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Page 2 of 45 Bis(bromoacetoxy)

- 2

- butene Registration Review Team

Human Health & Environmental Effects Pat Jennings James Breithaupt David Bays Tim Dole Tim McMahon Julie VanAlstine
Risk Management Stephen Savage Tina Pham Rose Kyprianou Terria Northern Jac queline Hardy

Office of General Counsel Philip RossDocket Number EPA

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Page 3 of 45 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 concentra tion 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 partitio n 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 max imum 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 solutionDocket Number EPA

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Page 4 of 45 ppb parts per billion ppm parts per million FWP Final Work Plan QSAR quantitative structure

- activity relationship RED Reregistration Eligibility Decision SAR structure activity relationship SF safety factor TGAI technical grade active ingredient TMDL total maximum daily loads UF uncertainty factor WWTPs wastewater treatment plantsDocket Number EPA

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Page 5 of 45 

### Table of Contents 1 Introduction

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

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

................................ ................................ ................................ .. 7 1.3 Case Overview

................................ ................................ ................................ ................. 8 1.4 Chemical Identification and Properties

................................ ................................ ............ 9 1.5 Use/Usage Description

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

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

................................ ................................ .................. 11 1.5.3 Usage Information

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

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

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

................................ ................................ ................................ ......................... 12 1.7.1 Human He alth

................................ ................................ ................................ ......... 12 1.7.2 Ecological

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

................................ ................................ ................................ ........ 13 3 Human Health Risk Assessment

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

................................ ................................ .................. 16 3.2 Dietary Exposure

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

................................ ................................ ................................ ........................ 17 3.2.2 Drinking Wat er

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

................................ ................................ ....... 17 3.3.1 Occupational Handler Exposure

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

................................ ................................ ............... 18 3.3.3 Residential Post

- Application Exposures

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

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

................................ ................................ .............................. 18 3. 4.2 Cumulative Exposures

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

................................ ................................ ........................... 18 4.1 Environmental Fate Assessment

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

................................ ................................ ................ 19 4.3 Ecological Effects Assessment

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

................................ ...................... 20 4.4 Exposure Analysis Plan

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

................................ ............ 21 4.5 Effects Analysis Plan

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

................................ ................................ . 22 6 Label Changes

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

................................ ................................ ................................ ............................. 23 8 References

................................ ................................ ................................ ............................. 24
Appendices Appendix A T oxicology Profile

................................ ................................ ............................... 26 Appendix B Environmental Fate

................................ ................................ ............................. 33 Appendix C Ecotoxicology Profile

................................ ................................ .......................... 39 Appendix D Down

- the

- Drain (DtD) Assessment

................................ ................................ .... 42Docket Number EPA

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Page 6 of 45 Appendix E Chemical and Physical Properties of BBAB and its Degradation Products

....... 43

List of Tables Table 1

– Summary of Anticipated Risk Assessments and Data Needs for Registration Rev iew: BBAB

................................ ................................ ................................ ................................ .............. 8 Table 2

– Anticipated Registration Review Schedule

................................ ................................ .... 9 Table 3

– Chemical Identification of BBAB

................................ ................................ .................. 9 Table 4

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

................. 10 Table 5

– Estimated Chemical, Phys ical, 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

................................ ............................... 16Docket Number EPA

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Page 7 of 45 

## 1 Int roduction

This document is the United States Environmental Protection Agency ’s ( USEPA, EPA or “the Agency ”) Final Work Plan ( FWP ) for 1,4

- bis

- bromoacetoxy

- 2

- butene , herein referred to as BBAB

. The FWP document explains what EPA's Office of Pesticide Programs (OPP) knows about BBAB , highlighting anticipated data and assessment needs, identifying the types of information that would be especially useful to the Agency in conducting the review, and providin g an anticipated timeline for completing BBAB review. The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows about BBAB and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on BBAB

. 

## 1.1 Statutory and Regulatory Authority The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pestic ides 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 registrat ion 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 enviro nment. 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 Ins ecticide, 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 CF R 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 a nd what additional risk analyses and data or information it believes are needed to make a registration review decision.


## 1.2 Updates to the Workplan Since the publication of the Preliminary Work Plan (PWP), the Agency has made the following updates:

• Updated Section 1.3, Case Overview.

• Updated Table 1 and Sections 1.5. 2 , 3. 3.1 , and 3.4 based on label changes submitted since the publication of the PWP, specifying closed loading only.

• Updated the timeline in Table 2, Anticipated Registration Review Schedule.Docket Number EPA

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Page 8 of 45 • Revised Table 7 , Studies Anticipated as Nee ded for the Registration Review to remove occupational exposure from open pour applications which are no longer needed , t o c larify neurotoxicity requirements , and added footnote to work with stakeholders to determine the appropriate test substance s.

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

. • Updated Section 6, Optional Label Changes to closed loading application label change and reduction in DCI requirements

. • Deleted Table 9, “ Occupational Handler Exposure Scenario for BBAB ” fro m section 3.3.1

. • Deleted the “Guidance for Commenters” S ection.

• Updated Section 7 and Next Steps

. No public comments were received on the initial docket

. M odifications were made to the anticipated data needs which did not change the registration review schedule of the BBAB PWP. This document makes final the work plan for the BBAB registration review process.


## 1.3 Case Overview
The docket for BBAB ( c ase 3030 ) has been established at http://www.regulations.gov in docke t number EPA

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. Documents associated with this registration review can be viewed in this docket. Tables 1

- 2 b elow summar ize 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 detail s)

Dietary (food) Yes 2000 Updated Developmental T oxicity S tudy in R abbits Reproduction and F ertility E ffects in R ats Chronic Toxicity in Rats Carcinogenicity in Rats Acute N eurotoxicity Immunotoxicity Dietary (drinking water) Yes 2000 New See above data needs for Dietary (food) Occupational Handler No (See Section 3.3. 1 ) 2000 None N one 1

Residential Handler No (See Section 3.3.2) 2000 None None 2

Resident i al Post Application No (See Section 3.3.3) 2000 None None 2
Aggregate Yes 2000 New See above data needs for Dietary (food)

Cumulative No (See Section 3.4 .2 ) 2000 None NoneDocket Number EPA

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Page 9 of 45 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 detail s)

Tolerance Review No (See Section 1. 6 .1) N/A N/A None

Ecological Yes 2000 Updated Biodegradability in WWTP Activated Sludge Respiration Inhibition Aerobic Aquatic M etabolism Acute E stuarine /Marine T oxicity T est Fish Early

- Life Stage T est Aquatic Invertebrate Life

- C ycle T est Aquatic Plant Growth (Algal) T est Aquatic Pla nt Growth (V ascular Plant) T est N/A = Not applicable 1 Application method was changed . BBAB is only applied in closed loading and delivery systems

. 2 R esidential use from 2000 assessment was cancelled. Currently , t here 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 Preli minary Work Plan 2015

- 03 2015

- 03

- 30 Close Public Comment Period 2015

- 05 2015

- 05

- 29 Phase 2: Case Development Issue Final Work Plan 2015

- 09 2015

- 09 Issue Data Call

- In (DCI) 2016

- 03 Receive Data to be Considered in Risk Assessment 2020

- 03 Open 30

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

- 09 Close Public Comment Period 2021

- 10 Phase 3: Registration Review Decision and Implementation Open 60

- Day Public Comment Period for Proposed Decision 2022

- 03 Close Public Comment Period 2022

- 05 Issue Final Decision 202 2

- 09 Begin Post

- Decision Follow

- up 2022 Total (years) 7

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

## 1.4 Chemical Identification and Properties

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

. Table 3

– Chemical Identification of BBAB
Chemical Name 1,4

- bis

- bromoacetoxy

- 2

- butene (BBAB) Chemical Classification Halogenated alkane PC Code 035605 CAS Number 20679

- 58

- 7 Smiles code BrCC(=O)OCC=CCOC(=O)CBrDocket Number EPA

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Page 10 of 45 Molecular Formula C 8 H 10 Br 2 O 4 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 Environ mental 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 o C (Log K ow ) 1.7 43376103

830.7840 Solubility in water (mg/L) 630 43376101 20 o C
830.7950 Vapor pressure (mmHg) 1.59 x 10

- 6 43376102 20 o C

None Henry's law constant at 25 o C (atm

- m 3 /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) 44458 401

atm

- m 3 /mol = atmosphere cubic meter per mole; o C = 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 incre ase 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 p hysical/chemical and environmental fate properties o f these degradates are presented in Table 5

. T able 5

– Estimated Chemical , Physical , and Environmental Fate Propertie s of Hydrolytic Degradation Compounds of BBAB 1 Compound

Test Guideline (OCSPP No.) BAAB BAHB BA

1 Except for hydrolysis half

- lives (MRID 44458401), all values in this table are from EPI

- WEB 4.11.Docket Number EPA

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Page 11 of 45

Chemical structure

Smiles code BrCC(=O)OCC=CCOC(=O)C BrCC(=O)OCC=CCO BrCC(=O)O Molecular formula C 8 H 11 BrO 4 C 6 H 9 B r O 3 C 2 H 3 BrO 2 Molecular weight (grams/mol) 251.08 209.04 138.95 Octanol

- water partition coefficient at 25 o C (Log K ow ) 830.7550 1.52 0.51 0.41
Solubility in water (mg/L) 830.7840 1,185 46,640 1.75 x 10 6 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 o C (atm

- m 3 /mol) CALCULATED

– No OCSPP N o. 6.1 x 10

- 6 3.7 x 10

- 9 2.6 x 10

- 7

Hydrolysis 835.2120 At pH 5, s table but not present in significant amounts (<10 % ) Not detected (pH 7 and 9) 43 days (pH 5) 29 hours (pH 7) 16 minutes (pH 9) Stable at pH 5, 7, and 9) Additional product chemistry information on BBAB and its degradates is available in Appendix E.


## 1.5 Use/Usage Description 1.5.1 Registrations There are two EPA

- registered products that contain BBAB as an active ingredient (a.i.). The produ cts include one manufacturing use product (MUP) and one end

- use product (EUP)

. The MUP (EPA Reg

. N o. 1448

- 374 ) contains 9 5 percent a.i. in the form of a liquid. The EUP (EPA Reg. No. 1448

- 353) contains 80 percent a.i. in the form of a ready

- to

- use solution in drums ranging from 55 to 330 gallons and permits application rates of 0.15

- 0.30 lbs of product (equivalent to 0.24 lb ai) per ton of paper produced

. 

### 1.5.2 Summary of Registered Uses

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

. BBAB can be applied by the following application methods: closed loading mete r pump.
Table 6

– Summary of BBAB Registered Uses

Use Application Method Application Rate Control of Microbial Slime in Pulp and Paper Mills Closed loading Meter pump 0.15

- 0.30 lb AI/ton paper B r O O O O

C H 3

B r O O O H

B r O O HDocket Number EPA

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Page 12 of 45 

### 1.5.3 Usage Information No usage information is available for BBAB in the Kline Biocides Report

. 2


## 1.6 Regulatory Histor y The first product containing BBAB as an active ingredient was registered in the United States in 1964. I n 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 S ection 1.2).

T he Agency intend s to issue a PDCI and complete product reregistration for all BBAB product s

. E xisting data gaps will be addressed during registration review.


### 1.6.1 Tolerance Information EPA has not established tolerances for residues of BBAB in or on raw agricultural commodities
o r 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 an d Drug Administration (US FDA) under FFDCA Section 409 for use in the manufacture of paper and paperboard that contact food ( 21CFR 17 6

. 300)

. 

## 1.7 Incidents 1.7.1 Human Health Individual Incident Reports

Incidents that are rated as moderate (HC) , major (HB) or fatality (HA) are reported as individual reports in the OPP Incident Data System (IDS). These reports include information regarding the causes of the incident and symptoms experienced. In the case of BBAB , two individu al reports

2 Special Biocides 2004

- 2005. A Global Series of Regional Market Analysis. Volume II: United States, Kline & Company, 2006. 3 The 2000 preliminary risk asse ssment 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

• Toxicol ogy 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 DecisionDocket Number EPA

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Page 13 of 45 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 i rritation 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 quarte rly). 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 the se incidents.


### 1.7.2 Ecological
No BBAB incidents have been reported in the Agency ’s Ecological Incident Information System (EIIS) as of December 8 , 2014

. 

## 2 A nticipated Data Needs

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

.Docket Number EPA

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Page 14 of 45 Table 7

– Studi es Anticipated as Needed for the Registration Review of BBAB

GLN Study Name Test Substance 1 Time Frame (Measured in months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data

Requirement Applicable Exposure Scenario
835.3110 2 835.3220 2 835.3240 2 835.3280 2 Biodegradability in WWTP TGAI, BAHB and BA degradates 12 Environmental exposure Pulp and paper mill s Ecological

850.3300 2 , 3 Activated Sludge Respiration Inhibition (ASRI) TGAI, BAHB, and BA degradates 12 Environmental exposure Pulp and paper mills Ecological

835.4300 4 Aerobic aquatic metabolism TGAI 24 Environmental exposure Pulp and paper mills Ecological
850.1075 Acute estuarine fish toxicity TGAI 12 Environmental effects Pulp and paper mills Ecological
850.1300 Aquatic invertebrate life

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

- stage TGAI 24 Environmental effects Pulp and paper mills Ecological

850.4500 5 Aquatic plant growth (algal) Tier II (dose response) TGAI 12 Environmental effects Pulp and paper mills Ecological

850.4550 5 Aquatic plant growth (aquatic vascular plant) Tier II (dose response) TGAI 12 Environmental effects Pulp and paper mills Ecological

870.3700 Developmental Toxicity Study in Rabbits TGAI 24 Aggregate Dietary Pulp and paper mills Food and Water

870.3800 6 Reproduction and fertility effects in rats TGAI 48 Aggregate Dietary Pulp and paper mills Food and Water

870.4100 7 Chronic toxicity in rats TGAI 48 Aggregate Dietary Pulp and paper mills Food and Water

870.4200 7 Carcinogenicity in rats TGAI 48 Aggregate Dietary Pulp and paper mills Food and Water

870.6200 8 Neurotoxicity screening battery TGAI 24 Aggregate Dietary Pulp and paper mills Food and Water

870.7800 9 Immunotoxicity TGAI 12 Aggregate Dietary Pulp and paper mills Food and WaterDocket Number EPA

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Page 15 of 45 1. The Agency intends to work with stakeholders to determine the appropriate test substance, based on BBAB’s pH dependent degrad ation pattern. This may result in data being required on certain degradates or may eliminate the need for certain data.

. 2. For BBAB, BAHB, and bromoacetic acid, t he results of the Activated Sludge Respiration Inhibition Test (ASRI) will determine which of these four biodegradation test s 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 wo uld 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 Biodegradabil ity 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 Tre atment: A. Activated Sludge Units, or c) the Porous Pot study would be anticipated to be required. 3. EPA published draft guidance under guideline 850.6800 and has since published final guidance for this study under guideline 8 50.3300: http://www.regulations. gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0021. OECD Test Guideline 209 can also be used as guidance for this study, available online at http://www.oecd

- ilibrary.org/content/book/9789264070080

- en. 4. The anticipated Data Call

- In Notice will provide that o n e study using parent BBAB may be conducted : aerobic aquatic metabolism studies measure parent compounds and degradates. 5. In a Federal Register Notice dated June 27, 2012, EPA split the Public Draft OPPTS 850.5400 test guideline into two test guid elines: OCSPP 850.4500 and OCSPP 850.4550. See “Final Test Guidelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0028

. 6. Results from a multi

- generation (EPA guideline 870.3800) or an extended on e

- generation reproductive and fertility effects study using OECD Test Guideline 443 ( http://www.oecd

- ilibrary.org/envi ronment/test

- no

- 443

- extended

- one

- generation

- reproductive

- toxicity

- study_9789264185371

- en ) will satisfy this anticipated requirement. 7. The use of BBAB in manufacture of pulp and paper is an indirect food use that triggers the need for chronic toxicity and carcinogenicity data (see 40 CFR §158.2230 footnotes 20 and 21) based on the expectation that use is likely to resu lt in repeated human exposure over a considerable portion of the human lifespan. The anticipated Data Call

- In Notice will provide that a combined chronic toxicity/carcinogenicity study (870.4300) may be conducted to fulfill these data needs in lieu of conducting separate chronic toxicity and carcinogenicity studies. 8. Acute (study due 12 months after receipt of DCI) and subchronic (study due 24 months after receipt of DCI) neurotoxicity studies are anticipated to be required. A protocol should be submitted to the agency for review prior to conducting the neurotoxicity studies. 9. All 90

- day subchronic studies in the rodent can be designed to si multaneously fulfill the requirements of the 90

- day immunotoxicity studies by adding separate groups of animals for testing of immunotoxicity parameters.Docket Number EPA

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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 assessmen t 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. T he 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, a nd 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 =100 a 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 = 3000 b 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

- , intermediate

long

- term Dermal 4.5 mg/kg/day (LOAEL) Target MOE = 300 c Subchronic toxicity study

– Rats ( MRID 44757001) (See above for effects) Short

- term inhalation 5 mg/kg/day (NOAEL) Target MOE =100 a Prenatal Developmental Toxicity Study

– Rats (MRID 44750901) (See above for effects) Intermediate

- and long

- term inhala tion 4.5 mg/kg/day (LOAEL) Target MOE = 1000 d 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 va riation factor, 3x for LOAEL/NOAEL extrapolation d 10x interspecies scaling factor, 10x intra

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## 3.2 Dietary Exposure

EPA anticipates the need to conduct a n upd ated dietary exposure (food and water ) assessment to support th e existing uses of BBAB during r egist ration r eview. 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 a n 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 bee n adjusted to account for the FQPA Safety Factor (SF). This calculation is performed for each population subgroup for which an endpoint exists. A risk estimate that is less than 100% of the acute or chronic PAD is not of concern. Acute and chronic dietary risk for BBAB will be assessed by comparing dietary exposure estimates expressed in mg/kg/day to the acute Population Adjusted Dose (aPAD) and chronic Population Adjusted Dose (cPAD).


### 3.2.1 Food The Agency anticipates the need to conduct a dietary (food) assessm ent for BBAB during registration review. A screening

- level (food only) assessment was completed in support of this FWP using updated assumptions (20% of food consumed in the human diet may contact paper; 100 pounds of slurry contains 1 pound of pulp by weight) and NHANES/WWEIA 2003

- 2008 consumption data. Exposure estimates utilized <1% of the aPAD and 9 % of the cPAD for the general U.S. population, and utilized <1% of the aPAD and 23 % of the cPAD for children 1

- 2 years old, the most highly

- exposed p opulation 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 S ection 4.1)

. 

## 3.3 Occupational and Residen tial Exposures

EPA does not anticipate the need to conduct a n updated occupational handler assessment for BBAB during registration r eview

. As the label s have been revised to specify that closed system loading and delivery systems be used for BBAB, oc cupational exposures are no longer anticipated during the closed system loading and delivery systems addition of BBAB into pulp and paper mill process tanks.Docket Number EPA

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Page 18 of 45 

### 3.3.1 Occupational Handler Exposure The Agency does not anticipa te the need to conduct an occupational handler exposure assessment because BBAB is only applied in closed loading and delivery systems

.


### 3.3.2 Residential Handler Exposures The Agency does not anticipate the need to conduct a residential handler assessment because BBAB i s used only i n 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 pr oducts 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 anticipate s the need to conduc t an aggregate assessment for BBAB

. Upon a re evaluation 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 as sessment will include dietary (food and water ) exposures

. R esidential e xposures , which
are normally included in an aggregate assess ment, are not anticipated for BBAB based on
cu rrently registered uses

. 

### 3.4.2 Cumulative Exposures

W ith 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 eff orts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/

. 

## 4 Environmental Risk Asse ssment

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 ch ronic 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 'noDocket Number EPA

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Page 19 of 45 effect' or 'may affect' federally listed threat ened 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) t he parent compound minus a bromine molecule (BAAB); (2) the parent compound minus one bromoacetic acid group (BAHB); and (3) bromoacetic acid (BA). Estimated p hysical /chemical and environmental fate properties of these degradates are presented in Table 5. The experimentally

- determined hydrolytic half

- life of BBAB is 8.3 days at pH 5, 7 hours at pH 7, and 4 minutes at pH 9. Based on this information, BBAB may be persistent enough in surface water that aquatic organisms may be exposed particularly at lower pH s

. O f the three hy drolytic 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. B romoacetic 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 sub mitted. Data on photodegradation in water for BBAB and its degradates are not anticipated to be required since these chemicals do not absorb light in the 290

- 800 nm range (Lyman et al., 1990). BBAB and its degradatio n 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 e nvironmental fate data on aerobic aquatic metabolism , biodegradability during wastewater treatment , and activated sludge respiration inhibition to further refine info rmation on the persistence of these chemicals in the environment. A more detailed discussion of the environmental fate of BBAB and its degradates is presented in Appendix B of this FWP

. 

## 4.2 Environmental Exposure Pathways Based on the registered use of BBA B 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 exposedDocket Number EPA

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Page 20 of 45 to BBAB and/or its degradates. The Agency has created conceptual models for potential routes of environmental expos ure which are included in “Conceptual Models for Environmental Exposure Pathways of Antimicrobial Pesticides ,” found in the docket at www.regulations.gov , EPA

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. 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 residue s that can reach surface water are parent BBAB and the degradates , BAHB and BA

. The Agency anticipates requiring add itional 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 tr eatment 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 forme d 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 mi ssing endpoints from the indicated data gaps may be updated during the risk assessment phase based on any additional submitted data or data found in the public literature.

Table 9

- Selected Ecological Effects Endpoints for Risk Assessment of BBAB
Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Reference (MRID)
Birds Mallard duck Acute Oral LD 50 = 196 mg/kg 43214201 Subacute Dietary LC 50 = >5000 mg/kg 43214202 Mammals Acute NOAEL = 5 mg/kg/day 44750901
Freshwater fish and amphibians Rainbow trout Acute LC 50 = 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 a nticipated to be required (aquatic invertebrate life

- cycle) --
Freshwater benthic invertebrates -- Subchronic or Chronic Data n ot 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 o yster (shell deposition/ embryo larval ) Acute Data anticipated to be required --Docket Number EPA

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Page 21 of 45 Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Reference (MRID) Mysid Acute Data anticipated to be required -- Estuarine/marine benthic invertebrates -- Subchronic or Chronic Data n ot anticipated to be required : Not expected to be associated with sediment Aquatic plant growth, algae Non

- listed Data anticipated to be
r equired -- Listed Aquatic p lant growth , vascular plants Non

- listed Data anticipated to be required -- Listed

Terrestrial Plants Vegetative Vigor Non

listed Data not anticipated to be required : N ot expected to come into contact with terrestrial plants in the environment Vegetative Vigor Listed 

## 4.4 E xposure Analysis Plan 4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates
Based on available information, t he 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 faciliti es that use BBAB to control slime formation. The Agency plans to use the General Population and Ecological Exposures from Industrial Releases module (hereinafter referred to as the Industrial Releases module) of E

- FAST (Exposure and Fate Assessment Screening Tool) to determine the number of days of exceedance of BBAB, BAHB, and bromoacetic acid concentrations of concern for aquatic organisms to predict the potential for exposures and risks to aquatic organisms downstream of pulp and paper mills where BBAB is used to control slime formation

. The use of BBAB to control slime formation at pulp and paper mills is an industrial use. Since a screening tool to analyze exposures and ecological risk from industrial uses is not currently available, a screening

- level down

- the

- drain analysis of these uses is not within the scope of this FWP (see Appendix D)

. To analyze potential exposures and ecological risks from this industrial use, the input data required to run the In dustrial 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 Ind ustrial 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.Docket Number EPA

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Page 22 of 45 

## 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 pesticide s

. 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, an d 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 exposu re 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 b e 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 assessme nts, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent r isk assessment for BBAB , EPA reviewed these data and selected the most sensitive endpoi nts for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA S ection 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 estro gen, 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 effe ct.
Under FFDCA S ection 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 i ngredients. A second list of chemicals

4 http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_reregistration_work group/esa_evalua tion_open_literature.htmDocket Number EPA

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Page 23 of 45 identified for EDSP screening was published on June 14, 2013 5 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

A s noted in Section 3.3, all registrations and labels were clarified to require closed loading and delivery systems where appropriate. D ermal and inhalation exposure stud ies are no longer anticipated to be needed to evaluate occupational exposure. In addition t he Agency invites any label amendments that could be considered to eliminate the anticipated need f or EPA to require certain data, reduce the possibility that EPA’s planned risk assessments overestimate risk due to reliance on conservative assumptions, and/or improve label clarity.

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

“ Anticipated Data Needs” S ection of this document. The Agency expects to issue the DCI by September of 20 16.

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

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- 0477

- 0074 for the final second list of

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## 8 References
Kline, 2005. Specialty Biocides North America 2004

- 2005, Volume II: United States, Kline and Company, Inc. Lyman, W.J., W.F. Reehl, and D.H. Rosenblatt. 1990. Handbook of Chemical Property Estimation Methods. American Chemical Society. ISBN O

- 8412

- 1761

- 0

MRID 431910 01

. Bettencourt, Michael J

. 1994

. BB AB

– 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 432142 02

. 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 NorthDocket Number EPA

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Page 25 of 45 Elizabeth Street, Spencerville, OH. SLI Study No. 3138.109, January 25, 1999. Unpublished.

U.S. Environmental Protection Agency (EPA). 2002. E COTOX 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.htmDocket Number EPA

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# Appendix A T oxicology 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 classi fied as toxicity category I for skin and eye irritation. It is assumed to be a positive dermal sensit izer 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 LD 50 = 292 mg/kg(M); 163 mg/kg (F); 220mg/kg (combined) II
870.1200/ Acute dermal toxicity 431524 01 LD 50 > 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 tox icity 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 high

dose groups, 4/20 males and 3/20 females died or were euthanized moribund due to treatment

related t oxicity

. 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

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Page 27 of 45 weights at the end of treatment (d ay 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, r espectively, 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 BBA B also resulted in irritative/corrosive effects on the stomach

. Mid

- and high

dose 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 (macroc ytes, 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 10 7% 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 multi ple findings in the nonglandular mucosa of the stomach including edema, hemorrhage, inflammation, hyperkeratosis, and hyperplasia. Ulcers (high

- dose) and erosion (mid

- and high

dose) of the nonglandular epithelium were also sometimes present.

Low

- dose male s 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 stomac h 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 (+1 1% 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 mid

dose 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

. A ll 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
m icroscopic findings of hyperkeratosis and hyperplasia of the non

- glandular mucosa of the stomach in both sexes and edema of the stomach in the female

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Page 28 of 45 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 inh alation 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, fluid

filled, 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 Ma zola ® 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/var iations.

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 decrease d (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 abso lute 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 a ny 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.Docket Number EPA

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Page 29 of 45 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/lit ter, 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 developmen tal toxicity study is classified as Acceptable/guideline and fulfills the OPPTS 870.3700 Prenatal Developm ental 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 p arts 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 carcin ogenicity study is expected to be required. The toxi cology 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 p arts 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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Page 30 of 45 

## 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 forw ard 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 se vere 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 micronuc leus test (MRID 431563 01), BBAB was negative for micronucleus induction in mice. 

## Other Toxicological Effects (Neurotoxicity/Immunotoxicity)
There are no submitted neurotoxicity data for BBAB

. S igns of neurotoxicity are noted in the following studies:

1. In t he 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 9 0 consecutive days

. Clinical signs observed in surviving 22.5 and 39.1 mg/kg/day doses animals included a dose

- related increase in salivation prior to and post dosing, and high

- dose animals additionally had decreased activity and wobbly gait

. The incidence rates and occurrence of decreased activity and wobbly gait were greater in males than females.

2. In the range

- finding prenatal developmental study (MRID 44739401), eight bred Crl:CD ® (SD)BR rats per group were administered BBAB (Lot/Batch No. K.D.D., 93.5% a.i.) in Mazola ® corn oil orally by gavage at doses of 0, 25, 50, 75, 100, or 150 mg/kg/day on gestation days (GD) 6

- 19, inclusive

. Numerous signs were observed in animals dosed with 50 mg/kg/day and higher

. Potential neurotoxic signs included hypoactivity; head held low; drooping/closed eyelid; body dragging, rocking, lurching or swaying while walking; flattened body/extended limbs; prostration; and abnormal respiration

. Additionally , one or more 50 mg/kg/day group dams occasionally exhibited circling, splayed hind limbs , walking on tiptoes, sporadic nasal clicks, hunched or unkempt appearance.
As there were no formal neurotoxicity measurements made in the available studies, a neurotoxicity screening battery in the rat (OCSPP 870.6200) is anticipated to be required.Docket Number EPA

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Page 31 of 45 There are no data on the i mmunotoxicity of BBAB. Data on immunotoxicity is anticipated to be required during registration review as i mmunotoxicity is a data requirement for all use patterns under the Antimicrobial Pesticide Data Requirements rule.Docket Number EPA

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Page 32 of 45 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 developme ntal 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 Lab oratories (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 431563 01

. 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

. UnpublishedDocket Number EPA

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Page 33 of 45 

# Appendix B Environmental Fate

Environmental Fate and Transport Properties of BBAB and its t ransformation product s 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 compound s 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 presente d 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 degr adate 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).

P arent BBAB and its degradation compounds , BAHB and BA , have the potential to be in papermill effluent s based on form ation 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 n ot 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 degradat ion 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 st udy 12 and reached significant concentrations ( > 10 % of applied parent compound)

.

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Page 34 of 45 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 BAH B 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

D ata on photodegradation i n 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 ar e anticipated to be required because BBAB and its degradates , BAHB and BA , have the potential to reach surface water f ro m 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. P arent BBAB , and degradates, BAHB and BA , are h ighly water soluble (Table s 4 and 5) and will preferentially partition to w ater 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 degradat ion 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, the se chemicals would be classif ied 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 a nd 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, d ata 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.htmDocket Number EPA

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Page 35 of 45 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 solubilit y values

. T he degradat ion compounds , BAAB, BAHB, and BA are also not expected to bioconcentrate in fish based on estimated log Kow and water so lubility 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 , Trans port, and Effects in WWTP Activated Sludge Respiration Inhibition Data on activated sludge respiration inhibition (AS R I) 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 b ased 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 n ote 19 of Environmental Fate Requirements Table ). Biodegradation in WWTP
For parent BBAB and the degradate s , BAHB and BA, d ata 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 Products 18 Study status Reference (MRID) and Comments
Hydrolysis 835.2120 DT 50 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 4 445 8 401

25 o C

15 Bioconcentr ation 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

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- pesticides 18 Significant degradation products formed at > 10 % of applied parent compoundDocket Number EPA

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Page 36 of 45 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 No t applicable Not anticipated to be required Not required based on use pattern

Anae robic soil metabolism 835.4 2 00 No data No t applicable Not anticipated to be required Not required based on use pattern

Aerobic aquatic metabolism 835.4300 No data Not applicable Anticipated to be r equired Required because BA degradate can be present in surface water downstream of WWTPs
Leaching

Adsorption

Desorption (unaged) 835.1230 Kocs (L/kg)

33

- 66 (parent) 17

- 43 (BAAB) 5

- 10 (BAHB) 1

- 2 (BA) No degradat io n products measured Not anticipated to be required based on lack of sorption and EPI

Suite predictions EPI

- Suite 4.11

Bioconcentration in Fish 850.1730 No data None Not anticipated to be required Bioconcentration of BBAB and degradat ion 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 rule 1 Environmental Fate Data Requirements table
Activated sludge respiration inhibition (ASRI) 850. 3300 or OECD 209 2 No data None Anticipated to be r equired BBAB, BAHB and BA have the potential to be present in pulpDocket Number EPA

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Page 37 of 45 and paper mill wastewater
Ready biodegradability or one of three biodegradation in activated sludge simulation tests 835.3110 3 835.3220 835.3240 835.3280 No data None Anticipated to be r equired BBAB, BAHB, and BA ha ve 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=E PA

- HQ

- OPPT

- 2009

- 0154

- 0021 . OECD Test Guideline 209 can also be used as guidance for this study, available online at http://www.oecd

ilibrary.org/content/book/9789264070080

- en. 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, t hen 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 th e 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.Docket Number EPA

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Page 38 of 45 Environmental Fate References Lyman, W.J., W.F. Reehl, and D.H. Rosenblatt. 1990. Handbook of Chemical Property Estimation Methods. Am erican 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 Environm ental 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

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- 2008

- 0110

. https://www.federalregister.gov/articles/2013/05/08/2013

- 10162/data

- requirements

- for

antimicrobial

- pesticides U.S. Environmental Protection Agency. 2012. EPI

- WEB 4.11. http://www.epa.gov/oppt/exposure/pubs/episuitedl.htmDocket Number EPA

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Page 39 of 45 

# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Receptors

Birds

An acute or al 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 gam ebird)

. 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 t his 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 432142 02)

. Mammals

Refer to the human toxicology chapter for details on the available mammalian toxicity studies

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Page 40 of 45 

## 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 431910 01 Bettencourt, MJ/1994 Core

Bluegill sunfish (Lepomis macrochirus ) 82 0.057 Very Highly Toxic 432301 01 Bettencourt, 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 fulfi lled (MRID#’s 43191001, 432301 01).

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 432045 01 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 432045 01)

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Page 41 of 45 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# 432301 01
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# 431910 01
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# 432142 01 BBAB: A Dietary LC50 Toxicity Study with the Mallard

. Wildlife International LTD

. Pro ject No.: 210

- 120

. FIFRA Guideline 71

- 1

. 1994

. Submitted to Buckman Laboratories International, Inc

. MRID# 432142 02Docket Number EPA

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Page 42 of 45 

# 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 s lime 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 resul ts are not applicable for releases to surface water from industrial uses.Docket Number EPA

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Page 43 of 45



# Appendix E Chemical and Physical Properties of BBAB and its Degradat ion Products

Tables E1 and E2 contain the chemical and physical properties of BBAB and its degradat ion products , respectively.
Table E1

– 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/ Comments

830.7000 pH 2. 79 at 25 o C 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 o C 43176301 5 mm Hg
830.7300 Density 1.76 g/ml 43176301 2 0 o C
830.7370 Dissociation constant (pKa) Not applicable No ionizable functional groups

830.7550 Octanol

- water partition coefficient at 25 o C (Log K ow ) 1.7 43376103

830.7840 Solubility in water (mg/L) 630 43376101 20 o C
830.7950 Vapor pressure (mmHg) 1.59 x 10

- 6 43376102 20 o C

None Henry's law constant at 25 o C (atm

- m 3 /mol) CALCULATED 1.1 x 10

- 9 None

atm

- m 3 /mol = atmosphere cubic meter per mole; o C = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury;
Table E2

– Chemical , Physical , and Environmental Fate Properties of BBAB Degradat ion Compounds 19 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 C 8 H 11 BrO 4 C 6 H 9 B r O 3 C 2 H 3 BrO 2

19 All values from EPI

- WEB 4.11. B r O O O O

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B r O O HDocket Number EPA

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Page 44 of 45

Molecular weight (grams/mol) 251.08 209.04 138.95 Octanol

- water partition coefficient at 25 o C (Log K ow ) 830.7550 1.52 0.51 0.41
Solubility in water (mg/L) 830.7840 1,185 46,640 1.75 x 10 6 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 o C (atm

- m 3 /mol) CALCULATED

– No OCSPP No. 6.1 x 10

- 6 3.7 x 10

- 9 2.6 x 10

- 7Docket Number EPA

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Page 45 of 45 Product Chemistry References MRID 43176301. Wells, D. (1994) BBAB

-- Product Chemistry Studies: Bis(bromoacetoxy )

- 2

- butene: Final Report: Lab Project Number: 93

- 8

- 4890: 995.0792.6155.875. Unpublished study prepared by Springborn Labs., Inc. 81 p. MRID 43376101. Wells, D. (1994) BBAB

-- Determination of the Solubility on Water and Selected Solvents: Final Report: Lab P roject 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