Page 2 of 74

Ortho-Phenyl Phenol and Salts Registration Review Team 

Human Health & Environmental Effects 

Antimicrobials Division 

Pat Jennings 

Srinivas Gowda 

Najm Shamim 

William Erickson 

Tim McMahon 

Timothy Dole 

William Hazel 

 

Environmental Fate and Effects Division 

Robin Sternberg 

He Zhong 

Health Effects Division 

Thurston Morton 

Risk Management 

Donna Kamarei 

Kelly Ballard 

Rose Kyprianou 

Ben Chambliss 

 
Page 3 of 74

Table of Contents 

1 Introduction ............................................................................................................................. 6

1.1 Statutory and Regulatory Authority ................................................................................. 6

1.2 Updates to the Workplan .................................................................................................. 7

1.3 Case Overview ................................................................................................................. 9

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

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

1.5.1 Summary of Registered Uses .................................................................................. 10

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

1.6.1 Recent/Pending Regulatory Actions ....................................................................... 13

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

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

1.7.2 Ecological ............................................................................................................... 14

2 Anticipated Data Needs ........................................................................................................ 14

3 Human Health Risk Assessment ........................................................................................... 21

3.1 Existing Toxicological Endpoints .................................................................................. 21

3.2 Dietary Exposure ............................................................................................................ 22

3.2.1 Tolerance Information ............................................................................................ 23

3.2.2 Food ........................................................................................................................ 23

3.2.3 Drinking Water ....................................................................................................... 24

3.3 Occupational and Residential Exposures ....................................................................... 24

3.3.1 Occupational Handler Exposure ............................................................................. 24

3.3.2 Residential Handler Exposures ............................................................................... 25

3.3.3 Residential Post-Application Exposures ................................................................. 26

3.4 Aggregate and Cumulative Exposure ............................................................................. 26

3.4.1 Aggregate Exposures .............................................................................................. 26

3.4.2 Cumulative Exposures ............................................................................................ 27

4 Environmental Risk Assessment........................................................................................... 27

4.1 Environmental Fate ........................................................................................................ 27

4.1.1 oPP and its Salts ...................................................................................................... 27

4.1.2 Photodegradates of oPP .......................................................................................... 28

4.1.3 Water Quality .......................................................................................................... 29

4.2 Conceptual Models for Environmental Exposure Pathways .......................................... 29

4.2.1 Residential Insecticidal Use Patterns ...................................................................... 29

4.2.2 Antimicrobial Use Patterns ..................................................................................... 30

4.3 Ecological Effects Assessment ....................................................................................... 40

4.3.1 Mechanism of Action .............................................................................................. 40

4.3.2 Measures of Effect (Ecotoxicology Endpoints) ...................................................... 40

4.4 Exposure Analysis Plan .................................................................................................. 41

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates ............................................ 42

4.4.2 Screening Level Down-the-Drain Analysis ............................................................ 43

4.5 Effects Analysis Plan ..................................................................................................... 44

5 Endocrine Disruptor Screening Program (EDSP) ................................................................. 44

6 Optional Label Changes ........................................................................................................ 45

7 Next Steps ............................................................................................................................. 46

8 References ............................................................................................................................. 47
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Appendix A Toxicology Profile ............................................................................................... 48

Appendix B Environmental Fate ............................................................................................. 56

Appendix C Ecotoxicology Profile .......................................................................................... 62

Appendix D Screening Level Down-the-Drain Analysis ........................................................ 69

Appendix E Product Chemistry ............................................................................................... 70

Appendix F Comments Received Concerning the Preliminary Work Plan ............................ 72

List of Tables 

Table 1 – Summary of Anticipated Risk Assessments and Data Needs for oPP and its Salts ....... 8

Table 2 – Anticipated Registration Review Schedule .................................................................... 8

Table 3 – Chemical Identification of oPP and its Salts .................................................................. 9

Table 4 – Physical-Chemical and Fate Properties for oPP and its Salts ......................................... 9

Table 5 – Summary of End Use Products Containing oPP or its Salts ......................................... 10

Table 6 – Summary of Registered Uses of oPP and its Salts ........................................................ 11

Table 7 - Incidents Reported for oPP and its Salts (July 2006 to July 2013) ............................... 13

Table 8 – Studies Anticipated as Needed for the Registration Review of oPP and its Salts ........ 15

Table 9 – Existing Toxicological Endpoints for oPP .................................................................... 21

Table 10 – Occupational Handler Exposure Scenarios for oPP ................................................... 25

Table 11 – Residential Handler Exposure Scenarios for oPP ....................................................... 25

Table 12 – Residential Post-Application Exposure Scenarios for oPP ......................................... 26

Table 13 – Selected Ecological Effects Endpoints for the Ecological Risk Assessment ............. 40

Table 14 – Summary of Screening Level Down-the-Drain Analysis Results .............................. 43

Table 15 – Acute Toxicity Studies for oPP .................................................................................. 48

Table 16 – Key Physical-Chemical Properties and Environmental Fate Characteristics of oPP and 

its Salts ................................................................................................................................... 58

Table 17 – Physical/Chemical and Environmental Fate Characteristics of PBQ and PHQ ......... 59

Table 18 – Avian Toxicity Data .................................................................................................... 62

Table 19 – Freshwater Fish Toxicity Data .................................................................................... 63

Table 20 – Freshwater Invertebrate Toxicity Data ....................................................................... 64

Table 21 – Estuarine/Marine Fish and Invertebrate Toxicity Data ............................................... 65

Table 22 – Aquatic Plants Toxicity Data ...................................................................................... 66

Table 23 – Emergent Rooted Aquatic Plant Toxicity Data .......................................................... 66

Table 24 – Product Chemistry of oPP and Salts ........................................................................... 70

List of Figures 

Figure 1 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic 

and Terrestrial Organisms from Sanitizer/Disinfectant and Material Preservative Cleaning 

Solution Uses ......................................................................................................................... 31

Figure 2 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic 

and Terrestrial Organisms from Antimicrobial Fruit and Vegetable Washes ....................... 32

Figure 3 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic 

and Terrestrial Organisms from Wood Preservatives for Sapstain Control .......................... 33

Figure 4 -- Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic 

and Terrestrial Organisms from Materials Preservatives in Metal Working Fluids .............. 34
Page 5 of 74

Figure 5 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic 

and Terrestrial Organisms from Swimming Pools, Spas, Ornamental Ponds, Aquaria, and 

Waterbed Water Uses ............................................................................................................ 35

Figure 6 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic 

and Terrestrial Organisms from Lakes, Ponds, and Reservoirs ............................................. 36

Figure 7 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic 

and Terrestrial Organisms from Cooling, Evaporative Condenser, Heat Exchanger, 

Industrial Scrubbing, and Paper Mill Water Systems ............................................................ 37

Figure 8 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic 

and Terrestrial Organisms from Biocides in Oil Drilling Muds/Fluids and Secondary 

Recovery Water ..................................................................................................................... 38

Figure 9 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic 

and Terrestrial Organisms from Material Preservative Uses Other Than Metal Working 

Fluids and Cleaning Solutions ............................................................................................... 39

 
Page 6 of 74

1 Introduction 

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

Agency”) Final Work Plan (FWP) for ortho-phenyl phenol (oPP) and its salts. The FWP 

document explains what EPA's Office of Pesticide Programs (OPP) knows about oPP and its 

salts, 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 oPP’s review. 

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

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

docket, to inform the public of what it knows about oPP and its salts and what types of new data 

or other information would be helpful for the Agency to receive as it moves toward a decision on 

oPP and its salts. 

1.1 Statutory and Regulatory Authority 

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

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

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

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

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

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

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

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

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

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

http://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 for ortho-phenyl phenol Preliminary Work Plan (PWP) was published on September 25, 

2013 and the 60- day comment period ended on November 25, 2013. Public comments received 

concerning the PWP and documents associated with this registration review can be viewed at 

http://www.regulations.gov in docket EPA-HQ-OPP-2013-0524. Below is a summary of the 

issues relevant to this registration review case. 
Page 7 of 74

1.2 Updates to the Workplan 

Since the publication of the PWP, the Agency has made the following updates: 

 Corrected the timeline in Table 2, the anticipated registration review table. 

 Updated Section 7, Next Steps. 

 Added Appendix F. 

The Agency received two submissions during the public comment period on the initial docket. 

See Appendix F for the Agency’s responses to these comments. 

Comments received did not result in a modification to the anticipated data needs or registration 

review schedule in the oPP PWP. This document makes final the work plan for the oPP and salts 

registration review process. 

 
Page 8 of 74

Table 1 – Summary of Anticipated Risk Assessments and Data Needs for oPP and its Salts 

Risk Assessment 

Assessment 

Necessary to 

Support 

Registration 

Review 

Date of Most 

Recent 

Assessment 

Type of 

Assessment 

Required 

Data Anticipated as Needed 

(See Table 8 for details) 

Dietary (food) Yes 7/28/2006 Updated None 

Dietary (drinking water) No (see 3.2.3) 7/28/2006 None None 

Occupational Handler 

(Dermal and Inhalation 

Exposure) 

Yes 7/28/2006 Updated Dermal and Inhalation Exposure Data

Residential Handler 

(Dermal and Inhalation 

Exposure) 

Yes 7/28/2006 Updated Dermal and Inhalation Exposure Data

Residential Post Application, 

Disinfected Floors 

(Incidental Oral Exposure) 

Yes 7/28/2006 Updated Surface Residue Data 

Residential Post Application, 

Treated Paints 

(Inhalation Exposure) 

Yes 7/28/2006 Updated Paint Chamber Emissions Data 

Residential Post Application, 

Air Sanitization 

(Inhalation Exposure) 

Yes 7/28/2006 Updated Inhalation Exposure Data 

Residential Post Application, 

Treated Plastics and 

Polymers 

(Incidental Oral Exposure) 

Yes None New Residue Migration Data 

Aggregate Yes 7/28/2006 New None 

Cumulative No (see 3.4.2) 7/28/2006 None None 

Tolerance Review Yes N/A Updated None 

Ecological Yes 2007 Updated Ecotoxicity and Environmental Fate 

data 

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 2013-09 2013-09-25 

Close Public Comment Period 2013-11 2013-11-25 

Phase 2: Case Development 

Issue Final Work Plan 2014-03 2014-03 

Issue Data Call-In (DCI) 2015-03 

Receive Data to be Considered in Risk Assessment 2017-03 

Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2018-09 

Close Public Comment Period 2018-10 

Phase 3: Registration Review Decision and Implementation 

Open 60-Day Public Comment Period for Proposed Decision 2019-03 

Close Public Comment Period 2019-05 

Issue Final Decision 2019-09 

Begin Post-Decision Follow-up 2019 

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).
Page 9 of 74

1.3 Case Overview 

The docket for the oPP and its salts case (Case 2575) has been established at 

http://www.regulations.gov in docket number EPA-HQ-OPP-2013-0524. 

1.4 Chemical Identification and Properties 

Table 3 presents the active ingredients to be assessed in Case 2575: ortho-phenyl phenol (oPP) 

(PC Code 064103); sodium ortho-phenyl phenate a sodium salt of oPP (Na-oPP; PC Code 

064104); and potassium ortho-phenyl phenate a potassium salt of oPP (K-oPP; PC Code 

064108). 

Table 3 – Chemical Identification of oPP and its Salts 

Chemical Name oPP Na-oPP K-oPP 

Common Name ortho-phenyl phenol; 

2-phenyl phenol 

Sodium ortho-phenyl phenate; 

oPP, sodium salt 

Potassium ortho-phenyl 

phenate; oPP, potassium salt 

Chemical 

Classification Phenol Phenol Phenol 

PC Code 064103 064104 064108 

CAS Number 90-43-7 132-27-4 13707-65-8 

Molecular 

Formula C12H10O C12H9NaO C12H9KO 

Molecular Weight 170.2 g/mole 192.19 g/mole 208.30 g/mole 

Molecular 

Structure 

Product chemistry and fate property information relevant to the risk assessment of oPP and its 

salts is summarized in Table 4. Details of the fate properties are included in Appendix B and 

details of the product chemistry information are included in Appendix E . In solution, the sodium 

(Na) and potassium (K) salts rapidly dissociate, releasing sodium and potassium cations (Na+ and 

K+, respectively) and the ortho-phenyl phenate anion (oPP-). The equilibrium in solution 

between the oPP-

 anion and the protonated or unionized oPP depends on the pH of the solution. 

The fate and transport data supporting oPP can be used to support the salts, and similarly, the 

fate and transport data supporting its Na and K salts may be used to support oPP. 

Table 4 – Physical-Chemical and Fate Properties for oPP and its Salts 

OPPTS 

Guideline No.

Physical and 

Chemical Properties oPP Na-oPP K-oPP 

830.7000 pH 6.1 in aqueous solution at 

22.7°C 

12 to 13.5 in saturated 

water solution at 25°C 

12 to 13.5 in saturated 

water solution at 25°C 

830.7050 UV/Visible 

Absorption 

245 to 287nm 

Not expected to absorb 

UV at λ > 300 nm 

-- -- 

830.7200 Melting point 56-58oC 230.07°C 

(Source: EPI Suite v4.1) 

230.07°C 

(Source: EPI Suite v4.1) 
Page 10 of 74

OPPTS 

Guideline No.

Physical and 

Chemical Properties oPP Na-oPP K-oPP 

830.7220 Boiling point 286oC at 760 mm Hg 537.41°C 

(Source: EPI Suite v4.1) 

537.41°C 

(Source: EPI Suite v4.1) 

830.7300 Density 1.213 g/cu cm at 25°C 1.3 g/cu cm at 25°C 1.3 g/cu cm at 25°C 

830.7370 Dissociation 

Constants in water 

pKa = 9.55 at 22.5°C 

pKa = 9.9 at 25°C 

pKa = 9.97 at 25°C 

It is a weak acid. 

Dissociates in water 

pKa: 9.84 at 20oC 

Dissociates in water 

pKa: 9.84 at 20oC 

830.7550 

Partition coefficient 

(n-octanol/water) 

Log Kow 

3.3 (EPI Suite v4.1) 

log Pow: 3.09-3.36 

log Pow: 3.12 (20°C, pH 

7) 

0.59 (EPI Suite v4.1) 0.59 (EPI Suite v4.1) 

830.7840 Water Solubility 

700 mg/L at 25°C in 

water 

0.760 g/1000 g in water 

(pH 5.67) (20oC). 

60.6 g/100 mL, 53.37% 

(w/w) (20oC) 

534 g/1000 g in water 

(pH 13.61) (20oC) 

Highly water soluble 

534 g/1000 g in water 

(pH 13.61) (20oC)

830.7950 Vapor pressure 

2.00 x 10-3 mm Hg at 

25°C (EPI Suite v4.1, 

experimental) 

1.6 x 10-3 mm Hg at 25oC

0.0017 mmHg at 25oC 

1.91 x 10-11 mm Hg at 25 

°C (Source: EPI Suite 

v4.1) 

1.8 x 10-9 mm Hg at 25oC 

1.91 x 10-11 mm Hg at 25 

°C (EPI Suite v4.1) 

Source: MRIDs 101697, 41914901, 41605001, 41609501, 41609502, 41609503, 41609504, 41609505, 42097001, 

42381901, 42441701, 42441702, 42441703, 42441704, 42457001, 42500201, 42500202, 42528701, and 43994201, 

EPI Suite v4.1 

1.5 Use/Usage Description 

1.5.1 Summary of Registered Uses 

Table 5 includes a summary of end use products that contain oPP or its salts as an active 

ingredient (a.i.). 

Table 5 – Summary of End Use Products Containing oPP or its Salts 

Chemical 

Name PC Code Number of Products Percent a.i. Formulations 

oPP 064103 77 0.014 to 99.5 Pressurized Liquid, Soluble Concentrate (SC), 

Ready to Use (RTU) Solution, Wipe 

Na-oPP 064104 19 0.21 to 71.7 SC, RTU Solution, Emulsifiable Concentrate, 

Pressurized Liquid (i.e., aerosol can) 

K-oPP 064108 3 0.159 to 55.6 SC, Pressurized Liquid 

Table 6 includes a summary of the registered oPP and salts uses that will be assessed in this 

registration review. Registered product uses include: disinfectants, bacteriocides/bacteriostats, 

deodorizers, algaecides, fungicides/fungistats, insecticides, miticides, molluscicides, sanitizers, 

termiticides, tuberculocides, and virucides. 
Page 11 of 74

Table 6 – Summary of Registered Uses of oPP and its Salts 

Use Application Method Application Rate

Agricultural Premises and Equipment

Greenhouse premises and equipment Sponge, Mop, Spray 233 to 268 ppm 

Cattle, Swine and Poultry Farms 

Hatching facilities and incubators 

Trucks and other vehicles 

Sponge, Mop, Spray 

RTU Spray 

194 to 782 ppm 

2,200 ppm 

Fogger 3,200 to 40,350 ppm in 

fogging solution 

Shoe sanitizer Shoe Bath Tray 233 to 476 ppm 

Aquatic Areas 

Sewage Disposal Lagoons1 Spray 4 lb ai/acre 

Commercial/Institutional/Industrial (CII) Premises and Equipment

Nonporous, nonfood contact surfaces including 

transportation facilities and vehicles, storage facilities, 

and general indoor premises. 

Sponge/Mop/Spray 

RTU Spray 

233 to 782 ppm 

140 to 4,000 ppm

Fogger 3,200 to 40,350 ppm in 

fogging solution

Utility pole junction boxes2 RTU Spray 2,100 ppm 

Post-Harvest Fruit Treatment and Wash 

Post-harvest fruit treatments and Fruit washes 

(Citrus, Peach, Pear)3 

Drench, Dip, Drip, Spray, 

Foam

3593 to 134,000 ppm 

359 to 4,300 ppm 

3,600 to 15,600 ppm

Food Handling Premises and Equipment

Food processing plants; non-food handling areas Spray (RTU) 500 to 2,200 ppm 

Sponge, Mop 258 to 2,200 ppm 

Eating establishment food handling areas Spray (RTU) 500 to 2,200 ppm 

Sponge, Mop 158 to 410 ppm 

Industrial Processes 

Air Washer, Cooling Tower and Paper Mill Water 

Systems Open Pour 6.2 to 12.4 ppm 

Oil Drilling Muds, Packer Fluids, Oil field water 

systems, Oil Recovery Water, Secondary Open Pour 86 to 4,300 ppm 6.2 to 12.4 ppm 

Material Preservative

Adhesives, Glues, Caulks and Sealants Open Pour 500 to 11,400 ppm 

Ceramic glazes Open Pour 375 to 5,600 ppm 

Cleaning Solutions Open Pour 375 to 4,600 ppm 

Vehicle polishes and waxes Open Pour 625 to 5040 ppm 

Concrete and Concrete Additives Open Pour 875 to 7,170 ppm 

Leather Dip and Spray 690 to 15,000 ppm 

 

1

 The Sewage Disposal Lagoons use is included on EPA Reg # 39967-116. 

2

 The Utility pole junction boxes use is included on EPA Reg # 9688-287. 

3

 Per Tolerances in 40 CFR 180.129. 
Page 12 of 74

Use Application Method Application Rate

Metal Working Fluids Open Pour 500 to 15000 ppm 

Paints, Stains and Coatings (In Can)4

Finger Paint5 Open Pour 500 to 5,700 ppm 

Paper Auxillaries and Additives Open Pour 400 to– 4300 ppm 

Plastics Open Pour 5000 ppm 

Polymer Dispersions and Emulsions (i.e. rubber) Open Pour 500 to 3,800 ppm 

Textile Auxillaries Open Pour 500 to 4,300 ppm 

Textiles (Awnings and Tarps) 

Textiles (Carpet and Upholstery) 

Textiles (Cotton) 

Open Pour 

8,700 to 56,600 ppm 

3,500 to 22,600 ppm 

2,600 to 17,000 ppm 

Medical Premises and Equipment 

Critical Items (Surgical Equipment) Immersion 84 to 536 ppm 

Hair Care Shavers and Scissors Immersion 22 to 782 ppm 

Dental Lines Circulate in Place 268 to 537 ppm 

Hard Surfaces (Noncritical Areas) 

Hard Surfaces (Critical Areas) Mop, Wipe, Spray 196 to 1,550 ppm 196 to 520 ppm 

Residential and Public Access Premises

Hard surfaces including floors and bathrooms Sponge, Mop or Spray 

RTU Spray 

194 to 1,550 ppm 

500 to 3,700 ppm 

Exterior roof, siding, trim, decks, fences Spray 

118 ppm acid equivalents (20 

gallons per 2,000 ft2 roof and 

20 gallons ft2 other structures 

Carpets and Upholstery RTU Spray 2,200 ppm 

Bedding and Mattresses RTU Spray 1,800 to 2,200 ppm 

Laundry and Footwear RTU Spray 1,000 to 2,200 ppm 

Portable Toilets Open Pour 409 to 288,000 ppm 

Garbage Cans Spray 

RTU Spray 

258 to 520 ppm 

140 to 4,000 ppm 

Wood Preservative including Sapstain Control

Fresh Cut Lumber, Construction Woods 

Fruit and Vegetable Containers, Pallets Dip or Spray 6,870 to 45,200 ppm 32,000 to 34,000 ppm 

Residential Lawn, Turf, and Surface Treatments 

Lawn, turf, outdoor soil and plant beds and vegetation 

adjacent to building foundations and structures 

including decks, porches, and fences; sidewalks, 

driveways, patios, and porches; ant hills 

Spray including spot 

treatments and crack-increvice treatments Up to 0.133 lb a.i./A 6

 

4

 The “In Can” designation refers to the a.i. added to preserve the material in the container prior to in-service use. 

5

 The finger paint use is included on EPA Reg # 39967-188. 

6

 This application rate assumes 4 houses per acre (quarter-acre lot per house) and that each homeowner applies the 

entire contents of one container of spray (=170 ounces). Therefore, the application rate in pounds a.i. per acre (lb 

a.i./A) is 0.133 (4 houses per acre x 1 container per house x 170 ounces per container x 1 gallon per 128 ounces (unit 

conversion) x 8.33 lb/gallon (density for water) x 0.003 (% a.i.)). 
Page 13 of 74

1.6 Regulatory History 

The first product containing oPP as an a.i. was registered in the U.S. in 1948. The first product 

containing Na-oPP as an active ingredient was registered in the U.S. in 1948. The first product 

containing K-oPP as an active ingredient was registered in the U.S. in 1996. The Agency 

completed a Reregistration Eligibility Decision (RED) for the oPP and its salts case in 2006. The 

post-RED Data Call-In (DCI) has not been issued. 

1.6.1 Recent/Pending Regulatory Actions 

An EDSP order for submission of oPP data was issued on January 14, 2010. Data have been 

submitted and are currently being reviewed. 

1.7 Incidents 

1.7.1 Human Health 

Incidents Reported in the OPP Incident Data System 

As of July 9, 2013, a total of 1147 human health incidents that have occurred since the 2006 

RED was published are listed in the Office of Pesticides Programs Incident System for oPP and 

its salts. Most (855) of these incidents involved dual purpose products that contain disinfectants 

and insecticides such as cyfluthrin, permethrin, and pyrethrin while a smaller number of 

incidents were associated with disinfectant only products. A listing of these incidents is given in 

Table 7. 

Table 7 - Incidents Reported for oPP and its Salts (July 2006 to July 2013) 

Product Type 

Number of Incidents 

Fatality Major Moderate Minor Unclassified Total

Disinfectant-Only 1 2 45 172 12 232 

Insecticide/Disinfectant (Cyfluthrin) 0 1 73 781 0 855 

Insecticide/Disinfectant (Pyrethrin) 0 0 11 49 0 60 

Total 1 3 129 1002 12 1147 

Most of the incidents are classified as Minor (1002 incidents) while a smaller number are 

classified as Moderate (129 incidents), Major (3 incidents) and Fatality (1 incident). The 

circumstances surrounding the fatality and the three major incidents are as follows: 

 The fatality involved a baby who was born six weeks early with excessive fluid in the 

abdomen. The mother used a product containing oPP on a regular basis while she was 

pregnant. 

 One of the disinfectant-only major incidents involved a man who had been using the 

product without gloves, who was hospitalized with acute pancreatitis and secondary 

respiratory failure. 

 The other disinfectant-only major incidents involved an employee who suffered 

respiratory arrest after being exposed to the product. 

 The disinfectant/insecticide major incident involved a person who had an intraventricular 

hemorrhage sometime shortly after spraying the product. 

With respect to the above incidents, the fact that they are listed in the incident data system does 

not necessarily mean that they were caused by the associated product. In the case of the 

intraventricular hemorrhage, for example, the emergency medical technicians on the scene 
Page 14 of 74

reported the presence of the product to aide in diagnosis, and it was later determined by the 

doctors at the hospital that the hemorrhage was not caused by the product. 

The moderate incidents involved a wide range of circumstances and effects. Some of the 

incidents were caused by misuse of the product on unregistered use sites such a toilet seats or 

over use of the product where too much product was applied or the product was applied too 

often. The reported effects included dermal irritation and hives, respiratory irritation and 

systemic effects such as dizziness and nausea. 

1.7.2 Ecological 

No incidents are reported in the Agency’s Incident Data System (IDS v. 1.8) for the time period 

spanning 2006 to 2013. 

2 Anticipated Data Needs 

Table 8 presents a summary of the data anticipated as being needed to support this registration 

review. 
Docket Number EPA-HQ-OPP-2013-0524 

www.regulations.gov 

Page 15 of 74

Table 8 – Studies Anticipated as Needed for the Registration Review of oPP and its Salts 

GLN Study Name Test Substance7

Time Frame 

(Measured in 

months from 

DCI Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) Triggering Anticipated 

Data Requirement Appli

Studies Anticipated to be Required through the Registration Review DCI 835.1110 Activated Sludge Sorption Isotherm TGAI 12 Ecological 

Sanitizer/Disinfectant; Materials preservatives; Antimicrobial fruit and vegetable washes; food contact sanitizer; Wood Preservative for sapstain control; Swimming pools, spas, ornamental ponds, aquaria, waterbed water; Commercial/Industrial Process and Water Systems; Biocides in oil drilling muds and secondary recovery water 

Transpoplants aexposusurface 

835.1230 Adsorption/Desorption TGAI 12 

Ecological 

Wood preservative; Exterior architectural paints and coatings material preservative; Exterior roof, siding, fence, and deck algaecide and antimicrobial treatment; Lawn, turf, surface soil, sidewalk, parking lot, patio, ant hill insecticide use 

Treated Exteriotreatmeimperv

835.1240 Leaching Studies, Soil TGAI 12 835.2240 Photodegradation in Water TGAI 12 Ecological All 

Industrand equpreservResidensurfacepaint/ststructurlawn an

835.2410 Photodegradation in Soil TGAI 12 Ecological 

Wood preservative; Exterior architectural paints and coatings material preservative; Exterior roof, 

LeachinExterioExterio

7 The Agency lacks information on the fate profile for oPP with regard to the potential for biotic degradates/transformation products to be 

the absence of information, the Agency will use a total toxic residue approach to determine potential toxicity to ecological organisms. Thmajor degradates formed would be as toxic as the parent. The Agency will consider conducting a more refined risk assessment if informamajor degradates identified is provided. 
Page 16 of 74

GLN Study Name Test Substance7

Time Frame 

(Measured in 

months from 

DCI Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) Triggering Anticipated 

Data Requirement Appli

835.4100 Aerobic Soil Metabolism TGAI 24 

siding, fence, and deck algaecide and antimicrobial treatment; Lawn, turf, surface soil, sidewalk, parking lot, patio, ant hill insecticide use 

treatmelawn an

835.4300 Aerobic Aquatic Metabolism TGAI 24 

Ecological All 

Transpoplant (Wrelease downstto surfasurface drain; dwater 

835.4400 Anaerobic Aquatic Metabolism TGAI 24 OECD 209 or 850.68008

Activated Sludge Respiration Inhibition (ASRI)

TGAI 12 

Ecological 

Sanitizer/Disinfectant; Materials preservatives; Antimicrobial fruit and vegetable washes; food contact sanitizer; Wood Preservative for sapstain control; Swimming pools, spas, ornamental ponds, aquaria, waterbed water; Commercial/Industrial Process and Water Systems; Biocides in oil drilling muds and secondary recovery water 

Transpoplant anbiodegrmicroor

835.3110 835.3220 835.3240 835.3280 

Ready biodegradability test or one of three biodegradation in activated sludge simulation tests9

TGAI 12 

8 EPA published draft guidance under guideline OPPTS 850.6800 and has since published final guidance for this study under guideline O

850.3300: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0021. The anticipated DCI will provide that OC

used in place of OECD 209 if the test substance is not sufficiently soluble to allow preparation of a concentrated stock solution in water. this study in 40 CFR 158(W). OECD Test Guideline 209 can also be used as guidance for this study, available online at http://www.oecdilibrary.org/content/book/9789264070080-en. 9 The results of the ASRI test will determine which of these four biodegradation tests is/are required. If the ASRI test EC50 is less than or 

either the (i)Biodegradation in Activated Sludge Study or (ii) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units o

is expected to be required. If the ASRI test EC50 is greater than 20 mg/L, then the registrant would likely be required to conduct either: (i

or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or c) the PorBiodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, the antimicrobial fBiodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Porous Pot study would likely be required. 
Page 17 of 74

GLN Study Name Test Substance7

Time Frame 

(Measured in 

months from 

DCI Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) Triggering Anticipated 

Data Requirement Appli

Special Study Leaching study, paint, stain and coatings; concrete TEP 24 Ecological Material Preservative (Paints, stains, and coatings; concrete and concrete additives; ceramic glazes) Leachin

service 

paints/s

concret

Special Study Leaching study, cotton textiles TEP 24 Ecological Material Preservative Textile 

Leachinto soil asurface textiles followewastewpotentiasurface 

850.1350 Aquatic invertebrate life cycle (saltwater) TGAI 24 Ecological 

All 

Transpoplant (Wrelease downstto surfasurface drain; dwater 

Non-guideline Whole sediment chronic toxicity10 TGAI 24 Ecological 850.1710 Oyster BCF TGAI 24 Ecological 850.1730 Fish BCF TGAI 24 Ecological 850.2100 Avian oral toxicity (passerine species) TGAI 24 Ecological Lawn, turf, surface soil, sidewalk, parking lot, patio, ant hill insecticide 

use 

Residensurface 850.2300 Avian reproduction11 TGAI 24 Ecological 

850.3020 Honey bee acute contact toxicity TGAI 12 Ecological Wood preservative; Lawn, turf, surface soil, sidewalk, parking lot, patio, ant hill insecticide use Treated 850.303012 Honey bee toxicity of residues on wood TGAI 12 Ecological Wood preservative Treated Special study Honey bee oral toxicity (adults)13 TGAI 12 Ecological Lawn, turf, surface soil, sidewalk, parking lot, patio, ant hill insecticide Residen

surface 

10 Results from studies conducted using Chironomus dilutus, Hyalella azteca, and Leptocheirus plumulosus are expected to be required to 

requirement 

11 Results from studies conducted using an upland game species and a waterfowl species are expected to be required to satisfy this anticip12 Protocol modifying study using wood should be submitted for review prior to conduct of the study. 
Page 18 of 74

GLN Study Name Test Substance7

Time Frame 

(Measured in 

months from 

DCI Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) Triggering Anticipated 

Data Requirement Appli

Special study Honey bee oral toxicity (larvae) 13 TGAI 12 Ecological use 850.4100 Seedling emergence (terrestrial plants)14 TGAI 12 Ecological Lawn, turf, surface soil, sidewalk, parking lot, patio, ant hill insecticide use; Exterior roof, siding, fence, and 

deck algaecide and antimicrobial treatment 

Residensurfacestructur

850.4150 Vegetative vigor (terrestrial plants) 14 TGAI 12 Ecological 850.6100 

Environmental Chemistry Methods and Associated Independent Laboratory Validation for water 

TGAI 12 Ecological 

Lawn, turf, surface soil, sidewalk, parking lot, patio, ant hill insecticide use 

Residensurfacestructur

875.1700 Product Use Information TGAI 12 Human Health All All 870.2300 Indoor Surface Residues TGAI 12 Human Health Residential and Public Access Sites Inciden

disinfec

870.3465 Inhalation Toxicity, 90 day TGAI 24 Human Health All All Non-Guideline Paint Chamber Emissions Study TGAI 12 Human Health Paints Inhalati

applica

Studies Expected to be Required through the Anticipated Post-RED DCI850.1075 Acute toxicity estuarine/marine fish TGAI 12 

Ecological All 

Industrand equpreservResidensurfacepaint/ststructurlawn an

850.1300 Aquatic invertebrate life cycle (freshwater)15 TGAI 12 850.1400 Fish early life stage16,17 TGAI 12 870.7800 Immunotoxicity TGAI 12 Human Health All All 13 Based on the “White Paper in Support of the Proposed Risk Assessment Process for Bees” as submitted to the FIFRA Scientific Advis

EPA-HQ-OPP-2012-0543-0004 at http://www.regulations.gov. 

14 Plant toxicity data with a monocot species, rice, have been submitted. Additional data are anticipated to be needed for six species of dic

families; one species must be soybean) and three species of monocots (from at least two families; one species must be corn). Of the specianticipated data need, at least one test species should be a root crop (either a monocot such as onion or a dicot such as carrot, table beet, o

15 Results from an acceptable Daphnia life cycle test may be used to calculate a chronic toxicity endpoint for estuarine/marine invertebra16 Results from studies conducted using a freshwater species and a saltwater species are expected to be required to satisfy this anticipated 17 Results from an acceptable freshwater fish early life stage test may be used to calculate a chronic toxicity endpoint for estuarine/marine 
Page 19 of 74

GLN Study Name Test Substance7

Time Frame 

(Measured in 

months from 

DCI Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) Triggering Anticipated 

Data Requirement Appli

875.1200 Indoor Dermal Exposure TGAI 24 Human Health

Material preservation, industrial process treatment, hard surface disinfection, preserved paints, sapstain 

treatment, carpets, air sanitizers, fingerpaints 

Occupa(1) Opepowderand ind

(2) Low handwasprayersurface fogging disinfec

spray foand sprResidenAerosoand wipcarpetssanitizespray foHand a

18 If labels are amended to require closed loading and delivery systems for liquid products and water soluble packaging for solid products 

preservation and industrial process treatment, the agency may consider waiving the need for the exposure study for open pouring of liqui

19 If labels are amended to require that fogging be done only by automatic equipment, the agency may consider waiving the need for the e

handheld fogging. 
Page 20 of 74

GLN Study Name Test Substance7

Time Frame 

(Measured in 

months from 

DCI Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) Triggering Anticipated 

Data Requirement Appli

875.1400 Indoor Inhalation Exposure TGAI 24 Human Health

Material preservation, industrial process treatment, hard surface disinfection, preserved paints, sapstain treatment, carpets, air sanitizers, fingerpaints 

Occupa(1) Opepowderand ind

(2) Low handwasprayersurface fogging disinfec

spray foand sprResidenAerosoand wipcarpetssanitizespray foHand a

875.2800 Descriptions of Human Activity TGAI 12 Human Health All All Special Study Migration Study for Plastics and Polymers TGAI 12 Human Health Material preservation of plastics and polymers 

IncidenHousehManufaPolyme

Studies no longer anticipated as needed 875.1600 Applicator Exposure Monitoring Data Reporting 
Page 21 of 74

3 Human Health Risk Assessment 

EPA anticipates the need to conduct a human health risk assessment for oPP and its salts. EPA 

expects to require additional data for use in conducting the registration review. 

3.1 Existing Toxicological Endpoints 

EPA anticipates the need to revise the existing toxicological endpoints as part of this registration 

review. The toxicological points of departure (PODs) for oPP are included in Table 9. These 

PODs were established in 2004 by the Antimicrobials Division’s Toxicology Endpoint Selection 

Committee (ADTC). These PODs have not been updated. All information, including existing 

toxicology studies, valid scientific literature and the studies that are expected to be required for 

registration review will be considered in the final risk assessment for oPP and its salts. 

Table 9 – Existing Toxicological Endpoints for oPP 

Exposure Scenario

Dose Used in 

Risk 

Assessment 

(mg/kg/day) 

Target Margin of Exposure 

(MOE), Uncertainty Factor 

(UF), FQPA Safety Factor 

(SF)

Study and Toxicological Effects 

Dietary Risk Assessments

Acute Dietary 

(general population 

and females 13- 49) 

No appropriate endpoints were identified that represent a single dose effect. Therefore, this risk 

assessment is not required. 

Chronic Dietary 

(all populations) 

NOAEL = 39 

mg/kg/day (43% 

dermal 

absorption) 

FQPA SF = 1 

UF = 100 (10x inter-species 

extrapolation, 10x intraspecies variation) 

Chronic RfD = 0.39 

mg/kg/day 

Chronic PAD = 0.39 

mg/kg/day 

Combined oral toxicity/carcinogenicity study in 

rats (MRID 43954301, 44852701, 44832201) 

LOAEL of 200 mg/kg/day based upon 

decreased body weight, body weight gain, food 

consumption and food efficiency, increased 

clinical and gross pathological signs of toxicity.

Non-Dietary Risk Assessments

Incidental Oral

Short-Term (1 - 30 

days) 

NOAEL 

(maternal) = 

100 mg/kg/day 

Target MOE = 100 

FQPA SF = 1 

UF = 100 (10x inter-species 

extrapolation, 10x intraspecies variation) 

Developmental (gavage) toxicity studies in rats 

(MRID 00067616, 92154037) and rabbits 

(MRID 41925003; co-critical developmental 

toxicity study) 

Maternal LOAEL of 300 mg/kg/day based upon 

clinical observations of toxicity, decreased 

weight gain, food consumption and food 

efficiency observed in the rat developmental 

toxicity study. 

Incidental Oral 

Intermediate-Term 

(1 - 6 months) 

NOAEL = 39 

mg/kg/day 

Target MOE = 100 

FQPA SF = 1 

UF = 100 (10x inter-species 

extrapolation, 10x intraspecies variation) 

Combined oral toxicity/carcinogenicity study in 

rats (MRID 43954301, 44852701, 44832201) 

LOAEL of 200 mg/kg/day based upon 

decreased body weight, body weight gain, food 

consumption and food efficiency, increased 

clinical and gross pathological signs of toxicity.

Dermal Short-Term 

(1 - 30 days) 

(residential and 

occupational) 

NOAEL 

(dermal) = 100 

mg/kg/day (200 

μg/cm2

)

 A 

Target MOE = 100 

FQPA SF = 1 

UF = 100 (10x inter-species 

extrapolation, 10x intraspecies variation) 

21-Day Dermal toxicity study in rats (MRID 

42881901) 

LOAEL (dermal) of 500 mg/kg/day based upon 

dermal irritation (erythema, scaling) at the site 

of test substance application. 

Dermal NOAEL = 39 Target MOE = 100 Combined oral toxicity/carcinogenicity study in 
Page 22 of 74

Exposure Scenario

Dose Used in 

Risk 

Assessment 

(mg/kg/day) 

Target Margin of Exposure 

(MOE), Uncertainty Factor 

(UF), FQPA Safety Factor 

(SF)

Study and Toxicological Effects 

Intermediate- and 

Long-Term (1 - 6 

months and >6 

months) 

(residential and 

occupational) 

mg/kg/day B FQPA SF = 1 

UF = 100 (10x inter-species 

extrapolation, 10x intraspecies variation) 

rats (MRID 43954301, 44852701, 44832201) 

LOAEL of 200 mg/kg/day based upon 

decreased body weight, body weight gain, food 

consumption and food efficiency (effects 

observed as early as 13 weeks in this study), 

increased clinical and gross pathological signs 

of toxicity. 

Inhalation ShortTerm (1 - 30 days) 

(residential and 

occupational) 

NOAEL 

(maternal) = 

100 mg/kg/day C

Target MOE = 100 

FQPA SF = 1 

UF = 100 (10x inter-species 

extrapolation, 10x intraspecies variation) 

Note: an additional 10x is 

necessary for route 

extrapolation. If results are 

below a MOE of 1,000, a 

confirmatory inhalation 

study may be required 

Developmental (gavage) toxicity studies in rats 

(MRID 00067616, 92154037) and rabbits 

(MRID 41925003; co-critical developmental 

toxicity study) 

Maternal LOAEL of 300 mg/kg/day based upon 

clinical observations of toxicity, decreased 

weight gain, food consumption and food 

efficiency observed in the rat developmental 

toxicity study. 

Inhalation 

Intermediate- and 

Long-Term (1 - 6 

months and >6 

months) 

(residential and 

occupational) 

NOAEL = 39 

mg/kg/day C

Target MOE = 100 

FQPA SF = 1 

UF = 100 (10x inter-species 

extrapolation, 10x intraspecies variation) 

Note: an additional 10x is 

necessary for route 

extrapolation. If results are 

below a MOE of 1,000, a 

confirmatory inhalation 

study may be required 

Combined oral toxicity/carcinogenicity study in 

rats (MRID 43954301, 44852701, 44832201) 

LOAEL of 200 mg/kg/day based upon 

decreased body weight, body weight gain, food 

consumption and food efficiency (effects 

observed as early as 13 weeks in this study), 

increased clinical and gross pathological signs 

of toxicity. 

Cancer (oral, 

dermal, inhalation) 

Classification: Ortho phenylphenol is classified as “Not likely to be carcinogenic below a 

specific dose range, without quantification of risk.” (OPP CARC) 

UF = uncertainty factor, DB UF = data base uncertainty factor, FQPA SF = special FQPA safety factor, NOAEL = 

no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a 

= acute, c = chronic), RfD = reference dose, MOE = margin of exposure 

A    2

2 200 μg cm 100 cm area of rat dosed

100 mg kg rat 0.200 kg rat 1000 μg mg   

B A dermal absorption factor of 43% was chosen based on the results of a submitted study (Timchalk et al., 1996) in 

humans. 

C The inhalation absorption factor of 100% (default value, assuming oral and inhalation absorption are equivalent) is 

used as an assumption since an oral endpoint was selected for the inhalation exposure scenarios. 

3.2 Dietary Exposure 

The Agency anticipates the need to revise the dietary (food) assessment conducted in support of 

the 2006 RED. Uses of oPP and its salts that may result in dietary exposures include sanitization 

use on counter tops, tables, refrigerators; on livestock premises; as a preservative in 

papermaking; as a preservative in adhesives; on mushroom premises; and as a postharvest fruit 

and vegetable coating to control storage pathogens. 
Page 23 of 74

Dietary risk is characterized in terms of the Population Adjusted Dose (PAD), which reflects the 

reference dose (RfD), either acute or chronic, that has been adjusted to account for the FQPA 

Safety Factor (SF). This calculation is performed for each population subgroup for which an 

endpoint exists. A risk estimate that is less than 100% of the acute or chronic PAD is not of 

concern. Acute dietary risk for oPP and salts will not be assessed because there are no adverse 

systemic effects attributable to a single dose. Chronic dietary risk for oPP and salts will be 

assessed by comparing dietary exposure estimates expressed in mg/kg/day to the chronic 

Population Adjusted Dose (cPAD). 

3.2.1 Tolerance Information 

EPA has established a tolerance exemption at 40 CFR 180.920 for use of Na-oPP as an 

intentionally-added inert ingredient (preservative) in pesticide formulations not to exceed 0.1% 

of the formulation to be applied to growing crops only. In addition, tolerances have been 

established (40 CFR 180.129) for the combined residues of oPP and Na-oPP from postharvest 

application on apple, cantaloupe, carrot, cherry, citrus fruit, cucumber, lemon, nectarine, orange, 

bell pepper, peach, pear, pineapple, plum, sweet potato, and tomato. 

The Food & Drug Administration (FDA) has established a number of food additive regulations 

for oPP and Na-oPP. For oPP, regulations have been established as a (an): 

 Fungicide at ≤0.01% by weight of the base polymer poly(phenyleneterephthalamide) 

used as a coating to finish fibers and yarn for single and repeat-use food contact (21 CFR 

177.1632); 

 Miscellaneous material to formulate defoaming agents used in paper and paperboard 

production (21 CFR 176.210); 

 Antioxidant/antioxonant to manufacture rubber articles for repeat-use food contact (21 

CFR 177.2600); 

 Preservative in the manufacture of food-contact adhesives (21 CFR 175.105); and 

 Food contact sanitizer at ≤400 ppm mixed with two other phenols [21 CFR 

178.1010(b)(20). 

For Na-oPP, regulations have been established as a: 

 Preservative of coatings only as a component of paper and paperboard in contact with 

aqueous and fatty foods (21 CFR 176.170); 

 Miscellaneous compound in defoaming agents used in the manufacture of paper and 

paperboard (21 CFR 176.210); 

 Preservative in animal glue in articles for food contact (21 CFR 178.3120); and 

 Component of closures at ≤0.05 % by weight used with sealing gaskets for food 

containers (21 CFR 177.1210). 

3.2.2 Food 

EPA anticipates the need to revise the chronic dietary risk assessment conducted in support of 

the 2006 RED; as there are no adverse systemic effects due to a single dose, an acute dietary risk 

assessment was not conducted in the 2006 RED and is not expected to be needed for this 

registration review. In support of the 2006 RED, exposures to residues expected to transfer to 
Page 24 of 74

food from various hard nonporous surfaces such as countertops, sinks and stoves were 

considered. The 2006 RED concluded that there were no risks of concern for chronic dietary 

exposures to oPP and its salts. For all supported uses, chronic dietary exposure estimates 

presented in the 2006 RED were below the Agency’s level of concern (<100% of the cPAD). 

3.2.3 Drinking Water 

Although dietary exposure to oPP via drinking water is expected to be minimal due to oPP’s 

degradation in soil and via photolysis and its immobility in soil (see Appendix B ), the agency 

will determine whether there is the potential for oPP and salts to contaminate drinking water 

upon evaluation of the anticipated environmental fate studies during the risk assessment stage of 

this registration review. 

3.3 Occupational and Residential Exposures 

The Agency anticipates the need to revise the occupational and residential assessments 

conducted in support of the 2006 RED based on an updated exposure database. Uses of oPP and 

its salts that may result in occupational and residential exposures are included in Table 10, Table 

11, and Table 12. 

3.3.1 Occupational Handler Exposure 

Occupational handler dermal and inhalation exposures to oPP were assessed in the 2006 RED for 

open pouring for material preservation, low and high pressure handwand application, aerosol can 

and trigger spray application and mopping and wiping. As there were no chemical-specific 

exposure data available, exposures were assessed using unit exposure data from the Pesticide 

Handlers Exposure Database (PHED) and the Chemical Manufacturer’s Association (CMA) 

study, as well as, product label maximum application rates, and related use information. In most 

scenarios assessed, the respective dermal and inhalation MOEs were not of concern as they were 

above the target MOE of 100. Some scenarios resulted in MOEs below 100, specifically: 

 Agricultural premises, fogging: intermediate-term PPE Total MOE = 98 

 Commercial/Institutional premises, wiping: short-term baseline dermal MOE= 74, 

intermediate-term baseline dermal MOE = 68, and intermediate-term baseline Total MOE 

= 64. 

 Medical premises, mopping: short-term baseline dermal MOE= 93, intermediate-term 

baseline dermal MOE = 84, and intermediate-term baseline Total MOE = 78. 

 Materials Preservatives, liquid pour preservation of textiles: short-term PPE dermal 

MOE= 92, intermediate-term PPE dermal MOE = 83, and intermediate-term Total MOE 

= 78. 

 Materials Preservatives, painter (applying paint post-preservation), airless sprayer: 

baseline dermal short-term MOE = 66. 

It is important to note that the open pouring of solids for materials preservation was not assessed 

in the RED, and this scenario could be of concern depending upon the dustiness of the 

formulation. It is also likely that handheld fogging would result in excessive exposure; however, 

this scenario was not assessed for the 2006 RED because exposure data were not available. 

With respect to agricultural applications, all occupational inhalation MOEs were above the target 

MOE of 1000, with the exception of fogger application, where the MOE was 880. For dermal 
Page 25 of 74

exposures involving agricultural applications, with the use of chemical-resistant gloves, shortterm dermal risks were not of concern for handlers. Short-term inhalation risks were not of 

concern without respiratory protection. Intermediate-/long-term dermal risks were not of concern 

when chemical-resistant gloves are used and intermediate-/long-term inhalation risks were not of 

concern. 

EPA anticipates the need to revise the occupational handler assessment conducted in support of 

the 2006 RED. All of the handler scenarios that were assessed in the 2006 RED will need to be 

revised during 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 2006 RED. In 

addition, it will be necessary to assess handler exposures for open pouring of soluble powder 

formulation for material preservation and handler exposures for hand held fogging applications. 

The occupational handler scenarios to be assessed are listed in Table 10. 

Table 10 – Occupational Handler Exposure Scenarios for oPP 

Scenario Exposure 

Route(s) Duration 

Open pour liquids and soluble powders for material preservation and 

industrial process treatments 

Dermal 

Inhalation 

Short, Intermediate, and 

Long Term 

Low pressure handwand, high pressure handwand, aerosol can, trigger 

sprayer, mop and wipe application for hard surface disinfection 

Dermal 

Inhalation 

Short, Intermediate, and 

Long Term 

Handheld fogger application for hard surface disinfection Dermal 

Inhalation 

Short and Intermediate 

Term 

Brush, roller and spray application of preserved paints Dermal 

Inhalation 

Short and Intermediate 

Term 

Dip and Spray application for sapstain treatment Dermal 

Inhalation 

Short, Intermediate and 

Long Term 

3.3.2 Residential Handler Exposures 

EPA anticipates the need to revise the residential handler assessment conducted in support of the 

2006 RED. Residential handler dermal and inhalation exposures to oPP were assessed in the 

2006 RED for spraying, mopping and wiping surfaces and for aerosol spray can application for 

“air sanitization.” In all cases, the respective dermal and inhalation MOEs were not of concern. 

Residential exposure may occur during application of oPP products used as a hard surface 

disinfectant (e.g., walls, floors, tables, fixtures), to textiles (e.g., clothing, diapers, mattresses, 

bedding) and to carpets. In addition oPP is used as a preservative in finger paints. As such, the 

Agency has selected representative scenarios for each use site that are believed to be 

representative of the oPP uses, based on end-use product application methods and use amounts. 

The residential handler exposure scenarios that will be assessed during registration review are 

listed in Table 11. 

Table 11 – Residential Handler Exposure Scenarios for oPP 

Scenario Exposure Route(s) Duration 

Aerosol can, trigger sprayer, mop and wipe application to hard 

surfaces and carpets. 

Dermal 

Inhalation 

Short and Intermediate 

Term 

Aerosol can application for air sanitization Inhalation Short and Intermediate 

Term 

Brush and roller application of paints treated with oPP Dermal 

Inhalation Short Term 
Page 26 of 74

Scenario Exposure Route(s) Duration 

Hand application of fingerpaints treated with oPP 

Dermal 

Incidental Oral 

Inhalation 

Short and Intermediate 

Term 

3.3.3 Residential Post-Application Exposures 

EPA anticipates the need to revise the residential post-application assessment conducted in 

support of the 2006 RED. Residential post-application exposures to residues arising from the 

hard surface disinfection of floors, treated diapers, treated clothing, treated plastic toys and 

household items, and sanitized air were assessed. The MOEs were not of concern for hard 

surface disinfection of floors but they were calculated using an assumption of cleaning solution 

coverage (1000 square feet per gallon) that possibly underestimates exposure and will have to be 

reassessed using updated values from the AEJV use surveys and/or the AEATF exposure studies. 

The MOEs were of concern for the clothing and diaper use. The dermal MOEs for the treated 

clothing ranged from <1 when 100 percent residue transfer was assumed to 17 when 5 percent 

transfer was assumed. Based on these concerns, the 2006 RED specified that the diaper use was 

ineligible for reregistration and that label statements be added requiring other treated textile 

articles be washed after treatment. The MOEs were not of concern for treated toys or household 

items. The inhalation MOEs for exposure to treated paint and air sanitization were above 100 

which means that they were not of concern; however, they were below 1000, which means that 

the requirement for an inhalation toxicity study was triggered. The residential post application 

exposure scenarios that will be assessed during registration review are listed in Table 12.

Table 12 – Residential Post-Application Exposure Scenarios for oPP 

Source of Exposure Exposure Route(s) Duration 

Floors disinfected with oPP Dermal 

Incidental Oral Short and Intermediate Term 

Areas painted with paints containing oPP Inhalation (Vapor) Short and Intermediate Term 

Mouthing Toys or Household Items Manufactured from 

Plastic or Polymers Preserved with oPP. Incidental Oral Short and Intermediate Term 

Air sanitized with oPP Inhalation Short and Intermediate Term 

3.4 Aggregate and Cumulative Exposure 

3.4.1 Aggregate Exposures 

The Agency anticipates the need to revise the chronic dietary aggregate risk that was conducted 

in support of the 2006 RED. The calculated total dietary exposure in the 2006 RED showed that 

there was no risk of concern from dietary sources of exposure. In addition, many of the 

tolerances and uses listed in the 2006 RED for direct food use of oPP have been revoked, which 

will result in a decrease in total dietary exposures. There is also no significant contribution to 

dietary risk from drinking water exposure, as was noted in the 2006 RED. 

The Agency anticipates the need to revise the short- and intermediate-term aggregate risk 

assessments for oPP. Dermal post-application risks to adults and children showed risks of 

concern in the 2006 RED and were not included in the dermal aggregate risk calculation. The 
Page 27 of 74

mitigation measures discussed in the 2006 RED to reduce dermal risk will need to be evaluated 

in the registration review risk assessment to determine if dermal post-application risks are 

mitigated. 

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 oPP and any other substances, and oPP does not 

appear to produce a toxic metabolite common to other substances. For the purposes of this 

registration review, therefore, EPA has not assumed that oPP has a common mechanism of 

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

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

chemicals, see the policy statements released by EPA’s Office of Pesticide Programs at 

http://www.epa.gov/pesticides/cumulative/. 

4 Environmental Risk Assessment 

4.1 Environmental Fate 

Ortho-phenyl phenol is a weak acid with a pKa of about 9.5 (MRID 42500204), indicating that 

oPP will primarily exist as the protonated acid in aqueous solution at environmental pH values (5 

- 9). The sodium (Na) and potassium (K) salts of oPP rapidly dissociate in water releasing 

sodium and potassium cations (Na+ and K+, respectively) and the ortho-phenyl phenate anion 

(oPP-). The oPP- anion will readily become protonated forming the neutral or unionized oPP. The 

equilibrium in solution between oPP- and protonated or unionized oPP depends on the pH of the 

solution. In aqueous medium the following equilibria is expected: at acidic pHs 4 - 6, the parent 

will essentially be in the protonated or undissociated oPP state; at pHs 7 - 9.5, the equilibria will 

have undissociated oPP and some dissociated oPP, with increasingly more dissociated oPP as pH 

becomes more alkaline; at pH 9.5, approximately 50% of the oPP will be dissociated and 50% 

undissociated; and at pH >9.5, the tendency is to be in the fully ionized state. Therefore, the fate 

and transport data supporting oPP can be used to support the salts, and similarly the fate and 

transport data supporting its Na and K salts may be used to support oPP. A summary of the fate, 

transport and degradation of oPP and its salts is provided here but details of the studies and 

information are provided in Appendix B. 

4.1.1 oPP and its Salts 

Ortho-phenyl phenol is hydrolytically stable under abiotic aqueous conditions (MRID 

43994201). It does photodegrade in abiotic aqueous medium forming three degradates; the two 

major degradates, phenylhydroquinone (PHQ) and phenylbenzquinone (PBQ), and hydroxyfuran 

as a minor degradate were identified (Tajeddine et al. 2010). The vapor pressure of oPP is 2.00 x

10-3 mm Hg at 25 °C (MRID 41609505 for Na-oPP and MRID 41642402 for oPP) indicating the 

potential for volatilization, but the half life of oPP in air is estimated to be 0.03 hours using 

EPISuite version 4.10. The salts are not expected to volatilize based on estimated vapor pressures 

on the order of 10-11 mm Hg (EPISuite version 4.10). oPP is immobile on soil surfaces and will 

not likely contaminate the ground water. Temperature appears to be an important factor in its 

biodegradation with half-lives ranging from 16 hours to 7 days during the summer season and a 

little to no biodegradation observed under cooler fall and winter conditions. While there is 
Page 28 of 74

information from a specific location indicating potential for aqueous aerobic biodegradation, the 

information needed to conduct a risk assessment is incomplete since the major biodegradates are 

not identified. There are no aqueous anaerobic sediment data. These data for oPP are anticipated 

as being required to conduct the risk assessment of oPP and its salts. Additionally, to model 

removal during wastewater treatment, data on the percent removal during wastewater treatment 

due to sorption and biodegradation (i.e., OCSPP 835.1110, 835.3110, 835.3220, 835.3240, 

835.3280) are anticipated to be required. 

oPP has a log Kow of 3.3, indicating it is potentially bioaccumulative; however, there are no data 

on bioaccumulation or bioconcentration in aquatic organisms. A bioconcentration study using 

oPP with fish, tracking the major degradates, is anticipated as being required to conduct the risk 

assessment of oPP and its salts. 

Na-oPP is applied to and leaches easily from sapstain treatment on wood surfaces, and almost 

75% is eliminated from wood surfaces within 14 days. The leach rate for 1% treated wood was 

71 μg of Na-oPP/cm2

 /day, and for 4% treated wood, the leach rate was 192 μg of Na-oPP /cm2

/day; after day 14, the leach rate was 0.5 to 0.2 μg /cm2

/day for both treated woods. A steady 

state is achieved after 14 days. Since Na-oPP ionizes in moist soils, it is more likely to be mobile 

from such soil surfaces. 

Based on the available fate, transformation, and transport data and registered use patterns, 

aquatic organisms are expected to be exposed to oPP and/or its major degradates both in the 

water column and sediment. There is potential for birds and mammals that eat fish and 

invertebrates to be exposed via the aquatic food web to oPP and its major toxic degradates. 

Additionally, there are registered uses that will result in exposure of terrestrial wildlife and plants 

to residues of oPP and its salts and major toxic degradates on dietary items through direct 

application, spray drift, and run-off. 

4.1.2 Photodegradates of oPP 

The Agency has used EPI Suite, version 4.1 to estimate physical/chemical as well as some 

environmental fate characteristics for the major photodegradates PHQ and PBQ. 

4.1.2.1 Phenylhydroxybenzquione (PHQ) 

The estimated physical/chemical property and environmental fate data on this compound from 

EPI Suite, version 4.1 (See Appendix B ) indicates that PHQ is highly water soluble, and its 

vapor pressure is not of concern for the exposure assessment. Its estimated half life is 15 days in 

water bodies, and about thirty days in soils, making it not that persistent in these environmental 

media. It could be stable and persistent in sediments with an estimated half life of 135 days. It is 

not stable in air, and the estimated half life is less than six hours in air. It is not likely to be 

bioaccumulative as its log Kow is less than 3. It appears to not readily biodegrade and may not be 

removed from wastewater treatment. It has a high Koc value making it immobile in soils; thus the 

probability of this chemical migrating to ground water is low, and so ground water 

contamination is not likely to happen. However, aquatic benthic organisms may be exposed. 

4.1.2.2 Phenylbenzquinone (PBQ) 

The estimated data on PBQ (EPI Suite, version 4.1) indicate that this substance is highly water 

soluble, and its vapor pressure is not of concern for the exposure assessment. Its estimated half 

life is 15 days in water bodies and about thirty days in soils, making it not that persistent in these 
Page 29 of 74

environmental media. It could be stable and persistent in sediments with an estimated half life of 

135 days. It is not stable in air, and the estimated half life is less than eight hours in air. It is not 

likely to be bioaccumulative as its log Kow is less than 2. It appears to be not readily 

biodegradable and may not be removed from the wastewater treatment plants. It has a high Koc

value making it immobile in soils; thus the probability of this chemical migrating to ground 

water is low, and so ground water contamination is not likely to happen. 

At this time the Agency cannot determine environmental risk concerns for these 

photodegradates, and no fate assessment was conducted. The Agency anticipates using a total 

toxic residue approach. If any fate data on these degradates becomes available which indicate 

environmental risk concerns, the Agency anticipates requiring additional fate data. 

4.1.3 Water Quality 

Ortho-phenyl phenol and its salts, Na-oPP and K-oPP, are not identified as a cause of 

impairment for any water bodies listed as impaired under section 303(d) of the Clean Water 

Act20. In addition, no Total Maximum Daily Loads (TMDL) have been developed for oPP, NaoPP, and K-oPP 21. More information on impaired water bodies and TMDLs can be found at 

EPA’s website22. 

4.2 Conceptual Models for Environmental Exposure Pathways 

4.2.1 Residential Insecticidal Use Patterns 

The environmental fate properties and use patterns of oPP and its salts indicate that direct spray, 

spray drift, atmospheric deposition, and run-off represent potential transport mechanisms of oPP 

and its salts to aquatic and terrestrial organisms. 

For terrestrial vertebrates, the major route of exposure to oPP and its salts is considered to be via 

dietary ingestion of food items such as seeds, plants, and/or animals that have oPP (and its salts) 

residues as a result of direct application, spray drift, and run-off. Exposure of birds and mammals 

to oPP and its salts through the consumption of drinking water alone is also considered to be an 

exposure pathway of concern based on the results of EFED’s Screening Imbibition Program (SIP 

v. 1.0). There is uncertainty regarding whether exposure to terrestrial vertebrates via inhalation is 

an exposure pathway of concern given the lack of acute inhalation toxicity data needed for 

analysis using EFED’s Screening Tool for Inhalation Risk (STIR v. 1.0). SIP and STIR are 

described in detail at: http://www.epa.gov/oppefed1/models/terrestrial/index.htm. 

For terrestrial invertebrates, the major routes of exposure to oPP and its salts are considered to be 

direct contact as a result of direct application and spray drift and dietary ingestion of plants, 

animals, and/or soil that have oPP (and its salts) residues as a result of direct application, spray 

drift, and run-off. 

For aquatic animal species, the major route of exposure to oPP and its salts is considered to be 

uptake via the respiratory surface (gills) or the integument from surface water/sediment that has 

oPP (and its salts) residues as a result of spray drift and run-off. 

 

20 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885 21http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant

_group_name=PESTICIDES

22 http://www.epa.gov/owow/tmdl/
Page 30 of 74

For terrestrial (upland and semi-aquatic) non-target plants, the major routes of exposure to oPP 

and its salts are considered to be direct contact as a result of direct application and spray drift and 

root uptake via soil contaminated via spray drift and run-off. 

For aquatic plants, the major route of exposure to oPP and its salts is considered to be uptake 

from surface water/sediment containing oPP (and its salts) residues as a result of spray drift and 

run-off. 

4.2.2 Antimicrobial Use Patterns 

Based on the summary of registered uses of oPP and salts presented in Table 8 and 

physical/chemical property and environmental fate data presented in Appendix B, the Agency 

has developed conceptual model diagrams for exposure of ecological organisms to oPP. These 

conceptual model diagrams for oPP specify the potential routes of exposure, possible ecological 

receptors, and attribute changes that might occur. 

There is some evidence that oPP is susceptible to biodegradation during wastewater treatment 

and in the aquatic environment. Based on studies using activated sludge, oPP was determined to 

be reduced by 50% in acclimated sludge within 3 hours and in unacclimated sludge within 24 

hours (MRID 439942-01). In addition, there are studies measuring evolved CO2 that demonstrate 

a 50% reduction of oPP in river water within a week (MRID 439942-01; Gonsior,1984). This 

paper did not identify and biodegradates. Based on its log Kow of 3.3, oPP may have potential to 

bioconcentrate in aquatic organisms. One study has indicated that oPP can photodegrade to form 

PBQ and PHQ (MRID 439942-01). 

The Agency has previously determined that the use of oPP and salts for sapstain treatment of 

freshly cut lumber has a potential to expose and cause detrimental acute impacts to aquatic 

organisms, including listed species. Measures to reduce leaching from freshly cut wood and 

reduce run-off from treatment sites have not yet been sufficiently implemented to reduce the 

exposure pathways and minimize exposure to aquatic organisms. Impacts from in-service use of 

treated wood also need to be considered. Chronic exposure of aquatic organisms also is possible 

and will be assessed when the required data are available. As a wood preservative for treatment 

to freshly cut lumber, oPP also has a potential to adversely affect honey bees that contact the 

treated wood, but toxicity data are not currently available to assess that potential hazard. Based 

on its log Kow (3.3), oPP has a potential to bioconcentrate in aquatic organisms. oPP entering 

the aquatic environment is expected to adsorb to sediment and may pose a potential risk to 

benthic organisms. 

oPP and salts have numerous registered uses. Use sites and corresponding figures of conceptual 

model diagrams are presented as follows: 

- Sanitizer/Disinfectant and Material Preservatives in Cleaning Solutions (Figure 1); 

- Antimicrobial Fruit and Vegetable Washes and Food Contact Sanitizer (Figure 2); 

- Wood Preservative for Sapstain Control (Figure 3); 

- Materials Preservatives in Metal Working Fluids (Figure 4); 

- Swimming Pools, Spas, Ornamental Ponds, Aquaria, Waterbed Water (Figures 5a/b); 

- Lakes, Ponds, and Reservoirs (Figure 6); and 

- Commercial/Industrial Water Cooling Systems; Evaporative Condenser Water 

Systems; Heat Exchanger Water Systems; Sewage Systems; Industrial Scrubbing 

Systems; Paper Mill Water Systems; and Air Washer Water Systems (Figure 7); 
Page 31 of 74

- Biocides in Oil Drilling Muds and Secondary Recovery Water (Figures 8a/b); and 

- Materials Preservatives Other than Those Used in Metal Working Fluids and 

Cleaning Solutions (Figure 9) 

Figure 1 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic and Terrestrial 

Organisms from Sanitizer/Disinfectant and Material Preservative Cleaning Solution Uses 

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption by

cells, roots, leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals(terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians, mollusks, crustaceans, etc.)

Ingestion

Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

Waste Water Disposal Down‐the‐Drain

Surface Water

Sediment

Sanitizer/Disinfectant and Materials Preservative Cleaning Solutiion

Uses
Page 32 of 74

Figure 2 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic and Terrestrial 

Organisms from Antimicrobial Fruit and Vegetable Washes 

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption by

cells, roots, leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals(terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians, mollusks, crustaceans, etc.)

Ingestion

Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Antimicrobial Fruit and Vegetable Washes and Food Contact Sanitizer

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

Down‐the‐drain disposal

Surface Water

Sediment
Page 33 of 74

Figure 3 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic and Terrestrial 

Organisms from Wood Preservatives for Sapstain Control 

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Surface Water/Sediment

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption/cell, roots,

leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals(terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians, mollusks, crustaceans, etc.)

**Noise barrier scenario may have releasesto WWTP

Ingestion

Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

Dip or Spray Treated

Wood

Facility Drain

Post‐Treated Wood

Product Storage

Leaching and Run‐off

In‐Use Service of Wood

Treated Wood Products

Leaching and Run‐off**
Page 34 of 74

Figure 4 -- Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic and 

Terrestrial Organisms from Materials Preservatives in Metal Working Fluids 

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption/cell, roots,

leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals(terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians, mollusks, crustaceans, etc.)

Ingestion

On‐Site/Off‐Site Waste Water Treatment Plant

(WWTP)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Use of Metal Working Fluids with Antimicrobials as a Materials Preservative

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

Wastewater disposal from container residues, dragout losses, filter

media and other recycling wastes, and spent metalworking fluid

Recovery of oil,

recycle, reuse

Surface Water

Sediment
Page 35 of 74

Figure 5 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic and Terrestrial 

Organisms from Swimming Pools, Spas, Ornamental Ponds, Aquaria, and Waterbed Water Uses 

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption/cell,

roots, leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals(terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians, mollusks, crustaceans, etc.)

Ingestion

Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Swimming Pools, Spas, Ornamental Ponds, Aquaria, Waterbed Uses

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

Disposal of Water to

sanitary drain system

Disposal of water to

stormwater drain

(A)

Surface Water

Sediment

Soil

See Figure (B)

Disposal of water to

ground surface

Stressor

Source/

Exposure

Media

Receptors

and Exposure

Routes

Attribute

Change(s)

Terrestrial insects

Individual organisms

Reduced survival

(emergence*)

Reduced growth

Reduced reproduction**

Food chain

Reduction in plant biomass

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary

productivity

Reduced cover

Community change

Modification of PCEs

related to habitat

Terrestrial plants

Grasses/forbs, fruit,

seeds, trees, shrubs

Terrestrial Animals

Birds (Reptiles, Amphibians)

Mammals

Soil

Ingestion Ingestion

Dermal uptake/

Ingestion Root uptake

Beneficial

Insects

Reduced

survival

*Refers to seedling emergence

**Vegetative vigor and seedling emergence endpoints are assumed to be as sensitive or more sensitive than reproduction

endpoint and  plant reproduction s not explicitly evaluated.

(B)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Swimming Pools, Spas, Ornamental Ponds, Aquaria, and Waterbed Water Uses

Disposal of water to

ground surface
Page 36 of 74

Figure 6 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic and Terrestrial 

Organisms from Lakes, Ponds, and Reservoirs 

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Lakes, Ponds, and Reservoirs

Leaching

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs

related to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake across gills or

integument and/or sediment

ingestion

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption by cell,

roots, or leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refersto animals(terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians,mollusks, crustaceans, etc.)

Ingestion

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Surface Water

Sediment
Page 37 of 74

Figure 7 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic and Terrestrial 

Organisms from Cooling, Evaporative Condenser, Heat Exchanger, Industrial Scrubbing, and Paper Mill 

Water Systems 

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Surface Water/Sediment

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption/cell, roots,

leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals(terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians, mollusks, crustaceans, etc.)

Ingestion

Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Industrial/Commercial Cooling Water Systems , Evaporative

Condenser Water Systems, Heat Exchanger Water Systems, Sewage

Systems, Industrial Scrubbing Systems, Paper Mill Water Systems,

and Air Washer Water Systems

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

Direct Discharge
Page 38 of 74

Figure 8 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic and Terrestrial 

Organisms from Biocides in Oil Drilling Muds/Fluids and Secondary Recovery Water 

 

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption/cell, roots,

leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals(terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians, mollusks, crustaceans, etc.)

Ingestion

Deep Well

Injection

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Biocides in Oil Drilling Muds/Fluids and Secondary Recovery Water

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

Recovered Water/Fluids (Flowback

and Produced), Muds Disposal

Migration into

Groundwater

(A)

Waste Water Treatment Plant (WWTP)

Migration into

Groundwater

Exposed Groundwater from

Soil Applications see Figure (B)

Surface Water

Sediment

Stressor

Source/

Exposure

Media

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

(emergence*)

Reduced growth

Reduced reproduction**

Food chain

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary

productivity

Reduced cover

Community change

Modification of PCEs

related to habitat

Terrestrial Animals

Birds (Reptiles, Amphibians)

Mammals

Ingestion

(B)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Recovered Water (Flowback and

Produced) Open Pit Storage or

Evaporation Pond

Irrigation Water

Recovered Water (Flowback and

Produced) Disposal

Terrestrial plants

Grasses/forbs, fruit,

seeds, trees, shrubs

Contact/Uptake

leaves, stems

Ingestion

*Refers to seedling emergence

**Vegetative vigor and seedling emergence endpoints are assumed to be as sensitive or more sensitive than reproduction

endpoint and  plant reproduction s not explicitly evaluated.

Soil

Root uptake

Soil Leaching

Groundwater

See Figure (A) for

aquatic exposure

pathways

Biocides in Oil Drilling Muds/Fluids and Secondary Water
Page 39 of 74

Figure 9 - Conceptual Model for Ecological Exposure and Effects of oPP and Salts to Aquatic and Terrestrial 

Organisms from Material Preservative Uses Other Than Metal Working Fluids and Cleaning Solutions

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEsrelated

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEsrelated to

habitat

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills or integument

Aquatic Plants

Non‐vascular

Vascular

Uptakeor sorption/cell, roots, leaves

Piscivorous**

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here thistermrefersto animals (terrestrialor aquatic)that eat notjustfish but any aquatic animal (e.g., amphibians,mollusks, crustaceans, etc.).

**Textiles, leather, plastic, and rubbermaterialpreservative uses are expected to resultin discharges down facility drains at manufacturinguse sites.

Ingestion

Waste Water Treatment Plant

Key

Mostlikely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Material PreservativeUses Other than Metal Working Fluids and Cleaning Solutions

WWTP

microorganisms

Uptakeor

sorption

Population

Respiration

inhibition

Outdoor Air SurfaceWater

Sediment

Volatilization Facility Drain Waste Disposal* Washing/Leaching

Material PreservativeApplication Site In‐ServiceUse of Preserved Materials

(A)

Stressor

Source/

Exposure

Media

Receptors

and Exposure

Routes

Attribute

Change(s)

Overspray*

Terrestrial insects

Individual organisms

Reduced survival

(emergence**)

Reduced growth

Reduced reproduction***

Food chain

Reduction in plant biomass

Reduction in prey

Modification of PCEsrelated

to prey availability

Habitat integrity

Reduction in primary

productivity

Reduced cover

Community change

Modification of PCEs

related to habitat

Terrestrial plants

Grasses/forbs, fruit,

seeds, trees, shrubs

Terrestrial Animals

Birds(Reptiles, Amphibians)

Mammals

Soil

Ingestion Ingestion

Dermal uptake/

Ingestion

Root uptake

Dermal contact

Contact/Uptake

leaves,stems

Beneficial

Insects

Reduced

survival

* Applicable to in‐service use of paints,stains and coatings.

**Refersto seedling emergence.

***Vegetative vigor and seedling emergence endpoints are assumedto be assensitive or more sensitive than reproduction

endpoint and  plant reproduction s not explicitly evaluated.

(B)

Key

Mostlikely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Exterior In‐ServiceUse of: Preserved Paints, Stains and Coatings; Preserved Concrete and

ConcreteAdditives

Leaching/Runoff
Page 40 of 74

4.3 Ecological Effects Assessment 

In the 2006 RED issued in August of 2006, the Agency conducted an aquatic ecological risk 

assessment for the antisapstain treatment of Na-oPP to freshly cut wood. Based on the toxicity 

data available at that time, the assessment was limited to acute risks to freshwater organisms, 

including fish, invertebrates, and algae. Exposure estimates were based on the Agency’s use of a 

sapstain model, which predicts post-treatment pesticide-leachate concentrations in diluted stormwater run-off that may enter the aquatic environment. The LOC for acute risk was exceeded for 

freshwater fish, freshwater invertebrates, and aquatic plants. Acute risk to estuarine/marine 

organisms and chronic risks to all aquatic organisms was not assessed due to lack of toxicity 

data. Possible acute and chronic risks from the in-service use of treated wood were not assessed. 

No other uses have been assessed. 

To mitigate the risks identified in the RED, the Agency specified that product labels with an 

antisapstain use bear the following label statement: “Treated lumber must be stored under cover, 

indoors, or at least 100 feet from any pond, lake, stream, wetland, or river to prevent possible 

run-off of the product into the waterway. Treated lumber stored within 100 feet of a pond, lake, 

steam, or river must be either covered with plastic or surrounded by a berm to prevent surface 

water run-off into the nearby waterway. If a berm or curb is used around the site, it should 

consist of impermeable material (clay, asphalt, concrete) and be of sufficient height to prevent 

run-off during heavy rainfall events.” 

The Agency has not conducted a risk assessment that supports a complete endangered species 

determination for oPP and salts. The ecological risk assessment planned during registration 

review will allow the Agency to refine its risk assessment to determine whether uses of oPP and 

salts have ‘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. 

4.3.1 Mechanism of Action 

The Agency found no information on the mechanisms of action of oPP in terrestrial and aquatic 

plants and animals. 

4.3.2 Measures of Effect (Ecotoxicology Endpoints)

Ecological effects data are used as measures of direct and indirect effects to aquatic and 

terrestrial organisms. Acute and chronic toxicity data will be used to evaluate the potential direct 

and indirect effects of oPP and salts to plants and animals. Relevant data from the open literature 

available in ECOTOX also may be used to evaluate potential direct and indirect effects. 

All data requirements and available ecotoxicity endpoints from studies submitted by registrants 

are tabulated in Appendix C. The Agency uses the most sensitive of these endpoints for assessing 

risk to each terrestrial and aquatic receptor group. The endpoints selected for the risk assessment 

for oPP and salts are provided in Table 13. Data gaps also are indicated. 

Table 13 – Selected Ecological Effects Endpoints for the Ecological Risk Assessment 

Receptor 

Group 

Surrogate 

Species 

Risk 

Scenario Toxicity Endpoint MRID Reference 
Page 41 of 74

Receptor 

Group 

Surrogate 

Species 

Risk 

Scenario Toxicity Endpoint MRID Reference 

Freshwater fish Bluegill Acute 96-h LC50 = 2.74 mg aeL 110232 

Chronic Data gap -- 

Freshwater invertebrates Waterflea Acute 48-h EC50 = 2.4 mg ae/L 110222 

Chronic Data gap -- 

Estuarine/marine fish -- Acute Data gap -- 

Chronic -- 

Estuarine/marine 

invertebrates 

Mysid shrimp Acute 96-h LC50 = 0.28 mg ae/L 467512-03 

Chronic Data gap -- 

Mollusk Acute 48-h IC50 = 0.66 mg ae/L 25816 

Sediment-dwelling 

invertebrates Freshwater Chronic Data gap -- 

Aquatic macrophytes/ 

Aquatic non-vascular 

plants 

Green algae Non-listed EC50 = 1.39 mg ae/L 

456882-01 

Blue-green algae Listed NOAEC = 0.03 mg ae/L 

Non-emergent aquatic 

macrophytes/Aquatic 

vascular plants 

Lemna Non-listed 7-day IC50 = 5.5 ppm ae/L 467512-09 

Listed 7-day IC05 = 0.73 ppm ae/L 

Emergent rooted aquatic 

macrophytes-Seedling 

emergence 

Rice 

Non-listed EC25 > 886 ppm ae 

467512-07 

Listed NOAEC = 886 ppm ae 

(7% emergence inhibition) 

Emergent rooted aquatic 

macrophytes-Vegetative 

vigor 

Rice 

Non-listed EC25 > 886 ppm ae 

467512-07 Listed NOAEC = 886 ppm ae 

(2% dry wt) 

Terrestrial plantsSeedling emergence -- Non-listed Data gap -- 

Listed Data gap -- 

Terrestrial plantsVegetative vigor -- Non-listed Data gap -- Listed Data gap 

Birds Northern 

Bobwhite 

Acute LD50 = 885 mg ae/kg-bwA 425002-04 

Chronic Data gap -- 

Mammals Rat Acute LD50 = 591 mg/kg-bw 433342-04 

Chronic NOAEL >500 mg/kg/day 439288-01 

Nontarget insects Honeybee 

Acute dermal 

(contact) Data gap -- 

Acute oral Data gap -- 

RT25-wood 

preservative Data gap -- 

A Value shown is based on available data but there is a passerine species data gap. 

4.4 Exposure Analysis Plan 

The Agency lacks information on the fate profile for oPP with regard to the potential for biotic 

degradates/transformation products to be formed. Consequently, in the absence of information, 

the Agency will use a total toxic residue approach to determine potential toxicity to ecological 

organisms. This approach assumes any major degradates formed would be as toxic as the parent. 

The Agency will consider conducting a more refined risk assessment if information on the 

toxicity of any major degradates identified is provided. 
Page 42 of 74

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates 

4.4.1.1 Antimicrobial Use Patterns 

Available OPP models that estimate exposures from both direct and indirect discharges to 

surface water (e.g., via a wastewater treatment plant) will be used to determine estimated 

environmental concentrations (EECs) in the aquatic environment. These exposure estimates will 

be compared to the toxicity endpoints to determine whether or not the Agency’s levels of 

concern for acute and chronic risks to aquatic organisms, including listed species, are expected to 

be exceeded for each receptor group. 

In the case of use patterns that result in antimicrobials entering surface water via indirect 

discharges to wastewater treatment facilities, the Agency will use a probabilistic approach that 

estimates the number of days of exceedance of concentrations of concern (COCs) for aquatic 

organisms located downstream of wastewater treatment plants. A more complete discussion of 

this approach as it relates to antimicrobials entering surface water via domestic wastewater 

treatment plants can be found in Appendix D. For those use patterns that result in antimicrobials 

entering surface water by way of industrial wastewater treatment plants, the Agency will use a 

different approach than that used for antimicrobials entering domestic wastewater treatment 

plants. The approach for assessing exposures for antimicrobials entering industrial wastewater 

treatment facilities relies upon estimating loadings of antimicrobials to industrial wastewater 

treatment plants and using the General Population Exposures from Industrial Releases module of 

E-FAST to estimate number of days of exceedance of COCs for aquatic organisms. 

The tool used to predict EECs from leaching and subsequent transport to soil and potential runoff to surface water from antimicrobials in wood and materials preservatives is expected to be 

PRZM/EXAMS. A pervious soil, impervious surface, and a combination of pervious and 

impervious surfaces is expected to be used to bound risks. 

4.4.1.2 Residential Insecticide Use Patterns 

Stressors of Concern 

Ecological Risk Assessment 

Environmental fate data used to determine environmental degradates of oPP and its salts are 

lacking. Following receipt of anticipated data, the major degradates (>10%) will be identified 

and then screened via ECOSAR for toxicity to determine how they will be assessed in the 

registration review risk assessment. In the absence of additional data, the stressors of ecological 

concern for terrestrial and aquatic organisms are oPP and its salts. 

Measures of Exposure 

The Agency will use standard available models to evaluate potential exposures to aquatic and 

terrestrial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm. 

Screening level calculations have suggested that exposure via drinking water may be significant 

for terrestrial vertebrates (i.e., birds and mammals). This exposure pathway may be further 

considered at the time of the risk assessment. 

Available Monitoring Data 

The Agency is aware of monitoring conducted by federal and state agencies, and this route of 

exposure will be considered in the assessment to the extent that data on oPP are available. 
Page 43 of 74

4.4.2 Screening Level Down-the-Drain Analysis 

The Down-the-Drain (DtD) module of E-FAST (Exposure and Fate Assessment Screening Tool) 

was used to determine the potential for aquatic organisms downstream of domestic wastewater 

treatment plants (WWTPs) that receive discharges from application of oPP and salts to be 

exposed to oPP and salts and/or any degradates that form from the point of application to the 

point of discharge following wastewater treatment. The results of the DtD module runs are 

expressed as number or days of exceedance of concentrations of concern for aquatic organisms. 

A detailed description of derivation of data for input parameters selected to run the DtD module 

and of the theoretical basis for this model is presented in Appendix E. A conservative assumption 

of no removal during wastewater treatment was used in DtD model runs. 

Table 14 presents high-end scenario results of a screening-level DtD analysis for oPP and salts 

based on laboratory toxicity data for freshwater organisms. Results are presented for a number of 

wastewater treatment plant influent volumes. Based on U.S. consumption in 2004 of 2,440,000 

pounds and assuming an average annual volume growth of 2.5% per year, Kline (2004) predicted 

that in 2009 consumption of oPP and salts would be 2,760,000 pounds. This corresponds to 

about 1,250,000 kilograms of oPP and salts forecast to be consumed in 2009. In one scenario, it 

was assumed that all of the oPP and salts that was forecast to be consumed in 2009 would be 

discharged to domestic wastewater treatment plants. At this presumed wastewater treatment plant 

influent volume, COCs would be exceeded 3 days per year for endangered freshwater fish and 4 

days per year for endangered freshwater invertebrates. 

To exceed the concentration of concern of 430 ug/L for endangered freshwater algae for one day 

a year, it would take a wastewater treatment plant influent volume of oPP of about 2,225,000 

kilograms per year. To exceed the acute concentration of concern of 1370 ug/L for freshwater 

fish for one day a year, it would take a wastewater treatment plant influent volume of about 

7,500,000 kilograms per year. To exceed the acute concentrations of concern of 1255 ug/L for 

freshwater invertebrates and 1390 ug/L for freshwater algae for one day per year, it would take a 

wastewater treatment plant influent volume of about 7,000,000 kilograms per year. 

Table 14 – Summary of Screening Level Down-the-Drain Analysis Results 

Influent Volume of oPP Acute Freshwater Fish 

(COC = 1370 ug/L) 

Endangered Freshwater Fish 

(COC = 137 ug/L) 

1,250,000 kilograms/year No exceedance Exceeded 3 days per year 

2,225,000 kilograms/year No exceedance Exceeded 11 days per year 

Influent Volume of oPP Acute Freshwater Invertebrates

(COC = 1255 ug/L) 

Endangered Freshwater Invertebrates 

(COC = 125.5 ug/L) 

1,250,000 kilograms/year No exceedance Exceeded 4 days per year 

2,225,000 kilograms/year No exceedances Exceeded 13 days per year 

Influent Volume of oPP Acute Freshwater Algae 

(COC = 1390 ug/L) 

Endangered Freshwater Algae 

(COC = 430 ug/L) 

1,250,000 kilograms/year No exceedance No exceedance 

2,225,000 kilograms/year No exceedance Exceeded 1 day per year 

Influent Volume of oPP Acute Vascular Plants 

 (COC = 6200 ug/L) 

Endangered Vascular Plants 

(COC = 2300 ug/L) 

1,250,000 kilograms/year No exceedance No exceedance 

2,225,000 kilograms/year No exceedance No exceedance 

This screening level analysis assumes that oPP and salts are released to domestic wastewater 

treatment plants. Based on registered uses of oPP and salts presented in Table 6 of this FWP, 
Page 44 of 74

there are some uses, such as commercial and industrial cooling water systems and paper mill 

water systems, for which discharges may enter industrial WWTPs rather than domestic WWTPs 

prior to entering surface water. Different methods and tools for assessing potential exposures and 

associated ecological risks will be applied for these other types of uses. 

There is considerable uncertainty regarding the amount of oPP and salts that could be expected 

to enter domestic wastewater treatment plants. There is also uncertainty about the potential for 

exposure to aquatic organisms from oPP and salts entering industrial wastewater treatment plants 

as a result of industrial uses of oPP and salts. Exceedances of concentrations of concern for 

endangered freshwater fish and invertebrates have been predicted at production volumes of oPP 

and salts projected by Kline for the year 2009 (Kline 2004), and there is evidence based on an 

evaluation of production data reported to the Agency that the Kline data tend to considerably 

underestimate the production volume of oPP and salts. The Agency does not have high quality 

data on the toxicity of oPP and salts to activated sludge microorganisms in wastewater treatment 

plants and does not have high quality data on biodegradation of oPP and salts during wastewater 

treatment. Consequently, the Agency anticipates needing the following data on oPP to fulfill data 

gaps regarding toxicity to activated sludge microorganisms and biodegradation of oPP and salts 

during wastewater treatment: 

1. Activated Sludge Respiration Inhibition (OECD 209) or Modified Activated 

Sludge Respiration Inhibition (OCSPP 850.6800); 

2. Ready biodegradability test (835.3110) or one of three biodegradation in activated 

sludge simulation tests (835.3220; 835.3280; 835.3240) 

For more information on these tests, refer to Table 8. 

4.5 Effects Analysis Plan 

Toxicity data presented in this work plan will be used to calculate risk quotients and/or calculate 

COCs. Any additional information submitted by the registrant(s), other interested parties or 

found in the open literature prior to conduct of the risk assessment will also be considered. The 

open literature studies will be identified using EPA’s ECOTOXicology (ECOTOX)23 database, 

which employs a literature search engine for locating chemical toxicity data for aquatic life, 

terrestrial plants, and wildlife. The ECOTOX database will be searched when the risk assessment 

for oPP and salts is prepared. The evaluation of these sources of data can also provide insight 

into the direct and indirect effects of pesticides on biotic communities from loss of species that 

are sensitive to the chemicals and from changes in structure and functional characteristics of the 

affected communities. 

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 

 

23 http://cfpub.epa.gov/ecotox 
Page 45 of 74

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

taxonomic groups. As part of its reregistration decision, for oPP, 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), oPP is subject to the endocrine 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

identified for EDSP screening was published on June 14, 201324 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. 

oPP is on List 1 for which EPA has received all the required Tier 1 assay data. The agency is 

currently reviewing all of the assay data received for the appropriate List 1 chemicals and 

planning to make the conclusions of those reviews available in early 2015. 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.25

6 Optional Label Changes 

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, registrants may consider amending product labeling. 

Some labels permit the use of handheld fogging. If the labels were amended to require that 

fogging be done only by automatic equipment, then EPA would likely no longer need the 

anticipated requirement for the indoor exposure study for handheld fogging. 

All of the labels permit open pour addition of liquids and soluble powders for material 

preservation and industrial process treatment. If the labels were amended to require that liquids 

be handled using closed loading and delivery systems and that powders be packaged in water 

 

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

chemicals. 25 http://www.epa.gov/endo/ 
Page 46 of 74

soluble packaging, then EPA would likely no longer need the anticipated requirement for the 

indoor exposure study for open pouring of liquids and soluble powders. 

7 Next Steps 

A DCI will be developed regarding the data needs listed under the “Risk Assessments and 

Anticipated Data Needs” section of this document. The Agency expects to issue the DCI by 

March of 2015. 
Page 47 of 74

8 References 

MRID 424417-01: Srivastava, R.; Chakrabarti, A.; Griffin, K. (1992) Vapor Pressure of Ortho-Phenylphenol 

Measured by the Knudsen-Effusion/Weight Loss Method: Lab Project Number: ML-AL 91-020408. 

Unpublished study prepared by Dow Chemical USA. 15 p. 

MRID 439942-01: Gonsior, SJ 1996. Study ID# ES-3034, Dow Chemical Company, Midland, MI: 48674). 

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

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

CalEPA, OrthoPhenylPhenol (OPP), and Sodium Ortho-Phenylphenol(SOPP), Risk characterization Document, 

Dietary Exposure, April 9, 2007, Department of Pesticide Regulation, California Environment Protection 

Agency. 

EPI Suite, Version 4.1 (accessed April 1, 2013). This is an EPA Estimation Program: 

www.epa.gov/opptintr/expsoure/pubs/episuite.html 

FAO, 1983, Food and Agricultural Organization: www.AO.org/publications/search/orthophenylphenol 

Health Canada (2008). 2-Phenylphenol: Proposed Re-Evaluation Decision, Jan. 2008, Document # PRVD2008-

04.Gonsior, SJ, Bailey, RE, Rhinehart, WL, and Spence, MW, 1984: Biodegradation of o-phenylphenol in 

river water and activated sludge, J.Agr.Food Chem, 32:593-596.

Gonsior, SJ, and Tryska, YJ, 1998: Evaluation of the ready biodegradability phenylphenol: Dow Chem Envir. Chem 

Res. Lab, USA, Report 971080 (23 pages, unpublished work). 

MRID# 466014-01: Memorandum dated Sept. 20, 2005, from Najm Shamim, Chemist, RMB 2 to Ben Chambliss, 

Team Leader, RM 2. 

Tajeddine, L, Montacer, H and Sarrakha, M (2010). Arabian Journal of Chemistry, 3:73-78.

Wick, LY, and Gschwend, PM, 1998a: source and chemodynamic behavior of diphenyl sulfone, and ortho-and parahydroxyphenylphenol in small lake receiving discharges from an adjacent superfund site. Environmental 

science and technology, 32:1319-1328.

Zbozinek, JV, 1984: Environmental transformations of DPA, SOPP, Benomyl, and TBZ; Residue Rev. 92:3351-

3358. 

MRID 466014-01: Determination of Leach Rates from Wood treated with SOPP: Dow Chemical Company 

MRID 46359: Pauli, O.; Franke, G. (1972) Behavior and degradation of technical preservatives in the biological 

purification of sewage. Proceedings of the International Biodeteriorating Materials Symposium 2:52-60. 

(Also in unpublished submission received Nov 27, 1979 under 464-403; submitted by Dow Chemical U.S.A., 

Midland, Mich.; CDL:242515-B) 

MRID 41609505: Chakrabarti, A. (1990) Vapor Pressure of the Sodium Ortho-phenyl- phenate Measured by the 

Knudsen-Effusion/Weight Loss Method: Lab Project Number: ML-AL 90-020313. Unpublished study 

prepared by Dow Chemical U.S.A.. 10 p. 

MRID 42441702: Srivastava, R.; Chakrabarti, A.; Griffin, K. (1992) Vapor Pressure of Ortho-Phenylphenol 

Measured by the Knudsen-Effusion/Weight Loss Method: Lab Project Number: ML-AL 91-020408. 

Unpublished study prepared by Dow Chemical USA. 15 p. 

MRID 42441703: Reim, R. (1992) Dissociation of Dowicide 1 Antimicrobial: Lab Project Number: ML-AL 92-

080459. Unpublished study prepared by The Dow Chemical Co. 15 p. 

MRID 42441704: Heimerl, J. (1992) Octanol/Water Partition Coefficient Determination of Dowicide 1 

Antimicrobial for Registration: Lab Project Number: ML-AL 92-080459. Unpublished study prepared by The 

Dow Chemical Co. 43 p. 

MRID 42500204: Reim, R. (1992) Dissociation of Dowicide A Antimicrobial: Lab Project Number: ML-AL 92-

041093. Unpublished study prepared by Dow Chemical, USA, Analytical Sciences. 15 p. 

MRID 43973501: Dullau (1990) Preventol O Extra Hydrolysis Study: (Ortho-phenylphenol): Lab Project Number: 

G 89/0056/02 LEV: ZF-DZA/OAL: K2011-0058701-95E. Unpublished study prepared by Bayer AG. 162 p. 

MRID 439994201: Gonsior, S. (1996) The Hydrolysis of o-Phenylphenol in Buffered Solutions: Lab Project 

Number: ES-3034. Unpublished study prepared by The Environmental Chemistry Research Laboratory, The 

Dow Chemical Co. 16 p. 

 
Page 48 of 74

Appendix A Toxicology Profile 

The most recent review of the toxicity data for ortho phenyl phenol was included in the 2006 

RED. No additional toxicology studies have been submitted to the Agency since publication of 

the RED, and no new toxicology studies are anticipated to be needed. 

Acute Toxicity for Product Labeling 

The acute toxicity database for oPP and salts shows that by the oral route, a Toxicity Category III 

is assigned based on results of two submitted studies (MRIDs 43334201 and 43334204) showing 

oral LD50 values of 2733 mg/kg (combined) and values of 846 and 591 mg/kg ( males and 

females respectively). By the dermal route, an LD50 value of > 5000 mg/kg was obtained in a 

submitted study (MRID 00078779). In a submitted acute inhalation toxicity study (MRID 

42333101), animals exposed nose-only to an aerosol of oPP (0.036 mg/L) showed no mortality; 

however, this study is currently not acceptable but could be upgraded if information is provided 

that an adequate (higher) atmospheric concentration of oPP could not be generated and that 

smaller particle sizes could not be achieved. A primary eye irritation study was conducted 

(MRID 00139884) but the study was considered unacceptable because the observation period 

employed in the study (7 days) was not long enough to assign a Toxicity Category. Ortho-phenyl 

phenol and its sodium salt are severe (Toxicity Category I) dermal irritants. Ortho-phenyl phenol 

and its sodium salt are not dermal sensitizers. 

Table 15 – Acute Toxicity Studies for oPP 

Guideline No./ Study 

Type MRID No. Results Toxicity Category

870.1100/ 

Acute oral toxicity 

oPP purity 99.9% 

43334201 LD50 = 2733 mg/kg III

870.1100/ 

Acute oral toxicity 

Na-oPP purity 99.1%

43334204 LD50 = 846 mg/kg (male)

LD50 = 591 mg/kg (female) III

870.1200/ 

Acute dermal toxicity 

oPP purity 99.73% 

00078779 LD50 > 5000 mg/kg IV

870.1300/ 

Acute inhalation toxicity 

oPP purity 99.9% 

42333101 Unacceptable study NA

870.2400/ 

Acute eye irritation 

Dowicide® 1

00139884 Unacceptable study NA

870.2500/ 

Acute dermal irritation 

oPP purity 99.9%

43334202 Primary Irritant I

870.2600/ 

Skin sensitization 

oPP purity 99.9%

43334203 Not a sensitizer. No

870.2600/ 

Skin sensitization 

Na-oPP purity 99.1%

43334205 Not a sensitizer. No

N/A=Not available 
Page 49 of 74

Subchronic Toxicity 

In a 90-day oral toxicity test (MRID 40760206) designed to determine the subchronic toxicity 

effects of repeated dietary exposure to oPP (>98% purity) in F344/DuCrj rats. Ortho-phenyl 

phenol was administered in feed to 10 rats/sex/dose at concentrations of 0, 0.156, 0.313, 0.625, 

1.25, or 2.5% (0, 182, 391, 761, 1669, or 2798 mg/kg/day and 0, 202, 411, 803, 1650, or 3014 

mg/kg/day for males and females, respectively) for 13 weeks. Animals were observed twice 

daily for changes in body weight and food and water consumption. 

Mortality occurred in treated animals within 2 weeks of initiating the study, with death in 20% of 

males (4 days into study) and 10% of females (8 days into study) in the 2.5% dose group. Food 

consumption was slightly decreased in males and females of the 1.25% dose group. Males 

administered 2.5% oPP exhibited significant decreases from control in food intake. The 

discrepancy in food intake was greatest in the first week but decreased as the study progressed. 

Females of this group also exhibited a reduction in food consumption that was significantly less 

than the control until week 8; however, the decreased food intake trend continued throughout the 

remainder of the study. Additionally, the 2.5% rats spilled an excessive amount of feed at the 

initial stage of the study and they tended to be thin throughout the study period. 

There were no other effects on food consumption in animals of the other dose levels except for 

males treated with 0.313% oPP. These rats showed significant increases in food consumption 

and food intake/body weight that appeared to be reflected in the body weight changes. Overall 

the feeding efficiency (increase in body weight over unit time in grams/feed intake in grams) was 

slightly lower in groups fed on feed containing high oPP concentrations. 

Water consumption was significantly decreased from controls in the first week of the study in the 

1.25 and 2.5% dose groups. There were no significant changes from controls in body weight gain 

in animals treated with oPP concentrations equal to or less than 0.625%. Weight gain was 

inhibited in males and females of the 1.25% dose group, with maximum inhibition ratios of 14 

and 7%, respectively. The significant weight loss of 1.25% females occurred in the first 8 weeks 

of the study. Body weight gain was significantly reduced from controls in both male and female 

rats in the 2.5% oPP dose group. 

The hemoglobin (Hgb) and mean red blood corpuscle hemoglobin concentration (MCHC) were 

significantly lower than controls in 1.25 and 2.5% females, while hematological analyses in the 

2.5% males showed significant decreases from controls in red blood corpuscles (RBC), Hgb, and 

MCHC. There was a slight tendency for animals to be anemic in groups fed higher dosages of 

oPP. No treatment-related effects were observed in the serum analyses. Pathological and 

histological observations indicated treatment-related inflammation of the kidneys in both male 

and female rats (most pronounced in the 2.5% group) and abnormal growth in the mucous 

membrane of the male bladder (most pronounced in the 1.25% group). 

The subchronic toxicity NOAEL is 0.625% (761 mg/kg/day, males; 803 mg/kg/day, 

females). The subchronic toxicity LOAEL is 1.25% (1669 mg/kg/day, males; 1650 

mg/kg/day, females), based on significant reductions in body weight gain and food and 

water consumption. 

In a 21-day dermal toxicity study (MRID 42881901) of systemic toxicity in Fischer 344 rats, 

male and female (5/sex/dose) were administered oPP (99.82% a.i.) over a 21 day study period for 

a total of 15 doses of 0, 100, 500, or 1000 mg/kg/day for 6 hours per day. 
Page 50 of 74

The highest dose tested, 1000 mg/kg/day, a limit dose for repeated dermal dosing regimens, 

produced no significant signs of systemic toxicity. Erythema and scaling was present in male and 

female rats at the 500 and 1000 mg/kg dose levels, with more severe irritation effects observed in 

the females. Microscopically, an increased incidence of acanthosis and hyperkeratosis was 

observed in male and female rats at the 500 and 1000 mg/kg dose levels. 

The systemic toxicity NOAEL is greater than or equal to 1000 mg/kg/day (highest dose 

tested), and the systemic toxicity LOAEL is greater than 1000 mg/kg/day (not established). 

The dermal toxicity NOAEL is 100 mg/kg/day based on an increased incidence of dermal 

irritation reactions in male and female rats observed at the LOAEL of 500 mg/kg/day. 

Developmental and Reproductive Toxicity 

In a prenatal developmental toxicity study (MRID 92154037, reformat of 00067616 and 

00164362), oPP (purity 99.69%) in cottonseed oil, was administered presumably by oral gavage 

(not specified) to groups of 37, 27, 27, and 26 rats/dose by gavage at dose levels of 0, 100, 300, 

or 700 mg/kg/day, respectively, from gestation days (GD) 6 to 15, inclusive. The animals were 

checked daily from gestation day 6 for indications of toxicity. Body weights were recorded daily 

from gestation days 6 through 15 and on gestation days 16 and 21. Food and water consumption 

were measured at 3 day intervals beginning on gestation day 6. Examinations at sacrifice 

consisted of a determination of the number and position of live, dead, and resorbed fetuses and 

staining of apparent nonpregnant uteri along with liver weights. 

Minimal maternal toxicity was noted in the mid-dose group (91% of control) and greater 

maternal toxicity was noted in the high dose group (79% of control) during the dosing period as 

a decrease in body weight gain. Food consumption and food efficiency were slightly reduced in 

the mid and high dose groups during the dosing period. Also, the high dose group had reduced 

liver weights. 

The maternal toxicity NOAEL is 100 mg/kg/day based on decreased body weight gains, 

food consumption and food efficiency. The maternal toxicity LOAEL is 300 mg/kg/day. 

No developmental toxicity was noted at the dose levels tested. The developmental toxicity 

NOAEL is greater than or equal to 700 mg/kg/day (highest dose tested). The developmental 

toxicity LOAEL is greater than 700 mg/kg/day (not established). 

In a prenatal developmental toxicity study in rabbits (MRID 41925001, 41925002, and 

41925003), inseminated New Zealand White rabbits (7 females/group) were administered oPP 

(99.88% a.i.) on days 7-19 of presumed gestation by oral gavage at doses of 0, 25, 100, or 250 

mg/kg/day. All animals were observed daily for signs of toxicity during the course of the study 

with body weights recorded on gestation days 0, 20, and 28 and then daily during the dosing 

period. Any animal that died or was sacrificed on study and all surviving animals at study 

termination were subjected to complete necropsy. Fetuses were examined for external, visceral, 

and skeletal alterations. 

Administration of ortho-phenylphenol produced evidence of systemic toxicity at the 100 

mg/kg/day (mid-dose) and 250 mg/kg/day (high-dose) levels. An increase in mortality occurred 

at the highest dose tested (three dams compared to one dam in the control group). Treatmentrelated alterations in microscopic kidney structure, primarily consisting of inflammation and 

tubular degeneration, were noted only in the high-dose animals. Observations of blood in the 

feces, urine, or cage pan was noted in the mid-dose (three dams compared to one control dam) 
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and high-dose (6 dams compared to one control dam) groups. Although the study author stated 

these effects to be of no toxicological significance because there was no correlation of these 

effects with signs of abortion and/or gross/microscopic pathologies, the EPA reviewer could not 

rule out this effect at the mid dose The maternal toxicity NOAEL is 25 mg/kg/day and the 

maternal toxicity LOAEL is 100 mg/kg/day based upon increased incidence of blood in 

feces, urine, and/or cage pan. 

There were no statistically or biologically significant treatment-related differences in the 

incidence of fetal malformations or variations in any of the dose groups tested. Findings were 

sporadic, not dose-related and/or within the range of historical control data. Therefore, the 

developmental toxicity NOAEL is greater than or equal to 250 mg/kg/day (highest dose 

tested) and the developmental LOAEL is greater than 250 mg/kg/day (not established). 

In a two-generation reproduction study (MRID 43928801) oPP (99+% a.i., Lot # PW08118LW) 

was administered to groups of 30 male and 30 female Sprague-Dawley rats in the diet at 

concentrations delivering doses of 0, 20, 100, or 500 mg/kg/day. Each group was administered 

the control or test diets continuously for 10 weeks prior to mating, during mating, gestation, and 

lactation through the production of two litters (F1a, F1b, F2a, and F2b) including a 14- or 20-day 

rest period after the first litters were weaned. The F1 parents were selected when the pups were 

21 days of age; the pups were weaned onto the same diets as received by their parents. The 

dietary concentrations were adjusted weekly based on the food consumption and body weight of 

the previous week to maintain a constant dose (mg/kg/day) except during gestation, lactation, 

and from weaning through week 3 of the premating period for F1 pups. During these times, the 

animals received the same dietary concentrations of test material as the respective groups during 

the last week of the F0 premating period. 

No treatment-related effects were observed in male or female adult rats administered oPP at 

concentrations of 20 or 100 mg/kg/day. No treatment-related effects were observed on overall 

mortality, except for one F0 male rat receiving 500 mg/kg/day that died due to kidney failure. 

The only treatment-related clinical sign of toxicity was urine staining in 5/30 (p<0.05) F0 and 

8/30 (p=0.01) F1 males given 500 mg/kg/day compared with 0/30 for each control group. A 500 

mg/kg/day, body weights at the end of the 70-day premating period were decreased by 2% (not 

significant) in F0 males, 7% (p<0.01) in F0 females, 11% (p<0.01) in F1 males, and 9% (p<0.01) 

in F1 females. At the end of the study (day 175), body weights were decreased by 5% (not 

significant) in the F0 males and by 11% (p<0.01) in F1 males administered 500 mg/kg/day. 

Corresponding reductions in weight gain during the 70-day premating period were -9 and -10% 

for F0 and F1 males and -19 and -8% for F0 and F1 females at 500 mg/kg/day compared with 

weight gain in the controls. Reductions in weight gain after 175 days of treatment were -19 and -

10% in the F0 and F1 males. In contrast to weight gain, food consumption by males and females 

of both parental generations administered 500 mg/kg/day generally exceeded that of controls, 

and the F1 dams weighed 6 to 8% less (P<0.05 or <0.01) than controls and the F1 dams weighed 

5% to 8% less (not significant, p<0.05 or p<0.01) than controls. Weight gain in 500 mg/kg/day 

group dams during gestation was similar to that of controls ranging from +1 to -7% of the control 

value for both parental generations; during lactation, weight gain for all treated groups in both 

generation ranged from -57 to +288% and showed no clear dose-related trends. For the first 124 

days of lactation, food consumption in dams receiving 500 mg/kg/day ranged from 103 to 112% 

of the control values. 
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Urinary bladder calculi observed grossly (F0: 4/30 vs. 0/30 for controls, not significant; F1: 7/30 

vs. 0/30 for controls, P<0.05) and microscopically (F0 and F1: 4/30 vs. 0/30, not significant) at 

500 mg/kg/day in adult males were considered to be related to treatment with the test material. 

Wet/stained ventrum observed (F0: 2/30 vs. 0/30 for control, not significant; F1: 5/30 vs. 0/30 for 

controls, not significant) at 500 mg/kg/day in adult males was considered to be treatment-related. 

Other microscopic lesions attributed to treatment of male rats with 500 mg/kg/day of the test 

material included simple transitional cell hyperplasia (F0: 22/30 vs. 1/30; F1: 27/30 vs. 0/30; 

p<0.05), nodular/ papillary transitional cell hyperplasia of the urinary bladder (F0: 16/30 vs. 1/30; 

F1: 19/30 vs. 0/30; p<0.05) and chronic inflammation in the urinary bladder (F0: 13/30 vs. 0/30; 

F1: 12/30 vs. 0/30; p<0.05). The average severity ratings but not the incidences were 

significantly increased (p<0.05) for chronic inflammation in the kidney [F0: 4/30 (2.8) vs. 0/30] 

debris in the renal pelvis [F1: 4/30 (2.5) vs. 0/30], and dilation of the ureter [F0: 4/30 (1.8) vs. 

0/30]. No treatment-related pathologic lesions were observed in adult females. 

No treatment-related effects on reproductive function or performance were observed in male or 

female rats of either generation. No treatment-related effects occurred on viability, clinical signs, 

litter size at birth, or at the end of lactation or sex ratio for the F1 or F2 pups. Body weights in 21-

day old pups in the 500 mg/kg/day group were decreased significantly (p<0.01) in both litters of 

each generation (-10 to -12%). F2b pups at 500 mg/kg/day weighed 7% less (p<0.05) than 

controls on day 14 of lactation; no other statistically significant effects on pup weights were 

observed. Pup weight gain at 500 mg/kg/day was reduced by 12 to 14% over the entire lactation 

period. The reduced pup weights and weight gain is not attributed to lactational effects in the 

dams, but is considered to be related to consumption of the treated food. 

The parental toxicity LOAEL is 500 mg/kg/day in males and females, based on reduced 

body weight and body weight gain in the adults, reduced body weight in 21-day old pups, 

clinical signs in adult male rats, microscopic lesions in the kidneys, and gross and 

microscopic lesions in the urinary bladder of adult male rats, and the death of one adult 

male rat due to kidney failure. The parental toxicity NOAEL is 100 mg/kg/day. No 

treatment-related reproductive toxicity occurred in male or female rats; therefore the 

reproductive NOAEL is >500 mg/kg/day. 

Chronic Toxicity and Carcinogenicity 

Combined chronic toxicity / Carcinogenicity – Rat 

In a combined chronic toxicity /carcinogenicity study (MRID 43954301) CDF rats from SASCO, 

Inc., Madison WI received oPP (99.5—100% a.i.; Batch # S-01-93, Mixture of Bayer AG, 

Leverkusen, Germany and Dow, Midland, Michigan) in the diet for 24 months at dose levels of 

0, 800, 4000 and 8000 ppm in males, and 0, 800, 4000, and 10000 ppm in females (39, 200, and 

402 mg/kg/day for males for the 800, 4000, and 8000 ppm dose groups and 49, 248, and 647 

mg/kg/day for females fat: the 800, 4000, and 10000 ppm dose groups). Interim sacrifice groups 

of twenty animals/sex for control and high dose groups and ten animals/sex for low and mid dose 

groups were sacrificed at 12 months. Systemic toxicity was noted as decreased body weights (p < 

0.05) and body weight gains in both males and females of the mid and high dose groups during 

the first 13 weeks of- the study (for the 2-year carcinogenicity group). At study termination, only 

the high dose groups had reduced body weights (p < 0.05) and body weight gains. Food 

consumption was slightly decreased in the 2- year carcinogenicity group in the high dose group 

at all time points measured and was decreased in the mid dose females at 13 weeks. Food 
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efficiency determined for the first 13 weeks was slightly decreased in the mid dose group and 

greatly decreased in the high dose, group. There was an increase in observed masses in the 

urinary bladder of high dose males at 24 months. High dose females had an increased incidence 

of kidneys with pitted zones at 24 months. Mid and high dose females had an increase in 

wet/stained ventrum at 12 months and both high dose males and females had a similar 

observation at 24 months, this was attributed to the urine and red staining in the perigenital area 

noted in the clinical observation data. Non-neoplastic observations noted an increase in incidence 

of calculus in the kidneys in high dose males at the 12 month sacrifice and the 24 month study 

termination. There was also increased hyperplasia of the urinary bladder at 12 and 24 months in 

high dose males (and high dose females at 24 months) along with an increase in congestion, 

hemorrhage, mineralization and necrosis of the urinary bladder at 24 months in high dose males. 

High dose males and females also had an increase in cysts of the kidney at 24 months. High dose 

females had an increase in hyperplasia of the kidney along with increased infarct, acute 

inflammation and mineralization of the kidney. Based on the results of this study, the Systemic 

Toxicity NOEL is equal to 800 ppm (39 mg/kg/day for males and 49 mg/kg/day for females 

and the Systemic Toxicity LOEL is equal to 4000 ppm (200 mg/kg/day for males and 248 

mg/kg/day for females) based on decreased body weight gains, decreased food consumption 

and reduced food efficiency, and increased clinical and gross pathological signs of toxicity. 

This study is classified as Acceptable – Guideline. 

In a carcinogenicity study (MRID# 43545501) B6C3F1 albino mice (50/sex/dose group) from 

Charles River Laboratory, Portage, MI received ortho-phenylphenol (99.88% a.i.; Lot# 8800005-

24, mixture of Dow Chemical Company and Miles, Inc. products) in the diet for 24 months at 

dose levels of 0 250, 500 and 1000 Mg/kg/day. A satellite group of ten animals/sex/dose group 

were sacrificed at 12 months. 

Systemic toxicity was noted in treated females at 3 months as decreased body weight gain (10-

12%), statistically significant but not dose related. At 12 and 24 months there was a 14-25% 

decrease in body weight gain in males and females of the mid dose and a 27-38% decrease in the 

high dose groups. Treated females had slightly reduced food consumption during the first 90 

days. Food efficiency for this period was slightly reduced for the male dose groups and variable 

for the female dosed groups (no dose response effect). At 1 year there was no treatment related 

effects on food consumption and at 2 years there was a slight increase in food consumption in all 

treated groups. There was an increase in absolute and relative liver weights at 12 and 24 months 

in all treated males and females; also, treated males had increased adrenal absolute and relative 

weights at 24 months. Spleen weights (absolute and relative) in the males and females were 

reduced in all treated groups. The Systemic Toxicity LOEL is less than or equal to 250 

mg/kg/day and the Systemic Toxicity NOEL lees than 250 mg/kg/day based on increased 

liver and reduced spleen weights and gross observations in the liver of all treated animals

This study is classified as Core-Minimum data and satisfies the guideline requirement (83-2b) 

for a carcinogenicity study in the mouse. 

Mutagenicity 

An analysis of the genetic toxicology data from over 130 studies with oPP was undertaken by 

Brusick (2005) who found that there was no indication of gene mutations in bacteria or in 

mammalian cells such as Chinese hamster ovary (CHO) cells and that positive results with 

mouse lymphoma (Tk+/-) were generally associated with cytotoxicity. Similarly, clastogenicity, 
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which was the most frequently observed type of genotoxicity, was consistently linked with 

cytotoxicity. For oPP, the most common type of structural chromosome damage was 

chromosome breaks, an event that Brusick describes as typically resulting in cell death. Mixed 

results were found in studies assessing direct interaction with DNA damage. Based on the 

weight-of -the-evidence analysis, it was concluded that positive findings in genetic toxicology 

tests were related to ‘excessive cytotoxicity, not direct DNA damage”. Furthermore, Brusick 

(2005) states that agents that shift the normal cellular antioxidative balance and induce 

cytotoxicity are considered threshold-dependent because exposure levels that do not produce 

alterations in homeostais do not produce DNA damage (i.e., genotoxicity). In other words, 

oxidative damage, eventually leading to cell lethality, only occurs at concentrations that have 

exceeded the levels that can be handled by normal homeostasis. This observation is supported by 

the analysis of the carcinogenic mechanism of 2-phenylphenate by Niho et al. (2002). From the 

dose- and time-response studies with oPP and urinary bladder carcinogenicity in rats, 

investigators found that the tumor induction was a high-dose phenomenon, producing a steep 

dose response at 15,000 and 20,000 ppm but negative at 10,000 ppm. Similarly, a steep time 

response curve was plotted with transitional cell carcinoma development only seen in 4% of the 

animals after 24 weeks of continuous oral exposure but increasing dramatically after 24 (53%) 

and 52 (71%) weeks. The non-linearity of this response suggested to the authors that the tumor 

response observed in these studies with oPP is consistent with a threshold effect. 

Metabolism and Pharmacokinetics 

The metabolism and pharmacokinetics of ortho-phenylphenol have been examined in studies 

from the peer reviewed scientific literature (Reitz et al., 1983; Bartels et al., 1998). An oral dose 

of ortho-phenylphenol can be directly conjugated with glucuronic acid or sulfate to form the 

glucuronide and sulfate conjugate or can be metabolized by cytochrome P-450 isozymes to form 

hydroxylated metabolites (phenylhydroquinone and 2,4 dihydroxybiphenyl) which are then in 

turn conjugated with glucuronic acid or sulfate. At doses below approximately 200 mg/kg, orthophenylphenol is found primarily in urine as the glucuronide and sulfate conjugates in both rats 

and mice. With increasing dose, however, the metabolic profile changes and this has been 

postulated to be related to the carcinogenic mode of action for ortho-phenylphenol. Briefly, 

Biotransformation of oPP initially involves formation of phenolic metabolites (such as 2,4'-

dihydroxyphenyl and phenylhydroquinone) in the liver through the action of cytochrome P-450 

(demonstrated by Ozawa et al. [Xenobiotica 30(10), 1005-1017, 2000], by rat CYP2C11 and 

possibly CYP2E1, and human CYP1A2. Ortho-phenyl phenol, phenylhydroquinone, and 2,4'-

dihydroxybiphenyl can themselves undergo conjugation reactions through the action of either 

sulfotransferase or glucuronidation phase II reactions. Phenylhydroquinone can also be 

converted to phenyl-1,4-benzoquinone by a secondary peroxidase-mediated activation in the 

kidney and/or bladder involving the prostaglandin endoperoxide synthase (PHS) complex. The 

involvement of PHS has been suggested on the basis of data submitted to the Agency (D203250), 

where in vitro incubations were conducted with microsomal PHS from ram seminal vesicles 

using oPP or the metabolites phenylhydroquinone (PHQ) and phenylbenzquinone (PBQ). This 

study demonstrated a role for PHS in conversion of PHQ to PBQ. 

The presence of PHS in the bladder epithelium has been proposed by Kolachana et al. 

(Carcinogenesis 12(1): 145-149, 1991) as possibly responsible for the activation of PHQ to 

reactive intermediates in the bladder and kidney. The generation of PBQ is considered dosedependent, appearing in increased quantity only at higher (>200 mg/kg/day) doses of oPP. The 
Page 55 of 74

shift in biotransformation products with increased dose of oPP has been postulated to be 

associated with the non-linear response observed in tumorigenicity of the urinary bladder and 

liver, involving oxidative damage to cells and subsequent regenerative hyperplasia. With 

continued exposure, this process leads to development of tumors. 

Dermal Absorption 

Dermal Absorption Factor: The Agency has not received any animal studies on the magnitude of 

dermal absorption of oPP. In the absence of these data, the Agency expects to use a default value 

of 100% for dermal absorption until such time that an acceptable dermal absorption study in 

animals is available. 

Classification of Carcinogenic Potential 

In accordance with the EPA Final Guidelines for Carcinogen Risk Assessment (March 29, 2005), 

the CARC classified oPP as “Not Likely to be Carcinogenic to Humans” based on convincing 

evidence that a non-linear mode of action for bladder tumors was established in rats. High doses 

of oPP lead to saturation of phase II detoxification enzyme pathways, resulting in increased 

amounts of the oxidative metabolites PHQ and/or PBQ. The generation of PBQ is considered 

dose-dependent, appearing in increased quantity only at higher doses of oPP (>200 mg/kg/day). 

The shift in biotransformation products with increased dose of oPP has been postulated to be 

associated with the non-linear response observed in tumorigenicity of the urinary bladder, 

involving oxidative damage to cells and subsequent regenerative hyperplasia. With continued 

exposure, this process leads to development of tumors. Evidence suggests that there are not 

sufficient oxidative metabolites generated in vivo to result in a genotoxic mode of action, but that 

a non-genotoxic mode of action is operative. 

Although there is some mode of action data for the mouse liver tumors, the nature of these 

tumors and their response (benign tumors in one sex at the limit dose and one-half the limit dose 

in a susceptible strain) would not be the basis for quantification of human risk. However, data do 

suggest that this tumor type may also arise from a non-linear mode of action. 

In addition, the non-cancer assessment for oPP established a chronic Reference Dose value of 39 

mg/kg/day from the combined chronic toxicity/carcinogenicity study in rats (MRIDs 43954301, 

44852701, 44832201) based on decreased body weight gains, decreased food consumption and 

reduced food efficiency, and increased clinical and gross pathological signs of toxicity at the 

LOAEL of 200 mg/kg/day. The selection of 39 mg/kg/day as the chronic RfD value is 

sufficiently protective of the key events involved in the carcinogenic mode of action, which are 

not present at doses below 200 mg/kg/day. Thus, the precursor events leading to development of 

bladder and liver tumors are not likely to occur using the selected chronic RfD value and this 

value is thus protective against development of tumors and, therefore, cancer is not an issue. 

Immunotoxicity

An immunotoxicity study is a data requirement for all antimicrobial pesticide chemicals under 40 

CFR Part 158W, Data Requirements for Antimicrobial Pesticides. The registrant can address this 

data requirement by either submitting a study according to the OCSPP 870.7800 guideline, 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. 

 
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Appendix B Environmental Fate 

EPA completed a RED on 2-Phenylphenol and sodium salt or ortho-phenylphenol and sodium 

salt in 2006 for the then registered antimicrobial use sites. In the present registration review 

document, the Agency has taken into account EPA’s RED assessment but also has identified 

additional exposure scenarios that were not considered in the 2006 RED. 

A number of risk assessments documents, including environmental fate and transport for these 

chemicals, have been completed by various organizations either before, during or after the 

Agency’s RED publication. These include: PMRA of Canada1 (2008), IRIS2, FAO3 (1999), and 

CalEPA4, Department of Pesticide Regulation (2007): Risk Characterization Document. 

Ortho-phenyl phenol is a weak acid with a pKa of about 9.95 at 25°C (MRID 41605001), 

indicating that oPP will in aqueous solution primarily exist as the protonated acid at 

environmental pH values (5 - 9). In solution, the sodium (Na) and potassium (K) salts of oPP 

rapidly dissociate releasing sodium and potassium cations (Na+

 and K+, respectively) and the 

ortho-phenyl phenate anion (oPP-

). Depending on the pH of the solution the oPP- anion will 

readily become protonated forming the neutral or unionized oPP or will readily release a proton 

to form the oPP- anion. The equilibrium in solution between oPP- and protonated or unionized 

oPP depends on the pH of the solution. Therefore, the fate and transport data supporting oPP can 

be used to support the salts and similarly the fate and transport data supporting its Na and K salts 

may be used to support oPP. 

Ortho-phenyl phenol is hydrolytically stable under abiotic conditions. It does photodegrade in 

abiotic aqueous medium forming three degradates. It is immobile on surfaces and will not 

contaminate the ground water. It is ready biodegradable. It has a high log Kow indicating it is 

potentially bioaccumulative; however, there is no data on bioaccumulation or bioconcentration in 

aquatic organisms. 

Na-oPP is applied to and leaches out easily from sapstain treatment on wood surfaces, and 

almost 75% is eliminated from wood surfaces within 14 days. Since Na-oPP ionizes in moist 

soils, it is more likely to be mobile from such soil surfaces. 

Abiotic Degradation of oPP 

Ortho-phenyl phenol is hydrolytically stable under abiotic conditions at pH 5, 7, and 9 (MRID 

439942-01); however it degrades photolytically when exposed to sunlight under neutral 

conditions. Exposure to ultraviolet (UV) light (257.7 nanometers (nm)) degrades oPP to form: 

phenylbenzoquinone (PBQ), phenylhydroquinone (PHQ) and 2-hydroxy benzofuran (MRID# 

439942-01). 

The half life of oPP in air is estimated at 14 hours (measured against the hydroxyl radical) (EPI 

Suit, version 4.1). Therefore, it is considered moderately stable in air. Its estimated Koc value of 

10,000 (EPISuite, version 4.1) indicates it is immobile in soils and shows no tendency to migrate 

into soils. It likely will not contaminate ground water. 

Biotic Degradation of oPP 

The half life of oPP in air is estimated to be 0.03 hours using EPISuite 4.10. A study report of 

Wick and Gschwend (1998a) on surface water showed the degradation rates of oPP ranged from 

16.5 to 38.4 hours in spring, summer, and fall seasons, but did not show any degradation in the 
Page 57 of 74

winter season. In a study using river water, Gonsior (1984) indicates that the half life of oPP is 

about 168 hours (7 days). Zbozinek (1984) studied microbial degradation of oPP in soil with 

half-lives ranging from 24 to 168 hours. None of these studies were of ultimate biodegradation or 

mineralization and also did not identify degradates. 

The river water study by Gonsior(1984) used water from Tittabawassee River in Midland, 

Michigan and carbon-14 (14C) radio-labeled oPP. A 50% reduction of 14C labeled oPP occurred 

within a week. After 16 days, carbon dioxide containing 14C (14CO2) reached the levels of 50%, 

65% and 50% from the radiolabeled oPP samples of 1.22, 12.3 and 123 μg/L. The results are 

indicative of mineralization and ready biodegradability of oPP. 

Gonsior (1984) also conducted a biodegradation study on an activated sludge with 14C-labeled 

oPP. The biodegradation process of radio-labeled oPP was examined with non-acclimated and 

acclimated activated sludge, which was obtained from East Lansing, MI. A 50% reduction of 

radiolabeled oPP was observed within 24 hours and 3 hours in non-acclimated and acclimated 

sludge respectively. Thus if oPP is adsorbed on activated sludge, it is ready biodegradable from 

such surfaces. The recovery of total radioactivity in non-acclimated sludge ranged from 90- to 

117%, and 78-100% for the acclimated sludge. 

In another lake study (Wick and Gschwend 1998) the biodegradation of oPP was conducted 

using a mixture of diphenyl sulfone, oPP, and para-phenylphenol (pPP) at respective 

concentrations of 45, 100, and 230 μg/L quantities entering into a lake in Woburn Massachusetts. 

The lake was located at a ground water discharge from a Superfund Site. All three substances 

readily biodegraded during the summer months, with less biodegradation occurring during the 

fall and almost none in the winter months. 

A more recent study (Tajeddine et al. 2010) on the photodegradation of oPP, and monuron, when 

placed on potassium- (K-) and iron (III)- (Fe(III))-monomorillonite clays showed that oPP 

degraded with a first order half life of 2 hours 3 minutes for K-montmorillonite, and 4 hours 18 

minutes for Fe(III) monotmorillonite clay. Photodegradation experiments were conducted in a 

photoreactor (Suntest) which provided the simulated sunlight. The study is a non-guideline study 

and the results are indicated of biodegradation tendency of oPP, Na-oPP, and K-oPP on various 

types of soil surfaces. 

Bioaccumulation of oPP

The Log Kow of 3.09 to 3.36 for oPP has been reported. This chemical is likely to be 

bioaccumulative. No concrete data on bioaccumulation or bioconcentration into aquatic 

organisms has been reported. 

Leaching of Na-oPP from Treated Wood

Na-oPP is used for sapstain treatment on woods. Leaching rates are reported from a study 

submitted by the registrants ((A Memo (Sept., 2005) from Najm Shamim, Chemist to Ben 

Chambliss, Team Leader in RMB2, MRID # 46601401)) where 1% and 4% solution of Na-oPP 

were applied as sapstain on wooden blocks. 1 % treated samples leached 52% of the active 

within the first day; 4% treated wood leached 58% of the active, and by day 14, 72-78 % of the 

active leaches out. The leach rate for 1% treated wood was: 71 μg of Na-oPP/cm2

 /day and for 

4% treated wood the leach rate was: 192 μg of Na-oPP /cm2

 /day; after day 14, the leach rate 

was: 0.5 to 0.2 μg /cm2

/day for both treated woods. At the end of the study, 20-24% of Na-oPP 

was extracted from the wooden blocks. 
Page 58 of 74

Degradates of oPP 

The Agency has used its internal database EPI Suite, version 4.1 to estimate physical/chemical as 

well as some environmental fate characteristics for the degradates PBQ and PHQ. 

Environmental Fate of the Photo-Degradates: PHQ and PBQ 

PHQ 

The estimated data on this compound (EPI Suite, version 4.1) indicates that this substance is 

highly water soluble, and its vapor pressure is not of concern for exposure assessment. Its 

estimated half life is 15 days in water bodies, and about thirty days in soils, making it not 

persistent in these environmental media. It could be stable and persistent in sediments with an 

estimated half life of 135 days. It is not stable in air and the estimated half life is less than six 

hours in air. It is not likely to be bioaccumulative as its log Kow is less than 3. It appears to be not 

readily biodegradable and may not be removed from the wastewater treatment plants. But with 

the half life of 15 days in water bodies, it may not reach the wastewater treatment plants. It has a 

high Koc value making it immobile in soils, thus the probability of this chemical migrating to 

ground water is low and so ground water contamination is not likely to happen. 

PBQ 

The estimated data on this compound (EPI Suite, version 4.1) indicates that this substance is 

highly water soluble, and its vapor pressure is not of concern for exposure assessment. Its 

estimated half life is 15 days in water bodies, and about thirty days in soils, making it not 

persistent in these environmental media. It could be stable and persistent in sediments with an 

estimated half life of 135 days. It is not stable in air and the estimated half life is less than eight 

hours in air. It is not likely to be bioaccumulative as its log Kow is less than 2. It appears to be not 

readily biodegradable and may not be removed from the wastewater treatment plants. It has a 

high Koc value making it immobile in soils, thus the probability of this chemical migrating to 

ground water is low and so ground water contamination is not likely to happen. 

Table 16 – Key Physical-Chemical Properties and Environmental Fate Characteristics of 

oPP and its Salts 

Property/Study oPP and its Salts Remarks/Conclusions 

Vapor pressure oPP: 

Na-oPP 

MRID 42441702, 41609505, 

The studies were acceptable and 

fulfill the date requirements 

Log Kow oPP:3.09-3.36 

Log Koc oPP: 10,000 (EPI Suite, version 4.1) Immobile in soils; will not 

contaminate ground water 

Solubility 

Acid dissociation 

constant pKa 9.2 MRID 42441703, 42500202 

Hydrolysis Hydrolytically stable at pH 5, 7, and 9 (oPP); MRID 43973501, 43994201 

Aqueous 

photodegradation 

A study with oPP was conducted at pH 7. 

Photodegrades in aquatic medium forming the 

degradates: PBQ, PHQ and 2-hydroxybenzofuran. 

The PBQ and PHQ are major degradates. Half-life n 

water both have half life of 15 days; in soil, both have 

half life of 30 days (EPI Suite, version 4.1) 

MRID 43973501 

The half lives for PBQ and PHQ are 

provided as estimates from EPI 

Suite (version 4.1); the study itself 

did not provide the half lives of the 

degradates. 

Air stability/persistence 

in air 

Is not stable or persistent in air; Half life in air: 14 

hours EPI Suite v4.1 
Page 59 of 74

Property/Study oPP and its Salts Remarks/Conclusions 

Soil photodegradation Photodegradation is fast for oPP in this type of soil

oPP: Under simulated sunlight in KMonomorillonite: half-life 3 hours 2 minutes; in 

Fe(III)-monomorillonite: half-life 4 hours and 18 

minutes. 

Major degradates: the study did not identify the 

degradates 

Arabian Journal of Chemistry, 

2010, volume 3, pp 73-78)./ 

Non-guideline study, Supplemental 

Aerobic Aquatic 

Metabolism 

River study: Samples from Tattabawsee river in 

Midland MI, were treated with oPP (1.26, 12.6 and 

126 microgram level. Ortho-phenyl phenol was 

radiolabeled: 50% degradation in seven days, and 50, 

65, and 50% degradation in sixteen days. 

Lake Study: Mixture of diphenyl sulfone, oPP, and 

para-phenylphenol: Ready biodegradable in during 

summer months, less in fall, and none in winter 

months. 

Major degradates: Not reported. 

Ortho-phenyl phenol is Ready 

biodegradable (Gonsoir et al. study: 

1984, J. Agr. Food Chemistry, 

volume 32, pp 593-596; 

Activated sludge; same study 

(Gonsoir et al.) 

Non-guideline study; supplemental 

Biodegradability dependent on 

seasons. Warmer months accelerate 

biodegradation, cooler months make 

it less likely (Wick et al., 1998, 

Environ. Sci. Technol., volume 32, 

pp 1319-1328) 

Non-guideline study 

Activated sludge study Ready biodegradable in the activated sludge. 

Activated sludge study: non-acclimated sludge: half 

life of radiolabeled oPP: 24 hours; acclimated sludge: 

radiolabeled: half life 3 hours. The sludge was 

obtained from East Lansing, MI. 

Major degradates: Not provided 

Non-guideline study MRID 46359. 

Leaching from sapstain 

treated wood 

Sapstain leaching: 1% treated wood: 52% first day; 

4% treated sapstain wood: 58% first day. 72-78% by 

day 14; Rate of leaching: 1%: treated wood: 

71 μg /cm2

/day 

Rate of leaching: 4% treated wood: 192 μg /cm2

/day; 

rate of leaching after 14 days: 0.5 to 0.2 μg /cm2/day 

for both treated wood. The sapstain study was 

conducted on Na-oPP. 

Na-oPP was chosen to increase 

water solubility; rate of leaching is 

high AD (Memo by Najm Shamim 

to Ben Chambliss, September, 

2005.( MRID# 466014-01) 

The study was a guideline study 

(based on Canadian guidelines, 

conducted by Dow Chemical 

Company, Study ID#: 051089, and 

DP Barcode: 319656The results 

show a very high leaching rate, and 

an equilibrium is reached within 

fourteen days. 

Key Degradates: phenylbenzoquinone (PBQ), phenylhydroquinone 

(PHQ) 

No experimental fate data is 

available for these degradates. 

The table below lists physical/chemical and environmental fate characteristics of: 

phenylbenzoquinone (PBQ) and phenylhydroquinone (PHQ)(EPI Suite, version 4.1, accessed on 

April 12, 2012) 

Table 17 – Physical/Chemical and Environmental Fate Characteristics of PBQ and PHQ 

Property 1,1-Biphenyl-2,5-diol 2,5-Cyclohexadiene-1,4-

dione-2-phenyl Source 

Common Name Phenylhydroquinone (PHQ) Phenylbenzoquinone (PBQ) EPI Suite (version 4.1) 

CAS # 1079-21-6 363-03-1 EPI Suite (version 4.1) 

MF/MW C12H10O2 / 186.21 C12H8O2 /184.20 EPI Suite (version 4.1) 

MP 126.99 o C 100.07 o C EPI Suite (version 4.1) 
Page 60 of 74

Property 1,1-Biphenyl-2,5-diol 2,5-Cyclohexadiene-1,4-

dione-2-phenyl Source 

VP 3.57 x10-5 mm Hg 9.23 x10-5 mm Hg EPI Suite (version 4.1) 

Solubility 798.2 mg/L 1135 mg/L EPI Suite (version 4.1) 

Kow 2.80 1.95 EPI Suite (version 4.1) 

Ready 

Biodegradability NO NO EPI Suite (version 4.1) 

STP 4.31% removal in wastewater 

treatment plant 

2.20% removal in wastewater 

treatment plant EPI Suite (version 4.1) 

Half life in Air 5.897 hours (against OH 

radical) 7.137 hours EPI Suite (version 4.1) 

Koc 8634 L/kg 800.8 L/kg EPI Suite (version 4.1) 

Half life in water 360 hours ( 15 days) 360 hours (15 days) EPI Suite (version 4.1) 

Half life in soil 720 hours (30 days) 720 hours (30 days) EPI Suite (version 4.1) 

Half life in sediment 3240 hours (135 days) 3240 hours (135 days) EPI Suite (version 4.1) 

Note: These two degradates are also detected in the mammalian toxicity (metabolism) study as discussed in the 

Health assessment section of this document. 

REFERENCES for Appendix B 

CalEPA, OrthoPhenylPhenol (OPP), and Sodium Ortho-Phenylphenol(SOPP), Risk characterization Document, 

Dietary Exposure, April 9, 2007, Department of Pesticide Regulation, California Environment Protection 

Agency. 

FAO, 1983, Food and agricultural Organization: www: AO.org/publications/search/orthophenylphenol 

Health Canada (2008) 2-Phenylphenol: Proposed Re-Evaluation Decision, Jan. 2008, Document # PRVD2008-04. 

EPI Suite, Version 4.1 (accessed April 1, 2013). This is an EPA Estimation Program: 

www.epa.gov/opptintr/expsoure/pubs/episuite.html 

Gonsior, SJ, Bailey, RE, Rhinehart, WL, and Spence, MW, 1984: Biodegradation of o-phenylphenol in river water 

and activated sludge, J.Agr.Food Chem, 32:593-596.

Gonsior, SJ, and Tryska, YJ, 1998: Evaluation of the ready biodegradability phenylphenol: Dow Chem Envir. Chem 

Res. Lab, USA, Report 971080 (23 pages, unpublished work). 

Memorandum dated Sept. 20, 2005 from Najm Shamim, Chemist, RMB 2 to Ben Chambliss, Team Leader, RMB 2 

Tajeddine, L, Montacer, H and Sarrakha, M (2010). Arabian Journal of Chemistry, 3:73-78.

Wick, LY, and Gschwend, PM, 1998a: source and chemodynamic behavior of diphenyl sulfone, and ortho-and parahydroxyphenylphenol in small lake receiving discharges from an adjacent superfund site. Environmental 

science and technology, 32:1319-1328.

Zbozinek, JV, 1984: Environmental transformations of DPA, SOPP, Benomyl, and TBZ; Residue Rev. 92:3351-

3358. 

MRID 466014-01: Determination of Leach Rates from Wood treated with SOPP: Dow Chemical Company, Study 

ID# 051089, DP Barcode: 319656) 

MRID 46359: Pauli, O.; Franke, G. (1972) Behaviour and degradation of technical preservatives in the biological 

purification of sewage. Proceedings of the International Biodeteriorating Materials Symposium 2:52-60. 

(Also in unpublished submission received Nov 27, 1979 under 464-403; submitted by Dow Chemical U.S.A., 

Midland, Mich.; CDL:242515-B) 

MRID 41609505: Chakrabarti, A. (1990) Vapor Pressure of the Sodium Ortho-phenyl- phenate Measured by the 

Knudsen-Effusion/Weight Loss Method: Lab Project Number: ML-AL 90-020313. Unpublished study 

prepared by Dow Chemical U.S.A.. 10 p. 

MRID 42441702: Srivastava, R.; Chakrabarti, A.; Griffin, K. (1992) Vapor Pressure of Ortho-Phenylphenol 

Measured by the Knudsen-Effusion/Weight Loss Method: Lab Project Number: ML-AL 91-020408. 

Unpublished study prepared by Dow Chemical USA. 15 p. 

MRID 42441703: Reim, R. (1992) Dissociation of Dowicide 1 Antimicrobial: Lab Project Number: ML-AL 92-

080459. Unpublished study prepared by The Dow Chemical Co. 15 p. 

MRID 42441704: Heimerl, J. (1992) Octanol/Water Partition Coefficient Determination of Dowicide 1 

Antimicrobial for Registration: Lab Project Number: ML-AL 92-080459. Unpublished study prepared by The 

Dow Chemical Co. 43 p. 
Page 61 of 74

MRID 42500204: Reim, R. (1992) Dissociation of Dowicide A Antimicrobial: Lab Project Number: ML-AL 92-

041093. Unpublished study prepared by Dow Chemical, USA, Analytical Sciences. 15 p. 

MRID 43973501: Dullau (1990) Preventol O Extra Hydrolysis Study: (Ortho-phenylphenol): Lab Project Number: 

G 89/0056/02 LEV: ZF-DZA/OAL: K2011-0058701-95E. Unpublished study prepared by Bayer AG. 162 p. 

MRID 439994201: Gonsior, S. (1996) The Hydrolysis of o-Phenylphenol in Buffered Solutions: Lab Project 

Number: ES-3034. Unpublished study prepared by The Environmental Chemistry Research Laboratory, The 

Dow Chemical Co. 16 p. 

 
Page 62 of 74

Appendix C Ecotoxicology Profile 

Toxicity to Terrestrial Receptors 

Birds 

Available acute oral studies categorize oPP and salts as being slightly to practically nontoxic to 

birds (Table 18). Neither acute oral data with a passerine species, nor chronic data have been 

submitted. Therefore, guidelines 850.2100and 850.2300) are expected to be required. 

Table 18 – Avian Toxicity Data 

Test Species 

Test 

Material 

(% a.i.)

Toxicity26 Toxicity 

Category

MRID/ 

Study Classification

Mallard 

(Anas platyrhynchos) 

oPP 

(99.2) 

LD50 > 2250 mg ae/kg-bw 

NOAEL > 2250 mg ae/kg-bw, 

no mortality or body weight gain 

effect 

Practically 

nontoxic 

00160150/ 

Acceptable 

Northern bobwhite 

(Colinus virginianus) 

Na-oPP 

(75.9)27

LD50 = 885 mg ae/kg-bw (1000 mg 

a.i./kg-bw) 

NOAEL = 55.3 mg ae/kg-diet (62.5 

mg a.i./kg-diet) 

Slightly toxic 42500204/ 

Acceptable 

Mallard 

(Anas platyrhynchos) 

oPP 

(99.2) 

LC50 > 5620 mg ae/kg-diet 

NOAEC = 3160 ae/kg-diet, 

reduction in body weight gain 

Practically 

nontoxic 

160151/ 

Acceptable 

Mallard 

(Anas platyrhynchos) 

Na-oPP 

(75.9)27

LC50 > 4980 mg ae/kg-diet (>5620 

mg a.i./kg-diet) 

NOAEC = 1580 mg ae/kg-diet (1780 

mg a.i./kg-diet), reduction in body 

weight gain 

Practically 

nontoxic 

42500206/ 

Acceptable 

Northern bobwhite 

(Colinus virginianus) 

oPP 

(99.2) 

LC50 > 5620 mg ae/kg-diet 

NOAEC > 5620 ae/kg-diet, no 

mortality or reduction in body 

weight gain 

Practically 

nontoxic 

160149/ 

Acceptable 

Northern bobwhite 

(Colinus virginianus) 

Na-oPP 

(75.9)27

LC50 > 4980 mg ae/kg-diet (>5620 

mg a.i./kg-diet) 

NOAEC = 1580 mg ae/kg-diet (1780 

mg a.i./kg-diet), reduction in body 

weight gain 

Practically 

nontoxic 

42500205/ 

Acceptable 

Nontarget Insects 

Nontarget insect toxicity data (850.3020, 850.3030) are expected to be required to support the 

assessment of the wood preservative use of oPP and salts. 

 

26 For oPP mg a.i. is equal to mg acid equivalent (ae), whereas mg a.i. of Na-oPP were converted to mg ae by 

multiplying by the molar weight ratio of oPP to Na-oPP (170.2/192.19 = 0.886). 27 The test substance is actually sodium ortho-phenylphenate tetrahydrate (Na-oPP·4H2O) but is represented in the 

table as Na-oPP without the weight percent of water. With the weight percent of water added, the purity of the test 

substance is >99%. 
Page 63 of 74

Toxicity to Aquatic Receptors 

Freshwater Fish 

The available acute toxicity studies (850.1075) categorize oPP and salts as being moderately 

toxic to freshwater fish (Table 19). The guideline (850.1075) for acute toxicity testing is 

satisfied. Chronic data (fish early-life stage, 850.1400) are expected to be required. 

Table 19 – Freshwater Fish Toxicity Data 

Species, Age or size 

Test 

Material 

(% a.i.) 

Exposure 

Type/ 

pH/ hardness28/

temperature 

Toxicity Endpoint29 Toxicity 

Category 

MRID/ 

Study 

Classification/ 

Comments 

Rainbow trout 

(Oncorhynchus 

mykiss) 

Na-oPP 

(71.48%) Flow-through -- -- 

46751206/ 

Unacceptable 

Percent recoveries 

were below 

acceptable range 

Rainbow trout 

(Oncorhynchus 

mykiss), 1.1 g 

oPP 

(95%) 

Static/ 7.1/ 35/ 

10+1 o

C 

96-h LC50 = 2.75 ppm ae

95% CI = 2.4-3.2 ppm ae

Probit slope = NA 

NOAEC = 2.4 ppm ae, 

mortality, loss of 

equilibrium, dark 

coloration 

Moderately 

toxic 

110232/ 

Supplemental/ 

Solvent 

concentration used 

unknown 

Rainbow trout 

(Oncorhynchus 

mykiss), 0.21 g, 2.8 cm 

SL 

oPP 

(99.25%) 

Static/ 7.4-8.2/ 

78/ 12.1-12.5 o

C

96-h LC50 = 4.0 ppm ae

95% CI = 3.6-4.5 ppm ae

Probit slope = NA 

NOAEC = 1.8 ppm ae, 

immobilization, 

melanized fish 

Moderately 

toxic 

156044/ 

Acceptable 

Bluegill sunfish 

(Lepomis 

macrochirus) 

Na-oPP 

(71.48%) Flow-through -- -- 

46751210 

Unacceptable 

Percent recoveries 

were below 

acceptable range 

Bluegill sunfish 

(Lepomis 

macrochirus), 1.0 g 

oPP 

(95%) 

Static/ 7.1/ 35/ 

20+1 o

C 

96-hr LC50 = 2.74 ppm 

ae 

95% CI = 2.4-3.1 ppm ae

Probit slope = 12.09 

NOAEC = 1.0 ppm ae, 

loss of equilibrium, dark 

coloration 

Moderately 

toxic 

110232/ 

Supplemental/ 

Solvent 

concentration used 

unknown 

Bluegill sunfish 

(Lepomis 

macrochirus), 0.4 g, 

37.9 mm 

NaoPP·4H20 

(97%) 

Static/ 7.0/ 51.3/ 

18.3 o

C 

96-h LC50 = 3.9 ppm ae 

(6.1 ppm ts) 

Probit slope = NA 

Moderately 

toxic 

110135 (TN 640), 

110203/ 

Supplemental 

 

28 As mg/L calcium carbonate (CaCO3). 29 For oPP mg a.i. is equal to mg ae, whereas mg a.i. of tests expressed as Na-oPP where converted to mg ae by 

multiplying by the molar ratio of oPP to Na-oPP (170.2/192.19 = 0.886) and results expressed as the tetrahydrate 

sodium salt (Na-oPP·4H20) were converted to mg ae by multiplying by the molar weight ratio of oPP to NaoPP·4H20 (170.2/264.28 = 0.664). 
Page 64 of 74

Species, Age or size 

Test 

Material 

(% a.i.) 

Exposure 

Type/ 

pH/ hardness28/

temperature 

Toxicity Endpoint29 Toxicity 

Category 

MRID/ 

Study 

Classification/ 

Comments 

Bluegill sunfish 

(Lepomis 

macrochirus), 0.15 g, 

2.0 cm SL 

oPP 

99.25% 

Static/ 7.5-7.9/ 

77/ 17.1-17.4 o

C

96-h LC50 = 4.6 ppm ae

95% CI = 4.4-4.8 ppm ae

Probit slope = 31.1 

NOAEC = 3.2 ppm ae, 

immobilization, 

abnormal swimming 

Moderately 

toxic 

156044/ 

Acceptable 

Fathead minnow 

(Pimephales 

promelas), 0.37 g, 2.8 

cm SL 

oPP 

99.25% 

Static/ 7.2-7.7/ 

76/ 16.8-17.3 o

C

96-h LC50 = 4.7 ppm ae

95% CI = 3.6-6.0 ppm ae

Probit slope = NA 

NOAEC = 3.6 ppm ae, 

mortality 

Moderately 

toxic 

156044/ 

Acceptable 

Fathead minnow 

(Pimephales 

promelas), 0.53 g, 3.4 

cm SL 

oPP 

99.25% 

Static/ 7.2-7.9/ 

76/ 17.1-17.4 o

C

96-h LC50 = 5.5 ppm ae

95% CI = 4.7-6.6 ppm ae

Probit slope = NA 

NOAEC = 5.1 ppm ae, 

mortality 

Moderately 

toxic 

156044/ 

Acceptable 

CI = confidence interval; NA: Not applicable; N.R. = Not reported; SL = standard length; TN = test number; ts = 

test substance not corrected for percent a.i. 

Freshwater Invertebrates 

The available acute toxicity studies for the waterflea categorize oPP and salts as being 

moderately toxic to freshwater invertebrates (Table 20). The guideline (850.1010) for acute 

toxicity testing is satisfied. Chronic data (daphnid life-cycle, 850.1300) are expected to be 

required. 

Table 20 – Freshwater Invertebrate Toxicity Data 

Test Species 

Test 

Material 

(% a.i.) 

Exposure Type/

pH/ 

hardness28/ 

temperature 

Toxicity Endpoint30 Toxicity 

Category 

MRID/ 

Study Classification/

Comments 

Waterflea 

(Daphnia magna), 

<24 hours old 

NaoPP·4H2O 

(97)

Static/ / / 25 oC 

(room) 

48-h EC50 = 2.4 ppm ae 

(3.8 ppm ts) 

95% CI = 2.0-3.0 ppm ae 

(3.1 – 4.6 ppm ts) 

Moderately 

toxic 

110222/ 

Acceptable 

Waterflea 

(Daphnia magna), 

<24 hours old 

oPP 

(99.2) 

Static/ 7.9-8.1/ 

148/ 19.7-21.0 o

C 

48-h EC50 = 2.51 ppm ae 

95% CI = 1.5-3.9 ppm ae 

NOAEC = 0.78 ppm ae 

Moderately 

toxic 

156044/ 

Acceptable 

CI = confidence interval; NA: Not applicable; N.R. = Not reported; SL = standard length; TN = test number; ts = 

test substance not corrected for percent a.i. 

Estuarine/Marine Fish and Invertebrates 

Two acute toxicity studies are available for invertebrates, but no data are available for fish. 

Ortho-phenyl phenol and salts are moderately to highly toxic to estuarine/marine invertebrates 

(Table 21). The guideline (850.1035, 850.1025 or 1055) for acute toxicity testing with 

estuarine/marine invertebrates is satisfied. Acute toxicity data (850.1075) are expected to be 

 

30 For oPP mg a.i. is equal to mg ae, whereas mg a.i. of the tetrahydrate sodium salt (Na-oPP·4H2O) were converted 

to mg ae by multiplying by the molar weight ratio of oPP to Na-oPP·4H2O (170.2/264.28 = 0.664). 
Page 65 of 74

required for fish. Chronic data are expected to be required for fish (early life-stage, 850.1400) 

and an invertebrate (mysid life-cycle, 850.1350). 

Table 21 – Estuarine/Marine Fish and Invertebrate Toxicity Data 

Test Species 

Test 

Material 

(% a.i.) 

Exposure Type/

pH/ salinity31/

temperature 

Toxicity Endpoint31 Toxicity 

Category 

MRID/ 

Study 

Classification/ 

Comments 

Sheepshead minnow 

(Cyprinodon 

variegatus) 

Na-oPP Flow-through -- -- 

46751208/ 

Unacceptable 

Percent recoveries 

were below 

acceptable range 

Mysid shrimp 

(Americamysis 

bahia), 5-6 days old32

Na-oPP 

(71.4833) 

Flow-through/ 

8.1-8.3/19-22 

ppt/ 19-26 o

C 

96-h LC50 = 0.28 ppm ae 

(0.32 ppm a.i.) 

95% CI: 0.23-0.37 ppm ae 

(0.26-0.42 ppm a.i.) 

96-h NOAEC = 0.063 ppm 

ae (0.071 ppm a.i.) 

Mean measured 

Highly 

toxic 

46751203/ 

Acceptable 

Eastern oyster 

(Crassostrea 

virginica) shell 

deposition, 43 + 3.4 

mm valve height 

Na-oPP 

(71.4833) 

Flow-through/ 

7.9 -8.1/ 30-32 

ppt/ 20-23 o

C 

96-h IC50 = 3.44 ppm ae 

(3.89 ppm a.i.) 

95% CI = 2.76-3.67 ppm ae 

(3.12-4.15 ppm a.i.) 

96-h NOAEC = 0.80 ppm ae 

(0.88 ppm a.i.) 

Moderately 

toxic 

46751202/ 

Acceptable 

Quahog clam 

(Mercenaria 

mercenaria), 2-cell 

embryo 

Na-oPP 

(75.934) Static 48-h IC50 = >8.86 ppm ae 

(>10 ppm a.i.) --- 

25816, 5002007/ 

Supplemental/ 

Mollusc guidelines 

not in existence at 

time of study. 

Unknown test 

temperature and 

water quality. A 

solvent control was 

not included but 

solvents were tested.

Quahog clam 

(Mercenaria 

mercenaria), 2 day 

old larvae 

Na-oPP 

(75.934) Static 

10-d IC50 = 0.66 ppm ae 

(0.75 ppm a.i.) 

(survival and length) 

Highly 

toxic 

CI = confidence interval; NA: Not applicable; N.R. = Not reported; SL = standard length; TN = test number; ts = 

test substance not corrected for percent a.i. 

Aquatic Plants 

Five aquatic plant studies are available to establish the toxicity of oPP and salts to vascular and 

non-vascular aquatic plants (Table 22). The guidelines for testing three algal species (850.4500) 

 

31 For oPP mg a.i. is equal to mg acid equivalent (ae), whereas mg a.i. of Na-oPP were converted to mg ae by 

multiplying by the molar weight ratio of oPP to Na-oPP (170.2/192.19 = 0.886). 32 Range finding was conducted with < 24 hour old and 5-6 day old mysids, no difference in sensitivity was 

observed in the range-finding between these age classes. 

33 The test substance is actually Na-oPP·4H2O but is represented in the table as Na-oPP without the weight percent 

of water. With the weight percent of water added the purity of the test substance Na-oPP·4H2O is 98.16%. 34 The test substance is actually Na-oPP·4H2O but is represented in the table as Na-oPP without the weight percent 

of water. With the weight percent of water added the purity of the test substance Na-oPP·4H2O is >99%. 
Page 66 of 74

and cyanobacteria (850.4550) are satisfied. Guideline 850.4400 for testing a vascular aquatic 

plant is not satisfied (the submitted study did not adhere to dosing progression standards). Data 

from this study and the non-vascular plant studies are expected to be sufficient to conduct the 

risk assessment and a new study is not expected to be required at this time. 

Table 22 – Aquatic Plants Toxicity Data 

Test Species 

Test 

Material 

(% a.i.) 

Exposure Type/

pH/ 

temperature 

Toxicity Endpoint31

MRID/ 

Study Classification/

Comments 

Duckweed 

(Lemna gibba) 

Na-oPP 

(71.4833) 

Static renewal 

days 3 & 5/ 7.8- 

8.0 new, 8.4-9.4 

aged / 24 o

C 

7-day IC50 = 5.5 ppm ae (6.2 ppm a.i.) 

7-day IC05 35 = 0.63 ppm ae (0.71 ppm 

a.i.) 

Mean measured concentrations 

46751209/ 

Supplemental36

Green algae 

(Selenastrum 

capricornutum) 

oPP 

(99.91) 

Static/ 7.41-8.90/ 

24+2 o

C 

96-h IC50 = 1.39 ppm ae 

96-h NOAEC = 0.42 ppm ae 

Mean measured concentrations 

45688201/ 

Acceptable 

Blue-Green alga 

(Anabaena flos-aquae) 

Na-oPP 

(71.4833) 

Static/ 6.8-7.8/ 

24+2 o

C 

96-h IC50 = 2.0 ppm ae (2.3 ppm a.i.) 

96-h NOAEC = 0.030 ppm ae (0.034 

ppm a.i.) 

46823801/ 

Supplemental/ 

4X dose progression, 

age of medium, 

reduced PAR 

Freshwater diatom 

(Navicula pelliculosa) 

Static/ 7.2-9.4/ 

24+2 o

C/ 

96-h IC50 = 1.7 ppm ae (1.9 ppm a.i.) 

96-h NOAEC = 0.52 ppm ae (0.59 

ppm a.i.) 

46751205/ 

Acceptable 

Marine diatom 

(Skeletonema 

costatum) 

96-h IC50 = 5.7 ppm ae (6.4 ppm a.i.) 

96-h NOAEC = 2.1 ppm ae (2.4 ppm 

a.i.) 

46751201/ 

Acceptable 

NA = Not applicable; N.R. = Not reported; ppt: parts per thousand; PAR = Photosynthetically active radiation 

Emergent Rooted Aquatic Macrophytes 

The available studies testing rice (Oryza sativa) are presented in Table 23. Inhibition of 

emergence and growth in rice was 7% and 5%, respectively, in Tier I tests. The guideline 

requirements (850.4225, 850.4250) are satisfied for Tier I testing. Tier II testing is not required, 

because inhibition in emergence and growth was less than 25% in the Tier I tests.

Table 23 – Emergent Rooted Aquatic Plant Toxicity Data 

Test Species 

Test 

Material 

(% a.i.) 

Toxicity Endpoint31

MRID/ 

Study Classification/

Comments 

Rice 

(Oryza sativa) 

– seedling 

emergence (Tier I) Na-oPP 

(71.4833) 

IC25 >886 ppm ae (>1000 mg a.i./L) 

NOAEC = 886 ppm ae (<1000 mg a.i./L) 

7% emergence inhibition after 14 days (1000 mg a.i./L) 

46751207 

Acceptable 

Rice – vegetative 

vigor (Tier I) 

IC25 >886 ppm ae (>1000 mg a.i./L) 

NOAEC = 886 ppm ae (<1000 mg a.i./L) 

2% inhibition in dry weight after 14 days (1000 mg 

a.i./L) 

46751204 

Acceptable 

 

35 Where a NOAEC cannot be calculated, an IC05 will be used as a surrogate. Because of the problems with the IC50

being lower than the LOAEC, the hypothesis method was deemed problematic and the IC05 used rather than asking 

for a repeat of the study. 

36 Dosing progression did not adhere to guideline standards (e.g., doses separated by a dilution factor of 4-5X 

instead of recommended 2X); results in this study occurred between highest and second highest treatment levels, 

making the IC50 lower than the LOAEC. 
Page 67 of 74

Terrestrial Plants 

Seedling emergence and vegetative vigor data are expected to be required (with the exception of 

data for rice). 

Sediment-dwellers 

No data are available. Chronic toxicity data (no guideline number) are expected to be required 

for sediment-dwelling freshwater (2 species) and estuarine/marine (1 specie) invertebrates, 

because oPP and salts are expected to sorb to soil and persist (i.e., half-life >10 days) in aquatic 

sediments. 

Appendix C References 

MRID 46010: Levenstein, I. (1964) To Observe the Effects of Lysol Spray Disinfectant When Sprayed Directly 

upon or in the Vicinity of Parakeets: Assay No. 46229. (Unpublished study received Aug 27, 1969 under 

777-20; prepared by Leberco Laboratories, submitted by Lehn & Fink Products Corp., Montvale, N.J.; CDL: 

100493-B). 

MRID 51597: McCann, J.A. (1974) Letter sent to Charles College dated Oct 22, 1974 Fish toxicity data. (U.S. 

Environmental Protection Agency, Animal Biology Laboratory, unpublished study; CDL:224700-T). 

MRID 110135: Pitcher, F. (1973) Dowicide A: Bluegill: Test No. 640. (U.S. Environmental Protection Agency, 

Pesticides Regulation Div., Animal Biology Laboratory; unpublished study; CDL:129165-A). 

MRID 110137: McCann, J. (1972) Nalco D-2303: Bluegill: Test No. 434. (U.S. Agricultural Research Service, 

Pesticides Regulation Div., Animal Biology Laboratory; unpublished study; CDL:129754-A). 

MRID 110171: WARF Institute, Inc. (1970) Report: WARF No. 9110671. (Unpublished study received Apr 21, 

1970 under 5590-106; submitted by ATI Research Center, Milford, CT; CDL:223189-B). 

MRID 110203: McCann, J. (1974) Letter sent to C. College dated Oct 22, 1974 Toxicity of Dowicide A to fish. 

(U.S. Environmental Protection Agency, Animal Biology Laboratory; unpublished study; CDL: 223721-A). 

MRID 110222: Batchelder, T.; McCarty, W. (1977) Toxicity of Dowicide A to Daphnids: ES-154. (Unpublished 

study received Oct 28, 1977 under 464-78; submitted by Dow Chemical U.S.A., Midland, MI; CDL: 

232113-A). 

MRID 110232: Bentley, R. (1975) Acute Toxicity of Dowicide CO to Bluegill and Rainbow Trout: GH-RC 62. 

(Unpublished study received Aug 25, 1976 under 464-126; prepared by Bionomics, EG & G Environmental 

Consultants, submitted by Dow Chemical U.S.A., Midland, MI; CDL:233706-A).MRID 118876: Vis-Ko, 

Inc. (1970) Effects of Dowicide 1 on Minnows. (Unpublished study received Mar 11, 1971 under 1773-8; 

CDL:006636-A). 

MRID 137908: Dow Chemical U.S.A. (19??) Fish, Snail and Daphnia Toxicity of Torsite M-2469-X-200. 

(Unpublished study received Sep 25, 1964 under unknown admin. no.; CDL:110833-C). 

MRID 156044: Dill, D.; Milazzo, D.; Bartlett, E.; et al. (1985) Evaluation of the Toxicity of Dowicide 1 

Antimicrobial, Technical O-Phenylphenol, to Representative Aquatic Organisms: ES-811. Unpublished 

study prepared by Dow Chemical U S A. 17 p. 

MRID 160149: Grimes, J. (1986) Ortho-phenylphenol Technical: A Dietary LC50 Study with the Bobwhite: Final 

Report: Project No. 103-246. Unpublished study prepared by Wildlife International Ltd. 17 p. 

MRID 160150: Grimes, J. (1986) Ortho-phenylphenol Technical: An Acute Oral Toxicity Study with the Mallard: 

Final Report: Project No. 103-248. Unpublished study prepared by Wildlife International Ltd. 18 p. 

MRID 160151: Grimes, J. (1986) Ortho-phenylphenol Technical: A Dietary LC50 Study with the Mallard: Final 

Report: Project No. 103-247. Un- published study prepared by Wildlife International Ltd. 18 p. 

MRID 164770: Vis Co, Inc. (1971) Effects of Dowicide 1 on Minnows and Determination of Fish Toxicity. 

Unpublished compilation. 4 p. 

MRID 42500204: Campbell, S.; Jaber, M. (1992) Sodium O-Phenylphenate (Dowicide A): An Acute Oral Toxicity 

Study with the Northern Bobwhite: Lab Project Number: ES-DR-0000-9198-6: ES-25-42: 103-383. 

Unpublished study prepared by Wildlife Int'l Ltd. 25 p. 

MRID 42500206: Campbell, S.; Jaber, M. (1992) Sodium O-Phenylphenate (Dowicide A): A Dietary LC50 Study 

with the Mallard: Lab Project Number: 103-382. Unpublished study prepared by Wildlife Int'l Ltd. 21 p. 
Page 68 of 74

MRID 45688201: Hicks, S. (2002) Ortho-Phenyl Phenol: Growth Inhibition Test with the Green Alga, Selenastrum 

capricornutum: Lab Project Number: 46980: 010167. Unpublished study prepared by ABC Laboratories, 

Inc. 55 p. {OPPTS 850.5400}. 

MRID 46751201: Hoberg, J. (2006) OPP/SOPP - Acute Toxicity to the Marine Diatom, Skeletonema costatum, 

Under Static Conditions. Project Number: 12550/6389, 050375. Unpublished study prepared by Springborn 

Smithers Laboratories. 68 p. 

MRID 46751202: Cafarella, M. (2006) OPP/SOPP - Acute Toxicity to Eastern Oyster (Crassostrea virginica) Under 

Flow-Through Conditions. Project Number: 12550/6382, 050368. Unpublished study prepared by 

Springborn Smithers Laboratories. 60 p. 

MRID 46751204: Teixeira, D. (2006) OPP/SOPP - Determination of Effects on Vegetative Vigor of Rice (Oryza 

sativa). Project Number: 12550/6385, 050371. Unpublished study prepared by Springborn Smithers 

Laboratories. 61 p. 

MRID 46751205: Hoberg, J. (2006) OPP/SOPP - Acute Toxicity to the Freshwater Diatom (Navicula pelliculosa). 

Project Number: 12550/6388, 050374. Unpublished study prepared by Springborn Smithers Laboratories. 63 

p. 

MRID 46751207: Teixeira, D. (2006) OPP/SOPP - Determination of Effects on Seedling Emergence of Rice (Oryza 

sativa). Project Number: 12550/6384, 050370. Unpublished study prepared by Springborn Smithers 

Laboratories. 60 p. 

MRID 46751208: Hoberg, J. (2006) OPP/SOPP - Acute Toxicity to Sheepshead Minnow (Cyprinodon variegatus) 

under Flow-through Conditions. Project Number: 12550/6381, 050367. Unpublished study prepared by 

Springborn Smithers Laboratories. 56 p. 

MRID 46751210: Hoberg, J. (2006) OPP/SOPP - Toxicity to Bluegill Sunfish (Lepomis macrochirus) Under FlowThrough Conditions: (Dowicide A Antimicrobial). Project Number: 12550/6391, 050412. Unpublished 

study prepared by Springborn Smithers Laboratories. 57 p. 

MRID 46751203: Hoberg, J. (2006) OPP/SOPP - Acute Toxicity to Mysids (Americamysis bahia) Under Flow - 

Through Conditions. Project Number: 12550/6383, 050369. Unpublished study prepared by Springborn 

Smithers Laboratories. 61 p. 

MRID 46751206: Hoberg, J. (2006) OPP/SOPP - Acute Toxicity to Rainbow Trout (Oncorhynchus mykiss) Under 

Flow-Through Conditions. Project Number: 12550/6390, 050411. Unpublished study prepared by 

Springborn Smithers Laboratories. 56 p. 

MRID 46823801: Hoberg, J. (2006) OPP/SOPP - Growth Inhibition Test with Freshwater Blue-Green Alga 

(Anabaena flos-aquae). Project Number: 12550/6387, 050373. Unpublished study prepared by Springborn 

Smithers Laboratories. 66 p. 

MRID 48135402: Caspers, N. (2010) OSRI Rationale: Ortho-Phenylphenol: EDSP Order Numbers: EDSP-064103-

225, EDSP-064103-226: Life Cycle Test with Water Fleas -- Daphnia magna. Project Number: 51/A/88. 

Unpublished study prepared by Bayer AG. 43 p. 

MRID 48135403: Caspers, N. (2010) OSRI Rationale: Ortho-Phenylphenol: EDSP Order Numbers: EDSP-064103-

225, EDSP-064103-226: Preventol O Extra: Daphnia magna Reproduction Test. Project Number: 

1092/A/01/DL. Unpublished study prepared by Bayer AG. 24 p. 

MRID 48135404: Caunter, J.; Williams, T. (2002) OSRI Rationale: Ortho-Phenylphenol: EDSP Order Numbers: 

EDSP-064103-225, EDSP-064103-226: Preventol O Extra: Determination of Effects on the Reproduction of 

Fathead Minnow (Pimephales promelas). Project Number: AH0603A, 07950/2000, BL7213/B. Unpublished 

study prepared by AstraZeneca UK, Ltd. 62 p. 

MRID 48672606: Lehman, C. ; Fiting, J. ; Hutchinson, K. ; et al. (2012) Ortho-PhenylPhenol: The Fish Short-Term 

Reproduction Assay Using the Fathead Minnow, Pimephales promelas. Project Number: 111032. 

Unpublished study prepared by The Dow Chemical Co. 147p. 

MRID 48672607: Lehman, C.; Hutchinson, K.; Fiting, J.; et al. (2011) Ortho-PhenylPhenol: The Amphibian 

Metamorphosis Assay Using the African Clawed Frog, Xenopus laevis. Project Number: 111018. 

Unpublished study prepared by The Dow Chemical Co. 202p. 

MRID 48916901: Lehman, C.; Hutchinson, K.; Fiting, J. et al. (2012) Ortho-Phenylphenol: The Amphibian 

Metamorphosis Assay Using the African Clawed Frog, Xenopus laevis. Project Number: 111018. 

Unpublished study prepared by The Dow Chemical Company. 204p. 

 
Page 69 of 74

Appendix D Screening Level Down-theDrain Analysis 

The Down-the-Drain (DtD) module of E-FAST (Exposure and Fate Assessment Screening Tool), 

version 2, was used to screen for the potential for aquatic organisms downstream of domestic 

wastewater treatment plants to be exposed to oPP and salts and/or their degradates. The DtD 

module uses daily per capita release of household wastewaters, stream dilution factors, and 

wastewater treatment plant removal efficiency to provide both high-end and median (average) 

time-averaged surface water concentrations of chemicals discharged from domestic wastewater 

treatment plants. The high-end scenario uses surface water concentrations downstream of 

domestic wastewater treatment plants based on the 10th percentile stream dilution factor (SDF); 

the average scenario uses surface water concentrations based on the 50th percentile SDF. SDF is 

defined as the ratio of the stream flow downstream of a wastewater treatment plant to the 

wastewater treatment plant flow. Inputs used to run the DtD module included concentrations of 

concern (COCs) for aquatic organisms, percent removal during wastewater treatment, and 

wastewater treatment plant (WWTP) influent volumes. Wastewater treatment plant influent 

volumes are often derived from information on maximum annual production volume or 

consumption volume of the chemical being assessed. Sometimes hypothetical WWTP influent 

volumes are used to estimate potential exposures to give an idea of how much influent volume 

would be needed to trigger a potential concern. 

The results of the DtD module are expressed as number of days of exceedance of COCs for 

aquatic organisms. COCs for acute effects were determined by dividing LC50 values from acute 

toxicity tests on aquatic vertebrates and invertebrates by 2. COCs for chronic effects for nonlisted species were based on No Observed Adverse Effects Concentration (NOAEC) values from 

tests on aquatic vertebrates and invertebrates. COCs for listed endangered and threatened aquatic 

organisms were determined by dividing LC50 values from acute toxicity tests on aquatic 

vertebrates and invertebrates by 20. Acute COCs for aquatic vascular plants and algae are based 

on EC50 values. COCs for endangered algae and aquatic vascular plants are based on NOAEC 

values. 

The DtD module was run using a high-end scenario to estimate exceedances of concentrations of 

concern for aquatic organisms. 

 
Page 70 of 74

Appendix E Product Chemistry 

Ortho Phenyl Phenol and Salts product chemistry information is summarized in Table 4 and 

Table 24 (source: MRIDs 101697, 41914901, 41605001, 41609501, 41609502, 41609503, 

41609504, 41609505, 42097001, 42381901, 42441701, 42441702, 42441703, 42441704, 

42457001, 42500201, 42500202, 42528701, 43994201 and EPI Suite v4.1). 

Table 24 – Product Chemistry of oPP and Salts 

OPPTS 

Guideline 

No. 

Physical and Chemical 

Properties oPP Na-oPP K-oPP 

830.1550 Product identity and 

composition Refer to Table 3. Refer to Table 3. Refer to Table 3. 

830.1600 

Description of materials 

used to produce the 

product 

Confidential Business 

Information (CBI) CBI CBI 

830.1620 Description of production 

process 

CBI CBI CBI 

830.1650 Description of Formulation 

Process CBI CBI CBI 

830.1670 Discussion of Formation of

Impurities CBI CBI CBI 

830.1700 Preliminary analysis CBI CBI CBI 

830.1750 Certified limits CBI CBI CBI 

830.1800 Enforcement analytical 

method Gas Chromatography (GC) GC GC 

830.1900 Submittal of samples CBI CBI CBI 

830.6302 Color White to light buff crystals White crystalline 

flakes White flakes 

830.6303 Physical State Solid (flakes) Solid (flakes) Solid (flakes) 

830.6304 Odor Slight phenolic odor Slight phenolic odor Slight phenolic odor 

830.6313 

Stability to normal and 

elevated temperatures, 

metals, and metal ions 

Stable at normal conditions. Stable at normal 

conditions. 

Stable at normal 

conditions. 

830.7000 pH 6.1 in aqueous solution at 22.7 

° C 

12 to 13.5 in 

saturated water 

solution at 25° C. 

12 to 13.5 in 

saturated water 

solution at 25° C. 

830.7050 UV/Visible Absorption 

245 to 287nm 

Not expected to absorb UV at 

λ > 300 nm 

------- ------- 

830.7200 Melting point 56-58 oC. 230.07 °C (Source: 

EPI Suite) 

230.07 °C (Source: 

EPI Suite) 

830.7220 Boiling point 286oC at 760 mm Hg 537.41 °C (Source: 

EPI Suite v4.1) 

537.41 °C (Source: 

EPI Suite v4.1) 

830.7300 Density 1.213 g/cu cm at 25° C. 1.3 g/cu cm at 25° C. 1.3 g/cu cm at 25° C.

830.7370 Dissociation Constants in 

water 

pKa = 9.55 at 22.5°C. 

pKa = 9.9 at 25°C. 

pKa = 9.97 at 25°C. 

It is a weak acid. 

Dissociates in water. 

pKa: 9.84 at 20oC. 

Dissociates in water. 

pKa: 9.84 at 20oC. 

830.7520 Particle size, fiber length, 

& diameter distribution 

Not Applicable; soluble in 

water 

Not Applicable; 

soluble in water 

Not Applicable; 

soluble in water 
Page 71 of 74

OPPTS 

Guideline 

No. 

Physical and Chemical 

Properties oPP Na-oPP K-oPP 

830.7550 

Partition coefficient (noctanol/water) 

Log Kow 

3.3 (Source: EPI Suite v4.1) 

log Pow: 3.09-3.36 

log Pow: 3.12 (20 °C, pH 7). 

0.59 (Source: EPI 

Suite v4.1). 

0.59 (Source: EPI 

Suite v4.1). 

830.7840 Water Solubility 

700 mg/L at 25°C in water. 

0.760 g/1000 g in water (pH 

5.67) (20oC). 

60.6 g/100 mL, 

53.37% (w/w) 

(20oC). 

534 g/1000 g in 

water (pH 13.61) 

(20oC). 

Highly water soluble.

534 g/1000 g in 

water (pH 13.61) 

(20oC).

830.7950 Vapor pressure 

2.00 x 10-3 mm Hg at 25° C 

(Source: EPI Suite version 

4.1, Experimental). 

1.6 x 10-3 mm Hg at 25oC. 

0.0017 mmHg at 25oC. 

1.91 x 10-11 mm Hg 

at 25 °C (Source: EPI 

Suite v4.1). 

1.8 x 10-9 mmHg at 

25oC. 

1.91 x 10-11 mm Hg 

at 25 °C (Source: EPI 

Suite v4.1). 

 
Page 72 of 74

Appendix F Comments Received 

Concerning the Preliminary Work Plan 

On September 25, 2013 EPA opened a 60-day public comment period on the preliminary work 

plan (PWP) for the registration review of for ortho-Phenyl Phenol and Salts. The comment 

period ended on November 25, 2013. During the public comment period the Agency received 

two submissions from: 

 The FIFRA Endangered Species Task Force (FESTF), and 

 The Physicians Committee for Responsible Medicine (PCRM) 

Submitter: PCRM 

1. Comment: We recommend that OECD Test Guideline 223, Avian Acute Oral Toxicity 

Test, be used as the protocol instead of EPA Guideline 850.2100 in the interest of 

reducing the numbers of animals used by up to 61%.37 We also refer the registrant to the 

“Guidance for Classifying Studies Conducted Using the OECD Test Guideline 223 

(TG223) (Acute Avian Oral Sequential Dose Study)” available on the Agency’s website. 

Response: The Agency concurs that the “Guidance for Classifying Studies Conducted 

Using the OECD Test Guideline 223 (TG223) (Acute Avian Oral Sequential Dose 

Study)” should be consulted if the registrant intends to submit an avian acute oral study 

based on OECD Test Guideline 223. The guidance can be found at: 

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_bio

logy_tech_team/review_avian_acute_oral_oecd_tg223.htm.

It should be noted that the guidance specifies that “a study conducted using TG223 may 

be classified as "acceptable" (i.e., adequate for use in risk assessment and fulfills a data 

requirement for avian acute oral toxicity data) if it is scientifically valid, is conducted 

using the "LD50- slope test" or "limit dose test" guidelines (the "LD50 - only test" is not 

adequate for fulfilling data requirements) (see APPENDIX A for details), and meets all 

of the following criteria: 

 The study is conducted using bobwhite quail (other test species may be acceptable if 

they have low background mortality in the laboratory and do not regurgitate during 

the study; however, if a species other than bobwhite quail is used, the study should be 

reviewed by the TBTT - see below; please note that the background mortality data for 

the species in question should be available from the submitting laboratory at the time 

of the TBTT review). 

 The chemical being tested does not cause delayed effects. 

 37 OECD. (2010). Test Guideline 223: Avian Acute Oral Toxicity Test Method. OECD Guidelines for the 

Testing of Chemicals. Website accessed on August 31, 2012 at 

http://lysander.sourceoecd.org/vl=3006812/cl=16/nw=1/rpsv/ij/oecdjournals/1607310x/v1n2/s33/p1 
Page 73 of 74

 For a "limit dose test", it is conducted at 2,000 mg a.i./kg-bw or the environmentally 

relevant concentration (whichever is greater). 

 For the "LD50 - slope test", the raw data and results are submitted electronically using 

the SEquential DEsign Calculator (SEDEC) (the Excel calculator that determines the 

placement of doses during testing and is used to estimate the LD50, slope and 

confidence limits for TG223 studies) (see APPENDIX A for details). 

 The study meets the same validity requirements as 850.2100 (e.g., a study should be 

invalidated if > 10% of the controls die). 

 Control birds are not added during the course of the study. 

Studies that deviate from the above criteria may be classified as "acceptable" or 

"supplemental" if they are considered adequate for use in risk assessment or "invalid" if 

they are not scientifically sound; however, consultation with the TBTT will need to 

confirm the classification for any TG223 study that deviates from the above criteria. If 

you have questions regarding this policy you may contact any of the project workgroup 

members listed at the end of Appendix A to this guidance memo.” 

2. Comment: With respect to the immunotoxicity study we found the following two studies 

on Toxnet that may fulfill the Agency’s needs without additional testing. Using such a 

weight-of-evidence approach, if possible, is consistent with Agency policy outlined in the 

Guiding Principles for Data Requirements document published on May 31, 2013.38 

o-Phenylphenol does not induce changes in immune function in mice following short 

term oral administration. This finding was confirmed in studies in which B6C3F1 mice 

were administered oral doses of o-phenylphenol (up to 200 mg/kg day) for 10 days and 

then examined for a variety of immune functions.39

 o-Phenylphenol was given with drinking water: 10, 100 ug/mL for 80 weeks to male and 

female BALB/c mice. On 80 weeks the spleen weights of the treated females were higher 

than in the control females. Treated female groups showed immunosuppression in the 

lymphocyte transforming test (LTT) and in the plaque forming assay (PFC). In the treated 

male groups there were no significant effects on immunoproerties.40

Response: The Agency thanks PCRM for this information and will consider these studies 

as it conducts the registration review and makes its registration review decisions. EPA’s 

issuance of a DCI is a public statement that the data is needed, and will be relied on, thus 

“triggering” the data compensation provisions of section 3(g)(2)(B) of FIFRA.

 38 EPA OPP. Guiding Principles for Data Requirements http://www.epa.gov/pesticides/regulating/datarequire-guide-principle.pdf 

39 DHHS/NTP; Toxicology and Carcinogenesis Studies of ortho-Phenylphenol alone and with 7,12-

Dimethylbenz(a)anthracene in Swiss CD-1 Mice. (Dermal Studies) p.14 (1986) Technical Rpt Series No. 301 NIH 

Pub No. 86-2557. 

40 European Commission, ESIS; IUCLID Dataset, Biphenyl-2-ol (90-43-7) p.124 (2000 CD-ROM edition). 

Website accessed on November 20, 2013 at http://esis.jrc.ec.europa.eu/
Page 74 of 74

Submitter: FIFRA Endangered Species Task Force 

3. Comment: FESTF requests that any technical registrant for ortho-phenyl phenol who is 

not a member of the FESTF (or a company having met its data compensation obligations) 

be asked to provide a formal offer-to-pay to FESTF for reliance on their data. In their 

comment, FESTF also noted that Dow AgroSciences LLC is an FESTF member. 

Response: The Agency thanks the FESTF for its comment and will consider all 

appropriate information as it conducts the registration review and makes its registration 

review decisions.