United States Prevention, Pesticides EPA 738-R-98-023
Environmental Protection And Toxic Substances December 1998
Agency (7508C)
&EPA Reregistration
Eligibility Decision (RED)
Hydramethylnon
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency has completed its
reregi strati on eligibility review and decisions on the pesticide chemical case Pyridinone which
includes the active ingredients Hydramethylnon. The enclosed Reregi strati on Eligibility Decision
(RED), which was approved on September 30, 1998 contains the Agency's evaluation of the data
base of these chemicals, its conclusions of the potential human health and environmental risks of
the current product uses, and its decisions and conditions under which these uses and products
will be eligible for reregistration. The RED includes the data and labeling requirements for
products for reregistration. It may also include requirements for additional data (generic) on the
active ingredients to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary of
Instructions for Responding to the RED." This summary also refers to other enclosed documents
which include further instructions. You must follow all instructions and submit complete and
timely responses. The first set of required responses is due 90 days from the receipt of this
letter. The second set of required responses is due 8 months from the date of this letter.
Complete and timely responses will avoid the Agency taking the enforcement action of suspension
against your products.
Please note that the Food Quality Protection Act of 1996 (FQPA) became effective on
August 3, 1996, amending portions of both pesticide law (FIFRA) and the food and drug law
(FFDCA). This RED takes into account, to the extent currently possible, the new safety standard
set by FQPA for establishing and reassessing tolerances. However, it should be noted that in
continuing to make reregistration determinations during the early stages of FQPA implementation,
EPA recognizes that it will be necessary to make decisions relating to FQPA before the
implementation process is complete. In making these early case-by-case decisions, EPA does not
intend to set broad precedents for the application of FQPA. Rather, these early determinations
will be made on a case-by-case basis and will not bind EPA as it proceeds with further policy
development and any rulemaking that may be required.
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If EPA determines, as a result of this later implementation process, that any of the
determinations described in this RED are no longer appropriate, the Agency will pursue whatever
action may be appropriate, including but not limited to reconsideration of any portion of this
RED.
If you have questions on the product specific data requirements or wish to meet with the
Agency, please contact the Special Review and Reregi strati on Division representative Cynthia
Williams at (703) 308-8195. Address any questions on required generic data to the Special
Review and Reregi strati on Division representative Dean Monos at (703) 308-8074.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregi strati on Division
Enclosures
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SUMMARY OF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISION (RED)
1 DATA CALL-IN (PCI) OR "90-DAY RESPONSE"-If generic data are required for
reregi strati on, a DCI letter will be enclosed describing such data. If product specific data are
required, a DCI letter will be enclosed listing such requirements. If both generic and product
specific data are required, a combined Generic and Product Specific DCI letter will be enclosed
describing such data. However, if you are an end-use product registrant only and have been
granted a generic data exemption (GDE) by EPA, you are being sent only the product specific
response forms (2 forms) with the RED. Registrants responsible for generic data are being sent
response forms for both generic and product specific data requirements (4 forms). You must
submit the appropriate response forms (following the instructions provided) within 90 days
of the receipt of this RED/DCI letter; otherwise, your product may be suspended.
2 TIME EXTENSIONS AND DATA WAIVER REOUESTS-No time extension requests
will be granted for the 90-day response. Time extension requests may be submitted only with
respect to actual data submissions. Requests for time extensions for product specific data should
be submitted in the 90-day response. Requests for data waivers must be submitted as part of the
90-day response. All data waiver and time extension requests must be accompanied by a full
justification. All waivers and time extensions must be granted by EPA in order to go into effect.
3 APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE"-You must
submit the following items for each product within eight months of the date of this letter
(RED issuance date).
a. Application for Reregistration (EPA Form 8570-1). Use only an original application
form. Mark it "Application for Reregistration." Send your Application for Reregistration (along
with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies of draft labeling which complies with the RED and current regulations
and requirements. Only make labeling changes which are required by the RED and current
regulations (40 CFR 156.10) and policies. Submit any other amendments (such as formulation
changes, or labeling changes not related to reregi strati on) separately. You may, but are not
required to, delete uses which the RED says are ineligible for reregistration. For further labeling
guidance, refer to the labeling section of the EPA publication "General Information on Applying
for Registration in the U.S., Second Edition, August 1992" (available from the National Technical
Information Service, publication #PB92-221811; telephone number 703-605-6000).
c. Generic or Product Specific Data Submit all data in a format which complies with
PR Notice 86-5, and/or submit citations of data already submitted and give the EPA identifier
(MRID) numbers. Before citing these studies, you must make sure that they meet the
Agency's acceptance criteria (attached to the DCI).
d Two copies of the Confidential Statement of Formula (CSF) for each basic and
each alternate formulation. The labeling and CSF which you submit for each product must
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comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal concentration.
You have two options for submitting a CSF: (1) accept the standard certified limits (see 40 CFR
§158.175) or (2) provide certified limits that are supported by the analysis of five batches. If you
choose the second option, you must submit or cite the data for the five batches along with a
certification statement as described in 40 CFR §158.175(e). A copy of the CSF is enclosed;
follow the instructions on its back.
e Certification With Respect to Citation of Data and Data Matrix Complete and
sign EPA forms 8570-34 and 8570-35 for each product.
4 COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE-Comments
pertaining to the content of the RED may be submitted to the address shown in the Federal
Register Notice which announces the availability of this RED.
5 WHERE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES)
By U.S. Mail:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
By express:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
Arlington, VA 22202
6. EPA'S REVIEWS—EPA will screen all submissions for completeness; those which are not
complete will be returned with a request for corrections. EPA will try to respond to data waiver
and time extension requests within 60 days. EPA will also try to respond to all 8-month
submissions with a final reregi strati on determination within 14 months after the RED has been
issued.
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REREGISTRATION ELIGIBILITY DECISION
HYDRAMETHYLNON
LIST B
CASE 2585
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TABLE OF CONTENTS
HYDRAMETHYLNON REREGISTRATION ELIGIBILITY DECISION TEAM i
EXECUTIVE SUMMARY v
I. INTRODUCTION 7
II. CASE OVERVIEW 8
A. Chemical Overview 8
B. Use Profile 8
C. Regulatory History 10
III. SCIENCE ASSESSMENT 10
A. Physical Chemistry Assessment 10
B. Human Health Assessment 12
1. Hazard Assessment 12
a. Acute Toxicity 12
b. Subchronic Toxicity 13
c. Chronic Toxicity and Carcinogenicity 16
d. Developmental Toxicity 18
e. Reproductive Toxicity 20
f. Mutagenicity 20
g. Metabolism 22
h. Neurotoxicity 22
i. Dermal Absorption 22
j. Incident Data 22
k. Potential Risks to Infants and Children 23
2. Dose Response Assessment 23
a. Determination of Susceptibility to Infants and Children 23
b. Toxicological Endpoints Selected for Risk Assessment 24
3. Dietary Exposure, Risk Assessment and Characterization 26
a. Dietary Exposure from Food Sources 26
b. Dietary Exposure from Drinking Water 29
c. Dietary Risk Assessment and Characterization 30
4. Occupational and Residential Exposure and Risk Assessment and
Characterization 30
a. Occupational and Residential Exposure 30
b. Post-Application Exposures and Assumptions 31
c. Occupational Handler Exposures 36
d. Residential Handler Exposures 36
5. Other Exposure and Risk Considerations 40
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C. Environmental Assessment 40
1. Ecological Effects 41
a. Toxicity to Terrestrial Animals 41
b. Toxicity to Aquatic Animals 43
c. Toxicity to Aquatic Plants 44
d. Environmental Fate Data 45
e. Environmental Fate Assessment 45
f. Environmental Fate and Transport 46
g. Water Resources 50
2. Exposure and Risk Characterization 52
a. Ecological Exposure and Risk Characterization 54
b. Environmental Risk Characterization 58
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 60
A. Determination of Eligibility 60
B. Determination of Eligibility Decision 61
1. Eligibility Decision 61
2. Eligible and Ineligible Uses 61
3. Tolerance Reassessment 62
4. Tolerance Revocations and Import Tolerances 62
5. Food Quality Protection Act Findings 63
6. Occupational Labeling Rationale/Risk Mitigation 65
7. Endocrine Disrupter Effects 66
8. Environmental Assessment 66
9. Restricted Use Classification 66
10. Endangered Species Statement 66
V. ACTIONS REQUIRED OF REGISTRANTS 67
A. Manufacturing-Use Products 67
1. Additional Generic Data Requirements 67
2. Labeling Requirements for Manufacturing-Use Products 67
B. End-Use Products 67
1. Additional Product-Specific Data Requirements 67
2. Labeling Requirements for End-Use Products 68
C. Tolerance Adjustments 78
D. Existing Stocks 78
VI. APPENDICES 79
A. Table of Use Patterns Subject to Reregistration 81
B. Table of the Generic Data Requirements and Studies Used to Make the
Reregistration Decision 82
C. Citations Considered to be Part of the Data Base Supporting the Reregistration
Decision 87
D. Combined Generic and Product Specific Data Call-In 94
1. Chemical Status Sheets 116
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2. Combined Generic and Product Specific Data Call-In Response Forms
(Insert A) Plus Instructions 118
3. Generic and Product Specific Requirement Status and Registrant's
Response Forms (Insert B) and Instructions 126
4. EPA Batching of End-Use Products for Meeting Data Requirements for
Reregistration 138
5. List of All Registrants Sent This Data Call-In (insert) Notice 141
E. List of Available Related Documents and Electronically Available Forms. 142
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HYDRAMETHYLNON REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis Assessment
Steve Nako
Doug Sutherland
Richard Peacock
Economic Analysis Branch
Herbicide and Insecticide Branch
Science Information Analysis Branch
Environmental Fate and Effects Risk Assessment
Arnet Jones
Gail Maske
Ed Odenkirchen
Mary Frankenberry
Health Effects Risk Assessment
David Hrdy
Steve Knizer
Jack Arthur
Ken Dockter
John Whalen
Registration Support Risk Assessment
Richard Gebken
Marion Johnson
Risk Management
Tom Luminello
Dean Monos
Steve Morrill
Cynthia Williams
Environmental Risk Branch 1
Environmental Risk Branch 1
Environmental Risk Branch 1
Environmental Risk Branch 1
Chemistry and Exposure Branch 2
Risk Characterization and Analysis Branch
Chemistry and Exposure Branch 2
Reregi strati on Branch 2
Toxicology Branch 2
Insecticide Branch
Insecticide Branch
Reregi strati on Branch 3
Reregi strati on Branch 3
Product Reregi strati on Branch
Product Reregi strati on Branch
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GLOSSARY OF TERMS AND ABBREVIATIONS
ADI Acceptable Daily Intake. A now defunct term for reference dose (RfD).
AE Acid Equivalent
a.i. Active Ingredient
ANSI American National Standard Institute
ARC Anticipated Residue Contribution
CAS Chemical Abstracts Service
CI Cation
CNS Central Nervous System
CSF Confidential Statement of Formula
DFR Dislodgeable Foliar Residue
ORES Dietary Risk Evaluation System
DWEL Drinking Water Equivalent Level (D WEL) The DWEL represents a medium specific (i.e. drinking
water) lifetime exposure at which adverse, non carcinogenic health effects are not anticipated to
occur.
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
FAO/WHO Food and Agriculture Organization/World Health Organization
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
FQPA Food Quality Protection Act
FOB Functional Observation Battery
GENEEC GENeric Expected Environmental Concentration. A surface water computer model.
GLC Gas Liquid Chromatography
GM Geometric Mean
GRAS Generally Recognized as Safe as Designated by FDA
HA Health Advisory (HA). The HA values are used as informal guidance to municipalities and other
organizations when emergency spills or contamination situations occur.
HOT Highest Dose Tested
HPLC High Pressure Liquid Chromatography. A type of residue analytical method
LC50 Median Lethal Concentration. A statistically derived concentration of a substance that can be
expected to cause death in 50% of test animals. It is usually expressed as the weight of substance
per weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause death in 50%
of the test animals when administered by the route indicated (oral, dermal, inhalation). It is
expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
LDlo Lethal Dose-low. Lowest Dose at which lethality occurs.
LEL Lowest Effect Level
LOG Level of Concern
LOD Limit of Detection
LOAEL Lowest Observed Adverse Effect Level
LOEL Lowest Observed Effect Level
MATC Maximum Acceptable Toxicant Concentration
MCLG Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulate
contaminants in drinking water under the Safe Drinking Water Act.
ug/g Micrograms Per Gram
ug/L Micrograms per Liter
ill
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mg/L Milligrams Per Liter
MOE Margin of Exposure
MP Manufacturing-Use Product
MPI Maximum Permissible Intake
MRID Master Record Identification (number). EPA's system of recording and tracking studies submitted.
MTD Maximum Tolerated Dose
N/A Not Applicable
NOAEL No Observed Adverse Effect Level
NOEC No Observable Effect Concentration
NOEL No Observed Effect Level
NPDES National Pollutant Discharge Elimination System
OP Organophosphate
OPP Office of Pesticide Programs
Pa Pascal, the pressure exerted by a force of one newton acting on an area of one square meter.
PADI Provisional Acceptable Daily Intake
PAG Pesticide Assessment Guideline
PAM Pesticide Analytical Method
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval
POTW Publicly Owned Treatment Works
ppb Parts Per Billion
PPE Personal Protective Equipment
ppm Parts Per Million
ppt Parts Per Trillion
PRN Pesticide Registration Notice
Q*! The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RBC Red Blood Cell
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose
RS Registration Standard
RUP Restricted Use Pesticide
SCI-GROW A new groundwater detection screening model for vulnerable sites
SLN Special Local Need (Registrations Under Section 24 C of FIFRA)
Tc Transfer coefficients. An exposure parameter.
TC Toxic Concentration. The concentration at which a substance produces a toxic effect.
TD Toxic Dose. The dose at which a substance produces a toxic effect.
TEP Typical End-Use Product
TGAI Technical Grade Active Ingredient
TLC Thin Layer Chromatography
TMRC Theoretical Maximum Residue Contribution
torr A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
WP Wettable Powder
WPS Worker Protection Standard
IV
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EXECUTIVE SUMMARY
The U. S. Environmental Protection Agency (hereafter referred to as "the Agency") has
completed its reregistration eligibility decision of the pesticide active ingredient tetrahydro-5,5-
dimethyl-2(lH)-pyrimidinone(3-(4-(trifluoromethyl)phenyl)-l-(2-(4-(trifluoromethyl)phenyl)ethenyl)-
2-propenylidene)hydrazone, also known as hydramethylnon. This decision includes a comprehensive
reassessment of the required data and the use patterns of all currently registered products.
Hydramethylnon is the active ingredient in the end use products Amdro, Combat, Maxforce,
Sensible, and Siege, which are sold in the United States by the basic producer, American Cyanamid
Company. These products are slow-acting toxicants used primarily to control ants in grasses and
rangelands and other non-crop lands such as lawns, turf, and non-bearing nursery stock.
Hydramethylnon is also registered for the control of household ant species and cockroaches in non-
food use areas in and around domestic dwellings and commercial establishments. The registered
granular formulation may be applied via broadcast or individual mound treatment for imported fire
ant control. For the control of ants and cockroaches in dwellings, the impregnated formulation may
be applied as a bait or as a crack and crevice treatment.
The product Sensible is a subterranean termiticide bait containing 0.3% hydramethylnon and
is intended for use by professional pest control operators as supplemental or alternative treatments
for controlling termites in and around buildings, decks, walls, fences, utility poles, or other wooden
structures which can be attacked by termites. The baits may be placed in or around the structure to
be protected, and may also be placed in the soil beneath concrete slabs, asphalt, paving stones,
landscaping timbers, or other ground coverings.
On August 3, 1996, the President signed the "Food Quality Protection Act of 1996" (FQPA)
which amended the Federal Food Drug and Cosmetic Act (FFDCA) and the Federal Insecticide,
Fungicide and Rodenticide Act (FIFRA). Among other things, the FQPA requires the Agency to
consider the special sensitivity of infants and children to a pesticide, aggregate exposure of a pesticide
from dietary, drinking water and non-occupational exposures, and cumulative effects from other
compounds with a common mode of toxicity when establishing or reassessing tolerances.
Hydramethylnon has established tolerances from use on grasses in pastures and rangeland and
the Agency is proposing to raise the tolerances. However, hydramethylnon is almost completely
metabolized within the body of ruminants and there are no detectable residues in meat, milk, or meat
byproducts. Therefore, per 40 CFR §180.6(a)(3), tolerances are not required for these commodities
even though hydramethylnon is considered a food use pesticide for the purposes of reregistration and
tolerance reassessment.
The Agency has not yet made a determination regarding the common mode/mechanism of
toxicity of hydramethylnon and whether it is appropriate to consider exposure from hydramethylnon
with other compounds in order to address potential cumulative effects. However, based on the
negligible residues from the grass and rangeland use, the unlikelihood of residues in drinking water,
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and minimal residential and occupational exposure, the Agency believes that the contribution of
hydramethylnon exposure to the exposure of other chemicals with a common mode/mechanism of
toxicity is likely to be minimal.
The Agency has also concluded that risk to freshwater and terrestrial nontarget organisms and
water resources will be minimal since hydramethylnon degrades rapidly in water and is of low acute
toxicity to terrestrial non-target species. Therefore, the insecticide uses of hydramethylnon have
been determined to be eligible for reregi strati on. Certain confirmatory data are being required of the
registrant including a reproductive test in birds.
Before reregistering the products containing hydramethylnon, the Agency is requiring that
product specific data, confirmatory ecological effects and environmental fate data, revised
Confidential Statements of Formula (CSF) and revised labeling be submitted within eight months of
the issuance of this document. These data include product chemistry for each registration and acute
toxicity testing. After reviewing these data and any revised labels and finding them acceptable in
accordance with Section 3(c)(5) of FIFRA, the Agency will reregister these products.
VI
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I. INTRODUCTION
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended to
accelerate the reregi strati on of products with active ingredients registered prior to
November 1, 1984. There are five phases to that reregi strati on process. The first four phases of the
process focus on identification of data requirements to support the reregi strati on of an active
ingredient and the generation and submission of data to fulfill the reregistration requirements. The
fifth phase is a review by the U.S. Environmental Protection Agency (hereafter referred to as "the
Agency") of all data submitted to support reregistration.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall determine whether
pesticides containing such active ingredients are eligible for reregistration" before calling in data on
products and either reregistering products or taking "other appropriate regulatory action." Thus,
reregistration involves a thorough review of the scientific data base underlying a pesticide's
registration. The purpose of the Agency's review is to reassess the potential hazards arising from the
currently registered uses of the pesticide; to determine the need for additional data on health and
environmental effects; and to determine whether the pesticide meets the "no unreasonable adverse
effects" criterion of FIFRA.
The Food Quality Protection Act of 1996 (FQPA) amended both the Federal Food, Drug, and
Cosmetic Act (FFDCA) and FIFRA. The FQPA amendments went into effect immediately. Among
other things, FQPA amended the FFDCA by establishing a new safety standard for the establishment
of tolerances. Because hydramethylnon is an insecticide that has tolerances on grasses, it is
considered a food use.
This document presents the Agency's decision regarding the reregistration eligibility of the
registered uses of hydramethylnon. The document consists of six sections. Section I is the
introduction. Section II describes hydramethylnon, its uses, data requirements, and regulatory
history. Section III discusses the human health and environmental assessment based on the data
available to the Agency. Section IV presents the reregistration decision for hydramethylnon. Section
V discusses the reregistration requirements for hydramethylnon. And, Section VI contains the
Appendices which support this Reregistration Eligibility Decision document. Additional details
concerning the Agency's review of applicable data are available on request.
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II.
CASE OVERVIEW
A.
B.
Chemical Overview
The following active ingredient is covered by this Reregi strati on Eligibility Decision:
Common Name:
Chemical Name:
i
Chemical Family:
CAS Registry Number:
OPP Chemical Code:
! Empirical Formula:
! Trade and Other Names:
i
Basic Manufacturer:
Hydramethylnon (ANSI)
Tetrahydro-5,5-dimethyl-2(lH)-pyrimidinone
[3-[4-(trifluoromethyl)phenyl]-l-[2-[4-
trifluoromethyl)phenyl]ethenyl]-2-
propenylidene]hydrazone (CAS)
amidinohydrazone
67485-29-4
118401
C25H24F6N4
Amdro, Combat, Maxforce, Sensible, Siege
American Cyanamid Company
Use Profile
Hydramethylnon is the active ingredient in the end use products, Amdro, Combat,
Maxforce, Sensible, and Siege and sold in the United States by the basic producer, American
Cyanamid, which developed the chemical compound in 1977. Hydramethylnon is a slow
activating stomach toxicant registered for the control of ants in grasses and non-crop lands
such as lawns, turfs, and non-bearing nursery stocks. It is also registered for the control of
ants and cockroaches in non-food use areas in domestic dwellings and commercial
establishments. Hydramethylnon is also registered for control of imported fire ants in areas
of the southern United States where infestations occur. The registered granular formulation
may be applied via broadcast or to individual mounds for ant control. The impregnated
formulation may be applied as a bait to control household ants and cockroaches.
Hydramethylnon is also used for control of subterranean termites in a bait package that is sold
to and only for use by certified Pest Control Operators (PCOs).
Although the Agency no longer differentiates between pasture and rangeland
(Chemistry Science Advisory Council meeting of September 17, 1997) tolerances are
established for residues of the insecticide in or on grass and grass hay (pasture and rangeland
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grasses) at 0.05 ppm (40 CFR § 180.395). Hydramethylnon is formulated as a bait for
control of imported fire ants, harvester ants, and leafcutting ants in rangeland and pastures.
The maximum registered application rate is 0.0176 Ib ai/A.
The following is information on the registered ant, cockroach, and termite uses with
an overview of use sites and application methods. A more detailed table describing the use
parameters is found in Appendix A.
For Hydramethylnon:
Type of Pesticide: Insecticide
Use Sites:
Food: Rangeland grasses, hay and forage.
Nonfood: Indoor and outdoor residential and agricultural areas (including in and around
homes, on lawns, in and around outside buildings^arns, right-of-ways/fencerows/hedgerows,
and uncultivated areas), agricultural crops/soils, indoor and outdoor commercial/industrial or
institutional premises and equipment (including food handling establishments), golf courses,
ornamental sod farms, wood or wood structure treatments. Nonagricultural uncultivated
areas (paths/patios, private roads/sidewalks), ornamental herbaceous plants, ornamental
woody shrubs and vines, ornamental and/or shade trees. Forest trees. Sewage systems
(bottom of manhole cover). Refuse/solid waste containers, commercial transportation
facilities, aircraft or railroad cars (food/feed empty). Animal sleeping quarters/kennels,
poultry houses, eating establishments non-food areas (non-food contact crack and crevice
treatment only), hospitals/medical institutions non critical premises. Indoor residential,
bathroom premises/hard surfaces, households/domestic dwellings.
Target Pests:
ANTS:
Acrobat, Argentine, Bigheaded, Black, Black Carpenter, Black Imported Fire, Carpenter,
Cornfield, Crazy, Grease-Eating, False Honey, Field, Fire, Florida Carpenter, Ghost,
Harvester, Honey, Leafcutting, Little black, Odorous house, Pavement, Pharoah, Pyramid,
Red imported fire, Sweeteating,Thief, Texas leafcutting
Cockroaches: Brownbanded, Wood, Asian, German, American, Smoky Brown, Oriental
Termites: Termites, Subterranean Termites(Coptoermes, Heterotemes, Reticulatehermes)
Other insects: crickets, silverfish, Palmetto Bugs,Waterbugs
Mode of Action: Slow Acting Poison
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C. Regulatory History
Hydramethylnon was first registered in the United States in August 1980 for use as
an insecticide. There is one (1) technical registration and twenty eight (28) end-use products
currently registered with the Agency.
When the accelerated reregi strati on program started after the revisions of FIFRA in
1988, the Agency issued the Phase 2 Data Call-In. The Phase 2 Data Call-In of 1989 focused
largely on obtaining additional toxicology and environmental fate and effects data. In
response, the registrant cited existing data and indicated that certain data requirements were
inapplicable.
In April 1991, in response to the correspondence and data citations or submissions
from American Cyanamid, the Agency issued the Phase 3 Data Call-In. This Call-In required
new or additional product chemistry data; a reduced set of ecological effects and
environmental fate data; toxicology; residue chemistry and worker exposure data to satisfy
the basic reregi strati on database.
The comprehensive Outdoor Residential (Turf) and Agricultural Reentry Data Call-Ins
were issued in March and October 1995, respectively. This Data Call-In required
submission of studies to satisfy the following guideline requirements: foliar residue
dissipation, dermal passive dosimetry exposure, and inhalation passive dosimetry exposure
studies. American Cyanamid is a member of the task force created to submit these data.
American Cyanamid commited to amend their product labels to comply with State
restrictions as outlined in Section V of this RED. The Agency has reviewed these labels and
approved the amended labels on September 30, 1998. American Cyanamid commited to
utilize these new labels on all product produced after December 1998.
This RED will discuss and propose for reregi strati on only currently approved uses.
Additional generic and product-specific data are required for hydramethylnon. In addition
to submitting the required data, the registrants must certify that the suppliers of beginning
chemical materials and the manufacturing processes for the hydramethylnon products have
not changed since the last comprehensive product chemistry review. Alternatively, the
registrants may elect to submit complete updated product chemistry data packages for their
products. The Agency considers these data to be confirmatory and does not expect them to
alter the risk eligibility decision for hydramethylnon presented herein. Appendix B includes
all data requirements identified by the Agency to support reregi strati on.
III. SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
10
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IDENTIFICATION OF ACTIVE INGREDIENT
Hy dramethylnon:
Empirical Formula:
Molecular Weight:
CAS Registry No.:
Shaughnessy No.:
C25H24F6N4
494.50
67485-29-4
118401
Technical hydramethylnon is a yellow to tan crystalline solid with a characteristic
vegetable oil odor and melting point of 189-191° C. It is insoluble in water, slightly soluble
in alcohols, and soluble in acetone, chlorobenzene, and 1,2-dichloroethane. The vapor
pressure is 2xlO"8 mm of Hg @ 25° C. The average partition coefficient (Kow) of
hydramethylnon between n-octanol and water was determined to be 27,965 (Log Kow =
4.45) in MRID 416125-02.
There is one registered hydramethylnon manufacturing-use product (MP) as described
in MRTD 416125-01. The registrant is American Cyanamid Company and the product is a
95% technical formulation (241-270) called Amdro Technical Insecticide.
PRODUCT CHEMISTRY
All pertinent generic and product-specific product chemistry data requirements are
satisfied for the American Cyanamid 95% manufacturing use (technical) product. New data,
guideline requirement 830.7050 (ultra violet/visible absorption for the pure active ingredient)
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is being called-in with this RED.
The generic product chemistry data base will be satisfied if the registrant either
certifies suppliers of beginning materials and manufacturing process for the hydramethylnon
TGAI have not changed since the last comprehensive product chemistry reviews or submits
a complete updated product chemistry data package.
B. Human Health Assessment
1. Hazard Assessment
The toxicology studies reviewed in performing this human health risk assessment
satisfy established guideline requirements for the registration of a food use pesticide. The
hydramethylnon toxicology database is complete and all requirements are satisfied.
a. Acute Toxicity
The Agency has evaluated the acute toxicology data base. The observed effects are
categorized from one to four, with toxicity category one being the most acutely toxic effect
and category four being the least toxic. Table 1 summarizes the results of the acute toxicity
studies for hydramethylnon:
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TABLE 1: ACUTE TOXICITY OF HYDRAMETHYLNON TGAI
Guideline
81-1
81-2
81-3
81-4
81-5
81-6
Study Type
Formulation
Acute Oral, Rats
95% A.I.
Acute Dermal, Rabbits
95% A.I.
Acute Inhalation, Rats
98.2% A.I.
Primary Eye Irritation,
Rabbits
95% A.I.
Primary Skin Irritation,
Rabbits
95% A.I.
Dermal Sensitization,
Guinea Pigs
92% & 3. 2% A.I.
MRID
41612503
41612504
42871101
41612505
41612506
00101560
Results
LD50 = 817 mg/kg (M), 1502 mg/kg (F), 1146 mg/kg
(combined)
Clinical signs included decreased activity, diuresis,
anorexia, ataxia, epistaxis, chromo dacryorrhea and
salivation.
LD50 >2000 mg/kg (limit test)
There was no evidence of toxicity.
2.9 mg/L (combined); 4-hour analytical, whole-body
exposure; Clinical signs included labored breathing,
eye closure, decreased activity, rales, excessive
salivation, yellow material on the fur, and decreased
weight gain.
Moderate corneal irritant; reversed in <7 days
Cornea! opacity and conjunctival redness, chemosis,
and discharge reversed within 7 days.
Hydramethylnon is a moderate irritant.
No irritation, there was no evidence of dermal
irritation or systemic toxicity.
Not a sensitizer.
Toxicity
Category
III
III
IV
III
IV
b. Subchronic Toxicity
In a 90 day feeding study in rats, MRID 00032641, groups of 20 male and
20 female Sprague-Dawley rats were dosed with hydramethylnon in their feed at 0,
50, 100, 200, or 400 ppm (equivalent to 0, 2.5, 5.0, 10.0 or 20.0 mg/kg/day). Due
to significant decreases in body weight gain and food consumption during the first
two weeks of the study at the highest dose (400 ppm, 20 mg/kg/day), this dose level
was reduced to 25 ppm (1.25 mg/kg/day) on study day 15. Thus, the dose levels
tested were 0, 25, 50, 100, or 200 ppm (0, 1.25, 2.5, 5.0, or 10.0 mg/kg/day).
No compound-related clinical signs were observed in any rats. On study day
68, a 50 ppm male was sacrificed moribund, and a 200 ppm (10.0 mg/kg/day) female
died. The 200 ppm female had a blood urea nitrogen (BUN) value 4-fold higher
than that of the controls on day 45. Histopathologic evaluation of this female
revealed nephrocalcinosis and hydronephrosis. The food consumption and body
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weight changes in the 400/25 ppm (equivalent to 20.0/1.25 mg/kg/day) group were
skewed by the fact that they were initially dosed at 400 ppm for two weeks. Their
feed consumption was decreased 27-45% during the first 2 weeks, but soon
approached, and then exceeded, control levels. Their body weights were as much
as 39% and 28% lower than control levels for the males and females, respectively,
during the first weeks of study, with a gradual improvement thereafter.
Compared to controls, food consumption in the 200 ppm (10.0 mg/kg/day)
group was reduced as much as 20% in the males and 19% in the females during the
first weeks of the study, with improvement as the study progressed. Body weights
were as much as 15% lower in males and 13% lower in females. Food consumption
and body weights were normal in the 50 and 100 ppm (2.5 and 5.0 mg/kg/day)
groups. There were no significant group clinical pathology anomalies. The only
dose-related organ weight anomalies were in the testes. Compared to the controls,
absolute testicular weights in the 400/25, 50, 100, or 200 ppm males (equivalent to
20.0/1.25, 2.5, 5.0 or 10.0 mg/kg/day) were decreased 34%, 11%, 34%, or 63%.
The corresponding relative testicular weight losses were 31%, 5%, 32%, and 56%.
The two weeks of dosing at 400 ppm had an effect on the testes in the "low" dose
group. There were no gross lesions in any rats. Testicular atrophy incidence in the
0, 400/25, 50, 100, or 200 ppm males (equivalent to 0, 20.0/1.25, 2.5, 5.0 or 10.0
mg/kg/day) was 0/20, 5/20, 1/20, 5/20, or 20/20, respectively. The single incidence
of atrophy in the 50 ppm (2.5 mg/kg/day) male was congenital (present before
treatment). No other histopathologic lesions were found. The NOAEL was 50
ppm (2.5 mg/kg/day) and the LOAEL was 100 ppm (5.0 mg/kg/day) based on small
soft testes, decreased testicular weights, and testicular atrophy in males, (MRTD
00032641). This study is classified as acceptable and satisfies guideline requirement
82-1 (a) for a 90-day feeding study in rodents.
In a subchronic toxicity study, MRTD 00061794, groups of 4 male and 4
female beagles received gelatin capsules containing hydramethylnon at doses of 0,
3.0, 6.0, or 12.0 mg/kg/day for 91 days. None of the control or low-dose dogs died,
but 3 males and 3 females in the mid-dose died or were sacrificed moribund between
days 27 and 75, and all high-dose dogs were sacrificed moribund between days 27
and 53. The mid and high-dose dogs began refusing their feed after week 2. During
the third week, the dry feed was replaced with canned meat in the mid and high-dose
groups. Decreased food consumption was most pronounced in females. Body
weights in the low, mid, and high-dose groups were decreased as much as 11%,
51%, and 34% in males; and 9%, 42%, and 37% in the females (body weight
decreases were greatest in the mid-dose dogs because they survived longer than the
high-dose dogs).
At month 2, serum glutamic pyruvic transaminase (SGPT) was increased 4
to 8-fold in the three surviving mid-dose males and 4-fold in 2 of the mid-dose
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females, compared to controls. There were no other clinical pathology anomalies.
All mid and high-dose dogs were cachectic at necropsy. Compared to controls, the
increase in absolute liver weights in the low-dose was 13% in males and 5 % in
females. Increase in relative liver weights in the low-dose was 29% in males and
10% in females. Organ weights were not presented for the mid and high-dose dogs.
Considering the small changes in organ weight and the absence of confirmatory
clinical pathology and histopathology, these weight changes are not considered
biologically significant. Microscopic evaluation revealed wasting of muscle and
subcutaneous fat, and testicular atrophy in the mid and high-dose dogs, but normal
tissues in the controls and low-dose dogs.
The 6 mg/kg/day dose caused lethality, as well as decreased food
consumption and body weight gain, increased SGPT, cachexia, wasting of muscle
and subcutaneous fat, and testicular atrophy. The LOAEL was 3 mg/kg/day (the
lowest does tested) based on decreased food consumption and body weight gain;
a NOAEL was not established. This study is classified as acceptable and satisfies
guideline requirement 82-l(b) for a 90-day feeding study in non-rodents.
In a 21-day dermal toxicity study in rabbits, MRTD 00101559, groups of 10
male and 10 female New Zealand White rabbits received a total of 15 repeated
dermal applications of hydramethylnon at doses of 0 (control), 10, 50, or 250
mg/kg/day, 6 hours/day, 5 days/week over a three week period. The occluded doses
were on the clipped skin of the dorsal trunk. The skin of half of each group was
abraded prior to treatment.
A 10 mg/kg/day male died on study day 12 of unknown causes. Gross skin
lesions, which were seen in the control and treated rabbits, included thickening,
crusting, matting, and reddening. Food consumption was depressed as much as
38% and 45% in the high-dose males and females, compared to controls. The high-
dose males and females weighed as much as 8% and 9% less than the controls. The
platelet count in the high-dose females at termination was 54% less than the control
count. Absolute organ weight changes observed in the high-dose male and female
rabbits included decreased heart weights of 12% and 16% and increased liver
weights of 12% and 7%, respectively. Relative organ weight changes observed in
the high-dose male and female rabbits included decreased heart weights of 4% and
8% and increased liver weights of 21% and 17%, respectively. There were no
corresponding clinical chemistry or histopathologic findings to suggest damage to
either of these organs.
Skin lesions observed in the control and treated rabbits included diffuse
acanthosis, hyperkeratosis, sloughing of superficial epidermis, acantholysis,
inflammatory cell infiltration in the dermis, edema, and acute inflammation of the
dermis. These lesions were most frequent in the control rabbits, so a dose-
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relationship could not be defined.
Toxicity observed at the highest dose tested (250 mg/kg/day) included
decreased food consumption in males and females as well as thrombocytopenia (a
persistent decrease in the number of blood platelets that is usually associated with
hemorrhagic conditions) in females. Although thrombocytopenia was observed at
this dose (250 mg/kg/day), it was not considered to be an adverse, or biologically
significant effect because it was seen in the presence of skin irritation in animals
having abraded skins. In addition, alterations in hematological parameters are often
seen in dermal toxicity studies in the presence of skin irritation. Therefore, the 250
mg/kg/day (the highest dos tested), in spite of the presence of this effect, is
considered to be the NOAEL for dermal and systemic toxicity; a LOAEL was not
established. MRID 00101559 is classified as acceptable and satisfies guideline
requirement 82-2 for a 21-dermal toxicity study in rats.
c. Chronic Toxicity and Carcinogenicity
In a 6-month study, MRID 00035529, groups of 4 male and 4 female
beagles dogs received gelatin capsules containing hydramethylnon at doses of 0,
0.33, 1.0, or 3.0 mg/kg/day for 26 weeks. The control group received 120
mg/kg/day of lactose. No dogs died. Dose-related clinical signs included an
increase in the incidence of soft stools, mucoid stools, and diarrhea in the high-dose
dogs. A high-dose male was removed from the study due to anorexia between study
days 42 and 98, and day 120 to termination. Food consumption, body weights,
clinical pathology, ophthalmologic examinations, and histopathology were normal.
Half of the high-dose dogs had yellow-tinged body fat, but this was not considered
to be a toxic effect. The only other dose-related anomalies were increases in
absolute and relative liver weights in the high-dose dogs of both sexes. Compared
to controls, the increases in absolute liver weights at the mid and high-dose were 7%
and 31% in males, and 4% and 11% in females. Compared to controls, the increases
in relative liver weights at the mid and high-dose were 2% and 29% in males, and
7% and 16% in females. In the absence of elevated liver enzymes and
histopathology, these elevated liver weights are considered to be the compensatory
response of healthy livers. The NOAEL was 1.0 mg/kg/day and the LOAEL was
3.0 mg/kg/day, based on increased incidence of soft stools, mucoid stools, and
diarrhea. This study is not a guideline requirement but does provide useful scientific
data.
In a chronic toxicity/carcinogenicity study, MRID 00101565, groups of 50
male and 50 female Charles River CD rats were fed diets containing hydramethylnon
at dose levels of 0, 25, 50, 100, or 200 ppm (0, 1.2, 2.4, 4.9, or 10.0 mg/kg/day in
males, and 0,1.5, 3.0, 6.2, or 12.1 mg/kg/day in females, respectively based on food
consumption) for two years. No compound-related clinical signs were observed.
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Survival was not affected by treatment. Body weights in the males were as much
as 17% less than the controls at 200 ppm, and 5% at 100 ppm. Body weights in the
females were as much as 42% less than the controls at 200 ppm, and 22% at 100
ppm. Body weights were comparable in the other groups. Food consumption was
reduced an average of 7% in the 200 ppm males, and 16% in the 200 ppm females.
The other groups were comparable.
There were no biologically significant clinical pathology anomalies, yet there
were dose-related organ weight anomalies. Absolute testicular weights were
reduced 59% in the 200 ppm males, and 27% in the 100 ppm males. Relative
testicular weights were reduced 51% in the 200 ppm males and 22% in the 100 ppm
males. Testicular weights were comparable in the lower doses. The only compound-
related gross lesions were small and softtestes in the 100 ppm (19/50) and 200 ppm
(42/50) males. Histopathology revealed testicular atrophy in these groups (23/47
and 46/50, respectively). Glomerulonephrosis was greater in the treated males and
females than in the controls, but there was no dose-response relationship.
On May 28, 1998, the Agency's Cancer Peer Review Committee concluded
that the dose levels of 100 ppm in males, and 50 ppm in females were adequate to
assess the carcinogenic potential of hydramethylnon in rats. This conclusion was
based on significant decreases in body weight at higher doses. The statistically
significant increases in tumors observed in the uterus (adenomatous polyps) and
adrenals (medullary adenomas) were not considered to be biologically significant
since they were seen at excessive doses (i.e., at 200 ppm).
Under the conditions of this study, theNOAEL was 50 ppm (2.4 mg/kg/day
in males, 3.0 mg/kg/day in females), and the LOAEL was 100 ppm (4.9 mg/kg/day
in males, 6.2 mg/kg/day in females) based on small, soft testes, decreased testicular
weights, and testicular atrophy in males; and decreased body weight gain in females.
This study is classified as acceptable and satisfies guideline requirement 83-5 for a
chronic feeding/carcinogenicity study in rodents.
In a carcinogenicity study, MRID 00101563, groups of 50 male and 50
female Charles River CD-I mice received diets containing hydramethylnon at dose
levels of 0, 25, 50, 100, or 200 ppm (0, 3.57, 6.93, 14.2, or 28.6 mg/kg/day in
males, and 0, 4.45, 6.87, 17.3, or 33.1 mg/kg/day in females, based on food
consumption) for 18 months. The 200 ppm males and females were sacrificed after
55 weeks because of high mortality. Survival after 18 months at the 50 and 100
ppm doses was 72% and 46% in males, and 66% and 46% in females (compared to
control survival of 86% in males and 76% in females).
Body weights in the 100 and 200 ppm groups were as much as 13% and
23% less than the controls in males, and as much as 6% and 19% less than the
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controls in females, respectively. Food consumption was reduced an average of
14% in the 200 ppm males, and 20% in the 200 ppm females. The other groups
were comparable. There were no compound-related gross lesions. Histopathologic
findings of testicular degeneration in the 50, 100, and 200 ppm males displayed a
dose-related pattern of incidence and severity, and included hypospermia, interstitial
cell hyperplasia of Leydig cells, and germinal cell degeneration. Dose-related
amyloidosis was seen in the kidneys of the 50 and 100 ppm females.
The Cancer Peer Review Committee (CPRC), based on mortality and
toxicity, concluded that a dose between 50 and 100 ppm would be adequate to
assess the carcinogenic potential of hydramethylon in both sexes of mice. The
Committee did not consider the hyperplasia and neoplasia observed in the lungs of
males to be lexicologically/biologically significant because they were seen at an
excessive dose (i.e., at200 ppm). The CPRC, however, did consider the statistically
significant increases in lung adenomas at 50 and 100 ppm (27% and 27%,
respectively) and combined lung adenomas/carcinomas at 25, 50, and 100 ppm
observed in females to be treatment-related and classified hydramethylnon to be
carcinogenic in female mice. For chronic toxicity, in males, the NOAEL was 25
ppm (3.57 mg/kg/day) and the LOAEL was 50 ppm (6.93 mg/kg/day) based on
testicular lesions. In females, the LOAEL was 25 ppm (4.45 mg/kg/day), based on
combined lung adenomas and carcinomas; a NOAEL was not established in females.
This study is classified as acceptable and satisfies guideline requirement 83-2 for a
carcinogenicity study in rodents.
d. Developmental Toxicity
In a prenatal developmental toxicity study, MRID 00061790, groups of 26
pregnant female Sprague-Dawley rats were given oral administration of
hydramethylnon at doses of 0, 3, 10, or 30 mg/kg/day on gestation days 6-15. The
vehicle controls were dosed with corn oil. The dams were sacrificed and examined
on gestation day 20.
There were two maternal deaths in the high-dose, presumably due to
intubation error. The mid-dose dams weighed as much as 8% less than the controls,
and the high-dose dams weighed as much as 16% less than the controls. Body
weight gain during the post-dosing interval (gestation days 15-20) was comparable
in all groups. There was an increased incidence of nasal mucus, alopecia, soft stool,
and staining of the ano-genital fur in the high-dose dams.
The mean number of corpora lutea and implantation sites was comparable
in all groups. The mid-dose dams had slightly more resorption than the other
groups. This is not considered a compound-related effect because the resorption
rate was within historical limits, and because the high-dose and control dams had
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nearly the same resorption rates. At necropsy, several of the mid and high-dose
dams had yellowish discoloration of the fat, and several high-dose dams had small
thymus.
Mean high-dose fetal weights were reduced 10% for both sexes, but the
other groups were comparable. There was no dose-related effect on sex ratios,
external malformations, visceral malformations, or skeletal malformations. Skeletal
variations were generally comparable in all groups, although the high-dose fetuses
had an increase in the incidence of rudimentary structures and \incompletely ossified
supraoccipitals.
For maternal toxicity, the NOAEL was 3 mg/kg/day and the LOAEL was
10 mg/kg/day, based on an 8% decrease in body weight and yellowish discoloration
of the fat. At 30 mg/kg/day, a 16% decrease in maternal body weight, increased
incidence of clinical signs (nasal mucus, alopecia, soft stool, staining of the ano-
genital fur), yellowish discoloration of the fat, and small thymus were observed. For
developmental toxicity, the NOAEL was 10 mg/kg/day and the LOAEL was 30
mg/kg/day, based on decreased mean fetal weights, increased incidence of
rudimentary structures, and increased incidence of incompletely ossified
supraoccipital. This study is classified as acceptable and satisfies guideline
requirement 83-3(a) for a developmental toxicity study in rats.
In a developmental toxicity study, MRTD 00101558, groups of 16
impregnated New Zealand rabbits received oral administration of hydramethylnon
at doses of 0, 5, 10, or 20 mg/kg/day on gestation days 6-18. The vehicle controls
were dosed with corn oil. The does were sacrificed and examined on gestation day
29.
Two high-dose does died during the post-treatment period of undetermined
causes. Six does aborted, 3 each in the mid and high-dose groups. Dose-related
clinical signs seen at the mid and high-dose included soft stool, reduced amount of
stool, and ano-genital matting and discharge. The high-dose body weights were as
much as 12% less than the controls (gestation day 24). The low and mid-dose body
weights were comparable, though slightly less than the controls.
The mean number of implantations, corpora lutea, post-implantation loss,
early or late resorptions, viable fetuses, and sex distribution were comparable in all
groups. The fetal weights in the low, mid, and high-dose groups were 8%, 16%,
and 25% lower than the controls; the low-dose was within historical limits. There
were no biologically significant external, visceral, or skeletal malformations, or
variations.
For maternal toxicity, the LOAEL was 5 mg/kg/day based upon body weight
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loss, soft stool, and reduced amount of stool; a maternal NOAEL was not
established. However, the incidence of soft stool, reduced amount of stool, and
body weight loss of less than 6%, at the low-dose, were not considered adverse. At
10 mg/kg/day, ano-genital matting and discharge was also observed, and the same
findings, with increased severity, were observed at the 20 mg/kg/day dose level. For
developmental toxicity, the NOAEL was 5 mg/kg/day and the LOAEL was 10
mg/kg/day, based upon decreased fetal weight (16%) mg/kg/day. The decreased
fetal weight observed at the 5 mg/kg/day was not considered to be treatment-related
since the incidences were within historical control ranges . This study is classified
as acceptable and satisfies guideline requirement 83-3(b) for a developmental
toxicity study in rabbits.
e. Reproductive Toxicity
In two-generation reproduction study, MRID 43741501, 98.2%
hydramethylnon was administered to Sprague-Dawley rats in their diet at 0, 2, 50,
or 75 ppm (0, 1.66, 3.32 or 5.05 mg/kg/day for males and 0, 2.02, 4.13, or 6.19
mg/kg/day for females) for two successive generations. For reproductive toxicity,
the NOAEL was 25 ppm (1.66 mg/kg/day for males) and the LOAEL was 50 ppm
(3.32 mg/kg/day for males), based upon histological findings in the testes
(degeneration of the germinal epithelium and aspermia) and the epididymides
(increased cellular debris); also at 75 ppm (5.05 mg/kg/day in males), reproductive
performance of the males was decreased, with longer precostal intervals, lower
pregnancy rates, reduced gestation weight gain for females, and smaller litters.
For offspring toxicity, the NOAEL was 75 ppm (highest dose tested); a
LOAEL was not established. This study is classified as acceptable and satisfies
guideline requirement 83-4 for a two-generation reproduction study in rats.
f. Mutagenicity
There are five acceptable mutagenicity (84-2) studies of hydramethylnon.
The findings of adverse effects on spermatocyte and/or spermatogonia in the
dominant lethal assay are consistent with the results of the 2-generation
reproduction study in rats showing that hydramethylnon is a reproductive toxicant
which appears to specifically target the germinal cells and/or tissues in the testes.
Based on the available toxicology data, there is no concern for mutagenicity at this
time. The following studies were evaluated:
Gene Mutations: In a Salmonella typhimurium/Escherichia coll reverse
gene mutation assay, MRID 42132701, both the spot test assay and the plate
incorporation assay are negative up to an insoluble dose (1000 jig/plate with or
without S9 activation) in S.typhimurium TA1535, TA1537, TA98 and TA100 and
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E. coli WP2 uvrA.
In a Schizosaccharomycespombe PI forward gene mutation assay, MRID
40407603, the test is negative up to the highest assayed levels (12.5 |ig/mL -S9; 50
Hg/mL +S9).
Chromosome Aberrations - Somatic Cells: The in vitro cytogenetic assay,
MRID 40422401, in Chinese Hamster Ovary (CHO) cells is negative up to a
cytotoxic dose (500 ng/mL -/+S9).
Chromosome Aberrations - Germinal Cells: The rat dominant lethal assay
MRID 0003 5897, is negative in male Sprague-Dawley rats in which hydramethylnon
was administered by gavage at doses of 3, 30, or 90 mg/kg/day for 5 days. By week
7 of study, 100% of the high-dose (90 mg/kg/day) males were infertile. Infertility
of a few animals was also observed at the mid-dose (30 mg/kg/day). At the high
dose, 50% of these infertile males recovered from this effect (two by week 11 of
study and 3 more by week 17 of study), and at the mid-dose, all of the males
recovered, within 12 weeks. There was no evidence of adverse effects on
implantation data in the high-dose group (90 mg/kg/day) through mating week 5.
At necropsy (week 17), 80% of the high-dose group had smaller testes and
epididymides. There was, however, no indication of a dominant lethal effect at any
dose. Overall, these findings suggest an adverse effect on spermatocyte and/or
spermatogonia.
It is noted that the findings of the rat dominant lethal study, including the
small testes and epididymides at the 90 mg/kg/day dose, are supported by other
study results. Testicular atrophy and/or degeneration was also observed in the 3-
month subchronic (MRID 00032641) and 2-year chronic feeding (MRIDs
00061768, 00101565, 00126106) studies in rats, the 18-month feeding studies in
mice (MRIDs 00035526, 00101563, 40871801), and the 3-month subchronic study
in dogs (MRID 00061794). Results of this dominant lethal study support the effects
seen in the reproductive toxicity study.
Other Mutagenic Mechanisms: In a Saccharomyces cerevisiae D4 mitotic
gene conversion assay, MRID 40407602, the test is negative up to the highest dose
tested (25 jig/plate +/-S9).
The data shows that hydramethylnon is not genotoxic in microbial test
systems or clastogenic in cultured mammalian cells and did not induce dominant
lethality in male rat germinal cells. The mutagenicity studies are classified as
acceptable and satisfy guideline requirements 84-2(a) and (b) and 84-4 for in vivo
and in vitro studies.
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g. Metabolism
In a metabolism study in rats, MRID 42343701, groups of male and female
Sprague-Dawley rats were dosed by gavage with hydramethylnon labeled 14C in
either the phenyl or pyrimidinyl ring. Rats received either a single low-dose (3
mg/kg), a single high-dose (100 mg/kg), or 14 consecutive doses of 2 mg/kg/day
unlabeled test material followed by a single 2 mg/kg dose with the 14C in either ring.
Urinary and fecal samples were collected over 7 days.
The majority of the administered dose of phenyl- or pyrimidinyl- 14C-
hydramethylnon was recovered in the feces (85-98%). Recovery in the urine was
minimal (1-2% of the administered dose). There were no sex or dose-related
differences in urinary or fecal elimination. Radiolabel retention in the tissues was
somewhat greater in the females. Distribution of the residues retained by all tissues
accounted for < 10% of the administered dose, with most of the radiolabeled material
accumulating in the carcass. Most of the radioactivity (94-99%) in the feces was
unchanged parent compound. In contrast, the urine contained traces of parent
compound and polar metabolites which may be benzoate, cinnamate, or
pyrimidinone derivates. Polar metabolites in the tissue were probably ketone,
pyrimidinone, cinnamate, and benzoate derivatives.
h. Neurotoxicity
Neurotoxicity studies are not required since hydramethylnon is neither an
organophosphate nor is structurally related to compounds that are known to induce
neurotoxicity.
i. Dermal Absorption
There are no acceptable dermal absorption data for the technical product.
Dermal absorption studies are available with the formulated gel product.
In one study, MRID 42989101, Sprague-Dawley rats received dermal
application of a gel formulation containing 2% a.i. (Max/orce Gel). The total dose
absorbed after 10 hours was 0.414%). In an another study, MRID 43093901,
Sprague-Dawley rats received dermal application of a gel formulation containing
2.16% a.i. (Siege). The total dose absorbed after 10 hours was 0.97%.
Based on the results of these two studies, the Toxicology Endpoint Selection
Committee determined a dermal absorption factor of 1% for use in risk assessments.
j. Incident Data
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There is no verified information available on human incidents related to use
of hydramethylnon from any of the available data bases consulted by the Agency.
There was a reported incident in 1998 involving the deaths of 17 chickens that may
have been caused by hydramethylnon. Like other baits placed inside and outside
homes, young children and pets are curious about them and tempted to handle or
bite the baits. However, hydramethylnon's relatively low acute toxicity combined
with the current voluntary use of child-resistant packaging reduces the hazard to a
minimum.
k. Potential Risks to Infants and Children
Hydramethylnon is considered a food use pesticide yet, infants and children
have little or no exposure to residues in milk, meat and meat byproducts. Currently,
the terminal residue to be regulated in the milk, meat, and meat byproducts of
ruminants is hydramethylnon per se. The Agency has determined that there is no
reasonable expectation of finite hydramethylnon residues of concern in the milk,
meat, and meat byproducts of ruminants [40 CFR §180.6(a)(3)] as a result of
hydramethylnon use on pastures or rangeland grasses. Hydramethylnon has one
non-food aquatic use site but since it rapidly hydrolyzes, drinking water exposure
is not likely. Consumer use in residential settings is the greatest source of possible
exposure to children, which as discussed above, is expected to be minimal.
2. Dose Response Assessment
a. Determination of Susceptibility to Infants and Children
The Reference Dose Committee made the following FQPA recommendations
and conclusions:
The Agency has reviewed an acceptable two-generation reproduction study
in rats and acceptable prenatal developmental toxicity studies in rats and rabbits.
There are no data gaps for the assessment of pre- and/or postnatal toxicity in rats
or rabbits.
The data provided no indication of increased sensitivity in rats or rabbits to
pre- and/or postnatal exposure to hydramethylnon. In the two-generation
reproduction study in rats, no toxicity to the offspring was observed at any dietary
level tested, while reproductive toxicity was produced in the parental animals at
dietary levels as low as 3.32 mg/kg/day. In the prenatal developmental toxicity
studies in rats and rabbits, gavage doses of hydramethylnon during the major period
of organogenesis resulted in delays in fetal development (retardation in skeletal
ossification and/or decreased fetal body weight). However, these effects were seen
only at doses which were maternally toxic (as evidenced by body weight loss and
23
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clinical signs of toxicity).
There is no evidence in the prenatal developmental toxicity studies in either
rats or rabbits of alterations to central nervous system development, nor is there any
indication of neurotoxicity in the other short or long-term oral studies in rats, mice,
or dogs. This chemical is a male reproductive toxicant which appears to specifically
target the germinal cells and/or tissues in the testes.
The data base for developmental and reproductive toxicity is largely
complete. An assessment of these data did not reveal evidence of an increased
sensitivity of perinatal animals to pre- and/or postnatal exposure to hydramethylnon.
Therefore, the lOx safety factor for protection of infants and children, as
required by FQPA, is not warranted and has been removed.
b. Toxicological Endpoints Selected for Risk Assessment
Acute Dietary
An acute dietary risk assessment is not required because studies indicate an
insignificant toxicological result from acute exposure to hydramethylnon. In
addition, no appropriate endpoint attributable to a single exposure (dose) could be
ascertained from the available oral toxicity studies, as determined in the July 7,
1993, Toxicology Endpoint Selection document.
Chronic Reference Dose
The Reference Dose Committee recommended that a Reference Dose
(RfD) for hydramethylnon be established on the basis of the chronic toxicity study
in dogs, MRID 00035529, and the two generation reproduction study in rats MRID
43741501.
The NOAEL for systemic toxicity in the chronic dog study was 1 mg/kg/day
based on an increased incidence of soft stool, mucoid stool, and diarrhea observed
at 3 mg/kg/day. The NOAEL for reproductive toxicity in the 2-generation rat
reproduction study was 25 ppm (1.66 mg/kg/day for males), and the reproductive
LOAEL was 50 ppm (3.32 mg/kg/day for males), based upon histological findings
in the testes (degeneration of the germinal epithelium and aspermia) and the
epididymides (increased cellular debris). At 75 ppm (5.05 mg/kg/day in males),
reproductive performance of the males was decreased, with longer precoital
intervals; and, there were lower pregnancy rates, reduced gestation weight gain for
females, and there were smaller litters.
An uncertainty factor of 100 was applied to account for interspecies
24
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extrapolation (10) and intra species variability (10). On this basis the RfD was
calculated to be 0.01 mg/kg/day.
Short Term Occupational and Residential (1-7 days)
The NOAEL established in the 21-day dermal toxicity study in rabbits,
MRID 00101559, will be used for this risk assessment.
A NOAEL of 250 mg/kg/day was established, based on nonadverse
decreased food consumption in males and females, and thrombocytopenia in females.
Although thrombocytopenia was observed at this dose (250 mg/kg/day), it was not
considered to be an adverse, or biologically significant, effect because it was seen
in the presence of skin irritation in animals having abraded skins. In addition,
alterations in hematological parameters are often seen in dermal toxicity studies in
the presence of skin irritation. Therefore, this dose, in spite of the presence of this
effect, is considered to be the NOAEL.
Intermediate Term Occupational and Residential (1 week to several months)
The NOAEL of 250 mg/kg/day in a 21-day dermal toxicity study in rabbits,
MRID 00101559, will be used for this risk assessment. Effects observed at the
NOAEL included decreased food consumption in males and females, and
thrombocytopenia in females; however, this latter effects not considered to be
adverse or biologically significant as previously stated.
Long-Term Occupational and Residential (several months to lifetime)
Based on the current use pattern the Agency does not believe chronic
exposure is likely. However, the Reference Dose Committee recommended the use
of a NOAEL of 1 mg/kg/day in the event that there is chronic exposure. The use
of a dermal absorption factor of 1% is necessary for this assessment since an oral
NOAEL was selected. This NOAEL was used to derive the Reference Dose.
Dermal Absorption
There are no dermal absorption data for the technical product. As discussed
earlier, a dermal absorption of 1% was estimated based on the results of two dermal
absorption studies with a formulation product.
Inhalation Exposure (any time period)
The acute 4-hour whole-body LC50 in rats is 2.9 mg/L for the combined
sexes (Table 1). This exceeds the limit concentration of 2 mg/L, and places
25
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hydramethylnon into Toxicity Category IV. Therefore, a risk assessment for the
inhalation route of exposure is not required. In addition, based on the low toxicity,
minimal use (maximum of 4 applications per year) and the methods of application,
there is negligible concern for potential exposure. Therefore an inhalation risk
assessment.
Classification of Carcinogenic Potential
The Cancer Peer Review Committee determined that hydramethylnon should
be classified as a Group C carcinogen, a possible human carcinogen, and
recommended that, for the purpose of risk characterization, the Reference Dose
approach should be used for quantification of human risk. This classification was
based upon statistically significant increases in lung adenomas at 50 and 100 ppm
(27% and 27%, respectively) and combined lung adenomas/carcinomas at 25, 50,
and 100 ppm (32%, 40%, and 35%, respectively) in female mice. The MTD is
between 50 ppm and 100 ppm in both sexes of mice.
Based on the Agency's Cancer Peer Review Committee recommendation that
the RfD approach be used, a quantitative dietary cancer risk assessment was not
performed. Dietary risk concerns due to long-term consumption of hydramethylnon
residues are adequately addressed by the Dietary Risk Evaluation System (ORES)
chronic exposure analysis using the RfD.
3. Dietary Exposure, Risk Assessment and Characterization
a. Dietary Exposure from Food Sources
GLN 860.1200: Directions for Use
The reregi strati on of hydramethylnon in the United States is being supported
by American Cyanamid Company. An Agency database search identified five
end-use products (EPs) with food/feed uses registered to American Cyanamid
Company. The sole hydramethylnon food site being supported for reregistration is
use on grass in pastures and rangelands. The application of hydramethylnon as a
bait in domestic dwellings and commercial establishments has been determined to
be a non-food use.
The conclusions regarding the reregistration eligibility decision of
hydramethylnon food/feed uses are based on the use patterns registered by the basic
producer/technical registrant, American Cyanamid Company.
26
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GLN 860.1300: Nature of the Residue - Plants
The reregi strati on requirements for plant metabolism are fulfilled. An
acceptable study, MRID 437445-01, depicting the qualitative nature of the residue
in grasses has been submitted and evaluated. The Agency's Metabolism Committee
has determined that hydramethylnon is the terminal residue (the final residue of
concern) to be regulated in/on plants. The current tolerance values for grasses must
be amended due to the zero day pre-grazing interval because hydramethylnon is used
on grasses for forage or hay.
GLN 860.1300: Nature of the Residue - Animals
The reregistration requirements for animal metabolism are fulfilled. An
acceptable ruminant metabolism study, MRID 428711-02, has been submitted and
evaluated. The terminal residue to be regulated in the milk, meat, and meat
byproducts of ruminants is hydramethylnon per se. The Metabolism Committee
previously determined that there is no reasonable expectation of finite
hydramethylnon residues of concern in the milk, meat, and meat byproducts of
ruminants [40 CFR §180.6(a)(3)] as a result of hydramethylnon use on grasses.
Therefore, tolerances for these animal commodities need not be established. A
poultry metabolism study is not required at this time because there are no poultry
feed items associated with grasses.
GLN 860.1340: Residue Analytical Method
The reregistration requirements for residue analytical methods are fulfilled.
Adequate methodology determined in MRTDs 00034020, 00034021 and 00034025,
is available for the enforcement of tolerances for residues of hydramethylnon per se
in/on plant commodities.
The Pesticide Analytical Manual (PAM) Vol. II lists a gas liquid
chromatography method with electron capture detection (GLC/ECD) for the
analysis of hydramethylnon residues in/on grass commodities (Pesticide Reg. Sec
180.395). The PAM Vol. II method, designated as Method I, has a detection limit
of 0.05 ppm. The Agency has forwarded to FDA a confirmatory high pressure
liquid chromatography (UPLC) method (American Cyanamid Method M2334) for
inclusion in PAM Vol. II as a lettered method. Method M2334 determines residues
of hydramethylnon per se in/on grass commodities, and has a detection limit of 0.05
ppm. Method M2334 has undergone successful independent laboratory validation.
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GLN 860.1340: Residue Analytical Method-Animals
Tolerances for animal commodities are not needed at this time. Therefore,
no analytical methodology is required for the determination of hydramethylnon
residues to be regulated in animal commodities.
GLN 860.1360: Multi-residue Method
The FDA PESTD AT A database of January 1994 (P AM Volume I, Appendix
I) indicates that recovery of hydramethylnon using multi-residue methods is unlikely.
GLN 860.1380: Storage Stability
The reregistration requirements for storage stability data are fulfilled. The
available storage stability data, MRIDs 428711-02,434852-01,436367-02,437445-
01, indicate that fortified residues of hydramethylnon per se are stable in/on grass
forage and hay for up to 24 months of frozen storage. Field trial samples of grass
forage and hay were stored frozen for up to 19 months.
GLN 860.1400: Water. Fish, and Irrigated Crops
Hydramethylnon is presently not registered for direct use on potable water
and aquatic food and feed crops. Therefore, residue chemistry data are not required
under these guideline topics.
GLN 860.1460: Food-Handling
The Agency has determined that the registered crack and crevice treatment
of hydramethylnon for the control of cockroaches in residential settings and food-
handling establishments is a non-food use. Therefore, data depicting magnitude of
the residue in food-handling establishments are not required for reregistration
purposes. Hydramethylnon is relatively non-volatile and is used only in enclosed
bait stations, therefore, the likelihood of residue transfer to food is low.
GLN 860.1480: Meat. Milk. Poultry, and Eggs
The reregistration requirements for data on magnitude of the residue in
animals are fulfilled. An acceptable cattle feeding study is available. However, the
Agency's Metabolism Committee has determined that from the currently registered
uses there are no reasonable expectations of finite hydramethylnon residues of
concern in milk, meat, and meat byproducts of ruminants [40 CFR §180.6(a)(3)].
Therefore, tolerances for these animal commodities need not be established. A
poultry feeding study is not required at this time because there are no poultry feed
28
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items associated with grasses.
GLN 860.1500: Crop Field Trials
Adequate grass field trial data for the areas infested by the imported fire ants
(Alabama, Arkansas, Florida, Georgia, Louisiana, Mississippi, North Carolina,
Oklahoma, South Carolina, Tennessee, Texas, and Virginia) have been submitted
and evaluated. Use on pastures and rangelands are permitted in these states only.
These data indicate that residues of hydramethylnon per se will exceed the
established tolerance following applications of a representative granular formulation
according to the parameters of use patterns which the registrant wishes to support.
Therefore, the tolerance levels are being increased. The reregi strati on requirements
for magnitude of the residue in/on grass forage and hay will be considered fulfilled
pending compliance by the registrant with the recommended label amendments and
tolerance proposals.
GLN 860.1520: Processed Food/Feed
Table 1, "Raw Agricultural and Processed Commodities and Feedstuffs
Derived From Crops," of OPPTS GLN 860.1000, states that there are no processed
commodities associated with grasses. Therefore, hydramethylnon processing data
are not required for reregi strati on. There is no need for an anticipated residue
calculation at this time.
GLNs 860.1850 and 860.1900: Confined/Field Accumulation in Rotational
Crops
Grasses are not typically rotated. Therefore, no residue chemistry data are
required under these guideline topics.
b. Dietary Exposure from Drinking Water
The Agency has considered registered uses and the available data on
hydramethylnon persistence and mobility. The Agency has determined, through a
qualitative risk assessment, that hydramethylnon will not significantly impact water
resources through labeled uses. In addition, hydramethylnon's physical and chemical
characteristics (i.e., insoluble in water, volatile, etc.) are such that it is unlikely to
impact water resources. In light of these findings, the Agency does not believe that
hydramethylnon poses a threat to human health through drinking water and that a
quantitative drinking water risk assessment is not warranted for this pesticide.
c. Dietary Risk Assessment and Characterization
29
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The food crop use which is being supported for reregi strati on is grasses
rangeland forage and hay. These uses have all been designated as food uses, based
on the application methods and OPPTS policy GLN 180.1000, and have tolerances.
Since these crops are not direct human foods and no dietary consumption is
expected there is no likelihood of residues of hydramethylnon being found through
transfer of residues on grasses to meat and milk. Therefore, a dietary risk
assessment is not necessary.
4. Occupational and Residential Exposure and Risk Assessment and
Characterization
a. Occupational and Residential Exposure
Summary of Use Patterns and Formulations
Formulation: Hydramethylnon, is an insecticide used to control various ant
species, cockroaches, and subterranean termites. It is the active ingredient in end-
use products formulated as a granular (concentration ranging from 0.73% to 1.0%),
liquid-ready-to-use gel (concentration ranging from 2.00% to 2.15%), and solid bait
(concentration ranging from 0.5% to 2.0%). Hydramethylnon end-use products are
employed in the following uses/sites:
Occupational and residential: Indoor residential use includes inside
domestic dwellings, including use on bathroom hard surfaces, garbage cans, and
other solid waste refuge sites within the dwellings. An indoor use on medical
institution premises also exists.
Outdoor residential use includes the following uses on and around domestic
dwellings, including garbage cans; ornamental trees, plants, lawns, shrubs and vines;
patios; sidewalks; and private roads. Terrestrial feed crops include grasses.
Terrestrial non-food crops include use on agricultural crops/soils; uncultivated areas;
golf course turf; outside commercial, institutional andindustrial premises; protection
of seasoned forest products; ornamental trees, plants, lawns, shrubs and vines; sod
farm turf; patios; paved roads; sidewalks; and recreational areas. Aquatic non-food
industrial use includes use in sewage systems.
Occupational use and/or residential use products: End-use products
containing the active ingredient hydramethylnon are marketed for both occupational
and residential use. Occupational use can range from large scale aerial application
of granular formulations for imported fire ant control to application of small dabs
of a ready-to-use gel injected into cracks and crevices for cockroach treatment.
30
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Residential use can take the form of small scale application of the granular
formulation with a hand held or push-type spreader, spoon, or scoop, or the
application of gel to cracks and crevices. Residential use also commonly includes
the strategic placement of hydramethylnon in self-contained, enclosed-bait discs
around the residence. The gel formulation is also used on the bottoms of man hole
covers.
Handler exposures and assumptions: The Agency has determined that
there is potential for exposures to loaders, applicators, and other handlers during
usual occupational and residential use-patterns associated with hydramethylnon.
Based on currently registered use patterns, eight major exposure scenarios were
identified for hydramethylnon handlers: 1) loading granular for aerial application;
2) application of granular by fixed-wing aircraft; 3) flagging for granular aerial
application; 4) loading and application of granular by tractor-drawn, drop-type
spreader; 5) hand distribution of granular bait; 6) loading and application of granular
by hand-held rotary spreader; 7) loading and application of granular by push-type
spreader; and, 8) hand application of gel from syringe-type container/applicator. A
ninth exposure scenario for the occupational and residential handling of self-
contained, child-resistant ant and roach bait discs was not included because
negligible exposure was expected from this activity. A tenth exposure scenario for
the occupational handling of tamper-proof termite bait stations (product is labeled
for sale to PCOs only) is also not included. The exposure from handling this solid
product is considered negligible with much less potential exposure than the handling
of granular products under scenario 5 (above).
b. Post-Application Exposures and Assumptions
Occupational and Residential Risk Assessment/Characterization
Risk from Dermal and Inhalation Exposures
Risk from Handler Exposure
Short-term and intermediate-term dermal exposure assessments using the
Pesticide Handlers Exposure Database (PHED) Version 1.1 surrogate data and
baseline risk calculations for occupational handlers are presented in Table 2.
Applicable exposure scenarios for residential handlers are represented by scenarios
5, 6, and 7 in Table 2 and scenario 8 as described below. Table 2 summarizes the
parameters specific to each exposure scenario and corresponding risk assessment.
31
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Table 2. EXPOSURE SCENARIO DESCRIPTIONS FOR USES OF HYDRAMETHYLNON
Exposure Scenario
(Number)
Data
Source
Standard
Assumptions3
(8-hr work
day)
Comments
Loader Descriptors
Loading Granular
Formulations (1)
PHED
VI. 1
300 acres for
aerial
applications
Baseline: "Best Available" grades: Hands = all grades; dermal = ABC grades. Hands = 10
replicates; Dermal = 33 to 78 replicates. Low confidence in dermal data.
PHED data used for baseline, no Protection Factors (PFs) were necessary.
Applicator Descriptors
Apply Granular Bait by
Fixed-wing Aircraft
(Enclosed Cockpit) (2)
PHED
VI. 1
300 acres
Engineering Controls: "Best Available" grades: Hands = all grades; dermal = C grade.
Hands = 4 replicates; dermal = 0 to 13 replicates. Low confidence in dermal data.
A 50% Protection Factor (PF) was applied to the total deposition data to represent a single
layer of clothing.
Flagger Descriptors
Flagging for Aerial
Application of Granular
Bait (3)
PHED
VI. 1
300 acres
Baseline: "Best Available" grades: Hands all grades; dermal = ABC grades. Hands = 4
replicates; Dermal = 16 to 20 replicates. Low confidence in dermal data.
A 50% PF was applied to the total deposition data to represent single layer of clothing.
Loader/Applicator Descriptors
32
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Exposure Scenario
(Number)
Data
Source
Standard
Assumptions3
(8-hr work
day)
Comments
Load/Apply Granular
Bait Using Drop-Type
Tractor-Drawn Spreader
(4)
PHED
VI.1
100 acres
Baseline Granular Loader: "Best Available" grades: Hands all grades; dermal = ABC
grades. Hands = 10 replicates; Dermal = 33 to 78 replicates. Low confidence in dermal data.
PHED data used for baseline, no PFs were necessary. Note: The loader data were combined
with the applicator data for a combined exposure.
Baseline Granular Spreader: "Best Available" grades: Hands and dermal acceptable
grades. Hands = 5 replicates; Dermal = 1 to 5 replicates. Low confidence in dermal data.
PHED data used for baseline, no PFs were necessary. Note: The applicator data were
combined with the loader data for a combined exposure.
Hand Apply Granular
Bait (5)
PHED
VI.1
(R) 1,000ft2
(O) 5,000ft2
Baseline: "Best Available" grades: Hand and dermal ABC grades. Hands = 15 replicates;
Dermal = 16 replicates. Low confidence in dermal data.
A no glove hand exposure value was back-calculated from the glove data for baseline dermal
exposure.
Load/Apply Granular
Bait Using Handheld
Rotary Spreader (6)
PHED
VI.1
(R) 1 acre
(O) 1 acre
Baseline: "Best Available" grades: Hands and dermal = ABC grades. Hands = 23
replicates; dermal = 29 to 45 replicates. Medium confidence in dermal data.
PHED data used for baseline, no PFs were necessary.
Load/Apply Granular
Bait Using Push-Type
Granular Spreader (7)
PHED
VI.1
(R) 1 acre
(O) 5 acres
Baseline: "Best Available" grades: Hands and dermal = ABC grades. Hands = 15
replicates; dermal = 0 to 15 replicates. Low confidence in dermal data.
PHED data used for baseline, no PFs were necessary.
Hand Apply Gel by
Syringe (8)
No Data
No Data
No Data
(R) Residential (O) Occupational
33
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Standard Assumptions based on an 8-hour work day as estimated by the Agency, except for scenarios 1 through
4. Assumptions for scenarios 1 through 4 are from information supplied to the Agency by the registrant.
Baseline dermal exposure is based on the worker wearing long pants, long sleeve shirt, and no gloves; and, if
applicable, employing open loading techniques and an open cab tractor. Where indicated, for some PHED data,
correction factors have been applied to arrive at these baseline scenarios.
"Best Available" grades are defined by the Agency for meeting Subdivision U Guidelines. Best available grades
are assigned as follows: matrices with grades A and B data and a minimum of 15 replicates; if not available,
then grades A, B, and C data and a minimum of 15 replicates; if not available, then all data regardless of the
quality and number of replicates. Data confidence are assigned as follows:
High = grades A and B and 15 or more replicates per body part.
Medium = grades A, B, and C and 15 or more replicates per body part.
Low = grades A, B, C, D, and E or any combination of grades with less than 15 replicates.
Table 3: BASELINE SHORT-TERM AND INTERMEDIATE-TERM EXPOSURE AND
RISK ASSESSMENTS FOR HYDRAMETHYLNON
Exposure
Scenario
Baseline
Dermal Unit
Exposure
(mg/lb ai)a
Maximum
Application
Rate
(Ib ai/acre)b
Maximum
Acres/Day0
Daily
Dermal
Exposure
(mg ai/day)d
Daily Dermal
Dose
(mg
ai/kg/day)e
Dermal
MOEf
Loader Exposure
1. Load Granular
Bait for Aerial
Application
0.0084
0.018
300
0.045
0.0006
420,000
Applicator Exposure
2. Apply
Granular Bait by
Fixed-wing
Aircraft
0.0024
0.018
300
0.013
0.0002
1,250,000
Flagger Exposure
3. Flagging for
Aerial
Application of
Granular Bait
0.003
0.018
300
0.016
0.0002
1,250,000
Applicator Exposure
4. Load/Apply
Granular Bait
Using Drop-type
Tractor-Drawn
Spreader (Open
Cab)g
5. Hand Apply
Granular Bait11
0.018
103.8
0.018
0.018
100
(R) 1,000 ft2
(0.023 A)
(O) 5,000 ft2
(0.11 A)
0.032
0.043
0.21
0.0005
0.0006
0.003
500,000
420,000
83,000
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Table 3: BASELINE SHORT-TERM AND INTERMEDIATE-TERM EXPOSURE AND
RISK ASSESSMENTS FOR HYDRAMETHYLNON
Exposure
Scenario
6. Load/Apply
Granular Bait
Using Handheld
Rotary Spreader
7. Load/Apply
Granular Bait
Using Push-Type
Granular
Spreader
8. Hand apply
Gel by Syringe
Baseline
Dermal Unit
Exposure
(mg/lb ai)a
10.4
2.9
See Page 32
Maximum
Application
Rate
(Ib ai/acre)b
0.018
0.018
N\A
Maximum
Acres/Day0
(R) 1
(0) 1
(R) 1
(0) 5
N\A
Daily
Dermal
Exposure
(mg ai/day)d
0.19
0.19
0.052
0.26
26.7
Daily Dermal
Dose
(mg
ai/kg/day)e
0.003
0.003
0.0007
0.004
0.38
Dermal
MOEf
83,000
83,000
360,000
62,000
660
(R) Residential (O) Occupational
a Baseline dermal unit exposure, taken from PHED Version 1.1, represents long pants, long sleeve shirt, no gloves,
open loading, open cab tractor (unless otherwise indicated). Note that for some PHED data correction factors
were applied to arrive at the baseline scenario.
b Application rate comes from maximum rates found in the hydramethylnon labels.
c Daily acres treated values are from Agency estimates of acreage that could be treated in a single day for each
exposure scenario of concern. Assumptions for scenarios 1 through 4 are from information supplied to the
Agency by the registrant.
d Daily Dermal Exposure (mg ai/day) = Unit exposure (mg/lb ai) x Application Rate (Ibs ai/acre) x Acres Treated.
e Daily Dermal Dose (mg/kg/day) = Daily Dermal Exposure (mg/day)/70 kg
f Dermal Margin of Exposure (MOE) = NOAEL (250 mg/kg/day)/Daily Dermal Dose (mg/kg/day)
g Unit exposure is sum of unit exposures for loading granular and applying granular with solid broadcast
spreader, open cab.
h Unit exposure from PHED is for individuals wearing gloves. Estimate entered here has been corrected by back
calculation to present the unit exposure for un-gloved hands, using a 90% protection factor for gloves.
Formulas for determining dermal exposure and risk to handlers are as follows:
Daily Exposure (mg ai/day) =
Unit Exposure (mg ai/lb ai) x Use Rate (Ib ai/acre) x Maximum Area Treated (acres/day)
Daily Dermal Dose (mg ai/kg bw/day) =
Daily Exposure (mg ai/day) /Body Weight (kg)
Margin of Exposure (MOE) =
NOAEL (mg/kg/day) / Daily Dermal Dose (mg/kg/day)
The following are important assumptions used in the occupational and residential exposure
35
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assessments:
! Assume exposed adult's body weight is 70 kg;
! Assume exposed child's body weight is 10 kg;
! Inhalation exposure is assumed to be negligible for all exposure scenarios due to the low vapor
pressure of the active ingredient (2xlO"8 mm of Hg at 25° C), the size of the granules (no free
particles below 140 microns), and the oily nature of the granular bait products (17 to 26%
soybean oil). For this reason and the lack of a toxicity concern for this route, inhalation
exposure is not figured into any of the exposure calculations for handlers;
! Assume that the tractor drawn drop-type spreader equipment would result in a reasonable
surrogate exposure scenario for the blower or rotary spreader that are sometimes actually used
for this granular product; and,
! Assume that the unit exposures for the loader is additive with the unit exposure for the
applicator using the tractor drawn, drop-type spreader.
! In addition, other assumptions are listed in Table 2.
c. Occupational Handler Exposures
Table 2 contains the results of exposure assessment calculations for the occupational
handler scenarios associated with hydramethylnon. Because neither actual data nor routine
methods for using surrogate information exist to evaluate gel formulations, the Agency utilized
the methodology and approach which had been submitted by the registrant and accepted by the
Agency. Exposure scenario 8 (hand application of gel in cracks and crevices by syringe
applicator) is described below.
d. Residential Handler Exposures
Common residential handler exposures would be described by scenarios 5, 6, and 7 (in
Table 2) as well as scenario 8 (described separately below due to lack of PHED data). For
handler exposure scenario 8 (for both occupational and residential use) hand application of gel
by syringe applicator assume:
! Repeated inadvertent exposure to dispenser and treated surfaces results in uniform layer
of gel on exposed hand surface.
! Exposure to half of the surface area of a hand using maximum values for hands as 1130
cm2. Therefore, 0.5 x 1130 cm2 = 622.5 cm2
36
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Diffusion of the active ingredient through the gel layer will be limited due to matrix effects
and high molecular weight of the active ingredient, so that multiple contacts during the
day, beyond those necessary to establish a uniform layer on the exposed skin will provide
no additional absorbed dose. The dermal dose is then calculated as follows:
Daily Dermal Dose = (weight fraction a.i.) x (density of formulation - assumed to be
same as water) x (film thickness) x (skin surface area) x (I/body weight) =
(0.0215) x (1 g/cm3) x (JO3 mg/g) x (2 x JO'3 cm) x (622.5 cm2)/ 70 kg =
0.38 mg a.i./kg/day
MOE = NOAEL = (250 mg/kg/day)/(0.38 mg/kg/day) = 658 (rounded to 660)
Post-Application Exposures and Assumptions
Occupational Post-Application Exposures
The potential for post-application occupational exposure exists. For example,
potential exposures would be expected for golf-course maintenance workers and for
harvesters and mowers on sod farms and to persons in buildings following indoor
applications. There are no chemical-specific data to use in assessing these potential
exposures, therefore, a range finder post-application exposure and risk assessment was
performed (Table 4). This assessment uses typical transfer coefficients (Tc) for low crops
and/or low exposure activities (1,000 cm2/hr) and for high crops and/or high exposure
activities (10,000 cm2/hr) and dislodgeable foliar residues (DFR) derived from the
application rate and an estimated 20 percent of rate available as dislodgeable. The Agency
believes that exposures following applications to crops are likely to represent a reasonable
worse-case post-application exposure to occupational workers. Post-application
occupational exposures following applications of the gel to crack and crevices are expected
to be minimal.
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TABLE 4: SURROGATE POSTAPPLICATION RANGE-FINDER ASSESSMENT
DAT3
Age
Group
Surrogate DFR
( g/cm2)"
Dermal Dose
(mg/kg/day)c
MOEd
Low Exposure Activities (Tc = 1,000 cmVhr)e
zero
zero
Adult
Child
0.040
0.040
0.005
0.032
54,000
7,800
High Exposure Activities (Tc = 10,000 cm2/hr)f
zero
zero
Adult
Child
0.040
0.040
0.046
0.32
5,400
780
a DAT is days after treatment based on an application rate of 0.0 1 8 Ib ai/acre.
b Surrogate DFR ( g/cm2) = Rate (Ib ai/A) x [(1 1 .2 g/cm2)/(l Ib ai/A) conversion factor] x percent (20 percent assui
rate available as dislodgeable
c Dermal Dose (mg/kg/day) = [DFR ( g/cm2) xTc (cm2/hr) x (1 mg/1,000 g unit conversion) x 8 hours/day] / Body Weight
(70 kg)
d MOE = NOAEL (250 mg/kg/day)/Dermal Dose (mg/kg/day)
e Low exposure crops/activities include crops, such as low-growing ornamentals and established turf (other than sod-farm turf),
and activities such as scouting and crop-advising.
f High exposure crops/activities including crops, such as ornamental trees, plants, shrubs, and vines and sod farm turf, and
activities such as harvesting, transplanting, and pruning.
Residential Post-Application Exposures
The potential exists for post-application residential exposure to adults and children. For
example, potential exposures would be expected following applications to lawns, and ornamental
gardens, and to indoor (in-home) sites. There are no chemical-specific data to use in assessing these
potential exposures, therefore, a range finder post-application exposure and risk assessment was
performed (Table 4). The assessment uses typical transfer coefficients (Tc) for low crops and/or
low exposure activities (1,000 cm2/hr), and for high crops and/or high exposure activities (10,000
cm2/hr) and dislodgeable foliar residues (DFR) derived from the application rate and an estimated
20 percent of rate available as dislodgeable. The Agency believes that exposures following
applications to plants, such as lawn-turfgrass, are likely to represent a reasonable upper bound post-
application exposure to residents. However, the Agency also estimated the post-application
residential exposure following applications of the gel to cracks and crevices.
Post-application dermal exposure to the gel product
The following evaluation is based on a methodology and approach which had been
submitted by the registrant, and accepted by the Agency in a previous waiver request
evaluation. Assume:
! Exposure to lower surface of hands and forearms. Using half of the maximum values for
38
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hands (1130 cm2) and forearms (1360 cm2), the total surface area exposed becomes:
(0.5 x 1130 cm2) + (0.5 x 1360 cm2) = 1245 cm2
! Maximum use-rate of 2.4 g/m2 of a 2.15% active ingredient formulation; and,
! Five contact events per day
Calculate the amount contacted per event as:
(2.4 g/m2) x (0.0215 a.i.) x (m2/104 cm2) x (lOOOmg/g) x (1245 cm2) =
6.4 mg a.i./event
Calculate the post-application exposure as:
Daily Exposure = (5 events/day) x (6.4 mg a.i./event) = 32 mg a.i./day
Daily Dermal Dose (DDD)= (32 mg a.i./day) / 70 kg = 0.46 mg a.i./kg/day
MOE = NOAEL/DDD = (250 mg/kg/day)/(0.46 mg/kg/day) = 540
Risk from Handler Exposures
The calculations for short-term and intermediate-term handler risk indicate that the MOEs
for handlers are much greater than 100 at baseline for all scenarios. It should be noted that the
PHED data for aerial fixed-wing application are used with enclosed cockpits. Data do not exist in
PHED for unit exposures from aerial application without this engineering control. The current label
for this use does not require this engineering control. However, because the MOE for this scenario
is much larger than 100 (1,250,000), even use of enclosed cockpits is unnecessary.
Risk from Post-Application Exposures
Post-application risk from use of the gel product would be primarily to the adult resident.
Children are expected to be less at risk than adults because the gel is likely to be applied in
inaccessible and untraveled areas. Assessment of potential risk, using upper bound assumptions for
body area exposed, result in a MOE of 540.
The range-finder calculations for short-term and intermediate-term post-application risk
from use of the granular formulation indicate that the MOEs from post-application exposures to
occupational workers and to residents (both adults and children) are much greater than 100 for risk
using the short term endpoint for exposures estimated immediately following application.
These assumptions reflect an upper bound estimate of exposure and hazard and, therefore,
reflect upper bound risk from handler and post-application exposure.
39
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Additional Occupational/Residential Exposure Studies
Handler Studies
There are data gaps for baseline and PPE data for applying granular formulations with fixed-
wing aircraft. However, because the toxicity of this substance is sufficiently low, the Agency is not
requiring studies for these scenarios at this time.
Post-Application Studies
No studies are required at this time.
5. Other Exposure and Risk Considerations
The Food Quality Protection Act (FQPA) of 1996 amends both FFDCA and FIFRA by
setting a new safety standard for the establishment of tolerances. In determining whether or not a
tolerance meets the new safety standard, FQPA directs EPA to consider information concerning:
the susceptibility of infants and children to residues of the pesticide in food; the potential for
aggregate exposure from dietary as well as non-occupational sources, such as pesticides used in and
around the home; and the potential for cumulative effects from a pesticide and other substances that
have a common mechanism of toxicity.
Because the use of hydramethylnon on grass in pastures and rangelands is considered a food
use and a tolerance has been established for hydramethylnon on grass and grass hay (i.e., pasture
and rangelands), certain determinations outlined in FQPA were required for this chemical. A
tolerance has been established for hydramethylnon on grass forage and grass hay. However, no
finite residues are anticipated in meat, milk, or meat byproducts. Therefore, the Agency has not
undertaken a dietary risk assessment because no dietary exposure is anticipated.
The Agency has completed an aggregate risk assessment from the other potential exposure
pathways (e.g. non- occupational sources). With regard to cumulative risk, hydramethylnon is
structurally similar to some other amidinohydrazone compounds; however, the Agency has not
made a determination regarding a cumulative risk assessment. For the purposes of this
Reregistration Eligibility Decision document, the Agency has considered only risks from
hydramethylnon. However, the contribution of hydramethylnon exposure to the exposure from
other chemicals with a common mode of toxicity is likely to be minimal since the MOEs are so high.
If required, cumulative risks will be assessed when methodologies for determining common mode
of toxicity and for performing cumulative risk assessment are finalized.
C. Environmental Assessment
The environmental fate and effects database on hydramethylnon is adequate and will support
reregi strati on eligibility. To support broadcast applications, an avian reproduction (GLN 71-4)
study is required for confirmatory data purposes.
40
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1. Ecological Effects
a. Toxicity to Terrestrial Animals
(1) Birds, Acute and Subacute
An acute oral toxicity study using the technical grade of the active ingredient (TGAI)
was conducted to establish the toxicity of hydramethylnon to birds. The preferred test
species is either mallard duck (a waterfowl) or bobwhite quail (an upland gamebird).
Results of this study are tabulated below.
Table 5: Avian Acute Oral Toxicity
Species
Northern bobwhite quail
(Colinus virginianus)
Mallard duck
(Anas platyrhynchos)
%ai
92%
92%
LD50
(mg/kg)
1828
2510
Toxicity
Category
Slightly toxic
Practically non-
toxic
MRID
00064576
00064575
Study
Classification
Acceptable
Acceptable
Since the LD50 falls in the range of 1828-2510 mg/kg, hydramethylnon is slightly
toxic to practically non-toxic to avian species on an acute oral basis. The guideline
requirement (71-la) is fulfilled.
Two subacute dietary studies using the TGAI were conducted to establish the
toxicity of hydramethylnon to birds. These studies were performed on the preferred test
species, mallard duck and bobwhite quail. Results of these tests are tabulated below.
Table 6: Avian Subacute Dietary Toxicity
Species
Northern bobwhite quail
(Colinus virginianus)
Mallard duck
(Anas platyrhynchos)
%ai
92%
92%
5-Day LC50
(ppm)1
1136
4355
Toxicity
Category
Slightly toxic
Slightly toxic
MRID
00064577
00085931
Study
Classification
Core
Core
1 Test organisms observed an additional three days while on untreated feed.
Since the LC50 falls in the range of 1136-4355 ppm, hydramethylnon is slightly toxic to
avian species on a subacute dietary basis. Guideline requirements (71-2 a and b) are fulfilled.
41
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(2) Birds, Chronic
No avian reproduction data are available for hydramethylnon. Observation of reproductive
effects in mammals suggests that oral exposure of other organisms to hydramethylnon may result
in chronic reproductive effects. In the absence of toxicological data to the contrary, the Agency
assumes that hydramethylnon has a potential to cause chronic reproductive effects in avian species.
Uncertainties regarding the potential for adverse reproductive effects in birds would be reduced if
avian reproduction toxicity data were available for the compound. Avian-specific toxicity thresholds
for reproductive effects would allow a more accurate comparison between bait concentrations and
toxicological effects thresholds. The Agency has requested such studies for other pesticides
including when (1) birds may be subject to repeated or continuous exposure to the pesticide,
especially preceding or during the breeding season; (2) the pesticide is stable in the environment to
the extent that potentially toxic amounts may persist in animal feed; (3) the pesticide is stored or
accumulated in plant or animal tissues; and/or (4) information derived from mammalian reproduction
studies indicates reproduction in terrestrial vertebrates may be adversely affected by the anticipated
use of the product. Because hydramethylnon meets condition (1), (2) and (4) above, the Agency
requires that avian reproduction data be submitted or that use patterns resulting in potential chronic
exposures be eliminated.
(3) Mammals, Acute and Chronic
Wild mammal testing is required on a case-by-case basis, depending on the results of lower
tier laboratory mammalian studies, intended use pattern and pertinent environmental fate
characteristics. In most cases, rat or mouse toxicity values obtained from the Agency's files
substitute for wild mammal testing. These toxicity values are reported below.
Table 7: Mammalian Toxicity
Species
Norway Rat
(Rattus
norvegicus)
Norway Rat
(Rattus
norvegicus)
%ai
95%
92%
Test Type
LD50
Reproduction
(3 generation)
Toxicity Value
(m) 817
(f) 1502
combined: 1146mg/Kg
NOEL= 50 ppm
LOEL= 100 ppm
Toxicity
Category
Slightly Toxic
Male infertility
was noted at
100 ppm
MRID
416125-03
35525
35526
101575
The results indicate that hydramethylnon is slightly toxic to small mammals on an acute oral
basis. Reproductive effects (male infertility) occurred at 100 ppm (NOEL= 50 ppm).
In a two generation study (MRID 43741501), 98.2% hydramethylnon was administered to
Sprague-Dawley rats. The reproductive NOAEL was 25 ppm and the reproductive LOEL was 50
42
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ppm based on histological findings in the testes and the epididymides. At 75 ppm, reproductive
performance of the males was decreased. As noted above, these findings are suggestive of the
potential for reproductive effects in other organisms including birds.
(4) Insects
A honey bee acute contact study using the TGAI was required for hydramethylnon because
its outdoor use may result in honey bee exposure. Results of this test are tabulated below.
Table 8: Nontarget Insect Acute Contact Toxicity
Species
Honey bee
(Apis mellifera)
%ai
96.8
LDso
( g/bee)
68.0
Toxicity
Category
Practically
non-toxic
MRID
416078-01
Study
Classification
Acceptable
The results indicate that hydramethylnon is practically non-toxic to bees on an acute contact
basis. The guideline (141-1) is fulfilled.
b. Toxicity to Aquatic Animals
(1) Freshwater Fish, Acute
Two freshwater fish toxicity studies using the TGAI are required to establish the toxicity
of hydramethylnon to fish. The preferred test species are rainbow trout (a coldwater fish) and
bluegill sunfish (a warmwater fish). Results of these tests are tabulated below.
Table 9: Freshwater Fish Acute Toxicity
Species/
(Flow-through or
Static)
Rainbow trout
(Oncorhynchus mykiss)
Bluegill sunfish
(Lepomis macrochirus)
Channel catfish
(Ictalurus punctatus)
%ai
92%
92%
92%
96-hour
LC50 (ppm)*
0.15
1.7
0.09
Toxicity
Category
Highly toxic
Moderately
toxic
Very highly
toxic
MRID
00052857
00061708
00061707
Study
Classification
Acceptable
Acceptable
Acceptable
*Note: LC50 concentrations exceed the water solubility of hydramethylnon. These concentrations were
achieved through the use of dimethyl formalin as a co-solvent.
Because the LC50 falls in the range of 0.09-1.7 ppm, hydramethylnon is moderately to very
highly toxic to freshwater fish on an acute basis. It should be noted that these LC50 values exceed
43
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the aqueous solubility of hydramethylnon and are therefore not likely to be of environmental
significance. The guideline requirement 72-1 is fulfilled.
(2) Freshwater Fish, Chronic
A freshwater fish early life-stage test using the TGAI may be required for hydramethylnon
because the end-use product may be transported to water from the intended use site, and conditions
are met with regard to the chemical's toxicity and expected environmental concentration. This test
would normally be required for hydramethylnon due to the compound's high toxicity (LC50< 1
mg/L) in rainbow trout and channel catfish. The preferred test species in this case would be the
channel catfish, as it is the freshwater species tested that is most sensitive to hydramethylnon. Water
solubility of hydramethylnon is 0.005 to 0.007 ppm (The Agrochemicals Handbook. Royal
Chemistry Society, 1987), an order of magnitude lower than the catfish LC50 of 0.09 ppm. In
addition, hydramethylnon photodegrades in water with a half-life of under one hour. In this case,
under natural conditions, susceptible species are not expected to be exposed to the chemical. This
study is not needed at this time, but may be required for future new uses. The guideline requirement
72-4 is reserved.
(3) Freshwater Invertebrates, Acute
A freshwater aquatic invertebrate toxicity test using the TGAI is required to establish the
toxicity of hydramethylnon to aquatic invertebrates. Results of this test are tabulated below.
Table 10: Freshwater Invertebrate Acute Toxicity
Species/(Static)
Waterflea
(Daphnia magna)
%ai
92%
48-hour LC50/
EC50 (ppm)
1.14
Toxicity
Category
Moderately toxic
MRID
00035877
Study
Classification
Acceptable
Since the LC50/EC50 is 1.14 ppm, hydramethylnon is moderately toxic to aquatic
invertebrates on an acute basis. The guideline requirement 72-2 is fulfilled.
(4) Freshwater Invertebrate, Chronic
A freshwater aquatic invertebrate life-cycle test using the TGAI is not required at this time
for hydramethylnon because of the very low aqueous solubility in water, its brief half-life there, and
the limited opportunity for residues to reach surface water for current use patterns. Any expansion
of the current use patterns may trigger the need for these data.
c. Toxicity to Aquatic Plants
Currently, aquatic plant testing is not required for pesticides other than herbicides and
fungicides, except on a case-by-case basis (e.g., labeling bears phytotoxicity warnings, incident data
44
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or literature that demonstrate phytotoxicity). The Agency does have data from 96 hour studies
(MRID 40098001) conducted with 96.2 % technical hydramethylnon indicating that
hydramethylnon is very highly toxic to aquatic plants as indicated by the following toxicity (EC50)
levels: green algae species (5-18 ppb); a marine haptophyte (2.9 ppb); and, marine diatoms (0.24-
0.26 ppb).
d. Environmental Fate Data
This environmental fate assessment of hydramethylnon is based on both acceptable
(hydrolysis, photo degradation on soil, aerobic soil metabolism, anaerobic aquatic metabolism,
unaged mobility, and accumulation in fish) and supplemental data (photo degradation in water and
terrestrial field dissipation) submitted for reregi strati on since 1989. Although some environmental
fate data requirements remain unfulfilled at this time, the available data provide enough information
to conduct a risk assessment for the parent compound. This is possible for aquatic exposure
scenarios because the observed toxic thresholds for parent hydramethylnon exceed solubility and
information on individual degradate identities is not likely to significantly alter risk calculations. For
terrestrial receptors, risks are based on exposures to parent hydramethylnon at concentrations
measured in baits. The Agency's conservative assumption of potential exposure levels expressed
in terms of parent compound is likely to, at worst, remain unchanged or be reduced if full
information on individual degradates becomes available.
e. Environmental Fate Assessment
Laboratory data indicate that the major routes of hydramethylnon dissipation on the soil
surface are abiotic photolysis and soil binding. Hydramethylnon's photolytic half-life in water is less
than or equal to 1 hour, while its photolysis on soil is biphasic, with half-lives of 4 days for the first
phase and in about 30 days for the second phase. Parent hydramethylnon was reported to adsorb
strongly to soils: loamy sand, sandy loam, loam, and silt loam soils with reported Kds of 1039-
1782 mL/g. The reported Kd values ranged from 3330 to 8667 mL/g. In addition, hydramethylnon
appears to dissipate very slowly by biotic processes (half-lives for aerobic soil metabolism were 385
days, and for anaerobic aquatic metabolism 445 to 552 days). It is stable to hydrolysis at pH 5, pH
7, and pH 9.
Field data appear to confirm the laboratory data. Half-lives of 3 days and 55 days were
reported for Florida and Texas field plots with no detections reported below the 0-6 inch soil depth.
Therefore, based on the low application rate hydramethylnon of hydramethylnon (0.0176 Ib a.i./A),
rapid photolysis, low soil mobility, and low solubility in water (7 to 9 ppb), hydramethylnon on soil
surfaces appears to be non-persistent and immobile. However, below the soil surface
hydramethylnon appears to be more persistent and immobile. Due to the lack of movement of
hydramethylnon in the soil profile under most conditions, hydramethylnon appears to have a low
potential for groundwater contamination, but may move horizontally on the soil surface through soil
erosion.
45
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During aqueous photolysis, a major degradate, (4H-pyrimido [2-l-c]as-triazio-4-one-
l,6,7,8-tetrahydro-7,7-dimethyl-3-[p-(trifluoromethyl)-styryl], represented 2 5.2% and 30.5% of the
recovered 14C-phenyl and 14C-pyrimidine radioactivity, respectively. A second major degradate,
l,5-bis(alpha, alpha, alpha-trifluoro-p-tolyl)-l,4-pentadien-3-one, represented 28.0% of recovered
phenyl labeled material. In addition, five unidentified compounds were discernible in the 2-
pyrimidine radio labeled and the phenyl radio labeled samples, ranging from 29.6% to 7.6% of
recovered radioactivity. Further analysis of these unknown degradates was either inconclusive
and/or indicated they were formed by specific conditions of confirmation analysis or rate of
formation and decline analysis. Two unidentified degradates in the hydramethylnon soil photolysis
data, which were found to make up 10% of the applied radioactivity, were determined to be
comprised of a mixture of products. Epoxide and ketone compounds of hydramethylnon comprised
the major degradates in these mixtures.
Hydramethylnon showed some tendency to accumulate in fish tissues with reported
bioconcentration factors of 1300X in whole fish, 780X in fillet, and 1900X in viscera. Slow
depuration (48 to 63% of residues depurated after a 14-day clearance period) was observed. The
current limited outdoor use patterns of hydramethylnon combined with its low aqueous solubility,
tendency to photodegrade in water, and high soil sorption affinity suggest low potential for
bioaccumulation in the environment.
f. Environmental Fate and Transport
(1) Degradation
Hydrolysis One guideline hydrolysis study (MRID 42194701) was submitted to the Agency.
This study was found to be acceptable to fulfill the data requirement (161-1). Hydramethylnon was
reported to be stable to hydrolysis at pH5, pH 7, and pH 9. In addition, the stability of
hydramethylnon does not appear to be affected by type or concentration of buffer at pH 7.
Photodegradation in water Photodegradation in water data submitted were found to be
supplemental but did not fulfill the data requirement (161-2). Two degradates were present at
concentrations of 29.6% and 15.6% of recovered radioactivity, but were not identified. In addition,
confirmatory analyses by LC/MS were inconclusive (MRTDs 42238201 and 42473301).
The photodegradation in water data indicate that hydramethylnon rapidly photodegrades in
pH 7 buffer solutions (half-life of <1 hour). Hydramethylnon was stable in the dark control
treatment.
A major photodegradate, 4H-pyrimido [2-l,c]as-triazio-4-one-l,6,7,8-tetrahydro-7,7-
dimethyl-3-[p-(trifluoromethyl)-styryl], represented 25.2% and 30.5% of the recovered 14C-phenyl
and 14C-pyrimidine radioactivity, respectively. A second major degradate, l,5-bis(alpha, alpha,
alpha-trifluoro-p-tolyl)-l,4-pentadien-3-one, represented 28.0% of recovered phenyl labeled
material. In addition, five unidentified compounds (Unknowns 1, 2, 3, 4, and 5) were discernible
46
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in test samples. Unknowns 1, 4, and 5 were detected in the 2-pyrimidine radiolabeled samples and
reached concentrations of 9.5, 29.6, and 7.7% of recovered radioactivity, respectively. Unknowns
3 and 5 were detected in the phenyl radiolabeled samples and reached concentrations of 7.6 and
15.6% of recovered radioactivity, respectively. Unknown 2 did not appear in the HPLC analyses
of the confirmatory samples, but was observed in the rates of formation and decline analyses.
Attempts to identify these unknowns by LC/MS indicated that Unknowns 1 and 2 were formed by
specific conditions of confirmatory analysis or of the rate of formation and decline analysis. In
addition, after further analysis of Unknown 3, the study authors believed that it was formed by
specific conditions of analysis, and/or is an insignificant degradate of hydramethylnon in photolysis.
Furthermore, additional analysis by LC/MS of Unknowns 4 and 5 was inconclusive. However,
these data did indicate that aqueous photolysis is a route of degradation for hydramethylnon.
The status of the photodegradation in water data is supplemental and cannot be used to
fulfill the data requirement (161-2). The study does not fulfill the guideline requirement because
1) photodegradation is a route of dissipation; 2) the structures of Unknowns 4 and 5 were not
identified; and, 3) these compounds were present at concentrations of 29.6% and 15.6% of
recovered radioactivity, respectively. However, this risk assessment is based on parent compound
and since the toxic effect concentrations of parent exceed aqueous solubility, risk to aquatic
organisms is not expected.
Photodegradation on soil One guideline photodegradation on soil study, MRTD 42353801,
was submitted to the Agency. Although problems with the study were identified (test soil was
sieved to 1 mm, removing the very coarse sand fraction thereby increasing the surface area and
potentially affecting the rate of photo degradation), it can be used to fulfill the data requirement
(161-3) at this time. Additional data may be needed to support additional outdoor uses of
hydramethylnon.
Photodegradation of hydramethylnon on loam (called sandy loam by author) soil did not
follow linear first order kinetics. Rapid degradation over the first 3 days was observed, which was
followed by a slower degradation rate. The half-life for the initial (rapid) phase was approximated
at 4 days (based on 24 hours light exposure) using first-order kinetics. The second (longer) phase
was reported to have a half-life of approximately 30 to 35 days (based on 24 hours light exposure)
using first order kinetics. This difference may be due to the light contact on the soil surface and
rapid adsorption of hydramethylnon to the soil. Hydramethylnon was stable in the dark control
treatment.
Two unidentified peaks, which comprised 10% of the applied radioactivity, were determined
to be a mixture of compounds. Hydramethylnon epoxide and ketone compounds comprised the
major degradates detected in these mixtures. The control samples were reported to show <10%
degradation during the testing period.
Aerobic metabolism in soil One guideline aerobic soil metabolism study, MRTD 42320801,
was submitted to the Agency. Hydramethylnon appears to degrade relatively slowly under aerobic
47
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conditions when applied to sandy loam soil at an exaggerated application rate (0.095 ppm, or 6
times the normal rate). After 1 year of aerobic incubation, first-order half-lives of 375 and 391 days
for the 14C-phenyl and 14C-pyrimidine labeled hydramethylnon were reported, respectively. One
unidentified degradate, which HPLC analysis indicated to contain both labels and be more polar than
the parent compound, was detected at concentrations of 15.6 and 16.8% of applied radioactivity
in the 14C-phenyl and pyrimidine labeled samples, respectively. The study author believes that
formation of this degradate was partially due to the soil extraction and analytical methodology of
the extracts and that it is unstable. Further attempts to identify this degradate by LS/MS were
unsuccessful. In addition, up to 18 minor degradates, all at concentrations <0.004 ppm, were
discernible in the soil extracts. Additional information on the identities of the 18 minor degradates
is not needed at present because of the low rate of occurrence of these compounds in the study.
This study was found acceptable to fulfill data requirement 162-1. Because of the relatively high
occurrence of the unidentified polar compound, expanded outdoor uses of hydramethylnon, may
necessitate additional information on this compounds identity and subsequent revision of the
exposure assessments.
Anaerobic aquatic metabolism One guideline anaerobic soil metabolism study, MRTD
42320801, was submitted to the Agency and will fulfill guideline requirement 162-2.
Hydramethylnon appears to be relatively persistent under anaerobic conditions. Half-lives
of 552 and 455 days were calculated for the phenyl and pyrimidine labeled hydramethylnon samples,
respectively. The concentration of 14C-phenyl and 14C-pyrimidine decreased from 90.7% and 82.6%
to 50.4% and 57.4%, respectively, of applied radioactivity by termination of testing period ( 1 yr).
Two additional peaks were discernible in test samples. Peak A was discernible at maximum
concentrations of 15 to 8.8% at 9 and 12 months post-treatment for phenyl and pyrimidine labeled
samples, respectively. Peak A was determined by HPLC and Thin Layer Chromatography (TLC)
to be mainly parent hydramethylnon. Peak B was determined to be a photolytic product formed
during sample analysis. Since Peaks A and B generated multiple peaks during HPLC and liquid-
liquid chromatography, they could not be identified. Peak B was reported to reach a maximum
concentration of'12.7% and 9.2% of applied radioactivity at 3 and 4 months post-treatment samples
in the phenyl and pyrimidine labeled test samples, respectively.
(2) Mobility
Leaching, adsorption/desorption Two guideline mobility studies were submitted to the
Agency. One of these is an unaged adsorption/desorption study, MRTD 41888302, and the other
is a TLC study, MRID 41888301. Both studies are considered scientifically valid. However, the
Agency does not accept soil TLC mobility data to fulfill the mobility data requirement (163-1) (aged
or unaged). The unaged data requirement is fulfilled by adsorption/ desorption mobility data, MRID
41888302. Therefore, no further unaged mobility data for hydramethylnon are needed at this time.
Because the current risk assessment is based on parent alone, no additional information on aged
mobility are needed at this time. However, since photolysis appears to be a major route of
48
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degradation, aged mobility data for photodegradation products may be needed to support any
additional uses of hydramethylnon.
Hydramethylnon appears to be relatively non-mobile (Kd values ranged from 1039-1782
mL/g). In addition, hydramethylnon was reported to be stable since only one major spot, which co-
chromatographed with non-labeled hydramethylnon, was discernible on the normal phase assays.
Soil TLC results indicate that hydramethylnon is relatively non-mobile in loamy sand, sandy loam,
loam, and clay loam soils.
(3) Accumulation
One guideline study, MRID 00101611, was submitted to the Agency. This study was found
to be acceptable to fulfill the guideline requirement 164-5. Hydramethylnon showed some tendency
to accumulate in fish tissues with reported bioconcentration factors of 1300X in whole fish, 780X
in fillet, and 1900X in viscera. Slow depuration (48 to 63% of residues depurated after a 14-day
clearance period) was observed. The current limited outdoor use patterns of hydramethylnon
combined with its low aqueous solubility, tendency to photodegrade in water, and high soil sorption
affinity suggest low potential for bioaccumulation in the environment.
(4) Field Dissipation
Terrestrial field dissipation Two studies, MRIDs 43293101 and 43293102, were submitted
to the Agency for guideline requirement 164-1. However, these data are supplemental since two
major photo degradation products were identified (4H-pyrimido [2-1,c]as-triazio-4-one-l,6,7,8-
tetrahydro-7,7-dimethyl 3-[p-(tri-fluoromethyl)-styryl] at 25.2% and 30.5% of the recovered 14C-
phenyl and 14C-pyrimidine labeled material respectively, and 1,5-bis(alpha, alpha, alpha-tri-fluoro-p-
tolyl)-l,4-pentadien-3-one at 28.0% of recovered phenyl labeled material). These degradation
products were not analyzed for in these two terrestrial field dissipation studies.
In addition, two unidentified photolysis products reached concentrations >10% of applied.
Major photo degradation (>10% of applied) and metabolism products should be analyzed for in
terrestrial field dissipation studies. Because the current risk assessment is limited to parent
hydramethylnon, no further testing is required at this time. However, since photolysis appears to
be a route of dissipation, additional field data on degradation products may be needed to evaluate
any additional uses of hydramethylnon in the future.
Hydramethylnon appeared to dissipate in Florida sand soil with a calculated half-life of 3
days. Average residues above the analytical detection limit (0.010 ppm) were not detected below
the 0-6 inch soil depth level. Hydramethylnon residues ranged from 115 ppb at immediately after
treatment (0.01 day test interval) to <10 ppb at 14 days post-treatment. There were no degradation
products identified during analysis of test samples for the entire testing period (152 days).
Hydramethylnon appeared to dissipate in Texas sandy loam soil with a calculated half-life
49
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of 55 days. Average residues above the analytical detection limit (0.010 ppm) were not detected
below the 0-6 inch soil depth level. Hydramethylnon residues ranged from 114 ppb at immediately
after treatment (0.01 day test interval) to <10 ppb at 148 days post-treatment. There were no
degradation products identified during analysis of test samples for the entire testing period (148
days).
Laboratory data indicated that hydramethylnon had a biphasic photodegradation pattern.
The first and most rapid phase of photodegradation may have been reflected in the Florida field test
study on sandy soil where a half-life of 3 days was reported . It is reasonable to assume that the
field dissipation half-life can range from 3 to 55 days, depending on the availability of residues to
photodegradation. It is not possible to confirm the role of photodegradation in this field study,
because photodegradates were not identified.
(5) Spray Drift
American Cyanamid is a member of the Spray Drift Task Force and are able to cite those
data. Although there are aerial broadcast application uses, the granular formulation is of a particle
size that would not be expected to drift during typical application.
g. Water Resources
The Agency does not believe that surface water or ground water resources will be affected
by the labeled use of hydramethylnon.
(1) Ground Water
No data on hydramethylnon residues in ground water are readily available. Hydramethylnon
is not included in the Pesticides in Ground Water Database, and it was not an analyte in the National
Pesticide Survey. A search of the World Wide Web provided no further environmental fate data
for hydramethylnon. No Maximum Contamination Limit (MCL) or Health Advisory (HA) has been
established for hydramethylnon residues in drinking water.
Due to the high binding affinity of hydramethylnon, it is not likely to contaminate ground
water. When a chemical has a Koc of greater than 9,995, the SCI-GROW screening model provides
a default estimate of 0.006 ppb in groundwater. In addition, there are limited data on the mobility
of hydramethylnon degradation products at this time.
The Agency notes there is uncertainty with surface and ground water assessments, because
the environmental fate data for hydramethylnon do not include the major photo transformation
products [e.g., (4H-pyrimido [2-l,c]as-triazio-4-one-l,6,7,8-tetrahydro-7,7-dimethyl-3-[p-
(trifluoromethyl)-styryl] and 1,5-bis (alpha, alpha, alpha-tri-fluoro-p-tolyl)-l,4-pentadien-3-one].
Additionally, the surface water assessment for bait uses was not evaluated because this type of use
does not constitute direct environmental exposure. Although there is uncertainty in the surface
50
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water assessment, the GENeric Expected Environmental Concentration Program (GENEEC)
estimated environmental concentration (EEC) for hydramethylnon is expected to be a conservative
estimate of the impact on surface water quality.
(2) Surface Water
The Agency uses a computer model to calculate expected environmental concentrations
(EECs) of pesticides using the GENEEC program. The EECs are used for assessing the surface
water concentrations of a chemical, and the acute and chronic risks to aquatic organisms.
GENEEC uses basic environmental fate data and pesticide label application information to
estimate the expected EECs following treatment of 10 hectares. The model calculates the
concentration (i.e. EEC) of a pesticide in a one-hectare, two meter deep pond, taking into account
the following: (1) adsorption to soil or sediment; (2) soil incorporation; (3) degradation in soil
before washoff to a water body; and (4) degradation within the water body. The model also
accounts for direct deposition of spray drift into the water body (assumed to be 1% and 5% of the
application rate for ground and aerial applications, respectively). When multiple applications are
permitted, the interval between applications is included in the calculations. The environmental fate
parameters used in the model and calculated EECs for this pesticide are tabulated in the tables
below.
The peak GENEEC estimated environmental concentration (EEC) of hydramethylnon in
surface water is 15 parts per trillion (ppt). This estimate is based on a maximum application rate
of 0.0176 Ib ai/acre. Hydramethylnon is persistent (t1/2= 385 days) and immobile (Koc= 217,442
ml/g) in terrestrial environments. Hydramethylnon dissipation appears to be dependent on photo
degradation and soil binding. Since hydramethylnon has a high binding affinity, it is expected to
move into surface waters on entrained sediments. Once in surface waters, hydramethylnon is
expected to be associated predominantly with the sediment.
Table 11: GENEEC EECs (ug/L)
Crops
Pasture
land
PEAK
Air
Applied
.014
Ground
Applied
.015
4 DAYS
Air
Applied
.004
Ground
Applied
.004
21 DAYS
Air
Applie
d
.0008
Ground
Applied
.0008
56 DAYS
Air
Applie
d
.0003
Ground
Applied
.0003
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Table 12: GENEEC Environmental Fate Input Parameters
DATA
Hydrolysis
Photo degradation
in Water
Aerobic Soil
Metabolism
Aerobic Aquatic
Metabolism
Batch Equilibrium
(Koc)
VALUE
Stable
t1/2 = < 1 hour
t1/2 = 385 days
Probably Stable
217,442 ml/g(mean)
DATA
ASSESSMENT
Acceptable
Supplemental
Acceptable
No Data Available
Acceptable
SOURCE
MRID 42194701
MRID 42238201
MRID 42320801
No Data Available
MRID 41888302
(3) Drinking Water
The Agency believes that hydramethylnon should not pose a major threat to
surface and ground water quality, because it has a high binding affinity (Kd>1039
ml/g) on soil, and the outdoor (non-bait) use is limited. However, the impact of
hydramethylnon photo transformation products on surface and ground-water quality
cannot be assessed due to insufficient data. If new uses or sites are added to label,
additional mobility data would be required to assess the environmental fate of photo
transformation products.
The peak GENEEC estimated environmental concentration (EEC) of
hydramethylnon in surface water is 0.015 ppb. Drinking water exposure through
ground water is estimated to be the SCI-GROW default value of 0.006 ppb.
2. Exposure and Risk Characterization
Risk characterization integrates the results of the exposure and ecotoxicity
data to evaluate the likelihood of adverse ecological effects. The means of
integrating the results of exposure and ecotoxicity data is called the quotient
method. For this method, risk quotients (RQs) are calculated by dividing exposure
estimates by ecotoxicity values, both acute and chronic.
RQ= EXPOSURE/TOXICITY
RQs are then compared to levels of concern (LOCs) determined by the
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Agency. These LOCs are the criteria used by the Agency to indicate potential risk
to nontarget organisms and the need to consider regulatory action. The criteria
indicate that a pesticide used as directed has the potential to cause adverse effects
on nontarget organisms. LOCs currently address the following risk presumption
categories: (1) acute high, potential for acute risk is high, regulatory action may be
warranted in addition to restricted use classification; (2) acute restricted use, the
potential for acute risk is high, but this may be mitigated through restricted use
classification; (3) acute endangered species, the potential for acute risk to
endangered species is high, regulatory action may be warranted; and, (4) chronic
risk, the potential for chronic risk is high, regulatory action may be warranted.
Currently, the Agency does not perform assessments for chronic risk to plants, acute
or chronic risks to nontarget insects, or chronic risk from granular/bait formulations
to mammalian or avian species.
The ecotoxicity test values (i.e., measurement endpoints) used in the acute
and chronic risk quotients are derived from the results of required studies.
Examples of ecotoxicity values derived from the results of short-term laboratory
studies that assess acute effects are: (1) LC50 (fish and birds); (2) LD50 (birds and
mammals; (3) EC50 (aquatic plants and aquatic invertebrates); and, (4) EC25
(terrestrial plants). Examples of toxicity test effect levels derived from the results
of long-term laboratory studies that assess chronic effects are: (1) LOEC (birds,
fish, and aquatic invertebrates); (2) NOEC (birds, fish, and aquatic invertebrates);
and, (3) MATC (fish and aquatic invertebrates). For birds and mammals, the NOEC
value is used as the ecotoxicity test value in assessing chronic effects. Other values
may be used when justified. Generally, the MATC (defined as the geometric mean
of the NOEC and LOEC) is used as the ecotoxicity test value in assessing chronic
effects to fish and aquatic invertebrates. However, the NOEC is used if the
measurement end point is production of offspring or survival. Risk presumptions,
along with the corresponding RQs and LOCs, are tabulated below.
TABLE 13: Risk Presumptions for Terrestrial Animals
Risk Presumption
RQ
LOC
Wild Mammals and Birds
Acute High Risk
Acute Restricted Use
Acute Endangered Species
Chronic Risk
EEC'/LCSO orLD50/sqft2 orLD50/day3
EEC/LC50 or LD50/sqft or LD50/day (or LD50
< 50 mg/kg)
EEC/LC50 or LD50/sqft or LD50/day
EEC/NOEC
0.5
0.2
0.1
1
53
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TABLE 14: Risk Presumptions for Aquatic Animals
Risk Presumption
Acute High Risk
Acute Restricted Use
Acute Endangered Species
Chronic Risk
RQ
EECVLC50orEC50
EEC/LC50orEC50
EEC/LC50orEC50
EEC/MATCorNOEC
LOC
0.5
0.1
0.05
1
1 EEC = (ppm or ppb) in water
TABLE 15: Risk Presumption for Plants
Risk Presumption
RQ
LOC
Terrestrial and Semi-Aquatic Plants
Acute High Risk
Acute Endangered Species
EEC'/EC25
EEC/EC05 or NOEC
1
1
Aquatic Plants
Acute High Risk
Acute Endangered Species
EEC2/EC50
EEC/EC05 or NOEC
1
1
1 EEC = lbsai/A
2 EEC = (ppb/ppm) in water
a. Ecological Exposure and Risk Characterization
Hydramethylnon is expected to have minimal acute impact other
than on the intended target pest. However, available mammalian reproduction data
suggest a potential for reproduction effects in terrestrial wildlife species.
(1) Exposure and Risk to Nontarget Terrestrial Animals
(a) Birds
Birds may be exposed to granular/bait pesticides such as hydramethylnon by
ingesting granules when foraging for food or grit. Hydramethylnon is formulated as a
granular bait utilizing soybean oil as the attractant for ants on various inert corn grit carriers.
Birds also may be exposed by other routes, such as by walking on exposed granules or
drinking water contaminated by granules. The number of lethal doses (LDSOs) that are
available within one square foot immediately after application (LD50s/ft2) is used as the risk
quotient for granula^ait products. Risk quotients are calculated for two separate weight
54
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class of birds: 1200 g (e.g., waterfowl), and 200 g (e.g., upland gamebird).
The acute risk quotients for broadcast applications of granular/bait products are
tabulated below.
TABLE 16: Avian Risk Quotients for Granular Products (Broadcast) Based on a quail LD50 of
1828 mg/kg and a mallard duck LD50 of 2510 mg/kg.
Site/
Application Method/Rate
in Ibs ai/A
Granular (Broadcast)
0.0176 Ibs ai/A
Rangel and/Turf/Recreati on
areas/Nonbearing nursery
stock/Nonagricultural
uncultivated areas/Terrestrial
feed crop (pastures)
0.0176 Ibs ai/A
% (decimal) of
Pesticide Left
on the Surface
1.0
1.0
Body Weight
(grams)
200
1200
LD50
(mg/kg)
1828
2510
Acute RQ1
(LD50/ft2)
0.00
0.00
1 RO = App. Rate (Ibs ai/A^) * (453.590 mg/lbs/43.560 ft2/A)
LD50 mg/kg * Weight of Animal (g) * 1000 g/kg
The results indicate that for broadcast applications of granular products, avian acute high
risk, restricted use, and endangered species levels of concern are not exceeded at registered
maximum single application rates of 0.0176 Ibs ai/A.
The lack of avian reproduction data for hydramethylnon precludes a quantitative assessment
of chronic risks of hydramethylnon baits to birds. However, the Agency assumes, in the absence
of data to the contrary, that avian reproductive endpoints may be as sensitive as mammalian
endpoints. Because the concentrations of hydramethylnon in baits (0.88 to 1.65 percent) exceeds
the dietary NOAEL (50 ppm) and the LOAEL (100 ppm) for mammalian reproductive effects, the
Agency's position is that outdoor uses of hydramethylnon baits may pose a reproductive risk to
avian species.
(b) Mammals
Birds and mammals have similar responses to xenobiotics, their differences being more
quantitative than qualitative. Birds have lower hepatic microsomal mono-oxygenase and A-esterase
activity than do mammals. Therefore, birds are more susceptible than mammals to many pesticides
in general. Since hydramethylnon does not present an acute risk to endangered birds, mammals are
also presumed to be protected from acute risks.
55
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Mammalian species also may be exposed to granular/bait pesticides by ingesting granules.
They also may be exposed by other routes, such as by walking on exposed granules and drinking
water contaminated by granules. The number of lethal doses (LDSO's) that are available within one
square foot immediately after application can be used as a risk quotient (LD50's/ft2) for the various
types of exposure to bait pesticides. Risk quotients are calculated for three separate weight classes
of mammals: 15 g, 35 g and 1000 g.
The acute risk quotients for broadcast applications of granular products are tabulated below.
TABLE 17: Mammalian Acute Risk Quotients for Granular Products (Broadcast) Based on
Rat LD50 of 817 mg/kg.
Rate in Ibs ai/A
0.0176
0.0176
0.0176
Amount of Pesticide
Left on the Surface
1.0%
1.0%
1.0%
Body Weight (g)
15
35
1000
Rat LD50
(mg/kg)
817
817
817
Acute RQ1
(LD50/ft2)
0.00
0.00
0.00
'RQ= App. Rate (Ibs ai/A) * (453.590 mg/lbs/43.560 ft2/A}
LD50 mg/kg * Weight of Animal (g) * 1000 g/kg
The results indicate that for broadcast granular products, mammalian acute high risk,
restricted use, and endangered species levels of concern are not exceeded at a registered maximum
application rate < 0.0176 Ib/ai/A.
Presently, the Agency has no standardized method for estimating small terrestrial mammal
chronic oral exposures to pesticides, like hydramethylnon, incorporated into bait formulations.
However, available information indicates that hydramethylnon concentrations in baits range from
0.88 to 1.65 percent active ingredient. This range in bait concentrations exceeds the mammalian
reproductive NOEC of 50 ppm, and encompasses the 100 ppm LOEC for male rat infertility. These
findings suggest a potential reproduction risk to terrestrial small mammals in areas of bait
application.
(c)
Insects
Currently, the Agency does not assess risk to nontarget insects. Results of acceptable
studies are used for recommending appropriate label precautions. As hydramethylnon is practically
non-toxic to honeybees, label precautions are not needed.
(2) Exposure and Risk to Nontarget Aquatic Animals
As noted above, the Agency calculates EECs using the GENeric Expected Environmental
Concentration Program (GENEEC). The EECs are used for assessing surface water concentrations
56
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and for assessing acute and chronic risks to aquatic organisms. Acute risk assessments are
performed using peak EEC values for single and multiple applications. Chronic risk assessments
are performed using the 21-day EECs for invertebrates and 56-day EECs for fish. EEC values were
presented in the Surface Water Assessment section of this document.
(3) Freshwater Fish
Acute risk quotients are tabulated below.
TABLE 18: Risk Quotients for Freshwater Fish
Site/
Application
Method/ Rate in
Ibs ai/A (No. of
Apps.)
Ag areas/aerial
0.0176 (1)
Ag areas/ground
umncorp.
0.0176(1)
LC50
(ppm)
0.09
0.09
NOEC/
MATC
(ppm)
NA
NA
EEC
Initial/Peak
(ppm)
0.000015
0.000015
EEC
56-day
avg.
(ppm)
Acute RQ
(EEC/LC50)
0.00
0.00
Chronic RQ
(EEC/NOEC or
MATC)
N/A
N/A
The results indicate that no aquatic acute levels of concern are exceeded for
freshwater fish at any registered single application rate (<0.0176 Ib ai/A).
Hydramethylnon appears to bioaccumulate in fish. Bioconcentration factors of
1300X in whole fish, 780X in fillet, and 1900X in viscera have been reported (MRID
00101611). The chemical was observed to depurate slowly. The binding of
hydramethylnon to soil may decrease its bioavailability to aquatic organisms, however.
(a)
Freshwater Invertebrates
The acute risk quotients are tabulated below.
TABLE 19: Risk Quotients for Freshwater Invertebrates
Site/
Application
Method/ Rate
in Ibs ai/A
(No. of Apps.)
Ag areas/aerial
0.0176 (1)
LC50
(ppm)
1.14
NOEC/
MATC
(ppm)
NA
EEC
Initial/
Peak
(ppm)
0.000015
EEC
21-Day
Average
Acute RQ
(EEC/LC50)
0.00
Chronic RQ
(EEC/NOEC
or MATC)
??
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TABLE 19: Risk Quotients for Freshwater Invertebrates
Site/
Application
Method/ Rate
in Ibs ai/A
(No. of Apps.)
Ag areas/ground
unincorp.
0.0176 (1)
LC50
(ppm)
1.14
NOEC/
MATC
(ppm)
NA
EEC
Initial/
Peak
(ppm)
0.000015
EEC
21-Day
Average
Acute RQ
(EEC/LC50)
0.00
Chronic RQ
(EEC/NOEC
or MATC)
NA
The results indicate that no aquatic acute levels of concern are exceeded for
freshwater invertebrates at any single registered application rate (<0.0176 Ib ai/A). There
are no data available to assess chronic risk.
The only aquatic use hydramethylnon has is a non-food industrial use in sewage
systems. To simulate direct exposure to aquatic organisms, a worst case direct application
to water during aerial applications to terrestrial sites was used. For such a case, the Agency
assumes simple dilution of the amount applied to a surface acre of water at depths varying
from 6 inches to 6 feet. The resulting EECs ranged from 0.0015 ppm to 0.009 ppm (note
0.009 ppm is consistent with the registrant's estimate of water solubility and slightly exceeds
published solubility maximum of 0.007 ppm). Since this worst case scenario of direct aerial
application to a body of water results in such a low estimate of exposure, the Agency
estimates that the exposure of aquatic organisms from use in sewer systems will be far less.
(4) Endangered Species
The Endangered Species Protection Program is expected to become final in the
future. Limitations in the use of hydramethylnon may be required to protect endangered and
threatened species, but these limitations have not been defined and may be formulation
specific. EPA anticipates that a consultation with the Fish and Wildlife Service will be
conducted in accordance with the species-based priority approach described in the Program.
After completion of consultation, registrants will be informed if any required label
modifications are necessary. Such modifications would most likely consist of the generic
label statement referring pesticide users to use limitations contained in county bulletins.
b.
Environmental Risk Characterization
Hydramethylnon is an insecticide used to control imported fire ants, harvester ants,
big-headed ants, and cockroaches indoors; on agricultural crops, pastures, and rangeland;
ornamental and shade trees; ornamental herbaceous plants; and ornamental lawns and turf.
In addition, hydramethylnon has been used in sewage systems to coat the backs of manhole
58
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covers. Agency data show that approximately 95% of the chemical's limited usage in
pounds per active ingredient is in non-agricultural use, such as homeowner bait use and
professional pest control application. About 5% of the total amount used may be in
agriculture, primarily on pastures and rangeland. Hydramethylnon is applied in bait boxes
or by ground, air, or by hand. The maximum application rate, formulated as a granular bait,
is 0.0176 Ib a.i./A.
Environmental Fate Summary
Laboratory data indicate that the major routes of hydramethylnon's dissipation on
the soil surface are abiotic photolysis and soil binding. The major route of dissipation below
the soil surface appears to be soil binding. Hydramethylnon appears to dissipate very slowly
by biotic processes. It is stable to hydrolysis at pH 5, pH 7, and pH 9. Furthermore, soil
TLC results indicate that hydramethylnon is immobile, and field data appear to confirm the
laboratory data as well.
Toxicity Summary
The available acute toxicity data on the TGAI indicate that hydramethylnon is
slightly toxic to practically non-toxic to birds, slightly toxic to small mammals, practically
non-toxic to bees, and moderately to very highly toxic to freshwater organisms.
Hydramethylnon induces male infertility in laboratory mammals. The exact mechanism for
these effects is not known at this time. However, hydramethylnon inhibition of electron
transport at site II (cytochrome b-Cl complex) may contribute to direct cellular or tissue
toxicity, or may result in some disruption of hormonally-mediated processes.
Risk Assessment/Characterization
For mammals, no acute risks are evident. However, there is a potential for chronic
risks to terrestrial mammals consuming hydramethylnon baits. Concentrations of
hydramethylnon in bait formulations exceed the mammalian reproduction NOEC and
encompass the LOEC. It is therefore possible that dietary incorporation of baits in the field
may result in oral exposures approximating reproductive toxicity thresholds in mammalian
wildlife. In addition, the Agency does have adverse incident data from the use of
hydramethylnon, although the certainty of the incidents is unknown at present.
No avian acute risks are evident. No toxicological data are available to
quantitatively assess chronic risks to avian species. However, observation of reproductive
effects in mammals suggest that oral exposure of other organisms to hydramethylnon may
result in chronic reproductive effects. In the absence of toxicological data to the contrary,
the Agency assumes that hydramethylnon has a potential to cause chronic reproductive
effects in avian species at concentrations representative of hydramethylnon use in bait
formulations. On the basis of this assumption, it is therefore possible that outdoor uses of
59
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hydramethylnon baits may pose a risk to avian wildlife.
No acute LOCs are exceeded for freshwater fish or invertebrates. Chronic risks
cannot be evaluated at the present due to lack of data. With regard to plants, aquatic plant
testing is not currently required for pesticides other than herbicides and fungicides, except
on a case-by-case basis.
The Agency has considered the importance of the mammalian and avian wildlife risk
assumptions with respect to the likelihood for terrestrial wildlife exposure. Such a
consideration is also useful in evaluating the importance of addressing the current avian
reproductive toxicity data gap. Available information indicates that agricultural uses of
hydramethylnon encompass approximately 60,000 acres and involve the use of less than
1,000 pounds of active ingredient. In addition, non-agricultural uses, which may account
for an additional 21,500 to 36,000 pounds of hydramethylnon, may also include outdoor
uses which may result in exposure to terrestrial organisms.
Although the future geographic extent of hydramethylnon usage is uncertain, the
Agency believes that the number of acres treated increases the potential for localized wildlife
effects. Therefore, the Agency requires that avian reproduction data be submitted to more
clearly define toxicological thresholds for such species or that measures be taken to
significantly reduce or eliminate the outdoor uses of hydramethylnon.
Drinking Water Assessment
The Agency believes that hydramethylnon should not pose a major threat to surface
and ground water quality because it has a high binding affinity (Kd>1039 ml/g) on soil and
the outdoor (non-bait) use is limited. However, the impact of hydramethylnon
phototransformation products on surface and ground-water quality cannot be assessed due
to insufficient data. Additional mobility data are needed to assess the environmental fate
of phototransformation products.
The peak GENEEC estimated environmental concentration of hydramethylnon in
surface water is 0.015 ppb. Drinking water exposure through ground water is estimated to
be the SCI-GROW default value of 0.006 ppb.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of relevant
data concerning an active ingredient, whether products containing the active ingredient are eligible
for reregistration. The Agency has previously identified and required the submission of the generic
(i.e. active ingredient specific) data required to support reregistration of products containing
60
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hydramethylnon. 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 products containing hydramethylnon.
Appendix B identifies the generic data requirements that the Agency reviewed as part of its
determination of reregi strati on eligibility of hydramethylnon and lists the submitted studies that the
Agency found acceptable.
The data identified in Appendix B were sufficient to allow the Agency to assess the
registered uses of hydramethylnon, and to determine that hydramethylnon can be used without
resulting in unreasonable adverse effects to humans and the environment. The Agency therefore
finds that all products containing hydramethylnon as the active ingredient are eligible for
reregistration. The reregistration of particular products is addressed in Section V of this document.
The Agency made its reregistration eligibility determination based upon the target data base
required for reregistration, the current guidelines for conducting acceptable studies to generate such
data, published scientific literature, etc. and the data identified in Appendix B. Although the Agency
has found that all uses of hydramethylnon are eligible for reregistration, it should be understood that
the Agency may take appropriate regulatory action, and/or require the submission of additional data
to support the registration of products containing hydramethylnon, if new information comes to the
Agency's attention or if the data requirements for registration (or the guidelines for generating such
data) change.
B. Determination of Eligibility Decision
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredient hydramethylnon,
the Agency has sufficient information on the health effects of hydramethylnon and on its
potential for causing adverse effects in fish and wildlife and the environment. The Agency
has determined that hydramethylnon products, labeled and used as specified in this
Reregistration Eligibility Decision, will not pose unreasonable risks or adverse effects to
humans or the environment. Therefore, the Agency concludes that products containing
hydramethylnon for all uses are eligible for reregistration.
2. Eligible and Ineligible Uses
The Agency has determined that all hydramethylnon uses as previously described are
eligible for reregistration.
The Agency has determined that registrants may distribute and sell hydramethylnon
products bearing old labels/labeling for 26 months from the date of issuance of this RED.
Persons other than the registrant may distribute or sell such products for 50 months from
the date of the issuance of this RED. Registrants and persons other than registrants remain
obligated to meet pre-existing Agency imposed label changes and existing stocks
61
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requirements applicable to products they sell or distribute.
The following is a summary of the regulatory positions and rationales for
hydramethylnon. Where labeling revisions are imposed, specific language is set forth in
Section V of this document.
3. Tolerance Reassessment
Existing tolerances of 0.05 ppm are currently established for the insecticide
hydramethylnon in or on grasses, forage (pasture and rangeland) and grasses, hay (pasture
and rangeland), respectively (40 CFR §180.395). The Agency no longer distinguishes
between rangeland and pastures. The Agency recommends that the grass forage tolerance
be increased to 2.0 ppm and the grass hay tolerance be increased to 0.1 ppm. These
tolerances have been corrected to a zero day (0-day) post harvest interval (PHI). The
Agency no longer allows a PHI restriction for use on grass. There is a 7-day baling
restriction for grass hay. The meat, milk, and meat byproducts tolerance will remain in
a 40 CFR § 180.6(a)3 status.
4. Tolerance Revocations and Import Tolerances
As part of EPA's reregi strati on eligibility decision for hydramethylnon, the existing
tolerances on grasses (pasture and rangeland) will be amended. If a pesticide use is no
longer registered in the United States, the related pesticide residue tolerance and/or
food/feed additive regulation generally is no longer needed. It is EPA's policy to propose
revocation of a tolerance, and/or food/feed additive regulation, following the deletion of a
related food use from a registration, or following the cancellation of a related food-use
registration. EPA has the responsibility under the Federal Food, Drug, and Cosmetic Act
(FFDCA) to revoke a tolerance/regulation on the grounds that the Agency cannot conclude
that the tolerance/regulation is protective of the public health.
The Agency recognizes, however, that interested parties may want to retain a
tolerance and/or food/feed additive regulation in the absence of a U.S. registration, to allow
legal importation of food into the U.S. To assure that all food marketed in the U.S. is safe,
under FFDCA, EPA requires the same technical chemistry and toxicology data for such
import tolerances (tolerances without related U.S. registrations) as are required to support
U.S. food use registrations and any resulting tolerances. See 40 CFR Part 158 for EPA's
data requirements to support domestic use of a pesticide and establishment and maintenance
of a tolerance and/or food/feed regulation. In addition, EPA requires residue chemistry data
(crop field trials) that are representative of growing conditions in exporting countries in the
same manner that EPA requires representative residue chemistry data from different U.S.
regions to support domestic use of the pesticide and the tolerance and/or regulation.
Additional guidance on the Agency's import tolerance policy will be published in an
upcoming Federal Register Notice.
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Codex Harmonization
No Codex Maximum Residue Levels (MRLs) have been established for
hydramethylnon; therefore, issues of compatibility between Codex MRLs and U.S.
tolerances do not exist.
5. Food Quality Protection Act Findings
a. Determination of Safety for U.S. Population
EPA has determined that the established tolerances for hydramethylnon, with
amendments and changes as specified in this document, meet the safety standards under the
FQPA amendments to FFDC A Section 408(b)(2)(D) for the general population. In reaching
this determination, EPA has considered the available information on the aggregate
exposures (both acute and chronic) from non-occupational sources, food and drinking
water.
For hydramethylnon, there is little likelihood of residues in water or food items and
non-accidental residential exposure will be minimal. Therefore, no acute or chronic dietary,
or drinking water risk assessments were conducted and aggregate risk assessments are not
necessary for hydramethylnon at this time.
The Agency has not yet made a determination regarding the common
mode/mechanism of toxicity of hydramethylnon and whether it is appropriate to consider
exposure from hydramethylnon with other compounds in order to address cumulative
effects. In general, after EPA develops a methodology for applying common mechanism of
toxicity issues to risk assessments, the Agency will develop a process (either as part of the
periodic review of pesticides or otherwise) to reexamine those tolerance decisions made
earlier. However, with respect to hydramethylnon tolerance reassessment, any future
cumulative risk determination regarding other chemicals that have a common mode of
toxicity with hydramethylnon will not include the uses of hydramethylnon discussed in this
document because the exposures from hydramethylnon use as described in this RED are so
unlikely. For the purposes of this reregi strati on decision, all hydramethylnon tolerances are
assumed to be reassessed.
However, based on the high MOEs for hydramethylnon and its negligible dietary
sources, drinking water and non-occupational exposures, the contribution of
hydramethylnon exposures to the risks of other compounds with a common
mode/mechanism of toxicity is likely to be minimal.
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b. Determination of Safety for Infants and Children
EPA has determined that the established tolerances for hydramethylnon, with
amendments and changes as specified in this document, meet the safety standards under the
FQPA amendments to FFDCA Section 408(b)(2)(C) for infants and children. The safety
determination for infants and children considers the factors noted above for the general
population, but also takes into account the possibility of increased dietary exposure due to
the specific consumption patterns of infants and children, as well as the possibility of
increased susceptibility to the toxic effects of hydramethylnon residues in this population
subgroup.
The Agency does not believe that exposure from the accidental ingestion of baits
should be used in making the tolerance safety finding under FQPA. These exposures are
accidental in nature and should not be considered as part of the FQPA calculus for non-
occupational exposure. In addition, the dietary and drinking water contributions from
hydramethylnon are negligible.
In determining whether infants and children are particularly susceptible to the toxic
effects from hydramethylnon residues, EPA considers the completeness and reliability of the
toxicity data base, the nature of the effects observed in toxicity studies, and other
information. The Agency evaluated a two-generation reproduction study in rats and a
prenatal developmental toxicity study in rats and rabbits. There was no evidence of pre or
post natal sensitivity in any of these studies. The developmental effects and effects on
offspring occurred at dose levels that were equal to or greater than the maternal NOAELs.
Thus, the Agency has concluded that there is no special sensitivity to infants and children
from hydramethylnon exposure.
In addition, the Agency believes there is little likelihood of direct exposure to infants
and children since hydramethylnon has one food use and will not result in drinking water
exposure. Any residential exposures are expected to be minimal and within safe MOEs.
The Agency does not have concerns for prenatal exposures based on the adequate MOEs,
the highest risk users, and the lack of increased susceptibility seen in the developmental and
reproduction studies.
In examining aggregate exposure, EPA takes into account available information
concerning exposures from dietary sources, drinking water and non-occupational sources.
As noted in the preceding paragraph, the primary source of hydramethylnon exposure is
occupationally related.
In deciding to continue to make reregi strati on determinations during the early stages
of FQPA implementations, EPA recognizes that it will be necessary to make decisions
relating to FQPA before the implementation process is complete. In making these early,
case-by-case decisions, EPA does not intend to set broad precedents for the application of
64
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FQPA to its regulatory determinations. Rather, these early decisions will be made on a
case-by-case basis and will not bind EPA as it proceeds with further policy development and
rulemaking that may be required.
EPA may determine, as a result of this later implementation process, that any of the
determinations described in this RED are no longer appropriate. In this case, the Agency
will consider itself free to pursue whatever action may be appropriate, including but not
limited to, reconsideration of any portion of this RED.
6. Occupational Labeling Rationale/Risk Mitigation
Hydramethylnon pesticide products that are intended for occupational use are within
the scope of the Worker Protection Standard.
The Worker Protection Standard (WPS)
On August 21, 1992, the Agency issued worker protection regulations affecting all
pesticide products whose labeling reasonably permits use in the production of agricultural
plants on any farm, forest, nursery or greenhouse. In general, products within the scope of
the Worker Protection Standard (WPS) had to bear complying labeling when sold or
distributed by the registrant after April 21, 1994.
The WPS labeling requirements pertaining to personal protective equipment (PPE),
restricted entry intervals (REI), and notification are interim. The interim WPS handler PPE
requirements are based solely on the acute dermal and inhalation toxicity and skin and eye
irritation potential of the end-use product. The interim WPS restricted-entry intervals for
agricultural workers are based solely on the acute dermal toxicity and skin and eye irritation
potential of the active ingredient. The interim WPS "double" notification requirement is
imposed if the active ingredient is classified as toxicity category I for acute dermal toxicity
or skin irritation potential. "Double" notification is the statement on the labels of some
pesticide products requiring employers to notify workers about pesticide-treated areas orally
as well as by posting of the treated areas. The WPS retained more stringent PPE, REI, and
notification requirements from existing labeling. These requirements are to be reviewed and
revised, as appropriate, during reregi strati on and other Agency review processes. During
reregi strati on, the Agency reviews risks resulting from WPS uses as well as from all other
occupational and residential uses.
Personal Protective Equipment for Handlers (Mixers, Loaders, Applicators)
Occupational handler exposures and risks are evaluated jointly. As a result of the
reregi strati on evaluation of the acute and other adverse effects of hydramethylnon, the
Agency has determined that risks to handlers do not warrant the establishment of active-
ingredient-based minimum personal protective equipment or engineering-control
65
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requirements that would apply to all hydramethylnon end-use products. The risks to
handlers are adequately mitigated with the addition of water resistant gloves for most
handler scenarios. Therefore, the Agency is requiring that all handlers wear water- resistant
gloves.
Worker Notification
Hydramethylnon is not classified as toxicity category I for select acute dermal
toxicity or skin irritation potential and is not classified as a severe skin sensitizer. EPA has
no special concerns about hydramethylnon for adverse effects where a single exposure can
trigger the effect and EPA has not established an unusually long restricted-entry interval.
Therefore, at this time, EPA is not requiring a WPS "double" notification statement on the
labeling of hydramethylnon end-use products.
7. Endocrine Disrupter Effects
EPA is required to develop a screening program to determine whether certain
substances (including all pesticides and inerts) "may have an effect in humans that is similar
to an effect produced by a naturally occurring estrogen, or such other endocrine effect..."
The Agency is currently working with interested stakeholders, including other government
agencies, public interest groups, industry and research scientists in developing a screening
and testing program and a priority setting scheme to implement this program. Congress has
allowed 3 years from the passage of FQPA (August 3, 1999) to implement this program.
At that time, EPA may require further testing of this active ingredient and end use products
for endocrine disrupter effects.
8. Environmental Assessment
Based upon available data, the Agency concludes that risk to freshwater and
terrestrial organisms and water resources will be minimal. No additional label statements
are required. Certain additional confirmatory data are being required.
9. Restricted Use Classification
Hydramethylnon does not require and is not being considered for restricted use.
10. Endangered Species Statement
The Agency has developed a program (the "Endangered Species Protection
Program") to identify pesticides whose use may cause adverse impacts on endangered and
threatened species, and to implement mitigation measures that will eliminate the adverse
impacts. At present, the program is being implemented on an interim basis as described in
a Federal Register notice (54 FR 27984-28008, July 3,1989), and is providing information
66
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to pesticide users to help them protect these species on a voluntary basis. As currently
planned, the final program will call for label modifications referring to required limitations
on pesticide uses, typically as depicted in county-specific bulletins or by other site-specific
mechanisms as specified by state partners. A final program, which may be altered from the
interim program, will be described in a future Federal Register notice. The Agency is not
imposing label modifications through the RED. Rather, any requirements for product use
modifications will occur in the future under the Endangered Species Protection Program.
The Agency will consult with the Fish and Wildlife Service and/or the National
Marine Fisheries Service if necessary to determine if steps need to be taken to protect newly
listed species or from proposed new uses of these hydramethylnon.
V. ACTIONS REQUIRED OF REGISTRANTS
This section specifies the data requirements and responses necessary for the reregi strati on
of both manufacturing-use and end-use products.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of hydramethylnon has been
reviewed and determined to be substantially complete. All product chemistry data
requirements will be satisfied when the registrant certifies that suppliers of beginning
materials and the manufacturing process for hydramethylnon have not changed since the last
comprehensive product chemistry review. The following guideline studies are new
requirements are now being called in:
GLN 71-4 Avi an Reproducti on
GLN 830.7050 UV/visible absorption for PAI
2. Labeling Requirements for Manufacturing-Use Products
To remain in compliance with FIFRA, manufacturing use product (MP) labeling
must be revised to comply with all current EPA regulations, PR Notices and applicable
policies. The MP labeling must bear the labeling contained in Table 20.
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.
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Registrants must review previous data submissions to ensure that they meet current EPA
acceptance criteria and if not, commit to conduct new studies. If a registrant believes that
previously submitted data meet current testing standards, then study MRID numbers should
be cited according to the instructions in the Requirement Status and Registrants Response
Form provided for each product.
The reregi strati on of hydramethylnon in the United States is being supported by
American Cyanamid Company. Agency records identified five end-use products (EPs) with
food/feed uses registered to American Cyanamid Company. The only hydramethylnon food
use being supported for reregi strati on is grass forage and grass hay. The application of
hydramethylnon as a bait in domestic dwellings and commercial establishments has been
determined to be a non-food use.
2. Labeling Requirements for End-Use Products
The labels and labeling of all products must comply with EPA's current regulations
and requirements as specified in 40 CFR 156.10 and other applicable notices. All end-use
product labels [e.g. multiple active ingredient (MAI) labels, SLN's, and products subject to
generic data exemption] must be amended such that they are consistent with the basic
producer labels. End use product labels must also bear labeling as specified in Table 20.
68
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Table 20: Summary of Required Labeling Changes for Hydramethylnon
Description
Required Labeling
Placement on
Manufacturing Use
One of these statements
may be added to a label
to allow reformulation
of the product for a
specific use or all
additional uses
supported by a
formulator or user
group
"Only for formulation into a insecticide for the following use(s) [fill blank only with those
uses that are being supported by MP registrant]."
"This product may be used to formulate products for specific use(s) not listed on the MP
label if the formulator, user group, or grower has complied with U.S. EPA submission
requirements regarding support of such use(s)."
"This product may be used to formulate products for any additional use(s) not listed on the
MP label if the formulator, user group, or grower has complied with U.S. EPA submission
requirements regarding support of such use(s)."
Directions for Use
End Use Products Intended for Occupational Use (WPS and Non-WPS))
Minimum (Baseline)
PPE Requirements
"Personal Protective Equipment (PPE)
Applicators and other handlers must wear:
Long-sleeve shirt and long pants
Water-resistant gloves
Shoes plus socks."
Precautionary
Statements:
Hazards to
Humans and
Domestic Animals
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User Safety
Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions
for washables exist, use detergent and hot water. Keep and wash PPE separately from other
laundry."
Precautionary
Statements:
Hazards to
Humans and
Domestic Animals
immediately
following the PPE
requirements
Engineering Controls
"Engineering Controls
When handlers use closed systems, enclosed cabs, or aircraft in a manner that meets the
requirements listed in the Worker Protection Standard (WPS) for agricultural pesticides (40
CFR 170.240(d)(4.6), the handler PPE requirements may be reduced or modified as
specified in the WPS."
Precautionary
Statements:
Hazards to
Humans and
Domestic Animals
(Immediately
following PPE and
User Safety
Requirements.)
User Safety
Recommendations
"User Safety Recommendations
Users should wash hands before eating, drinking, chewing gum, using tobacco, or using the
toilet.
Users should remove clothing/PPE immediately if pesticide gets inside. Then wash
thoroughly and put on clean clothing."
Users should remove PPE immediately after handling this product. Wash the outside of
gloves before removing. As soon as possible, wash thoroughly and change into clean
clothing."
Precautionary
Statements:
Hazards to
Humans and
Domestic Animals
(Must be placed in
a box.)
(Immediately
following
Engineering
Controls)
70
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Restricted-Entry
Interval
(required by Supplement
Three of PR Notice 93-
7)
Personal protective
equipment required for
early entry
A 12-hour restricted entry interval (REI) is required.
"The PPE required for early entry is:
Coveralls,
Water resistant gloves, and
Shoes plus socks."
Directions for Use,
Agricultural Use
Requirements Box
Application Restrictions
"Do not apply this product by any method not specified on this label."
"Do not apply this product in a way that will contact workers or other persons, either
directly or through drift. Only protected handlers may be in the area during application."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"Aerial Spray Drift Management"
"Avoiding spray drift at the application site is the responsibility of the applicator. The
interaction of many equipment-and-weather-related factors determine the potential for spray
drift. The applicator and the grower are responsible for considering all these factors when
making decisions."
Directions for Use
71
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The following language
must be placed on each
product that can be
applied aerially:
"The following drift management requirements must be followed to avoid off-target drift
movement from aerial applications to agricultural field crops. These requirements do not
apply to forestry applications, public health uses or to applications using dry formulations.
l.The distance of the outer most nozzles on the boom must not exceed 3/4 the length of the
wingspan or rotor.
2.Nozzles must always point backward parallel with the air stream and never be pointed
downwards more than 45 degrees.
Where states have more stringent regulations, they should be observed.
The applicator should be familiar with and take into account the information covered in the
Aerial Drift Reduction Advisory Information."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"Aerial Drift Reduction Advisory"
"This section is advisory in nature and does not supersede the mandatory label
requirements."
"INFORMATION ON DROPLET SIZE"
"The most effective way to reduce drift potential is to apply large droplets. The best drift
management strategy is to apply the largest droplets that provide sufficient coverage and
control. Applying larger droplets reduces drift potential, but will not prevent drift if
applications are made improperly, or under unfavorable environmental conditions (see Wind,
Temperature and Humidity, and Temperature Inversions)."
Directions for Use
72
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The following language
must be placed on each
product that can be
applied aerially:
"CONTROLLING DROPLET SIZE"
" ! Volume - Use high flow rate nozzles to apply the highest practical spray volume. Nozzles
with higher rated flows produce larger droplets.
! Pressure - Do not exceed the nozzle manufacturer's recommended pressures. For many
nozzle types lower pressure produces larger droplets. When higher flow rates are needed,
use higher flow rate nozzles instead of increasing pressure.
! Number of nozzles - Use the minimum number of nozzles that provide uniform coverage.
! Nozzle Orientation - Orienting nozzles so that the spray is released parallel to the airstream
produces larger droplets than other orientations and is the recommended practice.
Significant deflection from horizontal will reduce droplet size and increase drift potential.
! Nozzle Type - Use a nozzle type that is designed for the intended application. With most
nozzle types, narrower spray angles produce larger droplets. Consider using low-drift
nozzles. Solid stream nozzles oriented straight back produce the largest droplets and the
lowest drift."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"BOOM LENGTH"
"For some use patterns, reducing the effective boom length to less than 3/4 of the wingspan
or rotor length may further reduce drift without reducing swath width."
Directions for Use
73
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The following language
must be placed on each
product that can be
applied aerially:
"APPLICATION HEIGHT"
"Applications should not be made at a height greater than 10 feet above the top of the
largest plants unless a greater height is required for aircraft safety. Making applications at
the lowest height that is safe reduces exposure of droplets to evaporation and wind."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"SWATH ADJUSTMENT"
"When applications are made with a crosswind, the swath will be displaced downward.
Therefore, on the up and downwind edges of the field, the applicator must compensate for
this displacement by adjusting the path of the aircraft upwind. Swath adjustment distance
should increase, with increasing drift potential (higher wind, smaller drops, etc.)"
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"WIND"
"Drift potential is lowest between wind speeds of 2-10 mph. However, many factors,
including droplet size and equipment type determine drift potential at any given speed.
Application should be avoided below 2 mph due to variable wind direction and high
inversion potential. NOTE: Local terrain can influence wind patterns. Every applicator
should be familiar with local wind patterns and how they affect spray drift."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"TEMPERATURE AND HUMIDITY"
"When making applications in low relative humidity, set up equipment to produce larger
droplets to compensate for evaporation. Droplet evaporation is most severe when
conditions are both hot and dry."
Directions for Use
74
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The following language
must be placed on each
product that can be
applied aerially:
"TEMPERATURE INVERSIONS"
"Applications should not occur during a temperature inversion because drift potential is
high. Temperature inversions restrict vertical air mixing, which causes small suspended
droplets to remain in a concentrated cloud. This cloud can move in unpredictable directions
due to the light variable winds common during inversions. Temperature inversions are
characterized by increasing temperatures with altitude and are common on nights with
limited cloud cover and light to no wind. They begin to form as the sun sets and often
continue into the morning. Their presence can be indicated by ground fog; however, if fog is
not present, inversions can also be identified by the movement of smoke from a ground
source or an aircraft smoke generator. Smoke that layers and moves laterally in a
concentrated cloud (under low wind conditions) indicates an inversion, while smoke that
moves upward and rapidly dissipates indicates good vertical air mixing."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"SENSITIVE AREAS"
"The pesticide should only be applied when the potential for drift to adjacent sensitive areas
(e.g. residential areas, bodies of water, known habitat for threatened or endangered species,
non-target crops) is minimal (e.g. when wind is blowing away from the sensitive areas)."
Directions for Use
Application Restrictions
for all products with
uses on rangeland and
pasture (grass forage).
The label must state for use on grass forage. The terms "pasture" and "rangland grasses"
are no longer acceptable and must be removed from the label.
Post harvest inervals on grass forage must be removed.
Directions For Use
Products used to control
imported fire ants.
"This product may only be used in the following States: AL, AR, FL, GA, LA, MS, NC,
OK, SC, TN, TX, and VA.
Directions For Use
Products used on non-
bearing nursery stocks.
Labeling must be submitted restricting harvesting of food/feed within one year of application
on non-bearing nursery stocks.
Directions For Use
All Residential/Consumer/ Homeowner Use Products
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Application Restrictions.
"Do not apply this product in a way that will contact any person or pet, either directly or
through drift. Keep people and pets out of the area during application."
Directions For Use
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C. Tolerance Adjustments
Tolerances and labels for hydramethylnon on grasses should be adjusted so as to permit use
on grass forage (both pasture and rangeland grasses). The Agency no longer differentiates between
these sites. Tolerances for hydramethylnon on grass forage should be corrected to a 0-day post
harvest interval (PHI). The Agency publish a Federal Register Notice that announces the amended
tolerances. The labels should remove any PHI on grass forage as the Agency no longer permits this
restriction. Hydramethylnon as an imported fire ant bait on grasses is restricted to the following
states where infestation has been documented and supporting data is in place: Alabama, Arkansas,
Florida, Georgia, Louisana, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee,
Texas, and Virginia. Restrict against harvesting of food/feed within one year of application on non-
bearing nursery stocks.
D. Existing Stocks
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 (RED). Persons other than
the registrant may generally distribute or sell such products for 50 months from the date of the
issuance of 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.
The Agency has determined that registrants may distribute and sell hydramethylnon products
bearing old labels/labeling for 26 months from the date of issuance of this RED. Persons other than
the registrant may distribute or sell such products for 50 months from the date of the issuance of this
RED. Registrants and persons other than registrants remain obligated to meet pre-existing Agency
imposed label changes and existing stocks requirements applicable to products they sell or distribute.
77
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78
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VI. APPENDICES
79
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80
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Appendix A is 26 pages long and is not being included in this RED. Copies of Appendix A are available upon request
per the instructions in Appendix E.
81
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregi strati on for active ingredients within the case 2585
covered by this Reregi strati on Eligibility Decision Document. It contains generic data requirements that apply to
Hydramethylnon in all products, including data requirements for which a "typical formulation" is the test substance.
The data table is organized in the following format:
1. Data Requirement (Column 1). The data requirements are listed in the order in which they appear in 40 CFR Part
158. the reference numbers accompanying each test refer to the test protocols set in the Pesticide Assessment Guidelines,
which are available from the National Technical Information Service, 5285 Port Royal Road, Springfield, VA 22161 (703)
605-6000.
2. Use Pattern (Column 2). This column indicates the use patterns for which the data requirements apply. The
following letter designations are used for the given use patterns:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
O Indoor residential
3. Bibliographic citation (Column 3). If the Agency has acceptable data in its files, this column lists the identifying
number of each study. This normally is the Master Record Identification (MRID) number, but may be a "GS" number if no
MRID number has been assigned. Refer to the Bibliography appendix for a complete citation of the study.
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Hydramethylnon (118401)
REQUIREMENT
USE PATTERN
CITATION(S)
PRODUCT CHEMISTRY
61-1
61-2A
61-2 B
62-1
63-2
63-3
63-4
63-5
63-7
63-8
63-9
63-10
63-11
63-12
63-13
Chemical Identity
Start. Mat. & Mnfg. Process
Formation of Impurities
Preliminary Analysis
Color
Physical State
Odor
Melting Point
Density
Solubility
Vapor Pressure
Dissociation Constant
Octanol/Water Partition
pH
Stability
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
41612501
41612501
41612501
41612502
41612502
41612502
41612502
41612502
41612502
41612502
41612502
41612502
41612502
41612502
41612502
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Data Supporting Guideline Requirements for the Reregistration of Hydramethylnon (118401)
REQUIREMENT
USE PATTERN
CITATION(S)
ECOLOGICAL EFFECTS
71-1
71-2A
71-2B
72-1A
72-1B
72-2
141-1
Acute Avian Oral - Quail/Duck
Avian Dietary - Quail
Avian Dietary - Duck
Fish Toxicity Bluegill
Fish Toxicity Rainbow Trout
Invertebrate Toxicity
Honey Bee Acute Contact
BC
BC
BC
BC
BC
BC
BC
64575, 64576
64577, 98982
85931,98982
52858
35279
99779
41607801
TOXICOLOGY
81-1
81-2
81-3
81-4
81-5
81-6
82-1A
82-1B
Acute Oral Toxicity - Rat
Acute Dermal Toxicity - Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit
Dermal Sensitization - Guinea Pig
90-Day Feeding - Rodent
90-Day Feeding - NonRodent
ALL
ALL
ALL
ALL
ALL
ALL
BC
BC
41612503
41612504
42871101
41612505
41612506
101560
32641
61794
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Data Supporting Guideline Requirements for the Reregistration of Hydramethylnon (118401)
REQUIREMENT
USE PATTERN
CITATION(S)
82-2 21-Day Dermal - Rabbit
83-1A Chronic Feeding Toxicity - Rodent
83-1B Chronic Feeding Toxicity - Non-
Rodent
83-2A Oncogenicity - Rat
83-2B Oncogenicity - Mouse
83-3A Developmental Toxicity - Rat
83-3B Developmental Toxicity - Rabbit
83-4 2-Generation Reproduction - Rat
84-2A Gene Mutation - Ames
84-2B Structural Chromosomal
Aberration
84-4 Other Genotoxic Effects
85-1 General Metabolism
85-2 Dermal Penetration
ENVIRONMENTAL FATE
161-1 Hydrolysis
161-2 Photodegradation - water
161-3 Photodegradation - soil
BC
BC
BC
BC
BC
BC
BC
BC
BC
BC
BC
BC
BC
ALL
ALL
ALL
101559
61768,101565, 126106
61794, 35529
126106
35526, 101563,40871801
61790
101558
43741501
42132701
40422401, 35897
40407602
42448902
40407602
42194701
42238201, 42473301
42353801
85
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Data Supporting Guideline Requirements for the Reregistration of Hydramethylnon (118401)
REQUIREMENT
162-1
162-3
162-1
165-4
RESIDUE
171-4A
171-4B
171-4C
171-4C
171-4E
171-4K
Aerobic Soil Metabolism
Anerobic Aquatic Metabolism
Aerobic Soil Metabolism
Bioaccumulation in Fish
CHEMISTRY
Nature of Residue - Plants
Nature of Residue - Livestock
Residue Analytical Method - Plants
Residue Analytical Method -
Animals
Storage Stability
Crop Field Trials
-Grass forage and hay
USE PATTERN
BC
BC
BC
BC
BD
BD
BD
BD
BD
BC
42320801
43102701
42320801
101611
43744501
42871102
CITATION(S)
43345203, 43485201, 43632801
34024, 34025,
43636702
61797, 61798,
61804, 61805
43485201
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GUIDE TO APPENDIX C
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies considered relevant by
EPA in arriving at the positions and conclusions stated elsewhere in the Reregistration Eligibility Document.
Primary sources for studies in this bibliography have been the body of data submitted to EPA and its predecessor
agencies in support of past regulatory decisions. Selections from other sources including the published literature,
in those instances where they have been considered, are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In the case of published materials,
this corresponds closely to an article. In the case of unpublished materials submitted to the Agency, the Agency
has sought to identify documents at a level parallel to the published article from within the typically larger
volumes in which they were submitted. The resulting "studies" generally have a distinct title (or at least a single
subject), can stand alone for purposes of review and can be described with a conventional bibliographic citation.
The Agency has also attempted to unite basic documents and commentaries upon them, treating them as a single
study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted numerically by Master Record
Identifier, or "MRID number". This number is unique to the citation, and should be used whenever a specific
reference is required. It is not related to the six-digit "Accession Number" which has been used to identify
volumes of submitted studies (see paragraph 4(d)(4) below for further explanation). In a few cases, entries
added to the bibliography late in the review may be preceded by a nine character temporary identifier. These
entries are listed after all MRID entries. This temporary identifying number is also to be used whenever specific
reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry consists of a citation
containing standard elements followed, in the case of material submitted to EPA, by a description of the earliest
known submission. Bibliographic conventions used reflect the standard of the American National Standards
Institute (ANSI), expanded to provide for certain special needs.
a Author. Whenever the author could confidently be identified, the Agency has chosen to show a personal
author. When no individual was identified, the Agency has shown an identifiable laboratory or testing
facility as the author. When no author or laboratory could be identified, the Agency has shown the first
submitter as the author.
b. Document date. The date of the study is taken directly from the document. When the date is followed by
a question mark, the bibliographer has deduced the date from the evidence contained in the document.
When the date appears as (19??), the Agency was unable to determine or estimate the date of the
document.
c. Title. In some cases, it has been necessary for the Agency bibliographers to create or enhance a
document title. Any such editorial insertions are contained between square brackets.
d. Trailing parentheses. For studies submitted to the Agency in the past, the trailing parentheses include (in
addition to any self-explanatory text) the following elements describing the earliest known submission:
(1) Submission date. The date of the earliest known submission appears immediately following the
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word "received."
(2) Administrative number. The next element immediately following the word "under" is the
registration number, experimental use permit number, petition number, or other administrative
number associated with the earliest known submission.
(3) Submitter. The third element is the submitter. When authorship is defaulted to the submitter, this
element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the trailing parentheses
identifies the EPA accession number of the volume in which the original submission of the study
appears. The six-digit accession number follows the symbol "CDL," which stands for "Company
Data Library." This accession number is in turn followed by an alphabetic suffix which shows the
relative position of the study within the volume.
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BIBLIOGRAPHY
MRID
CITATION
00032641 Tegeris, A.S.; Sagartz, J.W.; Salib, M.H.; et al. (1979) AC 217, 300: 91-Day Study in the Rat: Report
No. 7866; Report No. P-98178-143-1. (Unpublished study received June 11, 1980 under 241260;
prepared by Pharmacopathics Research Laboratories, Inc., submitted by American Cyanamid Co.,
Princeton, N.J.; CDL: 099452-A)
00034020 Tondreau, R.E. (1979) CL 217,300: Validation of GC Method M-1000
for the Determination of CL 217,300 Residues in Pasture Grass: Report No. C-1597. Includes method
M-1000 dated Aug 24, 1979. (Unpublished study received June 11, 1980 under 241-260; submitted by
American Cyanamid Co., Princeton, N.J.; CDL:099454-A)
00034021 Tondreau, R.E.; Wang, T.; Williams, D.; et al. (1979) CL 217,300: Residues of 217,300 in Grass (GND;
FL, 1979) (C-1597): Report No. C-1598. (Unpublished study received June 11, 1980 under 241-260;
prepared in cooperation with U.S. Dept. of Agriculture, Science and Education Administration, submitted
by American Cyanamid Co., Princeton, N.J.; CDL:099454-B)
00034025 Tondreau, R.E.; Manuel, A.J. (1980) CL 217,300: Validation of GC or HPLC Method M-1046 for the
Determination of CL 217,300 Residues in Milk: Report No. C-1647. Includes method M-1046 dated Feb
4, 1980. (Unpublished study received June 11, 1980 under 241-260; submitted by American Cyanamid
Co., Princeton, N.J.; CDL: 099454-F)
00035525 Schroeder, R.E.; Rinehart, W.E. (1980) A Three-Generation Reproduction Study with AC 217,300 in
Rats: Status Report: Project No. 79-2412. (Unpublished study received July 1, 1980 under 241260;
prepared by Bio/dynamics, Inc., submitted by American Cyanamid Co., Princeton, N.J.; CDL:099489-A)
00035526 Jessup, D.C.; Homan, S.P.; Miller, P. (1980) Eighteen-Month Feeding Study of AC 217,300 to Mice
(6-Month Interim Report): IRDC 141-013. (Unpublished study received July 1, 1980 under 241-260;
prepared in cooperation with International Research and Development Corp., submitted by American
Cyanamid Co., Princeton, N.J.; CDL:099489-B)
00035529 Wolfe, G.W.; Marshall, P.M.; Weatherholtz, W.M.; et al. (1980) Twenty-Six Week Toxicity Study in
Dogs: AC 217,300: Project No. 362-156. Final rept. (Unpublished study received July 1, 1980 under
241-260; prepared by Hazleton Laboratories America, Inc., submitted by American Cyanamid Co.,
Princeton, N.J.; CDL: 099487-B)
00061790 Schroeder, R.E.; Rinehart, W.E.; Bshasso, L.; et al. (1979) Teratogenesis Study in Rats with AC
217,300: Project No. 79-2382. Final rept. (Unpublished study received July 1, 1980 under 241260;
prepared by Bio/dynamics, Inc., submitted by American Cyanamid Co., Princeton, N.J.; CDL:099770-G)
00061794 Tegeris, A.S.; Sagartz, J.W.; Myers, A.K.; et al. (1979) AC 217,300: 91-Day Study in the Dog: Report
No. 7864; Report No. P-981-78-142. (Unpublished study received July 1, 1980 under 241-260; prepared
89
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BIBLIOGRAPHY
MRID
CITATION
by Pharmacopathics Research Laboratories, Inc., submitted by American Cyanamid Co., Princeton, N.J.;
CDL: 099772-A)
00101558 Schardein, 1; Lang, P.; Laughlin, K.; et al. (1982) Teratology Study with AC 217,300 in Rabbits:
141-024. (Unpublished study received May 14, 1982 under 2F2627; prepared by International Research
and Development Corp., submitted by American Cyanamid Co., Princeton, NJ; CDL:070849-C)
00101559 Thompson, G.; Rao, G.; MacWilliams, P.; et al. (1982) Subchronic 21-day Dermal Toxicity Study of AC
217,300 in Rabbits: Raltech Study No. 80033. Final rept. (Unpublished study received May 14, 1982
under 2F2627; prepared by Hazleton Raltech, Inc., submitted by American Cyanamid Co., Princeton, NJ;
CDL:070849-D)
00101560 Siglin, J.; Becci, P. (1982) Dermal Sensitization Study in Guinea Pigs with AC 217,300 Technical (92%)
and AC 217,300 3.2% Concentrate: FDRL Study No. 7180. Final rept. (Unpublished study received
May 14, 1982 under 2F2627; prepared by Food and Drug Research Laboratories, Inc., submitted by
American Cyanamid Co., Princeton, NJ; CDL:070849-E)
00101563 Brewer, L. (1982) Eighteen-month Feeding Study of AC 217,300 to Mice: 141-013. (Unpublished study
received May 14, 1982 under 2F2627; prepared by International Research and Development Corp.,
submitted by American Cyanamid Co., Princeton, NJ; CDL: 070850-A; 070851; 070852; 070853;
070854)
00101565 Blair, M.; Brewer, L.; Kopplin, J. (1982) 24-month Feeding Study of AC 217,300 to Rats: 141-014.
(Unpublished study received May 18, 1982 under 241-260; prepared by International Research and
Development Corp., submitted by American Cyanamid Co., Princeton, NJ; CDL:070865-B; 070866;
070867; 070868; 070869)
00106033 Kim, D. (1982) Amdro Fire Ant Insecticide (Cl 217,300): Determination of the Vapor Pressure of Cl
217,300 by the Gas-saturation Technique: Report No. PD-A 18-1: 1-10. (Unpublished study received
June 23, 1982 under 241-267; submitted by American Cyanamid Co., Princeton, NJ; CDL:247831-A)
00101611 Barringer, D.; Stanley-Millner, P. (1982) Amdro Fire Ant Insecticide (CL 217,300): Identification and
Characterization of CL 217,300 and Its Metabolite in Bluegill Sunfish Exposed to 1.8 ppb of CL 217,300
in Water: Report No. PD-M 19-6:1-185. (Unpublished study received May 14, 1982 under 241-260;
submitted by American Cyanamid Co., Princeton, NJ; CDL:247502-D)
00164248 Morrissey, A. (1979) The Acute Toxicity of AC 217,300 to the Water Flea: Daphnia magna Straus:
UCES Project No. 11506-20-21. Unpublished study prepared by Union Carbide Environmental Services,
Union Carbide Corp. 10 p.
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BIBLIOGRAPHY
MRID
CITATION
40098001 Mayer, F., Ellersieck, M. (1986) Manual of Acute Toxicity: Interpretation and Data Base 410 Chemicals
and 66 Species of Freshwater Animals. US Fish and Wildlife Service; Resource Publication (160): 579 p.
41607801 Thompson, M.; Hoxter, K.; Smith, G. (1990) AC 217,300: An Acute Contact Toxicity Study with the
Honey Bee: Lab Project Number: 130-15 IB. Unpublished study prepared by Wildlife International Ltd.
26 p.
41612501 Long, D.; Cardaciotto, S.; Conley, J. (1990) Product Identity, Description of Manufacturing Process and
Discussion of Impurities for Technical AMDRO. Unpublished study prepared by American Cyanamid
Co. 151 p.
41612502 Long, D.; Teeter, J.; Mangels, G. (1990) EPA Pesticide Assessment Guidelines, Subdivision D-Product
Chemistry, Physical and Chemical Characteristics of the Technical/ Manufacturing Use Product:
Technical AMDRO: Lab Project Number: CHDVVOLUME30/REPORT. Unpublished study prepared
by American Cyanamid Co. 180 p.
41612503 Fischer, J. (1990) Oral LD50 Study in Albino Rats with AC 217,300 [Amdro Technical Insecticide]: Lab
Project Number: A90-117. Unpublished study prepared by American Cyanamid Co. 14 p.
41612504 Fischer, J. (1990) Dermal LD50 Study in Albino Rabbits with AC 217, 300 [Amdro Technical
Insecticide]: Lab Project Number: A90-114. Unpublished study prepared by American Cyanamid Co. 11
P-
41612505 Lowe, C. (1990) Eye Irritation Study in Albino Rabbits with AC 217, 300 [AMDRO Technical
Insecticide]: Lab Project Number: A90-140. Unpublished study prepared by American Cyanamid Co. 12
P-
41612506 Fischer, J. (1990) Skin Irritation Study in Albino Rabbits with AC 217, 300 [Amdro Technical
Insecticide]: Lab Project Number: A9095. Unpublished study prepared by American Cyanamid Co. 12
P-
41888302 Mangels, G. (1990) Hydramethylnon (AC217,300): Adsorption/Desorption: Lab Project Number:
E-90-21. Unpublished study prepared by American Cyanamid Co. 35 p.
42194701 Beckman, K.; Cranor, W. (1992) Hydrolysis of Hydramethylnon as a Function of pH at 25 C: Lab Project
Number: 38960. Unpublished study prepared by ABC Labs., Inc. 67 p.
42238201 Cranor, W.; Beckman, K. (1992) Determination of the Aqueous Photolysis Rate of Hydramethylnon
(Interim Report): Lab Project Number: 38961. Unpublished study prepared by ABC Labs, Inc. 51 p.
91
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BIBLIOGRAPHY
MRID
CITATION
42320801 Gorman, M. (1992) Aerobic Soil Metabolism of Hydramethylnon: Lab Project Number: 38977.
Unpublished study prepared by ABC Laboratories, Inc. 86 p.
42353801 Melcer, M. (1992) Hydramethylnon (AC 217,300): Photodegradation on Soil: Lab Project Number:
E-91-9. Unpublished study prepared by American Cyanamid Comp. 192 p
42473301 Cranor, W. (1992) Determination of the Aqueous Photolysis Rate of Hydramethylnon: [Final Report]:
Lab Project Number: 38961. Unpublished study prepared by ABC Labs, Inc. 79 p.
42871101 Hoffman, G. (1993) Acute Inhalation Toxicity Study with AC217,300 in Rats: Hydramethylnon: Lab
Project Number: 92-8399. Unpublished study prepared by Bio/dynamics, Inc. 197 p.
42871102 Hoffman, S.; Robinson, R. (1993) Hydramethylnon (CL217,300): Metabolism Fate of Carbon 14 Labeled
CL217,300 in Milk and Edible Tissues of the Lactating Goat: Lab Project Number: XBL91049:
M91A300NJ1: M 91A300NJ1. Unpublished study prepared by Hazleton Wisconsin, Inc. and Xeno
Biotic Labs, Inc. 423 p.
43093901 Sharp, D. (1993) Dermal Absorption of AC 217,300 Gel in Male Rats: Lab Project Number: HWI
6123-180. Unpublished study prepared by Hazleton Wisconsin, Inc. 88 p.
43293101 York, C. (1994) CL 217,300 (hydramethylnon/G): Rate of Dissipation of CL 217,300 Residues in Soil
after Treatment with AMDRO Fire Ant Insecticide (FL; 1992): Lab Project Number: RES/94/051.
Unpublished study prepared by American Cyanamid Co., Huntingdon Analytical Services. 120 p.
43293102 York, C. (1994) CL 217,300 (hydramethylnon/G): Rate of Dissipation of CL 217,300 Residues in Soil
after Treatment with AMDRO Fire Ant Insecticide (TX; 1992): Lab Project Number: RES/94/065.
Unpublished study prepared by American Cyanamid Co., Huntingdon Analytical Services. 119 p.
43485201 Schaefer, T. (1994) CL 217,300 (Hydramethylnon): Residues of CL 217,300 in Pasture/Rangeland Grass
after Ground Applications of AMDRO Granular Insecticide: Lab Project Number: CY78: RES 94-032:
RES 94-102. Unpublished study prepared by American Cyanamid Co. and Huntingdon Analytical
Services. 418 p.
43636702 Khunachak, A. (1995) CL 217,300: Freezer Stability of Residues of CL 217,300 in Pasture Grass: Lab
Project Number: RES 95-017: AM92PT02: A011.098. Unpublished study prepared by American
Cyanamid Co. and Huntingdon Analytical Services. 39 p.
43741501 Schoeder, R. (1995) A Two-Generation Reproduction Study with AC 217,300 in Rats: Final Report: Lab
Project Number: 92-4046: 971-92-115. Unpublished study prepared by Pharmaco LSR, Inc. 1658 p.
92
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BIBLIOGRAPHY
MRID CITATION
43744501 Lansinger, J. (1995) CL 217,300: Metabolism of Carbon-14 Labeled CL 217,300 in Rangeland Grass:
Lab Project Number: MET 95-013: M93P300CA1. Unpublished study prepared by American Cyanamid
Co. and Pan-Agricultural Labs, Inc. 378 p.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
GENERIC AND PRODUCT SPECIFIC
DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the active
ingredient identified in Attachment A of this Notice, the Data Call-In Chemical Status Sheet to
submit certain data as noted herein to the U.S. Environmental Protection Agency (EPA, the
Agency). These data are necessary to maintain the continued registration of your product(s)
containing this active ingredient. Within 90 days after you receive this Notice you must respond as
set forth in Section III below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its
Attachments 1 through 6; or
2. Why you believe you are exempt from the requirements listed in this Notice and in
Attachment 3 (for both generic and product specific data), the Requirements
Status and Registrant's Response Form, (see section III-B); or
3. Why you believe EPA should not require your submission of data in the manner
specified by this Notice (see section III-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply
with its requirements or should be exempt or excused from doing so, then the registration of your
product(s) subject to this Notice will be subject to suspension. We have provided a list of all of
your products subject to this Notice in Attachment 2. All products are listed on both the generic
and product specific Data Call-In Response Forms. Also included is a list of all registrants who
were sent this Notice (Attachment 5).
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide, Fungicide
and Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
95
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information is authorized under the Paperwork Reduction Act by OMB Approval No. 2070-0107
and 2070-0057 (expiration date 3-31-99).
This Notice is divided into six sections and six Attachments. The Notice itself contains
information and instructions applicable to all Data Call-In Notices. The Attachments contain
specific chemical information and instructions. The six sections of the Notice are:
Section I - Why You are Receiving this Notice
Section II - Data Required by this Notice
Section III - Compliance with Requirements of this Notice
Section IV - Consequences of Failure to Comply with this Notice
Section V - Registrants' Obligation to Report Possible Unreasonable Adverse Effects
Section VI - Inquiries and Responses to this Notice
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2 - Generic Data Call-In and Product Specific Data Call-In Response Formsflnsert A)
with Instructions
3 - Generic Data Call-In and Product Specific Data Call-In Requirements Status and
Registrant's Response Forms (Insert B) with Instructions
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregi strati on
5 - List of Registrants Receiving This Notice
SECTION I. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient(s) and reevaluated the
data needed to support continued registration of the subject active ingredient(s). This reevaluation
identified additional data necessary to assess the health and safely of the continued use of
products containing this active ingredient(s). You have been sent this Notice because you have
product(s) containing the subject active ingredient(s).
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The data required by this Notice are specified in the Requirements Status and
Registrant's Response Forms (Insert B) (for both generic and product specific data
requirements). Depending on the results of the studies required in this Notice, additional
studies/testing may be required.
II-B. SCHEDULE FOR SUBMISSION OF DATA
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You are required to submit the data or otherwise satisfy the data requirements
specified in the Requirements Status and Registrant's Response Forms (Insert B) within
the time frames provided.
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test
standards outlined in the Pesticide Assessment Guidelines for those studies for which
guidelines have been established.
These EPA Guidelines are available from the National Technical Information
Service (NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, VA 22161
(Telephone number: 703-605-6000).
Protocols approved by the Organization for Economic Cooperation and
Development (OECD) are also acceptable if the OECD recommended test standards
conform to those specified in the Pesticide Data Requirements regulation (40 CFR §
158.70). When using the OECD protocols, they should be modified as appropriate so that
the data generated by the study will satisfy the requirements of 40 CFR § 158. Normally,
the Agency will not extend deadlines for complying with data requirements when the
studies were not conducted in accordance with acceptable standards. The OECD
protocols are available from OECD, 2001 L Street, N.W., Washington, D.C. 20036
(Telephone number 202-785-6323; Fax telephone number 202-785-0350).
All new studies and proposed protocols submitted in response to this Data Call-In
Notice must be in accordance with Good Laboratory Practices [40 CFR Part 160].
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(cV2YB^ NOTICES
ISSUED BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede or
change the requirements of any previous Data Call-In(s). or any other agreements entered
into with the Agency pertaining to such prior Notice. Registrants must comply with the
requirements of all Notices to avoid issuance of a Notice of Intent to Suspend their
affected products.
SECTION III. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
You must use the correct forms and instructions when completing your response to this
Notice. The type of Data Call-In you must comply with (Generic or Product Specific) is specified
in item number 3 on the four Data Call-In forms (Attachments 2 and 3).
III-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice for generic and product
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specific data must be submitted to the Agency within 90 days after your receipt of this
Notice. Failure to adequately respond to this Notice within 90 days of your receipt will be
a basis for issuing a Notice of Intent to Suspend (NOIS) affecting your products. This and
other bases for issuance of NOIS due to failure to comply with this Notice are presented
in Section IV-A and IV-B.
III-B. OPTIONS FOR RESPONDING TO THE AGENCY
1. Generic Data Requirements
The options for responding to this Notice for generic data requirements are: (a)
voluntary cancellation, (b) delete use(s), (c) claim generic data exemption, (d) agree to
satisfy the generic data requirements imposed by this Notice or (e) request a data
waiver(s).
A discussion of how to respond if you choose the Voluntary Cancellation option,
the Delete Use(s) option or the Generic Data Exemption option is presented below. A
discussion of the various options available for satisfying the generic data requirements of
this Notice is contained in Section III-C. A discussion of options relating to requests for
data waivers is contained in Section III-D.
Two forms apply to generic data requirements, one or both of which must be used
in responding to the Agency, depending upon your response. These two forms are the
Data-Call-in Response Formdnsert A), and the Requirements Status and Registrant's
Response Formfdnsert B).
The Data Call-In Response Formsdnsert A) must be submitted as part of every response
to this Notice. The Requirements Status and Registrant's Response Formsdnsert B) also must be
submitted if you do not qualify for a Generic Data Exemption or are not requesting voluntary
cancellation of your registration(s). Please note that the company's authorized representative is
required to sign the first page of both Data Call-In Response Formsdnsert A) and the
Requirements Status and Registrant's Response Formsdnsert B) and initial any subsequent pages.
The forms contain separate detailed instructions on the response options. Do not alter the printed
material. If you have questions or need assistance in preparing your response, call or write the
contact person(s) identified in Attachment 1.
a. Voluntary Cancellation -
You may avoid the requirements of this Notice by requesting voluntary cancellation of
your product(s) containing the active ingredient that is the subject of this Notice. If you wish to
voluntarily cancel your product, you must submit completed Generic and Product Specific Data
Call-In Response Formsdnsert A), indicating your election of this option. Voluntary cancellation
is item number 5 on both Data Call-In Response Form(s). If you choose this option, these are the
only forms that you are required to complete.
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If you chose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice, which are contained in Section IV-C.
b. Use Deletion -
You may avoid the requirements of this Notice by eliminating the uses of your product to
which the requirements apply. If you wish to amend your registration to delete uses, you must
submit the Requirements Status and Registrant's Response Form (Insert B), a completed
application for amendment, a copy of your proposed amended labeling, and all other information
required for processing the application. Use deletion is option number 7 under item 9 in the
instructions for the Requirements Status and Registrant's Response Forms (Insert B). You must
also complete a Data Call-In Response Formflnsert A) by signing the certification, item number 8.
Application forms for amending registrations may be obtained from the Registration Support
Branch, Registration Division, Office of Pesticide Programs, EPA, by calling (703) 308-8358.
If you choose to delete the use(s) subject to this Notice or uses subject to specific data
requirements, further sale, distribution, or use of your product after one year from the due date of
your 90 day response, is allowed only if the product bears an amended label.
c. Generic Data Exemption -
Under section 3(c)(2)(D) of FIFRA, an applicant for registration of a product is exempt
from the requirement to submit or cite generic data concerning an active ingredient if the active
ingredient in the product is derived exclusively from purchased, registered pesticide products
containing the active ingredient. EPA has concluded, as an exercise of its discretion, that it
normally will not suspend the registration of a product which would qualify and continue to
qualify for the generic data exemption in section 3(c)(2)(D) of FIFRA. To qualify, all of the
following requirements must be met:
(i). The active ingredient in your registered product must be present solely because of
incorporation of another registered product which contains the subject active ingredient
and is purchased from a source not connected with you;
(ii). Every registrant who is the ultimate source of the active ingredient in your product
subject to this DCI must be in compliance with the requirements of this Notice and must
remain in compliance; and
(iii). You must have provided to EPA an accurate and current "Confidential Statement of
Formula" for each of your products to which this Notice applies.
To apply for the Generic Data Exemption you must submit a completed Data Call-In
Response Formflnsert A), Attachment 2 and all supporting documentation. The Generic Data
Exemption is item number 6a on the Data Call-In Response Formflnsert A). If you claim a generic
data exemption you are not required to complete the Requirements Status and Registrant's
99
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Response Form (Insert A). Generic Data Exemption cannot be selected as an option for
responding to product specific data requirements.
If you are granted a Generic Data Exemption, you rely on the efforts of other persons to
provide the Agency with the required data. If the registrant(s) who have committed to generate
and submit the required data fail to take appropriate steps to meet requirements or are no longer
in compliance with this Data Call-In Notice, the Agency will consider that both they and you are
not compliance and will normally initiate proceedings to suspend the registrations of both your
and their product(s), unless you commit to submit and do submit the required data within the
specified time. In such cases the Agency generally will not grant a time extension for submitting
the data.
d. Satisfying the Generic Data Requirements of this Notice
There are various options available to satisfy the generic data requirements of this Notice.
These options are discussed in Section III-C.l. of this Notice and comprise options 1 through 6 of
item 9 in the instructions for the Requirements Status and Registrant's Response Formdnsert B)
and item 6b on the Data Call-In Response Form (Insert A). If you choose item 6b (agree to
satisfy the generic data requirements), you must submit the Data Call-In Response Formdnsert A)
and the Requirements Status and Registrant's Response Formdnsert B) as well as any other
information/data pertaining to the option chosen to address the data requirement. Your response
must be on the forms marked "GENERIC" in item number 3.
e. Request for Generic Data Waivers.
Waivers for generic data are discussed in Section III-D.l. of this Notice and are covered
by options 8 and 9 of item 9 in the instructions for the Requirements Status and Registrant's
Response Formdnsert B). If you choose one of these options, you must submit both forms as well
as any other information/data pertaining to the option chosen to address the data requirement.
2. Product Specific Data Requirements
The options for responding to this Notice for product specific data are: (a) voluntary
cancellation, (b) agree to satisfy the product specific data requirements imposed by this Notice or
(c) request a data waiver(s).
A discussion of how to respond if you choose the Voluntary Cancellation option is
presented below. A discussion of the various options available for satisfying the product specific
data requirements of this Notice is contained in Section III-C.2. A discussion of options relating
to requests for data waivers is contained in Section III-D.2.
Two forms apply to the product specific data requirements one or both of which must be
used in responding to the Agency, depending upon your response. These forms are the
Data-Call-in Response Formdnsert A), and the Requirements Status and Registrant's Response
Formdnsert B), for product specific data. The Data Call-In Response Form (Insert A) must be
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submitted as part of every response to this Notice. In addition, one copy of the Requirements
Status and Registrant's Response Formdnsert B) also must be submitted for each product listed
on the Data Call-In Response Formdnsert A) unless the voluntary cancellation option is selected.
Please note that the company's authorized representative is required to sign the first page of the
Data Call-In Response Formdnsert A) and Requirements Status and Registrant's Response Form
(Insert B) (if this form is required) and initial any subsequent pages. The forms contain separate
detailed instructions on the response options. Do not alter the printed material. If you have
questions or need assistance in preparing your response, call or write the contact person(s)
identified in Attachment 1.
a. Voluntary Cancellation
You may avoid the requirements of this Notice by requesting voluntary cancellation of
your product(s) containing the active ingredient that is the subject of this Notice. If you wish to
voluntarily cancel your product, you must submit a completed Data Call-In Response Formdnsert
A), indicating your election of this option. Voluntary cancellation is item number 5 on both the
Generic and Product Specific Data Call-In Response Formsdnsert B). If you choose this option,
you must complete both Data Call-In response forms. These are the only forms that you are
required to complete.
If you choose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
b. Satisfying the Product Specific Data Requirements of this Notice.
There are various options available to satisfy the product specific data requirements of this
Notice. These options are discussed in Section III-C. of this Notice and comprise options 1
through 6 of item 9 in the instructions for the product specific Requirements Status and
Registrant's Response Formdnsert B) and item numbers 7a and 7b (agree to satisfy the product
specific data requirements for an MUP or EUP as applicable) on the product specific Data Call-In
Response Formdnsert A). Note that the options available for addressing product specific data
requirements differ slightly from those options for fulfilling generic data requirements. Deletion of
a use(s) and the low volume/minor use option are not valid options for fulfilling product specific
data requirements. It is important to ensure that you are using the correct forms and instructions
when completing your response to the Reregistration Eligibility Decision document.
c. Request for Product Specific Data Waivers.
Waivers for product specific data are discussed in Section III-D.2. of this Notice and are
covered by option 7 of item 9 in the instructions for the Requirements Status and Registrant's
Response Formdnsert B). If you choose this option, you must submit the Data Call-In Response
Formdnsert A) and the Requirements Status and Registrant's Response Formdnsert B) as well as
any other information/data pertaining to the option chosen to address the data requirement. Your
response must be on the forms marked "PRODUCT SPECIFIC" in item number 3.
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III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
1. Generic Data
If you acknowledge on the Generic Data Call-In Response Formflnsert A) that you agree
to satisfy the generic data requirements (i.e. you select item number 6b), then you must select one
of the six options on the Generic Requirements Status and Registrant's Response Formflnsert B)
related to data production for each data requirement. Your option selection should be entered
under item number 9, "Registrant Response." The six options related to data production are the
first six options discussed under item 9 in the instructions for completing the Requirements Status
and Registrant's Response Form. These six options are listed immediately below with information
in parentheses to guide you to additional instructions provided in this Section. The options are:
(1) I will generate and submit data within the specified timeframe (Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing
study that has been submitted but not reviewed by the Agency (Citing an Existing
Study)
Option 1. Developing Data
If you choose to develop the required data it must be in conformance with Agency
guidelines and with other Agency requirements as referenced herein and in the attachments. All
data generated and submitted must comply with the Good Laboratory Practice (GLP) rule (40
CFR Part 160), be conducted according to the Pesticide Assessment Guidelines (PAG) and be in
conformance with the requirements of PR Notice 86-5. In addition, certain studies require Agency
approval of test protocols in advance of study initiation. Those studies for which a protocol must
be submitted have been identified in the Requirements Status and Registrant's Response
Formdnsert B) and/or footnotes to the form. If you wish to use a protocol which differs from the
options discussed in Section II-C of this Notice, you must submit a detailed description of the
proposed protocol and your reason for wishing to use it. The Agency may choose to reject a
protocol not specified in Section II-C. If the Agency rejects your protocol you will be notified in
writing, however, you should be aware that rejection of a proposed protocol will not be a basis
for extending the deadline for submission of data.
A progress report must be submitted for each study within 90 days from the date you are
required to commit to generate or undertake some other means to address that study requirement,
such as making an offer to cost share or agreeing to share in the cost of developing that study.
This 90-day progress report must include the date the study was or will be initiated and, for
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studies to be started within 12 months of commitment, the name and address of the
laboratory(ies) or individuals who are or will be conducting the study.
In addition, if the time frame for submission of a final report is more than 1 year, interim
reports must be submitted at 12 month intervals from the date you are required to commit to
generate or otherwise address the requirement for the study. In addition to the other information
specified in the preceding paragraph, at a minimum, a brief description of current activity on and
the status of the study must be included as well as a full description of any problems encountered
since the last progress report.
The time frames in the Requirements Status and Registrant's Response Formflnsert B) are
the time frames that the Agency is allowing for the submission of completed study reports or
protocols. The noted deadlines run from the date of the receipt of this Notice by the registrant. If
the data are not submitted by the deadline, each registrant is subject to receipt of a Notice of
Intent to Suspend the affected registration(s).
If you cannot submit the data/reports to the Agency in the time required by this Notice
and intend to seek additional time to meet the requirements(s), you must submit a request to the
Agency which includes: (1) a detailed description of the expected difficulty and (2) a proposed
schedule including alternative dates for meeting such requirements on a step-by-step basis. You
must explain any technical or laboratory difficulties and provide documentation from the
laboratory performing the testing. While EPA is considering your request, the original deadline
remains. The Agency will respond to your request in writing. If EPA does not grant your request,
the original deadline remains. Normally, extensions can be requested only in cases of
extraordinary testing problems beyond the expectation or control of the registrant. Extensions will
not be given in submitting the 90-day responses. Extensions will not be considered if the request
for extension is not made in a timely fashion; in no event shall an extension request be considered
if it is submitted at or after the lapse of the subject deadline.
Option 2. Agreement to Share in Cost to Develop Data
If you choose to enter into an agreement to share in the cost of producing the required
data but will not be submitting the data yourself, you must provide the name of the registrant who
will be submitting the data. You must also provide EPA with documentary evidence that an
agreement has been formed. Such evidence may be your letter offering to join in an agreement and
the other registrant's acceptance of your offer, or a written statement by the parties that an
agreement exists. The agreement to produce the data need not specify all of the terms of the final
arrangement between the parties or the mechanism to resolve the terms. Section 3(c)(2)(B)
provides that if the parties cannot resolve the terms of the agreement they may resolve their
differences through binding arbitration.
Option 3. Offer to Share in the Cost of Data Development
If you have made an offer to pay in an attempt to enter into an agreement or amend an
existing agreement to meet the requirements of this Notice and have been unsuccessful, you may
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request EPA (by selecting this option) to exercise its discretion not to suspend your
registration(s), although you did not comply with the data submission requirements of this Notice.
EPA has determined that as a general policy, absent other relevant considerations, it will not
suspend the registration of a product of a registrant who has in good faith sought and continues to
seek to enter into a joint data development/cost sharing program, but the other registrant(s)
developing the data has refused to accept the offer. To qualify for this option, you must submit
documentation to the Agency proving that you have made an offer to another registrant (who has
an obligation to submit data) to share in the burden of developing that data. You must also submit
to the Agency a completed Certification with Respect to Citations of Data (in PR Notice 98-5)
(EPA Form 8570-34) . In addition, you must demonstrate that the other registrant to whom the
offer was made has not accepted your offer to enter into a cost-sharing agreement by including a
copy of your offer and proof of the other registrant's receipt of that offer (such as a certified mail
receipt). Your offer must, in addition to anything else, offer to share in the burden of producing
the data upon terms to be agreed to or, failing agreement, to be bound by binding arbitration as
provided by FIFRA section 3(c)(2)(B)(iii) and must not qualify this offer. The other registrant
must also inform EPA of its election of an option to develop and submit the data required by this
Notice by submitting a Data Call-In Response Formflnsert A) and a Requirements Status and
Registrant's Response Formflnsert B) committing to develop and submit the data required by this
Notice.
In order for you to avoid suspension under this option, you may not withdraw your offer
to share in the burden of developing the data. In addition, the other registrant must fulfill its
commitment to develop and submit the data as required by this Notice. If the other registrant fails
to develop the data or for some other reason is subject to suspension, your registration as well as
that of the other registrant normally will be subject to initiation of suspension proceedings, unless
you commit to submit, and do submit, the required data in the specified time frame. In such cases,
the Agency generally will not grant a time extension for submitting the data.
Option 4. Submitting an Existing Study
If you choose to submit an existing study in response to this Notice, you must determine
that the study satisfies the requirements imposed by this Notice. You may only submit a study that
has not been previously submitted to the Agency or previously cited by anyone. Existing studies
are studies which predate issuance of this Notice. Do not use this option if you are submitting
data to upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not acceptable, the
Agency will require you to comply with this Notice, normally without an extension of the required
date of submission. The Agency may determine at any time that a study is not valid and needs to
be repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of the
following three criteria must be clearly met:
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a. You must certify at the time that the existing study is submitted that the raw data
and specimens from the study are available for audit and review and you must
identify where they are available. This must be done in accordance with the
requirements of the Good Laboratory Practice (GLP) regulation, 40 CFR Part
160. As stated in 40 CFR 160.3, Raw data means any laboratory worksheets,
records, memoranda, notes, or exact copies thereof, that are the result of original
observations and activities of a study and are necessary for the reconstruction and
evaluation of the report of that study. In the event that exact transcripts of raw
data have been prepared (e.g., tapes which have been transcribed verbatim, dated,
and verified accurate by signature), the exact copy or exact transcript may be
substituted for the original source as raw data. 'Raw data' may include
photographs, microfilm or microfiche copies, computer printouts, magnetic media,
including dictated observations, and recorded data from automated instruments."
The term "specimens", according to 40 CFR 160.3, means "any material derived
from a test system for examination or analysis."
b. Health and safety studies completed after May 1984 must also contain all
GLP-required quality assurance and quality control information pursuant to the
requirements of 40 CFR Part 160. Registrants also must certify at the time of
submission of the existing study that such GLP information is available for post
May 1984 studies by including an appropriate statement on or attached to the
study signed by an authorized official or representative of the registrant.
c. You must certify that each study fulfills the acceptance criteria for the Guideline
relevant to the study provided in the FIFRA Accelerated Reregi strati on Phase 3
Technical Guidance and that the study has been conducted according to the
Pesticide Assessment Guidelines (PAG) or meets the purpose of the PAG (both
documents available from NTIS). A study not conducted according to the PAG
may be submitted to the Agency for consideration if the registrant believes that the
study clearly meets the purpose of the PAG. The registrant is referred to 40 CFR
158.70 which states the Agency's policy regarding acceptable protocols. If you
wish to submit the study, you must, in addition to certifying that the purposes of
the PAG are met by the study, clearly articulate the rationale why you believe the
study meets the purpose of the PAG, including copies of any supporting
information or data. It has been the Agency's experience that studies completed
prior to January 1970 rarely satisfied the purpose of the PAG and that necessary
raw data usually are not available for such studies.
If you submit an existing study, you must certify that the study meets all requirements of
the criteria outlined above.
If EPA has previously reviewed a protocol for a study you are submitting, you must
identify any action taken by the Agency on the protocol and must indicate, as part of your
certification, the manner in which all Agency comments, concerns, or issues were addressed in the
final protocol and study.
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If you know of a study pertaining to any requirement in this Notice which does not meet
the criteria outlined above but does contain factual information regarding unreasonable adverse
effects, you must notify the Agency of such a study. If such a study is in the Agency's files, you
need only cite it along with the notification. If not in the Agency's files, you must submit a
summary and copies as required by PR Notice 86-5 entitled "Standard Format for Data Submitted
under FIFRA".
Option 5. Upgrading a Study
If a study has been classified as partially acceptable and upgradeable, you may submit data
to upgrade that study. The Agency will review the data submitted and determine if the
requirement is satisfied. If the Agency decides the requirement is not satisfied, you may still be
required to submit new data normally without any time extension. Deficient, but upgradeable
studies will normally be classified as supplemental. However, it is important to note that not all
studies classified as supplemental are upgradeable. If you have questions regarding the
classification of a study or whether a study may be upgraded, call or write the contact person
listed in Attachment 1. If you submit data to upgrade an existing study you must satisfy or supply
information to correct all deficiencies in the study identified by EPA. You must provide a clearly
articulated rationale of how the deficiencies have been remedied or corrected and why the study
should be rated as acceptable to EPA. Your submission must also specify the MRID number(s) of
the study which you are attempting to upgrade and must be in conformance with PR Notice 86-5
entitled "Standard Format for Data Submitted under FIFRA."
Do not submit additional data for the purpose of upgrading a study classified as
unacceptable and determined by the Agency as not capable of being upgraded.
This option also should be used to cite data that has been previously submitted to upgrade
a study, but has not yet been reviewed by the Agency. You must provide the MRID number of the
data submission as well as the MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above, apply to all
data submissions intended to upgrade studies. Additionally, your submission of data intended to
upgrade studies must be accompanied by a certification that you comply with each of those
criteria, as well as a certification regarding protocol compliance with Agency requirements.
Option 6. Citing Existing Studies
If you choose to cite a study that has been previously submitted to EPA, that study must
have been previously classified by EPA as acceptable, or it must be a study which has not yet been
reviewed by the Agency. Acceptable toxicology studies generally will have been classified as
"core-guideline" or "core-minimum." For ecological effects studies, the classification generally
would be a rating of "core." For all other disciplines the classification would be "acceptable." With
respect to any studies for which you wish to select this option, you must provide the MRID
number of the study you are citing and, if the study has been reviewed by the Agency, you must
provide the Agency's classification of the study.
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If you are citing a study of which you are not the original data submitter, you must submit
a completed copy of EPA Form No. 8570-34, Certification with Respect to Citations of Data.
2. Product Specific Data
If you acknowledge on the product specific Data Call-In Response Formdnsert A) that
you agree to satisfy the product specific data requirements (i.e. you select option 7a or 7b), then
you must select one of the six options on the Requirements Status and Registrant's Response
Formdnsert B) related to data production for each data requirement. Your option selection
should be entered under item number 9, "Registrant Response." The six options related to data
production are the first six options discussed under item 9 in the instructions for completing the
Requirements Status and Registrant's Response Formdnsert B). These six options are listed
immediately below with information in parentheses to guide registrants to additional instructions
provided in this Section. The options are:
(1) I will generate and submit data within the specified time-frame (Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing
study that has been submitted but not reviewed by the Agency (Citing an Existing
Study)
Option 1. Developing Data - The requirements for developing product specific data are the same
as those described for generic data (see Section III.C.l, Option 1) except that normally no
protocols or progress reports are required.
Option 2. Agree to Share in Cost to Develop Data — If you enter into an agreement to cost share,
the same requirements apply to product specific data as to generic data (see Section III.C.l,
Option 2). However, registrants may only choose this option for acute toxicity data and certain
efficacy data and only if EPA has indicated in the attached data tables that your product and at
least one other product are similar for purposes of depending on the same data. If this is the case,
data may be generated for just one of the products in the group. The registration number of the
product for which data will be submitted must be noted in the agreement to cost share by the
registrant selecting this option.
Option 3. Offer to Share in the Cost of Data Development —The same requirements for generic
data (Section III.C.L, Option 3) apply to this option. This option only applies to acute toxicity
and certain efficacy data as described in option 2 above.
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Option 4. Submitting an Existing Study — The same requirements described for generic data (see
Section III.C.l., Option 4) apply to this option for product specific data.
Option 5. Upgrading a Study - The same requirements described for generic data (see Section
III.C.L, Option 5) apply to this option for product specific data.
Option 6. Citing Existing Studies - The same requirements described for generic data (see
Section III.C.l., Option 6) apply to this option for product specific data.
Registrants who select one of the above 6 options must meet all of the requirements
described in the instructions for completing the Data Call-In Response Formflnsert A) and the
Requirements Status and Registrant's Response Form (Insert B), and in the generic data
requirements section (III.C.l.), as appropriate.
III-D REQUESTS FOR DATA WAIVERS
1. Generic Data
There are two types of data waiver responses to this Notice. The first is a request for a
low volume/minor use waiver and the second is a waiver request based on your belief that the
data requirement(s) are not appropriate for your product.
a. Low Volume/Minor Use Waiver
Option 8 under item 9 on the Requirements Status and Registrant's Response
Formdnsert B). Section 3(c)(2)(A) of FIFRA requires EPA to consider the
appropriateness of requiring data for low volume/minor use pesticides. In implementing
this provision, EPA considers low volume pesticides to be only those active ingredients
whose total production volume for all pesticide registrants is small. In determining
whether to grant a low volume, minor use waiver, the Agency will consider the extent,
pattern and volume of use, the economic incentive to conduct the testing, the importance
of the pesticide, and the exposure and risk from use of the pesticide. If an active ingredient
is used for both high volume and low volume uses, a low volume exemption will not be
approved. If all uses of an active ingredient are low volume and the combined volumes for
all uses are also low, then an exemption may be granted, depending on review of other
information outlined below. An exemption will not be granted if any registrant of the
active ingredient elects to conduct the testing. Any registrant receiving a low
volume/minor use waiver must remain within the sales figures in their forecast supporting
the waiver request in order to remain qualified for such waiver. If granted a waiver, a
registrant will be required, as a condition of the waiver, to submit annual sales reports.
The Agency will respond to requests for waivers in writing.
To apply for a low volume/minor use waiver, you must submit the following information,
as applicable to your product(s), as part of your 90-day response to this Notice:
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(i). Total company sales (pounds and dollars) of all registered product(s)
containing the active ingredient. If applicable to the active ingredient, include foreign sales
for those products that are not registered in this country but are applied to sugar (cane or
beet), coffee, bananas, cocoa, and other such crops. Present the above information by year
for each of the past five years.
(ii) Provide an estimate of the sales (pounds and dollars) of the active ingredient
for each major use site. Present the above information by year for each of the past five
years.
(iii) Total direct production cost of product(s) containing the active ingredient by
year for the past five years. Include information on raw material cost, direct labor cost,
advertising, sales and marketing, and any other significant costs listed separately.
(iv) Total indirect production cost (e.g. plant overhead, amortized plant and
equipment) charged to product(s) containing the active ingredient by year for the past five
years. Exclude all non-recurring costs that were directly related to the active ingredient,
such as costs of initial registration and any data development.
(v) A list of each data requirement for which you seek a waiver. Indicate the type
of waiver sought and the estimated cost to you (listed separately for each data requirement
and associated test) of conducting the testing needed to fulfill each of these data
requirements.
(vi) A list of each data requirement for which you are not seeking any waiver and
the estimated cost to you (listed separately for each data requirement and associated test)
of conducting the testing needed to fulfill each of these data requirements.
(vii) For each of the next ten years, a year-by-year forecast of company sales
(pounds and dollars) of the active ingredient, direct production costs of product(s)
containing the active ingredient (following the parameters in item 2 above), indirect
production costs of product(s) containing the active ingredient (following the parameters
in item 3 above), and costs of data development pertaining to the active ingredient.
(viii) A description of the importance and unique benefits of the active ingredient
to users. Discuss the use patterns and the effectiveness of the active ingredient relative to
registered alternative chemicals and non-chemical control strategies. Focus on benefits
unique to the active ingredient, providing information that is as quantitative as possible. If
you do not have quantitative data upon which to base your estimates, then present the
reasoning used to derive your estimates. To assist the Agency in determining the degree of
importance of the active ingredient in terms of its benefits, you should provide information
on any of the following factors, as applicable to your product(s): (a) documentation of the
usefulness of the active ingredient in Integrated Pest Management, (b) description of the
beneficial impacts on the environment of use of the active ingredient, as opposed to its
registered alternatives, (c) information on the breakdown of the active ingredient after use
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and on its persistence in the environment, and (d) description of its usefulness against a
pest(s) of public health significance.
Failure to submit sufficient information for the Agency to make a determination
regarding a request for a low volume/minor use waiver will result in denial of the request
for a waiver.
b. Request for Waiver of Data
Option 9, under Item 9, on the Requirements Status and Registrant's Response
Form. This option may be used if you believe that a particular data requirement should not
apply because the requirement is inappropriate. You must submit a rationale explaining
why you believe the data requirements should not apply. You also must submit the current
label(s) of your product(s) and, if a current copy of your Confidential Statement of
Formula is not already on file you must submit a current copy.
You will be informed of the Agency's decision in writing. If the Agency determines
that the data requirements of this Notice are not appropriate to your product(s), you will
not be required to supply the data pursuant to section 3(c)(2)(B). If EPA determines that
the data are required for your product(s). you must choose a method of meeting the
requirements of this Notice within the time frame provided by this Notice. Within 30 days
of your receipt of the Agency's written decision, you must submit a revised Requirements
Status and Registrant's Response Form indicating the option chosen.
2. Product Specific Data
If you request a waiver for product specific data because you believe it is
inappropriate, you must attach a complete justification for the request including technical
reasons, data and references to relevant EPA regulations, guidelines or policies. (Note:
any supplemental data must be submitted in the format required by PR Notice 86-5). This
will be the only opportunity to state the reasons or provide information in support of your
request. If the Agency approves your waiver request, you will not be required to supply
the data pursuant to section 3(c)(2)(B) of FIFRA. If the Agency denies your waiver
request, you must choose an option for meeting the data requirements of this Notice
within 30 days of the receipt of the Agency's decision. You must indicate and submit the
option chosen on the product specific Requirements Status and Registrant's Response
Form (Insert B). Product specific data requirements for product chemistry, acute toxicity
and efficacy (where appropriate) are required for all products and the Agency would grant
a waiver only under extraordinary circumstances. You should also be aware that
submitting a waiver request will not automatically extend the due date for the study in
question. Waiver requests submitted without adequate supporting rationale will be denied
and the original due date will remain in force.
SECTION IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS
NOTICE
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IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice due
to failure by a registrant to comply with the requirements of this Data Call-In Notice, pursuant to
FIFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice of Intent to
Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of this
Notice.
2. Failure to submit on the required schedule an acceptable proposed or final protocol
when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a study
as required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this
Notice.
5. Failure to take a required action or submit adequate information pertaining to any
option chosen to address the data requirements (e.g., any required action or
information pertaining to submission or citation of existing studies or offers,
arrangements, or arbitration on the sharing of costs or the formation of Task
Forces, failure to comply with the terms of an agreement or arbitration concerning
joint data development or failure to comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of submitted
studies, as required by Section III-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in the cost of
developing data and provided proof of the registrant's receipt of such offer or
failure of a registrant on whom you rely for a generic data exemption either to:
a. Inform EPA of intent to develop and submit the data required by this Notice on
a Data Call-In Response Formflnsert A) and a Requirements Status and
Registrant's Response Formflnsert B).
b. Fulfill the commitment to develop and submit the data as required by this
Notice; or
c. Otherwise take appropriate steps to meet the requirements stated in this Notice,
unless you commit to submit and do submit the required data in the specified time
frame.
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9. Failure to take any required or appropriate steps, not mentioned above, at any time
following the issuance of this Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The grounds
for suspension include, but are not limited to, failure to meet any of the following:
1) EPA requirements specified in the Data Call-In Notice or other documents
incorporated by reference (including, as applicable, EPA Pesticide Assessment Guidelines,
Data Reporting Guidelines, and GeneTox Health Effects Test Guidelines) regarding the
design, conduct, and reporting of required studies. Such requirements include, but are not
limited to, those relating to test material, test procedures, selection of species, number of
animals, sex and distribution of animals, dose and effect levels to be tested or attained,
duration of test, and, as applicable, Good Laboratory Practices.
2) EPA requirements regarding the submission of protocols, including the
incorporation of any changes required by the Agency following review.
3) EPA requirements regarding the reporting of data, including the manner of
reporting, the completeness of results, and the adequacy of any required supporting (or
raw) data, including, but not limited to, requirements referenced or included in this Notice
or contained in PR 86-5. All studies must be submitted in the form of a final report; a
preliminary report will not be considered to fulfill the submission requirement.
IV-C EXISTING STOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing
stocks of a pesticide product which has been suspended or cancelled if doing so would be
consistent with the purposes of the Act.
The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3(c)(2)(B) data request is outstanding generally would not
be consistent with the Act's purposes. Accordingly, the Agency anticipates granting registrants
permission to sell, distribute, or use existing stocks of suspended product(s) only in exceptional
circumstances. If you believe such disposition of existing stocks of your product(s) which may be
suspended for failure to comply with this Notice should be permitted, you have the burden of
clearly demonstrating to EPA that granting such permission would be consistent with the Act.
You also must explain why an "existing stocks" provision is necessary, including a statement of
the quantity of existing stocks and your estimate of the time required for their sale, distribution,
and use. Unless you meet this burden, the Agency will not consider any request pertaining to the
continued sale, distribution, or use of your existing stocks after suspension.
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If you request a voluntary cancellation of your product(s) as a response to this Notice and
your product is in full compliance with all Agency requirements, you will have, under most
circumstances, one year from the date your 90 day response to this Notice is due, to sell,
distribute, or use existing stocks. Normally, the Agency will allow persons other than the
registrant such as independent distributors, retailers and end users to sell, distribute or use such
existing stocks until the stocks are exhausted. Any sale, distribution or use of stocks of voluntarily
cancelled products containing an active ingredient for which the Agency has particular risk
concerns will be determined on a case-by-case basis.
Requests for voluntary cancellation received after the 90 day response period required by
this Notice will not result in the agency granting any additional time to sell, distribute, or use
existing stocks beyond a year from the date the 90 day response was due, unless you demonstrate
to the Agency that you are in full compliance with all Agency requirements, including the
requirements of this Notice. For example, if you decide to voluntarily cancel your registration six
months before a 3-year study is scheduled to be submitted, all progress reports and other
information necessary to establish that you have been conducting the study in an acceptable and
good faith manner must have been submitted to the Agency, before EPA will consider granting an
existing stocks provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE
UNREASONABLE ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a
pesticide is registered a registrant has additional factual information regarding unreasonable
adverse effects on the environment by the pesticide, the registrant shall submit the information to
the Agency. Registrants must notify the Agency of any factual information they have, from
whatever source, including but not limited to interim or preliminary results of studies, regarding
unreasonable adverse effects on man or the environment. This requirement continues as long as
the products are registered by the Agency.
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by this
Notice, call the contact person(s) listed in Attachment 1, the Data Call-In Chemical Status Sheet.
All responses to this Notice must include completed Data Call-In Response Forms (Insert
A)and completed Requirements Status and Registrant's Response Forms (Insert B), for both
(generic and product specific data) and any other documents required by this Notice, and should
be submitted to the contact person(s) identified in Attachment 1. If the voluntary cancellation or
generic data exemption option is chosen, only the Generic and Product Specific Data Call-In
Response Formsdnsert A) need be submitted.
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The Office of Compliance (OC) of the Office of Enforcement and Compliance Assurance
(OECA), EPA, will be monitoring the data being generated in response to this Notice.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregi strati on Division
Attachments
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2 - Generic Data Call-In and Product Specific Data Call-In Response Forms with
Instructions
3 - Generic Data Call-In and Product Specific Data Call-In Requirements Status and
Registrant's Response Forms with Instructions
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregi strati on
5 - List of Registrants Receiving This Notice
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Hydramethylnon DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have product(s)
containing Hydramethylnon.
This Product Specific Data Call-In Chemical Status Sheet contains an overview of data
required by this notice, and point of contact for inquiries pertaining to the reregi strati on of
Hydramethylnon. This attachment is to be used in conjunction with (1) the Product Specific Data
Call-In Notice, (2) the Product Specific Data Call-In Response Form (Attachment 2), (3) the
Requirements Status and Registrant's Form (Attachment 3), (4) EPA's Grouping of End-Use
Products for Meeting Acute Toxicology Data Requirement (Attachment 4), (5) the EPA Acceptance
Criteria (Attachment 5), (6) a list of registrants receiving this DCI (Attachment 6) and (7) the Cost
Share and Data Compensation Forms in replying to this Hydramethylnon Product Specific Data Call-
in (Attachment 7). Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for Hydramethylnon are
contained in the Requirements Status and Registrant's Response. Attachment 3. The Agency has
concluded that additional data on Hydramethylnon are needed for specific products. These data are
required to be submitted to the Agency within the time frame listed. These data are needed to fully
complete the reregi strati on of all eligible Hydramethylnon products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding this product specific data requirements and procedures
established by this Notice, please contact Cynthia Williams at (703) 308-8195.
All responses to this Notice for the Product Specific data requirements should be submitted
to:
Cynthia Williams
Chemical Review Manager Team 81
Product Reregi strati on Branch
Special Review and Reregi strati on Branch 7508C
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: 2585
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Hydramethylnon DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Generic Data Call-In Notice because you have product(s) containing
Hydramethylnon.
This Generic Data Call-In Chemical Status Sheet, contains an overview of data required by
this notice, and point of contact for inquiries pertaining to the reregi strati on of Hydramethylnon. This
attachment is to be used in conjunction with (1) the Generic Data Call-In Notice, (2) the Generic Data
Call-In Response Form (Attachment 2), (3) the Requirements Status and Registrant's Form
(Attachment 2), (4) a list of registrants receiving this DCI (Attachment 4), (5) the EPA Acceptance
Criteria (Attachment 5), and (6) the Cost Share and Data Compensation Forms in replying to this
Hydramethylnon Generic Data Call In (Attachment F). Instructions and guidance accompany each
form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the generic database for
Hydramethylnon are contained in the Requirements Status and Registrant's Response. Attachment
C. The Agency has concluded that additional product chemistry data on Hydramethylnon are needed.
These data are needed to fully complete the reregi strati on of all eligible Hydramethylnon products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic data requirements and procedures established
by this Notice, please contact Dean Monos at (703) 308-8074.
All responses to this Notice for the generic data requirements should be submitted to:
Dean Monos, Chemical Review Manager
Reregi strati on Branch 3
Special Review and Registration Division (7508C)
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: 2585
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Instructions For Completing The "Data Call-In Response Forms" For The Generic And
Product Specific Data Call-In
INTRODUCTION
These instructions apply to the Generic and Product Specific "Data Call-In Response Forms"
(Insert A) and are to be used by registrants to respond to generic and product specific Data
Call-Ins as part of EPA's Reregi strati on Program under the Federal Insecticide, Fungicide, and
Rodenticide Act. If you are an end-use product registrant only and have been sent this DCI letter
as part of a RED document you have been sent just the product specific "Data Call-In Response
Forms."(Insert A) Only registrants responsible for generic data have been sent the generic data
response form. The type of Data Call-in (generic or product specific) is indicated in item
number 3 ("Date and Type of DCI") on each form.
Although the form is the same for both generic and product specific data, instructions for
completing these forms are different. Please read these instructions carefully before filling out the
forms.
EPA has developed these forms individually for each registrant, and has preprinted these forms
with a number of items. DO NOT use these forms for any other active ingredient.
Items 1 through 4 have been preprinted on the form. Items 5 through 7 must be completed by the
registrant as appropriate. Items 8 through 11 must be completed by the registrant before
submitting a response to the Agency.
The public reporting burden for this collection of information is estimated to average 15 minutes
per response, including time for reviewing instructions, searching existing data sources, gathering
and maintaining the data needed, and completing and reviewing the collection of information.
Send comments regarding the burden estimate or any other aspect of this collection of
information, including suggestions for reducing this burden, to Chief, Information Policy Branch,
Mail Code 2137, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, D.C.
20460; and to the Office of Management and Budget, Paperwork Reduction Project 2070-0107,
Washington, D.C. 20503.
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
INSERT A
Generic and Product Specific Data Call-In
Item 1. ON BOTH FORMS: This item identifies your company name, number and
address.
Item 2. ON BOTH FORMS: This item identifies the case number, case name, EPA
chemical number and chemical name.
ItemS. ON BOTH FORMS: This item identifies the type of Data Call-In. The date of
issuance is date stamped.
Item 4. ON BOTH FORMS: This item identifies the EPA product registrations relevant
to the data call-in. Please note that you are also responsible for informing the
Agency of your response regarding any product that you believe may be covered
by this Data Call-In but that is not listed by the Agency in Item 4. You must bring
any such apparent omission to the Agency's attention within the period required
for submission of this response form.
Item 5. ON BOTH FORMS: Check this item for each product registration you wish to
cancel voluntarily. If a registration number is listed for a product for which you
previously requested voluntary cancellation, indicate in Item 5 the date of that
request. Since this Data Call-In requires both generic and product specific data,
you must complete item 5 on both Data Call-In response forms. You do not need
to complete any item on the Requirements Status and Registrant's Response Forms
(Insert B)
Item 6a. ON THE GENERIC DATA FORM: Check this Item if the Data Call-In is for
generic data as indicated in Item 3 and you are eligible for a Generic Data
Exemption for the chemical listed in Item 2 and used in the subject product. By
electing this exemption, you agree to the terms and conditions of a Generic Data
Exemption as explained in the Data Call-In Notice.
If you are eligible for or claim a Generic Data Exemption, enter the EPA
registration Number of each registered source of that active ingredient that you use
in your product.
Typically, if you purchase an EPA-registered product from one or more other
producers (who, with respect to the incorporated product, are in compliance with
this and any other outstanding Data Call-In Notice), and incorporate that product
into all your products, you may complete this item for all products listed on this
form. If, however, you produce the active ingredient yourself, or use any
unregistered product (regardless of the fact that some of your sources are
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registered), you may not claim a Generic Data Exemption and you may not select
this item.
INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
INSERT B
Generic and Product Specific Data Call-In
Item 6b. ON THE GENERIC DATA FORM: Check this Item if the Data Call-In is for
generic data as indicated in Item 3 and if you are agreeing to satisfy the generic
data requirements of this Data Call-In. Attach the Requirements Status and
Registrant's Response Formflnsert B) that indicates how you will satisfy those
requirements.
NOTE: Item 6a and 6b are not applicable for Product Specific Data.
Item 7a ON THE PRODUCT SPECIFIC DATA FORM: For each manufacturing use
product (MUP) for which you wish to maintain registration, you must agree to
satisfy the data requirements by responding "yes."
Item 7b. For each end use product (EUP) for which you wish to maintain registration, you
must agree to satisfy the data requirements by responding "yes."
FOR BOTH MUP and EUP products
You should also respond "yes" to this item (7a for MUP's and 7b for EUP's) if
your product is identical to another product and you qualify for a data exemption.
You must provide the EPA registration numbers of your source(s); do not
complete the Requirements Status and Registrant's Response form. Examples of
such products include repackaged products and Special Local Needs (Section 24c)
products which are identical to federally registered products.
If you are requesting a data waiver, answer "yes" here; in addition, on the
"Requirements Status and Registrant's Response" form under Item 9, you must
respond with option 7 (Waiver Request) for each study for which you are
requesting a waiver.
NOTE: Item 7a and 7b are not applicable for Generic Data.
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
INSERT B CONTINUED
Generic and Product Specific Data Call-In
ItemS. ON BOTH FORMS: This certification statement must be signed by an
authorized representative of your company and the person signing must include
his/her title. Additional pages used in your response must be initialed and dated in
the space provided for the certification.
Item 9. ON BOTH FORMS: Enter the date of signature.
Item 10. ON BOTH FORMS: Enter the name of the person EPA should contact with
questions regarding your response.
Item 11. ON BOTH FORMS: Enter the phone number of your company contact.
Note: You may provide additional information that does not fit on this form in a
signed letter that accompanies your response. For example, you may wish to
report that your product has already been transferred to another company or
that you have already voluntarily canceled this product. For these cases,
please supply all relevant details so that EPA can ensure that its records are
correct.
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Instructions For Completing The "Requirements Status and Registrant's Response
Forms" (Insert B) For The Generic and Product Specific Data Call-in
INTRODUCTION
These instructions apply to the Generic and Product Specific "Requirements Status and
Registrant's Response Forms" and are to be used by registrants to respond to generic and product
specific Data Call-in's as part of EPA's reregi strati on program under the Federal Insecticide,
Fungicide, and Rodenticide Act. If you are an end-use product registrant only and have been
sent this DCI letter as part of a RED document you have been sent just the product specific
"Requirements Status and Registrant's Response Forms." Only registrants responsible for generic
data have been sent the generic data response forms. The type of Data Call-in (generic or
product specific) is indicated in item number 3 ("Date and Type of DCI") on each form.
Although the form is the same for both product specific and generic data, instructions for
completing the forms differ slightly. Specifically, options for satisfying product specific data
requirements do not include (1) deletion of uses or (2) request for a low volume/minor use
waiver. Please read these instructions carefully before filling out the forms.
EPA has developed these forms individually for each registrant, and has preprinted these
forms to include certain information unique to this chemical. DO NOT use these forms for any
other active ingredient.
Items 1 through 8 have been preprinted on the form. Item 9 must be completed by the
registrant as appropriate. Items 10 through 13 must be completed by the registrant before
submitting a response to the Agency.
The public reporting burden for this collection of information is estimated to average 30
minutes per response, including time for reviewing instructions, searching existing data sources,
gathering and maintaining the data needed, and completing and reviewing the collection of
information. Send comments regarding the burden estimate or any other aspect of this collection
of information, including suggestions for reducing this burden, to Chief, Information Policy
Branch, Mail Code 2137, U.S. Environmental Protection Agency, 401 M St., S.W., Washington,
D.C. 20460; and to the Office of Management and Budget, Paperwork Reduction Project
2070-0107, Washington, D.C. 20503.
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS" (Insert B)
Generic and Product Specific Data Call-In
Item 1. ON BOTH FORMS: This item identifies your company name, number and
address.
Item 2. ON THE GENERIC DATA FORM: This item identifies the case number, case
name, EPA chemical number and chemical name.
ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the case
number, case name, and the EPA Registration Number of the product for which
the Agency is requesting product specific data.
Item 3. ON THE GENERIC DATA FORM: This item identifies the type of Data
Call-In. The date of issuance is date stamped.
ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the type
of Data Call-In. The date of issuance is also date stamped. Note the unique
identifier number (ID#) assigned by the Agency. This ID number must be used in
the transmittal document for any data submissions in response to this Data Call-In
Notice.
Item 4. ON BOTH FORMS: This item identifies the guideline reference number of
studies required. These guidelines, in addition to the requirements specified in the
Data Call-In Notice, govern the conduct of the required studies. Note that series
61 and 62 in product chemistry are now listed under 40 CFR 158.155 through
158.180, Subpartc.
Item 5. ON BOTH FORMS: This item identifies the study title associated with the
guideline reference number and whether protocols and 1, 2, or 3-year progress
reports are required to be submitted in connection with the study. As noted in
Section III of the Data Call-In Notice, 90-day progress reports are required for all
studies.
If an asterisk appears in Item 5, EPA has attached information relevant to this
guideline reference number to the Requirements Status and Registrant's Response
Formdnsert B).
Generic and Product Specific Data Call-In
Item 6. ON BOTH FORMS: This item identifies the code associated with the use
pattern of the pesticide. In the case of efficacy data (product specific
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requirement), the required study only pertains to products which have the use sites
and/or pests indicated. A brief description of each code follows:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food crop
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
O Indoor residential
Item 7. ON BOTH FORMS: This item identifies the code assigned to the substance that
must be used for testing. A brief description of each code follows:
EUP
MP
MP/TGAI
PAI
PAI/M
PAI/PAIRA
PAIRA
PAIRA/M
PAIRA/PM
TEP
TEP %
TEP/MET
TEP/PAI/M
TGAI
TGAI/PAI
TGAI/PAIRA
End-Use Product
Manufacturing-Use Product
Manufacturing-Use Product and Technical Grade Active
Ingredient
Pure Active Ingredient
Pure Active Ingredient and Metabolites
Pure Active Indredient or Pute Active
Ingredient Radiolabelled
Pure Active Ingredient Radiolabelled
Pure Active Ingredient Radiolabelled and Metabolites
Pure Active Ingredient Radiolabelled and Plant Metabolites
Typical End-Use Product
Typical End-Use Product, Percent Active Ingredient
Specified
Typical End-Use Product and Metabolites
Typical End-Use Product or Pure Active Ingredient and
Metabolites
Technical Grade Active Ingredient
Technical Grade Active Ingredient or Pure Active
Ingredient
Technical Grade Active Ingredient or Pure Active
Ingredient Radiolabelled
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TGAI/TEP Technical Grade Active Ingredient or Typical End-Use
Product
MET Metabolites
IMP Impurities
DEGR Degradates
* See: guideline comment
Item 8. This item completed by the Agency identifies the time frame allowed for
submission of the study or protocol identified in item 5.
ON THE GENERIC DATA FORM: The time frame runs from the date of your
receipt of the Data Call-In notice.
ON THE PRODUCT SPECIFIC DATA FORM: The due date for submission
of product specific studies begins from the date stamped on the letter transmitting
the Reregistration Eligibility Decision document, and not from the date of receipt.
However, your response to the Data Call-In itself is due 90 days from the date of
receipt.
Item 9. ON BOTH FORMS: Enter the appropriate Response Code or Codes to show
how you intend to comply with each data requirement. Brief descriptions of each
code follow. The Data Call-In Notice contains a fuller description of each of these
options.
Option 1. ON BOTH FORMS: (Developing Data^) I will conduct a new study and
submit it within the time frames specified in item 8 above. By indicating
that I have chosen this option, I certify that I will comply with all the
requirements pertaining to the conditions for submittal of this study as
outlined in the Data Call-In Notice and that I will provide the protocols and
progress reports required in item 5 above.
Option 2. ON BOTH FORMS: (Agreement to Cost Shared I have entered into an
agreement with one or more registrants to develop data jointly. By
indicating that I have chosen this option, I certify that I will comply with all
the requirements pertaining to sharing in the cost of developing data as
outlined in the Data Call-In Notice.
However, for Product Specific Data, I understand that this option
is available for acute toxicity or certain efficacy data ONLY if the Agency
indicates in an attachment to this notice that my product is similar enough
to another product to qualify for this option. I certify that another party in
the agreement is committing to submit or provide the required data; if the
required study is not submitted on time, my product may be subject to
suspension.
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Option 3. ON BOTH FORMS: (Offer to Cost Share) I have made an offer to enter
into an agreement with one or more registrants to develop data jointly. I
am also submitting a completed "Certification of offer to Cost Share in the
Development of Data" form. I am submitting evidence that I have made an
offer to another registrant (who has an obligation to submit data) to share
in the cost of that data. I am including a copy of my offer and proof of the
other registrant's receipt of that offer. I am identifying the party which is
committing to submit or provide the required data; if the required study is
not submitted on time, my product may be subject to suspension. I
understand that other terms under Option 3 in the Data Call-In Notice
apply as well.
However, for Product Specific Data, I understand that this
option is available only for acute toxicity or certain efficacy data and only if
the Agency indicates in an attachment to this Data Call-In Notice that my
product is similar enough to another product to qualify for this option.
Option 4. ON BOTH FORMS: (Submitting Existing Data) I will submit an
existing study by the specified due date that has never before been
submitted to EPA. By indicating that I have chosen this option, I certify
that this study meets all the requirements pertaining to the conditions for
submittal of existing data outlined in the Data Call-In Notice and I have
attached the needed supporting information along with this response.
Options. ON BOTH FORMS: (Upgrading a Studv^) I will submit by the specified
due date, or will cite data to upgrade a study that EPA has classified as
partially acceptable and potentially upgradeable. By indicating that I have
chosen this option, I certify that I have met all the requirements pertaining
to the conditions for submitting or citing existing data to upgrade a study
described in the Data Call-In Notice. I am indicating on attached
correspondence the Master Record Identification Number (MRID) that
EPA has assigned to the data that I am citing as well as the MRID of the
study I am attempting to upgrade.
Option 6. ON BOTH FORMS: (Citing a Studv^) I am citing an existing study that
has been previously classified by EPA as acceptable, core, core minimum,
or a study that has not yet been reviewed by the Agency. If reviewed, I am
providing the Agency's classification of the study.
However, for Product Specific Data, I am citing another
registrant's study. I understand that this option is available ONLY for
acute toxicity or certain efficacy data and ONLY if the cited study was
conducted on my product, an identical product or a product which the
Agency has "grouped" with one or more other products for purposes of
depending on the same data. I may also choose this option if I am citing my
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own data. In either case, I will provide the MRID or Accession number (s).
If I cite another registrant's data, I will submit a completed "Certification
With Respect To Data Compensation Requirements" form.
FOR THE GENERIC DATA FORM ONLY: The following three options (Numbers
7, 8, and 9) are responses that apply only to the "Requirements Status and
Registrant's Response Form" (Insert B) for generic data.
Option 7. (Deleting Uses) I am attaching an application for amendment to my
registration deleting the uses for which the data are required.
Option 8. (Low Volume/Minor Use Waiver Request) I have read the statements
concerning low volume-minor use data waivers in the Data Call-In Notice
and I request a low-volume minor use waiver of the data requirement. I am
attaching a detailed justification to support this waiver request including,
among other things, all information required to support the request. I
understand that, unless modified by the Agency in writing, the data
requirement as stated in the Notice governs.
Option 9. (Request for Waiver of Data) I have read the statements concerning data
waivers other than lowvolume minor-use data waivers in the Data Call-In
Notice and I request a waiver of the data requirement. I am attaching a
rationale explaining why I believe the data requirements do not apply. I am
also submitting a copy of my current labels. (You must also submit a copy
of your Confidential Statement of Formula if not already on file with EPA).
I understand that, unless modified by the Agency in writing, the data
requirement as stated in the Notice governs.
FOR PRODUCT SPECIFIC DATA: The following option (number 7) is a response
that applies to the "Requirements Status and Registrant's Response Form" (Insert
B) for product specific data.
Option 7. (Waiver Request) I request a waiver for this study because it is
inappropriate for my product. I am attaching a complete justification for
this request, including technical reasons, data and references to relevant
EPA regulations, guidelines or policies. [Note: any supplemental data must
be submitted in the format required by P.R. Notice 86-5]. I understand that
this is my only opportunity to state the reasons or provide information in
support of my request. If the Agency approves my waiver request, I will
not be required to supply the data pursuant to Section 3(c) (2) (B) of
FIFRA. If the Agency denies my waiver request, I must choose a method
of meeting the data requirements of this Notice by the due date stated by
this Notice. In this case, I must, within 30 days-of my receipt of the
Agency's written decision, submit a revised "Requirements Status" form
specifying the option chosen. I also understand that the deadline for
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submission of data as specified by the original Data Call-In notice will not
change.
Item 10. ON BOTH FORMS: This item must be signed by an authorized representative of
your company. The person signing must include his/her title, and must initial and
date all other pages of this form.
Item 11. ON BOTH FORMS: Enter the date of signature.
Item 12. ON BOTH FORMS: Enter the name of the person EPA should contact with
questions regarding your response.
Item 13. ON BOTH FORMS: Enter the phone number of your company contact.
NOTE: You may provide additional information that does not fit on this form in a signed
letter that accompanies this your response. For example, you may wish to report that
your product has already been transferred to another company or that you have
already voluntarily cancelled this product. For these cases, please supply all relevant
details so that the Agency can ensure that its records are correct.
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EPA'S BATCHING OF AMDRO PRODUCTS FOR MEETING ACUTE TOXICITY DATA
REQUIREMENTS FOR REREGISTRATION
In an effort to reduce the time, resources and number of animals needed to fulfill the acute
toxicity data requirements for reregi strati on of products containing Amdro as the active ingredient,
the Agency has batched products which can be considered similar for purposes of acute toxicity.
Factors considered in the sorting process include each product's active and inert ingredients (identity,
percent composition and biological activity), type of formulation (e.g., emulsifiable concentrate,
aerosol, wettable powder, granular, etc.), and labeling (e.g., signal word, use classification,
precautionary labeling, etc.). Note that the Agency is not describing batched products as
"substantially similar" since some products within a batch may not be considered chemically similar
or have identical use patterns.
Using available information, batching has been accomplished by the process described in the
preceding paragraph. Notwithstanding the batching process, the Agency reserves the right to require,
at any time, acute toxicity data for an individual product should the need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or cite
a single battery of six acute toxicological studies to represent all the products within that batch. It is
the registrants' option to participate in the process with all other registrants, only some of the other
registrants, or only their own products within a batch, or to generate all the required acute
toxicological studies for each of their own products. If a registrant chooses to generate the data for
a batch, he/she must use one of the products within the batch as the test material. If a registrant
chooses to rely upon previously submitted acute toxicity data, he/she may do so provided that the
data base is complete and valid by today's standards (see acceptance criteria attached), the
formulation tested is considered by EPA to be similar for acute toxicity, and the formulation has not
been significantly altered since submission and acceptance of the acute toxicity data. Regardless of
whether new data is generated or existing data is referenced, registrants must clearly identify the test
material by EPA Registration Number. If more than one confidential statement of formula (CSF)
exists for a product, the registrant must indicate the formulation actually tested by identifying the
corresponding CSF.
In deciding how to meet the product specific data requirements, registrants must follow the
directions given in the Data Call-In Notice and its attachments appended to the RED. The DCI Notice
contains two response forms which are to be completed and submitted to the Agency within 90 days
of receipt. The first form, "Data Call-In Response," asks whether the registrant will meet the data
requirements for each product. The second form, "Requirements Status and Registrant's Response,"
lists the product specific data required for each product, including the standard six acute toxicity tests.
A registrant who wishes to participate in a batch must decide whether he/she will provide the data
or depend on someone else to do so. If a registrant supplies the data to support a batch of products,
he/she must select one of the following options: Developing Data (Option 1), Submitting an Existing
Study (Option 4), Upgrading an Existing Study (Option 5) or Citing an Existing Study (Option 6).
If a registrant depends on another's data, he/she must choose among: Cost Sharing (Option 2), Offers
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to Cost Share (Option 3) or Citing an Existing Study (Option 6). If a registrant does not want to
participate in a batch, the choices are Options 1, 4, 5 or 6. However, a registrant should know that
choosing not to participate in a batch does not preclude other registrants in the batch from citing
his/her studies and offering to cost share (Option 3) those studies.
Twenty-eight active products were found which contain Amdro as the active ingredient. These
products have been placed in three batches and a "no batch" group based on the active and inert
ingredients and formulation type. Furthermore, the following bridging/citing strategies may also be
employed:
- Products in batch 1 may cite category III/IV acute data performed with technical Amdro.
- With the exception of primary eye irritation, products in batch 2 may cite category III/IV acute data
performed with technical Amdro.
- With the exception of primary eye irritation, products in batch 3 may cite category III/IV acute data
performed with technical Amdro.
The technical Amdro acute toxicity values included in this document are for informational purposes
only. The data supporting these values may or may not meet the current acceptance criteria.
Batch
1
EPA Reg. No.
241-260
241-261
241-322
241-357
241-358
241-371
64240-1
64240-2
64240-25
64240-27
64240-28
64248-5
% Active Ingredient
0.88
0.88
0.73
0.73
0.88
0.31
1.0
2.0
1.0
0.5
0.65
2.15
Formulation Type
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Gel
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Batch
1
EPA Reg. No.
64248-6
64248-7
% Active Ingredient
1.0
0.65
Formulation Type
Solid
Solid
Batch
2
EPA Reg. No.
241-293
241-304
241-320
64240-3
64240-4
64240-5
64248-1
64248-2
64248-3
% Active Ingredient
1.65
1.0
0.9
0.9
1.0
0.9
2.0
1.0
1 0
Formulation Type
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Batch
3
EPA Reg. No.
241-313
64240-10
64240-35
64248-4
% Active Ingredient
2.0
2.0
2.15
2.0
Formulation Type
Solid
Solid
Solid
Solid
No
Batch
EPA Reg. No.
241-270
% Active Ingredient
95 0
Formulation Type
Solid
138
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This page has been inserted as a place marker and is replaced by an electronically generated PDCI
List of Registrants page number 1 in the actual Printed version of the Red document
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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 atwilliams.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
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 Restraints 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)
http://www.epa.gov/opprd001/forms/8570-l.pdf.
http://www.epa.gov/opprd001/forms/8570-4.pdf.
http://www.epa.gov/opprd001/forms/8570-5.pdf.
http://www.epa. gov/opprdOO l/forms/8570- 1 7.pdf.
http://www.epa.gov/opprd001/forms/8570-25.pdf.
http://www.epa.gov/opprd001/forms/8570-27.pdf.
http://www.epa.gov/opprd001/forms/8570-28.pdf.
http://www.epa.gov/opprd001/forms/8570-30.pdf.
http://www.epa.gov/opprd001/forms/8570-32.pdf.
http://www.epa.gov/opppmsdl/PR Notices/pr98-5.pdf.
http://www.epa.gov/opppmsdl/PR_Notices/pr98-5.pdf.
http://www.epa.gov/opppmsdl/PR Notices/pr98-l .pdf.
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8570-37
Self-Certification Statement for the
Physical/Chemical Properties (in PR Notice
98-1)
http://www.epa.gov/opppmsdl/PR Notices/pr98-l.pdf.
Pesticide Registration Kit
Dear Registrant:
www.epa.gov/pesticides/registrationkit/.
For your convenience, we have assembled an online registration kit which contains the following
pertinent forms and information needed to register a pesticide product with the U.S. Environmental
Protection Agency's Office of Pesticide Programs (OPP):
1. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug
and Cosmetic Act (FFDCA) as Amended by the Food Quality Protection Act (FQPA) 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
4. General Pesticide Information (Some of these forms are in PDF format and will require the
Acrobat reader.)
a. Registration Division Personnel Contact List
Biopesticides and Pollution Prevention Division (BPPD) Contacts
Antimicrobials Division Organizational Structure/Contact List
c. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data Requirements (PDF
format)
d. 40 CFR Part 156, Labeling Requirements for Pesticides and Devices (PDF format)
e. 40 CFR Part 158, Data Requirements for Registration (PDF format)
f. 50 F.R. 48833, Disclosure of Reviews of Pesticide Data (November 27, 1985)
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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)
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 1-800-858-7378 or through their Web site.
The Agency will return a notice of receipt of an application for registration or amended registration,
experimental use permit, or amendment to a petition if the applicant or petitioner encloses with his
submission a stamped, self-addressed postcard. The postcard must contain the following entries to be
completed by OPP:
Date of receipt
EPA identifying number
the Product Manager assignment
Other identifying information may be included by the applicant to link the acknowledgment of receipt
to the specific application submitted. EPA will stamp the date of receipt and provide the EPA identifying
File Symbol or petition number for the new submission. The identifying number should be used
whenever you contact the Agency concerning an application for registration, experimental use permit,
or tolerance petition.
To assist us in ensuring that all data you have submitted for the chemical are properly coded and
assigned to your company, please include a list of all synonyms, common and trade names, company
experimental codes, and other names which identify the chemical (including "blind" codes used when
a sample was submitted for testing by commercial or academic facilities). Please provide a CAS number
if one has been assigned.
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Documents Associated with this RED
The following is a list of available documents that may further assist in responding to this
Reregistration Eligibility Decision document. These documents may be obtained by the following
methods:
Electronic
File Format: Portable Document Format (.PDF) requires Adobe® Acrobat or compatible reader.
Electronic copies are available on our website at www.epa.gov/REDs. or contact Dean
Monos at (703) 308-8074.
1. PR Notice 86-5.
2. PR Notice 91-2
3. A full copy of this RED document
4. A copy of the fact sheet for Hydramethylnon
The following documents are part of the Administrative Record for this RED document and may
included in the EPA's Office of Pesticide Programs Public Docket. Copies of these documents are not
available electronically, but may be obtained by contacting the person listed on the respective Chemical
Status Sheet.
1. Health and Environmental Effects Science Chapters.
2. Detailed Label Usage Information System (LUIS) Report.
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