DCRoomPYS8621/Potomac-Yard-OnePage 2 of 42 Organic Esters of Phosphoric Acid (OEPA) Registration Review Team

Human Health & Environmental Effects Pat Jennings Srinivas Gowda James Breithaupt David Bays Timothy Dole Jenny Tao Don Wilbur

Risk Management SanYvette Williams R ose Kyprianou Zebora Johnson

Office of General Counsel Philip RossPage 3 of 42 

### Table of Contents
1 Introduction

................................ ................................ ................................ ............................. 5 1.1 Statutory and Regulatory Authority

................................ ................................ ................. 5 1.2 Case Overview

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

................................ ................................ ............ 7 1.4 Use/Usage Description

................................ ................................ ................................ ..... 9 1.4.1 Registrations

................................ ................................ ................................ ............. 9 1.4.2 Summary of Registered Uses

................................ ................................ .................... 9 1.5 Regulatory History

................................ ................................ ................................ ......... 10 1.5.1 Recent/Pending Regulatory Actions

................................ ................................ ....... 10 1.5.2 Tolerance Informat ion

................................ ................................ ............................ 10 1.6 Incidents

................................ ................................ ................................ ......................... 11 1.6.1 Human Health

................................ ................................ ................................ ......... 11 1.6.2 Ecological

................................ ................................ ................................ ............... 11 2 Anticipated Data Needs

................................ ................................ ................................ ........ 11 3 Human Health Risk Assessment

................................ ................................ ........................... 14 3.1 Existing Toxicological Endpoints

................................ ................................ .................. 14 3.2 Dietary Exposure

................................ ................................ ................................ ............ 16 3.2.1 Food

................................ ................................ ................................ ........................ 16 3.2.2 Drinking Water

................................ ................................ ................................ ....... 16 3.3 Occupational and Residential Exposures

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

................................ ................................ ............. 17 3.3.2 Residential Handler Exposures

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

- Application Exposures

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

................................ ................................ ............. 19 3.4.1 Aggregate Exposures

................................ ................................ .............................. 19 3.4.2 Cumulative Exposures

................................ ................................ ............................ 19 4 Environmental Risk Assessment

................................ ................................ ........................... 20 4.1 Environmental Fate

................................ ................................ ................................ ........ 20 4.1.1 Effect of Chemical and Physical Properties

................................ ............................ 21 4.1.2 Abiotic Processes

................................ ................................ ................................ .... 21 4.1.3 Biotic Processes

................................ ................................ ................................ ...... 21 4.1.4 Transport Processes

................................ ................................ ................................ 21 4.1.5 Water Quality

................................ ................................ ................................ .......... 21 4.2 Environmental Conceptual Model Exposure Path ways

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

................................ ................................ ....................... 23 4.3.1 Mode of Action

................................ ................................ ................................ ....... 23 4.3.2 Ecological Effects Endpoints

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

................................ ................................ ................................ .. 24 4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimat es

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

- the

- Drain Analysis

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

................................ ................................ ................................ ..... 25 5 Endocrine Disruptor Screening Program (EDSP)

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

................................ ................................ ................................ ........ 26 7 Guidance for Commenters

................................ ................................ ................................ .... 26 7.1 Preliminary Work Plan

................................ ................................ ................................ ... 26Page 4 of 42 7.1.1 Trade Irritants

................................ ................................ ................................ .......... 26 7.1.2 Water Quality

................................ ................................ ................................ .......... 27 7.1.3 Environmental Justice

................................ ................................ ............................. 27 7.1.4 Structure Activity Relationships

................................ ................................ ............. 27 7.1.5 Additional Information

................................ ................................ ........................... 28 8 Next Steps

................................ ................................ ................................ ............................. 28 9 References

................................ ................................ ................................ ............................. 29

Appendix A T oxicology Profile

................................ ................................ ............................... 30 Appendix B Environmental Fate

................................ ................................ ............................. 38 Appendix C Ecotoxicology Profile

................................ ................................ .......................... 39 Appendix D Screening Level Down

- the Drain Analysis

................................ ......................... 40 Appendix E Product Chemistry

................................ ................................ ............................... 41 Appendix E Product Chemistry...............................................

... . .....................37

List of Tables Table 1

– Summary of Anticipated Risk Assessments and Data Needs: OEPA

............................ 6 Table 2

– Anticipated Registration Revie w Schedule

................................ ................................ .... 7 Table 3

– Chemical Identification of Organic Esters of Phosphoric Acid (OEPA)

....................... 7 Table 4

– Physical

- Chemical and Fate Prop erties for OEPA

................................ ......................... 8 Table 5

– Summary of OEPA Registered Uses

................................ ................................ .............. 9 Table 6

– Studies Anticipated as Needed for the Registration Review of O EPA

........................ 12 Table 7

– Existing Toxicological Endpoints for OEPA

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

– Occupational Handler Exposure Scenarios for OEPA

................................ ................. 18 Table 9

– Residential Handler Exposure Scenarios for OEPA

................................ ..................... 18

List of Figures NonePage 5 of 42 

## 1 Introduction

This document is the Environmental Protection Agency’s (EPA or “the A gency” ) Preliminary Work Plan (PWP) for the organic esters of phosphoric acid (herein referred to as OEPA) . The PWP document explains what EPA's Office of Pesticide Programs knows about OEPA

, highlighting anticipated data and assessment needs, identifying the ty pes of information that would be especially useful to the Agency in conducting the review, and providing an anticipated timeline for completing the OEPA review.

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

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

- making process for this chemical.



## 1.1 Statutory and Regulatory Authority

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United States generally must be registered by the U.S. Environmental Protection Agency (USEPA, EPA, or the Agency) based on scient ific 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://www.epa.gov/oppsrrd1/registration_review/

. 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 ev ery 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 CF R 155.40. The Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a regi stration review decision. After reviewing and responding to comments and data received in the docket during this initial comment period, the Agency will develop and commit to a F inal W ork P lan (FWP) and anticipated schedule for the OEPA Case.

Documents as sociated with this registration review can be viewed at http://www.regulations.gov in docket EPA

- HQ

- OPP

- 2013

- 0373

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

.Page 6 of 42 Table 1

– Summary of Anticipated Risk Assessments and Data Needs : O EPA

Risk Assessment Assessment Necessary to Support Registration Review Date of Most Recent Assessment Type of Assessment Required (New/Updated) Data Anticipated as N eeded (See T able 6 for detail s) *

Dietary (food) No N/A None None
Dietary (drinking water) Yes N/A New None

Occupational Handler Yes 12/01/2007 Updated None

Residential Handler Yes 12/01/2007 Updated None

Residental Post Application

- Incidental Oral and Dermal Yes 12/01/2007 Updated None

Aggregate Yes 03/2008 Updated None

Cumulative No N/A None None

Tolerance Review No N/A N one None

Ecological Yes 11 /19 /2007 New Hydrolysis Direct photodegradation i n water Aerobic soil metabolism Aerobic and anaerobic aquatic metabolism Leaching

- adsorption

- desorption Activated Sludge Sorption Isotherm Activated Sludge or Modified Activated Sludge Respiration Inhibition Biodegradability test Textile leaching study Acu te avian oral toxicity study Acute freshwater invertebrate tox study Acute freshwater fish tox study Fish early

- life stage study Aquatic invertebrate life

- cycle study Aquatic plant growth algal study Aquatic plant growth vascular plant

s tudy Acute estuar ine and marine organisms toxicity Whole sediment acute freshwater invertebrates Whole sediment acute marine invertebrates N/A = Not applicable * Table 1 is a summary of the anticipated risk assessments and data n eeds for Registration Review. For data to be called in through the post

- RED DCI, see Table 6

.Page 7 of 42 Table 2

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

- Day Comment Period for Preli minary Work Plan 201 4

- 03 2014

- 03

- 26 Close Public Comment Period 2014

- 0 5 Phase 2: Case Development Issue Final Work Plan 2014

- 09 Issue Data Call

- In (DCI) 2015

- 09 Receive Data to be Considered in Risk Assessment 2017

- 09 Open 30

- Day Public Comment Period for Preliminary Risk Assessment(s) 2019

- 03 Close Public Comment Period 2019

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

- Day Public Comment Period for Pro posed Decision 2019

- 09 Close Public Comment Period 2019

- 11 Issue Final Decision 2020

- 03 Begin Post

- Decision Follow up 2020 Total (years) 6

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



## 1.2 Case Overview

The docket for o rganic e sters of p hosphoric a cid ( c ase 4122 ) has been established at http://www.regulations.gov in docket number EPA

- HQ

- OPP

- 2013

- 0373

.


## 1.3 Chemical Identification and Properties

Table 3 presents the active ingredients to be assessed in c ase 4122. Organic esters of phosphoric acid consists of a mixture of three chemicals: Phosphoric acid, mono(2

- eth ylhexyl)
ester (PC Code 111286)

, p hosphoric acid, bis(2

- ethylhexyl) ester, comp oun d with 2,2'

- (coco alkylimino)bis(ethanol) (PC Code 129079)

, and p hosphoric acid, mono(2

- ethylhexyl) ester,
comp ounds with diethanolamine N

- coco alkyl deriva tives (PC Code 12 9080). These chemicals cannot be divided into components for individual testing and the three of them will be referred to as

o rganic esters of phosphoric acid (OEPA) in this registration review.

Table 3

– Chemical Identification o f Organic Esters of Phosphoric Acid (OEPA)

Chemical Name Phosphoric acid, mono(2

- ethylhexyl) ester Phosphoric acid, bis(2

- ethylhexyl) ester, compd. with 2,2'

- (coco alkylimino)bis(ethanol) Phosphoric acid, mono(2

- ethylhexyl) ester, compds. with diethanolami ne N

- coco alkyl derivs. Chemical Names (Mixture) M ono (2

- ethylhexyl) phosphate

. Ethanol, 2,2'

- (cocoimino)bis, salt with phosphoric acid, bis(2

- ethylhexyl) ester (1:1) Ethanol, 2,2'

- (cocoimino)

- bis, salt with phosphoric acid, (mono) (2

- ethylhexyl) ester (1 :1)

Classification Organic esters of phosphoric acid

. Ester ; Phosphate

. Organic esters of phosphoric acid

. Alcohol ; Ester ; Imine ; Phosphate

. Organic esters of phosphoric acid

. Alcohol; Ester; Imine; Phosphate

. PC Code 111286 129079 129080
CAS No. 107 0

- 03

- 7 68649

- 38

- 7 120579

- 32

- 0Page 8 of 42 Molecular Formula C 8 H 19 O 4 P 1 C 32 H 70 O 6 P N C 24 H 54 O 6 P N

Molecular Weight 210.21 g/mol 595.87 g/mol 483.66 g/mol

Purity 17.7% 66.4 % 15.9 %

Molecular Structure

The OEPA product chemistry information (source: MRID 43265801 and Interface Research Corporation’s MSDS ) relevant to risk assessm ent is summarized in Table 4 and details of the product chemistry and environmental fate information are discussed in Appendix E and B, respectively

.

Table 4

– Physical

- Chemical and Fate P roperties for OEPA

OCSPP Guideline No. Physical and Chemical Properties Mixture of 3 AIs :

• Phosphoric acid, mono(2

- ethylhexyl) ester (17.7%)

• Phosphoric acid, bis(2

- ethylhexyl) ester, comp ound with 2,2'

- (coco alkylimino)bis(ethanol) (66.4%) and

• Phosphoric acid, mono(2

- ethylhexyl) ester, comp oun ds with diethanolamine N

- coco alkyl deriv ative s. (15.9%) 830.7000 pH 3.0 to 3.6 830.7050 UV/Visible Absorption Not reported

. 830.7200 Melting point Freezing point: < 32 ° F 830.7220 Boiling point Decomposes before boiling

. 830.7300 Density 1 .0 g/ ml

830.7370 Dissociation Constant Not applicable because of the very limited water solubility of the compound and the requirement to add surfactant to form a water stable emulsion it is very difficult to accurat ely determine the dissociation constant for the chemical

. 830.7550 Partition coefficient ( n

octanol/water) Not applicable for surface active chemicals.

830.7840 Solubility in water 0.0324 g/100 ml 324 mg/L

830.7860 Solubility in organic solvents S oluble in dimethyl sulfoxide (DMSO) 500 mg/ml

. Soluble in n

- octanol in all proportions at 20 ° C. Soluble in ethanol.

830.7950 Vapor pressure 1.0 x 10 - 2 mm H g at 20 ° C (water)Page 9 of 42 

## 1.4 Use/Usage Description

1.4.1 Registrations

There are two registered pesticide product s ( EPA Reg. Nos. 43670

- 01 and 43670

- 4) that contain OEPA. E P A Reg. No. 43670

- 1 contains 100 percent a.i. and EPA Reg. No. 43670

- 4 contains 80 percent a ctive ingredient

. The three organic esters of phosphoric acid never occur as a pesticide single active ingredient or in any other combination or ratio in a registered pesticide product (EPA Reg. Nos. 43670

- 1 and 43670

- 4)

.



### 1.4.2 Summary of Registered Uses

OEPA is registered for use as a materials preservative for a wide variety of materials as listed in Table 5

. No direct or indirect food contact uses are approved on registered end

- use product labels. Several uses that could conceivably result in indirect food contact already have been prohibited by such label language a s , "... to be used for purposes other than food storage." The application rates are not included on the most recently approved version of the labels

. The previously approved versions of the labels included technical data sheets which listed the applicati on rates; however, the technical data sheet s w ere not included in the most recently approved labels.

It should also be noted that the RED specified that the rates be lowered to 0.25 percent for paints

, 0.017 percent for carpet cleaners, 0.34 percent for te xtiles, and 1.1 percent for mattress covers. These mitigation measures need to be incorporated into the labels.

Table 5

– Summary of OEPA Registered Uses

Use (All are Material Preservative Uses) Application Rate

Carpets Not Li sted *

E poxy flooring, coating, tile and grout products Not Listed *

Vinyl (wall coverings, car tops, awnings, t arp s , tents, sails, drapes, shower curtains, cubicle curtains, film to be used for purposes other than food storage, and floor products) Not Lis ted *

Plastic furniture (excluding furniture used for food service and food storage) Not Listed *

Floor sealers ( acrylic

, urethane

, wax and varnish ), finishes and maintainers Not Listed *

Paints (polyvinyl acetate indoor and outdoor) Not Listed *

Polymeri c laminates (excluding la mi nates used for food preparation surfaces) Not Listed *

Polymer concrete Not Listed *

Textiles

, synthetic and non

- woven , ( wall coverings, car tops, awnings, t arp s , t ents, s ails, drapes, shower curtains, and cubicle curtains ) Not L isted *Page 10 of 42 Polymeric packaging film (to be used for purposes other than food storage) Not Listed *

Paints, Stains and Coatings

, water

- . oil and solvent base d ( interior and exterior substrates machinery and equipment including HVAC systems) Not Listed *

Molded polymeric and polymer concrete (bathtubs, showers, bathroom sinks, bathroom countertops, and bathroom accessories) Not Listed *

Molded polymer and polymer concrete products (household, industrial, commercial and health care use) Not Listed *

Polymeric se alants, adhesives, and caulking compounds (natural and synthetic) Not Listed *

Textile upholstery, mattresses, mattress ticking and mattress covers (incorporation) Not Listed *

Vinyl U pholstery

, M attresses , M attress ticking, and M attress covers Not Listed *

Textiles ( topical treatment of wall coverings

, car tops , awnings

, tarpaulins

, tents, sails. drapes. shower curtains, apparel, cubicle curtains. and industrial fabrics) Not Listed *

Air Filters (topical treatment or impregnation of air filters to be used in air purification devices, automobiles, and HVAC systems). Not Listed *

*The application rates are not listed on the most recently approved labels. Previously approved versions of the labels inclu ded
t echnical d ata s heet s, which listed the application rates; however, the technical data sheet s w ere not includ ed in the most recently approved labels

. 

## 1.5 Regulatory History

The first product containing OEPA as an active ingredient was registered in the United States in 1982. This product, as well as the only other registered product containing OEPA, is a blend of the three active ingredients in this case. The Agency completed a Reregistration Eligibility Decision (RED) for OEPA in 2008. A post

- RED Data Call

- In (DCI) is anticipated but has not yet be en issued.



### 1.5.1 Recent/Pending Regulatory Actions

There are no recent regulatory actions for OEPA . EPA anticipates issuing the post

- RED DCI

soon

.



### 1.5.2 Tolerance Information No tolerances, tolerance exemptions, or food additive regulations have been established for OEPA by ei ther EPA or FDA.Page 11 of 42 

## 1.6 Incidents

1.6.1 Human Health

No OEPA human health incidents have been reported in OPP’s Incident Data System (IDS) for the time period spanning 1998 to the present (database searched on 1 / 15 / 2014).



### 1.6.2 Ecological

No OEPA ecological incidents ha ve been reported in OPP’s Incident Data System (IDS) for the time period spanning 1998 to the present (database searched on 1/29/2014).


## 2 Anticipated Data Needs

T able 6 presents a summary of the data anticipated as being needed to support this registration review. If the Agency receives data or other sources of information that demonstrate that there would be negligible release of OEPA during incorporation into treated materials and negligible leaching from in

- servi ce use of treated materials or that OEPA and/or its degradates will not persist if released to the environment, some or all of the environmental fate (OCSPP 835 series) and ecological effects (OCSPP 850 series) data anticipated to be needed may not be requ ired (see Table 6 for details)

.

The environmental fate data requirements in Table 6 ar e presented in a tiered approach based on the results of laboratory studies that isolate specific routes of dissipation in the environment. Hydrolysis (835.2120) data are anticipated to be required for all uses. For th e uses that have the potential to resul t in environmental exposure (see Section 4.2), data anticipated to be required include: direct photodegradation in water (835.2240), aerobic soil metabolism (835.4100), aerobic aquatic metabolism (835.4300), anaerobic aquatic metabolism (835.4400), leachin g

adsorption

- desorption (835.1230), activated sludge sorption isotherm (835.1110), Activated Sludge Respiration Inhibit i on, ASRI ) ( OECD 209 or OCSPP 850.3300) , and a test to determine biodegradation potential in wastewater treatment plant (WWTP).Docket Number EPA

- HQ

- OPP

- 2013

- 0373 www.regulations.gov

Page 12 of 42 T able 6

– Studies Anticipated as Needed for the Registration Review of OEPA

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

Studies Anticipated to be Required through the Registration Review DCI

835.2120 Hydrolysis 2 TGAI 12 Environmental Fate , Ecological Effects All uses except those noted in Section 4.2 Manufacturing

or In

- Serv ice Use

835.2240 Direct photodegradation in
water 1 TGAI 12 Environmental Fate, Ecological Effects All uses except those noted in Section 4.2 Manufacturing or In

- Service Use

835.4100 Aerobic soil metabolism 1 TGAI 24 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

835.4300 Aerobic aquatic metabolism 2 TGAI 24 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

835.4400 Anaerobic aquatic metabolism 2 TGAI 24 Environmental Fate, Ecological Effects A ll uses Manufacturing or In

- Service Use

835.1230 Leaching

- adsorption

desorption 2 TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

835.1110 Sewage Sludge Sorption Isotherm 2 TGAI 12 Environmental Fate, Ecological Ef

fects All uses Manufacturing or In

- Service Use

850.3300 Activated Sludge or Modified Activated Sludge Respiration Inhibition (ASRI) 1,2 TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

835.3110 Ready Biodegradabili ty 2,3 TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

835.3220 Porous Pot Test 1,2 TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

835.3240 Simulation Test

– Aerobic Sewage Tr eatment: A. Activated Sludge Units 2,3 TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

835.3280 Simulation Test to Assess the Biodegradability of Chemicals Discharged to
wastewater 2,3 TGAI 12 Environmental Fate, Ecol ogical Effects All uses Manufacturing or In

- Service Use

Special Study Leaching from treated article TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

850.2100 Acute oral toxicity to mallard duck or northern bobwhite quail TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use 850.1075 Acute toxicity to rainbow TGAI 12 Environmental All uses ManufacturingPage 13 of 42 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

trout or bluegill sunfish Fate, Ecological Effects or In

- Service Use

850.1010 Acute toxicity to Daphnia
magna TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

850.5400 Aquatic plant growth (algal) tier II TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Us e

850.1300 Aquatic invertebrate life

cycle TGAI 24 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

850.1400 Fish early

- life stage TGAI 24 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

850 .4400 Aquatic plant growth (aquatic vascular plant) Tier II

- dose response TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

850.1025 Acute estuarine and marine organisms toxicity TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

850.1735 Whole sediment: acute freshwater invertebrates TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use

850.1740 Whole sediment; acute marine invertebrates TGAI 12 Environmental Fate, Ecological Effects All uses Manufacturing or In

- Service Use Studies Expected to be Required through the Anticipated Post

- RED DCI

870.2600 Dermal Sensitization Study TGAI 12 Human Health Effects All uses All

870.3250 90

- Day Dermal Toxicity TGAI 12 Human Health Effects All uses All

870.3465 90

- Day Inhalation Toxicity TGAI 12 Human Health Effects All uses All

870.3700b Prenatal Developmental Toxicity Study (non

- rodent) TGAI 12 Human Health Effects All uses All

870.3800 Re production and Fertility Effects TGAI 12 Human Health Effects All uses All

870.4300 Combined Chronic Toxicity/Carcinogenicity 7 TGAI 24 Drinking Water Assessment Some plastics,
epoxy flooring/tile, textile, paints, stains, adhesives, and caulk compounds M anufacturing or In

- service Use

870.7800 Immunotoxicity TGAI 12 Human Health Effects All uses All

875.1200 Dermal Indoor Exposure 4 TGAI 12 Occupational and Residential Handler All Uses See Note 3Page 14 of 42 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

875.1400 Inhalation Indoor Exposure 3, 4 TGAI 12 Occupational and Residential Handler All Uses See Note 3

875.1700 Product Use Information TGAI 12 Occupational and Residential Handler and Post Application All Uses All

875.2300 Indoor Surface Residue Dissipation 5,6 TGAI 12 Residential Post Application Vinyl Floorin g, Textiles and Mattress Covers See Notes 5 and 6

830.7050 UV Visible Sorption 1 TGAI 12 Environmental Fate, Ecological Effects All uses In

- Service Use

1 These anticipated data requirements are based on the potential for OEPA to leach from treated materials . Data are not expected to be required if information provided to the Agency demonstrates that OEPA releases to surface water are negligible. 2 The results of the Activated Sludge Respiration Inhibition Test (ASRI) expected to be required will determine whi ch of these four biodegradation tests would be anticipated to be required. If the ASRI test EC 50 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 EC 50 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. The appropriate Test Substances are the three components of OEPA. 3 O ccupational and Residential Handler Exposure Scenarios include Open Pour Liquids for Material Preservation, Brush Application of Preserved Paint, Airless Spray Application of Preserved Paint, and Trigger Spr ay Application of Carpet Cleaner 4 It may be possible to use proprietary surrogate exposure data if data compensation issues are appropriately and adequately addressed. 5 Residential Post Application Exposure Scenarios include dermal and incidental oral exposure t vinyl flooring, dermal and incidental oral exposure to textiles and dermal exposure to mattress covers. 6 If surface residue data are not available, then the standard assumption of 100 percent transferable surface residu e will be used which might overestimate the ris k. 7 Data are not expected to be required if i nformation provided to the Agency demonstrates that OEPA releases to s urface water are negligible.


## 3 Human Health Risk Assessment

The Agency anticipates the need to conduct a human health risk assessment for OEPA. The most recent risk assessment was conducted i n support of the 2008 RED. The Agency expect s to require additional data for use in conducting the registration review.



## 3.1 Existing Toxicological Endpoints
The Agency anticipates the need to revise the existing toxicological endpoints as part of this registration review. Table 7 presents the endpoints used in EPA’s most recent human health risk assessment in support of the 2008 RED. As previously stated, toxicological studies werePage 15 of 42 identified as data gaps in the RED

. All available information including existi ng toxicology studies, valid scientific literature, and the studies that are expected to be called in will be considered in establishing the endpoints to be used in the registration review risk assessment. A detailed description of the available toxicity studies is provided in Appendix A

.

Table 7

– Existing Toxicological Endpoints for OEPA
Exposure Scenario Dose Used in

Risk Assessment

(mg/kg/day) Target MOE, UF, for Risk Assessment St udy and

Toxicological Effects

Non

- Dietary Risk Assessments

Incidental Oral

Short

- Term

(1

- 30days) and Intermediate

- Term

( 30 days

- 6 months) NOAEL ( males ) = 62.5 MOE = 100 (10x inter

species extrapolation, 10x intra

- species variation) 90

- Day (Oral) Sub chronic Toxicity Study in Rats (MRID 41083601 )

L OAEL (males) = 200 mg/kg/day based on decreased body weights and body weight gain and food consumption

.

Dermal

Short

- Term

(1

- 30days) and Intermediate

- Term

( 30 days

- 6 months) NOAEL ( males ) = 62.5 MOE = 10 0 (10x inter

species extrapolation, 10x intra

- species variation) 90

- Day (Oral) Subchronic Toxicity Study in Rats (MRID 41083601 )

L OAEL (males) = 200 mg/kg/day based on decreased body weights and body weight gain and food consumption

.

Dermal

Long

- Term

(> 6 months) NOAEL ( males ) = 62.5 MOE = 300 (10x inter

species extrapolation, 10x intra

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

- term endpoint) 90

- Day (Oral) Subchronic Toxicity Study in Rats (MRID 41083601 )

L OAEL (males) = 200 mg /kg/day based on decreased body weights and body weight gain and food consumption

.

Inhalation

Short

- Term

(1

- 30days) and Intermediate

- Term

( 30 days

- 6 months) NOAEL ( males ) = 62.5 MOE = 1000 (10x inter

species extrapolation, 10x intra

- species variation, 10x
route

- to

- route extrapolation) 90

- Day (Oral) Subchronic Toxicity Study in Rats (MRID 41083601 )

L OAEL (males) = 200 mg/kg/day based on decreased body weights and body weight gain and foodPage 16 of 42 Exposure Scenario Dose Used in

Risk Assessment

(mg/kg/day) Target MOE, UF, for Risk Assessment St udy and

Toxicological Effects

consumption

.

NOAEL = no observed adverse effect level, LOAEL = l owest observed adverse effect level, MOE = margin of
exposure, UF = uncertainty factor

. 

## 3.2 Dietary Exposure

3.2.1 Food Pesticide products containing OEPA are registered for use to preserve a number of products by incorporation into the materials themselves. Prese rved materials that could potentially have food contact include epoxy tile, vinyl products, molded polymeric and polymer concrete products for household and commercial use, and natural and synthetic polymeric sealants and adhesives. The EP labels specifica lly prohibit the preservation of plastic furniture, polymeric laminates, and polymeric packaging film that may contact food but are silent on the other materials. The Agency concluded in the 2008 RED that human exposure to OEPA residues via food is not
exp ected. I t appears to the Agency that the registrant intends that their product (Intersept PC

- 20) be used to preserve materials intended for nonfood contact only, based on verbal communicati on between the Agency ’ s PM and registrant regarding the registrant ’ s intent t o amend their label accordingly

. Therefore, at this time, the Agency does not anticipate con ducting a dietary assessment for exposure to OEPA via food

. Further, residue chemistry data are not expected to be needed to characterize dietary exposure to OEPA. If the registrant does not am end their label during the comment period, the workplan may be amended to anticipate a dietary assessment.



### 3.2.2 Drinking Water A drinking water ass essment has not been conducted for OEPA. While there are no direct aquatic uses of OEPA, for several approved uses (including some plastics, epoxy flooring/tile, textile, paints, stains, adhesives, and caulk compounds) , the Agency cannot rule out the poten tial for OEPA to enter surface water during incorporation into treated materials and/or leaching from in

service use of treated materials and to subsequently be present in drinking water. There are no data or other sources of information indicating that th ere would be negligible potential for release of OEPA to surface water from incorporation into treated materials and from leaching from in

service use of treated materials. Therefore, the Agency anticipates needing certain environmental fate data listed i n Table 6 of this PWP. However, if the Agency receives data or other sources of information that demonstrate that there would be negligible release of OEPA during incorporation into treated materials and negligible leaching from in

- service use of treated materials or that OEPA and/or its degradates will not persist if released to the environment, thesePage 17 of 42 data may not be required. Upon receipt and review, these data and/or other sources of information will be used during the risk assessment stage of this Reg istration Review to determine the potential for discharged or leached residues of OEPA to result in human dietary exposure via drinking water, which may trigger a drinking water assessment.



## 3.3 Occupational and Residential Exposures
The occupational and resid ential exposures to OEPA were last assessed in D 347015 (EPA, 2007) which was conducted in support of the 2008 OEPA RED. The Agency anticipates the need to revise the occupational and residential assessments conducted in support of the 2008 OEPA RED since the Margins of Exposure (MOE)s were calculated using unit exposure data and transferable residue data that have underlying limitations and will need to be reassessed using updated values.



### 3.3.1 Occupational Handler Exposure There is the potential for both dermal and inhalation exposures during the open pouring of OEPA liquid formulations during material preservation and during the use of preserved materials such as paint. The exposures during the open pour liquid handling scenarios were not assessed in the OEPA RED because the RED specified the use of closed system loading ; however, this mitigation has not been implemented and the current labels do not require closed system loading. In the RED, t he ( PHED) unit exposure data were used for painting scenarios which included the paint brush and airless sprayer application methods. The dermal MOEs for paint brush and airless sprayer application ranged from 10 to 490 and 5 to 230, respectively, depending upon the application rate which ranged from 0.1 to 5 percent. G iven that the target MOE is 100, this meant that the risks would be of concern when the application rate exceeded 0.5 percent for brush application and when the application rate exceeded 0.2 percent for airless sprayer application. The inhalation MOEs for paint brush and airless sprayer application ranged from 6,300 to 310,000 and 210 to 11,000, respectively, depending upon the application rate. Although none of these MOEs are of concern, per se, because they all exceed the target MOE of 100, the MOE of 210 triggered the need for an inhalation toxicity study because it did not exceed 1000. This study was listed as a data requirement in the RED to be required by a DCI to be issued after the RED.

Because of the low MOEs discussed above for the application of treated paint, the OEPA RED specified that the rate for paints not exceed 0.25%; however, this mitigation measure has not been incorporated into the labels. In addition

, the use of closed system loading as s pecifed in the RED has not been incorporate d into the label.

The exposures during the open pour liquid handling scenarios were not assessed in the RED and will need to be assessed during registration review. The paint application scenarios

, which were assessed in the RED

, will also need to be r evised during registration review upon receipt of the unit exposure data that are anticipated to be required in the post

- RED DCI

. Occupational handler scenarios to be assessed are presented in Table 8.Page 18 of 42 Table 8

– Occupational Han dler Exposure Scenarios for OEPA

Handler Scenario s Exposure Route(s) Duration

Open Pour Liquids for materials preservation Dermal Inhalation Intermediate Term
Airless Sprayer and Brush Roller Application of Treated Paints Dermal Inhalation Intermed iate Term



### 3.3.2 Residential Handler Exposures Residential handler exposures to OEPA were last assessed in D 347015 (EPA, 2007) which was conducted in support of the 2008 OEPA RED. Residential handler exposures to OEPA during the application of treated paints wer e assumed to be short term in duration because painting is done on an episodic basis. T he residential handler MOEs as listed in the RED

, were slightly greater than those calculated for occupational handler exposures and some of the MOEs were of

concern a t the higher application rates.

Risks for a carpet cleaner handler scenario were also calculated for the RED and the MOEs were 350,000 and 7,000 for dermal and inhalation exposures, respectively and were not of concern.

Both of the above mentioned resi dential handler exposure scenarios will need to be assessed in registration review upon receipt of the unit exposure data that are anticipated to be required to supplement or replace the unit exposure data that were used in the RED. These scenarios are li sted in Table 9.

Table 9

– Residential Handler Exposure Scenarios for O EPA

Scenario Exposure Route(s) Duration
Application of Preserved Paint (Brush/Roller and Airless Spray) Dermal Inhalation Short Term

Application of Prese rved Carpet Cleaners (Low Pressure Hand Wand) Dermal Inhalation Short Term



### 3.3.3 Residential Post

- Application Exposures Residential post application risks were assessed in the RED for dermal and/or incidental oral exposures to carpet cleaners, vinyl floori ng, textiles and mattress covers. A summary of the MOEs is included in Table 10

.
Table 10

– MOEs for Residential Post Application Exposures to OEPA

Use Population Exposure Route Application Rate % Transferable Residue % MOEPage 1 9 of 42 Carpet Cleaner Toddler Der mal 0.1 5 or 100 110,000 or 5400 5.0 5 or 100 2100 or 110 Incidental Oral 0.1 5 or 100 44,000 or 880 5.0 5 or 100 2200 or 44 Vinyl Flooring Toddler Dermal 5.0 0.5 1,500 Incidental Oral 5.0 0.5 12,000

Clothing Toddler Dermal 0. 75 5 or 100 44 or 2 2 .0 5 or 100 17 or <1 Incidental Oral 0. 75 50 250 2 .0 50 93 Adult Dermal 0.75 5 or 100 69 or 3 2 .0 5 or 100 26 or 1

Mattress Covers Toddler Dermal 1.0 5 or 100 110 or 6 5 .0 5 or 100 23 or 1 Adult Dermal 1.0 5 or 100 190 or 9 5 .0 5 or 100 38 or 2

Because some of the MOEs were less than the target MOEs for the carpet cleaner, clothing and mattress cover uses, the RED specified that the rates be reduced to 0.017% for carpet cleaners, 0.34% for textiles, and 1 .1% for mattress covers. These mitigation measures have not been incorporated into the labels.

All of the above mentioned residential post application scenarios will need to be assessed in registration review upon receipt of the surface residue exposure data that are anticipated to be required to supplement or replace the surface residue assumptions that were used in the RED. These scenarios are listed in Table 11

.

Table 11

– Residential Post

- Application Exposure Scenarios for O EPA

Scenario Exposure Ro ute(s) Duration
Toddlers Playing on Carpets Cleaned with Treated Cleaners Dermal Incidental Oral Intermediate Term

Toddlers Playing on Vinyl Flooring Dermal Incidental Oral Intermediate Term

Adults

- treated textiles Dermal Intermediate Term

Todd lers

- treated textiles Dermal Incidental Oral Intermediate Term

Adults and toddlers sleeping on treated mattress covers Dermal Intermediate term



## 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures

Registered uses of OEPA are not expected to result in dietary (food) exposure. However, drinking water and residential exposures are expected and these will be aggregated to assess aggregate risk.



### 3.4.2 Cumulative ExposuresPage 20 of 42 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 OEPA and any other substances, and OEPA 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 OEPA 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 evalua te the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/

. 

## 4 Environmental Risk Assessment

The agency has not pr eviously conducted a risk assessment that supports a co mplete endangered species determination for OEPA. The previous assessment for OEPA (March 2008 RED) was conducted using p hosphoric a cid instead of O E PA. OEPA is a mixture of three esters of phosphoric acid and is chemically distinct from phosphoric acid. Phosphoric acid and OEPA have different chemical structures and have different chemical properties. Therefore

, none of the information found in the assessment will be of use for th e reg istration review of OEPA

. The ecological risk assessment planned du ring registration review will allow the agency to determine potential acute and chronic risks to aquatic organisms exposed to OEPA . Such sites include areas that receive water containing OEPA transported from treatment sites into the aquatic environment

. Minimal exposure would be expected to terrestrial organisms from these use patterns. The risk assessment also will allow the agency to determine whether each use of the OEPA has 'no effect' or 'may affect' federally listed threatened or endangered specie s (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use

m ay affect' a listed species or its designated critical habitat, the agency will consult with the U.S. Fish and Wildlife Service and/or National M arine Fisheries Services (the Services), as appropriate.



## 4.1 Environmental Fate

There are no data or other sources of information indicating that there would be negligible potential for release of OEPA to surface water from incorporation into treated material s and from leaching from in

- service use of treated materials. In addition, the registrant has not submitted environmental fate or leaching data for organic esters of phosphoric acid (OEPA) indicating the rate of dissipation or degradation products. As a result, the Agency assumes that OEPA has the potential to be present in the environment because of its water solubility (324 mg/l ) 7

2 and its potential to be released while being incorporated into treated materials and from leaching during in

- service use. The environmental fate and leaching data the Agency anticipates requir ing are presented in Table 6. If the Agency receives data or other sources of information that demonstrate that there would be negligible release of OEPA during incorporation into treat ed materials and negligible leaching from in

- service use of treated materials or that OEPA and/or its degradates will not persist if released to the environment, some or all of these anticipated environmental fate data may not be required.

2Page 21 of 42 

### 4.1.1 Effect of Chem ical and Physical Properties OEPA consists of phosphoric acid with either one

3 8 or two 9

4 ethylhexyl groups and a companion molecule.

5 10 OEPA is expected to create acid conditions in solution (pH 3.0

- 3.6) and is soluble in water to 324 mg/l (parts

- per

- mill ion, ppm). OEPA is not expected to volatilize from water based on the Henry’s Law constant 8.5 x 10 - 6 atm m 3 mol - 1 6 of the product. The EPI

- Suite 4.11 program was run to obtain the chemical and physical property values for the individual components.



### 4.1.2 A biotic Processes The registrant has not submitted data on the abiotic (chemical) degradation of OEPA, which includes hydrolysis (835.2120) and direct photodegradation in water (835.2240). In the absence of data and or other sources of information that d emonstrate that OEPA would not persist in the environment if it is released to the environment during incorporation into treated materials and/or from leaching during in

- service use of treated materials , the Agency assumes that OEPA has the potential to be present in the environment from the registered use as a materials preservative and anticipate s the need to require these data.


### 4.1.3 Biotic Processes The registrant has not submitted data on the biotic (microbial) degradation of OEPA, which includes aerobic soi l metabolism (835.4100), anaerobic aquatic metabolism (835.4400), and aerobic aquatic metabolism (835.4300). In addition, a test to determine biodegradation potential during wastewater treatment has also not been submitted. Results of an Activated Sludge Respiration Inhibition ( ASRI) test (OECD 209 or OCSPP 850.3300) would be used to determine whether a ready biodegradability test (835.3110) or one of the wastewater treatment plant biodegradation simulation tests (835.3220, 835.3240, or 835.3280) would be needed

. In the absence of data or other sources of information that demonstrate that OEPA would not persist in the environment if it is released to the environment during incorporation into treated materials and/or from leaching during in

- service use, th e Agency assumes that OEPA has the potential to be present in the environment from the registered use as a material preservative and anticipates the need to require these data.



### 4.1.4 Transport Processe s The registrant has not submitted data on the potential for environmental transport of OEPA. Data are required for leaching

- adsorption

- desorption (835.1230 and 835.1240), activated sludge sorption isotherm (835.1110), and for leaching from treated products (non

- guideline study). In the absence of data or oth er sources of information that would demonstrate OEPA’s potential to leach and/or sorb, the Agency anticipates the need to require these data.


### 4.1.5 Water Quality

3 8 Mono(2

- ethylhexyl ester) of phosphoric acid

4 9 Bis(2

- ethylhexyl ester) of phosphoric acid

5 10 2,2’

- (cocoimino)

- bis ethanol salt

11 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885Page 22 of 42 O EPA is not identified as a cause of impairment for any water bodies listed as impaired under secti on 303(d) of the Clean Water Act

. 11

7 In addition, no Total Maximum Daily Loads (TMDL) h as been developed for O EPA

. 12

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

. 13

9


## 4.2 Environmental Conceptual Model Exposure Pathways

T here are no data or other sources of information indicating that there would be negligible potential for release of OEPA to surface water from incorporation into treated materials and from leaching from in

- service use of treated materials.

The organic esters of phosphoric acid are to be incorporated into products as a fungistat and bacteriostat. There are no spray application (non

- incorporated) uses on the labels. The organic esters of phosphoric acids have two active labels, including Intersept 14

10 an d Intersept PC

- 20

. 15

11 Both products have all three active ingredients in this case with different percentages in each product. These registered products can be used in air filters for heating cooling systems, bedding materials, and textiles, paints and c aulks, and plastics.

The Intersept PC

- 20 label contains some uses that are not presumed to result in environmental
exposure , including air filters, vinyl upholstery, mattresses and mattress ticking, and polymeric packaging film since there is no potenti al for release to the aquatic environment and these treated items would be disposed in lined sanitary landfills.

However, there are some uses of OEPA for which the Agency cannot presume that environmental exposure will not occur. These uses include p lastics in polymeric concrete, vinyl, outdoor plastic furniture, and outdoor carpets and tile. Although the PC

- 20 label states “Once incorporated, there is no loss of efficacy due to washing or wear under normal use conditions”

, the Agency has found no evi dence that leaching and subsequent environmental exposure from these treated materials will not occur. Consequently, the Agency needs information demonstrating that incorporation of OEPA into plastics would not result in releases to surface
water.

• The fir st category of plastics is polymeric concrete ( 1

- 5 % OEPA w/w) which is used for
water

- exposed surfaces such as tile and grout, bath tubs, showers, bathroom sinks, and bathroom countertops. It can also be used building manhole covers because it is more

co rrosion resistant than traditional concrete. 16

12

12

8 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant _group_name=PESTICIDES

9 13 http://www.epa.gov/owow/tmdl/

10 14 Reg. No. 43 670

- 1, label dated 7/29/2005, http://www.epa.gov/pesticides/chem_search/ppls/043670

- 00001

- 20050729.pdf

11 15 Reg. No. 43670

- 4, label dated 9/20/1999, http://www.epa.go v/pesticides/chem_search/ppls/043670

- 00004

- 19990920.pdf

12 1 16 http://genevapolymerproducts.com/Page 23 of 42 • The second category of plastics for which the Agency cannot rule out the potential to create environmental exposure includes vinyl products such as car tops, awnings, tarpaulins, tents, sails, shower curta ins, and vinyl film.

• The third category of plastics for which the Agency cannot rule out the potential to create environmental exposure is plastic furniture ( 1

- 5 % w/w).

• The fourth category of plastics for which the Agency cannot rule out the potential to create environmental exposure is outdoor carpets (0.5

- 10 % w/w). The outdoor use in polymeric backing material ( 0.1

- 2 % w/w) for carpets is primarily restricted to outdoor carpets on decks and patios and in doormats. 17

13


## 4.3 Ecological Effects Assessment

For any registered active ingredient

, the Agency performs ecological hazard and environmental labeling assessments and requires the submission of four ecological effects studies: avian acute oral LD 50 , acute freshwater fish LC 50 , acute algae and acute fr eshwater aquatic invertebrate EC 50
. These studies are anticipated to be required for OEPA.

However, since the Agency has no eco

- toxicity data on OEPA , additional studies are anticipated
to be required for an ecological risk assessment

. These include five aquatic eco

- toxicity studies and two sediment studies that are expected to be required in order to access possible exposure from down the drain release of this chemical

. These are listed in Table 12.



### 4.3.1 M ode of Action

The mode of action of OEPA is unknown. Since there are no eco

- toxicity data for OEPA, ecotoxicity endpoints can not be determined at this time (Table 1 2 )

. A full suite of ecological effects data is anticipated to be required.



### 4.3.2 Ecological Effects Endpoints

Table 12

– Ecological Effects Endpoints Selected for Assessing Risks from Use of OEPA

Receptor

Group Surrogate Species Risk Scenario Toxicity Endpoint

Freshwater Fish One freshwater fish species Acute None

Freshwater invertebrates One freshwater invertebrate species Acute None

Freshwater benthic invertebrates One freshwater benthic invertebrate species Subchronic/ Chronic None

Estuarine/marine fish One estuarine/marine fish species Acute No ne
Estuarine/marine

invertebrates One estuarine/marine invertebrate species Ac ute No ne
Estuarine/marine benthic invertebrates One marine benthic invertebrate species Subchronic/ Chronic N one

13 17 http://www.americanfloormats.com/entrance

- mats

- runners/Page 24 of 42 Receptor

Group Surrogate Species Risk Scenario Toxicity Endpoint

Algae Selenastrum capricornutum Nonlisted None Aquatic vascular plants One aquatic vascular plant species Nonlisted None

Birds One avian s pecies Acute None



## 4.4 Exposure Analysis Plan

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates Exposure to terrestrial organisms is expected to be minimal based on the use patterns of OEPA as a materials preservative in several commercial, industrial and ho usehold products (Table 5)

. Terrestrial organisms will not come into contact with OPEA because the chemical is incorporated into materials such as tiles, carpets, paints and textiles. Due to p otential release of OPEA to aquatic environments after product ion of these materials, exposure to aquatic organisms cannot be discounted at this time (Section 4.2)

.



### 4.4.2 S creening Level Down

- the

- Drain Analysis There are no data or other sources of information indicating that there would be negligible potential for release of OEPA to surface water from incorporation into treated materials and from leaching from in

- service use of treated materials. In addition, there are no data or other sources of information that demonstrate that OEPA would not persist if it is released t o the aquatic environment or on the rate of formation and decline of any degradates of OEPA. Finally, there are no data or other sources of information on the aquatic toxicity of OEPA and/or any degradates it might form.

Unless the Agency receives data o r other sources of information that demonstrates that OEPA is not released to surface water or if it is released to surface water, OEPA and any degradates it forms do not persist or are not very toxic to aquatic organisms, the Agency will need to perform

a n ecological risk assessment for OEPA to assess potential releases of OEPA to surface water and subsequent exposures to aquatic organisms from incorporation into treated materials and from leaching from in

- service use of treated materials.

To perform a scr eening level assessment of potential exposures of aquatic organisms to OEPA due to leaching from in

- service use of treated materials, the Agency would use the Down

- the

Drain (DtD) module of the Exposure and Fate Assessment Screening Tool (E

- FAST) model. I nput parameters required to run the DtD module include percent removal during wastewater treatment, wastewater treatment plant influent volume, and concentrations of concern for aquatic organisms based on measurement effects endpoints. To determine wastew ater treatment plant influent volume, the Agency needs information on the maximum annual production volume of OEPA. Data or other sources of information on leaching potential from materials treated with OEPA would be applied to the maximum annual producti on volume to determine the wastewater treatment plant influent volume that would be used a s input to the DtD module. E

- FAST is available on EPA’s website at http://www.epa.gov/oppt/exposure/pubs /efast.htm

.Page 25 of 42 To perform a quantitative screening level assessment of potential exposures of aquatic organisms to OEPA that could be released to surface water during its incorporation into treated materials, the Agency would use an approach such as that us ed in General Population and Ecological Exposures from Industrial Releases module of E

- FAST (hereinafter referred to as the Industrial Releases module). This model requires the information that follows :

- SIC code classification for each category of treate d material into which OEPA would be incorporated or identification of locations of specific facilities at which OEPA would be incorporated into treated materials

- environmental release of OEPA to surface water in kg/site/day at each facility or category of facilities

.

- maximum number of days per year OEPA would be expected to be released to surface water at each facility or category of facilities

.

- percent removal of OEPA during wastewater treatment

.

- concentrations of concern for aquatic organism s.



## 4.5 Effec ts Analysis Plan
The Agency will use the results from the requested ecological studies to determine if any exposure occurs from the use pattern of O E PA.


## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews numerous stu dies 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 s ex 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 OEPA

, EPA review ed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), OEPA is subject to the endocrine screening part of the Endocrine Disruptor Scre ening 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 toPage 26 of 42 interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where E PA 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 dos e 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, 2013 18 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be c onstrued 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 websit e: http://www.epa.gov/endo/. 19

14



## 6 Optional Label Changes

The OEPA labels currently prohibit use on wood to be used in or near fresh water or salt water; these prohibitions are no longer considered to be practi cal or enforceable and need to be removed from the labels. Also, as noted in section 1.4.2 and elsewhere in this document , application rates should be lowered for certain OEPA uses, including for paints, carpet cleaners, textiles, and
mattress covers to ad dress RED mitigation

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



## 7 Guidance for Commenters

7.1 Preliminary Work Plan
The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency will carefully consider all comments as well as any addit ional information or data provided in a timely manner prior to issuing a final work plan for the o rganic e sters of p hosphoric a cid registration review case.



### 7.1.1 Trade Irritants

14 18 18 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the second list of chemicals.

19 http://www.epa.gov/endo/Page 27 of 42 Through the registration review process, the Agency intends to solicit informatio n on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Stak eholders are asked to comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the nature of the concern.



### 7.1.2 Water Quality

The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 20

15 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.



### 7.1.3 Environmental Justice EPA seeks to achieve environmental justice, the fair treatment an d meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to OEPA c ompared to the general population

. Please comment if you are aware of any sub

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



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

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

- making process. In the SAR process, a chemical's molecular structure is compared to that of other chemicals for which data are available. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties. Thus, the chemical’s physical, chemical, and biological properties are a function of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To

15 20 http://www.epa.gov/oppsrrd1 /registration_review/water_quality_sop.htmPage 28 of 42 devel op a QSAR, a selected set of measured data on a single physical, chemical, or biological property is used to derive a model (an equation) to predict the value of that property.

Since SAR assessments and QSAR modeling are another set of tools that are avai lable to Agency scientists, OPP has begun a process shift that envisions shifting from the current study

- by

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

- of

- the

evidence evaluation.

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

- lined, i.e., a screening

- level assessment procedure rather than multiple tiers of assessments with progressively more data requirements.

If stakeholders believe that submission of predicted data can fulfill one of the data needs for the OEPA c ase, then the Agency invites submission of this information. The submitter would be expected to supply a rationale describing the utility of the information and provide documentation on the scientific validity of the information. The determination that the predicted data fulfills the data requirement would be at the so le discretion of the Agency. Pre

- submission consultation with the Agency is encouraged.



### 7.1.5 Additional Information

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

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

1. Usage/use information for non

- agricultural uses (e.g., materials preservation) 2. State or local use restrictions 3. Ecologica l incidents (non

- target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency 4. Monitoring data



## 8 Next Steps

After the 60

- day comment period closes in May 2014 , the Agency will review and respond to any comments received in a timely manner, and then issue a Final Work Plan for the OEPA case.Page 29 of 42 

## 9 References

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

U.S. Environmental Protection Agency. High Production Volume Information System (HPVIS). http://www.epa.gov/hpvis/

44858901 Harrison, E. (1999) Aseptrol Deodorizing Drip Pad: Product Identity and Composition, B eginning Materials, Production Process and Formation of Impurities. Unpublished study prepared by Engelhard Corporation. 15 p. {OPPTS 830.1550, 830.1600, 830.1650, 830.1670} 23

- Jun

- 1999

. Interface Research Corporation’s Material Safety Data Sheet dated Jan uary 31, 2007.Page 30 of 42 

# Appendix A T oxicology Profile Acute Toxicity for Product Labeling

As listed in Table A1

, o rganic e sters of p hosphoric a cid was found to be low toxic (Toxicity Category IV) with a n observed lethal dose greate r than 5000 mg/kg for both acute oral and dermal toxicity . Mortality was observed at all concentrations in rabbits in an acute inhalation toxicity study , resulting in an LD 50 determination of 1.48 mg/ L (combined) ( Toxicity Category III). The o rganic este rs of p hosphoric a cid w ere shown to be mildly irritating to the e ye s ( Toxicity Category I I I) and is not a dermal irritant ( Toxicity Category IV ).

Table A1

– Acute Toxicity Studies for Organic Esters of P hosphoric Acid

Guideline No./Study Type MRID No. Re sults Toxicity Category 870.1100/ Acute oral toxicity

– rat 4 29079 01 LD 50 (M/F) > 5 000 mg/kg (observed) I V

870.1200/ Acute dermal toxicity

– rabbit 42907902 LD 50 (M/F) > 5 000 mg/kg (observed) I V

870.1300/ Acute inhalation toxicity

– rat 40423 801; 41365401 ; 41365402 LC 50 (M/F) = 1.48 mg/L LC 50 (M) = 1.43 mg/L LC 50 (M/F) = 1. 53 mg/L Unknown

870.2400/ Primary eye irritation

– rabbit 44858903 Mildly irritating I II

870.2500/ Primary dermal irritation

– rabbit 4 48589 0 4 Not irritating I V

87 0.2600/ Skin sensitization

– guinea pig 44761001 No conclusions could be drawn due to irritation . This study was identified as a data gap in the RED. N/A

N/A=Not available 

## Subchronic Toxicity

Adequacy of D atabase for Subchronic Toxicity : The databas e for subchronic toxicity is considered incomplete. Only a n acceptable 90

- day oral toxicity study in the rat (MRID 41083601 ) is available for addressing subchronic toxicity. A 90

- day dermal toxicity study in rats and an inhalation toxicity study are anti cipated to be required for the currently registered uses

.
870.3100 90

- Day Oral Toxicity

– Rat

In a 90

- day subchronic oral toxicity study (MRID 41083601 ) , groups of 10 male and 10 female Sprague

- Dawley rats were given Intersept (100% a.i., Lot/Batch #3.791 ) administered in the diet at 0, 62.5, 200 and 625 (weeks 1

- 6)/375 (weeks 7

- 13) mg/kg/day in males and 0, 37.5, 120 and 375 mg/kg/day in females. Doses were determined from a 14

- day dietary range

- finding study in rats (MRID 41665301).

No deaths occurred d uring this study, but the high dose in males was reduced from 625 mg/kg/day to 375 mg/kg/day after six weeks due to increasing weight loss in this group. The report stated that clinical signs were observed in mid

- and high

- dose rats, which includedPage 31 of 42 piloer ection (which progressed to rough haircoat) and fur staining. Actual data were not provided. Ophthalmoscopic examination revealed lenticular degeneration in 3/10 high

- dose males and 7/10 high

- dose females vs. 0/20 in control. Treatment

- related histopath ologic findings were forestomach lesions (gastritis/ulcer

- erosion/squamous hyperplasia hyperkeratosis) in intermediate

- and high

- dose males and lenticular degeneration in 5/10 high

- dose females and 1/10 high

- dose males (0/20 control).

Small, statistically significant changes in a few hematologic parameters (increased platelets, decreased hemoglobin, MCV, MCH and PCV) were reported, primarily in high

- dose females but these values were within reference ranges established previously at the test site. Changes i n clinical chemistry parameters included decreased GPT in high

- dose males (

- 28%) and low

- , mid

and high

- dose females (

- 17%,

- 15%, and

- 27%, respectively), total bilirubin in mid

- and high

dose males (

- 42% and

- 47%, respectively) and high

- dose females (

- 42 %), and phosphorus in mid

- and high

- dose females (

- 22% and

- 11%, respectively). In addition, creatinine was decreased in high

- dose males only (

- 7%, p ≤ 0.05). These changes, while statistically signifi

cant, were relatively small and were likely not biol ogically relevant because they were not correlated with any histopathologic findings.

Body weight was statistically significantly decreased in mid

- dose males (

- 9 to

- 15%) and high

dose males (

- 15 to

- 29%) and females (

- 10 to

- 13%) during the study. Total body weight gain was also decreased in mid

- dose males (

- 22%), and in high

- dose males (

- 42%) and females (

- 32%). Concomitant decreased food consumption was observed in mid

- dose males (

- 14%) and high

- dose males (

- 27%) and females (

- 17%).

Increases in kidney weight relative to body weight in both high

- dose males and females (+15%), and testes weight relative to body weight in mid

- and high

- dose males (+13% and +26%, respec

tively) were likely related to decreases in body weight. Liver weight relative to body weight was increased only in mid

- and high

- dose females (+12% and +25%, respectively), however, these increases were moderate and of unknown toxicologic significance in the absence of other toxic liver findings.

The systemic LOAEL in males is 200 mg/kg/da y based on decreased body weights, body weight gain, and food consumption and forestomach lesions (gastritis/ulcer

- erosion/squamous hyperplasia hyperkeratosis); the NOAEL in males is 62.5 mg/kg/day. The LOAEL in females is 375 mg/kg/day based on decreased body weight, body weight gain, food consumption, and lenticular degeneration; the NOAEL in females is 120 mg/kg/day

. 

## Developmental Toxicity

Adequacy of Database for Prenatal Developmental Toxicity: The database for prenatal developmental toxicity is con sidered inadequate for the currently registered uses. D evelopmental toxicity assessment for o rganic esters of p hosphoric a cid is based on a n acceptable developmental study in the rat ( MRID 41151601)

. A developmental toxicity study in

non

- rodent species i s anticipated to be required based on the adverse effects observed in the rat study and the currently registered uses.Page 32 of 42 870.3700 Prenatal Developmental Toxicity ( Gavage ) Study

– Rat

In a developmental toxicity study ( MRID 41151601), 25 presumed pregnant Ch arles River rats (Crl: CD ® BR) per group were administered Intersept ® (100.0% a.i.) by gavage at doses of 0, 125, 250 or 500, mg/kg/day on gestation days (GD) 6

- 15, inclusive. The controls were given vehicle (corn oil) only for the same dosing period. On GD 20, all dams were sacrificed, necropsied to assess gross pathology, and uteri and ovaries were removed. All fetuses were sexed, weighed, and examined for external malformations/variations prior to sacri fice. Approximately one

- half of the fetuses were fixed in ethanol and the remainder were placed in Bouin’s fixative and examined for visceral malformations/variations. The ethanol

- fixed fetuses were further processed, stained, and examined for skeletal malformations/variations.

Four treatment

- related d eaths occurred at 500 mg/kg/day. Clinical signs of toxicity observed at 500 mg/kg/day were salivation with red stain around the mouth (7) and nose (10), hypoactivity (8), urine stains (17), and fecal stains (4) compared to 0/25 control dams. Urine stains were also observed on one low

- dose animal and four mid

- dose animals. There were no statistically or biologically significant gross necropsy observations at maternal sacrifice. Absolute body weights were statistically significantly reduced (p ≤ 0.05 or 0.0 1) for 250 and 500 mg/kg/day dams during GD 8, 12, 16, and 20 and statistically significantly reduced body weight gain was observed for both treatment groups during GD 6

- 8 and GD 0

- 20 (11.1 and 20.6%, respectively during GD 0

- 20). Net body weight change f rom GD 0 was also statistically significantly reduced at 250 and 500 mg/kg/day (17.2 and 21.1%, respectively), compared to controls. Food consumption was not monitored. No treatment

- related maternal changes were noted at 125 mg/kg/ day.

The maternal toxic ity LOAEL is 250 mg/kg/day based on clinical signs of toxicity and reduced absolute body weights and weight gains. The maternal toxicity NOAEL is 125 mg/kg/day.

There were statistically significant increases (p ≤ 0.01) in total resorptions, early resorption s, and postimplantation losses at 500 mg/kg/day compared to controls. One high

- dose dam had com

plete litter resorption of two implantation sites. The increase in postimplantation loss resulted in slightly (n.s.) decreased number of fetuses per litter fo r the high

- dose group. Also at 500 mg/kg/day there were statistically significant decreases (p ≤ 0.01) in live mean fetal weight (9.5%) and live female fetal weight (10.1%) compared to controls. Gravid uterine weights were also lower than controls at 250 a nd 500 mg/kg/day (6.2 and 20.3%, respectively) but did not reach statistical significance.

The total fetuses (litters) with major external, visceral or skeletal malformations was 0 (0), 1 (1), 4 (2), and 17 (9) (p ≤ 0.05), in the control, low

- , mid

- , and hig h

- dose groups, respectively. A posi

tive trend for certain skeletal variations (delayed ossification of the hyoid, skull, pelvic girdle, vertebrae, sternebrae, and metatarsals) was also evident with increasing doses of Intersept ® with the 500 mg/kg/day gr oup generally statistically significantly increased (p ≤ 0.05) compared to controls. A dose

- related increase was also observed in the number of litters containing fetuses with increased renal pelvic cavitation and dilation of lateral ventricles of the brain

. At 0,125, 250, and 500 mg/kg/day, the number of fetuses/litters with external malformations were 0/0, 1/1, 4/2, and 8/6 (litter rate, p ≤ 0.05), respectively. External malformations at 500Page 33 of 42 mg/kg/day consisted of one fetus each with cleft palate and anopht halmia; umbilical hernia; umbilical hernia, microphthalmia, exencephaly, and spina bifida; extra hind limb; malformed head; humpback; and 2 with anophthalmia. At 250 mg/kg/day, malformations consisted of one fetus with gnathocephaly, and, from a different litter, a fetus with microphthalmia and two fetuses with umbilical hernia.

At 0,125, 250, and 500 mg/kg/day, the number of fetuses/litters with skeletal malformations were 0/0, 1/1, 1/1, and 6/4 (litter rate, p ≤ 0.05), respectively. Wavy or bent ribs were seen in 2 fetuses from 2 litters at 250 mg/kg/day and in 15 fetuses from 8 litters at 500 mg/kg/day compared to none in controls. Skeletal malformations at 500 mg/kg/day consisted of vertebral anomaly with or without associated rib anomaly in 3 fetuses f rom 2 litters; cervical vertebrae fused in 2 fetuses from 2 litters; and single incidences of exencephaly, forked/fused ribs, and supernumerary limbs.

No treatment

- related fetal effects were observed at 125 mg/kg/day.

The developmental toxicity LOAEL is 25 0 mg/kg/day based on dose

- related increases in the number of litters with fetuses with skeletal and visceral abnormalities. The developmental toxicity NOAEL is 125 mg/kg/day. 

## Reproductive Toxicity

Adequacy of Database for Reproductive Toxicity: There is no reproductive toxicity study available for organic esters of p hosphoric a cid and such a study is required under 40 CFR Part 158 W to support the currently registered uses. In addition, there are other toxicological concerns that need to be evaluated in a reproductive study. A two generation reproduction study is therefore anticipated to be needed for registration review. 

## Chronic Toxicity /Carcinogenicity

Adequacy of Database for Chronic Toxicity /Carcinogenicity : The database for c hronic toxicity/carc inogenicity is inadequate for the currently registered uses of organic esters of
p hosphoric a cid

. There is potential surface water exposure from incorporation of OEPA into some products, including some plastics, epoxy flooring/tile, textile, paints, stain s, adhesives, and caulk compounds. A drinking water assessment is anticipated to be conducted, which triggers the data requirement of chronic toxicity/carcinogenicity. A combined chronic toxicity/carcinogenicity study is anticipated to be required

. 

## Muta genicity

Adequacy of Database for Mutageni city: The database for mutagenicity is considered adequate for the currently registered uses based on the EPA's 1991 mutagenicity guidelines . Several mutagenicity studies have been submitted and reviewed by the O ffice of Pesticide Programs (OPP) and found acceptable. Organic e sters of p hosphoric a cid is found to be not mutagenic or genotoxic. The summaries of these studies are provided below.Page 34 of 42 Gene Mutation

In a reverse gene mutation assay in bacteria (MRID 40 564601), strains TA98, TA100, TA1535, TA1537 and TA1538 of S. typhimurium were exposed to Intersept® (Lot No. K13508 RJ, purity not provided) in DMSO at concentrations of 0.005, 0.01, 0.05, 0.1 and 0.5 μL/plate in the presence and absence of mammalian meta bolic activation (S9

- mix). Intersept® was tested up to cytotoxic concentrations. There was no evidence of induced mutant colonies over background.

In a reverse gene mutation assay in bacteria (MRID 40564602), strains TA98, TA100, TA1535, TA1537 and TA1 538 of S. typhimurium were exposed to Intersept® (Lot No. 2991, purity not provided) in DMSO at concentrations of 0.01 , 0.05, 0.1, 0.5 and 1.0 μL/plate in the presence and absence of mammalian metabolic activation (S9

- mix). Intersept® was tested up to cytotoxic concentrations. There was no evidence of induced mutant colonies over background.

Cytogenetics

In a mammalia n cell cytogenetics assay (chromosomal aberrations) (MRID 40564603), Chinese hamster ovary CHO

- WBL cell cultures were exposed to Intersept® (Lot No. P2991, purity not provided) in DMSO at concentrations of 2.5, 5.0, 7.5, 10.0 μg/mL with a 10 hour harvest t ime without S9

- mix and at concentrations of 10, 20, 30 and 40 μg/mL at a 20 hour harvest time without S9

- mix. Cells were exposed to concentrations of 5, 7.5 10, 25, 50, 75 and 100 μg/mL with a 10 hour harvest time with S9

- mix. Intersept® was tested up to cytotoxic concentrations. There was no evidence of chromosomal aberrations induced over background levels.

In a bone marrow micronucleus assay (MRID 47715601), 5 male CD

- 1 mice/dose were treated once via gavage (20.5 mL/kg) with Intercept (purity 98%

, Batch No. 1260809A) in corn oil at doses of 0, 500, 1000, or 2000 mg/kg (limit dose), and bone marrow cells were harvested at 24 hours after dosing. Additional groups of 5 male mice were similarly dosed at 0 or 2000 mg/kg, and bone marrow cells were harv ested at 48 hours post

- dosing. Cyclophosphamide (80 mg/kg) served as the positive control.

No mortality or clinical signs of toxicity were observed at the dose level up to 2000 mg/kg (limit dose)

. No significant decreases in the PCE:NCE ratio were observ ed in any treatment group compared to controls, indicating that the test material did not markedly inhibit th e growth of bone marrow cells (not cytotoxic to the bone marrow). No treatment

- related increases in the micronucleated polychromatic erythrocytes ( MPCE) frequency were observed in any treatment group at either harvest time when compared to controls. The positive control induced the appropriate response. Based on the test result, Intercept did not induce a treatment

- related increase in the frequenc y of micronucleated PCEs in bone marrow after any treatment time.

Although there was no indication of bone marrow growth inhibition, the animals were dosed at the limit dose (2000 mg/kg). Therefore, this study is classified as Acceptable/guideline and
sat isfies the guideline requirement (OPPTS 870.5395; OECD 474) for in vivo cytogenetic mutagenicity data.

In a mammalian cell cytogenetics assay (sister chromatid exchange [SCE]) (MRID 40564604), Chinese hamster ovary CHO

- WBL cell cultures were exposed to Int ersept® (Lot No. P2991, purity not provided) in DMSO at concentrat ions of 0.033, 0.10, 0.333, 1.00, 3.33, 10.0, 33.3,Page 35 of 42 100, 333, 1000 μg/mL with and without mammalian metabolic activation (S9

- mix). Cells were treated for 25 hours without S9

- mix and for 2 hours with S9

- mix and harvested 25.5 hours after termination of tre atment without S9

- mix and 2.5 hours after treatment with S9

- mix. The S9

- fraction was obtained from Aroclor 1254 induced male Sprague

- Dawley rat liver. Intersept® was tested up to cytotoxic concentrations. There was no evidence of SCEs induced over backg round levels. 

## Other Toxicological Effects

An i mmunotoxicity study is included as a data requirement for all antimicrobial pesticide chemicals under 40 CFR Part 158W, Data Requirements for Antimicrobial Pesticides. The registrant can address this antici pated data requirement by either submitting a study according to the OCSPP 870.7800 Guideline, by citing information from the scientific literature that addresses Immunotoxicity of (chemical), or by submitting a request for waiver of this study using the A gency’s published guidance, available at: http://www.epa.gov/pesticides/regulating/part158

- tox

- data

- requirement.pdf

. Toxicity Profile Table

Acute Toxicity Table

– See Table A1

Table A2 Subchronic, Chronic , and Other Toxicity

Guideline Number/

Study Type/

Test Substance (% a.i.) MRID Number (Year)/

Classification/ Doses Results

870.3250

90

- day oral

- Rat

Purity 100 % (Intersept ® ) MRID 41 083601/ 4 1 665301 (1989)

Acceptable

- Guideline

Rat, oral/diet ( 1 0/sex/group)

0, 62.5

, 2 00, or 375/625 mg/kg/day (male);

0, 37.5, 120 or 375 mg/kg/day (female), 90 days NOAEL male = 62.5 mg/kg/day

LOAEL male = 2 00 mg/kg/day , based on decreased body weights, body wei ght gain, and food consumption and forestomach lesions (gastritis/ulcer

- erosion/squamous hyperplasia hyperkeratosis) ;

NOAEL female = 120 mg/kg/day

LOAEL female = 375 mg/kg/day, based on decreased body weight and weight gain and lenticular degeneration.Page 36 of 42 Guideline Number/

Study Type/

Test Substance (% a.i.) MRID Number (Year)/

Classification/ Doses Results

870. 3700

Developmental (gavage)

- Rat

Purity 100 % MRID 411 51601/ 40 679502 (1989)

Acceptable

- Guideline

Females rats (25/dose)

0, 1 25

, 250 , or 500 mg/kg/day, GD 6

- 15, inclusive Maternal toxicity: NOAEL = 1 25 mg/kg/day

LOAEL = 25 0 mg/kg/day, based on clinical signs of toxicity and reduced absolute body weight and weight gain;

Developmental toxicity: NOAEL = 1 25 mg/kg/day

LOAEL = 250 mg/kg/day based on dose

related increases in the number of litters with fetuses with skeletal and visceral abnormalities.

870.526 5

Bacterial reverse mutation test

Purity not provided MRID 40 56460 1 (1986)

Acceptable

- Guideline

Strains TA98, TA100, TA1535, TA1537 and TA1538

0.00 5 , 0.0 1 , 0. 05 , 0. 1 , or 0 .5 μL /plate with and without S9 Negative

870.5265

Bacterial reverse mutatio n test

Purity not provided MRID 40564602 (1987)

Acceptable

- Guideline

Strains TA98, TA100, TA1535, TA1537 and TA1538

0.0 1 , 0. 05 , 0. 1

, 0 .5 or 1.0 μL /plate with and without S9 NegativePage 37 of 42 Guideline Number/

Study Type/

Test Substance (% a.i.) MRID Number (Year)/

Classification/ Doses Results

870.5375

In Vitro mammalian chromosome aberration test (hamster)

Puri ty not provided MRID 40564603 (1987)

Acceptable

- Guideline

2.5, 5.0, 7.5, 10.0 μg /mL (10

- hr harvest time) without S9 metabolic activation ;

10, 20, 30, 40 μg /mL (20

- hr harvest time) without S9 metabolic activation ;

5, 7.5, 10, 25, 50, 75, 100
μg /mL (10

- hr harvest time) with S9 metabolic activation Negative

10 870.5395

10.1.1 In Vivo Mammalian Cytogenetics

- Erythrocyte Micronucleus Assay ( M ouse)

Purity 9 8% (Intersept ® ) 10.1.2 MRID 47715601 (2009)

10.1.3 Acceptable

- G uideline

10.1.3

0, 500, 1000, or 2000 mg/kg (limit dose) Negati ve

870.5900

Mammalian cytogenetics (sister chromatid exchange)
assay ( hamster )

Purity not provided MRID 40564604 (1987)

Acceptable

- Guideline

0.033, 0.10, 0.333, 1.00, 3.33, 10.0, 33.3, 100, 333, 1000
μg /mL with and without S9 NegativePage 38 of 42 

# Appendix B Environmental Fate Environmental Fate Properties

No environmental fate data have been submitted for organic esters of phosphoric acid , which is a mixture of phosphoric acid with either one 21

16 or two 22

17 ethylhexyl groups and a companion molecule. 23

18 As a result, the Age ncy ant i cipate s requiring the environmental fate data contained in Table 6.

21

16 Mono(2

- ethylhexyl ester) of phosphoric acid
22

17 Bis(2

- ethylhexyl ester) of phosphoric acid
23

18 2,2’

- (cocoimino)

- bis ethanol saltPage 39 of 42 

# Appendix C E cotoxicology Profile

Toxicity to Terrestrial and Aquatic Receptors

No Terrestrial and aquatic eco

- toxicity studies are available for OEPA. Four eco

- toxicity studies are being required for O E PA and several studies are anticipated to be required depending on the exposure scenarios determined by the down

- the

- drain analysis (Table 12)

.Page 40 of 42 

# Appendix D Screening Level Down

- the Drain A nalysis

Unless the Agency receives data or other sources of information that demonstrates that OEPA is not released to surface water or if it is released to surface water, OEPA and any degradates it forms do not persist or are not very toxic to aquatic organisms, the Agency will need to pe rform an ecological risk assessment for OEPA to assess potential releases of OEPA to surface water and subsequent exposures to aquatic organisms from incorporation into treated materials and from leaching from in

- service use of treated materials.

To perfor m a screening level assessment of potential exposures of aquatic organisms to OEPA due to leaching from in

- service use of treated materials, the Agency would use the Down

- the

Drain (DtD) module of the Exposure and Fate Assessment Screening Tool (E

- FAST) mo del.

To perform a quantitative screening level assessment of potential exposures of aquatic organisms to OEPA that could be released to surface water during its incorporation into treated materials, the Agency would use an approach such as that used in Gen eral Population and Ecological Exposures from Industrial Releases module of E

- FAST (hereinafter referred to as the Industrial Releases module).

Information the Agency would need to assess potential exposures of aquatic organisms to OEPA due to leaching fro m in

- service use of treated materials and incorporation into treated materials is discussed in 4.4.2. of this preliminary work plan.Page 41 of 42 

# Appendix E Product Chemistry

Organic e sters of p hosphoric a cid chemistry information is summa rized in Table E1 (source: M RID 43265801 and Interface Research Corporation’s MSDS ).

Table E1

– P roduct Chemistry of Organic Esters of Phosphoric Acid

OCSPP Guideline No. Physical and Chemical Properties Mixture of 3 AIs

• Phosphoric acid, mono(2

- ethylhexyl) ester (17.7%)

• Phosphoric acid, bis(2

- ethylhexyl) ester, comp ound w ith 2,2'

- (coco alkylimino)bis(ethanol) (1:1) (66.4%) and

• Phosphoric acid, mono(2

- ethylhexyl) ester, comp oun ds with diethanolamine N

- coco alkylderivs. (1:1) (15.9%) 830.1550 Product identity and composition Refer to Table 3

830.1600 Description of materials used to produce the product Confidential Business Information (CBI)

830.1620 Description of production
process CBI

830.1650 Description of Formulation Process CBI

8 30.1670 Discussion of formulation of impurities CBI

830.1700 Preliminary analysis CBI 830.1750 Certified limits CBI 830.1800 Enforcement analytical method HPLC

- MS Gas Chromatography (GC) GC

- MS

. 830.1900 Submittal of samples CBI 830.6302 Color Yell ow viscous liquid

. Clear viscous liquid

. Pale to light amber viscous liquid.
830.6303 Physical State Viscous liquid

. 830.6304 Odor Sweet amine odor.
830.6313 Stability to normal and elevated temperature, metals/metal ions Stable. Stable at normal temperatures of use and storage. Conditions to avoid: Exposure to elevated temperatures.

830.6314 Oxidation/Reduction:

Chemical Incompatibility: Not applicable. Product contains no oxidizing or reducing agents.

Materials to avoid: Strong acids and base s.

830.6315 Flammability Non

- flammable. Flash point: Above 300 ° F 830.6316 Explodability Not applicable. Product is not explosive.
830.7000 pH 3.0 to 3.6 (10% in 75% ethanol) 830.7050 UV/Visible Absorption Not Reported.
830.7100 Viscosity Yellow vi scous liquid. 13,000 ±3000 cps @30 ° C 830.7200 Melting point:

Freezing point: Not applicable. Product is liquid at room temperature.

< 32 ° F 830.7220 Boiling point Decomposes before boiling.Page 42 of 42 OCSPP Guideline No. Physical and Chemical Properties Mixture of 3 AIs

• Phosphoric acid, mono(2

- ethylhexyl) ester (17.7%)

• Phosphoric acid, bis(2

- ethylhexyl) ester, comp ound w ith 2,2'

- (coco alkylimino)bis(ethanol) (1:1) (66.4%) and

• Phosphoric acid, mono(2

- ethylhexyl) ester, comp oun ds with diethanolamine N

- coco alkylderivs. (1:1) (15.9%) 830.7300 Density Density: 1.0 g/ ml Sp Gr 0.98 830.7370 Dissociation Constant ( pKa ) Not applicable because of the very limited water solubility of the compound and the requirement to add surfactant to form a water stable emulsion it is very difficult to accurately determine the dissociation constant for the che mical. 830.7520 Particle size, fiber length, & diameter distribution Not Applicable.

830.7550 Partition coefficient (Log Kow ) Not applicable for surface active chemicals.

830.7840 Solubility in water 0.0324 g/100 ml 324 mg/L Low water solubility. 8 30.7860 Solubility in organic solvents Soluble in d imethyl sulfoxide (DMSO) 500 mg/ml

. Soluble in n

- octanol in all proportions at 20 ° C. Soluble in ethanol. 830.7950 Vapor pressure 1.0 x 10 - 2 mm HG at 20 ° C (water) 0.01 mm Hg @ 20 ° C ( 1.33 Pa @ 20 ° C ) (wa ter)