Docket Number EPA-HQ-OPP-2013-0767 www.regulations.gov



## Iodine and Iodophors Final Work Plan

Registration Review: Initial Docket
Case Number 3080

Approved by:

Date: 

## June 2014

Susan Lewis

Director

Antimicrobials Division

Page 1 of47Docket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

Page 2 of 47 Iodine and Iodophors Regi stration Review Team

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

Risk Management
Sandra O’Neill
Demson Fuller
James Parker

Office of General Counsel Philip RossDocket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

Page 3 of 47 

### Table of Contents

1 Introduction .................................................................................................................. ........... 5

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

1.2 Updates to the Workplan .................................................................................................. 6

1.3 Case Overview ................................................................................................................. 8

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

1.5 Use/Usage Description ................................................................................................... 12

1.5.1 Registrations ........................................................................................................... 12

1.5.2 Summary of Regist ered Uses .................................................................................. 12

1.5.3 Usage Information .................................................................................................. 14

1.6 Regulatory History ......................................................................................................... 14

1.6.1 Recent/Pending Regulatory Actions ....................................................................... 15

1.6.2 Tolerance Information ............................................................................................ 15

1.7 Incidents ..................................................................................................................... .... 15

1.7.1 Human Health ......................................................................................................... 15

1.7.2 Ecological ............................................................................................................... 16

2 Anticipated Data 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 ............................................................................................................ 2 1
3.4 Occupational and Residential Exposures ....................................................................... 22

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

3.4.2 Residential Handler Exposures ............................................................................... 23

3.4.3 Residential Post-Applic ation 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 Sedi ment, Soil, and Air .......................................................... 26

4.2 Water Quality ................................................................................................................. 26
4.3 Environmental 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 Wild life Exposure Estimates ............................................ 28

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

5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 28

6 Next Steps .................................................................................................................... ......... 29

7 References .................................................................................................................... ......... 30

Appendix A Toxicology Profile ............................................................................................... 31Docket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

Page 4 of 47 Appendix B Environmental Fate ............................................................................................. 32 Appendix C Ecotoxicology Profile .......................................................................................... 33 Appendix D Product Chemistry ............................................................................................... 40 Appendix E Comments Received Concerning th e Preliminary Work Plan ............................ 42

List of Tables Table 1 – Summary of Anticipated Ri sk Assessments and Data Needs ......................................... 7 Table 2 – Anticipated Regist ration Review Schedule .................................................................... 7
Table 3 – Chemical Identifica tion 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 a nd Iodophors Registered Uses .................................................... 13 Table 7 – Studies Anticipated as Needed for th e Registration Review of Iodine and Iodophors . 17 Table 8 – Iodine Recommended Exposu re Levels and Background Exposure ............................ 20 Table 9 – Occupational Handler Expo sure Scenarios for Iodine .................................................. 22 Table 10 – Residential Handler Expo sure Scenarios for Iodine ................................................... 23 Table 11 – Residential Post-Applicati on Exposure Scenarios for Iodine ..................................... 23 Table 12 – Ecological Effects E ndpoints for the Ecological Risk Assessment of Iodine. ........... 27Docket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

Page 5 of 47 

## 1 Introduction

This document is the United States Environmen tal Protection Agency’s (USEPA, EPA or “the agency”) Final Work Plan (FWP) for Iodine and Iodophors. The PWP docu ment explains what EPA's Office of Pesticide Programs (OPP) know s about iodine and iodophors, highlighting anticipated data and assessment needs, identify ing the types of information that would be especially useful to the agency in conducting the review, and providing an anticipated timeline for completing iodine and iodophors’ review. Th e Iodine and Iodophors ca se (case 3080) was previously known as the Iodi ne and Iodophor Complexes case. The Reregistration Eligibility Decision (RED) for Iodine and Iodophor Complexe s issued in July of 2006, the Amendment to the RED issued in August, 2006, and the Revised Amendment to the RED issued in March, 2009, all pertain to the Io dine and Iodophors Case.

The registration review process was designed to include a publi c participation component to solicit input from interested stak eholders. The agency intends, by sh aring this information in the docket, to inform the public of what it knows ab out iodine and iodophors and what types of new data or other information would be helpful fo r the agency to receiv e as it moves toward a decision on iodine and iodophors.



## 1.1 Statutory and Regu latory Authority

The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the USEPA based on scientific data showing that they will not cause unreasonable risk s to human health or the environment when used as directed on produc t labeling. The registra tion review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable
adverse effects to human health or the environm ent. Changes in scien ce, public policy, and pesticide use practices will occur over time. Th rough the registration review program, the agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Inform ation on this program is provided at http://www.epa.gov/oppsrr d1/registration_review/

.

The agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing registra tion review begin at 40 CFR 155.40. The agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the agency’s opportunity to state what it knows about the pesticide and what additional risk analyses
and data or information it believes are needed to make a registration re view decision. The Iodine and Iodophors Preliminary Work Plan (PWP) was published on December 20, 2013 and the 60- day comment period ended on February 18, 2014. Public comments received concerning the
PWP and documents associated with this registration review can be viewed at http://www.regulations.gov in docket EPA- HQ-OPP-2013-0767. Below is a summary of the
issues relevant to this registration review case.Docket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

Page 6 of 47 

## 1.2 Updates to the Workplan

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

 Corrected formatting and typographical errors.

 Added the crystalline or pe lleted/tabled products applic ation method to Table 6 - Summary of Iodine and Iodophors Registered Uses.

 Updated test substances in Table 7 – Studies Anticipated as Needed for the Registration Review of Iodine and Iodophors.

 The agency determined that a 90 day inha lation study (GLN 870.3465) may be necessary to assess risks for iodine and iodophors during Registration Review. As a result, Sections 3.1 and 3.2, and Tables 1 and 7 have been updated.

The agency received comment submissions from two organizations during the public comment period on the initial docket. Most of the comments were received from the Iodophors Steering Committee/Joint Venture (IJV), whose memb ers include EPA registrants DeLaval Manufacturing/West Agro; Diversey, Inc.; Ecol ab, Inc.; and Wisconsin Pharmacal. The IJV’s comments sought to confirm the agency’s classifi cation of iodine and iodophor chemicals, and present technical corrections to the Summary of Iodine and Io dophors Registered Uses table in the PWP (Table 6).

The Agency received additional comments from Diversey, Inc. expressing support for the comments submitted by the IJV.

Please see Appendix E for the agency’s responses to these comments.

Comments received did not result in a modification to the anticipate d data needs detailed in the Iodine and Iodophors PWP. This document make s final the work plan for the Iodine and Iodophors registration review process.Docket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

Page 7 of 47 Table 1 – Summary of Anticipated Risk Assessments and Data Needs

Iodine

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 details)

Dietary (food) No (see 3.3) 3/17/2009 None None

Dietary (drinking water) No (see 3.3) 3/17/2009 None None

Occupational and
Residential Handler Inhalation Exposures Yes None New Inhalation Toxicity Data Inhalation Indoor Exposure Data

Residental Post Application Incidental Oral Exposures 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 1.6.2) N/A— Existing
tolerance exemption None None

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

Iodophors

Ecological Effects and
Environmental Fate Yes N/A New Fish Aquatic invertebrates Aquatic and semi-aquatic plants Leaching from paints and coatings Activated Sludge Respiration Inhibition, Ready biodegradability test or one of three biodegradation in activated sludge
simulation tests

N/A = Not applicable

Table 2 – Anticipated Regi stration Review Schedule

Anticipated Activity Target Date* Completion Date Phase 1: Openin g the Docket Open Docket and 60-Day Comment Period for Preliminary Work Plan 2013-12 2013-12-20

Close Public Comment Period 2014-02 2014-02-18 Phase 2: Case Development

Issue Final Work Plan 2014-06 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) 2018-12

Close Public Comment Period 2019-01 Phase 3: Registration Review Decision and ImplementationDocket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

Page 8 of 47 Open 60-Day Public Comment Period for Proposed Decision 2019-06

Close Public Comment Period 2019-08

Issue Final Decision 2019-12 Begin Post-Decision Followup 2019 Total (years) 6

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



## 1.3 Case Overview

The docket for the Iodine and Iodophors Ca se (Case 3080) has been established at http://www.regulations.gov in docket number EPA-HQ-OPP-2013-0767.Docket Number EPA-HQ-OPP-2013-0767www.regulations.govPage9of471.4Chemical Identification and PropertiesTable 3 presents the active ingredients tobe assessed in the iodineand iodophors case where iodophor is defined as a moleculeofiodine and a surface-active agent that releases iodine gradually and serves as a disinfectant. There are 10 compounds in the caseincluding elemental iodine (Iodine, I2) and nine iodophors. Elemental iodine and the nine other chemicals areessentially carriers ofelemental iodine. These nine substancescan be classified as polymers, resins, orsurfactants. The purpose of the iodophor isto slowthe release of iodine. Though several iodophorproducts are classified in EPA’s databaseas containing elemental iodine (PC Code046905), only one product actually containselemental iodine, while the other products contain one ofthe 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, compd. with methyloxirane polymer with oxirane (PC Code 046904);4.Iodine (I2) (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 ethanoliodine complex (PC Code 046905);8.Sodium N-cyclohexyl-N-palmytoyl-taurate-iodine complex (PC Code 046905);9.Sodium dodecyl benzene sulfonate-iodine complex (PC Code 046905);10.Polystyrene divinyl benzene quaternary ammonium anion exchange resin-iodine complex (PC Code no. 046905).Table 3 – Chemical Identification of Iodine and IodophorsChemicalNameOxirane, methyl-, polymer withoxirane, monobutyl ether, compd.with iodineNonylphenoxypoly ethoxyethanol-iodine complexIodine, compd. withmethyloxirane polymer withoxiraneIodine (I2)BetadinePolyvinylpyrrolidone - iodinecomplexChemicalClassificationHalogenIodophorHalogenIodophorHalogenIodophorHalogenHalogenIodophorPC Code046901046903046904046905046914CAS Number68610-00-411096-42-726617-87-87553-56-225655-41-8MolecularFormulaC9H20I2O3C17H28I2O2C5H10I2O2I2C6H9I2NOMolecularWeight(grams/mole)430.06518.21355.94253.809364.95Docket Number EPA-HQ-OPP-2013-0767www.regulations.govPage10of47ChemicalNameOxirane, methyl-, polymer withoxirane, monobutyl ether, compd.with iodineNonylphenoxypoly ethoxyethanol-iodine complexIodine, compd. withmethyloxirane polymer withoxiraneIodine (I2)BetadinePolyvinylpyrrolidone - iodinecomplexMolecularStructure(Monomer)Chemical Identification of Iodine and Iodophors Contd.ChemicalNamePolyethoxy polypropoxypolyethoxy ethanoliodine complexSodium N-cyclohexylN-palmytoyl-taurateiodine complexSodium dodecyl benzene sulfonate-iodine complexPolystyrene divinylbenzenequaternary ammoniumanion exchange resin-Iodine complexGlycine, hydriodide (4:1),compd. with iodine (4:5)ChemicalClassificationHalogenIodophorHalogenIodophorHalogenIodophorIodinated Anion ExchangeResin ComplexHalogenPC Code046905046905046905046905046923CAS Number7553-56-27553-56-27553-56-27553-56-27097-60-1MolecularFormulaC7H14I2O3C24H46I2NNaO4SC18H30O3I2NaS-----C16H42I7N8O164[(NH2CH2COOH)2HI] .5I2MolecularWeight(grams/mole)399.99721.49603.29-----1490.95Docket Number EPA-HQ-OPP-2013-0767www.regulations.govPage11of47ChemicalNamePolyethoxy polypropoxypolyethoxy ethanoliodine complexSodium N-cyclohexylN-palmytoyl-taurateiodine complexSodium dodecyl benzene sulfonate-iodine complexPolystyrene divinylbenzenequaternary ammoniumanion exchange resin-Iodine complexGlycine, hydriodide (4:1),compd. with iodine (4:5)MolecularStructure(Monomer)x11⁄4The iodine product chemistry information (MRIDs 44087501, 42440101, 41968702) relevant torisk assessment is summarized inTable 4. All the iodine and iodophors listed in Table 3 are iodine (I2) releasers. Therefore, the physical and chemical properties listedin Table 4 for Iodine (I2) are also applicableto all the iodine compounds listed in Table 3.Table 4 – Physical-Chemical Properties for IodineGuideline No.ParameterIodine (I2)Physical/Chemical Properties830.7000 pH at 25°C 5.4 (saturated solution)830.7050 UV/Visible Absorption Not Reported830.7200 Melting point 113.7°C830.7220 Boiling point 184.3°C830.7300 Density 4.933 g/cm3at 25°C (Solid)830.7370 Dissociation constant (pKa) NA. Doesn’t dissociate830.7550 Log KowNA830.7840 Solubility in water 330 mg/L at 25°C.830.7860 Solubility in organic solvents Soluble inmany organic solvents.830.7950 Vapor pressure 0.31 mm Hg at 25°Catm-m3/mol = atmosphere cubic meter per mole;oC = degrees Celsius; mg/L = milligrams per liter;mmHg = millimeters of mercury; NA = Not applicableDocket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

Page 12 of 47 

## 1.5 Use/Usage Description

1.5.1 

### Registrations

There are 41 end use products (EUPs) that contai n iodine or one of the iodophors. It should be noted that, although several of the products are classified in EPA’s da tabase as containing elemental iodine (PC Code 046905), only one produc t contains elemental iodine, while the other products contain one of the iodophors. EPA will identify the products that were registered using data for elemental iodine (PC Code 046905) as potentially containi ng iodophors and assess the need to reclassify those products during registra tion 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, Crystals,

Filter cartridge

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

046914 1 1.28 RTU Liquid

046923 1 6.68 Tablet

1.5.2 

### Summary of Registered Uses

Table 6 summarizes the registered uses of iodi ne 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 di pped or soaked in a treatment solution. Iodophors
can be used to treat water usi ng cartridge filters or tablets. There is also one product (EPA registration number 72897-2) that includes the open pour applic ation of iodine powder as a material preservative and one product (EPA registration number 47371-158) that includes open pour application of iodine soluti on as a material preservative.Docket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

Page 13 of 47 Table 6 – Summary of Iodine and Iodophors 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 treatment Circulate in place (CIP), 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 470 ppm

Commercial/Institutional/Industria l (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 processing 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 30 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, crystalline or pelleted/tabled products 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-HQ-OPP-2013-0767 www.regulations.gov

Page 14 of 47 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 186 ppm 25 to 111 ppm 78 to 186 ppm 85 to 157 ppm

*Labels specify that food contact appli cation rates do not exceed 25 ppm of titr atable 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.

1.5.3 

### Usage Information

According to the Kline market research repo rt (Kline and Company, 2006), iodine and iodophors are used mainly in animal husbandr y and dairy industries. They are used as surface sanitizers for food mixing equipment, tanks, vats, bottling and f ood packaging equipment. They are also used for wash down hoses, treatment of udders a nd as sanitizers for milking equipment.



## 1.6 Regulatory History

Products containing iodine as the active ingredie nt were initially regi stered in the United States by the U.S. Department of Agriculture in 1948.The agency completed a Reregistration Eligibility Decision (RED) in Ju ly, 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 iodine and iodophors regi stration review case (3080) c onsists of ten compounds (see Section 1.4).

In addition to these compounds, there are nine iodophor active ingredie nts that have no registered products; therefore, the following active ingredients will not be included in this registration review:

 PC Code 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)

 Potassium triiodide (PC C ode 046917, CAS Number 12298-68-9)

 Ethanesulfonic acid, 2-(cyclohexyl(1-oxohexa decyl)amino)-, sodium salt, compd. with iodine (PC Code 046919, CAS Number 53404-81-2)

 Benzenesulfonic acid, dodecyl-, sodium sa lt, compd. with iodine (PC Code 046920, CAS Number 53467-01-9)

 Alpha-Alkyl-omega-hydroxypoly(oxyethylene) - iodine complex *(100% C12-C15) (PC Code 046921, CAS Number 68439-47-4)Docket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

Page 15 of 47  Alkyl* poly(oxypropylene)poly( oxyethylene)-iodine complex *(43%C10, 30%C14, 12%C12, 10%C16, 5%C18) (PC Code 046925, no CAS Number in EPA’s database)

 Acetalized polyvinyl alcohol complexed with iodine (PC Code 046926, no CAS Number)

 Potassium iodide (PC Code 075701, CAS Number 7681-11-0).

1.6.1 

### Recent/Pending Regulatory Actions

There are no recent regulatory actions for the Iodine and Iodophors Case. EPA anticipates issuing the post-RED product-spec ific data call-in (PDCI) soon.

1.6.2 

### Tolerance Information

Iodine has a tolerance exemption in 40 CFR 180. 940. The tolerance exemption has a limit in place that states, “when ready fo r use, the total end-use concen tration of all iodide-producing chemicals in the solution is not to exceed 25 ppm of titratable iodine”. Labels under review that

are inconsistent with this tolerance are listed here:

EPA Reg. Nos. 1677-22, 1072-11, 3862-18, 4959-15, 4959-16, 8405-3, 67517-9, 4959-36, 10190-16, 84890-3, 47371-93, 4959-18. The agency is in co ntact with the registrants for these products and is working to process upda tes to the labels for these products.



## 1.7 Incidents

1.7.1 

### Human Health

As of 11/22/2013, the OPP Incident System contai ns sixteen human minor (HD) and five human moderate (HC) incidents that were submitted af ter the RED was completed in July, 2006. There are no details given for the HD incidents. Details fo r the five HC incidents 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 medi cations for asthma and the st udent’s parents are attempting
to determine if the asthma attacks are rela ted to the products used in the cafeteria.

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

arm.

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

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

5. An employee mixed an iodine-based product with a sodium hypochl orite based product and afterwards spilled some portion of the mixture. The employee reported respiratory irritation, was sent to the emergency room a nd subsequently diagnosed with pneumonia.Docket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

Page 16 of 47 It is should be noted that all of the above HC incidents involved iodine based products that also contain phosphoric acid which is corrosive. With respect to incident 5, the iodine product label includes a warning that contact with chlorina ted products (such as sodium hypochlorite) may cause the violent evolution of toxic gases.

1.7.2 

### Ecological

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



## 2 Anticipated Data Needs

Table 7 presents a summary of the data anticipate d as being needed to su pport this registration

review.Docket Number EPA-HQ-OPP-2013-0767www.regulations.gov17Table 7 – Studies Anticipated as Needed for theRegistration Review of Iodine and IodophorsGLNStudy NameTest SubstanceTime Frame(Measured in monthsfrom DCI Receipt)Risk Assessment(s)Data Will SupportUse Site(s) TriggeringAnticipated DataRequirementApplicableExposureScenarioStudies Anticipated to be Required through the Registration Review DCINo GLNaSpecial leaching from paintsand coatingsTGAI: polystyrenedivinyl benzenequaternary ammoniumanion exchange resiniodine complex6 Aquatic organismsExteriorpaints/stains/coatingsAquaticenvironments835.3110835.3220835.3280835.3240Ready biodegradability testor one of threebiodegradation in activatedsludge simulation testsbTGAI: iodophors only24Aquatic organismsAllg850.6800aActivated Sludge,Respiration Inhibition12850.4400aAquatic plants, vascularspeciescTGAI:iodine and iodophors12Aquatic plants850.4500aAquatic plants, non-vasculard12850.4550aCyanobacteria toxicityd12850.4225aSeedling emergence, riceeTEP: iodine andiodophors12 Semi-aquatic plants850.1400aFish early life-stage,freshwater speciesTGAI: iodine andiodophors12 Fish850.1010aAquatic invertebratetoxicity, freshwaterTEP: iodophors only 24Aquatic invertebrates850.1300aInvertebrate life cycle,freshwater speciesTGAI: iodine andiodphors12850.1075aFish acute toxicity,estuarine/marine, freshwaterspeciesTEP: iodophors only 18Estuarine/marineorganisms850.1035aMysid acute toxicity 1218GLNStudy NameTest SubstanceTime Frame(Measured in monthsfrom DCI Receipt)Risk Assessment(s)Data Will SupportUse Site(s) TriggeringAnticipated DataRequirementApplicableExposureScenario850.1025aor850.1055aOyster shell depositionorBivalve embryo larvaltoxicity testTGAI: iodine andiodophors12870.346590-Day Inhalation, RatTGAI:iodine only24 Occupational andResidential HandlerAllhInhalationExposuref875.1400Indoor Exposure Data -Inhalation12875.2300 Surface Residue DataTGAI:iodine only 12Residential PostApplicationHousehold floor sanitizers Incidental OralaIodophor molecule data are expected to be needed if thereis a likelihood for exposure to the carrier in aquatic systems. Theagency has limited data on thecarrier portion of these molecules. If it can be shown that there is no aquatic exposure, ecotoxicity data will not be necessary for the iodophors.bEPA published draft guidance under guideline OPPTS 850.6800 and has since published final guidance for this study under guideline OCSPP 850.3300:http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0021. The agency has included this study in 40 CFR 158(W). OECD TestGuideline 209 can also be used as guidance for this study, available online athttp://www.oecd-ilibrary.org/content/book/9789264070080-en. The results of thisASRI test will determine which of four biodegradation tests is/arerequired. If the ASRI test EC50 is less than or equal to 20mg/L, then either the(i)Biodegradation in Activated Sludge Study or (ii) Simulation Test – Aerobic Sewage Treatment: A.Activated Sludge Units or (iii) the Porous Pot Test isexpected to be required. If the ASRI test EC50 is greater than 20 mg/L, then the registrant would likely be required to conducteither: (i) Ready Biodegradabilityor (ii) a) Biodegradation in Activated Sludge or b) SimulationTest – Aerobic Sewage Treatment:A. Activated Sludge Units or c)the Porous Pot Test. If theReady Biodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, the antimicrobial fails the ReadyBiodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or c) thePorous Pot study would likely be required.cData would be required if the aquatic (algal) plant growth Tier II study withSelenastrum capricornutumdemonstrates detrimental effects at less than 1.0 ppm(mg/L).dOne Tier II (dose response) study, conducted withSelenastrum capricornutum,is expected to be required; if the results of this study exhibit detrimental effects(EC50less than 1.0 ppm or mg/L), then additional Tier II (dose response) studies would be expected to be required on three species(Anabaena flos-aquae,Navicula pelliculosa, and Skeletonema costatum).eData are expected to be required only ifthe risk quotient from any aquatic plant growth Tier II test exceeds a level of concern for aquatic plants.fThe inhalation exposure scenarios include open pouring of liquids and wettable powder for material preservation, low pressurehand wand, high pressurehandwand, trigger sprayer, mop and wipe application, and airless sprayer application of preserved paints.gData are anticipated to be required forall use patterns which have the potential toresult in contamination of surface water.hData are anticipated to be required for all use patterns which have the potential to result in human inhalation exposures. However, the agency is currentlyreviewing the TLV for iodine that is based on a human study to determine if the TLV could be used in lieu of the 90-day inhalation toxicity study for portal ofentry effects.Docket Number EPA-HQ-OPP-2013-0767 www.regulations.gov

19 

## 3 Human Health Risk Assessment

EPA anticipates the need to assess occupational a nd residential inhalation e xposures to iodine as an aerosol because these exposures were not as sessed in the 2006 RED. The agency expects to require additional inhalation data for use in conducting the regi stration review. EPA does not anticipate the need to re assess the dietary and drinking water e xposures that were assessed in the 2006 RED, and additional di etary data are not anticip ated to be required.



## 3.1 Human Toxicology Data

EPA has not formally selected endpoints to as sess the human health risks for iodine and iodophors because iodine is an essen tial nutrient with a long history of clinical use in humans. In
the most recent risk assessment for iodine and iodophors (EPA, 2009), dietary risks were assessed using the Tolerable Upper Intake Level (UL) while inhalation exposures were assessed using the American Conference of Government al Industrial Hygienis ts (ACGIH) Threshold Limit Value (TLV) of 0.1 ppm for iodine vapor.

However, additional inhalation toxicity data are an ticipated to be required for registration review based upon the need for re-evaluation of the toxico logy database as well as consideration of the current use patterns that may re sult in human exposure to iodine and iodophors. These labeled use patterns include open pouri ng of liquids and wettable powder for material preservation, low pressure hand wand, high pressure hand wand, tri gger sprayer, mop and wipe application, and airless sprayer application of preserved paints.

Oral Exposures

The National Academy of Sciences has set the Di etary Reference Intake (DRI) of iodine 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 DRIs for children are in the rang e of 90-150 μg/day (1-8 years: 90 μg/day; 9-13 years: 120 μg/day; 14-18 years: 150 μg/day). Th e DRIs for pregnant a nd lactating women are 220 μg/day and 290 μg/day, respectively.

A Tolerable Upper Intake Level (UL), the maximum le vel of daily intake that is likely to pose no risk of adverse effects, has been establishe d at 1,100 μg/day (0.016 mg/kg/day) for adult men
and women based on serum thyroptropin concentration in respons e to varying levels of ingested iodine. The ULs for children range from 200 - 6 00 μg/day (1-3 years: 200 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 pre gnant and lactating wome n 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 recomme nded that the only source of this essential nutrient for infants be from food and formula (NAS, 2001).

In 1978, the Food and Drug Administration deemed pot assium iodide a safe and effective means by which to block uptake of radioiodines by th e thyroid gland in the event of a radiation20 emergency under certain specified conditions of us e. 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. Th ese values range from 16,000 μg (16 mg) to 130,000 μg (130 mg) of potassium iodide.

There are no primary drinking wa ter standards (MCL) for iodine or its oxidized or reduced forms, as iodine is used in emergency disinfect ion of water and not in treatment of municipal water supplies. In addition, there are no Health Advisories (HA), sec ondary drinking water standards, or ambient water quality standards associated with iodine , iodate and iodi de. Iodine is approved by the Office of Water for emergency di sinfection of drinking wa ter. The guidelines for emergency disinfection can be accessed at: www.epa.gov/safewater/faq/emerg.htm

.

For comparison 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 Academ y 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 Agricu lture Continuing Survey of Food Intakes by Individuals (1994-1996) 190 to 210 μg/day for women

240 to 300 μg/day for men

Inhalation ExposuresThe ACGIH has adopted a Threshold Limit Value - Time Weighted Average (TLV-TWA) of 0.1 mg/m 3 for iodine and iodides as I nhalable Fraction and Vapor and a TLV – Short term Exposure Limit (STEL) of 1.0 mg/m 3 for iodine vapor (ACGIH, 2008). The TWA TLV was adopted in 2008 and is based on th e 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 st udy, 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). Th is TLV was used in the 2006 RED to assess exposures to workers.

The Occupational Safety and Health Administra tion (OSHA) has a permissible exposure limit (PEL) of 1 mg/m 3 for iodine (29 CFR 1910.1000). This PEL is a ceiling limit that cannot be exceeded at any time. The PEL was estab lished in 1970 and it was based on the 1963 TLV STEL of 1 mg/m 3 for iodine vapors.21 3.1.1 

### Human 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 re search involving inten tional 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 Bo ard (HSRB) review of certain rese arch involving intentional exposure of human subjects.



## 3.2 Proposed Toxicological Endpoints

Oral Exposures

Since no new information has become available th at would change the conclusions made in the RED Amendment of 2009, EPA will continue to use the tolerable upper intake level as a basis for assessing the human health risk s of iodine oral exposures.

Inhalation Exposures

Depending on the outcome of the HSRB review of the human studies that were used by NAS to develop the DRIs, EPA might use these same studi es to evaluate the systemic toxicity from iodine inhalation exposures. In addition, EPA is anticipating to require a 90 day inhalation toxicity study in rats to evaluate the portal of entry effects of iodi ne inhalation exposure.

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 per cent of absorption and
no new information has become availabl e that would change this conclusion.



## 3.3 Dietary Exposure

Uses of iodine and iodophors that may result in dietary exposure (food a nd water) include use as food-contact surface sanitizers (ute nsils and countertops, dairy pro cessing equipment), as fruits and vegetables sanitizing wash (military personnel only), egg washes, and in emergency drinking

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 expos ure assessment because 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 oral toxicological endpoints of concern. Therefore, dietary risks were assessed using the Tolerable Upper Intake Level (UL) established by NAS, whic h is the maximum level of daily intake that is likely to pose

1 U.S. EPA. Revised Amendment for Iodine Reregistra tion Eligibility Decision (RED) Case No. 3080. March 17,
2009.22 no risk of adverse effects (EPA, 2009). All of the calculated risks as well as the combined risks

are not considered to be of concern. The calcu lated dietary daily dose (mg/kg/day) was less than the UL for each population subgroup. Since the uses have not changed since the 2009 risk assessment, the agency 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, exces sive iodine intake by a lactating mother will
increase the iodine content of breast milk and ma y negatively affect the infant's health. Certain individuals appear to be sensitiv e to iodine and may react to ex cessive intake of it. For people with certain health conditions (e.g., thyroid dysf unction), excess iodine intake may interfere the person's treatment process. Therefore, the use of iodine and iodophors fo r use in drinking water
disinfection is limited to short-te rm situations only when potable water is not available. The 2009 amended RED specified that the following label st atement be included in the Directions for Use section for end use products where iodine or an iodophor is used as an emergency water disinfectant: “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 Re sidential Exposures

Occupational and residential exposures were only assessed in the 2006 RED for inhalation exposure to iodine as a vapor. To account for the proposed to xicological endpoint, inhalation exposures to iodine as an aer osol will need to be asse ssed during registration review.

3.4.1 

### Occupational Handler Exposure

The occupational handler exposure s cenarios that will need to be a ssessed for iodine are listed in

Table 9.

Table 9 – Occupational Handler Exposure Scenarios for Iodine

Scenario Exposure Route(s) Duration

Open pouring of liquid formulations during material preservation Inhalation Short and Intermediate

Term

Open pouring of powder formulations during material preservation Inhalation Short and Intermediate

Term

Applying disinfectant using low pressure handwands, high pressure handwands, trigger sprayers, mops and wipes. Inhalation Short, Intermediate, and Long Term

Airless Sprayer Application of preserved paints Inhalation Short and Intermediate

Term23 3.4.2 

### Residential Handler Exposures

The residential handler exposure sc enarios that will need to be a ssessed for iodine are listed in

Table 10.

Table 10 – Residential Handler Exposure Scenarios for Iodine

Scenario Exposure Route(s) Duration

Applying disinfectant to hard surf aces 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 e xposure scenarios that will need to be assessed for iodine are listed in Table 11. The agency anticipates the need to require a surface residue study (875.2300).

Table 11 – Residential Post-Application Exposure Scenarios 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 inhalation toxicity endpoints were not identified from the available studies/data on iodine and iodophors. Therefore, 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 me chanism of toxicity, EPA has not made a common mechanism of toxicity finding as to iodi ne and iodophors 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, th erefore, EPA has not a ssumed that iodine and iodophors have a common mechanism of toxicity with other substances. For information24 regarding EPA’s efforts to determine which ch emicals have a common me chanism 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 an ec ological risk assessment for the antimicrobial uses of iodine. A conventional use for drip-irr igation or direct soil- injection of potassium

triiodide 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 a ssessment noted that given the reactive nature of the active ingredient, the risks described in th e assessment were expected to occur only for a short time (hours) after applicati on. Data were not available to asse ss risks to aquatic plants or estuarine/marine organisms.

Further, EPA has not assessed environmental risks from the iodophor carrier molecules. Currently, however, the agency is assessing degr adation/transformation pr oducts that have the potential to affect the aquatic environment and notes that there is very little information available to the agency on the carrier molecu les’ environmental fate and toxi city to aquatic organisms.

The ecological risk assessment planned during re gistration 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 aquatic environment.

The agency has not conducted a risk assessmen t that supports a complete endangered species determination for iodine and iodophors. The ecologi cal risk assessment will allow the agency to
determine whether each use of the iodine has 'no eff ect' or 'may affect' fede rally listed threatened or endangered species (listed speci es) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a liste d species or its designated critical habitat, the agency will consult with the U.S. Fish and Wild life Service and/or National Marine Fisheries Services (the Services), as appropriate.



## 4.1 Environmental Fate Assessment

The potential exposure of non-ta rget organisms from the use of iodophors as antimicrobial pesticides is complicated since it consists of exposure to elemental iodine and nine other chemicals which are essentially ca rriers of elemental iodine. These nine substances can be classified as polymers, resins, or surfactants. The purpose of th e iodophor is to slow the release of iodine. The vapor pressure of iodine from these iodophors is decreased relative to the vapor pressure of iodine by itself as was shown in the EPA’s 2006 RED

. The iodine component of the iodophor can be as I 2, I 3 - or I 5 with various oxidation states simila r to other halogens like chlorine and bromine. In all cases, iodine pr ovides the antimicrobial activity.25 Iodine (I 2 ) is one of the halogens, and is a solid at room temperature. As discussed in the product chemistry section, iodine has a high vapor pressu re (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(gas) -  (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 -

The agency lacks fate information on most of the iodophors and therefore cannot predict concentrations of the iodophor carrier molecule s released to surface water. As a result, an activated sludge, respiration i nhibition (ASRI) study is antici pated to be required for iodophors which are expected to reach surface water. The resu lts of the ASRI test determine which of four biodegradation tests are expected to be required and determines the extent of impacts to Wastewater Treatment Plant (WTTP) or ganisms (as indicated in Table 7).

For two iodophors, the agency has sufficient fate information to determine that they are unlikely to be found in surface water; therefore, no addition al fate or ecotoxicity data are necessary for the following compounds:

1. Sodium dodecyl benzene sulf onate (PC Code 046905) is an alkylbenzene sulfonate (ABS) for which the agency published a prel iminary work plan in March 2013. Sodium dodecylbenzene sulfonate is readily bi odegradable 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, hydriodide (4:1), compd. with iodi ne (4:5) (PC Code 046923): tetraglycine is a peptide of the simplest amino acid glycine, wh ich is a naturally occurring substance. An EPI suite run (EPI Suite, ve rsion 4.11), on tetraglycine provided the following fate information of tetraglycine: “Tetraglycine is highly water soluble and has a low vapor pressure (VP = 1 x 10 -15 mm Hg). It is ready biodeg radable and is not likely to bioaccumulate (Log K ow = -3.75). It is not likely removed in the STP process. Its halflife in air is 2.4 hours. The agency does not an ticipate 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 en closed in a cartridge, if spent cartridges are considered to be solid waste.

4.1.1 Leaching for Paints, Stains, and Coatings

Polystyrene divinyl benzene qua ternary ammonium anion exchange resin-iodine complex (PC Code 046905) is an iodophor used in paints, stai ns and coatings. Iodine is released as a disinfectant. Iodophors also are us ed in filter media (as cartridges) and, for textiles, as a coating on tarps, gloves, and sports equipment. In order to assess the potential for aquatic exposure from26 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 en vironmental media (WHO, 1990).



## 4.2 Water Quality

Elemental iodine (or iodide ion, or tri-iodide ion, or pentaiodide ion ) is not identified as a cause of impairment for any water bodies listed as im paired 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 iodophors are not identif ied 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 deve loped 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 th ose inhabiting water bodies adjacent to or
downstream from sources of down-the-drain discha rges (e. g., waste water treatment plants) or from environmental transport of iodine and iodo phor carriers leached from application of paints and coatings to exterior sidi ng and roofing materials. Wate r bodies might include impounded bodies (e. g., ponds, lakes, reservoi rs) or flowing waterways (e. g., st reams, rivers). For uses in coastal areas, aquatic habitat al so includes marine ecosystems, including estuaries. Aquatic organisms likely to be acutely exposed to iodine and iodophor carriers include fish, invertebrates, aquatic stages of amphibians, and aquatic and semi-aquatic plants. Chronic exposure also is possible due to continuous or repeated exposures from residential and i ndustrial down-the-drain discharges.

For aquatic animals, the major route of exposure is considered to be uptake via the respiratory surface (gills) or the integument from surface wa ter that has iodine residues. 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 considered 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 toxi city data from registrant-submitted studies
conducted in accordance with the 850 OCSSP Harm onized 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

6 http://www.epa.gov/owow/tmdl/27 evaluate the potential direct a nd indirect effects of iodine a nd iodophor carriers to plants and aquatic animals. Relevant data from the open l iterature available in ECOTOX also may be used to evaluate potential direct and indirect effects. For iodine, additional data that are anticipated to be required are identif ied as data gaps in Table 12 below.

4.4.1 

### Mechanism of Action

Mortality in fish appears to be due to as phyxiation 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 12. Data gaps (resulting in anticipated data need s in Table 7) also are
indicated.

Table 12 – Ecological Effects Endpoints for th e Ecological Risk Assessment of Iodine.

Receptor

Group Test

Material Risk

Scenario Toxicity Endpoint Reference

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

Chronic Data gap N/A

Freshwater invertebrates TGAI Acute EC 50 = 0.33 mg 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

Invertebrates TGAI Acute and Chronic Not required N/A

Aquatic and semi-aquatic plants TGAI EC 50 NOAEC 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 i odophor 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 car rier molecules to surface water.

Open literature studies also will be iden tified through EPA’s ECOTOXicology (ECOTOX) database. The ECOTOX database will be searched when the risk assessment is prepared. Acute28 or chronic endpoints that are found to be more sens itive than what is currently available will be
used in the risk assessmen t and risk characterization.



## 4.5 Exposure Analysis Plan

4.5.1 

### Aquatic and Terrestrial Wildlife Exposure Estimates

Available OPP models that estimate exposures from both direct and indi rect discharges to surface water (including, but not limited to discha rges via a wastewater treatment plant, leaching from paints, and consumer product analysis from down-the-drain exposures) will be used to determine the estimated environmental concentration (EECs) in the aquatic environment. These exposure estimates will be compared to the toxic ity endpoints to determine whether or not the agency’s levels of concern for acute and chroni c risks to aquatic organi sms, including listed species, are expected to be ex ceeded for each receptor group.



## 4.6 Effects Analysis Plan

Additional open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX)

database. The ECOTOX database will be sear ched during the risk assessment phase of iodophors and the data will be reviewed followi ng the agency’s policy for reviewing public literature for use in assessing risks from pesticides 7 . Any acute or chronic endpoints more sensitive than what is currently available wi ll be used in the risk assessment and risk

characterization. ECOTOX was creat ed 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 num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of the 2006 RED for i odine and iodophors, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFD CA section 408(p), iodine and iodophors are subject to the endocrine screeni ng part of the Endocrine Disrup tor Screening Program (EDSP).

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

7 http://www.epa.gov/pesticides/science/efed/policy_guidan ce/team_authors/endangered_s pecies_reregistration_work group/esa_evaluation_open_literature.htm29 produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required
determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the agency must scr een all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 8 and includes some pesticides scheduled for registration review and chemicals found in water

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

For further information on the status of the ED SP, the policies and procedures, the list of chemicals, future lists, the test guidelines and the Tier 1 screening ba ttery, please visit our
website 9

.


## 6 Next Steps

A DCI will be developed regarding the data needs listed under the “Risk Assessments and Anticipated Data Needs” section of this document. The agency expects to issue the DCI in June

of 2015.

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

chemicals.

9 http://www.epa.gov/endo/30 

## 7 References

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

. Potassium Triiodide (KI 3 ): Ecological Risk Assessment, Ne w 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 iodine to channel catfish ( Ictalurus punctatus ). Bull.
Environ. Contam. Toxicol. 29:7-11.

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

WHO (World Health Organization); Poison Information Monographs 280: Iodine; 199031 

# Appendix A Toxicology Profile

The agency intends to conduct an ethics revi ew for human studies which may have involved intentional exposure to iodine , supporting the National Acad emy of Science’s 2001 report on Dietary Reference Intakes. EPA will ensure that all applicable regulatory requirements are met.32 

# Appendix B Environmental Fate

Environmental Fate and Transport Properties of Iodine

Water and Sediment

Hydrolysis, Aqueous Photolysis, Octanol-Wate r Partition Coefficient, Aerobic Aquatic Metabolism, and Anaerobic Aquatic Metabolism

The environmental and transport test guidelines we re 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 inorganic elements such as iodine. No additional data are anticipated to be required.

Soil

Soil Leaching/Adsorption/Desorption Batch Equ ilibrium, Aerobic Soil Metabolism, Anaerobic

Soil Metabolism

The environmental and transport test guidelines we re 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 inorganic elements such as iodine. No additional data are anticipated to be required.

REFERENCES for Appendix B

1. 1981, EPA Publication of Pesticide Registra tion Standard on Polyoxyethylene ethanol monoesters of 5 and 6 carboxy-4- hexyl-cyclohexene-1-octanoi c acid iodine composite. Not related to any of the present case of iodophors. Agency number was not assigned.

2. U.S. EPA. Reregistration Eligibility Decisi on (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 assessm ent 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) Iodphors were not part of this document.33 

# Appendix C Ecotoxicology Profile

The ecotoxicity profile is limited to the available ecotoxicity studies submitted to support iodine. The agency has no data to support the iodophor ca rrier molecules and anticipates the need to require ecotoxicology data (as noted in Table 7).



### Toxicity to Terrestrial Organisms

Birds

Two acceptable acute-oral (LD50) studies categori ze iodine as being slig htly to practically nontoxic to birds. The guideline (8 50.2100) is satisfied for iodine.

Avian Acute-Oral Toxicity

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

ID

Northern bobwhite ( Colinus virginianus ) Nonylphenoxypolyethoxyethanol (100%) LD50 = 1700 mg ai/kg bw Slightly toxic 00134577 Acceptable

Iodine (99.8%) LD50 >2000 mg ai/kg bw Practically nontoxic 431384-01 Acceptable

Tetraglycine hydroperiodide (100%) LD50 >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) st udies categorize iodine as bei ng practically nontoxic 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 patter ns of iodine/iodophors since the agency does not anticipate conducting a nont arget terrestrial animal risk assessment during registration
review.34 Avian Dietary Toxicity

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

ID

Northern bobwhite ( Colinus virginianus ) Nonylphenoxypolyethoxyethanol (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

Nonylphenoxypolyethoxyethanol (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 data for beneficial insects (850.3020, 850.3030) are not requ ired for the use patterns of iodine. However, two bee studies were submitted to support a conventional use (cut-flower treatment) that is no longer registered. The acute data categorize the pro duct 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 Fish35 The available acute toxicity stud ies categorize technical-grade i odine as being highly toxic to freshwater fish. Two additional studies categor ize a formulated product (Divosan MH, 2.9% ai) as being slightly toxic. The gui deline (850.1075) for acute toxicity testing is satisfied for iodine but not for the iodophor carrier molecules. No chr onic data are available. Because there may be continuous or repeated down-the-dr ain exposure, chronic data are an ticipated 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 Slightly 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
Nonylphenoxypolyethoxyethanol complex (20% iodine) 96-hr LC50 = 0.33 d Highly toxic TN0622 Supplemental e

Iodine (2.9% formulation) 96-hr LC50 = 37 Slightly 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 th e waterflea categorizes technical -grade iodine as being highly
toxic to freshwater invertebra tes. One study using a formulated product found that Divosan MH (2.9% ai) is slightly toxic to th e 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 exposur e, chronic data are anticipated to be required (life-cycle, 850.1300).

Freshwater Invertebrates

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

ID36 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 Supplemental 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 species (850.1075), a bivalve sp. (850.1025 or 850.1055), and one additional invertebrate sp. (850.1035) for iodine and iodophor carrier 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 iodophor carrier molecules. If any study
demonstrates detrimental effects at less than 1.0 ppm (mg/L), then additiona l data are anticipated to be required for a vascular species ( Lemna sp., 850.4400), two additional algal species ( Navicula pelliculosa and Skeletonema costatum , 850.4500), and cyanobacteria (Anabaena flosaquae , 850.4550).

Semi-aquatic Plants

No data are available for iodi ne and the iodophor carrier molecu les. 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

Sediment toxicity data are not anticipated to be required for iodine, based on its environmental fate properties (K d <50 L/kg).37 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. Macdona ld. 1995. 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 A quatic Biology Laboratory, Washington, DC.

TN0622 EPA. 1973. Biopal NR-20 (Nonyl phenoxyethoxyethanol--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 H oney Bees (Apis mellifera L.). Project Number: CAR/128/02. Unpublished study pr epared by California Agricultural Research Inc. 60 p.

46959337 Maggi, V. (2002) Evaluations of the Di etary Effect(s) of PlantPro-45 on Adult Honey Bees (Apis mellifera L.). Project Number: CAR/129/02. Unpublished study prepared by California Agricu ltural Research Inc. 50 p.

43044501 Zelinka, E.; Martin, K.; Swigert, J. (1993) IOBIO: A 96-Hour Flow-Through Acute Toxicity Test with the Bluegill (Lepom is macrochirus): Final Report: Lab Project Number: 355A/102. Unpublished study prepar ed 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: La b Project Number: 425-102: 425/052395/QLCSDT.WC/CHP92. Unpublishe d study prepared by Wildlife International Ltd. 44 p.38 43138401 Campbell, S.; Beavers, J. (1994) Iobio: An Acute Oral Toxicity Study with the Northern Bobwhite: Lab Project Numb er: 355-102. Unpublished study prepared by Wildlife International Ltd. 18 p.

42329101 Pedersen, C. (1991) Tetraglycine H ydroperiodide: 8-Day Acute Dietary LC50 Study in Bobwhite Quail: Lab Project Number: 90 QC 151. Unpublished study prepared by Bio-Life A ssociates, Ltd. 28 p.

42328301 Pedersen, C. (1991) Tetraglycine Hydr operiodide: 21-Day Acute Oral LD50 Study in Bobwhite Quail: Lab Project Numb er: 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 Cladocer an (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: 425A106. Unpublished study prepared by W ildlife International Ltd. 36 p.

43044501 Zelinka, E.; Martin, K.; Swigert, J. (1993) IOBIO: A 96-Hour Flow-Through Acute Toxicity Test with the Bluegill (Lepom is macrochirus): Final Report: Lab Project Number: 355A/102. Unpublished study prepar ed 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 macrochiru s): Final Report: Lab Project Number: 524A105. Unpublished study prepared by W ildlife International Ltd. 36 p.

44109808 Drottar, K.; Swigert, J. (1996) Divosan MH: A 96-Hour Static Acute Toxicity Test with the Rainbow Trout (Oncorhynshus (s ic) mykiss): Final Report: Lab Project Number: 425A-104. Unpublished study prepar ed 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: La b Project Number: 425-102:39 425/052395/QLCSDT.WC/CHP92. Unpublishe d 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 Numb er: 355-102. Unpublished study prepared by 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. Fi nal rept. (Unpublished study received Mar 22, 1979; Feb 6, 1979 under 1529-18; prep ared 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., Chem ical 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., Chem ical Div., New York, NY; CDL: 237871- B)40 

# Appendix D Product Chemistry

The iodine product chemistry information is summarized in Table D1 (source: MRIDs 44087501, 42440101, 41968702).

Table D1 – Product 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.

(strongly acidic oxide)

830.6315 Flammability Non flammability

830.6316 Explodability Not explodable41 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 information42 

# Appendix E Comments Received Concerning the Preliminary Work Plan

On December 20, 2013 EPA opened a 60-day public comment period on the preliminary work plan (PWP) for the registration review of i odine and iodophors. The comment period ended on February 18, 2014. During the public comment period the Agency received comments submissions from two organizations. Comments r eceived did not result in a modification to the anticipated data needs detailed in the Iodine and Iodophors PWP.

Most of the comments were received from the Iodophors Steering Committee/Joint Venture (IJV), whose members include EPA registrants DeLaval Manufacturing/West Agro; Diversey, Inc.; Ecolab, Inc.; and Wisconsin Pharmacal . The IJV’s comments sought to confirm the agency’s classification of iodine and iodophor chemicals, and presen t technical corr ections to the Summary of Iodine and Iodophor s Registered Uses table in the PWP (Table 6).

The Agency received additional comments from Diversey, Inc. expressing support for the comments submitted by the IJV.

The Antimicrobials Division (AD) generally used an outline format to address the comments (with name of submitter, comment and AD response, in that order).Page 43 of 47 Comments Received on the Registration Review Preliminary Work Plan for Iodine and Iodophors

Submitter: Iodophors Steering Committee/Joint Venture (IJV)

1. Comment: “In response to an IJV Case Over view including the grouping of various Iodine and Iodophor complexes, dated Se ptember 15, 2004, EPA concluded in a July 2002 memo that: ‘The Regulatory Management Branch II reviewed the latest grouping or classification of types of Iodine/Iodophor chemicals and/or complexes and RMBII found the groupings scientifically valid and accep table for the purpose of RED production’... The IJV is pleased the Agency continues to utilize the groupings for Reregistration and strongly suggests continuati on for Registration Review.”

The IJV Classification of Iodine/Iodophor Complexes are summarized as follows:

Group General Representation/names I a) Iodine b) Potassium Iodine II Surfactant-iodine complexes a) Polypropxypolyethoxyethanol-iodine complexes;, including: butoxypolypropxypolyethoxyehtanol-iodi ne complex; alpha-alkylomega-hydroxypoly(oxyethylene)-iodine complex; alkyl(C12- 14)poly(oxypropylene)poly(oxyethylene)-iodine complex* b) Phenoxypolyethoxyethanol –iodine complex, including: nonylphenoxypolyethoxyethanol-iodine complex; octylphenoxypolyethoxyethanol-iodine complex c) Polyvinylpyrrolidone-iodine complexes, including: polyvinylpyrrolidone-iodine complex

III Amino acid-iodine complex, including: tetraglycine hydroperiodide

IV Iodine resins, including: iodine bound to strong base anion exchange.

Table of Iodine Chemicals and Corres ponding Registrations Supported by the IJV
Members

Names And Subgroups PC Code R e g #

G

Iodine 46905 875-18 8

46905 875-18 3

46905 875-18 3

Potassium Iodide N/A N/A

N/A N/AGroup II: Surfactanta) Polypropxypolyethoxyethanol-iodine complexesPage 44 of 47 butoxypolypropxypolyethoxyehtanol-iodine complex 46901 1677-2 2

46901 1677-5 8

46905 875-18 8

46905 7546-1 3

46904 4959-1 8

Polyethoxypolypropoxypolyethoxyethanol-iodine (also called polypropoxypolyethoxyethanol-iodine) 46905 1677-8 9

46904 4959-38-4266 6

46904 4959-3 8

46904 4959-38-1138 8

Polyethoxy polypropoxy polyethoxy ethanol-iodine complexes 46904 4959-1 8

alpha-(p-nonylphenyl)-omega-hydroxypoly(oxyethylene)-iodine complex 46904 4959-1 6

46904 4959-13-A A

alpha-alkyl-omega-hydroxypoly(oxyethylene)-iodine complex N/A N/A

alkyl(C12-14)poly(oxypropylene)poly(oxyethylene)-iodine complex N/A N/A

b) Phenoxypolyethoxyethanol –iodine complex

nonylphenoxypolyethoxyethanol-iodine complex N/A N/A

octylphenoxypolyethoxyethanol-iodine complex N/A N/A

nonylphenoxypolyethoxyethanol-iodine complex 46904 4959-21-6266 6

Nonylphenoxypoly(ethyleneoxy)ethanol-iodine complex 46904 4959-23-6266 6

Polyethoxy polypropoxy polyethoxy ethanol-iodine complexs 46904 4959-23-6266 6

Sodium N-Cyclohexyl-N-Palmitoy Taureat Iodine Complex 46904 4959-9

Dodecyl benzene Sulfonic Acid-Iodine Complex 46904 4959-9

c) Polyvinylpyrrolidone-iodine complexes

polyvinylpyrrolidone-iodine complex N/A N/A Group III: Amino

tetraglycine hydroperiodide 46923 79533- 1

Group

iodine b ound t o s t rong b ase anion exchange N/A N/A

AD Response: AD thanks the IJV for its comment. AD will compare IJV’s reregistration
classification as submitted in the comment above to the agency’s current classification of iodine and iodophors during th e risk assessment phase.

2. Comment: “The IJV made substantive changes to Table 6 – Summary of Iodine and Iodophors Registered Uses... The information c ontained in the table was provided by all companies listed above [ DeLaval Manufacturing/West Agro; Diversey, Inc.; Ecolab, Inc.; and Wisconsin Pharmacal] and aggregated to ensure all inform ation is appropriately expressed.Page 45 of 47 [In regards to the Food Handling Premises a nd Equipment use category] Note that one company has a general statement of all t ypes of food plants e quipment/processing. The methods are flood, spray, mop, immerse, circul ate, wipe all at 12.5 to 25 ppm. Conveyors for different industries are specifically menti oned and are spray foam or ‘other means’.

One of the IJV members has a tetraglycine or tetraglycine-iodine complex product that is
in tablet form with 6.68% titr atable iodine. This registrant will remain on the IJV until final data requirements are established.”

Summary of Iodine and Iodophors Registered UsesPage 46 of 47Page 47 of 47 AD Response: The IJV members represent a por tion of all companies with EPA registered products with iodine and iodophors as an active ingredient. As such, AD will leave Table 6 unchanged as it represents the use categories of all registrants for the iodine and iodophors case.

Submitter:Diversey, Inc.

2. Comment: “ We are members of the Iodophors Jo int Venture (IJV) to address registration review matters. As such, we would like to express our support for the comments submitted by the IJV on the preliminary work plan (Case 3080 dated December 2013). We provided input on Tabl e 6 – Summary of Iodine and Iodophors Registered Uses and hope to have given meaningful dire ction for your review. We do appreciate the opportunity to comment on th e work plan and look forward to working with the Agency through the IJV.”

AD Response: AD appreciates submission of these comments. Please refer to the responses provided to the IJV’s comments above.