United States Prevention, Pesticides 739-R-06-010
Environmental Protection and Toxic Substances July 2006
Agency (751 OP)
Reregistration Eligibility
Decision For Iodine And
lodophor Complexes
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
This is to inform you that the Environmental Protection Agency (EPA) has completed its
review of the available data on the antimicrobial iodine and iodophor complexes. The enclosed
Reregistration Eligibility Decision (RED) document was approved on July 27, 2006.
Based on the Agency's review, the iodine and iodophor complexes Reregistration
Eligibility Decision (RED) and risk management decision with its associated human health and
environmental risk assessment are now being published. A Notice of Availability will be
published in the Federal Register announcing the publication of the RED.
The RED and supporting documents for iodine and iodophor complexes will be available
to the public from the U.S. Federal Government website www.regulations.goy. The docket
identification number is EPA-HQ-OPP-2006-0599.
The iodine and iodophor complexes RED was developed through EPA's public
participation process, published in the Federal Register on September 10, 2004, which provides
opportunities for public involvement in the Agency's pesticide tolerance reassessment and
reregistration programs. Developed in partnership with USDA and with input from EPA's
advisory committees and others, the public participation process encourages robust public
involvement starting early and continuing throughout the pesticide risk assessment and risk
mitigation decision making process. The public participation process encompasses foil,
modified, and streamlined versions that enable the Agency to tailor the level of review to the
level of refinement of the risk assessments, as well as to the amount of use, risk, public concern,
and complexity associated with each pesticide. Using the public participation process, EPA is
attaining its strong commitment to both involve the public and meet statutory deadlines.
Please note that the attached RED document pertains only to iodine and presents the
Agency's conclusions on the dietary, drinking water, occupational and ecological risks posed by
exposure to iodine and iodophor complexes alone. This document also contains product-specific
data that the Agency intends to require in Data Call-ins (DCIs). Note that DCIs, with all
pertinent instructions, will be sent to registrants at a later date. For product-specific DCIs, the
first set of required responses will be due 90 days from the receipt of the DCI letter. The second
set of required responses will be due eight months from the receipt of the DCI letter.
-------
As part of the RED, the Agency has determined that iodine and iodophor complexes will
be eligible for reregistration provided that all the conditions identified in this document are
satisfied.
If you have questions on this document or the label changes relevant to this reregistration
decision, please contact the Chemical Review Manager, Heather Garvie, at (703) 308-0034. For
question's about product reregistration and/or the Product DCI that will follow this document,
please contact Marshall Swindell at (703) 308-6341.
Sim
>anders
/ Director, Antimicrobials Division
-------
REREGISTRATION ELIGIBILITY
DECISION
for
Iodine
ListC
CASE 3080
rankr. Sanders
Director, Antimicrobials Division
July 27, 2006
-------
Table of Contents
Iodine and lodophor Complexes Reregistration Team i
Glossary of Terms and Abbreviations................ ii
Executive Summary iv
I. Introduction 1
II. Chemical Overview , 3
A. Regulatory History.................... 3
B. Chemical Identification 3
1. Iodine (includes Iodine & Potassium Iodide) 3
a. Iodine 3
b. Postassium Iodide 4
2. Surfactant-Iodine Complexes 5
a. Propoxyethoxy (PO/EO) Copolymer Carriers.............. 5
b. Phenoxypolyethoxyethanol Carriers 6
c. Polyvinylpyrrolidone Carriers 6
3. Aniino Acid-Iodine Complex 7
a. Tetraglycine hydroperiodide 7
4. lodinated Resin Complex 7
a. Quat Amine divinylbenzene/styrene copolymer 7
C. Use Profile....... 7
III. Summary of Iodine and lodophor Complexes Risk
Assessments 9
A. Human Health Risk Assessment 9
1. Toxicity of Iodine and lodophor Complexes 9
2. FQPA Safety Factor 11
3. Population Adjusted Dose (PAD) 11
4. Dietary and Residential Exposure 12
5. Aggregate Exposure 12
6. Occupational Exposure 13
7. Human Incident Data............... 13
B. Environmental Risk Assessment 13
1. Environmental Fate and Transport.... 13
2. Ecological Risk 14
3. Risk to Listed Species 15
IV. Risk Management, Reregistration, and Tolerance Reassessment Decision.... 16
A. Determination of Reregistration Eligibility 16
B. Public Comments and Responses 16
C. Regulatory Position.... 16
1. Food Quality Protection Act Findings 16
a. "Risk Cup" Determination 16
b. Determination of Safety to U.S. Population 17
-------
c. Determination of Safety to Infants and Children.. 17
d. Endocrine Disrupter Effects 17
e. Cumulative Risks. 18
2. Tolerance Summary 18
D. Regulatory Rationale 20
1. Listed Species Considerations.. 20
a. The Endangered Species Act 20
b. General Risk Mitigation 21
V. What Registrants Need to Do.... 22
A. Manufacturing-Use Products 23
1. Additional Generic Data Requirements........... 23
B. End-Use Products 23
1. Additional Product-Specific Data Requirements 23
VI. Appendices 26
A. Table of Use Patterns for Iodine and lodophor Complexes 27
B. Table of Generic Data Requirements and Studies Used to Make the
Reregistration Decision 40
C. Technical Support Documents 49
D. Bibliography Citations 50
E. Generic Data Call-In 56
F. Product Specific Data Call-In 57
G. Batching of End-Use Products 58
H. List of All Registrants Sent the Data Call-In 59
I. List of Available Forms 60
-------
Iodine and lodophor Complexes Reregistration Team
Health Effects Risk Assessment
Michelle Centra
Tim McMahon
Najm Shamim
Timothy Leighton
Jonathan Chen
Environmental Fate and Ecological Risk Assessment
Kathryn Montague
Najm Shamim
Use and Usage Analysis
Heather Garvie
Registration Support
Marshall Swindell
Risk Management
Heather Garvie
-------
LOG Level of Concern
LOD Limit of Detection
LOAEL Lowest Observed Adverse Effect Level
MATC Maximum Acceptable Toxicant Concentration
MCLG Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulate
contaminants in drinking water under the Safe Drinking Water Act,
mg/kg/day Milligram Per Kilogram Per Day
mg/L Milligrams Per Liter
MOE Margin of Exposure
MP Manufacturing-Use Product
MPI Maximum Permissible Intake
MRID Master Record Identification (number). EPA's system of recording and tracking studies submitted.
NA Not Applicable
N/A Not Applicable
NAWQA USGS National Water Quality Assessment
NOEC No Observable Effect Concentration
NOEL No Observed Effect Level
NOAEL No Observed Adverse Effect Level
NPDES National Pollutant Discharge Elimination System
NR Not Required
OP Organophosphate
OPP EPA Office of Pesticide Programs
OPPTS EPA Office of Prevention, Pesticides and Toxic Substances
Pa pascal, the pressure exerted by a force of one newton acting on an area of one square meter.
PAD Population Adjusted Dose
PADI Provisional Acceptable Daily Intake
PAG Pesticide Assessment Guideline
PAM Pesticide Analytical Method
PCA Percent Crop Area
PDF USDA Pesticide Data Program
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
ppm Parts Per Million
PRN Pesticide Registration Notice
PRZM/
EXAMS Tier II Surface Water Computer Model
Qt* The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RAC Raw Agriculture Commodity
RBC Red Blood Cell
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose
RQ Risk Quotient
RS Registration Standard
RUP Restricted Use Pesticide
SAP Science Advisory Panel
SCI-GROW Tier I Ground Water Computer Model
SF Safety Factor
SLC Single Layer Clothing
SLN Special Local Need (Registrations Under Section 24(c) of FIFRA)
iii
-------
TC Toxic Concentration. The concentration at which a substance produces a toxic effect.
TD Toxic Dose. The dose at which a substance produces a toxic effect.
TEP Typical End-Use Product
TGAI Technical Grade Active Ingredient
TLC Thin Layer Chromatography
TMRC Theoretical Maximum Residue Contribution
torr A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
TRR Total Radioactive Residue
UF Uncertainty Factor
mg/kg/day Micrograms Per Gram
mg/kg/L Micrograms Per Liter
USDA United States Department of Agriculture
USGS United States Geological Survey
UV Ultraviolet
WHO World Health Organization
WP Wettable Powder
WPS Worker Protection Standard
IV
-------
EXECUTIVE SUMMARY
The Environmental Protection Agency (hereafter referred to as EPA or the Agency) has
completed its human health and environmental review for iodine and iodophor complexes and is
issuing its risk management decision. The Agency has decided that iodine and iodophor
complexes are eligible for reregistration provided any data gaps are fulfilled within the allotted
timeframe described in Chapter V. There are a wide variety of uses for iodine and iodophor
complexes. Iodine is used primarily for emergency drinking water disinfection. Potassium iodide
is used to sanitize fresh fruits and vegetables. The surfactant iodophor complexes are used
primarily for sanitizing food-contact surfaces in food processing plants and food handling
establishments, and for disinfection of environmental surfaces in hospitals. The iodinated resins
are used to purity human drinking water, impart antimicrobial and antifungal activity to materials
and finished articles such as paints, stains, coatings and textiles, and microbial control in water
systems.
Several tolerance exemptions exist for iodine and iodophor complexes when used as
ingredients in antimicrobial pesticide formulations under 40 CFR 180.940 and 40 CFR 180.1022.
Approximately 2 million pounds of iodine and iodophor complexes are sold annually in the
United States for use in antimicrobial products registered by the US EPA.
This RED is inclusive of iodine and related compounds used as sanitizers and
disinfectants. It includes: iodine, sodium/potassium iodides and iodine embedded in organic
polymers (including polyvinlypyrrolodine/povidone and tetraglycine). The organic polymers are
called iodophors. When embedded with iodine these moieties are called iodophor complexes.
Technically, a complex would be defined as a chemical which is formed when a metal ion binds
with ligands through a coordinate covalent bond. In this sense the iodophor complexes are not
complexes. However, because the Agency has historically accepted the term iodophor complexes
for these chemicals, we will retain the term for the purpose of this RED.
Overall Risk Summary
Hazard Profile/Human Health Risk
Based on a review of the available toxicology data, the Agency has concluded that iodine
and iodophor complexes are of very low toxicity by the oral, dermal, and inhalation routes of
exposure. The toxicology database is adequate to characterize the hazard of iodine, and no data
gaps have been identified. There are no indications of special sensitivity of infants or children
resulting from exposure to iodine. Therefore, the FQPA Safety Factor has been removed (i.e.,
reduced to IX) for iodine. The Agency has not identified toxicological endpoints of concern for
iodine. Therefore, a quantitative human health risk assessment was not conducted for this RED
document. The Agency has no risk concerns for iodine and iodophor complexes with respect to
human exposure through dietary, drinking water, residential and occupational routes.
Environmental and Ecological Risk
The uses of iodine and iodophor complexes considered in this RED make it unlikely that
v
-------
any appreciable exposure to terrestrial or aquatic organisms would occur.
Regulatory Decision
The Agency has completed its review and has determined that the data are sufficient to
support reregistration of all supported products containing iodine and iodophor complexes.
Summary of Mitigation Measures
The Agency has determined that iodine and iodophor complexes are eligible for
reregistration. Since no risks of concern were identified, no specific mitigation measures are
needed for iodine and iodophor complexes.
Data Requirements
No additional confirmatory data is required to complete the reregistration of iodine and
iodophor complexes. However, product specific data is required for all products containing
iodine and iodophor complexes as described in Section V of this document.
VI
-------
I. INTRODUCTION
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988
to accelerate the reregistration of products with active ingredients registered prior to November 1,
1984 and amended again by the Pesticide Registration Improvement Act of 2003 to set time
frames for the issuance of Reregistration Eligibility Decisions. The amended Act calls for the
development and submission of data to support the reregistration of an active ingredient, as well
as a review of all submitted data by the Agency. Reregistration involves a thorough review of
the scientific database underlying a pesticide's registration. The purpose of the Agency's review
is to reassess the potential hazards arising from the currently registered uses of the pesticide; to
determine the need for additional data on health and environmental effects; and to determine
whether the pesticide meets the "no unreasonable adverse effects" criteria of FIFRA.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into
law. This Act amends FIFRA to require a tolerance reassessment. The Agency has decided that,
for those chemicals that have tolerances and are undergoing reregistration, the tolerance
reassessment will be initiated through this reregistration process. The Act also requires that by
2006, EPA must review all tolerances in effect on the day before the date of the enactment of the
FQPA. FQPA also amends the Federal Food, Drug, and Cosmetic Act (FFDCA) to require a
safety finding in the tolerance reassessment based on factors including consideration of
cumulative effects of chemicals with a common mechanism of toxicity. This document presents
the Agency's human health and ecological review and the Reregistration Eligibility Decision for
iodine.
Iodine and iodophor complexes are used for a variety of indoor antimicrobial uses. They
all function as microbiocides by releasing iodine. A few examples of currently registered uses
are: emergency drinking water purification, fresh food sanitization, food-contact surface
sanitization, hospital surface disinfection, materials preservation, and commercial and industrial
water cooling tower systems. Registered antimicrobial products account for approximately 2
million pounds of iodine and iodophor complexes annually.
The Agency has concluded that the FQPA Safety Factor for iodine and iodophor
complexes should be removed (equivalent to IX) because there is no pre- or post-natal evidence
of increased susceptibility for infants and children following exposure to iodine and this risk
assessment does not underestimate the potential risk for infants and children.
The evaluation summarized in this document concerns only potential exposures from the
use of the active ingredients iodine and iodophor complexes. The Food Quality Protection Act
(FQPA) requires that the Agency consider available information concerning the cumulative
effects of a particular pesticide's residues and other substances that have a common mechanism
of toxicity. The reason for consideration of other substances is due to the possibility that low-
level exposures to multiple chemical substances that cause a common toxic effect by a common
toxic mechanism could lead to the same adverse health effect that would occur at a higher level
of exposure to any of the substances individually. 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 for iodine and iodophor complexes and any other
1
-------
II. CHEMICAL OVERVIEW
A. Regulatory History
Products containing iodine as the active ingredient were initially registered in the United
States by the U.S. Department of Agriculture beginning in 1948. Approximately 2 million
pounds of iodine are sold annually in the United States for use in antimicrobial products.
Currently there are 69 products containing iodine or an iodophor complex as the active ingredient
registered by the Agency.
Iodine is used primarily for emergency drinking water disinfection. Potassium iodide is
mainly used to sanitize fresh fruits and vegetables. The surfactant iodophors are predominantly
used to sanitize food-contact surfaces in food-processing plants and food-handling
establishments and to disinfectant environmental surfaces in hospitals and institutions. The
amino acid-iodine complexes are primarily used to purify (on an emergency basis) human
drinking water. The iodinated resins are used to purify human drinking water, impart
antimicrobial and antifimgal activity to materials and finished articles such as paints, stains,
coatings and textiles, and microbial control in water systems.
This Reregistration Eligibility Document (RED) covers iodine, potassium iodide and
various iodine complexes. The iodine complexes are: 1) complexes of iodine with surfactants; 2)
complexes of iodine with an amino acid; and 3) iodinated resins. The iodophor complexes all
contain iodine as the active ingredient and function in the same manner by releasing molecular
iodine, which is the actual biocide, upon use. Iodine, potassium iodide and iodine complexes
have been divided into the following groups and sub-groups:
B. Chemical Identification
1. Iodine (includes Iodine and Potassium Iodide)
a. Iodine - PC Code: 046905/CAS # 7553-56-2
i. Chemical Overview
The chemical iodine is most commonly used in: sanitation, animal feed and
pharmaceutical production.
ii. Chemical Identification
• Name: Iodine
• Chemical Family: Halogen
Common/Trade Names: None
CAS Number: 7553-56-2
• Molecular Formula: \2
-------
iii. Physical/Chemical Properties
The following characteristics have been reported for iodine:
Technical Grade Active Ingredient (TGAI):
Molecular Weight: 253.809
Color: Bluish-black
Physical State: Solid; scales or plates
• Specific gravity: 4.93
Dissociation Constant: No data available
pH: No data available
Stability: No data available
Melting point: 113.6°C
Boiling point: 185.24°C
Water Solubility: 330mg/L at 25°C
Log KOW 0.40
Vapor Pressure: 0.305 mm Hg at 25°C
Manufacturers: Johnson Diversey, Inc., West Agro, Inc., Polar Equipment Inc., logold Systems
Inc., Baltimore AirCoil Company
b. Potassium Iodide PC Code: 075701/CAS # 7681-11-0
i. Chemical Overview
The chemical Potassium iodide is most commonly used in: sanitation, animal feed,
catalysts, and for treatment of radioiodide poisoning resulting from nuclear accidents.
ii. Chemical Identification
• Name: Potassium iodide
Chemical Family: Halogen
• Common/Trade Names: None
CAS Number: 7681 -11 -0
• Molecular Formula: KI
iii. Physical/Chemical Properties
The following characteristics have been reported for potassium iodide:
Technical Grade Active Ingredient (TGAI):
Molecular Weight: 166.02
• Color: Colorless or white
Physical State: Solid; crystals, granules, or powder
-------
• Specific gravity: 3.12
• Dissociation Constant: N/A: Completely ionized in aqueous medium
• pH: No data available
• Stability: Stable, but turn yellowish over prolonged period of
time
Melting point: 680°C
Boiling point: 1323°C
Water Solubility: 1429 g/L at 25°C
• pH; Aqueous Solution: neutral to basic: 7-9
Log KOW: 0.04
• Vapor Pressure: 9.9 x 10"18mmHg
Manufacturer: U.S. Army Research, Development & Engineering Command
2. Surfactant-Iodine Complexes
a, Propoxyethoxy (PO/EO) Copolymer Carriers or Polypropoxypolyethoxyethanol-
lodinc Complexes
i. Butoxypolypropoxypolyethoxyethanol: PC Code: 046901/CAS # 68610-00-4
Butoxypolypropoxypolyethoxyethanol is a polymer made from a mixture of propylene
oxide, ethylene oxide and butanol. It is synthesized by the ethoxylation reaction of
propylene oxide (PO) and ethylene oxide (EO) with a butanol "starter." For iodophor
production, so-called block copolymers are used. In the synthesis of these molecules, PO
and EO are added in sequential steps (rather than simultaneously) to form "blocks" of
polypropoxy and polyethoxy units within the molecule. The final polyalkylene glycol
(PAG) is not a single compound but is a mixture of polymer chains which have an
approximate normal distribution around the desired molecular weight. The molecular
weights used in iodophor production range from 2000 to 4000 a.m.u.
Manufacturers: Richardson Chemical Products, Co., Ecolab, West Agro Inc., National
Chemicals Inc., U.S. Chemical Corporation
ii. Polypropoxypolyethoxyethanol: PC Code 046904/CAS # 26617-87-8
Polypropoxypolyethoxyethanol is a polymer made from a mixture of propylene oxide,
ethylene oxide and water. It is synthesized by the ethoxylation reaction of propylene
oxide (PO) and ethylene oxide (EO) with a water "starter." Except for the initiator, these
polymers are the same as the butoxypolypropoxypolyethoxyethanol carriers.
Manufacturers: West Chemical Products, Inc., West Agro, Inc., Lonza, Inc., H&S Chemicals
Division
-------
b. Phenoxypolyethoxyethanol Carriers (Phenoxypolyethoxyethanol-iodine complexes)
i. Nonylphenoxypolyethoxyethanol: PC Code 046903/CAS # 11096-42-7
Nonylphenoxypolyethoxyethanols (nonylphenol polyethoxylates; NPE) are commonly
used surfactants in industrial cleaners, pesticide adjuvants, and, for the most commonly made 9-
mole ethoxylate, spermicides. It is a polymer made from a mixture of nonyphenol, ethylene oxide
and ethanol. A wide range of ethoxylation (approximately 4 to 100 moles of EO) are used to
provide different properties. The NPEs are produced by introducing the preferred molar ratio of
EO and nonylphenol (NP) into a reactor. The C9 chain of the NP is comprised of approximately
25-30 isomers with different branching. As with the EO/PO polymers discussed above, the final
products are not a single compound but are mixtures of chains which have an approximate
normal distribution around the desired molecular weight. For example, the most commonly
produced 9-mole ethoxylate (known as Nonoxynol in spermicide use) contains congeners ranging
from approximately 5 to 16 moles of EO. Therefore, each NPE is a complex mixture of isomers
of the nonene chain and congeners of the EO chain. Nonylphenoxypolyethoxyethanol is in the
form a blue liquid, with a specific gravity of 1.01. Nonylphenoxypolyethoxyethanol has a listed
pH factor of 9.5 ±2.
Manufacturers: Westfalia-Surge, Inc., An-Fo Manufacturing Comp., ABC Compounding Co.,
Inc., West Agro, Inc., Theochem/Time Products, Inc., Lonza, Inc., Webco Chemical Corp.,
Thatcher Co., H. Wilson Manufacturing Co., Inc., Controlled Release Technologies, Inc., Multi-
Wash Medical, Ltd., Preserve International, PM Resources, Inc., Dupont
c. Polyvinylpyrrolidone Carriers (Polyvinylpyrrolidone-iodine complexes)
i. Polyvinylpyrrolidone (Povidone): PC Code 046914/CAS # 25655-41-8
Povidone (PVP; CAS No. 9003-39-8) is a synthetic polymer principally consisting of
linear l-vinyl-2-pyrrolidone groups, produced as a series of products having mean molecular
weights ranging from about 10,000 to about 1 million a.m.u. or greater. The monomer molecular
weight is 11.1 a.m.u. In addition to its use in disinfectants, it is used as a dispersing agent, and
has been used as a tablet binder, coating agent, and viscosity-increasing agent in pharmaceutical
preparations.
PVP is an odorless faintly yellow powder and is soluble in water, ethanol, and chloroform
and insoluble in ether. PVP has a specific gravity of 1.1-1.3 and a pH ranging from 3.0 to 7.0 in
a 1:20 solution. The melting point is 100°C. The amide region of the pyrrolidone substituent
absorbs in the UV region at wavelengths below 235 nm.
Manufacturer: H&S Chemicals Division
-------
3. Amino Acid-Iodine Complex
a. Tetraglyeine hydroperiodide; PC Code 046923/CAS # 7097-60-1
For the iodophor used for emergency water disinfection (tetraglycine hydroperiodide), the
iodine and iodophor complex is formed by a catalyst driven reaction with the essential amino
acid glyeine, to produce the complex: 2[(CH2NH2COOH)8 • (HI)2 2.512]
Manufacturers: U.S. Army Research, Development, & Engineering Command, The Brita
Products Co., Wisconsin Pharmacal Comp, LLC.
4. lodinated Resin Complex
a. Quat Amine divinylbenzene/ styrene eopolymer: PC Code 046905/CAS # 7553-56-2
Triosyn® resin is a polymer made from a mixture of divinylbenzene quaternary amine
and styrene. It is produced by thermally fusing pure iodine crystals under high pressure with a
specialized quaternary amine divinylbenzene/styrene polymer. During this process, a stable
electrochemical bond is formed between the iodine and the polymer, allowing no free release of
iodine in the media employed. This electrochemical bond serves as a demand-release mechanism
that allows iodine molecules to be released from Triosyn® resin in the presence of demand-
causing microorganisms and in amounts required to eliminate the source of the demand.
Triosyn® is activated by the strong ionic charge of surface proteins that cover microorganisms
and then interacts with organisms through ionic transfer. Upon contact with a microorganism,
ionic molecular iodine is transferred from Triosyn® resin, to the more strongly charged surface
proteins of the microbe. The iodine immediately devitalizes the microorganism by removing
electrons from the organism's surface proteins which are necessary for life and reproduction.
This process provides disinfectant properties to items such as tent fabric and outdoor paint. There
is little human contact with the poymeric Triosyn® resin.
Manufacturers: The Purolite Comp., Triosyn Corp., MCV Manufacturing Inc., Water Solution
Technologies, Inc., Umpqua Research Company
C. Use Profile
The following is information on the currently registered uses of iodine and iodophor
complex products and an overview of use sites and application methods. A detailed table of the
use sites, method and rate of applications, and use limitations can be found in Appendix A.
-------
III. SUMMARY OF IODINE AND IODOPHOR COMPLEXES RISK ASSESSMENTS
The purpose of this summary is to assist the reader by identifying the key features and
findings of these risk assessments and to help the reader better understand the conclusions
reached in the assessments. The human health and ecological risk assessment documents and
supporting information listed in Appendix C were used to formulate the safety finding and
regulatory decision for iodine and iodophor complexes. While the risk assessments and related
addenda are not included in this document, they are available from the U.S. Federal Government
website at www.regulations.gov. The docket number is: EPA-HQ-OPP-2006-0599. Hard copies
of these documents may be found in the OPP public docket under the same docket number. The
OPP public docket is located in Room S-4400, One Potomac Yard, 2777 South Crystal Drive,
Arlington, VA, and is open Monday through Friday, excluding Federal holidays, from 8:30
a.m.to 4:00 p.m
A. Human Health Assessment
The Agency's use of human studies in the iodine and iodophor complexes risk
assessment is in accordance with the Agency's Final Rule promulgated on January 26, 2006,
related to Protections for Subjects in Human Research, which is codified in 40 CFR Part 26.
1. Toxicity of Iodine and Iodophor Complexes
A brief overview of the toxicity of iodine and iodophor complexes is presented below.
Further details on the toxicity of iodine and iodophor complexes can be found in the supporting
documentation for this RED. The Antimicrobials Division Toxicology Endpoint Selection
Committee (ADTC) memorandum, the toxicology chapter for the RED and other supporting
documentation are available from the Federal Government Public Docket at
www.regulations.gov.
The toxicological database for iodine and iodophor complexes is currently comprised of
published and unpublished studies either submitted to the Agency or obtained directly from the
open literature. Although the available studies may not meet the requirements of the Agency's
OPPTS harmonized test guidelines published in 1998, it was determined that these studies
contain useful information that is adequate for hazard characterization of iodine. These
acceptable non-guideline studies include acute, subchronic, chronic, developmental, and
reproductive toxicity, carcinogenicity, mutagenicity, metabolism/pharmacokinetic and dermal
absorption studies. Therefore, the Agency has determined that the toxicological database is
complete and sufficient for reregistration.
Major features of the toxicology profile are presented in Table 1. The acute toxicity of iodine
(99.5% a.i.) is low for dermal toxicity, but shows higher toxicity for acute oral toxicity,
inhalation toxicity, and primary dermal irritation. Iodine is not a dermal sensitizer.
-------
Table 1. Acute Toxicity of Iodine Technical Grade Active Ingredient (TGAI)
Guideline No.
870.1100
870,1200
870.1300
870. 2500
870.2600
Study Type
Acute Oral- Rats
Acute Dermal — Rats
Acute Inhalation -
Rats
Primary Dermal
Irritation — Rabbits
Dermal Sensitization-
Guinea Pigs
MRID#
42326704
42326705
42961002
42326706
42326707
Results
LD50 = 315mg/kg
LD50 = 3,333 mg/kg
LC50 = 0.363 mg/L
Corrosive; severe
edema, erythema,
and eschar
No sensitization
using Buehler
method
Toxicity
Category
II
III
11
I
N/A
N/A = Not applicable
General Toxicity Observations
Upon reviewing the published data on dermal absorption and toxicity of iodine, and the
estimated worst-case exposures from dermal and inhalation uses of iodine and iodophor
complexes in antimicrobial pesticide formulations, the Agency concluded that there are no
endpoints of concern for oral, dermal, or inhalation exposure to iodine. The Agency agreed that
the data for dermal absorption of iodine and iodophor complexes show a low percentage of
absorption (1%; ATSDR, 2004).
Carcinogenicitv Classification
A review of the available data has shown iodine and iodophor complexes to be negative
for carcinogenicity in studies conducted up to the testing limit doses established by the Agency.
Mutagenicitv Potential
The Agency has granted waiver requests for a mutagenicity battery conducted with iodine
for oral exposures to this chemical.
Metabolism and Excretion
Iodine is an essential dietary component and is required for synthesis of thyroid
hormones. The iodide salts, sodium and potassium iodide, are soluble in water and oral doses are
generally considered to have 100% gastrointestinal absorption. An acute exposure to iodine that
may be above the Recommended Daily Allowance (RDA) is usually a temporary effect to which
the body readily adapts through down-regulation of the iodine transporter mechanism in the
thyroid gland.
Developmental and Reproductive Toxicity
There is no concern for increased susceptibility of infants and children to the exposures
from antimicrobial uses of iodine and iodine complexes.
10
-------
Neurotoxicitv
There is no evidence in the available toxicity studies or scientific literature to indicate
neurotoxie effects of iodine in humans or laboratory animals.
Endocrine Disruption Potential
EPA is required under the Federal Food Drug and Cosmetic Act (FFDCA), as amended
by FQPA, to develop a screening program to determine whether certain substances (including all
pesticide active and other ingredients) "may have an effect in humans that is similar to an effect
produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator
may designate." Following recommendations of its Endocrine Disrupter and Testing Advisory
Committee (EDSTAC), EPA determined that there was a scientific basis for including, as part of
the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone
system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of
potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects in wildlife may help determine whether a substance may have an effect in humans,
FFDCA authority to require the wildlife evaluations. As the science develops and resources
allow, screening of additional hormone systems may be added to the Endocrine Disrupter
Screening Program (EDSP). When the appropriate screening and/or testing protocols being
considered under the Agency's Endocrine Disrupting Screening Program (EDSP) have been
developed, iodine and iodophor complexes may be subjected to additional screening and/or
testing to better characterize effects related to endocrine disruption.
2. FQPA Safety Factor
The FQPA Safety Factor (as required by the Food Quality Protection Act of 1996) is
intended to provide an additional 10-fold safety factor (10X), to protect for special sensitivity in
infants and children to specific pesticide residues in food, drinking water, or residential
exposures, or to compensate for an incomplete database. The FQPA Safety Factor has been
removed (i.e., reduced to IX) for iodine and iodophor complexes because there is no pre- or post-
natal evidence for increased susceptibility following exposure. Further, the Agency has
concluded that there are no endpoints of concern for oral, dermal, or inhalation exposure to
iodine and iodophor complexes based on the low toxicity observed in studies conducted at or
below the established testing limit doses. Therefore, a quantitative risk assessment was not
conducted for iodine.
3. Population Adjusted Dose (PAD)
Dietary risk is characterized in terms of the Population Adjusted Dose (PAD), which
reflects the reference dose (RfD), either acute or chronic, that has been adjusted to account for
the FQPA Safety Factor (SF). This calculation is performed for each population subgroup. A
risk estimate that is less than 100% of the acute or chronic PAD is not of concern. Since
toxicological endpoints for risk assessment were not identified based on the available data, RfDs
and PADs have not been calculated for iodine.
11
-------
4. Dietary and Residential Exposure
A residential exposure risk assessment is required for an active ingredient if: 1) certain
lexicological criteria are triggered; and 2) there is potential exposure to handlers (mixers, loaders,
applicators, etc.) during use or to persons entering treated sites after application is complete. For
iodine, the toxicological criteria are not met, and therefore, an assessment is not warranted.
Dietary exposure (food and drinking water) could potentially occur from the use of iodine
and iodophor complexes as a food contact sanitizer and water disinfectant. Although the Agency
has not identified any toxicological endpoints of concern for iodine or iodophor complexes,
iodine's role in the synthesis of thyroid hormones is long and well established. Too much or too
little dietary iodine can be deleterious. Therefore, the Agency conducted an exposure assessment
to ensure dietary exposures from the pesticidal uses of iodine fall within an acceptable range.
Based on calculations using current assumptions on food contact sanitizer uses, the tolerance
exemption noted in 180.940 for iodine and iodophor complexes of 25 ppm translates into a dose
of approximately 0.007 mg/kg/day for a 70 kg adult, and 0.033 mg/kg/day for a 15 kg child and
represent worst-case exposures. These calculated oral exposures represent worst-case exposures.
For adults and children, these estimated exposures fall between the RDA of 0.002 mg/kg/day and
the Tolerable Upper Intake Level of 0.016 mg/kg/day for adults and 0.01 - 0.04 mg/kg/day for
children 1-13. It is important to note that the tolerable upper intake level is the highest level of
daily nutrient intake that is likely to pose no risk of adverse health effects in almost all
individuals (Institute of Medicine, 2003), and that responses to intake of iodine and iodophor
complexes between the RDA and the upper intake level do not represent adverse responses, but
biological responses. Taking this into consideration, the Agency concluded that the calculated
oral exposures from food contact sanitizer use of iodine and iodine complexes represented no
risk of concern.
Again, an acute exposure to iodine and iodophor complexes that may temporarily be
above the RDA is usually a temporary effect to which the body readily adapts through down-
regulation of the iodine and iodophor transporter mechanism in the thyroid gland (ATSDR,
2004).
5. Aggregate Exposure
The Food Quality Protection Act amendments to the Federal Food, Drug, and Cosmetic
Act (FFDCA, Section 408(b)(2)(A)(ii)) require "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." Aggregate
exposure will typically include exposures from food, drinking water, residential uses of a
pesticide and other non-occupational sources of exposure.
Since toxicological endpoints for risk assessment were not identified based on the
available data, an aggregate risk assessment was not conducted for iodine.
12
-------
6. Occupational Exposure
An occupational exposure assessment addresses potential exposures and risks to humans
who may be exposed in "occupational settings". An occupational risk assessment is required for
an active ingredient if: 1) certain toxicological criteria are triggered; and 2) there is potential
exposure to handlers (mixers, loaders, applicators, etc.) during use or to persons entering treated
sites after application is complete. Although there are potential exposures from the use of these
products, there are no toxicological endpoints of concern. Therefore, the exposures and risks
have not been quantified.
7. Human Incident Data
In evaluating incidents to humans, the Agency reviewed reports from the National Poison
Control Centers (PCC), the Agency's Office of Pesticide Program's Incident Data System (IDS),
the California Department of Pesticide Regulation, and the National Pesticide
Telecommunications Network (NPTN).
A total of 8 individual human incident cases submitted to the EPA Office of Pesticide
Programs are associated with exposure to iodine and iodophor complexes containing compounds.
Inhalation and dermal are the two important routes of exposure. The most common symptoms
reported for cases of inhalation exposure were coughing, wheezing, tightness of chest and
shortness of breath. Dermal exposure caused skin burning, blisters and rashes. None of these
effects were considered severe effects. Incidences of death have been reported but these
incidence cases were linked to ingestion of excessively high quantities to iodine. Irritation
effects were reported with exposure to iodine compounds through oral, dermal or inhalation
routes of exposure.
B. Environmental Risk Assessment
A summary of the Agency's environmental review is presented below. For detailed
discussions of all aspects of the environmental review, see the Ecological Hazard and
Environmental Risk Assessment and Environmental Fate chapters available from the U.S.
Federal Government website at: www.regulations.gov. The docket number is EPA-HQ-OPP-
2006-0599.
1. Environmental Fate and Transport
The transfer of iodine from air, water, and land is due to the chemical's volatility. The
wet deposition of iodine is predominantly into soil. Iodine is not likely to volatilize from
iodophors due to lower vapor pressure. The vapor pressure of iodine when embedded in the
carrier polymer is less than when it is free (not bonded or embedded in ay polymer or resin).
Mobility of iodine in soil depends on the soil porosity, saturation and the amount of organic
matter and iron/aluminum oxides in the soil.
The Agency has evaluated iodine as an active and as an inert ingredient. In this
assessment, no potential environmental concerns for these pesticides (chemicals assessed were:
13
-------
(Colinus virginianus)
Bobwhite quail
(Colinus virginianus)
Mallard (Anas
platyrhynchos)
hydroperiodide,
100%
Nonylphenoxyp
olyethodyethan
ol-iodine
complex, 100%
Nonylphenoxyp
olyethodyethan
ol-iodine
complex, 100%
ppmai
NOEC= 2500
ppmai
LC50 > 5620
ppm
NOEC = 5620
ppm
LC50 > 5620
ppm
NOEC = 3 160
ppm
non-toxic
Practically
non-toxic
Practically
non-toxic
- analytical data for
diet not provided
- NOEC based on
reduction in body
weight
Yes
- core study
Yes
- core study
- NOEC based on
signs of toxicity
ACC238200
ACC238200
Acute Toxicity of Iodine and lodophors to Freshwater Fish
Bluegill sunfish
(Lepomis macmchirus)
Igepal CO-630
Atechnical®
lobio 99.8%
iodine
96hr LC50 =
7.9mg/L
96hr LC50 =
0.61
NOEC = .016
Moderately
toxic
Highly toxic
No
- supplemental study
- test substance did
not include iodine
complex
Yes
ACC238200
43044501
Acute Toxicity of Iodine and lodophors to Freshwater Invertebrates
Waterflea
(Daphnia magna)
Iodine, 99.8%
48-hr. EC5o =
0.33 (95%
conf. limits
0.20 - 0.37)
mgai/L
NOEC = 0.09
mgai/L
Very highly
toxic
Yes
- Core study
- NOEC based on
signs of toxicity
42961001
Based on the indoor use patterns of iodine and iodophor complexes, minimal
environmental exposure is expected, and, therefore, no ecological risk is anticipated.
3. Risk to Listed Species
Due to the low likelihood of exposure and low toxicity of iodine and iodophor
complexes, the Agency expects no effects to listed species or critical habitat and therefore makes
a "No Effect" determination for this chemical.
15
-------
IV. Risk Management, Reregistration and Tolerance Reassessment Decision
A, Determination of Reregistration Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether products containing the active ingredient
are eligible for reregistration. The Agency has previously identified and required the submission
of the generic (i.e. active ingredient-specific) data to support reregistration of products containing
iodine. The Agency has completed its review of these generic data, and has determined that the
data are sufficient to support reregistration of all supported products containing iodine and
iodophor complexes.
The Agency has completed its assessment of the dietary, drinking water, residential,
ecological and occupational risks associated with the use of pesticide products containing the
active ingredient iodine and iodophor complexes. Based on a review of these data, the Agency
has sufficient information on the human health and ecological effects of iodine and iodophor
complexes to make a decision as part of the tolerance reassessment process under FFDCA and
reregistration under FIFRA, as amended by FQPA. The Agency has determined that iodine and
iodophor complexes containing products are eligible for reregistration. Appendix A summarizes
the uses of iodine and iodophor complexes that are eligible for reregistration. Appendix B
identifies the generic data requirements that the Agency reviewed as part of its determination of
reregistration eligibility of iodine, and lists the submitted studies that the Agency found
acceptable.
B. Public Comments and Responses
Supporting documents for iodine and iodophor complexes were not issued for public
comment per the Agency's public participation process because no toxicological endpoints were
identified and, as such, a quantitative risk assessment was not conducted. To ensure that
opportunity is presented to the public to comment on the risk management decisions and
supporting documents for iodine, the Agency will implement a 60-day public comment period on
this RED document. A notice announcing the availability of this RED and the start of the public
comment period will be published in the Federal Register.
C. Regulatory Position
1. Food Quality Protection Act Findings
a. "Risk Cup" Determination
Upon reviewing the available toxicity information, the Agency has concluded that there are
no endpoints of concern for oral, dermal, or inhalation exposure to iodine. This conclusion is
based on the results of toxicity testing of iodine and iodophor complexes in which dose levels
near or above testing limits (as established in the OPPTS 870 series harmonized test guidelines)
were employed in experimental animal studies and no significant toxicity observed. The Agency
16
-------
has concluded that the exemption from the requirement for a tolerance is appropriate and is
considered reassessed as required by FQPA. An aggregate assessment was not conducted for
exposures through food, drinking water and residential exposure since toxicological endpoints
for risk assessment were not identified based on the available data. In reaching this
determination, EPA has considered the available information on the special sensitivity of infants
and children.
b. Determination of Safety to U.S. Population
As part of the FQPA tolerance reassessment process, EPA has concluded that there are no
endpoints of concern for oral, dermal, or inhalation exposure to iodine and iodophor complexes
based on the low toxicity observed in studies conducted at or below the established testing limit
doses. The Agency has determined that the established exemption from the requirement for a
tolerance for iodine and iodophor complexes meets the safety standards under the FQPA
amendments to section 408(b)(2)(D) of the FFDCA, and that there is a reasonable certainty no
harm will result to the general population or any subgroup from the use of iodine, hi reaching
this conclusion, the Agency has considered all available information on the toxicity, use practices
and exposure scenarios, and the environmental behavior of iodine.
Because no toxicological endpoints were identified for iodine, the Agency has determined
that exposure to it does not result in human health effects of concern. Therefore a quantitative
risk assessment was not necessary for this pesticide.
c. Determination of Safety to Infants and Children
EPA has determined that the established exemption from a requirement for a tolerance for
iodine and iodophor complexes meet the safety standards under the FQPA amendments to
section 408(b)(2)(C) of the FFDCA, that there is a reasonable certainty of no harm for infants
and children. The safety determination for infants and children considers factors of the toxicity,
use practices, and environmental behavior noted above for the general population, but also takes
into account the possibility of increased dietary exposure due to the specific consumption
patterns of infants and children, as well as the possibility of increased susceptibility to the toxic
effects of iodine and iodophor complex residues in this population subgroup.
In determining whether or not infants and children are particularly susceptible to toxic
effects from iodine and iodophor complexes residues, the Agency considered the completeness of
the database for developmental and reproductive effects, the nature of the effects observed, and
other information. The FQPA Safety Factor has been removed (i.e., reduced to IX) for iodine
and iodophor complexes because there is no pre- or post-natal evidence for increased
susceptibility following exposure.
d. Endocrine Disruptor Effects
EPA is required under the FFDCA, as amended by FQPA, to develop a screening program
to determine whether certain substances (including all pesticide active and other ingredients)
"may have an effect in humans that is similar to an effect produced by a naturally occurring
17
-------
estrogen, or other endocrine effects as the Administrator may designate." Following
recommendations of its Endocrine Disrupter Screening and Testing Advisory Committee
(EDSTAC), EPA determined that there was a scientific basis for including, as part of the
program, the androgen and thyroid hormone systems, in addition to the estrogen hormone
system. EPA also adopted EDSTAC's recommendation that EPA include evaluations of
potential effects in wildlife. For pesticides, EPA will use FIFRA and, to the extent that effects in
wildlife may help determine whether a substance may have an effect in humans, FFDCA
authority to require the wildlife evaluations. As the science develops and resources allow,
screening of additional hormone systems may be added to the Endocrine Disrupter Screening
Program (EDSP).
When the appropriate screening and/or testing protocols being considered under the EDSP
have been developed, iodine and iodophor complexes may be subject to additional screening
and/or testing to better characterize effects related to endocrine disruption.
e. Cumulative Risks
Risks summarized in this document are those that result only from the use iodine. The
Food Quality Protection Act (FQPA) requires that the Agency consider "available information"
concerning the cumulative effects of a particular pesticide's residues and "other substances that
have a common mechanism of toxicity." The reason for consideration of other substances is due
to the possibility that low-level exposures to multiple chemical substances that cause a common
toxic effect by a common toxic mechanism could lead to the same adverse health effect as would
a higher level of exposure to any of the substances individually. 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 for iodine. For information
regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity
and to evaluate the cumulative effects of such chemicals, see the policy statements released by
EPA's Office of Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a common mechanism on
EPA's website at http://www.epa.gov/pesticides/cunmlatiye/.
2. Tolerance Summary
The tolerance exemption for residues of iodine and iodophor complexes per se is
established under 40 CFR 180.940 (69 FR 23124, Apr.28, 2004).
Tolerance Exemptions/Reassessment
Ten tolerance exemptions exist for iodine and iodophor complexes when used as
ingredients in antimicrobial pesticide formulations under 40 CFR 180.940:
18
-------
Table 3, Tolerance Exemptions in 180.940, 40 CFR
Tolerance
Exemption
Expression
Iodine
Potassium Iodide
Sodium Iodide
Hydriodic Acid
CAS No.
7553-56-2
7681-11-0
7681-82-5
10034-85-2
40 CFR
180.940(a)(b)(c)
180.940(a)(b)(c)
180.940(c)
180.940(b)(c)
Limits
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
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
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
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
Residues of chemical substances listed in Sec. 180.940 are exempt from the requirement
of a tolerance when used in accordance with good manufacturing practice as ingredients in an
antimicrobial pesticide formulation, provided that the chemical substance is applied on a semi-
permanent or permanent food-contact surface (other than being applied on food packaging) with
adequate draining before contact with food. Under 180.940 (a) (b) (c), chemical substances
when used as ingredients in an antimicrobial pesticide formulation may be applied to (a) food-
contact surfaces in public eating places, dairy-processing equipment, and food-processing
equipment and utensils; (b) dairy processing equipment, and food-processing equipment and
utensils, and (c) food-processing equipment and utensils.
In addition, the following exemption is listed in 180.1022:
180.1022 Iodine-detergent complex; exemption from the requirement of a tolerance.
"The aqueous solution of hydriodic acid and elemental iodine, including one or both of
the surfactants (a) polyoxypropylene-polyoxyethylene glycol nonionic block polymers (minimum
average molecular weight 1,900) and (b) % -(p- nonylphenyl)-omega- hydroxypoly (oxyethylene)
having a maximum average molecular weight of 748 and in which the nonyl group is a propylene
trimer isomer, is exempted from the requirement of a tolerance for residues in eggs and poultry
when used as a sanitizer in poultry drinking water."
The Agency considers the ten tolerances for iodine, potassium iodide, sodium iodide and
hydriodic acid reassessed.
19
-------
or critical habitat and therefore makes a "no effect" determination for this chemical. Based on
the indoor use patterns of iodine and iodophor complexes, minimal environmental exposure is
expected, and, therefore, no ecological risk is anticipated.
b. General Risk Mitigation
Iodine and iodophor complex end-use products (EUPs) may also contain other registered
pesticides. Although the Agency is not proposing any mitigation measures for products
containing iodine and iodophor complexes specific to federally listed species, the Agency needs
to address potential risks from other end-use products. Therefore, the Agency requires that users
adopt all listed species risk mitigation measures for all active ingredients in the product. If a
product contains multiple active ingredients with conflicting listed species risk mitigation
measures, the more stringent measure(s) should be adopted.
21
-------
V. What Registrants Need To Do
The Agency has determined that iodine and iodophor complexes are eligible for
reregistration. No additional generic data are required at this time to support this decision.
For end-use products containing the active ingredient iodine or iodophor complexes, the
registrants need to submit the following items for each product:
Within 90 days from the receipt of the product-specific data call-in (PDCI):
1. completed response forms to the PDCI (i.e., PDCI response form and requirements
status and registrant's response form); and
2. submit any time extension or waiver requests with a full written justification.
Within eight months from the receipt of the PDCI:
1. two copies of the confidential statement of formula (EPA Form 8570-4);
2. a completed original application for reregistration (EPA Form 8570-1). Indicate on
the form that it is an "application for reregistration";
3. a completed form certifying compliance with data compensation requirements (EPA
Form 8570-34);
4. if applicable, a completed form certifying compliance with cost share offer
requirements (EPA Form 8570-32); and
5. the product-specific data responding to the PDCI.
Please contact Marshall Swindell at (703) 308-6341 with questions regarding product
reregistration and/or the PDCI. All materials submitted in response to the PDCI should be
addressed as follows:
By US mail: By express or courier service:
Document Processing Desk Document Processing Desk
Marshall Swindell Marshall Swindell
Office of Pesticide Programs (751 OP) Office of Pesticide Programs (751 OP)
U.S. Environmental Protection Agency U.S. Environmental Protection Agency
1200 Pennsylvania Ave., NW Room S-4900, One Potomac Yard
Washington, DC 20460-0001 2777 South Crystal Drive
Arlington, VA 22202
22
-------
A. Manufacturing-Use Products
There are no currently registered iodine and iodophor complexes manufacturing-use
products.
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of iodine and iodophor complexes for
the above eligible uses has been reviewed and determined to be substantially complete. Therefore
at this time, there are no generic data requirements.
B. End-Use Products
1. Additional Product-Specific and Efficacy Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific
data regarding the pesticide after a determination of eligibility has been made. Registrants must
review previous data submissions to ensure that they meet current EPA acceptance criteria and if
not, commit to conduct new studies. If a registrant believes that previously submitted data meet
current testing standards, then the study MRID numbers should be cited according to the
instructions in the Requirement Status and Registrants Response Form provided for each
product.
A product-specific data call-in, outlining data requirements, will be sent to registrants at a
later date. Possible efficacy studies that the Agency may call-in are listed in Table 4. The PDCI
will be based upon current efficacy-related requirements for antimicrobial pesticide products,
claims, or patterns of use. A summary of these requirements can be found on the Agency's
Antimicrobials Science Policy website at http://www.epa.gov/oppad001/sciencepolicy.htm.
23
-------
Table 4. Efficacy Data Requirements for Product Reregistration
Claim
Sanitizer
Sanitizer
Disinfectant
Disinfectant
3isinfectant
Water
'urification
Claim
Virucidal
Claim in
Conjunction
with
Disinfectant
Claim
Use Pattern
(non-food contact
surfaces - non-
residual)
previously cleaned
food-contact surfaces
(non residual)
Hard Inanimate
Surfaces
Toilet bowl, urinal
surfaces
rlurnan drinking water;
emergency water
supplies
Water treatment units
ncluding Emergency
water supplies
Any site/application
Guideline Study Name
Sanitizer Test for Hard Inanimate
Non — food contact surfaces
AOAC Germicidal and Detergent
Sanitizers Method
AOAC Use Dilution Test (hard water
and organic soil)
Or
AOAC Germicidal Spray Test
Or
AOAC Hard Surface Carrier Test
(distilled water only)
AOAC Use Dilution Test (hard water
and organic soil)
Or
AOAC Germicidal Spray Test
Or
AOAC Hard Surface Carrier Test
(distilled water only)
SPA Guide Standard and Protocol for
Testing Microbiological Water
*urifiers or Controlled or Simulated
"n-Use Study
5PA Guide Standard and Protocol for
Testing Microbiological Water
'urifiers
Virucidal Activity Method used in
conjunction with modifications of:
AOAC Hard Surface Carrier Test
distilled water only)
Or
AOAC Germicidal Spray Test
New OPPTS
Guideline No.
810.2100(1)
810.2100
(m)(2)
810.2100 (c),(d),
(e),
91-7 (a) (I)
810.2700 (b) (1)
81 0.2700 (b)(2),
0>)(3)
810.2100(g)
Old Guideline
No.
91-2(j)
91-2 (1)(2)
91-2 (b), (c) (d)
8 10.2600 (b)(l)
91-8 (a) (2)
91-l(a)(2),(a)(3),
9 1-8 (a) (2)
91-2(0
24
-------
Fungicidal
Claim
Tuberculocid
al Claim
Any site/application
Any site/application
AOAC Fungicidal Test or
AOAC Hard Surface Carrier Test
(distilled water only)
Or
AOAC Germicidal Spray Products
Test
AOAC Tuberculocidal Activity Test
Method (standard)
Or
AOAC Tuberculocidal Activity of
Disinfectants Test Method (modified)
Or
Quantitative Tuberculocidal Activity
Test Method
Or
AOAC Germicidal Spray Products
Test (modified for spray products)
810.2100(f)
810.2100(h)
91-2(e)
91-2 (g)
25
-------
VI. APPENDICES
26
-------
Appendix A: Use Patterns Eligible for Reregistration
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Agricultural premises and equipment
Farm Premises, Poultry
Houses, Livestock Barns
& Premises.
Transportation Vehicles
(Hard non-porous
surfaces)
Farm Equipment
Shoe Bath
Soluble
Concentrate
(reg no. 875-97)
(regno.4959-15)
(reg no. 67517-9)
(reg no. 66171-6)
(reg no. 34052-10)
(reg no. 71654-15)
(reg no. 66171-10)
(reg no. 6836-81)
(reg no. 47371-93)
(reg no. 4737 1-26)
Soluble
Concentrate
(reg no. 66171-6)
(reg no. 4737 1-26)
(reg no. 47371-93)
Soluble
Concentrate
(reg no. 875-97)
(reg no, 4959-15)
(reg no. 675 17-9)
Spray, mop
cloth, sponge
Immersion
Immersion
Vi oz per gallon of water
10 minute contact time
1 36 ppm
1:500 gallons (52 ppm)
68 ppm
68 ppm
5: 100 gallons
1:256 gallons (1.75%)
3 oz per gallon of water
immerse for 30 seconds
272 ppm
Empty all troughs, racks and other feeding
and watering appliances. Thoroughly
clean all surfaces with soap or detergent
and rinse with water.
Not stated
None stated
27
-------
Use Site
Mushroom Houses
(Food Contact Surfaces)
Poultry Drinking Water
Formulation
(reg no. 52-254)
(reg no. 71654-15)
Soluble
Concentrate
(reg. no 1677-89)
(reg no. 675 17-9)
(reg no. 67517-30)
Crystalline,
Impregnated
materials
(reg. no. 73158-1)
(reg no. 1677-89)
(reg no 875-97)
(reg no. 66171-6)
(reg no. 71654-15)
(reg no. 6836-81)
(reg no. 66171-8)
(reg no. 47371 -93)
(reg no. 473 7 1-26)
Method of
Application
Spray
metered
Application Rate/ No. of
applications
50ppm
1 oz solution/ 13 gallons
of water (25 ppm for
food contact)
spray for 2 minutes
(75 - 100 ppm non-food
contact surfaces)
12.5 mg/L of iodine in
reconstituted drinking
water to 300 mg/L of
iodine
Change recharge canister
when iodine and
iodophor complexes
levels fall below 2mg/L
1 ounce solution/ 52
gallons water 6 ppm.
1 oz per 10 gallons of
water
Use Limitations
Pre-clean to sanitize
Not stated
28
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
EggShell
Soluble
Concentrate
(reg.no. 875-183)
(reg no 875-97)
(reg no. 66171-10)
Not specified
1 fl, ounce in 9 gallons of
warm water (25ppm),
thoroughly wet
number of applications
not stated.
Potable water rinse only if eggs are broken
immediately
Dairy Farms - Udders/
Milking Equipment
Soluble
Concentrate
(reg no. 1677-89)
(reg no. 1677-58)
(reg no. 4959-48)
(reg no. 4959-23)
(reg no. 1317-87)
(reg no 1317-68)
(reg no. 6836-81)
(reg no. 71654-15)
(reg no. 8405-3)
(reg no. 3862-18)
(reg no. 1072-11)
(reg no. 4959-21)
(reg no. 4959-9)
(reg no. 52-254)
(reg no. 47371-26)
Spray or wash
with paper
towels
25 ppm titratable iodine
solution
Do not re-use solution. Do not dip used
towel back into sanitizing solution. Avoid
contamination of sanitizing solution by
dirt and soil.
29
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Food handling/storage establishments premises and equipment
Hand Sanitizer (food
handling and meat cutting
operations)
Eating Establishments
Premises (floors, walls,
countertops)
Egg Processing Plants/
hatcheries
Soluble
Concentrate
(reg no. 875-97)
(reg no. 4959-16)
(reg no. 71654-15)
(reg no. 66171-10)
Soluble
Concentrate
(reg no. 4959-27)
(reg no. 67517-20)
(reg no. 67517-9)
(ren no. 4959-15)
(ren no. 4959-16)
(reg no. 34052-10)
(reg no. 3862-18)
(reg no. 47371-93)
Soluble
Concentrate
(reg no. 6836-195)
(reg no 875-97)
(reg no. 4959-15)
(reg no. 4959-36)
(reg no. 66171-8)
Immersion
Mop, cloth
Mop, brush,
sponge, cloth
1 oz per 5 gallons of
water
25 ppm.
23-25 ppm titratable
iodine solution
68 ppm tiratable iodine
50 ppm to clean
25 ppm to sanitize after
preclean
thoroughly wet
None stated
None stated
Industrial use only
30
-------
Use Site
Beverage Processing
Equipment
Beverage Plant Premises
& Equipment
(non-food contact)
Brewery Processing
Equipment, (Storage
tanks, bottles, cans)
Formulation
(reg no. 875-183)
Soluble
Concentrate
(reg no. 875-183)
(reg no. 4959-36)
(reg no. 66171-8)
(reg no. 47371-26)
(reg no. 47371 -93)
Soluble
Concentrate
(reg no. 4958-38)
(reg no. 4959-36)
(reg no. 4959-48)
(reg no. 67517-20)
(ren no. 875-188)
(reg no. 4959-18)
Soluble
Concentrate
(reg no. 4959-38)
(reg no. 4959-36)
(reg no. 4959-48)
(re no. 52-254)
Method of
Application
Flood, coarse
Spray, mop or
immersion
Spray
Spray
Automated
cleaning
systems
Application Rate/ No. of
applications
12.5 ppm to 25 ppm
thoroughly wet all
surfaces. Allow surfaces
to drain and air dry
number of applications
not stated.
1 oz. per 13 gallons of
water
1 minute contact time
may be used continuously
25 ppm
25 ppm
1 minute contact time
8- 12 ppm
Use Limitations
Do not reuse circulated sanitizer for
additional sanitizing.
For Industrial use only.
For industrial use only.
31
-------
Use Site
Meat / Poultry Processing
Equipment (Frozen and
Fresh Pack)
Food Processing
Equipment
Formulation
reg no. 66171-8)
(reg no. 47371-93)
(reg no. 47371-26)
Soluble
Concentrate
(reg no. 875-183)
(reg no 1677-89)
(reg no. 1677-58)
(reg no. 6836-1 95)
(reg no. 4959-36)
(reg no. 66171-10)
(reg no. 3862-18)
(reg no. 1317-87)
Soluble
Concentrate
Emulsifiable
Concentrate
(reg no. 875-183)
(reg no. 875-97)
(reg no. 4959-15)
(reg no. 66171-6)
(reg no. 71654-15)
(reg no. 66171-10)
(reg no. 1317-68)
(reg no. 1317-87)
Method of
Application
Flood, coarse
Spray, mop or
immersion
Flood, coarse
Spray, mop or
immersion
Application Rate/ No. of
applications
12.5 ppm to 25 ppm
thoroughly wet all
surfaces. Allow surfaces
to drain and air dry
50 ppm (Initial Clean)
25 ppm (after preclean)
rinse with potable water
12.5 ppm to 25 ppm
thoroughly wet all
surfaces. Allow surfaces
to drain and air dry
5.50 to 6 ppm (2 minute
exposure time)
Use Limitations
Do not reuse circulated sanitizer for
additional sanitizing.
Do not reuse circulated sanitizer for
additional sanitizing.
32
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
(reg no. 3862-18)
(reg no. 5991-7)
(reg no. 61181-2)
(reg no 66171-8)
(reg no. 1317-87)
(reg no. 473 71-93)
Milk, and Ice Cream
Processing Plants
Fruit Processing Plants
Soluble
Concentrate
(reg no. 6836-195)
(reg no. 66171-8)
(reg no. 4959-48)
(reg no. 47371-93)
Spray
25 ppm
None stated
Dairy Processing
Equipment
Soluble
Concentrate
(reg no. 1677-58)
(reg no. 1317-68)
(reg no. 8405-3)
(reg no. 5991-7)
Immersion,
spray
12.5 ppm to sanitize
75 ppm to disinfect.
Prepared solutions may not be reused for
sanitizing but may be reused for other
purposes such as cleaning
Mess gear
Soluble
Concentrate
(reg no 40510-1)
Not specified
One solution: 300 mg/1 of
iodine and iodophor
complexes to treat 25
One solution per 100 mess kits
33
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
gallons of water
Rinse twice in
disinfectant solution
Fruits and Vegetables
Soluble
Concentrate
(reg no, 40150-1)
immersion
380 mg/1 of iodine in 20
gallons of water.
Immersion for 10
minutes
After immersion, rinse with potable water
Food Contact surfaces -
Kitchens & Lunchrooms
(Hard non porous)
Soluble
Concentrate
(reg no. 1677-22)
(reg no. 4959-15)
(reg no. 4959-16)
(reg no. 875-188)
(reg no. 66171-10)
(reg no. 1317-87)
(reg no. 6198-12)
Cloth, mop or
spray
J/2 oz. per l/2 gallons of
75-100 degree water
(25ppm)
Pre-clean. Not recommended for use on
silver and silverplate
Eating, Drinking and Food
Prep Utensils
Soluble
Concentrate
(reg no. 1677-22)
(reg no. 881-10)
(reg no. 6198-12)
(reg no. 875-97)
Immersion
1A oz. to 2 Vi gallons of
water. (12.5 - 25 ppm
titratable iodine)
immerse 1- 2 minutes or
contact time specified by
governing sanitizing code
Remove gross food particles by prescrape,
preflush and when necessary. Presoak.
Rinse with clear water. Air Dry.
34
-------
Use Site
Retort Cooling Water
Formulation
(reg no. 875-188)
(reg no. 7546-13)
(reg no. 4959-27)
(reg no. 4959-16)
(reg no. 881-10)
(reg no. 67517-20)
(reg no. 66171-10)
(reg no. 5991-7)
(reg no. 61181-2)
Soluble
Concentrate
(reg no. 875-97)
(reg no. 4959-36)
(reg no. 71654-15)
(reg no. 34052- 10)
Method of
Application
Metered
Application Rate/ No. of
applications
Renew application before
amber color disappears.
1 oz per 5-10 gallons of
retort water
12-25ppm
Use Limitations
None stated
Commercial, institutional and industrial premises and equipment
Schools, Institutions -
Hard Nonporous surfaces
(walls, floors,
countertops, tables chairs.)
Soluble
Concentrate
(reg no. 875-97)
(ren no. 4959-16)
(reg no. 4959-34)
(reg no. 34052-10)
(reg no. 66171-10)
(reg no. 6836-81)
Cloth, mop,
spray, sponge
1A oz per gallon of water
68ppm
Preclean heavily soiled areas.
35
-------
Use Site
Veterinary Clinics - Hard
Nonporous surfaces
(walls, floors,
countertops, tables chairs.)
Zoos
Kennels & Pet Shops
Bathroom Premises -
toilet Bowls and Urinals
Laboratory Equipment
Garbage Pails, Refuse
Containers
Formulation
Soluble
Concentrate
(reg no. 875-97)
(reg no. 34052-10)
(reg no, 7 1654- 15)
Soluble
Concentrate
(reg no. 66171-6)
Soluble
Concentrate
(reg no. 4959- 15)
(reg no. 61181-1)
(reg no 4959-34)
Soluble
Concentrate
(reg no. 34052-10)
(reg no. 4959-16)
(reg no. 7 1654- 15)
(reg no. 66171-10)
Soluble
Concentrate
(reg no. 52-254)
Soluble
Concentrate
Method of
Application
Cloth, mop,
spray, sponge
Spray
Mop, sponge,
brush,
immersion
Brush
Spray, flush,
sponge,
immersion
Swab, brush,
mop or flood
Application Rate/ No. of
applications
'/i oz per gallon of water
68ppm
5:100 gallons of water
(42 ppm)
3 ounces per 5 gallons of
water
100 ppm
1 oz . to bowl. Allow to
remain for 10 minutes
25 ppm
1 oz per gallon of water
Use Limitations
Preclean heavily soiled areas.
Remove animals and feed from premises
to assure surface coverage.
Remove all litter and manure from floors,
walls and all surfaces to be treated. Empty
all troughs, racks and other feeding and
watering appliances
Pre-flush, rinse metal parts with water
after disinfecting to prevent corrosion.
Not stated
Not stated
36
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
(reg no. 71654-15)
HVAC System
Soluble
Concentrate
(reg no. 59682-5)
Mechanical
sprayer, mops,
sponge, brush
8 oz to 2/1 gallons
Allow 10 minutes contact
time
Not Stated
Residential and public access premises
Hard Surfaces
Ready-to-use
Solution
(reg no. 61181-2)
Spray
None stated
None stated
Medical premises and equipment
Hospital/Medical
Institutions Non-critical
Premises
Impregnated
Material (reg no.
74245-5)
Cartridge
installation in
pick-up tube
in bottle water
system by a
dental
technician
Prior to daily use wash
the inside of the bottle
and rinse thoroughly;
wipe down the outside of
the cartridge, and make
sure intake end is not
obstructed
Change cartridge after 40 liters of water
usage or 60 calendar days after
installation; adhere to CDC/ADA
guidelines for aseptic procedures
including a 2 minute morning flush, a 20-
30 second flush between patients and hand
piece sterilization
piece stenlization
Remove heavy soil or gross filth prior to
disinfection
Hospital Hard non porous
surfaces (critical and non
critical premises)
Soluble
Concentrate
(reg no. 1677-22)
(reg no. 34052-10)
Cloth, mop or
spray
2/3 oz per gallon of
water. (75 ppm titratable
iodine)
68 ppm
wet surface
10 minute contact time
Mix fresh solution when
amber color fades
37
-------
Use Site
Formulation
(reg no. 67517-20)
(reg no. 61 181-1)
(reg no. 61181-2)
(reg no. 71654-15)
(reg no. 66171-10)
(reg no. 6836-81)
Method of
Application
Application Rate/ No. of
applications
noticeably.
l/2 oz per gallon of water
23 ppm
1 50 ppm
Use Limitations
Human drinking water systems
Human Drinking Water
Crystalline
(reg. 50233-1)
Pelleted/ Tableted
(reg no. 40510-3)
(reg no. 79533-1)
Impregnated
Materials
(reg no. 39444-12)
(reg no. 54625-2)
Add solution
to water
Add tablets to
water and
shake
filtration
2000 quarts of drinking
water per bottle
1 application per
container of water.
Two 8 mg tablets per one
quart of water
One application per
canteen
1 tablet per quart of
water/1 filter per 35
gallons or replace filter
every 2 months
Do not reuse bottle.
Wait 30 min. before drinking. Only use
when water is of questionable quality or
known to be substandard. Not to be used
on a continuous basis
Not Stated
Materials preservatives
Paints, stains, coating
systems
Wettable Powder
(reg. no. 72897-2)
Incorporated
during
manufacturing
process
Add at levels between
20% and 30% (wt/wt).
more may be required in
hot, humid areas, where
Not for use in HVAC filters or products
that come into contact with food. Finished
products may not make public health
claims relating to antimicrobial activity
38
-------
Use Site
Synthetic and non-woven
textile materials
(vacuum bags, air filters,
door mats, awnings)
Absorbent Clays
Formulation
Wettable Powder
(reg no. 72897-2)
Soluble
Concentrate (reg
no. 4737 1-1 58)
Method of
Application
Incorporated
during
manufacturing
process
Not stated
Application Rate/ No. of
applications
mildew is particularly
severe.
Add at levels between
12.5%and45%(wt/wt)
of the laminate.
0.2 Ibs of titratable iodine
per 2,000 Ibs. of clay
15-16 Ibs. of 1.28
titratable iodine solution
per 2,000 Ibs of clay
Use Limitations
without first obtaining the necessary
regulatory approvals.
Not for use in HVAC filters or products
that come into contact with food. Finished
products may not make public health
claims relating to antimicrobial activity
without first obtaining the necessary
regulatory approvals.
None stated
Industrial processes and water systems
Cooling Tower Water,
Evaporative Condensers
and fluid coolers
Cooling Water systems
Soluble
Concentrate
(reg no. 82097-1)
Impregnated
Materials
(reg no. 72897-3)
(reg no, 82097-1)
Metered.
Metered
Replace canister once per
year.
1 gal every 4 minutes for
7 hours for 1 00 gallon
tank
2- 4 times a month
Do not use this product with air washers
or direct air washers or direct evaporative
coolers
Do not discharge effluent containing this
active ingredient into lakes, streams,
ponds, estuaries, oceans or other waters
unless this product is specifically
identified and addressed in an NPDES
permit. Do not discharge effluent
containing this product to sewer systems
without previously notifying the sewage
treatment plant authority.
39
-------
Appendix B: Table of Generic Data Requirements and Studies Used to Make the Reregistration Decision
Guide To Appendix B
Appendix B lists the generic (not product specific) data requirements which support the re-registration of iodine. These
requirements apply to iodine and iodophor complexes in all products, including data requirements for which a technical grade
active ingredient is the test substance. The data table is organized in the following formats:
1. Data Requirement (Columns 1 and 2). The data requirements are listed by Guideline Number. The first column lists
the new Part 158 Guideline numbers, and the second column lists the old Part 158 Guideline numbers. Each Guideline Number
has an associated test protocol set forth in the Pesticide Assessment Guidance, which are available on the EPA website.
2. Use Pattern (Column 4). This column indicates the standard Antimicrobial Division use patterns categories for which
the generic (not product specific) data requirements apply. The number designations are used in Appendix B.
(1) Agricultural premises and equipment
(2) Food handling/ storage establishments premises and equipment
(3) Commercial, institutional and industrial premises and equipment
(4) Residential and public access premises
(5) Medical premises and equipment
(6) Human water systems
(7) Materials preservatives
(8) Industrial processes and water systems
(9) Anti fouling coatings
(10) Wood preservatives
(11) Swimming pools
(12) Aquatic areas
3. Bibliographic Citation (Column 5). If the Agency has data in its files to support a specific generic Guideline
requirement, this column will identify each study by a "Master Record Identification (MRID) number. The listed studies are
considered "valid" and acceptable for satisfying the Guideline requirement. Refer to the Bibliography appendix for a complete
citation of each study.
40
-------
DATA REQUIREMENT
New
Guideline
Number
ow
Guideline
Number
Study Title
Use Pattern
CITATION(S)
M RID Number
TECHNICAL GRADE ACTIVE INGREDIENT (TGAD CHEMISTRY
830.1550
830.1600
830.1620
830,1650
830.1670
61-1
6 1-2 A
61-2B
Product Identity and Composition
Starting Materials and Manufacturing Process
Formation of Impurities
2,3,4,5
2,3,4,5
2,3,4,5
43952701; 43955101; 42326701;
41333201; 4361 1801; 43918901;
43911001; 41808501; 43911701;
44059101; 4391 1601; 43919201;
43955101; 43966701; 44007701;
44011201; 43976701; 43979601;
43996601; 43916601; 44007801;
43919101; 43918001
43952701; 43955101; 43412002;
43919001; 4361 1801; 41559101;
41808501; 43911701; 44059101;
43911601; 43919201; 43976701;
43916601; 44007801; 43919101;
43952701; 43966701; 41968701;
43918901
43952701; 43955101; 42326701;
43919001; 4361 1801; 41559101;
41 808501 ; 43952701 ; 4391 1701 ;
44059101; 4391 1601; 43919201;
43911701; 43966701; 44007701;
44011201; 43976701; 43979601;
43996601; 439 16601; 44007801;
43919101; 41968701; 43918001;
41
-------
DATA RgQuij^j^jEj^
New
Guideline
Number
830.1700
830.1750
830.1800
Old
Guideline
Number
62-1
62-2
62-3
Study Title
Preliminary Analysis
Certification of Limits
Analytical Method
Use Pattern
2,3A5
2,3,4,5
2,3A5
CITATIONCS)
MMD Number
42440101; 43918901
43952701; 43955102; 42326702;
43919002; 4361 1801; 41559102;
41808501; 4391 1701; 43966301;
4391 1602; 43919202; 4391 1702;
43955102; 43966702; 44007702;
4401 1202; 43976702; 43979602;
43955102; 43996601; 43916602;
44007801; 43919102; 43966301;
43952701; 43966702; 42749901;
43918002; 42440101; 43918902
43952701; 43955102; 43919002;
4361 1801; 43911002; 41808501;
4391 1 702; 43966301 ; 4391 1602;
43919202; 43966702; 44007702;
43976702; 43996601; 43916602;
44007801; 43911602; 43919102;
43952701; 4391 1701; 43918002;
42440101; 4391 8902
43952701; 43955102; 42326702;
43919002; 4361 1801; 41808501;
4391 1702; 43966301; 4391 1602;
43919202; 43966702; 44007702;
4401 1202; 41647502; 43976702;
42
-------
DATA REQUIREMENT
New
Guideline
Number
830.6302
830.6303
830.6304
Old
Guideline
Number
63-2
63-3
63-4
Study Title
Color
Physical State
Odor
Use Pattern
2,3A5
2,3,4,5
2,3,4,5
CITATION(S)
MR1D Number
43996601; 43916602; 44007801;
43919102; 43952701; 42749901;
43918002; 42440101; 43918902
43952701; 43955103; 42326703;
41333201; 43919003; 4361 1801;
41559103; 4391 1003; 41808501;
44059102; 44007703; 4401 1203;
43976703; 44059102; 41333201;
41968702; 43918004; 42440101;
43918903
42326703; 41333201; 43611801;
41559103; 4391 1003; 41808501;
43911703; 43952701; 44059102;
43911603; 43919203; 43955103;
43966703; 44007703; 4401 1203;
43996601; 43916603; 44007801;
43919103; 43952701; 41333201;
4 1968702; 439 18004
43952701; 43955103; 42326703;
41333201; 43919003; 41559103;
43911003; 41808501; 4391 1703;
44059102; 4391 1603; 43919203;
43955103; 43966703; 44007703;
44011203; 43976703; 43996601;
43
-------
DATA REQUIREMENT
New
Guideline
Number
830.7200
830.7220
830.7300
830.7840
830.7860
Old
Guideline
Number
63-5
63-6
63-7
63-8
Study Title
Melting Point
Boiling Point
Density
Solubility
Use Pattern
2,3A5
2,3,4,5
2,3,4,5
2,3,4,5
CITATION(S)
MR1 1) Number
43916603; 44007801; 43919103;
43952701; 4391 1703; 41333201;
42440101; 43918903
43952701; 43955103; 42326703;
41333201; 43919003; 4361 1801;
41808501; 4391 1703; 44059102;
43911603; 43919203; 43966703;
44007703; 4401 1203; 43996601;
43916603; 44007801; 43919103;
43952701; 43955103; 43966703;
41968702; 43918004; 42440101;
43918903
Not Required
43952701; 43955103; 42326703;
41333201; 43919003; 4361 1801;
41559103; 4391 1003; 41808501;
4391 1703; 44059102; 4391 1603;
43919203; 43966703; 41647503;
43996601; 43916603; 44007801;
43919103; 44059102; 43952701;
41968702; 43918004; 42440101;
43918903
43952701; 43955103; 43412001;
41333201; 43919003; 4361 1801;
44
-------
BATA REQUIREMENT
New
Guideline
Number
830.7950
830,7370
830.7550
830,7560
830.7570
830.7000
830.6313
Old
Guideline
Number
63-9
63-10
63-11
63-12
63-13
Study Title
Vapor Pressure
Dissociation Constant in Water
Partition Coefficient (Octanol/Water)
pH
Stability
Use Pattern
2,3,4,5
2,3,4,5
2,3,4,5
253A5
2,3,4,5
CITATION(S)
M R 1 1) Number
41808501; 4391 1703; 44059102;
43911603; 43919203; 43966703;
44007703; 44011203; 43976703;
43996601; 43916603; 44007801;
43919103; 43952701; 43918004;
43918903
43952701; 43955103; 43412001;
41333201; 43919003; 4361 1801;
4391 1003; 41808501; 4391 1703;
44059102; 43911603; 43919203;
43966703; 44007703; 4401 1203;
43976703; 43955103; 43996601;
43916603; 44007801; 43919103;
44059102; 42440101; 41968702;
43918004; 43918903
Not Required
Not Required
Not Required
43952701; 43955103; 43752101;
43919003; 4361 1801; 4391 1003;
41808501; 4391 1703; 43952701;;
45
-------
DATA REQUIREMENT
New
Guideline
Number
830.6314
830.6315
830.6316
830.6317
830.7100
830.6319
830.6320
830.6321
850.2100
850.1075
850,1010
ow
Guideline
Number
63-14
63-15
63-16
63-17
63-18
63-19
63-20
63-21
71-1A
7 1-2 A
72- 1C
72-2A
Study Title
Oxidizing/Reducing Action
Flammability
Explodability
Storage Stability
Viscosity
Miscibility
Corrosion Characteristics
Dielectric breakdown voltage
Use Pattern
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
ECOLOGICAL EFFECTS
Avian Acute Oral Toxicity Test - Quail
Avian Acute Dietary - Quail
Fish Acute Toxicity - Bluegill sunfish or Rainbow trout
Acute Aquatic Invertebrate Toxicity - Daphnia Magna
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
crrATioN(S)
MRID Number
43919203; 43966703; 44007703;
44011203; 41647503; 43996601;
43916603; 44007801; 43911603;
43919103; 44059102; 43955103;
439 18004; 4391 8903
Not Required
Not Required
Not Required
Not Required
Not Required
Not Required
Not Required
Not Required
43138401
43191701
43044501
42961001
46
-------
DATA REQUIREMENT
N«w
Guideline
Number
Old
Guideline
Number
Study Title Use Pattern
CITATIONCS)
MR1 D Number
TOXICOLOGY
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
870.3100
870.3150
870.3250
870.3465
870.4100
870.4100
81-1
81-2
81-3
81-4
81-5
81-6
82- la
82- Ib
82-3*
82-4*
83-la
83-lb
83-2a
Acute Oral - Rat
Acute Dermal - Rabbit
Acute Inhalation - Rat
Acute Eye Irritation - Rabbit
Acute Skin Irritation - Rabbit
Dermal Sensitization- guinea pig
90-Day Feeding - nonrodent
90-Day Oral Subchronic -rodent
90-Day Dermal Subchronic - rodent
90-Day Subchronic Inhalation
Chronic Toxicity - rat
Chronic Toxicity - non-rodent
Oncogeni city-rat
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
42326704; 40937801; 43736601
42326705; 43736601; 43766401;
40937801; 43736001
42961 002; 40937801
40937801; 42421501; 43736601;
42326706; 42421501; 40937801;
42326707; 42421501; 43736601;
40937801
43736601; 43736603; 43736604;
43766403; 43766402; 40937801
Waived
40937801
Waived
Waived
Waived
Waived
47
-------
DATA REQUIREMENT
New
Guideline
Number
870.3700
870,3700
870.3800
870.5100
870.5300
870.7600
870.7485
Old
Guideline
Number
83-2b
83-3a
83-3b
83-4**
84-2a
84-2b
84-4
85-2
85-1
Study Title Use Pattern
Oncogenicity-mouse
Prenatal Developmental Toxicity - Rat
Prenatal Developmental Toxicity - Rabbit
Reproduction and fertility effects - Rat
Bacterial Reverse Mutation Test
In Vitro Mammalian Chromosome Aberration Test
Other genotoxic effects
Dermal penetration
Metabolism and Pharmocokinetics
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
2,3,4,5
CITATION(S)
MRID Number
Waived
43736610
Waived
Waived
40937801; 42421 501
42421501; 43736613
43551801
Waived
Waived
*For guidelines 82-3 and 82-4, at least one is required to be fulfilled; not both (for both food and non-food uses).
**Only required for food use.
ENVIRONMENTAL FATE
835.2120
161-1
Hydrolysis of Parent and Degradates
2,3,4,5
Not Required
Please Note: Although the Open Literature studies do not satisfy any of the Agency's testing guideline requirements, this information is considered adequate for
characterizing the potential hazard from exposure to IODINE, Therefore, no additional mammalian toxicity data will be required at this time.
48
-------
Appendix D. Bibliography Citations
Review Documents
ATSDR, 2004: lexicological Profile for Iodine. U.S. Department of Health and Human
Services.
lodophors Joint Venture, 2004: lodophor Carrier Molecules - Toxicology Review. Submitted to
the U.S. EPA on September 16, 2004.
National Academy of Science (NAS), 2003: 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.
Individual References
Arlington et al. (1965). Effects of Excess Dietary Iodine Upon Rabbits, Hamsters, and Swine.
Journal of Nutrition 87:394-398.
Astakhova LN, Anspaugh LR, Beebe GW, et al. (1998) Chernobyl-related thyroid cancer in
children in Belarus: A case-control study. Rad Res 150:349-356.
Bostanci I, Sarioglu A, Ergin H, et al. (2001) Neonatal goiter caused by expectorant usage.
Journal of Pediatric Endocrinology & Metabolism 14(8):1161-1162.
Boyages SC, Bloot AM, Maberly GF, et al. (1989) Thyroid autoimmunity in endemic goitre
caused by excessive iodine intake. Clin Endocrinol 31:452-465.
Boyages SC. (2000) The neuromuscular system and brain in hypothyroidism. In: Braverman LE,
Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and clinical text. 8 th ed.
Philadelphia, PA: Lippincott-Raven, 803-810.
Braverman LE, Ingbar SH, Vagenakis AG, et al. (1971) Enhanced susceptibility to iodide
myxedema in patients with Hashimoto's disease. J Clin Endocrinol 32:515-521.
Budavari S., O'Neil, MJ, Smith A., et al., eds. 1998. The Merck index: An encyclopedia of
chemicals, drugs, and biologicals. Whitehouse Station, NJ: Merck and Co., Inc.
Casara D, Rubello D, Saladini G, et al. (1993) Pregnancy after high therapeutic doses of iodine-
131 in differentiated thyroid cancer: Potential risks and recommendations. Eur J Nucl
Med 20:192-194.
50
-------
Cherstvoy ED, Nerovnya AM, Pozharskaya VP, et al. (1996) Thyroid carcinomas in children of
the Republic of Belarus. In: Nagataki S, Yarnashita S, eds. Nagasaki symposium
radiation and human health: Proposal from Nagasaki. Amsterdam, The Netherlands:
Elsevier, 43-48.
Coakley JC, Francis I, Gold H, et al. (1989) Transient primary hypothyroidism in the newborn:
Experience of the Victorian Neonatal Thyroid Screening Programme. Aust Paediatr J
25:25-30.
Conard RA. (1984) Late radiation effects in Marshall Islanders exposed to fallout 28 years ago.
In: Boice KD, Fraument JF, eds. Radiation carcinogenesis: Epidemiology and biological
significance. New York, NY: Raven Press, 57-71.
Drobyshevskaya IM, Astakhova LN, Nalivko AS, et al. (1996) Thyroid cancer in children of
Belarus following the Chernobyl accident. In: Nagataki S, Yarnashita S, eds. Nagasaki
symposium radiation and human health: Proposal from Nagasaki. Amsterdam, the
Netherlands: Elsevier, 49-65.
Galina MP, Avnet NL, Einhorn A. (1962) Iodides during pregnancy: An apparent cause of
neonatal death. N Engl J Med 267:1124-1127.
Gardner DF, Center RM, Utiger RD. (1988) Effects of low dose oral iodide supplementation on
thyroid function in normal men. Clin Endocrinol 28:283-288.
Goh K. (1981) Radioiodine treatment during pregnancy: Chromosomal aberrations and cretinsim
associated with maternal iodine-131 treatment. J Am Med Womens Assoc 36(8):262-265.
Hamilton TE, van Belle G, LoGerfo JP. (1987) Thyroid neoplasia in Marshall Islanders exposed
to nuclear fallout. JAMA 258(5):629-636.
Hassan Al, Aref GH, Kassem AS. (1968) Congenital iodide-induced goitre with hypothyroidism.
Arch Dis Child 43:702-704.
Howard B. Bluestein; Synoptic-Dynamic Meteorology in Midlatitudes: Volume II, Observations
and Theory of Weather Systems; Oxford University Press, Inc. 1993. pp. 608
Howard JE, Vaswani A, Heotis P. (1997) Thyroid disease among the Rongelap and Utirik
population-an update. Health Phys 73(1):190-198.
lancu T, Boyanower Y, Laurian N. (1974) Congenital goiter due to maternal ingestion of iodide.
Am J Dis Child 128:528-530,
ICRP (1981) Report of the task group on reference man. The International Commission on
Radiological Protection. Pergamon Press. IRCP Publ No. 23.
51
i
-------
Kahaly G, Dienes HP, Beyer J, et al. (1997) Randomized, double blind, placebo-controlled trial
of low dose iodide in endemic goiter. J Clin Endocrinol Metab 82(12):4049-4053.
Kahaly GJ, Dienes HP, Beyer J, et al. (1998) Iodide induced thyroid autoimmunity in patients
with endemic goitre: A randomised, double-blind, placebo-controlled trial. Eur J
Endocrinol 139:290-297.
Konno N, Taguchi H, Miura K, et al. (1993) Serum thyrotropin concentration in apparently
healthy adults, in relation to urinary iodide concentration. Clin Chem 39(1): 174-175.
Konno N, Makita H, Yuri K, et al. (1994) Association between dietary iodine intake and
prevalence of subclinical hypothyroidism in the coastal regions of Japan. J Clin
Endocrinol Metab 78(2):393-397.
Laurberg P, Pedersen KM, Hreidarsson A, et al. (1998) Iodine intake and the pattern of thyroid
disorders: A comparative epidemiological study of thyroid abnormalities in the elderly in
Iceland and in Jutland, Denmark. J Clin Endocrinol Metab 83(3):765-769.
Laverock, M.J., M. Stephenson, and C.R. Macdonald (1995) Toxicity of Iodine, Iodide, and
lodate to Daphnia magna and Rainbow Trout (Oncorhynchus mykiss).
Arch.Environ.Contam.Toxicol. 29(3):344-3SO,
Lee, J.Y. and Satow, Y. (year not reported) Developmental Toxicity of Potassium Iodide in
Rats. Department of Geneticopathology Research Institute for Nuclear Medicine in
Biology, Hiroshima University, Hiroshima; found in the Japanese Teratology Abstracts.
LeMar HJ, Georgotis WJ, McDermott MT. (1995) Thyroid adaptation to chronic tetraglycine
hydroperiodide water purification tablet use. J Clin Endocrinol Metab 80:220-223.
Li W, Qu C, Jia G, et al. (1987) Endemic goitre in Central China caused by excessive iodine
intake. Lancet, August 1:257-258.
Lide DR, ed. 2000. CRC Handbook of Chemistry and Physics. 81 st ed. Boca Raton, FL: CRC
Press
Longcope C. (2000a) The male and female reproductive systems in hypothyroidism. hi:
Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and
clinical text. 8 th Philadelphia, PA: Lippincott-Raven, 824-827.
Longcope C. (2000b) The male and female reproductive systems in thyrotoxicosis. In:
Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid: A fundamental and
clinical text. 8 th Philadelphia, PA: Lippincott-Raven, 653-658.
Macek, K.J. and S.F. Krzeminski. 1975. Susceptibility of Bluegill sunfish (Lepomis
macrochirus) to Nonionic Surfactants. Bui. Env. Contam. Toxicol. 13(3):377-384.
52
-------
Marking, L.L., J.J. Rach, and T.M. Schreier (1994) Evaluation of Antifungal Agents for Fish
Culture. Prog.Fish Cult. 56(4):225-231.
Martin MM, Rento RD. (1962) Iodide goiter with hypothyroidism in 2 newborn infants. J Pediatr
61:94-99.
Namba H, Yamashita S, Kimura H, et al. (1993) Evidence of thyroid volume increase in normal
subjects receiving excess iodide. J Clin Endocrinol Metab 76(3):605-608.
Pacini F, Vorontsova T, Demidchik EP, et al. (1997) Post-Chernobyl thyroid carcinoma in
Belarus children and adolescents: Comparison with naturally occurring thyroid carcinoma
in Italy and France. J Clin Endocrinol Metab 82(11):3563-3569.
Paul T, Meyers B, Witorsch RJ, et al. (1988) The effect of small increases in dietary iodine on
thyroid function in euthyroid subjects. Metabolism 37(2): 121-124.
Penfold JL, Pearson CC, Savage JP, et al. (1978) Iodide induced goitre and hypothyroidism in
infancy and childhood. Aust Paediatr J 14:69-73.
Pennington JT. (1990) A review of iodine toxicity reports. J Am Diet Assoc 90:1571-1581,
Reinhardt W, Luster M, Rudorff KH, et al. (1998) Effect of small doses of iodine on thyroid
function in patients with Hashimoto's thyroiditis residing in an area of mild iodine
deficiency. Eur J Endocrinol 139:23-38.
Robison LM, Sylvester PW, Birkenfeld P, et al. (1998) Comparison of the effects of iodine and
iodide on thyroid function in humans. J Toxicol Environ Health 55:93-106.
Szabolcs I, Podoba J, Feldkamp J, et al. (1997) Comparative screening for thyroid disorders in
old age in areas of iodine deficiency, long-term iodine prophylaxis and abundant iodine
intake. Clin Endocrinol 47:87-92.
Tajiri J, Higashi K, Morita M, et al. (1986) Studies of hypothyroidism in patients with high
Iodine intake. J Clin Endocrinol Metab 63:412-417.
Takahashi T, Sehoemaker MJ, Trott KR, et al. (2003) The relationship of thyroid cancer with
radiation exposure from nuclear weapon testing in the Marshall islands. J Epidemiol
13(2):99-107.
Tronko ND, Bogdanova TI, Epstein EV, et al. (1996) Thyroid cancer in children and adolescents
in Ukraine (analysis of the situation in 1994). In: Nagataki S, Yamashita S, eds. Nagasaki
symposium radiation and human health: Proposal from Nagasaki. Amsterdam, The
Netherlands: Elsevier, 3-13.
Vicens-Calvet E, Potau N, Carreras E, et al. (19fS) Diagnosis and treatment in utero of goiter
-------
with hypothyroidism caused by iodide overload. J Pediatr 133:147-148.
Yarzhombek, A.A., A.E. Mikulin, and A.N. Zhdanova (1991) Toxicity of Some Substances to
Fish in Relation to Form of Exposure. (Toksichnost Vestichestv diya ryb v Zavisimosti ot
Sposoba Vozdejstviya). J.Ichthyol 31(7):99-106; Vopr.Ikhtiol.31(3):496-502 (RUS).
Websites
http ://wwwBatsdr. cdc. gov/toxprofiles/tp 15 8 .html
http ;//www. epa. goy/ecotox/
http://toxnet.nlm.nih.goy/
http://www.incheiB.org/documeiits/pims/pharm/iodine.htni)
http://www.chemfinder.com
MRIDs
MRID 134104. Fink, R.; Beavers, J.; Grimes, J.; et al. (1978) Eight-day Dietary LCSO ?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 Internationl, Ltd. and Washington
College, submitted by GAP Corp., Chemical Div., New York, NY; CDL:237871-C)
MRID 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 GAP Corp., Chemical Div., New York, NY; CDL: 237871-A)
MRID 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 GAP Corp., Chemical Div., New York, NY; CDL: 237871-B)
MRID 42328301. Pedersen, C.A. 1991. Tetraglycine Hydroperiodide: 21-day Acute Oral LD50
Studt in Bobwhite Quail. Unpublished data. Conducted by Bio-Life Associates for the U.S.
Army Natick Research Development and Engineering Center.
MRID 42329101. Pedersen, C.A. 1991. Tetraglycine Hydroperiodide: 8-day Acute Dietary
LC50 Study in Bobwhite Quail. Conducted by Bio-Life Associates for the U.S. Army Natick
Research Development and Engineering Center.
MRID 42961001. Zelinka, E.A., C.M. Holmes, K.H. Martin, and J.P. Swigert. 1993. A 48-hour
Flow-through Acute Toxicity Test with the Cladoceran (Daphnia magna). Unpublished data.
Conducted by Wildlife International for the Baltimore Aircoil Company.
54
-------
SM' md J'a Beavers' 1994' IOBIO: A" Acute Oral Toxicity
Conducted by W,,dlife Rational for
- 1994' IOBIO: A Di
Study
55
-------
Appendix E. Generic Data Call-In
The Agency does not intend to issue a Generic Data Call-in at this time.
56
-------
Appendix F. Product Specific Data Call-in
The Agency intends to issue a Product Specific Data Call-in at a later date.
57
-------
Appendix G. Batching of End-Use Products
EPA's Batching of Iodine, ^/Products for Meeting Acute Toxicity Data Requirements for
Reregistration
In an effort to reduce the time, resources and number of animals needed to fulfill the acute
toxicity data requirements for reregistration of products containing any of the active ingredients in
the Reregistration Case Iodine, Kl, the Agency has batched products which can be considered
similar for purposes of acute toxicity. Factors considered in the sorting process include each
product's active and inert ingredients (identity, percent composition and biological activity), type
of formulation (e.g., emulsifiable concentrate, aerosol, wettable powder, granular), and labeling
(e.g., signal word, use elassification, precautionary labeling). Note that the Agency is not
describing batched products as "substantially similar," since they may not have similar use
patterns.
Using available information, batching has been accomplished by the process described in
the preceding paragraph. Notwithstanding the batching process, the Agency reserves the right to
require, at any time, acute toxicity data for an individual product should the need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or cite
a single battery of six acute toxicological studies to represent all the products within that batch. It
is the registrants' option to participate in the process with all other registrants, only some of the
other registrants, or only their own products within a batch, or to generate all the required acute
toxicological studies for each of their own products. If a registrant chooses to generate the data for
a batch, he/she must use one of the products within the batch as the test material. If a registrant
chooses to rely upon previously submitted acute toxicity data, he/she may do so provided that the
data base is complete and valid by today's standards (see partial list of acceptance criteria
attached), the formulation tested is considered by EPA to be similar for acute toxicity, and the
formulation has not been significantly altered since submission and acceptance of the acute
toxicity data. The Agency must approve any new or canceled formulations (that were presented to
the Agency after the completion of the RED) before data derived from them can be used to cover
other products in a batch. Regardless of whether new data is generated or existing data is
referenced, registrants must clearly identify the test material by EPA Registration Number. If
more than one confidential statement of formula (CSF) exists for a product, the registrant must
indicate the formulation actually tested by identifying the corresponding CSF.
In deciding how to meet the product specific data requirements, registrants must follow the
directions given in the Data Call-In (DCI) Notice and its attachments appended to the RED. The
DCI Notice contains two response forms which are to be completed and submitted to the Agency
within 90 days of receipt. The first form, "Data Call-In Response," asks whether the registrant will
meet the data requirements for each product. The second form, "Requirements Status and
Registrant's Response," lists the product specific data required for each product, including the
standard six acute toxicity tests. A registrant who wishes to participate in a batch must decide
58
-------
whether he/she will provide the data or depend on someone else to do so. If a registrant supplies
the data to support a batch of products, he/she must select one of the following options:
Developing Data (Option 1), Submitting an Existing Study (Option 4), Upgrading an Existing
Study (Option 5) or Citing an Existing Study (Option 6), If a registrant depends on another's data,
he/she must choose among: Cost Sharing (Option 2), Offers to Cost Share (Option 3) or Citing an
Existing Study (Option 6). If a registrant does not want to participate in a batch, the choices are
Options 1, 4, 5 or 6, However, a registrant should know that choosing not to participate in a batch
does not preclude other registrants in the batch from citing his/her studies and offering to cost
share (Option 3) those studies.
If a registrant would like to have the batching status of a product reconsidered, he/she
needs to submit detailed information on the product, including a detailed rationale for the inclusion
of the product into a batch. A Material Safety Data Sheet (MSDS) for each "inert" ingredient
should be included where possible. However, registrants and manufacturers should realize that the
more unusual their formulation is, the less likely it is to be able to batch that product.
67 registered products were found which contain any of the active ingredients in the Iodine,
Kl Reregistration Case. Each of the 67 products contains iodine, potassium iodide, or an iodophor
as an active ingredient. These products have been placed into nine primary batches, three
sub-batches, and a "No Batch" category, in accordance with the active and inert ingredients and
type of formulation. Any product in a batch may cite new or previously submitted acute toxicity
data (if it meets current Agency standards) from any other product in the same batch, except as
specified below:
• In Batch 2, each product must cite its own eye irritation data (or, if product is entirely a
repackaging of another Batch 2 product, the source product's eye irritation data may be
cited).
• In Batch 3A, each product must cite its own eye irritation data (Batch 3A products
otherwise are free to cite data from other Batch 3A or 3B products).
• In Batch 3B:
-Each Batch 3B product must cite its own eye irritation data.
-Batch 3B products may not cite skin irritation data from Batch 3A products.
-Batch 3B products may not cite Reg. No. 66171-9 skin irritation data - and 66171-9
may not cite theirs - if the study result is in Toxicity Category IV.
-Batch 3B products otherwise are free to cite data from other Batch 3B or 3A products.
» In Batch 4A, each product must cite its own eye irritation and skin irritation data.
Batch 4A products may not cite data from Batch 4B products.
• In Batch 4B, each product must cite its own eye irritation and skin irritation data
(Batch 4B products otherwise are free to cite data from other Batch 4B or 4A products).
59
-------
• In Batch 5 A, products may not cite data from Batch 5B products.
» In Batch 5B, however, products are free to cite data from Batch 5A products.
• In Batch 6, each product must cite its own eye irritation and skin irritation data, except as
specified in the note underneath the Batch 6 table below.
* In Batch 9, EPA Reg. No. 61181-1 and 61181-2 must each cite its own eye irritation data.
In the No Batch category, each product must cite its own data. I.e., registrants of these
products may only cite data obtained from the specific product itself to support the acute toxicity
data requirements for that product.
Note: If the pH of undiluted product is less than 2, a request for waiver of eye and/or skin
irritation data will be granted if the product label bears the applicable human-hazard wording for
potential irritation/corrosion effects. This wording includes, but is not limited to, the signal word
DANGER and, for eye effects, the word Corrosive.
In these tables, as in the body of the RED document, the term "complex" is used in
reference to an iodophor rather than a true chemical complex.
60
-------
IBatdii . -- .- ',:
Each Batch 1 product may cite
(its own data or) data from any
other Batch 1 product.
'iBtAkeg.!^ '
50233-1
73158-1
82097-1
r ,*:'..;' , |0ttae$0wee
Iodine, elemental
Iodine, elemental
Iodine, elemental
Batch2
Each Batch 2 product must cite
its own eye irritation data. (Or,
if product is entirely a
repackaging of another Batch 2
product, the source product's
eye irritation data may be cited.)
Batch 2 products otherwise are
free to cite data from other
Batch 2 products.
xriPAj%;>lp._
35917-2
39444-12
59454-2
72897-1
72897-2
72897-3
74245-5
74473-1
74473-2
^ xaV ' - Jpdine Sowce ,
Iodine bound to solid polymeric material
Iodine bound to solid polymeric material
Iodine bound to solid polymeric material
Iodine bound to solid polymeric material
Iodine bound to solid polymeric material
Iodine bound to solid polymeric material
Iodine bound to solid polymeric material
Iodine bound to solid polymeric material
Iodine bound to solid polymeric material
Batch 3A: '
Each Batch 3 A product must
cite its own eye irritation data.
Batch 3 A products otherwise
are free to cite data from other
Batch 3 A or 3B products.
• HPA.fteg, No. '
1072-19
9768-47
46183-13
foctinf Source
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
61
-------
: _;• BatehJB;. ", *'.!
Each Batch 3B product must
cite its own eye irritation data.
Batch 3B products may not cite
skin irritation data from Batch
3 A products.
Batch 3B products may not cite
Reg, No. 66171-9 skin irritation
data - and 66171-9 may not cite
theirs - if the study result is in
Toxicity Category IV.
Batch 3B products otherwise are
free to cite data from other
Batch 3B or 3A products.
•,ipA*4!fe.
4959-13
9152-23
66171-9
66171-11
, J ' v Mbe Source
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Batch 4A '-,' .' -.
Each Batch 4A product must
cite its own eye irritation and
skin irritation data.
Batch 4A products otherwise
are free to cite data from other
Batch 4A products.
However, Batch 4A products
may not cite data from Batch 4B
products.
' EPAReg.No. '
1317-87
1677-89
4959-36
4959-48
6836-195
66171-8
Iodine Source
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
62
-------
,Batefam,\r* X'*j
Each Batch 4B product must
cite its own eye irritation and
skin irritation data.
Batch 4B products otherwise are
free to cite data from other
Batch 4B or 4A products.
llBtyUt*. *fo.^
875-97
4959-15
4959-16
4959-23
6836-81
8405-3
34052-10
66171-10
71654-15
V:«sv>\ ' ' "Iodine Source -
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
' ;Baitgbt?A- .=•?;.; , ;
Batch 5A products may cite data
from other Batch 5 A products
but not from Batch 5B products.
,'lfA Reg,!!©.;'.
3862-18
4959-21
7546-13
67517-9
67517-20
67517-30
' ,s " • - >' •• Jddlne-Soarce
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
BstefrSB- ^ 1 ._
Batch 5B products may cite data
from other Batch 5B or 5A
products.
;&4MM;;
47371-26
47371-93
jjlf '*" ^"^ ' ' r\ Io^lQ0 Sostee
Surfactant-iodine complex
Surfactant-iodine complex
63
-------
K; r 't *»; ^BstcJt6 '_."v .
Each Batch 6 product must cite
its own eye irritation and skin
irritation data, except as
specified below.*
Batch 6 products otherwise are
free to cite data from other
Batch 6 products.
BPAkeg.,H»;I
875-188
881-10
4959-18
4959-27
6198-12
47371-158
4'~i ;;;, • . . _ - "Iodine Soiiree
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
*Reg. Nos. 4959-18 and 4959-27 may cite each other's skin irritation data if the study result is not
in Toxicity Category IV. Reg. Nos. 881-10 and 6198-12 also may cite each other's skin irritation
data if the study result is not in Toxicity Category W,
;;„> „ ; ~$atefe?.. , Vl./.'. "
Each Batch 7 product may cite
(its own data or) data from any
other Batch 7 product.
' BPAfbe&'Nd,1^
4959-34
59682-5
* •' 4 , , - 'Iodine Soiirce
Surfactant-iodine complex
Surfactant-iodine complex
-. ' '••: • ! Batch;? . ' •-.'.'}
Each Batch 8 product may cite
(its own data or) data from any
other Batch 8 product.
; EJAHeg, No,: -
40510-3
54625-2*
79533-1
'. ':• .- .,' , '•• '"' '"": .."; Iodi«» Scwsrpe". • . •
Tetraglycine hydroperiodide
Tetraglycine hydroperiodide
Tetraglycine hydroperiodide
*Reg. No. 54625-2 is a two-part product. Its placement into Batch 8 affects only the part - the
sub-package - that contains the tetraglycine hydroperiodide. Acute toxicity data is required for
each of the two parts.
64
-------
Batcli 9
Reg. No. 61181-1 and 61 181-2
must each cite its own eye
irritation data.
Batch 9 products otherwise are
free to cite data from other
Batch 9 products.
.'EPA Reg. >fe.
1072-11
1677-22
1677-58
61181-1
61181-2
' - ~ '• '; ',• . . "' Iodine Sowoe ' • .'.
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
a ^ t 5?"*f* A. v \ * ^
,,/,,/"Nom^ .^.-. , ,;
Each No Batch product must
cite its own data.
, ^X^eg.,Nt-,«
52-254
875-183
4959-9
4959-14
4959-38
6836-184
40510-1
47371-30
66171-6
, ^ • * .^Qdmg SoiBtee,,, •• ,^
Surfactant-iodine complex
Iodine and iodine monochloride
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Surfactant-iodine complex
Potassium iodide
Surfactant-iodine complex
Surfactant-iodine complex
65
-------
Appendix H. List of All Registrants Sent the Data Call-In
A list of registrants sent the data call-in will be posted at a later date.
66
-------
Appendix I. List of Available Forms
Pesticide Registration Forms are available at the following EPA internet site:
http://www.epa.gov/opprd001/foriiis/
Pesticide Registration Forms (These forms are in PDF format and require the Acrobat reader)
Instructions
1. Print out and complete the forms. (Note: Form numbers that are bolded can be filled
out on your computer then printed.)
2. The completed form(s) should be submitted in hardcopy in accord with the existing
policy.
3. Mail the forms, along with any additional documents necessary to comply with EPA
regulations covering your request, to the address below for the Document Processing
Desk.
DO NOT fax or e-mail any form containing 'Confidential Business Information' or 'Sensitive
Information.1
If you have any problems accessing these forms, please contact Nicole Williams at (703) 308-
5551 or by e-mail at williams.nicole@epa.gov.
The following Agency Pesticide Registration Forms are currently available via the internet at the
following locations:
8570-1
8570-4
8570-5
8570-17
8570-25
Application for Pesticide
Registration/ Amendment
Confidential Statement of Formula
Notice of Supplemental Registration of
Distribution of a Registered Pesticide
Product
Application for an Experimental Use
Permit
Application for/Notification of State
Registration of a Pesticide To Meet a
Special Local Need
http://www.epa.gov/opprd001/for
ms/8570-l.pdf
http://www.epa.gov/opprd001/for
ms/8570-4.pdf
http://www.epa.eov/opprd001/for
ms/8570-5.pdf
http://www.epa.gov/opprdOO I/for
ms/8570- 17.pdf
http://www.epa.aov/opprd001/for
ms/8570-25.pdf
67
-------
8570-27
8570-28
8570-30
8570-32
8570-34
8570-35
8570-36
8570-37
Formulator's Exemption Statement
Certification of Compliance with Data
Gap Procedures
Pesticide Registration Maintenance Fee
Filing
Certification of Attempt to Enter into an
Agreement with other Registrants for
Development of Data
Certification with Respect to Citations of
Data (PR Notice 98-5)
Data Matrix (PR Notice 98-5)
Summary of the Physical/Chemical
Properties (PR Notice 98-1)
Self-Certification Statement for the
Physical/Chemical Properties (PR Notice
98-1)
http ://ww w, epa. go v/opprdOO 1 /for
ms/8570-27.pdf
http://www.epa.gov/opprdOO 1 /for
ms/8570-28.pdf
http://www.epa.gov/opprd001/for
ms/8570-30.pdf
http://www.epa.gov/opprd001/fbr
ms/8570-32.pdf
http://www.epa.gOV/opppmsdl/P
R Notices/pr98-5.odf
http://www.epa.gov/opppmsd 1 /P
R Notices/pr98-5.pdf
http://www.epa.gOv/opppmsdl/P
R Notices/pr98-l.pdf
http://www.epa.gov/opppmsd 1 /P
R Notices/pr98-l.pdf
Pesticide Registration Kit
www. epa. go v/pesticides/registrationkit/
Dear Registrant:
For your convenience, we have assembled an online registration kit which contains the following
pertinent forms and information needed to register a pesticide product with the U.S.
Environmental Protection Agency's Office of Pesticide Programs (OPP):
1. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal
Food, Drug and Cosmetic Act (FFDCA) as Amended by the Food Quality Protection Act
(FQPA)ofl996.
2. Pesticide Registration (PR) Notices
a. 83-3 Label Improvement Program—Storage and Disposal Statements
b. 84-1 Clarification of Label Improvement Program
c. 86-5 Standard Format for Data Submitted under FIFRA
d. 87-1 Label Improvement Program for Pesticides Applied through Irrigation
68
-------
Systems (Chemigation)
e. 87-6 Inert Ingredients in Pesticide Products Policy Statement
f. 90-1 Inert Ingredients in Pesticide Products; Revised Policy Statement
g. 95-2 Notifications, Non-notifications, and Minor Formulation Amendments
h. 98-1 Self Certification of Product Chemistry Data with Attachments (This
document is in PDF format and requires the Acrobat reader.)
Other PR Notices can be found at http://www.epa.gov/opppmsdl/PR Notices
3. Pesticide Product Registration Application Forms (These forms are in PDF format and
will require the Acrobat reader).
a. EPA Form No. 8570-1, Application for Pesticide Registration/Amendment
b. EPA Form No. 8570-4, Confidential Statement of Formula
c. EPA Form No. 8570-27, Formulator's Exemption Statement
d, EPA Form No. 8570-34, Certification with Respect to Citations of Data
e. EPA Form No. 8570-35, Data Matrix
4. General Pesticide Information (Some of these forms are in PDF format and will require
the Acrobat reader).
a. Registration Division Personnel Contact List
b. Biopesticides and Pollution Prevention Division (BPPD) Contacts
c. Antimicrobials Division Organizational Structure/Contact List
d. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data Requirements
(PDF format)
e. 40 CFR Part 156, Labeling Requirements for Pesticides and Devices (PDF
format)
f. 40 CFR Part 158, Data Requirements for Registration (PDF format)
g. 50 F.R. 48833, Disclosure of Reviews of Pesticide Data (November 27, 1985)
Before submitting your application for registration, you may wish to consult some additional
sources of information. These include:
1. The Office of Pesticide Programs' website.
2. The booklet "General Information on Applying for Registration of Pesticides in the
United States", PB92-221811, available through the National Technical Information
Service (NTIS) at the following address:
National Technical Information Service (NTIS)
5285 Port Royal Road
Springfield, VA 22161
The telephone number for NTIS is (703) 605-6000.
69
-------
3, The National Pesticide Information Retrieval System (NPIRS) of Purdue University's
Center for Environmental and Regulatory Information Systems. This service does charge
a fee for subscriptions and custom searches. You can contact NPIRS by telephone at
(765) 494-6614 or through their website.
4. The National Pesticide Telecommunications Network (NPTN) can provide information
on active ingredients, uses, toxicology, and chemistry of pesticides. You can contact
NPTN by telephone at (800) 858-7378 or through their website: http://npic.orst.edu/
The Agency will return a notice of receipt of an application for registration or amended
registration, experimental use permit, or amendment to a petition if the applicant or petitioner
encloses with his submission a stamped, self-addressed postcard. The postcard must contain the
following entries to be completed by OPP:
1. Date of receipt;
2. EPA identifying number; and
3. Product Manager assignment.
Other identifying information may be included by the applicant to link the acknowledgment of
receipt to the specific application submitted. EPA will stamp the date of receipt and provide the
EPA identifying file symbol or petition number for the new submission. The identifying number
should be used whenever you contact the Agency concerning an application for registration,
experimental use permit, or tolerance petition.
To assist us in ensuring that all data you have submitted for the chemical are properly coded and
assigned to your company, please include a list of all synonyms, common and trade names,
company experimental codes, and other names which identify the chemical (including "blind"
codes used when a sample was submitted for testing by commercial or academic facilities).
Please provide a chemical abstract system (CAS) number if one has been assigned.
70
------- |