Page 2 of 60Page 3 of 60 Bioban P

- 1487 Registration Review Team

Human Health & Environmental Effects Nate Mottl Jenny Tao Jim Breithaupt Pat Jennings Bill Erickson Katelynn King Sumitra Biswas

Risk Management SanYvette Williams Karen Leavy Rose Kyprianou

Office of General Counsel Philip RossPage 4 of 60 TERMS, ABBREVIATIONS AND SYMBOLS

AD Antimicrobials Division A.I. or a.i. active ingredient aPAD a cute p opulation a djusted d ose ASRI a ctivated sludge r espiration i nhibition atm

- m 3 /mole a tmospheric pressure

- cubic meter per mole BCF b ioconcentration f actor °C d egrees Celsius CAS Chemical Abstracts Service CFR Code of Federal Regulations CHO Chinese h amster o vary CMA Chemical Manufacturers Association CO 2 c arbon dioxide COC c oncentration

- of

- c oncern cPAD c hronic p opulation a djusted d ose DCI data call

- in EC 50 m edian (or 50 percent) e ffect c oncentration EC 05 5 p ercent e ffect c oncentration ECOTOX ECOTOXicology EDI e stimated daily i ntake EDSP E ndocrine Disruptor Screening Program E

- FAST Exposure and Fate Assessment Screening Tool EPI Suite Estimation Program Interface Suite EPA Environmental Protection Agency FDA Food and Drug Administration FFDCA Feder al Food, Drug, and Cosmetic Act FGD f lue

- g as d esulfurization FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FWP Final Work Plan g/mol g rams per mole GLN guideline number HPV h igh production v olume IDS Incident Data System Koc o rganic carbon normalized soil

- water partition coefficient Kd s oil

- water partition coefficient Kow o ctanol

- water partition coefficient LC 50 m edian (or 50 percent) l ethal c oncentration LD 50 m edian (or 50 percent) l ethal d ose LOAEC l owest

- o bserved

- a dverse

- e ffect

- c oncentration LOEC l owest

- o bserved

- e ffect

- c oncentration LOAEL lowest

- observed

- adverse

- e ffect

- l evel Log K ow l ogarithm of the octanol

- water partition coefficient μg m icrogram ml/g m illiliter p er g ram mg/kg m illigram p er k ilogram mg/kg/day m illigram p er k ilogram p er d ay mg/L m illigram p er l iter mm Hg m illimeter of mercury MOE m argin of e xposurePage 5 of 60 MRID Master Record Identification Number MRL m aximum r esidue l imit N/A n ot a pplicable

nm n anometers NOAEC no

- observed

- adverse

- effect

- c oncentration NOAEL n o

- o bserved

- a dverse

- e ffect

- l evel OCSPP Office of Chemical Safety and Pollution Preventio n OECD Organization for Economic Co

- operation and Development OPP Office of Pesticide Programs PAD p opulation a djusted d ose PAI p ure active i ngredient PDM Probabilistic Dilution Model % p ercent PC Code Pesticide Chemical Code PCF p ounds p er c ubic foot pH power of h ydrogen or power of the con centration of the hydrogen ion PHED Pesticide Handler’s Exposure Data PIS primary i rritation s core pKa p ower of the acid dissociation constant or negative base

- 10 logarithm of the acid dissociation constant of a solution ppb p arts p er b illion ppm p arts p er m illion PWP Preliminary Work Plan QSAR q uantitative s tructure

- a ctivity r elationship RED Rere gistration Eligibility Decision SAR s tructure a ctivity r elationship SF s afety f actor SSTS Section Seven Tracking System TEP t ypical e nd

- u se p roduct TGAI t echnical grade active i ngredient TMDL total maximum daily l oads UF uncertainty factor UV/VIS ultraviolet/v isible light a bsorption % w / w p ercent weight per weight. WP w ettable powder WWTPs w astewater treatment plantsPage 6 of 60 

### Table of Contents 1 Introduction

................................ ................................ ................................ ............................. 8 1.1 Statutory and Regulatory Authority

................................ ................................ ................. 8 1.2 Updates to the Work plan

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

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

................................ ................................ .......... 10 1.5 Use/Usage Description

................................ ................................ ................................ ... 12 1.5.1 Registrations

................................ ................................ ................................ ........... 12 1.5.2 Summary of Registered Uses

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

................................ ................................ ................................ .. 13 1.6 Regulatory History

................................ ................................ ................................ ......... 13 1.6.1 Tolerance Information

................................ ................................ ............................ 13 1.7 Incidents

................................ ................................ ................................ ......................... 13 1.7.1 Human Health

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

................................ ................................ ................................ ............... 14 2 Anticipate d Data Needs

................................ ................................ ................................ ........ 14 3 Human Health Risk Assessment

................................ ................................ ........................... 17 3.1 Existing Toxicological Endpoints

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

................................ ................................ ................................ ............ 19 3.2.1 Food

................................ ................................ ................................ ........................ 19 3.2.2 Drinking Water

................................ ................................ ................................ ....... 19 3.3 Occupational and Residential Exposures

................................ ................................ ....... 19 3.3.1 Occupational Handler Exposure

................................ ................................ ............. 19 3.3.2 Occupational Post

- application Exposures

................................ ............................... 20 3.3.3 Residential Handler Exposures

................................ ................................ ............... 20 3.3.4 Residential Post

- Application Exposures

................................ ................................ . 20 3.4 Aggregate and Cumulative Exposure

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

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

................................ ................................ ............................ 21 4 Environmental Risk Assessment

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

................................ ................................ .................... 21 4.1.1 Fate and Effects during Wastewater Treatment

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

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

................................ ................................ ....................... 23 4.3.1 Mechanism of Action

................................ ................................ .............................. 23 4.3.2 Measure of Effects (Ecotoxicology Endpoints)

................................ ...................... 23 4.3.3 Open Literature

................................ ................................ ................................ ....... 24 4.4 Ex posure Analysis Plan

................................ ................................ ................................ .. 24 4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates

................................ ............ 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

................................ ................................ ............................. 47Page 7 of 60 Appendix C Ecotoxicology Profile

................................ ................................ .......................... 51 Appendix D Screening Level Down

- the

- Drain Analysis

................................ ........................ 56 Appendix E Product Chemistry

................................ ................................ ............................... 57 Appendix F Comments Received Concerning the Preliminary Work Plan

............................ 60

List of Tables Table 1

– Summary of Anticipated Risk Assessments and Data Needs for Registration Review: Bioban P

- 1487

................................ ................................ ................................ ................................ 9 Table 2

– Anticipated Registration Review Schedule

................................ ................................ .. 10 Table 3

– Chemical Identification of Bioban P

- 1487 Mixture

................................ ..................... 11 Table 4

– Physical

- Chemical and Environmental Fate Properties for Bioban P

- 1487

................. 11 Table 5

– Physical/Chemical Properties of Bioban P

- 1487 Degradates Based on Estimated Values from EPI

- Suite 4.11

................................ ................................ ................................ .......... 12 Table 6

– Summary of Bioban P

- 1487 Registered Uses

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

– Studies Anticipated as Needed for the Registration Review of Bioban P

- 1487

........... 15 Table 8

– Data Required by the February 23 and April 7, 2010 Data Call

- Ins for the Bioban P

1487 RED

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

– Existing Toxicological Endpoints for Bioban P

- 1487

................................ .................. 17 Table 10

– Available Ecological Effects Endpoints

................................ ................................ ..... 23Page 8 of 60 

## 1 Introduction

This document is the United States Environmental Protection Agency ’s ( USEPA, EPA or “ the agency ”) Final Work Plan ( F WP ) for Bioban P

- 1487 . The FWP document explains what EPA's Office of Pesticide Programs (OPP) knows about B ioban P

- 1487 , highlighting anticipated data and assessment needs, identifying the types of information that would be especially useful to the agency in conducting the re view, and providing an anticipated timeline for completing B ioban P

1487 ’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 i nformation in the docket, to inform the public of what it knows about B ioban P

- 1487 and what types of new data or other information would be helpful for the agency to receive as it moves toward a decision

. 

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

- reevaluation

. The agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standa rd 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 eac h 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 plan Since the publicati on of the Bioban P

- 1487 Preliminary Work Plan (PWP), the agency has made the following updates:

• Updated the timeline in Table 2, the “Anticipated Registration Review Table.”

• Updated 1.3 Case Overview

• Updated Tab le 7 to remove data requirement 875.2400 an d to correct data requirement number 875.1100 to 875.1200 and 875.1 2 00 to 875.1400

.Page 9 of 60 • Added neurotoxicity language to Table 7, Section 3 Human Health Risk Assessment and Appendix A Toxicity profile to reflect the need for a neurotoxicity screening battery.

• Deleted “Guidance for Commenters” section.

• Updated Section 7, “Next Steps.”

• Added Appendix F , which includes the agency’s response to comments submitted regarding the PWP.

• Corrected formatting and typographical errors.
The agency received one submission d uring the public comment period on the initial docket. See Appendix F for the agency’s response to this comment.
Comments received did not result in a modification to the anticipated data needs for the Bioban P

- 1487 work plan . This document makes final the work plan for the Bioban P

- 1487 registration review process.


## 1.3 Case Overview The Preliminary Work Plan (PWP) for Bioban P

- 1487 was published on March 30, 2015, and the 60

- day comment period ended on May 29, 2015. The agency received one submission during the public comment period on the initial docket. Documents associated with this registration review

case can be viewed at http://www.regulations. gov in docket EPA

- HQ

- OPP

- 2014

- 080 2

. Tables 1 and 2 b elow summarize the issues relevant to this registration review case and the anticipated registration review schedule

. Table 1

– Summary of Anticipated Risk Assessments and Data Nee ds for Registration Review : Bioban P

- 1487

Risk Assessment Assessment Necessary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Anticipated as Needed (See Table 7 for detail s)

Dietary (food) No N/A None None Dietary (drinking water) Yes N/A New None
Occupational Handler Yes September 2007 Updated See Table 7
Occupational Post

application Yes September 2007 Updated See Table 7

Residential Handler No N/A None None
Resident i al Post Application

- Incidental Oral and Dermal No N/A None None

Resident i al Post Application

- Inhalation No N/A None None
Aggregate No N/A None None
Cumulative No N/A None NonePage 10 of 60 Risk Assessment Assessment Necessary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Anticipated as Needed (See Table 7 for detail s)

Tolerance Review No N/A None None Ecological Yes N/A New See Table 7 N/A = Not applicable * Table 1 is a summary of the anticipated risk assessments a nd data needs for Registration Review. For data called in through the post

Reregistration Eligibility Decision (RED) Data Call

- In (DCI), see Table 8

.

Table 2

– Anticipated Registration Review Schedule Anticipated Activity Target Date * Completion Date Phase 1: Opening the Docket Open Docket and 60

- Day Comment Period for Preli minary Work Plan 2015

- 03 2015

- 03

- 30

Close Public Comment Period 2015

- 05 2015

- 05

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

- 09 2015

- 09

Issue Data Call

- In (DCI) 2016

- 09

Receive Data to be Considered in Risk Assessment 2018

- 09
Open 30

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

- 03

Close Public Comment Period 2020

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

- Day Public Comment Period for Pro posed Decision 2020

- 09

Close Public Comment Period 2020

- 11

Issue Final Decision 2021

- 03
Begin Post

- Decision Followup 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 chemical identification data for the active ingredient s

. Bioban P

- 1487 (case No. 3028) consists of two active ingredients: ( Ingredient I ) 4

- (2

- Nitrobutyl) morpholine ( 81% , PC code 100801 , Bioban P

- 1447 ) and ( Ingredient II ) 4,4’

- (2

- ethyl

- 2

- nitromethylene)dimorpholine (5 %, PC Code 100802, Bioban P

- 1490 ) . Ingredient I is called P

- 1447 and ingredient II is called P

- 1490. Together they comprise Bioban P

- 1487.Page 11 of 60 Table 3

– Chemical Identification of Bioban P

- 1487 Mixture

Chemical Name 4

- (2

- nitrobutyl)morpholine ( P

- 1447, 81%) 4,4’

- (2

- ethyl

- 2

- nitrotrimthyelene) dimorpholine (P

- 1490, 5%) Chemical Classification 1

- aza

- 4

- oxacyclohexane 1

- aza

- 4

- oxacyclohexane

PC Code 100801 10080 2 CAS N umber 2224

- 44

- 4 1854

- 23

- 5 Molecular Formula C 8 H 16 N 2 O 3 C 13 H 25 N 3 O 4 Molecular Weight (grams/mole) 208 287

Molecular Structure

4

- (2

- nitrobutyl) m orpholine; CAS # 2224

- 44

- 4 4,4’

- (2

- ethyl

- 2

- nitromethylene)dimorpholine; CAS # 1854

- 23

- 5

The Bioban P

- 1487 product chemistry information relevant to risk assessment is summarized in Table 4 . The details of the product chemistry information are discussed in Appendix E

. Table 4

– Physical

- Chemical and Environmental Fate Properties for Bioban P

- 1487

Guideline No. P arameter 4

- (2

- nitrobutyl) Morpholine P

- 1447 4,4’

- (2

- ethyl

- 2

- nitromethylene)dimor pholine P

- 1490 Source (MRID unless specified)

830.7050 UV Visible absorption Sorption below 210 nm (acid and neutral) and below 275 nm (basic) Sorption below 210 nm (acid and neutral) and below 275 nm (basic) 48511302

830.7550 Octanol

- water partition coefficient at 25 o C (Log K ow ) 0.18

- 0.54 EPI Suite 4.11

830.7840 Solubility in water (mg/L) 11 ,000 m g/L 11 ,000 m g/L 41995101

830.7950 Vapor pressure (mmHg) 20

- 43 mm Hg (90 o C) 20

- 43 mm Hg (90 o C) 41995101

7.58 x 10

- 3 (25 o C) 5.07 x10

- 6 (25 o C) EPI Suite (version 4.1)

None Henry’s Law (atm m 3 mol

- 1 ) 1.1 x10

- 10 1.51 x 10

- 15 EPI Suite (version 4.1)

o C = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury; Henry’s Law in atm m 3 mol

- 1 According to a hydrolysis study of Bioban P

- 1487 (MRID 43494001), the primary residues in the env ironment are expected to be P

- 1447 and degradates 2

- nitropropane, 2

- nitro

- 1

- butanol and 2

- nitro

- 1

- butene. Table 5 pre s ents the e stimated chemical and physical properties of these degradates.Page 12 of 60 Table 5

– Physical/Chemical Properties of Bioban P

- 1487 Degradates Based on Estimated Values from EPI

- Suite 4.11
P/Chem and Environmental Fate Property Degradate 2

- Nitropropane

CAS# 79

- 46

- 9 2

- Nitro

- 1

- Butanol CAS# 609

- 31

- 4 2

- Nitro

- 1

- Butene CAS# 2783

- 12

- 2 Structure

Molecular weight (g/mol) 89.9 119.2 101.12

Log Kow 0.87

- .101

- 0.101 Solubility in water (mg/L) 8 , 18 0 50 , 3 00 50 ,300
Log Koc 1.65 0.73 0.73 Vapor pressure (mm Hg) 15.5 0.056 0.43
Henry’s Law (atm

m 3 mol

- 1 ) 2.2 x 10

- 4 1.7 x 10

- 7 1.1 x 10

- 6



## 1.5 Use/Usage Description
1.5.1 Registrations

There are three antimicrobial products registered that contain the Bioban P

- 1487 mixture. Products containing Bioban P

- 1487 are registered for indoor use as a materials preservative and as a microbial growth inhibitor of slime

- forming fungi and bacteria.


### 1.5.2 Summary of Registered Uses For inhibition of microorganism growth, Bioban P

- 1487 is applie d to various sites, including industrial processes and water systems such as metalworking fluids; oil storage tank bottom water, fuel storage tank bottom water; and to diesel oil, fuel oil, gasoline, and kerosene, as a hydrocarbon preservative. As a materi als preservative, Bioban P

- 1487 is formulated into products such as metal die cast lubricants, corrosion inhibiting metal coatings, mold

- release agents (for the manufacture of plastics), and fuel conditioners (for diesel engines). It is not registered for direct or indirect food uses

. Table 6 presents a summary of the registered uses o f Bioban P

- 1487 that will be assessed in this registration review

.Page 13 of 60 Table 6

– Summary of Bioban P

- 1487 Registered Uses

Use Application Method Application Rate
Material Preservatives

Metal Working Machinist Exposure Liquid Pour Liquid Pump 2580 ppm 860 ppm 854 ppm Corrosion Inhibiting Metal Coatings and Mold

- Release agents* Unknown 100

- 3000 ppm

Fuel Liquid Pour Liquid Pump 860 ppm 854 ppm 155 ppm

* Directions for use for the corrosion inhibiting metal coatings and mold

- releasing agents do not specify an application method. In the absence of updated labels clarifying application method, EPA will assume products are applied by liquid pour or pump

. 

### 1.5.3 Usage Information According to the Kline Biocides Report for 2004/2005 (Kline, 2005), ~17 7,000 kg of Bioban P

1487 was estimated to be produced in 2005.


## 1.6 Regulatory Histor y
The first product containing Bioban P

- 1487 was registered on June 7, 1972. Currently, Bioban P

1487 consists of a mixture of two active ingre dients: compound I (P

- 1447 ) , 4

- (2

- nitrob utyl) morpholine
, and compound II (P

- 1490 ) , 4,4’

- (2

- ethyl

- 2

- nitromethylene) dimorpholine.

In 2007 , EPA completed the Reregistration Eligibility Decision ( RED ) for Bioban P

- 1487

. DCI’s were issued in February and Ap ril of 2010 for confirmatory data needed to support the RED

. 

### 1.6.1 Tolerance Information
For Bioban P

- 1487, there are no registered direct or indirect food contact uses . Therefore, EPA has not established tolerances or exemptions from tolerances in/on any raw agricultural commodities or processed food and feed products under the Federal Food, Drug and Cosmetic Act (FFDCA) Section 408. Bioban P

- 1487 has not been cleared as a food add itive by the US Food and Drug Administration (US FDA) under FFDCA Section 409.


## 1.7 Incidents
1.7.1 Human Health
No Bioban P

- 1487 human poisoning incidents have been reported in OPP’s Incident Data System (IDS) since 1992, based on the search conducted on January 2 8, 2015.Page 14 of 60 

### 1.7.2 Ecological

There are no Bioban P

- 1487 ecological incidents reported in OPP’s Incident Data System ( IDS ) as of January 28 , 201 5. 

## 2 A nticipated Data Needs

Several studies were required f ollowing the assessment of Bioban P

- 1487 in the 2007 Reregistration Eligibility Decision ( RED ) . In addition to the already

- required RED DCI data, studies listed in Table 7 are expected to be needed for the registration review of Bioban P

- 1487. Table 8 outlines the data required by the post

- RED DCI issued on February 23, 2010 and April 7, 2010. In addition to the parent compound, environmental fate and ecological effects data are expected to be required for three degradates, 2

- nitropropane, 2

- nitro

- 1

- butanol, and 2

- nitro

- 1

- butene ( s ee Section 4.1)

. The agenc y anticipates reviewing data received in response to the post

RED DCI as well as data that will be requ ired for this registration review prior to conducting the registration review risk assessments for Bioban P

- 1487

.Docket Number EPA

- HQ

- OPP

- 2014

- 0802 www.regulations.gov

Page 15 of 60 Table 7

– Studies Anticipated as Needed for the Registration Review of Bioban P

- 1487

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 E xposure Scenario

835.3110 1,2 835.3220 835.3240 835.3280 Biodegradability in WWTP Degradates 3 12 Environmental fate and transport

Metalworking fluids/ industrial coatings, preservative in plastic products, fuel/oil storage tank bottom water additive W aste water treatment plant ( WWTP )

850.3300 2 Activated sludge respiration inhibition (ASRI) Degradates 3 12 Environmental fate and transport WWTP

8 35

. 4300 Aerobic aquatic metabolism TGAI 12 Environmental fate and transport All

870.3465 90

- day inhalation toxicity TGAI 12 Human Health Exposure All

870.6200 6 Neurotoxicity screening battery 7 TGAI 24 Human Health Exposure Metalworking fluids
870.7800 Immunotoxicity TGAI 12 Human Health Exposure All

850.1010 Freshwater invertebrates, acute Degradates 3 12 Aquatic organisms Ecological

850.4500 Algal toxicity, freshwater and saltwater diatoms TGAI and Degradates 3 12 Aquatic plants Ecological

850.4550 Cyanobacteria toxicity TGAI and Degradates 3 12 Aquatic organisms Ecological

850.4400 Aquatic plant toxicity, Lemna sp. TGAI and Degradates 3 12 Aquatic organisms Ecological

850.1075 Freshwater and estuarine/marine fish, acute toxicity TGAI and Degradates 3 , 5 12 Saltwater organisms Ecological

850.1025

or 850.1055 Oyster, shell deposition

or Bivalve embryo larval toxicity TGAI and Degradates 3 12 Saltwater organisms Ecological

850.1035 Mysid, acute toxicity TGAI and Degradates 3 12 Saltwater organisms Ecological

850.1400 Fish, early life stage Degradates 4 24 Aquatic organisms Ecological

850.1300 Aquatic invertebrate, life cycle Degradates 4 24 Aquatic organisms Ecological

875.1 2 00 Dermal exposure EP 24 Occupational handler Metalworking fluids Fuel Liquid pour

875.1 4 00 Inhalation exposure EP 24 Occupational handler Metalworking fluids Fuel Liquid pourPage 16 of 60 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 E xposure Scenario

875.1700 Product use EP 12 Occupational handler Metalworking fluids Fuel Liquid pour Liquid pump

875. 2 500 Inhalation exposure 8 EP 24 Occupational handler Post

- application Metalworking fluids Liquid pour Liquid pump

875.2700 Product use EP 12 Occupational post

- application Metalworking fluids Occupational post

application (machinist)

875.2800 Description of human activity EP 12 Occupational post

- application Metalworking fluids Occupational post

application (machinist)

1 An ASRI study (MRID 47005503) was conducted on P

- 1487 and the IC 50 value was determined to be 306 mg/L, which is greater than the 20 mg/l threshold that would trigger a waste water treatment plant biodegradation simulation te st. Although a ready biodegradability study (MRID 4700550 2 ) was conducted, based on the results, it was determined that P

- 1487 was not
r eadily biodegradable. Hydrolysis leads to fairly rapid formation of degradates. Consequently for the degradates , one of the following: a) Biodegradation in Activated Sludge or b) Simulation Test

- Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study is expected to be required

. 2 An ASRI study is required for the degradates
, 2

- nitropropan e, 2

- nitro

- 1

- butanol, and 2

- nitro

- 1

- butene

. The results of the Activated Sludge Respiration Inhibition Test (ASRI) study will determine which of these four biodegradation tests would be anticipated to be required. If the ASRI test EC50 is less than or eq ual to 20 mg/L, then either the (i)Biodegradation in Activated Sludge Study or (ii) Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the Porous Pot Test would be anticipated to be required. If the ASRI test EC50 is greater th an 20 mg/L, then the DCI expected to be issued would provide that the registrant would choose to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units or c) the Porous Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, the antimicrobial fails the Ready Biodegradability study, then the a) Biodegradation in A ctivated Sludge or b) Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study would be expected to be required.

3 S tudy is expected to be required for any or all three degradates ( 2

- nitropropane, 2

- nitro1

- 1butanol and/or 2

- nitro

- 1

- butene) unless the registrant can demonstrate from environmental fate data that the degradate will not occur in wastewater discharge d into the aquatic environment or, for chronic studies, that the degradate will not persist in surface water

. 4 Testing should be done with the most sensitive species (either freshwater or estraurine/marine) as determined from the result s of the acute toxicity tests (EC50 freshwater invertebrate, acute LC50/EC50 estuarine/marine s pecies).

5 Testing is anticipated to be required on degradates only for freshwater species, but the TGAI and degradates for estuarine/ma rine species.

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

7 A protocol should be submitted to the agency for review before conducting the neurotoxicity study (ies).

8 Air monitoring data for machinists working in metalworking environments is anticipated to be required.

Table 8

– Data Required by the February 23 and April 7, 2010 Data Call

- In s for the Bioban P

- 1487 RED

GLN Study Name Status of DCI

850.1010 Aquatic Invertebrate Acute Toxicity Test, Freshwater Daphnids Satisfied for the parent.Page 17 of 60 870.3800 Reproductive and fertility effects Satisfied.

870.4300 Combined Chronic/carcinogenicity No data have been submitted; these studies are outstanding.



## 3 Human Health Risk Assessment

The a gency anticipates the need to conduct a h uman health risk assessment for Bioban P

- 1487

. The agency will evaluate the data required by the RED DCI

. A lso
, the a gency anticipates the need to require additional data for the registration review of Bioban P

- 1487 , based on the currently registered use s and the physiochemical properties of Bioban P

- 1487, particular as a volatile substance . These additional studies include mammalian toxicity data from a 90

- day inhalation toxicity study, a neurotoxicity screening battery, an immunotoxicity study , and all applicable exposure studies

. A detailed description of the available toxicity studies is provided in Appendix A.


## 3.1 Existing Toxicological Endpoints

The a gency anticipates the need to revise the existing toxicological endpoints included in the agency’s 2008 Reregistration Eligibility Decision (RED) document , shown in Table 9 , as part of th e registration review. All available information
, including existing and additionally required toxicology studies and valid scientific literature, will be considered in esta blishing the toxicology endpoints to be used in the registration review risk assessment.

Table 9

– Existing Toxicological Endpoints for Bioban P

- 1487 Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Target MOE, UF, Special FQPA SF, for Risk Assessment Study and Toxicological Effects

Dietary Risk Assessments Acute Dietary (all populations) NOAEL(maternal) = 10 UF = 100 (10x inter

species extrapolation, 10x intra

- species variation) FQPA SF = 10 Developmental Toxicity Study in Rats (MRID 416738801, 41978802)
LOAEL = 30 mg/kg/day based on excessive salivation and decreased body weight aRfD = 0.1 mg/kg/day aPAD 1 = 0.01 mg/kg/day Chronic Dietary (all populations) NOAEL(maternal) = 10 UF = 300 (10x inter

species extrapolation, 10x intra

- species variation, 3x for lack of chronic data) FQPA SF = 10 Developmental Toxicity Study in Rats (MRID 416738801, 41978802)

LOAEL = 30 mg/kg/day based on excessive salivation and decreased body weightPage 18 of 60 Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Target MOE, UF, Special FQPA SF, for Risk Assessment Study and Toxicological Effects

cRfD = 0.03 mg/kg/day cPAD 2 = 0.003 mg/kg/day Non

- Dietary Risk Assessments

Incidental Oral Short

- Term (1

- 30days) and Intermediate

Term (1

- 6 months) No endpoint identified due to lack of residential uses

.

Dermal Short

- Term (1

- 30 days) LOAEL (dermal) = 30 (dermal irritation) MOE = 30 (3x inter

species extrapolation, 3x intra

- species variation, 3x for use of a LOAEL value) 90

- Day (Dermal) Subchronic Toxicity Study in Rats (MRID 42440001, 41619302)
LOAEL = 30 mg/kg/day based on skin irritation (erythema and edema) at all doses tested. Dermal Intermediate

Term (1

- 6 months) NOAEL (systemic) =300 MOE = 100 (10x inter

species extrapolation, 10x intra

- species variation) 90

- Day (Dermal) Subchronic Toxicity Study in Rats (MRID 42440001, 41619302)
LOAEL = 1000 mg/kg/day based on decreased body weight, chronic inflammation of the urinary bladder in males and females. Dermal Long

- Term (> 6 months) NOAEL (systemic) =300 MOE = 300 (10x inter

species extrapolation, 10x intra

- species variation, 3x for use of a subchronic endpoint for the long

- term endpoint) 90

- Day (Dermal) Subchronic Toxicity Study in Rats (MRID 42440001, 41619302)
LOAEL = 1000 mg/kg/day based on decreased body weight, chronic inflammation of the urinary bladder in males and females. Inhalation (All Durations) NOAEL(maternal) = 10 MOE = 3000 (10x inter

species extrapolation, 10x intra

- species variation, 30x for severe adverse effects observed in the acute inhalation toxicity study, the lack of repeat inhalation exposure study, severe skin irritation and dermal sensitization, and

use of route extrapolation. Developmental Toxicity Study in Rats (MRID 416738801, 41978802)
LOAEL = 30 mg/kg/day based on excessive salivation and decreased body weightPage 19 of 60 Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Target MOE, UF, Special FQPA SF, for Risk Assessment Study and Toxicological Effects

Cancer (oral, dermal, inhalation) No carcinogenicity data available for Bioban P

- 1487 ; such information has been required in the post

- RED DCI

.
UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acut e, c = chronic), RfD = reference dose, MOE = margin of exposure

.

1 aPAD = aRfD ÷ FQPA SF = 0.1 mg/kg/day ÷ 10 = 0.01 mg/kg/day 2 cPAD = cRfD ÷ FQPA SF = 0.03 ÷ 10 = 0.003 mg/kg/day NOTE: The Special FQPA Safety Factor recommended by the A ntimicrobials D ivision T oxicity C ommittee (ADTC ) assumes that the exposure databases (dietary food, drinking water, and residential) are complete and that the risk assessment for eac h potential exposure scenario includes all metabolites and/or degradates of concern and d oes not underestimate the potential risk for infants and children. 

## 3.2 Dietary Exposure
3.2.1 Food
Based on the current labels, the registered uses of Bioban P

- 1487 are not expected to result in direct or indirect dietary (food) exposure. Therefore, a dietary (food ) assessment is not needed for this registration review and r esidue chemistry data are not anticipated to be required at this time.


### 3.2.2 Drinking Water The agency anticipates conducting a drinking water assessment as part of this registration review. The agency has not previously conducted a drinking water assess m e nt for Bioban P

- 1487 and its degradates

. Based on the registered uses in metalworking fluids , however, the agency

can not rule out the potential for exposure of humans to 4

- (2

- nitrobutyl)morpholi ne (P

- 1447) , one of the components of Bioban P

- 1487 and degradates of Bioban P

- 1487 including 2

- nitropropane, 2

- nitro

- 1

- butanol, and 2

- nitro

- 1

- butene in drinking water . There are uncert a in t i es with respect to the residues of concern in drinking water, incl uding the magnitude of residues
, mammalian toxicities, persisten ce in the environment , and potential to be removed during wastewater treatment. Therefore, the agency anticipates needing additional environmental fate data as noted in Table 7 . These data wil l be use d to determine whether and to what extent degradates of Bioban P

- 1487 pass through the Waste Water Treatment Plant ( WWTP ) . The agency anticipates acquiring data and information from other sources
, such as open literature
, during the risk assessment stage of registration review
, to determine the potential of discharged residues of 4

- (2

- nitrobutyl)morpholine (P

- 1447) and degradates of Bioban P

- 1487 to result in human dietary exposure through drinking water which may trigger drinking water assessment.


## 3.3 Occupational and Residential Exposures
3.3.1 Occupational Handler Exposure EPA anticipate s the need to revise the occupational handler assessment conducted in support of the 200 7 RED (D3 38283 ). Occupational handler dermal and inhalation exposures to Bioban P

-Page 20 of 60 1 487 were assessed in the RED for the following applications: liquid pour and liquid pump . For registration review, the liquid pump scenario is anticipated to be negligible. However, t he agency anticipate s the need for a new occupational handler risk assess ment for liquid pour based on the data submitted by the Antimicrobial Exposure Assessment Task Force ( AEATF )

.



### 3.3.2 Occupational Post

- application Exposures Metalworking Exposure
The RED assessed the dermal and inhalation exposure when a worker handles treated metalworking fluids with Bioban P

- 1487

. The previous exposure assessment had several uncertainties, which are identified below:

• There are no acceptable re peated dose inhalati on toxicity data.

• The toxicological endpoint was based on an oral NOAEL

. • Bioban P

- 1487 is a potential sensitizer and a severe irritant.

T he agency anticipates the need to re vise inhalation and dermal exposure using surrogate data available in the literature to estimate potential risk from exposure to mists and aerosols f or machi nists in industrial settings

.
Since the chemicals in the Bioban P

- 1487 mixture are volatile as per the RED (16 mm Hg at room temperature), the agency wou ld need air monitoring data to assess inhalation post

application vapor exposures. In the past machinist assessment, the Bioban P

- 1487 exposures were assessed using an assumption that the air concentration would be 5 mg/m3, which was the past OSHA PEL for oil mist. Th e machinist assessment MOEs in the RED were above a target MOE of 300. However, t he agency believes that the oil mist could potentially underestimate the true concentration of the volatile air concentrations of Bioban P

- 1487. As a result, air m onitoring data for machinists working in metal working environments is anticipated to be required

. 

### 3.3.3 Residential Handler Exposures Residential exposure is not expected to occur based on current labels and therefore, will not be assessed as part of this registration review.


### 3.3.4 Residential Post

- Application Exposures Residential exposure is not expected to occur based on current labels and therefore, will not be assessed as part of this registration review.


## 3.4 Aggregate and Cumulative Exposure
3.4.1 Aggregate Exposures

E PA anticipates that an aggregate assessment will not be needed for Bioban P

- 1487. Typically, dietary (food and drinking water) exposures would be aggregated with residential (dermal andPage 21 of 60 inhalation) exposures in an assessment, but there are no residenti al uses, so only drinking water exposures will need to be considered for Bioban P

- 1487.


### 3.4.2 Cumulative Exposures
With respect to cumulative exposure, unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to Bioban P

- 1487 and any other substances and Bioban P

- 1487 does not appear to produce a toxic metabolite produced by other substances. For the purposes of this registration review, there fore, EPA has not assumed that Bioban P

- 1487 has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such c hemicals, see http://www.epa.gov/pesticides/cumulative/

. 

## 4 Environmental Risk Assessment

In September 2007, the agency published its Reregistration Eligibility Decision (RED) for Bioban P

- 1487 (EPA739

- R

- 07

- 005). At that time, the agency considered all the registered uses of Bioban P

- 1487 to be “indoor uses” and therefore ruled out the potential for exposure to ecological organisms. Consequently, an ecological risk assessment was not performed . Since that time, the agency has determined that all uses may have the potential to lead to environmental exposure. Specifically, the potential for ecological exposures as a result of registered uses of Bioban P

- 1487 (i.e., industrial preservatives incor porated into metalworking cutting fluids, industrial coatings, plastic products, and as fuels/oil storage tank bottom water additives) cannot be ruled out
, and the potential for exposure and risk to m ust be evaluated.

The a gency has not previously conduc ted a complete endangered species determination for any of the antimicrobial uses of Bioban P

- 1487 considered as part of this case . The ecological risk assessment planned during registration review will allow the a gency to determine potential acute and ch ronic risks to aquatic organisms exposed to B ioban P

- 1487 and/ or any of its degradates that are transported from treatment sites into the aquatic environment. The risk assessment will allow the a gency to determine whether each use 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 a gency 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
Bioban P

- 1487 is a mixture of two morpholine

- derivatives : Ingredient I: 4,4’

- (2

- nitromethylene)dimorpholine (P

- 1490) and Ingredient II: 4

- (2

- nitrobutyl)morpholine (P

- 1447)

. According to a hydrolysis study performed under abiotic conditions at pH values of 5, 7, and 9 (MRID 43494001 ) , P

- 1490 is very hydrolytically unstable with a half

- life of 10 minutes. Degr adates formed include d the other morpholine derivative
, P

- 1447 , and 2

- nitro

- 1

- butene.Page 22 of 60 P

- 1447 was determined to have hydrolytic half

- lives of 22 hours at pH 5, 45 hours at pH 7, and 46 hours at pH 9. The hydrolytic degradates of P

- 1447 include 2

- nitroprop ane, 2

- nitro

- 1

- butanol, and 2

- nitro

- 1

- butene. Although the hydrolytic half

- life of P

- 1447 is relatively short, it is long enough that if a waste stream containing this chemical enters a wastewater treatment plant and is subsequently discharged to surface water, there would be potential for aquatic organisms to be exposed. In addition, aquatic organisms could also potentially be exposed to its hydrolytic degradates
, 2

- nitropropane, 2

- nitro

- 1

- butanol, and 2

- nitro

- 1

- butene.
Sorption to soil is not expected to be significant for Bioban P

- 1487. T he measured log Koc of 1.7 (50 L/kg) indicates that it prefer entially partitions to water in the presence of soil (MRID 45900901)

. The degradates are also expected to have limited sor ption to soil . Of the three degradates, 2

- nitropropane had the hig hest estimated L og Koc , 1 .65 (45 L/kg) (Table 5)

. Based on the Henry’s law constants (HLC) of approximately 10

- 10 and 10

- 15 atm m 3 mol

- 1 for P

1490 and P

- 1447, these chemicals may volatilize from water. Of the degradates, 2

- nitropropane has highest potential to volatilize from water based on its HLC of approximately 10

- 4 atm m 3 mol

- 1 followed by 2

- nitro

- 1

- butene with an HLC of approximately 10

- 6 atm m 3 mol

- 1 and approximately 10

- 7 atm m 3 mol

- 1 for 2

- nitro

- 1

- butanol (Table 5)

. Based on low estimated log Kow values for P

- 1447 and P

- 1490 (0.18 for the former and

- 0.58 for the latter) using EPI

- WEB 4.11 , these chemicals are not expected to bioaccumulate in aquatic animals.


### 4.1.1 Fate and Ef fects during Wastewater Treatment Based on the estimated log Kow of 0.18 for P

- 1487 , it would be expected to have very limited potential to sorb to activated sludge in a wastewater treatment plant. The estimated log Kow values for the degradates also indic ate that the potential for sorption to activated sludge would be limited. (The highest estimated log Kow value for 2

- nitropropane is 0.87 ) (Table 5).

Based on an IC 50 value of 306 mg/L (MRID 47005503) , results of a preliminary review of an activated sludge respiration inhibition (ASRI) study indicate that Bioban P

- 1487 must be present in much higher levels than expected to occur in a wastewater treatment plant for microorganism s to be inhibited

. No AS RI test data were found for degradates of Bioban P

- 1487. In a ready biodegradability study (MRID 47005502), Bioban P

- 1487 was found to be not readi ly biodegradable based on degradation of <60 % within a 10

- day period after the onset of biodegradation

. No test data on biodegradability in wastewater treatment w ere foun d for degradates of Bioban P

- 1487. In the absence of data on the degradates of Bioban P

- 1487 with regard to biodegradability during wastewater treatment and effects to wastewater treatment plant microorgani sms, the a gency anticipates requiring ASRI and WWTP biodegradation studies for each o f the degradates.


## 4.2 Conceptual Models for Environmental Exposure Pathways
The registered uses for the two chemicals included in Case 3028, Ingredient I: 4

- (2

- Nitrobutyl)morpholine and Ingredient II: 4,4’

- (2

- e thyl

- 2

- nitromethylene)dimorpholine are asPage 23 of 60 industrial preservatives incorporated into metalworking cutting fluids, industrial coatings, plastic products, and as fuels/oil storage tank bottom water addit ive s (see Table 6 for additional information). Based on these registered industrial uses, physical/chemical properties of the two parent chemicals and their degradates, and environmental fate information presented in Appendix B, the agency cannot rule out the potential for exposure of aquatic organisms downstream of w astewater treatment plant s that treat wastewater from these uses.

The agency has created conceptual models for potential routes of environmental exposure which are included in “Conceptual Mode ls for Environmental Exposure Pathways of Antimicrobial Pesticides” (EPA

- HQ

- OPP

- 2014

- 0638

- 0002) found at www.regulations.gov in docket EPA

- HQ

OPP

- 2014

- 0638. For metalworking cutting fluids, refer to slide 18 . Fo r in

- service use of industrial coatings
, refer to slide 24

. For industrial coatings, there may also be releases to the aquatic environment if process water is used to incorporate antimicrobials into coatings and is released to on

- site or off

- site treatmen t and subsequently discharged to surface water. For Fuels/oil storage tank bottom water additives, refer to slide 23

. Aquatic organisms potentially at risk include those inhabiting waters adjacent to or downstream from sources of down

- the

- drain discharges (e. g., waste water treatment plants). Water bodies might include ponds, lakes, and reservoirs or flowing waterways s uch as streams and rivers. For uses in coastal areas, aquatic habitat also includes marine ecosystems, including estuaries. Aquatic organisms likely to be exposed include fish, invertebrates, aquatic stages of amphibians, and aquatic and semi

- aquatic pla nts. The major route of exposure for aquatic animals is likely to be uptake via the respiratory surface (gills) or the integument from surface water that has pesticide residues. The major route of exposure for plants is considered to be uptake from surfa ce water or sediments.


## 4.3 Ecological Effects Assessment
4.3.1 Mechanism of Action
The Agency has no information on the mode of action of B ioban P

- 1487 to terrestrial and aquatic vertebrates and invertebrates.


### 4.3.2 Measure of Effects ( Ecotoxicology Endpoints )
Acute and chronic toxicity data from registrant

- submitted studies (850 OCSPP Harmonized Test Guidelines) will be used to evaluate the potential effects of B ioban P

- 1487 to aquatic and terrestrial nontarget organisms

. All available ecotoxicity endpoints , data requir ements, and data gaps are presented in Appendix C. OPP uses the most sensitive of the endpoints for assessing risks. The endpoints currently selected for B ioban P

- 1487 (TGAI) are provided in Table 1 0

. No data are currently available for the degradates (see Table 7 for data requirements).

Table 10

– Available Ecological Effects Endpoints Receptor

Group Test Material Scenario Toxicity Endpoint ReferencePage 24 of 60 Freshwater fish TGAI Acute LC50 = 0.75 mg ai/L 93055005 TGAI Chronic No data

--
Freshwater invertebrates TGAI Acute EC50 = 3.23 mg ai/L 47285301 Chronic No data

--
Estuarine/marine fish TGAI Acute No data

-- Chronic No data

-- Estuarine/marine

invertebrates TGAI Acute No data

-- TGAI Chronic No data

-- Algae TGAI EC50 and NOAEC EC50 = 0.352 mg ai/L NOAEC = 0.049 mg ai/L 47005504

Aquatic vascular plants TGAI EC50 and NOAEC No data

--

Birds TGAI Acute LD50 >1000 mg ai/kg 93055001 TGAI Dietary LC50 >3692 ppm 93055002 

### 4.3.3 Open Literature Open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database. The ECOTOX database will be searched when the risk assessment is prepared. ECOTOX was created and is maintained by the USEPA, Office of Research and Development, and the National Health and Environmental Effects Research Laboratory's Mid

- Continent Ecology Division. Any acute or chronic endpoints more sensitive than what are currently available will be evaluated for the risk assessment

. 

## 4.4 Exposure Analysis Plan
4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates
To predict the potential for exposures and risks to aquatic organisms downstream of facilities that release 4

- (2

- n itrobutyl)morpholine and 4,4’

- (2

- ethyl

- 2

- nitromethylene)dimorpholine and /or their degradates to su rface water, t he agency plans to use the General Population and Ecological Exposure from Industrial Releases module of E

- FAST (Exposure and Fate Assessment Screening Tool) to determine the number of days of exceedance of concentrations of concern for aquat ic organisms.

All end

- uses for this case are industrial uses. Since a screening tool to analyze exposures and ecological risk from industrial uses is not currently available, as stated in Appendix D, a screening

- level down

- the

- drain analysis of these uses is not within the scope of this preliminary work plan. Input data required to run the General Population and Ecological Exposure from Industrial Releases module of E

- FAST include: (1) percent removal of antimicrobial during wastewater treatment; (2) envi ronmental releases of antimicrobial to surface water in kg/site/day; (3) annual number of days of release of antimicrobial to surface water; (4) Standard Industrial Classification (SIC) codes to represent the industrial uses being assessed and (5) concentr ationsPage 25 of 60 of concern for aquatic animals and plants . The method used to estimate environmental releases of antimicrobial to surface water will be based on the specific end

- use being evaluated. 

## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental,

re productive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregna ncy 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 reregistrat ion decision , for B ioban P

- 1487 , EPA reviewed these data and existing hazard database. However, as required by FFDCA section 408(p), Bioban P

1487 is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has deve loped the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Admi nistrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androge n, 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 t he Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

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

- response relationship between the dose and the E, A, or T effect.

Under F FDCA section 408(p), the agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 1 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 end ocrine 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. 2

1 See http://www.regulations.gov/#!documentDe tail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.
2 http://www.epa.gov/endo/

.Page 26 of 60 

## 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 assumptions, and/or impro ve label clarity. Directions for use for the corrosion inhibiting metal coatings and mold

- releasing agents do not specify an application method. In the absence of updated labels clarifying application method, EPA will assume products are applied by liqui d pour or pump

. 

## 7 Next Steps

A DCI will be developed regarding the data needs listed under the “Anticipated Data Needs” section of this document. The agency anticipates issuing the DCI in 2016.Page 27 of 60 

## 8 References

MRID 43494001. Burke, B, 1994. Hydrolysis of 4

- (2

- nitrobutyl) morpholine and 4,4’

- (2

- ethyl

2

- nitromethylene) dimorpholine. Lab Project # PRT

- 23

- 4ANN

- 01

- PRT

- 23

- 4ANN

- 01

- 03. Unpublished study prepared by Plant Research Technologies, Inc. 228 pages

. MRID 45900901. Gonsoir, SJ, Rivard, MA, and Stock, MK, 2002. Estimating Soil Koc for a series of Biocides by HPLC Using OECD Method # 121. Biocides TS and D, The Dow Chemical Company, Midland, Michigan

. MRID 47005502. Gonsoir, S, Stock, M, and Rivard, M. 2002: Evaluation of Ready Biodegradability of Bioban P

- 1487 using OECD Method 301F: Manometric Respiratory Test; Project# 011131. Unpublished Study Prepared by Dow Chemical Company, 31 pages

. MRID 47005503. Gonsior, S.; Rivard, M.; Stock, M. (2002) Activated Sludge, Respiration Inhibition Test (OECD 209) fo r Bioban P

- 1487. Project Number: 011177. Unpublished study prepared by The Dow Chemical Company. 16 p.

MRID 47285303. Ponte, M. (2007) Aqueous Photolysis of Bioban P

- 1487 Biocide Under Artificial Sunlight. Project Number: 1625W, 070058. Unpublished study p repared by The Dow Chemical Co., 80 p.

Kline. 2005. Kl ine Biocides Report for 2004/2005 for Bioban P

- 1487.

U.S. EPA. 2012. EPI

- Suite 4.11. http://www.epa.gov/oppt/exposure/pubs/episuite dl.htm

. U.S. EPA. 2007 . Reregistration Eligibility Decision for Bioban P

- 1487. EPA 739

- R

- 07

- 005.
D338283. U.S. EPA. 2007 Occupational and Residential Exposure for Bioban. Memorandum from S. Mostaghimi, Ph.D. to Mark Hartman. EPA

- HQ

- OPP

- 2007

- 0402

- 0015.Page 28 of 60 

# Appendix A T oxicology Profile

Acute Toxicity for Product Labeling
Adequacy of D atabase for Acute Toxicity : The database for acute toxicity is considered complete. No additional studies are anticipated to be required.

Bioban P

- 1487 was found to be moderately toxic (Toxicity Category III), with a calculated median lethal dose of 620 mg/kg (combined) in an acute oral toxicity study in rat s (MRID 43558901 ) and 652 mg/kg (combined) in rabbits (MRID 41677601 )

. Catalepsy and tremors were observed at a dose of 500 mg/kg i n th e rat study, and at 800 mg/kg, lethargy, na s al discharge, and convulsions were observed. The acute dermal LD 50 was determined to be of 420 mg/kg (combined) in rabbits ( Toxicity Category II) (MRID s 4167760 2 / 41810801 )

. In a n old acute inhalation study (MRID 00094994), utilizing a n one

- hour exposure
, estimated a median lethal concentration of 746 mg/L (595

- 936 mg/L) in male rats, in addition to s ignificant clinical toxicity and blood in the urine at concentration of 200 mg/L as well as porphyrin discharge, corneal opacity, and conjunctivitis at 100 mg/L. A newer acute inhalation limit test (MRID 47394701; 4

- hour
, nose

- only) reported that one female rat died 3 days post

- dosing w ith hypoactivity, ventral staining, ocular and nasal red color discharge prior to the death. Red urine on the litter paper and around the penis in one surviving male rat, weight loss in the surviving animals in the first week of post

- dosing, and discolora tion and distention of the intestines at gross necropsy were also observed. The study author concluded a LC 50 of greater than 2.33 mg/L. Bioban P

- 1 487 i s corrosive to the eyes ( Toxicity Category I ) and severe ly irritating to the skin ( Toxicity Category I I ). It is a dermal sensitizer

. Table A1

– Acute Toxicity Profile for Bioban P

- 1487

Guideline Number Study Type/ Test substance (% a.i.) MRID Number/ Citation Results Toxicity Category 870.1100 Acute oral, rat (Purity 81%) 43558901 LD 50 =620 mg/kg (combined) III

870.1100 Acute oral, rabbit (Purity 92%) 41677601 LD 50 =625 mg/kg (combined) III

870.1200 Acute dermal, rabbit (Purity 92%) 41677602 (duplicate 41810801) LD 50 =420 mg/kg (combined ) II

870.1300 Acute inhalation, rat (Purity 94.6%) 47394701 LC 50 >2.33 mg/L (combined) IV

870.2400 Primary eye irritation, rabbit (Purity 92% a.i.) 41677603 Corrosive I

870.2500 Primary dermal irritation, rabbit (Purity 92%) 41677604 (duplicate 41810802) Severe irritant II

870.2600 Dermal sensitization, guinea pigs (Purity 90%) 000104805 Sensitizer NA

N/A

– Not applicablePage 29 of 60 

## Subchronic Toxicity
Adequacy of Database for Subchronic Toxicity: The database for subchronic toxicity is considered incomplete. There are several studies in the agency’s hazard database to address subchronic oral toxicity , including subchronic oral toxicity studies in rats as well as in dogs (MRIDs 47213801, 47394702 , 47394703, 49088901, and 49087501) and 90

- day dermal toxici ty studies in rats (MRIDs 41619 302 /41978801 and 42440001). A brief summary of the reviewed studies is provided below.

B ased on the currently registered uses for Bioban P

- 1 487 and its high volatility, a route

- specific subchronic inhalation toxicity study in r oden ts is anticipated to be required for registration review risk assessment

.
870.3100 90

- Day (13

- Week) Oral Toxicity

– Rat
(1) In a 90

- day oral toxicity study (MRID 4 7 3 947 0 2 ), Bioban P

- 1487 [4

- (2

- Nitrobutyl) morpholine; 9 4 .6% active ingredient ; lot # UD1731LAD7 ] in corn oil was administered to Crl:CD(SD) rats (10/sex/dose) via gavage at dose levels of 0, 5, 10, 25 or 50 mg/kg /day , 7 days a

we ek for 13 weeks.

All male rats in the 50 mg/kg/day dose group were sacrificed in extremis on D ay 32 due to excessive toxicity as evidenced by decreases in body weight (15.2% less than controls) and body weight gain (38.2% less than controls) on Day 29, in addition to one rat (5 mg/kg/day group) being euthanized on Day 88 due to a mechanical injury resulting in a broken muzzle. All other animals survived until study termination (90

- days).
Clinical signs for m ales and females in the 50 mg/kg/day dose group and to a lesser extent those in the 25 mg/kg/day dose group had a treatment

- related increase in the incidence of transient, clear perioral soiling (salivation) usually following dosing.
At study termination of Day 90, r educed mean body weights and b ody w eight gains were observed in males given 10 or 25 mg/kg/day test material and females given 10, 25 or 50 mg/kg/day test material. Female rats seemed being affected more than males, with as low as near 10% decrease in body weight and 18% decrease in body w eight gain, respectively, were observed. Additionally, statistically significant lower feed consumption (12

- 18.9% decrease) was reported for males given 25 or 50 mg/kg/day Bioban P

- 1487 and females given 50 mg/kg/day (10.4%), but only in the first week o f the study.
Hematuria occurred in one male given 25 mg/kg/day and may be a treatment

- related effect of the test material. At the high dose of 50 mg/kg/day, absolute and relative adrenal weights of females were elevated over those of the controls.

Gros s pathologic observations consisted of thickened nonglandular mucosa of the stomachs of males administered greater than or equal to 10 mg/kg/day and in females administered greater than or equal to 25 mg/kg/day Bioban P

- 1487. Treatment

- related histopathol ogical changes were present in the nasal tissue (olfactory mucosa), stomach, urinary bladder and adrenal glands of treated rats . A majority of females in the 50 mg/kg/day dose group and some females in thePage 30 of 60 25 mg/kg/day dose group had degenerative changes of the olfactory epithelium of the nasal cavity. Hyperplasia, hyperkeratosis and chronic active inflammation of the nonglandular stomach mucosa, as well as necrosis of the nonglandular stomach epithelium, were presented in a majority of males in the 25 mg /kg/day dose group, females in the 25 or 50 mg/kg/day dose groups and occasionally in males of the 10 mg/kg/day dose group. Changes in the urinary bladder (very slight, diffuse, hyperplasia of the lining epithelium) occurred in a majority of females in th e 50 mg/kg/day dose group; lymphoid cell aggregates were present under the urinary bladder epithelium (lamina propria) of males and females in 10 mg/kg/day and/or greater dose groups, consistent with a mild chronic inflammatory response. Hypertrophy in th e adrenal glands (zona fasciculata of the adrenal cortex), consistent with increased adrenal gland weights, occurred only in the high

- dose (50 mg/kg/day) females.

There were no treatment

- related effects in clinical observations, open

- field observations, functional tests (sensory evaluations, rectal temperature, grip performance and motor activity), ophthalmic observations, hematology, prothrombin time, or clinical chemistry parameters.
The LOAEL is 10 mg/kg/day based on decreased body weight and body weight gain (males and females), decreased feed consumption (males) and histopathology of the stomach (inflammation, hyperplasia, hyperkeratosis and thickening of the nonglandular mucosa in males) and urinary bladder (mononuclear lymphoid cell aggregates i n the lamina propria of males and females). The NOAEL is 5 mg/kg/day for male and female rats.

Th is study is classified A cceptable/Guideline

. (2) In a subchronic oral toxicity study (MRID 49088901), Bioban P

- 1487 [purity of 82.95% wt/wt 4

- (2

- Nitrobutyl)morpholine and 4.37% wt/wt 4,4'

- (2

- Ethyl

- 2

- nitro

- l,3

- propanediyl)bismorpholine ; lot# YH1031LAH4 ] was administered to F344/DuCrl rats (10/sex/dose), in diet, at dose levels of 0, 20, 60, or 125 mg/kg/day (time

- weighted average doses of 0, 11 .7, 45.9, and 95.2 mg/kg/day for males and 0, 11.5, 45.3, and 92.3 mg/kg/day for females), for at least 90 days. The study author(s) concluded that “Under the conditions of this study, based on treatment

- related higher reticulocyte counts and cholesterol levels of males at 60 mg/kg/day, the no

- observed

- effect level (NOEL) for male F344/DuCrl rats was the targeted dose of 20 mg/kg/day BIOBANTM P

- 1487 that corresponded to test material intake of 11.7 mg/kg body weight/day. The NOEL for female rats was 60 mg/k g/day that corresponded to test material intake of 45.3 mg/kg/day.” The final conclusion of the study will be available once the agency’s comprehensive review is completed.
(3) In a subchronic oral toxicity study (MRID 49087501), Bioban P

- 1487 [purity of 82.95% wt/wt 4

- (2

- Nitrobutyl)morpholine and 4.37% wt/wt 4,4'

- (2

- Ethyl

- 2

- nitro

- l,3

- propanediyl)bismorpholine ; lot# YH1031LAH4 ] was administered to F344/DuCrl rats (5/sex/dose), in diet, at dose levels of 0, 15, 50, or 150 mg/kg/day (time

- weighted average doses of 0, 8.82, 39.4, and 117 mg/kg/day for males and 0, 9.08, 39.3, and 114 mg/kg/day for females), for 29 days. The study author(s) concluded that “ Under the conditions of this study, based on the decrements in body weights/body weight gains, feed co nsumption in males and females given 150 mg/kg/day, and the slightly higher serum cholesterol levels of males given 150 mg/kg/day, the 28

- day dietary No

- Observed

- Effect

- Level (NOEL) for BIOBANTM P

- 1487 in F344/DuCrl rats was the targeted dose of 50 mg/kg/da y that corresponded to an actual time weighted averagePage 31 of 60 dose of 39.4 mg/kg/day in males and 39.3 mg/kg/day in females.” The final conclusion of the study will be available once the agency’s comprehensive review is completed.
(4) In a subchronic oral toxic ity study (MRID 47213801), Bioban P

- 1487 [ 4

- (2

- Nitrobutyl)morpholine; purity of 94.6%; lot# UD1731LAD7] in com oil was administered to Beagle dogs (2/sex/dose), via oral gavage, at dose levels of 0, 2.5, 10, or 25 mg/kg/day for at least 28 days. The stud y author(s) concluded that “The lack of incoordination and/or urinary tract lesions in the other animals given Bioban P

- 1487 makes it difficult to make a definitive conclusion as to the potential of P

- 1487 to cause significant toxicity in dogs. However, th e prominent incoordination of the hind limbs and the lesions of the urinary tract in one male given 25 mg/kg/day, and the vomiting and blood from the penis in the other male given 25 mg/kg/day may be treatment related. The no

- observed

- effect level (NOEL) w as 10 mg/kg/day for males and 25 mg/kg/day for females.” The final conclusion of the study will be available once the agency’s comprehensive review is completed

. (5 ) In a subchronic oral toxicity study (MRID 473 947 0 3 ), Bioban P

- 1487 [ 4

- (2

- Nitrobutyl)morpholine; purity of 94.6%; lot# UD1731LAD7] in com oil was administered to Beagle dogs ( 4 /sex/dose), via oral gavage, at dose levels of 0, 2.5, 10, or 25 mg/kg/day for at least 90 days. The study author(s) concluded that “The urinary tra ct was the primary site of toxicity for males and females given 25 mg/kg/day. Alterations in the urinary bladder, occurring with variable incidence in males and/or females, consist ed of: very or slight submucosal hemorrhage, very slight or slight hyperpla sia of the transitional epithelium, very slight or slight hyperplasia of the transitional epithelium, very slight or slight chronic inflammation of the submucosa or transitional epithelium, very slight or slight necrosis of individual transitional epitheli al cells, and slight ulceration of the transitional epithelium...... The no

- observed

- effect level (NOEL) was 10 mg/kg/day for both sex es.” The final conclusion of the study will be available once the agency’s comprehensive review is completed.

870.3250 Subchr onic (90

- day dermal) Toxicity

– Rat

In a 90

- day derma l t oxicity study (MRIDs 41619 302 /41978801 ), g roups of Sprague

- Dawley rats (20/sex/group) received Bioban P

- 1487 (85% a.i.) to the clipped dorsal area at doses of 0 (deionized water ), 30, 100, 300 (MRID 41619302), and 1000 mg/kg/day (MRID 42440001), 6 hours/day, 5 days/week for 13 weeks. The clipped dorsal area constituted approximately 10% of a total body surface. The appropriate amount of test material was applied evenly over one quarter of the clipped unabraded area, and the application site was rotated weekly over the four quadrants to prevent dermal irritation by the test material.
Skin reactions (erythema and edema) were evident at all dose levels tested. Hematocrit was sl ightly reduced in males at 100 and 300 mg/kg/day as was white cell count in females at 300 mg/kg/day. Creatinine was reduced in males at all dose levels. Body weight was reduced in both sexes, in the absence of any changes in food consumption. Food cons umption was slightly increased in males at the 100 and 300 mg/kg/day dose levels in weeks 7, 11, and 12. At the 1000 mg/kg/day dose level, acanthosis was observed at the site of skin application, and histological examination showed chronic inflammation of the urinary bladder in both males and females. T he s ystemic L OAEL i s 10 00 mg/kg/day , based on decreased body weight and chronicPage 32 of 60 inflammation of the urinary bladder in both sexes; the s ystemic NOAEL i s 300 mg/kg/day

. The dermal L OAEL was determined to be ≤ 30 mg/kg/day ( the lowest dose tested ), based on skin reactions (erythema and edema) observed at all dose levels tested; the dermal NOAEL was not established.
This study is classified Acceptable/Guideline

. 

## Developmental Toxicity
Adequacy of D atabase fo r Prenatal Developmental Toxicity : The database for prenatal developmental toxicity is adequate. There are developmental toxicity studies, one in the rat ( MRIDs 41673801 and 41978802 ) and another in the rabbit ( MRID 47865701 ) availa ble for Bioban P

- 1487

.
870.3700a Prenatal Developmental Toxicity (Gavage) Study

– Rat
In a developmental toxicity study in rats (MRID s 41673801 / 41978802 ), artificially inseminated female Sprague

- Dawley rats (25/group) were administered to Bioban P

- 1487 (79% 4

- (2

- nitrobutyl)morpholine, 4.8% 4, 4’

- (2

- ethyl

- 2

- nitrotrimethylene)dimorpholine), by gavage, at doses of 0, 10, 30, and 100 mg/kg/day in corn oil on ge station days 6 through 15. One maternal rat at 100 mg/kg was sacrificed in extremis on gestation day 11. Excessive salivation was observed in increased incidence at the 30 mg/kg and 100 mg/kg dose levels. Reduced body weight gain (36% reduction from con trol) was observed in maternal animals at 100 mg/kg for days 0

- 20, and a 12% reduction in weight gain was observed at the 30 mg/kg dose level for the 0

- 20 day time period. Food consumption was significantly affected at 30 and 100 mg/kg for maternal animal s during week 2 of the study (decreases of 12% and 30% respectively).
There were no significant adverse effects in fetal body weight, crown

- rump length, or external, visceral, or skeletal malformations at any dose tested. At the 100 mg/kg dose, there w as a slight reduction in live fetuses per dam (8.2 vs. 9.1 in control), total implants per dam (9.4 vs. 11.2 in control), but the incidences of these effects were not significantly different from control. The maternal LOAEL is determined to be 30 mg/kg/da y , based on increased salivation, accompanied by significantly reduced (p ≤ 0.05) body weight gain (and food consumption) ; the m aternal NOAEL is 10 mg/kg/day . The d evelopmental toxicity NOAEL is determined to be 100 mg/kg/day (the highest dose tested), an d the developmental toxicity LOAEL is not established.
This study is classified Acceptable/Guideline

.
870.3700b Prenatal Developmental Toxicity (Gavage) Study

– Ra bbi t
In a developmental toxicity study in rats (MRID 47865701), groups of 26 time

- mated fe male New Zealand white rabbits were administered BiobanTM P

- 1487 Antimicrobial (94.7% a.i.; Lot# UD 1731 LAD7) in polyethylene glycol 400 ( PEG

- 400 ) , by oral gavage, at targeted dose levels of 0, 15, 50, or 150 mg/kg/day from days 7 through 27 of gestation.Page 33 of 60 The predominant toxicological findings were observed in 150

- mg/kg/day females, including decreased body weight/body weight gains and decrease in food consumption, and resulted in removal of 5 rabbits from the treatment due to 10

- 14% body weight loss. An overall of 52% decrease in body weight gains, compared to controls, was observed through the treatment period (GD 7

- 28), while a decrease of 35

- 88% (of controls) in feed consumption was reported throughout most of the dosing period. Corresponding to these changes, an increased incidences of treatment

- related clinical observations included decrease in quantity of feces (including absent), soft feces, and soiling of the perioral (clear), perineal (fecal) and perinasal (clear) regions. In addition, absolute and relative liver weights were increased by 12 and 16%, respectively, compared to controls. The maternal toxicity LOAEL is 150 mg/kg/day, based on toxicological findings including significant (p < 0.05) reductions in body weights, bo dy weight gains, and food consumptions and increase in absolute and relative liver weights. The maternal toxicity NOAEL is 50 mg/kg/day.
At 150 mg/kg/day, decreased mean fetal body weights and gravid uterine weights of 16% and 20%, respectively, were obs erved, along with increased incidences of delayed ossification of the hyroid (reached statistically different), pubis, and talus. The developmental toxicity LOAEL is 150 mg/kg/day, based on significant (p < 0.05) decreases in fetal weights and delayed

oss ification of the hyroid, pubis, and talus. The developmental toxicity NOAEL is 50 mg/kg/day.
The study is classified Acceptable/Guideline

. 

## Reproductive Toxicity
Adequacy of D atabase for Reproductive Toxicity : The database for reproductive toxicity is

a dequate. The re is a 2

- generation reproductive toxicity study f or Bioban P

- 1487 (MRID 48126001), submitted in response to the post

- RED data

- call

- in (DCI)

.
In a 2

- gene ration reproduction study (MRID 48126001 ) , Bioban TM P

- 1487 (94.6% a.i., l ot # UD1731LAD7 ) was administered to 30 Crl:CD rats /sex/dose
, by gavage, at dose levels of 0, 1, 5, or 20 mg/kg /day. For both the F 1 and F 2 generations, there were 8 pups per litter (4 per sex, unless not possible) and 1 litter per successfu l mating female.
Results showed evidence of systemic toxicity in both sexes of P parental and F 1 animals

. The parental systemic LOAEL is identified as 20 mg/kg/day for males and females, based on lowered mean body weights, reduced body weight gains, re duced food consumption (and/or food efficiency), and histopathological changes seen in the non

- gland ular area of the stomach . The parental systemic NOAEL is 5 mg/kg/day.

There were no treatment

- related effects in F 1 or F 2 offspring. As a result, the offspring NOAEL is 20 mg/kg /day. Pups did not experience decreases in survival, lowered body weight, reduced body weight gain, or altered food consumption compared to controls. Therefore, a LOAEL cannot be identified for this study.Page 34 of 60 There were no changes in gonadal function, estrous cycles, mating, fertility, pregnancy, weaning, or other reproductive functions in either sex at any dose. The r eproductive NOAEL is 20 mg/kg /day in both sexes, based on a lack of reproductive effects in either sex of o ffspring. Therefore, a reproductive LOAEL is not established.
This study is Acceptable/Guideline

. 

## Chronic Toxicity
Adequacy of D atabase for Chronic Toxicity : The database for chronic toxicity is considered incomplete. There are no chronic toxicity st udies in the agency’s hazard database; these studies are anticipated to be required for registration review risk assessment, based on the currently registered uses for Bioban P

- 1487

. The chronic studies were identified as data gaps in the RED and are required by the post

- RED DCI

. 

## Carcinogenicity
Adequacy of D atabase for Carcinogenicity : The database for carcinogenicity is considered incomplete . There are no carcinogenicity studies in the agency’s hazard database; these studies are anticipa ted to be required for registration review risk assessment
, in order to adequately address the hazardous risks of Bioban P

- 1487 from the currently registered uses . The carcinogenicity study were identified as data gaps in the RED and are required by the p ost

- RED DCI

. 

## Mutagenicity
Adequacy of D atabase for M utagenicity : The database for mutagenicity is considered adequate. Several mutagenicity studies have been submitted and reviewed by the Office of Pesticide Programs (OPP) and found acceptable. The sum maries of these studies are provided below.

Gene Mutation
(1) In an Ames test ( MRID 4 16193 01 ), Bioban P

- 1487 (Purity: 85% 4

- (2

- nitrobutyl)morpholine, 10% 4, 4’

- (2

- ethyl

- 2

- nitrotrimethylene)dimorpholine; Lot 8K15

- DF28 ) was assessed in the standard battery of Salmonella his

– strains, TA98, TA 100, TA1535, and TA1537. All four tested strains, in triplicate cultures, were exposed to the graded test material for 65±2 hours, with and without S9 metabolic activation. The d ose range (0.007

- 7.5 μg/plate) was determined based on a preliminary range

- finding test. No induction of reverse mutations was shown with or without S9 activation in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 up to the highest dose lev el (7.5 μg/plate). The positive controls substances caused significant increases in reversions, 3 to 5 times higher than the solvent values. It was concluded that B ioban P

- 1487 was not mutagenic in Ames test with or without S9.
This study is classified Acceptable

.Page 35 of 60 ( 2 ) Bioban P

- 1487 ( 8 0.86 % 4

- (2

- nitrobutyl)morpholine
, 4.12 % 4, 4’

- (2

- ethyl

- 2

- nitrotrimethylene)dimorpholine; Batch # OJ0431LAN7 ) was evaluated for its ability to induce forward mutations at the TK locus in L5178Y +/

- mouse lymphoma cells (MRID 45655301). The dose range (0.25

- 30 μg/mL) was based on a preliminary range

- finding t est. The cell cultures were exposed to the test article for 4 hours in exposure medium, ±S9

. Bioban P

- 1487 treatments, +S9, resulted in significant increases in mutant f requency and increased mutant indices. A second assay, under the same conditions, confirmed the results of the first experiment. The sensitivity of the test system was clearly demonstrated by the positive responses elicited by the positive control compou nds. In this assay, Bioban P

- 1487 was found to be mutagenic with S9.
This study is classified Acceptable/Guideline

. Cytogenetics
(1) Bioban p

- 1487 ( 81% 4

- (2

- nitrobutyl)morpholine , 5% 4, 4’

- (2

- ethyl

- 2

- nitrotrimethylene)dimorpholine; Lot # 8K15

- DF28 ) was administered to Chinese hamster ovary (CHO) cells to assess its potential clastogenic effects (MRIDs 41298502 [main study]/ 41567901 [supplemental study] ) . CHO cell cultures, in duplicates, were exposed to the test article in doses ranging from 1x10

- 8 mL/m L to 1x10

- 4 mL/mL for 8 hours without activation (

- S9) and from 5x10

- 8 mL/mL to 5x10

- 4 mL/mL for 2 hours with activation (+S9). All cultures were exposed to colcemid (1x10

- 6 M) during the last 3 hours of incubation. In this assay, B ioban P

- 1487 did not induce chromosomal aberrations with or without S9.
This study is classified Acceptable

. (2) In a C D

- 1 m ice bone marrow micronucleus assay (MRID 47005501 ) , 6 male mice/dose were treated by single oral gavage on two consecutive days with Bioban P

- 1487 TM ( 4

- (2

- nitrobutyl)morphine [80.86%]; 4,4’(2

- ethyl

- 2

- nitromethylene)dimorphine [4.12%]
, Batch No.: OJ0431 LAN ) in corn oil at doses of 0, 125 , 250 , or 500 mg/kg based upon the results of a range

finding test in which significant mortalit y was observed in both sexes at 1000 mg/kg body weight. An additional group of 6 mice were treated with 500 mg/kg dose concentration. Bone

marrow cells were harvested 24

- hours post

- treatment (after second treatment). The positive control was cyclophosphamide monohydrate (120 mg/kg). Clinical signs of toxicity including decreased activity, perioral/periocular soiling, and urine and fecal perineal soiling languid were observed i n the 250 and 500 mg/kg animals.
No significant increases in micronucleated polychromatic erythrocytes (MN

- PCEs) frequencies were reported in any dose group, whereas, a significant increase in the frequencies of MN

- PCEs was observed in the positive cont rol group. The mean percent PCE values were significantly reduced at 500 mg/kg and for the positive control groups compared to the corresponding negative controls. Bioban P

- 1487 TM is considered negative in this mice bone marrow micronucleus assay under t he test condition.
This study is classified Acceptable/Guideline

.Page 36 of 60 Other Genotoxicity
(1) In an unscheduled DNA synthesis assay (MRID 46965903), 5 male rats/dose were exposed once by oral gavage to Bioban TM P

- 1487 (>93% pure; batch No.: OJ0431LAN7 ) in corn oil at doses of 450 or 900 mg/kg based upon the results of a range

- finding test, in which mortality was observed in all females at ≥750 mg/kg and in one male at 750 mg/kg two days post

- dosing. Hepatocytes were isolated from the liver of 4 male Fisch er 344 rats per group by the two

- step in

situ perfusion at 2

- 4 or 14

- 16 hours post

- treatment. The vehicle used was corn oil.
There were no unscheduled deaths and all animals appeared normal after dosing and prior to perfusion at the 2

- to 4

- hour time

- p oint. Clinical signs of toxicity were observed prior to perfusion in animals at the 14

- to 16

- hour time

- point. No significant increases in mean net nuclear grains (NNG), or in the percent of nuclei with five or more net grains, were reported at any dose level at any time point. This was comparable to the solvent controls. The positive control elicited a clear positive response. There was no evidence of induction of unscheduled DNA synthesis in rat primary hepatocytes over the background.
This study is classified Acceptable / Non

- guideline

. (2) Bioban P

- 1487 ( 81% 4

- (2

- nitrobutyl)morpholine , 5% 4, 4’

- (2

- ethyl

- 2

- nitrotrimethylene)dimorpholine; Lot No.: 8K15

- D F 28 ) was assayed in another unscheduled DNA synthesis assay (MRID 41298503). Following preliminary cytotoxicity testing (range, 1x10

- 3 mL/mL down to 5x10

- 7 mL/mL), coverslip cultures of freshly perfused rat hepatocytes (male Sprague

- Dawley rats) were exposed to test substance, in quadruplicate per treatment dose, for 18 hours, followed by a further 18

- hour treatment with 10 μ Ci/mL tritiated

- thymidine ( 3 H

Tdr). Negative and positive controls were used. No significant increases in mean net nuclear grains (NNG) were reported at any dose level at any time point. This was comparable to the solv ent controls. It is concluded that Bioban p

- 1487 was no t g en o toxic in prom o ting UDS in rat hepatocyte cultures.
This study is classified Acceptable

. 

## Neurotoxicity

870.6200 Neurotoxicity Screening Battery
Adequacy of Database for Neurotoxicity: The da tabase for neurotoxicity is considered incomplete. There are no neurotoxicity studies in the agency’s hazard database. A neurotoxicity screening battery is anticipated to be required for registration review risk assessment, based on the currently registe red use in metalworking fluids for Bioban p

- 1487

.Page 37 of 60 

## Immunotoxicity

870.7800 Immunotoxicity Study Adequacy of Database for Immunotoxicity: The database for immunotoxicity is considered incomplete . There are no immunotoxicity studies in the agency’s hazard database. An immunotoxicity study is anticipated to be required for registration review risk assessment
, based on the currently registered uses for Bioban p

- 1487

. 

## Other Toxicological Effects

Metabolism and Pharmacokinetics
In a metabolism study ( MRID 48239101), 14 C

- BIOBANTM P

- 1487 and unlabeled BIOBANTM P

1487 (radiolabeled purity 90.2%, Lot No. 3587

- 027; unlabeled purity 94.6%, Lot No. UD1731LAD7) were administered to groups of four Sprague Dawley rats/sex/ treatment group at oral doses of 2.0 mg/k g (Group 1) or 50 mg/kg /day (Group 2), by rep eated oral doses of 2.0 mg/kg /day with unlabeled test material followed by a single oral dose of 2.0 mg/kg radiolabeled material (Group 5), or by dermal application of 2.0 mg/kg radiolabeled test material (Group 6). Groups 1, 2, and 6 were jugular cannulated for pharmaco kinetic analysis. Blood was collected from these rats at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours for Group 1 rats with additional collection at 96, 120, 144, and 168 hours for Groups 2 and 6. Urine and feces were collected up to 72 hours after treatment for Group 1 rats with additional collection of urine and feces up to 168 hours after treatment for Groups 2, 5, and 6. CO 2 was collected up to 72 hours after treat

ment for rats in Grou ps 1, 2, 5, and 6. At the end of the study, the rats were sacrificed and selec

ted tissues collected for radioactivity analysis. In addition to the above treatment groups, two addi tional groups of four Sprague Dawley rats/sex/dose were treat ed with 2.0 mg/kg test material (Groups 3 and 4). Group 3 rats were sacrificed at C max (0.5 hours after treatment as determined from Group 1 analysis) and blood and tissues collected. Group 4 rats were sacrificed at 1⁄2C max (8 hours after treatment as determined by G roup 1 analysis) and blood, urine, feces and tissues collected.
Following oral treatment with 14 C

- BIO BANTM P

- 1487, the test material was rapidly absorbed without any apparent lag time. Plasma concentrations peaked between 0.25

- 4 hours post

- dos e and were ~0.75 μg/g in rats treated orally with 2.0 mg/kg and ~10 μg/g in rats treated orally with 50 mg/kg. A bi

- modal increase in plasma concentrations was observed, particularly in high

- dose rats. The 14 C

- BIOBAN TM P

- 1487

- derived radioactivity declined in the p lasma in a bi

- phasic manner with faster e limination at the low dose group ( t 1⁄2α 6 hours; t 1⁄2 β ~ 35 hours), compar ed to those of the high dose group ( t 1⁄2α ~ 14 hours; t 1⁄2 β ~60 hours). The rates of uptake and elim ina tion (based on the plasma time course) were similar in males and females. Peak plasma con cen

trations were roughly dose

- proportional between high

- and low

- dosed animals (13

- to 17

- fold difference for males and females , respectively ). AUCs were essentially dose

- proportional ( a 23

- fold difference between high

- and low

- dose for males and a 25

- fold difference for females).

Most 14 C

- BIOBANTM P

- 1487 was eliminated in the urine. The radioactivity re covered in urine from orally dosed animals (Groups 1, 2, and 5) ranged from 77 % to 89% of the administeredPage 38 of 60 dose, and most (>90%) was excre ted within 24 hours of treat ment

. Less than 5% of the orally administered radioactivity was asso ciated with tissues for rats sacrificed >72 hours after treat

ment

. Based on the r adioac tivity recovered in th e urine and tissues at sacrifice from the various dose groups, it was estimated that between 83 % and 93% of the oral dose was systemically absorbed.
Peak plasma 14 C concentrations follo wing dermal application of 2 mg /kg test material were lower than those observed following oral treatment; and the time to C max was longer. R adio

activity in plasma peaked between 8 and 12 hours after treatment at a concentration of ~0.03 μ g /g plasma (
~ 4% C max of rats dosed orally with 2 mg/kg test material). Based on the r adio ac

tivity recovered in the urine, feces
, and tissues of dermally dosed rats, it was estimated that 27% and 38% of the applied dose was systemically absorbed in male and female rats, respec tively. Most of the radioactivity was recovered in the urine with ~20% and ~30% of the adminis tered dose excreted by males and females, respectively.

14 C

- BIOBANTM P

- 1487 was highly metabolized by both male and female rats following oral or dermal treatment

. No parent compound was identified in the urine or fece s. Morpholine repre

sented
~ 65% of the admin istered dose in the urine of the oral treatment groups and ~ 21% of the administered dose in urine following dermal treatment. It was the only metabolite identified in the feces of all treatment groups

. It acc ounted for an average of 6.7% of the admin istered dose in the feces of the oral treatment groups , and 1.7% of administered dose in the feces of dermally

treated rats. A minor urinary metabolite representing
~ 1.3% of the admin istered dose of rats in Groups 1 and 2, ~ 9.3% of the administered dose in the repeat dose Group 5, and
~ 0.5% of administered dose in rats from Group 6 was N

- methyl morpholine N

- oxide. The formation of this metabo lite was through the transient metabolite N

- methylmor pholine, whi ch was not detected in the urine.
This metabolism study in the Sprague Dawley rat is classified Acceptable/Guideline

.Page 39 of 60 Table A 2

– Toxicity Profile for Bioban P

- 1487

Guideline No./

Study Type MRID No./ Study Classification Dosing and Animal Information Results Subchronic Toxicity 870.3100 90

- day Oral (Rat) MRID 47394702 Acceptable/Guideline Purity 94

. 6 %

10 Crl:CD(SD) rats /sex/ dose
0, 5, 10, 2 5, or 50 mg/kg/d in corn oil, gavage , once daily, 7 days/wk, for 13 wks N OAEL = 5 mg/kg/d LOAEL = 10 mg/kg/d , based on ↓ body weight and body weight gain ( both ♂ and ♀ ), ↓ feed consumption ( ♂ ) and histopathology of the stomach , including inflammation, hyperplasia, hyperkeratosis and thickening of the nonglandular mucosa in ♂ and urinary bladder (mononuclear lymphoid cell aggregate s in the lamina propria of ♂ and ♀ ) 870.3100 90

- day Oral (Rat) MRID 49088901
In the Agency’s review Purity 83 %

10 F344/DuCrl r ats / sex/ d o se 0, 20, 6 0, or 12 5 mg/kg/d ( time

weighted average doses ♂ : 0, 1 1

. 7 , 4 5

. 9 , or 9 5.2 mg/kg/d; ♀ : 0, 1 1. 5 , 45

. 3 , or 92. 3 mg/kg/d) , in diet, for at least 90 days The study author concluded:

N OAEL male = 20 mg/kg/d (corresponding to test material intake of 11.7 mg/kg/d) N OAEL fem ale = 60 mg/kg/d (corresponding to test material intake of 45.3 mg/kg/d) , based on treatment

- related higher reticulocyte counts and cholesterol levels of ♂ at 60 mg/kg/d 870.30 50 28

- day Oral (Rat) MRID 49087501
In the Agency’s review Purity 8 3 %

5 F344/DuCrl r ats / sex/ d o se 0, 15, 50, or 150 mg/kg/day (time

- weighted average doses ♂ : 0, 8.82, 39.4, or 117 mg/kg/d ; ♀ : 0, 9.08, 39.3, or 114 mg/kg/d, in diet, for 29 days The study author concluded:

N OAEL = 50 mg/kg/d (corresponding to test material intake ♂ : 39.4 mg/kg/d and ♀ : 39.3 mg/kg/d ) , based on the decrements in body weights/body weight gains, feed consumption in ♂ and ♀ given 150 mg/kg/d, and the slightly higher serum cholesterol levels of ♂ given 150 mg/kg/day Non

- guideline (range

finding study) 28

- day Oral ( Dog ) MRID 47213801
In the Agency’s review Purity 9 4 .6%
2 Beagle dogs/ sex/ d o se
0, 2.5 , 1 0, or 25 mg /kg/d in corn oil, oral gavage, for at least 28 days NOAEL male = 10 mg/kg/d NOAEL female = 25 mg/kg/d , based

on the prominent incoordination of the hind limbs and the lesions of the urinary tract in one male given 25 mg/kg/d, and the vomiting and blood from the penis in the other male given 25 mg/kg/dPage 40 of 60 Guideline No./

Study Type MRID No./ Study Classification Dosing and Animal Information Results
870.3 1 50 90

- day Oral Subchronic (Dog ) MRID 4739470 3
In the Agency’s review Purity 9 4 .6%

2 Beagle dogs/ sex/ d o se
0, 2.5 , 1 0, or 25 mg /kg/d in corn oil, oral gavage, for at least 90 days NOAEL male = 10 mg/kg/d NOAEL female = 25 mg/kg/d , based

on the a lterations in the urinary bladder , including very or slight submucosa l hemorrhage, very slight or slight hyperplasia of the transitional epithelium, very slight or slight hyperplasia of the transitional epithelium, very slight or slight chronic inflammation of the submucosa or transitional epithelium, very slight or slight n ecrosis of individual transitional epithelial cells, and slight ulceration of the transitional epithelium
870.3250 90

- day Dermal Subchronic (Rat ) MRID 41618302/42440001
Acceptable/Guideline Purity 85%
20/sex/group
0 (deionized water), 30, 100, 300 (MRID 41619302), and 1000 mg/kg/d (MRID 42440001), 6 hrs/d, 5 days/wk
, for 13 wks LOAEL dermal ≤ 3 0 mg/kg/day ( low est dose tested [ L DT]), based on skin reactions (erythema and edema) observed at all dose levels tested NOAEL dermal not established

NOAEL systemic = 30 0 mg/kg/d LOAEL systemic = 1000 mg/kg/d
, based on ↓ body weight and chronic inflammation of the urinary bladder in both sexes 870.3465 90

- day inhalation Subchronic A subchronic inhalation study is not available for Bioban P

- 1487.

Developmental Toxicity 870.3700a Developmental Toxicity (Rat) MRID 41673801/41978802
Acceptable/Guideline Purity 7 9 %

2 5 /dose

0, 1 0, 3 0, or 10 0 mg/kg/d, GD 6

- 15 NOAEL maternal = 1 0 mg/kg/d LOAEL maternal = 3 0 mg/kg/d , based

on ↑ salivation, accompanied by significantly ↓ (p ≤ 0.05) body weight gain (and food consumption)

NOAEL developmental ≥ 10 0 mg/kg/d (highest dose tested [HDT]). LOAEL developmental not established

.Page 41 of 60 Guideline No./

Study Type MRID No./ Study Classification Dosing and Animal Information Results
870.3700b Developmental Toxicity (Ra bbi t) MRID 47865701
Acceptable/Guideline Purity 9 4

. 7 %

2 6 NZ white ra bbit s/group
0, 15 , 5 0 or 150 mg/kg/d, GD 7

- 27 NOAEL maternal = 5 0 mg/kg/d LOAEL maternal = 150 mg/kg/d , based

on significant (p < 0.05) ↓ in body weights, body weight gains, and food consumptions and ↑ in absolute and relative liver weights

NOAEL developmental = 50 mg/kg/d LOAEL developmental = 1 50 mg/kg/d
, based on significant (p < 0.05) ↓ in fetal weights and delayed ossification of the hyroid, pubis, and talus Reproduction Toxicity 870.3800 Reproduction MRID 48126001
Acceptable/Guideline Purity 9 4 .6%

30 Crl:CD rats /sex/dose ; 8 pups/litter (4 per sex, unless not possible) for both F 1 & F 2 and 1 litter/successful mating female

0 , 1, 5, or 20 mg/kg /d , oral gavage NOAEL parental = 5 mg/kg/d LOAEL parental = 20 mg/kg/d , based

on lowered mean body weights, reduced body weight gains, reduced food consumption (and/or food efficiency), and histopathological changes seen in the non

- glandular area of the stomach

NOAEL offspring ≥ 20 mg/kg/d (highest dose tested [HDT]); LOAEL parental not established

NOAEL reproductive ≥ 20 mg/kg/d (HDT); LOAEL reproductive not established Chronic Toxicity 870.4100 Chronic Toxicity A chronic toxicity study is not available for Bioban P

- 1487

. Carcinogenicity 870.4200 Carcinogenicity A carcinogenicity study is not available for Bioban P

- 1487

. Mutagenicity 870.5100 Bacterial reverse mutation test MRID 41619301
Acceptable/Guideline Purity 85%
TA1535, TA1537, TA98, or TA100

0.007

- 7.5 μg/plate with and without S9 metabolic activation Negative

870.5300 Mammalian cell gene mutation test MRID 45655301
Acceptable/Guideline Purity 81 % mouse lymphoma cells (L5178Y TK +/

- )

0.25

- 30 μg/mL ± S9; for a period of 4 hours Posi tive (+S9)Page 42 of 60 Guideline No./

Study Type MRID No./ Study Classification Dosing and Animal Information Results
870.5300 Mammalian cell gene mutation test MRIDs 41298502 [main study] /41567901 [supplemental study]
Acceptable Purity 81 %
Chinese hamster ovary (CHO) cells

1x10

- 8

- 1x10

- 4 mL/mL for 8 hours
, - S9 ; 5x10

- 8

- 5x10

- 4 mL/mL for 2 hours
, +S9 Negative

870.5385 In vivo mammalian bone marrow chromosome aberration test (mouse) MRID 47005501
Acceptable/Guideline Purity 8 1 %

6 male mice
0, 125, 250, or 500 (12 mice) mg/kg Negative

870.5550 ( I

n vivo ) Unscheduled DNA synthesis MRID 46965903
Acceptable/ Non

Guideline Purity > 9 3 % Rat hepatocyte cells
0, 4 5 0 , or 90 0 mg/kg , 5 male rats, oral gavage Negative

870.5550 Unscheduled DNA synthesis MRID 41298503

A cceptable Purity 81 %

Rat (male) hepatocyte cells

5x10

- 7

– 1x10

- 3 m L/mL Negative

MetabolismPage 43 of 60 Guideline No./

Study Type MRID No./ Study Classification Dosing and Animal Information Results
870.7485 M etabolism and Pharmacokinetics MRID 48239101
Acceptable/Guideline Purity 90 .2% (radiolabeled); 9 4.6 % (non

- radiolabeled)

4 SD rats/sex/ group

O ral doses 2.0 mg/kg (Group 1) or 50 mg/kg (Group 2), by rep eated oral doses of 2.0 mg/kg /day with unlabeled test material followed by a single oral dose of 2.0 mg/kg radiolabeled test material (Group 5), or by dermal application of 2.0 mg/kg radiolabeled test material (Group 6) . A ddition ally, two addi tional groups of four Sprague Dawley rat s/sex/dose were treat ed with 2.0 mg/kg test material (Groups 3 and 4) ; Group 3 rats were sacrificed at C max (0.5 hours after treatment as determined from Group 1 analysis) and blood and tissues collected ; Group 4 rats were sacrificed at 1⁄2C max (8 hours aft er treatment as determined by Group 1 analysis) and blood, urine, feces and tissues collected

. 14 C

- BIOBANTM P

- 1487 was rapidly absorbed (estimated 83%

- 93%) following oral administration. Plasma concentrations peaked between 0.25

- 4 hours post

- dose and w ere ~0.75 and ~10 μg/g in rats treated orally with 2.0 and 50 mg/kg, respectively. A bi

- modal increase in plasma concentrations was observed, particularly in high

- dose rats. The 14 C

BIOBANTM P

- 1487

- derived radioactivity declined in the plasma in a bi

- phas ic manner with faster elimination at the low dose group ( t 1⁄2α 6 hours; t 1⁄2β ~ 35 hours), compar ed to those of the high dose group ( t 1⁄2α ~14 hours; t 1⁄2β ~60 hours). The rates of uptake and elim ina tion (based on the plasma time course) were similar in males a nd females. Peak plasma con cen

trations were roughly dose

- proportional between high

- and low

- dosed animals (13

- to 17

- fold difference for males and females, respectively). AUCs were essentially dose

- proportional (a 23

- fold difference between high

- and low

- dose for males and a 25

- fold difference for females). Most 14 C

- BIOBANTM P

- 1487 was eliminated in the urine (77%

- 89%).

It was estimated that 27% and 38% of the applied dose was systemically absorbed in male and female rats, respec tively
, following dermal application of 2 mg/kg test material. Peak plasma 14 C concentrations were lower than those observed following oral treatment; the time to C max was longer. Most of the radioactivity was recovered in the urine with ~20% and ~30% of the adminis tered dose excreted by males and females, respectively.

14 C

- BIOBANTM P

- 1487 was highly metabolized by both male and female rats following oral or dermal treatment. No parent compound was identified in the urine or feces. Morpholine repre sented ~65% of the admin istered dose in the urine of the oral treatment groups and ~21% of the administered dose in urine following dermal treatment. It was the only metabolite identified in the feces of all treatment groups.Page 44 of 60 Reference s for Mammalian Toxicity

MRID

000 94994 Goldenthal, E.I.; Wazeter, F.X.; Dean, W.P. (1973) Acute Inhalation Toxicity Study (LC 50 ) in Albino Rats: 267

- 009; Report No. PLR

- 11. (Unpublished study received Jan 14, 1981 under 271

- 30; prepared by International Research and Development C orp., sub

- mitted by International Minerals & Chemical Corp., Terre Haute, Ind.; CDL:244383

- F)

. 00104805 Wilbur, S. (1978) P

- 1487 Skin Sensitization: SW78/11. (Unpublished study received Apr 25, 1979 under 271

- 30; submitted by Inter

- national Minerals & Ch emical Corp., Terre Haute, IN; CDL: 238693

- A)

. 41298501 Desai, L. (1989) Ames Bacterial/microsomal Plate Incorporation Assay: Bioban P

- 1487 Antimicrobial Agent: Project Number 89G

- 0093. Unpublished study prepared by Toxikon Corp. 12 p.

41298502 Desai, L. (1989) Chromosome Aberrations in Chinese Hamster Ovary (CHO) Cells: Bioban P

- 1487 Antimicrobial Agent: Lab Project Number 89G

- 0095. Unpublished study prepared by Toxikon Corp. 15 p.

41298503 Desai, L. (1989) Unscheduled DNA Synthesis in Rat Liver Primary C ell Cultures: Bioban P

- 1487 Antimicrobial Agent: Lab Project Number 89G

- 0094. Unpublished study prepared by Toxikon Corp. 12 p.

41567901 Desai, L. (1989) Chromosome Aberration in Chinese Hamster Ovary (CHO) Cells: Lab Project Number: 89G

- 0095. Unpublished study prepared by Toxikon Corp. 6 p.

41619301 Lynn, S. (1990) Ames Mutagenicity Assay: Bioban P

- 1487: Lab Project Number: 90G/0526. Unpublished study prepared by Toxikon Corp. 14 p.

41619302 Griffin, T. (1990) Subchronic 90

- Day Dermal Toxicity Study of Bio

- ban P

- 1487 in Rats: Lab Project Number: 890202. Unpublished study prepared by Coulston International, Inc. 311 p.

41677601 Kreuzmann, B. (1990) Acute Oral Toxicity in Rats

- Median Lethal Dos

- age Determination: Lab Project Number: 90

- 4091

- 21 (A). Unpub

- l ished study prepared by Hill Top Biolabs, Inc. 16 p.

41677602 Kreuzmann, B. (1990) Acute Dermal Toxicity in Rabbits

-- Median Leth

- al Dosage Determination: Lab Project Number: 90

- 4091

- 21 (B). Unpublished study prepared by Hill Top Laboratories, Inc. 109 p.

41677603 Kreuzmann, B. (1990) Primary Eye Irritation Study in Rabbits: Bioban P

- 1487: Lab Project Number: 90

- 4091

- 21 (D). Unpublished study prepared by Hill Top Laboratories, Inc. 14 p.Page 45 of 60 41677604 Kreuzmann, B. (1990) Primary Skin Irritation Study in Rabbits : Bio

- ban P

- 1487: Lab Project Number: 90

- 4091

- 21 (C). Unpublished study prepared by Hill Top Laboratories, Inc. 14 p.

41810801 Kreuzmann, J. (1990) Acute Dermal Toxicity in Rabbits

- Median Lethal Dosage Determination: Lab Project Number: 90

- 4091

- 21 B. Unpu b

- lished study prepared by Hill Top Biolabs, Inc. 84 p.

41810802 Kreuzmann, J. (1990) Primary Skin Irritation Study in Rabbits: Lab Project Number: 90

- 4091

- 21 C. Unpublished study prepared by Hill Top Biolabs, Inc. 31 p.
41949403 Paika, I. (1991) Chromoso me Aberrations in Chinese Hamster Ovary (CHO) Cells: Lab Project Number: 90

- G

- 0536. Unpublished study prepared by Toxikon Corp. 56 p.

41949404 Paika, I. (1991) Unscheduled DNA Synthesis in Rat Liver Primary Cultures: Lab Project Number: 90

- G

- 0535. Unpublis hed study prepared by Toxikon Corp. 63 p.

41978801 Griffin, T. (1991) Supplemental Data to MRID No. 41619302: A Subchronic 90

- Day Dermal Toxicity Study of Bioban P

- 1487 in Rats. Unpublished study prepared by Coulston International, Inc. 5 p

. 42440001 Griff in, T. (1992) Subchronic 90

- day Dermal Toxicity Study of Bioban P

- 1487 in Rats (Limit Test): Lab Project Number: 910302. U npublished study prepared by Cou l st on Research, Inc. 228 p.

43558901 Fitzgerald, G (1995) Acute Oral Toxicity Study (in Rats): Bioban P

- 1487: Final Report: Lab Project Number: 94G

- 1937. Unpublished study prepared by Toxikon Corp. 18 p.

45655301 Linscombe, V.; Schisler, M.; Treadway, K. (2002) Evaluation of Bioban P

- 1487 in the Mouse Lymphoma (L5178Y TK+/

- ) Forward Mutation Assay: Lab Pro ject Number: 011110. Unpublished study prepared by The Dow Chemical Company. 39 p.

46965903 Cifone, M. (2002) In Vivo/In Vitro Unscheduled DNA Synthesis in Rat Primary Hepatocyte Cultures at Two Time points with a Dose Range finding Assay with Bioban P

- 1487. Project Number: 23633/0/494/OECD, 021036. Unpublished study prepared by Covance Laboratories, Inc. 52 p.

47005501 Spencer, P. (2003) Evaluation of Bioban p

- 1487 in the Mouse Bone Marrow Micronucleus Test. Project Number: 020146. Unpublished study p repared by The Dow Chemical Company. 74 p.

47213801 Stebbins, K.; Dryzga, M. (2007) P

- 1487 Antimicrobial: 28

- Day Oral Gavage Toxicity Study in Beagle Dogs. Project Number: 061185. Unpublished study prepared by The Dow Chemical Co. 131 p.Page 46 of 60 47394702 Thomas, J.; Andrus, A. (2007) Bioban P

- 1487 Biocide: 90

- day Oral Gavage Toxicity Study in CRL:CD(SD) Rats. Project Number: 061155. Unpublished study prepared by Dow Chemical Co. 459 p.

47394701 Durando, J. (2007) Acute Inhalation Toxicity Study in Rats

- Limit Tes t: Bioban P

- 1487. Project Number: P330/DOW, 21611, 070127. Unpublished study prepared by Product Safety Laboratories. 35 p.

47394702 Thomas, J. and Andrus, A.K. (2007) Bioban P

- 1487TM Biocide: 90

- day oral gavage toxicity study in CRL:CD(SD) rats. Toxicology & Environmental Research and Consulting, t he Dow Chemical Company, Midland, Michigan 48674, Laboratory Project Study ID 061155, June 19, 2007. Unpublished.

47394703 Stebbins, K.; Brooks, K. (2007) P

- 1487 Antimicrobial: 90

- day Oral Gavage Toxicity Study in Beagle Dogs. Project Number: 071059. Unpublished study prepared by Dow Chemical Co. 266 p.

47865701 Carney, E.; Marshall, V.; Ellis

- Hutchings, R. (2009) BIOBAN P

- 1487 Antimicrobial: Oral Gavage Developmental Toxicity Study in New Zealand White Rabbits. Pr oject Number: 081134. Unpublished study prepared by The Dow Chemical Company. 334 p.

48126001 Knapp, J. (2008) An Oral Gavage Two

- Generation Reproductive Toxicity Study of Bioban P

- 1487 Biocide in CRL:CD(SD) Rats: Final Report. Project Number: WIL/410006, 070157. Unpublished study prepared by WIL Research Laboratories, Inc. 3056 p.

48239101 Rick, D.; Clark, A.; Markham, D.; et al. (2008) Bioban P

- 1487 Antimicrobial Pharmacokinetics and Metabolism in Crl:CD(SD) Rats. Unpublished study prepared by The Dow Che mical Company. 122 p.

49087501 Thomas, J.; Murray, J.; Hukkanen, R. (2012) Bioban P

- 1487: 28

- Day Dietary Toxicity Study in F344/DuCrl Rats. Project Number: 101196. Unpublished study prepared by Dow Chemical Company. 252p.

49088901 Thomas, J.; Murray, J. (2 012) Bioban P

- 1487: 90

- Day Dietary Toxicity Study in F344/DuCrl Rats. Project Number: 111065. Unpublished study prepared by The Dow Chemical Company. 332p.Page 47 of 60 

# Appendix B Environmental Fate

Environmental Fate and Transport Properties of Bioban P

- 1487

Water and Sediment
Hydrolysis

A h ydrolysis stud y (MRID 43494001) w as performed on both derivatives of the Bioban P

- 1487 mixture: Bioban P

- 1447 (Ingredient I) and Bioban P

- 1490 (Ingredient II)

. The study consisted of two individual studies for each active ingr edient in the product at 25 o C

. For P

- 1490, the significant degradates formed were the active ingredient P

- 1447 and the degradate 2

- nitro

- 1

- butene after 10 minutes of hydrolysis. Bi oban P

- 1447 hydrolyzed with half

- lives of 22 hour s at pH 5, 45 hours at pH 7, and 4 6 hours at pH 9 in a study conducted for up to 73 hours. For P

1447, the significant ( present at >10 % of applied parent compound) degradates were 2

- nitro

- 1

- butanol, 1

- nitro

- propane, and 2

- nitro

- 1

- butene, all of which wer e either stable in the study or demonstrated enough persistence to be present throughout the wastewater treatment process.
Table B1. Hydrolysis Results for P

- 14 4 7

Degradate formation and decline (maximum formation at end of study unless stated) Active ingredient Half

- life (hours) 2

- nitro

- 1

- butanol 2

- nitropropane 2

- nitro

- 1

- butene

P

- 1447 22 (pH 5) 31 % 19 % 36 % (32

- 48 hours), decline to 22 % (end of study) 46 (pH 7) 21 % 18 % 19 % (6 hours), decline to 4 % (end of study) 46 (pH 9) 9 % 19

- 20 % 15 % Table B2. Hydrolysis Results for P

- 1490

Degradate formation and decline (maximum formation at end of study unless stated) Active ingredient Half

- life ( minutes ) P

- 1447 2

- nitro

- 1

- butene

P

- 14 90 <10 (pH 5) 15 % 64 %

<10 (pH 7) 61 % 28 %Page 48 of 60 <10 (pH 9) 40 % 25 %

Aqueous Photolysis
The registrant submitted a photodegradation in water study (MRID 47285303) for P

- 1487. The half

- lives were 14 hours for the irradiated treatment and 19 .4 hours for the dark control , with a dark

- control adjusted half

- life of 50 hours. Hydrolysis degraded P

- 1487 2.6X faster than photolysis. Due to the rapid hydrolysis of P

- 1447 and P

- 1490 , these two chemicals are not expected to persist long enough for aqueous photolysis to be an important competing environmental fate process. The study did not quantify the formation percentages of the degradates 2

- nitropropane, 2

- nitro

- 1

- butanol and 2

- nitro

- 1

- butene , but did state that the degradates formed in the dark controls, which represent hydrolysis, were the same as those in the irradiated treatments. There is no record of review of this study, which will be formally

reviewed in Registration Review.

Octanol

- Water Partition Coefficient
Log Kow values can indicate the potential for aquatic animals to bioaccumulate a chemical and for the potential for sorption of a chemical by activated sludge. The estimated log Kow is 0.18 for 4

- (2

- nitrobutyl)morpholine (P

- 1447) and

- 0.54 for 4,4

- (2

- ethyl

- 2

- nitromethylene) dimorpholine (P

- 1490) . The estimated log Kow values for the degrada tes of 4

- (2

- nitrobutyl)morpholine are 0.87 for 2

- nitropropane,

- 0.101 for both 2

- nitro

- 1

- butanol and 2

- nitro

1

- butene (Epi

- Suite 4.11) . Based on these low estimated values, bioaccumulation by aquatic animals and sorption by activated sludge would not be e xpected to be important environmental process es

. Aerobic Aquatic Metabolism

No information was found on the aerobic aquatic metabolism potential of P

- 1447 and its hydrolytic degradates . Since these chemicals appear to be highly soluble in water (Table E1 , Appendix E) , data are needed to determine whether or not they are persistent enough for aquatic organisms to be exposed to them.

A na erobic Aquatic Metabolism
Based on the estimated log Kow values for P

- 1447 and its hydrolytic degradates (Table E1 , Append ix E) , these chemicals are not expected to be likely to have a very high potential to sorb to suspended and benthic sediment . As a result, anaerobic aquatic metabolism data are not needed for these chemicals.

Soil
Soil Leaching/Adsorption/Desorption Batch EquilibriumPage 49 of 60 P

- 1487 is not expected to sorb strongly to soil and sediments based on t he measured log Koc of 1.7 (Koc of 50 ml/g) . As a result, any P

- 1487 present in water will be associated with water and not soil and sediment (MRID 4590 0901)

. Aerobic and Anaerobic Soil Metabolism
Data on aerobic and anaerobic soil metabolism are not required for P

- 1487 and its degradates because environmental pathways of release to soil are not expected from uses in metalworking fluids and fuels

. In the event of a spi ll, the high mobility (MRID 45900901) of P

- 1487 and its degradates (MRID 43494001) preclude the soil compartment as a potential sink. T he rapid hydrolysis of P

- 1487 and its degradates (MRID 43494001) is expected to prevent surface water or ground water con tamination from any potential exposure from spills.
Fate and Transport in WWTP 835.1110. Activated Sludge Sorption Isotherm (ASSI)

Data on sorption to activated sludge is not required because of the low log Kow values for the two morpholine derivatives of P

- 1487 and their degradates , which precludes the potential for sorption to activated sludge as a significant transport pathway. The highest estimated log Kow value was 0.18 for P

- 1447. 850.3300: Activated Sludge Respi ration Inhibition (ASRI)
The registrant submitted an ASRI study (MRID 47005503) in which an IC 50 value of 306 mg/L was determined for Bioban P

- 1487. The study appears to be valid, based on the IC 50 of 21 mg/L for the reference compound, 3,5

- dichlorophenol , and low variability in the controls (<15 %). There is no record of review for this study, which will be formally

- reviewed during registration review

. Biodegradation in a WWTP
In a ready biodegra da bility study (MRID 47005502), Bioban P

- 1487 was not foun d to be readily biodegradable in a 28

- day study . It did not degr ade >60% within the 10

- day period after the start of biodegradation process

. Since n o ASRI and WWTP biodegradability data were found for the degradates, 2

- n itropropane, 2

- nitro

- 1

- butanol, and 2

- nitro

- 1

- butene
, ASRI and WWTP biodegradability data are expected to be required for these degradates. Results of the ASRI studies will determine whether a ready biodegradability study or a simulation test will be required.Page 50 of 60 Reference s for Enviro nmental Fate of Bioban P

- 1487

MRID 43494001

. Burke, B, 1994. Hydrolysis of 4

- (2

- nitrobutyl) morpholine and 4,4’

- (2

- ethyl

2

- nitromethylene) dimorpholine. Lab Project # PRT

- 23

- 4ANN

- 01

- PRT

- 23

- 4ANN

- 01

- 03. Unpublished study prepared by Plant Research Technolog ies, Inc. 228 pages

. MRID 45900901

. Gonsoir, SJ, Rivard, MA, and Stock, MK, 2002. Estimating Soil Koc for a series of Biocides by HPLC Using OECD Method # 121. Biocides TS and D, The Dow Chemical Company, Midland, Michigan

. MRID 47005502

. Gonsoir, S, Sto ck, M, and Rivard, M. 2002: Evaluation of Ready Biodegradability of Bioban P

- 1487 using OECD Method 301F: Manometric Respiratory Test; Project# 011131. Unpublished Study Prepared by Dow Chemical Company, 31 pages

. MRID 47005503. Gonsior, S.; Rivard, M.; S tock, M. (2002) Activated Sludge, Respiration Inhibition Test (OECD 209) for Bioban P

- 1487. Project Number: 011177. Unpublished study prepared by The Dow Chemical Company. 16 p.

MRID 47285303. Ponte, M. (2007) Aqueous Photolysis of Bioban P

- 1487 Biocide Un der Artificial Sunlight. Project Number: 1625W, 070058. Unpublished study prepared by The Dow Chemical Co., 80 p.

U.S. EPA. 2012. EPI

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

. U.S. EPA. September, 2007. Reregistration Eligibility Decision for Bioban P

- 1487. EPA 739

- R

- 07

- 005.Page 51 of 60 

# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Organisms
Birds, acute oral and dietary

The available acute

- oral and dietary studies categorize technical

- grade Bioban P

- 1487 as being no more than slightly toxic to birds. No additional avian toxicity data are anticipated to be needed. The guidelines (850.2100, 850.2200) are satisfied.

Avia n Acute

- oral and Dietary Toxicity

Test Species Test Material (% ai) Toxicity Toxicity Category EPA Study ID

Mallard ( Anas platyrhynchos ) 90 LD50 >1000 mg ai/kg bw Slightly toxic at most 93055001 Supplemental

90 LC50 >3692 ppm Slightly toxic at most 93055003 Supplemental Northern bobwhite ( Colinus virginianus ) 90 LC50 >3692 ppm Slightly toxic at most 93055002 Supplemental



### Toxicity to Aquatic Organisms
Freshwater Fish, acute
The available acute toxicity studies categorize technical

- grade BIOBAN P

- 1487 as being highly toxic to freshwater fish. The guideline (850.1075) for acute toxicity testing is satisfied for the TGAI

. Data anticipated to be needed for any or all three degr adates (2

- nitropropane, 2

- nitro1

- 1butanol and/or 2

- nitro

- 1

- butene) unless the registrant can demonstrate from environmental fate data that each degradate will not occur in wastewater discharged into the aquatic environment.
Acute Toxicity to Freshwater Fis h
Test Species Test Material (% ai) 96

- h LC50 (mg ai/L) Toxicity Category EPA Study ID
Rainbow Trout ( Oncorhynchus mykiss) 90 0.75 Highly toxic 93055005 Acceptable Bluegill ( Lepomis macrochirus ) 90 0.83 Highly toxic 93055004 AcceptablePage 52 of 60 Freshwater Invertebrates, acute The one available study categorizes technical

- grade BIOBAN P

- 1487 as being moderately acutely toxic to freshwater invertebrates. The guideline (850.1010) for acute toxicity testing is satisfied for the TGAI. Data are anticipated to be needed for any or all three degradates (2

- nitropropane, 2

- nitro1

- 1butanol and/or 2

- nitro

- 1

- butene) unless the registrant can demonstrate from environmental fate data that each degradate will not occur in wastewater discharged into the aquatic environmen t. Acute Toxicity to Freshwater Invertebrates
Test Species Test Material (% ai) 48

- h EC50 (mg ai/L) Toxicity Category EPA Study ID
Water flea ( Daphnia magna) 94.6 3.23 Moderately toxic 47285301 Acceptable

Estuarine/Marine Fish and Invertebrates, acute

No data are available. Because BIOBAN P

- 1487 may reach the estuarine/marine environment from discharges from WWTPs, acute toxicity data are anticipated to be needed. Acute toxicity studies anticipated to be needed for the TGAI include tests for a fish sp. (850.1075), a bivalve sp. (850.1025 or 850.1055), and one additional invertebrate sp. (850.1035). Data also are anticipated to be needed for any or all three degradates (2

- nitropropane, 2

- nitro1

- 1butanol a nd/or 2

- nitro

- 1

- butene) unless the registrant can demonstrate from environmental fate data that each degradate will not occur in wastew ater discharged into the estuarine/marine environment.
Fish and Aquatic Invertebrates, chronic

No chronic data are availa ble. Because parent Bioban P

- 1487 degrades rapidly, any significant chronic exposure in waste water discharge would be to one or more degradates (2

- nitropropane, 2

- nitro1

- 1butanol and/or 2

- nitro

- 1

- butene ) . If the outstanding environmental fate studies id entify any degradates likely to occur and persist in waste water discharge waters, chronic data will be expected to be needed for one fish species (850.1400) and one invertebrate species (850.1300 or 850.1350)

. T esting sh ould be done with the most sensiti ve species (either freshwater or estuarine/marine) as determined from the results of the acute toxicity tests (acute EC50 freshwater invertebrates; acute LC50 freshwater fish; LC50/EC50 estuarine/marine species).
Aquatic Plants
Toxicity data are available for the green algae. Because that study shows that the EC50 is less than 1 mg ai/L, additional studies are triggered. To support the TGAI, Tier II testing is anticipated to be needed with a vascular species (850.4400), freshwater and marine dia toms (850.4500), and cyanobacteria (850.4550). Data also are anticipated to be needed for any or all three degradates (2

- nitropropane, 2

- nitro1

- 1butanol and/or 2

- nitro

- 1

- butene) unless the registrantPage 53 of 60 can demonstrate from environmental fate data that each degradate will not occur in wastewater discharged into the aquatic environment. Toxicity to Aquatic Plants
Test Species Test Material (% ai) Toxicity (mg ai/L) Toxicity Category EPA Study ID Green algae ( Selanastrum capricornutum ) 90 EC50 = 0.352 NOAEC = 0.049 NA 47005504 Acceptable

Benthic Invertebrates
Sediment toxicity tests for benthic invertebrates (850.1735, 850.1740) are not anticipated to be needed. The available environmental fate data indicate that BIOBAN P

- 1487 will partition into the water column (K oc = 3.4 and 12.4 L/kg) and will not accumulate in aquatic sediments.Page 54 of 60 Ecotoxicity References:

93055001 Trueblood, A. (1990) Angus Chemical Company Phase 3 Summary of MRID 00083017. BIOBAN P

- 1487: Single Oral Dose LD50 in Mallard Duck: Project No. 170

- 103. Prepared by Wildlife International, LTD. 13 p.

93055002 Trueblood, A. (1990) Angus Chemical Company P hase 3 Summary of MRID 00069609. BIOBAN P

- 1487: Eight

- Day Dietary LC50 in Bobwhite Quail: Project No. 170

- 101. Prepared by Wildlife International. 13 p.

93055003 Trueblood, A. (1990) Angus Chemical Company Phase 3 Summary of MRID 00083018. BIOBAN P

- 1487: Eight

- Day Dietary LC50 in Mallard Duck: Project No. 170

- 102. Prepared by Wildlife International. 12 p.

83017 Fink, R.; Beavers, J.B.; Brown, R.; et al. (1980) Fi nal Report: Acute Oral LD50

-- Mallard Duck: Project No. 170

- 103. (Unpub

- lished study, including submitter summary, received Jan 14, 1981 under 271

- 30; prepared by Wildlife International, Ltd. and Wash

- ington College, submitted by International Minerals & Chemical Corp., Terre Haute, Ind.; CDL:244373

- B)

. 69609 Fink, R.; Beavers, J.B.; Brown, R.; et al. (1980) Final Report: Eight

- day Dietary LC50

-- Bobwhite Quail: Project No. 170

- 101. (Unpublished study, including submitted summary and letter dated Apr 29, 1980 from C.P. Bouchard to C. Parekh, received Jan 14, 1981 under 271

- 30; prepared by Wildlife International, Ltd. and Washington College, submitted by International Minerals & Chemi

- cal Corp., Terre Haute, Ind., CDL:244373

- D)

. 83018 Fink, R.; Beavers, J.B.; Brown, R.; et al. (1980) Final Report: Eight

- day Dietary LC50

-- Mallard Duck: Project No. 170

- 102. (Un

- published study, including submitter summary and letter dated Apr 29, 1980 from C.P. Bouchard to C. Parekh, received Jan 14, 1981 under 271

- 30; pre pared by Wildlife International, Ltd. and Washington College, submitted by International Minerals & Chemi

- cal Corp., Terre Haute, Ind.; CDL:244373

- C)

. 69610 Griffen, J.; Thompson, C.M. (1980) Acute toxicity of Bioban P

- 1487 to Bluegill Sunfish (~Lepomis macrochirus~): Static Renewal Acute Bioassay Report # 25061. (Unpublished study, including submitter summary and letter dated Apr 29, 1980 from C.P. Bou

- chard to C. Parekh, received Jan 14, 1981 under 271

- 30; prepared by Analytical Bio Chemistry Laborato ries, Inc., submitted by International Minerals & Chemical Corp., Terre Haute, Ind.; CDL: 244373

- E)

. 69611 Griffen, J.; Thompson, C.M. (1980) Acute Toxicity of Bioban P

- 1487 to Rainbow Trout (Salmo gairdneri): Static Renewal Acute Bioassay Report # 25145. (Unpublished study, including submitter summary and letter dated Apr 29, 1980 from C.P. Bouchard to C. Pare kh, received Jan 14, 1981 under 271

- 30; prepared byPage 55 of 60 Analytical Bio Chemistry Laboratories, Inc., submitted by International Minerals & Chemical Corp., Terre Haute, Ind.; CDL:244373

- F)

.

93055004 Trueblood, A. (1990) Angus Chemical Company Phase 3 Summary of MRID 00069610. BIOBAN P

- 1487: Acute Toxicity Effects on Bluegill Sunfish Ninety

Six Hour LC 50: Project No. 25061. Prepared by Analytical Bio

- Chemical Labs. Inc. 12 p.
93055005 Trueblood, A. (1990) Angus Chemical Company Phase 3 Summary of MRID 00069 611. BIOBAN P

- 1487: Acute Toxicity Effects on Rainbow Trout Ninety

- Six Hour LC50: Project No. 25145. Prepared by Analytical Bio

- Chemical Labs. Inc. 11 p. 47005504 Kirk, H.; Staley, J.; McClymont, E.; et al. (2002) Bioban P

- 1487: Growth Inhibition Test wi th the Freshwater Green Alga, Selenastrum capricornutum Printz. Project Number: 021001. Unpublished study prepared by The Dow Chemical Company. 45 p. 47285301 Marino, T.; Najar, J.; Arnold, B. (2007) Bioban P

- 1487 Antimicrobial: An Acute Toxicity Study wi th the Daphnid, Daphnia magna . Project Number: 071054. Unpublished study prepared by The Dow Chemical Co., 43 p.Page 56 of 60 

# Appendix D Screening Level Down

- the

Drain Analysis

No screening

- level Down

- the

- Drain analysis was performed for this case since all uses for this case are industrial uses. Results from the Down

- the

- Drain module of E

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

- the

- drain to domestic wastewater treatment facilities. Such results are not applicable f or releases to surface water from industrial uses.Page 57 of 60 

# Appendix E Product Chemistry

The Biob an P

- 1487 product chemistry information is summar ized in Table E1 and Table E2 contains the product chemistry information for the degradates of P

- 1487.

Table E1

– Product Chemi stry of Bioban P

- 1487

Guideline No. Parameter Ingredient I: 4

- (2

- nitrobutyl) Morpholine (P

1447) Ingredient II: 4,4’

- (2

- ethyl

- 2

- nitromethylene)dimor pholine (P

- 1490) Source (MRID unless

specified)

830.1800 Enforcement analytical method Gas Chromatography and Reverse phase HPLC Gas Chromatography and Revers Phase HPLC 41995101C

830.6302 Color Yellow to brown Yellow to brown 41995101C 830.6303 Physical State Liquid Liquid 41995101C

830.6304 Odor Mild fish like odor characteristics of amines Mild fish like odor characteristics of amines 41995101C

830.6313 Stability Indefinitely stable at room temperature Indefinitely stable at room temperature 41995101C
830.7000 pH 9.5

- 10.0 9.5

- 10.0 41995101

830.7050 UV Visible absorption Sorption below 210 nm (acid and neutral)

and below 275 nm (basic) Sorption below 210 nm (acid and neutral) and below 275 nm (basic) 48511302

830.7220 Boiling point ( o C) 199

- 225 o C 199

- 215 o C 41995101 830.7300 Density 1.075 g/cc 1.075 g/cc 41995101

830.7550 Octanol

- water partition coefficient at 25 o C (Log K ow ) 0.18

- 0.54 EPI Suite / EPWEB 4.1
830.7840 Solubility in water (mg/L) 11 ,000 m g/L 11 ,000 m g/L 41995101

830.7950 Vapor pressure (mmHg) 20

- 43 mm Hg at 90 0 C 20

- 43 mm Hg at 90 0 C 41995101 Estimated:

7.5 x 10

- 3 mm Hg at 25 0 C Estimated: 5.07 x 10

- 6 mm Hg at 25 0 C EPI Suite/EPWEB 4.1 Henry’s Law (atm m 3 mol

- 1 ) 1.1 x 10

- 10 1.51 x 10

- 1 5 EPI Suite /EPWEB 4.1

o C = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury; Henry’s Law in atm m 3 mol

- 1Page 58 of 60 Table E2: Estimated Physical/Chemical Properties of Bioban P

- 1487 Degradates Based on EPI

Suite 4.11

P/Chem and Environmental Fate Property Degradate 2

- Nitropropane

CAS# 79

- 46

- 9 2

- Nitro

- 1

- Butanol CAS# 609

- 31

- 4 2

- Nitro

- 1

- Butene CAS# 2783

- 12

- 2 Structure

MP/BP ( o C) 101 (BP) 28 (MP) 28 ( MP ) Molecular weight (g/mol) 89.9 119.2 101.12

Log Kow 0.87

- .101

- 0.101 Solubility in water (mg/L) 8 , 18 0 50 , 3 00 50 ,300
Ready Biodegradability NO Yes Yes

Half

- life in air (days) 84 10.4 10.4
Log Koc 1.65 0.73 0.73 % removal in WWTP 7.5 1.85 1.85
Vapor pressure (mm Hg) 15.5 0.056 0.43
Henry’s Law (atm

m 3 mol

- 1 ) 2.2 x 10

- 4 1.7 x 10

- 7 1.1 x 10

- 6Page 59 of 60 References for Product Chemistry of Bioban P

- 1487
MRID 41995101. Bollimer, A, 1990. Product chemistry for Bioban P

- 1487. Unpublished study prepared by Angus Chemical Company, 28 pages

. MRID 48511302. O'Connor, B.; Woolley, S. (2011) Bioban P

- 1487: Determination of Physico

Chemical Properties. Project Number: 41005027, 24P/2010/036, GLP/2011/030. Unpublished study prepared by Harlan Laboratories, Ltd. 73 p.

U.S. EPA. 2012. EPI

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

.Page 60 of 60 

# Appendix F Comments Received Concerning the Preliminary Work Plan

On March 30, 2015, EPA opened a 60

- day public comment period on the preliminary work plan (PWP) for the registration review of Bioban P

- 1487. The comment period ended on May 29, 2015. During the public comment period the agency received one submission related to the Bioban P

- 1487 PWP. Table F 1 below lists the submitter.

Table F 1. Submitters of Comments on the “Bioban P

- 1487 Preliminary Workplan”
FIFRA Endangered Species Task Force (FESTF)

Comment

- The FIFRA Endangered Species Task Force (FESTF) submitted a comment noting that it has data that will assist the agency in conducting an endangered species risk assessment for Bioban P

- 1487.

EPA Response

- The agency thanks FESTF for its comment and will consider this information as it conducts the registration review and makes its registration review decisions.