Docket Number EPA-HQ-OPP-2014-0799

www.regulations.gov

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

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

PWP Preliminary 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 Case Overview ................................................................................................................. 7

1.3 Chemical Identification and Properties............................................................................ 9

1.4 Use/Usage Description................................................................................................... 11

1.4.1 Registrations ........................................................................................................... 11

1.4.2 Summary of Registered Uses.................................................................................. 11

1.4.3 Usage Information .................................................................................................. 11

1.5 Regulatory History ......................................................................................................... 11

1.5.1 Tolerance Information ............................................................................................ 12

1.6 Incidents......................................................................................................................... 12

1.6.1 Human Health ......................................................................................................... 12

1.6.2 Ecological ............................................................................................................... 12

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........................................................................................... 19

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

4.2 Environmental Exposure Pathways................................................................................ 20

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 Optional Label Changes........................................................................................................ 23

7 Guidance for Commenters.................................................................................................... 23

7.1 Preliminary Work Plan................................................................................................... 23

7.1.1 Trade Irritants.......................................................................................................... 23

7.1.2 Water Quality.......................................................................................................... 23

7.1.3 Environmental Justice............................................................................................. 24

7.1.4 Structure Activity Relationships............................................................................. 24

7.1.5 Additional Information ........................................................................................... 25

8 Next Steps ............................................................................................................................ 26

9 References............................................................................................................................. 27

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Appendices

Appendix A Toxicology Profile............................................................................................... 29

Appendix B Environmental Fate ............................................................................................. 36

Appendix C Ecotoxicology Profile.......................................................................................... 42

Appendix D Down-the-Drain (DtD) Assessment.................................................................... 45

Appendix E Chemical and Physical Properties of BBAB and its Degradation Products ....... 46

List of Tables

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

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

Table 2 – Anticipated Registration Review Schedule .................................................................... 8

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

Table 4 – Chemical, Physical, and Environmental Fate Properties for Parent BBAB................... 9

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

Table 9 – Occupational Handler Exposure Scenario for BBAB................................................... 18

Table 10 – Selected Ecological Effects Endpoints for Risk Assessment of BBAB..................... 20

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1 Introduction

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

Agency”) Preliminary Work Plan (PWP) for 1,4-bis-bromoacetoxy-2-butene, herein referred to 

as BBAB. The PWP 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.

The Agency encourages all interested stakeholders to review the PWP and to provide comments 

and additional information that will help the Agency’s decision-making process for this 

chemical.

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. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop and commit to a Final Work Plan (FWP) and 

anticipated schedule for the BBAB case. 

1.2 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 

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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 Yes 2000 Updated

90 Day Dermal Toxicity Study in Rats

90 Day Inhalation Toxicity Study in Rats

Developmental Toxicity Study in Rabbits

Reproduction and Fertility Effects in Rats

Acute Neurotoxicity 

Immunotoxicity 

Indoor Exposure – Inhalation

Indoor Exposure – Dermal

Residential Handler No

(See Section 3.3.2) 2000 None None1

Residential Post 

Application

No

(See Section 3.3.3) 2000 None None1

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

Cumulative No

(See Section 3.4.2) 2000 None None

Tolerance Review No

(See Section 1.5.1) N/A N/A None

Ecological Yes 2000 Updated

Biodegradability in WWTP

Aerobic Aquatic Metabolism

Activated Sludge Respiration Inhibition 

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 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

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Close Public Comment Period 2015-05

Phase 2: Case Development

Issue Final Work Plan 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).

1.3 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

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

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Guideline 

No. Parameter

EPA Reg. No. 707-234:

1,4-bis-bromoacetoxy-2-

butene, 87 % AI

Reference (MRID)/Comments

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

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

Br

O

O

O

O

CH3

Br

O

O

OH

Br

O

OH

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1.4 Use/Usage Description

1.4.1 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.

1.4.2 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: open pour or 

meter pump.

Table 6 – Summary of BBAB Registered Uses

Use Application Method Application Rate

Control of Microbial Slime in Pulp and Paper Mills Open Pour or Meter pump 0.15-0.30 lb AI/ton paper

1.4.3 Usage Information

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

2

1.5 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).

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

Existing data gaps will be addressed during registration review. 

1.5.1 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 (21CFR§176.300).

1.6 Incidents

1.6.1 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 

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.

1.6.2 Ecological

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

(EIIS) as of December 8, 2014.

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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 Substance

Time Frame 

(Measured in 

months from 

DCI Receipt)

Risk Assessment(s) 

Data Will Support

Use Site(s) 

Triggering 

Anticipated Data 

Requirement

Applicable 

Exposure 

Scenario

835.31101

835.32201

835.32401

835.32801

Biodegradability in WWTP

TGAI, BAHB 

and BA 

degradates

12 Environmental exposure Pulp and paper mills Ecological 

835.43002 Aerobic aquatic metabolism TGAI 24 Environmental exposure Pulp and paper mills Ecological

850.33001 Activated Sludge Respiration Inhibition (ASRI)

TGAI, BAHB, 

and BA 

degradates

12 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

850.45003 Aquatic plant growth (algal) Tier II (dose 

response) TGAI 12 Environmental effects Pulp and paper mills Ecological

850.45503 Aquatic plant growth (aquatic vascular plant) 

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

870.3250 90 Day Dermal toxicity study in rats TGAI 24 Occupational Pulp and paper mills Open pour liquids5

870.3465 90 Day Inhalation toxicity study in rats TGAI 24 Occupational Pulp and paper mills Open pour liquids5

870.3700 Developmental Toxicity Study in Rabbits TGAI 24

Aggregate

Dietary 

Occupational 

Pulp and paper mills

Food and Water

Open pour liquids5

870.38004 Reproduction and fertility effects in rats TGAI 48

Aggregate

Dietary 

Occupational 

Pulp and paper mills

Food and Water

Open pour liquids5

870.41006 Chronic toxicity in rats TGAI 48 Aggregate

Dietary Pulp and paper mills Food and Water

870.42006 Carcinogenicity in rats TGAI 48 Aggregate

Dietary Pulp and paper mills Food and Water

870.6200 Acute neurotoxicity TGAI 12

Aggregate

Dietary 

Occupational 

Pulp and paper mills

Food and Water

Open pour liquids5

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GLN Study Name Test Substance

Time Frame 

(Measured in 

months from 

DCI Receipt)

Risk Assessment(s) 

Data Will Support

Use Site(s) 

Triggering 

Anticipated Data 

Requirement

Applicable 

Exposure 

Scenario

870.7800 Immunotoxicity TGAI 12

Aggregate

Dietary 

Occupational 

Pulp and paper mills

Food and Water

Open pour liquids5

875.1200 Dermal Exposure – Indoor TGAI or 

surrogate 24 Occupational Pulp and paper mills Open pour liquids5

875.1400 Inhalation Exposure – Indoor TGAI or 

surrogate 24 Occupational Pulp and paper mills Open pour liquids5

1. 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.

2. 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.

3. 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.

4. 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.

5. If the label can be changed to require closed loading and delivery systems, then the open pour exposure scenario will not need to be assessed.

6. 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.

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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 1,3-PAD 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 

PWP 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 3.5% of the cPAD for the 

general U.S. population, and utilized <1% of the aPAD and 15% 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 anticipates the need to conduct an updated occupational handler assessment for BBAB 

during registration review. As the labels do not specify that closed system loading and delivery 

systems be used for BBAB, occupational exposures are anticipated during the open pour addition 

of BBAB into pulp and paper mill process tanks.

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3.3.1 Occupational Handler Exposure

EPA anticipates the need to revise the occupational handler exposure assessment conducted in 

the 2000 risk assessment for BBAB to account for toxicological and exposure data that are 

anticipated to be needed for registration review. The exposure scenario that will be assessed is 

listed in Table 9.

Table 9 – Occupational Handler Exposure Scenario for BBAB

Scenario Exposure Route(s) Duration

Open pour liquids for pulp and paper mill slime treatment Dermal 

Inhalation Short and Intermediate Term 

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/.

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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 

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 at pH 5 that aquatic organisms may be 

exposed.

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, based on the absence of double bonds, 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 PWP.

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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 

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 10 – 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) --

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Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Reference

(MRID)

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 --

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 

Vegetative Vigor Listed terrestrial plants in the environment

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 

PWP (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 Table 7 of this document, it is recommended that all registrations and labels be 

clarified to require closed loading and delivery systems where appropriate. If this occurs for all 

registrations and labels, then dermal and inhalation exposure studies will likely not be needed to 

evaluate occupational exposure.

The Agency invites comment on 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.

7 Guidance for Commenters

7.1 Preliminary Work Plan

The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a final work plan for the BBAB registration review case. 

7.1.1 Trade Irritants

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency

will work to harmonize tolerances and international maximum residue limits (MRLs) and may 

modify tolerance levels to do so, when possible. Stakeholders are asked to comment on any 

trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and 

MRLs in key export markets, providing as much specificity as possible regarding the nature of 

the concern.

7.1.2 Water Quality

BBAB and the degradates, BAAB and BAHB, are not identified as a cause of impairment for 

any water bodies listed as impaired under section 303(d) of the Clean Water Act.

7 In addition, no 

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/

7 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

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Total Maximum Daily Loads (TMDL) have been developed for BBAB and its degradates.

8 More 

information on impaired water bodies and TMDLs can be found at EPA’s website.

9

However, bromine (as bromate) and bromoacetic acid are listed as by-products of chlorine and 

chloramine disinfection of drinking water.

10 Bromate has a maximum concentration limit (MCL)

of 0.01 mg/l or 10 μg/l as an annual average. Bromoacetic acid is listed under the general 

category of haloacetic acids, which also include dichloroacetic acid, trichloroacetic acid, 

monochloroacetic acid, and dibromoacetic acid. While bromoacetic acid has no compound–

specific MCL, the MCL for the sum of the five haloacetic acid compounds is an annual average 

of 0.06 mg/l or 60 μg/l.

The Agency invites submission of water quality data for this pesticide. To the extent 

possible, data should conform to the quality standards in Appendix A of the OPP Standard 

Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in 

OPP’s Registration Review Risk Assessment and Management Process11 in order to ensure they 

can be used quantitatively or qualitatively in pesticide risk assessments.

7.1.3 Environmental Justice 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to BBAB compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population.

7.1.4 Structure Activity Relationships 

EPA must rely upon information of appropriate quality and reliability for each decision made by 

the Agency. In the OPP, the evaluation process for a pesticide chemical traditionally begins with 

the applicant’s submission of a set of studies conducted with the specific pesticide chemical of 

interest. The use of the results of such testing (measured data) is a logical, scientifically rigorous 

process that identifies the physical, chemical, and environmental fate properties of the pesticide, 

as well as the dose and endpoints at which an adverse effect can occur in various animal species. 

Today, there is significant interest in alternative techniques, i.e., techniques other than data 

generation that could significantly inform the Agency’s decision-making process. Recently, OPP 

has made increasing use of structure activity relationship (SAR) as part of its regulatory 

decision-making process. In the SAR process, a chemical’s molecular structure is compared to 

that of other chemicals for which data are available. These structural similarities are then used to 

make predictive judgments about a chemical’s physical, chemical, and biological properties. 

8

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

9 http://www.epa.gov/owow/tmdl/

10 http://water.epa.gov/drink/contaminants/basicinformation/disinfectionbyproducts.cfm 11 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm

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Thus, the chemical’s physical, chemical, and biological properties are a function of (or directly 

related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To 

develop a QSAR, a selected set of measured data on a single physical, chemical, or biological 

property is used to derive a model (an equation) to predict the value of that property. 

Since SAR assessments and QSAR modeling are another set of tools that are available to Agency

scientists, OPP has begun a process shift that envisions shifting from the current study-by-study 

approach to an approach in which the use of predicted data, generated using validated models, is 

considered along with information from open literature and studies specifically generated under 

Part 161 requirements. All relevant information would be considered as part of a weight-of-theevidence evaluation. 

At this time, EPA believes that for certain endpoints, especially physical/chemical and fate 

properties, that SAR and QSAR might be effectively utilized to fulfill these data requirements 

for many antimicrobial pesticide chemicals. When considering biological properties, at this time, 

EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of 

chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is 

appropriate because the risk assessment for lower toxicity chemicals can be stream-lined, i.e., a 

screening-level assessment procedure rather than multiple tiers of assessments with progressively 

more data requirements. 

If stakeholders believe that submission of predicted data can fulfill one of the data needs for the 

BBAB case, then the Agency invites submission of this information. The submitter would be 

expected to supply a rationale describing the utility of the information and provide 

documentation on the scientific validity of the information. The determination that the predicted 

data fulfills the data requirement would be at the sole discretion of the Agency. Pre-submission 

consultation with the Agency is encouraged. 

7.1.5 Additional Information 

Stakeholders are also specifically asked to provide available information and data that will assist 

the Agency in refining its risk assessments, including any species-specific ecological effects 

determinations. The Agency is interested in receiving the following information: 

1. Confirmation on the following label information: 

A. Sites of application 

B. Formulations 

C. Application methods and equipment 

D. Maximum application rates 

E. Frequency of application, application intervals and maximum number of 

applications 

F. Geographic limitations on use 

2. Use or potential use distribution 

3. Use history 

4. Usage/use information for non-agricultural uses (e.g., materials preservation) 

5. Typical application interval 

6. State or local use restrictions 

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7. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency

8. Monitoring data 

8 Next Steps

After the 60-day comment period closes in May 2015, the Agency will review and respond to 

any comments received in a timely manner, and then issue a Final Work Plan for the BBAB 

case.

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9 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 hindlimbs, walking on tiptoes, sporadic nasal clicks, hunched or unkempt 

appearance. 

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

neurotoxicity study 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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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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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

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