Page 2 of 42 Organic Esters of Phosphoric Acid (OEPA) Registration Review Team

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

Risk Management SanYvette Williams James Parker Zebora Johnson Eric Miederhoff

Office of General Counsel Philip RossPage 3 of 42 

### Table of Contents
1 Introduction .................................................................................................................. ........... 5 1.1 Statutory and Regulatory Authority ................................................................................. 5 1.2 Updates to the Final Work Plan ....................................................................................... 7 1.3 Case Overview ................................................................................................................. 7 1.4 Chemical Identification and Properties ............................................................................ 8 1.5 Use/Usage Description ..................................................................................................... 9 1.5.1 Registrations ............................................................................................................. 9 1.5.2 Summary of Regist ered Uses .................................................................................... 9 1.6 Regulatory History ......................................................................................................... 11 1.6.1 Recent/Pending Regulatory Actions ....................................................................... 11 1.6.2 Tolerance Information ............................................................................................ 11 1.7 Incidents ..................................................................................................................... .... 11 1.7.1 Human Health ......................................................................................................... 11 1.7.2 Ecological ............................................................................................................... 11 2 Anticipated Data Needs ........................................................................................................ 11 3 Human Health Risk Assessment ........................................................................................... 16 3.1 Existing Toxicological Endpoints .................................................................................. 16 3.2 Dietary Exposure ............................................................................................................ 1 7 3.2.1 Food ........................................................................................................................ 1 7 3.3 Occupational and Residential Exposures ....................................................................... 18 3.3.1 Occupational Handler Exposure ............................................................................. 18 3.3.2 Residential Handler Exposures ............................................................................... 19 3.3.3 Residential Post-Applic ation Exposures ................................................................. 19 3.4 Aggregate and Cumulative Exposure ............................................................................. 20 3.4.1 Aggregate Exposures .............................................................................................. 20 3.4.2 Cumulative Exposures ............................................................................................ 20 4 Environmental Risk Assessment........................................................................................... 21 4.1 Environmental Fate ........................................................................................................ 21 4.1.1 Effect of Chemical and Physical Properties ............................................................ 21 4.1.2 Abiotic Processes .................................................................................................... 22 4.1.3 Biotic Processes ...................................................................................................... 22 4.1.4 Transport Processes ................................................................................................ 22 4.1.5 Water Quality .......................................................................................................... 22 4.2 Environmental Conceptual M odel Exposure Pathways ................................................. 23 4.3 Ecological Effects Assessment ....................................................................................... 24 4.3.1 Mode of Action ....................................................................................................... 24 4.4 Exposure Analysis Plan .................................................................................................. 25 4.4.1 Aquatic and Terrestrial Wild life Exposure Estimates ............................................ 25 4.4.2 Screening Level Down-the-Drain Analysis ............................................................ 25 4.5 Effects Analysis Plan ..................................................................................................... 26 5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 26 6 Optional Label Changes ........................................................................................................ 27 7 Next Steps .................................................................................................................... ......... 27 8 References .................................................................................................................... ......... 28Page 4 of 42 Appendix A Toxicology Profile ............................................................................................... 29 Appendix B Environmental Fate ............................................................................................. 37 Appendix C Ecotoxicology Profile .......................................................................................... 38 Appendix D Screening Level Down-the Drain Analysis ......................................................... 39 Appendix E Product Chemistry ............................................................................................... 40 Appendix F Response to Comments ....................................................................................... 42

List of Tables Table 1 – Summary of Anticipated Risk Assessments and Data Needs: OEPA ............................ 6 Table 2 – Anticipated Regist ration Review Schedule .................................................................... 6 Table 3 – Chemical Identification of Organi c Esters of Phosphoric Acid (OEPA) ....................... 8 Table 4 – Physical-Chemical and Fate Properties for OEPA ......................................................... 9 Table 5 – Summary of OEPA Registered Uses ............................................................................ 10 Table 6 – Studies Anticipated as Needed for the Registration Review of OEPA ........................ 13 Table 7 – Existing Toxicologi cal Endpoints for OEPA ................................................................ 16 Table 8 – Occupational Handler Ex posure Scenarios for OEPA ................................................. 19 Table 9 – Residential Handler Exposure Scenarios for OEPA ..................................................... 19 Table 10 – MOEs for Residential Post Application Exposures to OEPA .................................... 19 Table 11 – Residential Post-Applicati on Exposure Scenarios for OEPA ..................................... 20 Table 12 – Ecological Effects E ndpoints Selected for Assessing Ri sks from Use of OEPA ....... 24Page 5 of 42 

## 1 Introduction

This document is the Environmen tal Protection Agency’s (EPA or “the Agency”) Final Work Plan (FWP) for the organic esters of phosphoric acid (herein referred to as OEPA). The FWP document explains what EPA's Office of Pe sticide Programs knows about OEPA, highlighting anticipated data and assessment needs, identify ing the types of information that would be especially useful to the agency in conducting the review, and providing an anticipated timeline for completing the OEPA review. This work pl an also addresses public comments received concerning the Preliminary Work Plan (PWP) whic h was posted in the OEPA registration review docket (EPA-HQ-OPP-2013-0373). Further, this doc ument makes final the work plan for the OEPA registration review process.



## 1.1 Statutory and Regu latory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the U.S. Environmental Protection Agency (USEPA, EPA, or the Agency ) based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The regist ration 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 th e statutory standard of no unreas onable 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 marketpl ace can be used safely. Information on this program is provided at http://www.epa.gov/oppsrrd 1/registration_review/.

The agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing registra tion review begin at 40 CFR 155.40. The agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the agency’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registrati on review decision. The preliminary work plan (PWP), published March 26, 2014, closed for public comment on May 19, 2014. No public comments were received in th e docket during this initial comment period, therefore, the agency has developed and is committing to a Final Work Plan (FWP) and anticipated schedule for the OEPA Case.

Documents associated with this registration re view can be viewed at http://www.regulations.gov in docket EPA-HQ-OPP-2013-0373. Table 1 summarizes the issues relevant to this registration review case. Table 2 is the anticipa ted registration review schedule.Page 6 of 42 Table 1 – Summary of Anticipated Risk Assessments and Data Needs: OEPA

Risk Assessment Assessment Necessary to Support Registration Review Date of Most Recent Assessment Type of Assessment Required (New/Updated) Data Anticipated as Needed

Dietary (food) No N/A None None

Dietary (drinking water) Yes N/A New Developmental Toxicity (non-rodent) Reproductive and Fertility Effects Immunotoxicity Chronic Toxicity/Carcinogenicity

Occupational Handler Yes 12/01/2007 Updated Dermal Indoor Exposure Inhalation Indoor Exposure 90-Day Dermal Toxicity 90-Day Inhalation Toxicity Developmental Toxicity (non-rodent) Reproductive and Fertility Effects Immunotoxicity Chronic Toxicity/Carcinogenicity

Residential Handler Yes 12/01/2007 Updated Same as above for occupational handler.

Residental Post Application - Incidental Oral and Dermal Yes 12/01/2007 Updated Indoor Surface Residue Dissipation 90-Day Dermal Toxicity Developmental Toxicity (non-rodent) Reproductive and Fertility Effects Immunotoxicity

Aggregate Yes 03/2008 Updated 90-Day Dermal Toxicity Developmental Toxicity (non-rodent) Reproductive and Fertility Effects Immunotoxicity Chronic Toxicity/Carcinogenicity

Cumulative No N/A None None

Tolerance Review No N/A None None

Ecological Yes 11/19/2007 New Environmental Fate WWTP studies, Ecotoxicology studies, Textile leaching studies, Leaching from treated articles (See Table 6 for further details.) N/A = Not applicable * Table 1 is a summary of the anticipated risk assessments and da ta needs for Registration Review. For data to be called in thr ough the post-RED DCI, see Table 6.

Table 2 – Anticipated Regi stration Review Schedule

Anticipated Activity Target Date* Completion Date Phase 1: Opening the Docket Open Docket and 60-Day Comment Period for Preliminary Work Plan 2014-03 2014-03-26 Close Public Comment Period 2014-05 2014-05-19 Phase 2: Case Development Issue Final Work Plan 2014-09Page 7 of 42 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 Proposed 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 Screening Program with respect to the active ingredients in this case).



## 1.2 Updates to the Final Work Plan

 Table 1 – Shortened ecological s ection by deleting individual studies and referring to Table 6.

 Section 2 – Updated this section to reflect additional human health toxicity studies necessary for the assessment of the currently registered uses of OEPA as a material preservative: 1) 90-day inhala tion toxicity study, 2) 90-da y dermal toxicity study, 3) developmental toxicity study in non-rodents, 4) two generation repr oductive toxicity study and 5) immunotoxicity study and 6) chronic t oxicity/carcinogenicity study for a drinking water exposure assessment.

 Table 6 - Moved 870.2600 (Dermal Sensitization study) and added 870.5395 (In vivo micronucleus test) to post-RED DCI section to reflect information currently in the postRED DCI. Revised Use Site(s) section fo r 870.3250 (90-day Dermal Toxicity study) to textile upholstery, mattresses and mattr ess covers, flooring and for 870.3465(90-day Inhalation Toxicity study) to paints, stains and coatings.

 4.2 Environmental Conceptual Model Exposure Pathway – Added a bullet referencing the “Conceptual Models for Environmental Exposur e Pathways of Antimicrobial Pesticides”

memo.

 Sec 4.3 Ecological Effects Assessment – Update d this section to be consistent with potential exposure pathways and added footnote 2 to Table 6.

 Section 4.5 Effects Analysis Plan – Added disc ussion of open literature search that will be performed.

 Appendix B – Updated the environmental fate data language regardi ng leaching from inservice use.

 Updated format, corrected typographical erro rs and made other editorial changes.



## 1.3 Case Overview
The docket for organic esters of phosphoric acid (case 4122) has been established at http://www.regulations.gov in docket number EPA-HQ-OPP-2013-0373.Page 8 of 42 

## 1.4 Chemical Identification and Properties
Table 3 presents the active ingred ients to be assessed in case 4122. Organic esters of phosphoric acid consists of a mixture of three chemicals: Phosphoric acid, mono(2-ethylhexyl) ester (PC Code 111286), phosphoric acid, bis(2-ethylhexyl) este r, compound with 2,2'-(coco alkylimino)bis (ethanol) (PC Code 129079), and phosphoric acid , mono(2-ethylhexyl) ester, compounds with diethanolamine N-coco alkyl derivatives (PC Code 129080). These chemicals cannot be divided into components for individual testing and the three of them will be referred to as organic esters of phosphoric acid (OEPA) in this registration review.

Table 3 – Chemical Identification of Or ganic 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- eth y lhex y l) ester, compds. with diethanolamine N-coco alkyl derivs. Chemical Names (Mixture) Mono (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. 1070-03-7 68649-38-7 120579-32-0 Molecular Formula C 8 H 19 O 4 P 1 C 32 H 70 O 6 PN C 24 H 54 O 6 PN

Molecular Weight 210.21g/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 assessment is summarized in Table 4 and details of the product chemistry and environmental fate info rmation are discussed in Appendix E and B, respectively.Page 9 of 42 Table 4 – Physical-Chemical and Fate Properties 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, compound with 2,2'- (coco alkylimino)bis(ethanol) (66.4%) and

 Phosphoric acid, mono(2-ethylhexyl) ester, compounds with diethanolamine N-coco al kyl derivatives. (15.9%) 830.7000 pH 3.0 to 3.6
830.7050 UV/Visible Absorption Not reported. 830.7200 Melting poin t Freezing point: < 32 ° F 830.7220 Boiling point Decomposes before boiling. 830.7300 Density 1.0 g/ml
830.7370 Dissociation Constant Not applicable.

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 (Relatively soluble in water)

830.7860 Solubility in organic solvents Soluble in dimethyl sulfoxide (DMSO) 500 mg/ml. Soluble in n -octanol in all proportions at 20 ° C. Soluble in ethanol.

830.7950 Vapor pressure ~1.8 x 10 -8 to 5.3 x 10 -8 mm Hg (Epi-Suite) for all three compounds.



## 1.5 Use/Usage Description

1.5.1 Registrations There are two registered pesticide products (EPA Reg. Nos. 43670-1 and 43670-4) that contain OEPA. EPA Reg. No. 43670-1 contains 100 percen t a.i. and EPA Reg. No. 43670-4 contains 80 percent active ingredient. The thr ee organic esters of phosphoric ac id never occur as a pesticide single active ingredient or in any other combina tion or ratio in a regi stered pesticide product (EPA Reg. Nos. 43670-1 and 43670-4).



### 1.5.2 Summary of Registered Uses OEPA is registered for use as a materials preserva tive for a wide variety of materials as listed in Table 5. No direct or indirect food contact uses are approve d on registered end-use product labels. Several uses that could conceivably result in indirect food contact already have been prohibited by such label language as, "...to be us ed 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 in cluded technical data sheets which listed the application rates; however, the technical data sheets were 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 textiles, and 1.1 percent for mattress covers. These mitigation measures need to be incorporated into the labels.Page 10 of 42 Table 5 – Summary of OEPA Registered Uses

Use (All are Material Preservative Uses) Application Rate

Carpets Not Listed*

Epoxy flooring, coating, tile and grout products Not Listed*

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

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 acetat e indoor and outdoor) Not Listed*

Polymeric laminates (excluding laminates used for food preparation surfaces) Not Listed*

Polymer concrete Not Listed*

Textiles, synthetic and non-woven, (wall coveri ngs, car tops, awnings, tarps, tents, sails, drapes, shower curtains, and cubicle curtains) Not Listed*

Polymeric packaging film (to be used for purposes other than food storage) Not Listed*

Paints, Stains and Coatings, water-. oil and solvent based (interior and exterior substrates machinery and equipment in cluding 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 sealants, adhesives, and caulking compounds (natural and synthetic) Not Listed*

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

Vinyl Upholstery, Mattresses, Mattr ess ticking, and Mattress covers Not Listed*

Textiles (topical treatment of wall coverings, car tops, awnings, tarpaulins, tents, sails. drapes. shower curtains, apparel, cubi cle 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 include d technical data sheets, which listed the application rates; however , the technical data sheets were not included in the most rec ently approved labels

.Page 11 of 42 

## 1.6 Regulatory History

The first product containing OEPA as an active ingr edient was registered in the United States in 1982. This product, as well as the only other regi stered 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 Ca ll-In (DCI) is anticipat ed to be issued in 2014.



### 1.6.1 Recent/Pending Regulatory Actions

There are no recent regulatory actions for OEPA . EPA anticipates issuing the post-RED DCI in 2014.



### 1.6.2 Tolerance Information No tolerances, tolerance exemptions, or food additive regulations have been established for OEPA by either EPA or FDA.



## 1.7 Incidents

1.7.1 Human Health No OEPA human health incidents have been repo rted in OPP’s Incident Data System (IDS) for the time period spanning 1998 to the pres ent (database sear ched on 1/15/2014).



### 1.7.2 Ecological No OEPA ecological incidents have been reported in OPP’s Incident Data System (IDS) for the time period spanning 1998 to the presen t (database searched on 1/29/2014).



## 2 Anticipated Data Needs

Table 6 presents a summary of the data anticipate d as being needed to su pport this registration review. If the Agency receives da ta or other sources of informa tion that demonstrate that there would be negligible release of OEPA during inco rporation into treated materials and negligible leaching from in-service use of treated material s or that OEPA and/or its degradates will not persist if released to the envir onment, some or all of the environmental fate (OCSPP 835 series) and ecological effects (OCSPP 850 series) data anticip ated to be needed may not be required (see Table 6 for details).

The environmental fate data requirements in Tabl e 6 are presented in a tiered approach based on the results of laboratory studies th at isolate specific routes of dissipation in the environment. Hydrolysis (835.2120) data are antici pated to be required for all uses. For the uses that have the potential to result 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), anaer obic aquatic metabolism (835.4400), leachingadsorption-desorption (835.1230), activated slud ge sorption isotherm (835.1110), ActivatedPage 12 of 42 Sludge Respiration Inhibition, ASRI) (OECD 209 or OCSPP 850.3300), and a test to determine biodegradation potential in wastewat er treatment plant (WWTP).

Based upon the currently registered uses of OEPA as a material preservative , toxicity studies in addition to those presented in the PWP are necessary for the assessment as specified in 40 CFR Part 158W Data Requirements for Antimicrobial Pe sticides: 1) 90-day inha lation toxicity study, 2) 90-day dermal toxicity study, 3) developmen tal toxicity study in non-rodents, 4) two generation reproductive toxicity study, and 5) immunotoxicity study. The chronic toxicity and carcinogenicity studies are also required because uses may potentially result in drinking water exposure. If the environmental fate data in dicate low potential for drinking water exposure, these studies will not be required.Page13of42Table 6 – Studies Anticipated as Neededfor the Registration Review of OEPAGLNStudy NameTestSubstanceTime Frame(Measured in monthsfrom DCI Receipt)Risk Assessment(s)Data Will SupportUse Site(s) TriggeringAnticipated DataRequirementApplicableExposureScenarioStudies Anticipated to be Required through the Registration Review DCI835.2120 Hydrolysis TGAI 12Environmental Fate,Ecological EffectsAll uses except those noted inSection 4.2Manufacturing orIn-Service Use835.2240Direct photodegradation inwater1,2,3TGAI 12Environmental Fate,Ecological EffectsAll uses except those noted inSection 4.2Manufacturing orIn-Service Use835.4100 Aerobic soil metabolism2TGAI 24Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use835.4300 Aerobic aquatic metabolism2,3TGAI 24Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use835.4400 Anaerobic aquatic metabolism2,3TGAI 24Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use835.1230 Leaching-adsorption-desorption2,3TGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use835.1110Activated Sewage Sludge SorptionIsotherm3TGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use850.3300Activated Sludge RespirationInhibition (ASRI)3,4TGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use835.3110835.3220835.3240835.3280Ready biodegradability or one ofthe three biodegradation inactivated sludge simulation tests.3,4TGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service UseSpecial Study1249Leaching from treated article TGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use850.2100Acute oral toxicity to mallard duckor northern bobwhite quailTGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use850.1075Acute toxicity to rainbow trout orbluegill sunfishTGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use850.1010 Acute toxicity toDaphnia magnaTGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use850.5400 Aquatic plant growth (algal) tier II TGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use850.1300 Aquatic invertebrate life-cycle2,3TGAI 24Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service UsePage14of42GLNStudy NameTestSubstanceTime Frame(Measured in monthsfrom DCI Receipt)Risk Assessment(s)Data Will SupportUse Site(s) TriggeringAnticipated DataRequirementApplicableExposureScenario850.1400 Fish early-life stage2,3TGAI 24Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use850.4400Aquatic plant growth (aquaticvascular plant) Tier II-doseresponse2,3TGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use850.1025Acute estuarine and marineorganisms toxicity2,3TGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use850.1735Whole sediment: acute freshwaterinvertebrates2,3TGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use850.1740Whole sediment; acute marineinvertebrates2,3TGAI 12Environmental Fate,Ecological EffectsAll usesManufacturing orIn-Service Use870.3250 90-Day Dermal Toxicity TGAI 12 Human Health EffectsTextile, upholstery,mattresses, mattress covers,flooringAll870.3465 90-Day Inhalation Toxicity TGAI 12 Human Health Effects Paints, stains and coatings All870.3700bPrenatal Developmental ToxicityStudy (non-rodent)TGAI 12 Human HealthEffects All uses All870.3800 Reproduction and Fertility Effects TGAI 12 Human Health Effects All uses All870.4300Combined ChronicToxicity/Carcinogenicity2,3TGAI 24Drinking WaterAssessmentSome plastics, epoxyflooring/tile, textile, paints,stains, adhesives, and caulkcompoundsManufacturing orIn-service Use870.7800 Immunotoxicity TGAI 12 Human Health Effects All uses AllStudies Expected to be Requiredthrough the Anticipated Post-RED DCI870.2600 Dermal Sensitization Study TGAI 12 Human Health Effects All uses All870.5395In vivo mammalian micronucleustest, Mammalian erythrocytemicronucleus testTGAI 12 Human HealthEffects All uses All875.1200 Dermal Indoor Exposure5,6TGAI 12Occupational andResidential HandlerAll Uses See Note 5875.1400 Inhalation IndoorExposure5,6TGAI 12Occupational andResidential HandlerAll Uses See Note 5875.1700 Product Use Information TGAI 12Occupational andResidential Handler andPost ApplicationAll Uses AllPage15of42GLNStudy NameTestSubstanceTime Frame(Measured in monthsfrom DCI Receipt)Risk Assessment(s)Data Will SupportUse Site(s) TriggeringAnticipated DataRequirementApplicableExposureScenario875.2300Indoor Surface ResidueDissipation7,8TGAI 12Residential PostApplicationVinyl Flooring, Textiles andMattress CoversSee Notes 7 and 81Not required when the electronic absorption spectra, measured at pHs 5, 7, and 9, ofthe chemical and its hydrolytic products,if any, show no absorption or tailing between 290 and 800 nm.2These anticipated data requirements are based on the potential forOEPA to leach from treated materials. Data are not expectedto be required if information provided to the Agencydemonstrate that leaching from in-service use results in negligible releases to surface water.3These anticipated data requirements are based on the potential forOEPA to be released to surface water via WWTPs as a result of incorporation into treated materials. Data are not expectedto be required if information provided to the Agency demonstrates that releases to WWTPs during incorporation of OEPA into treated materials is negligible.4The results of the Activated Sludge Respiration Inhibition Test (ASRI) expectedto be required will determine which of these four biodegradation tests would be anticipated to be required. Ifthe ASRI test EC50is 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 SludgeUnits or (iii) the Porous Pot Test would be anticipated to be required. If the ASRI test EC50is greater than 20 mg/L, then the DCI expected to be issued would provide that the registrantwould choose to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation inActivated 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 tobe required. If, however, the antimicrobial fails the ReadyBiodegradability study, then the a) Biodegradation in Activated Sludge or b) SimulationTest – Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study would beexpected to be required. The appropriate TestSubstances are the three components of OEPA.5Occupational and Residential Handler ExposureScenarios include Open Pour Liquids forMaterial Preservation, Brush Applicationof Preserved Paint and Airless Spray Application ofPreserved Paint.6It may be possible to use proprietary surrogate exposure data if data compensation issues are appropriately and adequately addressed.7Residential Post Application Exposure Scenarios include dermal and incidental oral exposure, vinyl flooring, dermal and incidental oral exposure to textiles and dermal exposure to mattresscovers.8If surface residue data are not available,then the standard assumption of 100 percent transferable surface residue will be used which might overestimate the risk.Docket Number EPA-HQ-OPP-2013-0373 www.regulations.gov

Page 16 of 42 

## 3 Human Health Risk Assessment

The Agency anticipates the need to conduct a hu man health risk assessment for OEPA. The most recent risk assessment was conducted in support of the 2008 RED. The Agency expects to require additional data for use in conducting th e registration review. This FWP lists several toxicity studies which were in advertently not included in the preliminary work plan (PWP).



## 3.1 Existing Toxicological Endpoints
The Agency anticipates the need to revise the ex isting toxicological endpoi nts 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 prev iously stated, toxicological studies were identified as data gaps in the RED. All av ailable information incl uding existing toxicology studies, valid scientific literature, and the studie s that are expected to be called in will be considered in establishing the endpoints to be used in the registration revi ew risk assessment. A detailed description of the available toxi city studies is provided in Appendix A .

Table 7 – Existing Toxicol ogical Endpoints for OEPA

Exposure Scenario Dose Used in

Risk Assessment

(mg/kg/day) Target MOE, UF, for Risk Assessment Study 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 interspecies extrapolation, 10x intra-species variation) 90-Day (Oral) Subchronic Toxicity Study in Rats (MRID 41083601)

LOAEL (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 = 100 (10x interspecies extrapolation, 10x intra-species variation) 90-Day (Oral) Subchronic Toxicity Study in Rats (MRID 41083601)

LOAEL (males) = 200 mg/kg/day based on decreased body weights and body weight gain and food consumption.Page 17 of 42 Exposure Scenario Dose Used in

Risk Assessment

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

Toxicological Effects

Dermal

Long-Term

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

LOAEL (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 interspecies extrapolation, 10x intra-species variation, 10x route-to-route extrapolation) 90-Day (Oral) Subchronic Toxicity Study in Rats (MRID 41083601)

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

NOAEL = no observed adverse effect level, LOAEL = lowest 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. Pres erved 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 EPA labels specifically 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 expected. It appears to the agency that the regist rant intends that their product (Inters ept PC-20) be used to preserve materials intended for nonf ood contact only, based on verbal communication between the agency’s PM and registrant regardi ng the registrant’s intent to amend their label accordingly. Therefore, at this time, the ag ency does not anticipate conducting 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.

A drinking water assessment has not been conducted for OEPA. While there are no direct aquatic uses of OEPA, for several approved uses (inc luding some plastics, e poxy flooring/tile, textile, paints, stains, adhesives, and caulk compounds) , the agency cannot rule out the potential for OEPA to enter surface water during incorporation into treated materials and/or leaching from in-Page 18 of 42 service use of treated materials and to subsequen tly be present in drinking water. There are no data or other sources of information indicating th at there would be negligible potential for release of OEPA to surface water from incorporation into treated materials and from leaching from inservice use of treated materials. Therefore, the agency anticipa tes needing certain environmental fate data listed in Table 6 of this PWP. However, if the agency receives data or other sources of information that demonstrate that there w ould be negligible re lease of OEPA during incorporation into treated mate rials and negligible leaching from in-service use of treated materials or that OEPA and/or its degradates will not persist if re leased to the environment, these data may not be required. Upon receipt and re view, these data and/or other sources of information will be used during the risk asse ssment stage of this Registration Review to determine the potential for discharged or leache d residues of OEPA to result in human dietary exposure via drinking water, which ma y trigger a drinking water assessment.



## 3.3 Occupational and Residential Exposures
The occupational and residential exposures to OEPA were last assessed in D347015 (EPA, 2007) which was conducted in support of the 2008 OEPA RE D. The agency anti cipates the need to revise the occupational and residential assessm ents 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 reasse ssed 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 materi al preservation and during the us e of preserved materials such as paint. The exposures during the open pour liquid handling scen arios 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, the (PHED) unit exposure data were used for painting scen arios which included the paint brush and airless sprayer application me thods. 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 per cent. Given 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 ra te exceeded 0.2 percent for airless sprayer application. The inhalation MOEs for paint brush and airless sp rayer application ranged from 6,300 to 310,000 and 210 to 11,000, respectively, de pending 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 inha lation 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 th e application of treate d 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 specified in the RED has not been incorporated into the labe l. These label changes should be made in advance of re-registration.Page 19 of 42 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 revi sed during registration review upon receipt of the unit exposure data that are anticipated to be required in the post-R ED DCI. Occupational handler scenarios to be assesse d are presented in Table 8.

Table 8 – Occupational Handler Exposure Scenarios for OEPA

Handler Scenarios 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 Intermediate Term



### 3.3.2 Residential Handler Exposures Residential handler exposures to OEPA were last assessed in D347015 (EPA, 2007) which was conducted in support of the 2008 OEPA RED. Resi dential handler exposur es to OEPA during the application of treated paints were assumed to be short term in duration because painting is done on an episodic basis. The residential handler MOEs as listed in the RED, were slightly greater than those calculated fo r occupational handler exposures a nd some of the MOEs were of concern at the higher application rates.

The above mentioned residential handler expos ure scenario will need to be assessed in registration review upon r eceipt 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. This scenario is shown in Table 9.

Table 9 – Residential Handler Exposure Scenarios for OEPA

Scenario Exposure Route(s) Duration

Application of Preserved Paint (Brush/Roller and Airless Spray) 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, vi nyl flooring, textiles and mattre ss 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 % MOE

Carpet Cleaner Toddler Dermal 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 1,500Page 20 of 42 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 ta rget 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 app lication 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-Applicat ion Exposure Scenarios for OEPA

Scenario Exposure Route(s) Duration
Toddlers Playing on Carpets Clean ed with Treated Cleaners Dermal Incidental Oral Intermediate Term

Toddlers Playing on Vinyl Flooring Dermal Incidental Oral Intermediate Term

Adults - treated textiles Dermal Intermediate Term

Toddlers - treated textiles Dermal Incidental Oral Intermediate Term

Adults and toddlers sleeping on treated ma ttress 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, the potential for drinking water and residential exposures cannot be discounted at this time. Aggregate risk will includ e pertinent drinking water and residential exposures.



### 3.4.2 Cumulative Exposures With respect to cumulative exposure, unlike other pesticides for which EPA has followed a cumulative risk approach based on a common me chanism of toxicity, EPA has not made a common mechanism of toxicity finding as to OE PA 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, ther efore, EPA has not assumed that OEPA has a common mechanism ofPage 21 of 42 toxicity with other s ubstances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity a nd to evaluate the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/.



## 4 Environmental Risk Assessment

The agency has not previously conducted a risk assessment that supports a complete endangered species determination for OEPA. The previ ous assessment for OEPA (March 2008 RED) was conducted using phosphoric acid instead of OEPA . OEPA is a mixture of three esters of phosphoric acid and is chemically distinct from phosphoric acid. Phos phoric acid and OEPA have different chemical structures and have different chemical prope rties. Therefore, none of the information found in the assessment will be of use for the registration review of OEPA. The ecological risk assessment planned during registra tion review will allow the agency to determine potential acute and chronic risk s to aquatic organisms exposed to OEPA. Such sites include areas that receive water containing OEPA trans ported from treatment sites into the aquatic environment. Minimal exposure would be expect ed 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 a ffect' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use may affect' a listed species or its designated critical habitat, the agency will consult with the U.S. Fish and Wildlife Service and/or National Mari ne Fisheries Services (the Services), as appropriate.



## 4.1 Environmental Fate

There are no data or other sour ces of information indicating th at 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, 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 assu mes that OEPA has the potential to be present in the environmen t because of its wate r solubility (324 mg/l) 7

1 and its potential to be released while being incorporated into treated materials and from leaching during in-service use. The environmental fate and le aching data the agency anticipates requiring are presented in Table 6. If the agency receives data or other sources of information that demonstrate that there would be negligible rel ease of OEPA during inco rporation into treated materials and negligible leaching from in-service us e 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.


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

2 8 or two 9

3 ethylhexyl groups and a companion molecule.

4 10 OEPA is expected to create acid conditi ons in solution (pH 3.0-3.6) and is soluble in

1

2 8 Mono(2-ethylhexyl ester) of phosphoric acid

3 9 Bis(2-ethylhexyl ester) of phosphoric acid

4 10 2,2’-(cocoimino)-bis ethanol saltPage 22 of 42 water to 324 mg/l (parts-per-million, 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 -15 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 Abiotic Processes The registrant has not submitted data on the abiotic (chemical) degradation of OEPA, which includes hydrolysis (835.2120) and direct photodegradation in wa ter (835.2240). In the absence of data and 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 of treated materials, the agency assumes that OEPA has the potential to be present in the environment from th e registered use as a materials preservative and anticipates 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 soil metabolism (835.4100), an aerobic 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) te st (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 te sts (835.3220, 835.3240, or 835.3280) woul d be needed. In the absence of data or other sources of information that demonstrate that OE PA would not persist in the environment if it is released to the envir onment during incorporation into treated materials and/or from leaching during in-service use, the 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 Processes 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 fro m treated products (non-guideline study). In the absence of data or other s ources of information that would demonstrate OEPA’s potential to leach and/or sorb, the agency anticipa tes the need to require these data.



### 4.1.5 Water Quality OEPA is not identified as a cause of impairme nt for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 11

6 In addition, no Total Maximum Daily Loads (TMDL)

11 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885Page 23 of 42 has been developed for OEPA. 12

7 More information on impaired water bodies and TMDLs can be found at EPA’s website. 13

8


## 4.2 Environmental Conceptual Model Exposure Pathways

There are no data or other sour ces of information indicating th at 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 ac id are to be incorporated in to products as a fungistat and bacteriostat. There are no spray application (non -incorporated) uses on th e labels. The organic esters of phosphoric acids have two active labels, incl uding Intersept 14

9 and Intersept PC-20. 15

10 Both products have all three activ e 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 caulks, and plastics.

The Intersept PC-20 label contains some uses that are not presum ed to result in environmental exposure, including air filters, vinyl upholstery, mattresses and mattress ticking, and polymeric packaging film since there is no potential for rele ase to the aquatic environment and these treated items would be disposed in lined sanitary landfills.

However, there are some uses of OEPA for whic h the agency cannot pres ume that environmental exposure will not occur. These us es include plastics in polymeri c concrete, vinyl, outdoor plastic furniture, and outdoor carpets and tile. Although the PC-20 label stat es “Once incorporated, there is no loss of efficacy due to washing or wear under normal use conditions”, the agency has found no evidence that leaching and subsequent environm ental exposure from these treated materials will not occur. Consequently, the agency needs in formation demonstrating that incorporation of OEPA into plastics would not result in releases to surface water.

 The first category of plastics is polymeric concrete (1-5 % OE PA 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 corrosion resistant than traditional concrete. 16

11
 The second category of plastics for which th e agency cannot rule out the potential to create environmental exposure includes vi nyl products such as car tops, awnings, tarpaulins, tents, sails, shower curtains, and vinyl film.

 The third category of plastics for which the ag ency cannot rule out the potential to create environmental exposure is plasti c furniture (1-5 % w/w).

12

7 http://iaspub.epa.gov/tmdl_waters10/a ttains_nation.tmdl_polluta nt_detail?p_pollutant_g roup_id=885&p_pollutant _group_name=PESTICIDES

8 13 http://www.epa.gov/owow/tmdl/

9 14 Reg. No. 43670-1, label dated 7/29/2005, http://www .epa.gov/pesticides/chem_search/ppls/043670-00001- 20050729.pdf

10 15 Reg. No. 43670-4, label dated 9/20/1999, http://www .epa.gov/pesticides/chem_search/ppls/043670-00004- 19990920.pdf

11 1 16 http://genevapolymerproducts.com/Page 24 of 42  The fourth category of plastics for which th e agency cannot rule out the potential to create environmental exposur e is outdoor carpets (0.5-10 % w/w). The outdoor use in polymeric backing material ( 0.1-2 % w/w) for carpets is pr imarily restricted to outdoor carpets on decks and patios and in doormats. 17

12
 Based on the antimicrobial uses of OEPA with active products in Table 5, the agency has created conceptual models for potential ro utes of environmental exposure which are included in “Conceptual Models for Environm ental Exposure Pathways of Antimicrobial Pesticides”, dated August 4, 2014. For the uses with active products, the relevant pages are 17 for down-the-drain exposure from polym eric concrete used in caulks, grouts and sealants and 9-10 for non-paint treatment of outdoor items su ch as vinyl products, plastic furniture and outdoor carpets. All relevant routes of e nvironmental exposure will be considered in the risk assessment.



## 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 freshwa ter aquatic invertebrate EC 50

. These studies are anticipated to be required for OEPA.

However, since the agency has no eco-toxicity data on OEPA, a dditional studies are anticipated to be required for an ecological risk assessment unless the agency receives data or other sources of information that demonstrate that there would be negligible release of OEPA during incorporation into treated mate rials and negligible leaching from in-service use of treated materials or that OEPA and/or it s degradates will not persist if released to the environment. These include five aquatic eco-toxicity studies and two sediment studies which are listed in Table 12.



### 4.3.1 Mode of Action

The mode of action of OEPA is unknown. Since there are no eco-toxicity data for OEPA, ecotoxicity endpoints cannot be determ ined at this time (Table 12).

Table 12 – Ecological Effects Endpoints Select ed for Assessing Risks from Use of OEPA

Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint

Freshwater Fish One freshwat er fish species Acute None

Freshwater invertebrates One freshwat er invertebrate sp ecies Acute None

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

Estuarine/marine fish One estuarine/ marine fish species Acute None

Estuarine/marine

invertebrates One estuarine/marine invertebrate species Acute None

12 17 http://www.americanfloormats. com/entrance-mats-runners/Page 25 of 42 Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint

Estuarine/marine benthic invertebrates One marine benthic invertebrate species Subchronic/ Chronic None

Algae Selenastrum capricornutum Nonlisted None
Aquatic vascular plants One aquatic vascular plant species Nonlisted None Birds One avian species 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 base d on the use patterns of OEPA as a materials preservative in several commercia l, industrial and househol d products (Table 5). Terrestrial organisms will not come into c ontact with OPEA because the chemical is incorporated into materials such as tiles, carpets, paints and textiles. Due to potential release of OPEA to aquatic environments after producti on of these materials, exposure to aquatic organisms cannot be discounted at this time (Section 4.2).



### 4.4.2 Screening Level Down-the-Drain Analysis

There are no data or other sour ces of information indicating th at 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 to the aquatic environment or on the rate of formation and dec line 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 or other sources of information that demonstrates that OEPA is not released to surface water or if it is released to surface wate r, OEPA and any degradates it forms do not persist or are not very toxic to aqua tic organisms, the agency will need to perform 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 perform a screening level assessment of pot ential exposures of aquatic organisms to OEPA due to leaching from in-service use of treated materials, the agency would use the Down-theDrain (DtD) module of the Exposure and Fate As sessment Screening Tool (E-FAST) model. Input parameters required to run the DtD module include per cent removal during wastewater treatment, wastewater treatment plant influent vol ume, and concentrations of concern for aquatic organisms based on measurement effects endpoints . To determine wastewater treatment plant influent volume, the agency needs informa tion 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 th e maximum annual production volume to determine the wastewater treatment plant influent volume that would be us ed as input to the DtD module. E-FAST is available on EPA’s website at http:// www.epa.gov/oppt/exposure/pubs/efast.htm .Page 26 of 42 To perform a quantitative screeni ng level assessment of potential exposures of aquatic organisms to OEPA that could be released to surface water during its incor poration into treated materials, the Agency would use an approach such as th at used in General Population and Ecological Exposures from Industrial Releases module of E-FAST (hereinafter referred to as the Industrial Releases module). This model requi res the information that follows:

-SIC code classification for each category of treated material into which OEPA would be incorporated or identification of locations of specific facili ties 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 cat egory of facilities.

-percent removal of OEPA during wastewater treatment.

-concentrations of concern for aquatic organisms.



## 4.5 Effects Analysis Plan
The agency will use the results from the requested ecological studies to determine if any exposure occurs from the use pattern of OEPA. Op en literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database. The ECOTOX database will be searched when the risk assessment is prepared. Any acute or chronic endpoints more sensitive than what is currently available will be us ed in the risk assessment.



## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its reregistration decision for OEPA, EPA reviewed these data and selected the most sensitive endpoi nts 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 Screenin g Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily requiredPage 27 of 42 determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pest icide active ingredient s and 9 inert ingredients. A second list of chemicals identified for EDSP sc reening 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 construed as a list of know n or likely endocri ne disruptors.

For further information on the status of the ED SP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening ba ttery, please visit our website: http://www.epa.gov/endo/. 19

13 

## 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 practical or enforceable and should be removed from the labels. Also, as noted in section 1.4.2 an d elsewhere in this docu ment, application rates should be lowered for certain OEPA uses, incl uding for paints, carpet cleaners, textiles, and mattress covers according to the label language specified in the RED. 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 possibi lity that EPA’s planned risk assessments overestimate risk due to reliance on conservative assumptions, and/or im prove label clarity.



## 7 Next Steps

After the FWP is issued, a data call in (DCI) wi ll be issued for the OEPA case. The agency will review and consider any label amendments or ot her information that might limit or eliminate the need for additional data for reevaluation of OEPA in the upcoming risk assessment.

13 18 18 See http://www.regulations.gov/#! documentDetail;D=EPA-HQ-OPPT-2009-0 477-0074 for the second list of chemicals.

19 http://www.epa.gov/endo/Page 28 of 42 

## 8 References

U.S. Environmental Protection Agency (E PA). 2002. ECOTOX User Guide: ECOTOXicology Database System. Version 3.0. Availa ble: http://www.epa.gov/ecotox/

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

44858901 Harrison, E. (1999) Aseptrol Deodoriz ing Drip Pad: Product Identity and Composition, Beginning Materials, Producti on Process and Formation of Impurities. Unpublished study prepared by Engelh ard Corporation. 15 p. {OPPTS 830.1550, 830.1600, 830.1650, 830.1670} 23-Jun-1999.

Interface Research Corporation’s Material Safety Data Sheet dated January 31, 2007.Page 29 of 42 

# Appendix A Toxicology Profile

Acute Toxicity for Product Labeling

As listed in Table A1, organic esters of phosphoric acid was found to be low toxic (Toxicity Category IV) with an observed lethal dose gr eater than 5000 mg/kg for both acute oral and dermal toxicity. Mortality was observed at all co ncentrations in rabbits in an acute inhalation toxicity study, resulting in an LD 50 determination of 1.48 mg/L (combined) (Toxicity Category III). The organic esters of phosphoric acid were shown to be mildly irritating to the eyes (Toxicity Category III) and is not a dermal i rritant (Toxicity Category IV). There are no acceptable dermal sensitization studies in the agency ’s hazard data base and it is a data gap. A dermal sensitization study is re quired for registration review.

Table A1 – Acute Toxicity Studies fo r Organic Esters of Phosphoric Acid

Guideline No./Study Type MRID No. Results Toxicity Category

870.1100/

Acute oral toxicity – rat 42907901 LD 50 (M/F) > 5000 mg/kg (observed) IV

870.1200/

Acute dermal toxicity – rabbit 42907902 LD 50 (M/F) > 5000 mg/kg (observed) IV

870.1300/

Acute inhalation toxicity – rat 40423801; 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 III

870.2500/

Primary dermal irritation – rabbit 44858904 Not irritating IV

870.2600/

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 availablePage 30 of 42 

## Subchronic Toxicity

Adequacy of Database for Subchronic Toxicity : The database for subchronic toxicity is considered incomplete. Only an acceptable 90-day oral toxicity study in the rat (MRID 41083601) is available for addressing subchronic toxi city. A 90-day dermal toxicity study in rats and a 90-day inhalation toxicity st udy are anticipated to be require d 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 determin ed from a 14-day dietary range-finding study in rats (MRID 41665301).

No deaths occurred during this study, but th e 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 si gns were observed in mid- and high-dose rats, which included piloerection (which progressed to rough haircoat) and fur stai ning. 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 contro l. Treatment-related histopathologic findings were forestomach lesions (gastritis/ulcer-ero sion/squamous hyperplasia hyperkeratosis) in intermediate- and high-dose males and lenticul ar 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 refere nce ranges established previously at the test site. Changes in clinical chemistry parameters included decrea sed GPT in high-dose males (-28%) and low-, midand high-dose females (-17%, -15% , and -27%, respectively), tota l bilirubin in mid- and highdose males (-42% and -47%, respectively) a nd 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 significant, were relatively small and were likely not biologically relevant because they were not correlated with any histopathologic findings.

Body weight was statistically si gnificantly decreased in mid-dos e males (-9 to -15%) and highdose 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 rela tive 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%, respectively) were likely related to decreases in body we ight. Liver weight rela tive to body weight was increased only in mid- and high-dose females (+12% and +25%, respectively), however, thesePage 31 of 42 increases were moderate and of unknown toxicologi cal 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 NOA EL in females is 120 mg/kg/day. 

## Developmental Toxicity

Adequacy of Database for Prenatal Developm ental Toxicity: The database for prenatal developmental toxicity is considered inadequate for the currently registered uses. Developmental toxicity assessment for orga nic esters of phosphoric acid is based on an acceptable developmental study in the rat (MRID 41151601). A developmental toxicity study in non-rodent species is anticipated to be re quired based on the adverse effects observed in the rat study and the currently registered uses.

870.3700 Prenatal Developmental T oxicity (Gavage) Study – Rat

In a developmental toxicity study (MRID 41151601), 25 presumed pregnant Charles 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 gestati on 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 malf ormations/variations prior to sacrifice. Approximately one-half of the fetuses were fixed in ethanol and the remainder were placed in Bouin’s fixative and examined for visceral malf ormations/variations. The ethanol-fixed fetuses were further processed, stained, and examin ed for skeletal malformations/variations.

Four treatment-related deaths oc curred at 500 mg/kg/day. Clinical signs of toxicity observed at 500 mg/kg/day were salivation with red stain ar ound the mouth (7) and no se (10), hypoactivity (8), urine stains (17), and fecal stains (4) compared to 0/25 contro l dams. Urine stains were also observed on one low-dose animal and four mid-dos e animals. There were no statistically or biologically significant gross necr opsy observations at maternal sa crifice. Absolute body weights were statistically significantly reduced (p  0.05 or 0.01) for 250 and 500 mg/kg/day dams during GD 8, 12, 16, and 20 and statistica lly significantly reduced body we ight gain was observed for both treatment groups during GD 6-8 and GD 0-20 (11.1 and 20.6%, resp ectively during GD 0- 20). Net body weight change from GD 0 was also statistically significantly reduced at 250 and 500 mg/kg/day (17.2 and 21.1%, respec tively), compared to controls . Food consumption was not monitored. No treatment-related maternal changes were noted at 125 mg/kg/day.

The maternal toxicity LOAEL is 250 mg/kg/day ba sed on clinical signs of toxicity and reduced absolute body weights and weight gains. Th e maternal toxicity NOAEL is 125 mg/kg/day.Page 32 of 42 There were statistically significant increases (p  0.01) in total resorptions , early resorptions, and postimplantation losses at 500 mg/kg/day comparedto controls. One high-dose dam had complete litter resorption of two implantation sites. The increase in postimplantation loss resulted in slightly (n.s.) decreased number of fetuses per litter for the high-dose group. Also at 500 mg/kg/day there were statis tically significant decreases (p  0.01) in live mean fetal weight (9.5%) and live female fetal weight (10.1%) compar ed to controls. Gravid uterine weights were also lower than controls at 250 and 500 mg/ kg/day (6.2 and 20.3%, resp ectively) but did not reach statistical significance.

The total fetuses (litters) with major external, vis ceral or skeletal malformations was 0 (0), 1 (1), 4 (2), and 17 (9) (p  0.05), in the control, low-, mid-, and high-dose groups, respectively. A positive trend for certain skeletal vari ations (delayed ossifi cation of the hyoid, s kull, pelvic girdle, vertebrae, sternebrae, and metatarsals) was al so evident with increas ing doses of Intersept ® with the 500 mg/kg/day group generally stat istically 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 fetu ses/litters with exte rnal malformations were 0/0, 1/1, 4/2, and 8/6 (litter rate, p  0.05), respectively. External malformations at 500 mg/kg/day consisted of one fetus each with cl eft palate and anophthalmia; 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 fetu ses/litters with skel etal malformations were 0/0, 1/1, 1/1, and 6/4 (litter rate, p  0.05), respectively. Wavy or be nt 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 malfor mations at 500 mg/kg/day consisted of vertebral anomaly with or without associated rib anomal y in 3 fetuses from 2 litters; cervical vertebrae fused in 2 fetuses from 2 litters; and single inci dences of exencephaly, forked/fused ribs, and supernumerary limbs.

No treatment-related fetal effect s were observed at 125 mg/kg/day.

The developmental toxicity LOAEL is 250 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 Toxici ty: There is no reproductive toxicity study available for organic esters of phosphoric acid and such a study is re quired under 40 CFR Part 158 W to support the currently registered uses. In addition, there ar e other toxicological concerns that need to be evaluated in a re productive study. A two generation reproduction study is therefore anticipated to be n eeded for registration review.Page 33 of 42 

## Chronic Toxicity/Carcinogenicity

Adequacy of Database for Chronic Toxicity /Carcinogenicity: The da tabase for chronic toxicity/carcinogenicity is inade quate for the currently registered uses of organic esters of phosphoric acid. There is potential surface water exposure from incorporation of OEPA into some products, including some plastics, epoxy floori ng/tile, textile, paints, stains, 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. 

## Mutagenicity

Adequacy of Database for Mutagenicity: The data base for mutagenicity is considered adequate for the currently registered uses based on th e EPA's 1991 mutagenicity guidelines. Several mutagenicity studies have been submitted and reviewed by the Office of Pesticide Programs (OPP) and found acceptable. Organic esters of p hosphoric acid is found to be not mutagenic or genotoxic. The summaries of thes e studies are provided below.

Gene Mutation

In a reverse gene mutation assay in bact eria (MRID 40564601), stra ins 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 μ L/plate in the presence and absence of mammalian metabolic activ ation (S9-mix). Inters ept® was tested up to cytotoxic concentrations. There was no evidence of induced mutant colonies over background.

In a reverse gene mutation assay in bact eria (MRID 40564602), stra ins TA98, TA100, TA1535, TA1537 and TA1538 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 μ L/plate in the presence and absence of mammalian metabolic activation (S9-mi x). Intersept® was te sted up to cytotoxic concentrations. There was no evidence of induced mutant colonies over background.

Cytogenetics

In a mammalian cell cytogenetics assay (chr omosomal aberrations) (MRID 40564603), Chinese hamster ovary CHO-WBL cell cultures were expos ed to Intersept® (Lot No. P2991, purity not provided) in DMSO at concentrations of 2.5, 5.0, 7.5, 10.0 μ g/mL with a 10 hour harvest time without S9-mix and at concentrations of 10, 20, 30 and 40 μ g/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 μ g/mL with a 10 hour harvest time with S9-mix. Intersep t® was tested up to cytotoxic concentrations. There was no evidence of chromosomal abe rrations 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 (p urity 98%, Batch No. 1260809A) in corn oil at doses of 0, 500, 1000, or 2000 mg/kg (limit dose), a nd bone marrow cells were harvested at 24 hours after dosing. Additional group s of 5 male mice were simila rly dosed at 0 or 2000 mg/kg,Page 34 of 42 and bone marrow cells were harvested 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 ob served in any treatment group compared to controls, indicating that the test material did not markedly inhibit the growth of bone marrow cells (not cytotoxic to the bone ma rrow). No treatment-related increases in the micronucleated polychromatic eryt hrocytes (MPCE) frequency we re observed in any treatment group at either harvest time when compared to controls. The positive control induced the appropriate response. Based on the test resu lt, Intercept did not induce a treatment-related increase in the frequency of micronucleated PCEs in bone marrow after any treatment time.

Although there was no indication of bone marrow gr owth inhibition, the animals were dosed at the limit dose (2000 mg/kg). Therefore, this stud y is classified as Acceptable/guideline and satisfies the guideline requireme nt (OPPTS 870.5395; OECD 474) for in vivo cytogenetic mutagenicity data.

In a mammalian cell cytogenetics assay (sis ter chromatid exchange [SCE]) (MRID 40564604), Chinese hamster ovary CHO-WBL cell cultures were exposed to Intersept® (Lot No. P2991, purity not provided) in DMSO at c oncentrations of 0.033, 0.10, 0.333, 1.00, 3.33, 10.0, 33.3, 100, 333, 1000 μ g/mL with and without mammalian metabol ic 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 treatment without S9-mix and 2.5 hours after treatment with S9-mix. The S9- fraction was obtained from Aroclo r 1254 induced male Sprague-Dawley rat liver. Intersept® was tested up to cytotoxic concen trations. There was no evidence of SCEs induced over background levels. 

## Other Toxicological Effects

An immunotoxicity study is included as a data requirement for all antimicrobial pesticide chemicals under 40 CFR Part 158W, Data Require ments for Antimicrobial Pesticides. The registrant can address this anticipated data re quirement by either submitting a study according to the OCSPP 870.7800 Guideline, by citing information from the scientific litera ture that addresses Immunotoxicity of (chemical), or by submitting a request for waiver of this study using the Agency’s published guidance, available at: http://www.epa.go v/pesticides/regulating/part158- tox-data-requirement.pdf.Page 35 of 42 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 41083601/41665301 (1989)

Acceptable - Guideline

Rat, oral/diet (10/sex/group)

0, 62.5, 200, 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 = 200 mg/kg/day, based on decreased body weights, body weight 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.

870.3700

Developmental (gavage) - Rat

Purity 100% MRID 41151601/40679502 (1989)

Acceptable - Guideline

Females rats (25/dose)

0, 125, 250, or 500 mg/kg/day, GD 6-15, inclusive Maternal toxicity: NOAEL = 125 mg/kg/day

LOAEL = 250 mg/kg/day, based on clinical signs of toxicity and reduced absolute body weight and weight gain;

Developmental toxicity: NOAEL = 125 mg/kg/day

LOAEL = 250 mg/kg/day based on doserelated increases in the number of litters with fetuses with skeletal and visceral abnormalities.

870.5265

Bacterial reverse mutation test

Purity not provided MRID 40564601 (1986)

Acceptable - Guideline

Strains TA98, TA100, TA1535, TA1537 and TA1538

0.005, 0.01, 0.05, 0.1, or 0.5 μL/plate with and without S9 NegativePage 36 of 42 Guideline Number/

Study Type/

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

Classification/Doses Results

870.5265

Bacterial reverse mutation test

Purity not provided MRID 40564602 (1987)

Acceptable - Guideline

Strains TA98, TA100, TA1535, TA1537 and TA1538

0.01, 0.05, 0.1, 0.5 or 1.0 μL/plate with and without S9 Negative

870.5375

In Vitro mammalian chromosome aberration test (hamster)

Purity 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

870.5395

In Vivo Mammalian Cytogenetics - Erythrocyte Micronucleus Assay (Mouse)

Purity 98% (Intersept ® ) MRID 47715601 (2009)

Acceptable-Guideline

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

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 37 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

14 or two 22

15 ethylhexyl groups and a companion molecule. 23

16 As a result, the agency anticipates requi ring the environmental fate data unless information provided to the agency demonstrates that leaching from in-service use results in negligible releases to surface water and/or releases to WWTPs during incorporation of OEPA into treated materials is negligible. See Table 6 for complete details.

21

14 Mono(2-ethylhexyl ester) of phosphoric acid

22

15 Bis(2-ethylhexyl ester) of phosphoric acid

23

16 2,2’-(cocoimino)-bis ethanol saltPage 38 of 42 

# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial and Aquatic Receptors

No terrestrial and aquatic eco-tox icity studies are available for OE PA. Four eco-toxicity studies are being required for OEPA and several studies ar e anticipated to be required depending on the exposure scenarios determined by the down-th e-drain analysis (see Table 12).Page 39 of 42 

# Appendix D Screening Level Down-the Drain Analysis

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 wate r, OEPA and any degradates it forms do not persist or are not very toxic to aqua tic organisms, the agency will need to perform 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 perform a screening level assessment of pot ential exposures of aquatic organisms to OEPA due to leaching from in-service use of treated materials, the agency would use the Down-theDrain (DtD) module of the Exposure and Fate Assessment Screening Tool (E-FAST) model.
To perform a quantitative screeni ng level assessment of potential exposures of aquatic organisms to OEPA that could be released to surface water during its incor poration into treated materials, the agency would use an approach such as th at used in General 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 pot ential exposures of aquatic organisms to OEPA due to leaching from in-service use of treated mate rials and incorporation in to treated materials is discussed in 4.4.2. of this preliminary work plan.Page 40 of 42 

# Appendix E Product Chemistry

Organic esters of phosphoric acid chemistry in formation is summarized in Table E1 (source: MRID 43265801 and Interface Research Corporation’s MSDS).

Table E1 – Product Chemistry of Or ganic 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, compound with 2,2'- (coco alkylimino)bis(ethanol) (1:1) (66.4%) and

 Phosphoric acid, mono(2-ethylhexyl) ester, compounds with diethanolamine N-coco al kylderivs. (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

830.1670 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 Yellow 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 bases.

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 viscous 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. 830.7300 Density Density: 1.0 g/mlPage 41 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, compound with 2,2'- (coco alkylimino)bis(ethanol) (1:1) (66.4%) and

 Phosphoric acid, mono(2-ethylhexyl) ester, compounds with diethanolamine N-coco al kylderivs. (1:1) (15.9%) 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 chemical. 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.
830.7860 Solubility in organic solvents Soluble in dimethyl sulfoxide (DMSO) 500 mg/ml. Soluble in n -octanol in all proportions at 20 ° C. Soluble in ethanol. 830.7950 Vapor pressure ~1.8 x 10 -8 to 5.3 x 10 -8 mm Hg (Epi-Suite) for all three compounds.Page 42 of 42 

# Appendix F Response to Comments

There were no public comments submitted to th e docket in response to this workplan.