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Page 2 of 43 Iodine and Io dophors Registration Review Team

Human Health & Environmental Effects Tim Dole Zoё Layton Michelle Centra William Erickson Srinivas Gowda Najm Shamim Siroos Mostaghimi

Risk Management Sandra O’Neill Demson Fuller Rose Kypriano u

Office of General Counsel Phil RossDocket Number EPA

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Page 3 of 43 

### Table of Contents
1 Introduction

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

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

................................ ................................ ................................ ................. 8 1.3 Chemical Identification and Properties

................................ ................................ ............ 9 1.4 Use/Usage Description

................................ ................................ ................................ ... 12 1.4.1 Registrations

................................ ................................ ................................ ........... 12 1.4.2 Summary of Registered Uses

................................ ................................ .................. 12 1.4.3 Usage Information

................................ ................................ ................................ .. 14 1.5 Regu latory History

................................ ................................ ................................ ......... 14 1.5.1 Recent/Pending Regulatory Actions

................................ ................................ ....... 15 1.5.2 Tolerance Information

................................ ................................ ............................ 15 1.6 Incidents

................................ ................................ ................................ ......................... 15 1.6.1 Human Health

................................ ................................ ................................ ......... 15 1.6.2 Ecological

................................ ................................ ................................ ............... 16 2 Anticipated Da ta Needs

................................ ................................ ................................ ........ 16 3 Human Health Risk Assessment

................................ ................................ ........................... 19 3.1 Human Toxicology Data

................................ ................................ ................................ 19 3.1.1 Human Studies

................................ ................................ ................................ ........ 21 3.2 Proposed Toxicological Endpoints

................................ ................................ ................. 21 3.3 Dietary Exposure

................................ ................................ ................................ ............ 21 3.4 Occupati onal and Residential Exposures

................................ ................................ ....... 22 3.4.1 Occupational Handler Exposure

................................ ................................ ............. 22 3.4.2 Residential Handler Exposures

................................ ................................ ............... 23 3.4.3 Residential Post

- Application Exposures

................................ ................................ . 23 3.5 Aggregate and Cumulative Exposure

................................ ................................ ............. 23 3.5.1 Aggregate Exposures and Risk Assessment

................................ ........................... 23 3.5.2 Cumulative Exposures

................................ ................................ ............................ 23 4 Environmental Risk Assessment

................................ ................................ ........................... 24 4.1 Environmental Fate Assessment

................................ ................................ .................... 24 4.1.1 Leaching for Paints, Stains, and Coatings

................................ .............................. 25 4.1.2 Iodine in Water and Sediment, Soil, and Air

................................ .......................... 26 4.2 Water Quality

................................ ................................ ................................ ................. 26 4.3 Enviro nmental Exposure Pathways

................................ ................................ ................ 26 4.4 Ecological Effects Assessment

................................ ................................ ....................... 26 4.4.1 Mechanism of Action

................................ ................................ .............................. 27 4.4.2 Measures of Effect (Ecotoxicology Endpoints)

................................ ...................... 27 4.5 Exposure Analysis Plan

................................ ................................ ................................ .. 28 4.5.1 Aquatic and Terrestrial Wildlife Exposure Estimates

................................ ............ 28 4.6 Effects Analysis Plan

................................ ................................ ................................ ..... 28 5 Endocrine Disruptor Screening Program (EDSP)

................................ ................................ . 28 6 Guidance for Commenters

................................ ................................ ................................ .... 29 6.1 Preliminary Work Plan

................................ ................................ ................................ ... 29 6.1.1 Trade Irritants

................................ ................................ ................................ .......... 29 6.1.2 Water Quality

................................ ................................ ................................ .......... 29 6.1.3 Environmental Justice

................................ ................................ ............................. 30Docket Number EPA

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Page 4 of 43 6.1.4 Structure Activity Relationships

................................ ................................ ............. 30 6.1.5 Additional Information

................................ ................................ ........................... 31 7 Next Steps

................................ ................................ ................................ ............................. 31 8 References

................................ ................................ ................................ ............................. 32

Appendix A T oxicology Profile

................................ ................................ ............................... 33 Appendix B Environmental Fate

................................ ................................ ............................. 34 Ap pendix C Ecotoxicology Profile

................................ ................................ .......................... 35 Appendix D Product Chemistry

................................ ................................ ............................... 42

List of Tables Table 1

– Summary of Anticipated Risk Assessments and Data Needs

................................ ......... 7 Table 2

– Anticipated Registration Review Schedule

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

– Chemical Identification of Iodine and Iodophors

................................ ........................... 9 Table 4

– Physical

- Chemical Properties for Iodine

................................ ................................ ...... 11 Table 5

– Distribution of Products by PC Code

................................ ................................ ........... 12 Table 6

– Summary of Iodine and Iodophors Registered Uses

................................ .................... 13 Table 7

– Studies Anticipated as Needed for the Registration Review of Iodine and Iodophors

. 17 Table 8

– Iodine Recommended Exposure Levels and Background Exposure

............................ 20 Table 9

– Occupational Handler Exposure Scenarios for Iodine

................................ .................. 22 Table 10

– Residential Handler Exposure Scenarios for Iodine

................................ ................... 23 Table 11

– Residential Post

- Application Exposure Scenarios for Iodine

................................ ..... 23 Table 12

– Ecological Effects Endpoints for the Ecological Risk Assessment of Iodine.

........... 27Docket Number EPA

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## 1 Introduction

This document is the United States Environmental Protection Agency’s ( USEPA, EPA or “the A gency”) Preliminary Work Plan (PWP) for Iodine and Io dophors . The PWP document explains what EPA's Office of Pesticide Programs (OPP) knows about iodine and iodophors , highlighting anticipated data and assessment needs, identifying the types of information that would be especially useful to the Agency in conducting the review, and providing an anticipated timeline for completing iodine and i odophor s ’ review. The Iodine and Iodophors case (case 3080) was previously known as the Iodine and Iodophor Complexes case

. The Reregistration Eligibility Decision (RED) for Iodi ne and Iodophor Complexes issued in July of 2006, the Amendment to the RED issued in August, 2006, and the Revised Amendment to the RED issued in M arch, 2009

, all pertain to the Iodine and I odophors C ase.
The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows about iodine and iodophors and what types of new data or other info rmation would be helpful for the Agency to receive as it moves toward a decision on iodine and io dophors

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

- making process for this chemical.



## 1.1 Statutory and Regulatory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United States generally must be registered by the U SEPA based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability to assess risk evo lves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur ov er time. Through the registration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/

. The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each reg istered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 CF R 155.40. The Agency will consider benefits information and data as required by FIFR A. 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. After reviewing and responding to comments and data received in the docket during this initial comment period, the Agency will develop and commit to a F inal W ork P lan (FWP) and anticipated schedule for the Iodi ne and Iodophors Case.Docket Number EPA

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Page 6 of 43 Documents associated with this registration review can be viewed at http://www.regulations.gov in docket EPA

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- 0 767 . Below is a summary of the issues relevant to this registration review case.Docket Number EPA

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Page 7 of 43 Table 1

– Summary of Anticipated Risk Assessments and Data Needs

I odine

Risk Assessment Assessment Necessary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Anticipated as Needed (See Table 7 for detail s)

Dietary (food) No (see 3.3 ) 3/17/2009 None None Dietary (drinking water) No (see 3.3 ) 3/17/2009 None None Occupational Handler Yes None N ew Inhalation Indoor Exposure Data

Residential Handler Yes None N ew Inhalation Indoor Exposure Data

Residental Post Application Yes None New Surface Residue Data

Aggregate No (see 3.5.1 ) 3/19/2009 None None

Cumulative No (see 3.4.2) 7/27/2006 None None

Tolerance Review No (see 1.5.2 ) N/A

— Existing tolerance exemption None None

Ecological Effects and Environmental Fate Yes N/A New Fish Aquatic invertebrates Aquatic and semi

- aquatic plant s Iodophor s

Ecological Effects and Environmental Fate Yes N/A New Fish Aquatic invertebrates Aquatic and semi

- aquatic plant s Leaching from paints and coatings A ctivated S ludge R espiration I nhibition, Ready biodegrada bility test or one of three biodegradation in activated sludge simulation tests N/A = Not applicable

Table 2

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

- Day Comment Period for Preli minary Work Plan 2013

- 12 2013

- 12

- 20 Close Public Comment Period 2014

- 02 Phase 2: Case Development Issue Final Work Plan 2014

- 06 Issue Data Call

- In (DCI) 2015

- 06 Receive Data to be Considered in Risk Assessment 2017

- 06 Open 30

- Day Public Comment Period for Preliminary Risk Assessment(s) 201 8

- 12 Close Public Comment Period 20 19

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

- Day Public Comment Period for Pro posed Decision 20 19

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Page 8 of 43 Close Public Comment Period 20 19

- 0 8 Issue Final Decision 20 19

- 12 Begin Post

- Decision Followup 20 19 Total (years) 6

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



## 1.2 Case Overview

The docket for the Iodine and Io dophors Case (Case 3080 ) has been established at http://www.regulations.gov in docket number EPA

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.Docket Number EPA

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Page 9 of 43 

## 1.3 Chemical Identification and Properties

Table 3 presents the active ingredients to be assessed in the iodine and iodophors c ase where iodophor is defined as a molecule of iodine and a surface

- active agent that releases iodine gradually and serves as a disinfectant. There are 10 compounds in the case including elemental iodine (Iodine, I 2 ) and nine iodophors

. E lemental iodine and the nine other chemicals are essentially carriers of elemental iodine. These nine substances can be classified as polymers, resins, or surfactants. The purpose of the iodophor is to slow the release of iodine

. Though several iodophor products are classified in EPA’s database as containing elemental iodine (PC Code 046905), only one product actual ly contains elemental iodine, while the other produc ts contain one of the iodophors

.

1. Oxirane, methyl

- , polymer with oxirane, monobutyl ether, compd. with iodine (PC Code 046901); 2. Nonylphenoxypoly ethoxy ethanol iodine complex (PC Code 046903); 3. Iodine, c ompd. with methyloxirane polymer with oxirane (PC Code 046904); 4. Iodine (I 2 ) (PC Code 046905); 5. Betadine (PC Code 046914) ; 6. Glycine, hydriodide (4:1), compd. with iodine (4:5) (PC Code 046923) ; 7. Polyethoxy polypropoxy polyethoxy ethanol iodine complex (PC Code 0 46905 ) ; 8. Sodium N

- cyclohexyl

- N

- palmytoyl

- taurat e

- iodine complex (PC Code 046905) ; 9. Sodium dodecyl benzene sulfonat e

- iodine complex (PC Code 046905) ; 10. Polystyrene divinyl benzene quaternary ammonium anion exchang e resin

- iodine complex (PC Code no. 046905 ).

Table 3

– Chemical Identification of Iodine and Iodophors

Chemical Name Oxirane, methyl

- , polymer with oxirane, monobutyl ether, compd. with iodine Nonylphenoxypoly ethoxy ethanol

- iodine complex Iodine, compd. with methyloxirane polymer with oxirane Iodine (I 2 ) Betadine Polyvinylpyrrolidone

- iodine complex Chemical Classification Halogen Iodophor Halogen Iodophor Halogen Iodophor Halogen Halogen Iodophor
PC Code 046901 046903 046904 046905 046914
CAS Number 68610

- 00

- 4 11096

- 42

- 7 26617

- 87

- 8 7553

- 56

- 2 25655

- 41

- 8 Molecular Formula C 9 H 20 I 2 O 3 C 17 H 28 I 2 O 2 C 5 H 10 I 2 O 2 I 2 C 6 H 9 I 2 NO

Molecular Weight (grams/mole) 430.06 518.21 355.94 253.809 364.95Docket Number EPA

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Page 10 of 43 Chemical Name Oxirane, methyl

- , polymer with oxirane, monobutyl ether, compd. with iodine Nonylphenoxypoly ethoxy ethanol

- iodine complex Iodine, compd. with methyloxirane polymer with oxirane Iodine (I 2 ) Betadine Polyvinylpyrrolidone

- iodine complex

Molecular Structure (Monomer)

Chemical Identification of Iodine and Iodophors Contd.

Chemical Name Polyethoxy polypropoxy polyethoxy ethanol iodine complex Sodium N

- cyclohexyl

- N

palmytoyl

- taurate

- iodine complex Sodium dodecyl benzene sulfonate

iodine complex Polystyrene divinyl benzene quaternary ammonium anion exchange resin

Iodine complex Glycine, hydriodide (4:1), compd. with iodine (4:5)

Chemical Classification Halogen Iodophor Halogen Iodophor Halogen Iodophor Iodinated Anion Exchange Resin Complex Halogen

PC Code 046905 046905 046905 046905 046923
CAS Number 7553

- 56

- 2 7553

- 56

- 2 7553

- 56

- 2 7553

- 56

- 2 7097

- 60

- 1

Molecular Formula C 7 H 14 I 2 O 3 C 24 H4 6 I 2 NNaO 4 S C 18 H3 0 O 3 I 2 NaS

----- C 16 H 42 I 7 N 8 O 16 4[(NH 2 CH 2 COOH) 2 HI] .5I 2 Molecular Weight (grams/ mole) 399.99 721.49 603.29

----- 1490.95Docket Number EPA

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Page 11 of 43 Chemical Name Polyethoxy polypropoxy polyethoxy ethanol iodine complex Sodium N

- cyclohexyl

- N

palmytoyl

- taurate

- iodine complex Sodium dodecyl benzene sulfonate

iodine complex Polystyrene divinyl benzene quaternary ammonium anion exchange resin

Iodine complex Glycine, hydriodide (4:1), compd. with iodine (4:5)

Molecular Structure (Monomer) x 1 1⁄4

The iodine product chemistry information (MRIDs 44087501

, 42440101, 41968702) relevant to risk assessment is summarized in Table 4

. All the iodine and iodophors listed in Table 3 are iodine (I 2 ) releasers. Therefore, the physica l and chemi cal properties listed in Table 4 for Iodine (I 2 ) are also applicable to all the io dine compounds listed in Table 3

.

Table 4

– Physical

- Chemical Properties for Iodine

Guideline No. Parameter Iodine (I 2 ) Physical/Chemical Properties 830.7000 pH at 25°C 5.4 (saturated solution) 830.7050 UV/Visible Absorption Not Reported
830.7200 Melting point 113.7°C 830.7220 Boiling point 184.3°C 830.7300 Density 4.933 g/cm 3 at 25°C (Solid)
830.7370 Dissociation constant (pKa) NA. Does n ’t dissociate 830.7550 Log K ow NA 830.7840 Solubility in water 330 mg/L at 25°C. 830.7860 Solubility in organic solvents Soluble in many organic solvents. 830.7950 Vapor pressure 0.31 mm Hg at 25°C

atm

- m 3 /mol = atmosphere cubic meter per mole; o C = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury; NA = Not applicableDocket Number EPA

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Page 12 of 43 

## 1.4 Use/Usage Description

1.4.1 

### Registrations

There are 41 end use products (EUPs) that contain iodine or one of the iodophors. It should be noted that

, although several of the products are classified in EPA’s database as containing elemental iodine (PC Code 046905)

, only one product contain s elemental iodine, while the other products contain one of the iodophors. E PA will identi fy the products that were registered using data for elemental iodine (PC Code 046905) as p otentially containing iodophors and assess the need to reclassify those products during registration review

. A listing of the number and types of iodophor products by PC Code is included in Table 5

.

Table 5

– Distribution of Products by PC Code

PC Code Number of EUPs Percent a.i Formulations Notes

046901 6 1.2 to 16 Liquid Concentrate

046903 13 1.75 to 20 Liquid Concentrate

046904 5 3.5 to 25 Liquid Concentrate

046905 15 0. 35 to 49.5 Liquid concentrate, C rystals,

Filter cartridge

Powder Crystals are in reusable bottle used to treat drinking water.

046914 1 1.28 RTU Liquid

046923 1 6.68 Tablet

1.4.2 

### Summary of Registered Uses Table 6 summarizes the registered uses of iodine and iodophors

, these uses will be assessed in this registration review

. The labels indicate that iodine and iodophors can be applied by circulate in place (CIP) treatments, surface treatments using sprays, mops or wipes or immersion treatments where the object to be treated is dipped or soaked in a treatment solution. Iod ophors can be use d to treat w ater using cartridge filters or tablets. There is also one product (EPA
reg istration n umber 72897

- 2) that includes the open pour application of iodine powder as a material preservative and one product ( EPA registration number 47371

- 158) that includes open pour application of iodine solution as a material preservative

.Docket Number EPA

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Page 13 of 43 Table 6

– Summary of Iodine and Iod ophors Registered Uses

Use Application Method Application Rate (as Iodine)
Agricultural Premises and Equipment *
Dairy cattle Dairy farm milk handling facilities/equipment Egg handling equipment (hatching) Fish hatchery buildings/areas (non

- aquatic) Livestock and swine feed lots Mushroom houses (empty premises/equipment) Poultry Drinking Water Poultry Feedlots Shoe Baths Udder t r eatment C irculate in place (C IP ) , soak Spray, mop wipe Spray, mop, wipe Spray, soak Spray, soak Water treatment Spray, mop, wipe, soak Step in Dip Tray 25 to 30 ppm 6 to 186 ppm 77 ppm 79 ppm 12 to 236 ppm 27 to 167 ppm

6 to 16 ppm 12 to 236 ppm 12 to 4 7 0 ppm Commercial/Institutional/Industrial (CII) Premises and Equipment

Hard Surfaces HVAC coils and drain pan Spray, mop, wipe Spray, mop, wipe 25 to 186 ppm 125 ppm
Food Handling Premises and Equipment *
Beverage processing plants, Breweries Canneries and frozen food plants Dairies/cheese processing plant equipment Eating establishments equipment/utensils Egg packing plants (commercial) Fish/seafood processing plant equipment Fresh fruit and vegetable packing/processing plants Gloved Hands Meat proce ssing plant equipment Pasteurizer/warmer/cannery cooling water systems Poultry processing plant equipment CIP * , Spray, mop, wipe, soak CIP, Spray, mop, wipe, soak CIP, Spray, mop, wipe, soak CIP, Spray, mop, wipe, soak CIP, Spray, mop, wipe, soak CIP, Spray, mop, wipe, soak CIP, Spray, mop, wipe, soak Dip CIP, Spray, mop, wipe, soak CIP CIP, Spray, mop, wipe, soak 7 to 52 ppm 26 to 52 ppm 8 to 30 ppm 25 to 354 ppm 26 to 186 ppm 3 0 ppm 26 to 30 ppm 34 ppm 26 to 354 ppm

6 to 26 ppm 26 to 354 ppm

Human Drinking Water Systems Drinking Water Cartridge Filter 378 ppm
Industrial Processes
Air conditioner/refrigeration condensate water systems Commercial/industrial water cooling systems Spray, brush, mop, sponge Cartridge 133 ppm 0.5 ppm

Material Preservative
Absorbent Clays A Paints

, Stains and Coatings B Plastic films

– diapers B Filter Media (HVAC and respirator) B Sorbents (cat litter) B Textiles and Fabrics (tarps, gloves, sports equipment) B Open pour liquids Open Pour Wettable Powder Open Pour Wettable Powder Open Pour Wettable Powder Open Pour Wettable Powder Open Pour Wettable Powder 100 ppm 0.11 to 20% 0.11 to 20% 0.11 to 20% 0.11 to 20% 0.11 to 20% Medical Premises and Equipment

Dental water lines Hospitals/medical institutions patient premises Morgues/mortuaries/autopsy/embalming rooms Cartridge Spray, mop, wipe, soak Spray, mop, wipe, soak 0.5 ppm 25 to 186 ppm 165 to 185 ppmDocket Number EPA

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Page 14 of 43 Use Application Method Application Rate (as Iodine)

Residential and Public Access Premises
Animal kennels/sleeping quarters , Zoos Bathroom premises/hard surfaces Hard non

- porous surface treatments Refuse/solid waste containers (garbage cans) Toilet Bowls and Urinals Spray, mop, wipe , soak Spray, mop, wipe Spray, mop, wipe Spray Open pour, Spray 12 to 236 ppm 31 to 1 8 6 ppm 25 to 111 ppm 78 to 186 ppm 85 to 157 ppm

* Labels specify that food contact application rates do not exceed 25 ppm of titratable iodine (with the exception of the labels listed in section 1.5.2

. )

. A. Only one product (EPA Reg no. 47371

- 158) is registered for this use. B. Only one product (EPA Reg no. 72897

- 2) is registered for this use.

1.4.3 

### Usage Information

According to the Kline m arket r esearch r eport (Kline and Company, 2006)

, iodine and iodophors are used mainly in animal husbandry and dairy industries. They are used as surface sanitizers for food mixing equipment, tanks, vats, bottling and food packaging equipment. They are also used for wash down hoses, treatment of udder s a nd as sanitizers fo r milking equipment.



## 1.5 Regulatory Histor y Products containing iodine as the active ingredient were initially registered in the United States by the U.S. Department of Agriculture in 1948. The Agency completed a Reregistration Eligibility Decision (RED) in July, 2006 and subsequently amended the RED in August 2006 to clarify the Agency's position on the toxicity of iodophors

. A second amendment was issued in March, 2009 to address additional information and comments from EPA’s Office of Water. Today, the iod ine and iodophors registration review case ( 3080 ) consists of ten compounds (see Section 1.3 ).

In addition to these compounds, the re are nine iodophor active ingr edients that have no registered products ; therefore, the following active ingredients will not be included in this regis tration review:

• PC C ode 046909

, CAS Number 26617

- 87

- 8 (no chemical name in EPA’s database )

• Poly(oxy

- 1,2

- ethanediyl), .alpha.

- (4

- (1,1, 3,3

- tetramethylbutyl)phenyl)

- .omega.

- hydroxy

- , compd. with iodine (PC C ode 046915

, CAS Number 53404

- 04

- 9)

• P otassium triiodide (PC C ode 046917 , CAS Number 12298

- 68

- 9)

• E thanesulfonic acid, 2

- (cyclohexyl( 1

- oxohexadecyl)amino)

- , sodium salt, compd. with iodine (PC C ode 046919 , CAS Number 53404

- 81

- 2)

• B enzenesulfonic acid, dodecyl

- , sodium salt, compd. with iodine (PC C ode 046920 , CAS Number 53467

- 01

- 9)

• A lpha

- Alkyl

- omega

- hydroxypoly(oxyethylene)

- iodine comp lex *(100% C12

- C15) (PC C ode 046921 , CAS Number 68439

- 47

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Page 15 of 43 • A lkyl* poly(oxypropylene)poly(oxyethylene)

- iodine complex *(43%C10, 30%C14, 12%C12, 10%C16, 5%C18) (PC C ode 046925 , no CAS Numbe r in EPA’s database )

• A cetalized polyvinyl alcohol complexed with iod ine (PC C ode 046926 , no CAS Number )

• P otassium iodide ( PC C ode 075701, CAS Number 7681

- 11

- 0)

.

1.5.1 

### Recent/Pending Regulatory Actions

There are no recent regulatory actions for the Iodine and Iodophors Case. EPA anticipates issu ing the post

- RED product

- specific data call

- in (PDCI) soon.

1.5.2 

### Tolerance Information

Iodine ha s a tolerance exemption in 40 CFR 180.940. The tolerance exemption has a limit in place that states, “when ready for use, the total end

- use concentration of all iodide

- producing chemicals in the solution is not to exceed 25 ppm of titratable iodine ”. L abels under review that

are in consistent with this tolerance are listed here:

EPA R eg

. Nos. 1677

- 22, 1072

- 11, 3862

- 18, 4959

- 15, 4959

- 16, 8405

- 3, 67517

- 9, 4959

- 36, 10 190

- 16, 84890

- 3 , 47371

- 93, 4 959

- 18. The Agency is in contact with the registrants for these products and is working to process updates to the labels for these products.



## 1.6 Incidents

1.6.1 

### Human Health

As of 11/22/2013, the OPP Incident System contains sixteen human minor (HD) and five human moderate (HC) incidents that were submitted after the RED was completed in July, 2006 . There are no details g iven for the HD incidents. D etails for the five HC inciden ts are listed below.

1. A student had asthma attacks ( 3 to 4 times a week) after eating in a school cafeteria

. The student is taking several medications for asthma and the student’s parents are attempting to determine if the asthma attacks are related to the product s used in the cafeteria.

2. A hotel worker experienced skin irritation and blistering , the worker had product on his

arm

.

3. A worker experienced pain in her chest and throat and was seen by a Medical Doctor (MD). No other information w as provided.

4. A person experienced irritation and minor burns ; this person had product in their eyes and was subsequently seen and successfully treated by a MD

.

5. An employee mixed an iodine

- based product with a sodium hypochlorite based product and afterwa rds spilled some portion of the mixture. The employee reported respiratory irritation, was sent to the emergency room and subsequently diagnosed with pneumonia.Docket Number EPA

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Page 16 of 43 It is should be noted that all of the above HC incidents involved iodine based products tha t also contain phosphoric acid which is corrosive. With respect to incident 5, the iodine product label includes a warning that contact with chlorinated products (such as sodium hypochlorite) may cause the violent evolution of toxic gases.

1.6.2 

### Ecological

No ecological incidents in the Incident Data System (IDS, v. 1.8) as of September 12, 2013.


## 2 A nticipated Data Needs

Table 7 presents a summary of the data anticipated as being needed to support this registration review.Docket Number EPA

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Page 17 of 43 Table 7

– Studies Anticipated as Needed for the Registration Review of Iodine and Iodophors

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

Requirement Applicable Exposure Scenario Studies Anticipated to be Required through the Registration Review DCI

No GLN a Special leaching from paints and coatings Polystyrene divinyl benzene quaternary ammonium anion exchange resin

iodine complex 6 Aquatic organisms E xterior paints/stains/coatings

Aquatic environments 835.3110 835.3220 835.3280 835.3240 Ready biodegradability test or one of three biodegradation in activated sludge simulation tests b Iodophors 24 Aquatic organisms

All g 850.6800 a Activated Sludge, Respiration Inhibition 12

850.4400 a Aquatic plants, vascular species c TGAI Iodine and Iodophors 12

Aquatic plants 850.4500 a Aquatic plants, non

vascular d 12 850.4550 a Cyanobacteria toxicity d 12 850.4225 a Seedling emergence, rice e 12 Semi

- aquatic plants

850.1400 a Fish early life

- stage, freshwater species 12 Fish

850.1010 a Aquatic invertebrate toxicity, freshwater 24 Aquatic invertebrates 850.1300 a Invertebrate life cycle, freshwater species 12

850.1075 a Fish acute toxicity, estuarine/marine, freshwater species 18

Estuarine/marine organisms 850.1035 a Mysid acute toxicity 12

850.1025 a or

850.1055 a Oyster shell deposition

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Page 18 of 43 GLN Study Name Test Substance Time Frame (Measured in months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data

Requirement Applicable Exposure Scenario

875.1400 Indoor Exposure Data

- Inhalation TGAI Iodine 12 Occupational and Residential Handler All Inhalation Exposure f

875.2300 Surface Residue Data 12 Residential Post Application Household floor sanitizers Incidental Oral

a Iodophor molecule data are expected to be needed if there is a likelihood for exposure to the carrier in aquatic systems. The Agency has limited data on the carrier portion of these molecules. If it can be shown that there is no aquatic exposure, ecotoxicity data will not be neces sary for the io dophors.
b EPA published draft guidance under guideline OPPTS 850.6800 and has since published final guidance for this study under guideline OCSPP 850.3300: http://www.regul ations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0021. The Agency has included this study in 40 CFR 158(W). OECD Test Guideline 209 can also be used as guidance for this study, available online at http://www.oecd

- ilibrary.org/content/book/9789264070080

- en . The results of this ASRI test will determine which of four biodegradation tests is/are required. If the ASRI test EC50 is less than or equal to 20 mg/L, then either the (i)Biodegr adation in Activated Sludge Study or (ii) Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the Porous Pot Test is expected to be required. If the ASRI test EC50 is greater than 20 mg/L, then the registrant would likely be requ ired to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units or c) the Porous Pot Test. If the Ready Biodegradability study is conducted and pas ses, then no further testing would be expected to be required. If, however, the antimicrobial fails the Ready Biodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units , or c) the Porous Pot study would likely be required.

c D ata would be required if the aquatic (algal) plant growth Tier II study with Selenastrum capricornutum demonstrates detrimental effects at less than 1.0 ppm ( mg/L )

. d O ne Tier II (dose response) study, conducted with Selenastrum capricornutum, is expected to be required; if the results of this study exhibit detrimental effects (EC 50 less than 1.0 ppm or mg/L), then additional Tier II (dose response) studies would be expe cted to be required on three species ( Anabaena flos

- aquae, Navicula pelliculosa, and Skeletonema costatum ).

e D ata are expected to be required only if the risk quotient from any aquatic plant growth Tier II test exceeds a level of concern for aquatic plant s

. f The inhalation exposure scenarios include open pouring of liquids and wettable powder for material preservation, low pressure hand wand, high pressure handwand, trigger sprayer, mop and wipe application, and airless sprayer application of preserved pa ints.

g Data are anticipated to be required for all use patterns which have the potential to result in contamination of surface water

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Page 19 of 43 

## 3 Human Health Risk Assessment

EPA anticipates the need to assess occupational and residential inhalation exposures to iodine as an aerosol because these exposures were not assessed in the 2006 RED. The Agency expects to require additional inhalation data for use in conducting the registration review. EPA does not anti ci pate the need to re assess t he dietary and drinking water exposures that were assessed in the 2006 RED

, and additional dietary data are not anticipated to be required

. 

## 3.1 Human Toxicolog y Data

EPA believes that the human toxicity of iodine is well characterized

. N o additional toxicity data

are anticipated to be required for registration review.

EPA has not formally selected endpoints to assess the human health risks for iodine and iodophors because iodine is an essential nutrient with a long history of clinical use in humans. In the m ost recent risk assessment for iodine and i odophors (EPA, 2009), dietary risks were assessed using the Tolerable Upper Intake Level (UL) while inhalation exposures were assessed using the American Conference of Governmental Industrial Hygienists (ACGIH) Th reshold Limit Value (TLV) of 0.1 ppm for iodine vapor.

Oral Exposures

The National Academy of Sciences has set the Dietary Reference Intake (DRI) of io dine for adult men and women at 150 μg/day (0.0021 mg/kg/day)

. This value was formerly known as the Recommended Dietary Allowance (RDA). For infants, the Adequate Intake (AI) is used as the DRI and is 110 μg/day for infants aged 0 to 6 months and 130 μg/day for infants aged 7 to 12 months. The DRI s for children are in the range of 90

- 150 μg/day (1

- 8 ye ars: 90 μg/day; 9

- 13 years: 120 μg/day; 14

- 18 years: 150 μg/day). The DRI s for pregn ant and lactating women are 220 μg/day and 290 μg/day, respectively.

A Tolerable Upper Intake Level (UL), the maximum level of daily intake that is likely to pose no risk of adverse effects, has been established at 1,100 μg/day (0.016 mg/kg/day) for adult men and women based on serum thyroptropin concentration in response to varying levels of ingested iodine. The ULs for children range from 200

- 600 μg/day (1

- 3 years: 20 0 μg/day; 4

- 8 years: 300 μg/day; 9

- 13 years: 600 μg/day). The ULs for adolescents and pregnant and lactating women ages 14

- 18 years is 900 μg/day and for pregnant and lactating women ages 19

- 50 years is 1,100 μg/day. For infants (0

- 12 months), no UL was determined. However, to prevent high intake of iodine, it is recommended that the only source of this essential nutrient for i nfants be from food and formula (NAS, 200 1 ).

In 1978, the F ood and D rug A dministration deemed potassium iodide a safe and effecti ve means by which to block uptake of radioiodines by the thyroid gland in the event of a radiation emergency under certain specified conditions of use. The recommended daily doses for different risk groups were revised in 2001 using data on thyroid cancer resulting from the Chernobyl reactor accident in 1986. These values range from 16,000 μg (16 mg) to 130,000 μg (130 mg) of potassium iodide.Docket Number EPA

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Page 20 of 43 T here are no primary drinking water standards (MCL) for iodine or its oxidized or reduce d forms, as iodine is u sed in emergency disinfection of water and not in treatment of municipal water supplies. In addition, there are no Health Advisories (HA), secondary drinking water standards, or ambient water quality standards associated with iodine, iodate and iodide. Io dine is approved by the Office of Water for emergency disinfection of drinking water. The guidelines for emergency disinfection can be accessed at: www.epa.gov/safewater/faq/emerg.htm

. For compariso n purposes, the recommendations for iodine daily exposure and the background
exposure amounts are given in Table 8

.

Table 8

– Iodine Recommended Exposure Levels and Background Exposure

Exposure Scenario Exposure Level

DRI set by the National Academy of Sciences for adult men and women. 150 μg/day or 0.0021 mg/kg/day

Tolerable Upper Intake Level set by the National Academy of Sciences for adult men and women 1100 μg/day or 0.016 mg/kg/day.

U.S. Estimated dietary adult intake established by the U.S. Department of Agriculture Continuing Survey of Food Intakes by Individuals (1994

- 1996) 190 to 210 μg/day for women

240 to 300 μg/day for men

Inhalation Exposures

The ACGIH has adopted a Threshold Limit Value

- Time We i ghted Average (TLV

- TWA) of 0.1 mg/m 3 for iodine and iodides as Inhalable Fraction and Vapor and a TLV

– Short term Exposure Limit (STEL) of 1 .0 mg/m 3 for iodine vapor (A C G IH, 2008). The TWA TLV was adopted in 2008 and i s based on the tolerable upper iodine intake level of 1.1 mg/day minus the DRI of 150 ug/day

, which yields approximately 1 mg/day. This value of 1.0 mg/day is divided by a daily inhalation volume of 10 m 3 , to yield the TLV

- TWA of 0 .1 mg/m 3

. This TLV was adopted after the 2006 RED was completed.

The TLV

- STEL of 1

. 0 mg/m 3 for iodine vapors is based upon respiratory effects observed in workers and it was adopted in 1963 . In one study

, an airborne concentration of 3.1 mg/m 3 was reported to make work intolerable while 1.1 mg/m 3 caused no irritating symptoms (Flury and Zernick, 1931 as cited in ACGIH, 2008 )

. This TLV was used in the 2006 RED to assess exposures to workers.

The Occupational Safety and Health Administration (O SHA) has a permissible exposure limit (PEL) of 1 mg/m 3 for i odine (29 CFR 1910.1000) . This PEL is a ceiling limit that cannot be exceeded at any tim e

. The PEL was established in 1970 and it was based on the 1963 TLV STEL of 1 mg/m 3 for iodine vapors.Docket Number EPA

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Page 21 of 43 3.1.1 

### Hu man Studies

The iodine DRIs developed by NAS have relied in part on several human studies

, which may have involved intentional exposure to iodine. In the course of registration review EPA will consider these studies

, as well as any other research involving intentiona l exposure of human subjects to iodine brought to its attention. EPA will ensure that all applicable regulatory requirements are met, including

, but not limited to

, the requirements for EPA ethics review and Human Studies Review Board review of certain research involving intentional exposure of human subjects

. 

## 3.2 Proposed Toxicological Endpoints
Oral Exposures

Since no new information has become available that would change the conclusions made in the RED Amendment of 2009

, EPA will continu e to use the tolerable upper intake level as a basis for assessing the human health risks of iodine oral exposures.

Inhalation Exposures

EPA will use the 2008 TLV

- TWA of 0.1 mg/m 3 for assessing inhalation exposures to iodine aerosols and the 1963 TLV

- S TEL of 1 mg/m 3 for assessing exposure to iodine vapors. The use of the 2008 TLV

- TWA of 0.1 mg/m 3 represents a change from the 2009 RED Amendment where only the TLV

- STEL of 1 mg/m 3 was used. However, i t should be noted that the TLV

- TWA is of 0.1 mg/m 3 is based on the same tolerable upper intake level that is used to assess oral exposures (ACGIH, 2008)

. Dermal Exposure

EPA does not plan to assess dermal exposures to iodine because it was previously concluded in the 2006 RED that the data for dermal absorption show less than one percent of absorption and no new information has become available that would change this conclusion

. 

## 3.3 Dietary Exposure

Use s of iodine and iodophor s that may result in dietary exposure (food and water) include use as food

- contact surface sanitizers (utensils and countertops, dairy processing equipmen t), as fruits and vegetables sanitizing wash (military personnel only), egg washes, and in emergency dr inking water disinfection. In March of 2009 1 a dietary exposure assessment was conducted in order to support the 2009 revised amendment to the 2006 RED. Fruit and vegetable washes and water treatment were not included in the dietary exposure assessment b ecause they are both used only in short

- term (emergency , backpacking, etc. ) circumstances.

Due to the reversible nature of subclinical hypothyroidism observed in humans exposed to iodine, the EPA, during the development of the 2006 RED, did not identify o ral toxicological

1 U.S. EPA. Revised Amendment for Iodine Reregistration Eligibility Decision (RED) Case No. 3080. March 17, 2009.Docket Number EPA

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Page 22 of 43 endpoints of concern. Therefore, dietary risks were assessed using the Tolerable Upper Intake Level (UL) established by NAS, which is the maximum level of daily intake that is likely to pose no risk of adverse effects (EPA, 2009). All of the calculated risks as well as the combined risks

are n ot considered to be of concern. The calculated dietary daily dose (mg/kg/day) w as less than the UL for each population subgroup. Since the uses have not changed since the 2009 risk
assessment , the A gency does not plan to revise the dietary risk assessment.

Although iodine is considered as an essential nutrient, if taken in excess it can cause health

concerns. Excessive intake of iodine during pregnancy may have adverse effects on the fetus without affecting the mother's health. Also, excessive iodine intake by a lactating mother will increase the iodine content of breast milk and may negatively affect the infant's health. Certain individuals appear to be sensitive to iodine and may react to excessi ve intake of it. For people with certain health conditions (e.g., thyroid dysfunction), excess iodine intake may interfere the person's treatment process. Therefore, the use of iodine and iodophor s for use in drinking water disinfection is limited to short

- term situations only when potable water is not available. The 2009 amended RED specified that the following label statement be included in the Directions for U se section for end use products where iodine or an iodophor is used as an emergency water d isinf ectant: “This product is for short

- term emergency use only when potable water is not available." This label statement is still specified for inclusion on the emergency water disinfectant labels

. 

## 3.4 Occupational and Residential Exposures
Occupational and resid ential exposures were only assessed in the 2006 RED for inhalation exposure to iodine as a vapor. To account for the proposed toxicological endpoint, inhalation exposures to iodine as an aerosol will need to be assessed during registration review.

3.4.1 

### Occupat ional Handler Exposure

The occupational handler exposure scenarios that will need to be assessed for iodine are listed in Table 9.

Table 9

– Occupational Handler Exposure Scenarios for Iodine

Scenario Exposure Route(s) Duration

Open p ouring of l iquid f ormulations during material preservation Inhalation Short and Intermediate Term
Open p ouring of p owder f ormulations during material preservation Inhalation Short and Intermediate Term Applying disinfectant using low pressure handwands, high pressure hand wands, trigger sprayers, mops and wipes. Inhalation Short, Intermediate, and Long Term

Airless Sprayer Application of preserved paints Inhalation Short and Intermediate TermDocket Number EPA

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Page 23 of 43 3.4.2 

### Residential Handler Exposures

The residential handler exposure scenarios that will need to be assessed for iodine are listed in Table 10.

Table 10

– Residential Handler Exposure Scenarios for Iodine

Scenario Exposure Route(s) Duration
Applying disinfectant to hard surfaces using trigger sprayers, mops and wipes Inhalation Short and Intermediate Term Airless sprayer application of preserved paints Inhalation Short Term

3.4.3 

### Residential Post

- Application Exposures

The residential post application exposure scenarios that will need to be assessed for iodine are listed in Table 1 1 . The Agency anticipates the need to require a surface residue study (875.2300).

Table 11

– Residential Post

- Application Exposure Scenario s for Iodine

Scenario Exposure Route(s) Duration
Hand to mouth exposure to floors sanitized with iodine Incidental Oral Short and Intermediate Term



## 3.5 Aggregate and Cumulative Exposure

3.5.1 

### Aggregate Exposures and Risk Assessment
The Food Quality Protection Act amendments to the Federal Food, Drug, and Cosmetic Act (FFDCA, Section 408(b)(2)(A)(ii) states that “the term ‘safe,’ with respect to a tolerance for a pesticide chemical residue, means that the Administrator has determined ‘ that there is a reasonable certainty that no harm will result from aggregate exposure to pesticide chemical residue, including all anticipated dietary exposures and other exposures for which there are reliable information." For aggregate risk assessment, exposures to a pesticide chemical resulting from food, drinking water, residential uses, and other non

- occupational sources are usually combined . A qualitative risk assessment was considered appropriate for iodine and iodophors because oral, dermal, and in halation toxicity endpoints were not identified from the available studies/data on iodine and iodophors. T herefore, an aggregate risk assessment was not conducted for the iodine and iodophors case in the past and is not planned for this registration review

. 3.5.2 

### Cumulative Exposures With respect to cumulative exposure, unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to iodine and iod ophors and any other substances and iodine and iodophors do not appear to produce a toxic metabolite produced by other substances. For the purposes of this registration review, therefore, EPA has not assumed that iodine and iodophors ha ve a common mechanis m of toxicity with other substances. For informationDocket Number EPA

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Page 24 of 43 regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/

. 

## 4 Environmental Risk Assessment

The Agency has not previously conducted a n ecological risk assessment for the antimicrobial uses of iodine. A conventional use for drip

- irrigation or direct soil

- injection of potassium
t riiodide as a fungicide for Iris grown for cut flowers was previously assessed by the Agency (EPA, 2008), and potential risks were identified. For aquatic organisms, Levels of Concern ( LOCs ) were exceeded for acute risk to listed and nonlisted aquatic invertebrates and listed fish. The LOC also was exceeded for acute risk to birds and mammals from inhalation exposure and for chronic risk to mammals. However, the assessment noted that g iven the re active nature of the active ingredient, the risks described in the assessment we re expected to occur only for a short time (hours) after application . Data were not available to assess risks to aquatic plants or estuarine/marine organisms.

Further, EPA has not assess ed enviro nmental risks from the iodophor carrier molecules

. Currently, however, the Agency is assessing degradation/transformation products that have the potential to affect the aquatic environment and notes that there is very little informat ion available to the Agency on the carrier molecules ’ environmental fate and toxicity to aquatic organisms.

The ecological risk assessment planned during registration review will allow the Agency to determine potential acute and chronic risks to aquatic organisms exposed to iodine and iodophor carrier molecules transported from antimicrobial use sites into the a quatic e nvironment.

The Agency has not conducted a risk assessment that supports a complete endangered species determination for iodine and iodophors

. The ecological risk assessment will allow the Agency to determine whether each use of the iodine has 'n o effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the Ag ency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate.



## 4.1 Environmental Fate Assessment

The potential exposure of non

- target organisms from the use of iodophors as antimicrobial pest icides is complicated since it consists of exposure to elemental iodine and nine other chemicals which are essentially carriers of elemental iodine. These nine substances can be classified as polymers, resins, or surfactants. The purpose of the iodophor is to slow the release of iodine

. T he vapor pressure of iodine from these iodophors is decrease d relative to the vapor pressure of iodine by itself as was shown in the EPA’s 2006 RED

. The i odine component of the iodophor can be as I 2

, I 3 - or I 5 with various oxidation states similar to other halogens like chlorine and bromine

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Page 25 of 43 Iodine (I 2 ) is one of the halogens, and is a solid at room temperature. As discussed in the product chemistry section

, i odine has a high vapor pressure (0.3 mm Hg), and has a tendency to sublime even at room temperature. Some basic chemical reactions in water and soils media govern the reactivity of iodine:

• Sublimation: I 2 (solid)

-----  2I(gas)

• Reduction: 2I(g as )

-  ( reduction) : 2I -

• Dissolution in water: I 2 (s) + H 2 O

--  HI + HOI

• HI  H + + I -

• I - + I 2 -  I 3 -

• I 3 - + I 2 -  I 5 -

T he A gency lacks fate information on most of the iodophors and therefore cannot predict concentrations of the iodophor carrier molecules released to surface water. As a result, an activated sludge, respiration inhibition ( ASRI ) study is anticipated to be required for iodophors which are expected to reach surface water . The results of the ASRI test determine which of four biodegradation tests are expected to be required and determines the extent of impacts to W astewater T reatment P lant (WTTP) organisms (as indicated in Table 7)

.

F or two iodophor s , the Agency has sufficient fate information to determine that they are unlike ly to be found in surface water; therefore, no additional fate or ecotoxicity data are necessary for the following compounds:

1. Sodium dodecyl benzene sulfonate ( PC Code 046905 ) is an alkylbenzene sulfonate (ABS) for which t he Agency published a preliminary work plan i n March 2013

. S odium dodecylbenzene sulfonate is read ily biodegradable and shows a tendency of mineralization in water and wastewater. The Agency does not anticipate the need to require additional data on this iodophor.

2. Glycine, h ydriodide (4:1), compd. wit h iodine (4:5) (PC Code 046923): t etraglycine is a
pep tide of the simplest amino acid glycine, which is a naturally occurring substance. An EPI suite run (EPI Suite, version 4.11), on tetraglycine provided the following fate info rmation of tetragl ycine: “Tetraglycine is highly water soluble and has a low vapor pressure ( VP = 1 x 10 - 15 mm Hg). It is ready biodegradable and is not likely to bioaccumulate ( Log K ow =
- 3.75)

. It is not likely removed in the STP process. Its half

life in air is 2.4 hours. The Agency does not anticipate the need to require additional data for the tetraglycine or the tetraglycine

- iodine complex.

Data are also not anticipated to be required for resins, which are enclosed in a cartridge, if spent cartridges are considered to be solid waste.

4.1.1 Leaching for Paints, Stains, and Coatings Polystyrene divinyl benzene quaternary ammonium anion exchange resin

- iodine complex (PC Code 046905) is an iodo phor used in paints, stains and coatings. Iodine is released as a disinfectant. Iodophors also are used in filter media (as cartridges) and, for textile s, as a coating on tarps, gloves, and sports equipment. In order to assess the potential for aquatic exposure fromDocket Number EPA

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Page 26 of 43 paints and coatings, information from a leaching study is anticipated to be required as indicated on Table 7.

4.1.2 Iodine in Water and Sediment , Soil, and Air

Iodine is present in all environmental media (WHO, 1990)

. 

## 4.2 Water Quality

Elemental iodine (or iodide ion, or tri

- iodide ion, or pentaiodide ion ) is no t identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act 2 . In addition, no Total Maximum Daily Loads (TMDL) have been developed for iodine 3

.
Iodine and i odophors are not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act 4 . In addition, no Total Maximum Daily Loads (TMDL) have been developed for iodine and iodophors 5

. More information on impaired water bodies and TMDLs can be found at EPA’s website 6

. 

## 4.3 Environmental Exposure Pathways
Aquatic organisms potentially at risk include those inhabiting water bodies adjacent to or downstream from sources of down

- the

- drain discharges (e. g., waste water treat ment plants) or from environmental transport of iodine and iodophor carriers leached from application of paints and coatings to exterior siding and roofing materials. Water bodies might include impounded bodies (e. g., ponds, lakes

, reservoirs ) or flowing waterways (e. g., streams
, rivers ) . For uses in coastal areas, aquatic habitat also includes marine ecosystems

, including estuaries. A quatic organisms likely to be acutely exposed to iodine and iodophor carriers include fish, invertebrates, aquatic stag es of amphibians , and aquatic and semi

- aquatic plants. Chronic exposure also is possible due to continuous or repeated exposures from residential and industrial down

- the

- drain discharges. For aquatic anima ls, the major route of exposure is considered to be uptake via the respiratory surface (gills) or the integument from surface water that has iodine res idues. Based on the K ow (1.8 to 2.5) , bioaccumulation of iodine in aquatic organisms is unlikely. For aquatic plants, the major route of exposure is con sidered to be uptake from surface water.



## 4.4 Ecological Effects Assessment
Ecological effects data are used as measures of direct and indirect effects to aquatic and terrestrial organisms . Acute and chronic toxicity data from registrant

- submitted studies condu cted in accordance with the 850 OCSSP Harmonized Test Guidelines will be used to

2 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885
3 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES
4 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885
5 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES
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Page 27 of 43 evaluate the potential direct and indirect effects of iodine and iodophor carriers to plants and aquatic animals

. Relevant data from the open literature available in ECOTOX a lso may be used to evaluate potential direct and indirect effects

. For iodine, additional data that are anticipated to be required are identified as data gaps in Table 1 2 below.

4.4.1 

### Mechanism of Action Mortality in fish appears to be due to asphyxiation caused by severe gill damage (LaValley

, 1982). Symptoms of iodine poisoning in fish appear to be similar to those caused by chlorine and include severe hemorrhaging and “clubbing” in gill filaments, sloughing of gill epithelium, and production of large amounts of mucous.

4.4.2 

### Measures of Effect (Ecotoxicology Endpoints)

All data and available ecotoxicity endpoints from studies submitted by registrants are tabulated in Appendix C. OPP uses the most sensitive of these endpoints for assessing risk to each terrestrial and aquatic receptor group. The endpoints selected for the risk assessment for iodine are provided in Table 1 2

. Data gaps (resulting in anticipated data needs in Tab le 7) also are indicated.

Table 12

– Ecological Effects Endpoints for the Ecological Risk Assessment of Iodine.

Receptor

Group Test Material Risk Scenario Toxicity Endpoint Reference

Freshwater fish TGAI Acute LC 50 = 0.30 m g ai/L TN2744

Chronic Data gap N / A

Freshwater invertebrates TGAI Acute EC 50 = 0.33 m g ai/L 429610

- 01

Chronic Data gap N / A

Estuarine/marine fish TGAI Acute Data gap N / A
Chronic Not required N / A

Estuarine/marine

invertebrates TGAI Acute Data gap N / A

Chronic Not required N / A

Sediment

- dwelling
I nvertebrates TGAI Acute and Chronic Not required N / A

Aquatic and semi

- aquatic plant s TGAI EC 50 NOAE C See Table 7 for anticipated need for these data N / A

Birds TGAI Acute LD50 = 1700 mg ai/kg 00134577

The Agency has no data for the iodophor carrier molecules . If the environmental fate data show that the carrier molecule is expected to reach aquatic environments, data on freshwater and estuarine animals and plants are anticipated to be required to assess the potential risks to aquatic systems from the movement of the carrier molecules to surface water.

O pen literature studies also will be identified through EPA’s ECOTOXicology (ECOTOX) database. The ECOTOX database will be searched whe n the risk assessment is prepared. A cuteDocket Number EPA

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Page 28 of 43 or chronic endpoints that are found to be more sensitive than what is currently available will be used in the risk assessment and risk characterization.



## 4.5 Exposure Analysis Plan

4.5.1 

### Aquatic and Terrestrial Wildlife Exposu re Estimates Available OPP models that estimate exposures from both direct and indirect discharges to surface water (including, but not limited to discharges via a wastewater treatment plant, leaching from paints, and consumer product analysis from down

- th e

- drain exposures) will be used to determine the estimated environmental concentration ( EECs ) in the aquatic environment. These exposure estimates will be compared to the toxicity endpoints to determine whether or not the Agency’s levels of concern for acu te and chronic risks to aquatic organisms, including listed species, are expected to be exceeded for each receptor group.



## 4.6 E ffects Analysis Plan

Additional open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database. The ECOTOX database will be searched during the risk assessment phase of iodophors and the data will be reviewed following the Agency’s policy for reviewi ng public literature for use in assessing risks from pesticide s 7

. Any acute or chronic endpoints more sensitive than what is currently available will be used in the risk assessment and risk characterization. ECOTOX was created and is maintained by the US EPA ’s , Office of Research and Development, and the National Health and Environmental Effects Research Laboratory's Mid

- Continent Ecology Division


## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity . These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of the 2006 RED for iodine and iodophors, EPA reviewed these d ata and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), iodine and iodophors are subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife si milar to an effect

7 http://www.epa.gov/pesticides/science/efed/polic y_guidance/team_authors/endangered_species_reregistration_work group/esa_evaluation_open_literature.htmDocket Number EPA

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Page 29 of 43 produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 1 1 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and establish a dose

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 8 and includes some pesticides scheduled for registration revi ew and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors

. For further information on the status of the EDSP, the policies and procedures, the list of chemicals, future lists, the test gu idelines and the Tier 1 screening battery, please visit our website 9

. 

## 6 Guidance for Commenters

6.1 Preliminary Work Plan
The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency will carefully consider all comments as well as a ny additional information or data provided in a timely manner prior to issuing a final work plan for the iodine and iodophors registration review

case.

6.1.1 

### Trade Irritants Through the registration review process, the Agency intends to solicit information on t rade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Stakeholde rs are asked to comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the nature of the concern.

6.1.2 

### Water Quality
The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard

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

- HQ

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- 2009

- 0477

- 0074 for the final second list of

chemicals.
9 http://www.epa.gov/endo/Docket Number EPA

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Page 30 of 43 Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 10 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

6.1.3 

### Environmental Justice EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the A gency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to iodine and iodophors compared to the general population. Please comm ent if you are aware of any sub

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

6.1.4 

### Structure Activity Relationships EPA must rely upon information of appropriate quality and reliability for each decision made b y the Agency. In the OPP, the evaluation process for a pesticide chemical traditionally begins with the applicant’s submission of a set of studies conducted with the specific pesticide chemical of interest. The use of the results of such testing (measured data) is a logical, scientifically rigorous process that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.

Today, there is significant interest in alternative techniques, i.e., techniques other than data generation that could significantly inform the Agency’s decision

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

- making process. In the SAR process, a chemical's molecular structure is compared to that of other chemicals for which data are available. These structural similarities are then used to make predictive judgments about a chemical’s phy sical, chemical, and biological properties. Thus, the chemical’s physical, chemical, and biological properties are a function of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To develop a QSAR, a sele cted set of measured data on a single physical, chemical, or biological property is used to derive a model (an equation) to predict the value of that property.

Since SAR assessments and QSAR modeling are another set of tools that are available to Agency

s cientists, OPP has begun a process shift that envisions shifting from the current study

- by

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

- of

- the

evidence evaluation.

At this time, EPA believes that for certain endpoints, especially physical/chemical and fate properties, that SAR and QSAR might be effectively utilized to fulfill these data requirements for many antimicrobial pesticide chemicals. When considering biological properties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the eval uation of

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Page 31 of 43 chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is appropriate because the risk assessment for lower toxicity chemicals can be stream

- lined, i.e., a screening

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

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

submission consultation with the Agency is encouraged.

6.1.5 

### Additional Information

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

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

1. Confirmation on the following label information: A. Sites of application B. Formulations C. Application methods and equipment D. Maximum application rates E. Frequency of application, application intervals and maximum number of applications F. Geo graphic limitations on use 2. Use or potential use distribution 3. Use history 4. Usage/use information for non

- agricultural uses (e.g., materials preservation) 5. Typical application interval 6. State or local use restrictions 7. Ecological incidents (non

- target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency 8. Monitoring data



## 7 Next Steps

After the 60

- day comment period closes in February 2014 , the Agency will review a nd respond to any comments received in a timely manner, and then issue a Final Work Plan for the I odine and I o dophors C ase.Docket Number EPA

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Page 32 of 43 

## 8 References

EPA. 2008. American Conference of Governmental Industrial Hygienists, ACGIH ® (2008) Iodine and Iodides: TLV Chemical Substances 7 th Edition Documentation

. Potassium Triiodide (KI 3 ) : Ecological Risk Assessment, New Chemical Registration (Section 3)

. Proposed Uses: Fungicide to control Fusarium sp. in Iris for cut flowers

. Proposed End Use Product: “AJI629 474EC”; EPA Reg. No. 71937

- R (474 g KI 3 /L; 33.1% w/w)

. Kline and Company, 2006: Specialty Biocides 2004

- 2005 A Global Series of Regional Market Analyses Volume II: United States.

LaValley, M.J. 1982. Acute toxicity of iod ine to channel catfish ( Ictalurus punctatus ). Bull. E nviron. Contam. Toxicol. 29:7

- 11.

National Academy of Science (NAS), 2001: Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington D.C.

WHO (World Health Organization); Poison Information Monographs 280: Iodine; 1990Docket Number EPA

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Page 33 of 43 

# Appendix A T oxicology Profile

The Agency intends to conduct an ethics review for human studies which may h ave involved intentional exposure to iodine , supporting the National Academy of Science’s 2001 report on Dietary Reference Intakes

. EPA will ensure that all applicable regulatory requirements are met

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Page 34 of 43 

# Appendix B Environmental Fate

Environmental Fate and Transport Properties of I odine

Water and Sediment

Hydrolysis , Aqueous Photolysis, Octanol

- Water Partition Coefficient, Aerobic Aquatic Metabolism , and A na erobic Aquatic Metabolism

The environmental and transport test guidelines were made to generate data for organics only. Inorganics do not undergo hydrolysis, aerobic or anaerobic metabolisms in aqeuous medium or in soils. Thus Test Guidelines Series 835 are not applicable for inorg anic elements such as iodine

. No additional data are anticipated to be required.

Soil

Soil Leaching/Adsorpt ion/Desorption Batch Equilibrium , Aerobic Soil Metabolism , A na erobic Soil Metabolism

The environmental and transport test guidelines were made to gen erate data for organics only. Inorganics do not undergo hydrolysis, aerobic or anaerobic metabolisms in aqeuous medium or in soils. Thus Test Guidelines Series 835 are not applicable for inorganic elements such as iodine. No additional data are anticipated to be required.

REFERENCES for Appendix B

1. 1981, EPA Publication of Pesticide Registration Standard on Polyoxyethylene ethanol monoesters of 5 and 6 carboxy

- 4

- hexyl

- cyclohexene

- 1

- octanoic acid iodine composite

. Not related to any of the present case of io dophors. Agency number was not assigned. 2. U.S. EPA. Reregistration Eligibility Decision (RED) for Iodine and Iodophor Complexes, Case No. 3080. July 27, 2006

. 3. OCSPP’s Office of Pesticides Programs’ Lower Risk Pesticides Chemical Group (RPCG). It conducted a risk assessment on iodine, KI, NaI< HI, and KIO 3 . Iodophors were not included in this document

. 4. World Health Organization Document: “Human Health Aspect of Iodine and Inorganic Iodides. Concise International Chemical Assessment”. Document 72 (2009) Iodp hors were not part of this document.Docket Number EPA

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Page 35 of 43 

# Appendix C Ecotoxicology Profile

The ecotoxicity p rofile is limited to the available ecotoxicity studies submitted to support iodine. The Agency has no data to support the iodophor carrier molecules and anticipates the need t o require ecotoxicology data (as noted in Table 7)

. 

### Toxicity to Terrestrial Organisms

Birds

Two acceptable acute

- oral (LD50) studies categorize iodine as being slightly to practically

non toxic to birds. The guideline (850.2100 ) is satisfied for iodine

.
Avian Acute

- O ral Toxicity

Test Species Test Material ( % ai) Toxicity Toxicity Category EPA Study ID

Northern bobwhite ( Colinus virginianus ) Nonylphenoxypoly

ethoxyethanol (100%) LD 50 = 1700 mg ai/kg bw Slightly toxic 00134577 Acceptable

Iodine (99.8%) LD 50 >2000 mg ai/kg bw Practically nontoxic 431384

- 01 Acceptable Tetraglycine hydroperiodide (100%) LD 50 >250 mg ai/kg bw Not determined 423283

- 01 Supplemental a

a did not determine an LD50 nor test up to 2000 mg ai/kg bw

Eight available dietary (LC50) studies categorize iodine as being practically non toxic to birds when administered in the diet

. No additional data are anticipated to be required for this guideline (850.2200) , which is not required for the use patterns of iodine/iodophors since the Agenc y does not anticipate conducting a nontarget terrestrial animal risk assessment during registration review

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Page 36 of 43 Avian Dietary Toxicity

Test Species Test Material ( % ai) Toxicity Toxicity Category EPA Study ID

Northern bobwhite ( Colinus virginianus ) Nonylphenoxypoly

ethoxyethanol (100%) LC50 >5620 ppm Practically nontoxic 00134576 Acceptable

Potassium triiodide (100%) LC50 >5000 ppm Practically nontoxic 469593

- 33 Acceptable Tetraglycine hydroperiodide (100%) LC50 >5000 ppm Practically nontoxic 423291

- 01 Supplemental a

Iodine (2.9% formulation) LC50 >5620 ppm Practically nontoxic 441098

- 06 Supplemental b

Iodine (99.8%) LC50 >5620 ppm Practically nontoxic 431917

- 01 Acceptable

Mallard ( Anas platyrhynchos ) Potassium triiodide (100%) LC50 >5620 ppm Practically nontoxic 431917

- 01 Acceptable

Nonylphenoxypoly

ethoxyethanol (100%) LC50 >5620 ppm Practically nontoxic 00134104 Acceptable

Potassium Triiodide ( 99.9%) LC50 >5000 ppm Practically nontoxic 469593

- 33 Acceptable

a no dietary analysis was conducted
b study was conducted on a formulated product (Divosan MH, 2.9% ai)

Nontarget Insects

Toxicity d ata for beneficial insects (850.3020, 850.3030) are not required for the use patterns of iodine. However, two bee studies were submitted to su pport a conventional use (cut

- flower treatment) that is no longer registered. The acute data categorize the product as being practically nontoxic to bees.

Toxicity to Honey Bees

Test Species Test Material ( % ai) Toxicity EPA Study ID

Honey bee ( Apis mellifera ) Potassium Triiodide ( PlantPro

- 45®, 3.06% iodine w/w ) LD50 = 70 μg ai/bee 469593

- 36 Acceptable

LC 50 = 34 μg ai/bee 469593

- 37 Acceptable



### Toxicity to Aquatic Organisms

Freshwater FishDocket Number EPA

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Page 37 of 43 The available acute toxicity studies categorize technical

- grade iodine as being highly toxic to freshwater fish. Two additional studies categorize a formulated product (Divosan MH, 2.9% ai) as being slightly toxic. The guideline (850.1075) for acute toxicity testing is satisfied for iodine but not for the iodophor carrier molecules. No chronic data are available . Because there may be continuous or repeated down

- the

- drain exposure, chronic data are anticipated to be required (fish early

- life stage, 850.1400).

Acute Toxicity of Iodine to Freshwater Fish

Test Species Test Material (% ai) Toxicity Endpoint (mg ai/L ) Toxicity Category EPA Study ID

Rainbow Trout ( Oncorhynchus mykiss) Nonylphenol (89.3%) 96

- hr LC50 = 0.30 Highly toxic TN2744 Supplemental a
Iodine (2.9% formulation) 96

- hr LC50 = 38 Slightl y toxic 441098

- 08 Supplemental b

I 2 (99%) 96

- hr LC50 = 0.53

- >10 (7 tests) Highly toxic Laverock et al. 1995 Supplemental c I - (99%) 96

- hr LC50 = 860

– 8230 (7 tests) Practically nontoxic Bluegill ( Lepomis macrochirus ) Iodine (99.8) 96

- hr LC50 = 0.61 Highly toxic 430445

- 01 Acceptable Nonylphenoxypoly

ethoxyethanol complex (20% iodine) 96

- hr LC50 = 0.33 d Highly toxic TN0622 Supplemental e

Iodine (2.9% formulation) 96

- hr LC50 = 37 Slightl y toxic 441098

- 07 Supplemental b

Channel catfish ( Ictalurus punctatus ) I 2 (reagent grade) 24

- hr LC50 = 0.44 Highly toxic LaValley 1982 Supplemental c

a test conducted at EPA Terrestrial and Aquatic Biology Lab., March 20, 1981
b study was conducted on a formulated product (Divosan MH, 2.9% ai)

c cited in EPA 2008
d value adjusted based on % iodine in the complex

e test conducted with Biopal NR

- 20 at USDA Animal Biology Lab., July 12, 1973

Freshwater Invertebrates

The acute toxicity studies for the waterflea categorize s technical

- grade iodine as being highly toxic t o freshwater invertebrates

. One study using a formulated product found that Divosan MH (2.9% ai) is slightly toxic to the waterflea. The guideline (850.1010) for acute toxicity testing is satisfied for iodine but not for the iodophor carrier molecules

. Because there may be continuous or repeated down

- the

- drain exposure, chronic data are anticipated to be required (life

- cycle, 850.1300)

.

Freshwater Invertebrates

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Page 38 of 43 Waterflea ( Daphnia
magna ) Iodine (99.8%) 48

- hr EC50 = 0.33 Highly toxic 429610

- 01 Acceptable

Iodine (2.9% formulation) 48

- h EC50 = 19 Slightly toxic 441098

- 09 S upplemental a

I 2 (99%) 96

- hr LC50 = 0.16

- 1.8 (7 tests) Highly toxic Laverock et al. 1995 Supplemental b I - (99%) 96

- hr LC50 = 0.17

– 0.83 (7 tests) Highly toxic

a study was conducted on a formulated product (Divosan MH, 2.9% ai)
b cited in EPA 2008

Estuarine/Marine Fish and Invertebrates

No acute or chronic data are available. Acute toxicity studies expected to be needed for the TGAI include tests for a fish sp ecies (850.1075), a bivalve sp. (850.1025 or 850.1055), and one additional invertebrate sp. (850.1035) for iodine and iodophor car rier molecules

. Chronic data
are not anticipated to be required

. Aquatic Plants

No data are available. A Tier II study (850.4500) is anticipated to be required for green algae ( Selenastrum capricornutum ) for iodine and the iodop hor carrier molecules . I f any study demonstrates detrimental effects at less than 1.0 ppm ( mg/L ), then additional data are anticipated to be required for a vascular species ( Lemna sp., 850.4400), two additional algal species ( Navicula pelliculosa and Skeletonema costatum

, 850.450 0), and cyanobacteria ( Anabaena flos

aquae , 850.4550).

Semi

- aquatic Plants

No data are available for iodine and the iodophor carrier molecules

. A seedling

- emergence study for rice (850.4225) is anticipated to be required only if the risk quotient from any aquatic plant growth Tier II test exceeds a level of concern for aquatic plants for iodine or the iodophor carrier molecules

. Sediment toxicity

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Page 39 of 43 REFERENCES for Appendix C

LaValley, M.J. Acute toxicity of iodine to channel catfish ( Ictalurus punctatus ). Bull. Environ. Contam. Toxicol. 29:7

- 11.

Laverock, M. J., M. Stephenson, and C.R. Macdonald. 1 995. Toxicity of iodine, iodide, and iodate to Daphnia magna and rainbow trout ( Oncorhynchus mykiss ). Arch. Environ. Contam. Toxicol. 29:344

- 350.

TN2744 EPA. 1981. Biological Report of Analysis: Nonylphenol (89.3%). Test #2744

- Rainbow trout ( Salmo gairdneri ), Terrestrial and Aquatic Biology Laboratory, Washington, DC.

TN0622 EPA. 1973. Biopal NR

- 20 (Nonylphenoxyethoxyethanol

-- iodine complex, 100%). Test no. 622

- Bluegill ( Lepomis macrochirus ), Animal Biology Laboratory, Beltsville, MD

.

46959336 Maggi, V. (2002) Evaluation of the Acute Contact Toxicity of Iodine, the Active Ingredient in PlantPro

- 45 on Adult Honey Bees (Apis mellifera L.). Project Number: CAR/128/02. Unpublished study prepared by California Agricultural Research Inc. 60 p.

46959337 Maggi, V. (2002) Evaluations of the Dietary Effect(s) of PlantPro

- 45 on Adult Honey Bees (Apis mellifera L.). Project Number: CAR/129/02. Unpublished study prepared by California Agricultural Research Inc. 50 p.

43044501 Zelinka, E.; Martin, K.; Swigert, J. (1993) IOBIO: A 96

- Hour Flow

- Through Acute Toxicity Test with the Bluegill (Lepomis macrochirus): Final Report: Lab Project Number: 355A/102. Unpublished study prepared by Wildlife International Ltd. 38 p.

43191701 Campbell, S.; Beavers, J. (1994) IOBIO: A Dietary LC50 Study with the Northern Bobwhite: Lab Project Number: 355

- 103. Unpublished study prepared by Wildlife International Ltd. 21 p.

44109806 Palmer, S.; Grimes, J.; Beavers, J. (1996) Divosan MH: A Dietary LC50 Study with the Northern Bobwhite: Lab Project Number: 425

- 102: 425/052395/QLCSDT.WC/CHP92. Unpublished study prepared by Wildlife International Ltd. 44 p.

43138401 Campbell, S.; Beavers, J. (1994) Iobio : An Acute Oral Toxicity Study with the Northern Bobwhite: Lab Project Number: 355

- 102. Unpublished study prepared byDocket Number EPA

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Page 40 of 43 Wildlife International Ltd. 18 p.

42329101 Pedersen, C. (1991) Tetraglycine Hydroperiodide: 8

- Day Acute Dietary LC50 Study in Bobwhite Q uail: Lab Project Number: 90 QC 151. Unpublished study prepared by Bio

- Life Associates, Ltd. 28 p.

42328301 Pedersen, C. (1991) Tetraglycine Hydroperiodide: 21

- Day Acute Oral LD50 Study in Bobwhite Quail: Lab Project Number: 90 QD 160. Unpublished study prepared by Bio

- Life Associates, Ltd. 35 p.

42961001 Zelinka , E.; Holmes, C.; Martin, K.; et al. (1993) IOBIO: A 48

- Hour Flow

- Through Acute Toxicity Test with the Cladoceran (Daphnia magna): Final Report: Lab Project Number: 355A

- 101. Unpublished study prepared by Wildlife International Ltd. 37 p.

44109809 Drottar, K.; Swigert, J. (1996) Divosan MH: A 48

- Hour Static Acute Toxicity Test with the Cladoceran (Daphnia magna): Final Report: Lab Project Number: 425A

- 106. Unpublished study prepared by Wildlife International Ltd. 36 p.

43044501 Zelinka, E.; Martin , K.; Swigert, J. (1993) IOBIO: A 96

- Hour Flow

- Through Acute Toxicity Test with the Bluegill (Lepomis macrochirus): Final Report: Lab Project Number: 355A/102. Unpublished study prepared by Wildlife International Ltd. 38 p.

44109807 Drottar, K.; Swigert, J. (1996) Divosan MH: A 96

- Hour Static Acute Toxicity Test with the Bluegill (Lepomis macrochirus): Final Report: Lab Project Number: 524A

105. Unpublished study prepared by Wildlife International Ltd. 36 p.

44109808 Drottar, K.; Swigert, J. (1996) Divo san MH: A 96

- Hour Static Acute Toxicity Test with the Rainbow Trout (Oncorhynshus (sic) mykiss): Final Report: Lab Project Number: 425A

- 104. Unpublished study prepared by Wildlife International Ltd. 36 p.

43191701 Campbell, S.; Beavers, J. (1994) IOBIO: A Dietary LC50 Study with the Northern Bobwhite: Lab Project Number: 355

- 103. Unpublished study prepared by Wildlife International Ltd. 21 p.

44109806 Palmer, S.; Grimes, J.; Beavers, J. (1996) Divosan MH: A Dietary LC50 Study with the Northern Bobwhite: Lab Project Number: 425

- 102: 425/052395/QLCSDT.WC/CHP92. Unpublished study prepared by Wildlife International Ltd. 44 p.

43138401 Campbell, S.; Beavers, J. (1994) Iobio: An Acute Oral Toxicity Study with the Northern Bobwhite: Lab Project Number: 355

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Page 41 of 43 Wildlife International Ltd. 18 p.

134104 Fink, R.; Beavers, J.; Grimes, J.; et al. (1978) Eight

- day Dietary LC50 (in) Mallard Duck: Biopal NR

- 20: Project No. 164

- 102. Final rept. (Unpublished study received Mar 22, 1979; Feb 6, 1979 under 1529

- 18; prepared by Wildlife International, Ltd. and Washington College, submitted by GAF Corp., Chemical Div., New York, NY; CDL:237871

- C)

134576 Fink, R.; Beavers, J.; Brown, R. (1978) Eight

- day Dietary LC50

-- Bobwhite Quail: Biopal NR

- 20: Project No. 164

- 101. Final rept. (Unpublished study received Mar 22, 1979 under 1529

- 18; pre

- pared by Wildlife International, Ltd. and Washington College, submitted by GAF Corp., Chemical Div., New York, NY; CDL: 237871

- A)

134577 Fink, R.; Beavers, J.; Grimes, J.; et al. (1978) Acute Oral LD50

-- Bobwhite Quail: Biopal NR

- 20: Project No. 164

- 103. Final rept. (Unpublished study received Mar 22, 1979 under 1529

- 18; pre

- pared by Wildlife International, Ltd. and Washington College, submitted by GAF Corp., Chemical Div., New York, NY; CDL: 237871

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Page 42 of 43 

# Appendix D Product Chemistry

The iodine product chemistry information is summarized in Table D 1 (source: MRIDs 44087501

, 42440101

, 41968702 ).

Table D 1

– P roduct Chemistry of Iodine and Iodophors

Guideline Numbers Parameters Iodine (I 2 ) 830.1550 Product identity and composition Refer to Table 8 830.1600 Description of materials used to produce the product CBI A

830.1620 Description of production process CBI A
830.1650 Description of Formulation Process CBI A
830.1670 Description of Formulation Process CBI A
830.1700 Preliminary analysis CBI A
830.1750 Certified limits CBI A
830.1800 Enforcement analytical method USP Assay (% iodine) for raw iodine

USP non

- volatile residue test for raw iodine 830.1900 Submittal of samples CBI

830.6302 Color

Bluish

- black scales, plates, or beads. Grey

- black flakes with metallic luster; sharp irritating halogen

- like odor Deep purple/black color.

830.6303 Physical State Solid; scales or plates or beads at room temperatures.

830.6304 Odor Sharp irritating halogen

- like odor. Slightly pungent, medicinal odor.

830.6313 Stability Stable under normal conditions. Sublimes at elevated temperatures and the vapor is corrosive.

830.6314 Oxidation/Reduction Iodine can exist in several oxidation
states:

- 1, 0, +1, +3, +5, and +7.

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Page 43 of 43 Guideline Numbers Parameters Iodine (I 2 ) 830.7000 pH at25 °C 5.4 (saturated solution) 830.7050 UV/Visible Absorption Not Reported 830.7200 Melting point (°C) 113.7 o C 830.7220 Boiling point (°C) 184.3 o C 830.7300 Density (g/cm 3 ) 4.933 g/cm 3 at 25 o C (Solid) 830.7100 Viscosity 830.7370 Dissociation Constant pKa(s) Not applicable. Doesn’t dissociate

830.7520 Particle size, fiber length, & diameter distribution -----
830.7550 Log Kow Not applicable 830.7840 Solubility in water (mg/L) at 25 o C 330 mg/L at 25°C. 830.7860 Solubility in organic solvents Soluble in many organic solvents. 830.7950 Vapor pressure (mm Hg) at 25 °C 0.31 mm Hg at 25°C

A Confidential business information