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 Ross 

 
Page 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 Registered 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 ............................................................................................................ 17

3.2.1 Food ........................................................................................................................ 17

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-Application 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 Model 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 Wildlife Exposure Estimates ............................................ 25

4.4.2 Screening Level Down-the-Drain Analysis ............................................................ 25

4.5 Effects Analysis Plan ..................................................................................................... 26

5 Endocrine Disruptor Screening Program (EDSP) ................................................................. 26

6 Optional Label Changes ........................................................................................................ 27

7 Next Steps ............................................................................................................................. 27

8 References ............................................................................................................................. 28
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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 Registration Review Schedule .................................................................... 6

Table 3 – Chemical Identification of Organic 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 Toxicological Endpoints for OEPA ................................................................ 16

Table 8 – Occupational Handler Exposure 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-Application Exposure Scenarios for OEPA ..................................... 20

Table 12 – Ecological Effects Endpoints Selected for Assessing Risks from Use of OEPA ....... 24

 
Page 5 of 42

1 Introduction 

This document is the Environmental 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 Pesticide Programs knows about OEPA, highlighting 

anticipated data and assessment needs, identifying the types of information that would be 

especially useful to the agency in conducting the review, and providing an anticipated timeline 

for completing the OEPA review. This work plan also addresses public comments received 

concerning the Preliminary Work Plan (PWP) which was posted in the OEPA registration review 

docket (EPA-HQ-OPP-2013-0373). Further, this document makes final the work plan for the 

OEPA registration review process. 

1.1 Statutory and Regulatory Authority 

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States generally must be registered by the U.S. 

Environmental Protection Agency (USEPA, EPA, or the Agency) based on scientific data 

showing that they will not cause unreasonable risks to human health or the environment when 

used as directed on product labeling. The registration review program is intended to make sure 

that, as the ability to assess risk evolves and as policies and practices change, all registered 

pesticides continue to meet the statutory standard of no unreasonable adverse effects to human 

health or the environment. Changes in science, public policy, and pesticide use practices will 

occur over time. Through the registration review program, the agency periodically reevaluates 

pesticides to make sure that as change occurs, products in the marketplace can be used safely. 

Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/. 

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

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

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

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

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

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

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

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

preliminary work plan (PWP), published March 26, 2014, closed for public comment on May 19, 

2014. No public comments were received in the 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 review 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 anticipated 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 data needs for Registration Review. For data to be called in through the post-RED 

DCI, see Table 6. 

Table 2 – Anticipated Registration Review Schedule 

Anticipated Activity Target 

Date*

Completion 

Date 

Phase 1: Opening the Docket 

Open Docket and 60-Day Comment Period for Preliminary Work Plan 2014-03 2014-03-26 

Close Public Comment Period 2014-05 2014-05-19 

Phase 2: Case Development 

Issue Final Work Plan 2014-09 
Page 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 section 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 inhalation toxicity study, 2) 90-day dermal toxicity study, 3) 

developmental toxicity study in non-rodents, 4) two generation reproductive toxicity study 

and 5) immunotoxicity study and 6) chronic toxicity/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 for 870.3250 (90-day Dermal Toxicity study) to 

textile upholstery, mattresses and mattress 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 Exposure Pathways of Antimicrobial Pesticides” 

memo. 

 Sec 4.3 Ecological Effects Assessment – Updated this section to be consistent with 

potential exposure pathways and added footnote 2 to Table 6. 

 Section 4.5 Effects Analysis Plan – Added discussion of open literature search that will be 

performed. 

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

 Updated format, corrected typographical errors 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 ingredients 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) ester, 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 Organic Esters of Phosphoric Acid (OEPA) 

Chemical 

Name 

Phosphoric acid, 

mono(2-ethylhexyl) 

ester 

Phosphoric acid, bis(2-ethylhexyl) ester, 

compd. with 2,2'-(coco 

alkylimino)bis(ethanol) 

Phosphoric acid, mono(2-

ethylhexyl) ester, compds. with 

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 

C8H19O4P1 C32H70O6PN C24H54O6PN

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 information 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 alkyl derivatives. (15.9%) 

830.7000 pH 3.0 to 3.6

830.7050 UV/Visible Absorption Not reported.

830.7200 Melting point Freezing point: < 32°F

830.7220 Boiling point Decomposes before boiling.

830.7300 Density 1.0 g/ml

830.7370 Dissociation Constant Not applicable. 

830.7550 Partition coefficient (noctanol/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 percent a.i. and EPA Reg. No. 43670-4 contains 80 

percent active ingredient. The three organic esters of phosphoric acid never occur as a pesticide 

single active ingredient or in any other combination or ratio in a registered pesticide product 

(EPA Reg. Nos. 43670-1 and 43670-4). 

1.5.2 Summary of Registered Uses 

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

Table 5. No direct or indirect food contact uses are approved on registered end-use product 

labels. Several uses that could conceivably result in indirect food contact already have been 

prohibited by such label language as, "...to be used for purposes other than food storage." The 

application rates are not included on the most recently approved version of the labels. The 

previously approved versions of the labels included technical data sheets which listed the 

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 acetate 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 coverings, 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 including HVAC systems) 

Not Listed* 

Molded polymeric and polymer concrete (bathtubs, showers, bathroom sinks, bathroom 

countertops, and bathroom accessories) Not Listed* 

Molded polymer and polymer concrete products (household, industrial, commercial and 

health care use) 

Not Listed* 

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

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

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

Textiles (topical treatment of wall coverings, car tops, awnings, tarpaulins, tents, sails. 

drapes. shower curtains, apparel, cubicle curtains. and industrial fabrics) 

Not Listed* 

Air Filters (topical treatment or impregnation of air filters to be used in air purification 

devices, automobiles, and HVAC systems). 

Not Listed* 

*The application rates are not listed on the most recently approved labels. Previously approved versions of the labels included 

technical data sheets, which listed the application rates; however, the technical data sheets were not included in the most recently 

approved labels 

.
Page 11 of 42

1.6 Regulatory History 

The first product containing OEPA as an active ingredient was registered in the United States in 

1982. This product, as well as the only other registered product containing OEPA, is a blend of 

the three active ingredients in this case. The Agency completed a Reregistration Eligibility 

Decision (RED) for OEPA in 2008. A post-RED Data Call-In (DCI) is anticipated 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 reported in OPP’s Incident Data System (IDS) for 

the time period spanning 1998 to the present (database searched 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 present (database searched on 1/29/2014). 

2 Anticipated Data Needs 

Table 6 presents a summary of the data anticipated as being needed to support this registration 

review. If the Agency receives data or other sources of information that demonstrate that there 

would be negligible release of OEPA during incorporation into treated materials and negligible 

leaching from in-service use of treated materials or that OEPA and/or its degradates will not 

persist if released to the environment, some or all of the environmental fate (OCSPP 835 series) 

and ecological effects (OCSPP 850 series) data anticipated to be needed may not be required (see 

Table 6 for details). 

The environmental fate data requirements in Table 6 are presented in a tiered approach based on 

the results of laboratory studies that isolate specific routes of dissipation in the environment. 

Hydrolysis (835.2120) data are anticipated to be required for all uses. For 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), anaerobic aquatic metabolism (835.4400), leachingadsorption-desorption (835.1230), activated sludge sorption isotherm (835.1110), Activated 
Page 12 of 42

Sludge Respiration Inhibition, ASRI) (OECD 209 or OCSPP 850.3300), and a test to determine 

biodegradation potential in wastewater 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 Pesticides: 1) 90-day inhalation toxicity study, 

2) 90-day dermal toxicity study, 3) developmental 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 indicate low potential for drinking water exposure, 

these studies will not be required. 

 
Page 13 of 42

Table 6 – Studies Anticipated as Needed for the Registration Review of OEPA 

GLN Study Name Test Substance Time Frame (Measured in months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Trigge

Anticipated Dat

Requirement 

Studies Anticipated to be Required through the Registration Review DCI 

835.2120 Hydrolysis TGAI 12 Environmental Fate, Ecological Effects All uses except those n

Section 4.2 

835.2240 Direct photodegradation in water1,2,3 TGAI 12 Environmental Fate, Ecological Effects All uses except those n

Section 4.2 

835.4100 Aerobic soil metabolism2 TGAI 24 Environmental Fate, Ecological Effects All uses 835.4300 Aerobic aquatic metabolism2,3 TGAI 24 Environmental Fate, Ecological Effects All uses 835.4400 Anaerobic aquatic metabolism2,3 TGAI 24 Environmental Fate, Ecological Effects All uses 835.1230 Leaching-adsorption-desorption2,3 TGAI 12 Environmental Fate, Ecological Effects All uses 835.1110 Activated Sewage Sludge Sorption Isotherm3 TGAI 12 Environmental Fate, Ecological Effects All uses 850.3300 Activated Sludge Respiration Inhibition (ASRI) 3,4 TGAI 12 Environmental Fate, Ecological Effects All uses 835.3110 835.3220 835.3240 835.3280 

Ready biodegradability or one of the three biodegradation in activated sludge simulation tests.3,4

TGAI 12 Environmental Fate, Ecological Effects All uses 

Special Study1249 Leaching from treated article TGAI 12 Environmental Fate, Ecological Effects All uses 

850.2100 Acute oral toxicity to mallard duck or northern bobwhite quail TGAI 12 Environmental Fate, Ecological Effects All uses 850.1075 Acute toxicity to rainbow trout or bluegill sunfish TGAI 12 Environmental Fate, Ecological Effects All uses 850.1010 Acute toxicity to Daphnia magna TGAI 12 Environmental Fate, Ecological Effects All uses 850.5400 Aquatic plant growth (algal) tier II TGAI 12 Environmental Fate, Ecological Effects All uses 850.1300 Aquatic invertebrate life-cycle2,3 TGAI 24 Environmental Fate, Ecological Effects All uses 
Page 14 of 42

GLN Study Name Test Substance Time Frame (Measured in months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Trigge

Anticipated Dat

Requirement 

850.1400 Fish early-life stage2,3 TGAI 24 Environmental Fate, Ecological Effects All uses 850.4400 

Aquatic plant growth (aquatic vascular plant) Tier II-dose response2,3

TGAI 12 Environmental Fate, Ecological Effects All uses 

850.1025 Acute estuarine and marine organisms toxicity2,3 TGAI 12 Environmental Fate, Ecological Effects All uses 850.1735 Whole sediment: acute freshwater invertebrates2,3 TGAI 12 Environmental Fate, Ecological Effects All uses 850.1740 Whole sediment; acute marine invertebrates2,3 TGAI 12 Environmental Fate, Ecological Effects All uses 870.3250 90-Day Dermal Toxicity TGAI 12 Human Health Effects 

Textile, upholstery, mattresses, mattress coflooring 

870.3465 90-Day Inhalation Toxicity TGAI 12 Human Health Effects Paints, stains and coati

870.3700b Prenatal Developmental Toxicity Study (non-rodent) TGAI 12 Human Health Effects All uses 

870.3800 Reproduction and Fertility Effects TGAI 12 Human Health Effects All uses 870.4300 Combined Chronic Toxicity/Carcinogenicity2,3 TGAI 24 Drinking Water Assessment 

Some plastics, epoxy flooring/tile, textile, pastains, adhesives, and ccompounds 

870.7800 Immunotoxicity TGAI 12 Human Health Effects All uses 

Studies Expected to be Required through the Anticipated Post-RED DCI

870.2600 Dermal Sensitization Study TGAI 12 Human Health Effects All uses 870.5395 

In vivo mammalian micronucleus test, Mammalian erythrocyte micronucleus test 

TGAI 12 Human Health Effects All uses 

875.1200 Dermal Indoor Exposure5,6 TGAI 12 Occupational and Residential Handler All Uses 875.1400 Inhalation IndoorExposure5,6 TGAI 12 Occupational and Residential Handler All Uses 875.1700 Product Use Information TGAI 12 

Occupational and Residential Handler and Post Application 

All Uses 
Page 15 of 42

GLN Study Name Test Substance Time Frame (Measured in months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Trigge

Anticipated Dat

Requirement 

875.2300 Indoor Surface Residue Dissipation7,8 TGAI 12 Residential Post Application Vinyl Flooring, Textile

Mattress Covers 

1 Not required when the electronic absorption spectra, measured at pHs 5, 7, and 9, of the chemical and its hydrolytic products, if any, show no absorption or ta

2 These anticipated data requirements are based on the potential for OEPA to leach from treated materials. Data are not expected to be required if information p

demonstrate that leaching from in-service use results in negligible releases to surface water. 

3 These anticipated data requirements are based on the potential for OEPA to be released to surface water via WWTPs as a result of incorporation into treated m

to be required if information provided to the Agency demonstrates that releases to WWTPs during incorporation of OEPA into treated materials is negligible. 

4 The results of the Activated Sludge Respiration Inhibition Test (ASRI) expected to be required will determine which of these four biodegradation tests would 

the ASRI test EC50 is less than or equal to 20 mg/L, then either the (i)Biodegradation in Activated Sludge Study or (ii) Simulation Test – Aerobic Sewage TreUnits or (iii) the Porous Pot Test would be anticipated to be required. If the ASRI test EC50 is greater than 20 mg/L, then the DCI expected to be issued would would choose to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: the Porous Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, the aBiodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or c) texpected to be required. The appropriate Test Substances are the three components of OEPA. 

5 Occupational and Residential Handler Exposure Scenarios include Open Pour Liquids for Material Preservation, Brush Application of Preserved Paint and Ai

Preserved Paint. 

6 It may be possible to use proprietary surrogate exposure data if data compensation issues are appropriately and adequately addressed. 7 Residential Post Application Exposure Scenarios include dermal and incidental oral exposure, vinyl flooring, dermal and incidental oral exposure to textiles a

covers. 

8 If surface residue data are not available, then the standard assumption of 100 percent transferable surface residue will be used which might overestimate the ri
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 human 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 the registration review. This FWP lists several 

toxicity studies which were inadvertently not included in the preliminary work plan (PWP). 

3.1 Existing Toxicological Endpoints 

The Agency anticipates the need to revise the existing toxicological endpoints as part of this 

registration review. Table 7 presents the endpoints used in EPA’s most recent human health risk 

assessment in support of the 2008 RED. As previously stated, toxicological studies were 

identified as data gaps in the RED. All available information including existing toxicology 

studies, valid scientific literature, and the studies that are expected to be called in will be 

considered in establishing the endpoints to be used in the registration review risk assessment. A 

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

Table 7 – Existing Toxicological Endpoints for OEPA 

Exposure Scenario Dose Used in 

Risk Assessment 

(mg/kg/day) 

Target MOE, UF, for Risk 

Assessment 

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. Preserved 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 registrant intends that their product (Intersept PC-20) 

be used to preserve materials intended for nonfood contact only, based on verbal communication 

between the agency’s PM and registrant regarding the registrant’s intent to amend their label 

accordingly. Therefore, at this time, the agency 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 (including some plastics, epoxy 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 subsequently be present in drinking water. There are no 

data or other sources of information indicating that there would be negligible potential for release 

of OEPA to surface water from incorporation into treated materials and from leaching from inservice use of treated materials. Therefore, the agency anticipates 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 would be negligible release of OEPA during 

incorporation into treated materials and negligible leaching from in-service use of treated 

materials or that OEPA and/or its degradates will not persist if released to the environment, these 

data may not be required. Upon receipt and review, these data and/or other sources of 

information will be used during the risk assessment stage of this Registration Review to 

determine the potential for discharged or leached residues of OEPA to result in human dietary 

exposure via drinking water, which may trigger a drinking water assessment.

3.3 Occupational and Residential Exposures 

The occupational and residential exposures to OEPA were last assessed in D347015 (EPA, 2007) 

which was conducted in support of the 2008 OEPA RED. The agency anticipates the need to 

revise the occupational and residential assessments conducted in support of the 2008 OEPA RED 

since the Margins of Exposure (MOE)s were calculated using unit exposure data and transferable 

residue data that have underlying limitations and will need to be reassessed using updated values.

3.3.1 Occupational Handler Exposure 

There is the potential for both dermal and inhalation exposures during the open pouring of OEPA 

liquid formulations during material preservation and during the use of preserved materials such 

as paint. The exposures during the open pour liquid handling scenarios were not assessed in the 

OEPA RED because the RED specified the use of closed system loading; however, this 

mitigation has not been implemented and the current labels do not require closed system loading. 

In the RED, the (PHED) unit exposure data were used for painting scenarios which included the 

paint brush and airless sprayer application methods. The dermal MOEs for paint brush and 

airless sprayer application ranged from 10 to 490 and 5 to 230, respectively, depending upon the 

application rate which ranged from 0.1 to 5 percent. 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 rate exceeded 0.2 percent for airless sprayer 

application. The inhalation MOEs for paint brush and airless sprayer application ranged from 

6,300 to 310,000 and 210 to 11,000, respectively, depending upon the application rate. 

Although none of these MOEs are of concern, per se, because they all exceed the target MOE of 

100, the MOE of 210 triggered the need for an inhalation toxicity study because it did not exceed 

1000. This study was listed as a data requirement in the RED to be required by a DCI to be 

issued after the RED. 

Because of the low MOEs discussed above for the application of treated paint, the OEPA RED 

specified that the rate for paints not exceed 0.25%; however, this mitigation measure has not 

been incorporated into the labels. In addition, the use of closed system loading as specified in 

the RED has not been incorporated into the label. 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 revised during registration review upon receipt of the 

unit exposure data that are anticipated to be required in the post-RED DCI. Occupational 

handler scenarios to be assessed are presented in Table 8. 

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. Residential handler exposures 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 for occupational handler exposures and some of the MOEs were of 

concern at the higher application rates. 

 The above mentioned residential handler exposure scenario will need to be assessed in 

registration review upon receipt of the unit exposure data that are anticipated to be required to 

supplement or replace the unit exposure data that were used in the RED. 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, vinyl flooring, textiles and mattress covers. A summary of the 

MOEs is included in Table 10. 

Table 10 – MOEs for Residential Post Application Exposures to OEPA 

Use Population Exposure Route Application 

Rate % 

Transferable 

Residue % 

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 1,500 
Page 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 target MOEs for the carpet cleaner, clothing and 

mattress cover uses, the RED specified that the rates be reduced to 0.017% for carpet cleaners, 

0.34% for textiles, and 1.1% for mattress covers. These mitigation measures have not been 

incorporated into the labels. 

All of the above mentioned residential post application scenarios will need to be assessed in 

registration review upon receipt of the surface residue exposure data that are anticipated to be 

required to supplement or replace the surface residue assumptions that were used in the RED. 

These scenarios are listed in Table 11. 

Table 11 – Residential Post-Application Exposure Scenarios for OEPA 

Scenario Exposure Route(s) Duration

Toddlers Playing on Carpets Cleaned with Treated Cleaners Dermal 

Incidental Oral Intermediate Term 

Toddlers Playing on Vinyl Flooring Dermal 

Incidental Oral Intermediate Term 

Adults - treated textiles Dermal Intermediate Term 

Toddlers - treated textiles Dermal 

Incidental Oral Intermediate Term 

Adults and toddlers sleeping on treated mattress covers Dermal Intermediate term 

3.4 Aggregate and Cumulative Exposure 

3.4.1 Aggregate Exposures 

Registered uses of OEPA are not expected to result in dietary (food) exposure. However, the 

potential for drinking water and residential exposures cannot be discounted at this time. 

Aggregate risk will include 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 mechanism of toxicity, EPA has not made a 

common mechanism of toxicity finding as to OEPA and any other substances, and OEPA does 

not appear to produce a toxic metabolite produced by other substances. For the purposes of this 

registration review, therefore, EPA has not assumed that OEPA has a common mechanism of 
Page 21 of 42

toxicity with other substances. For information regarding EPA’s efforts to determine which 

chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such 

chemicals, see http://www.epa.gov/pesticides/cumulative/. 

4 Environmental Risk Assessment 

The agency has not previously conducted a risk assessment that supports a complete endangered 

species determination for OEPA. The previous 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. Phosphoric acid and OEPA 

have different chemical structures and have different chemical properties. Therefore, none of the 

information found in the assessment will be of use for the registration review of OEPA. The 

ecological risk assessment planned during registration review will allow the agency to determine 

potential acute and chronic risks to aquatic organisms exposed to OEPA. Such sites include 

areas that receive water containing OEPA transported from treatment sites into the aquatic 

environment. Minimal exposure would be expected to terrestrial organisms from these use 

patterns. The risk assessment also will allow the agency to determine whether each use of the 

OEPA has 'no effect' or 'may affect' federally listed threatened or endangered species (listed 

species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 

may affect' a listed species or its designated critical habitat, the agency will consult with the U.S. 

Fish and Wildlife Service and/or National Marine Fisheries Services (the Services), as 

appropriate. 

4.1 Environmental Fate 

There are no data or other sources of information indicating that there would be negligible 

potential for release of OEPA to surface water from incorporation into treated materials and from 

leaching from in-service use of treated materials. In addition, the registrant has not submitted 

environmental fate or leaching data for organic esters of phosphoric acid (OEPA) indicating the 

rate of dissipation or degradation products. As a result, the agency assumes that OEPA has the 

potential to be present in the environment because of its water solubility (324 mg/l)71and its 

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

in-service use. The environmental fate and leaching data the agency anticipates requiring are 

presented in Table 6. If the agency receives data or other sources of information that 

demonstrate that there would be negligible release of OEPA during incorporation into treated 

materials and negligible leaching from in-service use of treated materials or that OEPA and/or its 

degradates will not persist if released to the environment, 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 one2

8

 or two93 ethylhexyl groups and a companion 

molecule.4

10 OEPA is expected to create acid conditions 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 salt 
Page 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 m3 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 water (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 the 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), anaerobic aquatic metabolism (835.4400), and 

aerobic aquatic metabolism (835.4300). In addition, a test to determine biodegradation potential 

during wastewater treatment has also not been submitted. Results of an Activated Sludge 

Respiration Inhibition (ASRI) test (OECD 209 or OCSPP 850.3300) would be used to determine 

whether a ready biodegradability test (835.3110) or one of the wastewater treatment plant 

biodegradation simulation tests (835.3220, 835.3240, or 835.3280) would be needed. In the 

absence of data or other sources of information that demonstrate that OEPA would not persist in 

the environment if it is released to the environment during incorporation into treated materials 

and/or from leaching during in-service use, 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 from treated products (non-guideline study). In 

the absence of data or other sources of information that would demonstrate OEPA’s potential to 

leach and/or sorb, the agency anticipates the need to require these data. 

4.1.5 Water Quality 

OEPA is not identified as a cause of impairment for any water bodies listed as impaired under 

section 303(d) of the Clean Water Act.116 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=885 
Page 23 of 42

has been developed for OEPA.127 More information on impaired water bodies and TMDLs can be 

found at EPA’s website.138 

4.2 Environmental Conceptual Model Exposure Pathways 

There are no data or other sources of information indicating that there would be negligible 

potential for release of OEPA to surface water from incorporation into treated materials and from 

leaching from in-service use of treated materials. 

The organic esters of phosphoric acid are to be incorporated into products as a fungistat and 

bacteriostat. There are no spray application (non-incorporated) uses on the labels. The organic 

esters of phosphoric acids have two active labels, including Intersept149 and Intersept PC-20.1510 

Both products have all three active ingredients in this case with different percentages in each 

product. These registered products can be used in air filters for heating cooling systems, bedding 

materials, and textiles, paints and caulks, and plastics. 

The Intersept PC-20 label contains some uses that are not presumed to result in environmental 

exposure, including air filters, vinyl upholstery, mattresses and mattress ticking, and polymeric 

packaging film since there is no potential for release to the aquatic environment and these treated 

items would be disposed in lined sanitary landfills. 

However, there are some uses of OEPA for which the agency cannot presume that environmental 

exposure will not occur. These uses include plastics in polymeric concrete, vinyl, outdoor plastic 

furniture, and outdoor carpets and tile. Although the PC-20 label states “Once incorporated, there 

is no loss of efficacy due to washing or wear under normal use conditions”, the agency has found 

no evidence that leaching and subsequent environmental exposure from these treated materials 

will not occur. Consequently, the agency needs information demonstrating that incorporation of 

OEPA into plastics would not result in releases to surface water. 

 The first category of plastics is polymeric concrete (1-5 % OEPA w/w) which is used for 

water-exposed surfaces such as tile and grout, bath tubs, showers, bathroom sinks, and 

bathroom countertops. It can also be used building manhole covers because it is more 

corrosion resistant than traditional concrete.1611 

 The second category of plastics for which the agency cannot rule out the potential to 

create environmental exposure includes vinyl products such as car tops, awnings, 

tarpaulins, tents, sails, shower curtains, and vinyl film. 

 The third category of plastics for which the agency cannot rule out the potential to create 

environmental exposure is plastic furniture (1-5 % w/w). 

 

127http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_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 

111

16 http://genevapolymerproducts.com/ 
Page 24 of 42

 The fourth category of plastics for which the agency cannot rule out the potential to 

create environmental exposure is outdoor carpets (0.5-10 % w/w). The outdoor use in 

polymeric backing material (0.1-2 % w/w) for carpets is primarily restricted to outdoor 

carpets on decks and patios and in doormats.1712 

 Based on the antimicrobial uses of OEPA with active products in Table 5, the agency has 

created conceptual models for potential routes of environmental exposure which are 

included in “Conceptual Models for Environmental Exposure Pathways of Antimicrobial 

Pesticides”, dated August 4, 2014. For the uses with active products, the relevant pages 

are 17 for down-the-drain exposure from polymeric concrete used in caulks, grouts and 

sealants and 9-10 for non-paint treatment of outdoor items such as vinyl products, plastic 

furniture and outdoor carpets. All relevant routes of environmental 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 LD50, acute freshwater fish LC50, acute algae and acute freshwater aquatic invertebrate EC50. 

These studies are anticipated to be required for OEPA. 

However, since the agency has no eco-toxicity data on OEPA, additional studies are anticipated 

to be required for an ecological risk assessment unless the agency receives data or other sources 

of information that demonstrate that there would be negligible release of OEPA during 

incorporation into treated materials and negligible leaching from in-service use of treated 

materials or that OEPA and/or its degradates will not persist if released to the environment. 

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 determined at this time (Table 12). 

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

Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint 

Freshwater Fish One freshwater fish species Acute None 

Freshwater invertebrates One freshwater invertebrate species Acute None 

Freshwater benthic 

invertebrates 

One freshwater benthic invertebrate 

species 

Subchronic/ 

Chronic None 

Estuarine/marine fish One estuarine/marine fish species Acute 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 based on the use patterns of OEPA 

as a materials preservative in several commercial, industrial and household products (Table 5). 

Terrestrial organisms will not come into contact with OPEA because the chemical is 

incorporated into materials such as tiles, carpets, paints and textiles. Due to potential release of 

OPEA to aquatic environments after production 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 sources of information indicating that there would be negligible 

potential for release of OEPA to surface water from incorporation into treated materials and from 

leaching from in-service use of treated materials. In addition, there are no data or other sources 

of information that demonstrate that OEPA would not persist if it is released to the aquatic 

environment or on the rate of formation and decline of any degradates of OEPA. Finally, there 

are no data or other sources of information on the aquatic toxicity of OEPA and/or any 

degradates it might form. 

Unless the agency receives data or other sources of information that demonstrates that OEPA is 

not released to surface water or if it is released to surface water, OEPA and any degradates it 

forms do not persist or are not very toxic to aquatic organisms, the agency will need to 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 potential 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. 

Input parameters required to run the DtD module include percent removal during wastewater 

treatment, wastewater treatment plant influent volume, and concentrations of concern for aquatic 

organisms based on measurement effects endpoints. To determine wastewater treatment plant 

influent volume, the agency needs information on the maximum annual production volume of 

OEPA. Data or other sources of information on leaching potential from materials treated with 

OEPA would be applied to the maximum annual production volume to determine the wastewater 

treatment plant influent volume that would be used 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 screening level assessment of potential exposures of aquatic organisms 

to OEPA that could be released to surface water during its incorporation into treated materials, 

the Agency would use an approach such as that used in General Population and Ecological 

Exposures from Industrial Releases module of E-FAST (hereinafter referred to as the Industrial 

Releases module). This model requires the information that follows: 

-SIC code classification for each category of treated material into which OEPA would be 

incorporated or identification of locations of specific facilities at which OEPA would be 

incorporated into treated materials 

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

facilities. 

-maximum number of days per year OEPA would be expected to be released to surface water at 

each facility or category of facilities. 

-percent removal of OEPA during wastewater treatment. 

-concentrations of concern for aquatic 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. Open 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 used in the risk assessment. 

5 Endocrine Disruptor Screening Program (EDSP) 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

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

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

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

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

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

taxonomic groups. As part of its reregistration decision for OEPA, EPA reviewed these data and 

selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), OEPA is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

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

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

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

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 
Page 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 estrogen, androgen, or thyroid (E, A, or T) hormonal 

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

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

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

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

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

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

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

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

of chemicals identified for EDSP screening was published on June 14, 201318 and includes some 

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

should be construed as a list of known or likely endocrine disruptors. 

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

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

website: http://www.epa.gov/endo/.1913

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 and elsewhere in this document, application rates 

should be lowered for certain OEPA uses, including 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 possibility that EPA’s planned risk assessments 

overestimate risk due to reliance on conservative assumptions, and/or improve label clarity. 

7 Next Steps 

After the FWP is issued, a data call in (DCI) will be issued for the OEPA case. The agency will 

review and consider any label amendments or other information that might limit or eliminate the 

need for additional data for reevaluation of OEPA in the upcoming risk assessment. 

 

13 

1818 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the second list of 

chemicals. 

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

8 References 

U.S. Environmental Protection Agency (EPA). 2002. ECOTOX User Guide: ECOTOXicology 

Database System. Version 3.0. Available: http://www.epa.gov/ecotox/ 

U.S. Environmental Protection Agency. High Production Volume Information System (HPVIS). 

http://www.epa.gov/hpvis/ 

44858901 Harrison, E. (1999) Aseptrol Deodorizing Drip Pad: Product Identity and 

Composition, Beginning Materials, Production Process and Formation of Impurities. 

Unpublished study prepared by Engelhard Corporation. 15 p. {OPPTS 830.1550, 

830.1600, 830.1650, 830.1670} 23-Jun-1999. 

Interface Research Corporation’s Material Safety Data Sheet dated 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 greater than 5000 mg/kg for both acute oral and 

dermal toxicity. Mortality was observed at all concentrations in rabbits in an acute inhalation 

toxicity study, resulting in an LD50 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 irritant (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 required for registration review. 

Table A1 – Acute Toxicity Studies for Organic Esters of Phosphoric Acid 

Guideline No./Study Type MRID No. Results Toxicity 

Category 

870.1100/ 

Acute oral toxicity – rat 

42907901 

LD50 (M/F) > 5000 mg/kg (observed) IV 

870.1200/ 

Acute dermal toxicity – rabbit 

42907902 LD50 (M/F) > 5000 mg/kg (observed) 

IV 

870.1300/ 

Acute inhalation toxicity – rat 

40423801;

41365401; 

41365402

LC50 (M/F) = 1.48 mg/L 

LC50 (M) = 1.43 mg/L 

LC50 (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 available 
Page 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 toxicity. A 90-day dermal toxicity study in rats 

and a 90-day inhalation toxicity study are anticipated to be required for the currently registered 

uses. 

870.3100 90-Day Oral Toxicity – Rat 

In a 90-day subchronic oral toxicity study (MRID 41083601), groups of 10 male and 10 female 

Sprague-Dawley rats were given Intersept (100% a.i., Lot/Batch #3.791) administered in the diet 

at 0, 62.5, 200 and 625 (weeks 1-6)/375 (weeks 7-13) mg/kg/day in males and 0, 37.5, 120 and 

375 mg/kg/day in females. Doses were determined from a 14-day dietary range-finding study in 

rats (MRID 41665301). 

No deaths occurred during this study, but the high dose in males was reduced from 625 

mg/kg/day to 375 mg/kg/day after six weeks due to increasing weight loss in this group. The 

report stated that clinical signs were observed in mid- and high-dose rats, which included 

piloerection (which progressed to rough haircoat) and fur staining. Actual data were not 

provided. Ophthalmoscopic examination revealed lenticular degeneration in 3/10 high-dose 

males and 7/10 high-dose females vs. 0/20 in control. Treatment-related histopathologic findings 

were forestomach lesions (gastritis/ulcer-erosion/squamous hyperplasia hyperkeratosis) in 

intermediate- and high-dose males and lenticular degeneration in 5/10 high-dose females and 

1/10 high-dose males (0/20 control). 

Small, statistically significant changes in a few hematologic parameters (increased platelets, 

decreased hemoglobin, MCV, MCH and PCV) were reported, primarily in high-dose females but 

these values were within reference ranges established previously at the test site. Changes in 

clinical chemistry parameters included decreased GPT in high-dose males (-28%) and low-, midand high-dose females (-17%, -15%, and -27%, respectively), total bilirubin in mid- and highdose males (-42% and -47%, respectively) and high-dose females (-42%), and phosphorus in 

mid- and high-dose females (-22% and -11%, respectively). In addition, creatinine was 

decreased in high-dose males only (-7%, p  0.05). These changes, while statistically significant, were relatively small and were likely not biologically relevant because they were not 

correlated with any histopathologic findings. 

Body weight was statistically significantly decreased in mid-dose 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 relative to body weight in both high-dose males and females (+15%), 

and testes weight relative to body weight in mid- and high-dose males (+13% and +26%, respectively) were likely related to decreases in body weight. Liver weight relative to body weight was 

increased only in mid- and high-dose females (+12% and +25%, respectively), however, these 
Page 31 of 42

increases were moderate and of unknown toxicological significance in the absence of other toxic 

liver findings. 

The systemic LOAEL in males is 200 mg/kg/day based on decreased body weights, body weight 

gain, and food consumption and forestomach lesions (gastritis/ulcer-erosion/squamous 

hyperplasia hyperkeratosis); the NOAEL in males is 62.5 mg/kg/day. The LOAEL in females is 

375 mg/kg/day based on decreased body weight, body weight gain, food consumption, and 

lenticular degeneration; the NOAEL in females is 120 mg/kg/day. 

Developmental Toxicity 

Adequacy of Database for Prenatal Developmental Toxicity: The database for prenatal 

developmental toxicity is considered inadequate for the currently registered uses. Developmental 

toxicity assessment for organic 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 required based on the adverse effects observed in the rat study and the 

currently registered uses. 

870.3700 Prenatal Developmental Toxicity (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 gestation days (GD) 6-15, inclusive. The controls were given 

vehicle (corn oil) only for the same dosing period. On GD 20, all dams were sacrificed, 

necropsied to assess gross pathology, and uteri and ovaries were removed. All fetuses were 

sexed, weighed, and examined for external malformations/variations prior to sacrifice. 

Approximately one-half of the fetuses were fixed in ethanol and the remainder were placed in 

Bouin’s fixative and examined for visceral malformations/variations. The ethanol-fixed fetuses 

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

Four treatment-related deaths occurred at 500 mg/kg/day. Clinical signs of toxicity observed at 

500 mg/kg/day were salivation with red stain around the mouth (7) and nose (10), hypoactivity 

(8), urine stains (17), and fecal stains (4) compared to 0/25 control dams. Urine stains were also 

observed on one low-dose animal and four mid-dose animals. There were no statistically or 

biologically significant gross necropsy observations at maternal sacrifice. Absolute body weights 

were statistically significantly reduced (p0.05 or 0.01) for 250 and 500 mg/kg/day dams during 

GD 8, 12, 16, and 20 and statistically significantly reduced body weight gain was observed for 

both treatment groups during GD 6-8 and GD 0-20 (11.1 and 20.6%, respectively during GD 0-

20). Net body weight change from GD 0 was also statistically significantly reduced at 250 and 

500 mg/kg/day (17.2 and 21.1%, respectively), compared to controls. Food consumption was not 

monitored. No treatment-related maternal changes were noted at 125 mg/kg/day. 

The maternal toxicity LOAEL is 250 mg/kg/day based on clinical signs of toxicity and reduced 

absolute body weights and weight gains. The maternal toxicity NOAEL is 125 mg/kg/day. 
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 compared to 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 statistically significant decreases (p0.01) in live mean fetal weight 

(9.5%) and live female fetal weight (10.1%) compared to controls. Gravid uterine weights were 

also lower than controls at 250 and 500 mg/kg/day (6.2 and 20.3%, respectively) but did not 

reach statistical significance. 

The total fetuses (litters) with major external, visceral or skeletal malformations was 0 (0), 1 (1), 

4 (2), and 17 (9) (p0.05), in the control, low-, mid-, and high-dose groups, respectively. A positive trend for certain skeletal variations (delayed ossification of the hyoid, skull, pelvic girdle, 

vertebrae, sternebrae, and metatarsals) was also evident with increasing doses of Intersept® with 

the 500 mg/kg/day group generally statistically significantly increased (p0.05) compared to 

controls. A dose-related increase was also observed in the number of litters containing fetuses 

with increased renal pelvic cavitation and dilation of lateral ventricles of the brain. 

At 0,125, 250, and 500 mg/kg/day, the number of fetuses/litters with external malformations 

were 0/0, 1/1, 4/2, and 8/6 (litter rate, p0.05), respectively. External malformations at 500 

mg/kg/day consisted of one fetus each with cleft 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 fetuses/litters with skeletal malformations 

were 0/0, 1/1, 1/1, and 6/4 (litter rate, p0.05), respectively. Wavy or bent ribs were seen in 2 

fetuses from 2 litters at 250 mg/kg/day and in 15 fetuses from 8 litters at 500 mg/kg/day 

compared to none in controls. Skeletal malformations at 500 mg/kg/day consisted of vertebral 

anomaly with or without associated rib anomaly in 3 fetuses from 2 litters; cervical vertebrae 

fused in 2 fetuses from 2 litters; and single incidences of exencephaly, forked/fused ribs, and 

supernumerary limbs. 

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

The developmental toxicity LOAEL is 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 Toxicity: There is no reproductive toxicity study 

available for organic esters of phosphoric acid and such a study is required under 40 CFR Part 

158 W to support the currently registered uses. In addition, there are other toxicological 

concerns that need to be evaluated in a reproductive study. A two generation reproduction study 

is therefore anticipated to be needed for registration review. 
Page 33 of 42

Chronic Toxicity/Carcinogenicity 

Adequacy of Database for Chronic Toxicity/Carcinogenicity: The database for chronic 

toxicity/carcinogenicity is inadequate 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 flooring/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 database for mutagenicity is considered adequate 

for the currently registered uses based on the EPA's 1991 mutagenicity guidelines. Several 

mutagenicity studies have been submitted and reviewed by the Office of Pesticide Programs 

(OPP) and found acceptable. Organic esters of phosphoric acid is found to be not mutagenic or 

genotoxic. The summaries of these studies are provided below. 

Gene Mutation 

In a reverse gene mutation assay in bacteria (MRID 40564601), strains TA98, TA100, TA1535, 

TA1537 and TA1538 of S. typhimurium were exposed to Intersept® (Lot No. K13508 RJ, purity 

not provided) in DMSO at concentrations of 0.005, 0.01, 0.05, 0.1 and 0.5 μL/plate in the 

presence and absence of mammalian metabolic activation (S9-mix). Intersept® was tested up to 

cytotoxic concentrations. There was no evidence of induced mutant colonies over background. 

In a reverse gene mutation assay in bacteria (MRID 40564602), strains TA98, TA100, TA1535, 

TA1537 and 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 μL/plate in the presence and 

absence of mammalian metabolic activation (S9-mix). Intersept® was tested up to cytotoxic 

concentrations. There was no evidence of induced mutant colonies over background. 

Cytogenetics 

In a mammalian cell cytogenetics assay (chromosomal aberrations) (MRID 40564603), Chinese 

hamster ovary CHO-WBL cell cultures were exposed to Intersept® (Lot No. P2991, purity not 

provided) in DMSO at concentrations of 2.5, 5.0, 7.5, 10.0 μg/mL with a 10 hour harvest time 

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

without S9-mix. Cells were exposed to concentrations of 5, 7.5 10, 25, 50, 75 and 100 μg/mL 

with a 10 hour harvest time with S9-mix. Intersept® was tested up to cytotoxic concentrations. 

There was no evidence of chromosomal aberrations induced over background levels. 

In a bone marrow micronucleus assay (MRID 47715601), 5 male CD-1 mice/dose were treated 

once via gavage (20.5 mL/kg) with Intercept (purity 98%, Batch No. 1260809A) in corn oil at 

doses of 0, 500, 1000, or 2000 mg/kg (limit dose), and bone marrow cells were harvested at 24 

hours after dosing. Additional groups of 5 male mice were similarly dosed at 0 or 2000 mg/kg, 
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 observed 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 marrow). No treatment-related increases in the 

micronucleated polychromatic erythrocytes (MPCE) frequency were observed in any treatment 

group at either harvest time when compared to controls. The positive control induced the 

appropriate response. Based on the test result, Intercept did not induce a treatment-related 

increase in the frequency of micronucleated PCEs in bone marrow after any treatment time. 

Although there was no indication of bone marrow growth inhibition, the animals were dosed at 

the limit dose (2000 mg/kg). Therefore, this study is classified as Acceptable/guideline and 

satisfies the guideline requirement (OPPTS 870.5395; OECD 474) for in vivo cytogenetic 

mutagenicity data. 

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

Chinese hamster ovary CHO-WBL cell cultures were exposed to Intersept® (Lot No. P2991, 

purity not provided) in DMSO at concentrations of 0.033, 0.10, 0.333, 1.00, 3.33, 10.0, 33.3, 

100, 333, 1000 μg/mL with and without mammalian metabolic activation (S9-mix). Cells were 

treated for 25 hours without S9-mix and for 2 hours with S9-mix and harvested 25.5 hours after 

termination of treatment without S9-mix and 2.5 hours after treatment with S9-mix. The S9-

fraction was obtained from Aroclor 1254 induced male Sprague-Dawley rat liver. Intersept® was 

tested up to cytotoxic concentrations. There was no evidence of SCEs induced over 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 Requirements for Antimicrobial Pesticides. The 

registrant can address this anticipated data requirement by either submitting a study according to 

the OCSPP 870.7800 Guideline, by citing information from the scientific literature that addresses 

Immunotoxicity of (chemical), or by submitting a request for waiver of this study using the 

Agency’s published guidance, available at: http://www.epa.gov/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 

NOAELmale = 62.5 mg/kg/day 

LOAELmale = 200 mg/kg/day, based on 

decreased body weights, body weight gain, 

and food consumption and forestomach 

lesions (gastritis/ulcer-erosion/squamous 

hyperplasia hyperkeratosis); 

NOAELfemale = 120 mg/kg/day 

LOAELfemale = 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 

Negative 
Page 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 

Negative 

 
Page 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 one2114 or two2215 ethylhexyl groups and a companion 

molecule.2316 As a result, the agency anticipates requiring 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.

 

2114 Mono(2-ethylhexyl ester) of phosphoric acid 

2215 Bis(2-ethylhexyl ester) of phosphoric acid 

2316 2,2’-(cocoimino)-bis ethanol salt 
Page 38 of 42

Appendix C Ecotoxicology Profile 

Toxicity to Terrestrial and Aquatic Receptors 

No terrestrial and aquatic eco-toxicity studies are available for OEPA. Four eco-toxicity studies 

are being required for OEPA and several studies are anticipated to be required depending on the 

exposure scenarios determined by the down-the-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 water, OEPA and any degradates it 

forms do not persist or are not very toxic to aquatic 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 potential 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 screening level assessment of potential exposures of aquatic organisms 

to OEPA that could be released to surface water during its incorporation into treated materials, 

the agency would use an approach such as that used in 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 potential exposures of aquatic organisms to OEPA 

due to leaching from in-service use of treated materials and incorporation into 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 information is summarized in Table E1 (source: 

MRID 43265801 and Interface Research Corporation’s MSDS). 

Table E1 – Product Chemistry of Organic Esters of Phosphoric Acid 

OCSPP 

Guideline 

No. 

Physical and Chemical 

Properties 

Mixture of 3 AIs 

 Phosphoric acid, mono(2-ethylhexyl) ester (17.7%) 

 Phosphoric acid, bis(2-ethylhexyl) ester, compound with 2,2'-

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

 Phosphoric acid, mono(2-ethylhexyl) ester, compounds with 

diethanolamine N-coco alkylderivs. (1:1) (15.9%) 

830.1550 Product identity and 

composition 

Refer to Table 3 

830.1600 Description of materials used 

to produce the product 

Confidential Business Information (CBI) 

830.1620 Description of production 

process 

CBI 

830.1650 Description of Formulation 

Process 

 CBI 

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/ml 
Page 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 alkylderivs. (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 the docket in response to this workplan.