Docket Number EPA-HQ-OPP-2013-0767 

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Iodine and Iodophors Final Work Plan 

Registration Review: Initial Docket 

Case Number 3080 

Approved by: 

Date: 

June 2014 

Susan Lewis 

Director 

Antimicrobials Division 

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Iodine and Iodophors Registration 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 Ross 

 
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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 Registered 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 ............................................................................................................ 21

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-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 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 Wildlife Exposure Estimates ............................................ 28

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

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

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

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

Appendix A Toxicology Profile ............................................................................................... 31
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Appendix B Environmental Fate ............................................................................................. 32

Appendix C Ecotoxicology Profile .......................................................................................... 33

Appendix D Product Chemistry ............................................................................................... 40

Appendix E Comments Received Concerning the Preliminary Work Plan ............................ 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. ........... 27

 
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1 Introduction 

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

agency”) Final Work Plan (FWP) for Iodine and Iodophors. 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 iodophors’ review. The Iodine and Iodophors case (case 3080) was 

previously known as the Iodine and Iodophor Complexes case. The Reregistration Eligibility 

Decision (RED) for Iodine 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 March, 

2009, all pertain to the Iodine and Iodophors Case. 

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 information would be helpful for the agency to receive as it moves toward a 

decision on iodine and iodophors. 

1.1 Statutory and Regulatory Authority 

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

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

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

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

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

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

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

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

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

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

http://www.epa.gov/oppsrrd1/registration_review/. 

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

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

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

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

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

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

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

and data or information it believes are needed to make a registration review decision. The 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. 
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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 pelleted/tabled products application 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 inhalation 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 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 

present technical corrections to the Summary of Iodine and Iodophors 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 anticipated data needs detailed in the 

Iodine and Iodophors PWP. This document makes final the work plan for the Iodine and 

Iodophors registration review process. 

 
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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 Registration Review Schedule 

Anticipated Activity Target Date* Completion Date

Phase 1: Opening the Docket 

Open Docket and 60-Day Comment Period for Preliminary Work Plan 2013-12 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 Implementation 
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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 Case (Case 3080) has been established at 

http://www.regulations.gov in docket number EPA-HQ-OPP-2013-0767. 
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1.4 Chemical Identification and Properties Table 3 presents the active ingredients to be assessed in the iodine and iodophors case where iodophor is defined 

iodine and a surface-active agent that releases iodine gradually and serves as a disinfectant. There are 10 compou

including elemental iodine (Iodine, I2) and nine iodophors. Elemental iodine and the nine other chemicals are ess

elemental iodine. These nine substances can be classified as polymers, resins, or surfactants. The purpose of the 

the release of iodine. Though several iodophor products are classified in EPA’s database as containing elemental 046905), only one product actually contains elemental iodine, while the other products contain one of the iodoph

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 ethanol iodine 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. 0

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 (I2)

BetadPolyvcomp

Chemical Classification 

Halogen 

Iodophor 

Halogen 

Iodophor 

Halogen 

Iodophor Halogen 

PC Code 046901 046903 046904 046905 CAS Number 68610-00-4 11096-42-7 26617-87-8 7553-56-2 Molecular Formula C9H20I2O3 C17H28I2O2 C5H10I2O2 I2 Molecular Weight (grams/mole) 

430.06 518.21 355.94 253.809 
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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 (I2)

BetadPolyvcomp

Molecular Structure (Monomer) 

Chemical Identification of Iodine and Iodophors Contd. 

Chemical Name 

Polyethoxy polypropoxy polyethoxy ethanol iodine complex 

Sodium N-cyclohexylN-palmytoyl-taurateiodine complex Sodium dodecyl benzene sulfonate- iodine complex Polystyrene divinyl benzene quaternary ammonium anion exchange resin- Iodine complex Gl

co

Chemical Classification 

Halogen Iodophor

Halogen Iodophor

Halogen Iodophor

Iodinated Anion Exchange Resin Complex 

PC Code 046905 046905 046905 046905 CAS Number 7553-56-2 7553-56-2 7553-56-2 7553-56-2 Molecular Formula C7H14I2O3 C24H46I2NNaO4S C18H30O3I2NaS ----- 

4[

Molecular Weight (grams/ mole) 

399.99 721.49 603.29 ----- 
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Chemical Name 

Polyethoxy polypropoxy polyethoxy ethanol iodine complex 

Sodium N-cyclohexylN-palmytoyl-taurateiodine complex Sodium dodecyl benzene sulfonate- iodine complex Polystyrene divinyl benzene quaternary ammonium anion exchange resin- Iodine complex Gl

co

Molecular Structure (Monomer) 

The iodine product chemistry information (MRIDs 44087501, 42440101, 41968702) relevant to risk assessment Table 4. All the iodine and iodophors listed in Table 3 are iodine (I2) releasers. Therefore, the physical and chemin Table 4 for Iodine (I2) are also applicable to all the iodine compounds listed in Table 3. 

Table 4 – Physical-Chemical Properties for Iodine 

Guideline No. Parameter Iodine (I2) 

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/cm3 at 25°C (Solid) 830.7370 Dissociation constant (pKa) NA. Doesn’t dissociate 830.7550 Log Kow NA 830.7840 Solubility in water 330 mg/L at 25°C. 830.7860 Solubility in organic solvents Soluble in many organic solv830.7950 Vapor pressure 0.31 mm Hg at 25°C 

atm-m3/mol = atmosphere cubic meter per mole; oC = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury; N
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1.5 Use/Usage Description 

1.5.1 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 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 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, 

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 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. Iodophors 

can be used to treat water using cartridge filters or tablets. There is also one product (EPA 

registration number 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. 
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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/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 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 ClaysA 

Paints, Stains and CoatingsB

Plastic films –diapersB

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 ppm 
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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 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. 

1.5.3 Usage Information 

According to the Kline market research report (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 udders and as sanitizers for milking equipment. 

1.6 Regulatory History 

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 iodine and iodophors registration review case (3080) consists of ten compounds (see 

Section 1.4). 

In addition to these compounds, there are nine iodophor active ingredients 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 Code 046915, CAS Number 53404-04-9) 

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

 Ethanesulfonic acid, 2-(cyclohexyl(1-oxohexadecyl)amino)-, sodium salt, compd. with 

iodine (PC Code 046919, CAS Number 53404-81-2) 

 Benzenesulfonic acid, dodecyl-, sodium salt, 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) 
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 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-specific 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 for use, the total end-use concentration 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 contact with the registrants for these 

products and is working to process updates to the labels for these products. 

1.7 Incidents 

1.7.1 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 given for the HD incidents. Details for 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 medications for asthma and the student’s parents are attempting 

to determine if the asthma attacks are related to the products 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 was 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 afterwards spilled some portion of the mixture. The employee reported respiratory 

irritation, was sent to the emergency room and subsequently diagnosed with pneumonia. 
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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 chlorinated 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 anticipated as being needed to support this registration 

review. 
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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) Trig

Anticipated D

Requireme

Studies Anticipated to be Required through the Registration Review DCI 

No GLNa Special leaching from paints and coatings 

TGAI: polystyrene 

divinyl benzene 

quaternary ammonium 

anion exchange resiniodine complex 

6 Aquatic organisms Exterior paints/stains/co

835.3110 835.3220 835.3280 835.3240 

Ready biodegradability test or one of three biodegradation in activated sludge simulation testsb TGAI: iodophors only 

24 

Aquatic organisms 

Allg

850.6800a Activated Sludge, Respiration Inhibition 12 850.4400a Aquatic plants, vascular speciesc 

TGAI: 

iodine and iodophors 

12 

Aquatic plants 850.4500a Aquatic plants, non- vasculard 12 

850.4550a Cyanobacteria toxicityd 12 850.4225a Seedling emergence, ricee TEP: iodine and iodophors 12 Semi-aquatic plants 850.1400a Fish early life-stage, freshwater species TGAI: iodine and iodophors 12 Fish 850.1010a Aquatic invertebrate toxicity, freshwater TEP: iodophors only 24 Aquatic invertebrates 850.1300a Invertebrate life cycle, freshwater species TGAI: iodine and iodphors 12 850.1075a

Fish acute toxicity, estuarine/marine, freshwater species 

TEP: iodophors only 18 Estuarine/marine 

organisms 

850.1035a Mysid acute toxicity 12 
18

GLN Study Name Test Substance

Time Frame 

(Measured in months 

from DCI Receipt)

Risk Assessment(s) 

Data Will Support

Use Site(s) Trig

Anticipated D

Requireme

850.1025a or 

850.1055a

Oyster shell deposition or Bivalve embryo larval toxicity test 

TGAI: iodine and 

iodophors 12 

870.3465 90-Day Inhalation, Rat 

TGAI:iodine only 

24 Occupational and 

Residential Handler Allh 

875.1400 Indoor Exposure Data - Inhalation 12 875.2300 Surface Residue Data TGAI:iodine only 12 Residential Post Application Household floor s

a Iodophor molecule data are expected to be needed if there is a likelihood for exposure to the carrier in aquatic systems. The agency hcarrier portion of these molecules. If it can be shown that there is no aquatic exposure, ecotoxicity data will not be necessary for the iodb EPA published draft guidance under guideline OPPTS 850.6800 and has since published final guidance for this study under guideline 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0021. The agency has included this study in 40 CFR 158

Guideline 209 can also be used as guidance for this study, available online at http://www.oecd-ilibrary.org/content/book/978926407008ASRI 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 (i)Biodegradation in Activated Sludge Study or (ii) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the 

expected to be required. If the ASRI test EC50 is greater than 20 mg/L, then the registrant would likely be required to conduct either: (ior (ii) a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or c) the P

Ready Biodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, the antim

Biodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. ActivatePorous Pot study would likely be required. 

c Data would be required if the aquatic (algal) plant growth Tier II study with Selenastrum capricornutum demonstrates detrimental effe

(mg/L). 

d One Tier II (dose response) study, conducted with Selenastrum capricornutum, is expected to be required; if the results of this study e

(EC50 less than 1.0 ppm or mg/L), then additional Tier II (dose response) studies would be expected to be required on three species (An

Navicula pelliculosa, and Skeletonema costatum). 

e Data are expected to be required only if the risk quotient from any aquatic plant growth Tier II test exceeds a level of concern for aquf The inhalation exposure scenarios include open pouring of liquids and wettable powder for material preservation, low pressure hand whandwand, trigger sprayer, mop and wipe application, and airless sprayer application of preserved paints.g Data are anticipated to be required for all use patterns which have the potential to result in contamination of surface water.h Data are anticipated to be required for all use patterns which have the potential to result in human inhalation exposures. However, the 

reviewing 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 toxentry effects. 
Docket Number EPA-HQ-OPP-2013-0767 

www.regulations.gov 

19 

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 

anticipate the need to reassess the 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 Toxicology Data 

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 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 Governmental Industrial Hygienists (ACGIH) Threshold 

Limit Value (TLV) of 0.1 ppm for iodine vapor. 

However, additional inhalation toxicity data are anticipated to be required for registration review 

based upon the need for re-evaluation of the toxicology database as well as consideration of the 

current use patterns that may result in human exposure to iodine and iodophors. These labeled 

use patterns include open pouring of liquids and wettable powder for material preservation, low 

pressure hand wand, high pressure hand wand, trigger sprayer, mop and wipe application, and 

airless sprayer application of preserved paints. 

Oral Exposures 

The National Academy of Sciences has set the Dietary 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 range of 90-150 μg/day (1-8 years: 90 μg/day; 9-13 

years: 120 μg/day; 14-18 years: 150 μg/day). The DRIs for pregnant 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: 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 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 infants be 

from food and formula (NAS, 2001). 

In 1978, the Food and Drug Administration deemed potassium iodide a safe and effective means 

by which to block uptake of radioiodines by the thyroid gland in the event of a radiation 
20

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. 

There are no primary drinking water standards (MCL) for iodine or its oxidized or reduced 

forms, as iodine is used 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. Iodine 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 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 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 ExposuresThe ACGIH has adopted a Threshold Limit Value - Time Weighted 

Average (TLV-TWA) of 0.1 mg/m3 for iodine and iodides as Inhalable Fraction and Vapor and a 

TLV – Short term Exposure Limit (STEL) of 1.0 mg/m3

 for iodine vapor (ACGIH, 2008). The 

TWA TLV was adopted in 2008 and is 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 m3

, to yield the TLV-TWA of 0.1 mg/m3. 

This TLV was adopted after the 2006 RED was completed. 

The TLV-STEL of 1.0 mg/m3

 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/m3

 was 

reported to make work intolerable while 1.1 mg/m3 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 (OSHA) has a permissible exposure limit 

(PEL) of 1 mg/m3

 for iodine (29 CFR 1910.1000). This PEL is a ceiling limit that cannot be 

exceeded at any time. The PEL was established in 1970 and it was based on the 1963 TLV 

STEL of 1 mg/m3

 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 research involving intentional 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 (HSRB) 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 continue to use the tolerable upper intake level as a basis 

for assessing the human health risks 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 studies 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 iodine 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 percent of absorption and 

no new information has become available that would change this conclusion. 

3.3 Dietary Exposure 

Uses of iodine and iodophors that may result in dietary exposure (food and water) include use as 

food-contact surface sanitizers (utensils and countertops, dairy processing equipment), as fruits 

and vegetables sanitizing wash (military personnel only), egg washes, and in emergency drinking 

water disinfection. In March of 20091 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 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, which is the maximum level of daily intake that is likely to pose 

 

1

 U.S. EPA. Revised Amendment for Iodine Reregistration 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 calculated 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, 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 excessive 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 iodophors 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 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 Residential 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 toxicological endpoint, inhalation 

exposures to iodine as an aerosol will need to be assessed during registration review. 

3.4.1 Occupational 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 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 

Term 
23

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 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 mechanism of toxicity, EPA has not made a 

common mechanism of toxicity finding as to iodine 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, therefore, EPA has not assumed that iodine and 

iodophors have a common mechanism of toxicity with other substances. For information 
24

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 an ecological risk assessment for the antimicrobial 

uses of iodine. A conventional use for drip-irrigation 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 assessment noted that given the reactive nature of 

the active ingredient, the risks described in the assessment were 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 assessed environmental 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 information 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 aquatic environment. 

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 'no effect' or 'may affect' federally listed threatened 

or endangered species (listed species) or their designated critical habitats. When an assessment 

concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the 

agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries 

Services (the Services), as appropriate. 

4.1 Environmental Fate Assessment 

The potential exposure of non-target 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 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. 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 I2, I3

-

 or I5 with various oxidation states similar to other halogens like chlorine 

and bromine. In all cases, iodine provides the antimicrobial activity. 
25

Iodine (I2) is one of the halogens, and is a solid at room temperature. As discussed in the product 

chemistry section, iodine 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: I2(solid) ----- 2I(gas) 

 Reduction: 2I(gas) - (reduction) : 2I-

 Dissolution in water: I2(s) + H2O -- HI + HOI 

 HI  H++ I- 

 I

-

 + I2 - I3

-

 

 I3

-

 + I2 - I5

-

 

The agency 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 

Wastewater Treatment Plant (WTTP) organisms (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 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 the agency published a preliminary work plan in March 2013. Sodium 

dodecylbenzene sulfonate is readily 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, hydriodide (4:1), compd. with iodine (4:5) (PC Code 046923): tetraglycine is a 

peptide 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 

information of tetraglycine: “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 Kow = -3.75). It is not likely removed in the STP process. Its halflife 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 iodophor used in paints, stains and coatings. Iodine is released as a 

disinfectant. Iodophors also are used 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 from 
26

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 not identified as a cause 

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

Act2. In addition, no Total Maximum Daily Loads (TMDL) have been developed for iodine3. 

Iodine and iodophors are not identified as a cause of impairment for any water bodies listed as 

impaired under section 303(d) of the Clean Water Act4

. In addition, no Total Maximum Daily 

Loads (TMDL) have been developed for iodine and iodophors5. 

More information on impaired water bodies and TMDLs can be found at EPA’s website6. 

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 treatment 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. 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 industrial 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 water that has iodine residues. Based on the Kow

(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 toxicity data from registrant-submitted studies 

conducted 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

6 http://www.epa.gov/owow/tmdl/
27

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 also 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 12 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 12. Data gaps (resulting in anticipated data needs in Table 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 LC50 = 0.30 mg ai/L TN2744 

Chronic Data gap N/A 

Freshwater invertebrates TGAI 

Acute EC50 = 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 EC50

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 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. 

Open literature studies also will be identified through EPA’s ECOTOXicology (ECOTOX) 

database. The ECOTOX database will be searched when the risk assessment is prepared. Acute 
28

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 Exposure 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-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 toxicity endpoints to determine whether or not the 

agency’s levels of concern for acute and chronic risks to aquatic organisms, including listed 

species, are expected to be exceeded for each receptor group. 

4.6 Effects 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 reviewing public 

literature for use in assessing risks from pesticides7. 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 data 

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

hazard database. However, as required by FFDCA section 408(p), 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 similar to an effect 

 

7

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_reregistration_work

group/esa_evaluation_open_literature.htm 
29

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

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

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

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

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

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

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

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

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

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

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

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

identified for EDSP screening was published on June 14, 20138

 and includes some pesticides 

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

construed as a list of known or likely endocrine disruptors. 

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

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

website9. 

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 Governmental Industrial Hygienists, ACGIH® (2008) 

Iodine and Iodides: TLV Chemical Substances 7th Edition Documentation. Potassium 

Triiodide (KI3): 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 KI3/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: 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; 1990

 
31

Appendix A Toxicology Profile 

The agency intends to conduct an ethics review for human studies which may have 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. 

 
32

Appendix B Environmental Fate 

Environmental Fate and Transport Properties of Iodine 

Water and Sediment 

Hydrolysis, Aqueous Photolysis, Octanol-Water Partition Coefficient, Aerobic Aquatic 

Metabolism, and Anaerobic 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 inorganic elements such as 

iodine. No additional data are anticipated to be required. 

Soil 

Soil Leaching/Adsorption/Desorption Batch Equilibrium, Aerobic Soil Metabolism, Anaerobic 

Soil 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 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 iodophors. 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 KIO3. 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 carrier 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 categorize iodine as being slightly to practically 

nontoxic to birds. The guideline (850.2100) 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 

Supplementala 

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 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 patterns of iodine/iodophors since the agency does 

not anticipate conducting a nontarget 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 

Supplementala 

Iodine 

(2.9% formulation) LC50 >5620 ppm Practically nontoxic 

441098-06 

Supplementalb

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 required 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 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

LC50 = 34 μg ai/bee 469593-37 

Acceptable

Toxicity to Aquatic Organisms 

Freshwater Fish 
35

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 

Supplementala 

Iodine 

(2.9% formulation) 96-hr LC50 = 38 Slightly toxic 441098-08 

Supplementalb 

I2 

(99%) 

96-hr LC50 = 0.53 - >10 

(7 tests) Highly toxic Laverock et al. 

1995 

Supplemental I c - 

(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 = 0.33d Highly toxic TN0622 

Supplementale 

Iodine 

(2.9% formulation) 96-hr LC50 = 37 Slightly toxic 441098-07 Supplementalb 

Channel catfish 

(Ictalurus punctatus) 

I2 

(reagent grade) 24-hr LC50 = 0.44 Highly toxic LaValley 1982 Supplementalc

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 categorizes technical-grade iodine as being highly 

toxic to 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

Test Species Test Material 

(% ai) 

Toxicity Endpoint 

(mg ai/L) 

Toxicity 

Category 

EPA Study 

ID 
36

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 

Supplementala 

I2 

(99%) 

96-hr LC50 = 0.16-1.8 

(7 tests) Highly toxic 

Laverock et al. 1995 

Supplementalb

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 additional data are anticipated 

to be required for a vascular species (Lemna sp., 850.4400), two additional algal species 

(Navicula pelliculosa and Skeletonema costatum, 850.4500), and cyanobacteria (Anabaena flosaquae, 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 

Sediment toxicity data are not anticipated to be required for iodine, based on its environmental 

fate properties (Kd <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. Macdonald. 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 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. 
38

43138401 Campbell, S.; Beavers, J. (1994) Iobio: An Acute Oral Toxicity Study with the 

Northern Bobwhite: Lab Project Number: 355-102. Unpublished study prepared by 

Wildlife International Ltd. 18 p. 

42329101 Pedersen, C. (1991) Tetraglycine Hydroperiodide: 8-Day Acute Dietary LC50 

Study in Bobwhite Quail: 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: 425A106. 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: 524A105. Unpublished study prepared by Wildlife International Ltd. 36 p. 

44109808 Drottar, K.; Swigert, J. (1996) Divosan 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: 
39

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 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. 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-

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 

(I2)

830.1550 Product identity and composition Refer to Table 8 

830.1600 Description of materials used to 

produce the product CBIA

830.1620 Description of production process CBIA

830.1650 Description of Formulation Process CBIA

830.1670 Description of Formulation Process CBIA

830.1700 Preliminary analysis CBIA

830.1750 Certified limits CBIA

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 explodable 
41

Guideline 

 Numbers 

Parameters Iodine 

(I2)

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 oC 

830.7300 Density (g/cm3) 4.933 g/cm3 at 25oC (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 oC 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 
42

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 iodine and iodophors. The comment period ended on 

February 18, 2014. During the public comment period the Agency received comments 

submissions from two organizations. Comments received 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 present technical corrections to the 

Summary of Iodine and Iodophors 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 Overview including the grouping of various 

Iodine and Iodophor complexes, dated September 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 acceptable for the purpose of RED production’... 

The IJV is pleased the Agency continues to utilize the groupings for Reregistration and 

strongly suggests continuation 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-iodine 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 Corresponding Registrations Supported by the IJV 

Members 

 Names And Subgroups PC Code Reg #

G

Iodine 46905 875-188

46905 875-183

46905 875-183

Potassium Iodide N/A N/A

N/A N/A

Group II: Surfactanta) Polypropxypolyethoxyethanol-iodine complexes
Page 44 of 47

butoxypolypropxypolyethoxyehtanol-iodine complex 46901 1677-22

46901 1677-58

46905 875-188

46905 7546-13

46904 4959-18

Polyethoxypolypropoxypolyethoxyethanol-iodine (also 

called polypropoxypolyethoxyethanol-iodine)

46905 1677-89

46904 4959-38-42666

46904 4959-38

46904 4959-38-11388

Polyethoxy polypropoxy polyethoxy ethanol-iodine complexes 46904 4959-18

alpha-(p-nonylphenyl)-omega-hydroxypoly(oxyethylene)-iodine complex 46904 4959-16

46904 4959-13-AA

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 4959-21-62666

Nonylphenoxypoly(ethyleneoxy)ethanol-iodine complex 46904 4959-23-62666

Polyethoxy polypropoxy polyethoxy ethanol-iodine complexs 46904 4959-23-62666

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 bound to strong base 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 the risk assessment phase.

2. Comment: “The IJV made substantive changes to Table 6 – Summary of Iodine and 

Iodophors Registered Uses... The information contained 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 information is appropriately expressed. 
Page 45 of 47

[In regards to the Food Handling Premises and Equipment use category] Note that one 

company has a general statement of all types of food plants equipment/processing. The 

methods are flood, spray, mop, immerse, circulate, wipe all at 12.5 to 25 ppm. Conveyors 

for different industries are specifically mentioned 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% titratable iodine. This registrant will remain on the IJV until 

final data requirements are established.” 

Summary of Iodine and Iodophors Registered Uses 
Page 46 of 47
Page 47 of 47

AD Response: The IJV members represent a portion 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 Joint 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 Table 6 – Summary of Iodine and Iodophors 

Registered Uses and hope to have given meaningful direction for your review. We do 

appreciate the opportunity to comment on the 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.