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Bis(bromoacetoxy)

- 2

- butene Registration Review Team

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

Office of General Counsel Philip Ross

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TERMS, ABBREVIATIONS AND SYMBOLS

A.I. or a.i. active ingredient aPAD acute population adjusted dose ASRI activated sludge respiration inhibition atm

- m3/mole atmospheric pressure

- cubic meter per mole BBAB bis(bromoacetoxy)

- 2

- butene °C degrees Celsius CAS Chemical Abstracts Service CFR Code of Federal Regulations cPAD chronic population adjusted dose DCI data call

- in EC50 median (or 50 percent) effect concentration ECOTOX ECOTOXicology EDSP End ocrine 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 octan ol

- water partition coefficient LC50 median (or 50 percent) lethal concentration LD50 median (or 50 percent) lethal dose LOAEL lowest

- observed

- adverse

- effect

- level Log Kow logarithm of the octanol

- water partition coefficient μg microgram ml/g milliliter per gram mg/kg milligram per kilogram mg/kg/day milligram per kilogram per day mg/L milligram per liter mm Hg millimeter of mercury MOE margin of exposure MRID Master Record Identification Number MRL maximum residue limit N/A not appli cable

nm nanometers NOAEL no

- observed

- adverse

- effect

- level OCSPP Office of Chemical Safety and Pollution Prevention OECD Organization for Economic Co

- operation and Development OPP Office of Pesticide Programs PC Code Pesticide Chemical Code pH power of hydrogen or power of the concentration of the hydrogen ion pKa power of the acid dissociation constant or negative base

- 10 logarithm of the acid dissociation constant of a solution

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ppb parts per billion ppm parts per million PWP Preliminary Work Pla n QSAR quantitative structure

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

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### Table of Contents 1 Introduction

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

................................ ................................ ................. 7 1.2 Case Overvi ew

................................ ................................ ................................ ................. 7 1.3 Chemical Identification and Properties

................................ ................................ ............ 9 1.4 Use/Usage Description

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

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

................................ ................................ .................. 11 1.4. 3 Usage Information

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

................................ ................................ ................................ ......... 11 1.5.1 Tolerance Information

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

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

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

................................ ................................ ................................ ............... 12 2 Anticipated Data Needs

................................ ................................ ................................ ........ 13 3 Human Healt h Risk Assessment

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

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

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

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

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

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

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

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

- Application Exposures

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

................................ ................................ ................................ .......... 23 7.1.2 Water Qua lity

................................ ................................ ................................ .......... 23 7.1.3 Environmental Justice

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

................................ ................................ ............. 24 7.1.5 Additional Information

................................ ................................ ........................... 25 8 Next Steps

................................ ................................ ................................ ............................ 26 9 References

................................ ................................ ................................ ............................. 27

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Appendices Appendix A T oxicology Profile

................................ ................................ ............................... 29 Appendix B Envi ronmental Fate

................................ ................................ ............................. 36 Appendix C Ecotoxicology Profile

................................ ................................ .......................... 42 Appendix D Down

- the

- Drain (DtD) Assessment

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

....... 46

List of Tables Table 1

– Summary of Anticipated Risk Assessments and Da ta Needs for Registration Review: BBAB

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

– Anticipated Registration Review Schedule

................................ ................................ .... 8 Table 3

– Chemical Identification of BBAB

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

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

................... 9 Table 5

– Estimated Chemical, Physical, and Environmental Fate Properties of Hydrolytic Degradation Compounds of BBAB

................................ ................................ .............................. 10 Table 6

– Summary of BBAB Registered Uses

................................ ................................ ............ 11 Table 7

– Studies Anticipated as Needed for the Registration Review of BBAB

........................ 14 Table 8

– Existing Toxicological Endpoints for BBAB

................................ ............................... 16 Table 9

– Occupational Handler Exposure Scenario for BBAB

................................ ................... 18 Table 10

– Selected Ecological Effects En dpoints for Risk Assessment of BBAB

..................... 20

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## 1 Introduction

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

- bis

- bromoacetoxy

- 2

- butene , herein referred to

as BBAB

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

. The Agency encourages all interested stakeholders to review the PWP and to provide comments and additional information that will help the Agency ’s decision

- makin g process for this chemical.


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

- reevaluation

. The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 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 f or each case. The docket is the Agency ’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registration review decision. After reviewing and responding to comme nts and data received in the docket during this initial comment period, the Agency will develop and commit to a F inal W ork P lan (FWP) and anticipated schedule for the BBAB case

. 

## 1.2 Case Overview

The docket for BBAB ( c ase 3030 ) has been established at http://www.regulations.gov in docket number EPA

- HQ

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- 2014

- 0799

. Documents associated with this registration review can be

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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 Nec essary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required

(New/ Updated) Data Anticipated as Needed (See Ta ble 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 Yes 2000 Updated 90 Day Dermal T oxicity S tudy in R ats 90 Day Inhalation T oxicity S tudy in R ats Developmental T oxicity S tudy in R abbits Reproduction and F ertility E ffects in R ats Acute N eurotoxicity Immunotoxicity Indoor Exposure

– Inhalation Indoor Exposure

– Dermal

Residential Handler No (See Section 3.3.2) 2000 None None 1

Resident i al Post Application No (See Section 3.3.3) 2000 None None 1
Aggregate Yes 2000 New See above data needs for Dietary (food)

Cumulative No (See Section 3.4 .2 ) 2000 None None

Tolerance Review No (See Section 1.5.1) N/A N/A None

Ecological Yes 2000 Updated Biodegradability in WWTP Aerobic Aquatic M etabolism Activated Sludge Respiration Inhibition 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 Plant Growth (V ascular Plant) T est N/A = Not applicable
1 Residential 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

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Close Public Comment Period 2015

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

- 09 Issue Data Call

- In (DCI) 2016

- 03 Receive Data to be Considered in Risk Assessment 2020

- 03 Open 30

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

- 09 Close Public Comment Period 2021

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

- Day Public Comment Period for Proposed Decision 2022

- 03 Close Public Comment Period 2022

- 05 Issue Final Decision 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).


## 1.3 Chemical Identification and Properties

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

. Table 3

– Chemical Identification of BBAB
Chemical Name 1,4

- bis

- bromoacetoxy

- 2

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

- 58

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

– Chemi cal , Physical, and Environmental Fate Properties for Parent BBAB

Guideline No. Parameter EPA Reg. No. 707

- 234: 1,4

- bis

- bromoacetoxy

- 2

- butene, 87 % AI Reference (MRID )/ Comments

830.7050 UV/Visible Absorption Not applicable Based on chemical structure, structure will not absorb light between 290 and 800 nm 830.7370 Dissociation constant (pKa) Not applicable No ionizable functional groups

830.7550 Octanol

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

830.7840 Solubility in water (mg/L) 630 43376101 20 o C

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Guideline No. Parameter EPA Reg. No. 707

- 234: 1,4

- bis

- bromoacetoxy

- 2

- butene, 87 % AI Reference (MRID )/ Comments

830.7950 Vapor pressure (mmHg) 1.59 x 10

- 6 43376102 20 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 increase as pH values decrease. In the hydrolysis study of BBAB (MRID 44458401 ), three straight

- chain hydrolytic degradation compounds were identified: (1) the parent compound minus a bromine molecule (BAAB); (2) the parent compound m inus 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 Properties of Hydrolytic Degradation Compounds of BBAB 1
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 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 Except for hydrolysis half

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

- WEB 4.11. B r O O O O

C H 3

B r O O O H

B r O O H

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## 1.4 Use/Usage Description
1.4.1 Registrations
There are two EPA

- registered products that contain BBAB as an active ing redient (a.i.). The products 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

. 

### 1.4.2 Summary of Registered Uses

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

. BBAB can be applied by the following application methods: open pour or meter pump.

Table 6

– Summary of BBAB Registered Uses

Use Application Method Application Rate Control of Microbial Slime in Pulp and Paper Mills Open Pour or Meter pump 0.15

- 0.30 lb AI/ton paper 

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

. 2


## 1.5 Regulatory 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 section 1.2).

2 Special Biocides 2004

- 2005. A Global Series of Regional Market Analysis. Volume II: United States, Kline & Company, 2006. 3 The 2000 preliminary risk assessment for BBAB includes the following documents:

• Executive Summary for the Reregistration Eligibilit y Decision (RED)

• Human Health Science Chapter (Revised)

• Addendum

- Final Draft of Human Health Chapter (Revised Dietary)

• Human exposure RED chapter

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

• Risk Characterization for the R eregistration 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 Sci ence Chapter

• Summary of Incident Data and Epidemiological Information for the Reregistration Eligibility Decision

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

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



### 1.5.1 Tolerance Information
EPA has not established tolerances for residues of BBAB in or on raw agricultural commodities or processed food and feed products under the Federal Food, Drug
, and Cosmetic Act (FFDCA) Section 408. There are also no tolerance exemptions for residues of BBAB under FFDCA Section 408. BBAB has been cleared as an indirect food additive by the US Food and Drug Administration (US FDA) under FFDCA Section 409 for use in the manufacture of paper and paperboard that contact food ( 21CFR § 17 6

. 300)

. 

## 1.6 Incidents
1.6.1 Human Health
Individual Incident Reports

Incidents that are rated as moderate (HC)
, major (HB) or fatality (HA) are reported as individual reports in the OPP Incident Data System (IDS). These reports include information regarding the causes of the incident and symptoms experienced. In the case of BBAB
, two individu al report s 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 diffi culty breathing. The dermal irritation was resolved with the use of a steroid treatment but the difficulty in breathing persisted and the worker later claimed to have “ Moderate Restricted Lung Disease .” The consulting doctor indicated however, that he did not believe that the product could be the cause of this condition. This incident was rated as HB.

• A feed line developed a leak at the location of post

- dilution with the city water supply. A worker in the facility had blistering on forearms and 2nd degree c hemical 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 cert ain time period (often quarterly). Typically these reports only contain basic information such as the date, location and product involved and more detailed information such the cause of the incident or symptoms experienced are not included. In the case of BBAB , there are 28 aggregate incidents listed in the IDS , as of January 13, 2015 for the time period from 1999 to 2014

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



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

.

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## 2 A nticipated Data Needs

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

.

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Ta ble 7

– Studies Anticipated as Needed for the Registration Review of BBAB

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

Requirement Applicable Exposure Scenario
835.3110 1 835.3220 1 835.3240 1 835.3280 1 Biodegradability in WWTP TGAI, BAHB and BA degradates 12 Environmental exposure Pulp and paper mill s Ecological

835.4300 2 Aerobic aquatic metabolism TGAI 24 Environmental exposure Pulp and paper mill s Ecological

850.3300 1 Activated Sludge Respiration Inhibition (ASRI) TGAI, BAHB, and BA degradates 12 Environmental exposure Pulp and paper mill s Ecological

850.107 5 Acute estuarine fish toxicity TGAI 12 Environmental effects Pulp and paper mill s 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 mill s Ecological

850.4500 3 Aquatic plant growth (algal) Tier II (dose response) TGAI 12 Environmental effect s Pulp and paper mill s Ecological

850. 4550 3 Aquatic plant growth (aquatic vascular plant) Tier II (dose response) TGAI 12 Environmental effects Pulp and paper mill s Ecological

870.3250 90 Day Dermal toxicity study in rats TGAI 24 Occupational Pulp and paper mill s Open pour liquids 5
870.3465 90 Day Inhalation toxicity study in rats TGAI 24 Occupational Pulp and paper mills Open pour liquids 5

870.3700 Developmental Toxicity Study in Rabbits TGAI 24 Aggregate Dietary Occupational Pulp and paper mill s Food and Water Open pour liquids 5

870.3800 4 Reproduction and fertility effects in rats TGAI 48 Aggregate Dietary Occupational Pulp and paper mill s Food and Water Open pour liquids 5

870.4100 6 Chronic toxicity in rats TGAI 48 Aggregate Dietary Pulp and paper mill s Food and Water

870.4200 6 Carcinogenicity in rats TGAI 48 Aggregate Dietary Pulp and paper mill s Food and Water

870.6200 Acute neurotoxicity TGAI 12 Aggregate Dietary Occupational Pulp and paper mill s Food and Water Open pour liquids 5

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

Requirement Applicable Exposure Scenario

870.7800 Immunotoxicity TGAI 12 Aggregate Dietary Occupational Pulp and paper mill s Food and Water Open pour liquids 5

875.1200 Dermal Exposure

– Indoor TGAI or surrogate 24 Occupational Pulp and paper mill s Open pour liquids 5

875.1400 Inhalation Exposure

– Indoor TGAI or surrogate 24 Occupational Pulp and paper mills Open pour liquids 5

1. For BBAB, BAHB, and bromoacetic acid, t he 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 requi red. If the ASRI test EC50 is greater than 20 mg/L, then the registrant would be anticipated to be required to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test

- Aerobic Sewage Treatment: A. Act ivated Sludge Units or c) the Porous Pot Test.

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

Biodegradability study, then the a) Bio degradation in Activated Sludge or b) Simulation Test

- Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study would be anticipated to be required. 2. The anticipated Data Call

- In Notice will provide that o ne study using parent BBAB m ay be conducted : aerobic aquatic metabolism studies measure parent compounds and degradates. 3. In a Federal Register Notice dated June 27, 2012, EPA split the Public Draft OPPTS 850.5400 test guideline into two test guid elines: OCSPP 850.4500 and OCSPP 850.4 550. See “Final Test Guidelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OP PT

- 2009

- 0154

- 0028

. 4. Results from a multi

- generation (EPA guideline 870.3800) or an extended one

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

- ilibrary.org/environment/test

- no

- 443

- extended

- one

- generation

- reproductive

- toxicity

- study_9789264185371

- en ) will satisfy this anticipated requirement. 5. If the label can be changed to require closed loading and delivery systems, then the open pour exposure scenario will not need to be assessed. 6. The anticipated Data Call

- In Notice will provide that a combined chronic toxicity/carcinogenicity study (870.4300) may be con ducted to fulfill these data needs in lieu of conducting separate chronic toxicity and carcinogenicity studies.

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## 3 Human Health Risk Assessment

The Agency anticipates the need to conduct a human health risk assessment for BBAB for the pulp and paper mill use of the chemical. The Agency expects to require additional toxicology data on BBAB (as noted in Table 7 of this document) to conduct this risk 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

- species variation facto r, 3x for LOAEL/NOAEL extrapola ion, 3x for subchronic to chronic extrapolation.

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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 referenc e dose (RfD), either acute or chronic, that has been adjusted to account for the FQPA Safety Factor (SF). This calculation is performed for each population subgroup for which an endpoint exists. A risk estimate that is less than 100% of the acute or chroni c PAD is not of concern. Acute and chronic dietary risk for 1,3

- PAD will be assessed by comparing dietary exposure estimates expressed in mg/kg/day to the acute Population Adjusted Dose (aPAD) and chronic Population Adjusted Dose (cPAD).



### 3.2.1 Food
The Agency an ticipates the need to conduct a dietary (food) assessment for BBAB during registration review. A screening

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

- 2008 consumption data. Exposure estimates utilized <1% of the aPAD and 3.5% of the cPAD for the general U.S. population, and utilized <1% of the aPAD and 15% of the cPAD for children 1

- 2 years old, the most highly

- exposed population subgroup (aPAD=0.05 mg/kg/day; cPAD = 0.0015 mg/kg/day).



### 3.2.2 Drinking Water
The Agency anticipates the need to conduct a drinking water assessment for BBAB and its degradates (BAHB and BA) during registration review. In 2000 , drinking water exposure to BBAB was not assessed because drinking water exposure was not expected. However, it has recently been determined that there is potential for human drinking water exposure to degradates of BBAB ( BAHB and BA) (see section 4.1)

. 

## 3.3 Occupational and Residential Exposures

EPA anticipates the need to conduct a n updated occupational handler assessment for BBAB during registration r eview

. As the label s do not specify that closed system loading and delivery syst ems be used for BBAB, oc cupational exposures are anticipated during the open pour addition of BBAB into pulp and paper mill process tanks.

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### 3.3.1 Occupational Handler Exposure
EPA anticipates the need to revise the occupational handler exposure assessment conducted in the 2000 risk assessment for BBAB to account for toxicological and exposure data that are anticipated to be needed for registration review

. The exposure scenario t hat will be assessed is listed in Table 9.

Table 9

– Occupational Handler Exposure Scenario for BBAB

Scenario Exposure Route(s) Duration Open pour liquids for pulp and paper mill slime treatment Dermal Inhalation Short and Intermediate Ter m



### 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 products such as paint, household cleaning products, plastics, textiles that lead to residential exposure

. The residential use that was considered in the 2000 assessment (paint) w as 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 conduct 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 assessment 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 efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/c umulative/

.

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## 4 Environmental Risk Assessment

The Agency has not previously conducted a risk assessment that supports a complete endangered species determination for BBAB . The ecological risk assessment planned during registration review will allow the Agency to determine potential acute and chronic risks to aquatic organisms exposed to BBAB transported from treatment sites into the aquatic environment. The risk assessment also will allow the Agency to determine whether each use of the BBAB has 'no effect' or ' may affect' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the Agency will cons ult 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 degradati on 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 of these de gradates are presented in Table 5. The experimentally

- determined hydrolytic half

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

O f the three hydrolytic degradates, BAHB and BA appear to have the potential to be persistent enough to be released to surface water downstream of WWTPs that receive pulp and paper mill discharges. Based on a hydrolytic half

- life of 43 days at pH 5 and 29 hours at pH 7, BAHB was determined to be a significant degradate that could potentially be persistent enough to enter surface water following discharge from pulp and paper mill effluent. 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 photo degradation in water for BBAB and its degradation compounds have been submitted. Data on photodegradation in water for BBAB and its degradates are not anticipated to be required since , based on the absence of double bonds, these chemicals do not absorb lig ht in the 290

- 800 nm range (Lyman et al., 1990).
BBAB and its degradation compounds are highly water soluble and are expected to have limited potential for sorption to soil and sediment (Table 4 and 5)

. Based on Henry’s Law constants of 10

- 6 or less for BBAB and its degradates , these chemicals are unlikely to volatize from water into air (Table 4 and 5).
For BBAB, BAHB, and BA, the Agency anticipates requiring e nvironmental fate data on aerobic aquatic metabolism
, biodegradability during wast ewater treatment , and activated sludge respiration inhibition to further refine information on the persistence of these chemicals in the environment. A more detailed discussion of the environmental fate of BBAB and its degradates is presented in Appendix B of this PWP.

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## 4.2 Environmental Exposure Pathways Based on the registered use of BBAB in pulp and paper mill systems as well as physical/chemical properties and environmental fate data for BBAB and its degradates
, the Agency cannot rule out the possibility th at aquatic organisms downstream of wastewater treatment facilities that receive pulp and paper mill discharges have the potential to be exposed to BBAB and/or its degradates. The Agency has created conceptual models for potential routes of environmental ex posure 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 Ag ency anticipates requiring additional ecological effects studies based on this potential exposure from effluent to reduce the uncertainties in the risk assessment (See Table 7)

. Appendix C contains the previously

- submitted toxicity data

. The additional aqu atic testing listed in Table 10 is anticipated to be required based on the persistence of BBAB and its degradates in the aquatic environment and the possibility of the exposure of nontarget organisms in water downstream from wastewater treatment plants that receive pulp and paper mill discharges

. Since the degradates are formed within hours of the onset of testing , testing the parent compound (BBAB) would be sufficient to determine the toxicity of these degradates, since they will be formed during the d uration of the aquatic tests. Therefore, no degradate ecotoxicity testing is expected to be necessary for BBAB.



### 4.3.1 Measures of Effect (Ecotoxicology Endpoints) Ecotoxicity endpoint data are used as measures of effects to aquatic and terrestrial organisms

. All available ecotoxicity endpoints in the Agency ’s files from BBAB and its degradation products
, studies submitted by registrants or other interested parties, federal laboratory data, or from the public literature are tabulated in Appendix C

. The most sensitive values for each receptor group will be used for the risk assessment ( Table 10 )

. These selected endpoints and the missing endpoints from the indicated data gaps may be upda ted during the risk assessment phase based on any additional submitted data or data found in the public literature.

Table 10

– Selected Ecological Effects Endpoints for Risk Assessment of BBAB Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Reference (MRID)
Birds Mallard duck Acute Oral 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) --

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Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Reference (MRID) 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

-- 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 facilities that use BBAB to control slime formation. The Agency plans to use the General Population and Ecological Exposures from Industrial Releases module (hereinafter referred to as the Industrial Releases module) of E

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

o f 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 co ntrol 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 s cope of this PWP (see Appendix D)

. To analyze potential exposures and ecological risks from this industrial use, the input data required to run the Industrial Releases module of E

- FAST include:

- Percent removal of antimicrobial or degradate during wastewater treatment;

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

- Annual number of days of release to surface water;

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

- Concentrations of concern for aquatic animals and plants.
Any information on processes that would be expected to reduce concentrations of BBAB, BAHB, and bromoacetic acid released via pulp and mill discharges will be considered by the Agency to determine whether potential exposures of aquatic organisms to these chemicals can be mitigated.

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## 4.5 Effects Analysis Plan
Additional open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database

. The ECOTOX database will be searched during the risk assessment phase of BBAB and the data reviewed following the Agency ’s policy for reviewing public literature for use in assessing risks from 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, and the National Health and Environmental Effects Research Laboratory ’ s Mid

- Continent Ecology Division. 

## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopatho logy, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and rep roductive 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 endpoints for relevant risk assessment scenarios from the existing hazard database. However, as re quired by FFDCA section 408(p), BBAB is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).
EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

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

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

- response relationship between the dose and the E, A, or T effect.
Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, E PA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals

4 http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_reregistration_work group/esa_evaluation_open_literature.htm

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identified for EDSP screening was published on June 14, 2013 5 and includes some pest icides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.
For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 6 

## 6 Optional Label Changes

As noted in Table 7 of this document, it is recommended that all registrations and labels be clarified to require closed loa ding and delivery systems where appropriate. If this occurs for all registrations and labels, then dermal and inhalation exposure stud ies will likely not be needed to evaluate occupational exposure.

The Agency invites comment on any label amendments that could be considered to eliminate the anticipated need for EPA to require certain data, reduce the possibility that EPA’s planned risk assessments overestimate risk due to reliance on conservative assumptions, a nd/or improve label clarity. 

## 7 Guidance for Commenters

7.1 Preliminary Work Plan The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a final work plan for the BBAB registration review case.



### 7.1.1 Trade Irritants Through the registration review process, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps tow ard facilitating irritant resolution. The Agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Stakeholders are asked to comment on any trade irritant issues resul ting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the nature of the concern.



### 7.1.2 Water Quality
BBAB and the degradate s , BAAB and BAHB
, are not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act

. 7 In addition, no

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

- HQ

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- 2009

- 0477

- 0074 for the final second list of

chemicals.
6 http://www.epa.gov/endo/
7 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

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

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

. 9

However, bromine (as bromate) and bromoacetic acid are listed as by

- product s of chlorine and chloramine disinfection of drinking water

. 10 Bromate has a maximum concentration limit ( MCL ) of 0.01 mg/l or 10 μg/l as an annual avera ge. Bromoacetic acid is listed under the general category of haloacetic acids, which also include dichloroacetic acid, trichloroacetic acid, monochloroacetic acid, and dibromo acetic acid

. While bromoacetic acid has no compound

– specific MCL, the MCL for the sum of the five haloacetic acid compounds is an annual average of 0.06 mg/l or 60 μ g/l.

The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendi x A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 11 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.



### 7.1.3 Environmental Justice EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, may h ave atypical, unusually high exposure to BBAB compared to the general population. Please comment if you are aware of any sub

- populations that may have atypical, unusually high exposure compared to the general population.


### 7.1.4 Structure Activity Relationships
E PA must rely upon information of appropriate quality and reliability for each decision made by the Agency . In the OPP, the evaluation process for a pesticide chemical traditionally begins with the applicant’s submission of a set of studies conducted with t he specific pesticide chemical of interest. The use of the results of such testing (measured data) is a logical, scientifically rigorous process that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.
Today, there is significant interest in alternative techniques, i.e., techniques other than data generation that could significantly inform the Agency ’s decision

- making process . Recently, OPP has made increasing use of structure activity relationship (SAR) as part of its regulatory decision

- making process. In the SAR process, a chemical ’ s molecular structure is compared to that of other chemicals for which data are available. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties.

8 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES
9 http://www.epa.gov/owow/tmdl/ 10 http://water.epa.gov/drink/contaminants/basicinformation/disinfectionbyproducts.cfm
11 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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Thus, the chemical’s physi cal, chemical, and biological properties are a function of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To develop a QSAR, a selected set of measured data on a single physical, chemical, or biologica l property is used to derive a model (an equation) to predict the value of that property.
Since SAR assessments and QSAR modeling are another set of tools that are available to Agency scientists, OPP has begun a process shift that envisions shifting from the current study

- by

- study approach to an approach in which the use of predicted data, generated using validated models, is considered along with information from open literature and studies specifically generated under Part 161 requirements. All relevant information would be considered as part of a weight

- of

- the

evidence evaluation.
At this time, EPA believes that for certain endpoints, especially physical/chemical and fate properties, that SAR and QSAR might be effectively utilized to fulfill these data requirements for many antimicrobial pesticide chemicals. When considering biological properties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of chemicals that exhibit lower toxicity for human health and/o r ecotoxicity parameters. This is appropriate because the risk assessment for lower toxicity chemicals can be stream

- lined, i.e., a screening

- level assessment procedure rather than multiple tiers of assessments with progressively more data requirements.
If stakeholders believe that submission of predicted data can fulfill one of the data needs for the BBAB ca se, then the Agency invites submission of this information. The submitter would be expected to supply a rationale describing the utility of the infor mation and provide documentation on the scientific validity of the information. The determination that the predicted data fulfills the data requirement would be at the sole discretion of the Agency . Pre

- submission consultation with the Agency is encouraged

. 

### 7.1.5 Additional Information
Stakeholders are also specifically asked to provide available information and data that will assist the Agency in refining its risk assessments, including any species

- specific ecological effects determinations. The Agency is inte rested in receiving the following information:

1. Confirmation on the following label information: A. Sites of application B. Formulations C. Application methods and equipment D. Maximum application rates E. Frequency of application, application intervals and maximum number of applications F. Geographic limitations on use 2. Use or potential use distribution 3. Use history 4. Usage/use information for non

- agricultural uses (e.g., materials preservation) 5. Typical application interval 6. State or local use restrictions

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7. Ecological incidents (non

- target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency 8. Monitoring data


## 8 Next Steps

After the 60

- day comment period closes in M ay 2015 , the Agency will review and respond to any comments received in a timely manner, and then issue a Final Work Plan for the BBAB

case.

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## 9 References

Kline, 2005. Specialty Biocides North America 2004

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

- 8412

- 1761

- 0

MRID 431910 01

. Bettencourt, Michael J

. 1994

. BBAB

– Acute Toxicity to Rainbow Trout ( Oncorhynchus mykiss ) Under Flow

- thro ugh 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 Guidel ine 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 Inte rnational, 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

. W ells, 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 P artition 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 Aqueo us 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. (SL I), Ohio Research Center, 640 North

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

U.S. Environmental Protection Agency (EPA). 2002. ECOTOX User Guide: ECOTOXicology Database System. Version 3.0. Available: http://www.epa.gov/ecotox/
U.S. Environmental Protection Agency. 2012. EPI

- WEB 4.11. http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

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# Appendix A 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 sensitizer in the absence of data.

Table A1

– Acute Toxicity Studies for BBAB Guideline No./ Study Type MRID Number Results Toxicity Category 870.1100/ Acute oral toxicity 43181101 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 redu ced 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 ad ditionally exhibited decreased activity (11/20 and 3/20, respectively) and a wobbly gait (8/20 and 3/20, respectively)

. High

- dose females had decreased mean absolute body

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weights at the end of treatment (day 90; 92% of controls; p<0.05)

. Reductions in mean body weight gains during treatment were biologically significant in high

- dose males and females, with the greatest reduction occurring toward the end of treatment on days 57

- 90 (58% and 70% of controls, respectively, statistical analysis not conducted)

. S tatistically significant decreases (p<0.05; 0.01) in food consumption in the high

- dose males (82

- 93%) and females (80

- 90%) and mid

- dose females (80

- 90%) may have been treatment

- related

. Treatment with BBAB also resulted in irritative/corrosive effects on the stomach

. Mid

- and 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 an emia in mid

- and high

- dose animals was evidenced by generally statistically significant increases in MCV and MCH, changes in red blood cell morphology that are consistent with immature erythrocytes (macrocytes, polychromasia, and anisocytosis), and minimal to moderate splenic extramedullary hematopoiesis observed during microscopic examination.
High

- dose animals additionally had enlarged spleens and increased absolute and relative spleen weights (94 and 107% vs. the controls for males, respectively; 146 an d 163% vs. the controls for females, respectively)

. Eroded and thickened areas of the stomachs of mid

- and high

- dose animals were observed during gross necropsy, while microscopic examination revealed multiple findings in the nonglandular mucosa of the stom ach 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 males and females had a slightly increased incidence of minimal hyperkeratosis (3/10 for both) and hyperplasia (2/10 and 4/10, respectively) of the nonglandular mucosa of the stomach (controls: 0/10 for both lesions)

. In the female, minimal edema of the stomach and minimal extramedullary hematopoiesis were see n in 1/10 animals compared to 0/10 in the control group for both lesions.
Clinical chemistry analysis revealed statistically significantly elevated levels of serum chloride in mid

- and high

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

. Microscopic evaluation of the liver revealed minimal to marked periportal hepatocyte vacuolation in 10/12 high

- dose males, and minimal to mild vacuolation in 2/10 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

. All remaining indicators of toxicity observed during tre atment were generally comparable to controls or were not biologically significant following the recovery phase.
The LOAEL is 4.5 mg/kg/day (lowest dose tested) in male and female rats and is based on microscopic findings of hyperkeratosis and hyperplasia o f the non

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

. An NOAEL was not determined.

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This subchronic toxicity study is classified as Acceptable and satisfied the OPPTS 870.3100 guideline.

There are no 90

- day dermal or inhalation studies for BBAB. A 90 day dermal and 90 day inhalation toxicity study are anticipated as being needed for registration review of BBAB to assess occupational hazard from dermal and inhalation exposures. 

## Developmental Toxicity

There is an ava ilable 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 h igher

. 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 ar eas) 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 weig hts, and gravid uterine weights

. In the definitive developmental toxicity study (MRID 44750901), 25 bred Crl:CD ® (SD)BR rats per group were administered BBAB (Lot/Batch No. K.D.D., 93.5% a.i.) in Mazola ® corn oil orally by gavage at doses of 0, 5, 20, or 3 5 mg/kg/day on gestation days (GD) 6

- 19, inclusive

. On GD 20, dams were sacrificed, subjected to gross necropsy, and all fetuses examined externally, viscerally, and skeletally for malformations/variations.

One mid

- dose female was found dead on GD 16 from gavage trauma

. All other animals survived to scheduled necropsy

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

. During the treatment period of GD 6

- 20, dose

- related, increased salivation prior to dosing correlated with observation of clear and tan matting around mouth at the time of dosing and 1

- hour post

- dosing in both the mid

- and high

- dose groups. The treatment related increased salivation was considered to be associated with the corrosivity of BBAB

. In addition, the 35 mg/kg/day gr oup also had statistically significant decreases in mean maternal absolute body weights, body weight gains, and food consumption

. Mean absolute body weights were statistically significantly decreased (p<0.05; 0.01) starting on GD 12 and continuing to study termination on GD 20 (93% to 95% of controls)

. For the overall treatment period (GD 6

- 20), high

- dose dams gained 20% less weight and consumed 9% less food than controls (p<0.01), and had final absolute and corrected body weights 7% and 8% less than contro ls, respectively (p<0.01).

No treatment

- related differences in body weights, body weight gains, or food consumption were noted in low

- or mid

- dose dams

. No treatment

- related effects were noted in any of the treatment groups during gross necropsy.

Therefo re, the maternal toxicity LOAEL is 20 mg/kg/day based on an increased incidence of salivation, and the maternal toxicity NOAEL is 5 mg/kg/day.

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Mean fetal body weight was statistically significantly (p ≤ 0.05) decreased in the high

- dose group (3.5 g) as compa red with controls (3.7 g)

. No dose

- or treatment

- related, statistically significant effects on pregnancy rates, number of corpora lutea, pre

- or post

- implantation losses, resorption/dam, fetuses/litter, or fetal sex ratios were observed in the treated grou ps as compared with the controls

. No dams had complete litter resorption.

No treatment

- related external, visceral, or skeletal malformations/variations were observed in any litter

. Most treated and control litters contained fetuses with minor variations in skeletal ossification.
Therefore, the developmental toxicity LOAEL is 35 mg/kg/day based on decreased mean fetal body weights, and the developmental toxicity NOAEL is 20 mg/kg/day.
This developmental toxicity study is classified as Acceptable/guideline a nd 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 f or 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 r esidue 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 carcinogenicity study is expected to be required. The toxi cology data

r equirements 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 t han 200 parts per billion (< 200 ppb ) if the use of the pesticide is likely to result in significant human exposure over a considerable portion of the human lifespan ( in terms of frequency, time, duration, and/or magnitude of exposure )

.

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## Mutagenicity
The database for BBAB mutagenicity is considered adequate based on EPA ’ s 1991 mutagenicity guidelines.
In an Ames test (MRID 43201001), BBAB was not mutagenic to Salmonella typhimurium tester strains TA98, TA100, TA1535, and TA1537 with or without the micr osomal S9activation

. In the mouse lymphoma assay (MRID 43202601), cultures of mouse lymphoma (L5178Y) cells were exposed to BBAB solutions for determination of potential to induce forward mutation at the thymidine kinase (TK+ to TK

- ) locus

. Under S9 activa tion, a dose related increased frequency of mutant colonies occurred at a level of moderate toxicity

. Without S

- 9 activation, however, BBAB was active in the presence of moderate to severe cytotoxicity

. This effect was deemed “equivocal” because mutagenic activity is only obvious in the presence of excessive toxicity (<10% of total growth); however a possible clastogenic effect was suggested

. In an in vivo ICR mouse bone marrow micronucleus test (MRID 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 the subchronic toxicity study (MRID 44757001),10 Sprague

- Dawley Crl:CD ® (S D)IGS BR rats/sex/group were administered BBAB (Lot No. KDD, Batch # 9, 93.1% a.i.) in Mazola ® corn oil orally by gavage at doses of 0, 4.5, 22.5, or 39.1 mg/kg/day for a minimum of 90 consecutive days

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

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

- dose animals additionally had decreased activity and wobbly gait

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

2. In the range

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

- 19, inclusive

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

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

. Additionally, one or more 50 mg/kg/day group dams occasionally exhibited circling, splayed hindlimbs, walking on tiptoes, sporadic nasal clicks, hunched or unk empt appearance.
As there were no formal neurotoxicity measurements made in the available studies, an acute neurotoxicity study in the rat (OCSPP 870.6200) is anticipated to be required.

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There are no data on the 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.

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Toxicolo gy 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.
Cappo n, G

. (1999) A prenatal developmental toxicity study of BBAB in rats

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

. Laboratory Study No.: WIL

- 94052, January 14, 1999

. MRID 44750901

. Unpublished.
Douds, D.A

. (1994) An Acute Toxicity Study in Rats with BBAB

. Springborn Laboratories (SLS), Spencerville, OH

. Laboratory Study No.: SLS 3138.99, March 22, 1994

. MRID 43181101

. Unpublished
Douds, D.A

. (1994) An Acute Dermal Toxicity Study in Rabbits with BBAB

. Springborn Laboratories (SLS), Spencer ville, OH

. Laboratory Study No.: SLS 3138.100, February 28, 1994

. MRID 43152401

. Unpublished
Putnan, D.C

. And Young, R.R

. (1994) Micronucleus Cytogenetic Assay in Mice

. Microbiological Associates Inc. (MAI), Rockville, MD. Laboratory Study No.: (MAI) TE064 .122

. March 04, 1994

. MRID 43156301

. Unpublished.
Rush, R. (1999)

. A 90

- day oral (gavage) toxicity study in rats with a 28

- day recovery phase

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

. SLI Study No. 3138.109, January 25, 1999

. MRID 44757001

. Unpublished

. San, R.C. and Clarke, J.J

. (1994) L5178Y/TK +/

- Mouse Lymphoma Mutagenesis Assay

. Microbiological Associates Inc. (MAI), Rockville, MD. Laboratory Study No.: (MAI) TE064.702020, April 5, 1994

. MRID 43202601

. Unpublished.
San, R.C. and Klug, J.J

. (1994) Salmonella Plate Incorporation Mutagenicity Assay (Ames Test) with a Confirmatory Assay

. Microbiological Associates Inc. (MAI), Rockville, MD. Laboratory Study No.: (MAI) TE064.501014, April 6, 1994

. MRID 43201001

. Unpublished

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# Appendix B Environmental Fate

Environmental Fate and Transport Properties of BBAB and its 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 m inus a bromine molecule (BAAB).
Based on the chemical and physical properties ( Table 4 ) and a hydrolysis study of BBAB (MRID 44458401) , three straight

- chain hydrolytic degradation compounds were identified: (1) the parent compound minus a bromine molecule (BAAB); (2) the parent compound minus one bromoacetic acid group (BAHB); and (3) bromoacetic acid (BA). Physical/chemical and environmental fate prope rties of these degradates are presented in Table 5. Of the three hydrolytic degradates, BAHB and BA appear to have the potential to be persistent enough to be released to surface water downstream of WWTPs that receive pulp and paper mill discharges. BAHB w as determined to be a significant degradate that did demonstrate some breakdown at pH values of 5 and 7
, but bromoacetic acid did not demonstrate any degradation at pH values of 5, 7 and 9. Consequently, there may be the potential for aquatic organisms downstream of wastewater treatment plants receiving pulp and paper mill effluent to be exposed to BBAB, BAHB, and BA

. BBAB and its degradation compounds are highly water soluble and are expected to have limited potential for sorption to soil and sediment ( Table 4 and 5). Based on Henry’s Law constants of 10

- 6 or less for BBAB and its degradates, these chemicals are unlikely to volatize from water into air (Table 4 and Table 5).

P arent BBAB and its degradation compounds
, BAHB and BA
, have the potential to be in papermill effluent s based on formation in significant ( > 10 % of applied parent compound) amounts and stability in the hydrolysis study

. Because additional environmental fate data on aerobic aquatic metabolism and fate in wastewater treatment plants (AS RI and biodegradation studies) have not been submitted, they are anticipated to be required to reduce the uncertainty for the risk assessment

. Water and Sediment
Hydrolysis
BBAB degraded in buffered solutions with half

- lives of 8.3 days at pH 5 , 6.9 hours at pH 7 , and 4.2 minutes at pH 9. Three 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, B A increased until the end of the study 12 and reached significant concentrations ( > 10 % of applied parent compound)

.

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At all pH values, BAHB reached significant concentrations and declined to 19

- 20, 5.5, and 0 % by the end of the study at pH 5, 7, and 9, resp ectively

. The half

- lives of the BAHB degradate

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

. BAAB reached significant concentrations at pH 5 and declined to 8

- 8.8 %, but was not detected at pH 7 and 9 (MRID 44458401 ). 13
Aqueous Ph otolysis

D ata on photodegradation in water for BBAB and its degradates are not anticipated to be required since, based on the absence of double bonds, these chemicals do not absorb light in the 290

- 800 nm range (Lyman et al., 1990).
Aerobic Aquatic Metabol ism
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 and its degradates to sorb to biosolids would be expected. Since release of BBAB and its degradates to soil media would be expected to be negligible, d ata on aerobic and ana erobic soil metabolism are not anticipated to be required

.

13 D251932, Robert Quick to Norm Cook, 2/28/2000.
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Bioconcentration in Fish Parent BBAB is not likely to bioconcentrate in fish based on the low measured log Kow value of 1.7 (Table 4)

. The measured low log Kow is <3, which is the general Agency level of concern for bioconcentration

. 15 Parent BBAB also has a high measured water solubility of 630 mg/l ; compounds that have a tendency to bioconcentrate generally have low water 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 solubility values from EPI

- WEB 4.1

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

. The estimated water solubility values from EPI

- WEB 4.1 were 1185 mg/L for BAAB, 46,640 mg/L for BAHB, and 1.75 million mg/L for BA

. Fate , Transport, and Effects in WWTP Activated Sludge Respiration Inhibition Data on activated sludge respiration inhibition (AS R I) are anticipated to be required since BBAB and its degrad ates 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 note 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 t o 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 Bioconcentration in fish 850.1730 tests guideline states that log Kow values of >3 indi cate high potential for bioconcentration. 16 EPA, 2012 17 https://www.federalregister.gov/articles/2013/05/08/2013

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- requir ements

- for

- antimicrobial

- pesticides
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BAHB half

- lives of 43 days, 29 hours, and 16 minutes at pH 5, 7, and 9

BAAB detected at pH 5 only (stable)
Photodegradation in water 835.2240 No data Not applicable Not anticipated to be required BBAB is not expected to absorb light in the 290

- 800 nm range
Aerobic soil metabolism 835.4100 No data 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 pulp

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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

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- 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.

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Environmental Fate References Lyman, W.J., W.F. Reehl, and D.H. Rosenblatt. 1990. Handbook of Chemical Property Estimation Methods. American Chemical Society. ISBN O

- 8412

- 1761

- 0

MRID 44458401

. Cohen, S. (1997) Hydrolysis of cis 1,4

- Bisbromoacetoxy

- 2

- butene (BBAB) in Buffered Aqueous Solutions: Final Report: Lab Project Number: ME 9600202. Unpublished study prepared by Pittsburgh Enviro nmental Research Lab., Inc. 97 p. Quick, Robert

. February 28, 2000

. Risk Assessment and Science Support Branch: Final Draft Environmental Fate Science Chapter of Science Chapter for 1,4

- Bis(bromoacetoxy)

- 2

- butene

. PC Code 035606, Case 3030, Barcode D251932

. U.S. Environmental Protection Agency

. May 8, 2013. Data Requirements for Antimicrobial Pesticides; Final Rule. Docket identification number EPA

- HQ

- OPP

- 2008

- 0110

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

- 10162/data

- requirements

- for

antimicrobial

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

- WEB 4.11. http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

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# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Receptors

Birds
An acute oral toxicity study using the technical grade of the active ingredient (TGAI) is available to establish the toxicity of 1,4

- bis(bromoacetoxy)

- 2

- butene to birds

. The preferred test species is either mallard duck (a waterfowl) or bobwhite quail (an upland gamebird)

. Results of this test are tabulated below.

Table C1

- Avian Acute Oral Toxicity Species % ai LD50 (mg/kg) Toxicity Category MRID No. Author/Year Study Classification

Mallard duck (Anas platyrhynchos) 82 196 moderately toxic 43214201 Wildlife International, LTD/1994 Core

1,4

- bis(bromoacetoxy)

- 2

- butene has an LD50 of 196 mg/kg and is categorized as moderately toxic to avian species on an acute oral basis

. The guideline (71

- 1/850.2100) is fulfilled (MRID 43214201)

. A subacute dietary study using the TGAI of 1,4

- bis(bromoace toxy)

- 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 Cate gory 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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## Toxicity to Aquatic Receptors

F reshwater 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)

. R esults 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) Toxicit y 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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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

- th rough 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

. Project No.: 210

- 120

. FIFRA Guideline 71

- 1

. 1994

. Submitted to Buckman Laboratories International, Inc

. MRID# 432142 02

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# Appendix D Down

- the

- Drain (DtD) Assessment

No screening

- level down

- the

- drain analysis was performed for this case since the use of BBAB to control slime in pulp and paper mills is an industrial use. Results from the Down

- the

- Drain module of E

- FAST are only applicable for chemicals that are incorporated in products that are released down

- the

- drain to domestic wastewater treatment facilities. Such results are not applicable for releases to surface water from industrial uses.

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# Appendix E Chemical and Physical Properties of BBAB and its 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

C H 3

B r O O O H

B r O O H

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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

- 7

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

-- Product Chemistry Studies: Bis(bromoacetoxy)

- 2

- butene: Final Report: Lab Project Number: 93

- 8

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

-- Determination of the Solubility on Water and Selected Solvents: Final Report: Lab Project Number: 94

- 3

- 5218: 995.0792.6156.700. Unpublished study prepared by Springborn Labs, Inc. 41 p.
MRID 43376102. Wells, D. (1994) BBAB

-- Determination of Vapor Pressure: Amended Final Report: Lab Project Number: 94

- 7

- 5355: 995.0792.158.740. Unpublished study prepared by Springborn Labs, Inc. 50 p.

MRID 43376 103. 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. 20 12. EPI

- WEB 4.11. http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

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