman Laboratories 

International, Inc. MRID# 43214201

BBAB: A Dietary LC50 Toxicity Study with the Mallard. Wildlife International LTD. Project 

No.: 210-120. FIFRA Guideline 71-1. 1994. Submitted to Buckman Laboratories 

International, Inc. MRID# 43214202
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Appendix D Down-the-Drain (DtD) 

Assessment

No screening-level down-the-drain analysis was performed for this case since the use of BBAB 

to control slime in pulp and paper mills is an industrial use. Results from the Down-the-Drain 

module of E-FAST are only applicable for chemicals that are incorporated in products that are 

released down-the-drain to domestic wastewater treatment facilities. Such results are not 

applicable for releases to surface water from industrial uses.
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Appendix E Chemical and Physical 

Properties of BBAB and its Degradation 

Products

Tables E1 and E2 contain the chemical and physical properties of BBAB and its degradation 

products, respectively.

Table E1 – Chemical, Physical, and Environmental Fate Properties for Parent BBAB

Guideline 

No. Parameter

EPA Reg. No. 707-234):

1,4-bis-bromoacetoxy2-butene, 87 % AIReference/Comments

830.7000 pH 2.79 at 25oC 43176301

1 ppm w/v solution in water

830.7050 UV/Visible Absorption Not applicable Based on chemical structure, structure will 

not absorb light between 290 and 800 nm

830.7220 Boiling point 130 + 2.52 oC 43176301

5 mm Hg

830.7300 Density 1.76 g/ml 43176301

20 oC

830.7370 Dissociation constant (pKa) Not applicable No ionizable functional groups

830.7550 Octanol-water partition 

coefficient at 25 oC (Log Kow) 1.7 43376103

830.7840 Solubility in water (mg/L) 630 43376101

20 oC

830.7950 Vapor pressure (mmHg) 1.59 x 10-6 43376102

20 oC

None

Henry's law constant at 25 oC 

(atm-m3/mol)

CALCULATED

1.1 x 10-9 None

atm-m3/mol = atmosphere cubic meter per mole; oC = degrees Celsius; mg/L = milligrams per liter; mmHg = 

millimeters of mercury;

Table E2 – Chemical, Physical, and Environmental Fate Properties of BBAB Degradation 

Compounds19

Compound

Test Guideline (OCSPP No.) BAAB BAHB BA

Chemical structure 

Smiles code BrCC(=O)OCC=CCOC(=O)C BrCC(=O)OCC=CCO BrCC(=O)O

Molecular formula C8H11BrO4 C6H9BrO3 C2H3BrO2

 19 All values from EPI-WEB 4.11. 

Br

O

O

O

O

CH3

Br

O

O

OH

Br

O

OH
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Page 44 of 45

Molecular weight (grams/mol) 251.08 209.04 138.95

Octanol-water partition coefficient 

at 25 oC (Log Kow)

830.7550

1.52 0.51 0.41

Solubility in water (mg/L)

830.7840 1,185 46,640 1.75 x 106

Vapor pressure (mm Hg)

830.7950 2.2 x 10-2 6.31 x 10-4 1.2 x 10-1

Henry’s law constant at 25 oC 

(atm-m3/mol)

CALCULATED – No OCSPP No.

6.1 x 10-6 3.7 x 10-9 2.6 x 10-7
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Page 45 of 45

Product Chemistry References

MRID 43176301. Wells, D. (1994) BBAB--Product Chemistry Studies: Bis(bromoacetoxy)-2-

butene: Final Report: Lab Project Number: 93-8-4890: 995.0792.6155.875. Unpublished 

study prepared by Springborn Labs., Inc. 81 p.

MRID 43376101. Wells, D. (1994) BBAB--Determination of the Solubility on Water and 

Selected Solvents: Final Report: Lab Project Number: 94-3-5218: 995.0792.6156.700. 

Unpublished study prepared by Springborn Labs, Inc. 41 p.

MRID 43376102. Wells, D. (1994) BBAB--Determination of Vapor Pressure: Amended Final 

Report: Lab Project Number: 94-7-5355: 995.0792.158.740. Unpublished study prepared 

by Springborn Labs, Inc. 50 p.

MRID 43376103. Mao, J. (1994) BBAB--Determination of the n-Octanol/Water Partition 

Coefficient: Amended Final Report: Lab Project Number: 94-4-5244: 

995.0792.6157.705. Unpublished study prepared by Springborn Labs, Inc. 35 p.

U.S. Environmental Protection Agency. 2012. EPI-WEB 4.11. 

http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm