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Iodine and Iodophors Registration Review Team

Human Health & Environmental Effects

Tim Dole

Zoё Layton

Michelle Centra

William Erickson

Srinivas Gowda

Najm Shamim

Siroos Mostaghimi

Risk Management

Sandra O’Neill

Demson Fuller

Rose Kyprianou

Office of General Counsel

Phil Ross
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Table of Contents

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

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

1.2 Case Overview ................................................................................................................. 8

1.3 Chemical Identification and Properties............................................................................ 9

1.4 Use/Usage Description................................................................................................... 12

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

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

1.4.3 Usage Information .................................................................................................. 14

1.5 Regulatory History ......................................................................................................... 14

1.5.1 Recent/Pending Regulatory Actions....................................................................... 15

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

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

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

1.6.2 Ecological ............................................................................................................... 16

2 Anticipated 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 Guidance for Commenters.................................................................................................... 29

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

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

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

6.1.3 Environmental Justice............................................................................................. 30
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6.1.4 Structure Activity Relationships............................................................................. 30

6.1.5 Additional Information ........................................................................................... 31

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

8 References............................................................................................................................. 32

Appendix A Toxicology Profile............................................................................................... 33

Appendix B Environmental Fate ............................................................................................. 34

Appendix C Ecotoxicology Profile.......................................................................................... 35

Appendix D Product Chemistry............................................................................................... 42

List of Tables

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

Table 2 – Anticipated Registration Review Schedule .................................................................... 7

Table 3 – Chemical Identification of Iodine and Iodophors........................................................... 9

Table 4 – Physical-Chemical Properties for Iodine ...................................................................... 11

Table 5 – Distribution of Products by PC Code ........................................................................... 12

Table 6 – Summary of Iodine and Iodophors Registered Uses .................................................... 13

Table 7 – Studies Anticipated as Needed for the Registration Review of Iodine and Iodophors. 17

Table 8 – Iodine Recommended Exposure Levels and Background Exposure ............................ 20

Table 9 – Occupational Handler Exposure Scenarios for Iodine.................................................. 22

Table 10 – Residential Handler Exposure Scenarios for Iodine ................................................... 23

Table 11 – Residential Post-Application Exposure Scenarios for Iodine..................................... 23

Table 12 – Ecological Effects Endpoints for the Ecological Risk Assessment of Iodine. ........... 27
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1 Introduction

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

Agency”) Preliminary Work Plan (PWP) 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. The Agency encourages all interested stakeholders to review 

the PWP and to provide comments and additional information that will help the Agency’s 

decision-making process for this chemical.

1.1 Statutory and Regulatory Authority

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

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

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop and commit to a Final Work Plan (FWP) and 

anticipated schedule for the Iodine and Iodophors Case. 
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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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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 Handler Yes None New Inhalation Indoor Exposure Data

Residential Handler Yes None New Inhalation Indoor Exposure Data

Residental Post 

Application Yes None New Surface Residue Data

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

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

Tolerance Review No (see 1.5.2)

N/A—

Existing 

tolerance 

exemption

None None

Ecological Effects and 

Environmental Fate Yes N/A New

Fish

Aquatic invertebrates

Aquatic and semi-aquatic 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

Phase 2: Case Development 

Issue Final Work Plan 2014-06

Issue Data Call-In (DCI) 2015-06

Receive Data to be Considered in Risk Assessment 2017-06

Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2018-12

Close Public Comment Period 2019-01

Phase 3: Registration Review Decision and Implementation 

Open 60-Day Public Comment Period for Proposed Decision 2019-06
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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).

1.2 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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1.3 Chemical Identification and Properties

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

iodine and a surface-active agent that releases iodine gradually and serves as a disinfectant. There are 10 compounds in the case 

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

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

the release of iodine. Though several iodophor products are classified in EPA’s database as containing elemental iodine (PC Code 

046905), only one product actually contains elemental iodine, while the other products contain one of the iodophors. 

1. Oxirane, methyl-, polymer with oxirane, monobutyl ether, compd. with iodine (PC Code 046901); 

2. Nonylphenoxypoly ethoxy ethanol iodine complex (PC Code 046903); 

3. Iodine, 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. 046905).

Table 3 – Chemical Identification of Iodine and Iodophors

Chemical Name

Oxirane, methyl-, polymer with 

oxirane, monobutyl ether, compd. 

with iodine

Nonylphenoxypoly ethoxy 

ethanol-iodine complex

Iodine, compd. with 

methyloxirane polymer with 

oxirane

Iodine (I2)

Betadine

Polyvinylpyrrolidone - iodine 

complex

Chemical

Classification

Halogen

Iodophor

Halogen

Iodophor

Halogen

Iodophor Halogen HalogenIodophor

PC Code 046901 046903 046904 046905 046914

CAS Number 68610-00-4 11096-42-7 26617-87-8 7553-56-2 25655-41-8

Molecular 

Formula C9H20I2O3 C17H28I2O2 C5H10I2O2 I2 C6H9I2NO

Molecular 

Weight 

(grams/mole)

430.06 518.21 355.94 253.809 364.95
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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)

Betadine

Polyvinylpyrrolidone - iodine 

complex

Molecular 

Structure

(Monomer)

Chemical Identification of Iodine and Iodophors Contd. 

Chemical 

Name

Polyethoxy polypropoxy 

polyethoxy ethanol 

iodine complex

Sodium N-cyclohexyl-Npalmytoyl-taurate-iodine 

complex

Sodium dodecyl benzene sulfonateiodine complex

Polystyrene divinyl benzene 

quaternary ammonium 

anion exchange resinIodine complex

Glycine, hydriodide (4:1), 

compd. with iodine (4:5)

Chemical

Classification 

Halogen

Iodophor

Halogen

Iodophor

Halogen

Iodophor

Iodinated Anion Exchange 

Resin Complex Halogen

PC Code 046905 046905 046905 046905 046923

CAS Number 7553-56-2 7553-56-2 7553-56-2 7553-56-2 7097-60-1

Molecular 

Formula C7H14I2O3 C24H46I2NNaO4S C18H30O3I2NaS -----

C16H42I7N8O16

4[(NH2CH2COOH) 2HI] 

.5I2

Molecular 

Weight 

(grams/ 

mole)

399.99 721.49 603.29 ----- 1490.95
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Chemical 

Name

Polyethoxy polypropoxy 

polyethoxy ethanol 

iodine complex

Sodium N-cyclohexyl-Npalmytoyl-taurate-iodine 

complex

Sodium dodecyl benzene sulfonateiodine complex

Polystyrene divinyl benzene 

quaternary ammonium 

anion exchange resinIodine complex

Glycine, hydriodide (4:1), 

compd. with iodine (4:5)

Molecular 

Structure

(Monomer) 

x 11⁄4

The iodine product chemistry information (MRIDs 44087501, 42440101, 41968702) relevant to risk assessment is summarized in 

Table 4. All the iodine and iodophors listed in Table 3 are iodine (I2) releasers. Therefore, the physical and chemical properties listed 

in 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 solvents.

830.7950 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; NA = Not applicable
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1.4 Use/Usage Description

1.4.1 Registrations

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

noted that, although several of the products are classified in EPA’s database as containing 

elemental iodine (PC Code 046905), only one product 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

1.4.2 Summary of Registered Uses

Table 6 summarizes the registered uses of iodine and iodophors, these uses will be assessed in 

this registration review. The labels indicate that iodine and iodophors can be applied by circulate 

in place (CIP) treatments, surface treatments using sprays, mops or wipes or immersion 

treatments where the object to be treated is dipped or soaked in a treatment solution. 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 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.

1.4.3 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.

1.5 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 1.3). 

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).

1.5.1 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. 

1.5.2 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.

1.6 Incidents

1.6.1 Human Health 

As of 11/22/2013, the OPP Incident System contains sixteen human minor (HD) and five human 

moderate (HC) incidents that were submitted after the RED was completed in July, 2006. There 

are no details 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.

1.6.2 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) Triggering 

Anticipated Data 

Requirement

Applicable 

Exposure 

Scenario

Studies Anticipated to be Required through the Registration Review DCI

No GLNa Special leaching from paints 

and coatings

Polystyrene 

divinyl benzene 

quaternary 

ammonium anion 

exchange resiniodine complex

6 Aquatic organisms Exterior 

paints/stains/coatings

Aquatic

environments

835.3110

835.3220

835.3280

835.3240

Ready biodegradability test 

or one of three 

biodegradation in activated 

sludge simulation testsb Iodophors 

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, nonvasculard

12

850.4550a Cyanobacteria toxicityd 12

850.4225a Seedling emergence, ricee 12 Semi-aquatic plants

850.1400a Fish early life-stage, 

freshwater species 12 Fish

850.1010a Aquatic invertebrate toxicity, 

freshwater 24

Aquatic invertebrates

850.1300a Invertebrate life cycle, 

freshwater species 12

850.1075a

Fish acute toxicity, 

estuarine/marine, freshwater 

species

18

Estuarine/marine 

organisms

850.1035a Mysid acute toxicity 12

850.1025a or

850.1055a

Oyster shell deposition

or

Bivalve embryo larval 

toxicity test

12
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GLN Study Name Test Substance

Time Frame (Measured 

in months from DCI 

Receipt)

Risk Assessment(s) Data 

Will Support

Use Site(s) Triggering 

Anticipated Data 

Requirement

Applicable 

Exposure 

Scenario

875.1400 Indoor Exposure Data -

Inhalation TGAI Iodine

12 Occupational and 

Residential Handler All Inhalation Exposuref

875.2300 Surface Residue Data 12 Residential Post 

Application Household floor sanitizers Incidental Oral

a Iodophor molecule data are expected to be needed if there is a likelihood for exposure to the carrier in aquatic systems. The Agency has limited data on the 

carrier portion of these molecules. If it can be shown that there is no aquatic exposure, ecotoxicity data will not be necessary for the iodophors. b EPA published draft guidance under guideline OPPTS 850.6800 and has since published final guidance for this study under guideline OCSPP 850.3300: 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0021. The Agency has included this study in 40 CFR 158(W). OECD Test Guideline 

209 can also be used as guidance for this study, available online at http://www.oecd-ilibrary.org/content/book/9789264070080-en. The results of this ASRI test 

will determine which of four biodegradation tests is/are required. If the ASRI test EC50 is less than or equal to 20 mg/L, then either the (i)Biodegradation in 

Activated Sludge Study or (ii) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the Porous Pot Test is expected to be required. If 

the ASRI test EC50 is greater than 20 mg/L, then the registrant would likely be required to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in 

Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or c) the Porous Pot Test. If the Ready Biodegradability study is 

conducted and passes, then no further testing would be expected to be required. If, however, the antimicrobial fails the Ready Biodegradability study, then the a) 

Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study would likely be 

required.

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

(mg/L). d One Tier II (dose response) study, conducted with Selenastrum capricornutum, is expected to be required; if the results of this study exhibit detrimental effects 

(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 (Anabaena flos-aquae, 

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 aquatic plants. f The inhalation exposure scenarios include open pouring of liquids and wettable powder for material preservation, low pressure hand wand, high pressure 

handwand, trigger sprayer, mop and wipe application, and airless sprayer application of preserved paints. g Data are anticipated to be required for all use patterns which have the potential to result in contamination of surface water.
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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 believes that the human toxicity of iodine is well characterized. No additional toxicity data 

are anticipated to be required for registration review. 

EPA has not formally selected endpoints to assess the human health risks for iodine and 

iodophors because iodine is an essential nutrient with a long history of clinical use in humans. In 

the 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.

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 

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. 
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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 Exposures

The 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.
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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 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 

EPA will use the 2008 TLV-TWA of 0.1 mg/m3 for assessing inhalation exposures to iodine 

aerosols and the 1963 TLV-STEL of 1 mg/m3 for assessing exposure to iodine vapors. The use 

of the 2008 TLV-TWA of 0.1 mg/m3 represents a change from the 2009 RED Amendment where 

only the TLV-STEL of 1 mg/m3 was used. However, it should be noted that the TLV-TWA is of 

0.1 mg/m3 is based on the same tolerable upper intake level that is used to assess oral exposures

(ACGIH, 2008). 

Dermal Exposure

EPA does not plan to assess dermal exposures to iodine because it was previously concluded in 

the 2006 RED that the data for dermal absorption show less than one percent of absorption and 

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

3.3 Dietary Exposure

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 

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

2009.
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endpoints of concern. Therefore, dietary risks were assessed using the Tolerable Upper Intake 

Level (UL) established by NAS, which is the maximum level of daily intake that is likely to pose 

no risk of adverse effects (EPA, 2009). All of the calculated risks as well as the combined risks 

are 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
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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 
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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. 
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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 
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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/
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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 
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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 pesticides

7

. Any acute or chronic endpoints more 

sensitive than what is currently available will be used in the risk assessment and risk 

characterization. ECOTOX was created and is maintained by the US EPA’s, Office of Research 

and Development, and the National Health and Environmental Effects Research Laboratory's 

Mid-Continent Ecology Division

5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

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

taxonomic groups. As part of the 2006 RED for iodine and iodophors, EPA reviewed these 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
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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 Guidance for Commenters

6.1 Preliminary Work Plan

The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a final work plan for the iodine and iodophors registration review 

case. 

6.1.1 Trade Irritants

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency 

will work to harmonize tolerances and international maximum residue limits (MRLs) and may 

modify tolerance levels to do so, when possible. Stakeholders are asked to comment on any 

trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and 

MRLs in key export markets, providing as much specificity as possible regarding the nature of 

the concern.

6.1.2 Water Quality

The Agency invites submission of water quality data for this pesticide. To the extent 

possible, data should conform to the quality standards in Appendix A of the OPP Standard 

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

chemicals. 9 http://www.epa.gov/endo/
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Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in 

OPP’s Registration Review Risk Assessment and Management Process10 in order to ensure they 

can be used quantitatively or qualitatively in pesticide risk assessments.

6.1.3 Environmental Justice 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to iodine and iodophors compared to the general population.

Please comment if you are aware of any sub-populations that may have atypical, unusually 

high exposure compared to the general population.

6.1.4 Structure Activity Relationships 

EPA must rely upon information of appropriate quality and reliability for each decision made by 

the Agency. In the OPP, the evaluation process for a pesticide chemical traditionally begins with 

the applicant’s submission of a set of studies conducted with the specific pesticide chemical of 

interest. The use of the results of such testing (measured data) is a logical, scientifically rigorous 

process that identifies the physical, chemical, and environmental fate properties of the pesticide, 

as well as the dose and endpoints at which an adverse effect can occur in various animal species. 

Today, there is significant interest in alternative techniques, i.e., techniques other than data 

generation that could significantly inform the Agency’s decision-making process. Recently, OPP 

has made increasing use of structure activity relationship (SAR) as part of its regulatory 

decision-making process. In the SAR process, a chemical's molecular structure is compared to 

that of other chemicals for which data are available. These structural similarities are then used to 

make predictive judgments about a chemical’s physical, chemical, and biological properties. 

Thus, the chemical’s physical, chemical, and biological properties are a function of (or directly 

related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To 

develop a QSAR, a selected set of measured data on a single physical, chemical, or biological 

property is used to derive a model (an equation) to predict the value of that property. 

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

scientists, OPP has begun a process shift that envisions shifting from the current study-by-study 

approach to an approach in which the use of predicted data, generated using validated models, is 

considered along with information from open literature and studies specifically generated under 

Part 161 requirements. All relevant information would be considered as part of a weight-of-theevidence evaluation. 

At this time, EPA believes that for certain endpoints, especially physical/chemical and fate 

properties, that SAR and QSAR might be effectively utilized to fulfill these data requirements 

for many antimicrobial pesticide chemicals. When considering biological properties, at this time, 

EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of 

 10 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is 

appropriate because the risk assessment for lower toxicity chemicals can be stream-lined, i.e., a 

screening-level assessment procedure rather than multiple tiers of assessments with progressively 

more data requirements. 

If stakeholders believe that submission of predicted data can fulfill one of the data needs for the 

Iodine and Iodophors Case, then the Agency invites submission of this information. The 

submitter would be expected to supply a rationale describing the utility of the information and 

provide documentation on the scientific validity of the information. The determination that the 

predicted data fulfills the data requirement would be at the sole discretion of the Agency. Presubmission consultation with the Agency is encouraged. 

6.1.5 Additional Information 

Stakeholders are also specifically asked to provide available information and data that will assist 

the Agency in refining its risk assessments, including any species-specific ecological effects 

determinations. The Agency is interested in receiving the following information: 

1. Confirmation on the following label information: 

A. Sites of application 

B. Formulations 

C. Application methods and equipment 

D. Maximum application rates 

E. Frequency of application, application intervals and maximum number of 

applications 

F. Geographic limitations on use 

2. Use or potential use distribution 

3. Use history 

4. Usage/use information for non-agricultural uses (e.g., materials preservation) 

5. Typical application interval 

6. State or local use restrictions 

7. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency 

8. Monitoring data 

7 Next Steps

After the 60-day comment period closes in February 2014, the Agency will review and respond 

to any comments received in a timely manner, and then issue a Final Work Plan for the Iodine 

and Iodophors Case.
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8 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
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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.
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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.
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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 ToxicityCategory

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 431384-01Acceptable

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. 
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Avian Dietary Toxicity

Test Species Test Material

(% ai) Toxicity ToxicityCategory

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 StudyID

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 
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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 TN2744Supplementala

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

Supplementalc I

-

(99%)

96-hr LC50 = 860 – 8230

(7 tests)

Practically 

nontoxic

Bluegill

(Lepomis macrochirus)

Iodine

(99.8) 96-hr LC50 = 0.61 Highly toxic 430445-01Acceptable

Nonylphenoxypolyethoxyethanol 

complex

(20% iodine)

96-hr LC50 = 0.33d Highly toxic TN0622

Supplementale

Iodine

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

Channel catfish

(Ictalurus punctatus)

I2

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

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
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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 441098-09Supplementala

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).
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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. 

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 
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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: 425A-106. 

Unpublished study prepared by Wildlife International Ltd. 36 p. 

43044501 Zelinka, E.; Martin, K.; Swigert, J. (1993) IOBIO: A 96-Hour Flow-Through Acute 

Toxicity Test with the Bluegill (Lepomis macrochirus): Final Report: Lab Project 

Number: 355A/102. Unpublished study prepared by Wildlife International Ltd. 38 p. 

44109807 Drottar, K.; Swigert, J. (1996) Divosan MH: A 96-Hour Static Acute Toxicity Test 

with the Bluegill (Lepomis macrochirus): Final Report: Lab Project Number: 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: 

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 
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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) 
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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
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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