United States Prevention, Pesticides EPA739-R-07-010
Environmental Protection and Toxic Substances December 2007
Agency (7510P)
Reregistration Eligibility Decision
for Sodium Fluoride
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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 (hereafter referred to as
EPA or the Agency) has completed its review of the available data and public comments
received related to the draft risk assessments for the antimicrobial sodium fluoride. The enclosed
Reregi strati on Eligibility Decision (RED) document was approved on December 20, 2007.
Public comments and additional data received were considered in this decision.
Based on its review, EPA is now publishing its Reregi strati on Eligibility Decision (RED)
and risk management decision for sodium fluoride and the associated human health and
environmental risks. A Notice of Availability will be published in the Federal Register
announcing the publication of the RED.
The RED and supporting risk assessments for sodium fluoride are available to the public
in EPA's Pesticide Docket EPA-HQ-2007-0833 at: http://www.regulations.gov.
The sodium fluoride RED was developed through EPA's public participation process,
published in the Federal Register on October 10, 2007, which provides opportunities for public
involvement in the Agency's pesticide tolerance reassessment and reregi strati on 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 full, 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 sodium fluoride risk assessment and the attached RED document
concern only this particular pesticide. This RED presents the Agency's conclusions on the
dietary, residential, occupational and ecological risks posed by exposure to sodium fluoride
alone. This document also contains both generic and 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. Additionally, 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.
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As part of the RED, the Agency has determined that sodium fluoride will be eligible for
reregistration provided that all the conditions identified in this document are satisfied, including
implementation of the risk mitigation measures outlined in Section IV of the document. Sections
IV and V of this RED document describe labeling amendments for end-use products and data
requirements necessary to implement these mitigation measures. Instructions for registrants on
submitting the revised labeling can be found in the set of instructions for product-specific data
that accompanies this document.
Should a registrant fail to implement any of the risk mitigation measures outlined in this
document, the Agency will continue to have concerns about the risks posed by sodium fluoride.
Where the Agency has identified any unreasonable adverse effect to human health and the
environment, the Agency may at any time initiate appropriate regulatory action to address this
concern. At that time, any affected person(s) may challenge the Agency's action.
If you have questions on this document or the label changes necessary for reregistration,
please contact the Chemical Review Manager, SanYvette Williams-Foy, (703) 305-7702. For
questions about product reregistration and/or the Product DCI that will follow this document,
please contact Adam Heyward at (703) 308-6422 or heyward.adam@epa.gov.
Sincerely,
Frank Sanders, Director
Antimicrobials Division (751OC)
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REREGISTRATION ELIGIBILITY
DECISION
for
Sodium fluoride
ListC
Case 3132
Approved by:
Frank T. Sanders
Director, Antimicrobials Division
of-
Date " *~
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Table of Contents
Sodium Fluoride Reregistration Team i
Glossary of Terms and Abbreviations ii
Abstract iv
I. Introduction 1
II. Chemical Overview 3
A. Regulatory History 3
B. Chemical Identification 3
C. Use Profile 4
III. Summary of Sodium Fluoride Risk Assessments 5
A. Human Health Risk Assessment 5
1. Toxicity of Sodium Fluoride 5
2. FQPA Safety Factor 8
3. Dietary Exposure Assumptions & Dietary Risk Assessment 9
a. Dietary Risk from Drinking Water 9
4. Residential Risk Assessment 9
5. Aggregate Risk Assessment 9
6. Occupational Risk 9
a. Occupational Toxicity 10
b. Occupational Handler Exposure 11
i. Sodium Fluoride Application Methods 13
ii. Application Rates and Amounts Handled 14
c. Occupational Handler Risk Summary 15
d. Occupational Post-application Risk Summary 18
7. Human Incident Data 18
B. Environmental Risk Assessment 18
1. Environmental Fate and Transport 19
2. Ecological Risk 19
a. Environmental Toxicity 19
b. Ecological Exposure and Risk 21
c. Risks to Listed Species 22
IV. Risk Management, Reregistration, and Tolerance Reassessment Decision... 23
A. Determination of Reregistration Eligibility 23
B. Public Comments and Responses 23
C. Regulatory Position 23
1. Food Quality Protection Act Findings 24
a. "Risk Cup" Determination 24
b. Determination of Safety to U.S. Population 24
c. Determination of Safety to Infants and Children 24
d. Endocrine Disrupter Effects 25
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e. Cumulative Risks 25
D. Regulatory Rationale 25
1. Human Health Risk Management 26
a. Dietary (Food) Risk Mitigation 26
b. Drinking Water Risk Mitigation 26
c. Residential Risk Mitigation 26
d. Occupational Risk Mitigation 26
i. Handler Risk Mitigation 26
ii. Post-Application Risk Mitigation 27
2. Environmental Risk Management 27
3. Other Labeling Requirements 27
4. Listed Species Considerations 28
a. The Endangered Species Act 28
b. General Risk Mitigation 28
V. What Registrants Need to Do 30
A. Manufacturing Use-Products 32
1. Additional Generic Data Requirements 32
2. Labeling for Technical and Manufacturing-Use Products 32
B. End-Use Products 32
1. Additional Product Specific Data Requirements 32
2. Labeling for End-Use Products 32
a. Label Changes Summary Table 34
VI. Appendices 35
A. Table of Use Patterns for Sodium fluoride 36
B. Table of Generic Data Requirements and Studies Use to Make the
Reregistration Decision 40
C. Technical Support Documents 44
D. Bibliography Citations 46
E. Generic Data Call-In 55
F. Product Specific Data Call-In 56
G. Batching of End-Use Products 57
H. List of All Registrants Sent the Data Call-In 58
I. List of Available Forms 59
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Sodium Fluoride Reregistration Team
Science Team
Jonathan Chen, Ph.D., Senior Toxicologist
Timothy Leighton, Environmental Scientist
Timothy F. McMahon, Ph.D., Senior Toxicologist
Richard C. Petrie, Agronomist
A. Najm Shamim, PhD., Chemist
Risk Management
SanYvette Williams-Foy
Diane Isbell
Registration Support
Adam Heyward
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Glossary of Terms and Abbreviations
a.i. Active Ingredient
aPAD Acute Population Adjusted Dose
APHIS Animal and Plant Health Inspection Service
ARTF Agricultural Re-entry Task Force
BCF Bioconcentration Factor
CDC Centers for Disease Control
CDPR California Department of Pesticide Regulation
CFR Code of Federal Regulations
ChEI Cholinesterase Inhibition
CMBS Carbamate Market Basket Survey
cPAD Chronic Population Adjusted Dose
CSFII USDA Continuing Surveys for Food Intake by Individuals
CWS Community Water System
DCI Data Call-in
DEEM Dietary Exposure Evaluation Model
DL Double layer clothing {i.e., coveralls over SL}
DWLOC Drinking Water Level of Comparison
EC Emulsifiable Concentrate Formulation
EDSP Endocrine Disrupter Screening Program
EDSTAC Endocrine Disrupter Screening and Testing Advisory Committee
EEC Estimated Environmental Concentration. The estimated pesticide concentration in an environment,
such as a terrestrial ecosystem.
EP End-Use Product
EPA U.S. Environmental Protection Agency
EXAMS Tier II Surface Water Computer Model
FDA Food and Drug Administration
FFDCA Federal Food, Drug, and Cosmetic Act
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FOB Functional Observation Battery
FQPA Food Quality Protection Act
FR Federal Register
GL With gloves
GPS Global Positioning System
HIARC Hazard Identification Assessment Review Committee
IDFS Incident Data System
IGR Insect Growth Regulator
IPM Integrated Pest Management
RED Reregistration Eligibility Decision
LADD Lifetime Average Daily Dose
LC50 Median Lethal Concentration. Statistically derived concentration of a substance expected to cause
death in 50% of test animals, usually expressed as the weight of substance per weight or volume of
water, air or feed, e.g., mg/1, mg/kg or ppm.
LCO Lawn Care Operator
LD50 Median Lethal Dose. Statistically derived single dose causing death in 50% of the test animals
when administered by the route indicated (oral, dermal, inhalation), expressed as a weight of
substance per unit weight of animal, e.g., mg/kg.
LOAEC Lowest Observed Adverse Effect Concentration
LOAEL Lowest Observed Adverse Effect Level
LOG Level of Concern
LOEC Lowest Observed Effect Concentration
mg/kg/day Milligram Per Kilogram Per Day
MOE Margin of Exposure
MP Manufacturing-Use Product
MRID Master Record Identification (number). EPA's system of recording and tracking studies submitted.
11
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MRL Maximum Residue Level
N/A Not Applicable
NASS National Agricultural Statistical Service
NAWQA USGS National Water Quality Assessment
NG No Gloves
NMFS National Marine Fisheries Service
NOAEC No Observed Adverse Effect Concentration
NOAEL No Observed Adverse Effect Level
NPIC National Pesticide Information Center
NTP National Toxicology Program
NR No respirator
OP Organophosphorus
OPP EPA Office of Pesticide Programs
ORETF Outdoor Residential Exposure Task Force
PAD Population Adjusted Dose
PCA Percent Crop Area
PDCI Product Specific Data Call-In
POP USDA Pesticide Data Program
PF10 Protections factor 10 respirator
PF5 Protection factor 5 respirator
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
PRZM Pesticide Root Zone Model
RBC Red Blood Cell
RAC Raw Agricultural Commodity
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose
RPA Reasonable and Prudent Alternatives
RPM Reasonable and Prudent Measures
RQ Risk Quotient
RTU (Ready-to-use)
RUP Restricted Use Pesticide
SCI-GROW Tier I Ground Water Computer Model
SF Safety Factor
SL Single layer clothing
SLN Special Local Need (Registrations Under Section 24(c) of FIFRA)
STORET Storage and Retrieval
TEP Typical End-Use Product
TGAI Technical Grade Active Ingredient
TRAC Tolerance Reassessment Advisory Committee
TTRS Transferable Turf Residues
UF Uncertainty Factor
USDA United States Department of Agriculture
USFWS United States Fish and Wildlife Service
USGS United States Geological Survey
WPS Worker Protection Standard
in
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ABSTRACT
The Environmental Protection Agency (EPA or the Agency) has completed the human
health and environmental risk assessments for sodium fluoride and is issuing its risk
management decision. The risk assessments, which are summarized below, are based on the
review of the required target database supporting the use patterns of currently registered products
and additional information received through the public docket. After considering the risks
identified in the revised risk assessments, comments received, and mitigation suggestions from
interested parties, the Agency developed its risk management decision for uses of sodium
fluoride that pose risks of concern. As a result of this review, EPA has determined that sodium
fluoride containing products are eligible for reregi strati on, provided that risk mitigation measures
are adopted and labels are amended accordingly. That decision is discussed fully in this
document.
IV
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I. Introduction
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended
in 1988 to accelerate the reregi strati on 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 Reregi strati on Eligibility Decisions. The
amended Act calls for the development and submission of data to support the
reregi strati on of an active ingredient, as well as a review of all submitted data by the U.S.
Environmental Protection Agency (EPA or the Agency). Reregi strati on 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 or not 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 reregi strati on assessments of chemicals
registered prior to 1984. The Agency has decided that, for those chemicals that have
tolerances and are undergoing reregi strati on, 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 tolerance reassessment based on factors including consideration of cumulative
effects of chemicals with a common mechanism of toxicity. This document presents the
Agency's revised human health and ecological risk assessments; and the Reregistration
Eligibility Decision (RED) for sodium fluoride.
Sodium fluoride is used for commercial use only as a wood preservative for utility
poles and railroad ties. Sodium fluoride products are used as supplemental wood
treatments and are not intended for primary wood preservative or pressure treated wood
preservation.
The Agency has concluded that no special hazard-based safety factor under the
Food Quality Protection Act (FQPA) of 1996 is needed for sodium fluoride based on its
current registered use patterns.
Risks summarized in this document are those that result only from the use of the
active ingredients sodium fluoride. The FFDCA 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 the pesticides for which EPA
has followed a cumulative risk approach based on a common mechanism of toxicity, EPA
has not yet initiated a review to determine if there were any other chemicals that have a
mechanism of toxicity common with that of sodium fluoride. Risks summarized in this
document are those that result only from the use of sodium fluoride. Therefore, the
Agency did not perform a cumulative risk assessment as part of this RED for sodium
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fluoride. For purposes of this RED, the Agency has assumed that sodium fluoride does
not have a common mechanism of toxicity with other substances. If the Agency
identifies other substances that share a common mechanism of toxicity with sodium
fluoride, the Agency will perform aggregate exposure assessments on each chemical, and
will begin to conduct a cumulative risk assessment. Upon the Agency's request and
according to a schedule determined by the Agency, the Registrant must submit such
information as needed in order to evaluate issues related to whether sodium fluoride
shares a common mechanism of toxicity with any other substance. 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/cumulative .
This document presents the Agency's decision regarding the reregi strati on
eligibility of the registered uses of sodium fluoride. In an effort to simplify the RED, the
information presented herein is summarized from more detailed information, which can
be found in the technical supporting documents for sodium fluoride referenced in this
RED. The revised risk assessments and related addenda are not included in this
document, but are available in the Public Docket at www.regulations.gov (Docket #
EPA-HQ-2007-0833).
This document consists of six sections. Section I is the introduction. Section II
provides a chemical overview, a profile of the use and usage of sodium fluoride and its
regulatory history. Section III, Summary of sodium fluoride Risk Assessment, gives an
overview of the human health and environmental assessments, based on the data
available to the Agency. Section IV, Risk Management, Reregistration, and Tolerance
Reassessment Decision, presents the reregi strati on eligibility and risk management
decisions. Section V, What Registrants Need to Do, summarizes the necessary label
changes based on the risk mitigation measures outlined in Section IV. Finally, the
Appendices list all use patterns eligible for reregi strati on, bibliographic information,
related documents and how to access them, and Data Call-In (DCI) information.
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II. Chemical Overview
A. Regulatory History
Sodium fluoride products were initially registered in 1964. Sodium fluoride was
originally sold to the U.S. telecommunications company in the 1930s as a wood
preservative for utility poles lumber, timbers, posts, poles, ties, pilings, and all exterior
wood exposed to moisture or weather. There are six registered products. There are no
inert uses or tolerances for this chemical.
B.
Chemical Identification
i
Common Name:
Chemical Name:
Other Name(s):
CAS Registry Number:
OPP Chemical Code:
Case Number:
Empirical Formula:
Molecular Weight:
Basic Manufacturer:
Chemical Properties:
Figure 1. Molecular Structure of Sodium Fluoride
Chemifluoro, Dentafluoro, Villiaumite
Sodium fluoride
Floridine, Florocid
7681-49-4
075202
3132
NaF
42.00
Osmose Inc.
Sodium fluoride (TGAI) is a yellow powder with a weak
musty odor and melting point of 993 ° C. The boiling point
for sodium fluoride is 1704° C. Sodium fluoride (TGAI)
has an estimated log Kow of -0.77 l and a vapor pressure of
5.43 x 10'26 mm Hg (25 ° C)1*. Sodium fluoride (TGAI) is
soluble in water at .4.10 g/100 ml; at 15°C and 4.3 g/100
ml at 25 ° C. Sodium fluoride (TGAI) is readily soluble in
many organic solvents and has a density of 2.55 g/cm3.
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The pH for sodium fluoride is slightly alkaline and stable
under normal storage conditions. The Henry Law Constant
(air/water partition constant) is 5.04 x 10"33 atm mVmole1
C. Use Profile
The following is information on the currently registered uses of sodium fluoride,
including an overview of use sites and application methods. A detailed table of the uses
of sodium fluoride eligible for reregi strati on is available in Appendix A.
Type of Pesticide: Fungicide
Target Pests: Fungi
Formulation Types: Powder (Technical Grade Active Ingredients (TGAI)); Soluble
Concentrate (Manufacturing Use Products (MP)); Soluble
Concentrate, Ready-to-use Solution, Pelleted/tablet (End Use
Products (EP))
Use Sites: Wood Preservative- (Exterior use only) Lumber, Timber, Posts,
Poles, Ties, Pilings, and Other Wood Products.
Methods and Rates of Application:
Wood Preservative: For control of internal decay, fill decay pockets and voids using a
grease gun or other pressurized applicator. Plug application holes
with secure-fitting dowels
Using air or mechanical pressure pump, apply solution to interior
cavity of wood structure through prepared opening.
Typical pole application is from 3 inches above to 18 inches below
the ground line and lower where deeper decay is suspected.
Application on poles to be restored should extend the length of
wrap around type repair systems. Wrap the treatment area with
water proof bandage.
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III. Summary of Sodium fluoride Fluoride (NaF) 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 Sodium Fluoride (NaF). While
the risk assessments and related addenda are not included in this document, they are
available from the OPP Public Docket EPA-HQ-OPP-2007-0833, and may also be
accessed from www.regulations.gov. Hard copies of these documents may be found in
the OPP public docket. The OPP public docket is located in Room S-4900, One Potomac
Yard, 2777 South Crystal Drive, Arlington, VA 22202, and is open Monday through
Friday, excluding Federal holidays, from 8:30 a.m. to 4:00 p.m.
The Agency's use of human studies in the NaF 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.
A. Human Health Risk Assessment
1. Toxicity of Sodium Fluoride
A brief overview of the toxicity studies used for determining endpoints in the risk
assessment is outlined below in Table 1. Further details on the toxicity of NaF can be
found in the document titled "Toxicology Chapter for Sodium Fluoride RED," dated July
23, 2007. These documents are available on the Agency's website in the EPA Docket at:
http://www.regulations.gov (Docket ID #EPA-HQ-OPP-2007-0833).
The Agency has reviewed all toxicity studies submitted for sodium fluoride and
has determined that the toxicological database is sufficient for reregistration. The studies
have been submitted to support guideline requirements. The acute toxicity data for
sodium fluoride is summarized below in Table 1.
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Table 1. Acute Toxicity Data for Sodium Fluoride
Guideline Number
870.1100
(§81-1)
870.1200
(§81-2)
870.1300
(§81-3)
870.2400
(§81-4)
870.2500
(§81-5)
870.2600
(§81-6)
870.2600
(§81-6)
Study Type/Test substance (% a.i.)
Acute Oral - Rat
Purity 95.6% - Sodium
Fluoride
Acute Dermal - Rat
Purity 95.6% - Sodium
Fluoride
Acute Inhalation - Rat
Purity 95.6% - Sodium
Fluoride
Primary Eye Irritation -
Rabbit
Purity 95.6% - Sodium
Fluoride
Primary Dermal Irritation-
Rabbit
purity 95.6% - Sodium
Fluoride
Dermal Sensitization - Guinea
Pig
purity 95.6 % - Sodium
Fluoride
Dermal Sensitization - Guinea
Pig
purity not reported
MRID Number
/ Citation
43778501
43778502
43778503
43778504
43778505
43778506
40866801
Results
LD50 (combined) =
105 (93-1 19 CL)
Male LD50 = 120
mg/kg
Female LD50 = 89
mg/kg
LD50 > 2000 mg/kg
LC50= l.OOmg/L
Severely irritating to
unwashed eyes
Slightly Irritating
Buehler: Not a skin
sensitizer
Not a dermal
sensitizer
Toxicity
Category
II
III
III
II
IV
No
No
Notes: LC = Lethal Concentration; LD = Lethal Dose; NA = Not Applicable
General Toxicity Observations
Acute Toxicity
For the technical grade active ingredient, sodium fluoride has a high order of
toxicity via the oral route of exposure (Toxicity Category II) and a moderate order of
toxicity via the dermal and inhalation routes of exposure (Toxicity Category III).
Primary eye irritation studies classify sodium fluoride as corrosive (Toxicity Category I)
whereas dermal irritation studies classify sodium fluoride as a mild or slight irritant
(Toxicity Category IV). Sodium fluoride is not a dermal sensitizer.
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Acute and Chronic Reference Dose (RfDs)
Dietary exposure to NaF is not expected. Therefore, acute and chronic dietary
endpoints were not selected.
Incidental Oral Exposure
Incidental oral exposure to NaF is not expected, based on registered use patterns.
Therefore, incidental oral endpoints were not selected.
Dermal Exposure
For short-term dermal exposures, a LOAEL of 20 mg/kg/day was selected from a
oral subchronic toxicity study in rats based on significant reductions in body weight gain
and suppressed spontaneous motor activity. The target MOE is 300 for the short-term
(ST) dermal exposures, based on lOx for inter-species extrapolation, lOx for intra-species
variation, and 3x for use of a LOAEL. For intermediate-term dermal exposures, a
NOAEL of 1.5 mg/kg/day was selected from a six month National Toxicology Program
(NTP) oral toxicity study in the mouse based on histopathology observed in bone with
degeneration in tibias and femurs of animals. The target MOE is 100, based on lOx inter-
species extrapolation and lOx for intra-species variation. For long-term dermal
exposures, a LOAEL of 1.3 mg/kg/day was selected from a 2 year NTP chronic
toxicity/carcinogenicity study in rats, based on dentine dysplasia in males and females,
and ameloblast degeneration in males. The target MOE is 300 for the short-term (LT)
dermal exposures, based on lOx for inter-species extrapolation, lOx for intra-species
variation, and 3x for use of a LOAEL. Dermal absorption is assumed to be 100% in the
absence of actual dermal absorption data. Sodium fluoride is not a dermal sensitizer.
Inhalation Exposure
For short-term inhalation exposures, a LOAEL of 20 mg/kg/day was selected
from an oral subchronic toxicity study in rats. Effects observed at the LOAEL of 20
mg/kg/day included significant reductions in body weight gain and suppressed
spontaneous motor activity. The target MOE is 300 for occupational exposures (10X for
interspecies extrapolation, 10X for intraspecies variability, and 3x for use of a LOAEL).
For intermediate-term inhalation exposures, a NOAEL of 1.5 mg/kg/day was selected
from a six month National Toxicology Program (NTP) oral toxicity study in the mouse
based on histopathology observed in bone with degeneration in tibias and femurs of
animals. The target MOE is 100, based on lOx inter-species extrapolation, and lOx for
intra-species variation. For long-term inhalation exposures, a LOAEL of 1.3 mg/kg/day
was selected from a 2 year NTP chronic toxicity/carcinogenicity study in rats, based on
dentine dysplasia in males and females, and ameloblast degeneration in males. The target
MOE is 300 for the long-term (LT) inhalation exposures, based on lOx for inter-species
extrapolation, lOx for intra-species variation, and 3x for use of a LOAEL.
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Carcinogenicity
Based on the available data, sodium fluoride has been classified as a "Group D"
(inadequate evidence of carcinogenicity). This conclusion is consistent with the recent
report by the National Academy of Sciences which concluded that "the evidence on the
potential of fluoride to initiate or promote cancers, particularly of the bone, is tentative
and mixed."
Mutagenicity Potential
Positive mutagenicity results have been reported in mouse lymphoma assays, in
chromosome aberration assays, in unscheduled DNA synthesis assays, and in in vitro
sister chromatid exchange assays.
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,
OIT 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 (lOxX), 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. Sodium fluoride is
not used in food and therefore, the toxicological database is considered to be complete
with respect to assessing the increased susceptibility to infants and children as required
by FQPA. There are no food tolerances for NaF and the use patterns considered for the
reregi strati on eligibility decision (RED) document do no involve dietary exposure. As a
result, an FQPA safety finding is not applicable.
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3. Dietary Exposure Assumptions & Dietary Risk Assessment
Based on registered uses, no dietary exposure to NaF is anticipated and no
toxicological dietary endpoints were identified. Therefore, no dietary assessment has
been conducted.
a. Dietary Risk from Drinking Water
The antimicrobial uses of sodium fluoride are not expected to pose a hazard to
groundwater or surface water. Therefore, a drinking water exposure and risk assessment
has not been performed.
4. Residential Risk Assessment
Based on registered uses, negligible residential exposures to NaF are anticipated.
No residential assessment has been conducted. Although remedial wood treatment for
poles and beams on bridges do not occur in high traffic areas for bystanders, distribution
utility poles are numerous and often located in people's front yards. The vapor pressure
of sodium fluoride is negligible (i.e., 5.43 x 10"26 mmHg at 25 C), and therefore, no vapor
will be released in the vicinity of treated poles. Additionally, label directions to cap
treated holes after application will minimize any potential for dermal contact. Likewise,
groundline treatments are also covered (i.e., brush-on and wrap treatments are below the
groundline and then covered with dirt) and will minimize potential dermal contact to
children playing in areas of treated poles.
5. Aggregate Risk Assessment
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 typically includes exposures from food,
drinking water, residential uses of a pesticide, and other non-occupational sources of
exposure.
Since there are no dietary, residential or other non-occupational sources of
exposure to NaF, an aggregate exposure assessment was not performed.
6. Occupational Risk
Workers can be exposed to a pesticide through mixing, loading, and/or applying a
pesticide, or re-entering treated sites. Sodium fluoride is used as an antimicrobial
pesticide as a remedial wood treatment for the protection against decay producing fungi.
Potential occupational exposure can occur in various use sites, which include treatment of
railroad ties and groundline treatment around utility poles. Additional information can
be found in the document titled, "Revised Occupational and Residential/Bystander
Assessment of the Antimicrobial Use (Remedial Wood Treatment) of Sodium Fluoride
for the Reregi strati on Eligibility Decision (RED) Document. Case Number 3132. PC
Code 075202," dated October 1, 2007.
-------
a. Occupational Toxicity
The doses and toxicological endpoints used in the occupational handler
assessment of NaF scenarios are summarized in Table 2 below.
Table 2. Sodium Fluoride for Use in Human Risk Assessment
Exposure
Scenario
Dose (mg/kg/day) used in
risk assessment
UF
Special FQPA SF and Level
of Concern for Risk
Assessment
Study and Toxicological
Effects
Dietary Risk Assessments
Acute Dietary
(general population and
females 13-49)
Chronic Dietary
No appropriate endpoints were identified that represent a single dose effect.
Therefore, this risk assessment is not required.
No appropriate endpoints were identified that represent a chronic dose effect.
Therefore, this risk assessment is not required.
Non-Dietary Risk Assessments
Short -Term Dermal
(1 - 30 Days)
Intermediate -Term
Dermal
(30 Days- 6 months)
Long-Term Dermal (> 6
months)
Short-term Inhalation
(1-30 days)
LOAEL = 20 mg/kg/day
NOAEL= 1.5
mg/kg/day
LOAEL=1.3g/kg/day
LOAEL = 20 mg/kg/day
Target MOE=300 (lOx
inter-species
extrapolation, lOx intra-
species variation, 3x for
use of LOAEL)
Target MOE=100 (lOx
inter-species
extrapolation, lOx intra-
species variation)
TARGET MOE = 300
(lOx inter-species
extrapolation, lOx intra-
species variation and 3x
for use of LOAEL)
Target MOE=300 (lOx
inter-species
extrapolation, lOx intra-
species variation, 3x for
use of LOAEL)
Note: lOx route
extrapolation for
confirmatory inhalation
study.
Oral Subchronic
Toxicity - Rat (Sodium
Fluoride)
LOAEL = 20
mg/kg/day, based on
significant reductions in
body weight gain and
suppressed spontaneous
motor activity.
6-month NTP oral
toxicity study-mouse
LOAEL = 7.5
mg/kg/day based on
histopathology observed
in bone with
degeneration in tibias
and femurs of animals
2-year NTP chronic
toxicity /carcinogeniciry
study in rats
LOAEL = 1.3
mg/kg/day, based on
dentine dysplasia in
males and females, and
ameloblast degeneration
in males
Oral Subchronic
Toxicity - Rat (Sodium
Fluoride)
LOAEL = 20
mg/kg/day, based on
significant reductions in
body weight gain and
suppressed spontaneous
motor activity.
10
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Exposure
Scenario
Intermediate-term
Inhalation
Long-term Inhalation
Cancer
Dose (mg/kg/day) used in
risk assessment
UF
NOAEL= 1.5
mg/kg/day
LOAEL = 1.3
mg/kg/day
Special FQPA SF and Level
of Concern for Risk
Assessment
Target MOE=100 (lOx
inter-species
extrapolation, lOx intra-
species variation)
Note: 1 Ox route
extrapolation for
confirmatory inhalation
study.
TARGET MOE =300
(lOx inter-species
extrapolation, lOx intra-
species variation, 3x for
use of LOAEL)
Note: 1 Ox route
extrapolation for
confirmatory inhalation
study.
Study and Toxicological
Effects
6-month NTP oral
toxicity study-mouse
LOAEL = 7.5
mg/kg/day based on
histopathology observed
in bone with
degeneration in tibias
and femurs of animals
2-year NTP chronic
toxicity /carcinogenicity
study in rats
LOAEL = 1.3
mg/kg/day, based on
dentine dysplasia in
males and females, and
ameloblast degeneration
in males
Sodium fluoride has been classified as a "Group D" (not classifiable as to
carcinogenicity). This conclusion is consistent with the recent report by the
National Academy of Sciences which concluded that 'the evidence on the
potential of fluoride to initiate or promote cancers, particularly of the bone, is
tentative and mixed. '
Notes: UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL =
lowest observed adverse effect level.
b. Occupational Handler Exposure
Occupational risk for all potentially exposed populations is measured by a Margin
of Exposure (MOE), which determines how close the occupational exposure comes to a
No Observed Adverse Effect Level (NOAEL) from toxicological studies. Occupational
risk is assessed for exposure at the time of application (termed "handler" exposure).
Application parameters are generally defined by the physical nature of the formulation
(e.g., formula and packaging), by the equipment required to deliver the chemical to the
use site and by the application rate required to achieve an efficacious dose.
Potential occupational handler exposures can occur when sodium fluoride is used
as a remedial wood treatment for the protection against decay producing fungi. The
Agency evaluated representative occupational handler scenarios to assess and determine
dermal and inhalation exposures. For sodium fluoride, handler scenarios were assessed
by using unit exposure data to estimate occupational exposures. Unit exposures are
estimates of the amount of exposure to an active ingredient a handler receives while
performing various handler tasks and are expressed in terms of micrograms or milligrams
of active ingredient per pounds of active ingredient handled. A series of unit exposures
have been developed that are unique for each scenario typically considered in
assessments (i.e., there are different unit exposures for different types of application
equipment, job functions, and level of protection).
11
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Application techniques include a product-specific dispenser, grease/caulking
guns, pressurized sprayers, preservative cartridges, brush-on and/or trowel-on
applications. The personal protective equipment (PPE) listed on the label range from a
minimum protection of goggles to a maximum protection of goggles, gloves, and
respirators.
Chemical-specific exposure data were not submitted to support the remedial wood
applications. Therefore, the Agency developed a screening-level assessment using
surrogate data to determine the potential risks associated with remedial wood treatment.
Based on the label review listed in Table 3 below, there are two basic remedial
applications: (1) applying product into pre-drilled holes; and (2) applying product around
the circumference of poles at or below the groundline. The brush on treatment represents
the high-end exposures for the trowel on and impregnated wraps. Each remedial
application can be applied using various techniques and PPE. Surrogate exposure data
are not available for all application techniques specified on the label. Representative
exposure scenarios (i.e., application techniques) are used to represent the potential worker
short-, intermediate, and in some cases long-term durations of inhalation and dermal
exposures. Inhalation exposure is expected to be minimal for the groundline treatments
because of the viscosity of the product as well as its low vapor pressure. Table 3 presents
a summary of sodium fluoride labels.
Table 3. Summary of Sodium Fluoride Labels
EPA Reg
No.
3008-58
75340-2
75341-6
75341-4
75341-5
75341-12
%ai
97.5
54.92
92.6
70.6
44.4
8.39
Signal Word
Danger
Warning
Danger
Danger
Danger
Danger
PPE
Respirator, goggles
Gloves
Gloves
Gloves, goggles
Goggles
Gloves, goggles,
respirator, and
Label Directions
(e.g., application techniques, rates,
etc.)
Includes a non pesticide statement
TIE-GARD dispenser; grease gun;
pressurized applicator; Apply to drilled
holes to "fill" and cap; Used on rail road
ties and structural timbers such as bridge
pilings and posts.
FLURODS (i.e., preservative cartridges,
solid sticks) placed into drilled holes and
capped. For treating poles, posts,
timbers, crossties, etc. Rate: 39.2
grams/cubic foot wood.
Pole Wrap. Groundline treatment. Dig
20 inches around pole, wrap down to 18
inches below groundline to 2 inches
above groundline and cover with dirt.
Used in combination with copper
naphthenate. Brush-on, trowel-on,
grease gun. 1716th of an inch rate 18
inches below and 3 inches above
groundline and covered with a wrap.
Also used in drilled holes applied by a
grease gun and capped (paste density 12
Ibs/gallon).
Used in combination with copper
naphthenate. Mix 1 gallon of product
12
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75341-13
44.42
Warning
respirator when
spraying for
continued or
prolonged use or
frequent use
Goggles, face shield
or safety glasses,
protective clothing,
and chemical
resistant-gloves
with 1.5 gallons of water. Apply using
air or mechanical pressure pump into
prepared opening (assume pre-drilled).
Rate: 1 gallon of treatment solution per
cubic foot of wood.
Used in combination with copper
naphthenate. Brush-on, trowel-on,
grease gun. 1716th of an inch rate 18
inches below and 3 inches above
groundline and covered with a wrap.
Also used in drilled holes applied by a
grease gun and capped.
i. Sodium Fluoride Application Methods
TIE-CARD andFLUROD Applications
TIE-GARD and FLURODS are sodium fluoride products that are inserted into
pre-drilled holes and capped and are expected to result in minimal inhalation and dermal
handler exposure because the products are engineered to be closed systems. The
FLURODS are solid sticks that are placed in the pre-drilled holes. TIE-GARD is a gel
product containing sodium fluoride. The automated rail tie use is packaged in 30 gallon
PVC closed head drums. It is applied from high capacity rubber track machinery that
rides on railroads and automatically injects the gel product into rail ties. Applicator
exposure from these uses is expected to be negligible. Any potential for exposure from
leaks/spills from these products (i.e., TIE GARD and FLURODS) is believed to be best
mitigated by the label requirement for the availability of PPE such as chemical resistant
gloves, goggles, long pants, and long sleeved-shirts in the event of a spill. Therefore, the
handler risks to pre-packaged products are assumed to be minimal and are not quantified.
Spray/Injection Applications
Although EPA does not have a specific surrogate exposure scenario for injection
of pesticides into wooden poles, similar exposure data for hand-held application
equipment exist. The spray application is believed to represent the high end of exposure
to the grease gun. The exposure data for hand-held applications that are available to EPA
include data from the Pesticide Handlers Exposure Database (PHED) and the Outdoor
Residential Exposure Task Force (ORETF). The data available from these sources are
for garden hose-end sprayers, low pressure hand-wands, backpack sprayers, high pressure
handwands, and rod shank termiticide applications. The most representative data
available for an injection-type hand-held devise is the rod shank termiticide application
from PHED. Other equipment types are not believed to be as representative because each
one involves a spray and the injection into the pole will minimize spray.
The rod shank termiticide injection data in PHED are used to develop a screening-
level assessment for the pole use. The dermal unit exposure (UE) for combined liquid
pour and termiticide injection is based on 17 replicates with the test subjects wearing a
single layer of clothing and chemical resistant gloves with AB grades (i.e., guideline
13
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recommendations for analytical quality). The dermal UE is 0.36 mg/lb ai. The inhalation
UE is based on the same 17 replicates and the grades are also AB. The inhalation UE is
0.0022 mg/lb ai. Although not all of the labels currently specify the use of chemical
resistant gloves (e.g., EPA Reg. No. 75341-5), the "gloved" clothing scenario is the only
one available to assess risks.
Groundline Treatments
Groundline treatments consist of brush and trowel-on applications as well as
impregnated wraps around poles. Once applied, the pole treatment is covered with dirt.
The most representative surrogate exposure data available to assess the high-end of the
exposure potential are for painting with a paint brush. The product is expected to have a
much higher viscosity then paint. Because of the high viscosity and low vapor pressure,
inhalation exposure is expected to be minimal. Dermal unit exposure values for paint
brush applications from PHED were used (single layer of clothing). The dermal unit
exposure is 24 mg/lb a.i. for the painting scenario for a test subject wearing long pants,
long-sleeved shirt, and chemical resistant gloves.
ii. Application Rates and Amounts Handled
Label directions indicate that sodium fluoride is applied into poles, timbers, etc,
via four different formulations; paste, bandage or wrap, liquid and solid rods. The
application for these formulations is very different from each other due to the physical
properties and percentage of sodium fluoride present in each formulation. Typically
paste formulations are applied by brush-on application around the groundline area of pole
and then wrapped with a protective barrier before being backfilled with soil. The dry
impregnated wrap is applied around the groundline portion of the pole. Liquid
formulations are normally applied to internal voids through means of pressurized
injection and rods are applied by drilling application holes, inserting the rods into the
holes and then plugging them.
Labeled application rates for pastes are to apply by brush to a thickness of 1/16th
inch. The dry wrap is applied by cutting the wrap to match the circumference of the pole.
Liquid application instructions include filling application holes to refusal and more
specific instructions such as 1 gallon of diluted solution per cubic foot of wood.
However, label directions are not provided to determine neither the number of holes per
pole nor the number of cubic feet per pole to be treated with sodium fluoride. Therefore,
for this assessment 1 cubic foot of wood per pole is assumed to be treated for the
spray/injection application.
Specific amounts of sodium fluoride applied by workers daily are not available.
Therefore, in addition to the number of cubic feet treated per pole, the number of poles
treated per day (i.e., pre-drilled treatments, not groundline applications) with sodium
fluoride was also estimated.
14
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The amount of paste applied to each pole for groundline treatments is estimated to
be 0.167 gallons/pole for distribution poles and 0.255 gallons per transmission pole (i.e.,
21 inch wide treatment x up to 34 inch circumference for distribution poles and 50 inches
for transmission poles x 1/16 inch thickness of product treatment).
• Distribution Poles - the smaller diameter wooden distribution poles (-140 million
distribution poles in service) are treated at a high end rate of-24 per day (for
short-term duration). Workers treat these types of poles as their main work
function, treating 5 days per week, on a yearly basis (i.e., 250 days/year). This
scenario is represented by the short-, intermediate- and long-term exposure
durations.
• Transmission Poles - the larger wooden transmission poles are treated at a rate of
30 per day. Workers treat these types of poles as their main work function,
treating 5 days per week, on a yearly basis (i.e., 250 days/year). This scenario is
represented by the short-, intermediate- and long-term exposure durations.
c. Occupational Handler Risk Summary
Table 4 presents the representative exposure scenarios used to assess the labeled
remedial wood treatment uses.
Table 4. Occupational Handler Exposure Scenarios
Remedial
Applications
Pre-drilled holes
Groundline
High-end Exposure
Scenarios
Closed systems
Sprays
Brush-on
Application Techniques Represented by the High-end
Exposure Scenario
TIE CARD dispenser for rail ties; FLURODS (solid sticks)
Grease/caulking gun; air or mechanical pressure pump
Brush; Trowel; Pole Wrap (dry wrap)
Evaluation of the spray applications into pre-drilled holes, indicates no dermal
risks of concern for the short-term duration for the distribution pole. Dermal risks,
however, are triggered for the intermediate- and long-term durations. The intermediate-
and log-term dermal MOEs are 26 and 22, respectively, with a target MOE of 300. No
inhalation risks are triggered for the distribution poles at any timeframe.
For the spray applications into pre-drilled holes for the transmission poles, the
inhalation (all durations) and short-term dermal risks are not of concern. However, the
short-, intermediate- and long-term dermal risks for the transmission poles are of concern.
The short-, intermediate- and long-term dermal MOEs are 280, 21 and 18, respectively,
with a target MOE of 300 for short-term and long-term and 100 for intermediate-term.
All of the dermal MOEs are below the target MOE of 300 for short-term and
long-term and 100 for intermediate-term for the groundline brush-on treatments (MOEs
less then or equal to 1). The brush-on treatment also represents the high-end exposures
for the trowel-on and impregnated wraps. Inhalation exposure is expected to be minimal
15
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for the groundline treatments because of the viscosity of the product as well as its low
vapor pressure.
The exposure and risks to handlers of the TIE-GARD product used in the
automated rail tie treatment system and the solid stick FLURODS are expected to be
minimal and are not quantified. Table 5 presents the potential dermal and inhalation
short-, intermediate-, and long-term inhalation and dermal exposures and risks for the
remedial pole treatment uses of sodium fluoride.
16
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Table 5. Dermal and Inhalation Exposure and Risks for Remedial Applications of Sodium Fluoride to Poles.
Application
Spray
(Distribution
Poles)
Spray
(Transmission
Poles)
Brush-on
(Distribution
Poles)
Brush-on
(Transmission
Poles)
Dermal UE
(mg/lb a.i)
0.36
0.36
24
24
Inhalation
UE
(mg/lb a.i)
0.0022
0.0022
NA
NA
Rate
(gal/pole)
1
1
0.225
0.368
Rate
Ob a.i/gal)
0.47
0.47
5.33
5.33
# poles
24
30
24
30
Dermal dose
(mg/kg/day)
0.058
0.073
9.87
20.2
Inhalation
dose
(mg/kg/day)
0.00035
0.00044
NA
NA
Dermal MOEs
ST
(300)
350
280
2
1
IT
(100)
26
21
<1
NA
LT
(300)
22
18
<1
NA
Inhalation MOEs
ST (300)
56,000
45,000
IT
(100)
4200
3400
LT
(300)
3700
2900
NA
NA
NA = Not applicable (e.g., short-term (ST) MOEs are only applicable for the high treatment frequency of poles).
ST = short-term; IT = intermediate-term; LT = long-term.
UE are from PHED for termiticide MLAP, liquid pour, rod shank injection
Dermal UE is single layer of clothing and chemical resistant gloves.
Treatment solution for spray from EPA Reg. No. 75341-12 (i.e., 1 gal product x 8.34 Ib/gal x 8.39% a.i /1.5 gallons water = 0.47 Ib a.i/gal treatment
solution)
Brush-on rate EPA Reg No 75341-5 is 44.4% a.i; density of 121b/gal = 5.331b a.i./gallon
# poles = registrant estimate during the reregistration phase 1 error comment period (Distribution is 24 poles per day and transmission is 30 poles per day
Dermal (mkd) = Dermal UE x rate x # poles x l/70kg
Inhalation dose (mkd) = Inhalation UE x rate x #poles x l/70kg
MOE ST Dermal & inhalation = LOAEL 20 mkd / dose; UF = 300
MOE IT Dermal & Inhalation = NOAEL 1.5 mkd / dose; UF = 100
MOE LT Dermal & Inhalation = LOAEL 1.3 mkd / dose; UF = 300
17
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d. Occupational Post-application Risk Summary
Occupational post-application exposure is not anticipated for the antimicrobial uses of
sodium fluoride. The vapor pressure of sodium fluoride is negligible (i.e., 5.43x 10"26 mmHg at
25 °C), and therefore, no vapor will be released in the vicinity of treated poles. Additionally,
label directions to cap treated holes after application will minimize any potential for dermal
contact. Likewise, groundline treatments are also covered (i.e., brush-on and wrap treatments are
below the groundline and then covered with soil).
7. Human Incident Data
The Agency reviewed available sources of human incident data for incidents relevant to
sodium fluoride. EPA consulted the following sources of information for human poisoning
incidents related to naphthenate salts use: (1) OPP Incident Data System (IDS) - The Office of
Pesticide Programs (OPP) Incident Data System contains reports of incidents from various
sources, including registrants, other federal and state health and environmental agencies and
individual consumers, submitted to OPP since 1992; (2) California Department of Pesticide
Regulation (1982-2004) - The California Department of Pesticide Regulation pesticide
poisoning surveillance program consists of reports from physicians of illness suspected of being
related to pesticide exposure since 1982; (3) National Pesticide Information Center (NPIC) -
NPIC is a toll-free information service supported by OPP that provides a ranking of the top 200
active ingredients for which telephone calls were received during calendar years 1984-1991; (4)
National Poison Control Centers (PCC) (1993-1996): and (5) Published Scientific Literature on
Incidents.
There are only limited acute incidents associated with sodium fluoride used in wood
preservatives. All the symptoms are classified as either minor or moderate. Historically, there
have been some fatal incidents associated with oral exposure to sodium fluoride. These fatalities
occurred when sodium fluoride was ingested at a much higher concentration than is used in
antimicrobial wood treatment.
The potential bystander inhalation exposure to sodium fluoride is minimized by the
extremely low vapor pressure. The potential for dermal exposure to bystanders (i.e., children,
capping of pre-drilled holes and groundline applications covered with soil).
B. Environmental Risk Assessment
A summary of the Agency's environmental risk assessment is presented below. Sodium
fluoride use as a wood preservative could result in environmental exposures. The following risk
characterization is intended to describe the magnitude of the estimated environmental risks
associated with sodium fluoride use and any potential uncertainties.
For a detailed discussion of all aspects of the environmental risk assessment, refer to the
Environmental Risk Assessment (Section 8) in the "Sodium Fluoride Draft Risk Assessment for
the Reregi strati on Eligibility Decision (RED) Document. PC Code: 075202 (active). Case No.
3132," dated August 14, 2007; the "Ecological Hazard and Environmental Risk Assessment
18
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Chapter for Sodium Fluoride RED," dated July 23, 2007; and the "Environmental Fate Science
Chapter for Sodium Fluoride RED," dated August, 2007.
1. Environmental Fate and Transport
The Agency evaluated the environmental fate of this chemical, using a search of
published literature. The results of the literature search are provided below. Additional
information can be found in the document titled, "Environmental Fate Risk Assessment Science
Chapter for the Sodium Fluoride RED," dated July 26, 2007.
Sodium fluoride is an organic substance which does not undergo hydrolysis but is water
soluble and dissociates in water to sodium and fluoride ions. Fluoride ions undergo hydrolysis to
form hydrogen fluoride acid and hydroxide ions which can shift the pH to alkaline. Sodium
fluoride does not adversely affect soil biomass, microflora and macro invertebrates, and is not
expected to be bio-accumulative. A field monitoring study of sodium fluoride treated poles
found that sodium fluoride ions occasionally exceed background levels and do not migrate
outward from treated poles more than 10 cm or for more than 50 cm deep. Elevated levels
returned to background by the end of the 18 month study. Sodium fluoride is not expected to
pose a hazard to groundwater or surface waters.
2. Ecological Risk
The Agency's ecological risk assessment compares toxicity endpoints from ecological
toxicity studies to estimated environmental concentrations based on environmental fate
characteristics and pesticide use data. A summary of the submitted data is provided below. A
summary of acute ecological toxicity is provided in Table 6 below.
a. Environmental Toxicity
Toxicity to Birds
Available data indicate that sodium fluoride is moderately toxic to birds on an acute oral
basis and practically nontoxic to avian species through subacute dietary exposure.
Toxicity to Terrestrial Animals
Based on the results of mammalian studies conducted to meet human toxicity data
requirements, sodium fluoride exhibits high toxicity via the oral route; moderate dermal, and
inhalation toxicity (toxicity category III). For primary eye irritation, sodium fluoride is corrosive
(toxicity category I). Sodium fluoride is classified as a mild skin irritant (toxicity category IV)
and is not classified as a dermal sensitizer.
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Toxicity to Aquatic Animals
Freshwater acute toxicity tests indicate that sodium fluoride is practically nontoxic to fish
on an acute basis. Based on available data, sodium fluoride is practically nontoxic to freshwater
invertebrates.
Since sodium fluoride is not expected to reach the estuarine or marine environment from
the currently registered use patterns, an evaluation of its impact on estuarine or marine species
was not evaluated.
Because of the limited use pattern with low potential for chronic exposure to aquatic
organisms, sodium fluoride is not expected to present a chronic aquatic toxicity.
Toxicity to Plants
Current sodium fluoride wood treatment use patterns are limited and are not expected to
result in surface water residues of sufficiently large quantities to adversely affect terrestrial or
aquatic plant species. Therefore, non-target plant toxicity studies are not required for the current
wood treatment use patterns.
Non-target Insects
Honeybees should not be exposed to sodium fluoride wood treatments due to the
requirement to wrap the treated area with a waterproof barrier or the requirement to inject
sodium fluoride into the wood and then seal the bore hole. Beehives should not be constructed
from wood treated with sodium fluoride. The product label(s) must state: "Sodium fluoride
must not be used to treat wood intended for construction or maintenance of beehives."
Otherwise, the following bee toxicity and honey residue studies are needed: 850.3020, 850.3030
and 860.1500.
A summary of the submitted acute ecological toxicity data, avian sub-acute dietary
toxicity data, chronic freshwater fish toxicity data, data for sodium fluoride are provided in Table
6.
20
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Table 6. Ecological Toxicity of the Sodium Fluoride
Species
Chemical,
% Active
Ingredient
(a.i.)
Tested
Endpoint
Toxicity
Category
Comments
Reference
(MRID
No.)
Acute Avian Toxicitv
Bobwhite quail
(Colinus
virginianus)
Sodium
Fluoride
95%
LD50 = >387 mg/kg
NOAEL = 45 mg/kg
Moderately toxic
436115-01
Subacute Avian Toxicitv
Bobwhite quail
(Colinus
virginianus)
Mallard duck
(Anas
platyrhynchos)
Sodium
Fluoride
95%
Sodium
Fluoride
95%
LC50(diet)=>5620
ppm
NOAEC = 1000 ppm
LC50 (diet) = >5620
ppm
NOAEC = 5620 ppm
Practically
nontoxic
Practically
nontoxic
- 8-day test
duration
- 8-day test
duration
435931-02
435931-01
Acute Freshwater Fish Toxicitv
Bluegill Sunfish
(Lepomis
macrochirus)
Rainbow Trout
(Oncorhynchus
mykiss)
Sodium
Fluoride
95%
Sodium
Fluoride
95%
LC50 = 830 mg/L
NOAEC = 350 mg/L
LC50 = 317mg/L
NOAEC <26 mg/L
Practically
nontoxic
Practically
nontoxic
- 96-hr test
duration
- static renewal
test system
- 96-hr test
duration
- static test
system
43648201
43648202
Acute Freshwater Invertebrates Toxicitv
Waterflea
(Daphnia
magna)
Sodium
Fluoride
95%
EC50>120mg/L
NOAEC = 120 mg/L
Practically
nontoxic
- 48-hr test
duration
- static test
system
43648203
b. Ecological Exposure and Risk
Because of the limited use patterns for sodium fluoride, environmental exposure is
expected to be low. In addition, product labels require applicators to follow certain precautions,
such as waterproof wraps and sealed injections into utility poles, to prevent release into the
terrestrial or aquatic environment. Some exposure to woodpeckers and wood boring insects may
occur, however, sodium fluoride is practically nontoxic to avian and aquatic species tested. Any
incidental exposure is not expected to be toxic to non-target species. Therefore, an
environmental risk assessment was not conducted for the sodium fluoride wood treatment uses.
21
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c. Risk to Listed Species
Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2), requires all
federal agencies to consult with the National Marine Fisheries Service (NMFS) for marine and
anadromous listed species, or the United States Fish and Wildlife Services (FWS) for listed
wildlife and freshwater organisms, if they are proposing an "action" that may affect listed species
or their designated habitat. Each federal agency is required under the Act to insure that any
action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a
listed species or result in the destruction or adverse modification of designated critical habitat.
To jeopardize the continued existence of a listed species means "to engage in an action that
reasonably would be expected, directly or indirectly, to reduce appreciably the likelihood of both
the survival and recovery of a listed species in the wild by reducing the reproduction, numbers,
or distribution of the species." 50 C.F.R. ' 402.02.
To facilitate compliance with the requirements of the Endangered Species Act subsection
(a) (2) the Environmental Protection Agency, Office of Pesticide Programs has established
procedures to evaluate whether a proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed species in the wild by
reducing the reproduction, numbers, or distribution of any listed species (U.S. EPA 2004). After
the Agency's screening-level risk assessment is performed, if any of the Agency's Listed Species
LOG Criteria are exceeded for either direct or indirect effects, a determination is made to identify
if any listed or candidate species may co-occur in the area of the proposed pesticide use. If
determined that listed or candidate species may be present in the proposed use areas, further
biological assessment is undertaken. The extent to which listed species may be at risk then
determines the need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.
This preliminary analysis indicates that current sodium fluoride wood treatment uses are
not likely to enter the environment in sufficient quantities to adversely affect terrestrial or aquatic
species; however, an endangered species effects determination will not be made at this time.
22
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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 or not products containing the active
ingredient are eligible for reregi strati on. The Agency has previously identified and required the
submission of the generic (i.e., active ingredient-specific) data required to support reregi strati on
of products containing sodium fluoride as an active ingredient. The Agency has completed its
review of these generic data and has determined that the data are sufficient to support
reregi strati on of all supported products containing sodium flouride.
The Agency has completed its assessment of the occupational, residential, and ecological
risks associated with the use of pesticide products containing the active ingredient sodium
fluoride. Based on a review of these data and on public comments on the Agency's assessments
for the active ingredient sodium fluoride, the Agency has sufficient information on the human
health and ecological effects of sodium fluoride to make decisions as part of the tolerance
reassessment process under FFDCA and reregi strati on process under FIFRA, as amended by
FQPA. The Agency has determined that sodium fluoride-containing products are eligible for
reregi strati on provided that: (i) current data gaps and confirmatory data needs are addressed; (ii)
the risk mitigation measures outlined in this document are adopted; and (iii) label amendments
are made to reflect these measures. Label changes are described in Section V. Appendix A
summarizes the uses of sodium fluoride that are eligible for reregi strati on. Appendix B identifies
the generic data requirements that the Agency reviewed as part of its determination of the
reregi strati on eligibility of sodium fluoride and lists the submitted studies that the Agency found
acceptable. Data gaps are identified as generic data requirements that have not been satisfied
with acceptable data.
Based on its evaluation of sodium fluoride, the Agency has determined that sodium
fluoride products, unless labeled and used as specified in this document, would present risks
inconsistent with FIFRA. Accordingly, should a registrant fail to implement the risk mitigation
measure identified in this document, the Agency may take regulatory action to address the risk
concerns from the use of sodium fluoride. If all changes outlined in this document are
incorporated into the product labels, then all current risks for sodium fluoride will be
substantially mitigated for the purposes of this determination. Once an Endangered Species
assessment is completed, further changes to these registrations may be necessary as explained in
Section III of this document.
B. Public Comments and Responses
Through the Agency's public participation process, the EPA worked with stakeholders
and the public to reach the regulatory decision for sodium fluoride. The EPA released its
preliminary risk assessment for sodium fluoride for a 60-day public comment on October 10,
2007. The Agency received one comment on the sodium fluoride risk assessments noting that
the product should not be manufactured or sold because of the availability for safer alternatives.,
The agency has considered this comment in making its registration determination.
23
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C. Regulatory Position
1. Food Quality Protection Act Findings
a. "Risk Cup" Determination
There are no registered uses of sodium fluoride that are expected to result in dietary or
residential exposure. There are no tolerances. As a result, the only risks assessed for sodium
fluoride are those associated with occupational exposures. Therefore a "risk cup" determination
is not warranted
b. Determination of Safety to U.S. Population
The Agency has determined that sodium fluoride, with amendments and changes
specified in this document, 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 sodium fluoride. In reaching this conclusion,
the Agency has considered all available information on the toxicity, use practices and exposure
scenarios, and the environmental behavior of sodium fluoride.
A dietary risk assessment was not conducted for sodium fluoride because the use patterns
are not expected to result in dietary exposure. Therefore, sodium fluoride does not pose a dietary
risk. Similarly, the Agency does not anticipate significant contamination of drinking water as a
result of the registered uses of sodium fluoride and did not conduct a drinking water assessment.
The Agency considered the potential pathways of non-dietary exposure to residents in
determining the need to conduct an aggregate assessment. The Agency does not anticipate
residential exposure as a result of the registered uses of sodium fluoride and did not conduct a
residential risk assessment or an aggregate risk assessment.
c. Determination of Safety to Infants and Children
EPA has determined that the currently registered uses of sodium fluoride, with changes as
specified in this document, meet the safety standards under the FQPA amendments to section
408(b)(2)(C) of the FFDCA, and 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 susceptibility to the toxic effects of sodium fluoride residues
in this population subgroup.
The Agency has determined that analysis of the potential need for a special hazard-based
safety factor under the FQPA is not needed at this time. The Agency does not anticipate dietary
or drinking water or residential exposures based on the registered use patterns and there are no
tolerances or tolerance exemptions for the use of sodium fluoride as an active ingredient.
Therefore, an FQPA hazard analysis is not necessary at this time.
24
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d. Endocrine Disrupter 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 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, sodium fluoride 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 of sodium
fluoride. 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 forsodium
fluoride. 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/cumulative/.
D. Regulatory Rationale
The Agency has determined that sodium fluoride is eligible for reregi strati on provided
that additional required data confirm this decision, the risk mitigation measures outlined in this
document are adopted, and label amendments are made to reflect these measures.
The following is a summary of the rationale for managing risks associated with the uses
of sodium fluoride. Where labeling revisions are warranted, specific language is set forth in the
summary tables of Section V of this document.
25
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1. Human Health Risk Management
a. Dietary (Food) Risk Mitigation
A dietary risk assessment was not conducted for sodium fluoride because the use patterns
are not expected to result in residues on food and, thus, dietary exposure. Therefore, sodium
fluoride does not pose as a dietary risk and no mitigation measures are needed at this time.
b. Drinking Water Risk Mitigation
Sodium fluoride is not expected to come into contact with or be exposed to drinking
water and, therefore, the Agency did not conduct a drinking water exposure assessment. Sodium
fluoride is not used for potable water treatment and effluents containing this chemical are not
expected to significantly contaminate fresh water environments. Therefore, no mitigation
measures are necessary at this time.
c. Residential Risk Mitigation
Based on registered uses, negligible residential exposures to sodium flouride are
anticipated. No residential assessment has been conducted. Although remedial wood treatment
for poles and beams on bridges do not occur in high traffic areas for bystanders, distribution
utility poles are numerous and often located in residential front yards. The vapor pressure of
sodium fluoride is negligible (i.e., 5.43 x 10"26 mmHg at 25 C), and therefore, no vapor will be
released in the vicinity of treated poles. Additionally, label directions to cap treated holes after
application will minimize any potential for dermal contact. Likewise, groundline treatments are
also covered (i.e., brush-on and wrap treatments are below the groundline and then covered with
dirt) and will minimize potential dermal contact to children playing in areas of treated poles.
Moreover, the results of a field monitoring study of sodium fluoride treated poles found that
outward migration did not exceed 10 cm (i.e., <4 inches) further indicating little to no likelihood
of residential exposure.
d. Occupational Risk Mitigation
i. Handler Risk Mitigation
Occupational handler dermal risks (IT and LT) of concern were identified for the
remedial wood treatment applications of sodium fluoride for several use scenarios (Target MOE
= 100 and 300 respectively). These include the application as a spray (MOEs range from 18 to
26) and as a brush-on treatment (MOEs <1). The dermal risk assessment is considered to be very
conservative because a default dermal absorption assumption of 100% was used to estimate
exposures. The Agency does not expect actual dermal absorption to be significant based on the
chemical attributes of sodium fluoride. To confirm that dermal absorption is significantly lower
than 100% a 90-day dermal toxicity study will be required.
26
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To mitigate the dermal risks of concern for the following steps must be taken:
• All labels will need to include increased levels of PPE including elongated elbow-
length chemical-resistant coverings, face shield and chemical-resistant aprons.
• Equipment for the brush-on applications will be limited to only brushes that have
handles several feet in length to reduce the potential for exposure.
• To confirm the effectiveness of the mitigation measures a dermal exposure study
will need to be conducted.
• Require all labels to include training and passage of company-developed
competency examinations prior to workers handling sodium fluoride products.
These programs are already in place but have not previously been included on
labels;
No inhalation risks of concern were identified in the risk assessment.
The Agency also considered the potential benefits of the use of sodium fluoride in
making its determination. There are limited alternatives available for the remedial treatment of
existing transmission and distribution poles. There are economic benefits associated with the use
of remedial treatments in that they increase the service life of the treated poles thus deferring or
avoiding replacement costs. Additionally, a benefit of remedial treatments is the reduction in the
use of heavy-duty wood preservatives which would be needed to treat replacement poles.
ii. Post-Application Risk Mitigation
Occupational post-application exposure is not anticipated for the antimicrobial uses of
sodium fluoride. The vapor pressure of sodium fluoride is negligible (i.e., 5.43x 10"26 mmHg at
25 °C), and therefore, no vapor will be released in the vicinity of treated poles. Additionally,
label directions to cap treated holes after application will minimize any potential for dermal
contact. Likewise, groundline treatments are also covered (i.e., brush-on and wrap treatments are
below the groundline and then covered with soil)
2. Environmental Risk Management
Because of the use patterns for sodium fluoride, environmental exposure is expected to be
low. In addition, product labels require applicators to follow certain precautions, such as
waterproof wraps and sealed injections into utility poles, to prevent release into the terrestrial or
aquatic environment. Some exposure to woodpeckers and wood boring insects may occur,
however, sodium fluoride is practically nontoxic to avian and aquatic species tested. Any
incidental exposure is not expected to be toxic to non-target species. Therefore, an
environmental risk assessment was not conducted for the sodium fluoride wood treatment uses.
3. Other Labeling Requirements
In order to be eligible for reregi strati on, various use and safety information will be
included in the labeling of all end-use products containing sodium fluoride. For the specific
labeling statements and a list of outstanding data, refer to Section V of this RED document.
27
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4. Listed Species Considerations
a. The Endangered Species Act
Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2), requires all
federal agencies to consult with the National Marine Fisheries Service (NMFS) for marine and
anadromous listed species, or the United States Fish and Wildlife Services (FWS) for listed
wildlife and freshwater organisms, if they are proposing an "action" that may affect listed species
or their designated habitat. Each federal agency is required under the Act to insure that any
action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a
listed species or result in the destruction or adverse modification of designated critical habitat.
To jeopardize the continued existence of a listed species means "to engage in an action that
reasonably would be expected, directly or indirectly, to reduce appreciably the likelihood of both
the survival and recovery of a listed species in the wild by reducing the reproduction, numbers,
or distribution of the species." 50 C.F.R. § 402.02.
To facilitate compliance with the requirements of the Endangered Species Act subsection
(a)(2) the Environmental Protection Agency, Office of Pesticide Programs has established
procedures to evaluate whether a proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed species in the wild by
reducing the reproduction, numbers, or distribution of any listed species (U.S. EPA 2004). After
the Agency's screening-level risk assessment is performed, if any of the Agency's Listed Species
LOG Criteria are exceeded for either direct or indirect effects, a determination is made to identify
if any listed or candidate species may co-occur in the area of the proposed pesticide use. If
determined that listed or candidate species may be present in the proposed use areas, further
biological assessment is undertaken. The extent to which listed species may be at risk then
determines the need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.
For certain use categories, the Agency assumes there will be minimal environmental
exposure, and only a minimal toxicity data set is required (Overview of the Ecological Risk
Assessment Process in the Office of Pesticide Programs U.S. Environmental Protection Agency -
Endangered and Threatened Species Effects Determinations, 1/23/04, Appendix A, Section IIB,
pg.81). Chemicals in these categories therefore do not undergo a full screening-level risk
assessment, and are considered to fall under a "no effect" determination.
This preliminary analysis indicates that current sodium fluoride wood treatment uses are
not likely to enter the environment in sufficient quantities to adversely affect terrestrial or aquatic
species; however, an endangered species effects determination will not be made at this time.
b. General Risk Mitigation
Sodium fluoride end-use products (EPs) may also contain other registered pesticides.
Although the Agency is not proposing any mitigation measures for products containing sodium
fluoride 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
28
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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.
29
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V. What Registrants Need to Do
The Agency has determined that sodium fluoride is eligible for reregi strati on provided
that: (i) additional data that the Agency intends to require confirm this decision; (ii) the risk
mitigation measure outlined in this document is adopted; and (iii) label amendments are made to
reflect this measure. To implement the risk mitigation measures, the registrants must amend
their product labeling to incorporate the label statement set forth in the Label Changes Summary
Table in Section B below (Table 7). The additional data requirements that the Agency intends to
obtain will include, among other things, submission of the following:
For the sodium fluoride technical grade active ingredient products, the registrant needs to
submit the following items:
Within 90 days from receipt of the generic data call-in (DCI):
1. Completed response forms to the generic DCI (i.e., DCI response form and
requirements status and registrant's response form); and
2. Submit any time extension and/or waiver requests with a full written justification.
Within the time limit specified in the generic DCI:
1. Cite any existing generic data which address data requirements or submit new generic
data responding to the DCI.
Please contact Diane Isbell at (703) 308-8154 with questions regarding generic reregi strati on.
By US mail: By express or courier service:
Document Processing Desk
Diane Isbell
Office of Pesticide Programs
(751OP)
U.S. Environmental Protection Agency
1200 Pennsylvania Ave., NW
Washington, DC 20460-0001
Document Processing Desk
Diane Isbell
Office of Pesticide Programs
(751OP)
U.S. Environmental Protection Agency
One Potomac Yard, Room S-4900
2777 South Crystal Drive
Arlington, VA 22202
30
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For end-use products containing sodium fluoride as an active ingredient the registrant needs 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 reregi strati on (EPA Form 8570-1). Indicate on
the form that it is an "application for reregi strati on";
3. Five copies of the draft label incorporating all label amendments outlined in Table 23
of this document;
4. A completed form certifying compliance with data compensation requirements (EPA
Form 8570-34);
5. If applicable, a completed form certifying compliance with cost share offer
requirements (EPA Form 8570-32); and
6. The product-specific data responding to the PDCI.
Please contact Adam Heyward at (703) 308-6422 with questions regarding product reregi strati on
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
Adam Heyward Adam Heyward
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
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A. Manufacturing Use Products
1. Additional Generic Data Requirements
The generic database supporting the reregi strati on of sodium fluoride has been reviewed
and determined to be substantially complete. However, the following additional data
requirements have been identified by the Agency as confirmatory data requirements and will be
included in the generic data call in (DCI) for this RED.
• Dermal toxicity study (90-day) (870.3250)
• Dermal exposure outdoor (875.1100,875.1600)
2. Labeling for Technical and Manufacturing Use Products
To ensure compliance with FIFRA, technical and manufacturing-use product (MP)
labeling should be revised to comply with all current EPA regulations, PR Notices and
applicable policies. The Technical and MP labeling should bear the labeling contained in Table
7, Label Changes Summary Table.
B. End-Use Products
1. Additional Product-Specific 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. The Registrant
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 will be issued at a later date.
2. Labeling for End-Use Products
Labeling changes are necessary to implement measures outlined in Section IV above.
Specific language to incorporate these changes is specified in Table 7, Label Changes Summary
Table.
Registrants may generally distribute and sell products bearing old labels/labeling for 26
months from the date of the issuance of this Reregi strati on Eligibility Decision document.
Persons other than the registrant may generally distribute or sell such products for 52 months
from the approval of labels reflecting the mitigation described in this RED. However, existing
stocks time frames will be established case-by-case, depending on the number of products
involved, the number of label changes, and other factors. Refer to "Existing Stocks of Pesticide
Products; Statement of Policy," Federal Register, Volume 56, No. 123, June 26, 1991.
32
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a. Label Changes Summary Table
In order to be eligible for reregi strati on, all product labels must be amended to
incorporate the risk mitigation measure outlined in Section IV of the sodium fluoride RED. The
following table describes how language on the labels should be amended.
33
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Table 7. Labeling Changes Summary Table
Description
Amended Labeling Language
Placement on Label
All End Use Products
Environmental Hazards
Statements Required by the
RED and Agency Label Policies
"Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans,
or other waters unless in accordance with the requirements of a National Pollution Discharge
Elimination System (NPDES) permit and the permitting authority has been notified in writing
prior to discharge. Do not discharge effluent containing this product to sewer systems without
previously notifying the local sewage treatment plant authority. For guidance contact your
State Water Board or Regional Office of the EPA."
Precautionary
Statements
PPE Requirements
"Applicators must wear chemical resistant gloves and a face shield while handling or applying
sodium fluoride."
"Applicators must wear elongated chemical-resistent sleeves while handling or applying
sodium fluoride."
Immediately
following^elow
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
For all brush-on application
products
"Equipment for the brush-on applications is limited to only brushes that have handles that are
several feet in length."
Directions for Use
Training
"All users must be trained and pass a company-developed competency examination prior to
handling sodium fluoride products"
Directions for Use
34
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VI. APPENDICES
35
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Appendix A
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Wood preservatives
(Exterior use only)
Lumber, timber's, posts,
poles, ties, pilings, and
other wooden members,
all exterior wood exposed
to moisture or weather
Impregnated
materials
Reg: 75341-4
Staples or
tacks
Dig around the ground line
of the pole to be treated to
a depth of approximately
20 inches. Remove
hardened creosote and
rotted wood. Inspect pole
as to remaining
serviceability. Clean the
surface of the pole to be
treated. Measure the
circumference of the pole.
Cut from the roll of
impregnated material the
length needed. Apply to the
pole to the depth of
approximately 18 inches
below ground line, and 2
inches above ground line.
Attach to pole by means of
staples or tacks. Be sure
bandage is pulled tight to
be in close contact with the
wood pole. Back fill and
tamp the earth around the
pole to 2 inches above
original ground line.
Proper use includes the covering of any
exposed product above the groundline in
areas where children or livestock may come
in contact with it.
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Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
(Exterior use only)
Lumber, timber's, posts,
poles, ties, pilings, and
other wooden members,
all exterior wood exposed
to moisture or weather
Ready to use
Reg: 75340-2
Approved
dispenser/
pressurized
applicator
RAILROAD TIES:
Product is to be placed in
the adzed portion of the
railroad tie by approved
dispenser/applicator.
Treated areas should be
completely covered by tie
plate.
STRUCTURAL
TIMBERS: For control of
internal decay, fill decay
pockets and voids using a
grease- gun or other
pressurized applicator. Fill
to refusal. Plug application
holes with secure-fitting
dowels.
(Exterior use only)
Lumber, timber's, posts,
poles, ties, pilings, and
other wooden members,
all exterior wood exposed
to moisture or weather
Ready to use
Reg: 75341-5
Brush or
trowel
EXTERNAL
TREATMENT: Excavate
the soil from the
groundline of the pole for a
depth of 18", or deeper
where specified. Remove
rotted wood. Clean the
surface of the pole to be
treated. Apply by brush or
Application of this product may produce a
strong, lingering unpleasant odor.
37
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Use Site
(Exterior use only)
Lumber, timber's, posts,
poles, ties, pilings, and
Formulation
Pellets/tablets
Reg: 75341-6
Method of
Application
Insertion
Application Rate/ No. of
applications
trowel to a thickness of
l/16"on poles and timber.
Typical application is from
3" above to 18" below
groundline and lower
where deeper decay is
suspected. Application on
poles to be restored should
extend the length of wrap-
around type repair systems.
Wrap the treated area with
water-proof bandage.
INTERNAL
TREATMENT: For control
of internal decay in poles
and other timbers, holes
may be drilled in areas of
the poles or timber where
protection Is required. Fill
drilled holes, decay
pockets, and voids using a
caulking/grease gun. Plug
application holes with
secure-fitting dowels.
Specific number of
preservative cartridges is
dependent on the
Use Limitations
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Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
other wooden members,
all exterior wood exposed
to moisture or weather
volume of wood to be
treated. The recommended
minimum dosage is 39.2
grams per cubic foot of to
be protected.
Drill a hole or holes that
will accommodate the
number of preservative
cartridges needed. After
insertion of the
preservative cartridges, cap
with a wood or plastic
plug, or seal
with a filler such as putty.
(Exterior use only)
Lumber, timber's, posts,
poles, ties, pilings, and
other wooden members,
all exterior wood exposed
to moisture or weather
Soluble
Concentrate
Reg: 75341-
12
Air or
Mechanical
pressure
pump
Stir before using. Dilute 1
gallon of this concentrate
with 1 l/2 gallons of water.
Shake or stir well. Using
air or mechanical pressure
pump, apply solution to
interior cavity of wood
structure through prepared
opening. Apply one gallon
(maximum per cu.ft of
wood) or to refusal.
Application of this product may produce a
strong, lingering unpleasant odor.
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APPENDIX B: Sodium fluoride (case 3132)
Appendix B lists the generic (not product specific) data requirements which support the re-registration of sodium fluoride. These
requirements apply to sodium fluoride in all products, including data requirements for which a technical grade active ingredient is the
test substance.
DATA REQUIREMENT
New
Guideline
Number
Old
Guideline
Number
Study Title
Use
Pattern
CITATION(S)
MRID Number
PRODUCT CHEMISTRY
830.1550
830.1600
830.1620
830.1650
830.1670
830.1700
830.1750
830.1800
830.6302
830.6303
830.6304
830.7200
830.7300
61-1
61-2a
61-2b
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-7
Product Identity and Composition
Starting Materials and Manufacturing Process
Formation of Impurities
Preliminary Analysis
Certification of Limits
Analytical Method
Color
Physical State
Odor
Melting Point
Density
43563101
43563101
43563101
43563101
43563101
43563101
43563101
43563101
43563101
43563101
43563101
40
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DATA REQUIREMENT
New
Guideline
Number
830.7840
830.7860
830.7000
835-2120
Old
Guideline
Number
63-8
63-12
161-1
Study Title
Solubility
PH
Hydrolysis
Use
Pattern
CITATION(S)
MRID Number
43563101
43563101
Open Literature
850.1010
850.1075
850.1075
850.2100
850.2200
850.2200
850.3020
850-3030
72-2
72- la
72-lb
71-1
72-1
72-1
141-1
141-2
Acute Aquatic Invertebrate Toxicity
Fish Acute Toxicity - Freshwater (Bluegill)
Fish Acute Toxicity - Freshwater (Rainbow Trout)
Avian Acute Oral Toxicity Test (Quail)
Avian Dietary Toxicity-quail
Avian Dietary Toxicity-duck
Honey Bee acute contact toxicity
Honey Bee toxicity of residues on foliage
43648203
43648201
43648202
43611501
43593102
43593101
Reserved
Reserved
RESIDUE CHEMISTRY
860.1500
171-4k
Crop Field Trails
Reserved
TOXICOLOGY*
870.1100
81-1
Acute Oral - Rat
162945, 40928201,40932003,
43778501
41
-------
DATA REQUIREMENT
New
Guideline
Number
870.1200
870.1300
870.2400
870.2500
870.2600
870.3100
870.3250
870.3700
870.3700
870.3800
870.4100
870.4200
870.4200
870.4300
870.5100
870.5300
Old
Guideline
Number
81-2
81-3
81-4
81-5
81-6
82-la
82-3
83-3a
83-3b
83-4
83-la
83-2a
83 -2b
83-5
84-2
84-2
Study Title
Acute Dermal - Rabbit
Acute Inhalation - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit
Dermal Sensitization
90-Day Feeding-Rodent
90-Day Dermal Toxicity-Rodent
Developmental Toxicity -Rat
Developmental Toxicity -Non rodent
Reproduction and fertility effects
Chronic Toxicity-Rat
Carcinogenicity-Rat
Carcinogeni city -Mouse
Combined chronic toxicity/ Carcinogenicity
Bacterial Reverse Mutation Assay
Detection of gene mutations in somatic cells
Use
Pattern
CITATION(S)
MRID Number
162946,40928202,40932002,437
78502
43778503
162948,40928204,40932001,412
04001,43778504
162947,40928203,40932004,437
78505
40866801,40866901,43778506
NTP study
Data Gap
Open Literature
Open Literature
Open Literature
Open Literature
Open Literature
NTP study
NTP study
NTP study
NTP study
42
-------
DATA REQUIREMENT
New
Guideline
Number
870.5375
870.5380
870.5385
870.5395
870.5500
870.5550
870.5900
870.5915
870.7485
Old
Guideline
Number
84-2
84-2
84-2
84-2
84-2
84-2
84-2
84-2
85-1
Study Title
In Vitro mammalian chromosome aberration test
Mammalian spermatogonial chromosome aberration
test
Mammalian bone marrow chromosome aberration
test
Mammalian erythrocyte micronucleus test
Bacterial DNA damage or repair test
Unscheduled DNA synthesis in mammalian cell
culture
In Vitro sister chromatid exchange assay
In Vitro sister chromatid exchange assay
General metabolism and pharmokinetics
Use
Pattern
CITATION(S)
MRID Number
NTP study
Open Literature
Open Literature
Open Literature
Open Literature
Open Literature
NTP study
Open Literature
Open Literature
43
-------
Appendix C. Technical Support Documents for Sodium Fluoride
Additional documentation in support of this RED is maintained in the OPP
docket, located in Room 119, Crystal Mall #2, 1801 Bell Street, Arlington, VA. It is open
Monday through Friday, excluding legal holidays, from 8:30 am to 4 pm.
OPP public docket is located in Room S-4400, One Potomac Yard (South Building),
2777 South Crystal Drive, Arlington, VA, 22202 and is open Monday through Friday,
excluding Federal holidays, from 8:30 a.m. to 4:00 p.m.
The docket initially contained the 10/10/2007 preliminary risk assessment and the
related documents. EPA then considered comments on these risk assessments (which are
posted to the e-docket) and revised the risk assessments. The revised risk assessments
will be posted in the docket at the same time as the RED.
All documents, in hard copy form, may be viewed in the OPP docket room or
downloaded or viewed via the Internet at www.regulations.gov
These documents include:
• Sodium fluoride Preliminary Risk Assessment; Notice of Availability,
10/10/2007.
Preliminary Risk Assessment and Supporting Science Documents:
• Sodium Fluoride Risk Assessment for the Reregistration Eligibility Decision
(RED) Document. PC Code: 075202 (active). Case No. 3132, September 30,
2007.
• Revised Occupational and Residential/Bystander Assessment of the Antimicrobial
Use (Remedial Wood Treatment) of Sodium Fluoride for the Reregistration
Eligibility Decision (RED) Document. Case Number 3132. PC Code 075202.
October 1, 2007. Timothy Leighton, Ph.D.
• Environmental Fate Science Chapter on Sodium Fluoride for RED Process. Case
Number 3132. PC Code 075202. September 25, 2007. A. Najm Shamim, Ph.D.
• Sodium Fluoride Toxicology Chapter for the Reregistration Eligibility Decision
(RED) Document. PC Code: 075202. Case No. 3132. September 30, 2007.
Timothy F. McMahon, Ph.D.
• Product Chemistry Science Chapter For: Sodium Fluoride Reregistration
Eligibility Decision (RED). Case Number 3132. PC Code 075202. September
25, 2007. A. Najm Shamim, Ph.D.
• Ecological Hazard and Environmental Risk Assessment Chapter for Sodium
44
-------
Fluoride. Case Number 3132. PC Code 075202. September 25, 2007. Richard
Petrie, Agronomist.
• Sodium Fluoride - Incident Report Summary. Case Number 3132. PC Code
075202. Jonathan Chen, Ph.D. August 3, 2007
45
-------
Appendix D. Citations Considered to be Part of the Data Base Supporting the
Reregistration Decision (Bibliography)
1. MRID Studies
MRID#
162945
162946
162947
162948
40866801
40866901
40928201
40928202
40928203
Citation
Wingard, B. (1984) Acute Oral LD50 Study in Rats Using NG-84:
Study No. 410-1844. Unpublished study prepared by Toxigenics,
Inc. 26 p.
Kreuger, J. (1984). Acute Dermal Toxicity Study in Rabbits Using
NG-84at a Dose Level of 2 Grams per Kilogram of Body Weight:
Study No. 410-1845. Unpublished study prepared by Toxigenics,
Inc. 14p.
Mellon, K. (1984). Primary Dermal Irritation Study in Rabbits
Using NG-84: Study No. 410-1846. Unpublished study prepared
by Toxigenics, Inc. 14 p.
Doyle, G. (1984). Primary Eye Irritation Study in Rabbits Using
NG-84: Study No. 410-1847. Unpublished study prepared by
Toxigenics, Inc. 16 p.
Siglin, J. (1988). Delayed Contact Hypersensitivity Study in
Guinea Pigs with Patox-Lite: Final Report: SLS Study No. 3191.8.
Unpublished study prepared by Springborn Life Sciences, Inc. 24
P-
Siglin, J. (1988). Delayed Contact Hypersensitivity Study in
Guinea Pigs with Adz-Pad (EPA): Final Report: SLS Study No.
3191.9. Unpublished study prepared by Springborn Life Sciences,
Inc. 23 p.
Naas, D. (1988). Acute Oral Toxicity (LD50) Study in Albino Rats
with Copper Naphthenate/Sodium Fluoride Grease: Final Report:
Project No. WIL-127001. Unpublished study prepared by WIL
Research Laboratories, Inc. 21 p.
Naas, D. (1988). Acute Dermal Toxicity (LD50) Study in Albino
Rabbits with Copper Naphthenate/Sodium Fluoride Grease: Final
Report: Project ID WIL-127002. Unpublished study prepared by
WIL research Laboratories, Inc. 29p
Naas, D. (1988). Primary Dermal Irritation Study in Albino
Rabbits with Copper Naphthenate/ Sodium Fluoride Grease: Final
46
-------
40928204
40932001
40932002
40932003
40932004
41204001
43563101
43593101
43593102
43611501
Report: Project IN WIL 127003. Unpublished study prepared by
WIL Research Laboratories, Inc. 17 p.
Naas, D. (1988). Primary Irritation Study in Albino Rats with
Copper Naphthenate/Sodium Fluoride Grease: Final Report:
project ID WIL-127004. Unpublished study prepared by Bioassay
Systems Corp. 19 p.
Goodband , J. (1982). Primary Eye Irritation Test Performed on
Osmoplastic: Project No. 11005. Unpublished study prepared by
Bioassay Laboratories, Inc. 21 p.
Goodband, J. (1982). Acute 14-Day Dermal Range Finding
Determination Performed on Osmoplastic, Batch No. C059:
Project No. 11005. Unpublished study prepared by Bioassay
Systems Corp. lOp.
Goodband, J. (1982). Acute Oral LD50 Determination Performed
on Osmoplastic: Project No. 11005. Unpublished study prepared
by Bioassay Systems Corp. 19p.
Goodband, J. (1982). Primary Dermal Irritation Test Performed on
Osmoplastic: Project No. 11005. Unpublished study prepared by
Bioassay Systems Cor. 12 p.
Naas, D. (1989). Primary Eye Irritation Study in Albino Rabbits
with Patox II: Project ID WIL-127009. Unpublished
Muchow, T. (1994). Product Chemistry Data: Sodium Fluoride.
Unpublished study prepared by Osmose Wood Preserving, Inc. 27
P-
Campbell, S.; Beavers, J. (1995) Osmose Sodium Fluoride: A
Dietary LC50 Study with the Mallard: Lab Project Number: 391-
102. Unpublished study prepared by Wildlife International Ltd. 29
P-
Campbell, S.; Beavers, J. (1995) Osmose Sodium Fluoride: A
Dietary LC50 Study with the Northern Bobwhite: Lab Project
Number: 391-101. Unpublished study prepared by Wildlife
International Ltd. 31 p.
Campbell, S. and J. Beavers. 1995. "Osmose Sodium Fluoride:
An Acute Oral Toxicity Study with the Northern Bobwhite": Lab
Project Number: 391/103. Unpublished study prepared by
Wildlife International Ltd. 31p.
47
-------
43648201
Collins, M. 1995. "Osmose Sodium Fluoride CTM—Acute
Toxicity to Bluegill Sunfish (Lepomis macrochirus) Under Static-
Renewal Conditions": Final Report: Lab Project Number:
94/9/5477; 1325/0594/6102/100. Unpublished study prepared by
Springborn Labs, Inc. 65p.
43648201
43648202
43648202
43648203
43778501
43778502
43778503
Collins, M. 1995. "Osmose Sodium Fluoride CTM—Acute
Toxicity to Bluegill sunfish (Lepomis macrochirus) Under Static-
Renewal Conditions": Final Report: Lab Project Number:
94/9/5477; 1325/0594/6102/100. Unpublished study prepared by
Springborn Labs, Inc. 65p.
Collins, M. 1995. "Osmose Sodium Fluoride CTM—Acute
Toxicity to Rainbow Trout (Oncorhynchus mykiss) Under Static-
Renewal Conditions": Final Report: Lab Project Number:
94/10/5489: 1325/0594/6101/103. Unpublished study prepared by
Springborn Labs, Inc. 64p
Collins, M. 1995. "Osmose Sodium Fluoride CTM—Acute
Toxicity to Rainbow Trout (Oncorhynchus mykiss) Under Static-
Renewal Conditions": Final Report: Lab Project Number:
94/9/5477; 1325/0594/6102/100. Unpublished study prepared by
Springborn Labs, Inc. 65p.
Collins, M. (1995) Osmose Sodium Fluoride CTM-Acute
Toxicity to Daphnids (Daphnia magna) Under Static Conditions:
Final Report: Lab Project Number: 94/9/5480:
1325/0594/6103/110. Unpublished study prepared by Springborn
Labs, Inc. 64 p.
Wnorowski G. (1995). Acute Oral Toxicity Defined LD50 (in
Rats): Composite NaF: Lab Project Number: 3719:P320.
Unpublished study prepared by Product Safety Labs. 28 p.
Wnorowski G. (1995). Acute Dermal Toxicity Limit test (in Rats):
Composite NaF: Lab Project Number: 3722:P322. Unpublished
study prepared by Product Safety Labs. 15 p.
Wnorowski, G. (1995). Acute Inhalation Toxicity Defined LC50
(in Rats): Composite NaF: Lab project Number: 3724:P330.
Unpublished study prepared by Product Safety Labs. 42p.
48
-------
43778504 Wnorowski, G. (1995). Primary Eye Irritation (in Rabbits):
Composite NaF: Lab project Number: 3720:P324. Unpublished
study prepared by product Safety Labs. 26 p.
43778505 Wnorowski, G. (1995). Primary Skin Irritation (in Rabbits):
Composite NaF: Lab Project Number: 3721: P326. Unpublished
study prepared by Product Safety Labs. 16 p.
43778506 Wnorowski, G. (1995). Dermal Sensitization Test-Buehler Method
(in Guinea Pigs): Composite NaF: Lab Project Number: 3723:
P328. Unpublished study prepared by Product Safely Labs. 24 p.
Open Literature
Citation
Aardema MJ, et al. (1989). Sodium Fluoride-Induced Chromosome Aberrations in
Different Stages of the Cell Cycle: A Proposed Mechanism. Mutation Research
223:191-203.
Abukurah AR, Moser AM Jr, Baird CL, et al. 1972. Acute sodium fluoride poisoning.
JAMA 222:816-817.
Agency for Toxic Substances and Disease Registry (ATSDR), 2003. Toxicological
Profile for Fluoride, Hydrogen Fluoride, and Fluorine. U.S. Dept. of Health and
Human Services. Public Health Service.
Albanese. (1987). Sodium Fluoride and Chromosome Damage (In Vitro Human
Lymphocyte and In Vivo Micronucleus Assays). Mutagenesis 2:497-499.
Araibi et al. (1989). The Effect of High Fluoride on the Reproductive Performance of the
Male Rat. J. Biol. Sc. Res. 20:19-20.
Bates et al. (1994). Final report on the developmental toxicity of sodium fluoride (Cas
No. 7681-49-4) in Sprague-Dawley rats. RTI, RTF NC, forNTP (PB95-110193).
Bernstein DS, Sadowsky N, Hegsted DM, et al. 1966. Prevalence of osteoporosis in high-
and low fluoride areas in North Dakota. JAMA 198(5):85-90.
Bohatyrewicz, A. (1999). Effects of Fluoride on Mechanical Properties of Femoral Bone
in Growing Rats. Fluoride 32:47-54.
Camarasa JG, Serra-Baldrich E, Lluch M, et al. 1993. Contact urticaria from sodium
fluoride. Contact Dermatitis 28(5):294.
Caspary, W. et al. (1987). Mutagenic Activity of Fluorides in Mouse Lymphoma Cells.
Mutation Res 187:165-180
49
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Chinoy and Patel. (2001). Effects of Sodium Fluoride and Aluminum Chloride on Ovary
and Uterus of Mice and Their Reversal by Some Antidotes. Fluoride 1:9-20.
Collins, T et al. (1995). Developmental Toxicity of Sodium Fluoride in Rats. Fd Chem
Toxicol 33:951-960.
Collins, T et al. (2001). Developmental Toxicity of Sodium Fluoride Measured During
Multiple Generations. Fd Chem Toxicol 39:867-876.
Collins, T et al. (2001). Multigenerational Evaluation of Sodium Fluoride in Rats. Food
and Chemical Toxicology 39.6:601-13.
De Lopez O et al. (1976). Plasma Fluoride Concentrations in Rats Acutely Poisoned with
Sodium Fluoride. Toxicology and Applied Pharmacology 37:75-83.
Dreisbach, R.H. 1987. Handbook of Poisoning. 12th ed. Norwalk, CT: Appleton and
Lange, p. 217 Cited in Hazardous Substances Data Bank (HSDB) 2007-06-04
Update.
Elbetieha, A et al. (2000). Fertility Effects of Sodium Fluoride in Male Mice. Fluoride
33:128-134.
E. M. Michalenko et al., AWPA, Volume 89, 1993, pp22-50.
Erickson JD. 1978. Mortality in selected cities with fluoridated and non-fluoridated water
supplies. N. Eng J Med 298:1112-1116.
Essman et al. (1981). Histaminergic Mediation of the Response of Rat Skin to Topical
Fluorides. Arch Dermatol Res 21:325-340
Freni SC, Gaylor DW. 1992. International trends in the incidence of bone cancer are not
related to drinking water fluoridation. Cancer 70(3):611-618.
Gelberg KH, Fitzgerald EF, Hwang S-A, et al. 1995. Fluoride exposure and childhood
osteosarcoma: A case-control study. Am J Pub Health 85(12): 1678-1680.
Gocke et al. (1981). Mutagenicity of Cosmetics Ingredients Licensed by the European
Communities. Mutation Research 90.2:91-109.
Gosselin RE, Smith RP, Hodge HC. 1984. Clinical toxicology of commercial products.
5th ed. Baltimore, MD: Williams & Wilkens, 112, 185-193.
Hagan TL, Pasternack M, Scholz GC. 1954. Waterborne fluorides and mortality. Public
Health Rep. 69:450-454.
50
-------
Hall et al. (1977). Kinetic Model of Fluoride Metabolism in the Rabbit. Environmental
Research 13:285-302.
Haworth et al. (1983). Salmonella Mutagenicity Test Results for 250 Chemicals. Env.
Mutagenesis Supplement 1:3-142.
Hayes WJ Jr. 1975. Ingestion of sodium fluoride as roach powder caused 47 deaths in
260 cases in U.S.A. In: Toxicology of pesticides. Baltimore, MD: Williams &
Wilkins, 323.
Heasman MA, Martin AE. 1962. Mortality in areas containing natural fluoride in their
water supplies. Mon Bull Minist Health Public Health Lab Serv 21:150-173.
Hoover etal. 1976.
Heindel, J. et al. (1996). Developmental Toxicity Evaluation of Sodium Fluoride
Administered to Rats and Rabbits in Drinking Water. Fund Applied Toxicol
30:162-177.
Heindel, J. et al. (1996). Developmental Toxicity Evaluation of Sodium Fluoride
Administered to Rats and Rabbits in Drinking Water. Fund Applied Toxicol
30:162-177.
Hoover RN, McKay FW, Fraumeni JF Jr. 1976. Fluoridated drinking water and the
occurrence of cancer. JNatl Cancer Inst 57(4):757-768.
Jansen I, Thomson HM. 1974. Heart deaths and fluoridation. Fluoride 7:52-57.
Khalil A, Da'Dara A. (1994). The Genotoxic and Cytotoxic Activities of Inorganic
Fluoride in Cultured Rat Bone Marrow Cells. Arch Environ Contam Toxicol
26:60-63.
Khalil. (1995). Chromosome Aberrations in Cultured Rat Bone Marrow Cells Treated
with Inorganic Fluorides. Mutation Research 343:67-74.
Leone NC, Leatherwood EC, Petrie IM, et al. 1964. Effect of fluoride on thyroid gland:
Clinical study. J Am Dental Assoc 69:179-180.
Li Y, et al. (1987). Genotoxic Effects of Fluoride Evaluated by Sister-Chromatid
Exchange. Mutation Res 192:191-201.
Li, Dunipace, and Stookey. (1987). Effect of Fluoride on the Mouse Sperm Morphology
Test. J. Dent. Res. 66:1509-1511.
Li, Y., Dunipace, A., Stookey, G. (1987). Absence of Mutagenic and Antimutagenic
Activities of Fluoride in Ames Salmonella Assays. Mutation Res 190:229-236.
51
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Lim et al. (1978). LD50 of SnF2, NaF, and Na2PO3 in the Mouse Compared to the Rat.
Caries Res. 12:177-179.
Luoma H. 1980. Fluoride and magnesium, two ions in the prevention of calcium salt
imbalance, including caries prevention, in man and animals. Proc Finn Dent Soc
76:73-81.
Mahoney MC, Nasca PC, Burnett WS, et al. 1991. Bone cancer incidence rates in New
York State: Time trends and fluoridated drinking water. Am J Public Health
81(4):475-479.
Martin, G. et al. (1979). Lack of Cytogenic Effects in Mice or Mutations in Salmonella
Receiving Sodium Fluoride. Mutation Res 66:159-167.
Maurer et al. (1990). Two-Year Carcinogenicity Study of Sodium Fluoride in Rats. J.
Natl. Cancer Inst. 82:1118-1126.
McGuire SM, Vanable ED, McGuire JA, et al. 1991. Is there a link between fluoridated
water and osteosarcoma? J Am Dent Assoc 122:38-45. NAS, 2006.
Messer et al. Influence of Fluoride Intake on Reproduction in Mice. J. Nutr. 103:1319-
1326.
Mohamed and Chandler. (1982). Cytological Effects of Sodium Fluoride on Mice. Dept.
of Biology and School of Medicine, University of Kansas City, Missouri.
Presented at the 12th I.S.F.R. Conference.
Mullenix et al. (1995). Neurotoxicity of Sodium Fluoride in Rats. Neurotoxicology and
Teratology 17:169-177.
National Academy of Science (NAS). 2006. Fluoride in Drinking Water: A Scientific
Review of EPA's Standards. The National Academies Press. United States.
NTP. 1990. NTP technical report on the toxicology and carcinogenesis studies of sodium
fluoride in F344/N Rats and B6C3F1 mice (drinking water studies). Washington,
DC: Department of Health, Education, and Welfare, National Toxicology
Program. NTP TR 393, NIH publication no. 90-2848.
Oberly et al. (1990). An Evaluation of the CHO/HGPRT Mutation Assay Involving
Suspension Cultures and Soft Agar Cloning: Results for 33 Chemicals.
Environmental and Molecular Mutagenesis 16:260-271.
Pati and Bhunya. (1987). Genotoxic effect of an environmental pollutant, sodium
fluoride, in mammalian in vivo test system. Carylogia 40:79-87.
52
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Paul, V. et al. (1998). Effects of Sodium Fluoride on Locomotor Behavior and a Few
Biochemical Parameters in rats. Environmental Toxicol and Pharmacol 6:187-
191.
Pillai et al. (1987). Acute Toxicity of Fluoride to Mice. Fluoride 20.2:68-70.
Pillai et al. (1988). Effect of Subacute Dosage of Fluoride on Male Mice. Toxicology
Letters 44:21-29.
Ream et al. (1983). Bone Morphology of Weaning Rats from Dams Subjected to
Fluoride. Cell Tissue Res 233:689-691.
Rogot E, Sherrett AR, Feinleib M, et al. 1978. Trends in urban mortality in relation to
fluoridation status. Am JEpidemiol 107:104-112.
Shahshi et al. (1994). Effect of Long-term Administration of Fluoride on Levels of
Protein, Free Amino Acids and RNA in Rabbit Brain. Fluoride 27.3:155-159.
Shivarajashankara et al. (2002). Histological Changes in the Brain of Young Fluoride-
Intoxicated Rats. Fluoride 35:12-21.
Skare J et al. (1986). Lack of DNA-Strand Breaks in rat Testicular Cells after In Vivo
Treatment with Sodium Fluoride. Mutation Res 170:85-92.
Taves DR. 1977. Fluoridation and cancer mortality. In: Origins of human cancer: Book
A: Incidence of cancer in humans. Cold Spring Harbor Conferences on Cell
Proliferation 4:357-366.
Taves DR. 1978. Fluoridation and mortality due to heart disease. Nature 272:361-362.
Tong et al. (1988). The Lack of Genotoxicity of Sodium Fluoride in a Battery of Cellular
Tests. Cell Biology and Toxicology 4.2:173-186.
Toxicology and Carcinogenesis Studies of Sodium Fluoride (CAS No. 7681-49-4) in
F344/N Rats and B6C3F1 Mice (Drinking Water Studies). National Toxicology
Program, Technical Report Series No. 393, NIH Publication No. 91-2848,
December 1990, Pgs. 1-477.
Trabelsi, M et al. (2001). Effect of Fluoride on Thyroid Function and Cerebellar
Development in Mice. Fluoride 34: 165-173.
Tsutsui T, et al. (1984). Sodium Fluoride-Induced Morphological and Neoplastic
Transformation, Chromosome Aberrations, Sister Chromatid Exchanges, and
Unscheduled DNA Synthesis in Cultured Syrian Hamster Embryo Cells. Cancer
Research 44.3:938-941.
53
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Tsutsui, T., N. Suzuki, et al. (1984). Cytotoxicity, Chromosome Aberrations and
Unscheduled DNA Synthesis in Cultured Human Diploid Fibroblasts Induced by
Sodium Fluoride. Mutation Research 139:193-198.
Turner et al. (1995). Fluoride Reduced Bone Strength in Older Rats. J. Dent Res.
74:1475-1481.
Varner, J.A. et al. (1998). Chronic Administration of Aluminum-Fluoride and Sodium
Fluoride to Rats in Drinking Water: Alterations in Neuronal and Cerebrovascular
Integrity. Brain Research 784:284-298.
Water and Wastewater Calculations Manual by Shundarin Lin, McGraw Hill, 2001, pp
461-463.
Zeiger et al. (1994). Cytogenetic Studies of Sodium Fluoride in Mice. Mutagenesis
9:467-471.
2. Website References
Citation
Committee on Fluoride in Drinking Water, National Research Council. Fluoride in
Drinking Water: A Scientific Review of EPA's Standards. The National Academies
Press. Last accessed on July 30, 2007.
http://www.nap.edu/catalog.php7record id=11571#toc
3. Other Supporting Documents
Citation
Handbook of Physics and Chemistry, 74th Edition
Hawley's Condensed Chemical Dictionary, 13th Edition, Editor: Richard Lewis, Sr; John
Wiley Publishers)
Merck Index, 12 Edition.
Personal communication with Bob Butera, Osmose (716-319-3269) and Tim Leighton,
USEPA/OPP/AD (703-305-7435) on April 1, 2004.
USEPA. 2007. Toxicological endpoint selection memorandum.
54
-------
Appendix E. Generic Data Call-In
The Agency intends to issue a Generic Data Call-In at a later date. See Chapter V of the
sodium fluoride RED for a list of studies that the Agency plans to require.
55
-------
Appendix F. Product Specific Data Call-In
The Agency intends to issue a Product Specific Data Call-In for sodium fluoride at a later
date.
56
-------
Appendix G. Batching of sodium fluoride Products for Meeting Acute Toxicity
Data Requirements for Reregistration.
The Agency intends to add at a later date.
57
-------
Appendix H. List of All Registrants Sent the Data Call-In
The Agency intends to add at a later date.
58
-------
Appendix I. List of Available Related Documents and Electronically Available Forms
Pesticide Registration Forms are available at the following EPA internet site:
http://www.epa.gov/opprdOO I/forms/
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.'
If you have any problems accessing these forms, please contact Nicole Williams at (703) 308-
5551 or by e-mail at williams.nicole@epamail.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
8570-27
8570-28
8570-30
8570-32
8570-34
8570-35
8570-36
8570-37
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
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 (in PR
Notice 98-5)
Data Matrix (in PR Notice 98-5)
Summary of the Physical/Chemical Properties (in PR
Notice 98-1)
Self-Certification Statement for the Physical/Chemical
Properties (in PR Notice 98-1)
http://www.epa.sov/opprd001/forms/8570-l.pdf
http://www.epa.sov/opprd001/forms/8570-4.pdf
http://www.epa.sov/opprd001/forms/8570-5.pdf
http://www.epa.sov/opprd001/forms/8570-17.pdf
http://www.epa.sov/opprd001/forms/8570-25.pdf
http://www.epa.sov/opprd001/forms/8570-27.pdf
http://www.epa.sov/opprd001/forms/8570-28.pdf
http://www.epa.sov/opprd001/forms/8570-30.pdf
http://www.epa.sov/opprd001/forms/8570-32.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
5.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
5.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
l.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
l.pdf
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Pesticide Registration Kit
www.epa.gov/pesticides/registrationkit/.
Dear Registrant:
For your convenience, we have assembled an online registration kit that 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) of 1996.
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 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
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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' Web Site
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. Please note that EPA is
currently in the process of updating this booklet to reflect the changes in the registration
program resulting from the passage of the FQPA and the reorganization of the Office of
Pesticide Programs. We anticipate that this publication will become available during the
Fall of 1998.
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 Web site.
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 Web site: http://npic.orst.edu .
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