### 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 a nd 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 Regist ered 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 ............................................................................................................ 2 2 3.2.1 Tolerance Information ............................................................................................ 23
3.2.2 Food ........................................................................................................................ 2 3 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-Applic ation 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 o PP and its Salts ...................................................................................................... 27
4.1.2 Photodegradates of o PP .......................................................................................... 28 4.1.3 Water Quality .......................................................................................................... 29
4.2 Conceptual Models for Envir onmental 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 Wild life Exposure Estimates ............................................ 42
4.4.2 Screening Level Down-the-Drain Analysis ............................................................ 43
4.5 Effects Analysis Plan ..................................................................................................... 44
5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 44
6 Optional Label Changes ........................................................................................................ 45
7 Next Steps .................................................................................................................... ......... 46 8 References .................................................................................................................... ......... 47

### Page 4 of 74 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 th e Preliminary Work Plan ............................ 72

List of Tables Table 1 – Summary of Anticipated Ri sk Assessments and Data Needs for o PP and its Salts ....... 8 Table 2 – Anticipated Regist ration Review Schedule .................................................................... 8 Table 3 – Chemical Identification of o PP and its Salts .................................................................. 9 Table 4 – Physical-Chemical and Fate Properties for o PP and its Salts ......................................... 9 Table 5 – Summary of E nd Use Products Containing o PP or its Salts ......................................... 10 Table 6 – Summary of Registered Uses of o PP and its Salts ........................................................ 11 Table 7 - Incidents Reported for o PP and its Salts (July 2006 to July 2013) ............................... 13 Table 8 – Studies Anticipated as Need ed for the Registration Review of o PP and its Salts ........ 15 Table 9 – Existing Toxicological Endpoints for o PP .................................................................... 21 Table 10 – Occupational Handl er Exposure Scenarios for o PP ................................................... 25 Table 11 – Residential Handler Exposure Scenarios for o PP ....................................................... 25 Table 12 – Residential Post-App lication Exposure Scenarios for o PP ......................................... 26 Table 13 – Selected Ecological Effects Endpoi nts for the Ecological Risk Assessment ............. 40 Table 14 – Summary of Screening Level Down-the-Drain Analysis Results .............................. 43 Table 15 – Acute Toxicity Studies for o PP .................................................................................. 48 Table 16 – Key Physical-Chemical Properties a nd Environmental Fate Characteristics of o PP and its Salts ..................................................................................................................... .............. 58 Table 17 – Physical/Chemical and Environmenta l Fate Characteristics of PBQ and PHQ ......... 59 Table 18 – Avian Toxicity Data ................................................................................................ .... 62 Table 19 – Freshwater Fish Toxicity Data .................................................................................... 6 3 Table 20 – Freshwater Invertebrate Toxicity Data ....................................................................... 64 Table 21 – Estuarine/Marine Fish a nd Invertebrate Toxicity Data ............................................... 65 Table 22 – Aquatic Plants Toxicity Data ...................................................................................... 66 Table 23 – Emergent Rooted Aqua tic Plant Toxicity Data .......................................................... 66 Table 24 – Product Chemistry of o PP and Salts ........................................................................... 70

List of Figures Figure 1 - Conceptual Model for Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Sanitizer/Disin fectant and Material Preservative Cleaning Solution Uses ................................................................................................................. ........ 31 Figure 2 - Conceptual Model for Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Antimicr obial Fruit and Vegetable Washes ....................... 32 Figure 3 - Conceptual Model for Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Wood Preservatives for Sapstain Control .......................... 33 Figure 4 -- Conceptual Model for Ecological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Materials Preservatives in Metal Working Fluids .............. 34

### Page 5 of 74 Figure 5 - Conceptual Model for Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Swimming Pool s, Spas, Ornamental Ponds, Aquaria, and Waterbed Water Uses ........................................................................................................... . 35 Figure 6 - Conceptual Model for Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from La kes, Ponds, and Reservoirs ............................................. 36 Figure 7 - Conceptual Model for Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Orga nisms from Cooling, Evaporativ e Condenser, Heat Exchanger, Industrial Scrubbing, and Paper Mill Water Systems ............................................................ 37 Figure 8 - Conceptual Model for Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organi sms from Biocides in Oil Drill ing Muds/Fluids and Secondary Recovery Water ................................................................................................................ ..... 38 Figure 9 - Conceptual Model for Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Material Preservative Uses Other Than Metal Working Fluids and Cleaning Solutions ............................................................................................... 3 9

### Page 6 of 74 

# 1 Introduction

This document is the United States Environmen tal Protection Agency’s (USEPA, EPA or “the Agency”) Final Work Plan (FWP) for ortho -phenyl phenol ( o PP) and its salts. The FWP document explains what EPA's Office of Pesticide Programs (OPP) knows about o PP and its salts, highlighting anticipated da ta and assessment needs, identif ying the types of information that would be especially useful to the Ag ency in conducting the re view, and providing an anticipated timeline for completing o PP’s review.

The registration review process was designed to include a publi c participation component to solicit input from interested stak eholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows abou t oPP and its salts and wh at types of new data or other information would be helpful for the Agen cy to receive as it moves toward a decision on

o PP and its salts.



# 1.1 Statutory and Regu latory Authority

The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the USEPA based on scientific data showing that they will not cause unreasonable risk s to human health or the environment when used as directed on produc t labeling. The registra tion 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 environm ent. Changes in scien ce, 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. Inform ation on this program is provided at http://www.epa.gov/oppsrr d1/registration_review/

.
The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing registra tion review begin at 40 CFR 155.40. The Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are n eeded to make a registration review decision.

The for ortho -phenyl phenol Preliminary Work Pl an (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 an ticipated registration review table.

 Updated Section 7, Next Steps.

 Added Appendix F.

The Agency received two submissions during th e 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 anticipa ted data needs or registration review schedule in the o PP PWP. This document makes final the work plan for the o PP and salts registration review process.

### Page 8 of 74 Table 1 – Summary of Anticipated Ri sk Assessments and Data Needs for o PP 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 Regi stration Review Schedule Anticipated Activity Target Date* Completion Date Phase 1: Openin g 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 o PP and its salts case (Case 25 75) 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 ingredie nts to be assessed in Case 2575: ortho -phenyl phenol ( o PP) (PC Code 064103); sodium ortho -phenyl phenate a sodium salt of o PP (Na- o PP; PC Code 064104); and potassium ortho -phenyl phenate a potassium salt of o PP (K- o PP; PC Code 064108).

Table 3 – Chemical Identification of o PP and its Salts

Chemical Name o PP Na- o PP K- o PP

Common Name ortho -phenyl phenol; 2-phenyl phenol Sodium ortho -phenyl phenate;

o PP, sodium salt Potassium ortho -phenyl phenate; o PP, 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 C 12 H 10 O C 12 H 9 NaO C 12 H 9 KO

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

Molecular Structure



### Product chemistry and fate property informa tion relevant to the risk assessment of o PP 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 in cluded 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 ( o PP

- 

### ). The equilibrium in solution between the o PP

- 

### anion and the protonated or unionized o PP depends on the pH of the solution. The fate and transport data supporting o PP can be used to support the salts, and similarly, the fate and transport data su pporting its Na and K salts may be used to support o PP.

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

OPPTS Guideline No. Physical and Chemical Properties o PP Na- o PP K- o PP

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 o C 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 o PP Na- o PP K- o PP

830.7220 Boiling point 286 o C 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 K ow 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, 4244 1703, 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 o PP or its salts as an active ingredient (a.i.).
Table 5 – Summary of End Use Products Containing o PP or its Salts

Chemical

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

o PP 064103 77 0.014 to 99.5 Pressurized Liquid, Soluble Concentrate (SC), Ready to Use (RTU) Solution, Wipe

Na- o PP 064104 19 0.21 to 71.7 SC, RTU Solution, Emulsifiable Concentrate, Pressurized Liquid (i.e., aerosol can)

K- o PP 064108 3 0.159 to 55.6 SC, Pressurized Liquid


### Table 6 includes a summary of the registered o PP and salts uses that will be assessed in this registration review. Registered pr oduct uses include: disinfectants , bacteriocides/bacteriostats, deodorizers, algaecides, fungicides/fungistats, in secticides, miticides, molluscicides, sanitizers, termiticides, tuberculocides, and virucides.

### Page 11 of 74 Table 6 – Summary of Registered Uses of o PP 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 Lagoons 1 Spray 4 lb ai/acre

Commercial/Institutional/Industria l (CII) Premises and Equipment

Nonporous, nonfood cont act surfaces including transportation facilities and ve hicles, 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 boxes 2 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 Paint 5 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 ft 2 roof and 20 gallons ft 2 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 includi ng 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 spottreatments 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 (quarte r-acre lot per house) and that each homeowner applies the entire contents of one container of spray (=170 ounces). Ther efore, 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 o PP as an a.i. was registered in the U.S. in 1948. The first product containing Na- o PP as an active ingredient was register ed in the U.S. in 1948. The first product containing K- o PP as an active ingredient was registered in the U.S. in 1996. The Agency completed a Reregistration Eligibility Decision (RED) for the o PP 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 o PP 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 o PP and its salts. Most (855) of these incidents involved dual purpose produc ts that contain disinfectants and insecticides such as cyfluthrin, permet hrin, 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 o PP 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 inci dents), Major (3 incidents) an d 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 o PP on a regular basis while she was pregnant.

 One of the disinfectant-only major incident s involved a man who had been using the product without gloves, who wa s hospitalized with acute pa ncreatitis and secondary respiratory failure.

 The other disinfectant-only major incide nts involved an employee who suffered respiratory arrest after be ing exposed to the product.

 The disinfectant/insecticide ma jor 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 in cident data system does not necessarily mean that they were caused by the associated product. In the case of the intraventricular hemorrhage, for example, th e 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 hemo rrhage 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 irri tation and hives, resp iratory irritation and systemic effects such as dizziness and nausea.



## 1.7.2 Ecological

No incidents are reported in the Agency’s Inci dent 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 anticipate d as being needed to su pport this registration review.Docket Number EPA-HQ-OPP-2013-0524www.regulations.govPage15of74Table 8 – Studies Anticipated as Needed for the Registration Review of oPP and its SaltsGLNStudy NameTestSubstance7Time Frame(Measured inmonths fromDCI Receipt)RiskAssessment(s)Data WillSupportUse Site(s) Triggering AnticipatedData RequirementApplicable Exposure ScenarioStudies Anticipated to be Required through the Registration Review DCI835.1110Activated Sludge SorptionIsothermTGAI 12 EcologicalSanitizer/Disinfectant; Materialspreservatives; Antimicrobial fruit andvegetable washes; food contactsanitizer; Wood Preservative forsapstain control; Swimming pools,spas, ornamental ponds, aquaria,waterbed water;Commercial/Industrial Process andWater Systems; Biocides in oil drillingmuds and secondary recovery waterTransport to wastewater treatmentplants and potential subsequentexposure to aquatic organisms insurface water835.1230 Adsorption/Desorption TGAI 12EcologicalWood preservative; Exteriorarchitectural paints and coatingsmaterial preservative; Exterior roof,siding, fence, and deck algaecide andantimicrobial treatment; Lawn, turf,surface soil, sidewalk, parking lot,patio, ant hill insecticide useTreated wood; Exterior paint/stain;Exterior building and structuretreatment; Residential lawn andimpervious surface835.1240 Leaching Studies, Soil TGAI 12835.2240 Photodegradation in Water TGAI 12 Ecological AllIndustrial processes; DtD premiseand equipment uses; Materialpreservatives with DtD releases;Residential lawn and impervioussurface; Treated wood; Exteriorpaint/stain; Exterior building andstructure treatment; Residentiallawn and impervious surface835.2410 Photodegradation in Soil TGAI 12 EcologicalWood preservative; Exteriorarchitectural paints and coatingsmaterial preservative; Exterior roof,Leaching from treated wood;Exterior paint/stain; Leaching fromExterior building and structure7The Agency lacks information on the fate profile for oPP withregard to the potential for biotic degradates/transformation products to be formed. Consequently, inthe absence of information, the Agency will use a total toxic residue approach to determine potential toxicity to ecological organisms. This approach assumes anymajor degradates formed would be as toxic as the parent. The Agency will consider conducting a more refined risk assessment ifinformation on toxicity of anymajor degradates identified is provided.Page16of74GLNStudy NameTestSubstance7Time Frame(Measured inmonths fromDCI Receipt)RiskAssessment(s)Data WillSupportUse Site(s) Triggering AnticipatedData RequirementApplicable Exposure Scenario835.4100 Aerobic Soil Metabolism TGAI 24siding, fence, and deck algaecide andantimicrobial treatment; Lawn, turf,surface soil, sidewalk, parking lot,patio, ant hill insecticide usetreatment; Run-off to Residentiallawn and impervious surface835.4300Aerobic AquaticMetabolismTGAI 24Ecological AllTransport to wastewater treatmentplant (WWTP) and subsequentrelease to surface waterdownstream; leaching and run-offto surface water; transport tosurface water via stormwaterdrain; direct discharge to surfacewater835.4400Anaerobic AquaticMetabolismTGAI 24OECD 209 or850.68008Activated SludgeRespiration Inhibition(ASRI)TGAI 12EcologicalSanitizer/Disinfectant; Materialspreservatives; Antimicrobial fruit andvegetable washes; food contactsanitizer; Wood Preservative forsapstain control; Swimming pools,spas, ornamental ponds, aquaria,waterbed water;Commercial/Industrial Process andWater Systems; Biocides in oil drillingmuds and secondary recovery waterTransport to wastewater treatmentplant and potential effects to andbiodegradation by WWTPmicroorganisms835.3110835.3220835.3240835.3280Ready biodegradability testor one of threebiodegradation in activatedsludge simulation tests9TGAI 128EPA published draft guidance under guideline OPPTS 850.6800 and has since published final guidance for this study under guideline OCSPP850.3300:http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0021. The anticipated DCI will provide that OCSPP 850.3300 may beused in place of OECD 209 if the test substance is not sufficiently soluble to allow preparation ofa concentrated stock solution in water. The Agency has includedthis study in 40 CFR 158(W). OECD Test Guideline 209 can alsobe used as guidance for this study, available online athttp://www.oecdilibrary.org/content/book/9789264070080-en.9The results of the ASRI test will determine which of these four biodegradation tests is/are required. If the ASRI test EC50is less than or equal to 20 mg/L, theneither the (i)Biodegradation in Activated Sludge Study or (ii)Simulation Test – Aerobic Sewage Treatment: A. Activated SludgeUnits or (iii) the Porous Pot Testis expected to be required. If the ASRI test EC50is greater than 20 mg/L, then the registrant would likely be required to conduct either: (i) Ready Biodegradabilityor (ii) a) Biodegradation in Activated Sludge or b) SimulationTest – Aerobic Sewage Treatment:A. Activated Sludge Units or c)the Porous Pot Test. If the ReadyBiodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, the antimicrobial fails the ReadyBiodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or c) thePorous Pot study would likely be required.Page17of74GLNStudy NameTestSubstance7Time Frame(Measured inmonths fromDCI Receipt)RiskAssessment(s)Data WillSupportUse Site(s) Triggering AnticipatedData RequirementApplicable Exposure ScenarioSpecial StudyLeaching study, paint, stainand coatings; concreteTEP 24 EcologicalMaterial Preservative (Paints, stains,and coatings; concrete and concreteadditives; ceramic glazes)Leaching/run-off from exterior in-service use of preservedpaints/stains/coatings, concrete andconcrete additivesSpecial StudyLeaching study, cottontextilesTEP 24 Ecological Material Preservative TextileLeaching and subsequent transportto soil and potential run-off tosurface water; leaching fromtextiles via washing textilesfollowed by transport towastewater treatment plants andpotential subsequent transport tosurface water850.1350Aquatic invertebrate lifecycle (saltwater)TGAI 24 EcologicalAllTransport to wastewater treatmentplant (WWTP) and subsequentrelease to surface waterdownstream; leaching and run-offto surface water; transport tosurface water via stormwaterdrain; direct discharge to surfacewaterNon-guidelineWhole sediment chronictoxicity10TGAI 24 Ecological850.1710 Oyster BCF TGAI 24 Ecological850.1730 Fish BCF TGAI 24 Ecological850.2100Avian oral toxicity(passerine species)TGAI 24 EcologicalLawn, turf, surface soil, sidewalk,parking lot, patio, ant hill insecticideuseResidential lawn and impervioussurface850.2300 Avian reproduction11TGAI 24 Ecological850.3020Honey bee acute contacttoxicityTGAI 12 EcologicalWood preservative; Lawn, turf,surface soil, sidewalk, parking lot,patio, ant hill insecticide useTreated wood850.303012Honey bee toxicity ofresidues on woodTGAI 12 Ecological Woodpreservative Treated woodSpecial studyHoney bee oral toxicity(adults)13TGAI 12 EcologicalLawn, turf, surface soil, sidewalk,parking lot, patio, ant hill insecticideResidential lawn and impervioussurface10Results from studies conducted usingChironomus dilutus,Hyalella azteca, andLeptocheirus plumulosusare expected to be requiredto satisfy this anticipatedrequirement11Results from studies conducted using an upland game species and a waterfowl species are expected to be required to satisfy this anticipated requirement.12Protocol modifying study using wood should be submitted for review prior to conduct of the study.Page18of74GLNStudy NameTestSubstance7Time Frame(Measured inmonths fromDCI Receipt)RiskAssessment(s)Data WillSupportUse Site(s) Triggering AnticipatedData RequirementApplicable Exposure ScenarioSpecial studyHoney bee oral toxicity(larvae)13TGAI 12 Ecologicaluse850.4100Seedling emergence(terrestrial plants)14TGAI 12 EcologicalLawn, turf, surface soil, sidewalk,parking lot, patio, ant hill insecticideuse; Exterior roof, siding, fence, anddeck algaecide and antimicrobialtreatmentResidential lawn and impervioussurface; Exterior building andstructure treatment850.4150Vegetative vigor (terrestrialplants)14TGAI 12 Ecological850.6100Environmental ChemistryMethods and AssociatedIndependent LaboratoryValidation for waterTGAI 12 EcologicalLawn, turf, surface soil, sidewalk,parking lot, patio, ant hill insecticideuseResidential lawn and impervioussurface; Exterior building andstructure treatment875.1700 Product Use Information TGAI 12 Human Health All All870.2300 Indoor Surface Residues TGAI 12 Human Health Residential and Public Access SitesIncidental oral exposure todisinfected floors.870.3465 Inhalation Toxicity, 90 day TGAI 24 Human Health All AllNon-GuidelinePaint Chamber EmissionsStudyTGAI 12 Human Health PaintsInhalation exposure followingapplication of treated paints.Studies Expected to be Requiredthrough the Anticipated Post-RED DCI850.1075Acute toxicityestuarine/marine fishTGAI 12Ecological AllIndustrial processes; DtD premiseand equipment uses; Materialpreservatives with DtD releases;Residential lawn and impervioussurface; Treated wood; Exteriorpaint/stain; Exterior building andstructure treatment; Residentiallawn and impervious surface850.1300Aquatic invertebrate lifecycle (freshwater)15TGAI 12850.1400 Fish early life stage16,17TGAI 12870.7800 Immunotoxicity TGAI 12 Human Health All All13Based on the “White Paper in Support of the Proposed Risk Assessment Process for Bees” as submitted to the FIFRA Scientific Advisory Panel, docket numberEPA-HQ-OPP-2012-0543-0004athttp://www.regulations.gov.14Plant toxicity data with a monocot species, rice, have been submitted. Additional dataare anticipated to be needed for six species of dicots (from at least fourfamilies; one species must be soybean) and three species of monocots (from at least two families; one species must be corn). Ofthe species selected to satisfy thisanticipated data need, at least one test species should be a rootcrop (either a monocot such asonion or a dicot such as carrot, table beet, or sugar beet).15Results from an acceptableDaphnialife cycle test may be used to calculate a chronictoxicity endpoint for estuarine/marine invertebrates.16Results from studies conducted using a freshwater species and asaltwater species are expected to be required to satisfy thisanticipated requirement.17Results from an acceptable freshwater fishearly life stage test may be used to calculate a chronic toxicity endpoint for estuarine/marine fish.Page19of74GLNStudy NameTestSubstance7Time Frame(Measured inmonths fromDCI Receipt)RiskAssessment(s)Data WillSupportUse Site(s) Triggering AnticipatedData RequirementApplicable Exposure Scenario875.1200 Indoor Dermal Exposure TGAI 24 Human HealthMaterial preservation, industrialprocess treatment, hard surfacedisinfection, preservedpaints, sapstaintreatment, carpets, air sanitizers,fingerpaintsOccupational handler scenarios:(1) Open pour liquids and solublepowders for material preservationand industrial process treatment18,(2) Low pressure/high pressurehandwand, aerosol can, triggersprayer, mop and wipe for hardsurface disinfection, (3) Handheldfogging for hard surfacedisinfection19, (4) Brush, roller andspray for preserved paints, (5) Dipand spray for sapstain treatment.Residential handler scenarios: (1)Aerosol can, trigger sprayer, mopand wipe for hard surfaces andcarpets, (2) Aerosol can airsanitizers, (3) Brush, roller andspray for preserved paints, (4)Hand application of finger paints.18If labels are amended to require closed loading and delivery systems for liquid products and water soluble packaging for solidproducts used for materialpreservation and industrial process treatment, the agency may consider waiving the need for the exposure study for open pouringof liquids and soluble powders.19If labels are amended to require that fogging be done only byautomatic equipment, the agencymay consider waiving the need for the exposure study forhandheld fogging.Page20of74GLNStudy NameTestSubstance7Time Frame(Measured inmonths fromDCI Receipt)RiskAssessment(s)Data WillSupportUse Site(s) Triggering AnticipatedData RequirementApplicable Exposure Scenario875.1400 Indoor Inhalation Exposure TGAI 24 Human HealthMaterial preservation, industrialprocess treatment, hard surfacedisinfection, preserved paints, sapstaintreatment, carpets, air sanitizers,fingerpaintsOccupational handler scenarios:(1) Open pour liquids and solublepowders for material preservationand industrial process treatment18,(2) Low pressure/high pressurehandwand, aerosol can, triggersprayer, mop and wipe for hardsurface disinfection, (3) Handheldfogging for hard surfacedisinfection19, (4) Brush, roller andspray for preserved paints, (5) Dipand spray for sapstain treatment.Residential handler scenarios: (1)Aerosol can, trigger sprayer, mopand wipe for hard surfaces andcarpets, (2) Aerosol can airsanitizers, (3) Brush, roller andspray for preserved paints, (4)Hand application of finger paints.875.2800Descriptions of HumanActivityTGAI 12 Human Health All AllSpecial StudyMigration Study for Plasticsand PolymersTGAI 12 Human HealthMaterial preservation of plastics andpolymersIncidental Oral Exposure toHousehold Items and ToysManufactured from Plastics andPolymers preserved withoPP.Studies no longer anticipated as needed875.1600Applicator ExposureMonitoring Data Reporting

### Page 21 of 74 

# 3 Human Health Risk Assessment

EPA anticipates the need to conduct a human health risk assessment for o PP 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 t oxicological endpoints as pa rt of this registration review. The toxicological poi nts of departure (PODs) for o PP are included in Table 9. These PODs were established in 2004 by the Antimicrobi als 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 ar e expected to be required for registration review will be considered in the final risk assessment for o PP and its salts.
Table 9 – Existing Toxicological Endpoints for o PP

Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Tar g et Mar g in of Exposure (MOE), Uncertaint y 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 repr esent 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-speciesextrapolation, 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-speciesextrapolation, 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-speciesextrapolation, 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/cm 2 ) A Target MOE = 100 FQPA SF = 1 UF = 100 (10x inter-speciesextrapolation, 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) Tar g et Mar g in of Exposure (MOE), Uncertaint y 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-speciesextrapolation, 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 gr oss 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-speciesextrapolation, 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-speciesextrapolation, 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 gr oss 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 cm μ g 200 dosed rat of area cm 100 mg μ g 1000 rat kg 200

. 0 rat kg mg 100

  

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, a ssuming 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 th e dietary (food) assessment conducted in support of the 2006 RED. Uses of o PP 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 perf ormed for each population subgroup for which an endpoint exists. A risk estimate th at is less than 100% of the ac ute or chronic PAD is not of concern. Acute dietary risk for o PP and salts will not be assessed because there are no adverse systemic effects attributable to a si ngle dose. Chronic dietary risk for o PP and salts will be assessed by comparing dietary exposure estimate s expressed in mg/kg/day to the chronic Population Adjusted Dose (cPAD).



## 3.2.1 Tolerance Information

EPA has established a tolerance exemp tion at 40 CFR 180.920 for use of Na- o PP as an intentionally-added in ert ingredient (preservative) in pes ticide formulations not to exceed 0.1% of the formulation to be app lied to growing crops only. In ad dition, tolerances have been established (40 CFR 180.129) for the combined residues of o PP and Na- o PP from postharvest application on apple, cantaloupe, ca rrot, cherry, citrus fruit, cucu mber, lemon, nectarine, orange, bell pepper, peach, pear, pineapple, plum, sweet potato, and tomato.
The Food & Drug Administration (FDA) has establis hed a number of food additive regulations for o PP and Na- o PP. For o PP, regulations have been established as a (an):

 Fungicide at ≤ 0.01% by weight of the base polym er 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 defoam ing agents used in paper and paperboard production (21 CFR 176.210);

 Antioxidant/antioxonant to manufacture rubber articles for repeat-u se 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- o PP, regulations have b een 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 artic les 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 chroni c dietary risk assessment conducted in support of the 2006 RED; as there are no adverse systemic eff ects 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 resi dues 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 conclude d that there were no risks of concern for chronic dietary exposures to o PP 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 o PP via drinking water is expected to be minimal due to o PP’s degradation in soil and via photolys is and its immobility in soil (see Appendix B ), the agency will determine whether there is the potential for o PP and salts to contaminate drinking water upon evaluation of the anticipated environmental fate studies duri ng the risk assessment stage of this registration review.


# 3.3 Occupational and Re sidential 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 o PP and its salts that may result in occupational and re sidential exposures are included in Table 10, Table 11, and Table 12.



## 3.3.1 Occupational Handler Exposure

Occupational handler dermal and inhalation exposures to o PP were assessed in the 2006 RED for open pouring for material preser vation, low and high pressure ha ndwand application, aerosol can and trigger spray application and mopping and wiping. As there were no chemical-specific exposure data available, exposures were assesse d 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 inhala tion 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 ba seline dermal MOE= 93, intermediate-term baseline dermal MOE = 84, and interm ediate-term baseline Total MOE = 78.

 Materials Preservatives, liquid pour preservation of textil es: short-term PPE dermal MOE= 92, intermediate-term PPE dermal MOE = 83, and intermediate-term Total MOE
= 78.

 Materials Preservatives, painte r (applying paint post-prese rvation), airless sprayer: baseline dermal short-term MOE = 66. It is important to note that th e open pouring of solids for materi als 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 resu lt in excessive exposure; however,
this scenario was not assessed for the 2006 RED b ecause exposure data were not available.
With respect to agricultural applications, all o ccupational inhalation MOEs were above the target MOE of 1000, with the exception of fogger a pplication, where the MOE was 880. For dermal

### Page 25 of 74 exposures involving agricu ltural applications, with the use ofchemical-resistant gloves, shortterm dermal risks were not of concern for handl ers. 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 inte rmediate-/long-term inhalation risks were not of

concern. EPA anticipates the need to revise the occupa tional handler assessment conducted in support of the 2006 RED. All of the handler scenarios that we re 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 exposur e 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 preser vation and handler exposures fo r hand held fogging applications. The occupational handler scenarios to be assessed are listed in Table 10.
Table 10 – Occupational Handler Exposure Scenarios for o PP

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 resident ial handler assessment conducted in support of the 2006 RED. Residential handler derm al and inhalation exposures to o PP 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 inhalati on MOEs were not of concern.
Residential exposure may o ccur during application of o PP products used as a hard surface disinfectant (e.g., walls, floors, tabl es, fixtures), to textiles (e. g., clothing, diapers, mattresses, bedding) and to carpets. In addition o PP is used as a preservative in finger paints. As such, the Agency has selected representative scenarios fo r each use site that are believed to be representative of the o PP 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 o PP

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 o PP Dermal Inhalation Short Term

### Page 26 of 74 Scenario Exposure Route(s) Duration

Hand application of fingerpaints treated with o PP Dermal Incidental Oral Inhalation Short and Intermediate
Term



## 3.3.3 Residential Post-Application Exposures

EPA anticipates the need to revise the reside ntial post-application a ssessment conducted in support of the 2006 RED. Resident ial post-application exposures to residues arising from the hard surface disinfection of floors, treated diap ers, 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 possi bly underestimates exposure and will have to be reassessed using updated values from the AEJV us e surveys and/or the AE ATF 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 residu e 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 stat ements 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 treat ed paint and air sani tization 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 resi dential post application exposure scenarios that will be assessed during registration review are listed in Table 12.

Table 12 – Residential Post-Application Exposure Scenarios for o PP Source of Exposure Exposure Route(s) Duration

Floors disinfected with o PP Dermal Incidental Oral Short and Intermediate Term

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

Mouthing Toys or Household Items Manufactured from Plastic or Polymers Preserved with o PP. Incidental Oral Short and Intermediate Term

Air sanitized with o PP 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 th e 2006 RED for direct food use of o PP have been revoked, which will result in a decrease in total dietary exposur es. There is also no significant contribution to dietary risk from drinking water expo sure, as was noted in the 2006 RED.
The Agency anticipates the need to revise th e short- and intermediate-term aggregate risk assessments for o PP. 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 me chanism of toxicity, EPA has not made a common mechanism of toxicity finding as to o PP and any other substances, and o PP 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 o PP has a common mechanism of toxicity with other s ubstances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity a nd to evaluate the cumulative effects of such chemicals, see 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 pK a of about 9.5 (MRID 42500204), indicating that

o PP will primarily exist as the protonated acid in aqueous solution at environmental pH values (5 - 9). The sodium (Na) and potassium (K) salts of o PP rapidly dissociate in water releasing sodium and potassium cations (Na + 

### and K + 

### , respectively) and the ortho -phenyl phenate anion ( o PP

- 

### ). The o PP

- 

### anion will readily become protonated forming the neutral or unionized o PP. The equilibrium in solution between o PP

- 

### and protonated or unionized o PP depends on the pH of the solution. In aqueous medium the fo llowing equilibria is expected: at acidic pHs 4 - 6, the parent will essentially be in the protonated or undissociated o PP state; at pHs 7 - 9.5, the equilibria will have undissociated o PP and some dissociated o PP, with increasingly more dissociated o PP as pH becomes more alkaline; at pH 9.5, approximately 50% of the o PP 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 o PP can be used to support the sa lts, and similarly the fate and transport data supporting its Na a nd K salts may be used to support o PP. A summary of the fate, transport and degradation of o PP and its salts is provided here but details of the studies and information are provided in Appendix B.



## 4.1.1 o PP and its Salts

Ortho -phenyl phenol is hydrolytic ally 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 o PP is 2.00 x 10 -3 

### mm Hg at 25 °C (MRID 41609505 for Na- o PP and MRID 41642402 for o PP) indicating the potential for volatilizatio n, but the half life of o PP 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). o PP is immobile on soil surfaces and will not likely contaminate the ground water. Temperatur e 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 obser ved under cooler fall and winter conditions. While there is

### Page 28 of 74 information from a specific location indicating po tential for aqueous aerob ic 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 o PP are anticipated as being required to con duct the risk assessment of o PP and its salts. Additionally, to model removal during wastewater treatment, data on th e percent removal during wastewater treatment due to sorption and biodeg radation (i.e., OCSPP 835.1110, 835.3110, 835.3220, 835.3240, 835.3280) are anticipated to be required.

o PP has a log K ow 

### of 3.3, indicating it is potentially bi oaccumulative; however, there are no data on bioaccumulation or bioconcentration in aqua tic organisms. A bioconcentration study using

o PP with fish, tracking the major degradates, is antic ipated as being required to conduct the risk assessment of o PP and its salts.

Na- o PP is applied to and leaches easily from sa pstain 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- o PP/cm 2 

### /day, and for 4% treated wood, the leach rate was 192 μg of Na- o PP /cm 2 

### /day; after day 14, the leach rate was 0.5 to 0.2 μg /cm 2 

### /day for both treated woods. A steady state is achieved after 14 days. Since Na- o PP 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 o PP 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 o PP and its major toxic degradates. Additionally, there are registered uses that will result in expos ure of terrestrial wildlife and plants to residues of o PP and its salts and major toxic degrad ates on dietary items through direct application, spray drift, and run-off.



## 4.1.2 Photodegradates of o PP
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 envi ronmental 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 estim ated half life is 15 days in water bodies, and about thirty days in soils, maki ng it not that persistent in these environmental media. It could be stable and persistent in sedime nts with an estimated half life of 135 days. It is not stable in air, and the estimated half life is le ss than six hours in air. It is not likely to be bioaccumulative as its log K ow 

### is less than 3. It appears to no t readily biodegrade and may not be removed from wastewater treatment. It has a high K oc 

### 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. Howeve r, 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 subs tance is highly water soluble, and its vapor pressure is not of concern for the exposur e 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 sediment s with an estimated half life of 135 days. It is not stable in air, and the estimated half lif e is less than eight hour s in air. It is not likely to be bioaccumulative as its log K ow 

### 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 K oc 

### value making it immobile in soils; thus the pr obability of this chemical migrating to ground water is low, and so ground water cont amination is not likely to happen.
At this time the Agency cannot determin e environmental risk concerns for these photodegradates, and no fate assessment was con ducted. The Agency anticipates using a total toxic residue approach. If any fa te data on these degradates b ecomes available which indicate environmental risk concerns, the Agency an ticipates requiring additional fate data.



## 4.1.3 Water Quality

Ortho -phenyl phenol and its salts, Na- o PP and K- o PP, are not identified as a cause of impairment for any water bodies listed as impa ired under section 303(d) of the Clean Water Act 20 

### . In addition, no Total Maximum Daily Lo ads (TMDL) have been developed for o PP, Nao PP, and K- o PP 21 

### . More information on impaired water bodies and TMDLs can be found at EPA’s website 22



### . 

# 4.2 Conceptual Models for Enviro nmental Exposure Pathways

4.2.1 Residential Insecticidal Use Patterns

The environmental fate properties and use patterns of o PP and its salts indicate that direct spray, spray drift, atmospheric deposition, and run-off represent potential tran sport mechanisms of o PP and its salts to aquatic an d terrestrial organisms.
For terrestrial vertebrates, the major route of exposure to o PP and its salts is considered to be via dietary ingestion of food items such as s eeds, plants, and/or animals that have o PP (and its salts) residues as a result of direct application, spray drift, and run-off. Expos ure of birds and mammals

to o PP and its salts through the consumption of drinki ng water alone is also considered to be an exposure pathway of concern based on the result s of EFED’s Screening Imbibition Program (SIP v. 1.0). There is uncertainty regard ing 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 I nhalation 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, th e major routes of exposure to o PP and its salts are considered to be direct contact as a result of di rect application and sp ray drift and dietary ingestion of plants, animals, and/or soil that have o PP (and its salts) residues as a resu lt of direct application, spray drift, and run-off.
For aquatic animal species, the major route of exposure to o PP and its salts is considered to be uptake via the respiratory surface (gills) or the integument from surface water/sediment that has

o PP (and its salts) residues as a re sult of spray drift and run-off.

20 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

21 http://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-targ et plants, the major routes of exposure to o PP and its salts are considered to be direct contact as a result of dire ct 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 o PP and its salts is cons idered to be uptake from surface water/sediment containing o PP (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 o PP 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 o PP. These conceptual model diagrams for o PP specify the potential routes of exposure, possible ecological receptors, and attribute changes that might occur.

There is some evidence that o PP is susceptible to biodegrada tion during wastewater treatment and in the aquatic environment. Ba sed on studies using activated sludge, o PP 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 CO 2 

### that demonstrate a 50% reduction of o PP in river water within a week (MRID 439942-01; Gonsior,1984). This paper did not identify and biodegrad ates. Based on its log Kow of 3.3, o PP may have potential to bioconcentrate in aquatic organism s. One study has indicated that o PP can photodegrade to form PBQ and PHQ (MRID 439942-01).
The Agency has previously determined that the use of o PP and salts for sapstain treatment of freshly cut lumber has a potenti al to expose and cause detrim ental 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 ye t 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. Chroni c exposure of aquatic organisms also is possible and will be assessed when the required data are av ailable. As a wood preservative for treatment to freshly cut lumber, o PP 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), o PP has a potential to bioconcentr ate in aquatic organisms. o PP entering the aquatic environment is expected to adsorb to sediment and may pose a potential risk to benthic organisms.

o PP and salts have numerous registered uses. Use sites and corresponding fi gures of conceptual model diagrams are presented as follows:

- Sanitizer/Disinfectant and Material Preser vatives in Cleaning So lutions (Figure 1);

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

- Wood Preservative for Sapstain Control (Figure 3);

- Materials Preservatives in Meta l Working Fluids (Figure 4);

- Swimming Pools, Spas, Ornamental Ponds, A quaria, Waterbed Wate r (Figures 5a/b);

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

- Commercial/Industrial Water Cooling Sy stems; 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 Seconda ry Recovery Water (Figures 8a/b); and

- Materials Preservatives Other than Thos e Used in Metal Working Fluids and Cleaning Solutions (Figure 9)

Figure 1 - Conceptual Model for Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Sanitizer/Disinf ectant and Material Preservat ive 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 Ec ological Exposure and Effects of o PP 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 Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Wood Preservat ives 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 ma y have releases to 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 Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Materials Pr eservatives 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 Ec ological Exposure and Effects of o PP 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 Ec ological Exposure and Effects of o PP 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 refers to 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 Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Cooling, Evaporative Condenser, He at 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 Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Biocides in Oil Drilling Mu ds/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 Ec ological Exposure and Effects of o PP and Salts to Aquatic and Terrestrial Organisms from Material Preservative Uses Other Th an 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 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 .). **Textiles, leather, plastic, and rubber material preservative uses are expected to result in discharges down facility drains at manufacturing use sites. Ingestion Waste Water Treatment Plant

Key
Most likely

exposure pathway contributing to risk
Low likelihood of contributing to risk Material Preservative Uses Other than Metal Working Fluids and Cleaning Solutions

WWTP microorganisms Uptake or sorption

Population Respiration inhibition Outdoor Air Surface Water
Sediment Facility Drain Waste Disposal* Volatilization Washing/Leaching In

‐ Service Use of Preserved Materials Material Preservative Application Site (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 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 Dermal contact Contact/Uptake leaves, stems

Beneficial

Insects Reduced
survival

* Applicable to in

‐ service use of paints, stains and coatings. **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 Exterior In

‐ Service Use of: Preserved Paints, Stains and Coatings; Preserved Concrete and

Concrete Additives

Leaching/Runoff

### Page 40 of 74 

# 4.3 Ecological Effects Assessment

In the 2006 RED issued in August of 2006, the Ag ency conducted an aquatic ecological risk assessment for the antisapstain treatment of Na- o PP 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 pe sticide-leachate concentra tions in diluted stormwater run-off that may enter the aquatic environm ent. The LOC for acute risk was exceeded for freshwater fish, freshwater inve rtebrates, and aquatic plants. Ac ute risk to estuarine/marine organisms and chronic risks to all aquatic organi sms was not assessed due to lack of toxicity data. Possible acute and chronic ri sks from the in-servi ce 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 pl astic 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, c oncrete) and be of sufficient height to prevent run-off during heavy rainfall events. ”
The Agency has not conducted a risk assessmen t that supports a complete endangered species determination for o PP and salts. The ecological risk a ssessment planned during registration review will allow the Agency to refine its risk assessment to determine whether uses of o PP and salts have ‘no effect’ or ‘may affect’ federally listed threatened or enda ngered 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 crit ical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Ma rine Fisheries Services (the Services), as appropriate.



## 4.3.1 Mechanism of Action

The Agency found no information on the mechanisms of action of o PP 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 ch ronic toxicity data will be used to evaluate the potential direct
and indirect effects of o PP and salts to plants and animals. Relevant data from the open literature available in ECOTOX also may be used to eval uate potential direct and indirect effects.
All data requirements and available ecotoxic ity endpoints from studies submitted by registrants are tabulated in Appendix C. The Agency uses th e most sensitive of these endpoints for assessing risk to each terrestrial and aqua tic receptor group. The endpoints se lected for the risk assessment for o PP and salts are provided in Table 13. Data gaps also are indicated.
Table 13 – Selected Ecological Effects Endpo ints 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 LC 50 = 2.74 mg aeL 110232 Chronic Data gap --

Freshwater invertebrates Waterflea Acute 48-h EC 50 = 2.4 mg ae/L 110222 Chronic Data gap --

Estuarine/marine fish -- Acute Data gap -- Chronic --

Estuarine/marine

invertebrates Mysid shrimp Acute 96-h LC 50 = 0.28 mg ae/L 467512-03 Chronic Data gap --

Mollusk Acute 48-h IC 50 = 0.66 mg ae/L 25816
Sediment-dwelling invertebrates Freshwater Chronic Data gap --

Aquatic macrophytes/ Aquatic non-vascular plants Green algae Non-listed EC 50 = 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 IC 50 = 5.5 ppm ae/L 467512-09 Listed 7-day IC 05 = 0.73 ppm ae/L
Emergent rooted aquatic

macrophytes-Seedling

emergence Rice Non-listed EC 25 > 886 ppm ae
467512-07 Listed NOAEC = 886 ppm ae (7% emergence inhibition) Emergent rooted aquatic macrophytes-Vegetative vigor Rice Non-listed EC 25 > 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 LD 50 = 885 mg ae/kg-bw A 425002-04 Chronic Data gap --

Mammals Rat Acute LD 50 = 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 --
RT 25 -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 o PP 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 degrad ates 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 degrad ates 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 indi rect discharges to surface water (e.g., via a wastewater treatment pl ant) will be used to determine estimated environmental concentrations (EECs) in the a quatic environment. These exposure estimates will be compared to the toxicity e ndpoints to determine whether or not the Agency’s levels of concern for acute and chronic risk s to aquatic organisms, including listed species, are expected to be exceeded for each receptor group.
In the case of use patterns that result in an timicrobials entering surface water via indirect discharges to wastewater treatment facilities, th e 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 trea tment plants. A more complete discussion of this approach as it relates to antimicrobial s entering surface water vi a 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 wastew ater treatment plants, the Agency will use a different approach than that used for antimicrobials entering domestic wastewater treatment plants. The approach for assessing exposures fo r antimicrobials entering industrial wastewater treatment facilities reli es upon estimating loadings of antimic robials to industrial wastewater treatment plants and using the General Population Exposures from Industrial Releases module of E-FAST to estimate number of days of ex ceedance 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 a nd materials preservatives is expected to be PRZM/EXAMS. A pervious soil, impervious su rface, 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 de termine environmental degradates of o PP and its salts are lacking. Following receipt of an ticipated data, the major degrad ates (>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 absen ce of additional data, the stressors of ecological concern for terrestrial an d aquatic organisms are o PP 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 ha ve 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 agenci es, and this route of exposure will be considered in the as sessment to the extent that data on o PP are available.

### Page 43 of 74 

## 4.4.2 Screening Level Down-the-Drain Analysis

The Down-the-Drain (DtD) module of E-FAST (E xposure 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 o PP and salts to be exposed to o PP and salts and/or any degrad ates that form from the poi nt of application to the point of discharge following wastewater treatm ent. 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 pr esented in Appendix E. A conservative assumption of no removal during wastewater treatment was used in DtD model runs.
Table 14 presents high-end scenario result s of a screening-level DtD analysis for o PP and salts based on laboratory toxicity data for freshwater organisms. Results are pr esented for a number of wastewater treatment plant influent volume s. Based on U.S. consumption in 2004 of 2,440,000 pounds and assuming an average annual volume grow th of 2.5% per year, Kline (2004) predicted that in 2009 consumption of o PP and salts would be 2,760,000 pounds. This corresponds to about 1,250,000 kilograms of o PP and salts forecast to be consum ed in 2009. In one scenario, it was assumed that all of the o PP and salts that was forecast to be consumed in 2009 would be discharged to domestic wastewater treatment plants. At this pres umed 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 o PP of about 2,225,000 kilograms per year. To exceed the acute concen tration of concern of 1370 ug/L for freshwater fish for one day a year, it would take a wastew ater 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 vo lume of about 7,000,000 kilograms per year.
Table 14 – Summary of Screening Leve l Down-the-Drain Analysis Results

Influent Volume of o PP 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 o PP 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 o PP 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 o PP 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 o PP and salts are released to domestic wastewater treatment plants. Based on registered uses of o PP 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 ente r 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 uncerta inty regarding the amount of o PP and salts that could be expected to enter domestic wastewater trea tment plants. There is also uncer tainty about the potential for exposure to aquatic organisms from o PP and salts entering industrial wastewater treatment plants as a result of industrial uses of o PP and salts. Exceedances of c oncentrations of concern for endangered freshwater fish and invertebrates ha ve been predicted at production volumes of o PP and salts projected by Kline for the year 2009 (K line 2004), and there is evidence based on an evaluation of production data reported to the Agen cy that the Kline data tend to considerably underestimate the production volume of o PP and salts. The Agency does not have high quality data on the toxicity of o PP and salts to activated sludge micr oorganisms in wastewater treatment plants and does not have high qua lity data on biodegradation of o PP and salts during wastewater treatment. Consequently, the Agency an ticipates needing th e following data on o PP to fulfill data gaps regarding toxicity to activated sl udge microorganisms and biodegradation of o PP and salts during wastewater treatment:

1. Activated Sludge Respiration Inhibiti on (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 wo rk plan will be used to calculat e 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 wi ll be identified using EPA’s ECOTOXicology (ECOTOX) 23 

### database, which employs a literature search engine for lo cating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The ECOTOX databa se will be searched when the risk assessment for o PP and salts is prepared. The ev aluation of these sources of da ta 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 num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and

23 http://cfpub.epa.gov/ecotox

### Page 45 of 74 chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its reregistration decision, for o PP, EPA reviewed these data and selected the most sensitive endpoi nts for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), o PP is subject to the endocrine screening part of the Endocrine Di sruptor Screening Program (EDSP).

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

Under FFDCA section 408(p), the agency must scr een all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredient s. A second list of chemicals identified for EDSP screening was published on June 14, 2013 24 

### 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.

o PP is on List 1 for which EPA has received all th e 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, pleas e visit our website. 25



# 6 Optional Label Changes

To eliminate the anticipated need for EPA to re quire certain data, reduce the possibility that EPA’s planned risk assessments overestimate risk due to reliance on conservative assumptions, and/or improve label clarity, registrant s 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 indoo r exposure study for handheld fogging.
All of the labels permit open pour addition of liquids and soluble powders for material preservation and industrial proce ss treatment. If the labels were amended to require that liquids be handled using closed loading and delivery sy stems 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 long er 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 docum ent. 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 Pr oduction 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, 20 13). 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 r eady 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 sm all lake receiving discharges fro m an adjacent superfund site. Environmental science and technology, 32:1319-1328. Zbozinek, JV, 1984: Environmental transforma tions 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 Chem ical 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 Pa rtition 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 Ch emical, 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 o PP and salts shows that by the oral route, a Toxici ty Category III is assigned based on results of two submitted studies (MRIDs 43334201 and 43334204) showing oral LD 50 

### values of 2733 mg/kg (combined) and values of 846 and 591 mg/kg ( males and females respectively). By the dermal route, an LD 50 

### 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 o PP (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 o PP could not be generated and that smaller particle sizes could not be achieve d. 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 l ong enough to assign a Toxicity Category. Ortho -phenyl phenol and its sodium salt are severe (T oxicity Category I) dermal irritants. Ortho -phenyl phenol and its sodium salt are not dermal sensitizers.
Table 15 – Acute Toxicity Studies for o PP Guideline No./ Study Type MRID No. Results Toxicity Category
870.1100/ Acute oral toxicity

o PP purity 99.9% 

### 43334201 LD 50 

### = 2733 mg/kg III

870.1100/ Acute oral toxicity
Na- o PP purity 99.1% 

### 43334204 LD 50 

### = 846 mg/kg (male)
LD 50 

### = 591 mg/kg (female) III

870.1200/ Acute dermal toxicity

o PP purity 99.73% 

### 00078779 LD 50 

### > 5000 mg/kg IV

870.1300/ Acute inhalation toxicity

o PP purity 99.9% 

### 42333101 Unacceptable study NA

870.2400/ Acute eye irritation Dowicide® 1 

### 00139884 Unacceptable study NA

870.2500/ Acute dermal irritation

o PP purity 99.9% 

### 43334202 Primary Irritant I

870.2600/ Skin sensitization

o PP purity 99.9% 

### 43334203 Not a sensitizer. No

870.2600/ Skin sensitization
Na- o PP purity 99.1% 

### 43334205 Not a sensitizer. No

N/A=Not available

### Page 49 of 74 

# Subchronic Toxicity

In a 90-day oral toxicity te st (MRID 40760206) designed to dete rmine the subchronic toxicity effects of repeated dietary exposure to o PP (>98% purity) in F344/DuCrj rats. Ortho -phenyl phenol was administered in feed to 10 rats /sex/dose at concentr ations 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 anim als 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 male s and females of the 1.25% dose group. Males administered 2.5% o PP exhibited significant decreases fr om control in food intake. The discrepancy in food intake was gr eatest 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 inta ke trend continued throughout the remainder of the study. Additionally , the 2.5% rats spilled an exce ssive 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% o PP. 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 gr ams/feed intake in grams) was slightly lower in groups fed on feed containing high o PP 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 significan t changes from controls in body weight gain in animals treated with o PP concentrations equal to or less than 0.625%. Weight gain was inhibited in males and females of the 1.25% dos e group, with maximum inhibition ratios of 14 and 7%, respectively. The significan t weight loss of 1.25% females occurred in the first 8 weeks of the study. Body weight gain was significantly re duced from controls in both male and female rats in the 2.5% o PP dose group.
The hemoglobin (Hgb) and mean red blood corpus cle 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 co ntrols in red blood corp uscles (RBC), Hgb, and MCHC. There was a slight tendency for animals to be anemic in groups fed higher dosages of

o PP. No treatment-related effects were observe d in the serum analyses. Pathological and histological observations indicated treatment-related inflamma tion 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 LOA EL is 1.25% (1669 mg/k g/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 t oxicity in Fischer 344 rats, male and female (5/sex/dose) were administered o PP (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, w ith more severe irritation effects observed in the females. Microscopically, an increased in cidence 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 toxic ity study (MRID 92154037, reformat of 00067616 and 00164362), o PP (purity 99.69%) in cottonseed oil, was ad ministered 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 gesta tion 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 gr oup (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/d ay based on decreased body weight gains, food consumption and food efficiency. The maternal toxicity LOAEL is 300 mg/kg/day.
No developmental toxicity was not ed at the dose levels tested. The developmental toxicity NOAEL is greater than or equal to 700 mg/kg/d ay (highest dose tested). The developmental toxicity LOAEL is greater than 700 mg/kg/day (not established).
In a prenatal developmental toxic ity study in rabbits (MRID 41925001, 41925002, and 41925003), inseminated New Zealand White rabbits (7 females/group) were administered o PP (99.88% a.i.) on days 7-19 of presumed gestatio n by oral gavage at doses of 0, 25, 100, or 250 mg/kg/day. All animals were observed daily for si gns 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 sacrifi ced 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-phenylphe nol produced evidence of syst emic 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 compar ed to one dam in the control group). Treatmentrelated alterations in microsc opic kidney structure, primarily consisting of inflammation and tubular degeneration, were noted only in the hi gh-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)

### Page 51 of 74 and high-dose (6 dams compared to one cont rol dam) groups. Although th e study author stated these effects to be of no toxicological signifi cance because there was no correlation of these effects with signs of abortion a nd/or gross/microscopic pathologi es, the EPA reviewer could not rule out this effect at the mid dose The maternal toxicity NOA EL 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 treatmen t-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 histor ical 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 grea ter than 250 mg/kg/day (not established).
In a two-generation reproduction study (MRID 43928801) o PP (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 w eeks prior to mating, during mating, gestation, and lactation through the pro duction of two litters (F 1a 

### , F 1b 

### , F 2a 

### , and F 2b 

### ) including a 14- or 20-day rest period after the first litters were weaned. The F 1 

### 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 ad justed weekly based on the food consumption and body weight of the previous week to maintain a constant dose (mg/kg/day) ex cept during gestation, lactation, and from weaning through week 3 of the premating period for F 1 

### pups. During these times, the animals received the same dietary concentrations of test material as the respective groups during the last week of the F 0 

### premating period.

No treatment-related effects were observed in male or female adult rats administered o PP at concentrations of 20 or 100 mg/kg/day. No treat ment-related effects we re observed on overall mortality, except for one F 0 

### male rat receiving 500 mg/kg/day that died due to kidney failure. The only treatment-related clinical sign of t oxicity was urine staining in 5/30 (p<0.05) F 0 

### and 8/30 (p=0.01) F 1 

### 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 F 0 

### males, 7% (p<0.01) in F 0 

### females, 11% (p<0.01) in F 1 

### males, and 9% (p<0.01) in F 1 

### females. At the end of the study (day 175), body weights were decreased by 5% (not significant) in the F 0 

### males and by 11% (p<0.01) in F 1 

### males administered 500 mg/kg/day. Corresponding reductions in weight gain during th e 70-day premating period were -9 and -10% for F 0 

### and F 1 

### males and -19 and -8% for F 0 

### and F 1 

### females at 500 mg/kg/day compared with weight gain in the controls. Reduc tions in weight gain after 175 days of treatment were -19 and - 10% in the F 0 

### and F 1 

### males. In contrast to weight gai n, food consumption by males and females of both parental generations administered 500 mg /kg/day generally exceeded that of controls, and the F 1 

### dams weighed 6 to 8% less (P<0.05 or <0.01) than controls and the F 1 

### 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 sim ilar to that of controls ranging from +1 to -7% of the control value for both parental generati ons; during lactation, weight gain for all treated groups in both generation ranged from -57 to +288% and showed no clear dose-related tr ends. 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.

### Page 52 of 74 Urinary bladder calculi observed grossly (F 0 

### : 4/30 vs. 0/30 for cont rols, not significant; F 1 

### : 7/30 vs. 0/30 for controls, P<0.05) and microscopically (F 0 

### and F 1 

### : 4/30 vs. 0/30, not significant) at 500 mg/kg/day in adult males were considered to be related to treatment w ith the test material. Wet/stained ventrum observed (F 0 

### : 2/30 vs. 0/30 for control, not significant; F 1 

### : 5/30 vs. 0/30 for controls, not significant) at 500 mg /kg/day in adult males was consid ered to be treatment-related. Other microscopic lesions attributed to treatment of male rats with 500 mg/kg/day of the test material included simple tr ansitional cell hyperplasia (F 0 

### : 22/30 vs. 1/30; F 1 

### : 27/30 vs. 0/30; p<0.05), nodular/ papillary tr ansitional cell hyperplasia of the urinary bladder (F 0 

### : 16/30 vs. 1/30;
F 1 

### : 19/30 vs. 0/30; p<0.05) and chronic in flammation in the urinary bladder (F 0 

### : 13/30 vs. 0/30;
F 1 

### : 12/30 vs. 0/30; p<0.05). The average sever ity ratings but not the incidences were significantly increased (p<0.05) for ch ronic inflammation in the kidney [F 0 

### : 4/30 (2.8) vs. 0/30] debris in the renal pelvis [F 1 

### : 4/30 (2.5) vs. 0/30], and dilation of the ureter [F 0 

### : 4/30 (1.8) vs. 0/30]. No treatment-related pathologic le sions were observed in adult females.
No treatment-related effects on reproductive functi on or performance were observed in male or female rats of either generation. No treatment-rela ted effects occurred on viability, clinical signs, litter size at birth, or at the end of lactation or sex ratio for the F 1 

### or F 2 

### pups. Body weights in 21- day old pups in the 500 mg/kg/day group were decrea sed significantly (p<0.01) in both litters of each generation (-10 to -12%). F 2b 

### pups at 500 mg/kg/day wei ghed 7% less (p<0.05) than controls on day 14 of lactation; no other statistically significa nt effects on pup weights were observed. Pup weight gain at 500 mg/kg/day was re duced by 12 to 14% over the entire lactation period. The reduced pup weights and weight gain is not attributed to lact ational effects in the dams, but is considered to be relate d 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 a dults, reduced body weight in 21-day old pups, clinical signs in adult male rats, microsc opic 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 paren tal toxicity NOAEL is 100 mg/kg/day. No treatment-related reproductive toxicity occur red 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 /carcinogeni city study (MRID 43954301) CDF rats from SASCO, Inc., Madison WI received o PP (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, a nd 8000 ppm dose groups and 49, 248, and 647 mg/kg/day for females fat: the 800, 4000, and 10000 pp m 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 t oxicity was noted as decreased body weights (p < 0.05) and body weight gains in both males and fe males of the mid and high dose groups during the first 13 weeks of- the study (f or the 2-year carcinogenicity group). At study termination, only the high dose groups had reduced body weight s (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 decrea sed in the mid dose females at 13 weeks. Food

### Page 53 of 74 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 observati on 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 m onths) along with an increase in congestion, hemorrhage, mineralization and necr osis 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 bo dy weight gains, decreased food consumption and reduced food efficiency, and increased clinic al and gross pathological signs of toxicity.
This study is classified as Acceptable – Guideline

. In a carcinogenicity study (MRID# 43545501) B6 C3F1 albino mice (50/sex/dose group) from Charles River Laboratory, Portage, MI receiv ed ortho-phenylphenol (99.88% a.i.; Lot# 8800005- 24, mixture of Dow Chemical Comp any 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 fema les 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 eff ect). At 1 year there was no treatment related effects on food consumption and at 2 years there was a slight increa se 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 T oxicity NOEL lees than 250 mg/kg/day based on increased liver and reduced spleen weights and gross obser vations in the liver of all treated animals
This study is classified as Co re-Minimum data and satisfies th e guideline requirement (83-2b) for a carcinogenicity study in the mouse. 

# Mutagenicity

An analysis of the genetic toxicol ogy data from over 130 studies with o PP 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 cy totoxicity. Similarl y, clastogenicity,

### Page 54 of 74 which was the most frequently observed type of genotoxicity, was cons istently linked with cytotoxicity. For o PP, the most common type of stru ctural chromosome damage was chromosome breaks, an event that Brusick describe s as typically resulting in cell death. Mixed results were found in studies assessing dire ct 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 ‘excessi ve cytotoxicity, not direct DNA damage”. Furthermore, Brusick (2005) states that agents th at 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 da mage (i.e., genotoxicity). In other words, oxidative damage, eventually lead ing to cell lethality, only occurs at concentrations that have exceeded the levels that can be handled by norma l homeostasis. This observation is supported by the analysis of the carcinogenic m echanism of 2-phenylphenate by Niho et al . (2002). From the dose- and time-response studies with o PP and urinary bladder carcinogenicity in rats, investigators found that the tumor induction was a high-dose phenome non, producing a steep dose response at 15,000 and 20,000 ppm but negativ e 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 exposur e but increasing dramatically after 24 (53%) and 52 (71%) weeks. The non-linearity of this re sponse suggested to the authors that the tumor response observed in these studies with o PP 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 scie ntific literature (Reitz et al ., 1983; Bartels et al ., 1998). An oral dose of ortho-phenylphenol can be dir ectly 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 (phenyl hydroquinone and 2,4 dihydroxybiphe nyl) which are then in turn conjugated with glucuronic acid or sulfate. At doses belo w approximately 200 mg/kg, orthophenylphenol is found primarily in urine as the gl ucuronide and sulfate co njugates 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 o PP initially involves formation of ph enolic 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), 1005-1 017, 2000], by rat CYP2C11 and possibly CYP2E1, and human CYP1A2. Ortho -phenyl phenol, phenylhydroquinone, and 2,4'- dihydroxybiphenyl can themselves undergo conjugati on reactions through th e action of either sulfotransferase or glucuronidation phase II reactions. Phenylhydroquinone can also be converted to phenyl-1,4-benzoquino ne 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 o PP 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 ep ithelium 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 increas ed quantity only at higher (>200 mg/kg/day) doses of o PP. The

### Page 55 of 74 shift in biotransformation products with increased dose of o PP 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 deve lopment of tumors. 

# Dermal Absorption

Dermal Absorption Factor: The Agency has not r eceived any animal studies on the magnitude of dermal absorption of o PP. 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 o PP as “Not Likely to be Carcinog enic to Humans” based on convincing evidence that a non-linear mode of action for blad der tumors was established in rats. High doses of o PP lead to saturation of phase II detoxifica tion enzyme pathways, resulting in increased amounts of the oxidative metabolit es PHQ and/or PBQ. The generation of PBQ is considered dose-dependent, appearing in increased quantity only at higher doses of o PP (>200 mg/kg/day). The shift in biotransformation products with increased dose of o PP has been postulated to be associated with the non-linear response observe d in tumorigenicity of the urinary bladder, involving oxidative damage to cells and subseq uent regenerative hyperplasia. With continued exposure, this process leads to development of tumors. Eviden ce suggests that there are not sufficient oxidative metabolites ge nerated in vivo to re sult 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 o PP established a chronic Reference Dose value of 39 mg/kg/day from the combined chronic toxic ity/carcinogenicity study in rats (MRIDs 43954301, 44852701, 44832201) based on decreased body weight ga ins, 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 even ts 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, can cer is not an issue. 

# Immunotoxicity

An immunotoxicity study is a data requirement fo r all antimicrobial pesticide chemicals under 40 CFR Part 158W, Data Requirements for Antimicrobial Pesticides. The regist rant 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 us ing the Agency’s published guidance, available at: http://www.epa.gov/pesticides/regulat ing/part158-tox-da ta-requirement.pdf.

### Page 56 of 74 

# 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 pres ent 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, includi ng environmental fate and transport for these chemicals, have been completed by various orga nizations either before, during or after the Agency’s RED publication. These include: PMRA of Canada 1 

### (2008), IRIS 2 

### , FAO 3 

### (1999), and CalEPA 4 

### , 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 o PP will in aqueous solution primarily exist as the protonated acid at environmental pH values (5 - 9). In solution, the sodium (Na) and pot assium (K) salts of o PP rapidly dissociate releasing s odium and potassium cations (Na + 

### and K + 

### , respectively) and the ortho -phenyl phenate anion ( o PP

- 

### ). Depending on the pH of the solution the o PP

- 

### anion will readily become protonated forming the neutral or unionized o PP or will readily release a proton to form the o PP

- 

### anion. The equilibrium in solution between o PP

- 

### and protonated or unionized

o PP depends on the pH of the solution. Therefor e, the fate and transport data supporting o PP 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 o PP.

Ortho -phenyl phenol is hydrolytically stable under abiotic conditions. It does photodegrade in abiotic aqueous medium forming three degradat es. It is immobile on surfaces and will not contaminate the ground water. It is r eady biodegradable. It has a high log K ow 

### indicating it is potentially bioaccumulative; however, there is no data on bioaccumulation or bioconcentration in aquatic organisms.

Na- o PP 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- o PP ionizes in moist soils, it is more likely to be mobile from such soil surfaces.
Abiotic Degradation of o PP

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 o PP to form: phenylbenzoquinone (PBQ), phenylhydroquinone (PHQ) and 2-hydroxy benzofuran (MRID# 439942-01).

The half life of o PP in air is estimated at 14 hours (measur ed against the hydroxyl radical) (EPI Suit, version 4.1). Therefore, it is considered moderately stable in air. Its estimated K oc 

### value of 10,000 (EPISuite, version 4.1) indicate s it is immobile in soils a nd shows no tendency to migrate into soils. It likely will not contaminate ground water.
Biotic Degradation of o PP

The half life of o PP in air is estimated to be 0.03 hours using EPISuite 4.10. A study report of Wick and Gschwend (1998a) on surface wa ter showed the degr adation rates of o PP 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 o PP is about 168 hours (7 days). Zbozinek ( 1984) studied microbial degradation of o PP in soil with half-lives ranging from 24 to 168 hour s. 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 ( 14 

### C) radio-labeled o PP. A 50% reduction of 14 

### C labeled o PP occurred within a week. After 16 days, carbon dioxide containing 14 

### C ( 14 

### CO 2 

### ) reached the levels of 50%, 65% and 50% from the radiolabeled o PP samples of 1.22, 12.3 and 123 μg/L. The results are indicative of mineralization and r eady biodegradability of oPP.
Gonsior (1984) also conducted a biodegra dation study on an activ ated sludge with 14 

### C-labeled

o PP. The biodegradation pr ocess of radio-labeled o PP was examined with non-acclimated and acclimated activated sludge, which was obtaine d from East Lansing, MI. A 50% reduction of radiolabeled o PP was observed within 24 hours and 3 hours in non-acclimated and acclimated sludge respectively. Thus if oPP is adsorbed on ac tivated sludge, it is re ady biodegradable from such surfaces. The recovery of total radioactivity in non-acclim ated sludge ranged from 90- to 117%, and 78-100% for the acclimated sludge.
In another lake study (Wick and Gschwend 1998) the biodegradation of o PP was conducted using a mixture of diphenyl sulfone, o PP, and para -phenylphenol ( p PP) 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 discharg e from a Superfund Site. All three substances readily biodegraded during the summer months, with less biode gradation occurr ing during the fall and almost none in the winter months.
A more recent study (Tajeddine et al . 2010) on the photodegradation of o PP, and monuron, when placed on potassium- (K-) and iron (III)- (Fe( III))-monomorillonite clays showed that o PP 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. Photode gradation experiments were conducted in a photoreactor (Suntest) which provided the simu lated sunlight. The study is a non-guideline study and the results are indicated of biodegradation tendency of o PP, Na- o PP, and K- o PP on various types of soil surfaces.

Bioaccumulation of o PP
The Log K ow 

### of 3.09 to 3.36 for o PP has been reported. This ch emical is likely to be bioaccumulative. No concrete data on bio accumulation or bioconcentration into aquatic organisms has been reported.
Leaching of Na- o PP from Treated Wood

Na- o PP 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- o PP were applied as sapstain on wooden blocks. 1 % treated samples leach ed 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- o PP/cm 2 

### /day and for 4% treated wood the leach rate was: 192 μg of Na- o PP /cm 2 

### /day; after day 14, the leach rate was: 0.5 to 0.2 μg /cm 2 

### /day for both treated woods. At the end of the study, 20-24% of Na- o PP was extracted from the wooden blocks.

### Page 58 of 74 Degradates of o PP
The Agency has used its internal database EPI Su ite, version 4.1 to estimate physical/chemical as well as some environmental fate characteris tics for the degradates PBQ and PHQ.

Environmental Fate of the Ph oto-Degradates: PHQ and PBQ

PHQ
The estimated data on this compound (EPI Suite, version 4.1) indicates th at this substance is highly water soluble, and its va por pressure is not of concer n 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 estim ated half life is less than six hours in air. It is not likely to be bioaccumulative as its log K ow 

### 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 tr eatment plants. It has a high K oc 

### value making it immobile in soils, thus the probability of this chemical migrating to ground water is low and so ground water c ontamination is not likely to happen.

PBQ
The estimated data on this compound (EPI Suite, version 4.1) indicates th at this substance is highly water soluble, and its va por pressure is not of concer n 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 estim ated half life is less than eight hours in air. It is not likely to be bioaccumulative as its log K ow 

### 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 K oc 

### value making it immobile in soils, thus the probability of this chemical migrating to ground water is low and so ground water c ontamination is not likely to happen.
Table 16 – Key Physical-Chemical Properties a nd Environmental Fate Characteristics of

o

PP and its Salts
Property/Study o PP and its Salts Remarks/Conclusions

Vapor pressure o PP:
Na- o PP MRID 42441702, 41609505, The studies were acceptable and fulfill the date requirements Log Kow o PP:3.09-3.36 Log Koc
o PP: 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 ( o PP); MRID 43973501, 43994201 Aqueous photodegradation A study with o PP 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 o PP and its Salts Remarks/Conclusions Soil photodegradation Photodegradation is fast for o PP in this type of soil

o PP: 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 o PP (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, o PP, 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 b iodegradation, 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 biodegr adable in the activated sludge. Activated sludge study: no n-acclimated sludge: half life of radiolabeled o PP: 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 leachin g: 1%: treated wood: 71 μg /cm 2 /day

Rate of leaching: 4% treated wood: 192 μg /cm 2 /day; rate of leaching after 14 days: 0.5 to 0.2 μg /cm 2 /day for both treated wood. The sapstain study was conducted on Na- o PP. Na- o PP 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 Environmen tal 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 C 12 H 10 O 2 / 186.21 C 12 H 8 O 2 / 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)
K ow 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)

K oc 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 de tected 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, 20 13). 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 r eady 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 sm all lake receiving discharges fro m an adjacent superfund site. Environmental science and technology, 32:1319-1328. Zbozinek, JV, 1984: Environmental transforma tions of DPA, SOPP, Benomyl, and TBZ; Residue Rev. 92:3351- 3358. MRID 466014-01: Determination of Leach Rates from Wo od 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 Chem ical 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 Pa rtition 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 Ch emical, 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 o PP and salts as being slightly to practically nontoxic to birds (Table 18). Neither acute or al data with a passerine specie s, 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.) Toxicity 26 Toxicity Category MRID/ Study Classification

Mallard ( Anas platyrhynchos ) o PP (99.2) LD 50 > 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- o PP (75.9) 27 LD 50 = 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 ) o PP (99.2) LC 50 > 5620 mg ae/kg-diet NOAEC = 3160 ae/kg-diet, reduction in body weight gain Practically nontoxic 160151/ Acceptable

Mallard ( Anas platyrhynchos ) Na- o PP (75.9) 27 LC 50 > 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 ) o PP (99.2) LC 50 > 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- o PP (75.9) 27 LC 50 > 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 o PP and salts.

26 For o PP mg a.i. is equal to mg acid equi valent (ae), whereas mg a.i. of Na- o PP were converted to mg ae by multiplying by the molar weight ratio of o PP to Na- o PP (170.2/192.19 = 0.886).

27 The test substance is actually sodium ortho -phenylphenate tetrahydrate (Na- o PP·4H 2 O) but is represented in the table as Na- o PP without the weight percent of water. With the weig ht 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 o PP and salts as being moderately toxic to freshwater fish (Table 19). The gui deline (850.1075) for acute toxicity testing is satisfied. Chronic data (fish early-life stag e, 850.1400) are expected to be required.
Table 19 – Freshwater Fish Toxicity Data

Species, Age or size Test Material (% a.i.) Exposure Type/ pH/ hardness 28 /

temperature Toxicity Endpoint 29 Toxicity Category MRID/ Study Classification/

Comments

Rainbow trout ( Oncorhynchus mykiss ) Na- o PP (71.48%) Flow-through -- -- 46751206/ Unacceptable Percent recoveries were below acceptable range

Rainbow trout ( Oncorhynchus mykiss ), 1.1 g o PP (95%) Static/ 7.1/ 35/
10+1 o C 96-h LC 50 = 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 o PP (99.25%) Static/ 7.4-8.2/ 78/ 12.1-12.5 o C 96-h LC 50 = 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 -o PP (71.48%) Flow-through -- -- 46751210 Unacceptable Percent recoveries were below acceptable range

Bluegill sunfish ( Lepomis macrochirus ), 1.0 g o PP (95%) Static/ 7.1/ 35/
20+1 o C 96-hr LC 50 = 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 Nao PP·4H 2 0

(97%) Static/ 7.0/ 51.3/
18.3 o C 96-h LC 50 = 3.9 ppm ae (6.1 ppm ts) Probit slope = NA Moderately toxic 110135 (TN 640), 110203/ Supplemental

28 As mg/L calcium carbonate (CaCO 3 ).

29 For o PP mg a.i. is equal to mg ae, wh ereas 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 (170.2/1 92.19 = 0.886) and results expressed as the tetrahydrate sodium salt (Na- o PP·4H 2 0) were converted to mg ae by multiplying by the molar weight ratio of o PP to Nao PP·4H 2 0 (170.2/264.28 = 0.664).

### Page 64 of 74 Species, Age or size Test Material (% a.i.) Exposure Type/ pH/ hardness 28 /

temperature Toxicity Endpoint 29 Toxicity Category MRID/ Study Classification/

Comments

Bluegill sunfish ( Lepomis macrochirus ), 0.15 g, 2.0 cm SL o PP 99.25% Static/ 7.5-7.9/ 77/ 17.1-17.4 o C 96-h LC 50 = 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 o PP 99.25% Static/ 7.2-7.7/ 76/ 16.8-17.3 o C 96-h LC 50 = 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 o PP 99.25% Static/ 7.2-7.9/ 76/ 17.1-17.4 o C 96-h LC 50 = 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 stud ies for the waterflea categorize o PP and salts as being moderately toxic to freshwater invertebrate s (Table 20). The guideline (850.1010) for acute toxicity testing is satisfied. Chronic data (d aphnid life-cycle, 850.1300) are expected to be required.
Table 20 – Freshwater Invertebrate Toxicity Data

Test Species Test Material (% a.i.) Exposure Type/ pH/

hardness 28 / temperature Toxicity Endpoint 30 Toxicity Category MRID/ Study Classification/ Comments

Waterflea ( Daphnia magna ), <24 hours old Nao PP·4H 2 O (97) Static/ / / 25 o C (room) 48-h EC 50 = 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 o PP (99.2) Static/ 7.9-8.1/ 148/ 19.7-21.0

o C 48-h EC 50 = 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 av ailable for invertebrates, but no data are available for fish. Ortho -phenyl phenol and salts are moderately to hi ghly 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 da ta (850.1075) are expected to be

30 For o PP mg a.i. is equal to mg ae, whereas mg a.i. of the tetrahydrate sodium salt (Na- o PP·4H 2 O) were converted to mg ae by multiplying by the molar weight ratio of o PP to Na- o PP·4H 2 O (170.2/264.28 = 0.664).

### Page 65 of 74 required for fish. Chronic data ar e expected to be required for fish (early life-stage, 850.1400) and an invertebrate (m ysid life-cycle, 850.1350).
Table 21 – Estuarine/Marine Fish and Invertebrate Toxicity Data

Test Species Test Material (% a.i.) Exposure Type/ pH/ salinity 31 / temperature Toxicity Endpoint 31 Toxicity Category MRID/ Study Classification/

Comments

Sheepshead minnow ( Cyprinodon variegatus ) Na- o PP Flow-through -- -- 46751208/ Unacceptable Percent recoveries were below acceptable range

Mysid shrimp ( Americamysis bahia ), 5-6 days old 32 Na- o PP (71.48 33 ) Flow-through/ 8.1-8.3/19-22 ppt/ 19-26 o C 96-h LC 50 = 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- o PP (71.48 33 ) Flow-through/ 7.9 -8.1/ 30-32 ppt/ 20-23 o C 96-h IC 50 = 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- o PP (75.9 34 ) Static 48-h IC 50 = >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- o PP (75.9 34 ) Static 10-d IC 50 = 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 availa ble to establish the toxicity of o PP and salts to vascular and non-vascular aquatic plants (Table 22). The gui delines for testing thr ee algal species (850.4500)

31 For o PP mg a.i. is equal to mg acid equi valent (ae), whereas mg a.i. of Na- o PP were converted to mg ae by multiplying by the molar weight ratio of o PP to Na- o PP (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- o PP·4H 2 O but is represented in the table as Na- o PP without the weight percent of water. With the weight percent of water added the purity of the test substance Na- o PP·4H 2 O is 98.16%.

34 The test substance is actually Na- o PP·4H 2 O but is represented in the table as Na- o PP without the weight percent of water. With the weight percent of water added the purity of the test substance Na- o PP·4H 2 O is >99%.

### Page 66 of 74 and cyanobacteria (850.4550) are satisfied. Guid eline 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-vasc ular plant studies are expected to be sufficient to conduct the risk assessment and a new study is not e xpected to be required at this time.
Table 22 – Aquatic Plants Toxicity Data

Test Species Test Material (% a.i.) Exposure Type/ pH/ temperature Toxicity Endpoint 31 MRID/ Study Classification/ Comments

Duckweed ( Lemna gibba ) Na- o PP (71.48 33 ) Static renewal days 3 & 5/ 7.8- 8.0 new, 8.4-9.4

aged / 24 o C 7-day IC 50 = 5.5 ppm ae (6.2 ppm a.i.) 7-day IC 05 35 = 0.63 ppm ae (0.71 ppm a.i.) Mean measured concentrations 46751209/ Supplemental 36

Green algae ( Selenastrum capricornutum ) o PP (99.91) Static/ 7.41-8.90/
24+2 o C 96-h IC 50 = 1.39 ppm ae 96-h NOAEC = 0.42 ppm ae Mean measured concentrations 45688201/ Acceptable

Blue-Green alga ( Anabaena flos-aquae )

Na- o PP (71.48 33 ) Static/ 6.8-7.8/
24+2 o C 96-h IC 50 = 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 IC 50 = 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 IC 50 = 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 pe r 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 te sting is not required, because inhibition in emergence and growth was less than 25% in the Tier I tests.
Table 23 – Emergent Rooted Aq uatic Plant Toxicity Data

Test Species Test Material (% a.i.) Toxicity Endpoint 31 MRID/ Study Classification/ Comments
Rice ( Oryza sativa ) – seedling emergence (Tier I) Na- o PP (71.48 33 ) IC 25 >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) IC 25 >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 IC 05 will be used as a surrogate. B ecause of the problems with the IC 50 being lower than the LOAEC, the hypothesis method was deemed problematic and the IC 05 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 IC 50 lower than the LOAEC.

### Page 67 of 74 Terrestrial Plants
Seedling emergence and vegetative vi gor data are expected to be required (with the exception of data for rice).

Sediment-dwellers

No data are available. Chronic toxicity data (no guideline numb er) are expected to be required for sediment-dwelling freshwater (2 species) an d estuarine/marine (1 specie) invertebrates,
because o PP and salts are expected to sorb to soil a nd persist (i.e., half-life >10 days) in aquatic
sediments.
Appendix C References

MRID 46010: Levenstein, I. (1964) To Observe the Effe cts of Lysol Spray Disinfectant When Sprayed Directly upon or in the Vicinity of Para keets: Assay No. 46229. (Unpublishe d study received Aug 27, 1969 under 777-20; prepared by Leberco Laboratories, submitted by Lehn & Fink Products Co rp., 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: Blueg ill: 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 In stitute, Inc. (1970) Repor t: 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, 19 76 under 464-126; prep ared 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 u nder 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 LC 50 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 LC 50 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. Unpub lished 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) O PP/SOPP - Acute Toxicity to the Fres hwater 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) O PP/SOPP - Toxicity to Bluegill Sunfis h (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 (E xposure and Fate Assessment Screening Tool), version 2, was used to screen for the potential for aquatic organisms downstream of domestic wastewater treatment plan ts to be exposed to o PP and salts and/or thei r degradates. The DtD module uses daily per capita re lease of household wastewaters, stream dilution factors, and wastewater treatment plant removal efficiency to provide both high-e nd and median (average) time-averaged surface water concentrations of ch emicals discharged from domestic wastewater treatment plants. The high-end scenario uses surface water concentrations downstream of domestic wastewater treatm ent plants based on the 10 th 

### percentile stream d ilution factor (SDF); the average scenario uses surface wa ter concentrations based on the 50 th 

### percentile SDF. SDF is defined as the ratio of the stream flow downs tream of a wastewater treatment plant to the wastewater treatment plant flow. Inputs used to run the DtD module incl uded concentrations of concern (COCs) for aquatic organisms, percen t removal during wastewater treatment, and wastewater treatment plant (WWT P) influent volumes. Wastewat er treatment plant influent volumes are often derived from informa tion on maximum annual production volume or consumption volume of the chemical being a ssessed. 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 ar e expressed as number of days of exceedance of COCs for aquatic organisms. COCs for acute e ffects were determined by dividing LC 50 

### values from acute toxicity tests on aquatic verteb rates and invertebrates by 2. COCs for chronic effects for nonlisted species were based on No Observed Advers e Effects Concentration (NOAEC) values from tests on aquatic vertebrates and invertebrates. CO Cs for listed endangered and threatened aquatic organisms were determined by dividing LC 50 

### values from acute toxicity tests on aquatic vertebrates and invertebrates by 20. Acute COCs for aquatic vascul ar plants and algae are based on EC 50 

### values. COCs for endangered algae and a quatic 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 chemistr y 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 o PP and Salts

OPPTS Guideline No. Physical and Chemical Properties o PP Na- o PP K- o PP

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 o f 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 (flak es) 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 o C. 230.07 °C (Source: EPI Suite) 230.07 °C (Source: EPI Suite)

830.7220 Boiling point 286 o C 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 o PP Na- o PP K- o PP

830.7550 Partition coefficient ( n

octanol/water) Log K ow 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 pub lic 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 Guid eline 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 Se quential Dose Study)” availabl e on the Agency’s website.

Response: The Agency concurs that the “Guida nce for Classifying Studies Conducted Using the OECD Test Guideline 223 (TG 223) (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 speci fies 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 "LD 50 

### - slope test" or "limit dose test" guidelines (the "LD 50 

### - 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 use d, the study should be reviewed by the TBTT - see below; please note that the background mortality data for the species in question should be availabl e from the submitting laboratory at the time of the TBTT review).

 

### The chemical being tested doe s 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 "LD 50 

### - slope test", the raw data and re sults 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 LD 50 

### , slope and confidence limits for TG223 studies ) (see APPENDIX A for details).

 

### The study meets the same va lidity requirements as 850.2100 ( e.g., a study should be invalidated if > 10% of the controls die).

 

### Control birds are not added dur ing the course of the study.

Studies that deviate from th e above criteria may be clas sified as "acceptable" or "supplemental" if they are considered adequate for use in risk asse ssment or "invalid" if they are not scientifically sound; however, consultation with the TBTT will need to confirm the classification for any TG223 study th at deviates from the above criteria. If you have questions regarding this policy you may contact any of th e project workgroup members listed at the end of Appe ndix A to this guidance memo.”

2. Comment: With respect to the immunotoxicity st udy we found the following two studies on Toxnet that may fulfill the Agency’s need s without additional te sting. Using such a weight-of-evidence approach, if possible, is co nsistent with Agency policy outlined in the Guiding Principles for Data Requi rements 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-phenylphe nol (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 wa ter: 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 fe male groups showed immunosuppression in the lymphocyte transforming test (LTT) and in the plaque forming assay (PFC). In the treated male groups there were no signifi cant 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 registra tion review decisions. EPA’s issuance of a DCI is a public statement that th e data is needed, and will be relied on, thus “triggering” the data compensation provi sions 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, Biphe nyl-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 re gistrant for ortho-phenyl phenol who is not a member of the FESTF (or a company ha ving 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 Ag roSciences LLC is an FESTF member.

Response: The Agency thanks the FESTF for its comment and will consider all appropriate information as it conducts the re gistration review and makes its registration review decisions.