Docket Number EPA-HQ-OPP-2015-0256 www.regulations.gov



## Busan 77 Final Work Plan

Registration Review: Initial Doc ket Case Number 3034

March 2016

Approved by:

# ~ Steve Knizner Director Antimicrobials Division

Date: 

## 3 /l'i!J 6

Page 1 of 64Docket Number EPA

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Page 2 of 64 Busan 77 Registration Review Team

Human Health & Environmental Effects Nathan Mottl Julie VanAlstine Michelle Centra David Bays Jim Breithaupt Siroos Mostaghimi

Risk Management Stephen Savage Rose Kyprianou Jacqueline Hardy Stacey GrigsbyDocket Number EPA

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Page 3 of 64 TERMS, ABBREVIATIONS AND SYMBOLS

A.I. or a.i. active ingredient ASRI activated sludge respiration inhibition
atm

- m 3 /mole atmospheric pressure

- cubic meter per mole °C degrees Celsius CAS Chemical Abstracts Service CFR Code of Federal Regulations CHO Chinese hamster ovary CMA Chemical Manufacturers Association CO 2 carbon dioxide COC concentration

- of

- concern cPAD chronic population adjusted dose DCI data call

- in EC 50 median (or 50 percent) effect concentration ECOTOX ECOTOXicology EDI estimat ed daily intake EDSP Endocrine Disruptor Screening Program E

- FAST Exposure and Fate Assessment Screening Tool EPA Environmental Protection Agency FDA Food and Drug Administration FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticid e, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FWP Final Work Plan g/mol grams per mole GLN guideline number IDS Incident Data System Koc organic carbon normalized soil

- water partition coefficient Kow octanol

- water partition coefficient LC 50 median (or 50 percent) l ethal concentration LD 50 median (or 50 percent) l ethal dose LOAEC lowest

- observed

- adverse

- effect

- concentration LOEC lowest

- observed

- effect

- concentration LOAEL lowest

- observed

- adverse

- effect

- level Log K ow logarith m of the octanol

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

nm nanometers NOAEC no

- observed

- adverse

- effect

- concentration NOAEL no

- observed

- adverse

- effect

- level OCSPP Office of Chemical Safety and Pollution PreventionDocket Number EPA

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Page 4 of 64 OECD Organization for Eco nomic Co

- operation and Development OPP Office of Pesticide Programs PAD population adjusted dose PDM Probabilistic Dilution Model PC Code Pesticide Chemical Code pH power of hydrogen or power of the concentration of the hydrogen ion ppb parts per bill ion
ppm parts per million PWP Preliminary Work Plan QSAR quantitative structure

- activity relationship RED Reregistration Eligibility Decision SAR structure activity relationship SF safety factor TEP typical end

- use product TGAI technical grade active ingredient TMDL total maximum daily loads UF uncertainty factor UV/VIS ultraviolet/visible light absorption % w/w percent weight per weight. WP wettable powder WWTPs wastewater treatment plantsDocket Number EPA

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Page 5 of 64 

### Table of Contents 1 Introduction

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

................................ ................................ ................. 7 1.2 Updates to the Work Plan

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

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

................................ ................................ ............ 9 1.5 Use/Usage D escription

................................ ................................ ................................ ... 10 1.5.1 Registrations

................................ ................................ ................................ ........... 10 1.5.2 Summary of Registered Uses

................................ ................................ .................. 10 1.5.3 Usage Information

................................ ................................ ................................ .. 11 1.6 Regulatory History

................................ ................................ ................................ ......... 11 1.6.1 Tolerance Information

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

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

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

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

................................ ................................ ................................ ........ 12 3 Human Health Risk Assessment

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

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

................................ ................................ ................................ ............ 18 3.2.1 Food

................................ ................................ ................................ ........................ 18 3.2.2 Drinking Water

................................ ................................ ................................ ....... 18 3.3 Occupational and Residential Exposures

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

................................ ................................ ............. 19 3.3.2 Residential Handler Exposures

................................ ................................ ............... 19 3.3.3 Residential Post

- Application Exposures

................................ ................................ . 20 3.4 Aggregate and C umulative Exposure

................................ ................................ ............. 20 3.4.1 Aggregate Exposures

................................ ................................ .............................. 20 3.4.2 Cumulative Exposures

................................ ................................ ............................ 20 4 Environmental Risk Assessment

................................ ................................ ........................... 21 4.1 Environmental Fate Assessment

................................ ................................ .................... 21 4.1.1 Water Quality

................................ ................................ ................................ .......... 22 4.2 Conceptual Models for Environmental Exposure Pathways

................................ .......... 22 4.3 Ecological Effects Assessment

................................ ................................ ....................... 23 4.3.1 Measures of Effect (Ecotoxicology Endpoints)

................................ ...................... 23 4.4 Exposure Analysis Plan

................................ ................................ ................................ .. 24 4.4.1 Aquatic an d Terrestrial Wildlife Exposure Estimates

................................ ............ 24 4.4.2 Screening Level Down

- the

- Drain Analysis

................................ ............................ 24 4.5 Effects Analysis Plan

................................ ................................ ................................ ..... 24 5 Endocrine Disruptor Screening Program (EDSP)

................................ ................................ . 25 6 Optional Label Changes

................................ ................................ ................................ ........ 26 7 Next Steps

................................ ................................ ................................ ............................. 26 8 References

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

Appendix A T oxicology Profile

................................ ................................ ............................... 28 Appendix B Environmental Fate

................................ ................................ ............................. 47 Appendix C Ecotoxicology Profile

................................ ................................ .......................... 50Docket Number EPA

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Page 6 of 64 Appen dix D Screening Level Down

- the

- Drain Analysis

................................ ........................ 61 Appendix E Product Chemistry

................................ ................................ ............................... 62 Appendix F Comments Received Concerning the P reliminary Work Plan

............................ 64

List of Tables Table 1

– Summary of Anticipated Risk Assessments and Data Needs for Registration Review: Busan 77

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

– Anticipated Registration Review Schedule

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

– Chemical Identification of Busan 77

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

– Physical

- Chemical and Environmental Fate Properties for Busan 77

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

– Summary of Busan 77 Registered Uses

................................ ................................ ........ 11 Table 6

– Studies Anticipated as Needed for the Registration Review of Busan 77

.................... 13 Table 7

– Data Needs Required by Data Call

- In GDCI

- 069183

- 30193

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

– Existing Toxicological Endpoints

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

– Occupational Handler Exposure Scenarios for Busan 77

................................ ............. 19 Table 10

– Residential Handler Exposure Scenarios for Busan 77

................................ .............. 19 Table 11

– Residential Post

- Application Exposure Scenarios for Busan 77

................................ 20 Table 12

– Ecological Effects Endpoints Selected for Assessing Risks from Busan 77

.............. 23Docket Number EPA

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Page 7 of 64 

## 1 Introduction

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

- 1,2

- ethanediyl(dimethyliminio)

- 1,2

- ethanediyl(dimethyliminio)

- 1,2

- ethanediylchloride (1:2)] , herein referred to as Busan 77

. The FWP document explains what EPA's Office of Pesticide Programs (OP P) knows about Busan 77

, 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 Busan 77 ’s review

. The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows about Busan 77 an d what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on Busan 77

. 

## 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 m ust be registered by the USEPA based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy, and pesticide u se practices will occur over time. Through the registration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Information on this program is provided at http://www2.epa.gov/pesticide

- reevaluation

.
The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and wil l review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 CF R 155.40. The Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency ’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registration review decision.



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

• Updated the timeline in Table 2, “ Anticipat ed Registration Review Schedule ”

• Revised timeframe for guid eline study 870.3465 in Table 6Docket Number EPA

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Page 8 of 64 • Updated Section 3.4.2 hyperlink for, “ Cumulative Exposures ”

• Updated Section 7

, “ Next Steps ”

• Deleted the “Guidance for Commenters”

• Added Appendix F

, “C omments Received Concerning the Preliminary Work Plan ”

The Agency recei ved two submission s during the public comment period on the initial docket. See Appendix F for the Agency’s response to these comments.

No m odifications were made to the anticipated data needs and there is no change to the registration review schedule of Busan 77 . This document makes final the work plan for the Busan 77 registration review process.



## 1.3 Case Overview

The docket for Busan 77 ( case 3034 ) has been established at http://www.regulations.gov in docket numb er EPA

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. Documents associated with this registration review can be viewed in this docket. Tables 1 and 2 below summarize the issues relevant to this registration review case and the anticipated registration review schedule.

Table 1

– Summary of Anticipated Risk Assessments and Data Needs for Registration Review : Busan 77

Risk Assessment Assessment Necessary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Antici pated as Needed (See Table 6 for detail s) *

Dietary (food) No 0 7 /27/07 None None Dietary (drinking water) Yes 0 7/27/07 Updated See Table 6 Occupational Handler Yes 07/27/07 Updat ed Product Use (875.1700) Occupational Post

application No N/A None None

Residential Handler Yes 07/27/07 Updated Product Use (875.2700)

Resident i al Post Application ( Incidental Oral and Dermal ) Yes 07/27/07 Updated See Table 6

Aggregate Yes N/A N ew None

Cumulative No N/A None None

Tolerance Review No 07/27/07 None None

Ecological Yes N/A New ASRI, sorption to soil and sludge

, Aq u a tic invertebrate life

- cycle study Freshwater duckweed study N/A = Not applicable * Table 1 is a summary of the a nticipated risk assessments and data needs for Registration Review. For data called in through the post

- Reregistration Eligibility Decision ( RED ) Data Call

- In ( DCI ) , see Table 7

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Page 9 of 64 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

- 09 2015

- 10

- 02 Close Public Comment Period 2015

- 11 2015

- 12

- 01 Phase 2: Case Development

Issue Final Work Plan 2016

- 03 2016

- 03

Issue Data Call

- In (DCI) 2017

- 03

Receive Data to be Considered in Risk Assessment 2019

- 03

Open 30

- Day Public Comment Period for Preliminary Risk Assessment(s) 2020

- 09

Close P ublic Comment Period 2020

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

- Day Public Comment Period for Proposed Decision 2021

- 03

Close Public Comment Period 2021

- 05

Issue Final Decision 2021

- 09

Begin Post

- Decision Follow

- up 2021
Total (years) 6

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



## 1.4 Chemical Identification and Properties

Table 3 presents the active ingredient to be assessed in case 3034 : Busan 77 (PC Code 069183)

.

Table 3

– Chemical Identification of Busan 77

Chemical Name Busan 77 Chemical Classification Polymeric quaternary am monium

Chemical Name Poly[oxy

- 1,2

- ethanediyl(dimethyliminio)

- 1,2

- ethanediyl(dimethyliminio)

- 1,2

- ethanediyl di chloride (1:2)]

PC Code 069183

CAS Number 31512

- 74

- 0

Molecular Formula C 10 H 25 N 2 O (monomer without chlorines) Molecular Weight (grams/mole) 189 .32 (monomer) 1 3,368 (polymer) 2

1 EPIWEB 4.11 2 Average, 7/10/91 Buckman le tterDocket Number EPA

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Page 10 of 64 Molecular Structure

Smiles Code CCOCCN(C)(C)CCN(C)(C) [includes 2 chlorines as counter ions]

The Busan 77 product chemistry information relevant to risk assessment is summarized in Table 4 and the details of the product chemistry information are discussed in Appendix E

.

Table 4

– Physical

- Chemical and Environmental Fate Properties for Busan 77

Guideline No./

Study Type Results Reference/Comments ( MRID unless specified)

Water Solubility(mg/L) 10,0 00 Assumed based on miscibility

830.7050 UV visible sorption N/A 49176301 Compound has no double bonds to absorb UV light
830.7370 Dissociation constant Waived 47120304/42372401

830.7550 Partition coefficient Waived 47120304

830.7950 Vapor pressure Neg ligible 47 12 0304 Manufacturing Use Product is 60 % polymer and 40 % water

Henry’s Law Constant 8.5 x 10

- 12 Volatility from water not likely to occur given the high MW, solubility, and positive charges that will enhance sorption to solids.



## 1.5 Use/Usage Des cription

1.5.1 Registrations

There are 9 8 EPA

- registered products that contain Busan 77 as an active ingredient (a.i.). The products include one product that contain s 5

- chloro

- 2

- methyl

- 3(2H)

- isothiazolinone (CMI T ) and 2

- methyl

- 3(2H)

- isothiazolinone (MI T )

, and o th er products that contain other a.i. ’s. The percent a.i

. ranges from 1.7 percent to 60 percent and the formulations include : ready

- to

- use, flowable concentrates, dry flowables, soluble concentrates and granulars

. There are 2 manufacturing use products (EP A Registration Number 1448

- 32 and 83451

- 24 ) that contain 60 percent Busan 77.



### 1.5.2 Summary of Registered Uses

Busan 77 is currently registered as an active ingredient in end use products as an algaecide, bacteriostat, fungicide, microbiocide/microbiostat and mo lluscicide. P roducts containing Busan 77 are used in swimming pools, spas, whirlpools, hot tubs, metal working fluids, fire water protection systems, cooling water towers, petroleum secondary recovery systems, paper mill process water, air washer water sys tems, and ornamental ponds. Table 5 presents a summary of the registered uses of Busan 77 that will be assessed in this registration review

. Busan 77 can be applied by the following application methods: liquid pour

, liquid pump , solid pour, and solid place

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Page 11 of 64 Table 5

– Summary of Busan 77 Registered Uses

Use Application Method Application Rate Industrial Processes and Water Systems

Air Washer Systems Liquid Pour 45 ppm Liquid Pump

Heat Exchange r Water Systems Liquid Pump 18 ppm

Cooling Water Liquid Pour 34 ppm Liquid Pump

Secondary Oil Recovery Liquid Pour 45 ppm Liquid Pump Aquatic Areas

Aquatic Areas Liquid Pour 45 ppm Liquid Pump

Ornamental Ponds Liquid Pour 11 ppm Liquid Pump Swimming Pools

Swimming Pools, Exterior Spas, Whirlpools and Hot Tubs Liquid Pour

9 ppm Liquid Pump

Solid Pour

Solid Place

Material Preservatives

Metalworking Fluids Liquid Pour 600 ppm Liquid Pump

Pulp and Paper Liquid Pour 0.26 lb. a

. i

. /ton (150 ppm) Liquid Pump * Only maximum application rates are captured. 

### 1.5.3 Usage Information

EPA did not find any specific distribution of usage or market data in the Kline Report for Busan 77 (Kline, 2004).



## 1.6 Regulatory Histor y

The first product contai ning Busan 77 as an active ingredient was registered in the United States in 1971 . The Agency completed a Reregistration Eligibility Decision (RED) for Busan 77 in 200 7 . The post

- RED Data Call

- In (DCI) was issued in September 2011. Products containing Busa n 77 were previously registered for use in textiles and the last product with this use was cancelled

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Page 12 of 64 

### 1.6.1 Tolerance Information

EPA has not established tolerances for residues of Busan 77 in or on raw agricultural

c ommodities or processed food and feed product s under the Federal Food, Drug

, and Cosmetic Act (FFDCA) Section 408. There are also no tolerance exemptions for residues of Busan 77 under FFDCA Section 408. Busan 77 has been cleared as an indirect food additive by the US Food and Drug Administration (US FDA) under FFDCA Section 409 as a component of paper and paperboard in conta ct with aqueous and fatty foods ( 21CFR § 176.170 )

.



## 1.7 Incidents

1.7.1 Human Health Thirty four incidents were reported in I ncident Data System (IDS) for the RED from the use of Busan 77; although limited, incidents reported in OPP IDS support that exposure to Busan 77 may cause some irritation through dermal, inhalation, and/or ocular exposures. Most of the symptoms are considered minor. The most common symptoms reported for cases of derma l exposure were skin irritation/burning, rash, itching and skin discoloration/redness. The most common symptoms reported for cases of inhalation exposure were minor respiratory irritation/burning. In some cases, a headache is reported after inhalation expo sure. The symptoms associated with ocular exposure include blurred vision, edema and irritation around eyes. Since the date of the RED (12/2007), there were two additional human health incidents listed in the OPP IDS for the period 12/2007 to present (sear ch conducted on 5/28/2015). These new reported incidents were minor.


### 1.7.2 Ecological No ecological incidents have been reported in the Agency’s Ecological I ncident I nformation System (EIIS) from 2005 until the present (search conducted on 7/16/2015).


## 2 A nticipat ed Data Needs

Several studies were required from the assessment of Busan 77 in the 2007 Reregistration Eligibility Decision ( RED ) . In addition to the already

- required RED DCI data, the following studies as listed in Table 6 are expected to be needed for the registration review of Busan 77

. Table 7 outlines the data requirements required by the post

- RED DCI GDCI

- 069183

- 30193 issued on September 29, 2011

. The Agency anticipates reviewing any data received in re sponse to the post

- RED DCI as well as data anticipated to be requested for this registration review prior to conducting the registration review risk assessments for Busan 77

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Page 13 of 64 Table 6

– Studies Anticipated as Needed for the Registra tion Review of Busan 77

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

835.1110 Activated sludge sorpti on isotherm 1, 2 TGAI 12 Ecological
R ecirculating cooling towers, air washer systems, petroleum secondary recovery systems, and metalworking fluids Ecological
exposure

835.1230 Leaching

- adsorption

- desorption TGAI 12 Ecological Ecological
exposure

850 .3300 Activated sludge respiration inhibition 2 , 3, 4 TGAI 12 Ecological Ecological
exposure

850.1300 Aquatic invertebrate life

- cycle study TGAI 12 Ecological Ecological
exposure

850.4400 Freshwater floating macrophyte duckweed study TGAI 12 Ecological Ecological
exposure

870.3465 90

- Day Inhalation Toxicity

- rat TGAI 24 Human Health

R ecirculating cooling towers, air washer systems, petroleum secondary recovery systems, metalworking fluids

, swimming pools Occupational
exposure and Residential
exposu re

870.5300

or 870.5375 In Vitro Mammalian Gene Mutation TGAI 12 Human Health (Weight of Evidence

for Mutagenicity) Occupational
exposure and Residential
exposure

870.6200 Acute Neurotoxicity Screening Battery

- rat; 90

- Day Neurotoxicity Screening Batte ry

rat 5, 6 TGAI 24 Human Health Occupational
exposure and Residential
exposure

870.7800 Immunotoxicity TGAI 12 Human Health Occupational
exposure and Residential
exposure
875.1700 Product Use EP 12 Human Health Recirculating cooling towers, air washer systems, Occupational
exposureDocket Number EPA

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Page 14 of 64 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 petroleum secondary recovery systems, and metalworking fluids
Swimming pools and spas Residential
exposure
875.2700 Product Use EP 12 Human Health Swimming pools and spas Residential
exposure 1 EPA has a published fina l guideline for this study: http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0152

- 0003

. 2 Anticipated to be required because registered uses lead to D own

- the

- Drain (DtD) exposure. 3 EPA published draft guidance under guideline 850.6800 and has since published final guidance for this study under guideline 8 50.3300: http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0021

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

- i library.org/content/book/9789264070080

- en

. 5 Acute (study due 12 months after receipt of DCI) and subchronic (study due 24 months after receipt of DCI) neurotoxicity stud ies are anticipated to be required. 6 A protocol should be submitted for approval prior t o testing.

Table 7

– Data Needs Required by Data Call

- In GDCI

- 069183

- 30193

GLN Study Name Test Substance Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data Requ irement Status

850.1300 Daphnid Chronic Toxicity Test TGAI Ecological

R ecirculating cooling towers, air washer systems, petroleum secondary recovery systems, metalworking fluids , swimming pools and textiles 1 Unsatisfied

850.1740 Whole sediment: Acute Ma rine Invertebrates TGAI Ecological MRID 49300901

- Under review

850.1400 Fish early

- life stage study TGAI Ecological MRID 49362401

- Satisfied

850.1735 Whole sediment, acute invertebrates (freshwater) TGAI Ecological MRID 4871580 1

- S atisfied

850.4225 Seedling emergence, Tier II Rice TGAI Ecological UnsatisfiedDocket Number EPA

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Page 15 of 64 GLN Study Name Test Substance Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data Requ irement Status

850.4400 Aquatic Plant Toxicity Test using Lemna spp., Tiers I & II TGAI Ecological MRID 49327001

– Under review

850.5400 Algal Toxicity, Tiers I & II TGAI Ecological MRID 49453501

- Partially satisfied 1

875.1100 Dermal Exposure, Outdoor EP NA NA Waived

875.1200 Dermal Exposure, Indoor EP Occupational Handler Residential Handler All Unsatisfied

875.1300 Inhalation Exposure, Outdoor EP NA NA Waived

875.1400 Inhalation Exposure, Indoor EP Occupational Handler Residential Handler All Unsatisfied

875.1600 Application Exposure Monitoring Data Reporting NA NA NA Waived

875.2300 Indoor Surface Residue Dissipation 2 EP Residential Post

- applica tion Textiles Unsatisfied

SS

- AFM

- 1 Aquatic Field Monitoring, Once

- Through Cooling Water Systems Once

- Through Cooling Water Systems Unsatisfied

Footnotes
NA = not applicable

1. Guideline recommends green algae and diatom study. 2. Products containing Busan 7 7 were previously registered for use in textiles and the last product with this use was voluntarily cancelled (18

- Jul

- 2006). The GDCI is still listed as unsatisfied but data will no longer be required for 875.2300

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Page 16 of 64 

## 3 Human Health Risk Assessment

The Agency anticipates the need to conduct a human health risk assessment for Busan 77 . The Agency expects to require additional data for use in conducting the registration review

. 

## 3.1 Existing Toxicological Endpoints

EPA anticipates the need to revise the existing toxi cological endpoints as part of this registration review. Table 8 presents the endpoints used in EPA’s most recent human health risk assessment in support of the 200 7 RED. Although mammalian toxicological stu dies were not identified as data gaps in the RED

, four toxicity studies are identified in the registration review as anticipated data needs based on currently registered uses. All available information including existing toxicology studies, valid scie ntific literature, and the studies that are expected to be required for registration review will be considered in establishing the endpoints to be used in the registr ation review risk assessment. Appendix A provides a detailed desc ription of the toxicity s tudies

.

Table 8

– Existing Toxicological Endpoints

Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Target Margin of Exposure (MOE), Uncertainty Factor (UF), FQPA Safety Factor (SF) Study and Toxicological Effects

Acute D ietary (females 13+) A single

- dose effect in developing animals was not identified in the toxicity data base for Busan 77 and therefore, this risk assessment is not required. Acute Dietary (gen pop) A single

- dose effect in adult animals was not identified in the toxicity data base for Busan 77 and therefore, this risk assessment is not required.

Chronic Dietary (gen pop) NOAEL = 100 mg/kg/day UF A = 10 UF H = 10 Total UF = 100 FQPA SF = 1

Chronic RfD = NOAEL ÷ Total UF = 100 ÷ 100 = 1.0 mg/kg/day

Chronic cPAD = Chronic RfD ÷ FQPA = 1 ÷ 1 = 1 mg/kg/day Chronic Toxicity /Carcinogenicity

- Rats (MRID 41809101/41561301)

LOAEL = 300 mg/kg/day based upon body weight gain (M), reduced total protein (M), reduced inorganic phosphorus (M&F), increased urine pH (F) a nd a dose related

- increase in blood y crusts

.

Incidental Oral Short

- Term (1

– 30 Days) NOAEL = 500 mg/kg/day UF A = 10 UF H = 10 Target MOE = 100 Prenatal Developmental Toxicity

- Rats (MRID 41423001/93062018)

LOAEL = 700 mg/kg/day based upon increased mor tality and morbidity (convulsions, lethargy and pathological changes in lung, brain, stomach and intestines).

Incidental Oral Intermediate

- Term ( 1

– 6 Months ) NOAEL = 221 mg/kg/day UF A = 10 UF H = 10 Target MOE = 100 Subchronic Oral Toxicity

– Rats (MRID 40025001/93662014)

LOAEL = 752 mg/kg/day based upon mineralization of renal tubules with decreases in body weights, absolute organ weights (heart, liver, kidney and gonads), equivocal decrease in RBCDocket Number EPA

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Page 17 of 64 Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Target Margin of Exposure (MOE), Uncertainty Factor (UF), FQPA Safety Factor (SF) Study and Toxicological Effects

counts, elevated leukocyte counts,

non

- suppurative infl ammation in the chorid plexus of the brain and increased animal death observed at the higher doses of 2554 and 3685 mg/kg/day.

Dermal Short

- Term (1

– 30 Days) NOAEL = 10 mg/kg/day (125 μg/cm 2 ; a TGAI based dermal endpoint = 10 mg/kg x 0.2 kg rat x 1000 μ g /mg) ÷ 16

cm 2 ) UF A = 10 UF H = 10 Target MOE = 100 Subchronic Dermal Toxicity

– Rats (MRID 40170601)

LOAEL = 100 mg/kg/day based upon
treatment

- related dermatological changes consistent with chronic irritation/inflammation. The skin lesions consisted of o ne or more combinations of ulceration of the epidermis, chronic inflammation of the dermis, acanthosis, hyperkeratosis, parakeratosis, folliculitis and epidermatitis.
Dermal Intermediate

- Term (1

– 6 months) and Long

- Term (> 6 months) No endpoint identifi ed in the toxicity data base for Busan 77 and therefore, this risk assessment is not required.

Inhalation Short

- Term (1

– 30 Days) NOAEL = 500 mg/kg/day UF A = 10 UF H = 10 UF DB = 10 Target MOE = 1000 Prenatal Developmental Toxicity

- Rats (MRID 41423001/9 3062018)

LOAEL = 700 mg/kg/day based upon increased mortality and morbidity (convulsions, lethargy and pathological changes in lung, brain, stomach and intestines).

Inhalation Intermediate

- Term (1

– 6 months) NOAEL = 221 mg/kg/day UF A = 10 UF H = 10 UF DB = 10 Target MOE = 1000 Subchronic Oral Toxicity

– Rats (MRID40025001/93662014)

LOAEL = 752 mg/kg/day based upon mineralization of renal tubules with decreases in body weights, absolute organ weights (heart, liver, kidney and gonads), equivocal decrease i n RBC counts, elevated leukocyte counts,

non

- suppurative inflammation in the chorid plexus of the brain and increased animal death observed at the higher doses of 2554 and 3685 mg/kg/day.

Inhalation Long

- Term (> 6 Months) NOAEL = 100 mg/kg/day UF A = 10 U F H = 10 UF DB = 10 Target MOE = 1000 Chronic Toxicity/Carcinogenicity

- Rats (MRID 41809101/41561301)Docket Number EPA

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Page 18 of 64 Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Target Margin of Exposure (MOE), Uncertainty Factor (UF), FQPA Safety Factor (SF) Study and Toxicological Effects

LOAEL = 300 mg/kg/day based upon body weight gain (M), reduced total protein (M), r educed inorganic phosphorus (M&F), increased urine pH (F) and a dose re lated

- increase in blood y crusts

.

Cancer Busan 77 was classified a Group “D” carcinogen based upon increased thyroid C

- cell adenomas in rats by the HED RfD Committee (1994). Under registration review, the Agency anticipates conducting a carcinogenicity ass e ssment, pending the outcome of review of Busan 77 carcinogenicity data by the HED CARC.



## 3.2 Dietary Exposure

3.2.1 Food

The most recent Busan 77 dietary exposure and risk assessment was conducted in the RED in 2007 for pulp and paper manufacturing uses . The 2007 dietary assessment indicated that there were no dietary risks of concern. Based on the current Busan 77 labels, the only use pattern that could potentially result in dietary (food) exposures is the use in the manufacture of pulp, paper, and paperboard prod ucts. There are four labels with pulp, paper, and paperboard uses (57787

- 23; 75538

- 1; 83451

- 20; 1448

- 42); however, all of these labels clearly indicate that Busan 77 is not to be used in the manufacture of paper products that contact food. As a result, eve n though Busan 77 has been cleared as an indirect food additive by the US FDA, a dietary assessment by EPA is not required as part of Registration Review since there are no FIFRA

- registered food contact

uses. A dietary assessment will be required if any fo od

- contact pulp, paper, and/or paperboard uses are proposed in the future. Since there are no dietary (food) exposures based on the current use patterns, food contributions will not be included in the aggregate assessment.



### 3.2.2 Drinking Water

T he Agency plans to conduct a drinking water assessment during this registration review unless the expected environmental fate data show low potential for surface water exposure. While Busan 77 is a polycationic compound that is expected to sorb tightly to soil, sediment, and sludge, the Agency does not have adequate fate data on sorption to determine the potential for contamination of drinking water. Busan 77 is resistant to both chemical and microbial degradation and to volatility, and therefore sorption is expected to be the primary route of dissipation. These fate data are anticipated to be required during registration review.



## 3.3 Occupational and Residential Exposures

The Agency anticipates the need to revise the occupational and residential assessments

c onducted in support of the 200 7 RED

. The occup ational exposure assessment utilized surrogate databases, for which uncertainties have been identified and needs to be updated

. O ccupational
exposure s may occur from liquid pour applications

, machinist exposure from metalworking fluids

, metalworking fluids, pulp and paper, and secondary oil recovery in injection water

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Page 19 of 64 Residential exposures include handler exposures from liquid pour and solid pour from swimming pool/spa/whirlpool applications

. Residential post

- application exposure s occur from swimming /bathing

.


### 3.3.1 Occupational Handler Exposure EPA anticipates the need to revise the occupational handler assessment conducted in support of the 200 7 RED. The Occupational and Residential Exposure (ORE) assessment was conducted on July 27, 2 007 and is available in the docket to the RED

. 3 Occupational handler dermal and inhalation exposures to Busan 77 were assessed in the RED for the following applications : liquid
pour , liquid pump, powders, and machinists. The Agency expects to conduct new a ssessments for liquid pour , solid pour and will also assess machinist exposure for metalworking fluids upon receipt of the anticipated exposur e data expected from the RED DCI. It should be noted that the Agency does not anticipate the need to re assess liqu id pump exposures from metered pumps

, which are now considered minimal exposures

. T he Agency anticipate s that it will need to

reassess handler exposure for the following use categories: industrial water systems, metalworking fluid s, pulp and paper, seconda ry oil recovery in injection water, and swimming pools . The Agency expects to conduct new risk assessment s upon the receipt of acceptable exposure data called in during the RED and also expect s to refine exposure assumptions using the product use informati on for registration review

. Table 9 lists the scenarios that the Agency anticipates will need to be reassessed in registration review

.

Table 9

– Occupational Handler Exposure Scenarios for Busan 77

Scenario Exposure Route(s) Durati on Occupational Exposures Liquid pour applications for industrial water systems, metalworking fluids, pulp and paper, secondary oil recovery in injection water, and swimming pools Dermal Inhalation Short and Intermediate

- Term

Machinist exposure to me tal working fluids Dermal Inhalation Short

, Intermediate and Long Term



### 3.3.2 Residential Handler Exposures

EPA anticipates the need to revise the residential handler assessment conducted in support of the 200 7 RED. The Agency expects to refine exposure assu mptions using the product use information for registration review. Residential handler dermal and inhalation exposures to Busan 77 were assessed in the RED for swimming pool s , and whirlpool/spa s

. Table 10 lists the residential handler scenarios that the Ag ency anticipates will need to be reassessed in registration review

.

Table 10

– Residential Handler Exposure Scenarios for Busan 77

Scenario Exposure Route(s) Duration

3 2007 RED Docket Number: EPA

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Page 20 of 64 Residential Exposures
Liquid pour swimming pools, spas, and w hirlpools Dermal Inhalation Short and Intermediate Term
Solid place swimming pools, spas, and whirlpools Dermal Inhalation Short and Intermediate Term



### 3.3.3 Residential Post

- Application Exposures

EPA anticipates the need to revise the residential post

- appl ication assessment conducted in support of the 200 7 RED. Residential post

- application exposures could result when bystanders (adults and children) come in contact with Busan 77 in areas where pesticide end

- use products have recently been applied (e.g., swi mming pool and spas/whirlpool ), or when children incidentally ingest the pesticide residues through swallowing treated swimming pool water. Note that inhalation exposures (vapor) are not expected due to the n egligible vapor pressure of Busan 77; therefore , these exposures were not assessed. Table 11 lists the residential post

- application scenarios that the Agency anticipates that will be need to be reassessed in registration review

.

Table 11

– Residential Post

- Application Exposure S cenarios for Busan 77

Scenario Exposure Route(s) Duration
Residential Exposures
Post application exposure to swimming pools and spas/whirlpool Dermal Incidental Oral Short and Intermediate Term



## 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposure s
Th e Agency anticipates the need to conduct an aggregate assessment which will include both drinking water and res idential exposures ( i.e

. swimming pool s /spas )

. Since there are no dietary (food) exposures based on the current use patterns, food contribut ions will not be included in the aggregate assessment.


### 3.4.2 Cumulative Exposures

With respect to cumulative exposure, unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a

comm on mechanism of toxicity finding as to Busan 77 and Busan 77 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 Busan 77 has a common mechanism of to xicity 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/pesticide

- science

- and

- assessing

- pesticide

- risks/cumulative

- assessment

- risk

pesticides

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Page 21 of 64 

## 4 Environmental Risk Assessment

The Agency anticipates the need to conduct and ecological risk assessment and may call in data in support of the assessment. The ecological risk assessment planned during registration review will allow the Agency to determine potential acute and chronic risks to aquatic organisms exposed to Busan 77 transported from treatment sites into the aquatic environment. Such sites include recirculating cooling towers, air washer systems, petroleum secondary recovery systems, and metalworking fluids

. T here is no evidence of degradation of Busan 77 by either abiotic or biotic routes . T he primary exposure is expected to be to sediment

- dwelling organisms based on the sorption potential from the positively

- charged parent compound. However, bioconcentration is not expected because of the miscibility in water (Table 4).

The Agency has not previously conducted a risk assessment that supports a complete endangered species determination for Busan 77. The risk assessment planned for regi stration review also will allow the Agency to determine whether each use of the Busan 77 has 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate.



## 4.1 Environmental Fate Assessment
Busan 77 is miscible in water (Table 4) and is not expected to degrade by either abiotic processes ( MRID s 41407401 and 41420901) or biotic processes ( MRIDs 40334101

, 40165201, 40165202)

. Movement from water or soil into air is also not expected to occur f or most uses based on the negligible vapor pressure and Henry’s Law values (Table 4 ) , but the air washer use may have the potential to create aerial exposure because the Busan 77 dissolved in water can volatilize with the water. Bioconcentration in aquatic organisms is also not expected based on the water miscibility and low log P values (Table 4 )

. Sorption to soil, sediment, and sludge is expected to be the primary route of dissipation since Busan 77 is a quaternary ammonium compound that has a positive el ectrical charge. However, data for sorption to soil and sludge have not been submitted and are anticipated to be required.

Busan 77 has the potential to reach Waste Water Treatment Plants (WWTPs) from the registered uses, and data on activated sludge sorp tion isotherm (ASSI) and activated sludge respiration inhibition (ASRI)

. WWTP biodegradability studies (835.3110, 835.3220, 835.3240, and 835.3280) are normally required for chemicals that have the potential to reach wastewater treatment plants. However, i n the case of Busan 77, there is no apparent route of chemical or microbial degradation, and therefore degradation studies in a WWTP would not be expected to provide additional information and are not anticipated to b e required

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### 4.1.1 Water Quality

Busan 77 is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act

. 4 In addition, no Total Maximum Daily Loads (TMDL) have been developed for Busan 77

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

. 6



## 4.2 Conceptual Model s for Environmental Exposure Pathways

Based on the summary of registered uses of Busan 77 presented in Table 5

, physical/chemical properties in Table 4, and environmenta l fate data presented in Table 4 and Appendix B, the Agency has developed conceptual model diagrams for exposure of ecological organisms to parent Busan 77

. Busan 77 is stable to both abiotic and biotic proc esses and is unlikely to move from soil or water into air based on its negligible vapor pressure and Henry’s law values ( Table 4) with the exception of the air washer use which creates the potential for aerial exposure through co

- distillation

. Chemicals th at are released down

- the

- drain can typically take from a few to several hours to reach wastewater treatment plant intakes following their discharge and from several hours to roughly a day following their discharge from wastewater treatment plants to reach surface water. Data on WWTP dissipation have not been submitted for Busan 77, but the primary route of dissipation is expected to be sorption to sludge and biodegradation is expected to be limited

.
The Agency has created conceptual models for potential ro utes of environmental exposure which are included in “Conceptual Models for Environmental Exposure Pathways of Antimicrobial Pesticides ,” found in the docket at www.regulations.gov , EPA

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- 0638

.

Use site s and corresponding figures of conceptual model diagrams are as follows:

• Recirculating cooling towers and air washer systems ( slides 13 and 14)

• Metalworking fluids ( slide 18)

• Paper manufacturing ( slide 26)

• Petroleum secondary recovery systems ( slides 19 an d 20) , and

• Swimming pools, spas, whirlpools, hot tubs, ornamental ponds , aquaria, waterbeds ( Slides 27 and 28)

The screening

- level risk assessment that will be conducted as part of this registration review will evaluate potential risks to ecological org anisms from exposure to parent Busan 77 only because it did not degrade by abiotic processes (MRIDs 41407401 and 41420901) or biotic processes (MRIDs 40334101, 40165201, 40165202).

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

5 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_polluta nt_ group_name=PESTICIDES

6 http://www.epa.gov/owow/tmdl/Docket Number EPA

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Page 23 of 64 

## 4.3 Ecological Effects Assessment
Previously an ecological risk assessment was not typically conducted for the types of uses registered for Busan 77

, except for the once

- through cooling water use. A risk assessment for

once

- through cooling water uses

, using maximum application rates and the toxicity values for various organisms

, was conducted during the RED (2007) process

. The results of the assessment of once

- th r ough cooling water uses indicate that there may be high risk to freshwater fish, freshwater invertebrates and estuarine/marine invertebrates from the use of Busan 77. A ll ot her uses were considered indoor at the time of the RED assessment and were thought to have minimal to no environmental exposure potential following use. During the reg istration review process, all of the current uses of Busan 77 will be evaluated and an up dated assessment of the

on c e

- through cooling water uses will be conducted.



### 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 chemical studies submitted by registrants or other interested parties, federal laboratory data, or from the public literature are tabulated in Appendix C along with the data requirements and data gaps. T he most sensitive values for each receptor group are used for the risk assessment

. The selected endpoints from the RED assessment ( Table 12 ) will be updated during the risk assessment phase of registration review based on any addi tional submitted data or data found in the public literature.

Table 12

– Ecological Effects Endpoints Selected for Assessing Risks from Busan 77

Receptor

Group Surrogate Species Risk Scenario Toxicity Endpoint Reference (MRID)

F reshwater fish Rainbow trout Acute 96

- h LC 50 = 0.047 mg/L 41352001
Fathead minnow Chronic NOAEC = 0.019 mg/L 49362401
Freshwater invertebrates Daphnia magna Acute 48

- h EC 50 = 0.28 mg/L 41352003 Chronic Data Gap

--
Estuarine/marine fish Sheepshead mi nnow Acute 96

- h LC 50 = >360 mg/L 40139202 Chronic Not required 1

--

Estuarine/marine

invertebrates Quahog clam Acute 48

- hr EC 50 = 0.21 mg/L 40334201

Mysid Shrimp Acute 96

- hr LC 50 = 7.8 mg/L 40139203 Chronic Not required 1

-- Algae Green alga Non

- li sted 96

- hr EC 50 = 0.003 mg/L 49453501 Aquatic vascular plants Duckweed Non

- listed Data G ap 2

--
Seedling Emergence Oat Non

- listed EC 25 = >73 mg/L 42038101

Vegetative vigor Corn Non

- listed EC 25 = >74 mg/L 42038101

Birds Mallard duck Acute LD 50 = 497 mg/kg 41654801

Bobwhite quail Subacute dietary LC 50 = >3462 mg/kg 00159307

Chronic Not required 1

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Page 24 of 64 Receptor

Group Surrogate Species Risk Scenario Toxicity Endpoint Reference (MRID)
Chronic NOAEL = 100 mg/kg/day 41234501
Nontarget insects Honey bee Acute Not r equired 1

--

1 Not required for this use pattern.

2 Submitted study 420 13301 is supplemental and did not provide an endpoint.



## 4.4 Exposure Analysis Plan

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates

Available OPP models will be used to dete rmine the estimated environmental concentration (EECs) in the aquatic environment. Resulting exposure estimates will be compared to the toxicity endpoints to determine if levels of concern are exceeded for each receptor group.



### 4.4.2 Screening Level Down

- the

- Dra in Analysis A screening Down

- the

- Drain (DtD) assessment was not conducted for Busan 77 and degradates. Since Busan 77 is expected to sorb strongly to soils, but no quantitative sorption data are available, risk estimates from the screen would have little v alue.

Further, the DtD screen only pertains to domestic wastewater treatment p lants. Based on registered uses of Busan 77 presented in Table 5 of this FWP , there are some uses, such as commercial and industrial cooling water systems and paper mill wate r systems, for which discharges may enter industrial WWTPs rather than domestic WWTPs prior to entering surface water. Different methods and tools for assessing potential exposures and associated ecological risks will be applied for these other types of us es. The Agency does not have high quality data on the toxicity of Busan 77 to activated sludge microorganisms in wastewater treatment plants or data on sorption to sludge . Consequently, the Agency anticipates needing data on Busan 77 to fulfill data gaps r egarding toxicity to activated sludge microorganisms and during wastewater treatment

. 

## 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 Busan 77 and the data reviewed following the Agency ’s policy for reviewing public literature for use in assessing risks from pesticide s

. 7 Those ecotoxicity values found in the public literature to be more sensitive than those curr ently in Table 12 and or which satisfy an existing data gap(s) will be used during the risk assessment phase of Busan 77 to update Table 12

. ECOTOX was created

7 http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_reregistration_wor kgroup/esa_evaluation_open_literature.htmDocket Number EPA

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Page 25 of 64 and is maintained by the USEPA, Office of Re search 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 ad verse 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 inc lude endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its reregistration decision f or Busan 77 , EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA S ection 408(p), Busan 77 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 effect s as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estr ogen, 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 eff ect.

Under FFDCA S ection 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 8 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 9

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

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- 2009

- 0477

- 0074 for the final second list of

chemicals.

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## 6 Optional Label Changes

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


## 7 Next Steps

A DCI will be developed requ iring generation and submission of the data listed under the “Anticipated Data Needs” Section of this document. The Agency expects to issue the DCI by March of 2017.Docket Number EPA

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## 8 References

MRID 42372401. Bowles, D. (1991) Product Chemistry for WSCP: Lab Project Number: NA 909218/1. Unpublished study prepared by Twin City Testing Corp. and NATEC Institut fur Naturwissenschaftlich

- technische Dienste GmbH. 88 p.

MRID 46915602. Wo, C. (2006) Physical and Chemical Characteristics (830 Series, Group B): Algae Clean Out W. Unpublished study prepared by Product Safety Laboratories. 6 p.

MRID 47120304. Tillman, A. (2007) Waiver Request for Certain Data Requirements for WSCP MUP. Project Number: KT/200704. Unpublished study prepar ed by Kerley Trading, Inc. 7 p.

MRID 49176301. Dotse, A.; Grabowicz, J. (2013) Product Chemistry for WSKT: Ac tive Ingredient and Physical/ Chemical Properties: Final Report. Unpublished study prepared by Buckman Laboratories, Inc. 27p.

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 . High Production Volume Information System (HPVIS). http://www.epa.gov/hpvis/

U.S. Environmental Protection Agency (US EPA). 1999. Evaluation of Chemical Manufacturers Association Antimicrobial Exposure Assessment Study. Memorandum from Siroos Mostaghimi, Ph.D., USEPA, to Julie Fairfax.Docket Number EPA

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# Appendix A T oxicology Profile

Acute Toxicity for Product Labeling

The acute toxicity database for Busan 77 is considered complete and testing re sults are summarized in Table A1

. Busan 77 tested at 60

- 61.6% active ingredient has a moderate order of acute toxicity via the oral , dermal and inhalation route s of exposure (Toxicity Categor y III ). For dermal irritation, Busan 77 has a low order of acute toxicity (Toxicity Category IV) and is a slight eye irritant (Toxicity Category IV). Busan 77 is not a dermal sensitizer

.
Table A1

– Acute Toxicity Studies for Busan 77 (60

– 61.6% active ingredie nt)

Guideline No./

Study Type MRID No. Results Toxicity Category 870.1100/ Acute oral toxicity 41373401 93062009 LD 50 = 1951 (1727

- 2203) mg/kg )M) LD 50 = 2587 (2059

- 3250) mg/kg (F) III

870.1200/ Acute dermal toxicity 41327101 93062010 LD 50 > 2000 mg/ kg III

870.1300/ Acute inhalation toxicity 41877501 LC 50 = 4.0 (2.3

- 7.1) mg/L (M) LC 50 = 2.4 (1.7

- 3.3) mg/L (F) LC 50 = 2.9 (2.3

- 3.7) mg/L (combined) III

870.2400/ Acute eye irritation 41361701 93062011 Redness, cleared on day 3 post

- application III

870.2500/ Acute dermal irritation 41298601 93062012 Slight irritant I V

870.2600/ Skin sensitization 40750301 93062013 Not a sensitizer N/A

N/A=Not applicable ; M = males; F = Females 

## Subchronic Toxicity

Subchronic toxicity studies ( MRIDs 40170601/9 3062015 and 40025001/93662014) indicate that the dermal route did not result in systemic effects when tested to the limit dose (1,000 mg/kg/day). However, signs of chronic irritation/inflammation were noted in both males and females at the 100 and 1,000 mg /kg/day dose level (skin lesions included ulceration of the epidermis, chronic inflammation of the edermis, acanthosis, hyperkeratosis, parakeratosis, folliculitis, and epidermatitis). The oral route led to toxic effects at 1,000 mg/kg/day (mineralization of renal tubules). 

## Developmental Toxicity

Developmental toxicity studies (MRIDs 41423001/93062018 and 41248001/93062019) through the oral route showed developmental effects occurred at greater than or equal dose levels as maternal effects. A study conduct ed in rats had maternal effects occurring at 350 mg/kg/day (decreased food consumption and body weight gain, which were not statistically significant) and became severe at 700 mg/kg/day (mortality, morbidity observed, including lungs, brain, stomach,Docket Number EPA

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Page 29 of 64 and i ntestines). No developmental effects were observed in the doses tested in this study. In a study in rabbits, maternal effects (increased incidence of abortions, clinical signs including reduced defecations and emaciation, significantly reduced feed consump tion and body weight gain) were seen at the same dose, 45 mg/kg/day, as developmental effects (increased incidence of ribs and unossified sternabrae). 

## Reproductive Toxicity

In a reproduction study in rats (MRID 40578201/93062020)

, systemic effects (reduce d body weight, reduced absolute and relative liver weight, inflammation of the choroid plexus in the brain, and tubular mineralization of the kidney were seen at doses ~300 mg/kg/day and above) were seen at lower doses than reproductive effects (decrease i n number of live pups on days 0 and 4 after birth in both generations at ~600 mg/kg/day) in rats. 

## Chronic Toxicity

A chronic toxicity study in dogs (MRID 41234501/93062016) by the oral route showed signs of toxicity in males (testicular hypoplasia, atroph y/degeneration, aspermia, dysplasia and cellular debris of testicular origin in the epididymis at 500 mg/kg) at lower doses than females (G

- I disturbances, emaciation and nervous symptoms at 1,000 mg/kg).

Two chronic, feeding studies were conducted with Bu san 77; a combined chronic toxicity/carcinogenicity study in rats (MRID 41809101 /41561301) and a chronic toxicity study in mice (MRID 41494301/93062017). For additional chronic toxicity information, see “carcinogenicity” section below. 

## Carcinogenicity

In a combin ed chronic/ carcinogenicity study (MRID 41809101 /41561301 )

, rats exposed to 0, 100, 300 or 900 mg/kg/day ( 0, 2000, 6000 and 18000 ppm in males and females) a chronic NO A EL of 100 and LO A EL of 300 mg/kg/day , was based on reduced body weight gain (F), reduced albumin ( CM), reduced total protein (CM), reduced p hosphorus ( i norganic) (M & F), increased urine pH (F) and a dose

- related increase in blood y crusts (M). In addition, at 900 mg/kg/day , hyperesthesia, bloody crusts, decreas e d body weight gain, dec reased phosphorus ( i norganic) , globulin and total protein and increased brain

- to

- body weight ratio associated with mineralization of the brain in the thalamic region, in males and females; decreased albumin, glucose and cholesterol in males and increased u rine pH in females, were observed. In the carcinogenicity study, for females, there was a possible increased incidence of thyroid C

- cell adenomas in the 300 and 900 mg/kg/day groups and a positive trend in males and females.

In a carcinogenicity study in m ice (MRID 41494301/93062017) , t here was a dose related increase in proteinaceous casts in the renal tubules of males and renal pelvic and tubular dilatation in males and females. It could not be defini tively determined whether increased incidences of ro u gh hair coat, bloody crusts and red ears in males an d convulsions in females occurred at the low or high dose, 600 or 2400 mg/kg/day, respectiv e ly. Busan 77 in the diet was determined to be non

- carcinogenic in mice up to 2,400 mg/kg / day.Docket Number EPA

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Page 30 of 64 Carcinogenic Poten tial

There was an increased incidence of thyroid C

- cell adenomas in females at the mid

- and high

dose levels and in males at the high dose level in the combined chronic toxicity/carcinogenicity in rats. The increase in the overall incidence of thyroid C

- c ell adenomas in males did not attain a statistically significant level when compared with the concurrent controls. However, there was a statistically significant positive dose

- related trend in males and females for this type of tumor. The incidence of C

- ce ll adenomas in females was outside the range and higher than the mean of historical control incidences. Historical control incidences for this type of tumor in this strain of rat were as follows: a) in females, the range was 0

- 14% with a mean value of 4.5 %, b) in males, the range was 1.7

- 11% with a mean value of 5.8%. Only one C

- cell carcinoma (1/24; 4.1%) was observed in the mid

- dose males. The increase in tumor incidences in rats might have been due to alteration of the normal metabolic pathways, biotran sformation and/or elimination of the chemical as a result of compromised liver and kidney function

. In contrast, Busan 77 did not induce tumors in Crl:CD

- 1 (ICR) BR mice up to 16,000 ppm (2,400 mg/kg/day) in the diet and therefore, is not carcinogenic. Con sequently

, Busan 77 was classified a “Group D” carcinogen based upon increased thyroid C

- cell adenomas in rats by the HED RfD C ommittee (1994). Under registration review, t he Agency anticipates conducting a carcinogenicity assessment, pending the outcome of a review of Busan 77 carcinogenicity data by the HED CARC

. 

## Mutagenicity

The mutagenicity battery previously submitted for Busan 77 showed no evidence of mutagenicity or genotoxicity. Busan 77 was not mutagenic in a reverse mutation assay in bacteria in the presence or absence of mammalian metabolic activation (MRID 41573701), produced no increase in sex

- linked recessive lethal genes in Drosophila flies (MRID 00151205), did not increase micronuclei in mice (MRID 00151206/93062021) and did not increase

uns cheduled DNA synthesis in primary rat hepatocytes (MRID 40978701/93062022).

However, this mutagenicity battery is now considered incomplete. Under current standards, this data gap can be fulfilled via conduct of either an in vitro mammalian cell gene muta tion assay (OCSPP 870.5300) or an in vitro mammalian chromosome aberration test (OCSPP 870.5375) with the Busan 77 technical grade active ingredient. 

## Other Toxicological Effects
Neurotoxicity

There was evidence of neurological effects in the existing tox icity database for Busan 77. C onvulsions w ere observed in the mouse carcinogenicity study (MRID 41494301/93062017) with Busan 77 at a dose of 8000 ppm (~1200 mg/kg) in males (10/50 mice vs. 6/50 mice in controls). In females, there appeared to be increased incidence of convulsions at 4000 ppm (~600 mg/kg) (7/50 mice vs. 3/50 mice in controls). However, t he time of appearance and duration of this clinical sign was not established in this study

. In a chronic toxicity/carcinogenicity study inDocket Number EPA

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Page 31 of 64 rats (MRID 418091 01/41561301) , mineralization of the thalamic region of the brain was observed at a dose of 900 mg/kg/day at week 105 as was an increased incidence of hyperplasia in males and females at this dose (36/60 males; 21/60 females vs. 0/60 controls for both sexes ). A d evelopmental toxicity study in rats (MRID 41423001 /93062018 ) showed dilated meningeal vessels and/or hemorrhage in maternal rats at a dose of 700 mg/kg/day. In a two

- generation reproduction toxicity study (MRID 40578201/93062020) , increased incidence of inflammation of the choroid plexus of the brain was observed in parental animals of both generations at doses of 300 mg/kg/day and above. Based on this evidence, potential neurotoxic effects can occur in humans exposed to Busan 77. Therefore, a neuroto xicity battery in rats (OCSPP 870.6200) that includes both acute and subchronic (90

- day) neurotoxicity screening studies are anticipated to be required for Busan 77.



## Metabolism and Pharmacokinetics

Metabolism of Busan 77 (MRID 40268601/93062024) showed no expired 14 CO 2 . Under intravenous injection, roughly half (52

- 55%) of the radioactivity was excreted after 7 days through urine (38

- 44%) and feces (11

- 14%), while tissues contained 43

- 55% of the dose. The major route of excretion after single oral and repe ated oral doses was feces (85

- 103%), urine was minor (3%). Of the oral dose groups the highest residual radioactivity was found in kidneys, liver and spleen. Recoveries of doses in the tissues, including carcass (≤0.14%) indicated a minimal potential for b ioaccumulation after oral dosing.



## Dermal Penetration

In a dermal penetration study (MRID 40139201/93062025), 14 C

- Busan 77 (purity 60%), was administered dermally to male CRL:CD BR rats(24/group) at single dose levels of 0, 2, 20 or 300 mg/rat, (0.16, 1.59 or 15.97 mg/cm 2 , respectively). Less than 0.2% of the 14 C

- Busan 77 was absorbed. Mean % recovery of radioactive dose ranged from 74.5

- 92.7%. The m ajority of the dose was recovered in the skin rinse (65.5%

- 88.6%) and at the skin site (0.4%

- 13.7%).



## Det ermination of Special Susceptibility

There is an adequate database for determining potential sensitivity of Busan 77 to offspring. Two developmental toxicity studies conducted with rats and rabbits demonstrated developmental toxicity effect levels that wer e at the same or higher dose levels than those doses causing maternal toxicity. In the rat, a developmental toxicity LOAEL was not established; the NOAEL was 500 mg/kg/day. The maternal LOAEL of 350 mg/kg/day in this study was based on decreased body weigh t gain and food consumption. In rabbits, the maternal and developmental toxicity LOAELs were the same, 45 mg/kg/day. Maternal effects consisted of increased abortions, reduced defecation and emaciation, reduced food consumption, and decreased weight gain. Offspring effects at this dose consisted of increased incidence of 13 th rudimentary ribs and unossified sternebrae #5 and #6. In the two

- generation reproduction toxicity study, the reproductive LOAEL was >900 mg/kg/day, whereas the parental LOAEL was 600 m g/kg/day. The weight of evidence from these data indicates no increased sensitivity of the offspring in either the developmental or reproductive toxicity studies to the adverse effects of Busan 77. ThisDocket Number EPA

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Page 32 of 64 conclusion is supported by the previous conclusion of the HED RfD/Peer Review Committee in 1994. 

## FQPA Considerations

The FQPA Safety Factor (as required by the Food Quality Protection Act of 1996) is intended to provide an additional 10

- fold safety factor (10X), to protect for special sensitivity in infants and children to specific pesticide residues in food, drinking water, or residential exposures, or to compensate for an incomplete database. The Antimicrobials Division’s Toxicology Endpoint Selection Committee (ADTC) has recommended that the special hazard

- based FQPA safety factor for Busan 77 be removed. This conclusion is based upon the (1) availability of acceptable developmental and reproductive toxicity studies conducted with Busan 77 that adequately characterize the dose

- response of this compound (2) the lack of evidence for any sensitivity of fetuses or offspring to the adverse effects of Busan 77 and (3) the risk assessment does not underestimate the potential exposure for infants and children.Docket Number EPA

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## Toxicity Profile for Busan 77

Table A2

– Subchronic, Ch ronic, and other Toxicity Profiles for Busan 77

Guideline Number/ Study Type Test Substance (% a.i.) MRID Number (Year) /Citation/ Classification / Doses Results

870. 3050 28

- day oral (mice )

Purity: not reported MRID 40362601 Kehoe, D.F. (1987). Four

- Week Toxicity Study with Busan 77 in Mice. Buckman Labs, Inc., Memphis, TN. Study #: 6176

- 108

Not reviewed

Busan 77 administered orally in the diet at 0, 2500, 5000, 10000, 20000 ppm for 28 days

5 rats/sex/dose NOAEL = 10,000 ppm LOAEL = 20,000 ppm Body we ights, food consumptions, and ante mortem observations were recorded at initiation and then weekly for at least 4 weeks. At the end of the study, all surviving mice were bled for hematology and clinical chemistry tests. The mice were then anesthetized, exs anguinated, and necropsied. A female mouse that died on test was also necropsied and representative tissues were collected. At the scheduled necropsies, macroscopic observations were recorded, selected organs were weighed, and representative tissues were c ollected a; required by the protocol. Specified tissues from mice given 0 or 20,000 ppm were examined microscopically. Representative samples of gross lesions and rectums were also examined microscopically from all groups.

No treatment

- related ante mortem observations were seen in animals fed Busan 77; and no treatment

- related changes occurred in body weight or food consumption the Cumulative body weight gains were significantly lower during Week 1, 2 and 4 in males fed 20,000 ppm Busan 77. Although female s fed 20,000 ppm had a lower body weight when compared with the control group, there were no statistically significant differences.

There were no treatment

- related effects on the clinical pathology data, organ weight data, or microscopic observations. The only microscopic lesions that may have been treatment related were small foci of neutrophils at the anorectal junction of mice given 20,000 ppm Busan 77.
870. 3100 9 0

- day oral (rat )

Purity: not reported MRID 40025001/93662014 Tisdel, Merrill (1986). Thi rteen Week Subchronic Toxicity Study With Busan 77 in Rats. Buckman Labs, Inc. Memphis, TN. Study #: 6176

- 106.

Core

- Minimum NOAEL = 3,000 ppm(2000 mg/kg) LOAEL = 10,000 ppm (752 mg/kg) based on mineralization of renal tubules. At 30,000 ppm and 40,000 ppm (approx. 2554 and 3685 mg/kg/d, resp.) the following were observed: decreases in body weights and pos sibly absolute organ weights (heart, liver, kidney and gonads); an equivocal decrease in red blood cell counts; elevated leukocyte counts; non

- suppurative inflammation in the choroid plexus of the brain; death.Docket Number EPA

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Page 34 of 64 Guideline Number/ Study Type Test Substance (% a.i.) MRID Number (Year) /Citation/ Classification / Doses Results

Busan 77 administered orally in the diet at 0, 3000, 10,000, 30,000 and 40,000ppm (0, 300 1000, 3000, and 4000 mg/kg ) for 13 week s

10 rats/sex/dose The occurrence of increased kidney weight an d mineralization at 10,000 ppm and above suggests a treatment

— related response. Severity of mineralization was not discussed. Chronic inflammation of the choroid plexus was observed at the two highest dose levels only, suggesting a treatment

— related respon se in this parameter. The decrease in actual numbers of animals affected at the highest dose level (40,000 ppm) is a function of the mortality that was observed at that level (8 males, 2 females). 870. 3250 90

- day dermal (rabbit )

Purity: 60% MRID 40170601 /93062015 Spindler, M. (1987). 13

- Week Dermal Toxicity Study with Busan 77 in Rabbits. Buckman Laboratories, Inc. Memphis, TN. Study #: 6176

- 118

Acceptable /Guideline

Busan 77 applied dermally at 0, 10, 100, 1000 mg/kg for 13 weeks

10 rabbits/sex/dose S ystemic Toxicity NOAEL > 1000 mg/kg/day (HDT) LOAEL = Not established

Dermal Toxicity NOAEL = 10 mg/kg/day LOAEL = 100 mg/kg/day based on treatment related dermatological changes consistent with chronic irritation/inflammation. The skin lesions consisted of one or more combinations of ulceration of the epidermis, chronic inflammation of the dermis, acanthosis, hyperkeratosis, parakeratosis, folliculitis and epidermatitis.

Following the dermal application of Busan 77 to male and female rabbits at dose lev els of 0, 10, 100 and 1,000 mg/kg/day, 6 hours/day, 5 days/week for 13 weeks, there were no treatment

- related changes in the body weights, food consumption, hematology, clinical chemistry, organ weights and organ

— to

- body weight ratios and gross and/or hist opathological changes of internal organs of males and females. However, there was treatment related dermatological changes consistent with chronic irritation/inflammation were seen in males and females receiving 100 and 1,000 mg/kg/day. The skin lesions co nsisted of one or more combinations of ulceration of the epidermis, chronic inflammation of the dermis, acanthosis, hyperkeratosis, parakeratosis, folliculitis and epidermatitis. The doses tested did not establish the MTD, however, the highest dose tested reached Limit Dose. 870.3700 Developme ntal Toxicity

– oral gavage (rat )

Purity: 97% MRID 41423001/93062018 Nemac, Marc D. (1987). A Teratology Study in Rats with Busan 77. Buckman Laboratories, Inc. Study #: WIL

- 94020.

Core

- Minimum/Guideline Maternal Toxicity NOAEL = 70 mg/kg/day LOAEL = 350 mg/kg/day , based on decreased food consumption and body weight gain. Mortality observed at 700 mg/kg/dayDocket Number EPA

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Busan 77 administered orally at 0, 70, 350 500 mg/kg/day on GD 6

- 15

25 rats/dose group Developmental Tox icity NOAEL = 500 mg/kg/day LOAEL > 500 mg/kg/day (HDT)

Busan 77 was toxic to rat dams, causing decreases in food consumption and (non

- statistically significant) decreases in body weight gains at 350 mg/kg/d and 500 mg/kg/d, and death and morbidity at 70 0 mg/kg/d. The dose response curve appears to be inordinately steep, since 1) none of the toxicity (convulsions, lethargy and pathological changes in lung, brain, stomach and intestines) observed at 700 mg/kg/d was observed at 500 mg/kg/d, which is only ‘/ , of a log dose lower; and 2) the profile of other adverse effects such as decrease food consumption (Table 2) suggests a more gradual slope. However, absence of effects at lower dose levels cannot be adequately verified from the data submitted with this s tudy (see Deficiencies Section above). It is also remarkable that liver and/or kidney effects were not reported as being observed, even at levels that killed 25% of the dams.

Busan 77 appears to cause a dose

- related increase in embryonal death, as manifes ted by a statistically significant increase In early resorptions, at 500 mg/kg/d. 870.3700 Developme ntal Toxicity

– oral gavage (rabbit )

Purity: 60.8% MRID 41248001/93062019 Rodwell, Dean E. (1989). Teratology Study in Rabbits with Busan 77. Buckman Labo ratories, Inc. Study #: 3138.29

Core/Guideline

Busan 77 administered via gavage at 0, 15, 45 and 125 mg/kg on GD 6

- 18 inclusive

20 rabbis/dose group Maternal Toxicity NOAEL = 45 mg/kg/day LOAEL = 125 mg/kg/day, based upon increased incidence of aborti ons, clinical signs including reduced defecation and emaciation, significantly reduced feed consumption and body weight gain during
treatment.

Developmental Toxicity NOAEL = 45 mg/kg/day LOAEL = 125 mg/kg/day Based upon increased incidence of 13th rudim entary ribs and unossified sternebrae #5 and #6.

The data reporting was thorough and the summary means that were validated were supported by the individual animal data, except for minor discrepancy in reporting the mean body weight gain of 80 instead of 1 83 for the high dose dams during gestation Day 24

- 29 (Report summary Table 4). The error had been factored in, in theDocket Number EPA

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calculation of body weight gain of dams and will not alter the conclusions of the study.

It was reported that the doses were selected b ased upon a range finding study, but no details were provided. While this information should have been included in the report, the deficiency is not a factor since results of current study indicate maternal toxicity at 125 mg/kg/day.

a. Maternal Toxicity: At 125 mg/kg/day, increased incidence of abortions, clinical signs including reduced defecation and emaciation, significantly reduced feed consumption and body weight gain occurred during treatment.

b. Developmental Toxicity: At 125 mg/kg/day, the incide nce of 13th rudimentary ribs and unossified sternebrae #5 and #6 was increased significantly (P 0.05). The litter incidences for 13th rudimentary rib (93.3 vs. 89.5 of historical controls) and unossified sternebrae #5 and/or #6 (40.0 vs. 36.8 of historical controls) are slightly above the corresponding historical controls values. Although, the incidence lacked a trend or dose

- relationship and occurred at a maternally toxic dose, the increases are considered treatment

- related. 870.3800 Reproduction and F e rtility E ffects (rat)

Purity: not reported MRID 40578201/93062020 MacKenzie, K.M. (1988). Two

- Generation Reproduction Study with Busan 77 in Rats (One Litter per Generation). Buckman Laboratories, Inc., Memphis, TN. Study #: HLA 6176

- 104.

Core

- Minimum/Gu ideline

Busan 77 administered in the diet at 0, 6000, 12000 and 18000 (0, 300, 600 and 900 mg/kg/day) for two generations

25 rats/sex/dose Maternal Toxicity NOAEL: not established LOAEL: 300 mg/kg/day, based on decreased body weight, inflammation of cho roid plexus, tubular mineralization of the kidney.

Reproductive Toxicity: NOAEL = 600 mg/kg/day LOAEL = 900 mg/kg/day based on decreased live pups.Docket Number EPA

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870.4100 Chronic Toxicity (dog)

Purity: not reported MRID 41234501/93062016 Kehoe, Daniel F. (1989). One

- Year Chronic Toxicity Study with Busan 77 in Dogs. Buckman Laboratories, Inc. Memphis, TN. Study #: HLA 6176

- 111

Supplementary

Busan 77 administered orally at 0, 10000, 20000 and 40000 ppm (0, 250, 500, 1000 mg/kg) for 52 weeks

4 dogs/sex/dose NOAEL: 2 50 mg/kg/day (M); 500 mg/kg/day (F)

LOAEL = 500 mg/kg/day (M) based on testicular hypoplasia, atrophy/degeneration, aspermia, dysplasia and cellular debris of testicular origin in epididymis.

LOAEL = 1,000 mg/kg/day (F) based on G

- I disturbances, weight loss and nervous symptoms (bloody stools, emaciation and ataxia, respectively).

Administration of Busan 77 in the feed for up to 52 weeks had no effect on mortality. However, an increased incidence of vomits and abnormal stools (soft and bloody) was obser ved with increasing dose. In the KTD group, all males and females exhibited bloody stools at 12 (1) and 26 (2) weeks, respectively. Probably this is related to treatment. At necropsy, thickened wall of duodenum (3 males and 2 females), jejunum (2 males) an d ileum (1 male) were observed in the 40,000 ppm group. Microscopic examination of these tissues did not reveal any changes associated with the treatment and is probably of no toxicological significance. In addition, microscopic examination of
rectum or co lon of all HDT males revealed changes associated with chronic inflammatory processes and was probably treatment related. Body weight gain of males and females in the 40,000 ppm group decreased significantly when compared to controls. Body weight gain of ma les and females was reduced by 39 and 42%, respectively, at 12 weeks when compared to controls. In the 20,000 ppm group, the mean body weight gain decreased non

- significantly in males and females 17 and 6%, respectively, at 12 weeks when compared to contro ls; and decreased in males and females 30 and 14%, respectively, at termination (52 weeks) when compared to controls and it may not be related to treatment. Food consumption was significantly decreased in the males and females in the 40,000 ppm group at se veral intervals. At week 13, food consumption of males and females in the 40,000 ppm group decreased 46 and 53%, respectively, when compared to controls.

At 26 weeks, males and females in the 40,000 ppm group had a significant increase in Hct, MCV, MCH an d platelets, and in females a significant increase in Hb was observed. Also, a significant decrease in RBC was seen in males and females at the 26 week time interval. The low RBC and increased MCV may signal mild anemia; however,Docket Number EPA

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histopathology of bone mar row smears and bone sections did not correspond to morphological changes. These changes in the HTD group may be in part/whole related to mild anemia, emaciation and dehydration. Significant increases in MCV in the 10,000 and 20,000 groups in males/females are of questionable biological significance because of the sporadic nature of occurrence.

Total protein, albumin and creatinine were significantly decreased in males and females in the 40,000 ppm group at 26 weeks, probably due to anemia and emaciation an d may be treatment related. Also, a significant decrease in K, glucose in males and P hosphorus (inorganic), Na and Cl in females were also observed at this interval. This is probably due to dehydration, associated with vomition/diarrhea. Changes noticed in the 10,000 ppm group and in the 20,000 ppm group for K, and P hosphorus (i norganic ) at 26 weeks, are of sporadic nature and have no toxicological significance. The significant (slight) increase of SGPT in males at 26 weeks, in the 40,000 ppm group and of S COT at 52 weeks, in the 10,000 and in the 20,000 ppm groups at 52 weeks, is probably of no toxicological significance, since the histopathology revealed no treatment related affects. At 52 weeks, males and females had significantly reduced cholesterol in t he 20,000 ppm group; the toxicological significance of this is uncertain.

U rine pH in males was significantly reduced in the 40,000 ppm group at 26 weeks and in the 10,000 and in the 20,000 ppm groups at 52 weeks. Also, higher urinary blood pigment was no ticed in the 40,000 ppm group. The significance of low urine pH and higher urinary blood pigment on the urinary tract is of questionable values, since there was no corresponding histopathological changes.

Organ to body weight ratios for brain, liver and k idney increased (significantly) 52, 19 and 47%, respectively for males in the 20,000 ppm group at termination, when compared to controls. The actual weights of the brain, liver, and kidney in males were 1,

- 18 and

- 13 %, respectively, when compared to cont rols. Females exhibited significant increases of 4 and 47 %, respectively, in the body weight ratio of kidney and liver. The apparent increase in the organ to body weight ratios, and actual decrease in the absolute organ weights without corresponding histo pathological changes, suggest that the changes seen grossly may be due to in part/whole to body weight loss, especiallyDocket Number EPA

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water loss from vomiti ng and diarrhea. In addition, testes relative organ weights were not affected, whereas actual weights decreased 27 , 20 and 58 % in the LTD, MTD, and NW, respectively, when compared to controls. Reduced testicular weights corresponded to testicular hypoplasia on histopathology, evidenced by atrophy/degeneration, aspermia, dysplasia and presence of cellular debris of te sticular origin in the epididymis of all males in the 40,000 ppm group and 2 males in the 20,000 ppm group.

870.4200 Carcinogenicity (mice)

Purity: 60.8% MRID 41494301/93062017 Kehoe, Daniel F. (19 90 ). 18 Month Study Chronic Toxicity Study with Busan 77 in Mice

. Buckman Laboratories, Inc. Memphis, TN. Study #: HLA 6176

- 1 09

Core

- Minimum/Guideline

Busan 77 administered orally at 0, 4000, 8000 and 16000 ppm (0, 600, 1200, and 2400 mg/kg)for 18 months

50 mice/sex/dose NOAEL= not established

LOAEL <600 m g/kg/day, based on enlarged kidney pelvis, diffuse rough kidney I females; dose

- related increase in proteinaceous casts in the renal tubules of males, and renal pelvic and tubular dilation in males and females.

It could not be definitively determined whet her increase incidence of rough hair coat, bloody crusts and red ears in males and convulsions in females had a LEL of 4,000 or 16,000 ppm.

At the 8000 and above, all of the above findings and including convulsions (M & F), urine scams (H & F), rough hair coat (F), bloody crusts (F)

, swollen abdomen (M & F), swollen anus (M), red tails (H & F), red ears (F), reduced body weight gains (H & F), diffuse rough kidneys (H & F), large kidney pelvis (H & F), relative kidney weights (high dose males, and mid and h igh dose females), proteinaceous casts (F), cortical fibrosis/scarring (F) and cysts (F), were observed.

870.4300 Combined chronic toxicity/carcinogenicity (rat)

Purity: 60% MRID 41809101/41561301 Kehoe, Daniel F. (1991). Combined Chronic Toxicity Study and Carcinogenicity Study with Busan 77. Buckman Laboratories, Inc. Memphis, TN. Study #: HLA 6176

- 107.

Core

- Minimum/Guideline

Busan 77 administered orally at 0, 2000, 6000 and 18,000 ppm (0, 100, 300 and 900 mg/kg./day)

50 rats/sex/dose Chronic: NOAEL = 100 mg/kg/day LOAEL = 300 mg/kg/day , based on reduced body weight gain (F), reduced albumin (M), reduced total protein (M), reduced p hosphorus ( i norganic) (M&F), increased urine pH (F) and a dose related

- related increase i n blood y crusts.

Carcinogenici ty: I n females, possible increased incidence of thyroid C

- cell adenoma at 300 and 900 mg/kg/day, and positive trend for this tumor in both sexes.Docket Number EPA

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Page 40 of 64 Guideline Number/ Study Type Test Substance (% a.i.) MRID Number (Year) /Citation/ Classification / Doses Results

The RfD Committee considered the data in this study and classified Busan 77 as a Group “ D ” carcinogen.

Mutagen icity 870.5100 Reverse mutation assay

– S almonella typh i murium

.

Purity: not reported MRID 41573701 Lawler, T.L. and DaCosta, K. (1990). Mutagenicity Test on Busan 77 in the SalmonellaJMammalian

— Microsome Reverse Mutation Assay with Confirmatory Assay. Bu ckman Laboratories, Inc. Study #: 12144

- 0

- 401R.

Acceptable

Busan 77 doses of 66.7, 100, 333, 667, 1000 and 3330μg/plate

Strains: salmonella (TA1535, TA1537, TA1538, TA98 and TA100 Negative In the initial mutagenic assay (Table 3), using strains TA1535, TA1537, TA1538, TA100 and TA98 in the presence and absence of S9 activating system, at doses of 66.7, 100, 333, 667, 1,000 and 3,330 Mg/plate, did not increase in the number of histidine revertants were observed, either in the presence or absence of S9 sy stem. The experiment was repeated and all data were acceptable except for strain TA9B for which the means were outside the acceptable range both in the presence and absence of S9. The TA98 strain was retested both in the presence/absence of activation syst em and the results were acceptable (Table 4). Revertants frequencies for all doses of Busan 77 in all strains approximated or were less than those observed in the concurrent negative controls (Tables 1 and 2). All positive controls produced positive respon ses expected of the chemicals.

Based on the results of the Salmonella Reverse Mutation Assay the test article Busan 77 did not cause a positive increase in the number of histidine revertants per plate.Docket Number EPA

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870.5275 Sex

- linked recessive lethal test

Purity: 1 00% MRID 00151205 McCarroll, N. (1985). Drosophila Sex

- linked Recessive Lethal Assay [with WSCP (Busan 77)]: Hazelton Laboratories, Inc. Project #: 197

- 183. Unpublished

Acceptable

Busan 77 administered at 0.08, 0.3 and 0.8 mg/ml

Test strain: drosophila melanogaster Negative A dose

- related increase in sterility was observed in the mated P1 males to increasing concentration of the test material when compared to the solvent control. No significant difference in the percentage of sex

linked recessive lethal s was observed between the Busan

- 77 treated groups and the medium control group.

870.53 85 In vivo micronucleus assay (mice)

Purity: 100% MRID 00151206/93062021 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 00151206. Busan 77

- in Vivo Mouse Micronucleus Assay: Laboratory ID 197

- 182. Prepared by Hazleton Biotechnologies Corporation. 8 p.

Acceptable

Busan 77 administered via gavage at 0.08, 0.3 and 0.8 mg/ml

15 mice/sex/dose Negative

The test compound WSCP (Bu5an 77) is considered non

- mu tagenic in mice under the condition of this assay.

The test compound WSCP (Busan 77) did not induce a significant increase of the PCE containing micronuclei in the treated mice when compared to that of the vehicle control value.

The positive control comp ound cyclophosphamide induced a significant increase of the PCE containing micronuclei, which indicated the sensitivity of the assay system (p < 0.0001).

870.5550 Unscheduled DNA synthesis in mammalian cells in culture (rat)

Purity: not reported MRID 4 0978701/93062022 Cifone, M. (1989) Mutagenicity Test on Busan 77 in the in vivo/in vitro Rat Primary Hepatocyte Unscheduled DNA Synthesis Assay: Project ID: HLA Study No. 10280

- 0

- 494. Unpublished study pre

- pared by Hazleton Laboratories America, Inc. 26 p

. Acceptable

Busan 77 administered at 188, 375, 750 and 1500 mg/kg

3 rats/group Negative

Hepatocyte viability/attachment efficiency ranged from 85.4 to 95.2%/66.2 to 81.5%. Busan at a concentration of 188, 375, 750 and 1,500 mg/kg resulted in hepato cyte viability (attached cells) of 93.9, 93.2, 94.9 and 93.3%, respectively; i.e

. , no toxicity (see Appendix 2). None of the treatments with Busan resulted in a significant increase in nuclear labeling, when compared to the controls and did not meet the mi nimum criteria for UDS assay for mean net nuclear grain count exceeding 6, or at least 10% of the nuclei containing 6 or more grains, or at least 2% of the nuclei containing 20 or more grains, to conclude a positive response (see Appendix 1). Furthermore, there was no dose

related trend observed. Positive control treated cultures exhibited greatly exceeded all three criteria used to indicate UDS.Docket Number EPA

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Page 42 of 64 Guideline Number/ Study Type Test Substance (% a.i.) MRID Number (Year) /Citation/ Classification / Doses Results

870.7485 Metabolism and pharmacokinetics (rat)

Purity: 60% MRID 40268601/93062024 Puhl, R. (1987) Metabolism Study with Busan 77 (WSCP) in Rats: Final Report: Laboratory Project ID: HLA 6176

- 115. Unpublished study prepared by Hazleton Laboratories America, Inc. 98 p.

Acceptable/Guideline

14 C

- labeled Busan 77 administered oral and i.v. single of 10 mg/kg; single oral dose of 1000 mg/kg; repeated oral dose of 10 mg/kg

5 rats/sex/dose Intravenous excretion at 10 mg/kg; urine, 38

- 44% feces, 11

- 14%. Tissue contained 43

- 55% of the dose. Single and repeated oral dose excretion: urine, 3% of dose, feces 85

- 105% of dos e. Tissue levels low in these groups (0.14% highest levels in any tissue)

Oral 1000 mg/kg dose: urine, 14

- 17%; feces 68

- 71% of dose.

Expired CO2 was not detected. In the intravenous dose group, the major routes of excretion of radioactivity were via urin e and feces. Over a 7

- day period, approximately 52

- 55% of the test material administered was excreted in the urine (38

— 44%) and feces (11

— 14%); 43

— 55% was, found in the tissues. In a single repeated oral dosed groups 88

- 106% of the test compound administer ed was excreted in the urine (3%) and feces (85

— 105%); kidneys, liver, and spleen had a highest residue level. In these groups, tissue residue levels were low in all tissues, except kidneys. Not more than 0.14% of the administered dose was recovered in tis sues. Potential for bioaccumulation at the single, or repeated oral is minimal. At the highest oral dose, 85% of the administered dose was recovered in urine (14

— 17%) and feces (68

— 71%). The information provided by the sponsor explains that almost the enti re administered dose was excreted in the feces unchanged and remaining 40% of the composition of the technical or radiolabeled material was water.

870.7600 Dermal penetration (rat)

Purity: 60% MRID 40139201/93062025 Bosch, A. (1987) Dermal Absorption of [Carbon 14]

- Busan 77 (WSCP) in Male Rats: HLA Study No. 6176

- 117: Final Report. Unpublished study prepared by Hazleton Laboratories America, Inc. 52 p.

Acceptable/Guideline

single dermal administration to male rats at 2, 20, or 200 mg/rat (0.16, 1.59, or 15.97 mg/cm2, respectively)

24 rats/group The total amount of Busan 77 absorbed (expressed as percent of 14 C

dose) from rats at various times following dermal administration of ‘4C

- Busan 77 at 2, 20 or 200 mg/animal is negligible (less than 0.2% of the d ose). Also, no radioactivity was found in carcass and blood of all treated animals indicating no dermal absorption of Busan 77.

Only less than 0.2% of the Busan 77 was absorbed. Mean % recovery of radioactive dose ranged from 74.5

- 92.7%. Majority of the dose was recovered in the skin rinse (65.5%

- 88.6%) and at the skin site (0.4%

- 13.7%).Docket Number EPA

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Page 43 of 64 Toxicology References

MRID 00151205 McCarroll, N. (1985) Drosophila Sex

- linked Recessive Lethal Assay [with WSCP (Busan 77)]: Final Report: Project No. 197

- 183. U n

- published study prepared by Hazleton Laboratories. 20 p.

MRID 00151206 Cortina, T. (1984) In vivo Micronucleus Assay in Mice: WSCP: Final Report: Project No. 197

- 182. Unpublished study prepared by Hazleton Laboratories America, Inc. 38 p.

MRID 40025001 Tisdel, M. (1986) Busan 77

-- Thirteen

- week Subchronic Toxicity Study in Rats: Project ID: Study No. 6176

- 106. Unpublished study prepared by Hazleton Laboratories of America, Inc. 285 p.

MRID 40139201 Bosch, A. (1987) Dermal Absorption of [Carbon 14]

- Busan 7 7 (WSCP) in Male Rats: HLA Study No. 6176

- 117: Final Report. Unpublished study prepared by Hazleton Laboratories America, Inc. 52 p.

MRID 40170601 Spindler, M. (1987) 13

- Week Dermal Toxicity Study with Busan 77 in Rabbits: Laboratory Project ID: HLA 6176

- 1 18. Unpublished study prepared by Hazleton Laboratories America, Inc. 290 p.

MRID 40268601 Puhl, R. (1987) Metabolism Study with Busan 77 (WSCP) in Rats: Final Report: Laboratory Project ID: HLA 6176

- 115. Unpublished study prepared by Hazleton Laboratories America, Inc. 98 p.

MRID 40578201 MacKenzie, K. (1988) Two

- Generation Reproduction Study with Busan 77 in Rats (One Litter per Generation): Project ID: HLA 6176

- 104. Unpublished study prepared by Hazleton Laboratories America, Inc. 952 p.

MRID 40750301 Gl aza, S. (1987) Dermal Sensitization Study in Guinea Pigs with WSCP: Proj. ID 70303995. Unpublished study prepared by Hazleton Laboratories America, Inc. 30 p.

MRID 40978701 Cifone, M. (1989) Mutagenicity Test on Busan 77 in the in vivo/in vitro Rat Primary Hepatocyte Unscheduled DNA Synthesis Assay: Project ID: HLA Study No. 10280

- 0

- 494. Unpublished study pre

- pared by Hazleton Laboratories America, Inc. 26 p.

MRID 41234501 Kehoe, D. (1989) One

- Year Chronic Toxicity Study with Busan 77 in Dogs: Laboratory Project ID HLA 6176

- 111. Unpublished study prepared by Hazleton Laboratories America, Inc. 301 p.

MRID 41248001 Rodwell, D. (1989) Teratology Study in rabbits with Bu s an 77: SLS Study No. 3138.29. Unpublished study prepared by Springborn Life Sciences, Inc . 229 p

.
MRID 41298601 Rush, R. (1989) Primary Skin Irritation Study in Rabbits with Busan 77: SLS Study No. 3138.49. Unpublished study prepared by Springborn Laboratories, Inc. 19 p.Docket Number EPA

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Page 44 of 64 MRID 41327101 Rush, R. (1989) Acute Dermal Toxicity Study in Rabbits wi th Busan 77: Lab Project Number: 3138.50. Unpublished study prepared by Springborn Laboratories, Inc. 26
p.

MRID 41361701 Rush, R. (1989) Primary Eye Irritation Study in Rabbits with Busan 77 (EPA

FIFRA): Lab Project Number: 3138/52. Unpublished study prep ared by Springborn Laboratories, Inc. 25 p.

MRID 41373401 Rush, R. (1990) Acute Oral Toxicity Study in Rats with Busan 77: SLS Study No. 3138.51. Unpublished study prepared by Springborn Laboratories, Inc. 65 p.

MRID 41423001 Nemec, M. (1987) A Teratology Study in Rats with Busan 77: Final Report: Lab Project Number: WIL

- 94020. Unpublished study prepared by WIL Research Laboratories, Inc. 281 p.

MRID 41494301 Kehoe, D. (1990) 18

- Month Study with Busan 77 in Mice: Lab Project Number: HLA 6176

- 109. Unpublish ed study prepared by Haz leton Labs America, Inc. 924
p.

MRID 41561301 Kehoe, D. (1990) Combined Chronic Toxicity and Carcinogenicity Study with Busan 77 in Rats: Draft Report: Lab Project Number: HLA 6176

- 107. Unpublished study prepared by Hazleton Laborat ories America, Inc. 1511 p.

MRID 41573701 Lawlor, T.; DaCosta, K. (1990) Mutagenicity Test on Busan 77 in the Salmonella/Mammalian

- Microsome Reverse Mutation Assay (Ames Test) with Confirmatory Assay: Lab Project Number: 12144

- 0

- 401R. Unpublished study pre pared by Hazleton Laboratories America, Inc. 33 p.

MRID 41809101 Kehoe, D. (1991) Combined Chronic Toxicity and Carcinogenicity Study with Busan 77 in Rats: Final Report (Supplement to MRID 41561301): Lab Project Number 6176

- 107. Unpublished study pre

- par ed by Hazleton Labs America, Inc. 1511 p.

MRID 41877501 Hoffman, G. (1991) An Acute Inhalation Toxicity Study of Busan 77 in the Rat: Lab Project Number: 90

- 8305. Unpublished study prepared by Bio/dynamics, Inc. 105
p.

MRID 93062009 Drake, K. (1990) Buckma n Labs Inc. Phase 3 Summary of MRID 41373401. Busan 77

- Acute Oral Toxicity Study in Rats: Laboratory ID: 3138/51. Prepared by Springborn Laboratories, Inc. 9 p.

MRID 93062010 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 41327101. Busan 77

- A cute Dermal Toxicity Study in Rabbits: Laboratory ID 3138/50. Prepared by Springborn Laboratories, Inc. 6 p.Docket Number EPA

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Page 45 of 64 MRID 93062011 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 41361701. Busan 77

- Primary Eye Irritation in the Rabbit: Laboratory ID 3 138.52. Prepared by Springborn Laboratories, Inc. 7 p.

MRID 93062012 Drake, K. (1990) Buckman Labs Inc. Phase 3 Sum mary of MRID 41298601. Busan 77

- Primary Dermal Irritation in the Rabbit: Laboratory ID 3138/49. Prepared by Springborn Laboratories, Inc. 6 p.

MRID 93062013 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 40750301. Busan 77

- Dermal Sensitization in the Guinea Pig (Close Patch Technique): Laboratory ID 70303995. Prepared by Hazleton Laboratories America, Inc. 6 p.

MRID 93062014 Drake , K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 40025001. Busan 77

- Thirteen Week Subchronic Toxicity Study in Rats Laboratory ID: HLA 6176

- 106. Prepared by Hazleton Laboratories America, Inc. 12 p.

MRID 93062015 Drake, K. (1990) Buckman Labs Inc. Ph ase 3 Summary of MRID 40170601. Busan 77

- 13 Week Dermal Toxicity Study in Rabbits: Laboratory ID 6176

- 118. Prepared by Hazleton Laboratories America, Inc. 6 p.

MRID 93062016 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 41234501. Busan 77

- On e Year Chronic Toxicity Study in Dogs: Laboratory ID HLA 6176

- 111. Prepared by Hazleton Laboratories America, Inc. 8 p.

MRID 93062017 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 41494301. Busan 77

- 18 Month Study in Mice: Laboratory ID: HLA 6176

- 109. Prepared by Hazleton Laboratories America, Inc. 10 p.

MRID 93062019 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 41248001. Busan 77

- Teratology Study in Rabbits: Laboratory ID: SLS Study No. 3138

- 29. Prepared by Springborn Laborator ies, Inc. 9 p.

MRID 93062020 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 40578201. Busan 77

- Two Generation Reproduction Study in Rats: Laboratory ID HLA 6176

- 104. Prepared by Hazleton Laboratories America, Inc. 9 p.

MRID 93062021 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 00151206. Busan 77

- in Vivo Mouse Micronucleus Assay: Laboratory ID 197

- 182. Prepared by Hazleton Biotechnologies Corporation. 8 p.

MRID 93062022 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 40 978701. Busan 77

- in Vivo/In Vitro Rat Primary Hepatocyte Unscheduled DNA Synthesis Assay: Laboratory ID: 10280

- 0

- 494. Prepared by Hazleton Laboratories America, Inc. 8 p.Docket Number EPA

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Page 46 of 64 MRID 93062024 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 40268601. Busan 77

- Metabolism Study in Rats: Laboratory ID HLA 6176

- 115. Prepared by Hazleton Laboratories America, Inc. 17 p.

MRID 93062025 Drake, K. (1990) Buckman Labs Inc. Phase 3 Summary of MRID 40139201. Busan 77

- Dermal Absorption: Laboratory ID: HLA 6176

- 117. Prepared by Hazleton Laboratories America, Inc. 11 p.

EPA DOCUMENTS

EPA (2007a) Poly(oxyethylene(dimethylminino) ethylene(dimethyliminio) ethylenedichloride) Busan 77

– Revised Report of the Antimicrobials Division’s Toxicology Endpoint Selection Comm ittee (ADTC), 7/10/07, Timothy F. McMahon, Ph.D.

EPA (2007 b ) Poly(oxyethylene (dimethylminino) ethylene(dimethyliminio) ethylenedichloride) Busan 77: Toxicology Disciplinary Chapter for the Reregistration Eligibility Decision Document, PC Code 069183, Case 3034, Antimicrobials Division, 7/26/07, Timothy F. McMahon, Ph.D.

EPA (2007 c ) Poly(oxyethylene(dimethylminino)ethylene(dimethyliminio) ethylenedichloride): Preliminary Risk Assessment for the Reregistration Eligibility Decision, PC Code 069183, Case 3034, Antimicrobials Division, 8/04/07.Docket Number EPA

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Page 47 of 64 

# Appendix B Environmental Fate

Environmental Fate and Transport Properties of Busan 77

Busan 77 is miscible in water (Table 4) and is not expected to degrade by either abiotic processes ( MRID s 41407401 and 41420901) or biotic processes (MRIDs 40334101

, 40165201, 40165202)

. Movement from water or soil into air is also not expected to occur most uses based on the lack of vapor pressure and Henry’s Law values (Table 4), but the air washer use has the potential to create aerial exp osure because the Busan 77 dissolved in water can volatilize with the water. Bioconcentration in aquatic organisms is also not expected based on the water miscibility and low log P values (Table 4). Sorption to soil, sediment, and sludge is expected to be the primary route of dissipation based on the fact that is a quaternary ammonium compound that has a positive electrical charge. However, data for sorption to soil and sludge have not been submitted and are anticipated to be required. Busan 77 has the pote ntial to reach WWTPs from the registered uses, and data on activated sludge sorption isotherm (ASSI) and activated sludge respiration inhibition (ASRI)

. WWTP biodegradability studies (835.3110, 835.3220, 835.3240, and 835.3280) are normally required for ch emicals that, based on the registered uses, have the potential to reach wastewater treatment plants. However, in the case of Busan 77, there is no apparent route of chemical or microbial degradation, and therefore degradation data in a WWTP

are not anticip ated to be required

.

Water and Sediment

Hydrolysis and Aqu eous Photoly s is

Busan 77 is stable to abiotic hydrolysis and to photodegradation in water at pH 5, 7, and 9 at 25

o C (MRID 41407401 for hydrolysis and MRID 41420901 for photodegradation in water )

.
Octanol

- Water Partition Coefficient and Bioconcentration in Fish

Busan 77 is miscible in water (Table 4), and as a result, is not expected to bioconcentrate in fish and other aquatic organisms.

Aerobic Aquatic Metabolism

Busan 77 was essentially s table u nder aerobic aquatic conditions. Sediment percentages of applied material increased from 30.5 % at time zero to 93.5

- 106.6 % by 7

- 31 days after treatment, and water levels decreased from 66.1 % at time zero to 1.2

- 5.2 % by 7

- 31 days (MRID 40334101 )

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Page 48 of 64 A n a e robic Aquatic Metabolism

Busan 77 was essentially stable under anaerobic aquatic conditions. Sediment percentages of applied material were approximately 100 % of the total, and water never contained more than 2.2 % of applied (MRID 40165201)

.
Soil

Soil Le aching/Adsorption/Desorption Batch Equilibrium

Batch equilibrium studies on Busan 77 have not been submitted and are anticipated to be required.

Aerobic Soil Metabolism

Based on a cursory review, Busan 77 was stable in aerobic soil at 23

- 25 o C (MRID 401652 02). This study will be evaluated in Registration Review.

A n a erobic Soil Metabolism

Data on anaerobic soil metabolism were not submitted, but they are not anticipated to be required because acceptable data were submitted for anaerobic aquatic metabolism.

Fate and Transport in WWTP
Activated Sludge Sorption Isotherm

Data on activated sludge sorption isotherm (ASSI) sorption to activated sludge are anticipated to be required because the registered uses of Busan 77 can create exposure to w astewater treatment plants (WWTPs)

. While the 158W regulations do not require ASSI data for those compounds with log P (log Kow) values of < 3, Busan 77 is a quaternary ammonium compound that is expected to sorb to sludge because of its positive electrical charge

.
Activated Sludge Respiration Inhibition
Data on activated sludge respiration inhibition (ASRI) are anticipated to be required because the registered uses of Busan 77 can create exposure to WWTPs.
Activated Sludge Biodegradation
Busan 77 has the potential to reach W WTPs from the registered uses, and data on activated sludge sorption isotherm (ASSI) and activated sludge respiration inhibition (ASRI) are anticipated to be required

. WWTP biodegradability studies (835.3110, 835.3220, 835.3240, and 835.3280) are normally required for chemicals that, based on the registered uses, have the potential to reach wastewater treatment plants. However, in the case of Busan 77, there is no apparent route of chemical or microbial degradation, and therefore degradation data in a WWTP

are not anticipated to be required

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Page 49 of 64 Environmental Fate References

MRID 40165201 Obrist, J. (1987) Anaerobic Aquatic Metabolism of Busan 77: Final Report: Laboratory Project Identification: HLA 6015

- 250. Unpublished study prepared by Hazleton Laboratories America, Inc. 50 p.

MRID 40165202 Das, Y. (1987) Aerobic Soil Metabolism of WSCP: Biospheric No. 84E

- 301A. Unpublished study prepared by Biospheric Inc. 50 p.

MRID 40334101 Obrist, J. (1987) Aerobic Aquatic Metabolism of Busan 77: Laboratory Project ID: HLA 6015

- 251: Final Report. Unpublished study prepared by Hazleton Laboratories America, Inc. 69 p.

MRID 41407401 Smith, A. (1990) Determination of Aqueous Hydrolysis Rate Constant and Half

- life of Busan 77: Final Report: Lab Project Number: 995

- 1089

- 6116

- 715: Lab Report Number 90

- 2

- 3216. Unpublished study prepared by Springborn Laboratories, Inc. 32 p.

MRID 41420901 Smith, A. (1990) Determination of Aqueous Photolysis Rate Constant and Half

- life of Busan 77: Lab Project Number: 995

- 1089

- 6117

- 720; 90

- 3

- 32 51. Unpublished study prepared by Springborn Laboratories, Inc. 37 p.E PA

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Page 50 of 64 

# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Receptors

Birds

In order to establish the toxicity of Busan 77 to avian species, the Agency requires an acute oral toxicity study using the technical grade active ingredient (TGAI). The preferred

- test species is either mallard duck (a waterfowl) or bobwhite quail (an upland game bird). The results of two acute oral toxicity studies, submitted for Busan 77, are provided in the following ta ble (Table C 1).

Table C1

– Acute Oral Toxicity of Busan 77 to Birds

Species Chemical,

% Active Ingredient

(a.i.)
Tested Endpoint

(mg/kg a.i.) Toxicity Category Satisfies Guidelines/

Comments Reference

(MRID No. unless specified )

Mallard duck

( An as platyrhynchos ) Busan 77 61.7% LD 50 = 497
NOAEL = 51 Moderately toxic Yes (core)

- 14

- day test duration

- 36 weeks of age 41654801

Bobwhite quail

( Colinus virginianus ) Busan 77 % purity unknown LD 50 = 690
NOAEL = <172 ( Based on the assumption of 60% a .i.) Slightly toxic No (supplemental)

- 21

- day test duration

- young adult

- study conducted before adoption of GLP principles ID 0522

- 010

- 20

These two acceptable acute oral toxicity studies indicate that Busan 77 is moderately toxic to slightly toxic to birds on an acute oral basis.

Birds, Subacute

A subacute dietary study using the TGAI may be required on a case

- by

- case basis depending on the results of lower

- tier ecological studies and pertinent environmental fate characteristics in order to establish the toxicity of a chemical to avian species. This testing was required for Busan 77. The preferred

- test species is either the mallard duck or bobwhite quail. The results of twoE PA

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Page 51 of 64 subacute dietary toxicity studies, submitted for Busan 77, are provided in the following table (Table C 2).

Table C2

– Subacute Oral Toxicity of Busan 77 to Birds

Species Chemical,

% Active Ingredient

(a.i.)
Tested Endpoint

(ppm a.i.) Toxicity Category Satisfies Guidelines/

Comments Reference

(MRID

No.)

Mallard duck ( Anas platyrhynchos ) Busan 77 60.3% LC 50 (diet) = >12,000 NOAEC = 3,000 Relatively nontoxic No (supplemental)

- 8

- day test duration

- 10 days of age

- study conducted

before adoption of GLP principles 41411501

Bobwhite quail ( Colinus virginianus) Busan 77 61.6 % LC 50 (diet) = >3,462 NOAEC = 3,462 Slightly toxic Yes (core)

- 8

- day test duration

- 11 days of age 00159307

The results of these two acceptable studies indicate that Busan 77 is slightly toxic to relatively nontoxic to avian species through subacute dietary exposure.

Mammals

Acute and Chronic Toxicity

Wild mammal testing is not required by the Agency. In most cases, rat toxicity values obtained from studies conducted to support data requirements for human health risk assessments substitute for wild mammal testing.

Terrestrial Plants

One study that evaluates the toxicity of Busan 77 to several species of terrestrial plants (seedling
emergence

- tier I and vegetative vigor

- tier I and tier II) and five studies that evaluate the toxicity of Busan 77 to fr eshwater aquatic plants have been submitted. Results of the terrestrial plant study are presented in Tables C3

- C5 and results of the aquatic plant studies are presented in Table C 10.E PA

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Page 52 of 64 Table C3

– Seedling Emergence (Tier I) Toxicity of Busan 77 to Terrestri al Plants*

Species Chemical,

% Active Ingredient

(a.i.)
Tested Endpoint

(ppm a.i.)* Satisfies Guidelines/

Comments Reference

(MRID No.)

Monocot Oat ( Avena sativa ) Busan 77 60.3% EC 25 = >73
NOAEC = 73 Yes (core)

- 14

- day test duration

- most sensi tive

parameter: shoot length (14% reduction) 42038101

Dicot

Lettuce ( Lactuca sativa ) Busan 77
60.3% EC 25 = >73
NOAEC = 73 Yes (core)

- 14

- day test duration

- most sensitive parameter: shoot length (17% reduction) 42038101

* Data are listed for most sens itive species and most sensitive parameter. Species tested were cabbage, carrot, cucumber, lettuce, soybean, tomato, corn, oats, onion and ryegrass.

Table C4

– Vegetative Vigor (Tier I) Toxicity of Busan 77 to Terrestrial Plants

Species Chemical,

% Act ive Ingredient

(a.i.)
Tested Endpoint**

(ppm a.i.) Satisfies Guidelines/

Comments Reference

(MRID No.)

Monocot Corn ( Zea mays ) Busan 77 60.3% EC 25 = >74
NOAEC = 74 Yes (core)

- 14

- day test duration

- most sensitive parameter: shoot weight (39% reducti on) 42038101

Dicot

Cucumber ( Cucumis sativus ) Busan 77 60.3% EC 25 = >74
NOAEC = 74 Yes (core)

- 14

- day test duration

- most sensitive parameter: root weight (31% reduction) 42038101

* Data are listed for most sensitive species and most sensitive paramet er. Species tested were cabbage, carrot, cucumber, lettuce, soybean, tomato, corn, oats, onion and ryegrass. **EC 25 value for corn based on shoot length and root weight. EC 25 for cucumber based on shoot length and shoot weight.E PA

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Page 53 of 64 Table C5

– Vegetative Vigor (Tier II) To Toxicity of Busan 77 to Terrestrial Plants *

Species Chemical,

% Active Ingredient

(a.i.)
Tested Endpoint*

(ppm a.i.) Satisfies Guidelines/

Comments Reference

(MRID No.)

Monocot Ryegrass ( Lolium
perenne ) Busan 77 60.3% EC 25 = >74
NOAE C = 74 No (supplemental)

- 14

- day test duration

- most sensitive

parameter: root weight (0% reduction) 42038101

Dicot

Tomato ( Lycopersicon esculentum ) Busan 77
60.3% EC 25 = >74
NOAEC = 74 No (supplemental)

- 14

- day test duration

- most sensitive paramet er: shoot weight (15% reduction) 42038101

* Data are listed for most sensitive species and most sensitive parameter.



## Toxicity to Aquatic Receptors

Freshwater Fish

In order to establish the acute toxicity of Busan 77 to freshwater fish, the Agency requires freshwater fish toxicity studies using the TGAI. The preferred test species are rainbow trout (a cold water fish) and bluegill sunfish (a warm water fish). The results of 3 freshwater fish acute studies submitted for Busan are presented in Table C6

.

Table C6

– Acute Toxicity of Busan 77 to Freshwater Fish

Species Chemical,

% Active Ingredient

(a.i.)
Tested Endpoint

(mg a.i./L) Toxicity Category Satisfies Guidelines/

Comments Reference

(MRID

No.)

Rainbow Trout ( Oncorhynchus mykiss) Busan 77
61. 9% LC 50 = 0.047
NOAEC = 0.037 Very highly toxic Yes (core)

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Page 54 of 64 Species Chemical,

% Active Ingredient

(a.i.)
Tested Endpoint

(mg a.i./L) Toxicity Category Satisfies Guidelines/

Comments Reference

(MRID

No.)

Bluegill sunfish ( Lepomis macrochirus ) Busan 77 61.9% LC50 = 0.21
NOAEC = 0.13 Highly toxic Yes (core)

- 96

- hr test duration

- static test sys tem 41352002

Rainbow Trout ( Oncorhynchus mykiss) Busan 77
60% LC 50 = 0.26
NOAEC = 0.11 Highly toxic No (supplemental)

- 96

- hr test duration

- static test system

- study lacks

important information

- study conducted

before adoption of GLP principles 00107 207

Freshwater acute toxicity tests indicate that Busan 77 is very highly toxic to highly toxic to fish on an acute basis.

Freshwater Invertebrates

The Agency requires a freshwater aquatic invertebrate study using the TGAI to establish the acute toxicit y to freshwater invertebrates. The preferred test species is Daphnia magna

. The results of two studies submitted for Busan 77 are provided in the following table (Table C7 ).

Table C7

– Acute Toxicity of Busan 77 to Freshwater Invertebrates

Species Chemi cal,

% Active Ingredient

(a.i.)
Tested Endpoint

(mg a.i./L) Toxicity Category Satisfies Guidelines/

Comments Reference

(MRID

No.)

Waterflea ( Daphnia
magna ) Busan 77
61.9% EC 50 = 0.280
NOAEC = 0.130 Highly toxic Yes (core)

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Page 55 of 64 Species Chemi cal,

% Active Ingredient

(a.i.)
Tested Endpoint

(mg a.i./L) Toxicity Category Satisfies Guidelines/

Comments Reference

(MRID

No.)

Chironomus riparius Busan 77 99.8% LC 50 = 3.56 in overlying
water LC 50 = >966 in sediment Moderate l y toxic in
water Practically nontoxic in sediment Yes (supplemental)

- 28

- day test duration

- insufficient number of replications 48 715801

The results of the waterflea study indicates that Busan 77 is highly toxic to freshwater invertebrates on an acute basis. The sediment study indicated that Busan 77 is moderately toxic to freshwater invertebrates in the overlying water and practic ally nontoxic in the sediment.

Estuarine/Marine Fish and Invertebrates

Acute toxicity testing with estuarine and marine organisms using the TGAI is required when the end

- use product is intended for direct application to the marine/estuarine environment or effluent containing the active ingredient is expected to reach this environment. The preferred fish test species is the sheepshead minnow. The preferred invertebrate test species are mysid shrimp and eastern oysters. This testing is required for Busan 77 based on the chemical’s potential to reach estuarine and marine environments. The results of three toxicity studies submitted for Busan 77 are presented in Table C8

.
Table C8

– Acute Toxicity of Busan 77 to Estuarine and Marine Organisms

Species Chemic al,

% Active Ingredient

(a.i.)
Tested Endpoint

(mg a.i./L) Toxicity Category Satisfies Guidelines/

Comments Reference

(MRID

No.)

Sheepshead minnow ( Cyprinodon variegates ) Busan 77

60.0% LC 50 > 360
NOAEC = 360 Relatively nontoxic Yes (core)

- 96

- hr test duration

- static test system 40139202E PA

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Page 56 of 64 Species Chemic al,

% Active Ingredient

(a.i.)
Tested Endpoint

(mg a.i./L) Toxicity Category Satisfies Guidelines/

Comments Reference

(MRID

No.)

Mysid shrimp ( Mysidopsis bahia ) Busan 77

60.0% LC 50 = 7.8
NOAEC <7.8 Moderately toxic Yes (core)

- 96

- hr test duration

- static test system 40139203

Quahog clam ( Mercenaria mercenaria ) Busan 77

60.0% EC 50 = 0.21
NOAEC = 0.14 Highly toxic Yes (core)

- 48

- hr test duration

- static test system

- embryo/larval stage 40334201

The results of these three acceptable studies indicate that Busan 77 is highly toxic to moderately toxic to estuarine/marine invertebrate s on an acute basis and relatively nontoxic to estuarine/marine fish on an acute basis.

Chronic Toxicity

Chronic toxicity testing (fish early life stage and aquatic invertebrate life cycle) is required for pesticides when certain conditions of use and env ironmental fate apply. The preferred freshwater fish test species is the fathead minnow. The preferred freshwater invertebrate is Daphnia magna

. This testing is required for the Busan 77 once

- through cooling water uses. The results of two toxicity studies submitted for Busan 77 are presented in Table C9

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Page 57 of 64 Table C9

– Chronic Toxicity of Busan 77 to Freshwater Organisms

Species Chemical,

% Active Ingredient

(a.i.)
Tested Endpoint

(mg a.i./L) Satisfies Guidelines/

Comments Reference

(MRID No.)

Waterfle a ( Daphnia magna ) Busan 77
60.3% LOEC = 0.020
NOAEC = 0.012 No (supplemental)

- 21

- day test duration

- static renewal test system

- organisms not distributed or fed properly

- excess mortality 42479601

Fathead minnow ( Pimephales promelas ) Busan 77 (59. 8% ai) LOAEC 33 ug ai/L NOAEC 19 ug ai/L Yes (Acceptable)

- flow

- through 49453501

The fathead minnow study indicates that Busan 77 is very highly toxic to fathead minnow. The study on the waterflea does not fulfill the guideline requirement for a chro nic aquatic invertebrate study.

Aquatic Plants

Non

- target plant phytotoxicity testing is required for pesticides when certain conditions of use and environmental fate apply. This testing is required for the once

- through cooling water uses of Busan 77. Tes ting has been conducted with Busan 77 on several aquatic plant species. Testing is normally conducted with one species of aquatic vascular plant ( Lemna gibba ) and four species of algae: (1) freshwater green alga, Selenastrum capricornutum, (2) marine diato m, Skeletonema costatum, (3) freshwater diatom, Navicula pelliculosa, and (4) bluegreen cyanobacteria, Anabaena flos

- aquae. The rooted aquatic macrophyte rice ( Oryza sativa ) is also tested in seedling emergence and vegetative vigor tests.E PA

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Page 58 of 64 Table C10

– Toxic ity of Busan 77 to Aquatic Plants

Species Chemical,

% Active Ingredient

(a.i.)
Tested Endpoint

(mg a.i./L) Satisfies Guidelines/

Comments Reference

(MRID No.)

Marine diatom ( Skeletonema
costatum ) Busan 77
60.3% EC 50 = 0.090
NOEC < 0.024 No (supple mental)

- 120

- hour test duration

- static test system 42013302

Freshwater diatom ( Navicula pelliculosa ) Busan 77 60.3% EC 50 = 0.083
NOEC = 0.044 Yes (core)

- 96

- hour test duration

- static test system 42013303

Bluegreen cyanobacteria ( Anabaena flos

aquae ) Busan 77 60.3% EC 50 = 0.11
NOEC = 0.05 Yes (core)

- 120

- hour test duration

- static test system 42013304

Green alga e ( Selenastrum capricornutum ) Busan 77 60.3% EC 50 = 0.0088
NOEC < 0.001 No (supplemental)

- 120

- hour test duration

- static test system 42 013305

Duckweed ( Lemna gibba ) Busan 77
60.3% EC 50 > 0.65
NOEC = 0.043 No (supplemental)

- 14

- day test duration

- static renewal test system

- maximum concentration tested produced only 30% growth inhibition 42013301

Green alga ( Pseudokirchner iella subcapi tata ) Busan 77 59.8% EC 50 = 3.0 ug/L Yes (supplemental)

- 96

- hour test duration

- test material sorbing to test vessel glass 49453501E PA

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Page 59 of 64 Ecotoxicity R eferences

MRID 00107207 Knott, W.B. 1970. Busan 77 (WSCP)

- Evaluation of Acute LC 50 for Rainbow Trout. St udy performed by Woodward Research Corporation for Buckman Laboratories, Inc., Memphis, TN.

MRID 00159307 Beaver, J.B. 1985. Busan 77

- A Dietary LC 50 Study with the Bobwhite. Project No. 210

- 104. Study performed by Wildlife International, Ltd. for Buckman Laboratories, Inc., Memphis, TN.

MRID 052201020 WARF Institute, Inc. 1971. Report on Acute Oral LD 50 in Bobwhite Quail. Prepared for Buckman Laboratories, Inc., Memphis, TN.

MRID 40139202 Surprenant, D.C. 1987a. Acute Toxicity of Busan 77 to Sheepshead Mi nnow ( Cyprinodon variegates ). Report No. BW

- 87

- 2

- 2294. Study performed by Springborn Bionomics, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 40139203 Surprenant, D.C. 1987b. Acute Toxicity of Busan 77 to Mysid Shrimp ( Mysidopsis bahia ). Report No . BW

- 87

- 3

- 2346. Study performed by Springborn Bionomics, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 40334201 Surprenant, D.C. 1987c. Acute Toxicity of Busan 77 to Embryos

- Larvae of the Quahog Clam ( Mercenaria mercenaria ). Report No. BW

- 87

- 8

- 245 9. Study performed by Springborn Bionomics, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 41352001 LeLievre, M.K. et al. 1990c. (Busan 77)

- Acute Toxicity to Rainbow Trout ( Oncorhynchus mykiss ) Under Static Conditions. Report No. 89

- 12

- 3182. Stud y performed by Springborn Laboratories, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 41352002 LeLievre, M.K. et al. 1990a. "(Busan 77)

- Acute Toxicity to Bluegill ( Lepomis macrochirus ) Under Static Conditions. Report No. 89

- 12

- 3176. Study perfor med by Springborn Laboratories, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 41352003 LeLievre, M.K. et al. 1990b. (Busan 77)

- Acute Toxicity to Daphnids ( Daphnia magna ) Under Static Conditions. Report No. 89

- 11

- 3181. Study performed by Springbo rn Laboratories, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 41411501 Bodden, R.M. 1974. Busan 77

- Acute Avian Dietary Toxicity Study in Mallard Ducks. Report No. 4043621. Study performed by the WARF Institute, Inc. for Buckman Laboratories, In c., Memphis, TN.

MRID 41654801 Campbell, S. et al

. 1990. Busan 77: An Acute Oral Toxicity Study with the Mallard. Project No. 210

- 114A. Study performed by Wildlife International, Ltd. for Buckman Laboratories, Inc., Memphis, TN.

MRID 42013301 Hoberg, J.R. 1991b. Busan 77

- Toxicity to the Duckweed Lemna gibba G3. Report No. 91

- 5

- 3749. Study performed by Springborn Laboratories, Inc. for Buckman Laboratories, Inc., Memphis, TN.E PA

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Page 60 of 64 MRID 42013302 Hoberg, J.R. 1991c. Busan 77

- Toxicity to the Marine Diatom Skele tonema costatum. Report No. 91

- 9

- 3864. Study performed by Springborn Laboratories, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 42013303 Hoberg, J.R. 1991d. Busan 77

- Toxicity to the Freshwater Diatom Navicula pelliculosa. Report No. 91

- 4

- 3728. Study performed by Springborn Laboratories, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 42013304 Hoberg, J.R. et al. 1991e. Busan 77

- Toxicity to the Freshwater Bluegreen Algae Anabaena flos

- aquae. Report No. 91

- 4

- 3726. Study performed by Sprin gborn Laboratories, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 42013305 Hoberg, J.R. 1991f. Busan 77

- Toxicity to the Freshwater Green Algae Selenastrum capricornutum. Report No. 91

- 4

- 3732. Study performed by Springborn Laboratories, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 42038101 Hoberg, J.R. 1991a. Busan 77

- Determination of Effects on Seed Germination, Seedling Emergence, and Vegetative Vigor of Ten Plant Species. Report No. 91

- 3

- 3695. Study performed by Springborn Laborator ies, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 42479601 Putt, A.E. et al. 1992. Busan 77

– Chronic Toxicity to Daphnids ( Daphnia
magna ) Under Static Renewal Conditions. Report No. 92

- 7

- 4343. Study performed by Springborn Laboratories, Inc. for Buckman Laboratories, Inc., Memphis, TN.

MRID 48715801 Kranzfelder, J.A., L. Stuerman, and D. Malorin. 1998. Sediment bioassay procedure for determining the toxicity of WSCP to Chironomus sp. Report No. 44908. Study performed by ABC Laboratories for Buckm an Laboratories International, Memphis, TN.

MRID 49362401 Schwader, A.L. 2014. WSCP; Early life

- stage toxicity test with fathead minnow ( Pimephales promelas ), following OECD guideline #210 and OSCPP guideline 850.1400. Smithers Viscient, Wareham, MA. Stud y No. 995.6187. Submitted by Buckman Laboratories, Inc., Memphis, TN.

MRID 49453501 Softcheck, K.A. 2014. [ 14 C]WSCP

– 96

- hour toxicity test with the freshwater green algae, Pseudokirchneriella subcapitata , following OCSPP guideline 850.4500. Smithers Visc ient, S t udy No. 995.6190. Sponsored by Buckman Laboratories, Inc., Memphis, TN.E PA

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# Appendix D Screening Level Down

- the

Drain Analysis

The Down

- the

- Drain (DtD) module was not run for Busan 77.

Generally, the Agency uses the DtD module of E

- FAST (Exposure and Fate Assess ment Screening Tool), [version 2] to screen for the potential for aquatic organisms downstream of domestic wastewater treatment plants to be exposed to antimicrobial pesticides.

The Down

- the

- Drain module uses daily per capita release of household wastewat ers, stream dilution factors, and wastewater treatment plant removal efficiency to provide both high

- end and median (average) time

- averaged surface water concentrations of chemicals discharged by domestic wastewater treatment plants. The high

- end scenario uses surface water concentrations downstream of domestic wastewater treatment plants based on the 10 th percentile stream dilution factor (SDF); the average scenario uses surface water concentrations based on the 50 th percentile SDF. SDF is defined as the r atio of the stream flow downstream of a wastewater treatment plant to the wastewater treatment plant flow.

Inputs used to run the DtD module include concentrations of concern (COCs) for aquatic organisms, percent removal during wastewater treatment, and h ypothetical wastewater treatment plant influent volumes. The results of the DtD module are expressed as number of days of exceedance of COCs for aquatic organisms. COCs are grouped into 3 categories: acute, endangered/listed, and chronic. Acute COCs for fr eshwater fish and invertebrates are derived by dividing LC 50 values for freshwater organisms by 2. Endangered/listed COCs for freshwater fish and invertebrates are derived by dividing LC 50 values by 20. EC 50 values for plants are used to establish acute CO Cs for plants. NOAEC values for plants are used to establish endangered/listed COCs for plants. Chronic COCs for freshwater fish and invertebrates are based on NOAEC values. For acute and endangered listed COCs, there may be potential concern for freshwate r organisms if the COC is exceeded for 1 day or more. For chronic COCs, there may be potential concern for freshwater organisms if the COC is exceeded 20 days or more.

The Down

- the

- Drain module are run using both a high

- end scenario and an average scenario to determine whether the model predicted exceedences of concentrations of concern.E PA

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# Appendix E Product Chemistry

Table E1 presents the active ingredient to be assessed in case 3034 : Busan 77 (PC Code 069183)

.
Table E1

– Chemical Identification of Busan 77

Chem ical Name Busan 77 Chemical Classification Polymeric quaternary ammonium

Chemical Name Poly[oxy

- 1,2

- ethanediyl(dimethyliminio)

- 1,2

- ethanediyl(dimethyliminio)

- 1,2

- ethanediylchloride (1:2)]

PC Code 069183

CAS Number 31512

- 74

- 0

Molecular Formula C 10 H 25 N 2 O (monomer without chlorines ) Molecular Weight (grams/mole) 189.32 (monomer) 10 3,368 (polymer) 11

Molecular Structure

Smiles Code CCOCCN(C)(C)CCN(C)(C) (includes 2 chlorines as counter ions)

The Busan 77 product chemistry information relevant to ri sk assessment is summarized in Table E2

.
Table E2

– Physical

- Chemical and Environmental Fate Properties for Busan 77

Guideline No./

Study Type Results Reference/Comments (MRID unless specified)

Water Solubility(mg/L) 10,000 Assumed based on miscibility

8 30.7050 UV visible sorption N/A 49176301 Compound has no double bonds to absorb UV light 830.7370 Dissociation constant Waived 47120304/42372401

830.7550 Partition coefficient Waived 47120304

830.7950 Vapor pressure N egligible 47 12 0304 Manufacturing Use Product is 60 % polymer and 40 %
water Henry’s Law Constant 8.5 x 10

- 12 Volatility from water not likely to occur given the high MW, solubility, and positive charges that will enhance sorption to solids.

10 EPIWEB 4.11 11 Average, 7/10/91 Buckman letterE PA

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Page 63 of 64 Product Chemistry References

MRID 42372401 Bowles, D. (1991) Product Chemistry for WSCP: Lab Projec t Number: NA 909218/1. Unpublished study prepared by Twin City Testing Corp. and NATEC Institut fur Naturwissenschaftl ich

- technische Dienste GmbH. 88 p.

MRID 46915602 Wo, C. (2006) Physical and Chemical Characteristics (830 Series, Group B): Algae Clean Ou t W. Unpublished study prepared by Product Safety Laboratories. 6 p.

MRID 47120304 Tillman, A. (2007) Waiver Request for Certain Data Requirements for WSCP MUP. Project Number: KT/200704. Unpublished study prepar ed by Kerley Trading, Inc. 7 p.

MRID 491763 01 Dotse, A.; Grabowicz, J. (2013) Product Chemistry for WSKT: Active Ingredient and Physical/ Chemical Properties: Final Report. Unpublished study prepared by Buckman Laboratories, Inc. 27p.E PA

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# Appendix F Comments Received Concerning the Preliminary Work Plan

On Sep tember 25, 2015 EPA opened a 60

- day public comment period on the preliminary work plan (PWP) for the registration review of Busan 77 . The comment period ended on December 01, 2015 . The comments received did not result in a modification to the anticipated d ata needs detailed in the Busan 77 PWP.

The Agency received submission s from the Physicians Committee for Responsible Medicine and Kathleen A. Rose during the public comment period on the initial docket.

Comment: T he Physicians Committee for Responsible Me dicine recommends that registrant(s) apply for waiver for immunotoxicity data using the Agency’s retrospective analysis document located at http ://www2.ep a.gov/pesticide

- registration/retrospective

- analysis

- immunotoxicity

study

. Agency Response: The Agency thanks the submitter for the information and the web link. The Agency reviews all pertinent information when considering waiver requests.

Comment: Ms. Ro se is concerned that the use of neonics ( n eonicotinoid s) pose potential risk to bees and other pollinators and recommends that the Agency ban neonics.
Agency Response: The Agency thanks the submitter for their comments

. Busan 77 is a
p olymeric quaternary ammonium chemical and not associated with neonicotinoids. The Agency provides pollinator reference information at http://www.epa.gov/pollinator

- protection

.