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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 Ross
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TERMS, ABBREVIATIONS AND SYMBOLS

AD Antimicrobials Division

A.I. or a.i. active ingredient

aPAD acute population adjusted dose 

ASRI activated sludge respiration inhibition

atm-m3

/mole atmospheric pressure-cubic meter per mole

BCF bioconcentration factor 

°C degrees Celsius

CAS Chemical Abstracts Service 

CFR Code of Federal Regulations 

CHO Chinese hamster ovary

CMA Chemical Manufacturers Association

CO2 carbon dioxide

COC concentration-of-concern

cPAD chronic population adjusted dose 

DCI data call-in

EC50 median (or 50 percent) effect concentration

EC05 5 percent effect concentration

ECOTOX ECOTOXicology

EDI estimated daily intake

EDSP Endocrine Disruptor Screening Program 

E-FAST Exposure and Fate Assessment Screening Tool

EPI Suite Estimation Program Interface Suite

EPA Environmental Protection Agency 

FDA Food and Drug Administration 

FFDCA Federal Food, Drug, and Cosmetic Act

FGD flue-gas desulfurization

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FQPA Food Quality Protection Act 

FWP Final Work Plan

g/mol grams per mole

GLN guideline number

HPV high production volume

IDS Incident Data System 

Koc organic carbon normalized soil-water partition coefficient

Kd soil-water partition coefficient

Kow octanol-water partition coefficient

LC50 median (or 50 percent) lethal concentration

LD50 median (or 50 percent) lethal dose

LOAEC lowest-observed-adverse-effect-concentration 

LOEC lowest-observed-effect-concentration

LOAEL lowest-observed-adverse-effect-level

Log Kow logarithm of the octanol-water partition coefficient

μg microgram

ml/g milliliter per gram

mg/kg milligram per kilogram

mg/kg/day milligram per kilogram per day 

mg/L milligram per liter

mm Hg millimeter of mercury

MOE margin of exposure 
Page 5 of 60

MRID Master Record Identification Number

MRL maximum residue limit 

N/A not applicable 

nm nanometers

NOAEC no-observed-adverse-effect-concentration

NOAEL no-observed-adverse-effect-level

OCSPP Office of Chemical Safety and Pollution Prevention

OECD Organization for Economic Co-operation and Development

OPP Office of Pesticide Programs

PAD population adjusted dose

PAI pure active ingredient

PDM Probabilistic Dilution Model

% percent

PC Code Pesticide Chemical Code

PCF pounds per cubic foot

pH power of hydrogen or power of the concentration of the hydrogen ion

PHED Pesticide Handler’s Exposure Data

PIS primary irritation score

pKa power of the acid dissociation constant or negative base-10 logarithm of the acid 

dissociation constant of a solution

ppb parts per billion 

ppm parts per million

PWP Preliminary Work Plan

QSAR quantitative structure-activity relationship

RED Reregistration Eligibility Decision

SAR structure activity relationship

SF safety factor

SSTS Section Seven Tracking System

TEP typical end-use product

TGAI technical grade active ingredient

TMDL total maximum daily loads

UF uncertainty factor

UV/VIS ultraviolet/visible light absorption

% w/w percent weight per weight.

WP wettable powder

WWTPs wastewater treatment plants
Page 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 Anticipated 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 Exposure 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 Toxicology Profile............................................................................................... 28

Appendix B Environmental Fate ............................................................................................. 47
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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 P1487 RED...................................................................................................................................... 16

Table 9 – Existing Toxicological Endpoints for Bioban P-1487.................................................. 17

Table 10 – Available Ecological Effects Endpoints..................................................................... 23
Page 8 of 60

1 Introduction

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

agency”) Final Work Plan (FWP) for Bioban P-1487. The FWP document explains what EPA's 

Office of Pesticide Programs (OPP) knows about Bioban P-1487, highlighting anticipated data 

and assessment needs, identifying the types of information that would be especially useful to the 

agency in conducting the review, and providing an anticipated timeline for completing Bioban P1487’s review.

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The agency intends, by sharing this information in the 

docket, to inform the public of what it knows about Bioban 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 Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States generally must be registered by the USEPA 

based on scientific data showing that they will not cause unreasonable risks to human health or 

the environment when used as directed on product labeling. The registration review program is 

intended to make sure that, as the ability to assess risk evolves and as policies and practices 

change, all registered pesticides continue to meet the statutory standard of no unreasonable 

adverse effects to human health or the environment. Changes in science, public policy, and 

pesticide use practices will occur over time. Through the registration review program, the agency

periodically reevaluates pesticides to make sure that as change occurs, products in the 

marketplace can be used safely. Information on this program is provided at 

http://www2.epa.gov/pesticide-reevaluation.

The agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The agency

will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

agency’s opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. 

1.2 Updates to the Work plan

Since the publication 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 Table 7 to remove data requirement 875.2400 and to correct data requirement 

number 875.1100 to 875.1200 and 875.1200 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 during 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-2014-0802. Tables 1 

and 2 below summarize the issues relevant to this registration review case and the anticipated 

registration review schedule.

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

Review: 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 details)

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 Postapplication Yes September 

2007 Updated See Table 7

Residential Handler No N/A None None

Residential Post 

Application - Incidental 

Oral and Dermal 

No N/A None None

Residential Post 

Application - Inhalation No N/A None None

Aggregate No N/A None None

Cumulative No N/A None None
Page 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 details)

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 and data needs for Registration Review. For data called in through the postReregistration 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 Preliminary 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 Proposed 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 ingredients. 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 100802

CAS Number 2224-44-4 1854-23-5

Molecular Formula C8H16N2O3 C13H25N3O4

Molecular Weight (grams/mole) 208 287

Molecular Structure

4-(2-nitrobutyl)morpholine;

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.

Parameter

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 oC (Log 

Kow)

0.18 -0.54 EPI Suite 4.11

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

830.7950 Vapor pressure (mmHg)

20-43 mm Hg (90 oC) 20-43 mm Hg (90 oC) 41995101

7.58 x 10-3 (25 oC) 5.07 x10-6 (25 oC) EPI Suite 

(version 4.1)

None Henry’s Law (atm m3 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 m3 mol-1

According to a hydrolysis study of Bioban P-1487 (MRID 43494001), the primary residues in 

the environment are expected to be P-1447 and degradates 2-nitropropane, 2-nitro-1-butanol and 

2-nitro-1-butene. Table 5 presents the estimated 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)

8,180 50,300 50,300

Log Koc 1.65 0.73 0.73

Vapor pressure (mm 

Hg)

15.5 0.056 0.43

Henry’s Law (atm 

m3 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 applied 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 materials 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 of 

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), ~177,000 kg of Bioban P1487 was estimated to be produced in 2005. 

1.6 Regulatory History

The first product containing Bioban P-1487 was registered on June 7, 1972. Currently, Bioban P1487 consists of a mixture of two active ingredients: compound I (P-1447), 4-(2-nitrobutyl) 

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 April 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 additive 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 28, 2015.
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1.7.2 Ecological

There are no Bioban P-1487 ecological incidents reported in OPP’s Incident Data System (IDS)

as of January 28, 2015.

2 Anticipated Data Needs

Several studies were required following 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 (see Section 4.1). The agency anticipates reviewing data received in response to the postRED DCI as well as data that will be required 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 

Exposure 

Scenario

835.31101,2

835.3220

835.3240

835.3280

Biodegradability in 

WWTP Degradates3 12

Environmental 

fate and 

transport

Metalworking 

fluids/ 

industrial 

coatings, 

preservative in 

plastic 

products, 

fuel/oil storage 

tank bottom 

water additive

Waste water 

treatment plant

(WWTP)

850.33002

Activated sludge 

respiration inhibition 

(ASRI)

Degradates3 12

Environmental 

fate and 

transport

WWTP

835.4300 Aerobic aquatic 

metabolism TGAI 12

Environmental 

fate and 

transport

All

870.3465 90-day inhalation 

toxicity TGAI 12 Human Health Exposure All

870.62006 Neurotoxicity 

screening battery7 TGAI 24 Human Health Exposure

Metalworking 

fluids

870.7800 Immunotoxicity TGAI 12 Human Health 

Exposure All

850.1010 Freshwater 

invertebrates, acute Degradates3 12 Aquatic organisms Ecological

850.4500

Algal toxicity, 

freshwater and 

saltwater diatoms

TGAI and 

Degradates3 12 Aquatic plants Ecological

850.4550 Cyanobacteria 

toxicity

TGAI and 

Degradates3 12 Aquatic organisms Ecological

850.4400 Aquatic plant 

toxicity, Lemna sp.

TGAI and 

Degradates3 12 Aquatic organisms Ecological

850.1075

Freshwater and 

estuarine/marine 

fish, acute toxicity

TGAI and 

Degradates3, 5 12 Saltwater 

organisms Ecological

850.1025

or

850.1055

Oyster, shell 

deposition

or

Bivalve embryo 

larval toxicity

TGAI and 

Degradates3 12 Saltwater 

organisms Ecological

850.1035 Mysid, acute toxicity TGAI and 

Degradates3 12 Saltwater organisms Ecological

850.1400 Fish, early life stage Degradates4 24 Aquatic 

organisms Ecological

850.1300 Aquatic invertebrate, 

life cycle Degradates4 24 Aquatic organisms Ecological

875.1200 Dermal exposure EP 24 Occupational 

handler

Metalworking 

fluids

Fuel

Liquid pour

875.1400 Inhalation exposure EP 24 Occupational

handler

Metalworking 

fluids

Fuel

Liquid pour
Page 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 

Exposure 

Scenario

875.1700 Product use EP 12 Occupational 

handler

Metalworking 

fluids

Fuel

Liquid pour

Liquid pump

875.2500 Inhalation exposure8 EP 24

Occupational 

handler

Post-application

Metalworking 

fluids Liquid pour

Liquid pump

875.2700 Product use EP 12 Occupational 

post-application

Metalworking 

fluids

Occupational postapplication 

(machinist)

875.2800 Description of 

human activity EP 12 Occupational 

post-application

Metalworking 

fluids

Occupational postapplication 

(machinist)

1An ASRI study (MRID 47005503) was conducted on P-1487 and the IC50 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 test. Although a 

ready biodegradability study (MRID 47005502) was conducted, based on the results, it was determined that P-1487 was not 

readily 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. 

2An ASRI study is required for the degradates, 2-nitropropane, 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 equal to 20 mg/L, then either the (i)Biodegradation in Activated 

Sludge Study or (ii) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the Porous Pot Test would 

be anticipated to be required. If the ASRI test EC50 is greater than 20 mg/L, then the 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 Activated 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 Study 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 discharged into 

the aquatic environment or, for chronic studies, that the degradate will not persist in surface water.

4Testing should be done with the most sensitive species (either freshwater or estraurine/marine) as determined from the results of 

the acute toxicity tests (EC50 freshwater invertebrate, acute LC50/EC50 estuarine/marine species).

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

species.

6Acute (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).

8Air 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-Ins 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 agency anticipates the need to conduct a human health risk assessment for Bioban P-1487.

The agency will evaluate the data required by the RED DCI. Also, the agency anticipates the 

need to require additional data for the registration review of Bioban P-1487, based on the 

currently registered uses 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 agency 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 

the registration review. All available information, including existing and additionally required 

toxicology studies and valid scientific literature, will be considered in establishing 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 interspecies 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

 aPAD1 = 0.01 mg/kg/day

Chronic Dietary

(all populations)

NOAEL(maternal) = 10 UF = 300 (10x interspecies 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 weight 
Page 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

 cPAD2 = 0.003 mg/kg/day

Non-Dietary Risk Assessments

Incidental Oral

Short-Term 

(1-30days) and 

IntermediateTerm

(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 interspecies 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

IntermediateTerm

(1-6 months)

NOAEL (systemic) 

=300 

MOE = 100 (10x interspecies 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 interspecies 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 interspecies 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 weight 
Page 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 = acute, 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 Antimicrobials Division Toxicity Committee (ADTC) assumes

that the exposure databases (dietary food, drinking water, and residential) are complete and that the risk assessment for each 

potential exposure scenario includes all metabolites and/or degradates of concern and does 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 residue 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 assessment for Bioban P-1487

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

cannot rule out the potential for exposure of humans to 4-(2-nitrobutyl)morpholine (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 uncertainties with respect to 

the residues of concern in drinking water, including the magnitude of residues, mammalian 

toxicities, persistence 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 will be used 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 anticipates the need to revise the occupational handler assessment conducted in support of 

the 2007 RED (D338283). Occupational handler dermal and inhalation exposures to Bioban P-
Page 20 of 60

1487 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, the agency 

anticipates the need for a new occupational handler risk assessment 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 repeated dose inhalation toxicity data.

• The toxicological endpoint was based on an oral NOAEL.

• Bioban P-1487 is a potential sensitizer and a severe irritant.

The agency anticipates the need to revise inhalation and dermal exposure using surrogate data

available in the literature to estimate potential risk from exposure to mists and aerosols for

machinists 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 would need air monitoring data to assess inhalation postapplication 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. The machinist assessment MOEs in the RED were above a target 

MOE of 300. However, the 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 monitoring 

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

EPA 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 and 
Page 21 of 60

inhalation) exposures in an assessment, but there are no residential 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, therefore, 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 chemicals, 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 incorporated 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 must be evaluated. 

The agency has not previously conducted 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 agency to determine potential acute 

and chronic risks to aquatic organisms exposed to Bioban P-1487 and/or any of its degradates 

that are transported from treatment sites into the aquatic environment. The risk assessment will 

allow the agency 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 agency will consult with the U.S. Fish and Wildlife Service and/or National Marine 

Fisheries Services (the Services), as appropriate. 

4.1 Environmental Fate Assessment

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. 

Degradates formed included 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-nitropropane, 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. The measured log Koc of 

1.7 (50 L/kg) indicates that it preferentially partitions to water in the presence of soil (MRID 

45900901). The degradates are also expected to have limited sorption to soil. Of the three 

degradates, 2-nitropropane had the highest estimated Log Koc, 1.65 (45 L/kg) (Table 5).

Based on the Henry’s law constants (HLC) of approximately 10-10 and 10-15 atm m3 mol-1 for P1490 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 m3

mol-1 followed by 2-nitro-1-butene with an HLC of approximately 10-6 atm m3 mol-1and 

approximately 10-7 atm m3 mol-1for 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 Effects 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 indicate 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 IC50 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 microorganisms

to be inhibited. No ASRI 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 readily 

biodegradable based on degradation of <60 % within a 10-day period after the onset of 

biodegradation. No test data on biodegradability in wastewater treatment were found 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 microorganisms, the agency 

anticipates requiring ASRI and WWTP biodegradation studies for each of 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-ethyl-2-nitromethylene)dimorpholine are as 
Page 23 of 60

industrial preservatives incorporated into metalworking cutting fluids, industrial coatings, plastic 

products, and as fuels/oil storage tank bottom water additives (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 wastewater treatment plants that treat wastewater from these uses.

The agency has created conceptual models for potential routes of environmental exposure which 

are included in “Conceptual Models for Environmental Exposure Pathways of Antimicrobial 

Pesticides” (EPA-HQ-OPP-2014-0638-0002) found at www.regulations.gov in docket EPA-HQOPP-2014-0638. For metalworking cutting fluids, refer to slide 18. For 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 treatment 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 such 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 plants. 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 

surface 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 Bioban 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 Bioban P-1487 to aquatic and 

terrestrial nontarget organisms. All available ecotoxicity endpoints, data requirements, and data 

gaps are presented in Appendix C. OPP uses the most sensitive of the endpoints for assessing 

risks. The endpoints currently selected for Bioban P-1487 (TGAI) are provided in Table 10. 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 Reference
Page 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-nitrobutyl)morpholine and 4,4’-(2-ethyl-2-nitromethylene)dimorpholine and/or

their degradates to surface water, the 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 

aquatic 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) environmental 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) concentrations 
Page 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, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its reregistration decision, for Bioban P-1487, EPA reviewed these 

data and existing hazard database. However, as required by FFDCA section 408(p), Bioban P1487 is subject to the endocrine screening part of the Endocrine Disruptor Screening Program 

(EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

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

Under FFDCA section 408(p), the agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals 

identified for EDSP screening was published on June 14, 20131 and includes some pesticides 

scheduled for registration review and chemicals found in water. Neither of these lists should be 

construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website.2

 1 See http://www.regulations.gov/#!documentDetail;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 improve 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 liquid 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-ethyl2-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) 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 Under 

Artificial Sunlight. Project Number: 1625W, 070058. Unpublished study prepared by The Dow 

Chemical Co., 80 p.

Kline. 2005. Kline Biocides Report for 2004/2005 for Bioban P-1487.

U.S. EPA. 2012. EPI-Suite 4.11. http://www.epa.gov/oppt/exposure/pubs/episuitedl.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 Toxicology Profile

Acute Toxicity for Product Labeling 

Adequacy of Database 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 rats (MRID 

43558901) and 652 mg/kg (combined) in rabbits (MRID 41677601). Catalepsy and tremors 

were observed at a dose of 500 mg/kg in the rat study, and at 800 mg/kg, lethargy, nasal 

discharge, and convulsions were observed. The acute dermal LD50 was determined to be of 420 

mg/kg (combined) in rabbits (Toxicity Category II) (MRIDs 41677602/41810801). In an old

acute inhalation study (MRID 00094994), utilizing an one-hour exposure, estimated a median 

lethal concentration of 746 mg/L (595-936 mg/L) in male rats, in addition to significant 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 with 

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 discoloration and distention of the intestines at 

gross necropsy were also observed. The study author concluded a LC50 of greater than 2.33 

mg/L. Bioban P-1487 is corrosive to the eyes (Toxicity Category I) and severely irritating to the 

skin (Toxicity Category II). 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 LD50 =620 mg/kg 

(combined)

III

870.1100 Acute oral, rabbit

(Purity 92%)

41677601 LD50 =625 mg/kg 

(combined)

III

870.1200 Acute dermal, rabbit

(Purity 92%)

41677602

(duplicate 41810801)

LD50 =420 mg/kg 

(combined)

II

870.1300 Acute inhalation, rat

(Purity 94.6%)

47394701 LC50 >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 applicable
Page 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 toxicity 

studies in rats (MRIDs 41619302/41978801 and 42440001). A brief summary of the reviewed 

studies is provided below.

Based on the currently registered uses for Bioban P-1487 and its high volatility, a route-specific 

subchronic inhalation toxicity study in rodents 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 47394702), Bioban P-1487 [4-(2-Nitrobutyl) 

morpholine; 94.6% 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 

week for 13 weeks. 

All male rats in the 50 mg/kg/day dose group were sacrificed in extremis on Day 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 males 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, reduced mean body weights and body weight 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 weight 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 of 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.

Gross 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 histopathological 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 the 
Page 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 the 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 the 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 in the lamina propria of males and females). 

The NOAEL is 5 mg/kg/day for male and female rats.

This study is classified Acceptable/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/kg/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 consumption 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/day that corresponded to an actual time weighted average 
Page 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 toxicity 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 study 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, the 

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) was 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 47394703), 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 tract 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, consisted of: very or slight submucosal

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 necrosis of individual transitional 

epithelial cells, and slight ulceration of the transitional epithelium......The no-observed-effect 

level (NOEL) was 10 mg/kg/day for both sexes.” The final conclusion of the study will be 

available once the agency’s comprehensive review is completed.

870.3250 Subchronic (90-day dermal) Toxicity – Rat

In a 90-day dermal toxicity study (MRIDs 41619302/41978801), groups 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 

slightly 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 consumption 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. 

The systemic LOAEL is 1000 mg/kg/day, based on decreased body weight and chronic 
Page 32 of 60

inflammation of the urinary bladder in both sexes; the systemic NOAEL is 300 mg/kg/day. The 

dermal LOAEL 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 Database for 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) available for 

Bioban P-1487.

870.3700a Prenatal Developmental Toxicity (Gavage) Study – Rat

In a developmental toxicity study in rats (MRIDs 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 gestation 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 control) 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 animals 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 was 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/day, based on increased salivation, accompanied 

by significantly reduced (p ≤ 0.05) body weight gain (and food consumption); the maternal 

NOAEL is 10 mg/kg/day. The developmental toxicity NOAEL is determined to be 100 

mg/kg/day (the highest dose tested), and the developmental toxicity LOAEL is not established.

This study is classified Acceptable/Guideline.

870.3700b Prenatal Developmental Toxicity (Gavage) Study – Rabbit

In a developmental toxicity study in rats (MRID 47865701), groups of 26 time-mated female 

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, body 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 observed, 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 

ossification 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 Database for Reproductive Toxicity: The database for reproductive toxicity is 

adequate. There is a 2-generation reproductive toxicity study for Bioban P-1487 (MRID 

48126001), submitted in response to the post-RED data-call-in (DCI). 

In a 2-generation reproduction study (MRID 48126001), BiobanTM P-1487 (94.6% a.i., lot # 

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 F1 and F2 generations, there were 8 pups per litter (4 per sex, 

unless not possible) and 1 litter per successful mating female. 

Results showed evidence of systemic toxicity in both sexes of P parental and F1 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, reduced food consumption (and/or food 

efficiency), and histopathological changes seen in the non-glandular area of the stomach. The 

parental systemic NOAEL is 5 mg/kg/day.

There were no treatment-related effects in F1 or F2 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 reproductive NOAEL is 

20 mg/kg/day in both sexes, based on a lack of reproductive effects in either sex of offspring. 

Therefore, a reproductive LOAEL is not established.

This study is Acceptable/Guideline.

Chronic Toxicity 

Adequacy of Database for Chronic Toxicity: The database for chronic toxicity is considered 

incomplete. There are no chronic toxicity studies 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 Database for Carcinogenicity: The database for carcinogenicity is considered 

incomplete. There are no carcinogenicity studies in the agency’s hazard database; these studies 

are anticipated 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 post-RED 

DCI.

Mutagenicity 

Adequacy of Database for Mutagenicity: 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 summaries of these studies are provided below.

Gene Mutation

(1) In an Ames test (MRID 41619301), 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 dose 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 level (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 Bioban

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 (80.86% 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 test. 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 frequency 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 compounds. 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/mL 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, Bioban P-1487 did not 

induce chromosomal aberrations with or without S9.

This study is classified Acceptable.

(2) In a CD-1 mice bone marrow micronucleus assay (MRID 47005501), 6 male mice/dose were 

treated by single oral gavage on two consecutive days with Bioban P-1487TM (4-(2-

nitrobutyl)morphine [80.86%]; 4,4’(2-ethyl-2-nitromethylene)dimorphine [4.12%], Batch No.: 

OJ0431LAN) in corn oil at doses of 0, 125, 250, or 500 mg/kg based upon the results of a rangefinding test in which significant mortality 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 in 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 control 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-1487TM is considered negative in this mice bone marrow 

micronucleus assay under the 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 BiobanTM 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 Fischer 344 rats per group by the two-step insitu 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-point. 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-DF28) 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 μCi/mL tritiated-thymidine (3HTdr). 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 

solvent controls. It is concluded that Bioban p-1487 was not genotoxic in promoting UDS in rat 

hepatocyte cultures.

This study is classified Acceptable.

Neurotoxicity

870.6200 Neurotoxicity Screening Battery

Adequacy of Database for Neurotoxicity: The database 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 registered 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), 14C-BIOBANTM P-1487 and unlabeled BIOBANTM P1487 (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/kg (Group 1) or 50 mg/kg/day (Group 2), by repeated 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 pharmacokinetic 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. CO2 was collected up to 72 hours after treatment for rats in Groups 1, 2, 5, and 6. At the end of the study, the rats were sacrificed and selected tissues collected for radioactivity analysis. In addition to the above treatment groups, two 

additional groups of four Sprague Dawley rats/sex/dose were treated with 2.0 mg/kg test material 

(Groups 3 and 4). Group 3 rats were sacrificed at Cmax (0.5 hours after treatment as determined 

from Group 1 analysis) and blood and tissues collected. Group 4 rats were sacrificed at 1⁄2Cmax (8 

hours after treatment as determined by Group 1 analysis) and blood, urine, feces and tissues 

collected.

Following oral treatment with 14C-BIOBANTM P-1487, the test material was rapidly absorbed 

without any apparent lag time. Plasma concentrations peaked between 0.25 - 4 hours post-dose

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 14C-BIOBANTM P-1487-derived radioactivity declined in the plasma in a bi-phasic

manner with faster elimination at the low dose group (t1⁄2α 6 hours; t1⁄2β ~35 hours), compared to 

those of the high dose group (t1⁄2α ~14 hours; t1⁄2β ~60 hours). The rates of uptake and elimination 

(based on the plasma time course) were similar in males and females. Peak plasma concentrations 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 14C-BIOBANTM P-1487 was eliminated in the urine. The radioactivity recovered in urine 

from orally dosed animals (Groups 1, 2, and 5) ranged from 77% to 89% of the administered 
Page 38 of 60

dose, and most (>90%) was excreted within 24 hours of treatment. Less than 5% of the orally 

administered radioactivity was associated with tissues for rats sacrificed >72 hours after treatment. Based on the radioactivity recovered in the 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 14C concentrations following dermal application of 2 mg/kg test material were 

lower than those observed following oral treatment; and the time to Cmax was longer. Radioactivity in plasma peaked between 8 and 12 hours after treatment at a concentration of ~0.03 

μg/g plasma (~4% Cmax of rats dosed orally with 2 mg/kg test material). Based on the radioactivity 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, respectively. 

Most of the radioactivity was recovered in the urine with ~20% and ~30% of the administered 

dose excreted by males and females, respectively. 

14C-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 represented ~65% of the administered 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 accounted for an average of 6.7% of the administered dose in 

the feces of the oral treatment groups, and 1.7% of administered dose in the feces of dermallytreated rats. A minor urinary metabolite representing ~1.3% of the administered 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-methylmorpholine N-oxide. The formation of 

this metabolite was through the transient metabolite N-methylmorpholine, which was not 

detected in the urine. 

This metabolism study in the Sprague Dawley rat is classified Acceptable/Guideline.
Page 39 of 60

Table A2 – 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, 25, or 50 mg/kg/d in corn 

oil, gavage, once daily, 7 

days/wk, for 13 wks

NOAEL = 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 

aggregates in the lamina propria of ♂ 

and ♀)

870.3100

90-day Oral (Rat)

MRID 49088901

In the Agency’s review

Purity 83%

10 F344/DuCrl rats/sex/dose

0, 20, 60, or 125 mg/kg/d (timeweighted average doses ♂: 0, 

11.7, 45.9, or 95.2 mg/kg/d; ♀: 0, 

11.5, 45.3, or 92.3 mg/kg/d), in 

diet, for at least 90 days

The study author concluded:

NOAELmale = 20 mg/kg/d

(corresponding to test material 

intake of 11.7 mg/kg/d)

NOAELfemale = 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

870.3050

28-day Oral (Rat)

MRID 49087501

In the Agency’s review

Purity 83%

5 F344/DuCrl rats/sex/dose

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:

NOAEL = 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 (rangefinding study)

28-day Oral (Dog)

MRID 47213801

In the Agency’s review

Purity 94.6%

2 Beagle dogs/sex/dose

0, 2.5, 10, or 25 mg/kg/d in corn 

oil, oral gavage, for at least 28 

days

NOAELmale = 10 mg/kg/d

NOAELfemale = 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/d
Page 40 of 60

Guideline No./

Study Type

MRID No./

Study Classification Dosing and Animal Information Results

870.3150

90-day Oral 

Subchronic (Dog)

MRID 47394703

In the Agency’s review

Purity 94.6%

2 Beagle dogs/sex/dose

0, 2.5, 10, or 25 mg/kg/d in corn 

oil, oral gavage, for at least 90 

days

NOAELmale = 10 mg/kg/d

NOAELfemale = 25 mg/kg/d, based 

on the alterations in the urinary 

bladder, including very or slight 

submucosal 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 necrosis 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

LOAELdermal ≤ 30 mg/kg/day

(lowest dose tested [LDT]), based on 

skin reactions (erythema and edema) 

observed at all dose levels tested

NOAELdermal not established

NOAELsystemic = 300 mg/kg/d

LOAELsystemic = 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 79%

25/dose

0, 10, 30, or 100 mg/kg/d, 

GD 6-15

NOAELmaternal = 10 mg/kg/d

LOAELmaternal = 30 mg/kg/d, based 

on ↑ salivation, accompanied by 

significantly ↓ (p ≤ 0.05) body 

weight gain (and food consumption)

NOAELdevelopmental ≥ 100 mg/kg/d

(highest dose tested [HDT]).

LOAELdevelopmental not established.
Page 41 of 60

Guideline No./

Study Type

MRID No./

Study Classification Dosing and Animal Information Results

870.3700b

Developmental 

Toxicity (Rabbit)

MRID 47865701

Acceptable/Guideline

Purity 94.7%

26 NZ white rabbits/group

0, 15, 50 or 150 mg/kg/d, 

GD 7-27

NOAELmaternal = 50 mg/kg/d

LOAELmaternal = 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

NOAELdevelopmental = 50 mg/kg/d

LOAELdevelopmental = 150 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 94.6%

30 Crl:CD rats/sex/dose;

8 pups/litter (4 per sex, unless not 

possible) for both F1 & F2 and 1 

litter/successful mating female

0, 1, 5, or 20 mg/kg/d, oral 

gavage

NOAELparental = 5 mg/kg/d

LOAELparental = 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

NOAELoffspring ≥ 20 mg/kg/d

(highest dose tested [HDT]);

LOAELparental not established

NOAELreproductive ≥ 20 mg/kg/d

(HDT);

LOAELreproductive 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

Positive (+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 81%

6 male mice

0, 125, 250, or 500 (12 mice)

mg/kg

Negative

870.5550

(In vivo) Unscheduled 

DNA synthesis 

MRID 46965903

Acceptable/NonGuideline

Purity >93%

Rat hepatocyte cells

0, 450, or 900 mg/kg, 5 male rats,

oral gavage

Negative

870.5550

Unscheduled DNA 

synthesis

MRID 41298503

Acceptable

Purity 81%

Rat (male) hepatocyte cells

5x10-7 – 1x10-3 mL/mL

Negative

Metabolism
Page 43 of 60

Guideline No./

Study Type

MRID No./

Study Classification Dosing and Animal Information Results

870.7485

Metabolism and 

Pharmacokinetics

MRID 48239101

Acceptable/Guideline

Purity 90.2% (radiolabeled); 

94.6% (non-radiolabeled)

4 SD rats/sex/group

Oral doses 2.0 mg/kg (Group 1) 

or 50 mg/kg (Group 2), by 

repeated 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). Additionally, two additional 

groups of four Sprague Dawley 

rats/sex/dose were treated with 

2.0 mg/kg test material (Groups 3 

and 4); Group 3 rats were 

sacrificed at Cmax (0.5 hours after 

treatment as determined from 

Group 1 analysis) and blood and 

tissues collected; Group 4 rats 

were sacrificed at 1⁄2Cmax (8 hours 

after treatment as determined by 

Group 1 analysis) and blood, 

urine, feces and tissues collected.

14C-BIOBANTM P-1487 was rapidly 

absorbed (estimated 83% - 93%) 

following oral administration. Plasma 

concentrations peaked between 0.25 - 4 

hours post-dose and were ~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 14CBIOBANTM P-1487-derived radioactivity 

declined in the plasma in a bi-phasic 

manner with faster elimination at the low 

dose group (t1⁄2α 6 hours; t1⁄2β ~35 hours), 

compared to those of the high dose group 

(t1⁄2α ~14 hours; t1⁄2β ~60 hours). The rates 

of uptake and elimination (based on the 

plasma time course) were similar in 

males and females. Peak plasma concentrations 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 14C-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, respectively, 

following dermal application of 2 mg/kg 

test material. Peak plasma 14C 

concentrations were lower than those 

observed following oral treatment; the 

time to Cmax was longer. Most of the 

radioactivity was recovered in the urine 

with ~20% and ~30% of the administered 

dose excreted by males and females, 

respectively. 

14C-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 represented 

~65% of the administered 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

References for Mammalian Toxicity

MRID

00094994 Goldenthal, E.I.; Wazeter, F.X.; Dean, W.P. (1973) Acute Inhalation Toxicity 

Study (LC50) in Albino Rats: 267-009; Report No. PLR- 11. (Unpublished study 

received Jan 14, 1981 under 271-30; prepared by International Research and 

Development Corp., 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 & 

Chemical 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 Cell 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- lished 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. Unpub- 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) Chromosome 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. Unpublished 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 Griffin, T. (1992) Subchronic 90-day Dermal Toxicity Study of Bioban P-1487 in 

Rats (Limit Test): Lab Project Number: 910302. Unpublished study prepared by 

Coulston 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 Project 

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 prepared 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 Test: 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, the 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. Project 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 Chemical 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. (2012) 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 hydrolysis study (MRID 43494001) was 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 ingredient in the product at 25 oC. 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. Bioban P-1447 hydrolyzed with half-lives of 22 hours at 

pH 5, 45 hours at pH 7, and 46 hours at pH 9 in a study conducted for up to 73 hours. For P1447, 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 were either stable in the study or 

demonstrated enough persistence to be present throughout the wastewater treatment process. 

Table B1. Hydrolysis Results for P-1447

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-1490 <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 formallyreviewed 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 degradates of 4-(2-

nitrobutyl)morpholine are 0.87 for 2-nitropropane, -0.101 for both 2-nitro-1-butanol and 2-nitro1-butene (Epi-Suite 4.11). Based on these low estimated values, bioaccumulation by aquatic 

animals and sorption by activated sludge would not be expected to be important environmental 

processes.

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. 

Anaerobic Aquatic Metabolism

Based on the estimated log Kow values for P-1447 and its hydrolytic degradates (Table E1, 

Appendix 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 Equilibrium
Page 49 of 60

P-1487 is not expected to sorb strongly to soil and sediments based on the 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 45900901). 

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 spill, the high mobility (MRID 45900901) of P-1487 and its 

degradates (MRID 43494001) preclude the soil compartment as a potential sink. The rapid 

hydrolysis of P-1487 and its degradates (MRID 43494001) is expected to prevent surface water 

or ground water contamination 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 Respiration Inhibition (ASRI)

The registrant submitted an ASRI study (MRID 47005503) in which an IC50 value of 306 mg/L 

was determined for Bioban P-1487. The study appears to be valid, based on the IC50 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 biodegradability study (MRID 47005502), Bioban P-1487 was not found to be readily 

biodegradable in a 28-day study. It did not degrade >60% within the 10-day period after the start 

of biodegradation process. Since no ASRI and WWTP biodegradability data were found for the 

degradates, 2-nitropropane, 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

References for Environmental Fate of Bioban P-1487

MRID 43494001. Burke, B, 1994. Hydrolysis of 4-(2-nitrobutyl) morpholine and 4,4’-(2-ethyl2-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) 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 Under 

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. 

Avian Acute-oral and Dietary Toxicity

Test Species Test Material

(% ai) Toxicity ToxicityCategory

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 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 environment.

Acute Toxicity to Freshwater Fish

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

Acceptable
Page 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 environment.

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 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 estuarine/marine environment.

Fish and Aquatic Invertebrates, chronic

No chronic data are available. 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 identify 

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). Testing should be done with the most sensitive 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 diatoms 

(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 registrant 
Page 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 (Koc = 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 Phase 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) Final 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; prepared 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 Laboratories, 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. Parekh, received Jan 14, 1981 under 271-30; prepared by 
Page 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 NinetySix 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 

00069611. 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 with 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 with 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-theDrain 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 for releases to surface 

water from industrial uses.
Page 57 of 60

Appendix E Product Chemistry

The Bioban P-1487 product chemistry information is summarized in Table E1 and Table E2 

contains the product chemistry information for the degradates of P-1487.

Table E1 – Product Chemistry of Bioban P-1487 

Guideline 

No.

Parameter

Ingredient I: 

4-(2-nitrobutyl) 

Morpholine (P1447)

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 oC 199-215 oC 41995101

830.7300 Density 1.075 g/cc 1.075 g/cc 41995101

830.7550

Octanol-water partition 

coefficient at 25 oC (Log 

Kow)

0.18 -0.54 EPI Suite / 

EPWEB 4.1

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

830.7950 Vapor pressure (mmHg)

20-43 mmHg at 900

C 20-43 mmHg at 900C 41995101

Estimated: 

7.5 x 10-3mm Hg at 

250C

Estimated: 

5.07 x 10-6mm Hg at 

250C

EPI 

Suite/EPWEB 

4.1

 Henry’s Law (atm m3 mol-1) 1.1 x 10-10 1.51 x 10-15 EPI Suite 

/EPWEB 4.1 o

C = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury; Henry’s Law in atm m3 mol-1
Page 58 of 60

Table E2: Estimated Physical/Chemical Properties of Bioban P-1487 Degradates Based on EPISuite 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)

8,180 50,300 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 

m3 mol-1)

2.2 x 10-4 1.7 x 10-7 1.1 x 10-6
Page 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 PhysicoChemical 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 F1 below lists the submitter. 

Table F1. 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.