United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508W)
EPA-738-F-97-QQ8
August 1997
R.E.D. FACT
Diflubenzuron
Pesticide
Reregistration
All pesticides sold or distributed in the United States must be
registered by EPA, based on scientific studies showing that they can be
used without posing unreasonable risks to people or the environment.
Because of advances in scientific knowledge, the law requires that
pesticides which were first registered before November 1, 1984, be
reregistered to ensure that they meet today's more stringent standards.
In evaluating pesticides for reregistration, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency develops
any mitigation measures or regulatory controls needed to effectively reduce
each pesticide's risks. EPA then reregisters pesticides that can be used
without posing unreasonable risks to human health or the environment.
When a pesticide is eligible for reregistration, EPA explains the basis
for its decision in a Reregistration Eligibility Decision (RED) document.
This fact sheet summarizes the information in the RED document for
reregistration case 0144, diflubenzuron.
Diflubenzuron is an acaricide/insecticide (insect growth regulator)
used to control many leaf eating larvae of insects feeding on agricultural,
forest and ornamental plants (e.g. gypsy moths, mosquito larvae, rust
mites). Diflubenzuron is used primarily on cattle, citrus, cotton,
mushrooms, ornamentals, standing water, forestry trees and in programs to
control mosquito larvae and gypsy moth populations. Formulations include
a soluble concentrate, flowable concentrate, wettable powder and a
pelleted/tableted. Diflubenzuron is applied by airblast, aircraft and
hydraulic sprayers.
Regulatory Diflubenzuron was first registered as a pesticide in the U.S. in 1976.
History EPA issued a Registration Standard for diflubenzuron in September 1985
(PB86-176500). A November-1991 Data Call-in (DCI) required additional
. residue chemistry and ecological effects data. Currently, 29 diflubenzuron
products are registered.
Use Profile
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Human Health
Assessment
Toxicity
In studies using laboratory animals, diflubenzuron generally has been
shown to be slightly toxic on an acute basis. It is absorbed by the dermal
route and has been placed in Toxicity Category IH (the second lowest of
four categories). It has also been placed in Toxicity Category IV (the
lowest of four categories) for ifigestion by the~oral and inhalation routes.
Dietary Exposure
People may be exposed to residues of diflubenzuron through the diet.
Tolerances or maximum residue limits have been established for
diflubenzuron (please see 40 CFR 180.377). All tolerances for
diflubenzuron residues are currently expressed in terms of diflubenzuron
per se [40 CFR § 180.377(a) and (b) and § 186.2000]. The Agency has
concluded that the tolerance expression should be changed to address
combined residues of diflubenzuron and metabolites convertible to
parachloroaniline (PCA), expressed as diflubenzuron. • EPA has reassessed
the diflubenzuron tolerances and found that data for cotton gin by-products,
cottonseed, grass forage, liver, milk, mushrooms, pasture grass hay,
soybeans and walnuts are required for the continued registration of
diflubenzuron.
EPA has assessed the dietary risk posed by diflubenzuron. For the
overall U.S. population and 22 subgroups, exposure from all current
diflubenzuron tolerances represents less than 1% of the Reference Dose
(RfD), or amount believed not to cause adverse effects if consumed daily
over a 70-year lifetime. The exposure level of the most highly exposed
subgroup, children (aged 1-6), represents 1% of the RfD. Therefore, it
appears that chronic dietary risk is minimal.
Occupational and Residential Exposure
Based on current use patterns, handlers (mixers, loaders, and
applicators) may be exposed to diflubenzuron during and after normal use
of applications in agricultural and other settings. The Agency is
establishing a short-term (1 to 7 days) toxicological endpoint of
sulfhemoglobinemia and intermediate-term (1 week to several months)
toxicological endpoint of methemoglobinemia.
Human Risk Assessment
Diflubenzuron generally is of low acute toxiciry, but affects the
hemoglobin of animal in studies. Although the Agency has determined that
there is no evidence of carcinogenicity for difluhenzuron^e/- se (Group E);
p-chloroaniline (PCA), a metabolite of diflubenzuron, is a probable human
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Environmental
Assessment
carcinogen (Group B2).: The Agency has also determined that p-
chlorophenylurea (CPU), a metabolite of diflubenzuron that is closely
related to PCA but has no adequate carcinogenicity data, is considered as
having the same carcinogenicity potential (Q1 *) as PCA. The total cancer
risk estimate for PCA and related metabolites for the overall U.S.
population is 1 X lO"6. The Rfd is 0.02 mg/kg/day, based on the NOEL of
2.0 mg/kg/day in the 52-week chronic oral study in dogs with a safety
factor of 100 to account for interspecies extrapolation and intraspecies
variability. .
Of greater concern is the risk posed to diflubenzuron handlers,
particularly mixers/loaders/applicators. The risk for short-term
occupational exposure is acceptable for handlers wearing long-sleeved
shirts, long pants and chemical-resistant gloves. The risk for intermediate-
term occupational exposure is also acceptable, provided dust/mist
respirators (TC-21C) are required for mixers, loaders and applicators when
working with diflubenzuron for certain higher risk application methods.
Post-application reentry workers will be required to observe a 12-hour
Restricted Entry Interval, as set by the WPS.
Under the Food Quality Protection Act of 1996, the Agency has
determined that there is a reasonable certainty that no harm will result to
infants and children from aggregate exposure to diflubenzuron. The total
dietary cancer risk for the published tolerances for the overall U.S.
population is approximately 1 x W6. Since there are no detections of
diflubenzuron in ground water, dietary risk from drinking water are
expected to be negligible. Based on very low residues detected in forestry
dissipation studies, a low dermal absorption rate, and extremely low dermal
and inhalation toxicity, occupational uses of diflubenzuron in residential
locations, parks, or forests treated with diflubenzuron are expected to result
in insignificant risk.
Environmental Fate
Diflubenzuron appears to be relatively non-persistent and immobile
under normal use conditions. The major route of dissipation appears to be
biotic processes (half-life of approximately 2 days for aerobic soil
metabolism). Diflubenzuron is stable to hydrolysis and photolysis.
Available data indicate that it is unlikely that'diflubenzuron will
contaminate ground water or surface water. Additional data are needed to
confirm this conclusion.
Ecological Effects
Diflubenzuron is practically non-toxic to avian species, small '
mammals, freshwater fish and maririe/estuarine fish on an acute oral dietary
basis, while it is slightly toxic to avian species on a subacute dietary basis.
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Diflubenzuron is non-toxic to bees. The results indicate that diflubenzuron
is very highly toxic to freshwater aquatic invertebrates, including
marine/estuarine Crustacea, while it is highly toxic to marine/estuarine .
mollusks. The results indicate that diflubenzuron affects reproduction,
growth and survival in freshwater invertebrates as well as reproduction in
marine/estuarine invertebrates.
Ecological Effects Risk Assessment
The risk assessment conducted using available data indicates that
levels of concern are not exceeded for avian species, mammals, insects or
freshwater fish. Although the use of diflubenzuron is expected to cause
some adverse chronic effects to estuarine/marine fish at the highest
application rate (forestry), these effects are not as widespread as those
associated with freshwater and estuarine/marine invertebrates. The use of
diflubenzuron is expected to cause adverse acute and chronic effects to bom
freshwater and estuarine/marine invertebrates, including endangered
species.
The risk to aquatic invertebrates is also expected to be substantial
when diflubenzuron is applied to control mosquito larvae. Since this use
involves direct application to water and/or near water, no mitigation is
currently proposed. -
Risk Mitigation To lessen the environmental risks posed by diflubenzuron, EPA is requiring
the following risk mitigation measures:
o row crops and orchard uses must include a 150 foot buffer,zone for
aerial applications and a 25 foot vegetative buffer strip to decrease
runoff in all cases (buffer strip will also serve as a buffer zone for
spray drift from.ground applications);
o aerial applications must include the most current spray drift language;
and
o all products must bear a hazards statement warning about possible
adverse effects to aquatic organisms.
Additional Data EPA is requiring the following additional generic studies for •
Required diflubenzuron to confirm its regulatory assessments and conclusions:
ecological effects, toxicity, residue chemistry,..and occupational and
residential exposure. ' * " .
The Agency also is requiring product-specific data including product
chemistry and acute toxicity studies, revised Confidential Statements of
Formula (CSFs), and revised labeling for reregistration.
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Product Labeling All diflubenzuron end-use products must comply with EPA's current
Changes Required pesticide product labeling requirements. For a comprehensive list of
: labeling requirements, please see the diflubenzuron RED document.
Regulatory The use of currently registered products containing diflubenzuron in
Conclusion accordance with approved labeling will not pose unreasonable risks or
adverseieffects to humans or the -environment. Therefore; all uses of these
products are eligible for reregistration.
Diflubenzuron products will be reregistered once the required product
specific data, revised Confidential Statements of Formula, and revised
labeling are received and accepted by EPA.
For More
Information
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for diflubenzuron during a 60-day time period,
as announced in a Notice of Availability published in the Federal Register.
To obtain a copy of the RED document or to submit written comments,
please contact the Pesticide Docket, Public Response and Program
Resources Branch, Field Operations Division (7506C), Office of Pesticide
Programs (OPP), US EPA, Washington, DC 20460, telephone
703-305-5805. •
Electronic copies of the RED and this fact sheet can be downloaded
from the Pesticide Special Review and Reregistration Information System
at 703-308-7224. They also are available on the Internet on EPA's gopher
server, GOPHER.EPA.GOV, or using ftp on FTP.EPA.GOV, or using
WWW(World Wide Web) on WWW.EPA.GOV.
Printed copies of the RED and fact sheet can be obtained from EPA's
National Center for Environmental Publications and Information
(EPA/NCEPI), PO Box 42419, Cincinnati, OH 45242-0419, telephone
513-489-8190, fax 513-489-8695.
Following the comment period, the diflubenzuron RED document
also will be available from the National Technical Information Service
(NTIS), 5285 Port Royal Road, Springfield, VA 22161, telephone 703-487-
4650.
For more information about EPA's pesticide reregistration program,
the diflubenzuron RED, or reregistration of individual products containing
diflubenzuron, please contact the Special Review and Reregistration
Division (7508W), OPP, US EPA, Washington, DC 20460, telephone 703-
308-8000. .
For information about the health effects of pesticides, or for assistance
in recognizing and managing pesticide poisoning symptpms, please contact
the National Pesticides Telecommunications Network (NPTN). Call toll-
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free 1-800-858-7378, between 9:30 am and 7:30 pm Eastern Standard
Time, Monday through Friday.
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Sft)
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
SEP 17 1997
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency has completed its
reregistration eligibility review and decisions on the pesticide chemical case that includes the
active ingredient diflubenzuron. The enclosed Reregistration Eligibility Decision (RED),
which was signed on 5/22/97, contains the Agency's evaluation of the data base of this
chemical, 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 th& data and labeling requirements for products
for reregistration. It also includes requirements for additional data (generic) on the active
ingredient 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 are due 90 days from
the date of your receipt of this letter. The second set of required responses are 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.
If you have questions on the product specific data requirements or wish to meet with
the Agency, please contact the Special Review and Reregistration Division representative
Venus Eagle at (703) 308-^8045. Address any questions on required generic data to the Special
Review and Reregistration Division representative Susan Jennings at (703) 308-7130.
Sincerely yours,
tor
Special Review and
Reregistration Division
Enclosures
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SUMMARY OF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISIO
1. DATA CALL-IN (T>CB OR "90-DAY RESPONSE"-If generic data are required for
reregistration, a DCI letter will be enclosed describing such data. If product specific data are
required, another DCI letter will be enclosed listing such requirements. If both generic and
product specific data are required, a combined Generic and Product Specific letter will be
enclosed describing such data. Complete the two response forms provided with each DCI
letter (or four forms for the combined) by following the instructions provided. You must
submit the response forms for each product and for each DCI within 90 days of the
receipt of this letter (RED issuance date); 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 data waivers must be submitted as part of the
90-day response. Requests for time extensions should be submitted in the 90-day response,
but certainly no later than the 8-month response date. 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 reregistration) separately. You may
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-
487-4650).
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
comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal
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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 Data Compensation Requirements Complete
and sign EPA form 8570-31 for each product.
4 COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTTCE-Cnmrnftntg
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^ ANT>
APPLICATIONS FOR REREGISTRATION f8-MQNTH RESPONSES^
Bv U.S. Mail:
Document Processing Desk (RED-SRKD-PKB)
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 reregistratipn determination within 14 months after the RED
has been issued. .
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REREGISTRATION ELIGIBILITY DECISION
t DIFLUBENZURON
LIST A
CASE 0144
• , ErWIRONMENTAL'PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
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TABLE OF CONTENTS
DIFLUBENZURON REREGISTRATION ELIGIBILITY DECISION TEAM i
EXECUTIVE SUMMARY ' ' . v
I. INTRODUCTION i 1
H. CASE OVERVIEW '. '...'. .2
A. Chemical Overview 2
B. Use Profile :....' 2
C. Estimated Usage of Pesticide '. ; 3
D. Data Requirements . 4
E. Regulatory History 4
HI. SCIENCE ASSESSMENT 6
A. Physical Chemistry Assessment 6
B. Human Health Assessment 7
1. Toxicology Assessment i :..... 7.... 7
a. Acute Toxicity 7
b. Subchronic Toxicity . 8
c. Chronic Toxicity 10
d. Carcinogenicity 12
' e. Developmental Toxicity 14
f. Reproductive Toxicity . .. :' 14
g. Mutagenicity 14
h. Metabolism 15
i. Toxicology Endpoints of Concern .....; ; . . 16
j. Reference Dose 17
2. Exposure Assessment 18
a. Dietary 18
b. Occupational and Residential 29
3. Risk Assessment 30
a. Dietary Risks 30
b. Occupational Risks 32
4. Food Quality Protection Act Considerations 38
a. Potential Risks to Infants and Children 38
b. Aggregate Exposure/Risk 40
c. Cumulative Effects 42
C. Environmental Assessment . 44
1. Ecological Toxicity Data 44
a. Toxicity to Terrestrial Animals 44
b. Toxicity to Aquatic Animals 47
c. Toxicity to Plants . . :....' 54
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2. Environmental Fate .55
a. Environmental Fate Assessment . . 55
b. Environmental Fate and Transport 57
c. Water Resources . 61
3. Ecological Exposure and Risk Characterization . 63
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 72
A. Determination of Eligibility ...........; 72
B. Determination of Eligibility Decision 73
1. Eligibility Decision 73
2. Eligible and Ineligible Uses 73
C. Regulatory Position . . . . . . 73
1. Food Quality Protection Act Findings ; . . 73
« 2. Tolerance Reassessment : . 75
3. . Summary of Risk Management Decisions : 79
a. Human Health . 1 .79
b. Environmental .81
4. Occupational Labeling Rationale . . 84
5; Endangered Species Statement 89
V. ACTIONS REQUIRED OF REGISTRANTS 89
A. Manufacturing-Use Products . . ., . . . 89
1. Additional Generic Data Requirements ..'.:. 89
2. Labeling Requirements for Manufacturing-Use Products 90
B. End-Use Products 90
1. Additional Product-Specific Data Requirements 91
2. Labeling Requirements for End-Use Products 91
3. Occupational/Residential Labeling . .......92
C. Existing Stocks 99
VI. APPENDICES .101
APPENDIX A. Table of Use Patterns Subject to Registration 1Q2
APPENDIX B. Table of the Generic Data Requirements and Studies Used to
Make the Reregistration Decision :...... 121
APPENDIX C. Citations Considered to be Part of the Data Base Supporting
the Reregistration of Diflubenzuron . 133
APPENDIX D. Combined Generic and Product Specific Data Call-In ... 153
Attachment 1. Chemical Status Sheets : . . . 175
Attachment 2. Combined Generic and Product Specific Data Call-in
Response Forms (Form A inserts) Plus
•Instructions . . . ..."....... 177
Attachment 3. Generic and Product Specific Requirement Status and
Registrant's Response Forms (Form B inserts) and
. Instructions 181
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Attachment 4.
Attachment 5.
Attachment ,6.
APPENDIX E.
EPA Batching of End-Use Products for Meeting Data
Requirements for Reregistration 188
List of All Registrants Sent This Data Call-in (insert)
Notice 191
Cost Share, Data Compensation Forms, Confidential
Statement of Formula Form and Instructions .... 192
List of Available Related Documents 197
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DIFLUBENZURON REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis Assessment
Arthur Grube
Gabe Patrick
Economic Analysis Branch
Biological Analysis Branch
Environmental Fate and Effects Assessment
Andrew Bryceland
Mary Powell
Gail Maske
Health Effects Assessment
Edwin Budd
Jeff Evans
Richard Griffin
Steven Knizner
Tom Myers
Registration Support Risk Assessment
David Ritter
Paul Schroeder
x
Risk Management
Susan Jennings
Lawrence Schnaubelt
Ecological Effects Branch
Science Analysis and Coordination Staff
Environmental Fate and Groundwater Branch
Toxicology Branch I
Occupational and Residential Exposure Branch
Risk Characterization and Analysis Branch
Reregistration Support Chemistry Branch
Risk Characterization and Analysis Branch
Registration Support Branch
Insecticide-Rodenticide Branch
Reregistration Branch
Reregistration Branch
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11
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ADI
AE
a.i.
ARC
CAS
CI
CNS
CSF
DFR
ORES
DWEL
EEC
' EP
EPA
FAO/WHO
FDA
FIFRA ..
FFDCA
FOB
GLC
GM
CrRAS
HA
HDT
LC
50
LD,
LEL
LOG
LOD
LOEL
MATC
MCLG
mg/L
MOE'
MP
MPI
MRID
N/A
GLOSSARY OF TERMS AND ABBREVIATIONS
Acceptable Daily Intake. A now defunct term for reference dose (RED).
' Acid Equivalent •
Active Ingredient '
Anticipated Residue Contribution
Chemical Abstracts Service
Cation . - "
Central Nervous .System
Confidential Statement of Formula
Dislodgeable Foliar Residue .
. Dietary Risk Evaluation System
Drinking Water Equivalent Level (DWEL) The DWEL represents a medium specific (i.e. drinking
water) lifetime exposure at which adverse, non carcinogenic health effects are not anticipated to
occur.
Estimated Environmental Concentration. The estimated pesticide concentration in an environment,
such as a terrestrial ecosystem.
End-Use Product
U.S. Environmental Protection Agency
Food and Agriculture Organization/World Health Organization
Food and Drug Administration •
Federal Insecticide, Fungicide, and Rodenticide Act
Federal Food, Drug, and Cosmetic Act
Food Quality Protection Act ' .
FunctionalObservation Battery
Gas Liquid Chromatography
Geometric Mean
Generally Recognized as Safe as Designated by FDA
Health Advisory (HA)., The HA values are used as informal guidance to municipalities and other
organizations when emergency spills or contamination situations occur.
Highest Dose Tested " .
Median Lethal Concentration. A statistically derived concentration of a substance that can b e
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.
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 i s
expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
Lethal Dose-low. Lowest Dose at which lethality occurs.
Lowest Effect Level
Level of Concern
Limit of Detection -
Lowest Observed Effect Level
Maximum Acceptable Toxicant Concentration ,
Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulate
contaminants in drinking water under the Safe Drinking Water Act.
Micrograms Per Gram ,
Milligrams Per Liter
Margin of Exposure , '
Manufacturing-Use Product • '
Maximum Permissible Intake ' .
Master Record Identification (number). EPA's system of recording and tracking studies submitted.
Not Applicable
111
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GLOSSARY OF TERMS AND ABBREVIATIONS
NOEC
NPDES
NOEL
NOAEL
OP
OPP
Pa
PADI
PAG
PAM
PHED
PHI
ppb
PPE
ppm
PRN
Q*,
RBC
RED
REI
RfD
RS
RUP
SLN
TC
TD
TEP
TGAI
TLC
TMRC
torr
WP
WPS
No effect concentration
National Pollutant Discharge Elimination System
No Observed Effect Level
No Observed Adverse Effect Level
Organophosphate
Office of Pesticide Programs
pascal, the pressure exerted by a force of one newton acting on an area of one square meter. '
Provisional Acceptable Daily Intake
Pesticide Assessment Guideline
Pesticide Analytical Method
Pesticide Handler's Exposure Data
Preharvest Interval
Parts Per Billion
Personal Protective Equipment
Parts Per Million ,
Pesticide Registration Notice
The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
Red Blood Cell
Reregistration Eligibility Decision
Restricted Entry Interval
Reference Dose
Registration Standard
Restricted Use Pesticide
Special Local Need (Registrations Under Section 24 (c) of FIFRA)
Toxic Concentration. The concentration at which a substance produces a toxic effect. .
Toxic Dose. The dose at which a substance produces a toxic effect.
Typical End-Use Product
Technical Grade Active Ingredient
Thin Layer Chromatography
Theoretical Maximum Residue Contribution
A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
Micrograms per liter
Wettable Powder-
Worker Protection Standard .
IV
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EXECUTIVE SUMMARY
Background .
This Registration Eligibility Decision (RED) addresses the reregistration eligibility
of the pesticide diflubenzuron, N-[[(4-chlorophenyl)amino] carbonyl]-2,6-difluorobenzamide
or l-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea. Diflubenzuron is used primarily on citrus,
cattle, cotton, forestry, mushrooms, ornamentals, pastures, soybeans, standing water, sewage '
systems, and wide-area general outdoor treatment sites. The insecticide behaves as a chitin
inhibitor to inhibit the growth of many leaf-eating larvae, mosquito larvae, aquatic midges,
rust mite, bollweevil, and flies. .
Diflubenzuron was first registered in the United States in 1979 for use as an
insecticide: The Agency issued a Registration Standard for diflubenzuron in September,
1985, (NTIS #PB86-176500). In November, 1991, the Agency issued a Data Call-in for
diflubenzuron requiring additional residue chemistry and ecological effects data. This
Reregistration Eligibility Decision reflects a reassessment of all data which were submitted in
response to the Registration Standard and subsequent Data. Call-in.
Reregistration Eligibility
EPA has completed its reregistration eligibility decision regarding the pesticide
diflubenzuron, case 0144. This decision includes a comprehensive reassessment of the
required target data base supporting the use patterns of currently registered products. This
decision considered the requirements of the recently enacted "Food Quality Protection Act of
1996" that amended the Federal Food Drug and Cosmetic Act and the Federal Insecticide,
Fungicide and Rodenticide Act, the two Federal statutes that provide the framework for
pestiqide regulation in the United States. FQPA became effective immediately upon signature
and all reregistration eligibility decisions (REDs) signed after August 3, 1996, are accordingly
being evaluated under the new standards imposed by FQPA.
In establishing or reassessing tolerances, the Food Quality Protection Act (FQPA,
Public Law 104-170) requires the Agency to consider aggregate exposures to pesticide
residues, including all anticipated dietary exposures and other exposures for which there is
reliable information, as well as the potential for cumulative effects from a pesticide and other
compounds with a common mechanism of toxicity. The Act further directs EPA to consider
the potential for increased susceptibly of infants and children to the toxic effects of pesticide
residue.
The Agency considered the appropriateness of an additional uncertainty factor to
account for situations where available data indicate increased sensitivity of infants and
children and concluded .that it is not warranted based on an evaluation of the toxicology
database. Regarding aggregate exposure, the Agency only considered dietary exposure
because there are no residential or other non-occupational uses of diflubenzuron and exposure
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to diflubenzuron from drinking water is not of concern. In the case of diflubenzuron, EPA
has not yet determined whether or how to include this chemical in a cumulative risk
assessment. This reassessment determination therefore does not take into account common
mechanism issues. 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.
The Agency has determined that diflubenzuron, labeled and used as specified in this
Reregistration Eligibility Decision, will not cause unreasonable risk to humans or the
environment and that these uses are eligible for reregistration. The Agency is requiring
additional toxicity, ecological effects, environmental fate, occupational and residential
exposure, residue and product chemistry data that are expected to confirm the risk assessment.
Health Effects
The Agency has determined that there is evidence of non-carcinogenicity in humans
for diflubenzuron (Group E). However, p-chloroaniline (PCA), a metabolite of
diflubenzuron, is a probable human carcinogen (Group B2). The Agency has determined that
the Qi* for PCA, based upon spleen sarcoma rates in male rats, is 6 x lO'^mg/kg/day)"1 in
human equivalents. The Agency has also determined that p-chlorophenylurea (CPU), a
metabolite of diflubenzuron that is closely related to PCA with no adequate carcinogenicity
data, is considered as having the same carcinogenicity potential (Qi*) as PCA. The sum of
PCA and CPU residues in ingested food, plus the amount of the metabolites formed in vivo
(2%), were used to estimate the dietary exposure of humans to the carcinogenic metabolites of
diflubenzuron. The total cancer risk estimate for PCA and related metabolites for the overall
U.S. population is 1 x 10"6. Where no PCA or CPU are present, the toxicological endpoint for
diflubenzuron per se will be used for risk assessments. The RfD is 0.02 mg/kg/day, based on
the NOEL of 2.0 mg/kg/day in the 52-week chronic oral study in dogs with a safely factor of
100 to account for interspecies extrapolation and intraspecies variability.
A tolerance reassessment was performed and is included with this document. Data for
cotton gin by-products, mushrooms, grass forage are essential to reassess the tolerances.
Confirmatory data are also required for cottonseed, liver, milk, pasture grass hay, soybeans
and walnuts.
Occupational/Residential Exposure and Risk
For occupational and residential exposure, the Agency is establishing a short-term
toxicological endpoint of sulfhemoglobinemia observed in a mouse 14-day subchronic oral
study. The NOEL in this study was 40 mg/kg/day and the LEL was 200 mg/kg/day. The
intermediate term endpoint is methemoglobinemia observed in a 13-week subchronic feeding
study in dogs. The NOEL was 2 mg/kg/day and the LEL was 6.24 mg/kg/day. Although the
risk assessment produced low MOEs for certain mixing/loading activities, these risks are v
VI
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expected to be minimized to acceptable levels by requiring mixers and loaders to wear a
dust/mist respirator (TC-21C).
Environmental Fate. Ecological Effects and Risk ,
Diflubenzuron appears to be relatively non-persistent and immobile under normal use
conditions. The major route of dissipation appears to be biotic processes (half-life of
approximately 2 days for aerobic soil metabolism). Diflubenzuron is stable to hydrolysis and
photolysis:
Available data indicate that it is unlikely that diflubenzuron will contaminate ground
water or surface water. Additional adsorption/desorption data on the degradates are needed to
confirm this conclusion. Additional storage stability data on diflubenzuron and its degradates
are necessary to validate the submitted forestry dissipation study. To support aquatic uses,
additional information is required for aerobic aquatic metabolism, aquatic (sediment)
dissipation, accumulation in irrigated crops, and accumulation in aquatic non-target
organisms. To estimate spray drift a drift field evaluation study is required, however, the
registrants may elect to satisfy this requirement through participation in the Spray Drift Task
Force.
The risk assessment conducted using available data indicates that levels of concern are
not exceeded for avian species, mammals, insects or freshwater fish. Although the use of
diflubenzuron is expected to cause some adverse chronic effects to estuarine/marine fish at
the highest application rate (forestry), these effects are not as widespread as those associated
with freshwater and estuarine/marine invertebrates. The use of diflubenzuron is expected to
cause adverse acute and chronic effects to both freshwater and estuarine/marine invertebrates,
including endangered species. To mitigate these risks, the Agency is requiring a 25-foot
vegetative buffer strip to decrease runoff and to serve as a buffer zone for spray drift from
ground applications. For aerial applications, the Agency is requiring a 150-foot buffer zone.
The risk to aquatic invertebrates is also expected to be substantial when diflubenzuron
is applied to control mosquito larvae. Since this use involves direct application to water
and/or near water, no mitigation is currently proposed.
Before reregistering the products containing diflubenzuron, the Agency is requiring
that product specific 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 a product.
vn
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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. The amended Act provides a schedule for the reregistration process to be
completed in nine years. There are five phases to the reregistration process. The first four
phases of the process focus on identification of data requirements to support the reregistration
of an active ingredient and the generation and submission of data to fulfill the requirements.
,The fifth phase is a review by the U.S. Environmental Protection Agency (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 ingredient 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.
. On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA, Public Law 104-
170) was signed into law. FQPA amends both the Federal Food, Drug, and Cosmetic Act
(FFDCA), 21 USC et seq., and the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA), 7 USC 136 et seq. The FQPA amendments went into effect immediately. Among
other things, the FQPA amended the FFDCA by establishing a new safety standard for the
establishment of tolerances. The FQPA did not, however, amend any of the existing
reregistration deadlines set.forth in section 4 of FIFRA. Thus, the Agency is embarking on an
intensive process, including consultation with registrants, States, and other interested
stakeholders, to make decisions on the new policies and procedures that will be appropriate as
a result of enactment of FQPA. This process will include a more in-depth analysis of the new
safety standard and how it should be applied to both food and non-food pesticide applications.
However, in light of the unaffected statutory deadlines with respect to reregistration, the
Agency will continue its ongoing reregistration program while it continues to determine how
to implement FQPA.
This document presents the Agency's decision regarding the reregistration. eligibility of
the registered uses of diflubenzuron. The document consists of six sections. Section I is the
introduction. Section n describes diflubenzuron, 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
diflubenzuron. Section V discusses the reregistration requirements for diflubenzuron. Finally,
Section VI is the Appendices which support this Reregistration Eligibility Decision.
Additional details concerning the Agency's review of applicable data are available on request.
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CASE OVERVIEW
A. Chemical Overview '
The following active ingredient is covered by this Reregistration Eligibility
Decision:
Common Name:
Chemical Name:
Chemical Family:
CAS Registry Number:
OPP Chemical Code:
Diflubenzuron
N-[[(4-chlorophenyl)amino] carbonyl]-2,6-
difluorobenzamide or l-(4-chlorophenyl)-3-(2,6-
difluorobenzoyl)urea
Urea derivative
35367-38-5
108201
B.
. Empirical Formula: C14H9C1F2N2O2
Trade and Other Names: Dimilin, Vigilante, Micromite, Adept
Basic Manufacturer: Uniroyal Chemical Company, Incorporated
Use Profile
The following is information on the currently (up to and including August 1,
1995) registered uses with an overview of use sites and application methods. A
detailed table of these uses of diflubenzuron is in Appendix A.
Type of Pesticide:
Use Sites:
Acaricide/Insecticide (insect growth regulator)
Terrestrial Food/Feed Crops
Citrus, cotton, mushrooms, pastures, soybeans
Terrestrial Non-Food
Ornamentals, wide-area general outdoor treatment
Aquatic Non-Food
Standing water and sewage system uses
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Target Pests:
Forestry
Forest trees, forest lands
Residential Outdoor
Ornamentals
Indoor Food
' Cattle
Many leaf-eating larvae of insects feeding on
agricultural, forest and ornamental plants (e.g. "
gypsy moth, forest tent caterpillar, Nantucket pine
tip mottX velvet bean caterpillar, Mexican bean
beetle, green cloverworm, beet armyworm,
• mosquito larvae, aquatic midge, rust mite,
bollweevil, citrus root weevil complex, West
N . Indian sugarcane rootstalk borer/weevil, sciarid
fly and face fly)
Formulation Types Registered: soluble concentrate, flowable concentrate,
wettable powder, pelleted/tableted
Method and Rates of Application:
Equipment - aerial, airblast and hydraulic sprayers
Method - broadcast, compost treatment, soil incorporation, cattle
bolus, spray, ultra low volume
Rates - see Appendix A
Timing - at pinhead square (cotton), before spawning (mushroom),
post-harvest, as needed
Use Practice Limitations: Restricted Use Pesticide for sale and use by
certified pesticide applicators or person under their supervision due to toxicity
to aquatic invertebrates
C. Estimated Usage of Pesticide
, This section summarizes the best estimates available for the pesticide uses of
diflubenzuron. These estimates are derived from a variety of published and
proprietary sources available to the Agency. The data, reported on an aggregate and
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site (crop) basis, reflect annual fluctuations in use patterns as well as the variability in
using data from various information sources.
The following table summarizes diflubenzuron use by site:
Site
Cattle (mostly dairy)
Cotton
Forestry
Mushrooms
Soybeans
Acre$ Planted
(WQ's)
13,600
59,300
%«f Sites
Treated
< 1
<3
<100
<1
Volume Applied
(OOOlbs.a.i)
<5
<75
<50
<50
' < 75 .
' 4
Acres Treated
{thousands)
<300
<750
<300
These data, when available, are based on public and proprietary data arid
verified with data provided by the registrant. Adequate data are not available to
estimate the use of diflubenzuron on citrus, ornamentals, walnuts or in mosquito
control programs.
D. Data Requirements
Data requested in the September 1985 Registration Standard for diflubenzuron
include studies on product chemistry, ecological effects, environmental fate, residue
chemistry and human toxicity. These data were required to support the uses listed in
the Registration Standard. Appendix B includes all data requirements identified by the
Agency for currently registered uses needed to support reregistration.
E. Regulatory History
Dimilin, active ingredient diflubenzuron, was first registered in 1976 for use
against gypsy moth larvae in forested areas, including Christmas tree plantations and
nursery crops grown in proximity to gypsy moth infested areas. Most spraying against
gypsy moth larvae is done using products containing either diflubenzuron or B.t.
(Bacillus thuringiensis). due to their efficacy and minimal effects on non-target
organisms.
Cotton was added to the registration in 1979 to control certain lepidopterous
larvae and boll weevils during the growing season and at the end of the growing
season to reduce the size of the boll weevil population. Use of diflubenzuron reduces
the number of weevils overwintering, the number of eggs deposited by surviving
weevils and the percentage egg hatch. It is useful in the campaign to eradicate boll
weevils in the United States.,
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Soybeans were added to the registration in 1982 to control lepidopterous larvae
such as green cloyerworm and velvetbean caterpillar. Diflubenzuron is used
particularly when there is a surge in the population of these larvae or resistance
precludes use of standard insecticides.
Mushrooms were added to the label in 1983 primarily to control fungus gnats
or mushroom flies. Diflubenzuron is incorporated into the casing when it is applied or
as a drench after the casing is spread, covering the compost containing the spawn.
These small flies, Sciaraspp. and related fungus gnats are peculiar in that larvae may
become sexually mature and reproduce without leaving the mushroom bed.
Insecticides must be carefully incorporated into the compost and/or casing to assure
acceptable results. •
Boluses for cattle, first were registered in 1985 under the brand name Vigilante,
are applied with a balling gun to control flies breeding in manure. The bolus stays in
the stomach of treated animals, slowly eroding and releasing diflubenzuron which
prevents molting by maggots of flies breeding in manure.
In 1985 control of mosquitoes breeding in irrigation water tailings, waste water
drained from irrigated fields after furrow irrigation was completed, was added to the
registration. This use was added using the 24(c), special local need process to make
available an effective larvacide to control mosquitoes acting as vectors for equine
encephalitis. This use is for waste water where fish and other non-target organisms are
not of concern'. A tolerance was established for pasture grass to support this use since
livestock are allowed to graze in the area into which irrigation water tailings drain.
Alabama, Florida, Hawaii, and Nevada have issued special local need registrations for
control of mosquitoes in waste water.
Oranges, grapefruit, and tangerines were added to the registration in 1995 to
control the citrus rust mite. Because of concern about the effects of drift from spray
applications affecting non-target arthropods restrictions were attached to the
registration of products containing diflubenzuron to be used on orange, grapefruit, and
tangerine groves.
In July 1995 the patent and all other interests in diflubenzuron were acquired
by Uniroyal Chemical Company. Uniroyal is continuing to develop products
containing diflubenzuron with plans for adding to the label control of grasshoppers on ',
rangeland, control of rice water weevil attacking rice, control of mites and insects on
apples and pears, incorporation into animal feeds to control insects which breed in
manure, and indoors to control household pests.
A Registration Standard for diflubenzuron was issued in September 1985
(NTIS #PB86-176500). The Agency issued a Data Call-in in November 1991 for
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diflubenzuron requiring additional residue chemistry and ecological effects data. This
Reregistration Eligibility Decision, reflects a reassessment of all data which were
submitted in response to the Registration Standard and subsequent Data Call-in.
ffl. SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
Diflubenzuron [l-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea] is an
insecticide/acaricide (insect growth regulator) primarily-used on cotton, mushrooms,
forests, and ornamentals.
Figure A. l-(4-chlorophenyl)-3-(2,6-difluordbenzoyl)urea
o o ,
Empirical Formula:
Molecular Weight:
CAS Registry No.:
OPPCodeNo.:
C14H<,C1F2N2O2
310.7
35367-38-5
108201
Diflubenzuron is a white crystalline solid with a melting point of 210-230 °C.
Diflubenzuron is nearly insoluble in water (0.2 mg/L), but is soluble in organic
solvents including acetonitrile (2 g/L), acetone (6.5 g/L), dimethylsulfoxide and
dimethylformamide (120 g/L), and N-methylpyrolidone (200 g/L).
There are currently two diflubenzuron manufacturing-use products (MPs)
registered to Uniroyal Chemical Company, Incorporated, under Pesticide Chemical
Code 108201: the 95% technical (T; EPA Reg. No. 400-467) and 90% formulation
intermediate (FI; EPA Reg. No. 400-466).
Data for preliminary analysis, guideline 62-1, pertaining to the presence of
parachloroaniline using a method validated to 1 ppm remain outstanding. The
registrant must submit data required for the TGAI and either certify that the suppliers
of starting materials and the manufacturing processes for the TGAI and MPs have not
changed since the last comprehensive product chemistry review or submit complete
updated product chemistry data packages.
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B. Human Health Assessment
1. Toxicology Assessment
The toxicological data base on diflubenzuron is adequate and will support
reregistration eligibility, however, the following data are still required: ,
82-4 21-day inhalation toxicity rat
The Agency is requiring a repeat of the 21-day inhalation study to provide
more accurate assessments of the inhalation hazards to workers and handlers exposed
to diflubenzuron. This study is required to demonstrate a NOEL for
methemoglobinemia and/or sulfhemoglobinemia. Methemoglobinemia results when
large quantities of methemoglobin, caused by some chemicals that convert the ferrous
iron in hemoglobin to ferric iron, accumulate in the blood. Methemoglobin may
interfere with the oxygen carrying capacity of the blood. Sulfhemoglobinemia results
when certain chemicals react with hemoglobin to form sulfhemoglobin, another
abnormal form of hemoglobin, which again cannot react nbrmaily with oxygen: This
study is expected to confirm the results of this risk assessment.
a. Acute Toxicity
The following table presents the results of the acute mammalian toxicity. data
for diflubenzuron:
Acute Mammalian Toxicity
Test
Oral LD50~rat
: Dermal LD,0--rat
Inhalation LC,n— rat
Eye irritation—rabbit*
Dermal irritation—rabbit*
Skin sensitization— -guinea
Pig*
% AI
90%
90%
• 90%
90%
90%
• 95%
MRID
00157103
00157104
00163311
00157105
00157106
42251101
Results
> 5,000 mg/kg-
> 2,000 mg/kg
> 2.49 mg/L
Mild irritant
No irritation
Negative
Category
IV
; m
IV
in
IV
N/A
Data pertaining to eye irritation, dermal irritation and dermal sensitization are not required to support the
reregistration of the TGAI. These data are presented for informational purposes.
7
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b. Subchronic Toxicity
Technical grade diflubenzuron was administered by gavage to male mice daily
for 14 days at dose levels of 0 (control), 8, 40, 200, 1000 or 5000 mg/kg/day. At 15
days, significantly increased levels of methemoglobin were observed at 1000 and 5000
mg/kg/day and significantly increased levels of sulfhemoglobin were observed at dose
levels of 200 mg/kg/day and above. The percentage of erythrocytes containing Heinz
bodies was highly increased at 1000 and 5000 mg/kg/day. No effects on body, weights
or organs and tissues examined at autopsy were observed. The NOEL is 40
mg/kg/day. The LEL is 200 mg/kg/day, based on increased sulfhemoglobin. (MRJDD
00099713)
In a 28-day feeding study technical grade diflubenzuron was administered in
the diet to rats at dose levels of 0 (control), 800, 4000, 20000 or 100000 ppm
(equivalent to 0, 40, 200, 1000 or 5000 mg/kg/day). Methemoglobin was increased in
males at all dose levels and in females at dose levels of 200 mg/kg/day and higher.
Sulfhemoglobin was increased in all treated males and females. At 5000 mg/kg/day
males and females experienced decreased erythfooyte counts, packed cell volumes and
hemoglobin. Dose-related increases in spleen weights at all dose levels and in liver
weights at dose levels of 200 mg/kg/day and higher were also observed. No NOEL
was established in this study since treatment-related effects were observed at 40
mg/kg/day, the lowest dose level tested. The LEL is 40 mg/kg/day, based on increased
methemoglobin in males, increased sulfhemoglobin in males and females and
increased spleen weights in males and females. (MRID 00070018)
In a 13-week feeding study technical grade diflubenzuron was administered in
the diet to rats at dose levels of 0 (control), 160, 400, 2000, 10000 or 50000 ppm
(equivalent to 0, 8, 20, 100, 500 or 2500 mg/kg/day). Methemoglobinemia was
observed in male and female rats at all dose levels. Sulfhemoglobinemia occurred in
male and female rats at dose levels of 100 mg/kg/day and above. Heinz bodies were
observed at dose levels of 500 and 2500 mg/kg/day. The study also notes decreased
erythrocyte counts and decreased hemoglobin in male and female rats at all dose levels
and increased reticulocytes at dose levels of 20 mg/kg/day and above. The terminal
sacrifice showed elevated spleen and liver weights at dose levels of 20 mg/kg/day and
higher. At all dose levels, histopathological examinations indicated dose related
increases of hemosiderosis and congestion of the spleen, hemosiderosis and chronic
hepatitis of the liver, and mild erythroid hyperplasia of the bone marrow. This study
did not establish a NOEL since treatment-related effects were observed at the lowest
dose level tested. The LEL is 8 mg/kg/day, based on increased methemoglobin and
signs of hemolytic anemia, erythrocyte destruction in the spleen and liver and
regeneration of erythrocytes in the bone marrow. A subsequent submission used
regression analysis to calculate NOELs of 2.1 and 1.5 mg/kg/day for males and
females, respectively, for methemoglobinemia and NOELs of 3.1 and 9.1 mg/kg/day
8
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for males and females, respectively, for sulfhemoglobinemia. (MRIDs 00064550 and
00074534)
In a 14-week feeding study technical grade diflubenzuron was administered in
the diet to mice at dose levels of 0 (control), 80, 400, 2000, 10000 or 50000 ppm
(equivalent to 0, 12, 60, 300, 1500 or 7500 mg/kg/day). Methemoglobinemia and
sulfhemoglobinemia (accompanied by Heinz bodies) were observed in male and
female mice at all dose levels. The study noted decreased erythrocyte counts,
decreased packed cell volume, and increased reticulocytes at dose levels of 60
mg/kg/day and higher. The terminal sacrifice showed the following effects: increased
spleen weights at 60/mg/kg/day dose levels and above; increased liver weights and
decreased seminal vesicle weights at dose levels of 300 mg/kg/day and above; and
decreased kidney weights at dose levels of 1500 mg/kg/day and above. At dose levels
of 60 mg/kg/day and above, histopathological examinations indicated hemosiclerosis
of the spleen and in the liver, hepatocytic enlargement, hepatocytic cytoplasmic
vacuolation, inflammatory foci and necrosis in varying degrees. This study did not
establish a.NOEL. The LEL is 12 mg/kg/day, based on increased methemoglobinemia
and sulfhemoglobinemia. A subsequent submission used regression analysis to
calculate NOELs of 3.3 and 1.9 mg/kg/day for males and females, respective^, for
methemoglobinemia and a NOEL of 2.6 mg/kg/day for males for sulfhemoglobinemia.
(MRIDs 00074534 and 00114330)
In a 13-week feeding study technical grade diflubenzuron was administered in
the diet to beagle dogs at dose levels of 0 (control), 10, 20, 40 or 160 ppm (equal to" 0,
0.42, 0.84, 1.64 or 6.24 mg/kg/day). Ophthalmoscopic examinations were negative.
Methemoglobinemia was observed in the dogs at 6.24 mg/kg/day (after 6 weeks). No
gross necropsy, organ weight or histopathological changes were reported at any level
that could be related to treatment. The NOEL is 1.64 mg/kg/day. The LEL is 6.24
mg/kg/day, based on increased methemoglobinemia. (MRID 00038706)
In a 21-day dermal study 21.5%, 10% or 4.64% suspensions of technical grade
diflubenzuron were applied 5 days/week to New Zealand white rabbits at the rate of
1.5 mL/kg/day. The skin of one-half of the animals in each group was abraded. Slight
erythema was occasionally observed in some animals, but was sporadic and could not
be related to the test material. All groups treated with test material displayed increased
methemoglobin. Gross necropsies, organ weight measurements and histopathological
examination of tissues were negative. This study did not establish a NOEL since
treatment-related effects were observed at the lowest dose level tested. The LEL is 69,
mg/kg/day (based on a 4.64% suspension being applied at the rate of 1.5 mL/kg/day).
(MRID 00038716)
In another 21-day dermal study, technical diflubenzuron (96.7% a.i.) was
administered in 0.25% gum tragacantn in distilled deionized water to the dorsal skin
on the backs of 10 rats/sex/dose at 0, 20, 500; or 1000 mg/kg bwt/day for 6 hour
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periods each day. -At 1000 mg/kg/day, dermal irritation was seen in the males as a
trace of acanthosis and hyperkeratosis. Females also exhibited the same type and
degree of dermal irritation at 1000 mg/kg/day. Kidney and liver changes of trace
levels of mineralization and chronic inflammation of the liver were similar to that seen
in the controls of both male and female test animals. Only increased absolute organ
weight changes of testes were reported in the mid- and high-dose males. Relative
organ weights were unaffected. There was no significant toxicity with regard to
mortality, clinical signs, body weight changes, or food consumption. Hematological
changes included elevated WBC count in males in the mid- and high-dose groups
when compared to controls. Males exhibited small reductions in hemoglobin and
hematocrit values at the 1000 mg/kg dose level. Though not statistically significant,
the mid-dose males showed increasing instances of elevated methemoglobin, while
that in the high-dose animals was significantly increased. Treated females at the top
two doses showed reduced red blood cells, hemoglobin and hematocrit values (p <
0.05). The highest dose also showed elevated levels of methemoglobin. Erythrocyte
morphology (anisocytosis), hypochromasia and polychromasia indicated +1 to +2
changes in both males and females indicating loss and replacement of red cells at the
highest two doses. Slight numbers of+1 changes in both sexes at the lowest dose
could not be discerned from control values. Based on the red blood cell changes, this
study established an LOEL of 500 mg/kg/day and a NOEL of 20 mg/kg/day. (MRID
43954101)
A 21-day inhalation study designed to study methemoglobinemia exposed rats
to dust concentrations of 0 (control), 0.121, 0.866 or 1.85 mg/liter of diflubenzuron
25% WP for 1 hour/day, 5 days/week for 3 weeks. An increase in methemoglobin was
observed in all treated groups of both sexes. Reticulocyte counts were unaffected by
treatment. This study did not establish a NOEL since treatment-related effects were
observed at the lowest dose level tested. The LEL is 0.121 mg/liter of 25% WP. A
new study is required. (MRID 00044325)
c. Chronic Toxicity
In a 104-week rat chronic feeding study technical grade diflubenzuron was
administered in the diet to rats at dose levels of 0 (control), 10, 20, 40 or 160 ppm
(equivalentto 0, 0.35, 0.70, 1.43 or 5.83 mg/kg/day in males and 0, 0.43, 0.88, 1.73 or
7.05 mg/kg/day in females). This study established a NOEL for methemoglobinemia
and sulfhemoglobinemia in chronic oral rat studies. Examinations of blood were
conducted at weeks 13, 26, 52, 78 and 102. Sulfhemoglobin and methemoglobin
formation were assayed for the control, 40 and 160 ppm groups only. Sulfhemoglobin
formation was non-detectable in this study. The NOEL for methemoglobinemia in this
study was 1.43 mg/kg/day in males and 1.73 mg/kg/day in females. The LEL is 5.83
mg/kg/day in males and 7.05 mg/kg/day in females. (MREDs 00044329 and
00099712)
10
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In a 104-week rat chronic feeding study technical grade diflubenzuron was
administered in the diet to rats at dose levels of 0 (control), 156, 625, 2500 or 10000
ppm (equivalent to 0, 7.8, 31, 125 or 500 mg/kg/day). Statistically significant
increases in methemoglobin and sulfhemoglobin were consistently observed in male
and female rats at 52 and 104 weeks at all treatment levels tested. The increases
tended to be dose-related. At higher dose levels (particularly at 125 mg/kg/day and
above), signs of hemolytic anemia were observed in males and females at 52 weeks.
No such signs were observed at 104 weeks. At similar dose levels increased
reticulocytes were also noted in females at 104 weeks and in both males and females at
52 weeks. Increased spleen and liver weights were observed in males and females at
dose levels of 125 mg/kg/day and above. Histopathological signs of erythrocyte
destruction andLcompensatory regeneration were observed in both males and females
at dose levels of 7.8 mg/kg/day and higher. No NOEL was established in this study.
The LEL is 7.8 mg/kg/day, the lowest dose level tested. (MRID 00145467)
In a 91-week mouse chronic feeding study technical diflubenzuron was
administered in the diet to mice at dose levels of 0 (control), 16, 80, 400, 2000 or
10000 ppm (equivalentto 0, 2.4, 12, 60, 300 or 1500 mg/kg/day). Mortality, body
weights, food consumption, blood chemistries and urinalyses were not affected by
treatment. Dose-related, statistically significant increases in methemoglobin and
sulfhemoglobin were consistently observed in male and female mice throughout the
study at dose levels of 12 mg/kg/day and higher. A blue/gray discoloration of the skin
and extremities as well as dark eyes accompanied the increased methemoglobin and
sulfhemoglobin. At higher dose levels (particularly 300 mg/kg/day and above), both .
males and females showed signs of hemolytic anemia, erythrocyte destruction and
compensatory regeneration. At similar dose levels, histopathological effects in the
liver were also observed, including hepatocyte enlargement, hepatocyte vacuolation
and congested/dilated centrilobular sinusoids. The study also reported increased
platelet counts at dose levels of 60 mg/kg/day and higher in both males and females.
The NOEL in this study is 2.4 mg/kg/day. The LEL is 12 mg/kg/day, based on
methemoglobinemia and sulfhemoglobinemia. (MRID 00142490)
In.a 52-week chronic oral study technical grade diflubenzuron was.
administered in gelatin capsules to beagle dogs once each day (7 days/week) at dose
levels of 0 (control), 2, 10, 50 or 250 mg/kg/day. Except for a slight decrease in mean
body weight gain observed in female dogs at 250 mg/kg/day, body weights were not
affected. Ophthalmoscopic examinations, clinical chemistries and urinalyses were
negative. Statistically significant increases in methemoglobin and sulfhemoglobin
were observed in male and female dogs at dose levels of 10 mg/kg/day and above.
Heinz bodies were also observed ,in the erythrocytes of male dogs at 250 mg/kg/day
and in those of female dogs at dose levels of 50 mg/kg/day and above. At similar dose
levels, signs of hemolytic anemia, destruction of erythrocytes and compensatory
regeneration of erythrocytes were observed. These signs were accompanied by
increased platelet counts in females. Absolute spleen and liver weights, but not
11
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relative organ body weight ratios, increased in male dogs at 50 and 250 mg/kg/day.
Organ weights did not increase in female dogs. The NOEL in this study is 2
mg/kg/day and the LEL is 10 mg/kg/day, based pn methemoglobinemia and
sulfhemoglobinemia. (MEJDD 00146174)
d. Carcinogenicity
In a 104-week carcinogenicity study technical grade diflubenzuron was
administered in the diet to rats at dose levels of 0 (control), 156, 625, 2500 or 10000
ppm (equivalent to 0, 7.8, 31, 125 or 500 mg/kg/day). Mortality, clinical signs, body
weights and food consumption were not affected by treatment. Increases in
methemoglobin and sulfhemoglobin occurred at all treatment levels!
Histopathological signs of erythrocyte destruction and compensatory regeneration
were observed at dose levels of 7.8 mg/kg/day and higher. Signs of hemolytic anemia,
increased reticulocytes and increased spleen and liver weights were noted at dose
levels of 125 mg/kg/day and higher. Treatment with diflubenzuron was not associated
with an increased incidence of neoplastic lesions in either males or females. Dosing
was adequate since the highest dose level tested, 500 mg/kg/day, approached the limit
dose of 1000 mg/kg/day for carcinogenicity studies and significant toxicity was
observed at this dose level. (MRBD 00145467)
In a 91-week carcinogenicity study technical grade diflubenzuron was
administered in the diet to mice at dose levels of 0 (control), 16, 80, 400, 2000 or
10000 ppm (equivalent to 0, 2.4, 12, 60, 300 or 1500 mg/kg/day). Mortality, body
weights and food consumption were not affected by treatment. Increases in
methemoglobin and sulfhemoglobin were consistently observed in male and female
mice throughout the study at dose levels of 12 mg/kg/day and higher. A blue/gray
discoloration of the skin and extremities and dark eyes accompanied the increased
methemoglobin and sulfhemoglobin. At higher dose levels (particularly 300
mg/kg/day and higher), signs of hemolytic anemia, erythrocyte destruction and
compensatory regeneration were observed as were histopathological effects in the
liver. Treatment with diflubenzuron was not associated with.an increased incidence of
neoplastic lesions in either males or females. Dosing was adequate since the highest
dose tested, 1500 mg/kg/day, exceeded the limit dose of 1000 mg/kg/day for
carcinogenicity studies. (MRJD 00142490)
Carcinogenicity Studies on p-Chloroaniline (Metabolite of Diflubenzuron)
In a 24-month carcinogenicity study p-chloroaniline (PCA) of greate'r than 99%
purity was administered by gavage (5 days/week) to rats at dose levels of 0 (control),
2, 6 or 18 mg/kg/day. Hematology examinations and methemoglobin measurements
were conducted on 15 rats/sex/group at 6, 12, 18 and 24 months. Increased survival
was observed in male rats at 2 and 6 mg/kg/day and in female rats at 2, 6 and 18
mg/kg/day relative to control rats. The study attributed the increased survival in these
12
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treatment groups to a decreased incidence of mononuclear cell leukemia in the same
groups. Mean body weights for treated male and female groups generally remained
within 5% of the control male and female weights throughout the study. Hematology
examinations and methemoglobin measurements showed mild hemolytic anemia and
dose-related increases in methemoglobin at dose levels of 6 and 18 mg/kg/day.N Male
rats at 6 and 18 mg/kg/day and female rats at 18 mg/kg/day had blue extremities
indicative of cyanosis. Histopathological examinations indicated nori-neoplastic
treatment-related effects in the spleen, liver, bone marrow and adrenal gland. A
treatment-related increased incidence of uncommon sarcomas of the spleen was
observed in the male rats in this study. These sarcomas included fibrosarcomas,
hemangiosarcomas and osteosarcomas, many of which metastasized to other sites.
The combined incidence of these sarcomas in male rats was 0/49, 1/50, 3/50 and 38/50
at dose levels of 0, 2, 6 and 18 mg/kg/day respectively. In female rats, 1 fibrosarcoma
was observed at 6 mg/kg/day and 1 osteosarcoma at 18 mg/kg/day. No additional
uncommon sarcomas of the spleen were observed in the female rats in this study. A
marginally increased incidence of pheochromocytomas was also observed in the
adrenal gland of male and female rats at 18 mg/kg/day. For male rats, the incidence
was 13/49, 14/48, 15/48 and 26/49 and for female rats was 2/50, 3/50, 1/50 and 6/50 at
dose levels of 0, 2, 6 and 18 mg/kg/day respectively. Decreased incidence of
mononuclear cell leukemia and of malignant lymphomas were also noted in the treated
male and female rats in this study. (National Toxicology Program (NTP) Report No
351; July, 1989)
In a 24-month carcinogenicity study p-chloroaniline (PC A) of greater than 99%
purity was administered by gavage (5 days/week) to mice at dose levels of 0 (control),
3, 10 or 30 mg/kg/day. Male mice experienced increased mortality at 10 mg/kg/day
after 99 weeks, but not at 30 mg/kg/day. Mortality in female mice and mean body
weights in both males and females were not affected. At 24 months, hemosiderin was
observed in the Kupffer cells of the livers of male and female mice and in the renal
tubules of female mice at 30 mg/kg/day. The livers of female mice exhibited a
proliferation of hematopoietic cells at all treatment levels. Male mice exhibited
increased incidence of combined hepatocellular adenomas/carcinomas. Incidence
were 11 /5 0, 21 /49, 20/50 and 21 /5 0 at dose level s of 0, 3, 10 and 3 0 mg/kg/day
respectively. A dose-related increase in hepatocellular carcinomas caused the increase .
in combined tumors as follows: 3/50, 7/49, 11/50 and 17/50 at 0, 3, 10 and 30
mg/kg/day respectively. Many of these carcinomas metastasized to the lungs (1/50,
1/49, 2/50 and 9/50 at 0, 3, 10 and 30 mg/kg/day respectively). Male mice at 30
mg/kg/day experienced increased incidence of hemangiosarcomas in the spleen and/or
liver of 4/50, 4/49, 1/50 and 10/50 at dose levels of 0, 3, 10 and 30 mg/kg/day
respectively. Incidence of malignant lymphomas were decreased in the treated male
and female mice. No evidence of carcinogenicity was observed in the female mice in
this study. (National Toxicology Program (NTP) Report No. 351; July, 1989)
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e. Developmental Toxicity
In a developmental toxicity study technical grade diflubenzuron was
administered by gavage to groups of 24 female rats on days 6 through 15 of gestation
at dose levels of 0 (control) or 1,000 mg/kg/day (limit-dose study). No maternal
toxicity or toxicity to the developing fetus was observed: The NOEL for maternal
toxicity is 1,000 mg/kg/day and the NOEL for developmental toxicity is greater than
1,000 mg/kg/day. (MRED 41703504)
In a separate developmental toxicity study technical grade diflubenzuron was
administered by gavage to groups of 16 female rabbits on days 7 through 19 of
gestation at dose levels of 0 (control) or 1,000 mg/kg/day (limit-dose study). No
maternal toxicity or toxicity to the developing fetus was observed. The NOEL for
maternal toxicity is greater than 1,000 mg/kg/day and the NOEL for developmental
toxicity is 1,000 mg/kg/day. (MRH3 41703505)
f. Reproductive Toxicity
In a 2-generation reproduction study technical grade diflubenzuron was
administered in the diet to rats at dose levels of 0 (control), 500, 5000 or 50000 ppm
(equivalent to about 0, 25, 250 or 2500 mg/kg/day). Starting at 6 weeks of age, FO
animals were treated continuously for 10 weeks prior to mating at 16 weeks of age
until completion of weaning of all Fl litters at 21 days postpartum. Direct treatment of
the F1 generation (28/sex/dose level) began at about 4 weeks of age and continued
through mating at 16 weeks until weaning for all of the F2 litters. FO and Fl adults
exhibited treatment-related effects at all dose levels. The most prominent of these
effects were increased methemoglobin levels, hemolytic anemia and signs of
erythrocyte destruction. FO and Fl animals exhibited additional signs of toxicity at
250 and 2500 mg/kg/day, including pathological effects in the spleen and liver. No
effects on reproductive performance were observed at any dose level in FO or Fl males
or females. Litter and mean pup weights decreased slightly from birth to 21 days post-
partum in Fl offspring at 2500 mg/kg/day. This study does not identify a NOEL for
parental adults. The LEL is 25 mg/kg/day, based on methemoglobinemia, hemolytic
anemia, destruction of erythrocytes, and pathological changes in the spleen and liver.
The NOEL for reproductive performance in parental adults is 2500 mg/kg/day. The
NOEL for developmental toxicity in progeny is 250 mg/kg/day and the LEL is 2500
mg/kg/day, based on decreased body weights in Fl pups from birth to 21"days post-
partum. (MBJDD 43578301)
g. Mutagenicity
A Salmonella/mammalian microsome plate incorporation assay exposed strains
TA98, TA100, TA1535, TA1537 and TA1538 to technical grade diflubenzuron with
and without S9 metabolic activation at concentrations of 0, 8, 40, 200 or 1000
14
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jag/plate. The high dose was selected on the basis of slight compound precipitation at
1000 ^g/plate. Diflubenzuron was not cytotoxic with or without S9 activation in any
of the Salmonella strains in this assay. There was no evidence of induced mutant
colonies over background levels at any of the evaluated concentrations. (MRJD
41703503)
An in vitro chromosome damage assay exposed cultures of Chinese hamster
ovary (CHO) cells to technical grade diflubenzuron with and'without S9 metabolic
activation. The test material was tested at concentrations up to cytotoxic/precipitating
levels of 200-250 ug/mL. The test material did not increase the, structural
chromosome aberrations over background levels at any of the evaluated
concentrations. (MRID 41703502) "
An unscheduled DNA synthesis (UDS) assay exposed cultures of primary rat
hepatocytes to technical grade diflubenzuron at concentrations ranging from 0.1 to 333
ug/mL. At the high dose of 333 ug/mL, cytotoxicity was observed (36% cell survival,
in an initial assay and 8% cell survival in a confirmatory assay). The test material did
not cause an appreciable increase in net nuclear grain counts compared to the solvent
control at any of the evaluated concentrations. Diflubenzuron did not induce a
genotoxic effect in this assay system. (MRID 41703501)
h.
Metabolism
In an absorption, distribution, metabolism and excretion study diflubenzuron
was administered by gavage as an oral dose of 14C-diflubenzuron to male and female
rats at single dose levels of 5 or 100 mg/kg or at a dose level of 5 mg/kg following 14
days of unlabeled diflubenzuron in the diet at a dose level of 5 mg/kg/day. An
additional group of rats with cannulated bile ducts was also administered a single oral
dose of 5 mg/kg of 14C-diflubenzuron. The rats only partially absorbed diflubenzuron
from the gastrointestinal tract. In the bile duct cannulated rats, about 33% of the
administered dose was absorbed and about 50% of the 33% (17% of the administered
dose) was excreted in the bile. By the seventh day 19-21% of the administered dose
had been recovered from the urine and 77-80% from the feces of rats receiving the
lower doses of 5 mg/kg. Also by the seventh day 3% of the administered dose had
been recovered from the urine and 96% from the feces of rats receiving the higher
dose of 100 mg/kg. Radioactivity in expired air was negligible. The half-life of
radioactivity in blood was about 14 hours. Over 98% of the administered radioactivity
had been excreted by the seventh day. Very little bioaccumulation in tissues was
observed. The highest levels of radioactivity were observed in the erythrocytes and
liver at 48 hours. Ten urinary metabolites were identified, including p-chloroaniline
(PCA) and p-chlorophenylurea (CPU), which together accounted for about 2% of the
administered dose (at 5 mg/kg). In the feces, only unchanged parent compound was
detected. (MRIDs 41720901 and 41919001)
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The chemical structures of diflubenzuron and its residues of concern in plants
and animals are:
o
H -J
o
Cl
Diflubenzuron: l-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea
4-chlorophenyIurea: CPU
4-chloroaniIine: PCA
i. Toxicology Endpoints of Concern
One day single dose oral studies in rats and mice indicated only marginal
effects on methemoglobin levels at a dose level of 10,000 mg/kg of a 25% wettable
powder formulation. Sulfhemoglobin levels and Heinz bodies were not affected.
Therefore, there is no acute dietary endpoint and a risk assessment for acute dietary
exposure (1 day) is not necessary.
The toxicology endpoint for short term occupational or residential exposure (1
to 7 days) is sulfhemoglobinemia based on the 14-day subchronic oral study in mice
dosed with technical grade diflubenzuron. The NOEL in this study was 40 mg/kg/day
and the LEL was 200 mg/kg/day. (MRJD 00099713)
The toxicology endpoint for intermediate term occupational or residential
exposure (1 week to several months) is methemoglobinemia based on the 13-week
subchronic feeding study in dogs. Since the Agency does not use lower NOELs for
shorter term'exposures than for longer term exposures to conduct risk assessments, the
NOEL of 1.64 mg/kg/day in this study is considered to be 2 mg/kg/day. The 2
mg/kg/day NOEL will be consistent with the NOEL of 2 mg/kg/day in the chronic
study used to calculate the RfD. The LEL in this study was 6.24 mg/kg/day. (MRID
00038706)
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In a dermal absorption study, young adult Sprague-Dawley rats were dosed
,dermally with, 14C-diflubenzuron at 0.005 and 0.05 mg/cm2 (0.2 and 2.0 mg/kg).
Exposure periods were 1, 4, and 10 hours for each dose. A standard material balance
was performed at termination. All absorbed material was found in the carcass. Blood
concentrations were below the limit of detection (less than 23 ng/mL). This is
particularly important as the toxic effects occur in the blood. The pattern for
diflubenzuron is typical of a chemical that enters the body through the skin, but cannot
proceed further into the organism where it produces its toxic effect. In diflubenzuron
this limitation is due to its very low water solubility (0.5 ppm). Based on this study,
the dermal absorption rate for exposures of 1 to 10 hours is 0.5%. (MRID 44053101)
Carcinogenicity: Based on the available evidence, which included adequate
carcinogenicity studies in rats and mice and a battery of negative mutageniciry studies,
diflubenzuron per se is classified as Group E (evidence of non-carcinogenicity for
humans). A metabolite of diflubenzuron, prchloroaniline (PCA), is classified as Group
B2 (probable human carcinogen) based on the results of a National Toxicology
Program (NTP) study1 which administered p-chloroaniline hydrochloride by gavage to
rats and mice for 2 years. Please see the Carcinogenicity section above for a thorough
discussion of this study. The results of several mutagenicity studies on PCA were also
included in-the same NTP report. PCA was mutagenicin Salmonella strains TA98 and
TA100 with metabolic activation. PCA induced gene mutations in cultured mouse
lymphoma cells with and without metabolic activation. In cultured Chinese hamster
ovary (CHO) cells, treatment with PCA produced significant increases in sister
chromatid exchanges (SCEs) with and without metabolic activation. Chromosomal
aberrations were also significantly increased in CHO cells in the presence of metabolic
activation.
The Agency has determined that the Qj* (estimated unit risk) for PCA, based -
upon spleen sarcoma rates in male rats, is 6.38 x 10"2 (mg/kg/day)"1 in human
equivalents. Where no PCA and/or CPU are present, the toxicological endpoint for
diflubenzuron per se should be used for risk assessments.
j. Reference Dose
The RfD is 0.02 mg/kg/day, based on the NOEL of 2.0 mg/kg/day in the 52-
week chronic oral study in dogs. The LEL in this study is 10 mg/kg/day, based on
methemoglobinemia and sulfhemoglobinemia. When determining the RfD an
uncertainty factor of 100 was included to account for the interspecies extrapolation
and intraspecies variability. (MRID 00146174)
Likewise, the FAO/WHO joint committee on pesticide residues reviewed
diflubenzuron in 1985 and established an Acceptable Daily Intake (ADI) of 0.02
National Toxicology Program (NTP) Report No. 351; July, 1989
' ' ' 17
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mg/kg/day. The ADI was based upon a one-year oral toxicity study in dogs with a
NOEL of 2.0 mg/kg/day. A safety factor of 100 was applied to account for the
interspecies extrapolation and intraspecies variability.
2. Exposure Assessment
a. Dietary
Tolerances are established for residues of diflubenzuron per se in/on various
raw agricultural commodities and animal feeds [40 CFR §180.377 (a) and (b), and40
CFR §186.2000]. Tolerances range from 0.05 ppm in/on soybeans to 3.0 ppm in/on
rangeland grass. Tolerances of 0.05 ppm have also been established for residues of
diflubenzuron in animal commodities. Adequate enforcement methods are available
for the determination of these residues. •
A National Toxicological Program (NTP) Report concluded thatp-
chloroaniline (PC A), a metabolite of diflubenzuron, may have oncogenic potential.
The Agency has calculated a Qx* for PCA and has determined that definitive analytical
data are needed on the presence of PCA and its potential precursors and metabolites
containing the/?-chlorophenylamine moiety. As indicated above, tolerances should be
expressed in terms of the combined.residues of diflubenzuron and metabolites
convertible to PCA expressed as diflubenzuron.
171 -4(ij}: Plant Metabolism
For purposes of reregistration and risk assessment, the qualitative nature of the
residue in plants is adequately understood based on data from citrus, mushroom, and
soybean metabolism studies. The residues of concern in plants are diflubenzuron,
PCA and CPU.
Responding to reports that PCA may have oncogenic potential, in 1991 the
Agency required a new metabolism study on cotton or soybean and required that the
study use methodology capable of detecting PCA and CPU residues at the 1 ppb level.
The Agency also concluded that the nature of the residue in mushrooms was
adequately understood and cited two mushroom metabolism studies. In the first
metabolism study, residues of parent, CPU, and 2,6-difluorob.enzoic acid (DFBA)
were qualitatively identified in mushrooms grown in [14C]diflubenzuron treated
compost. In a related residue study conducted at 0.5X and IX the label rate, parent
and CPU residues were found at comparable levels (-0.07 ppm) while DFBA residues
(0.6 ppm) were about 10 times higher than the other metabolites. In the other
mushroom metabolism study, residues of parent, CPU, DFBA and PCA were detected
at up to 0.18, 0.6, 3.96, and 0.02 ppm, respectively, in mushrooms treated at less than
IX.
18
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A separate mushroom metabolism study was submitted for reregistration
purposes. Mushrooms were grown in either compost or casing soil which had been
treated with diflubenzuron at IX and 5X the maximum label rate respectively. For
mushrooms grown in compost treated with diflubenzuron, the major identified
radioactive residue was DFBA, accounting for 33% to 138% of Total Radioactive
Residue (TRR) (0.04 to 0.33 ppm). CPU and PCA were identified, ranging from 0.2%
to 0.4% TRR (0.005 - 0.001 ppm) and 0.6% to 2.7% TRR (0.001 to 0.004 ppm)
respectively. Although bound residues accounted for up to 19% TRR (0.03 ppm), no
efforts were made to release the ,bound residues. For mushrooms grown in casing
treated with diflubenzuron, the major identified radioactive residue was DFBA,
accounting for 82% to 224% TRR with ppm levels ranging from 5.3 to 8.8 pprn. CPU,
and PCA were identified,, ranging from 0.3 to 2.3% TRR (0.02 - 0.08 ppm) and 0.04%
to 4.7% TRR (0.002 to 0.16 ppm) respectively.' No efforts were made to release the
bound residues that were present at up to 0.42 ppm.
In a soybean metabolism study, greenhouse grown plants were treated by
syringe with double-ring labeled [14C]diflubenzuron at 0.25 Ib ai/A (IX) at bloom and
again 3 weeks later. Levels of radioactive residues in treated leaves and immature
pods were not presented; however, more than 90% of the TRR remained as unchanged
parent in leaves collected the day of the first application, leaves and pods collected the
day of the second application, and leaves collected at harvest. No DFBA, CPU, or
PCA was detected (LOD 0.05 - 0.16 ppm) in/on leaves and immature pods.
Radioactive residue were 7.55-17.22 ppm in hulls and from less than 0.01 to 0,038
ppm in seeds collected at maturity, 6 weeks after the last application. In hulls, 81.4-
97.9,% of the TRR (6.57-17.5 ppm) was identified as unchanged parent; the
metabolites CPU, DFBA, and PCA were non-detectable (less than 0.3 ppm).
Radioactive residues in seeds were not characterized. These data indicate that
diflubenzuron is not metabolized to any significant extent in soybeans and that
diflubenzuron is not translocated (i.e., is non-systemic) in soybean plants. ,
In a citrus metabolism study, orange fruit and adjacent leaves were treated
twice at a 14-day interval with [14C]diflubenzuron at a rate equivalent to 0.31 Ib ai/A
(Ix). Radioactive residues in fruit harvested 21 days after the second application
consisted almost entirely of unchanged diflubenzuron (0.63 ppm); no detectable levels
(less than 1 ppb) of PCA, CPU and DFBA were reported. (MRID 00156581)
171-4(b): Animal Metabolism
The nature of the residue in animals is adequately understood based on poultry
and ruminant metabolism studies reflecting oral dosing. Terminal residues identified
in animal tissues, milk, and eggs include diflubenzuron, 2-hydroxydifiubenzurori
(2HDFB), 2,6-difluorobenzamide (DFBAM), DFBA, CPU, and PCA.
19
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In a poultry metabolism study, laying hens were dosed orally via capsule for 1-
28 consecutive days with double ring-labeled [14C]diflubenzuron at rates equivalent to
0.05, 0.5, and 5 ppm in the diet. Soybean seeds (0.05 ppm) and hulls (0,5 ppm) are
the only poultry feed tolerances for diflubenzuron. Therefore, the maximum
theoretical dietary exposure of poultry to diflubenzuron is 0.121 ppm with dose rates
in the metabolism study equivalent to 0.41X, 4. IX and 41X the maximum theoretical
dietary exposure.
Radioactive residues in eggs and tissues of hens plateaued by the tenth day of
dosing. Total radioactive residues(TRR) of [14C]diflubenzuron in hens from the 5 ppm
dosing level were as follows: 0.078-1.16 ppm in fat; 0.059-0.453 ppmun liver; 0.068-
0.338 ppm in kidney; less than 0.005 ppm in muscle; and from less than 0.032 to
0.833 ppm in eggs. After 7 days of dosing, tissue and egg samples from the 5 ppm
dosing level were used for characterization of 14C-residues. Diflubenzuron accounted
for 100% of the TRR in fat, 63.4-66.3% of the TRR in muscle, 18.6% of the TRR in
liver, 23.8% of the TRR in kidney, and 68.8% of the TRR in eggs. The metabolite
CPU accounted for 13-22.1% of the TRR in muscle, 49.8% of the TRR in liver, 40%
of the TRR in kidney, and 11.2% of the TRR in eggs. Minor amounts of DFBA were
also isolated from muscle (7-9% TRR), liver (7.4% TRR), and eggs (3.7% TRR), small
amounts of PCA were tentatively identified in some samples.
171-4(c) and (d): Residue Analytical Methods - Plants and Animals
Adequate analytical methodology is available for enforcing tolerances of
diflubenzuron in/on plant and animal commodities. Three enforcement methods for
diflubenzuron are published in PAM, Vol. II as Methods I, II, and HI. Method I is a
GC/ECD method that determines diflubenzuron in plants, as derivatized PCA. Method
H is a GC/ECD method that can separately determine residues of diflubenzuron, 4-
CPU, and PCA in eggs, milk, and animal tissues, each as derivatized PCA. A
HPLC/UV method (Method HE) is also available that determines diflubenzuron per se
in eggs, milk, and animal tissues. Although all three methods have undergone
successful Agency validations and are acceptable for enforcement purposes; Methods I
and II are the preferred enforcement methods as these methods are easier to perform,
have fewer interferences, and are more sensitive.
For residue data collection, adequate GC and HPLC methods are available for
the analysis of diflubenzuron. Residue data submitted for tolerance reassessment were
predominately collected using Methods I and in, or minor variations of these two
methods. .
Due to Agency concerns about residues of PCA in plant and animal
commodities, the registrant is required to develop data collection methods capable of
determining PCA residues down to 1 ppb levels.
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The FDA PESTDATA database dated 1/94 (Pam Vol. I, Appendix H) contains
no information on diflubenzuron recovery using multiresidue methods PAM, Vol. I
Sections 302, 303, and 304. The registrant has submitted Multiresidue testing data
that the Agency has forwarded to the FDA.
I7l-4(e): Storage Stability
The reregistration requirements for storage stability data are not fully satisfied.
Additional confirmatory storage stability data are required for grass forage, cottonseed,
mushrooms, soybeans and walnuts. Additional confirmatory information regarding
the stability of PC A and CPU in milk and liver are also required.
Acceptable storage stability studies have been conducted using fortified control
samples of cottonseed, oranges, mushrooms, milk, eggs, and beef and poultry tissues.
These data indicate that residues of diflubenzuron per se are stable in frozen
cottonseed for up to 3 months, in frozen oranges for up to 16 months, and in
mushrooms, beef tissue, milk, poultry muscle, and eggs stored at temperatures of at
least -20 °C for up 12 months.
Data from fortified mushrooms are available. These data indicate that CPU is
stable for up to 6 months in frozen mushrooms, however, no storage stability data are
available for residues of PCA. If samples from the requested magnitude of the residue-
study on mushrooms are analyzed within 30 days of sampling, then no additional data
will be required. Otherwise additional storage stability data for diflubenzuron
metabolites in mushrooms are required.
Data are also available that appear to demonstrate the stability of residues of
PCA and CPU in milk and liver stored frozen for 22 months at -10 °C; however, the
actual dates of sample fortification, extraction and analysis are required before the
Agency can evaluate these data. (MRIDs 41702102, 42060901 and 42494201 - "
42494203) ' - '
The registrant has submitted information on storage intervals and conditions for
residue samples used to support tolerances. Based upon these storage intervals and the
available storage stability data, additional data are required depicting the stability of
•residues of diflubenzuron per se in frozen samples of cottonseed and grasses stored up
to 6 months, walnuts stored up to 21 months, and soybean seeds stored up to 10
months. Storage stability data for soybean seeds, cottonseed, and walnuts may be
generated using only one of these commodities.
171-4(k): Magnitude of the Residue in Plants
The reregistration requirements for magnitude of the residue in plants are
fulfilled for the following commodities: cottonseed, soybean seeds, pasture and
22
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rangeland grass forage, orange, grapefruit, tangerine and walnuts. Adequate field trial
data depicting residues of diflubenzuron following applications made according to the
maximum or proposed use patterns have been submitted for these commodities.
Geographical representation is adequate and a sufficient number of trials reflecting
representative formulation classes were conducted. Additional data are required on
pasture grass hay, mushrooms, and cotton gin by-products.
Mushrooms: The available mushroom data are inadequate to support the 0.2 ppm
tolerance on mushrooms; additional residue data are required. For purposes of risk
assessment, results from the mushroom metabolism study will be used to estimate
diflubenzuron, CPU and PCA levels in mushrooms. .
Data are available from tests conducted in California and Pennsylvania in
which diflubenzuron (WP) was incorporated into the mushroom composts at the time
of spawning at 1 Ib ai/2500 ft2 (0.4X) and at the time of casing at 0.2 Ib ai/2500 ft2
(0.4X). Mature mushrooms were harvested at each of up to five breaks and were
analyzed separately for residues of diflubenzuron per se, CPU, and DFBA. Residues
of diflubenzuron per se were non-detectable, ranging from less than 0.01 to 0.049
ppm; residues of CPU ranged from less than 0.01 to 0.015 ppm; and residues of DFBA
ranged from 0.01 to 0353 ppm. Maximum total residues of diflubenzuron and CPU
were 0.064 ppm. These data are inadequate as the compost was not treated at the
maximum label rate and no data were provided on residues of PCA in the mushrooms.
Data are required depicting the residues of diflubenzuron, CPU and PCA in/on
first, second, third, fourth, and fifth flush mushrooms treated at the maximum label
rate (1 Ib ai/1000 ft2 at spawning and again at casing at 0.21 Ib ai/1000 sq ft). The
analytical method for PCA must be sensitive to'the 1 ppb level. A minimum of three
field trials are required with two independently composited samples being taken at
each harvest for each test. Two field trials should take place in PA (60% of U.S.
mushroom production) and one in CA (20% of U.S. mushroom production). All
samples should be analyzed within 6 months of harvest and should be stored frozen (-
20 C) until analysis. If samples are not analyzed within 30 days of harvest, storage
stability data for PCA, preferably concurrent, should be generated reflecting the
longest storage intervals.
171-4(T): Magnitude of the Residue in Processed Food/Feed"
The reregi strati on requirements for magnitude of the residue in processed
food/feed commodities are fulfilled for cottonseed, and soybeans. Acceptable
processing studies are also available for citrus commodities. A summary of the
available processing data is presented below.
Citrus: Processing studies indicate that residues of diflubenzuron per se concentrate
by 0.2-1.9X in dehydrated citrus pulp and by 71-147X in citrus oil. Diflubenzuron
23
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residues did not concentrate in citrus juice, wet pulp, or molasses. In addition, in the
most recent orange metabolism study, residues of diflubenzuron per se concentrated
by a factor of 68X in citrus oil processed from whole oranges bearing 0.63 ppm
residues of [14Cjdiflubenzuron. In this same study, the metabolites CPU, DFBA and
PCA were non-detectable in both whole fruit (1 ppb) and oil (less than 2 ppb). Based
on Agency policies, no additional tolerances are required for dried citrus pulp.
(MRIDs 00153407, 00156581, 41079301 and 41079302)
Data are also available from a study in which orange juice was fortified with
0.52 ppm of diflubenzuron and pasteurized at 100 C for 15 minutes. Residues of PCA
were non-detectable (less than 1 ppb) in the pasteurized juice.
Cottonseed: Residues of diflubenzuron do not concentrate in any cottonseed
processed commodities. Therefore, no additional tolerances are required for the
processed commodities of cottonseed.
Soybeans: Residues of diflubenzuron in commodities processed from soybean seeds
fortified with diflubenzuron at Q.I 12 ppm were 0.92 ppm in hulls, less than 0.05 to
0.08 ppm in meal and crude and refined oils, and 0.19 ppm in soapstock.
Concentration of residues occurred only in hulls (8.2X) and soapstock (1.7X), The
available data adequately support the established tolerances soybean hulls (0,5 ppm)
and soapstock (0.1 ppm).
As the commodity soybean soapstock has been deleted from Subdivision 0,
Table II (June, 1994), the feed additive tolerance for soybean soapstock is no longer
appropriate and should be revoked.
171-4CJ): Magnitude of the Residue in Meat. Milk. Poultry, and Eggs
Tolerances of 0.05 ppm have been established for residues of diflubenzuron
per se in eggs, rnilk, animal fat, meat, and meat by-products.
Livestock Dietary Burden Calculations: Based upon currently established tolerances,
the maximum theoretical dietary burden of diflubenzuron residues is 11.29 ppni for
beef cattle, 6.89 ppm for dairy cattle, 0.070 ppm for swine, and 0.121 ppm for poultry.
Data used to calculate maximum dietary burdens of diflubenzuron for livestock are
presented on the following page.
24
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Potential Dietary Contributions of Diflubenziirori
Feed Item
Grass forage
(rangeland)
Grass forage
(pasture)
Cottonseed
Soybean seed
Soybean hulls
Citrus pulp,
dehydrated
Bolus,
controlled
release"
Toler-
ance
(ppm)
3.0
1.0
0.2
0.05
0.5
0.5'
—
%Dry
Matter
25 '
25
88
89
90
91
.
/
Percent in Feed
Beef
Cattle
60
60
25
15
20
33
—
Dairy
Cattle
_._.
70
25
20
20
33
—
Swine
NA
NA
NA
25
10
10
Poultry
NA
NA
NA
20
20
NA
—
Maximum' Dietary Intake (ppm)"*"
Beef
Cattle
7.20
2.40
0.057
0.008
0.111
0.182
4.00
Dairy
Cattle
__.
2.80
0.057
0.011
0.111
0.182
4.00
Swine
0.014
0.056
0.055
—
Poultry
-
_i
0.011
0.111
~
Lactating dairy cattle are not fed on rangeland
" The controlled released bolus has been calculated to contribute 4.0 ppm to the dietary burden for cattle
"" Maximum dietary burden for cattle calculations assume: i) cattle were treated with the controlled release bolus; ii) beef cattle
diet was 60% grass forage (rangeland), 20% soybeans, 10% soybean hulls, and 10% cottonseed; and iii) dairy cattle diet was
70% grass forage (pasture), 10% soybeans, 10% soybean hulls, and 10% cottonseed.
For purposes of reregistration, acceptable data are available for residues of
diflubenzuron in milk, meat, and fat of ruminants. In one cattle study, three groups of
four lactating cows each were given daily oral doses of [14C] diflubenzuron at levels of
0.05, 0.5, or 5.0 ppm in the diet for 28 days; and one additional cow was dosed for 8
days with [14C] diflubenzuron at 250 ppm. All milk samples from the 0.05 and 0.5 ppm
feeding levels contained no detectable (less than 0.001 ppm) radioactivity. Total
radioactivity in milk at the 5 ppm level plateaued at 0.013 ppm within a few days and
declined to non-detectable after a 4-day withdrawal period. The only radioactivity
detected in tissues was in liver (0.54 ppm) at the 5 ppm level. Following 8
consecutive days of feeding at 250 ppm, radioactivity was 6.17-0.22 in milk, 1.038
ppm in kidney, and 6.04 ppm in liver; radioactivity was non-detectable (less than
0.337 ppm) in fat and muscle.
In another cattle study, lactating cows were dosed orally twice a day with
diflubenzuron at either 25 or 250 ppm in the diet for up to 28 consecutive days.
Residues of diflubenzuron were non-detectable (less than 0.05 ppm) in milk from both
feeding levels sampled following 1 to 28 days of dosing. Residues of diflubenzuron
were also non-detectable (less than 0.05 ppm) in the fat, muscle, liver, and kidneys of
cows sacrificed after 8, 18, and 28 days of dosing at 25 ppm. For cows sacrificed after
dosing at 250 ppm for 8, 18 and 28 days, residues of diflubenzuron were non-
25
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detectable (less than 0.05 ppm) in the muscle and kidney, 0.06-0.08 ppm in fat, and
0.09-0.1 in liver. "
Three additional ruminant feeding studies were also submitted for a cattle feed-
through use for diflubenzuron. In two of these studies, six beef cattle and nine
lactating dairy cows were dosed through their feed for 28 consecutive days with
diflubenzuron at a rate of 0.2 mg ai/kg body weight, which was equivalent to
approximately 13 ppm in the diet. Milk samples were collected after 0, 3, 7, 14, 21
and 28 days of dosing. The animals were sacrificed for tissue collection within 8
hours of consuming the final dose. Diflubenzuron residues were non-detectable (less
than 0.01 ppm) in all milk and non-detectable (less than 0.05 ppm) in all tissue
samples, except for one liver sample that contained 0.06 ppm of diflubenzuron.
(MRIDs 00138248, 00155419, 00155420, 00155425 and 00155426)
In the third study, four dairy bull calves were fed diflubenzuron at a rate of 2.8
mg ai/kg body weight per day for 4-5 months and two were sacrificed. Then three
others were fed at 1 mg ai/kg body weight per day for another year and sacrificed.
The 2.8 and 1.0 mg/kg doses were equivalent to approximately 180 and 65 ppm,
respectively. Following dosing at 2.8 mg/kg, residues of diflubenzuron were 0.02 ppm
in liver and kidney, 0.04-0.08 ppm in fat, and less than 0.02 ppm in muscle.
Diflubenzuron residues of were non-detectable (less than 0.02 ppm) in tissues from
animals dosed at 1 mg/kg.
Residue data are also available to support the use of the 9.7% diflubenzuron
bolus in beef and dairy cattle. In this study, dairy and beef cattle were each treated
once with two 50 gram boluses of 10% diflubenzuron (2X the label rate). This dose
was calculated to be equivalent to approximately 8 ppm in the diet. Diflubenzuron
residues were non-detectable (less than 0.04 ppm) in milk collected 20, 30 and 60 days
after treatment. In tissue samples collected 32, 62 and 99 days after treatment,
diflubenzuron residues were non-detectable (less than 0.04 ppm) in muscle and
kidney, from less than 0.04 to 0.06 ppm in fat, and from less than 0.04 to 0.07 ppm in
liver.
Data are also available for residues of diflubenzuron in eggs, meat, meat
byproducts, and fat of poultry. In one study, laying hens were orally dosed via capsule
for 1-28 consecutive days at 0.05, 0.5, or 5 ppm of [14C]diflubenzuron in the diet.
Hens were sacrificed at 3- to 7-day intervals throughout the study. Total radioactive
residues, expressed as diflubenzuron, ranged from non-detectable (less than 0.0006
ppm) to 0.0067 ppm in fat, kidney, liver,, muscle, and eggs of hens dosed at 0.05 ppm,
and were non-detectable (less than 0.005 ppm) to 0.044 ppm in fat, kidney, liver,
muscle, and eggs of hens dosed at 0.5 ppm. Total radioactive residues in hens at the 5
ppm dosing level were 0.078-1.16 ppm in fat, 0.059-0.453 ppm in liver, 0.068-0.338
ppm in kidney, less than 0.005 in muscle and from less than 0.032 to 0.833 ppm in
eggs. Residues of diflubenzuron per se were 0.21 ppm in fat for hens dosed at 5 ppm
26
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(41X) for 7 days. After 24 days of dosing at 5 ppm, residues of diflubenzuron per se
were 0.05 ppm in muscle and kidney, 0.16 ppm in liver, and 0.14 ppm in eggs.
Another study fed Black Barred Rock-Rhode Island Red (BBR/RIR) and White
Leghorn (WL) hens feed containing diflubenzuron at 10 ppm (83X) for 15 weeks.
Residues of diflubenzuron plateaued in eggs after approximately 2 weeks and
remained constant at approximately 0.3-0.6 ppm for the remainder of the dosing
period. Hens were sacrificed after a 3-day withdrawal period. For BBR/RIR hens,
average residues of diflubenzuron were 1.17 ppm in fat, 0.12 ppm in liver, and non-
detectable (less than 0.01 ppm) in muscle at the end of the dosing period. For WL
hens, average residues of diflubenzuron were 1.85 ppm in fat, 0.45 ppm in liver, and
non-detectable (less than 0.01 ppm) in muscle at the end of the dosing period.
Male Hubbard chickens in another study were dosed for 98 days with feed
containing diflubenzuron at 2.5 and 250 ppm, five hens at each level. At the 2.5 ppm
feeding level (21X), diflubenzuron residues were 2.2-6.9 ppm in fat, 0.09-0.45 ppm in
muscle and skin, and 0.06-0.72 ppm in liver. At the 250 ppm feeding level,
diflubenzuron residues were 23-62 ppm in fat, 0.9-3.3 ppm in muscle and skin, and
0.8-3.8 ppm in liver.
An additional study dosed New Hampshire and WL hens for six successive 3-
week periods (18 weeks total) with feed containing diflubenzuron. For the first 3-
week interval diflubenzuron in the feed was at 50 ppm; diflubenzuron in the feed was
then halved at each successive 3-week interval (25, 12.5, 6.2, 3.1 and 1.6 ppm).
Samples of eggs were collected at the end of each 3-week interval. Diflubenzuron
residues in eggs were 0.03-0.05 ppm from the 1.6 ppm dosing level, 0.1-0.25 ppm
from the 3.1 ppm dosing level, 0.23-0.55 ppm from the 6.2 ppm dosing level, 0.3-1.0
ppm from the 12.5 ppm dosing level, 0.9-r2.1 ppm from the 25 ppm dosing level, and
1.2-2.9 ppm from the 50 ppm dosing level. Residues were always higher in WL eggs.
Several other poultry feeding studies have been submitted in conjunction with
petitions for a feed-through use of diflubenzuron on poultry. In one study, ten Warren
and WL hens were dosed with feed containing diflubenzuron at 7.2-8.7 ppm for 28
consecutive days. Eggs were sampled at the end of the second, third, and forth weeks
and separated into yolks and whites; hens were sacrificed at the end of the dosing
period. For the Warren hens, residues of diflubenzuron were 1.31-1.78 ppm in fat,
0.11-0.19 ppm in liver, 0.05-0.08 in muscle, 1.04-1.24 in egg yolks, and less than 0.04
ppm in egg whites. For the WL hens, residues of diflubenzuron were 1.96-3.13 ppm
in fat, 0.48-0.61 ppm in liver, 0.13-0.19 in muscle, 1.74-2.42 in egg yolks, and less
than 0.04 ppm in egg whites. (MRIDs 00144931, 00152501, 00156015, 00156779-
00156783)
27
-------
In another study, hens were fed diets containing diflubenzuron at 7.5 ppm for
80 days. Residues in eggs plateaued by the tenth day and remained constant at 0.3.3-
0.46 ppm throughout the remainder of the dosing period.
!
165-1: Confined Rotational Crops . . • •
The nature of the residue in rotational crops is adequately understood for
purposes of reregistration. Although the Agency concluded that the available confined
rotational crop study was inadequate to fully satisfy guideline 165-1 reregistration
requirements, another confined rotational crop study will not be required because the
data were sufficient to allow the Agency to make regulatory, conclusions regarding the
need for limited rotational crop studies (guideline 165-2) and to comment on the
appropriateness of the currently established plantback interval on diflubenzuron end-
use product labels. • • *
In the confined rotational crop study, [14C]diflubenzuron was applied to a sandy
loam soil at a rate equivalent to 1 Ib ai/A'(2.7X). The soil was aged in a greenhouse
for approximately 1, 4, and 12 months prior to planting radish, spinach, and wheat as
representative rotational crops. The total radioactive residues in the rotational crops
were highest in commodities from the 1-month plant-back interval (FBI) and declined
steadily at each increasing FBI interval. Radioactive residues in raw agricultural
commodities (RACs) from the 1-month FBI were highest in radish tops (0.636 ppm)
and lowest in spinach and wheat grain (about 0.06 ppm). In RACs from the 12-month
FBI, 14C-residues were less than 0.02 ppm in spinach, radish roots and tops, and wheat
forage, and ranged from less than 0.039 to less than 0.104 ppm in wheat straw, grain,
and hulls. The principle 14C-residues identified in spinach were diflubenzuron and
CPU, which together accounted for 31.2% of the TRR (0.019 ppm) in spinach from
the 1-month FBI and 35.3% of the TRR (0,012 ppm) in spinach from the 4-month FBI.
Minor amounts (about 3% TRR) of DFBA were also detected in spinach. In radish,
the principle 14C-residue isolated was CPU, accounting for 54.1% and 35.5% of the'
TRR in tops from the 1- and 4-month PBIs, respectively, and 21.9 and 8.6% of the
TRR in roots from the 1- and 4-month PBIs, respectively. Minor amounts of
diflubenzuron (less than 2% TRR) and DFBA (4-6% TRR) were also isolated. In
wheat forage from the 1- and 4-month PBIs, only minor amounts (less than 5% TRR
and less than 0.01 ppm) of diflubenzuron, DFBA, and CPU were detected although
50-62% of the TRR was solvent extractable. In addition, approximately 64% of the
TRR remained unextracted from wheat straw from the 1- and 4-month PBIs. Of the
14C-residues extracted from wheat straw (36% TRR), the major metabolites identified
were DFBA (11-17% TRR) and CPU (7-17% TRR). 14C-Residues in wheat grain and
hulls were not characterized. '
165-2: Field Rotational Crops
Residue data on field-grown rotational crops are not available. Although the
28 ' '
-------
confined study was deemed inadequate, the available data indicate that diflubenzuron
and CPU may exceed 0.01 ppm in rotational crops planted up to 4 months after a IX
application of diflubenzuron to the primary crop and in cereal grains planted up to 12
months after a Ix application. Since the registrant has indicated that they wish to
maintain the 6-month FBI currently specified on their product labels, limited rotational
field studies are required at two sites using a representative leafy vegetable, root and
tuber vegetable, and a cereal grain. The six trials should be conducted on a specific
crop in each of the three crop groups which the registrant intends to have as a
rotational crop on the label. The soil and/or primary crop should be treated at the
maximum label rate and the appropriate crops should be planted after the minimum
aging interval. For the rotational crops, all of the plant parts prescribed in Subdivision
0, Table n (June, 1994) should be harvested and analyzed for the residues of concern
(diflubenzuron, CPU, and PCA). These data are expected to confirm the conclusions
reached in this risk assessment.
b. Occupational and Residential
Handler Exposures & Assumptions
EPA has determined that there is an exposure potential for mixers, loaders,
applicators or other handlers using diflubenzuron. These handlers may be exposed to
diflubenzuron when:
• Mixing/Loading prior to wide-area outdoor (forests, shelterbelts, aquatic
systems), orchard crops (citrus, walnuts), field crops (soybeans, cotton,
mushroom compost and casing soil treatments), greenhouse and field
grown ornamentals (chrysanthemums) applications;
• Using aerial, ground-boom, airblast and hand-held equipment;
• Working as flaggers to support aerial applications; and
• Dispensing the oral bolus doses administered to livestock.
Mixer/loader/applicator (M/L/A) exposure data for diflubenzuron were, not
required previously, as no toxicological criteria had been triggered. Data for most of
the M/L/A scenarios are provided in the Pesticide Handlers Exposure Database
(PHED).
The daily exposure for handlers (mg'ai/kg bw/day) is calculated using the
following formula:
Daily Exposure
= unit exposure fang ai/lb ai handled) x Ib ai/A x daily acres treated
body weight (70 kg)
29
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Post-Application Exposures & Assumptions
EPA has determined that there is an exposure potential for persons entering
treated sites. Potential exposures are to:
• Harvesters entering treated citrus orchards;
• Scouts and other crop advisors entering treated soybean and cotton
fields;
• Harvesters and persons disbudding treated chrysanthemums;
• Mushroom house workers handling treated compost and casing soil;
• Mushroom harvesters;
• ' Swimmers in treated waters; • .
.• People in residential locations being treated for ornamental infestations
or by wide-area .gypsy moth programs
There are no data available to address post-application exposure for persons
reentering areas treated with diflubenzuron. Since most post-application exposures are
intermediate-term exposures (greater than 1 week), these exposures are of concern.
Due to the low dermal absorption of diflubenzuron, EPA willretain the 12-hour REI
until confirmatory data are submitted and evaluated.
Although there are no data available to estimate .swimmer exposure; it appears
that sites treated with diflubenzuron would not be used for swimming. Based on the
toxicologic concerns for diflubenzuron, a swimmer restriction is required for any
current labels having use directions for treating aquatic sites.
There are no data available to evaluate bystander exposures for people,in
residential locations or forests treated with diflubenzuron; however, based on very low
residues detected in forestry dissipation studies, substantial exposure, outside of
contact with direct sprays is unlikely. In addition, since the dermal absorption rate is
low, and exposure is expected to be of a short-term duration, bystander exposure data
are hot required at this time.
3. Risk Assessment
a. Dietary Risks
• As stated earlier, a risk assessment for acute dietary exposure (1 day) is not
necessary. The Agency did conduct a chronic dietary analysis using DRES to
calculate the Theoretical Maximum Residue Contribution (TMRC) for the overall U.S.
population and 22 population subgroups. This analysis used tolerance level residues
listed in Section IV. The group of non-nursing infants is the most highly exposed
subgroup based on percentage of RfD, as shown below. Refinements in residue and
percent crop treated information Were considered in calculating the Anticipated
30 , '
-------
Residue Contribution (ARC) for those same population subgroups. Using the ARC,
which is considered the more accurate estimate of dietary exposure, children from 1 to
6 years old were the most highly exposed subgroup. These exposure estimates were
then compared to the RfD for diflubenzuron, 0.02 mg/kg/day, to calculate estimates of
dietary risk.
Using Tolerances:
The Theoretical Maximum Residue Contributions for the overall U.S.
population and the most affected subgroups from supported published tolerances are:
Overall U.S. population: 0.00190 mg/kg/day
Non-nursing infants: 0.00605
Children, 1-6 years: • 0.00517
Using Anticipated Residues:
10% RfD
31%
26% >
Using the ARCs for the overall U.S. population and subgroups from published
supported tolerances, the chronic dietary risks to the most affected populations are:
Overall U.S. population: 0.000080 mg/kg/day < 1% RfD
Non-nursing infants: 0.000163 < 1%
Children, 1-6 years: 0.000211 1%
Cancer risk from PCA and related metabolites:
Estimations of the carcinogenic risk to humans resulting from lifetime dietary
exposure were performed for food commodities containing PCA and/or CPU. For the
purpose of calculating dietary risk assessments, the Agency has developed the
following procedure:
1) CPU (a diflubenzuron metabolite that is structurally related to PCA and for
which no adequate carcinogenicity data are available) is considered as having
the same carcinogenic potential (Qj*) as PCA;
2) The sum of PCA and CPU residues in ingested food are used to estimate the
dietary exposure of humans to the carcinogenic metabolites of diflubenzuron;
and
3) In addition to ingested residues of these two metabolites, amounts of PCA
and/or CPU formed in vivo following ingestion of diflubenzuron are included
when estimating the total exposure of humans to the carcinogenic metabolites
of diflubenzuron. The in vivo conversion of ingested diflubenzuron to PCA
31
-------
and/or GPU was estimated to be 2.0%, based on data in the rat metabolism
study. (MRIDs 41720901 and 41919001)
, The Agency used results from mushroom metabolism studies to determine the
percent of total radioactive residue (TRR) present as PC A or CPU in mushrooms,
Then, using tolerance levels for diflubenzuron in animal commodities, and adjusting
for percent crop treated of feed items, total levels of PCA and related compounds were
estimated for mushrooms (using 0.69 ppm / 100% crops treated) as 0.000015.
mg/kg/day (9.4 x 10'7 Carcinogenic Risk) and for milk/liver (using anticipated residue
/ percent crops treated) of 0.000004 mg/kg/day (2.7 x 10'7 Carcinogenic Risk) based
on the overall U.S. population.
Based on the results of a rat metabolism study, an assumption of a 2.0%
conversion of diflubenzuron to PCA in humans is assumed for the PCA risk
assessment. The upper bound of the total cancer risk estimate from PCA and related
metabolites in the overall U.S. population is 1 x 10'6. The U.S. population and all of
the population subgroups have ARCs for chronic dietary risk from diflubenzuron well
below the RfD when all tolerances or anticipated residues are considered. If additional
uses are added to diflubenzuron for commodities not covered by this assessment, the
total cancer risk estimate for diflubenzuron will increase.
b. Occupational Risks
The Agency has determined that the risks to humans resulting from dermal
and/or inhalation exposures to PCA and/or CPU occurring during occupational or
residential exposures to diflubenzuron are likely to be negligible, since exposure to
these metabolites is not anticipated. Only in the event that direct exposure to one or
more of these metabolites of diflubenzuron is demonstrated would it be necessary to
perform such risk assessments. .
Risk to Handlers
To quantify the risk to handlers from mixing/loading/applying diflubenzuron,
the Agency has developed Margins of Exposure (MOEs) for each use pattern.
Margins of Exposure provide a quantification of the likelihood of the expected
exposure to reach the toxicological endpoint. The Agency considers MOEs to be
acceptable if they are greater than 100. MOEs are calculated using the following
formulae:
Short Term Exposure MOE =
NQEL=.
Dose'
40 mg/kg/dav
Daily Exposure
32
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Intermediate Term Exposure MOE =
'NOEL =
Dose
2 mg/kg/dav
Daily Exposure
Handler Risks from Agricultural/Horticultural Uses
Since there are no data to evaluate the handler exposure from the ULV
formulation, mushroom applications and administering the oral bolus dose, the
Agency has made several assumptions. For the mushroom use, the Agency assumed
that the exposure to applicators will not exceed that to mixers/loaders. Assuming that
a mushroom applicator would treat 5000 square feet per treatment, MOEs are greater
than 100 for both short-term and intermediate-term exposure. For the oral bolus
treatment, the Agency assumed that the use of balling guns to administer the pesticide
would limit applicator exposure. The assessment also assumes that exposure from the
ULV applications would not be greater than that of the airblast applications.
For the agricultural/horticultural applications, it is assumed that intermediate-
term exposure applies to aerial applicators and those mixer/loaders supporting those
aerial applications. Intermediate-term exposure is also expected to be of concern for
commercial applicators treating cotton and soybeans with ground equipment. MOEs
for short-term exposure are greater than 100 for handlers wearing long-sleeved shirts,
long pants, and chemical resistant gloves. Some intermediate-term MOEs for
mixer/loaders supporting aerial applications are below 100, however, these levels are
increased to greater than 100 by the use of a dust/mist respirator (TC-21C).
Handler Risk from Forestry and Ornamental Applications
The treatment of trees and shrubs for insect pests (gypsy moth, Nantucket pine
tip moth) includes the treatment of:
Residential, municipal and shade tree areas;
Recreational areas such as campgrounds, golf courses, parks, parkways;
Ornamental, shade-tree, and forest nurseries;
Forests;
Shelterbelts; and
Rights-of-way and other easements.
These treatments are made by using aircraft, airblast equipment, and hydraulic
ground equipment (hand-gun). Exposure estimates for these handlers are provided in
the table entitled "Forestry and Ornamental Uses, Summary Exposure/Risk Values for
Handlers Using Diflubenzuron While Wearing Long-Sleeved Shirt, Long Pants, and
Chemical Resistant Gloves."
33
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Margins of Exposure (MOE) are acceptable to handlers with short-term
exposure while wearing long-sleeved shirts, long pants, and chemical resistant gloves.
However, some intermediate-term exposure MOEs are low for mixer/loaders handling
wettable powders supporting aerial applications. These MOEs are greater than 100
when a dust/mist respirator (TC-21C) is used.
Handler Risk from Aquatic Uses
For aquatic treatments, granular formulations of diflubenzuron are applied
using aerial and ground equipment. The wettable powder formulations are mixed with
oil and sand to carry the pesticide through vegetation into the water. Exposure
estimates for these handlers are provided in the following table entitled "Aquatic Uses,
Summary Exposure/Risk Values for Handlers Using Diflubenzuron While Wearing
Long-Sleeved Shirt, Long Pants, and Chemical Resistant Gloves." '.
Margins of Exposure (MOE) are acceptable for handlers during short- and
intermediate-term exposures while wearing long-sleeved shirts, long pants, and
chemical resistant gloves.
There is also a California Special Local Need (FIFRA 24(c)) registration for the
treatment of anchor worms in ponds containing ornamental, bait, or aquarium feeder
fish. Because each treatment lasts for 30 to 60 days and because of the limited scope
of the operations, exposures and risks should be far less than those of the commercial
applications discussed above.
34
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4. Food Quality Protection Act Considerations
The Food Quality Protection Act of 1996 (FQPA) amended the FFDCA by
setting a new safety standard for the establishment of tolerances. In determining
whether a tolerance meets the new safety standard, section 408(b)(2)(C) directs EPA to
consider information concerning the susceptibility of infants and children-to pesticide
residues in food, and available information concerning aggregate exposure to infants
and children of such residues, as well as the potential for cumulative effects from
pesticide residues and other substances that have a common mechanism of toxicity.
The FQP A amendments to section 408(b)(2)(C) require EPA to apply an
additional 10-fold uncertainty (safety) factor unless reliable data demonstrate that the
additional factor is unnecessary to protect infants and children.
Section 408(b)(2)(D) establishes factors that the Agency must consider in
determining whether the safety standard is met in deciding to issue or reassess
tolerances. These factors include the consideration of available information on the
aggregate exposures to the pesticide from dietary sources including drinking water as
well as non-occupational exposures such as those derived from pesticides used in and
around the home; The Agency must also consider the potential cumulative effects of
the pesticide for which a tolerance is being sought as well as other substances that
have a common mechanism of toxicity.
Because difiubenzuron has food uses, specific consideration, of the risks to
infants and children, as well as aggregate exposures and potential cumulative effects is
warranted.
a. Potential Risks to Infants and Children
In determining whether an additional uncertainty factor is or is not appropriate
for assessing risks to infants and children, EPA uses a weight of evidence approach
taking into account the completeness and adequacy of the toxicity data base, the nature
and severity of the effects observed in pre- and post-natal studies, and other
information such as epidemiological data.
For purposes of assessing the pre- and post-natal toxicity of difiubenzuron,
EPA has evaluated two developmental and one reproduction study. Based on current
toxicological data requirements, the pre- and post-natal toxicity data base for
difiubenzuron is complete. However, as EPA fully implements the requirements of
FQP A, additional data related to the special sensitivity of infants and children may be
required.
38
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Developmental and Reproductive Effects
The effects observed in the diflubenzuron developmental and reproduction
studies can be summarized as follows:
In a developmental toxicity study, technical grade diflubenzuron was ,
administered by gavage to groups of 24 Sprague-Dawley strain female rats on days 6
through 15 of gestation at dose levels of 0 (control) or 1000 mg/kg/day (limit-dose
study). No maternal toxicity or toxicity to the developing fetus was observed. The
NOEL for maternal toxicity is greater than 1000 mg/kg/day and the NOEL for
developmental toxicity is 1000 mg/kg/day.
In a second developmental toxicity study;, technical grade diflubenzuron was
administered by gavage to groups of 16 New Zealand white strain female rabbits on
days 7 through 19 of gestation at dose levels of 0 (control) or 1000 mg/kg/day (limit-
dose study). No maternal toxicity or toxicity to the developing fetus was observed.
The NOEL for maternal toxicity is greater than 1000 mg/kg/day and the NOEL for
developmental toxicity is 1000 mg/kg/day.
In a 2-generation reproduction study, technical grade diflubenzuron was
administered in the diet to Sprague-Dawley strain rats at dose levels of 0 (control),
500, 5000 or 50000 ppm (equivalent to about 0, 25, 250 or 2500 mg/kg/day). Starting
at 6 weeks of age, FO animals (32/sex/dose level) were treated continuously for 10
weeks prior to mating at 16 weeks of age and until completion of weaning of all Fl
litters at 21 days post-partum. Direct treatment of the Fl generation (28/sex/dose
level) was initiated at about 4 weeks of age and continued to mating at 16 weeks of
age and until all of the F2 litters were weaned. Treatment-related effects were
observed in FO and Fl adults at all dose levels. The most prominent of these effects
were increased methemoglobin levels, hemolytic anemia and signs of erythrocyte
destruction. Additional signs of toxicity observed at 250 and 2500 mg/kg/day in FO
and Fl animals included pathological effects in the spleen and liver. No effects on
reproductive performance were observed at any dose level in FO or Fl males or
females in this study. Regarding litter parameters, litter and mean pup weights were
slightly decreased from birth to 21 days post-partum in Fl offspring at 2500
mg/kg/day. A NOEL for parental adults was not identified in this study. The LOEL is
25 mg/kg/day, based on methemoglobinemia, hemolytic anemia, destruction of
erythrocytes, and pathological changes in the spleen and liver. The NOEL for
reproductive performance in parental adults is 2500 mg/kg/day. The NOEL for
developmental effects in offspring is 250 mg/kg/day. The LOEL is 2500 mg/kg/day,
based on decreased body weights in Fl pups from birth to 21 days post-partum.
The developmental and reproductive data for diflubenzuron indicate that there
is no evidence of an increased sensitivity to diflubenzuron from pre- or post-natal
39
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- exposures. In both the rat and rabbit developmental toxicity study, no maternal
toxicity or toxicity to the developing fetus was observed at the highest dose tested.
Further, no effects on reproductive performance were observed at any dose level in FO
or Fl males or females in the 2-generation reproduction study in which parental
toxicity (methemoglobinemia, hemolytic anemia, destruction of erythrocytes, and
pathological changes in the spleen and liver) was observed at all doses tested (i.e., a
NOEL was not established). Therefore, the Agency has concluded that an additional
uncertainty factor is not warranted for pre- and post-natal effects.
Uncertainty Factor
Based on the considerations outlined above, and the absence of any incident or
epidemiological data for diflubenzuron, the Agency concludes that an additional
uncertainty factor to account for any special sensitivity to infants and children is not
warranted for the diflubenzuron risk assessment.
b. Aggregate Exposure/Risk
« . - - - /
In examining aggregate exposure, FQP A directs EPA to take into account
available information concerning exposures from pesticide residues in food and all
other exposures for which there is reliable information. These other sources of
exposures include drinking water and non-occupational exposures, e.g., to pesticides
used in and around the home. For estimating acute and chronic risks the Agency
considers aggregate exposures from the diet and from drinking water. Exposures from
uses in and around the home that may be of a short-term, intermediate or other
duration may also be aggregated as appropriate for specific chemicals. i
Diflubenzuron products are used as insect growth regulators and act by
blocking the synthesis of chitin. Formulations of diflubenzuron are applied to
agricultural crops (cherries, citrus, cotton, soybeans, walnuts, and mushrooms),
ornamental crops (including greenhouse grown crops), forests and shelterbelts, aquatic
systems, and as a feed through treatment for livestock. Diflubenzuron also has a wide-
area general outdoor applications used to control gypsy .moths and mosquitoes.
Although diflubenzuron may be applied by certified applicators in residential areas; it
is a restricted use pesticide and, therefore, is not available for use by homeowners.
Chronic Dietary Exposure - Food Source: Tolerances are established for
residues of diflubenzuron per se in/on various raw agricultural commodities and
animal feeds [40 CFR §'180.377 (a) and (b),, and 40 CFR §186.2000]. Tolerances
range from 0.05 ppm in/on soybeans to 3.0 ppm in/on rangeland grass. Tolerances of
0.05 ppm have also been established for residues of diflubenzuron in animal
commodities. Tolerances have been established for residues of diflubenzuron/?er se in
soybean hulls (0.5 ppm) and soapstock (0.1 ppm).
40
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Chronic Dietary Exposure - Drinking Water Source: No detections of
diflubenzuron have been reported in the Agency's Pesticides In Ground Water
Database and no incidents were found in OPP's Ecological Incident Information
System.
Non-occupational Exposure: Diflubenzuron is a restricted use pesticide and
therefore not available for use by homeowners. However, occupational uses of
diflubenzuron may expose people in residential locations, parks, or forests treated with
diflubenzuron. Based on very low residues detected in forestry dissipation studies,
low dermal absorption rate (0.05%), and extremely low dermal and inhalation toxicity,.
these uses are expected to result in insignificant risk, and will, therefore, not be
included in the aggregate risk assessment.
Acute Dietary Risk, food source: The Agency has concluded that an acute
dietary risk assessment is not required for diflubenzuron because of its low acute oral
toxicity. Therefore, an acute dietary risk assessment was not conducted.
Chronic Dietary Risk, food source: The chronic DRES analysis used tolerance
level residues and 100% crop treated to calculate the Theoretical Maximum Residue
Contribution (TMRC) for the overall U.S. population and 22 population subgroups.
The TMRC for the overall U.S. population and the most affected subgroups are 10%
of the RfD for the U.S. general population, 31% for non-nursing infants (younger than
1 year old), and 26% for children 1-6 years old. Refinements in residue and percent
crop treated information were considered in calculating the Anticipated Residue
Contribution (ARC) for those same population subgroups. The ARC is considered the
more accurate estimate of dietary exposure. Using the ARC the dietary risks are
calculated to be less than 1% of the RfD for the U.S. general population, less than 1%
for non-nursing infants (younger than 1 year old), and 1% for children 1-6 years old.
Cancer Risk, food source: The Agency has determined that estimations of the
carcinogenic risk to humans resulting from dietary exposure be performed for food
commodities that contain PC A and/or CPU. For the purpose of calculating dietary risk
assessments, the following procedure was recommended:
1) CPU should be considered to be potentially carcinogenic and to have the
same carcinogenic potency (Qj*) as PCA;
2) The sum of PCA and CPU residues in ingested food should be used to
estimate the dietary exposure of humans to the carcinogenic metabolites of
diflubenzuron;
3) In addition to ingested residues of these two metabolites, amounts of PCA
and/or CPU formed in vivo following ingestion of diflubenzuron should also be
41
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included when estimating the total exposure of humans to the carcinogenic
metabolites of diflubenzuron (estimated to be 2.0%, based on data in the rat
metabolism study);
The cancer risk estimate for combined residues of PC A and related metabolites
for the overall U.S. population is approximately 1 x 10'6. The U.S. population and all
the DRES subgroups have ARCs for chronic dietary risk from diflubenzuron well
below the RfD when all tolerances or anticipated residues are considered.
Drinking water: Since no detections of diflubenzuron have been reported in the
Agency's Pesticides In Ground Water Database and no incidents were found in OPP's
Ecological Incident Information System, dietary risk from drinking water will be
assumed to be negligible. Consequently neither a chronic nor an acute quantitative
drinking water assessment was performed. Although data are not available to estimate
residues of diflubenzuron degradates in drinking water, residue levels that could lead
to significant risk are not expected. This conclusion may be reevaluated when
additional required data on adsorption/desorption of degradates is received by the
Agency.
Conclusions on Chronic Aggregate Exposure/Risk to Diflubenzuron
The Agency concludes that aggregate risks to the general U.S. population, and
to the population subgroup of infants and children, resulting from diflubenzuron uses
are not of concern.
The total dietary cancer risk for the published tolerances for the overall U.S.
population is approximately Ix lO"*3.
Since there are no detections of diflubenzuron in ground water, dietary risk
from drinking water are expected to be negligible.
Based on very low residues detected in forestry dissipation studies,'a low
dermal absorption rate (0.05%), and extremely low dermal and inhalation toxicity,
occupational uses of diflubenzuron in residential locations, parks, or forests are
expected to result in insignificant risk to people in these areas and, therefore, will not
be included in the aggregate risk assessment.
c.
Cumulative Effects
In reassessing existing tolerances to determine whether they meet the standard
for issuance of a tolerance under section 408 of the FFDCA, EPA.is required to
consider "available information" concerning the cumulative effects of a particular
pesticide's residues and "other substances that have a common mechanism of toxicity."
42
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The Agency believes that "available information" in this context might include not
only toxicity, chemistry, and exposure data, but also policies and methodologies for
conducting cumulative risk assessments. 'While the Agency has some information in
its files that may turn out to be helpful in eventually determining whether a pesticide
shares a common mechanism of toxicity with any other substances, EPA does not at
this time have the methodology to fully resolve the scientific issues concerning
common mechanism of toxicity in a meaningful way. EPA has begun a pilot process
to study this issue further through the examination of particular classes of pesticides.
The Agency hopes that the results of this pilot process will enable it to develop and
apply policies for evaluating the cumulative effects of chemicals having a common
mechanism of toxicity. At present, however, the Agency does not know how to apply
the information in its files concerning common mechanism issues to most risk
assessments.
i
In reassessing tolerances before the Agency hasHeveloped an acceptable
methodology to apply common mechanism of toxicity issues to risk assessments, the
Agency will determine whether:
1) it has sufficient information to determine that a pesticide does not appear to
share a common mechanism of toxicity with other substances; or
2) it is unable to conclude that a pesticide does not share a common mechanism
of toxicity with other substances.
i .
For pesticides falling into the first category, the Agency will explain its
determination and factor the determination into the tolerance reassessment. For
pesticides falling into the second category, the Agency will conclude that it does not
have sufficient available information concerning common mechanism of toxicity to
scientifically apply that information to the tolerance decision, the reassessment
decision will be reached based upon the best available and useful information for the
individual chemical, and a risk assessment will be performed for the tolerance action
assuming that no common mechanism of toxicity exists. However, reassessment
decisions falling into the second category will be reexamined by the Agency after EPA
establishes methodologies and procedures for integrating information concerning
common mechanism into its risk assessments. In such circumstances, registrants
should be on notice that the Agency at that time may well require pursuant to FIFRA
section 3(c)(2)(B) the submission of such data as may be necessary to evaluate
common mechanism of toxicity issues in a risk assessment.
In the case of difiubenzuron, EPA has not yet determined whether or how to
include this chemical in a cumulative risk assessment. This reassessment
determination therefore does not take into account common mechanism issues. After
EPA develops a methodology for applying common mechanism of toxicity issues to
43
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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.
C. Environmental Assessment
1. Ecological Toxicity Data
Most of the data requirements for assessing the ecological toxicity of
difiubenzuron have been satisfied, however, an estuarine/marine toxicity study on fish
(guideline.72-3a) is still required. The estuarine/marine fish toxicity data requirement
was originally required by the September 1985 Registration Standard. An acceptable
study was submitted using the 25% formulation, however, data are still needed using
technical difiubenzuron that are expected to confirm the results of this risk assessment.
a. Toxicity to Terrestrial Animals
(1) Birds, Acute and Subacute
To establish the toxicity of difiubenzuron to birds, the Agency requires an
avian single-dose oral (LD50) study and two subacute dietary studies (LC50), one on
waterfowl and the other on upland game bird. All studies must be performed using the
technical grade of the active ingredient. The following tables summarize the available
data: .
-. •. •* -i "• '
Avian Acute Oral ToxMty Findings , ' -
Species
Bobwhite Quail
Mallard Duck
Red-Winged
Blackbird
% A.I.
99.4
Technical
Technical
LDso
(mg/kg)
>5000
' > 5000
>3763
MRID
Q0073935
00073936
00038614
Toxicity
Category
practically
non-toxic
practically
non-toxic
practically
non-toxic
Guideline
Yes
Yes
Supplemental
44
-------
; n *_,'•••. . *
Avian Subacwte Dietary Toxicity Findings
Species
Bobwhite
Quail
Mallard Duck
Red-Winged
Blackbird
% A.I.
Technical
Technical
1% Granular
LC50
(mg/kg)
>4640
> 4640
> 20,000
'MRID
00039080
00038613
00060381
Toxicity
Category
Slightly Toxic
Slightly Toxic
NA
Guideline
Yes
Yes
Supplemental
These results indicate that diflubenzuron is practically non-toxic to avian
species on an acute oral dietary basis and slightly toxic on a subacute dietary basis.
The guideline requirements for avian acute and subacute toxicity are fulfilled.
(MRIDs 00038613, 00038614, 00039080, 00039085, 00060381, 00073935 and
00073936) .
(2) Birds, Chronic
The Agency requires avian reproduction studies when birds may be repeatedly
or continuously exposed to a pesticide. This determination is based on factors such as
the pesticide's persistence, tendency to bioaccumulate, whether multiple applications
are made, or if mammalian reproduction tests indicate a reproductive hazard. Avian
reproduction studies were required for diflubenzuron because repeat applications may
occur and reproductive impairment is suggested by the available data. The following
table summarizes the available data.
Avian Reproduction Findings
Species
Bobwhite
Quail
Mallard Duck
Bobwhite
Quail
% A.I.
97.6
97.6
NOEL (ppm)
500
500
No effects to
250
LOEL
(ppm)
1000
1000
NA
Endpoints
Affected
egg
production
eggshell
thickness
NA
MRID
41668002
41668001
00099719
Guideline
Yes
Yes
Supplemental
45
-------
Avian Reproduction findings
Species
Bobwhite
Quail .
• Mallard
Bobwhite
Quail
% A.I.
NOEL (ppm)
Reproductive
parameters
significantly
affected @ 10
ppm (eggs
embryonated)
and 40 ppm
(eggs laid)
No effects to
40 -
No effects to
250
LOEL
(ppm)
NA
NA
Endpoints
Affected
NA'
NA •
MRID
00099862
00099730
Guideline
Supplemental
Supplemental
The avian reproductive studies indicate that diflubenzuron affects egg
production in bobwhite quail and eggshell thickness in mallard duck at concentrations
of over 500 ppm. The guideline requirements are fulfilled. (MRIDs 00099719,
00099730, 00099862, 41668001 and 41668002)
(3)
Mammals
The Agency requires wild mammal testing on a case-by-case basis, depending
on the results of the lower tier studies, use pattern, and pertinent environmental fate
characteristics of a pesticide. In most cases, an acute oral LD50 from the submitted
health effects data is used to determine toxicity to mammals. For diflubenzuron, the
acute oral LD50 was 5000 mg/kg in both mice and rats, indicating that diflubenzuron is
practically non-toxic to small mammals on an acute oral basis. (MRID 001.57103)
(4) Insects
The Agency requires a honey bee acute contact LD50 study when pesticide use
will result in honey bee exposure. Two studies conducted with technical
diflubenzuron exhibited contact LD50s of greater than 30 /zg a.i./bee and 114.8 jj.g
a.i./bee. One of the studies also exhibited an oral LD50 of greater than 30 /zg a.iTbee.
These results indicate that diflubenzuron is non-toxic to bees. The guideline
requirement is fulfilled. (MRIDs 00040601 and 05001991)
46
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b. Toxicity to Aquatic Animals .
(1) Freshwater Fish
To establish the toxicity of a pesticide to freshwater fish the Agency requires at
least two freshwater fish toxicity studies, one using a coldwater species (preferably
rainbow trout) and the other a warmwater species (preferably bluegill sunfish). Both
studies must use the technical grade of the active ingredient. The following table
summarizes the available diflubenzuron data'.
-Freshwater Fish Acute Toxicity findings ,,
Species
Rainbow trout
Bluegill sunfish
Rainbow trout
Brook trout
Channel catfish
Bluegill sunfish
Yellow perch
Bluegill Sunfish
Fathead Minnow
Cutthroat trout
Rainbow trout
Fathead Minnow
Channel Catfish
Bluegill Sunfish
Bluegill Sunfish
Rainbow trout
Common Carp
Rainbow trout.
Bluegill Sunfish
Rainbow trout
% A.I.
Technical
Technical
Technical
Technical
Technical
Technical ,
Technical
Technical
Technical
25% WP '
25% WP
25% WP
25% WP
25% WP
25% WP
25% WP
25% WP
25% WP
1%
Granular
1%
Granular
LCSO
(ppm)
140
135
>100
>50
>100
>100
>25
> 100
>500
57
240
>100
>100
> 100
230
195
390
342
> 1000
>1000
MRTO
00056150
00056150
40094602
00056035
00060376
40094602
00056150
00060384
00060380
Toxicity Category
Practically Non-toxic
Practically Non-toxic
Practically Non-toxic
Slightly Toxic
Practically Non-toxic
Practically Non-toxic
Slightly Toxic
Practically Non-toxic
Practically Non-toxic
Slightly Toxic
Practically Non-toxic
Practically Non-toxic
Practically Non-toxic
Practically Non-toxic
Practically Non-toxic
Practically Non-toxic
Practically Non-toxic .
Practically Non-toxic
Practically Non-toxic
Practically Non-toxic
Guideline
Yes
Yes
Yes
Supplemental
Yes
Yes
Supplemental
Supplemental
Supplemental
Supplemental
Yes
Supplemental
Supplemental
Yes
Yes
Yes i
Supplemental
Yes
Supplemental
Supplemental
The 96-hour acute toxicity studies indicate that diflubenzuron is
practically non-toxic to freshwater fish. The guideline requirements for 96-
hour acute toxicity studies in freshwater fish are fulfilled for the technical grade
47
-------
and 25% WP formulations. (MRIDs 00056035, 00056150, 00060380,
00060384 and 40094602)
(2) Freshwater Invertebrates
To assess the hazard of a pesticide to freshwater invertebrates the Agency
requires a freshwater aquatic invertebrate toxicity test, preferably using first instar
Daphnia magna or early instar amphipods, stoneflies, mayflies or midges. The
following table summarizes the data available for diflubenzuron.
Freshwater Invertebrate ToxMty Findings
Species
Daphnia magna
Gammams
pseudolimnaeus
Gammams
pseudolimnaeus
(mature)
Daphnia magna
Daphnia magna
Daphnia magna
G. pseudolimnaeus
% A.I.
Technic
al '
95%
95%
97.6%
25% ,
25%
25%
EC50
(PPb)
48hrLC50 = 3.7
96hrLC30 = 45
96hrLC50 = 30'
48hrEC50 = 7.1
48hrEC50 = 15
48hrEC50=16
96hrLC50 = 25
MRID
43665801,
40098001
40094602
40840502
40098001
40094602
40094602
Toxicity
Category
Very Highly
Toxic
Very Highly
Toxic
Very Highly
Toxic
Very Highly
Toxic
Very Highly
Toxic
Very Highly
Toxic
Very Highly
Toxic
Guideline
Yes .
Supplemental
Supplemental
Yes
Supplemental
Supplemental
Supplemental
The results indicate that diflubenzuron is very highly toxic to freshwater
aquatic invertebrates. Guideline requirements for freshwater invertebrate toxicity
testing for the technical and 25% WP formulations are fulfilled. (MRIDs 40094602,
40098001, 40840502 and 43665801) '
(3) Estuarine and Marine Animals
The Agency requires acute toxicity testing with estuarine and marine organisms
when an end-use product is intended for direct application to the marine/estuaririe
environment or is expected to reach this environment in significant concentrations'.
The terrestrial non-food use of diflubenzuron may result in exposure to the estuarine
48
-------
environment. Therefore, the Agency requires a 96-hour LCSO for an estuarine fish, a
96-hour LCSO for shrimp, and either a 48-hour embryo-larvae study or a 96-hour shell
deposition study using oysters. The following table summarizes the available data.
'•' % V , ' .-•••• ....._
; s •• - " ' ' * ' ' ' ,' ;
- - Estuarm«yMarine AcatB Tdxicrfy Findings *
Species
Mysidopsis bahia
Mysidopsis bahia
Quahogs (Mercenaria)
Grass Shrimp
(Palaemontes pugio )
Mummichog
(Fimdulus
heteroclitus )
Eastern Oyster
(Crassostrea
virginiaa")
Quahogs (Mercenaria
mercenaria)\
Anodonta sp. ; Uca
pugilator; Carcinus
maenas
%AI
99
95
97.6
100
25 WP
25 WP
25 WP
LCSO/EC50
(ppb, ppm)
2.0 ppb
2.1 ppb
> 0.32 ppm
0.64 ppm
255 ppm
130 ppm
> 1000 ppm
MRID
43662001
40098001
41392001
00038612
00056150
0003861 1
00039088
Toxicity
Category
Very
Highly
Toxic '
Very
Highly
Toxic
Highly
Toxic
Highly
Toxic
Practically
non-toxic
Practically
Non-toxic
Practically
Non-toxic
Guideline
Yes
Yes
Yes
Supplemental
Yes
Supplemental
Supplemental
These results indicate that diflubenzuron is very highly toxic to
marine/estuarine Crustacea and highly toxic to marine/estuarine mqllusks. The
guideline requirements are fulfilled for an acute marine/estuarine mollusk study and
for an acute marine/estuarine Crustacea study. Testing of an estuarine crustacean
species with the 25% formulation is waived. No further data are required at this time.
Results of the 96-hour acute toxicity study indicate that diflubenzuron is
practically non-toxic to marine/estuarine fish. No further data are needed to support
the 25% wettable powder formulation, however, a confirmatory 96-hour acute toxicity
study with an estuarine/marine fish is still outstanding for technical grade ,
49
-------
diflubenzurpn. (MRIDs,00038611, 00038612, 00039088, 00056150, 00060377,
40098001, 41392001, and 43662001)
(4) Freshwater and Estuarine/Marine Chronic Results
Aquatic Invertebrates .
• i "
The Agency requires early life-stage tests or life-cycle tests if: 1) the product is
applied directly to water or expected to be transported to water from the intended use
site, and if the pesticide is intended for use such that its presence in water is likely to
be continuous or recurrent regardless of toxicity; or 2) any acute LC50 or EC50 is less
than 1 mg/L; or 3) the EEC in water is equal to or greater than 0.01 of any acute EC50
or LC50 value; or 4) the actual or estimated environmental concentration in water
resulting from use is less than 0.01 of any acute EC50 or LC50 value and either,studies
of other organisms-indicate the reproductive physiology offish and/or invertebrates
may be affected, physicochemical properties indicate cumulative effects, or the
pesticide is persistent in water (e.g. half-life greater thati 4 days).
The Agency required aquatic invertebrate chronic testing for diflubenzuron
because of its repeated applications, an aquatic invertebrate acute LC50 of less than 1
mg/L, and direct application to water as a mosquito larvicide. Additionally, available
information indicates the potential for chronic hazard to aquatic invertebrates.
'\ ,
The Agency also required'finfish chronic testing based on repeated applications
of diflubenzuron, and the pesticide's direct application to water as a mosquito
larvicide. ,
50 .
-------
The following table summarizes the available data.
Aquatic Invertebrate Life-Cycle Toxicity Findings
Species
Daphnia magna
Daphnia magna
Brine Shrimp
{Anemia salina )
Mysidopsis bahia
Mysidopsis bahia
Daphnia magna
% A.I.
99
100
99
97.6
97.6
NOEL
< 0.06 ppb
< 0.09 ppb
> 10 ppb
None
45ppt
40ppt
LOEL
0.06 ppb
0.09 ppb
>10ppb
0.075 ppb
86ppt
93ppt
MRED
Test#2424
Beltsville
00010865
00073933 .
43662001
40237501
40840501
Endpoints
Affected
Reproduction
Survival
Reproduction ,
Survival
Reproduction
Reproduction
Mortality
Growth
Reproduction
Survival
Growth
Reproduction
Guideline
Supplemental
Supplemental
Supplemental
Supplemental
Core
Core
The results indicate that diflubenzuron affects reproduction, growth and
survival in freshwater invertebrates as well as reproduction in marine/estuarine
invertebrates. The guideline requirement is fulfilled for the 25% WP formulation with
a freshwater invertebrate. The guideline requirements are also fulfilled for aquatic
invertebrate life-cycle toxicity studies with freshwater and estuarine species using the
technical grade active ingredient. (Beltsville Lab Test 2424 and MRIDs 00010865,
00073933,40130601 and 40840501)
Fish
The Agency requires a fish life-cycle test when an end-use product is intended
to be applied directly to water or is expected to be transported to water from the
intended use site, as long as any of the following conditions apply: the EEC is equal to
or greater than one-tenth of the NOEL in the fish early life-stage or invertebrate life-
cycle test; or if studies of other organisms indicate the reproductive physiology offish
may be affected.
51
-------
The following table summarizes the available data.
$8sh life-Cycle Texieity Finding*
Species
Fathead
minnow
(Pimephales
promelas}
Mummichog
* (Fundulus
hetroclitus)
% A.I.
99.4
Tech
NOEL
(ppm)
0.10
0.05
LOEL
>0.10ppm
NA
MATC
>0.10ppm
NA
MRID
00099755
00099722
End-
point
None
None
Guideline
Yes
Supplemental
4-10% of first generation juveniles (test and control) developed'abnormally. Several different
statistical analyses showed no dose-dependent reactions with respect to abnormalities or
mortalities. No significant difference in growth (wet weight) and # eggs/female. Second
generation showed no dose-dependent relationship for any observed relationship. Study did not
provide adequate test of the effects of diflubenzuron on reproductive success.
These results indicate that diflubenzuron does not affect reproduction in
freshwater fish. The guideline requirement is fulfilled for a freshwater fish life-cycle
study; however, the submitted life-cycle study for estuarine/marine fish did not
adequately test the effects on reproduction, a major objective of this test. The study
was designed inadequately, since there were no dose-response reactions. The
magnitude or types of chronic risk cannot be determined with the present study,
however, no new data are being required. The available data are sufficient for the
Agency to conduct a chronic risk screening for fish. (MRIDs 00099722 and
00099755)
(5) Aquatic Field Testing
Twelve freshwater invertebrate field studies were reviewed in the September
1985 Registration Standard. The following table summarizes these field'studies.
52
-------
'- -" ' - ' -,"', \"'',' ' '", '" , < ' '»,,,..
, ,'- s '' JFresJiwatej- feverteferate Fieia Testing ' '-,,'-''.' , '/,
Description
1% granular product @0. 1 and 0.2 Ib. a.i./A applied to
finger areas on residential-recreational lakes in CA.
Observed 9 weeks post-treatment
25% WP @ 2.5, 5, and 10 ppb applied to farm pond
and small lake
25% WP @ 0.4 Ib. a.i./A applied to small ponds in
UT, post-treatment samples were taken 30 and 80
days.
25% WP @0.03 and 0. 12 Ib. a.i./A applied 4 times at
2-week intervals to small ponds in VA. Samples
taken once pre- and once post-treatment
25% WP @0.18 Ib. a.i./A applied to forest in Canada
to control spruce budworm. Samples take pre- and 3
days post-treatment.
25% WP @0.03 Ib. a.i./A applied 4 times at 2 week
intervals to man-made ponds stocked with
representative fauna. Samples taken pre-treatment and
10 days after final treatment.
1% granular and 25% WP @ 0.025, 0.05 Ib. a.i./A
applied to replicated ponds. Observations were up to
13 days post-treatment
25% WP @ 0.01 to 0.25 Ib. a.i./A applied to flooded
rice fields, one sample was taken 80 days post-
treatment.
25% WP @ 0.03, 0.12 Ib. a.i./A applied to ponds 4
times at 2 week intervals in TX. Samples taken pre-
treatment and 10 days after last treatment.
25% WP @ 0.03, 0. 12 Ib. a.i./A applied 4 times at 2
week intervals to ponds in AR. Samples taken pre-
treatment and 10 days post-treatment.
25% WP @0.03, 0.12 Ib. a.i./A applied 4 times at 2
week intervals to ponds in NC. Samples were taken
pre- and 9 days post-treatment.
Result
Reductions to cladocerans,
copepods and amphipods.
Crustacean zooplankton
suppressed at all rates for up to
6 weeks, with recovery noted
thereafter
Immature aquatic insect
populations were reduced 30
days post-treatment.
Cladocerans were reduced at
both treatment levels.
Amphipod and aquatic beetle
larvae populations removed.
Copepods and ostracods may
have been impacted
Invertebrate populations were
susceptible with cladocerans
particularly depressed.
Non-target organisms reduced,
cladocerans affected more than
the target species.
Certain non-target aquatic
insects reduced and others
increased (due to reduction in
predators).
Certain bentbic and zooplankton
organisms reduced or eliminated
at both treatment levels.
Copepods reduced but '
minimally impact when applied
in December.
May have eliminated certain
sensitive and reduced other
species.
MRID
05000841
00099897
00038213
00099791
00071210
00099891
00099839
00038212
00039090
00039091
00039092
53. ,
-------
, ,, /' , ' Fr«sitwaterittTepte&rai«.11ei3T-esi«ttg * - ,, , -"
1% granular @ 0.02, 0.04 Ib. a.i./A applied to marsh
habitat on Eraser .River, BC, Canada. Samples taken
up to 7 1 days post-treatment
Reduced zooplankton and non-
target insects.
00095416
All twelve freshwater invertebrate field studies demonstrated similar effects
attributed to diflubenzuron when directly applied to an aquatic environment.
Generally, aquatic invertebrate fauna (especially cladocerans) were markedly reduced
with some recovery noted.
Three estuarine invertebrate field studies are summarized below:
Estuarkie Invertebrate FM
-------
(2) Aquatic
All insecticides require Tier I aquatic plant testing, except those intended only
for indoor uses and outdoor domestic homeowner uses. Tier I test results that show
effects of more than 50% for aquatic plants trigger Tier II data requirements. Tier I
testing should include Selenastrum capricornutum, Lemna gibba, Skeletonema
costatum, Anabaenaflosaquae and a freshwater diatom.
A supplemental diflubenzuron study on Selenastrum capricornutum indicated
an EC50 of 0.20 mg/L. The guideline requirements for aquatic plant testing are not
fulfilled at this time. (MRED 42487101)
2.
Environmental Fate
The environmental fate database is largely complete, however, the following
data requirements are still outstanding: ,
162-4 Aerobic aquatic metabolism2
163-1 Adsorption/Desorption3 , -
164-2 Aquatic (sediment) dissipation5
164-3 Forestry dissipation4
165-3 Accumulation in irrigation crops5
165-5 Accumulation in aquatic non-target organisms5
202-1 Drift field evaluation5
These data are not expected to significantly change the basic environmental
fate assessment for diflubenzuron, but to confirm our position and increase our degree
of certainty in estimating the environmental impact of the use of diflubenzuron. Please
see the appropriate section below for a full discussion of each data requirement.
a.
Environmental Fate Assessment
Based on acceptable laboratory and supplemental and acceptable field data,
diflubenzuron appears to be relatively non-persistent and immobile under normal use
Required to support aquatic uses, 24(c) (Special Local Need/State) registrations in FL, CA, HI, NV and
AL, for aquatic uses to control mosquitoes and/or midges in non-potable water, irrigation ditches,
tailings, livestock wastewater lagoons, non-crop lakes, stockpiled rubber tires, sewage effluent, etc.
Study should be conducted on CPU and bare ground data from typical use area(s) in the north
Storage stability data are required for diflubenzuron and its degradates using the same type of soil, litter,
and leaves that were used in the submitted forestry dissipation study. These data are necessary to
validate the existing study.
The registrants may elect to satisfy this requirement by participating in the Spray Drift Task Force.
55
-------
conditions. The major route of dissipation appears to be biotically mediated processes
(half-life of approximately 2 days for aerobic soil metabolism). Binding to soil
organic matter appears to contribute to the dissipation of diflubenzuron (with K [n=l]
values for sand clay, silty clay loam, silt loam, sand loam, sandy clay loam, clay, clay
hydrosoil, and peat hydrosoil of 40, 40, 20, 25, 130, 110, 150, and 3500, respectively).
Anaerobic aquatic metabolism was reported to be slower (half-life of approximately 34
days). Other laboratory data indicate that diflubenzuron is stable to hydrolysis (with
an approximate half-life of 30-80 days for pH 5-9) and photolysis (with an
approximate half-life of 80 days for aquatic) and is relatively immobile in soil (Rf
values were 0.01, 0.07, 0.14, and 0.34 for silty clay loam, clay loam, and two sand
loam soils, respectively). ' -
Supplemental and acceptable field data confirm the laboratory data with
reported half-lives of 5.8 to 60 days. Diflubenzuron was discernible only in the 0-15
cm soil depth segments, however, calculated half-lives for California and Oregon
orchard applications were higher (half-life of approximately 68 - 78 days).
Diflubenzuron has not been detected in well monitoring6. In addition, based on
chemical and physical properties and LOCs, diflubenzuron does not trigger ground
water concerns, meet the triggers for ground water restricted use chemicals, or exceed
the ground water levels of concern.
Under aerobic conditions diflubenzuron appears to degrade to 4-chlorophenyl
urea (CPU), reaching a maximum concentration of 30.8% of applied levels at 7 days
post-treatment. The other major degradate, CO2, was reported to reach a maximum
concentration of 26.8% of applied levels by day 21 post-treatment Three minor
degradates, 2,6-difluorobenzoic acid, 2,6-difluorobenzamide, and p-chloroaniline,
each reaching a maximum concentration of less than 10% of applied levels, were
identified in the aerobic study. These metabolites were also discernible in an
anaerobic metabolism study. Due to the stability of diflubenzuron to abiotic processes,
limited data are available on the persistence and mobility of diflubenzuron metabolites.
One column leaching study did report CPU in leachate (approximately 15 to 30% of
applied). Even though CPU appears to be mobile under laboratory conditions, it has
not been reported below the 0 to 15 cm soil depth segment in the field.
Diflubenzuron appears to accumulate at low levels and depurate rapidly in fish
tissue. The reported bl concentration factors ranged from 34 to 200X for fillet, 78 to
360X for whole fish, and 100 to 500X for viscera. In addition, the depuration rate
indicates a rapid decrease (99%) of accumulated residues in tissue during the 14 day
depuration period.
National Summary-Pesticides in Ground Water Database-A Compilation of Monitoring Studies: 1971-
1991 compiled by the EPA
56
-------
b. Environmental Fate and Transport
(1) Degradation
Hvdrolvsis ri61-n
Diflubenzuron appears to be stable to hydrolysis at pH 5 and pH 7 (90%
unchanged after 4 weeks). At pH 9, a 32-day hydrolytic half-life was reported.
This data requirement is fulfilled. (MRIDs 40859801 and 41087801)
Photodegradation in water (161-2)
Diflubenzuron appears stable to unsensitized aqueous photolysis at pH 7. The
data reported an extrapolated natural light half-life of 80 days. This data
requirement is fulfilled. (MRIDs 40816301 and 41087802)
Photodegradation on soil (161-3)
Diflubenzuron had a reported half-life of 11.3 and 3.7 days for light exposed
and control samples, respectively. Five degradates, p-chlorophenyl urea
(CPU), 2,6-difluorobenzoic acid (DFBA), two unidentified degradates (labeled
SP1 and PK1), and 14CO2, were discernible in the light exposed and control
samples. The maximum concentration reported for DFBA, CPU, SP1, and
PK1 in the light exposed samples were 3.0% (Day 7), 12.9% (Day 10), 0.6%
(Day 10), and 0.1% (Day 16) of applied radioactivity, respectively. The .
maximum concentration for DFBA, CPU, SP1, and PK1 (2.1% at Day 2,
21.1% at Day 7, 3.5% at Day 10, and 0.2% at Day 10 & 16, respectively) in the
control samples were similar. This data requirement is fulfilled. (MRID
42251201)
Aerobic soil metabolism (162-1)
Diflubenzuron, applied to sandy loam soil, was calculated to have a half-life of
2-14 days (depending on soil texture) when incubated at 24 ± 1°C and
maintained at 77% of 0.33 bar moisture capacity. The major degradate, 4-
chlorophenyl urea, reached a maximum concentration of 30.8% to 37% of the
applied radioactivity at 7 to 14 days post-treatment. The other major degradate,
CO^ reached a maximum concentration of 26.3% of applied radioactivity by
day 21 post-treatment. Three minor degradates, 2,6-difluorobenzoic acid, 2,6,
difluorobenzamide, and 4-chloroaniline, which each had a maximum
concentration of less than 10% of applied radioactivity were identified, as well.
This data requirement is fulfilled. (MRIDs 00039473, 00039474, and
41722801)
57
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Anaerobic soil metabolism (162-2 and 162-3)
Difiubenzuron degraded with a half-life of 2 to 14 days when applied to sandy
loam soil and incubated at 14°C and 24°C. The major degradate, 4-
chlorophenyl urea, reached a maximum concentration of 37% of applied
radioactivity at days 2 to 14 (depending on temperature). The other major
degradate, 2,6-difiuorobenzoic acid, reached a maximum concentration of 23%
of the applied radioactivity; however, bound residues increased to 37% .of the
applied radioactivity as extractable residues decreased during the testing
period. This data requirement is fulfilled. (MKDDs 00040782 and 41837601)
Anaerobic aquatic metabolism (162-3)
The study reported a half-life of 34 days for difiubenzuron when applied to silt
loam soil and incubated at 24°G under anaerobic conditions. The study
identified three degradates (2,6-difluorobenzoic acid, 4-chlorophenyl urea, and
4-chloroaniline) at maximum concentrations of 0.42 ug/g, 0.33 ug/g, and 0.004
ug/g in fioodwater and maximum concentrations of 0.38 ug/g, 1.15 ug/g, and
0.02 ug/g in soils, respectively. This data requirement is fulfilled. (MRID
41837601) .
(2) Mobfflty
Leaching/adsorption/desorption (163 -1)
Two mobility studies containing column leaching data and
adsorption/desorption data combined to fulfill the
leaching/adsorption/desorption requirement. Reported adsorption values (40,
40, 20, 25, 130, 110, 150, and 3500 for a sand clay, a silty clay loam, a silt
loam, a sand loam, a sandy clay loam, a clay, a clay hydrosoil, and a peat
hydro-soil, respectively) indicate that difiubenzuron is relatively immobile and
adsorbs preferentially to soil organic matter over remaining in solution. There
did appear to be some desorption, but desorption was not quantified as percent
of adsorption.
14,
C-Difiubenzuron residues (mainly p-chlorophenyl urea) were mobile in sandy
loam-loamy sand, sandy loam, silt Loam, and clay loam-clay soils treated with
14C-diflubenzuroh at «2.2 Ib ai/A and leached with 30 inches of water over a 20
day period. Of the applied radioactivity (residues not identified in top areas),
36.4-56.9% remained within 1, inch of the treated surface, 78.2-102.9%
remained in the soil, and 18.9-34.3% leached from the 24 inch columns. More
than 90% of the radioactivity in each leachate was in the form of p-
chlorophenyl urea.
58
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14C-Diflubenzuron was immobile in clay loam and silty clay loam soils (Rfs =
0.01 - 0.07) and had a low mobility in sandy loam soils (Rfs = 0.14 - 0.34), as
well, based on a thin layer chromatography test. Although this technique is no
longer acceptable for a guideline study, these data provided sufficient
information to make a regulatory decision and the data requirement is fulfilled.
(MRIDs 00039476, 0003 9477, 00040777 and 00157842)
(3) Accumulation
Bioaccumulation in Fish (165-4)
Difiubenzuron appears to accumulate and depurate from all fish tissues.
Bluegill sunfish exposed to 0.0093 (±0.0021) ppm for 28 days were reported to
have bioconcentration factors of 34 to 200X for fillet, 78 to 360X for whole
fish, and 100 to 550X for viscera. By day 3 to 7 of the uptake phase, the
accumulation of 14C-residues appeared to have peaked and leveled to a steady
state concentration in all tissues. The maximum uptake tissue concentrations
were 1.7 mg/kg for fillet, 3.3 mg/kg for whole fish, and 4.7 mg/kg for viscera.
A depuration of 99% of accumulated 14C-residues from all sampled tissue was
reported for the 14 day depuration period. During the depuration period, 14C-
residues dropped to less than 0.06 mg/kg in fish tissues. This data requirement
is fulfilled. (MRID 42258401)
(4) Field Dissipation
Terrestrial field dissipation (164-1)
Eight guideline terrestrial field dissipation studies were submitted. Three of the
field dissipation studies were performed in California (one orchard and two
field dissipation studies), two in Oregon (one orchard and one bare ground),
one in Louisiana, one in Arkansas, one in a Florida citrus orchard, and one in a
New York apple orchard. The combined studies fulfill the bare soil and
orchard terrestrial field dissipation requirement.
The orchard and bare ground data reported similar observed half-lives (from
5.8 to 13.2 days), however, calculated half-lives for the California citrus and
the Oregon apple orchards ranged from 68.2 to 78 days.
P-Chlorophenyl urea appears to be the major degradate in field dissipation data
with maximum concentrations ranging from less than 0.02 to 0.06 ppm.
Another discernible degradate, 2,6-difluorobenzoic acid, had reported
concentrations ranging from not detected (ND) to 0.01 ppm. Difiubenzuron
and its degradates were not detected below the top 30 cm soil depth.
59
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Forestry Dissipation ' '''•',
One guideline forestry dissipation study furnished supplemental data but did
not fulfill the data requirement for forestry dissipation (164-3). Addenda to this
study "partially addressed concerns in the original review of analytical
methodology; however, the storage stability data could not adequately address
the storage stability of diflubenzuron and its degradates when applied to soil,
litter, and leaves. Further storage stability data are needed for difiubenzufon
and its degradates using the same type of soil, litter, and leaves that were used
in the forestry dissipation study.
Residues of diflubenzuron either did not occur or did not persist in flowing
water or ponds, sediment, or soil. In addition, the degradate, 4-chlorophenyl
urea, was not detected in exposed soil samples. Residues in leaf litter increased
for 60 days post-treatment to a peak of 1.5 ppm, and then declined slowly with
an apparent calculated half-life of 70 days. Residues in laurel leaves reached a
maximum concentration of 1.3 ppm at 14 days post-treatment, and then
declined steadily with an apparent calculated half-life of 30 days. Conifer and
hardwood leaf residues declined steadily with an apparent calculated half-life
of 30 to 35 days, respectively. (MRTDs 00163853 and 41922201-41922210)
(5) Spray Drift
Droplet size spectrum (201-1)
The droplet size spectrum data indicated that smaller droplets are more likely to
move off target. Droplets 122 ^m and smaller are readily airborne and
transported in the atmosphere as drift loss. This data requirement is fulfilled
(MRID 42151701 and addendum)
Drift field evaluation f202-1)
Two field spray studies have been submitted. These studies furnish
supplemental data, but do not fulfill the data requirement for drift field
evaluation.
The spray drift data indicate that approximately 4% of applied diflubenzuron
drifted 110 feet from the edge of a citrus orchard sprayed with Dimilin 25 W at
a rate of 1.25 Ib ai/25Q gallon (4X max label rate) by air blast orchard sprayers.
At a distance of 300 feet, drift was only 0.5% of applied. The concentration of
diflubenzuron collected by high volume air samplers during the course of the
event at 300, 600, and 1200 feet was 0.22 ^g/ft3, and 0.02 /zg/ft3, respectively.
(MRIDs 42151701 and 42151702)
60
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Although additional drift field evaluation data are required to fully characterize
diflubenzuron drift, this requirement may be satisfied by data from the Spray
Drift Task Force, provided the registrant is a member. These data are currently
under review and may ultimately affect the Agency's conclusions on
diflubenzuron drift.
c. Water Resources
(1) Ground Water
Diflubenzuron exceeded the Ground Water Leaching Criteria for Field
dissipation half-life, Hydrolysis half-life and Henry's Law Constant. Exceeding
only these three criteria is not sufficient reason to trigger concerns based on -
chemical and physical properties. Diflubenzuron also does not exceed the
proposed triggers for classification as a candidate for restricted use based on <
ground water concerns. Diflubenzuron did not exceed any Ground Water
Levels Of Concern (LOCs). No detections of diflubenzuron have been
reported in EPA's Pesticides in Ground Water Data Base and no incidents were
found in OPP's Ecological Incident Information System.
Potential diflubenzuron contamination of ground water using the Patriot
model on sandy citrus soils in Highlands County, Florida was simulated as an
example of a highly vulnerable use area located in the Central Ridge of Florida.
While twelve sandy Highland County soils with orange production were
modeled, only one scenario resulted in any mass leaching to ground water. The
model predicted the mass leached to the top of a water table to be 0.025%
kg/HA of applied diflubenzuron. This is not considered significant.
P-chlorophenyl urea (CPU) and p-chloroaniline (PCA) are
toxicologically significant degradates of diflubenzuron. Since PCA is
carcinogenic, metabolites that are chemically related to PCA should be
evaluated as PCA unless there is evidence that they are not carcinogenic.
In the bare ground plot studies, the volume of water (rainfall plus
irrigation) in the Louisiana and Arizona plots may have caused CPU to fall
below the detection limits in the 6-30 inch soil depth segments. To better
understand the environmental fate of CPU, adsorption/desorption data on CPU
and bare ground field dissipation data from a typical use area(s) further north
with less rainfall and irrigation are needed. These data should provide a better
understanding of the mobility and persistence of CPU in the environment to
determine its potential as a ground water contaminant.
61
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(2) Surface Water
F ?
Substantial amounts of diftubenzuron could be available for runoff to
surface waters for several days to weeks post-application (half lives of 2 days
to 2 weeks for aerobic soil metabolism, 2-14 days for anaerobic soil
metabolism and 5.8, 13, 68, and 78 days for terrestrial field dissipation). The
intermediate to high soil/water partitioning of diflubenzuron (Kds of 20, 25, 40,
40, 120, 130 and a 150, SCS/ARS database Koc of 9000) indicates that
diflubenzuron runoff will often be primarily via adsorption to eroding soil. In
cases where the runoff volume is much greater than the sediment yield, runoff
via dissolution in runoff water could also contribute significantly to the total
pesticide runoff. ,
Diflubenzuron is not susceptible to direct aqueous photolysis, to abiotic
hydrolysis at pH 5 or 7, or to volatilization from water (estimated Henry's Law
constant = 1.8 X 10'9 atm*m3/mol). It has only moderate susceptibility to
abiotic hydrolysis at pH 9 (half-life of 32 days). The stability of diflubenzuron
to abiotic processes (except at highly alkaline pHs) and low volatility indicate
that the dissipation of diflubenzuron in aquatic systems will depend primarily
upon biodegradation and non-volatile transport. -
The susceptibility of diflubenzuron to biodegradation under both
aerobic and anaerobic conditions varies substantially as evidenced by a
variance in terrestrial laboratory and field half-lives of 2 to 78 days. Similar
variations may occur in the rates of biodegradation in aquatic systems possibly
with significant differences in biodegradation rates in terrestrial and aquatic
systems. Consequently, the persistence of diflubenzuron in aquatic systems
witivlong hydrological residence times is uncertain and may vary substantially,
ranging from low to intermediate. The persistence of diflubenzuron in aquatic
systems with shorter hydrological residence times should be lower due to
removal of diflubenzuron dissolved and adsorbed to suspended sediment
However, the intermediate to high soil/water partition coefficient indicates that
much of the diflubenzuron in aquatic systems will be adsorbed to bottom
sediment.
The two major degradates of diflubenzuron are 4-chlorophenyl urea in
soil under both aerobic and anaerobic conditions and 2,6-difluorobenzoic acid
under anaerobic conditions. There are not enough data to adequately assess the
fate and mobility of those degradates.
62
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3. * Ecological Exposure and Risk Characterization
Levels of Concern (LOCs) are used to measure potential risk to nontarget
organisms. There are two general'categories of LOCs (acute and chronic) for each of
the four non-target faunal groups and one category (acute) for each of two non-target
floral groups. To determine if an LOG has been exceeded, a risk quotient (RQ) is
derived and compared to the LOC. A risk quotient is calculated by dividing an
appropriate exposure estimate, such as the estimated environmental concentration
(EEC), by an appropriate toxicity test effect level.
Typical acute effect levels include the EC25 for terrestrial plants, the ECSO for
aquatic plants and invertebrates, the LCSO for fish and birds, and the LD50 for birds and
mammals. Typical chronic test results include the no observed effect level (NOEL),
sometimes referred to as the no observed effect concentration (NOEC) for avian and
mammalian reproduction studies; and either the NOEL or the maximum allowable
toxicant concentration (MATC) for chronic aquatic studies. The MATC is the
geometric mean of the NOEL and the lowest observable effect level (LOEL),
sometimes referred to as the lowest observable effect concentration (LOEC).
When the risk quotient exceeds the LOC for a particular category, potential risk
to that category is assumed. Risk presumptions and the corresponding LOCs are
shown below.
Levels of Concern (LOC) and Associated Risk Presumption
Mammals and Birds
IF THE
acute RQ >
acute RQ >
acute RQ >
chronic RQ >
LOC PRESUMPTION
0.5 High acute risk
0.2 Risk that may be mitigated through restricted use
0.1 Endangered species may be acutely affected
1 Chronic risk
Endangered species may be chronically affected
63
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Fish and Aquatic invertebrates
IF THE LOG PRESUMPTION
acute RQ> 0.5
acute RQ> 0.1
acute RQ> 0.05
chronic RQ > 1
High acute risk
Risk that may be mitigated through restricted use
Endangered species may be acutely affected
Chronic risk
Endangered species may be chronically affected
For this assessment, the diflubenzuron uses are categorized into three groups
based on the application rate and use characteristics. The non-bearing citrus group
includes non-bearing citrus trees, walnuts and cherries; the cotton group includes
cotton, soybeans, pastures, ornamental1 herbaceous plants [chrysanthemums], and wide
area and general indoor/outdoor treatments; while the forestry group includes forest
trees and plantings, Christmas tree plantations, pine, ornamentals, sewage systems,
bogs, swamps, standing water, rights of way, and household or domestic dwellings.
The assessment used application rates of 0.125 Ib ai/A for the forestry and cotton
groups, 0.312 Ib ai/a for bearing citrus trees, and 0.666 Ib ai/A for non-bearing citrus
group.
a. Exposure and Risk to Nontarget Terrestrial Animals
(1) Birds
Residues found on dietary food items following diflubenzuron application may
be compared to LC50 values to predict hazard. The maximum residues of
diflubenzuron on avian food items would not be expected to exceed 160 ppm (0.67 Ib
ai/a on short grass). Using this exposure and an avian LC50 of 4640 ppm yields an
acute RQ of 0.03 and a chronic RQ of 0.32, neither of which exceeds the LOG for risk
to birds. Since the maximum application rate did not indicate a risk to birds or
endangered bird species, the lower application rates are expected to present minimal
risk. .
(2) Mammals
Small mammal exposure is addressed using acute oral LD50 values converted, to
estimate a LC50 value for dietary exposure. The estimated LCSO is derived using the
following formula:
LCSO = LD;p x body weight (g)
food consumed per day (g) -
64
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The estimated LCSO values are shown in the following table.
/ - ' " '"'
Small Mammal Food Consumption (ppm) . ' '
(Based on an LD5fr— ntg/kg)A ' ', - ,
Small Mammal
Meadow vole
Adult field mouse
Least shrew
Body Weight (g)
46
13
5
% Weight
Eaten Daily
61
16
110
Food Consumed .
per day (g)
•28.1
.2.1
5.5
Estimated LC50
per day (ppm)
8185
30952
4545
Based on information contained inPrinciples of Mammologvbv D. E. Davis and F. Golly, published by Reinhold
Corporation, 1963.
Using application rates ranging from 0.125 to 0.67 Ib ai/A, the risk assessment
estimated that the maximum residues on mammal food items is 160 ppm (0.67 Ib ai/a
on short grass). Using this maximum exposure and an estimated mammal LC50 of
4545, the assessment yields an acute RQ of 0.04, which does not exceed the LQC for
risk to mammals. Since the maximum application rate did not indicate a risk to
mammals, including endangered species, the lower application rates are not expected
to result in acute risk to endangered or non-endangered mammals.
b. Exposure and Risk to Nontarget Aquatic Animals
Expected Aquatic Concentrations
There are jno available monitoring data concerning the concentrations of
difiubenzuron in surface water, however, refined EECs were calculated for the citrus
and cotton usage groups. Computer modeling was used to generate Tier 2 (single site
over multiple years) EECs for difiubenzuron in a 1 hectare (ha) surface area, 2 meters
deep pond draining a 10 ha citrus grove and a 10 ha cotton field.
Adamsville Sand in Florida was modelled for citrus and a Loring Silt Loam in
Mississippi for cotton. Each was simulated over 36 years. The model simulated one
application/year at 0.667 Ibs ai/acre for citrus, with an assumed air blast drift of 3%,
and 6 applications/year each at 0.063 Ibs ai/acre for cotton, with an assumed aerial
spray drift of 5%. Distributions of annual maximum initial, 96 hour, 21 day, 60 day,
and 90 day EECs over the 36 years for the citrus and cotton usage groups were
calculated. • .
The standard models do not apply to the forestry usage group. Water resources
in forests generally consist of streams and rivers. Habitats of this type typically
65
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contain cool and cold water fisheries. Such fisheries are almost wholly dependent on
invertebrate forage. Large scale impact on invertebrate resources may negatively
affect these fisheries resources. The direct application scenario is a high-exposure
scenario resulting in the high risk quotients calculated for the forestry usage group.
The EECs for the forestry usage group were calculated using a direct
application to water scenario. These estimates assume diflubenzuron is applied to a
one acre body of water 6" deep. The direct application to water scenario addresses the
concern that foliar treatments used in the forestry usage group may result in the
pesticide dripping down onto waterbodies below the trees. It also addresses the
concern of direct spray onto waterbodies in forests. The direct application scenario
lead to high risk quotients which were calculated for the forestry usage group.
The use rates and application methods for cotton are similar to several other
uses of diflubenzuron, such as soybeans and ornamentals. The forestry usage group is
representative of the mosquito use (direct application to water). The use on
mushrooms is considered to be an indoor use. The only ecological concern with the
use on mushrooms would be that of an accidental discharge. ''
The following table shows the estimated EECs for the citrus, cotton and
forestry usage groups.
'<•,-. / s-> f / f • s f f •• "•*• f '''' % s "•' " \ f s
" ' ~ '? ' E^»aiedE»^wam«JttMe(»c<»irafi&M®p;ECs)
' Usage
, Group
Non-bearing
Citrus*
Cotton and
Bearing
Citrus*
Forestry
Application
Method
ground or
aerial
ground or
aerial
'Directly to
Water
Application
, Rate
(Ibs a.i./A)
0.67
0.38 (6 @
0.06)
0.02
0.03
0.06
0.13
Initial
EEC
(ppb)
8.1
4.3
4-day
EEC
(PPb)
5:8
3.4
21-day
EEC
(PPb)
2.3 •
1.9
60-day
EEC
(PPb)
1.1
1.1
90-day
EEC
(ppb)
0.74
0.87
EEC from Direct Application to Water
11.7
22.8
46.2
91.8
Use on citrus at 0.666 Ib ai/A was modeled because it represents the maximum application rate for diflubenzuron.
More typically, diflubenzuron is applied to bearing citrus at 0.3125 Ib ai/A. EECs from this lower rate would
probably be lower and may be closer to those estimated from the cotton use. The cotton EECs will therefore be used
to represent exposure and risk to aquatic organisms from treating bearing citrus.
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(1) Freshwater Fish
The RQs for freshwater fish were calculated using the results from the most
sensitive species and the above EECs. They are shown in the following table.
Risk Quotients
-------
(2) Freshwater Invertebrates
The RQs for freshwater invertebrates were calculated using the toxicity results
from the most sensitive species and the above EECs. They.are shown in the following
table. :
-, Bisk Quotients 38
>31
> 196
>379
>771
> 1529
The application rate for bearing citrus is slightly lower than that for cotton, however, the resulting
, exposure is expected to be similar enough to estimate risk.
Diflubenzuron exceeds all LOCs based on risk quotients using the acute LC50
and chronic NQELs for the most sensitive freshwater invertebrate species tested
(Citrus, Cotton, Forestry usage groups). Use of difiubenzuron is expected to cause
adverse acute and chronic effects to non-endangered and endangered freshwater
invertebrates.
\ •
Twelve freshwater invertebrate field studies were reviewed and all
demonstrated similar effects attributed to diflubenzuron when directly applied to an
aquatic environment: Generally, aquatic invertebrate fauna (especially cladocerans)
were markedly reduced with some recovery noted. The freshwater field studies were
performed with the formulated product of diflubenzuron (25% and 1% a.i.). Acute
and chronic laboratory studies, performed with the technical grade of diflubenzuron,
also indicate that diflubenzuron is very highly toxic to freshwater invertebrates.
From these data it can be concluded that these uses of diflubenzuron may.
negatively affect the freshwater invertebrate populations. If there is a decrease In the
various invertebrates this may cause adverse effects on the populations of higher
organisms that feed on them. Higher organisms would be gamefish, waterfowl,
shorebirds, small mammals, reptiles, and amphibians. ,
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(3) Estuarine and Marine Animals
The RQs for estuarine/marine animals were calculated using the most sensitive
species and the above aquatic EECs. They are shown in the following table.
Risk <5uoticnts(RQ> for Estuarine aod Marine Organisms - , , _ \ •
Usage Group / Application Rate
Non-bearing Citrus/
0.67 Ib ai/A
Cotton/0.38 Ib ai/A and
Bearing Citrus/0.31 Ib ai/A""
Forestry 0.02 Ib ai/A
Forestry 0.03 Ib ai/A
Forestry 0.06 Ib ai/A
Forestry 0.13 Ib ai/A
Species
M. bahia
M. mercenaria
F. heteroclitus
M. bahia
M. mercenaria
F. heteroclitus
M. bahia
M. mercenaria
F. heteroclitus
M. bahia
M. mercenaria
F. heteroclitus
M. bahia
M. mercenaria
F. heteroclitus
M. bahia
M. mercenaria
F. heteroclitus
Acute RQ
(96-hr)
4
<0.05
< 0.05"
2
<0.05
< 0.05"
6
<0.05
< 0.05"
12
<0.05
<0.05"
23
0.14
< 0.05"
47
0.29
< 0.05"
Chronic RQ
(21-day)'
51
N/A
<1
41
N/A .
<1
261
N/A
<1
506
N/A
<1 .
1028
N/A
< 1
2039
N/A
2
21-day EEC used for the invertebrate chronic RQ and 90-day EEC for the fish chronic RQ
Acute risk quotient is based on an acute study endpoint with a 25% formulation on F. heteroclitus.
The application rate for bearing citrus is slightly lower than that for cotton, however, the resulting
exposure is expected to be similar enough to estimate risk.
Diflubenzuron exceeds all LOCs based on RQs using the acute LC50s and
chronic NOELs for the most sensitive estuarine/marine invertebrate species tested for
the citrus, cotton, and forestry usage groups. Therefore use of diflubenzuron may
69
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cause adverse acute and chronic effects to marine/estuarine invertebrates. Endangered
marine/estuarine invertebrate species may be affected acutely and chronically.
Diflubenzuron exceeds restricted use LOCs based on RQs using the acute
estuarine/marine mollusk LC50s, for 0.06 Ibs ai/A and 0.13 Ib ai/A application rates, for
forest trees and forest plantings uses. Endangered species acute LOCs were exceeded
at rates as low as 0.03 Ib ai/A for the forestry use.
Diflubenzuron exceeds chronic LOCs based on RQs using the chronic NOEL
for the most sensitive marine/estuarine fmfish species tested for the forestry usage
group at the 0.13 Ib ai/A application rate. Therefore use of diflubenzuron may
adversely affect endangered and non-endangered marine/estuarine fmfish from chronic
exposures at the highest use ra;te for the forestry usage group.
The quotients to estimate risk to shrimp from runoff (cotton and citrus) exceed
the LOG by sizeable margins lending higher certainty that effects will occur.
However, of special note is the magnitude of the risk quotients if diflubenzuron is
directly applied to shallow estuarine habitats. The frequency of this occurring is
unknown, so the ecological significance of these numbers is uncertain. However, if
direct application does occur, there is a strong probability that diflubenzuron will
significantly impact estuarine/marine invertebrate populations.
Further support for this conclusion is based on three marine/estuarine
invertebrate field studies that were reviewed^ Two demonstrated similar effects
attributed to diflubenzuron when directly applied to an aquatic environment.
Generally, aquatic invertebrate fauna were markedly reduced. The third
marine/estuarine field study showed no effects. The marine/estuarine field studies
were performed with the formulated product of diflubenzuron (25% a.i.). Acute and
chronic laboratory studies, performed with the technical grade of diflubenzuron, also
indicate that diflubenzuron is very highly toxic to marine/estuarine invertebrates.
If there is a decrease in the various invertebrates this may cause adverse effects
on the populations of higher organisms that feed on them. Some of these organisms
would be crabs, bivalves, yarious crustaceans (e.g. shrimp), water fowl, shore birds,
and gamefish. Commercially important marine/estuarine invertebrates and finfish may
be affected.
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c. Exposure and Risk to Nontarget Plants
(1) Terrestrial and Semi-aquatic
Because terrestrial and semi-aquatic plant toxicity data are not available,
terrestrial and semi-aquatic plant risk assessments cannot be performed at this time for
diflubenzuron.
(2) Aquatic
Exposure to non-target aquatic plants may occur through either runoff or drift
from aerial application.
Expected Aquatic Concentrations: The EECs calculated above for aquatic animal
exposure are also used for aquatic plants. The only available toxicity data for aquatic
plants is the ECSO for Selenastrum capricornutum (0.20 mg/L). This value was used to
calculate the following risk quotients.
RQ and EEC* Values for Aquatic Plant Species '* ~ ,:
Usage Group
Non-bearing Citrus
Cotton and Bearing Citrus
, at0.31251bai/A"
Forestry
Maximum
Application Rate
0&ai/A.>
0.67
0.38
0.02
0.03
0.06
0.13
Type of Plant
vascular (Lemna)
Algae or diatom
vascular (Lemna)
Algae or diatom
vascular (Lemna)
Algae or diatom
vascular (Lemna)
Algae or diatom
vascular (Lemna)
Algae or diatom
vascular (Lemna)
Algae or diatom
EEC
, (Pl*>
'N/A
8
N/A
4
N/A
12
N/A
23
N/A
46
.N/A
92
Risk Quotient
(EEC/EC50)
N/A •
0.04
N/A
0.02
N/A
0.06
N/A
0.11
N/A
0.23
N/A
0.46
EEC's based on direct application to water for the forest trees and forest plantings uses.
The application rate for bearing citrus is slightly lower than that for cotton, however, the resulting exposure is
expected to be similar enough to estimate risk.
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Diflubenzuron does not exceed LOCs based on RQs using the acute LC50 for
the freshwater alga species tested for the citrus, cotton, and forestry usage groups.
d. Endangered Species
Acute and chronic LOCs for endangered species are exceeded for freshwater
and estuarine/marine aquatic invertebrates for the citrus, cotton arid forestry usage
groups. A chronic LOG was exceeded for estuarine/marine fish for the highest
' forestry use rate (0.13 Ib ai/A). The acute LOG for estuarine/marine mollusks was
exceeded for the three highest forestry use rates.
,-'.'/
IV. MSK MANAGEMENT AND JREREGISTRATION DECISION
A. Determination of Eligibility
, Section 4(g)(2)(A) of FEFRA 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 diflubenzuron
as an active ingredient. The Agency has completed its review of these generic data,
and has determined that the data are sufficient to support reregistration of all products
containing diflubenzuron. Appendix B identifies the generic data requirements that
the Agency reviewed as part of its determination of reregistration eligibility of
diflubenzuron, 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 diflubenzuron and to determine that diflubenzuron can be used,
with mitigation imposed by this document, without resulting in unreasonable adverse
effects to humans and the environment.. The Agency therefore finds that all products
containing diflubenzuron as an active ingredient are eligible for reregistration. The
reregistration of particular products is addressed and a list of additional data required
for the technical formulation is contained in Section V of this document.
The Agency made its reregistration eligibility determination based upon the
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 diflubenzuron 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 diflubenzuron, if new information
conies to the Agency's attention or if the data requirements for registration (or the
guidelines for generating such data) change. ,
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B. Determination of Eligibility Decision
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredient
diflubenzuron, the Agency has sufficient information on the health effects of
diflubenzuron and on its potential for causing adverse effects in fish and
wildlife and the environment. The Agency has determined that diflubenzuron
products, labeled and used as specified in this Reregistration Eligibility
Decision, will not pose unreasonable risks or adverse effects to humans or the
environment. Under the Food Quality Protection Act of 1996, the Agency has
determined that there is a reasonable certainly that no harm will result to infants
• and children from aggregate exposure to diflubenzuron. The total dietary
cancer risk for the published tolerances for the overall U.S. population is
approximately 1 x 10"6. Since there are no detections of diflubenzuron in
ground water, dietary risk from drinking water is expected to be negligible.
Based on very low residues detected in forestry dissipation studies, a low
dermal absorption rate, and extremely low dermal and inhalation toxicity,
occupational uses of diflubenzuron in residential locations, parks, or forests are
expected to result in insignificant risk to people in these areas. Therefore, the
Agency concludes that products containing diflubenzuron, once labels have
been amended to reflect the risk mitigation measures outlined in this RED, are
eligible for reregi strati on.
2. Eligible and Ineligible Uses
The Agency has determined that all uses of diflubenzuron are eligible
for reregistration under the conditions specified in this RED.
C. Regulatory Position
The following is a summary of the regulatory positions and rationales for
diflubenzuron. Where labeling revisions are imposed, specific language is set forth in
Section V of this document.
1. Food Quality Protection Act Findings
a. Determination of Safety for U.S. Population
EPA has determined that the established tolerances for diflubenzuron, with
amendments and changes as specified in this document, meet the safety standards •
under the FQPA amendments to section 408(b)(2)(D) for the general population. In
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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, as well as the possibility of cumulative effects from diflubenzuron and
other compounds that may have a similar mode/mechanism of toxicity.
Diflubenzuron is a restricted use pesticide and has no homeowner uses,
however, diflubenzuron does have occupational uses in residential areas. Based on
very low residues detected in forestry dissipation studies, a low dermal absorption rate,
and extremely low dermal and inhalation toxicity, occupational uses of diflubenzuron '
in residential locations, parks, or forests are expected to result in insignificant risk to
people in these areas. Additionally, residues/exposure to diflubenzuron in.drinking
water is not expected and therefore is not a concern (outstanding absorptiori/desorption
data are expected to confirm this conclusion), ,
Due to the low acute oral toxicity of diflubenzuron, the Agency has determined
that an acute dietary risk assessment is not required.
. - The chronic dietary risk assessment showed'that the percent of the RfD utilized
by dietary exposure to residues of diflubenzuron is less than 1% for the general U.S.
population. Additionally, the total cancer risk estimates for PC A and related
metabolites for the overall U.S. population is 1 X 10"6.
In the case of diflubenzuron, EPA has not yet determined whether or how to
include this chemical in a cumulative risk assessment. This reassessment
determination therefore does not take into account common mechanism issues. 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.
b. Determination of Safety for Infants and Children
EPA has,determined that,the established tolerances for diflubenzuron, with
amendments and changes as specified in this document, meet the safety standards
under the FQPA amendments to 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 diflubenzuron residues
in this population subgroup.
In determining whether or not infants and children are particularly susceptible
to toxic effects from diflubenzuron residues, EPA considered the completeness of the-
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database for developmental and reproductive effects, the nature and severity of the
effects observed, and other information.
Based on the current data requirements, difiubenzuron has a complete database
for developmental and reproductive toxicity. In the developmental studies no maternal
toxicity or toxicity to the developing fetus was observed. In the reproduction study, no
effects on reproductive performance were seen. Furthermore, no effects on
reproductive performance were observed at any dose level in FO or Fl males or
females in the 2-generation reproduction study in which parental toxicity
(methemoglobinemia, hemolytic anemia, destruction of erythrocytes and pathological
changes in the spleen and liver) was observed at all doses tested (i.e., a NOEL was not
established). Therefore, EPA concludes that it is unlikely that there is additional risk
concern for immature or developing organisms. Finally, the Agency has no
epidemiological information suggesting special sensitivity of infants and children to
difiubenzuron. Therefore, the Agency finds that the uncertainty factor (100X)
routinely used in RfD calculations is adequately protective of infants and children,
and an additional uncertainty factor is not warranted for difiubenzuron.
EPA estimates that difiubenzuron residues in the diet of non-nursing infants
(less than I year) account for less than 1% of the RfD and 1% of the RfD for children
aged 1-6 years. Furthermore, residues in drinking water are not expected. Therefore,
the Agency has determined that there is reasonable certainty that dietary exposure to
difiubenzuron will not cause harm to infants and children.
In deciding to continue to make reregistration 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 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.
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
consider itself free to pursue whatever action may be appropriate, including but not
limited to, reconsideration of any portion of this RED.
2.
Tolerance Reassessment
All tolerances for difiubenzuron residues are currently expressed in terms of
difiubenzuron per se [40 CFR §180.377(a) and (b) and §186.2000]. The Agency's
Metabolism Committee has concluded that the tolerance expression should be changed
to address combined residues of difiubenzuron and metabolites convertible to
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parachloroaniline (PCA), expressed as diflubenzuron. The following table
summarizes the tolerance reassessment and recommended modifications in commodity
definitions for diflubenzuron.
Tolerance Reassessment Sutamary for Biflobenzuron
Commodity
Current Tolerance
(ppm)
Tolerance
Reassessment (ppm)
Comment/Correct Commodity
Definition
, Tolerances listed under 40 CFR 180.377(a):
Cattle, fat
Cattle,mbyp
Cattle, meat
Cotton, seed
Eggs
Goats, fat
Goats, mbyp
Goats, meat
"Grapefruit
Hogs, fat
Hogs, mbyp
Hogs, meat
Horses, fat
Horses, mbyp
Horses, meat
.Milk
Mushrooms
Orange
Poultry, fat
Poultry, mbyp
Poultry, meat
Sheep, fat
Sheep, mbyp
Sheep, meat
Soybeans
Tangerine ,
Walnuts
0.05
0.2 '
0.05
0.05
0.5
• 0.05
0.05
0.05
0.2
0.5 '
0.05
0.05
0.05 " <
0:5
0.1
0.05
0.2
0.05
0.05
0.5
0.05
0.05
0.05
TBD7
0.5
- 0.05
0.05
0.05
0.5
0.1
Cotton, undelinted seed
-\
Data required
Soybean, seed
Tolerances listed under 40 CFR 180.377(b):
Grasses, pasture
Grasses, range
1 1.0
3.0
1.0 .
. 3.0
Grass, pasture, forage
Grass, rangeland
Feed Additive Tolerances listed under 40 CFR §186.2000:
Soybeans, hulls
0.5
0.5
To be determined. Reassessment of tolerance(s) cannot be made at this time. Additional data are
required..
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Tolerance Reassessment Summary for Biflabenzurau , ;
Commodity
Soybeans, soapstock
Current Tolerance
(ppm)
0.1
Tolerance
Reassessment (ppm)
Revoke
Comment/Correct Commodity
Definition
Soybean soapstock is no longer
a regulated commodity.
New Tolerances Required under 40 CFR §180.377(a):
Cotton, gin by-products
Soybeans, forage
Soybeans, hay
' None
None
None
TBD
TBD
TBD
... ,
Data are required.
Data are required. Feeding
restriction may be allowed.
Data are required. Feeding
restriction may be allowed.
New Tolerances Required under 40 CFR §180.377(b):
Grass, pasture, hay
None
TBD
Data are required.
Proposed Tolerances under 40 CFR §180.377(a):
Citrus oil
Citrus pulp, dried
None
None
75.0
liO
Petition pending (proposed
under 40 CFR § 185.2000).
Petition pending (proposed
under 40 CFR §186.2000)
Tolerances Listed Under 40 CFR S180.377(a):
Sufficient data are available to ascertain the adequacy of the established
tolerances listed for cottonseed, soybeans, oranges, grapefruit, tangerines, and walnuts,
provided that storage stability issues are adequately resolved. Additional magnitude of
the residue data are required for mushrooms before the tolerance can be reassessed.
Sufficient data are also available to ascertain the adequacy of the established
tolerances listed for milk, eggs, meat, meat byproducts, and fat from livestock. The
available data adequately support the 0.05 ppm tolerances for diflubenzuron residues
in milk, eggs, meat, fat, and meat byproducts.
Tolerances Listed Under 40 CFR S180.377ftA:
The tolerances listed in 40 CFR §180.377(b) are for a regional registration as
defined in 180.1(n) for residues of diflubenzuron per se in/on pasture and rangeland
grass forage. Sufficient data are available to ascertain the adequacy of these
established tolerances, provided that storage stability issues are adequately resolved.
A petition (PP #5E4499) seeking an increase in the tolerance for rangeland grass from
3.0 to 5.0 ppm has been rejected/
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Tolerances Listed Under 40 CFR S 186.2000:
Sufficient data are available to ascertain the adequacy of the established feed
additive tolerances listed for soybean hulls and soapstock. Since soybean soapstock is
no longer a registered commodity, this tolerance should be revoked. The soybean
hulls tolerance needs to be moved to 40 CFR'§180.377(a).
New Tolerances Required Under 40 GFR §180.377^:
Table II (June, 1994) indicates that data on cotton gin byproducts (cotton gin
trash) are required. A tolerance must be proposed for this commodity once adequate
data have been submitted and evaluated.
Proposed Tolerances Under 40 CFR S180-.377(a):
, \ .
A food additive tolerance (FAP#1H5301) is currently pending for residues of
diflubenzuron in citrus oil in conjunction with the tolerances for oranges and
grapefruit. Sufficient data are available to ascertain the adequacy of the proposed 75
ppm tolerance for residues of diflubenzuron in citrus oil and the Agency has
recommended that this tolerance be established (proposed under 40 CFR §185.2000).
Feed additive tolerances are currently pending for residues of diflubenzuron in
dried citrus pulp (FAP#5H5472). Sufficient data are available to ascertain the1
adequacy of the proposed 1 ppm tolerance for residues of diflubenzuron in dried citrus
pulp and the Agency has recommended that this tolerance be established (proposed
under 40 CFR §186.2000).
New Tolerances Required Under 40 CFR S180.377ft)V
Table TJ (June, 1994) indicates that data on grass hay are required. Tolerances
must be proposed for pasture grass hay once adequate data have been submitted and
evaluated.
Codex Harmonization .
Maximum residue limits (MRLs) have been established by Codex for various
commodities. Codex MRLs and the applicable U.S. tolerances are listed in the
following table.' Codex and U.S. tolerance definitions are presently equivalent as both
are expressed in terms of diflubenzuron/?er se, however, the Agency is recommending
that the U.S. tolerance expression be changed to "the combined residues of
diflubenzuron-and metabolites convertible to /?-chloroaniline, expressed as
diflubenzuron." The Agency is basing its risk assessment on the total toxic residues of
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diflubenzuron. Once this change is made Codex and U.S. tolerance definitions will no
longer be compatible.
','" 'tty&xM^ " '',>'",';
Commodity
Brussels sprouts
Cabbages, head
Citrus fruits '-
Cottonseed
Edible offal (Mammalian)
Eggs
Meat
Milks
Mushrooms
Plums (including prunes)
Poultry meat
Soybeans (dry)
Tomatoes
MKL
(mg/kg)
1
1
1
0.2
0.05
0.05
0.05
0.05
0.1
1
0.05
0.1
1
U.S. Tolerance
(ppm)
None
None
0.5
0.2
0.05
0.05
0.05
0.05
0.2
None
0.05
0.05
None
3. Summary of Risk Management Decisions
a. Human Health
(1) Dietary
Acute Dietary
The Agency has determined that a risk assessment for acute dietary risk
is not necessary, since one day single dose oral studies in rats and mice
indicated no toxic effects other than marginal effects on methemoglobin levels
at a dosage of 10,000 mg/kg of a 25% wettable powder formulation.
Chronic Dietary (including cancer)
The Agency has evaluated the chronic dietary risk associated with the
use of diflubenzuron based on established and proposed tolerance levels. The
RfD was established at 0.02 mg/kg/day based on a chronic toxicity (52-week)
study in dogs with a NOEL of 2.0 mg/kg/day. The LEL in the same study was
10 mg/kg/day based on methemoglobinemia and sulfhemoglobinemia. The
chronic exposure analysis results in an ARC that is less than 1% of the RfD for
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the overall U.S. population. Children, aged 1 to 6 years, comprise the
subpopulation with the greatest exposure levels at 1% of the RfD. The Agency
considers exposures of 100% or less of the RfD to be adequately protective.
The Agency also conducted a risk assessment to determine the dietary
risk from the diflubenzuron metabolites PCA and CPU, The total cancer risk
estimates for PCA and related metabolites for the overall U.S. population does
not exceed the Agency's risk level of concern.
(2) Worker (Mixer/Loader/Applicator)
Short-Term and Intermediate Term
The Agency has determined that there is a potential dermal exposure to
pesticide handlers. The risk assessment for short term exposure is based on a
NOEL of 40 mg/kg/day indicated by the 14-day subehronic oral study in mice
that displayed a toxicology endpoint of sulfhemoglobinemia. The MOEs for
short term occupational exposure MOEs are acceptable (greater than 100) for
handlers wearing long-sleeved shirts, long pants and chemical- resistant gloves.
The risk assessment for intermediate term exposure is based on a NOEL
of 2«ig/kg/day from a 13-week subehronic feeding study in dogs with a
toxicology endpoint of methemoglobinemia. The MOEs for intermediate term
occupational exposure MOEs range from 26 to greater than 1000. These
calculations, based on current label information, exceed the Agency's level of
concern for 3 of the 34 scenarios. The risk for the unacceptable scenarios will
be mitigated by requiring dust/mist respirators (TC-21C) for all mixers, loaders
and applicators.
Regarding potential carcinogenic risks to humans resulting from dermal
and/or inhalation exposures to PCA and/or CPU occurring during occupational
or residential exposures to diflubenzuron, it has been determined that these
risks are likely to be negligible since exposure to these metabolites is not
anticipated. Only in the event that direct exposure to one or more of these
metabolites of diflubenzuron is demonstrated would it be necessary to perform
such risk assessments.
(3) Bystander
- Due to very low residues detected in forestry dissipation studies,
bystander exposure to people in residential locations or forests treated with
diflubenzuron is unlikely, outside of contact with direct sprays. In addition, ,
since the dermal absorption rate is low, and exposure is expected to be of a
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short-term duration, risk to bystanders during wide-area general outdoor
treatments is expected to be minimal.
Although there are no data available to estimate swimmer exposure in
treated waters; it appears that sites treated with diflubenzuron would not be
used for swimming. Based on the toxicologic concerns for diflubenzuron, a
swimmer restriction is required for any current labels having use directions for
treating aquatic sites.
b. Environmental
(1) Avian .
The Agency has evaluated data to determine the acute and chronic
effects of diflubenzuron to birds. The risk quotients for all uses were less than
0.5, the LOG for presuming adverse effects to avian species. The Agency
concludes that there will be no adverse effects to birds resulting from the use of
diflubenzuron. ,
(2) Mammals
The Agency has evaluated data to determine the acute and chronic
effects of diflubenzuron to mammals. The risk quotients are all less than 0.5,
the LOG for presuming adverse effects to mammalian species. Therefore, the
Agency concludes that there will be no adverse effects to mammals resulting
from the use of diflubenzuron.
(3) Insects
Based on acute honey bee studies, diflubenzuron is practically non-toxic
to honey bees. Therefore, honey bees are not likely to be. adversely affected by
the use of diflubenzuron.
(4) Freshwater Fish
. The Agency has evaluated data to determine the acute and chronic
effects of diflubenzuron to freshwater fish. The risk quotients were all less than
0.1, the LOG for presuming adverse effects to endangered freshwater fish. The
Agency concludes that there will be no adverse effects to freshwater fish
resulting from the use of diflubenzuron.
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(5) Aquatic Invertebrates
The Agency has evaluated data to determine the acute and chronic
effects of diflubenzuron to aquatic invertebrates. The risk quotients range from
1 to greater than 1,500, exceeding all LOCs. Based on this assessment, the
Agency concludes that the use of diflubenzuron is expected to cause adverse
acute-and chronic effects to non-endangered and endangered freshwater
invertebrates. If there is a decrease in the various invertebrates this may cause
adverse effects on the populations of higher organisms that feed on them.
Higher organisms would be gamefish, waterfowl, shorebirds, small mammals,
reptiles, and amphibians.
Diflubenzuron is currently a Restricted Use pesticide due to its toxicity
to aquatic invertebrates. After reviewing the data submitted to support
reregistration, the Agency has determined that this classification is appropriate
and that diflubenzuron should remain a Restricted Use pesticide.
To provide additional protection for aquatic invertebrates, the Agency
and the registrant have agreed to the following risk mitigation measures:
• row crops and orchard uses must include a 150 foot buffer zone
for aerial applications and a 25 foot vegetative buffer strip to
decrease runoff in all cases. This buffer strip will also serve as a
buffer zone for spray drift from ground applications.
• aerial applications must include the most current spray drift
language (see description under Section V)
• all products must bear a hazards statement warning about
possible adverse effects to aquatic organisms
(6) Estuarine and Marine Fish
The aquatic EEC from direct application of diflubenzuron to 6 inches of
water, as would be expected from the forestry use, at the highest use rates
(0.125 Ib a.i./acre) exceeds the estuarine fish NOEL (50 ppb). This indicates
the possibility of chronic risk to estuarine fish from this use. Since this
application rate is not used on a widespread basis, the Agency believes that no
additional risk mitigation is necessary.
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(7) Estuarine and Marine Invertebrates
Diflubenzuron exceeds all LOCs based on RQs using the acute LCSOs
and chronic NOELs for the most sensitive estuarine/marine invertebrate species
tested. Although this analysis indicates that estuarine/marine animal
populations may be adversely effected by the use of diflubenzurbn, the Agency
believes that the risk mitigation measures discussed above will help to reduce
this risk.
(8) Non-target Plants
Although there is no acceptable data for plants, a supplemental study
indicates that diflubenzuron does not exceed LOCs based on RQs using the
LCSO for the freshwater alga species tested. Therefore, the Agency does not
expect any adverse effects to non-target plants resulting from the use of
diflubenzuron.
(9) Endangered Species
The Agency has concerns about the exposure of threatened and
endangered aquatic invertebrate species to diflubenzuron, as discussed above in
the science assessment chapter. Endangered species LOCs have been exceeded
for both acute and chronic effects for freshwater and estuarine/marine aquatic
invertebrates. The risk mitigation measures specified above will reduce
exposure and risk to threatened and endangered species.
(10) Surface Water
The Agency has1 determined that substantial amounts of diflubenzuron
could be available for runoff to surface waters for several days to weeks post-
application. This runoff is expected to be primarily via adsorption to eroding
soil. Only in cases where the runoff volume is much greater than the sediment
yield would dissolution in runoff water contribute significantly to the total
pesticide runoff. Since much of the diflubenzuron in aquatic systems will be
adsorbed to bottom sediment, the Agency does not expect diflubenzuron to
contaminate surface waters.
(11) Ground Water
Diflubenzuron does not exceed any groundwater LOCs and no
diflubenzuron detections have been reported in EPA's Pesticides in Ground
Water Database. Although there are no indications that diflubenzuron per se is
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a concern to groundwater, the Agency is requiring additional data to better
understand the mobility and persistence of CPU in the environment.
• • • i ' . '
4. Occupational Labeling Rationale
i '
Any product whose labeling reasonably permits use in the production of
an agricultural plant on any farm, forest, nursery, or greenhouse must comply
with the labeling requirements of PR Notice 93-7, "Labeling Revisions
Required by the Worker Protection Standard (WPS), and PR Notice 93-11,
"Supplemental Guidance for PR Notice 93-7, which reflect the requirements of
EPA1 s labeling regulations for worker protection statements (40 CFR part 156,
subpart K). These labeling revisions are necessary to implement the Worker
Protection Standard for Agricultural Pesticides (40 CFR part 170) and must be
completed in accordance with, and within the deadlines specified in, PR
Notices 93-7 and 93-11. Unless otherwise specifically directed in this RED, all
statements required by PR Notices 93-7 and 93-11 are to be on the product
label exactly as instructed in those notices.
After April 21, 1994, except as otherwise provided in PR Notices 93-7
and 93-11, all products within the scope of those notices must bear WPS PR
Notice complying labeling when they are distributed or sold by the primary
registrant or any supplementally registered distributor.
After October 23, 1995, except as otherwise provided in PR Notices
93-7 and 93-11, all products within the scope of those notices must bear WPS
PR Notice complying labeling when they are distributed or sold by any person.
Some of the registered uses of diflubenzuron are within the scope of the
Worker Protection Standard and some uses are outside the scope of the WPS.
Those uses that are outside the scope of the WPS including the following:
• mosquito abatement, gypsy moth control, or similar goverament-
sponsored'wide-area public pest control programs;
• on livestock or other animals;
• aquatic sites for mosquito control;
• plants that are in ornamental gardens, parks, golf courses, and
public or private lawns and grounds and that are intended, only
for decorative or environmental benefit; and
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• those uses not directly related to the production of agricultural
plants, including, for example, control of vegetation along rights-
of-way, in hedgerows and fencerows and in other non-crop
areas.
The labels and labeling of all products must comply with EP A's current
regulations and requirements as specified in 40 GFR §156.10 and other
applicable notices.
Occupational-Use-Products fWPS and Non-WPS Usesl
The PPE requirements will pertain to both the WPS and non-WPS uses,
since the potential exposure to occupational handlers is similar for all uses.
For each occupational end-use product, PPE requirements for pesticide
handlers will be set during reregistration in one of two ways:
1. If EPA has no special concerns about the acute or other adverse effects
of an active ingredient, the PPE for pesticide handlers will be based on
the acute toxicity of the end-use product. For occupational-use
products, PPE will be established using the process described in PR
Notice 93-7 or more recent EPA guidelines.
2. If EPA has special concerns about an active ingredient due to very high
acute toxicity or to certain other adverse effects, such as allergic effects
or delayed effects (cancer, developmental toxicity, reproductive effects,
etc), then EPA may establish minimum or baseline handler PPE
requirements that pertain to all or most occupational end-use products
containing that active ingredient. EPA will then compare the minimum
PPE requirements with the PPE designated on the basis of the acute
toxicity of each end-use product.
Personal protective equipment requirements usually are set by
specifying one or more pre-established PPE units — sets of items that are
almost always required together. For example, if chemical-resistant gloves are
required, then long-sleeve shirts, long pants, socks and shoes are assumed and
are also included in the required minimum attire. If the requirement is for two
layers of body protection (coveralls over a long- or short-sleeve shirt and long
or short pants), the minimum must also include (for all handlers) chemical-
resistant footwear and chemical-resistant headgear for overhead exposures and
(for mixers, loaders and persons cleaning equipment) chemical-resistant
aprons.
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AH Formulations
The data EPA used to assess the handler risks resulting from exposures
to diflubenzuron were based on exposure scenarios where mixers/loaders
supporting ground and aerial applications and mixer/loader/applicators using
hand-held application equipment wore chemical-resistant gloves in addition to
long-sleeve shirts, long pants, shoes and socks. Therefore, chemical-resistant,
gloves are required for all such handlers for all formulations, except oral bolus
pellet or tablet formulations.
Oral bolus Pellet or Tablet Formulations
There are no special risk concerns that warrant the establishment of
active-ingredient-based minimum (baseline) PPE for handlers of oral bolus
formulations because the use of balling guns to administer the pesticide is
expected to limit applicator exposure.
Wettable Powder Formulations
There are no special risk concerns for handlers based on their potential
for short-term exposure to wettable powders. The MOEs for short-term
exposures were calculated as being acceptable for mixers, loaders, flaggers and
applicators of such formulations.
For intermediate-term exposure, EPA has determined that regulatory
action must be taken for mixers and loaders. The MOEs for mixer/loaders
supporting aerial agricultural/horticultural and wide-area tree insect
applications are not acceptable unless dust/mist filtering respirators (and
' chemical-resistant gloves) are worn. As a prudent risk-reduction measure, the
Agency is requiring dust/mist filtering respirators (and chemical-resistant
gloves) for all mixers and loaders handling wettable powder,formulations to
support aerial applications. For mixer/loaders supporting ground applications,
tree insect uses, chemical-resistant gloves plus long-sleeved shirts and long
pants will provide acceptable MOEs.
Liquid/Flowable Formulations
For the liquid/fiowable formulations, EPA has determined that no
regulatory action must be taken for handlers based on their potential for short-
term or intermediate-term exposure. The MOEs for short-term arid
intermediate-term exposures were calculated as being acceptable for mixers,
loaders, flaggers and applicators of such formulations.
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Homeowner-Use Products
There are at this time no known formulations of diflubenzuron intended
for home use.
Post-Application/Entry Restrictions
Occupational-Use Products (WPS Uses)
Restricted-Entry Interval: Under the Worker Protection Standard (WPS),
interim restricted entry intervals (REI) for all uses within the scope of the WPS
are established on the basis of the acute toxicity of the active ingredient. The
toxicity categories of the active ingredient for acute dermal toxicity, eye
irritation potential, and skin irritation potential are used to determine the interim
WPS REI. If one or more of the three acute toxicity effects are in toxicity ,
category I, the interim WPS REI is established at 48 hours. If none of the acute
toxicity effects are in category I, but one or more of the three is classified as
category n, the interim WPS REI is established at 24 hours. If none of the
three acute toxicity effects are in category I or n, the interim WPS RED is
established at 12 hours. A 48 hour REI is increased to 72 hours when an
organophosphate pesticide is applied outdoors in arid areas. In addition, the
WPS specifically retains two types of REIs established by the Agency prior to
the promulgation of the WPS: product-specific REIs established on the basis of
adequate data and interim REIs that are longer than those that would be
established under the WPS.
For occupational end-use products containing diflubenzuron as an
active ingredient, EPA is retaining the interim 12-hour restricted-entry interval
for each use of the product that is within the scope of the Worker Protection
Standard (WPS). The basis for this recommendation is that diflubenzuron has
a low dermal absorption rate, however, diflubenzuron also has a toxipological
endpoint of concern for systemic toxicity for intermediate-term exposure that
impacts several post-application scenarios. These post-application scenarios
(such as citrus and chrysanthemum harvest) have the potential for higher
exposure than some of the handler scenarios identified in this RED. This
interim REI shall be in effect until specific reentry data are submitted and
reviewed. EPA notes that the WPS places very specific restrictions on entry
during restricted-entry intervals when that entry involves contact with treated
surfaces. EPA believes that existing WPS protection is sufficient to mitigate
post-application exposures of workers who contact surfaces treated with
diflubenzuron.
87
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The WPS interim REI in effect until now was 12 hours (based on acute
dermal Toxicity Category III). The WPS interim REI was established through
labeling modifications specified in PR Notice 93-7, which implemented the
labeling requirements of the 1992 Worker Protection Standard.
Early-Entry PPE: The WPS establishes very specific restrictions on entry by
workers to areas that remain under a restricted-entry by workers if the entry
involves contact with treated surfaces. Among those restrictions are a
prohibition of routine entry to perform hand labor tasks and requirement that
personal protective equipment be worn. Personal protective equipment
requirements for persons who must enter areas that remain under a restricted-
entry interval are based on the toxicity concerns about the active ingredient.
The requirements are set in one of two ways.
1. If the Agency has no special concerns about the acute or other adverse
effects of an active ingredient, it establishes the early-entry PPE requirements
based on the acute dermal toxicity, skin irritation potential, and eye irritation
potential of the active ingredient.
2. If the Agency has special concerns about an active ingredient due to very
high acute toxicity or to certain other adverse effects, such as allergic effects,
cancer, developmental toxicity, or reproductive effects, it may establish early-
entry PPE requirements that are more stringent than would be established
otherwise.
There are special risk concerns about the wettable powder arid
liquid/flowable formulations, since diflubenzuron has a toxicological endpoint
of concern for systemic toxicity and low MOEs for some handlers. In addition,
there are no data to evaluate the post-application risk to this chemical. Due to
diflubenzuron's low dermal absorption rate EPA is not establishing PPE for
dermal protection that is more stringent than the PPE that would otherwise be
established based on the acute toxicity of the active ingredient. Since
diflubenzuron is classified as category in for eye irritation potential, protective
eyewear is not required.
Occupational-Use Products (Non-WPS Uses)
The Agency is establishing entry restrictions for all non-WPS
occupational uses of diflubenzuron end-use products; For specific language,
refer to Section V of this document.
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5. Endangered Species Statement
Currently, the Agency is developing a program ("The Endangered
Species Protection Program") to identify all pesticides whose use may cause
adverse impacts on endangered and threatened species.and to implement
mitigation measures that will eliminate the adverse impacts. The program
would require use modifications or a generic product label statement, requiring
users to consult county-specific bulletins. These bulletins would provide
information about specific use restrictions to protect endangered and threatened
species in the county. Consultations with the Fish and Wildlife Service will be
necessary to assess risks to newly listed species or from proposed new uses.
The Agency plans to publish a description of the Endangered Species
Program in the Federal Register in the future. Because the Agency is taking
this approach for protecting endangered and threatened species, it is not
imposing label modifications at this time through the RED. Rather, any
requirements for product use modifications will occur in the future under the
Endangered Species Protection Program.
V. ACTIONS REQUIRED OF REGISTRANTS
This section specifies the data requirements and responses necessary for the
reregistration 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 diflubenzuron for
the above eligible uses has been reviewed and determined to be substantially
complete. However, in order to more fully understand the effects of
diflubenzuron and confirm the assumptions upon which this reregistration
eligibility decision is based, the following data are required:
72-3 Estuarine/Marine toxicity fish
82-4 21-day inhalation
132-l(a) Foliar residue dissipation (tree crops such as citrus, medium-
height crops such as cotton or soybeans, and greenhouse-grown
crops such as chrysanthemums)
132-l(b) Soil residue dissipation (mushroom crops only)
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133-3,4 , Dermal and inhalation passive dosimetry exposure8
162-4 Aerobic aquatic metabolism
163-1 Adsorption/Desorption (on CPU and bare ground data from
- typical use areas in the north)
164-2 Aquatic (sediment) dissipation
164-3 Forestry dissipation
165-2 Field rotational crops
165-3 Accumulation in irrigated crops
165-5 Accumulation in aquatic non-target organisms
171-4c : Residue analytical methods .
171-4e Storage stability
171-4k Magnitude of residue in plants
202-1 Field drift evaluation , -
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 following statement under
Directions for Use:
"Only for formulation into an insecticide for the following
uses:__ (fill blank only with those uses that are being
supported by MP registrant)."
f :
An MP registrant may, at his/her discretion, add one of the following
statements to an MP label under Directions for Use to permit the reformulation of the
product for a specific use or all additional uses supported by a formulator or user
group: '
(a) "This product may be used to formulate products for specific use(s) not listed
oh the MP label if the formulator, user group or grower has complied with U.S.
EPA submission requirements regarding the support 6f such use(s).
(b) "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 the support of such use(s).
B. End-Use Products
Requirement may be satisfied with data generated by the Agricultural Reentry Task Force and Outdoor Residential
Exposure Task Force, provided the registrant is a member.
90 ,
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1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FEFRA calls for the Agency to obtain any needed
product-specific data regarding the pesticide after a determination of eligibility
has been made. The product specific data requirements are listed in Appendix
G, the Product Specific Data Call-in Notice.
Registrants must review previous data submissions to ensure that they
meet current EPA acceptance criteria (Appendix F; Attachment E) 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.
2. Labeling Requirements for End-Use Products
Restrictions prohibiting the cutting of treated grass hay for livestock
must be deleted from all labels. All labels allowing repeated applications must
be amended to list the minimum retreatment interval.
Non-granular End-Use Products
"This pesticide is toxic to aquatic invertebrates. For terrestrial uses, do not
apply directly to water, or to areas where surface water is present or to interticlal
areas below the mean high-water mark. Drift and runoff may be hazardous to
aquatic organisms in neighboring areas. Do not contaminate water when
disposing of equipment wastewater or rinsate."
Aquatic Use Sites (mosquito larvicides)
"This pesticide is toxic to aquatic invertebrates. Fish and aquatic inverterates
may be killed where this pesticide is used. Do not contaminate water when
disposing of equipment or rinsate. Consult with State agency in charge offish
and game before applying to public waters to determine if a permit is required."
"Do not use in potable water or in water used for swimming,"
Row Crop and Orchard Uses .
"Do not apply within 25 feet of bodies of water such as lakes, reservoirs, rivers,
permanent streams, natural ponds, marshes or estuaries."
91
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3. Occupational/Residential Labeling .
a. PPE Requirements for Pesticide Handlers
All end-use products containing diflubenzuron have only one active ingredient.
Therefore, 'all labels must be revised to adopt the handler personal protective
equipment requirements set forth in this section. Any conflicting PPE
requirements on their current labeling must be removed.
Products intended Primarily for Occupational Use
Minimum (baseline) PPE requirements — Some of the registered uses of
diflubenzuron are within the scope of the WPS and some are outside the scope
of the WPS. The minimum (baseline),PPE requirements pertain to both the
WPS and nonWPS uses by occupational handlers, since the potential exposure
is similar for WPS and nonWPS uses.
Oral Bolus Pellet/Tablet Formulations
/
There are no minimum (baseline) PPE requirements for diflubenzuron
end-use products formulated as oral bolus pellets or tablets.
Wettable Powder Formulations
The minimum (baseline) PPE for applicators and other handlers
(other than mixers and loaders) for all occupational uses of diflubenzuron
erid-use products formulated as wettable powders is:
"Applicators and other handlers (other than mixers and loaders must wear:
Long-sleeved shirt and long pants
Chemical-resistant gloves
Shoes plus socks
~ A dust/mist respirator (MSHA/NIOSH approval number TC-21C)"
The minimum mixer/loader (baseline) PPE requirements for
occupational uses of diflubenzuron end-use products formulated as wettable
powders in water soluble packets:
92
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"Mixers and loaders must wear:
Long-sleeved shirt and long pants
Chemical-resistant gloves
Shoes plus socks
A dust/mist respirator (MSHA/NIOSH approval number TC-21C)"
Liquid and Flowable Formulations
The minimum (baseline) handler PPE requirements for occupational
uses of diflubenzuron end-use products formulated as liquids or flowables is:
"Applicators and other handlers (other than mixers and loaders must wear:
Long-sleeved shirt and long pants
Chemical-resistant gloves when mixing and loading and also when
using hand-held equipment
Shoes plus socks"
Actual end-use product PPE requirements — The PPE that would otherwise
be established based on the acute toxicity of each end-use product must be
compared to the minimum (baseline) personal protective equipment, if any,
specified above. The more protective PPE must be placed on the product
labeling. For guidance on which PPE is considered more protective, see PR
Notice 93-7.
Placement in labeling — The personal protective equipment must be placed on
the end-use product labeling in the location specified in PR Notice 93-7 and the
format and language of the PPE requirements must be the same as is specified
in PR Notice 93-7.
Products Intended primarily for Occupational Use
WPS uses
Restricted-entry interval -- a 12-hour restricted entry interval (REI) is
required for uses within the scope of the WPS (see PR Notice 93-7) on all end-
use products with WPS uses(see tests in PR Notices 93-7 and 93-11).
Early-entry personal protective equipment (PPE) ~
The PPE required for early entry following applications of both the wettable
powder and flowable concentrate formulations is:
93
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Coveralls
Chemical-resistant gloves,
Shoes plus socks
Placement in labeling ~ The REI must be inserted into the standardized REI
statement required by Supplement Three of PR Notice 93-7. The PPE required
for early entry must be inserted into the standardized early entry PPE statement
required by Supplement Three of PR Notice 93-7.
i -
Non-WPS uses
Entry restrictions— For all applications (except aquatic sites and wide-area
government-sponsored pest control programs, such as for mosquito or gypsy-
moth control):
"Do not enter or allow others to enter the treated area until sprays have dried."
Placement in labeling —
If WPS uses are also on the label: Follow the instructions in PR Notice 93-7
for establishing a Non-Agricultural Use Requirements box and place the
appropriate nbn-WPS entry restriction in that box.
If no WPS uses are on the label: Add the appropriate nonWPS entry
restriction to the labels of all end-use products, except products primarily
intended for homeowner use, in a section in the Directions For Use with the
heading; "Entry Restrictions:"
4. Other Labeling Requirements
Products Intended Primarily for Occupational Use
The Agency is requiring the following labeling statements to be located
on all end-use products containing diflubenzuron that are intended primarily for
occupational use.
Application Restrictions (except wide-area government-sponsored pest
control programs, such as for mosquito or gypsy-moth control):
"Do not apply this product in a way that will contact workers of other persons,
either directly or through drift. Only protected handlers may be in the area
during application." .
94
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"Do not apply this product to bodies of water where swimming is likely."
Engineering Controls:
—For all formulations:
"When handlers use closed systems (including water soluble bags), 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." '
User Safety Requirements:
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such
instructions for washable, use detergent and hot water. Keep and wash PPE
separately from other laundry."
User Safety Recommendations:
"Users should was hands before eating, drinking, chewing gum, using tobacco,
or using the toilet."
"Users should remove clothing 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."
Respirator Type:
The following type of respirator is appropriate to mitigate diflubenzuron
inhalation concerns:
"A dust/mist filtering respirator (MSHA/NIOSH approval number prefix TC-
21C) ,
Additional Labeling Requirements
The Agency is requiring additional labeling statements to be located on
all end-use products containing diflubenzuron. For specific language, refer to
Section V of this document.
95
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5. Spray Drift Labeling
The following language must be placed on each product label that can be
applied aerially:
Do not apply within 150 feet of bodies of, water such as lakes,
reservoirs, rivers, permanent streams, natural ponds', marshes or
estuaries. ,
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.
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.
1. 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 shall be observed.
The applicator.should be familiar with and take into account the
information covered in the Aerial Drift Reduction Advisory
Information.
The following aerial drift reduction advisory information must be
contained in the product labeling:
[The Spray Drift Labeling 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
96
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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).
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.
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.
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 safely. Making applications at the lowest height that is safe
reduces exposure of droplets to evaporation and wind.
97
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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.)
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.
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.
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.
-98
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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).
C. Existing Stocks
Registrants may generally distribute and sell products bearing old
labels/labeling for 26 months from the date of the issuance of this Reregistration
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
diflubenzuron 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.
99
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100
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for
active ingredients within the case Diflubenzuron covered by this Reregistration Eligibility
Decision Document. It contains generic data requirements that apply to Diflubenzuron 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 CFRPart 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) 487-4650.
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 (MRDD) 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.
121
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133
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GUIDE TO APPENDIX C
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 Reregi strati on 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. -
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.
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.
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
b.
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.
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
134
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as (19??), the Agency was unable to determine or estimate the date of the
document.
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.
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 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.
135
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BIBLIOGRAPHY
MRID
CITATION
00010865
00038212
00038213
00038611
00038612
00038613
00038614
LeBlanc, G. (1975) The Chronic Toxicity of Altosids(R), TH-6040, and
R-20458 to Daphnia magna. (unpublished study recieved Feb. 8, 1977 under
20954-1; prepared by EG&G, Bionomics, submitted by Zoecon Corp Palo
Alto, CA; CDL:231488-1)
Steelman, C.D.; Farlow, I.E.; Breaud, T.P.; et al. (1975) Effects of Insect
Development Inhibiting Chemicals on Psorophora columbiae (Dyar and Knab).
and Non-target Aquatic Insect Species in Rice Fields. (Unpublished study
received Feb 10, 1976 under 6G1744; prepared by Louisiana State Univ.,
Depts. of Entomology and Experimental Statistics, submitted by Thompson-
Hayward Chemical Co., Kansas City, KS; CDL:094969-G)
Booth, G.M. (1975) The Impact of Dimilin W-25 on Non-target Invertebrates
in Ponds Located in Salt Lake County, Utah. Final rept. (Unpublished study
received Feb 10, 1976 under 6G1744; prepared by Brigham Young Univ.,
Dept. of Zoology, submitted by Thompson-Hayward Chemical Co.; Kansas
City, KS; CDL:094969-H)
Marine Research Institute (1973) Oyster Bioassays: 96-Hour EC50 with
Fertilized Eggs, Larva and Post-Juveniles. (Unpublished study received Feb
10, 1976 under 6G1744; submitted by Thompson-Hayward Chemical Co.,
Kansas City, KS; CDL:094974-C)
Bionomics-EG&G, Incorporated (1975) The Acute and Subchrqnic Toxicity
of R-20458, Altosid and TH-6040 to the Grass Shrimp, Palaemonetespuglio.
Final rept. (Unpublished study received Feb 10, 1976 under 6G1744;
submitted by Thompson-Hayward Chemical Co., Kansas City KS-
CDL:094974-D) •
Fink, R.; Petrocelli, S.R. (1973) Final Report: Eight-Day Dietary
LC50-Mallard Ducks: Project No. 553-118. (Unpublished study received Feb
10, 1976 under 6G1744; prepared by Environmental Sciences Corp., submitted
by Thompson-Hayward Chemical Co., Kansas City, KS; CDL:094974-E)
Alsager, D.F.; Cook, D.A. (1975) Acute Oral Toxicity Studies (LD50) of
TH6040 Insecticide to Red Winged Blackbirds (Agelaiusphoeniceus: CBSC
No. TR-112-75. (Unpublished study received Feb 10, 1976 under 6G1744;
prepared by Canadian Bio-Scientific Consultants, Ltd. and Univ. of Alberta,
136
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BIBLIOGRAPHY
MRID
CITATION
Dept. of Pharmacology, submitted by Thompson-Hayward Chemical Co.,
Kansas City, KS; CDL:094974-G)
00039080 Fink, R. (1973) Final Report: Eight-Day Dietary LC50~Bobwhite Quail:
Project No. 553-117. (Unpublished study received Apr 7, 1976 under
148-1259; prepared by Environmental Sciences Corp., submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:096227-F)
00039085 Reinert, H.K.; Cannon, G.E. (1976) Report: The Evaluation of TH 6040 in Four
Avian Species: Laboratory No. 5E-8680 A-D. (Unpublished study received
Apr 7, 1976 under 148-1259; prepared by Cannon Laboratories, Inc., submitted
by Thompson-Hayward Chemical Co., Kansas City, KS; CDL:096227-K)
000390*88 Union Carbide Corporation (1976) Acute Toxicity of Dimilin W-25 to
Anodonta sp.; Mercenaria mercenaria; Uca pugilator; Carcinus maenas.
(Unpublished study received Apr 7, 1976 under 148-1259; submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:096227-D)
00039090 Union Carbide Corporation (1976) The Effect of the Mosquito Larvicide'
Dimilin on the Freshwater Environment of Three Test Ponds in Texas.
(Unpublished study received Apr 7, 1976 under 148-1259; submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:096228-A)
0003 9091 Union Carbide Corporation (1976) The Effect of the Mosquito Larvicide
Dimilin on the Freshwater Environment of Three Test Ponds in Arkansas.
(Unpublished study received Apr 7, 1976 under 148-1259; submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:096228-B)
0003 9092 Union Carbide Corporation (1976) The Effect of the Mosquito Larvicide
Dimilin on the Freshwater Environment of Three Test Ponds in North Carolina.
(Unpublished study received Apr 7, 1976 under 148-1259; submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:096228-C)
00039473 Nimmo, W.B.; De Wilde, P.C. (1975) Degradation of Diflubenzuron in Soil
and Natural Water: Report No. 56635/37/1975. (Unpublished study received
Feb 10, 1976 under 6G1744; prepared by Philips-Duphar, B.V., submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:094972-B)
137
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BIBLIOGRAPHY
MRID
CITATION
00039474 Nimmo, W.B.; De Wilde, P.C. (1973) The Fate of PH 60-40 in the
Environment; Part One. Natural Waterand Soil/Water Systems: Report
5,6635/33/1973. Interim rept (Unpublished study received Feb 10, 1976 under
6G1744; prepared by Philips-Duphar, B.V., submitted by Thompson-Hayward
'. Chemical Co., Kansas City, KS; CDL:094972-C)
i
0003 9476 Helling, C.S. (1975) Interim Report: Soil Mobility of Three
Thompson-Hayward Pesticides-. (U.S. Agricultural Research Service,
Agricultural Research Center-West, Pesticide Degradation Laboratory,
unpublished study; CDL:094972-E)
00039477 Rieck, C.E. (19??) Soil Column Leaching Study: TH-6040. (Unpublished
study received Feb 10, 1976 under 6G1744; prepared by Univ. of Kentucky,
Agronomy Dept, submitted by Thompson-Hayward Chemical Co., Kansas
City, KS; CDL:094972-F)
00040601 Atkins, E.L.; Greywood-Hale, E.A.; Macdonald, R.L.; et al. (1974) Effect of
Pesticides on Apiculture: 1974 Annual Report: Project No. 1499.
(Unpublished study received October 21, 1976 under 6F1696; prepared by
University of California — Riverside, Agricultural Experiment Station,,
Department of Entomology, Citrus Research Center, submitted by E.I. duPont
de Nemours & Company, Inc., Wilmington, Del., CDL:095326-K)
00040777 Rieck, C.E. (1975) Soil Column Leaching Study. (Unpublished study received
Apr 7, 1976 under 148-1259; prepared by Univ. of KenLucky,~Dept. of
Agronomy, submitted by Thompson-Hayward Chemical Co., Kansas City, KS;
CDL:096229-G)
00040782 Nimmo, W.B.; De Wilde,,P.C. (1974) The Fate of PH 60-40 in the
Environment: Part Two. Hydrosoils and Agricultural Soils: Report
56635/19/1974. (Unpublished'study received Apr 7, 1976 under 148-1259;
prepared by Phillips,-Suphar, B.V., submitted by Thompson-Hayward Chemical
Co., Kansas City, KS; CDL:096230-W) . . .
00056035 Pitcher, F.G. (1973) TH 6040: Bluegill (Lepomis macrochirus). (U.S.
Agricultural Research Service, Pesticides Regulation Div., Animal Biology
Laboratory, unpublished study; CDL:132525-A)
138
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BIBLIOGRAPHY
MRID
CITATION
00056150 Marshall, B.L.; Hieb, B.L. (1973) 96-Hour LC50: Salmo gairdneri, Lepomis
macrochirus and Fundulus heteroclitus. (Unpublished study received Apr 5,
1974 under 148-1170; prepared by Marine Research Institute, submitted by
Thbmpson-Hayward Chemical Co., Kansas City, KS; CDL:224671-O)
00060376 Reiner, H.K.; Parke, G.S.E. (1975) Report: Static 96-Hour Toxicity Study of
Thompson-Hayward Chemical Company. Sample TH 6040 in Fathead
Minnows: Laboratory No. 5E-6095. (Unpublished study received Jul 31, 1978
under 148-1259; prepared by Cannon Laboratories, Inc., submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:234513-S)
00060377 Marshall, B.L. (1974) 96-Hour LC50-Shrimp-TH 6040 W-25. (Unpublished
study received Jul 31, 1978 under 148-1259; prepared by Marine Research
Institute, submitted by Thompson-Hayward Chemical Co., Kansas City, KS;
CDL:234513-T)
00060380 Reinert, H.K.; Parke, G.S.E. (1976) Report: Static 96-Hour Toxicity Study of
Dimilin 1.0% Granular in Bluegill Sunfish and Rainbow Trout: Laboratory No.
6E-2035. (Unpublished study received Jul 31, 1978 under 148-1259; prepared
by Cannon Laboratories, Inc., submitted by Thompson-Hayward Chemical Co.,
Kansas City, KS; CDL:234513-W)
00060381 Roberts, S.; Parke, G.S.E. (1976) Report: 8-Day Dietary LC50 Study of
Dimilin 1G: Bobwhite Quail and Mallard Ducks: Laboratory No. 6E-2036.
(Unpublished study received Jul 31, 1978 under 148-1259; prepared by
Cannon Laboratories, Inc., submitted by Thompson-Hayward Chemical Co.,
Kansas City, KS; CDL:234513-X)
00060384 Fraser, W.D.; Pell, IB. (1977) The Acute Toxicity of Du 112307 (Dimilin 25%
WP) to the Common Corp (Cyprinus carpio) and the Rainbow Trout (Salmo
gairdneri): Report No. 55645/1/77. (Unpublished study received Jul 31, 1978
under 148-1259; prepared by Huntingdon Research Centre, England, submitted
by Thompson-Hayward Chemical Co., Kansas City, KS; CDL: 234513-AB)
00064550 Burdock, G.A.; Wentz, K.L.; Purvis, D.; et al. (1980) Subchronic Dietary
Toxicity Study in Rats: Difiubenzuron: Project No. 553119, Final rept.
(Unpublished study received Nov 21, 1980 under 148-1268; prepared by
Hazleton Laboratories America, Inc., submitted by Thompson-Hayward
139
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BIBLIOGRAPHY
MRID
CITATION
Chemical Co., Kansas City, KS; CDL:243807-A; 243808, 243809; 243805'
243806) , ••..•'
00070018
00070024
00071210
00073933
•00073935
00073936
00074534
Palmer, A.K.; Allen, P.A.; Street, A.E.; et al. (1977) Preliminary Assessment of
the Effect of Du 112307 on the Rat: PDR 243/77208: (Unpublished study
received Jun 22, 1977 under 6F1773; prepared by Huntingdon Research
Centre, England, submitted by Thompson-Hayward Chemical Co., Kansas
City, KS; CDL:096166-F) " • . ,
Koopman, T.S.M.; Offringa, O.R (1977) Acute Oral Toxicity Study with Du
112307 (Technical) in Mice: Report No. 56645/4/77, (Unpublished study
received Jun 22, 1977 under 6F1773; prepared by Philips-Duphar, B.V.,
Netherlands, submitted by Thompson-Hayward Chemical Co. Kansas City
KS; CDL:Q96166-K)
Buckner, C.H.; McLeod, B.B.; Kingsbury, P.D. (1975) The Effect of an
Experimental Application of Dimilin(R) upon Selected Forest Fauna: Report
CC-X-97. (Canada—Environment, Forestry Service, Chemical Control
Research Institute; unpublished study; CDL:096232-K)
Cunningham, P.A. (1975?) Effects of Dimilin (TH-6040) on Reproduction in
the Brine Shrimp, Artemia salina. (Unpublished study received Dec 23, 1976
under 148-1258; prepared by North Carolina State Univ., Dept. of Genetics,
submitted by Thompson-Hayward Chemical Co., Kansas City, KS;
CDL:095663-L)
Roberts, S.; Parke, G.S.E. (1976) Acute Oral Toxicity in Bobwhite Quail
Compound: T H 6040 99.4% Pure (Air Milled): Laboratory No. 6E-2430 A.
(Unpublished study received Dec 23, 1976 under 148-1258; prepared by
Cannon Laboratories, Inc., submitted by Thompson-Hayward Chemical Co.,
Kansas City, KS; CDL:095663-N) •
Roberts, S.; Parke, G.S.E. (1976) Acute..Oral Toxicity in Mallard Ducks:
Laboratory No. 6E-2430 B. (Unpublished study received Dec 23, 1976 under
148-1258; prepared Cannon Laboratories, Inc., submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:095663-O)
Keet, C.MJ.F. (1981) An Evaluation of the Relative Sensitivity of the Rat, Cat,
and the Mouse to Diflubenzuron Induced Metand Sulphhaemoglobin and the
140
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BIBLIOGRAPHY
MRBD
CITATION
Total of Oxidized Haemoglobin Formation:, Report No. 56645/8/81.
(Unpublished study received Jun 8, 1981 under 148-1268; prepared by Duphar
B.V., The Netherlands, submitted by Thompson-Hay ward Chemical Co.,
Kansas City, KS; CDL:245235-A)
00095416 Wan, M.T.K.; Wilson, D.M. (1977) Impact of Insect Growth Regulators on
Selected Non-target Organisms Co-existing with Mosquito Larvae: Report No.
EPS 5-PR-77-1. (U.S. Environmental Protection Service, Pacific Region,
Pollution Abatement Branch; unpublished study; CDL:234512-U)
00099678 Farlow, J. (1976) Ecological Impact of Dimilin ... on the Aquatic Founa of a
Louisiana Coastal Marsh. Doctoral dissertation, Louisiana State Univ. and
Agricultural and Mechanical College, Dept. of Entomology. (Unpublished
study received Dec 23, 1976 under 148-1258; submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:095650-K)
00099713 Keet, M.; Boschman, A.; Saxena, S.; et al. (1977) The Effect of Du 112307
(Technical) in Male Mice after Daily Oral Administration, for a Period of 14
Days, on Bodyweight, Methaemoglobin, Sulphhaemoglobin and Heinz Body
Formation and Gross Pathology: Report No. 56645/33/77. (Unpublished study
received Feb 6, 1978 under 148-1259; prepared by Philips-Duphar, B.V., the
Netherlands, submitted by Thompson-Hayward Chemical Co., Kansas City,
KS; CDL:096787-C)
00099719 Booth, G.; Johnson, S.; Human, D.; et al. (1977) The Effect of Diflubenzuron
on the Reproduction of Bobwhite Quail. (Unpublished study received Feb 6,
1978 under 148-1259; prepared by Brighan Young Univ., Depts. of Statistics
and Zoology and Univ. of Illinois, School of Life Sciences, submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:096787-J)
00099722 Livingston, R.; Koenig, C. (1977) Life Cycle Toxicity Tests Concerning the
Acute and Chronic Effects of a Pesticide (TH-6040) on the Mummichug
(Fundulus heteroclitus Walbaum), and Egg-laying Topminnow. (Unpublished
study received Feb 6,1978 under 1481259; prepared by Environmental
Planning & Analysis, submitted by Thompson-Hayward Chemical Co., Kansas
City, KS; CDL:096787-M)
00099730 Roberts, S.; Parke, G.; Charles, S. (1977) Reproduction Study of Airmilled
Technical Diflubenzuron in Bobwhite Quail: Laboratory No. 7E-6032.
141
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BIBLIOGRAPHY
MRID
CITATION
(Unpublished study receivedFeb 6, 1978 under 148-1259; prepared by Cannon
Laboratories, Inc., submitted by Thompson-Hayward Chemical Co., Kansas
City, KS; CDL: 096788-J)
00099755 Cannon, G.; Krize, J. (1976) TH-6040 Egg to Egg Reproduction Study in
Fathead Minnows: Laboratory No. 5E-6094. (Unpublished study received Jul
19, 1976 under 148-1262; prepared by Cannon Laboratories, Inc., submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:096209-1; 225306)
00099791 Birdsong, R. (1965) Field Test of Dimilin on Non-target Organisms in Virginia:
File #179. Final rept. (Unpublished study repeived Jul 19, 1976 under
14.8-1262; prepared by Environmental Consultants, Inc., submitted by
; Thompson-Hayward Chemical Co., Kansas City, KS; CDL:096204-H)
00099839 Mulla, M.; Majori, .G.; Darwazeh, H. (1975) Effects of the Insect Growth
Regulator TH-6040 on Mosquitoes and Some Nontarget Organisms.
(Unpublished study received Jan 29, 1975 under unknown admin, no.; prepared
by Univ. of California—Riverside, Dept. of Entomology, submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:225930-K)
00099862 Reinert, H.; Parke, G. (1975) Reproductive Study of TH-6040 in Bobwhite
Quail and Mallard Ducks: Laboratory Nos. 5E-6092 and 5E-6093.
(Unpublished study received Jan 12, 1976 under 1481170; prepared by Cannon
Laboratories, Inc., submitted by Thompson-Hayward Chemical Co., Kansas
City, KS; CDL:225306-H),
00099891 Jackson, G. .(1976) Dimilin (TH6040): Biologic Impact on Pond Organisms.
(Unpublished study received Jul 31, 1978 under 148-1259; prepared in
cooperation with U.S. Fish and Wildlife Service, Southeastern Fish Cultural
. Laboratory, submitted by Thompson-Hayward Chemical Co., Kansas City, KS;
CDL:234511-W)
00099895 McAlonan, W. (1975) Effects of Two Insect Growth Regulators on Some
Selected Saltmarsh Non-target Organisms. (Unpublished study received Jul 31,
1978 under 148-1259; submitted by Thompson-Hayward Chemical Co.,
Kansas City, KS;CDL:234511-AA)
00099897 Apperson, C.; Schaefer, C.; Colwell, A. (1977) Effects of Diflubenzuron on
Chaoborus astictopus Dyar and Shannon (Diptera: Chaoboridae) and Nontarget
142
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BIBLIOGRAPHY
MRID
CITATION
Organisms, and Persistence of Diflubenzuron in Lentic Habitats. (Unpublished
study received Jul 31, 1978 under 148-1259; prepared by North Carolina State
Univ., Dept. of Entomology, Univ. of California, Mosquito Control Research
Laboratory, and Lake County (California), Mosquito Abatement District,
submitted by Thompson-Hayward Chemical Co., Kansas City, KS;
CDL:234511-AC)
00114330 Colley, J.; Batham, P.; Heywood, R.; et al. (1981) The Effects of Dietary
Administration of Diflubenzuron to Male and Female HC/CFLP Mice for 14
Weeks: Volume 1: HRC Report No. PDR/294/ 80185. Final rept.
(Unpublished study received Aug 10, 1981 under 148-1268; prepared by
Huntingdon Research Centre, Eng., submitted by Thompson-Hayward
Chemical Co., Kansas City, KS; CDL:245651-A; 245652)
00038706 Chesterman, H.; Heywood, R.; Barker, M.H.; et al. (1974) Du 112307: Toxicity
in Repeated Dietary Administration to Beagle Dogs (Repeated Administration
for 13 Weeks): PDR169/74157. (Unpublished study received Feb 10, 1976
under 6G1744; prepared by Huntingdon Research Centre, submitted by
Thompson-Hayward Chemical Co., Kansas City, KS; CDL:094963-G)
00038716 Davies, R.E.; Elliott, P.H.; Street, A.E.; et al. (1975) Effect of Repeated
Applications of Du 112307 to the Skin of Rabbits for Three Weeks: PDR
200/74851. (Unpublished study received Feb 10, 1976 under 6G1744;
prepared by Huntingdon Research Centre, submitted by Thompson-Hayward
Chemical Co., Kansas City, KS; CDL:094964-K)
00044325 Berczy, Z.S.; Cobb, L.M.; Street, A.E. (1975) Subacute Inhalation Toxicity to
the Rat of Du 1123 07 Insecticide Powder (Evaluation of
Methaemoglobinaemia): PDR197/741013. (Unpublished study received Feb
10, 1976 under 6G1744; prepared by Huntingdon Research Centre, England,
submitted by Thompson-Hayward Chemical Co., Kansas City, KS;
CDL:094965-B)
00044329 Hunter, B.; Colley, J.; Street, A.E.; et al. (1975?) Effects of Du 112307 in
Dietary Administration to Rats for 104 Weeks. (Unpublished study received
Feb 10, 1976 under 6G1744; prepared by Huntingdon Research Centre,
England, submitted by Thompson-Hayward Chemical Co., Kansas City, KS;
CDL:094966-A; 094967; 094968)
143
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BIBLIOGRAPHY
MRID
CITATION
00099712
00138248
00142490
00144931
00145467
00146174
00152501
00153407
00155419
Colley, J.; Offer, J. (1977) Effects of Du 112307 in Dietary Administration to
Rats for 104 Weeks: Revaluated Pathological Data: PDR171/75945.
(Unpublished study received Feb 6, 1978 under 148-1259; prepared by
Huntingdon Research Centre, England, submitted by Thompson-Hayward
Chemical Co., Kansas City, KS; CDL:096787-B)
Miller, R.; Cecil, H.; Carey, A.; et al. (1979) Effects of feeding difiubenzuron
to young male Holstein cattle. Bull. Erivironm. Contain. Toxicol. 23:482-486.
(Also in unpublished submission received Apr 11, 1984 under 37100-EX-3;
submitted by DupharB.V., S-Graveland, Neth.; CDL:252985-B)
Colley, J.; Heywood, R.; Street, A. (1984) The Effect of Difiubenzuron Given
by Oral Administration with the Feed on Toxicity and Tumour Development in
Male and Female HC/CFLP Mice: Final Report: PDR 360/831096/B.
' Unpublished study prepared by Huntingdon Research Centre. 2716 p.
Opdyeke, J.; Miller, R.; Menzer, R. (1982) In Vivo and Liver Microsomal
Metabolism of Difiubenzuron by Two Breeds of Chickens. Journal of
Agricultural and Food Chemistry 30(6): 1227-1233.
Burdock, G. (1984) Oncogenicity Study in Rats: Final Report: Project No.
553-122. Unpublished study prepared by Hazleton Laboratories America Inc
4230 p.
Greenough, R.; Goburdhun, R.; Hudson, P. et. al. (1985) Difiubenzuron 52
Week Oral Toxicity Study in Dogs: Project No. 630146. Unpublished study
prepared by Inveresk Research International. 353 p.
Opdy eke, J.; Menzer, R. (1984) Pharmacokinetics of difiubenzuron in two
types of chickens. Journal of Toxicology and Environmental Health
12:721-733.
Uniroyal Chemical (1985) Difiubenzuron Residue in California Citrus.
Unpublished compilation. 29 p.
Romano, M.; Biroc, S.; Colavita, J.; et al. (1985) A Tissue Residue Study
Utilizing a Vigilante 0.77% Difiubenzuron (DFB) Premix in Cattle when Fed at
a Rate of 0.2 mg DFB/kg Body Weight. Unpublished study prepared by
American Cyanamid Co. 46 p.
144
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BIBLIOGRAPHY
MRID
CITATION
00155420 Garces, T.; Colavita, J. (1985) Residues of Diflubenzuron in Milk Following
the Feeding of a Diflubenzuron 0.77% Premix-concentrate Mixture to
Lactating Dairy Cows for 28 Consecutive Days. Unpublished study prepared
by American Cyanamid Co. 69 p.
00155425 Romano, M.; Biroc, S.; Colavita, J.; et al. (1985) A Tissue Residue Study
Utilizing a Vigilante 0.77% Diflubenzuron (DFB) Premix in Cattle when Fed at
a Rate of 0.2 mg DFB/kg Body Weight: Experiment B-85-37. Unpublished
study prepared by American Cyanamid Co. 46 p.
00155426 Garces, T.; Colavita, J. (1985) Residues of Diflubenzuron in Milk Following
the Feeding of a Diflubenzuron 0.77% Premix-concentrate Mixture to
Lactating Dairy Cows for 28 Consecutive Days. Unpublished study prepared
by American Cyanamid Co. 67 p.
00156015 . Buisman, P.; Verhaar, L. (1985) Residues of Diflubenzuron in Chicken Feed,
Chicken Eggs and Chicken Tissues from a Feedthrough Experiment (The
Netherlands, 1985): Project No. C5/303/54: Report No. 56630/208/85.
Unpublished study prepared "by DupharB.V., Weesp. 60 p.
00156581 Philips Duphar, B.V. (1986) Diflubenzuron Residues in California Citrus:
Uniroyal Residue Report No. UR405 A. Unpublished study. 15 p.
00156779 Philips-Duphar B.V. (19??) Name, Chemical Identity and Composition of
Vigilante Insecticide Feed-Through Premix for Layers. Unpublished
composition. 35 p.
00156780 De Winter, M. (1986) Overview of Metabolism and Egg and Tissue Residues
of Diflubenzuron in White and Brown Chicken: Report No. 56637/01/1986.
Unpublished compilation prepared by Duphar B. V. 18 p.
00156781 Cecil, H.; Miller, R.; Corley, C. (1981) Feeding three insect growth regulators
to White Leghorn Hens: Residues in eggs and tissues and effects on production
and reproduction. Poultry Science 60:2017-2027.
00156782 Buisman, P.; Verhaar, L. (1985) Residues of Diflubenzuron in ChickFeed,
Chicken Eggs and Chicken Tissues from a Feed-through Experiment (The
Netherlands, 1985): Report No. 56630/208/85: Project C5.303.54.
Unpublished study prepared by Duphar B. V. 92 p.
145
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BIBLIOGRAPHY
MRID
CITATION
00156783
00157103
00157104
00157105
00157106
00157842
00163311
00163853
05000841
05001991
Buisman, P. (1985) Preliminary Results of Diflubenzuron Residues in Manure
from a Feed-through Chicken Trial at Muiden (The Netherlands) Deluding
Methods of Detection". Unpublished compilation prepared by Duphar B V
38 p. • -
Koopman, T. (1985) Acute Oral Toxicity Study with Diflubenzuron VC-90 in
Rats: Int. Doc. No. 56645/30/84. Unpublished study prepared by Duphar B.V.
Up-
Koopman, T. (1985) Acute Dermal Toxicity Study with Diflubenzuron VC-90
in Rats: Int. Doc. No. 56645/31/84. Unpublished study prepared by Duphar
B.V: 12 p.
Koopman, T. (1985) Primary Irritation of Diflubenzuron VC-90 to the Rabbit
Eye: Int. Doc. No. 56645/29/84: Report No. H. 133.40,1. Unpublished study
prepared by Duphar B.V, lip.
Koopman, J. (1985) Primary Irritation of Diflubenzuron VC-90 to the Rabbit
Skin: Int. Doc. No. 56645/44/84. Unpublished study prepared by Duphar B V
9 p.
Nimmo, W. (1986) Adsorption of Diflubenzuron to Soils: Report No.
56635/07/86. Unpublished study prepared by Duphar B.V. 12 p.
Greenough; R.; McDonald, P. (1986) Acute Inhalation Toxicity Study in Rats
-(Limit Test): Diflubenzuron VC 90: IRI Project No. 635296: Report No. 3545.
Unpublished study prepared by Inveresk Research International. 23 p.
Van Den Berg, G. (1986) Dissipation of Diflubenzuron Residues after
Application of Dimilin WP-25 in a Forestry Area in N.Carolina (USA) and
Some Ecological Effects: [includes All References": Report No.
56637/47/1986. Unpublished study prepared by Duphar B.V. 161 p.
Ali, A.; Mulla, M-S. (1978) Effects of chironomid larvicides and diflubenzuron
on nontarget invertebrates in residential recreational lakes. Environmental
Entomology 7(1 ):21-27.
Stevenson, J.H. (1978) The acute toxicity of unformulated pesticides to worker
honey bees (Apis mellifera). Plant Pathology 27(1):38-40.
146
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BIBLIOGRAPHY
MRID
CITATION
40094602 Johnson, W. and Finley, M.R. (1980) Handbook of Acute Toxicity of
Chemicals to Fish and Aquatic Invertebrates. USDI Publication 137,
Washington DC.
40098001 Mayer, F.; Ellersieck, M. (1986) Manual of Acute Toxicity: Interpretation and
Database 410 Chemicals and 66 Species of Freshwater Animals. US Fish &
Wildlife Service; Resource Publication (160):579 p.
40130601 Hall, D. (1986) Toxicity of Two Insect Growth Regulators on Ceriodaphnia
dubia. Unpublished study prepared by Colorado State University, Department
of Fishery & Wildlife. 168 p.
40237501 Bretefer, R. (1987) Chronic Toxicity of Diflubenzuron to Mysid Shrimp
(Mysid opsis bahia), Part n, Supplemental Studies: Laboratory Project ID:
11493-0886-6100-530 and #BW-87-5-2400. Unpublished compilation
prepared by Springborn Bionomics, Inc. 44 p.
40816301 Boelhouwers, E.; Joustra, K.; Stegman, K. (1987) Photodegradation of Carbon
14-Iabelled Diflubenzuron in Water: Laboratory Project ID C.303.62.003.
Unpublished study prepared by Duphar B.V. 41 p.
40840501 Surprenant, D. (1988) The Chronic Toxicity of Carbon 14-Diflubenzuron to
Daphnia magna under Flow-through Conditions: Laboratory Project ID:
11493.0188.6109.130. Unpublished study prepared by Springborn Life
Sciences, Inc. 54 p.
40840502 Kuijpers, L. (1988) The Acute Toxicity of Diflubenzuron to Daphnia magna:
Laboratory Project ID: C.303.51.008. Unpublished study prepared by Duphar
B.V. 16 p. '
40859801 Boelhouwers, E.; Joustra, K.; Nijssen, O.; et al. (1988) Hydrolysis of 0carbon
14 [-Labelled Diflubenzuron in Buffer Solutions at pH 5,pH 7 and pH 9: Project
ID: C.303.62.006. Unpublished study prepared by Duphar B.V. 46 p.
41079301 Joustra, K.; Van Kampen, W.; Walstra, P. (1989) Metabolism of Carbon 14
Diflubenzuron in Citrus Fruit: Analytical Report: Proj. ID C.303.60.022.
Unpublished study prepared by Duphar B.V. 54 p.
147
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BIBLIOGRAPHY
MRID
CITATION
41079302
41087801
41087802
41392001
416$8001
41668002
41702102
41703501
Nigg, H. (1989) Metabolism of Carbon 14-Diflubenzuron in Citrus Fruits: Field'
Operations Report: Proj. ID C.303;60.022, Unpublished study prepared by
University of Florida, IF AS. 23 p, •- • ," •
De Boer, F. (1989) Addendum to Report on Hydrolysis in Water (Originally
Reported in Report No. 56630/137/1988, EPA MRID No. 40859801):
j^Dimilin |: Project ID: 56637/30/1989. Unpublished study prepared by Duphar
B.V. 6p:
DeBoer, F. (1989) Addendum To Report on Photolysis in Water (Originally)
Reported in Report No. 56630/35/1988, EPA MRID No. 40816301): Dimilin:
Project ED: 56637/29/1989. Unpublished study prepared by Duphar B.V. 6 p.
Surprenant, D. (1989) Acute Toxicity of Diflubenzuron to Quahogs
(Mercenaria mercenaria) Embryo-Larvae Under Static Conditions: Lab Project
Number: 89-3-2945: C 303.51.009. Unpublished study prepared by
Springborn Laboratories, Inc. 25 p. .'
Beavers, J.; Corbitt, A.; Hawrot, R.; et al. (1990) Diflubenzuron: A
One-Generation Reproduction Study with the Mallard (Anas platyrhynchos):
Lab Project Number: 225-103: C.303.40.014: 56645 /07/90. Unpublished
study prepared by Wildlife International Ltd. 140 p.
Beavers, J.; Corbitt, A.; Hawrot, R.; et al. (1990) Diflubenzuron: A
One-Generation Reproduction Study with the Bob white (Colinus virginianus):
Lab Project Number: 225-102: C.303.40.013. Unpublished study prepared by
Wildlife. International Ltd. 143 p
Dijksman, J.; van der Stel, D.; Jochem, E.; et al. (1990) A Method for the
Determination of Trace Levels of 4-Chloroaniline in Goat Milk, Development,
Validation and Application: Int. Doc. No. 56630/292/89; IRI Project 138261;'
CPD Project C.303.63.002. Unpublished study prepared by Duphar B.V. 87 p.
Enninga, I. (1990) Evaluation of DNA Repair Inducing Ability of
Diflubenzuron in a Primary Culture of Rat Hepatocytes (with Independent
Repeat): Lab Project Number: 002418: C.303.40.026: 56645/114/90.
Unpublished study prepared by RCCNotox B.V. 34 p.
148
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BIBLIOGRAPHY
MRID
CITATION
41703502 Taalman, R.; Hoorn, A. (1986) Mutageniciry Evaluation of Diflubenzuron
Technical in an in vitro Cytogenetic Assay Measuring Chromosome Aberration
Frequencies in Chinese Hamster Ovary (CHO) Cells: Final Report: Lab Project
Number: 56645/36/1986. Unpublished study prepared by Hazleton
Biotechnologies Corp. 25 p.
41703503 Koom, J. (1990) Study to Examine the Possible Mutagenic Activity of
Diflubenzuron in the Ames Salmonella/Microsome Assay: Lab Project
Number: DT 90/27: 56645/74/90. Unpublished study prepared by Duphar B.V.
23 p.
41703504 Kavanagh, P. (1988) Diflubenzuron: Oral (Gavage) Rat Teratology Limit
Study: Lab Project Number: PHD/11/87: 56645/68/87. Unpublished study
prepared by Toxicol Laboratories Ltd. 91 p.
41703505 Kavanagh, P. (1988) Diflubenzuron: Oral (Gavage) Rabbit Teratology Limit
Study: Lab Project Number: PHD/12/87: 56645/79/87. Unpublished study
prepared by Toxicol Laboratories Ltd. 78 p.
41720901 Dunsire, J.; Cameron, B.; Speirs, G. (1990) The Disposition of Carbon 14
Diflubenzuron in the Rat: Lab Project Number: 139197: 4924: 56654/13/90.
Unpublished study prepared by Inveresk Research International. 82 p.
41722801 Walstra, P.; Joustra, K. (1990) Aerobic Soil Metabolism of Diflubenzuron in
Sandy Loam: Lab Project Number: C.303.62.015. Unpublished study prepared
by Duphar B.V. 38 p.
41837601 Thus, J.; Van Dijk, N; Rompa-Van der Veldt, c.; et al. (1991) Anaerobic
Aquatic Metabolism of Diflubenzuron: Lab Project No. 56635/34/91:
C.303.62.010. Unpublished study prepared by Duphar B. V. 36 p.
41919001 Cameron, B; Henderson, A.; McGuire, G. (1990) The Metabolism of Carbon
14 Diflubenzuron in the Rat: Profiling of Radioactivity in Urine, Faeces and
Bile: Lab Project Number: 139768: 56629/64/90:6255. Unpublished study
prepared by Inveresk Research International. 74 p.
41922201 Pouwelse, A. (1986) Addendum to: Residues of Diflubenzuron in Water Soil,
Sediment, Leaf Litter,"Leaves and Residues of 4-Chlorophenylurea, A
Breakdown Product of Diflubenzuron, in Soil From a Dissipation Study in a
149
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BIBLIOGRAPHY
MRID
CITATION
Forestry Area: Lab Project Number: 85-11: O.303.60.704. Unpublished study
prepared by DupharB.V. 86 p.
41922202
41922203
41922204
41922205
41922206
41922207
41922208
41922209
Heekin, J.; Rich, P. (1987) Diflubenzuron - Stability on Wheat and
Milling/Baking Residue Studies: Lab Project Number: 56637/13/1991.
.Unpublished study prepared by Wellcome Research Laboratories. 29 p.
. Buisman, P.; Snijders, A. (1987) Stability of Diflubenzuron Residues in Pig
Manure on Storage at Ambient Temperature: Lab Project Number: C7.303.61:
56630/123/87. Unpublished study prepared by DupharB.V. 17 p.
Buisman, P.; Snijders, A. (1987) Stability of Diflubenzuron Residues in.
Chicken Manure on Storage at Ambient Temperature: Lab Project Number:
85-9: C7.303.61: 56630/110/87. Unpublished study prepared by Duphar B V
15 p.
Buisman, P.; Van Zijtveld, J. (1986) 3-Months Storage Stability of
Diflubenzuron Residues in Pig Feed at Ambient Temperature: Lab Project
Number: 85-6: C7.303.61: 56630/101/87. Unpublished Study prepared by
DupharB.V. lip. .
Buisman, P.; Verhaar, L. (1986) 1-Year Storage Stability at-20C of,
Diflubenzuron Residues in Chicken's Eggs White and Egg-Yolk: Lab Project
Number: 85-10: C7.303.61: 56630/77/87. Unpublished Study prepared by
DupharB.V. 17 p.
Buisman, P.; Verhaar, L. (1986) 1-Year Storage Stability at-20C of
Diflubenzuron Residues in Cow's Milk: Lab Proj ect Number: 85-7: C7.303.61:
56630/79/87. Unpublished study prepared by Duphar B.V. 15 p.
Buisman, P.; De Wilde, P. (1986) Storage Stability, of Diflubenzuron on Apples
at +4C for 6 Weeks and at-20C for 12 Months: Lab Proj ect Number: 78-13:
C9.303.60: 56630/172/87. Unpublished study prepared by Duphar B.V. 14 p.
Buisman, P.; Van Zijtveld, J. (1987) Storage Stability of Diflubenzuron '
Residues in Pond Water at-20C: Lab Project Number: 85-1 IF: C7.303.60:
56630/208/87. Unpublished study prepared by Duphar B.V. 19 p.
150
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BIBLIOGRAPHY
MRID
CITATION
41922210 De Boer, F. (1988) Storage Stability of Diflubenzuron on Apples at +4C for 6
Weeks and at-20C for 12 Months: Addendum to Report 56630/172/87: Lab
Project Number: C9.303.60: 56637/71/88. Unpublished study prepared by
DupharB.V. 10 p.
42060901 Cameron, B.; Dunsire, J.; Gifford, L.; et al. (1989) The Disposition of Carbon
14-Diflubenzuron in the Lactating Goat: Lab Project Number: 138261: 4990:
56654/02/90. Unpublished study prepared by Invaresk Research International.
63 p.
42151701 Minter, T.; Akesson, N. (1991) Dimilin Citrus Orchard Air-Carrier Drift Study:
Lab Project Number: C 303 60 024. Unpublished study prepared by Florida
Pesticide Research, Inc. 127 p.
42151702 Allan, E.; van Loo, T.; Verhaar, L. et al. (1991) Determination of
. Diflubenzuron on Glass Fiber Filters from a Dimilin Citrus Orchard Air-Carrier
Drift Study (Florida, 1991): Lab Project Number: C.303.60.024. Unpublished
study prepared by Solvay Duphar B.V. 88 p. •
42251101 Prinsen, M. (1992) Sensitization Study with Diflubenzuron Technical in
Guinea Pigs: Lab Project Number: B 91-0063/04. Unpublished study prepared
by TNO Tox. and Nutrition Institute; 24 p.
42251201 Saxena, A.; Marsh, S.; Koebel, D.; et al. (1992) Photodegradation of Carbon 14
Diflubenzuron on a Sandy Loam Soil under Artificial Sunlight Irradiation: Lab
Project Number: SC900150: 56630/215/91. Unpublished study prepared by
Battelle Memorial Institute. 85 p.
42258401 Burgess, D. (1989) Uptake, Depuration and Bioconcentration of carbon
14-diflubenzuron by Bluegill Sunfish (Lepomis macrochirus): Lab Project
Number: 37511. Unpublished study prepared by Analytical Bio-Chemistry
Laboratories, Inc. 41 p.
42487101 " Berends, A.; Thus, J. (1992) The Toxicity of Diflubenzuron to the Alga
Selenastrum capricornutum: Lab Project Number: C.303. 51.012: 56635/49/92.
Unpublished study prepared by Solvay Duphar, B.V. 23 p.
42494201 Timmerman, B.; Van Eck, M.; Ruijten, H. (1992) Charaterization of Residues
of Carbon 14 Diflubenzuron in Lactating Goat, Volume I of III: Metabolite
151
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BIBLIOGRAPHY
MRID
CITATION
Patterns: Lab Project Number: 56629/83/90: C.303.63.002. Unpublished study
prepared by Solvay Duphar B.V. Pharma Analysis Dept. 153 p.
42494202
42494203
43578301
43662001
43665801
44053101
Cameron, B.; Phillips, M. (1985) The Residue Kinetics of Carbon
14-Difiubenzuron in the Domestic Pig: Lab Project Number: 4041:
56654/34/85: 131690. Unpublished study prepared by Inveresk Research
Corp. 58 p. •
Van Berkel, M,; Van Eck, M.; De Bree, H. et al. (1986) Metabolite Patterns of
Carbon 14-Diflubenzuron in Liver, Kidney and Excreta of Pigs after Multiple
Oral Dosing: Lab Project Number: C.303.650: 56630/86/86. Unpublished
study prepared by Duphar B.V. Analytical Dept. 19 p.
Brooker, A. (1995) Diflubenzuron Technical: The Effect on Reproductive
Function of Two Generations in the Rat: Lab Project Number: PDR 569:
56345/83/94: PDR 569/932539. Unpublished study prepared by Huntingdon
Research Centre Ltd. 416 p.
Nimmo, D.; Hamaker, T.; Matthews, E.; et al. (19??) An overview of the acute
and chronic effects of first and second generation pesticides on an estuarine
mysid. Biological Monitoring of Marine Pollutants p. 3-14,16.
US EPA (1975) (Aquatic Toxicity in the Daphnia magna Using TH 6040): Lab
Project Number: 855. Unpublished study. 1 p.
Andre, J. (1996) Dermal Absorption of (carbon 14)-Diflubenzuron by Male
Sprague-Dawley Rats: Lab Project Number: 6615-95-0275-AM-001:
6615-95-0275-AM-000-001. Unpublished study prepared by Ricerca, Inc. 120
p. '
152
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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
AUG 26 1997
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 HI below. Your response must state: —
1. How you will comply with the requirements set forth in this Notice and its
Attachments 1 through 7; 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 IH-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 (FEFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
153
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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 seven 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
Section II
Section IE
Section IV
Section V
Section VI
Why You are Receiving this.Notice
Data Required by this Notice
Compliance with Requirements of this Notice
Consequences of Failure to Comply with this Notice
Registrants' Obligation to Report Possible Unreasonable Adverse
Effects
Inquiries and Responses to this Notice
The Attachments to this Notice are:
1 -
2-
3 -
4-
5-
6-
Data Call-in Chemical Status Sheet
Generic Data Call-In and Product Specific Data Call-in Response Forms with
Instructions (Form A)
Generic Data Call-In and Product Specific Data Call-in Requirements Status
and Registrant's Response Forms with Instructions (Form B)
EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
List of Registrants Receiving This Notice
Confidential Statement of Formula. Cost Share and Data Compensation Forms
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
revaluation identified additional data necessary to assess the health and safety of the
continued use of products containing this active ingredient(s). You have been sent this Notice
because you have produces) containing the subject active ingredients.
SECTION n. 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: Attachment 3 (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. ,
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H-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements
specified in the Requirements Status and Registrant's Response Forms (Attachment 3) within
the timeframes provided.,
n-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 PortRoyal Road, Springfield, Va22161 (Telephone number:
703-487-4650).
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 202-785-03 50). . .
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].
n-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(cVDCB^ 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 ID.
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).
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HI-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice for generic and product
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.
IH-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 IH-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 Form and the Requirements Status and Registrant's Response Form
(contained in Attachments 2 and 3, respectively).
The Data Call-In Response Forms must be submitted as part of every response to this
Notice. The Requirements Status and Registrant's Response Forms 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 Forms and the Requirements Status and
Registrant's Response Forms (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 subj ect of this Notice. If you wish
to voluntarily cancel your product, you must submit completed Generic and Product Specific
Data Call-in Response Forms (Attachment 2), indicating your election of this option.
156
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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.
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 (Attachment 3), 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.
You must also complete a Data Call-in Response Form 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,
aJl 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.
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To apply for the Generic Data Exemption you must submit a completed Data Call-in
Response Form, Attachment 2 and all supporting documentation. The Generic Data
Exemption is item number 6a on the Data Call-in Responsa Fnrm if you claim a generic data
exemption you are not required to complete the Requirements Status and Registrant's
Response Form. 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 registrants) 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 HI-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
Form and item 6b on the Data Call-in Response Form If you choose item 6b (agree to satisfy
the generic data requirements), you must submit the Data Call-in Response Form and the
Requirements Status and Registrant's Response Form 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 IH-D. 1. 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 Form. 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 m-C.2. A discussion of
options relating to requests for data waivers is contained in Section IH-D.2.
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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 Form, and the Requirements Status and Registrant's Response Form.
for product specific data (contained in Attachments 2 and 3, respectively). The Data Call-In
Response Form must be submitted as part of every response to this Notice. In addition, one
copy of the Requirements Status and Registrant's Response Form also must be submitted for
each product listed on the Data Call-in Response Form 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 Form and Requirements Status and Registrant's
Response Form (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
FormT indicating your election of this option. Voluntary cancellation is item number 5 on both
the Generic and Product Specific Data Call-In Response Forms. 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 DI-C.2. 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 Form 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 Form. 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
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are covered by option 7 of item 9 in the instructions for the Requirements Status and
Registrant's Response Form. If you choose this option, you must submit the Data Call-in
Response Form and the Requirements Status and Registrant's Response Form 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.
IH-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
1. Generic Data
If you acknowledge on the Generic Data Call-in Response Form 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 Form
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
deadlines 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 Form 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
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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 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 Form 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
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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 request EPA (by selecting this option) to exercise its discretion not to suspend your
registration(s), although you do 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 EPA Form 8570-32, Certification
of Offer to Cost Share in the Development of Data, Attachment 7. 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 Form and a Requirements Status and Registrant's Response Form
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
f \ ,
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
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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:
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 data1 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
data1 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 also 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
submitting 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
Reregistration 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 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
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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. i
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.
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 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. • '
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.
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
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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 MRJQD 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.
If you are citing a study of which you are not the original data submitter, you must
submit a completed copy of EPA Form 8570-31, Certification with Respect to Data
Compensation Requirements.
2. Product Specific Data •
If you acknowledge on the product specific Data Call-in Response Form 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
Form 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 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)
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Option 1. Developing Data — The requirements for developing product specific data are the
same as those described for generic data (see Section IH.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
IH.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 IILC.L, Option 3) apply to this option. This option only applies to acute
toxicity and certain efficacy data as described in option 2 above.
Option 4. Submitting an Existing Study - The same requirements described for generic data
(see Section m.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 IH.C. 1., 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. 1., 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 Form and the
Requirements Status and Registrant's Response Form, and in the generic data requirements
section (III.C.I.), as appropriate.
m-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
Form. 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,
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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:
(i). Total company sales (pounds and dollars) of all registered produces)
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
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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 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 produces) 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 productfsl you must choose a
method of meeting the requirements of this Notice within the time frame provided hy
this Notice. Within 30 days of your receipt of the Agency's written decision, you must
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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. 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
JTV-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.
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5.
7.
8.
I
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). .
Failure to submit supportable certifications as to the conditions of submitted
studies, as required by Section ffl-C of this Notice.
.Withdrawal of an offer to share in the cost of developing required data,
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:
i. Inform EPA of intent to develop and submit the data required by this Notice
on a Data Call-in Response Form and a Requirements Status and Registrant's
Response Form. .
ii. Fulfill the commitment to develop and submit the data as required by this
Notice; or ' "
iii. Otherwise take appropriate steps to meet the requirements stated in this
Notice, ,
9.
unless you commit to submit and do submit the required data in the specified
time frame. /
"",*''"'•.
Failure to take any required or appropriate steps, not mentioned above, at any
time following the issuance of this Notice.
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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.
171
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If you request a voluntary cancellation of your produces) 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 mariner must have been submitted to the Agency, before EPA,
will c'onsider 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 VL 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
(Attachment 2)and completed Requirements Status and Registrant's Response Forms
(Attachment 3), 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 Forms need be submitted.
172
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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
iois 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
6 - Confidential Statement of Formula. Cost Share and Data Compensation Forms
173
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174
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DIFLUBENZURON DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have product(s)
containing Diflubenzuron.
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 reregistration of
Diflubenzuron. 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) a list of
registrants receiving this DCI (Attachment 5) and (6) the Cost Share and Data Compensation
Forms in replying to this Diflubenzuron Product Specific Data Call-In (Attachment 6).
Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for Diflubenzuron are
contained in the Requirements Status and Registrant's Response. Attachment 3. The Agency has
concluded that additional data on Diflubenzuron 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 reregistration of all eligible Diflubenzuron products.
INOUIRmS AND RESPONSES TO THIS NOTICE
If you have any questions regarding this product specific data requirements and
procedures established by this Notice, please contact at (703) .
All responses to this Notice for the Product Specific data requirements should be
submitted to:
Chemical Review Manager Team 81
Product Reregistration Branch
Special Review and Reregistration Branch 7508W
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460 ,
RE: Diflubenzuron
175
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DIFLUBENZURON DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Generic Data Call-in Notice because you have produces)
containing Diflubenzuron.
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 reregistration of Diflubenzuron.
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 5), and
(6) the Cost Share and Data Compensation Forms in replying to this Diflubenzuron Generic Data
Call In (Attachment 6). Instructions and guidance accompany each form. ' '
DATA REQUIRED BY THIS NOTTCR
The additional data requirements needed to complete the, generic database for
Diflubenzuron are contained in the Requirements Status and Registrant's Responser Attachment
C. The Agency has concluded that additional product chemistry data on Diflubenzuron are
needed. These data are needed to fully complete the reregistration of all eligible Diflubenzuron
products.
INQUIRIES AND RESPONSES TO THIS NQTTCR
If you have any questions regarding the generic data requirements and procedures
established by this Notice, please contact Susan Jennings at (703) 308-8021.
All responsades to this Notice for the generic data requirements should be submitted to:
Susan Jennings, Chemical Review Manager
Reregistration Branch
Special Review and Registration Division (H7508W)
Office of Pesticiafde Programs
U.S. Environmental Protection Agency.
Washington, D.C. 20460 ,
RE: Diflubenzuron
176
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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" and are to be used by registrants to respond to generic and product specific Data .
Call-ins as part of EPA's Reregistration 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." 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 2136, 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.
177-
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
Generic and Product Specific Data Call-in
Item 1.
Item 2.
Item 3.
Item 4.
Item 5.
Item 6a.
ON BOTH FORMS: This item identifies your company name, number and
address.
ON BOTH FORMS: This item identifies the case number, ease name, EPA
chemical number and chemical name.
ON BOTH FORMS: This item identifies the type of Data Call-in. The date
of issuance is date stamped.
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.
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.
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 registered), you may not claim a Generic Data Exemption and you may not
select this item.
178
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Item6b. 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 Form 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.
Item 8. 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 initialled 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.
179
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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 thatyour product has already been transferred to another company or that you have already voluntarily cancelled this product For
thesecases,pleasesupPlyallrelevant-detailssothatEPAcanensurethatitsrecordsarecorrect
180
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Instructions For Completing The "Requirements Status and Registrant's Response
Forms" 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 2136, 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.
181
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Generic and Product Specific Data Call-in
Item 1.
Item 2.
ItemS.
Item 4.
Item 5.
Item 6.
ON BOTH FORMS: This item identifies your company name, number and
address.
i •
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.
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. -
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. ' _
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 HI 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 Form.
ON BOTH FORMS: This item identifies the code associated with the use
pattern of the pesticide. In the case of efficacy data (product specific
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
182
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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
PALM
PALPA1RA
PAIRA
PAIRA/M
PAIRA/PM
TEP
TEP %
TEP/MET
TEP/PAI/M
TGAI
TGAI/PAI
TGAI/PAIRA
TGAI/TEP
MET
IMP
DEGR
*
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
Technical'Grade Active Ingredient or Typical End-Use
Product
Metabolites
Impurities
Degradates
See: guideline comment
183
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Item 8.
Item 9.
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 Reregi strati on 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.
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 Share! I have entered into an
agreement with one or more registrants to develop data jointly. By
indicating that! 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.
Option 3. ON BOTH FORMS: COffer to Cost Shared 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
184
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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.
Option 5. ON BOTH FORMS: (Upgrading a StudyV 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 Study) 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
registrants 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 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.
185
-------
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" 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 Datai 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 th'e 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 BAT A; The following option (number 7) is a
response that applies to the "Requirements Status and Registrant's Response ,
Form" 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 FBFRA. 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 submission of data as specified by the
original Data Call-in notice will not change.
186
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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
187
-------
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