United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508W)
EPA738-R-98-010
September 1998
&EPA Reregistration
Eligibility Decision (RED)
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United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances'
(7508W)
EPA-738-F-95-010
APRIL 1998
R.E.D. FACTS
DEET
Pesticide
Registration
Use Profile
Regulatory
History
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 mitiga-
tion measures or regulatory controls needed to effectively reduce each pesti-
cide'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
0002, N,N-diethyl-meta-toluamide and other ispmers (DEET).
N,N-diethyl-meta-tbluamide (DEET) is ah insect repellent used in
households/domestic dwellings, on the human body and clothing being worn,
on cats, dogs, horses and pet living/sleeping quarters. There are no food uses.
It is used to control biting flies, biting midges, black flies, chiggers, deer flies,
fleas, gnats, horse flies, mosquitoes, no-see-ums, sand flies, small flying insects,
stable flies, and ticks. Formulations include liquids, pressurized liquids, ready-
to-use formulations and impregnated material. DEET is applied by aerosol
can, by hand, non-aerosol pump sprayer, package applicator, and pump spray
bottle. . .'"-'','
DEET was first registered in the U.S. in 1957 after first being developed
by the U.S. Army in 1946 for use by military personnel in
insect-infested areas. A Registration Standard for DEET was issued in De-
cember, 1980 (PBS 1-207722), and a subsequent Data Call-In (DCI)-.
for DEET (issued September, 1988) required additional animal and avian
toxicity data. "
Currently, 225 DEET products are registered. DEET products that are
applied directly to the skin and/or clothing are available in numerous formula-
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tion types (e.g. aerosol and non-aerosol sprays, creams, lotions, sticks, foams,
and towelettes). Product concentrations range from ~4% a.i. to 100% a.i.
" ' ' " ' ' ' '" " ' ' " ''
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Human Health
Assessment
Environmental
Assessment
, .. .. , . , , ..... :. . - . , ,.
Toxicity
In studies using laboratory animals, DEBT generally has been shown to
be of low acute toxicity. It is slightly toxic by the eye, dermal and oral routes
arid has been placed in Toxicity Category III (the second lowest of four
categories) for these effects.
[NOTE: For acute oral, dermal, ocular and inhalation toxicity:
Category I = very highly or highly toxic
Category II = moderately toxic
Category III = slightly toxic
Category IV = practically non-toxic]
Dietary Exposure
Because of its use pattern, people are not exposed to residues of DEBT
through the diet.
Occupational and Residential Exposure
Based on DEBT'S indoor/residential use pattern, handlers (mixers,
loaders, and applicators) are not exposed to DEBT.
Human Risk Assessment
pEET generally is of low acute toxicity, and, based on the available
tpxicological data, the Agency believes that the normal use of DEBT does not
present a health concern to the general U.S. population (the Agency's human
risk assessment has identified no lexicologically significant effects in animal
studies.) DEBT, has been classified as a Group D carcinogen (not classifiable
as a human carcinogen.)
Although DEET's use has been implicated in seizures among children,
the Agency believes that the incident data are insufficient to establish DEBT as
the cause of the reported effects. However, because of DEET's unusual use
pattern (direct application to human skin and clothing) and its association with
seizure incidents, the Agency believes it is prudent to require clear, common
sense use directions arid improved label warnings and restrictions on all DEBT
product labels.
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Environmental Fate
Because of its limited use pattern, the only environmental fate study
required for DEBT was hydrolysis. From that data, it was concluded that
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DEBT is stable to hydrolysis at pH levels found in me environment
Ecological Effects
Because DEBT is only applied directly to the human body /clothing, cats,
dogs, pet quarters and household/domestic dwellings, it is considered to be, an
"indoor residential" use. A limited set of toxicity data for indoor-use pesticides
..... :' ........ ..... , . - . - c .............. .....
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Risk Mitigation
Additional Data
Required
Product Labeling
Changes Required
is required to determine precautionary label statements and for assessing
environmental hazards in case of spills. The available data characterize DEBT
as slightly toxic to birds, fish, and aquatic invertebrates and as practically
, nontoxic to mammals.
Ecological Effects Risk Assessment
Ecological risk assessments are not conducted for pesticides with
exclusively indoor use patterns. Application of DEBT to the human
body/clothing, cats, dogs, pet quarters, and household/domestic dwellings, is
not likely to adversely affect terrestrial wildlife or aquatic organisms.
DEBT is a personal insect repellent that is widely used among the U.S.
population, including children, and is one of the few residential-use pesticides
that is applied directly to the skin. Although the available toxicological data to
not indicate a health concern under normal use conditions, DEET's use has
been associated with possible adverse effects. For all of these reasons, the
Agency believes it is prudent to require improved label warnings and product
restrictions. A listing of the requured labeling statements for DEBT
formulations is included in the RED, Section V. The Agency had deferred its
decision on the combination DEET/sunscreen products until it has solicited the
views of various governmental agencies and other groups. Sunscreen products
are intended for frequent, generous use, and DEBT products are intended for
spare, infrequent use. The Agency is concerned that use of the combination
products may promote greater use of DEBT than is needed for pesticidal
efficacy and thus pose unnecessary exposure to DEBT, In addition, child-
safety claims must be removed from all end-use product labels in order to be
reregistered. Child-safety claims are misleading and irreconcilable with the
intended use and pesticidal ingredients of DEBT products. From the
toxicological data reviewed by the Agency for DEBT, and from DEBT incident
data, there appears to be no correlation between the percent active ingredient
in the product and its safety. Therefore,' the Agency does not believe that
certain DEBT formulations are inherently safer for children. DEBT
uses/formulations with labels that make cosmetic claims must be labeled such
that label statements and use directions regarding insect repellency appear first
and more prominently on the label.
EPA is not requiring additional generic studies for DEBT to confirm its
regulatory assessments and conclusions.
The Agency is requiring product-specific data including product
chemistry and acute toxicity studies, product efficacy data, revised Confidential
Statements of Formula (CSFs), and revised labeling for reregistration.
All DEBT end-use products must comply with EP A's current pesticide
product labeling requirements and with those labeling requirements imposed in
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Regulatory
Conclusion
this RED. For a comprehensive list of labeling requirements, please see section
V. of Hie DEBT RED document.
1. All products must incorporate a series of 14 statements informing the
consumer on the method of application, special precautions for children, and
directions for medical attention.
2. For aerosol and pump spray formulations: labels must direct the consumer
not to spray in enclosed areas, avoid direct spraying on the face and must be
packaged in containers which will ensure the product will not be inadvertently
sprayed in the eyes.
3. Other labeling requirements include: specifying percent active ingredient in
terms of DEBT; use of the term "first aid"; addition of a toll-free number for
consumer support; requirement to use permanent labels; all cosmetic claims
must be less prominent that the term "Insect repellent"; and all direct or
indirect claims of child safety must be removed.
With the exception of products/formulations that combine DEBT and
sunscreen, all uses/formulations of DEBT are eligible for reregistration
provided all labels are amended as specified in the RED. The use of currently
registered products containing DEBT in accordance with approved labeling
will not pose unreasonable risks or adverse effects to humans or the
environment. Therefore, all uses of these products are eligible for
reregistration. The Agency will defer its decision regarding the reregistration
eligibility of products/formulations that combine DEBT and sunscreen until the
Agency has solicited the views of various governmental agencies and other
groups^ Additionally, the Agency will not act on any pending registration
applications under section,3 until that time.
DEBT products will be reregistered once the required product-specific
data, including efficacy data, revised Confidential Statements of Formula, and
revised labeling are received and accepted by EPA Products which contain
active ingredients in addition to DEBT will be reregistered when all of their
other active ingredients also are eligible for reregistration.
For More
information
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for DEBT 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
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server, GOPHER.EPA. GOV, or using ftp on FTP.EPA. GOV, or using WWW
(World Wide:Web) on WWW.EPA.GQV.
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 DEBT 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
DEBT RED, or reregistration of individual products containing DEBT, please
contact the Special Review and Reregistration Division (7508W), OPP, US
EPA, Washington, DC 20460, telephone 703-308-8000.
For information abo.ut the health effects of pesticides, or for assistance hi
recognizing and managing pesticide poisoning symptoms, please contact the
National Pesticides Telecommunications Network (NPTN). Call
toll-free 1 -800-858-7378, between 9:30 am and 7:30 pm Eastern Standard
Time, Monday through Friday.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
DEC -ฃ 1998
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 0002 which includes
, the active ingredients N,N-diethyl-meta-toluamide (DEBT). The enclosed Reregistration
Eligibility Decision TRED). which was approved oh April 13, 1998 contains'the Agency's
evaluation of the data base of these chemicals, its conclusions of the potential human health and
environmental risks of the current product uses, and its decisions and conditions under which
these uses and products will be eligible for reregistration. The RED includes the data and labeling
requirements for products for reregistration. It may also include requirements for additional data
(generic) on the active ingredients to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary of
Instructions for Responding to the RED." This summary also refers to other enclosed documents
which include further instructions. You must follow all instructions and submit complete and
timely responses. The first set of required responses is due 90 days from the receipt of this
letter. The second set of required responses is due 8 months from the date of this letter.
Complete and timely responses will avoid the Agency taking the enforcement action of suspension
against your products. - . . -
- ' ' ' ' ' " "
Please note that the Food Quality Protection Act of-1996 (FQPA) became effective oil
August 3, 1996, amending portions of both pesticide law (FIFRA) and the food and drug law
(FFDCA). This RED takes into account, to the extent currently possible, the new safety standard
set by FQPA for establishing and reassessing tolerances. However, it should be noted that in
continuing to make reregistration determinations during the early stages of FQPA implementation,
EPA recognizes that it wiU be necessary to make decisions relating to FQPA before the
implementation process is complete. In making these early case-by-case decisions, EPA does not
intend to set broad precedents for the application of FQPA. Rather, these early determinations
will be made on a case-by-case basis and will not bind EPA as it. proceeds with further policy
development and any rulemaking that may be required.
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If EPA determines, as a result of this later implementation process, that any of the
determinations described in this RED are no longer appropriate, the Agency will pursue whatever
action may be appropriate, including but not limited to reconsideration of any portion of this
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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 Jane
Mitchell (703) 308-8061.
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Enclosures
i!
"jfl
Lois A. Rossi, BUfector
Special Review and
Reregistration Division
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SUMMARY OF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISION
1 DATA CALL-IN (PCD 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, a DCI letter will be enclosed listing such requirements. If both generic and product
-specific data are required, a combined Generic and Product Specific DCI letter will be enclosed
describing such data. However, if you are an end-use product registrant only and have been
granted a generic data exemption (GDE) by EPA, you are being sent only the product specific
response forms (2 forms) with the RED. Registrants responsible for generic data are being sent
response forms for both generic and product specific data requirements (4 forms). You must
submit the appropriate response forms (following the instructions provided) within 90 days
of the receipt of this RED/DCI letter; otherwise, your product may be suspended.
2-_ TIME EXTENSIONS AND DATA WAIVER REOUESTS-No time extension requests
will.be granted for the 90-day response. Time extension requests may be submitted only with
respect to actual data submissions. Requests for time extensions for product specific, data should
be submitted in the 90-day response. Requests for data waivers must be submitted as part of the
90-day response. All data waiver and time extension requests must be accompanied by a full
justification. All waivers and time extensions must be granted by EPA in order to go into effect.
3. APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE"-You must
submit the following items for each product within eight months of the date of this letter
(RED issuance date). ../ '
a- Application for Reregistration (EPA Form 8570-1). Use only an original application
form. Mark it "Application for Reregistration." Send your Application for Reregistration (along
with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies of draft labeling which complies with the RFD anH p.nrrpnt 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 i
changes, or labeling changes not related to reregistration) separately. You may, but are not
required to, delete uses which the RED says are ineligible for reregistration. For further labeling
guidance, refer to the labeling 'section of the EPA publication "General Information on Applying '
for Registration in the U.S., Second Edition, August 1992" (available fronithe National Technical
Information Service, publication #PB92-22181 1; 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 fCSF^ for each basic and
each alternate formulation. ' The labeling and CSF which you submit for each product.must
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comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal,concentration.
You have two options for submitting a CSF: (1) accept the standard certified limits (see 40 CFR
ง158.175) 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 ง158.l75(e). A copy of the CSF is enclosed;
follow the mstructions on its back.
e. Certification With Respect to Data Compensation Requirements. Complete and
sign EPA form ง570-31 for eachi product.
4. COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE-Comments
pertaining to me content of the RED may be submitted, to the adclress shown in the Federal
Register Notice which announces the availability of this RED.
5. WHERE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES)
BvU.S.MaiI:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C, 20460-0001
Bv express;
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pocument Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
f Arlington, VA 22202 ..... | ' ;' ' ' . " "" _ '' ^ " '
6. EPA'S REVIEWSEPA 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 reregistration determination within 14 months after the RED has been
issued.
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REREGISTRATION ELIGIBILITY DECISION
DEET '. ' . ' ' '
. ,. . ' : LIST A, .'.'.' ,'.-.;. .'"
CASE 0002
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
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TABLE OF CONTENTS
EXECUTIVE SUMMARY .'.:,:..... .'. ...... .^........ ... . v
I. INTRODUCTION ................ ... ....,....._.... .... 1 :
H. CASE OVERVIEW ...... r.............. .............. 1
A. Chemical Overview ...., ...^................. 1
C. Estimated Usage of Pesticide 3
D. Data Requirements : ; .. 5
E. Regulatory History ;, 5
III. SCIENCE ASSESSMENT . '.' ...................;-........ 5
A. Physical Chemistry Assessment '! 5
1. Identification of Active Ingredient 5
B. Human Risk Assessment .. 6
1. Toxicology Assessment ."...' ... g
b. Subchronic Toxicity - - 7
c. Chronic Toxicity and Carcinogenicity 12
d. Reproduction ...>.... 14
e. Developmental Toxicity .14
f. Mutagenicity ..-. _ 16
g. Metabolism 15
h. Neurotoxicity 19
i. Special Studies: Synergistic Effect of DEET with Other
" Insecticides ........ ^ ... 20
j. Incident Data 22
2. Toxicological Endpoints for Risk Assessment 24
3. Children's Special Sensitivity ............ ;........ 26
4. Dietary Exposure and Risk Characterization 27
5. Residential Exposure and Risk Characterization .. ..... 27
C. Environmental Assessment . ..........'...... .32
1. Ecological Toxicity Data .... 32
a. ; Toxicity to Terrestrial Animals .... ............ .. ...... 32
b. Toxicity to Aquatic Animals . 33
2. Environmental Fate .....34
a. Environmental Fate Assessment .....34
3. Exposure and Risk Characterization . 34
a. Ecological Exposure and Risk Characterization .......... 34
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 34
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li ! S1 'i ' '' IIP ' i' ' i ',.,',, , ' Y i ' . '
A. Determination of Eligibility 34
B. Determination of Eligibility Decision '.". 35
"l. Eligibility Decision 35
2. Eligible and Ineligible Uses 37
C. Regulatory Position 37
1. Labeling Rationale 37
ACTIONS REQUIRED OF REGISTRANTS .38
A. Manufacturing-Use Products 38
1. Additional Generic Data Requirements 38
2. Labeling Requirements for Manufacturing-Use Products 38
B. End-Use Products .'.'.'. 39
1. Additional Product-Specific Data Requirements 39
" is ' Labeling Requirements for End-Use Products 39
'C. " Existing Stocks .' '.....'.. '.'.'.'...'.'.'IV '.-.'..".',.."...I. ...41
APPENDICES ...
; APPENDIX A."
APPENDIX B.
APPENDIX C.
.APPENDIX''',,!). ,',
Attachment
Attachment
''',,' " H'! ' ". "' ' ",! . 'i,"l' '
Attachment 3.
Attachment
Attachment
APPENDIX E.
, , .. ,, ,
Table of Use Patterns Subject to Reregistration 44
Table of the Generic Data Requirements and Studies Used to
Make the Reregistration Decision 50
Citations Considered to be Part of the Data Base Supporting the
Reregistration of DEET .55
Product Specific Data Call-In .............. ........ 63
, i. '" ,' Chemical Status Sheets ...........'..,....,..'.'.'..... ..76
2. Product Specific Data Call-In Response Forms (Form A
inserts) Plus Instructions 76
Product Specific Requirement Status and Registrant's
Response Forms (Form B inserts) and Instructions .. 80
4. EPA Batching of End-Use Products for Meeting Data
Requirements for Reregistration 88
5. Cost Share, Data Compensation Forms, Confidential
Statement of Formula Form and Instructions ..... 104
List of Available Related Documents .". 116
-jc'.jir: ,., , i ,,
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DEET REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Environmental Fate and Effects Assessment
Mary Powell
William Ericksqn
Health Effects Assessment
Kathleen Martin . - '
Whang Phang
William Sette
Olga Odiott
Jerry Blondell
Biological and Economic Assessment
Wilfred Bun-
Alan Halvorson
Thomas Harris
Eric Riddick
Risk Management Assessment
Tina Levine
Richard Keigwin
Robert Brennis
Marion Johnson
Kevin Sweeney..
Jane Mitchell
Judith Coombs
Linda Werrell
Science Analysis and Coordination Staff
Ecological Effects Branch
Risk Characterization and Analysis Branch
Toxicology Branch II '
Toxicology Branch
Occupational and Residential Exposure Branch
Occupational and Residential Exposure Branch
Herbicide and Insecticide Branch
Economic Analysis Branch
LUIS >
Herbicide and Insecticide Branch
Registration Support Branch
Insecticide-Rodenticide Branch
Insecticide-Rodenticide Branch
Insecticide-Rodenticide Branch
Insecticides Branch
Reregistration Branch
Reregistration Branch
Reregistration Branch
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ADI
AE
a.i.
ARC
CAS
CI
CNS
CSF
DFR
DRES
DWEL
EEC :' . .
EP
EPA
FAO/WHO
FDA ,
FIFRA
FFDCA
FOB
FQPA
GLC
GM
GRAS
HA
HOT
LCSO
LD<(
LDlo
LEL
LOC
LOD
LOEL
MATC
MCLG
mg/L
MOE
MP.
MPI
GLOSSARY OF TERMS AND ABBREVIATIONS
Acceptable Daily Intake. A now defunct term for reference dose (RflD).
Acid Equivalent
Active Ingredient
, Anticipated Residue Contribution . ,
Chemical Abstracts Service ., . - -
Cation . .
Central Nervous System ' ,
Confidential Statement of Formula .'.''. ' ' t
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 nran
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 .
Functional Observation Battery
Food Quality Protection Act
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 be
expected to cause death in 50% of test animals. It is usually expressed as the weight of substance
per weight or volume of water, air or feed, e;g., nig/1, rag/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 is
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
ill
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GLOSSARY OF TERMS AND ABBREVIATIONS
MRID Master Record Identification (number). EPA's system of recording and tracking studies submitted.
N/A Not-Applicable
NOEC No effect concentration
J4PDES National Pollutant Discharge Elimination System
NOEL No Observed Effect Level
NOAEL No Observed Adverse Effect Level ,
0P Organophosphate' ' - "
OPP Office of Pesticide Programs
PADI Provisional Acceptable Daily Intake
PAG frssticide Assessment Guideline
PAM Pesticide Analytical Method
PHED Pesticide Handler's Exposure Data ,
PHI Preharyest Interval
ppb ' Parts Per Billion
PPE Personal Protective Equipment ,
ppm Parts Per Million
PRN Pesticide Registration Notice
Q", The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RBC Red Blood Cell
RED Reregistration Eligibility Decision
REI Restricted Entry Interval . ,
RfD Reference Dose t
RS Registration Standard
RUP Restricted Use Pesticide
SLN Special Local Need (Registrations Under Section 24 (c) of FIFRA)
TC Toxic Concentration. The concentration, at which a substance produces a toxic effect.
TD Toxic Dose. The dose at which a substance produces a toxic effect.
TEP typical End-Use Product
TGAI Technical Grade Active Ingredient
TLC Thin Layer Chromatography
TMRC Theoretical Maximum Residue Contribution
torr Ji J*nit of pressure needed to support a column of mercury 1 mm high under standard conditions.
ug/L Micrograms per liter
WP Wettable Powder .
WPS Worker Protection Standard
IV
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EXECUTIVE SUMMARY
*
! ' . -
The U.S. Environmental Protection Agency (EPA) has completed its Reregistration Eligibility
Decision (RED) for the pesticide N,N-diemyl-meta-toluamide (DEBT), which includes ,the active
ingredient N,N-diemyl-meta-to|uamide and its isomers. This decision includes a comprehensive
reassessment of the required target data and the use patterns of currently registered products. DEBT
is an insect and acarid repellent used in households/domestic dwellings, on the human body and
clothing being worn, on cats, dogs and horses and in pet living/sleeping quarters. DEBT is used to
repel biting flies, biting midges, black flies, chiggers, deer flies, fleas, gnats, horse flies, mosquitoes,
no-see-ums, sand flies, small flying insects,, stable flies and ticks. DEBT products, which are applied
directly to skin and/or clothing, are available in numerous formulation types (e.g., aerosol sprays,
non-aerosol spray s, creams, lotions, sticks, foams, and towelettes) and concentrations (products range
from ~4% a.i. to 100% a.i.). The Agency is requiring the submission of product efficacy data as part
of the Product-Specific Data Call-In for the reregistration of DEBT end-use products.
The Agency has concluded that DEET insect repellents will generally not cause unreasonable
risks to humans or the environment. However, because DEET is: (1) so widely used among the U.S.
population, including children; (2) is .one of the few residential-use pesticides that is applied directly
to the skin; and (3) has been thought to be associated with incidents of seizure, the Agency believes
that it is prudent to require improved label warnings and restrictions for DEET products. The
Agency believes that such common sense measures will be especially protective of children and other
individuals who may be more sensitive to chemical substances. Product labels-must be revised as
specified in this RED to be more protective of the people using them, especially children.
With the exception of products/formulations that combine DEET and sunscreen, all
uses/formulations of DEBT are eligible for reregistration provided all labels are amended as specified.
Registrants with products that make child safety claims must remove such claims from the product
labels. The scientific data and incident data reviewed for DEET do not support label claims that infer
that certain DEET products (e.g., those with lower percentage active ingredient) are safer to use on
children than others. These claims are therefore misleading. Cosmetic claims may appear on DEBT
product labels, however, with certain restrictions that are listed in section V.B.2. "Labeling
Requirements for End-Use Products." In addition, the ingredient statement on all DEET product
labels must be listed as "DEET" (the common name) instead of _ the chemical name "N, N-diethyl-
meta-toluamide and its isomers." Label requirements and restrictions for all DEET end-use products
are listed in Section V of this RED document.
The Agency will defer its decision regarding the reregistration eligibility of
products/formulations that combine DEET and sunscreen until the Agency has solicited the views of
various governmental agencies and other groups. Additionally, the Agency will not act on any
pending registration applications under section 3 until that time. The Agency is concerned about
consumer use of products that combine sunscreen and DEET, since directions to reapply sunscreens
generously and frequently may promote greater use of DEET than needed for pesticidal efficacy and
thus pose unnecessary exposure to DEET. As stated in the amended Reregistration Standard (dated
-------
March 1985), the Agency will not register products whose acute toxicity falls into Toxicity Category
I or II. Additionally, end-use products must not be corrosive to the eye or cause corneal involvement
6r irritation persisting for 21 days or more.
VI
-------
I.
INTRODUCTION
In 1^88, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended to
accelerate the reregistration 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. ' ,
This document presents the Agency's decision regarding the reregistration eligibility of the
registered uses of N,N-diethyl-meta-toluamide (DEBT). The document consists of six sections.
Section I is the introduction. Section II describes DEBT, 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 DEBT. Section V
discusses the reregistration requirements for DEBT. 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. ,
II.
CASE OVERVIEW
A.
Chemical Overview
The following active ingredient is covered by this Reregistration Eligibility Decision
document: ,
Common Name:
Chemical Name:
Chemical Family:
DEBT (ESA) .
N,N-diethyl-m-toluamide and other isomers
N,N-dialkylamides
-------
r .
'"in: "! ' ซl"
,"x
::i"ป'i'
CAS Registry Number: 134-62-3
OPP Chemical Code: 080301
Empirical Formula:
C12H17NO
Multiple Active Ingredient Products Contain:
011901 Butpxypolypropylene glycol
057001 N-Octyl bicyclopheptene dicaboximide
109301 Fenvalerate
047201 Dipropyl isocinchromeronate
057001 N-Octyl bicyclopheptene dicarbqximide
Trade and Other Names: DEBT, OFF, Delphene, MGK diethyltoluamide,
Detamine, Metadelphene, Chemform,
.';:'' Chiggar-Wash, Muskol, Cutter, Repel, Old Time
Woodsman. ,
Basic Manufacturer:
McLaughlin, Gormley, King Company,
S.C. Johnson, Clariant Corp., Schering-Plough, .
Morflex Inc.
B. Use Profile
Tfie following is information on the currently registered uses with an overview of
use sites and application methods. A detailed table of these" uses of DEBT is in
Appendix A.
For N.N-Diethvl-meta-toluamide:
Type of Pesticide:
ป !l|!!| , i in '1
Insect and acarid repellent
tfงe Sites: IJ^OORI^SIpENTIAL: Hqusehp^s/Dpmestic Dwellings,
Human body/clothing while being worn (insect repellent), Cats
(adults/kittens), Dogs/canines (adults/puppies), Horses,
Pet living/sleeping quarters . .
Target Pests:
Biting flies, biting midges, black flies, chiggers (redbugs), deer flies,
fleas, gnats, horse flies, mosquitoes, no-see-ums, sand flies, small
., ,,!' I, ' ' ", ', liป . " i , '',', , , '. . T .,, ,i ,, ,, ' ,;. ,, ,' ' i,' ... ' h , . . / ! ' ." , ป ,ii ' !' i, .i|lป PI"'1 '
i flying insects, stable flies and ticks
-------
Formulation Types Registered:
Technical grade active ingredient
Manufacturing products
End Use products
Impregnated material t
Liquid - RTU
Pressurized liquid
Sunscreen/DEET
100%
17.5 to 88.89%
7.15 to 82.00%
7.00 to 100%
3.99 to 80.00%
7.13 to 20.00%
Methods of Application:
Types of Treatment - Animal bedding/litter treatment; animal
treatment(spray); clothing treatment; skin
contact treatment; spot treatment
Equipment - - Aerosolcan; by hand; non^aerosol pump
sprayer; package applicator; pump spray bottle
C. Estimated Usage of Pesticide
When needed
This section summarizes the best estimates available for the pesticide uses of DEBT.
These estimates are derived from a variety of published and proprietary sources available to the
Agency. The data, reported on an aggregate and site basis, reflect annual fluctuations in use
patterns as well as the variability in using data from various information sources.
Based on pesticide usage information mainly for 1990, an average annual estimate of the
domestic usage of N,N-diethyl-meta-toluamide (DEBT) is 4 million pounds (active ingredient).
About 30% of the U.S. population uses DEBT annually as an insect repellent (about 27% of adult
males, 31% of adult females and 34% of children). Approximately 21% of U.S. households use
DEBT annually. About 19% of households use it on household members, and about 4% of
households that have cats and/or dogs use DEBT on those pets. The table below summarizes use
of the pesticide by site.
-------
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rbitrarily assumed to be 50% greater than averages.
Central, MA = Mid-Atlantic, MW = Midwest, SA = So.
es excluding group quarters, institutions and military and
seholds are arbitrarily assumed to have cats and/or dogs.
treatments by applicators certified in five non-agricultura
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Pesticides Sold in California for 1 990.
imer Markets for Pesticides and Fertilizers, 1990 Update.
nstitute, National Home and Garden Household Use Surv
nstitute, Results of the 1993 Certified/Commercial Pestici
erce, Bureau of the Census, Census of Agriculture, 1992.
erce, Bureau of the Census, Statistical Abstract of the Uni
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-------
D. Data Requirements
" i -. , . .
Data requested in the 1980 Registration Standard for N,N-diethyl-meta-toluamide and its
isomers(DEET) include studies on product chemistry, product efficacy, toxicology, and ecological
effects. 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. The Agency is not requiring any additional generic data for
DEBT at this time; however, product chemistry data (including product efficacy) and acute
toxicity. data are being called in with this RED for the reregistration of DEBT end-use products.
; - . '/-,.
E. Regulatory History
DEET was registered in the United States in 1957 for use by the general public, after first
being developed by the U.S. Army in 1946 for use by military personnel in insect-infested areas.
It is used to repel biting pests such as mosquitos and ticks, including ticks that may carry Lyme
disease. A Registration Standard for DEBT was issued in December 1980 (NTIS #PB81-
207722), and a subsequent Data Call-In (DCI) for DEBT (issued September, 1988) required
additional animal and avian toxicity data. This Reregistration Eligibility Decision (RED) document
reflects a reassessment of all data submitted in response to the Registration Standard.
HI.:' SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
B
o
(C H )
2 5 2
B.
1. Identification of Active Ingredient
DEBT (N,N-diethyl-meta-toluamide), is an all-purpose individual insect repellent
which contains a minimum of 95% of the meta isomer, the most effective form of diethyl
toluamide, as a technical active ingredient
Technical DEET is a nearly colorless liquid with a faint characteristic odor.
It is relatively stable, highly hygroscopic and sensitive to light. Technical DEET is
practically insoluble in water and glycerin but miscible with several organic solvents.
Human Risk Assessment
-------
1 - V , ;'',::;. : ,,.':'.; -- ;;v
Jvr?N-diethyl-meta-toluainide (DEBT) was developed and patented by the U.S. Army
in 1946 for use by military personnel in insect-infested areas. Because DEBT was recognized
as one of the few products effective against mosquitoes and biting flies, it was registered for
use by trie general public in 1957. Today, DEBT is a widely-used insect repellent. Most
DEBT products are registered for human use; there are a few products registered for
veterinary uses.
The use of effective insect repellents provides certain public health benefits.
,i '" ! " ,;" !!|,i!!|i ! . ", :, :'"Vi:!:i!i| > " " .f^.' , , * , ,, ,, f , , ,,, , , ,, * ,,,, , , ,,
Application of DEBT insect repellents to the skin and clothing can help prevent bites from
ticks and other biting insects that may cause disease. Lyme Disease may develop from the
bite of an infected deer tick, and mosquitoes can transmit malaria, yellow fever, dengue fever
and encephalitis.
DEET's exposure pattern is unusual in that it is one of the few residential-use
pesticides that is applied directly to skin and clothing. Users of DEBT are expected to be
exposed to the product intermittently for days or weeks (subchronic exposure). Except in the
most unusual circumstances, long-term exposure (chronic) is not expected.
1. Toxicology Assessment ,
The toxicological database on DEBT is adequate and will support
|8registratioh eligibility. In addition to acute effects, DEBT has also been tested for
an entire battery of subchronic and chronic toxicity effects. Although some minor
effects were seen at the doses tested, the data do not show DEBT to be carcinogenic,
significantly developmentally toxic, nor mutagenic.
.:,"! ซ " " l|l' ih ' , | , "I, . . '! / " I '' " "', ' ,: '' i ป'',!' ' ; ; ,V r" ' f-i, ' '' , ' ' '" ' ' .'"' ' . ':
a. Acute Toxicity
Jable 2, Acute Toxicity Values for DEBT Technical
Study and Guideline
Oral LDjo-rat (81-1)
Dermal LDjo-rabbit (81-2)
Acute inhalation LDso-rat (81-3)
Eye irritation-rabbit (81-4)*
Dermal irritation-rabbit (8 1-5)*
Dermal sensitization (81-6)*
MRID
00134359
43763201
00134359
00134359
00134359
00134359
00134359
Results
2170 to 3664 mg/kg
4280 mg/kg
5.95 mg/L
Eye irritation and corneal opacity cleared
by day seven and three, respectively.
Minimal irritation-cleared by day seven:
Not a skin sensitizer.
Toxicity Category
III
III
IV
in
IV
!i.*D.ata pertaining to guidelines 81-4 through 81-6 are not required to support the reregistration of the TGAI. They are
presented here for informational purposes.
*-'!,;'
-------
b; Subchronic Toxicity
In the initial two 90-day dose range-finding studies, an increase in the
incidence of renal lesions was seen in all treated male rats when DEBT was
administered by either the oral or dermal route to CDฎ rats. The renal lesions were
characterized by granular casts, inflammation, regeneration, and hyaline droplets in
the renal tubules. The registrant believed that the renal lesions seen in the males were
due to an increased accumulation of a2(t-globulin which led to granular casts and other
related lesions in the renal tubules. The accumulation of a2[1-globulin can initiate a
sequence of events that appear to lead to renal tubule tumor formation.
The Agency has extensively examined the issue of chemically-induced
accumulation of cc2M-globulin, a low molecular weight protein in the renal tubules.
After analyzing all the data, it was concluded that chemically-induced accumulation
of a2(l-globulin and its associated renal lesions should be distinguished from other
renal lesions. In addition, the a2fl-globulin-related nephropathy occurs specifically in
the male rats.
The registrant conducted additional 90-day studies in micropigsฎ, castrated
male rats, different strains of rats, and hamsters to show that the renal lesions were
unique to males rats and related to the accumulation of a2(1-globulin. When the results
of all these studies were evaluated collectively, they provided sufficient evidence to
indicate that the renal lesions seen in DEET-treated male rats were related to
chemically-induced cc2(1-globulin accumulation.
i .
The combined data from all these studies provide sufficient information for
understanding the subchronic toxicity of DEBT in rodents. Provided below are
summaries .of the toxicity tests and results for 90-day oral toxicity in rodent studies,
90-day oral toxicity in non-rodent studies, and 90-day dermal toxicity studies.
90-Day Oral Toxicity - Rodent
90-Dav Oral Dose-Range Finding Study in CDฎ Rats
Groups of rats (15/sex/dose) received DEBT (technical grade) in the diet at
doses of 0,100, 500,1000,2000, or 4000 mg/kg for 90 days. The following effects
were seen:
At 4000 mg/kg, an increase in the incidence of deaths; all animals in
this dose group were sacrificed at week three of the study.
Decreased body weights and food consumption in animals that
received DEBT at doses of 500 mg/kg or above.
7
-------
An increase in absolute kidney weights in 500 mg/kg males and an
increase in absolute and relative liver weights in all treated groups
except 100 mg/kg females.
i;! i ;."" . " - . ' ' . ( i . ; ' r ; " ; 'ฅ'
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" An increase in the incidence of renal lesions, which were characterized
" n |," i ' ป''; , '" , ' ",, , 'ป '- , -'. ซ' '":,,'' '.",''', ! i'1 ; ' . ; "",.'' " i ' '!" :, ' ' !i , j' i.1,'':"
by granular casts, inflammation, regeneration, and hyaline droplets in
the kidneys of all treated males.
Although the study was well designed, executed, and reported, due to the last
finding (i.e., an increase in the incidence of renal lesions...) a NOEL could not be
established. By itself, the study did not meet the data requirements for a subchronic
toxicity study in rats (Guideline 82-1) (MRID 40241703).
90-Dav Feeding Study in CDฎ. Fischer, and NBR Male Rats
The objective of this study was to establish an association between the renal
toxicity seen in DEET-treated male rats and the a2u-globulin mechanism of renal
tqkiciry.
Groups of CDฎ, Fischer, and NBR male rats (10/group) received either a
control diet or DEET-treated diet at a concentration that would lead to a dose level
of 400"mg/kg/day for 90 days. The following effects were seen:
In CDฎ male rats, DEBT treatment produced an increased Incidence
ป of hyaline droplets in the renal tubules, renal tubular regeneration,
chronic inflammation in the renal cortex, and granular casts in the
."ill ' ' ." , '. . >.' . ' ". - ' ' - , :, ' .' *'.'" '. ', - ' , ,, .". i it
renal tubules.
In Fischer rats, DEBT did not affect hyaline droplet formation. In the
Fischer control rats, the kidney contained trace amounts of hyaline
droplets. In the .Fischer DEET-treated rats, there was an increase in
the incidence of kidney lesions, characterized by the presence of
hyaline droplets, regenerative tubule, and chronic inflammation.
In NBR rats, no renal effects were found.
The report was considered unacceptable due to conflicting information on the
actual dose and missing information on renal lesions (MRID 42518101).
Subsequently, the registrant submitted the missing data, which was reviewed and
considered to be sufficient to fulfill the missing information^ The supplemental data
OviRlD 44279961) showed that the actual dose was 400 mg/kg body weight/day and
the findings of renal tubular dilation and tubular necrosis were not seen in this study.
Therefore, the previous submission (MRID 42518101) is upgraded to acceptable/non-
guideline.
-------
90-Day Range-Finding Study in Hamsters :
Groups of hamsters (15/sex/dose) received 0,1000,5000,10,000, or 15,000
ppm of DEBT in the diet for 90 days (0, 61, 305, 624, or 940 mg/kg/day for males
and females). Compound-related effects were seen in animals that received 5000 ppm
DEBT or above. At 5000 ppm in males, there was a consistent drop in food
consumption and body weight. The decrease in body weight and food consumption
was more marked in 10,000 and 15,000 ppm males and females. The increase in the
incidence of gross pathologic and histblogic changes in testes and epididymides were
found in 10,000 and 15,000 ppm males. The gross pathologic changes were small
testes and epididymides; microscopically these changes were degeneration of the
testes and cellular debris in the epididymal tubules. At 15,000 ppm, there were deaths
in both males and females. Based upon these observations, the NOEL was 1000 ppm;
the LEL was 5000 ppm. '
The renal lesions seen in the DEET-treated CDฎ male rats were not found in
the hamsters that received DEBT up to 15,000 ppm. This study satisfies the data
requirements for. a 90-day feeding study in rodents (Guideline 82-1) (MRID
41344101). '
90-Day Dose-Range Finding Study in Mice t
Groups of CR CD-I mice (15/sex/dose) received DEBT at dietary
concentrations of 0,300,1000,3000,6000, or 10,000 mg/kg/day body weight for 13
weeks. A marked decrease in the food intake and body weights were found in the
6000 and 10,000 mg/kg/day groups during the first week of the study. These groups
were terminated at week three. A decrease in body weight was seen in 3000
mg/kg/day mice of both sexes. A statistically-significant increase in the liver weight.
was seen in 1000 and 3000 mg/kg/day mice of both sexes. A slight increase in liver
weight was also seen in 300 mg/kg/day male arid female mice. Based on the increase
in liver weights, a NOEL could not be established in mice for this 90-day study
(MRID 40241704). , ' ;
90-Day Oral Toxicity - Non-Rodent
Eight-Week Feeding/Dose Range-Finding Study in Dogs
Groups of beagle dogs (2/sex/dose) received DEBT in the diet at
concentrations of 0,300, 1000, 3000, or 6000/4500/3000 ppm1 (8.4, 28.6, 93.3, or
During the first two weeks of the study, the highest dose male and female dogs received 6000 ppm test diet, but the
dogs rejected the test diet. The treatment diet was withdrawn at the end of the second week and the animals were given the
basal diet for about one week. The dosage was then reduced at week four from 6000 ppm to 4500 ppm and at week seven
from 4500 ppm to 3000 ppm. At week six, this dose group of dogs was again given the basal diet.
-------
j."
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hi1
1|.5 mg/kg/day for males or 9.7, 30.6, 91.8, or li.5 mg/kg/day for females). The
Control animals received basal diet. ^
Under the conditions of this study, bEET did not produce any toxicity at
dietary concentrations of 3000 ppm or less. At a concentration of 6000/4500/3000
ppm, DEBT caused food rejection which led to a decrease in body weight, thin
appearance, fat depletion, organ weight decrease, and histological changes in kidneys
(cytbplasmic vacuolation of tubules in the kidney cortex), bone marrow, and thymus.
The reliability of the results of this study is compromised by the small number
of dogs used (i.e., 2/sex/dose); the test guidelines recommend 4 dogs/sex/dose. Thus,
a useful NOEL and LEL could not be established. In summary, this study does not
meet the data requirements for a subchronic oral toxicity study hi dogs (Guideline 82-
1) (MRID 43514202).
Eight-Week Oral Toxicitv Dose-Range Finding Study in Dogs
'' ''' (Gelatin Capsule) "
Groups of beagle dogs (2/sex/dose) received DEBT in a gelatin capsule at
dose levels of 0,50,100,200, or 400 mg/kg/day. The control animals received white
mineral oil in gelatin capsule. The following results were obtained:
.';*! ' ' ,. " '. c.. ,! .': '' ' '-: .. '" . v'.' .-:',!' - ;ซ;:ป' ; V '" ,' ''...i, *- ..,:. ,,.!<:: >ซ ;riป f
.ijljl i.: '. '. !' '.',' :?ll , , 1- ;, ., ;. , " '.' ( 'j , . . :- ;-,( '.;,.' ~!i':,,'! ..':,' ,,. '}. , - -1 ' : ';>,ป, V-.';;":.,!' < yliif ,K
Clinical observation data showed a significant increase in ptyalism in
100 mg/kg/day or above hi males and females and an increase in
abnormal head movements in 400 mg/kg/day males.
, A decrease hi body weight gains was found in 400 mg/kg/day males
* and females; and that hi female dogs was more marked.
Food consumption was substantially, reduced in 400 mg/kg/day
1 ; females. -
There was a decrease hi cholesterol level in 400 mg/kg/day male dogs.
A decrease hi testis/epididymis weight was found hi 400 mg/kg/day
males. However, both gross'examination and histopathology did not
indicate any changes hi the testis or any other organs.
The reliability of the results of this study is compromised by the small number
of dogs used. (Le., 2/sex/dose); a useful NOEL and LEL could not be established.
This study does not meet the data requirements for a subchronic oral toxicity study
In dogs (Guideline 82-1) (MRID 435l420l).
90-Day Dermal Toxicity
10
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'90-Day Dermal Toxicitv Study iruRats
, Groups of CDฎ rats (15/sex/dose) received DEBT (technical) at doses of 0,
100, 300, or 1000 mg/kg/day. The following effects were found: -
An increase in the incidence of acanthosis and hyperkeratosis of the
; dermal application sites of all compound-treated rats.
. - , A decrease in the body weights of high-dose males.
An increase in liver weight in mid- and high-dose females and high-
dose males. ,
Increased absolute and relative kidney weights (kidney/body weight
and kidney/brain weight) in mid- and high-dose males and increased
relative kidney weights in high-dose females.
Increased incidence of renal lesions that included granular casts,
inflammation, tubular regeneration, hyaline droplets in all treated
males; and marginal renal effect in high-dose females. This type of
renal lesion was also seen in the 90-day feeding study in CDฎ rats
(MRID 40241703).
Although the study was well-designed, executed, and reported, due to the
rinding of ah increased incidence of renal lesions in all treated males, a NOEL could
not be established. By itself, the study did not meet the data requirements for a
subchronic toxicity study in rats (Guideline 82-1) (MRID 40241702).
90-Day Dermal Toxicitv Study in Castrated Male Rats
The objective of this study was to determine the cause of the increase in the
incidence of hyaline droplets in the renal tubules of DEET-treated CDฎ male rats
seen in a 90-day dermal toxicity study (MRID 40241702). Prior to this study, the
registrant thought that this increase might be strongly influenced by the male sex
hormone testosterone: In this study, groups of castrated male CDฎ rats (15/group)
received DEBT by dermal application at dose levels of 0. or 1000 mg/kg/day for 90
days. The results showed that castration did not protect the DEET-treated animals
from hyaline droplet formation and other related findings of kidney lesions.
. ' \ ' ' ' ' ' . .
Because this is a special study conducted to clarify a specific finding
previously seen in another study, it did not meet the data requirements for a
subchronic toxicity study in rats (Guideline 82-1) (MRID 41199301).
11
-------
*:!
11 -; i1
'I:
90-Day Dermal Toxicity Study in Micropigsฎ
The purpose of this study was to determine if a renal lesion related to an
increase hi hyaline droplet formation and the presence of a2|a-globulin hi the kidney
tubules observed in male rats of previously conducted 90-day dermal and oral toxicity
studies (MRIDs 40241702 and 40241703, respectively) would occur in micropigsฎ!
DEBT was dermally applied to groups of micropigsฎ (4/sex/dose) at dose
levels of 0 (water), 100, 300, or 1000 mg/kg/day b.w. for 13 weeks.2 The results
indicated that DBET did not produce any mortality or changes in body weights,
hematologicai and biochemical parameters, gross pathology, and organ weights. At
the skin application sites, gross pathology showed that the DEET-treated animals had
,an increase in the incidence of desquamation and/or dry skin; histopathology showed
an increase hi the incidence of acanthosis and/or hyperkeratosis at the skin application
sites.
Under the conditions of this study, DEBT did not produce any renal lesions
in micropigsฎ. It also did not cause any renal lesions hi hamsters that received DEBT
in dietary concentrations up to 15,000 ppm (=940 mg/kg/day) (MRlD 41344101).
These findings indicate that the renal lesion produced by DEBT was unique to male
.fats. ' ^ .'''.'' ,. , .' ' ',
This study meets the data requirements for a non-rodent 90-day toxicity study
|nd satisfies Guideline 82-lb (MRID 41987401).
c'.\ Chronic Toxicity and Carcinogenicity
Combined Chronic and Carchiogenicity Study in Rats
In a combined two-year chronic toxicity/carcinogenicity in rats, groups of
CDฎ rats (60 sex/dose) received DEBT (98.3% purity) in the diet at dose levels of
'(C 10, 30, or 100 mg/kg/day for males and 30, 100, or 400 mg/kg/day for females.
Two control groups were run concurrently. The animals were treated for two years.
In the 400 mg/kg/day female rats, there were progressive and statistically-
sjgnificant decreases in body weights, a decrease in food consumption, and a
statistically-significant increase (=25 to 50%) in cholesterol levels at various intervals.
Isfo compound-related uicreases innon-neoplastic or neoplastic lesions were seen. No
fQxicity was seen hi any dose groups of male rats.
Based on the results of this study, the NOEL for the chronic toxicity of DEBT
in females is. 100 mg/kg/day and the LEL is 400 mg/kg/day (based on decreased bbdy
111,"1::: 3 .;;
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1000 mg/kg/day was a maximum dose which could be applied without significant runoff.
|, ., ,, ' .a; * ij i. ' ;r , '',',!, , ':l1' ' ' ' ,';!' "' ' Yf If '; '
' '..Ji . ::;" ' , '/ -12 '
-------
weights and food consumption and increased cholesterol levels in female rats). The
. NOEL for the chronic toxicity of DEBT in males is 100 mg/kg/day (i.e., die highest
dose tested or HDT).
This study meets, the data requirements for a combined chronic
toxicity/oncogenicity -study in female rats (Guideline 83-5). With respect to male rats,
the test animals clearly could have tolerated higher doses (MRID 43 514203).
Chronic Toxicitv Study in Dogs rone-vearV
Groups of beagle dogs (4/sex/dose) received DEBT hi a gelatin capsule at
dose levels of 0, 30,100, or 400 mg/kg/day/day for one year. The control animals
received white mineral oil in gelatin capsule. Each daily dose was divided into two
equal administrations. Under the conditions of this study, DEBT, at dosages of 3Q
and 100 mg/kg/day, did not produce systemic toxicity. However, at 400'mg/kg/day
DEBT produced the following effects:
An increase in the incidence of ptyalism in both males and females. A
male and a female dog showed signs of tremor. Most of the clinical
signs were observed within 30 minutes after dosing.
A decrease in food intake and body weights hi males and females
during me first five weeks of the treatment.
A decrease in cholesterol level in males.
An increased incidence of thin males and females.
An increase in platelet level in female dogs.
Hyperplasia of uterine epithelium.
Based on the finding.of the decreases in food consumption and body weights,
an increase in the incidence of ptyalism, and a decrease hi cholesterol levels hi 400
mg/kg/day dogs, the NOEL for chronic toxicity in dogs is 100 mg/kg/day and the
. LEL is 400 mg/kg/day. This study meets the data requirements for a chronic toxicity
study in dogs (Guideline 83-lb) (MRID 43320101).
Carcinogenicitv Study in Mice
Groups of mice (60/sex/dose) received DEBT at dietary concentrations of 0,
250, 500, or 1000 mg/kg/day for 78 weeks. A statistically-significant decrease in
mean body weight, body weight gams, and food consumption for both male and
female mice were seen in the 1000 mg/kg/day group.
Based on these findings, a NOEL for systemic toxicity was established at 500
mg/kg/day and a LEL at 1000 mg/kg/day. No evidence of carcinogenicity was found.
. 13 ' .
-------
a
This study satisfies the data requirements for a mouse carcinogenicity study
(Guideline 83-2b)(MRID 41351501).
d. Reproduction
Two-Generation Reproduction Study (Rats')
! r! ' ''"' '''. |i'1',1 .-,'' -," ,., . '"' , , /'ป' / '.' - I, ' ,,,'"' /, lj ' ''" ,' ' v-
v;j|, ' . ;. '. ".-' ,' ' '. ". .-: ';; i ', . "> ' ; .-.:"/ ,'' , .,,{1;' -. i: ', ' , '... : . -j', . _' v: i
Groups of Sprague-Dawley rats (28/sex/dose) received DEBT at dietary
concentrations of 0, 500, 2000, or 5000 ppm for two consecutive generations.
Kidney effects were seen in all treated males, including mottling, inflammation,
presence Of hyaline droplets, granular cast formation, and tubular regeneration.
Therefore, a NOEL for parental toxicity could not be established.
Np compound-related effects on the reproductive parameters such as fertility,
gestation, and viability were noted. A significant reduction in the body weights of
pups from the high-dose group beginning at day seven of lactation for males and day
14 of lactation for females was found at 2000 ppm. This reduction in body weights
in the pups was considered as systemic toxicity. The reproductive toxicity NOEL was
5000 ppm (or 250 mg/kg/day based on standard conversion, 20 ppm = 1 mg/kg/day),
which is the Highest Dose Tested (HDT). This study satisfies the data requirement
for a reproduction study (Guideline 83-4) (MRID 40979001).
e. Developmental Toxicity
Developmental Toxicity Study in Rats
Groups of 25 mated female CDฎ rats received DEBT at doses of 0,125,250,
or 750 mg/kg/day from days six to 15 of gestation. In the high-dose dams (750
nig/kg/day), clinical signs such as hypoactivity, ataxia, decreased muscle tone, foot
splay, perinasal encrustation, and perioral wetness were observed; some of these signs
were suggestive of neurotoxicity hi this dose group because none of these signs were
seen hi the controls. Some of these clinical signs were seen only sporadically hi the
Other treated groups. In the high-dose dams, there was an increase hi mortality rate,
a reduction in body weight gain and food consumption, .and an increase in mean liver
Weights. ,
A slight increase hi percent post-implantation loss was seen in the high-dose
group and a statistically-significant decrease hi mean fetal body weight/litter was seen
in the high-dose group. No additional compound-related effects were found.
Based on the increase in the clinical signs, reduced body weights and food
consumption, increased mortality rate, and an increase in mean liver weight, the
NOEL for maternal tpxicity was 250 mg/kg/day and the LEL was 750 mg/kg/day.
NOEL for developmental toxicity was 250 mg/kg/day and the LEL was 750
'"!>:,
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14
-------
mg/kg/day (based on a statistically-significant decrease in mean fetal body
weight/litter). This study satisfies the data requirements for a developmental toxicity
study in rats (Guideline 83-3a)(MRID 41351401).
:- Developmental Toxicitv in Rabbits
Groups of presumed pregnant female New Zealand white rabbits (16/group)
received DEBT at doses of 0,30,100, or 325 mg/kg/day body weight from .gestation
day six through day eighteen. Under the conditions of this study, DEBT did not
produce any compound-related maternal toxicity or developmental toxicity. The
NOEL for maternal and developmental toxicity was 325 mg/kg/day (i.e., the HDT).
The results indicate that the test animals could have tolerated higher dose levels. The
report failed to present any explanation for dose selection.
.Supplemental data, which consisted of a dose-range finding developmental
toxicity study in rabbits (MRID 44279903), were submitted to upgrade this study.
In the dose-range finding developmental toxicity study, groups of timed-pregnant NZ
white rabbits (5/dose group) received DEBT (98.7%) by gavage at dose levels of 0
.(corn oil), 62.5,, 125,250, 500, or 1000 mg/kg/day from gestation days 6 through 18.
The results indicated that at doses of 250 mg/kg/day or above there was a
non-dose-related increase in the incidence of rapid respiration in the maternal animals.
The incidence seen in 250 and 1000 mg/kg/day were statistically, significant. At 1000
mg/kg, clinical signs of hypoactivity, ataxia, and prostration were also seen.
Deaths were found in 500 and 1000 mg/kg/day groups. The individual
necropsy data showed that the animals that died at 500 and 1000 mg/kg/day groups
all had sloughing and/or ulceration of the stomach lining. In contrast, the survivors
did not show any gross pathology of the stomach. At doses of 500 mg/kg and above,
the corrosive effect of DEBT to the gastric lining appeared to be linked to the death
of these animals. No evidence of treatment-related developmental toxicity was
reported in any treatment groups. In the surviving litters, there was no evidence of
pre- or post-implantation loss in treated groups as compared to the controls. Based
on these results, the investigator of the study recommended 0, 30, 100, and 325
mg/kg/day be employed for the definitive developmental toxicity study in rabbits.
The results of the definitive study (MRID 42141101), in which no maternal
nor developmental toxicity was observed at doses of 325 mg/kg/day were consistent
with the results of the dose rangerfinding study, in which toxic effect was not seen in
animals which were treated at doses below 500 mg/kg/day. In reviewing the
definitive and the dose range-finding developmental toxicity studies together, the
results indicate that the highest possible dose, which would not result in stomach
ulceratiqn and death for a gavage developmental toxicity. study in rabbits, would
probably be approximately 400 mg/kg/day, The difference between 400 mg/kg/day
and 325 mg/kg/day in a toxicological study is riot marked. The highest dose tested
in me definitive rabbit developmental toxicity study (325 mg/kg/day) has been
* ' " - 15 ' ' " , ' ' ' .
-------
Sit': ^
Wi '
adequately high to assess the maternal and the developmental toxicity of DEBT.
Little would fee gained by conducting an additional study to establish a more precise
NOEL and LEL, especially in light of the severe maternal toxicity noted at 500
jpg/kg/day and above in the dose range-finding study.. Therefore, the developmental
foxicity study in rabbits (iV/GRlD 42141101) Is upgraded to acceptable.
'"lil.lf',1 "" " ."' :' . , ,,! : ;i,i' , 1Hi , n ป r ' , n " >, , . \ir l"1!1"." !' , " ',",',;' ,, n^ / \>\ - , ,,, ' y\ , "',,,1 ,'! ','!,:'! T l!l!i'".i'
f. Mutagenicity
lid"! , ,'',, j ; '"', ' '"., '' ''' ' ; * '''" ' '' ' ' :"' ' ','! '!,', "' '' '" ' i1 ' '!'' ' , '' ' ' ' i|,' ' 'I
/''J i ;ซ.'' ป ;.'*n . '* M i.. !l | | ;.,''," i ^ S; "^ ' , ], ปi, ;N ;, .,'!'' J ;'',' " ' ", ' ' ' "h
The required mutagenicity battery for DEBT has been met and the results are
all negative. DEBT is not mutagenic under the conditions of the test assays.
Provided below are the results of the Ames, Chromosomal Aberration, and
IJnscheduled DNA Synthesis assays.
Ames Assay
In an Ames assay, DEBT was tested over a concentration of 28 to 8333
ug/plate with Salmonellatvphimurium strains TA1535, TA1537, TA1538, TA98, and
TA100 in the presence and absence of S9 activation. The results indicated that DEBT
Jt^s nbt mutagenic in this test system. This study satisfies the data requirements for
a gene mutation assay (Guideline 84-2a) (MRID 41344801).
Chromosomal Aberration Assay
In a chromosomal aberration assay using Chinese hamster ovary cells, DEBT
was tested at concentrations ranging from 0.125 to 1.0 uL/mL in the absence of S9
activation and from 0.063 to 6.50 uL/mL in the presence of S9 activation. The results
s,hpwea! that DEBT5 was not clastogenic. The study satisfies the data requirements for
a structural chromosomal aberration assay (Guideline 84-2b)(MRID 41344401).
Unscheduled DNA Synthesis OJDS) Assay
In an UDS assay using primary rat hepatocytes, DEBT was tested at doses of
0.003 to 0.3 uL/mL. The results showed mat DEBT was tested'to a cytotoxic level
with no evidence of a genotoxic effect. The study satisfies the data requirements for
an assay on other genotoxic effects (Guideline 84-4) (MRlI) 41344301).
g. Metabolism and Dermal Absorption
, Metabolism Study in Rats
-f" !,:'"', !- i,*!:!1!');,!'1"1
A series of experiments that consisted of-a preliminary and six definitive
experiments was conducted to determine the absorption, distribution, elimination, and
Metabolism of DEBT.
In the preliminary experiment, groups of CDฎ rats (4/sex) received a single
dose (100 mg/kg/day b.w.) of radiolabeled DEBT by either oral (gavage) or dermal
administration; the blood radioactivity levels were measured at various intervals for
24 hours to determine the peak blood 14C-level.
16
-------
In the definitive experiments, groups of rats.(5/sex/dose regimen) received
DEBT by single oral low dose (100 mg/kg), .single oral high dose (500 mg/kg),
repeated oral low dose (100 mg/kg), or single dermallow dose (100 mg/kg). Two
groups (5 rats/sex/group) a single oral low dose and a single dermal low dose group
were sacrificed at peak'blood 14C level to determine the radioactivity levels in
various tissues. The results were as follows:
With oral dosing, the peak blood level was reached in one-half hour
- , after dosing in males while in females it took about two hours. With
dermal application, no peak blood level was found; instead a blood
level plateau, which began approximately one and
one-half hours after dosing and persisted until the termination of the-
study (24 hours after dosing), was found in both male and female rats.
These data indicated that when DEBT was dermally applied to rats,
a small amount of the test compound was continuously absorbed from
the application site.
At the time of peak 14C-blood level, the fraction of the administered
dose reaching the systemic circulation and the residue levels in tissue
following oral administration was substantially higher than that
following dermal application. At peak 14G-blood levels, approximately
17% arid 5.3% of the defmally-applied dose was absorbed by males
and females, respectively; in comparison, approximately 53.3% and
65.25% of the orally administered dose was absorbed by males and
females, respectively. - ',. .
The major route of DEBT elimination in both male and female rats
was via the urine. No marked difference was found in the total
urinary or fecal radioactivity among the different dosing regimens or
, between male and female rats of different dosing regimens. However,
there was a difference in the rate of urinary elimination of DEBT
among the different dose groups. For example, repeated oral dose
. groups or pretreatment groups showed the fastest rate of urinary
elimination during the first four hours after dosing than any other dose
groups. In contrast, the single dermal low-dose groups showed the
slowest rate of urinary excretion; this finding might reflect the slow
rate of dermal absorption.
The -liver, kidneys, lung, spleen, whole blood, and the carcass
contained higher radioactivity than any other tissues. .However, the
total radioactivity found in ;all the tissues of various groups ranged
17
-------
from only 0.15% to 0.67% of the administered dose. Therefore, very
little DEBT was sequestered in the body.
The metabolism data indicated that the absorbed DEBT was
quantitatively metabolized, and the intact DEET was below the
detection limit. Two major metabolites were found. One was formed
by oxidation of the methyl group on the aromatic ring, and it
. represented 50% of the administered DEET. The other one was
derived from oxidation of the methyl group of the aromatic ring and
N-dealkylation of an ethyl substituerit on the amide moiety. The
second metabolite represents 18% of the administered DEET.
; *' '
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.Mi' .1 c,
This study, along with its addendum (MRID 41 994402), satisfies the data
requirements for a metabolism study (Guideline 85-l)(MRID 41994401).
Human Dermal Absorption Study
In ahuman dermal absorption study, radiolabeled DEET in either 1 5% ethanol
solution (12 mg; -36 uCi) or undiluted (15 mg; -37 uCi) was dermally-applied to
tjvp groups of healthy human volunteers (6 males/group; ages ranged from 20-29
years). The test material was applied on an area of 4x6 cm2 of the forearm for eight
hours. The results showed that a small percentage of dermally applied DEET was
absorbed. The rate and amount of absorption were greater in the individuals who
were treated with the 15% DEET solution. . The level of radioactivity in the plasma
declined rapidly after cessation of exposure.
Trie radioactivity found in the urine expressed as the percentage of the applied
radioactivity was 8.41% and 5.63% for a 15% solution of DEET and undiluted
DEFT, respectively. Very little radioactivity was found in the feces (mean <0.1%).
With dermal application, the majority of the applied radioactivity remained
unabsorbed on the application site (=78% of the applied dose for a 15% solution of
DEET and 83% of the applied dose for undiluted DEET) and was recovered in skin
rinsates, swabs, and protective coverings. Based on the amount administered,
|Uminated, found in tepe-strippihg, and unabsorbed (recovered in skmrinsa^
applicator, and protective coverings), the amount of DEET penetrating into the skin
was conservatively calculated to be =26% of the administered dose for 15% DEET
and 12% for undiluted DEET. It should be noted that there was a difference in the
total recovery between the two DEET treatment groups: in the 15% group, the total
recovery was 89% of the administered dose while in the undiluted group, the total
recovery waง 94% of the administered dose. This difference is reflected in the
variations seen in the calculated dermal absorption values (i.e., 20% vs. 12%).
Essentially all of the absorbed DEET was metabolized prior to elimination in
the urine. A total of six metabolites were found; two of them were major metabolites
that were found to be similar to those seen in a rat metabolism study (MRID
18
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-------
41994401). One metabolite resulted from oxidation of the methyl moiety on the
aromatic ring of DEBT to carboxylic acid while the other one was formed through N-
dealkylation of an ethyl group from the amide moiety and the oxidation of the methyl
group on the ring. ,
The study satisfied the data requirement for a dermal absorption study
(Guideline 85-2)(MRID 42578501).
h. Neurotoxicity
Acute Neurotoxicity Screening Study in Rats
An acceptable acute neurotoxicity screening study in. rats was available.
Groups of Crl:CD VAF/Plus rats (lO/sex/dose) received a single dose of DEBT by
gavage at levels of 0, 50, 200, or 500 mg/kg. The test animals were then observed
for 14 days. At 500 mg/kg/day, rats showed signs of piloerection, increased
vocalization, a decrease in horizontal and vertical activity, and an increase in the
response time to heat. In general, these clinical signs were seen approximately one
hour after dosing with recovery 24 hours after dosing. At 200 mg/kg, a decrease in
vertical activity was observed during the first 15 minutes of the first trial at one hour
after dosing. At 50 mg/kg, ,no effect was seen in any test animals. The NOEL was
established at 50 mg/kg; the LOEL at 200 mg/kg (satisfies Guideline 81-7; MRID
41368501).
, ' ' . . /'
The Agency's Office of Pesticide Programs (OPP) Health Effects Division
Toxicity Endpoint Selection (TES) Committee debated the results of this study were
extensively. The TES Committee concluded that the decrease in vertical activity seen
at 200 mg/kg was an isolated and transient effect; the toxicological significance of this
finding is not certain. This set of data was also evaluated by Robert McPhil, Ph.D.
of the Neurotoxicity Division, Office of Research and Development, RTP, N.C. His
conclusion was similar to that of the TES Committee. Additionally, this set of data
was presented to the FIFRA Scientific Advisory Panel (SAP). The members of the
SAP also agreed with the conclusion derived by the TES Committee (i.e., the
toxicological significance of the effect seen at 200 mg/kg is uncertain). Therefore, the
NOEL for this study was then set at 200 mg/kg; the LEL at 500 mg/kg.
Multi-Generation Exposure Neurotoxicity Study in Rats
Sprague-Dawley rats were selected from the second generation (F2) offspring
from a rat multigeneration study (MRID 40979001). Whenever possible, two males
and two females were selected from each litter of each dose group'. These F2 rats had
been exposed to DEBT inutero and during lactation, and were then exposed for an
additional nine months, at dietary concentrations of 500, 2000, or 5000 ppm. A
19
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control group was also included in this study. Following the nine-month exposure,
pile male and one female from each litter and each dose group were selected for
neurotoxicity evaluations.
An increase in motor activity was seen in the 5000 ppm rats at the beginning
of the evaluation session (this effect was transient, occurring early during the test
Session.) Based on this effect, the NOEL for neurotoxicity was established as 2060
ppm (100 mg/kg/day based on standard conversion, 20 ppm = 1 mg/kg/day) and the
LOEL as 5000 ppm (250 mg/kg/day).
Although this study was not designed as a subchronic neurotoxicity screening
battery (Guideline 82-7), the duration of exposure and the parameters examined meet
lie data requirements for a 90-day neurotoxicity study (MRID 41368401). In
addition, although this study was not designed as a developmental neurotoxicity study
(Guideline 83-), it provided an abbreviated assessment of functional development
following in utero and postnatal exposure to DEBT. However, because the animals
Were not evaluated until they were adults, the effect of treatment with DEET on the
ontogeny (i.e., the history of the development of an individual) of functional
development was not assessed.
i. Special Studies: Synergistic Effect of DEET with Other
Insecticides
In addition to the required toxicity data that have been submitted to the
Agency, the following studies, which examine the synergistic effects of DEET,
pyridostigmine bromide (PB), and permethrin (PERM), have been considered. The.
Agency would like to note that there are no available data on the mechanism of action
for DEET, other than the information presented below, on the enhancement of
toxicity of PB + PERM with concurrent administration of DEET in hens and rats.
Department of Defense
As part of the Department of Defense1 s research efforts to investigate potential
pauses of illnesses resulting from service in the Persian Gulf War, a study was
iindertaken to examine the health effects of three chemicals used in the War: DEEt,
PERM, and PB. PERM is another insect repellent mat is often imbedded into
clothing and PB is an anti-nerve gas agent.
In a comparative acute oral toxicity study in male Sprague-Dawley rats,
groups of males (10/dose) received (by gavage) either DEET, PERM, or PB at doses
ranging from 2000 to 5016 mg/kg for DEET, 316 to 2000 mg/kg for PERM, and 50
to 126 mg/kg for PB. With probit analysis, the results indicated that the oral LD50 for
20
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DEBT was 3664 mg/kg; PERM, 1000 mg/kg/day; and PB, 61.36 mg/kg. These LD50
values are consistent with existing data.
In the interaction portion of the study, groups of animals (6 males/dose group)
received (by gavage) a single dose which was composed of different combinations of
DEBT, PERM, and PB. The combinations consisted of varying doses of one chemical
(DEBT, 0 to 6898 mg/kg; PERM, 279 to 3576 mg/kg; PB, 45.76 to 83.24 mg/kg)
while keeping the other two chemicals at a constant dosage which corresponded to
the LD16 (DEBT, 1946 mg/kg; PERM, 279 mg/kg; PB," 45.76 mg/kg). The results
indicated that combining PB with either PERM or DEBT resulted in a statistically-
significant potentiation in mortality which was substantially greater than the, expected
additive effect (at a dose which corresponds to LD16: 2X for PB + PERM; 3X for PB
+ DEBT). In contrast, combining DEBT and PERM yielded a mortality rate that was
less than the expected additive effect.
The author of the report offered an explanation for the potentiation of
mortality produced by the combination of PB with either DEBT or PERM A
possible mechanism for DEBT is that when PB is combined with DEBT, DEBT may
facilitate the absorption of PB leading to an increase hi the PB level in the blood, an
increase hi inhibition of cholinesterase activity, and higher mortality. A possible
mechanism for the observed potentiation produced by a combination of PB arid
PERM is the inhibition of the detoxification system by PB, leading to an increase in
the residence tune of PERM in the body (MRID 43763201).
While this study provides suggestive evidence of interactions between DEBT
and PERM/PB when used in combination, it does not provide significant information
concerning the tpxicity of DEBT when it is used by itself.
.: Duke University
In this published study} groups of egg-laying leghorn hens (5/group) received
DEBT (>97%, 500 mg/kg/day, sc); permethrin (=94%, 500 mg/kg/day, sc); or PB
(ฃ 99%, 5 mg/kg/day, po) individually or in combinations of two or three for 2 months
(5 days/week). Under the conditions of this study, the following compound-related
effects were seen:
Combination Treatments. No deaths were seen in the hens treated with
individual chemicals. However, with combination treatments, 1/5, 2/5, and
2/5 hens died in PB+permethrin, PB+DEET, and DEET+permethrin treated
groups, respectively. Only 1 hen survived when DEBT, permethrin, and PB
, .were administered concurrently to 5 hens. '
21
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Individual Administration. With individual administration, DEBT produced
clinical signs characterized by rapid shallow breathing and tendency toward
inactivity shortly after dosing, but the treated hens recovered within 24 hours.
A slight decrease in body weight was also found in this group of hens.
Histopathology showed a small increase in the incidence of slightly enlarged
axons (2/4). An inhibition of plasma cholinesterase activity (20%) was seen.
PB produced mild and transient signs of cholinergic toxicity characterized by
decreased activity and diarrhea. Plasma butyl cholinesterase (BuChE) was
inhibited by as much as 83%. Permethrin did not produce clinical signs, but
it induced minor neuropathological changes characterized by slightly enlarged
axons. Brain ChE activity was not affected by any of these three chemicals.
I i, " !"H, ' i "' ' i ,ป' 'i ,',','',, : ' ' ', , ,',' ' ""' : " ' ' ' 'V -'' ' ,"' ,i , V ' ' ',' ' J
In general, hens treated with a combination of two chemicals produced more
toxicity than the individual compound did; however, the enhanced toxicity did not
approach an additive effect. The combination of the three chemicals yielded even
more toxicity, and again the toxicity was less than the additive effects. The enhanced
toxicity seen in the combined treatment in hens of this study was consistent with the
findings of an acute oral toxicity study in male rats (MRID 43763201).
In this study, the subcutaneous injection of DEBT results in direct access to
the blood'. A dose of 500 mg/kg/day sc is rather large. The dermal absorption data,
derived from a study with human volunteers, indicated that approximately 12% of the
, iM ;." i,;1' , i, i .viti =. . , ,. . , ",ii," ..i i,"! . -'ff, ,,; , ., r ., i,
administered dose on the forearm was absorbed (MRID 42578501). To achieve a
,: iijjj, ,',','' . ' i; i, , , >;:,i'!1', ill"1 "'Js; J'i i1! i'1 ; i i'.1 ' iir''i "i11, ;""! i ! .11 " " ' ' ;. 'ii, ' ,,,,''";! "ill1,1 'H " ;'! "ire'IP"' !'! '' " ' i ' 'H ,' '' ' " ;.ii, < ' "i!M '' ' .,'i'' I!":1, I1 V.!i' iii: '."ji111 iiiiiH,,
subcutaneous dose of 500 mg/kg/day in humans would have required a dermal dose
(Jill V ,,- ., ,i-:l-f I '!"!,,", f '.'' J.'l >, -,~f ฐ ' , I. ::, . " - .. 1
of approximately 4,167 mg/kg/day, which is an excessive dose. For an average
person with a body weight of 70 kg, an amount of 292 g of DEBT would be required
to achieve this dose. Therefore, the results derived from this study are relevant to
excessive exposure to DEBT and coexposure to PB and/or permethrin. Currently,
ihere are no data to indicate whether or not an interaction would take place at lower
- doses. ' ' "' ' ' "
'nil* 1
i It
j. Incident Data
'\i~ t 1 >;', '. . ..'. ' -., ..'',' : ' -,: ', ': ., .,'*' . - .' , "i . v ..'':;' ', . " ,;.ป!', i. 'iV ป
DEBT has been commercially marketed for use as a personal insect repellent
Since 1965 (Veltri, et al., 1994). Today, it is a widely used insect repellent in the
United States and the world., Currently, approximately 30% of the U.S. population
Sses DEBT annually (Veltri, et al., 1994).
Prior to a cluster episode in 1989, there were six cases of seizure in children
(all female, aged 1-8 years) reported in the medical literature. Three of these children
died and all had received very frequent and/or extensive applications of DEBT. In
TJiifl'SiT :;I'M'; , ; ป,ป, : !j ',, < ;;" ,< , 11' "'/ ^ ;,' * j ,, .^\ ; ,. i,- ^ ,,| 4 , i, : - *
1989, the New York State Department of Health received notification of five cases
of generalized seizures, including four children and one adult. All of these cases were
22
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males and four of the five had fewer than three previous applications. None of the
cases died (Oransky, 1989). .,
Between 1989 and 1995, the Agency was notified of three cases of seizure
related to dermal application of DEBT. Two of the cases were children, a 3-year old
girl and a 2-year old boy. Both of the cases recovered, although the girl reportedly
went into cardiac arrest and was revived with CPR. The third case was an adult male
who applied the product twice, had a seizure arid died from choking on the food he
was eating at the time of the seizure. ,
; Two annual reports have been submitted by the DEBT Joint Venture covering
all cases reported in 1995 and 1996. There were 32 cases that mentioned some type
of seizure activity in 1995 and 1996 that coukTnot be ascribed to some other likely
cause based on the information initially collected. A number of the cases reported
in 1995 and 1996 are still undergoing follow-up to obtain medical records and
complete the supplemental questionnaire forms. Once this review is completed, some
of the cases will be more likely due to other causes besides DEBT exposure. Until
this review is .completed, however, no firm_c6nclusions should be drawn concerning
these 32 cases. ,: -
In summary, since 1960, there have been 14 cases of seizure, including four
deaths, potentially related to DEBT exposure, for which other more likely causes have
not been identified. An additional 32 cases of seizure reported to the national DEBT
registry are currently under review. Thus, the final number of potential DEET-
associated seizures will fall between 14 and 46 cases since 1960. This range is subject
to both over- and under-reporting. Seizure coinciding with DEBT use can be
expected, given an estimated 15,000-20,000 afebrile/(occurring without a fever)
seizures in children (aged 0-19 years) estimated annually and an estimated 1.7. million
children using DEBT perhaps as often as 10 times a year. On the other hand,
physicians may fail to check for history of DEBT use or fail to report cases of seizure
subsequent to DEBT use. As noted in the Morbidity and Mortality Weekly Report
editorial on the five cases in 1989, "Anecdotal reports of seizures are difficult to
interpret. None of the recent cases in New York and Connecticut have been clearly
established as DEBT toxicity" (Oransky, 1989). Taking all the cases together, it does
appear that some of the cases are likely related to DEBT toxicity, though it is not
possible with certainty to say which ones. ~ .
In 1989, the Agency notified the Centers for Disease Control and Poison
Control Centers through a physician's advisory of our concern forthese health effects
and asked them to report any new cases. The Agency also urged the manufacturer
to undertake a review of Poison Control Center records. Neither the manufacturer's
review of over 9,000 DEBT exposures nor the Agency's physician advisory revealed
any new cases of seizure that could be substantiated with medical records. Given only
14 to 32 cases since 1960 (the first case.was reported in 1961) and 50-80 million
23
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11 ! :; i' i1
people using DEBT each year, the observed incidence of recognized seizures is about
brie per 100 million users.
2. Toxicological Endpoints for Risk Assessment
Exposure to DEBT occurs in the short to intermediate term; chronic exposure
is not expected. The Agency's Office of Pesticide Programs (OPP) Health Effects
Division Toxicity Endpoint Selection (TES) Committee considered subchronic dermal
and neurotoxicity data for the short and intermediate-term endpoint. Even though
chronic exposure is not expected, the Agency's OPP Health Effects Division RfD Peer
Review Committee established a chronic endpoint to be used in the evaluation of
potential chronic exposure. These endpoints are discussed in detail below.
a. Carcinogenicity Classification '
The RfD Peer Review Committee has recommended that DEBT be classified
as Group D (i.e., not classifiable as a human carcinogen) because the mouse and rat
Carcinogenicity studies did not demonstrate any carcinogenic potential and because
the Committee believed that the male rats could have tolerated higher doses. A
Group D classification is generally used for agents with inadequate human and animal
evidence of Carcinogenicity or for which no data are available.
b. Other Toxicological Endpoints
On October 18? 1995 the TES Committee met to discuss the toxicological
gndppints to be used in the risk characterization for DEBT. Exposure to DEBT
occurs in the short to intermediate term; chronic exposure is not expected. Because
f! ' ,'i,, , - i v , ri ,: , 'i.h' ; ,,. ^ Mi : .,' / :> *'y ..' , ,. ,'!!:: "I1,/ >:,' '.ซ', ' ': , ' M - >i '. 'S T
e reported incidences were neurological in nature (i.e., seizures), the Committee
evaluated the entire toxicology database on DEBT with emphasis on the available
acute and subchronic neurotoxicity screening studies. The Committee concluded that
the observed toxicological effects from laboratory data are not toxicologically
significant with respect to the labeled use of DEBT; the following provides the
Committee's rationale for this conclusion.
Neurotoxicitv
In a subchronic neurotoxicity screening study in rats (MRID 41368401),
groups of rats received DEBT in the diet at concentrations of 0, 500,2000, or 5000
ppm over two generations. There was an increase in horizontal activity and a
decrease in body weight of rats dosed at 5000 ppm. The LEL was established as
5000 ppm (250 mg/kg/day, based on a standard conversion of 20 ppm = 1
rng/kg/day); NOEL, 2000 ppm (100 mg/kg/day).
In an acute neurotoxicity screening study (MRID 41368501), groups of rats
(10/sex/dose) received DEBT by gavage at dose levels of 0, 50, 200, or 500
24
-------
mg/kg/day. A suggestive increase in the horizontal activity was seen in 500 .
mg/kg/day females on day 14 after cessation of treatment: However, at one and 24
hours after dosing, there was a significant decrease in horizontal and vertical activities ;
in 500 mg/kg/day rats.
Subchronic Dermal Toxicity .
Two subchronic dermal toxicity studies were considered: One 90-day dermal
toxicity study in micropigsฎ and the second a 90-day dermal toxicity study in. rats.
In the micropigฎ study (MRID 41987401), DEBT was dermally-applied to groups
of micropigsฎ at dose levels of 0 (water), 100, 300, or 1000 mg/kg/day b.w, for 13
weeks. Under the conditions of the study, DEBT did not produce any systemic
effects at any dose levels. At the skin application sites, DEBT produced skin irritation
and histological changes which would be reversible upon termination of the treatment.
Therefore, the NOEL for systemic toxicity is 1000 mg/kg/day (i.e., the HDT).
In the rat study (MRID 40241702), groups of CDฎ rats (15/sex/dose) '.
received DEBT by dermal application at doses of 0,100,300, or 1000 mg/kg/day for
90 days. In the high dose males, there was a decrease in body weight. An increase.
in kidney and liver weights was seen in high dose males. An increase in the incidence
of renal lesions was seen in all treated males. The renal lesions were characterized by
inflammation, tubular regeneration, hyaline droplets, and granular casts in the renal
tubules. Marginal increases in the incidence of renal lesions were also seen in high
dose females. Skin irritation at the application sites was seen in all compound-treated
rats. , , , . . . .
The renal lesions seen in all treated males were shown to be associated with
the accumulation of c^-globulin in the renal tubules of the affected rats, and they
were shown to be unique to DEBT treated male rats. ,The a2fl-globulin-associated
renal lesions were evaluated by the Agency, and the Agency concluded that they
should not be used as an endpoint for determining non-carcinogenic hazards hi
humans. Therefore, based on a decrease in body weight gain and an increase hi liver
weights, the LEL is 1000 mg/kg/day (i.e., the HDT) and the NOEL is 300 mg/kg/day.
Endpoint Selection
A -
The TES Committee determined that the possible neurotoxic effect in the two
neurotoxicity screening studies was not robust enough to provide an adequate basis
for risk assessment for the following reasons: (1) the increase hi horizontal activity
seen in the 225 mg/kg/day dose of the subchronic toxicity test was transient with
significance only at the first measuring period; (2) the effect was not accompanied by
any clinical signs or histopathological changes; and (3) the magnitude of the effect
25
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was small. The members of the Committee proceeded to consider the subchronic
dermal toxicity data.
The Committee debated the probability of using the NOEL of 300 mg/kg/day
firpm the subchronic dermal tpxicity study in rats (MRID 40241702) as an endpoint
o'r any significant alterations hi biochemical parameters which are frequently
associated with liver injury. Therefore, the increase in liver weight could be an
adaptive response. The decrease in body weight gain was modest. In addition, 1000
mg/kg/day is a relative high dose and it is also the limit dose for chronic toxicity and
oncogenicity studies. Based on these considerations and the labeled dermal use of
DEET, the Committee concluded that the minor effects seen in such a high dose
(i 000 mg/kg/day) were not sufficient to justify setting a short and intermediate term
endpoint for conducting a quantitative risk assessment.
3. Children's Special Sensitivity
Children may be more or less sensitive to the potentially harmful effects oif
pesticides than adults (because of body size, physiology, etc.). To determine if there
are any special sensitivities to children, the Agency looks at the overall use pattern
(e.g., food-use, non food-use, residential exposure, etc.) along with the available
f ^productive and developmental toxicity data. DEET is a non-food use pesticide that
is vised almost exphisively in a residential setting; the few non-residential uses are for
veterinary applications. With respect to the additional uncertainty factor for
enhanced sensitivity of infants and children (as required by FQPA), EPA has
concluded that it is not warranted; the rationale is outlined below.
In a.two-generation reproductive toxicity study in rats (MRID 40979001), no
compound-related effects on the reproductive parameters such as fertility, gestation,
and viability were noted up to dietary doses of 5000 ppm, A systemic effect
(reduction in the body weights of pups hi late lactation) was noted hi the highest dose
fisted, which is 5000 ppm (or 250 mg/kg/day, based on standard conversion, 20 ppm
= 1 mg/kg/day). In parental animals, no NQEL was established; kidney effects were
observed in adult males at all treatment levels.
In a developmental toxicity study in rats (MRTD 41351401), some signs that
are suggestive of neurotoxicity (e.g., hypoactivity, decreased muscle tone), were
ilbted in the high-dose dams (750 mg/kg/day); however, these effects were transient.
Also, in the high-dose dams, there was an increase in mortality rate, a reduction in
tปpdy weight gain and food consumption, and an increase in mean liver weights.
Further, in the high-dose dams, a slight increase in post-implantation loss and a
statistically-significant decrease in mean fetal body weight/litter was seen. No
26
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additional compound-related effects were found. Based on these findings, the NOEL
for maternal toxicity was 250 mg/kg/day and the LEL was 750 mg/kg/day. The
NOEL for developmental toxicity was 250 mg/kg/day and the LEL was 750
mg/kg/day (based on a statistically-significant decrease in mean fetal body
weight/litter).
In a developmental toxicity study in rabbits (MRID 42141101), no compound-
related maternal or developmental toxicity was noted. The NOEL for maternal and
developmental toxicity was 325 mg/kg/day (i.e., the HDT). Although the study
results indicated that the test animals could have tolerated higher dose levels, these
data are useful in that they confirm the results of a much earlier developmental study
.in rabbits where pregnant rabbits received DEET by dermal application at doses as
high as 5000 mg/kg/day and no developmental toxicity was seen.
Based on the existing reproductive and developmental toxicity data, there is
no evidence that would lead the Agency, to believe that DEBT is uniquely toxic to
infants and/or children. This conclusion is based on the following evidence:
The reproductive study shows that DEET produces systemic toxicity (i.e:,
reduced body weights) in the offspring at a dietary treatment level of 500
mg/kg/day, while in adult males, kidney effects were observed in all treatment
, .levels, including the LDT (22.5 mg/kg/day). - - ,
Among the developmental studies where effects were noted (i.e., the rat
study), the NOEL for the developing offspring was the same as that of the
mother (i.e., 250 mg/kg/day). .
4. Dietary Exposure and Risk Characterization
A dietary exposure and risk characterization for DEET is not required, based
on the current use pattern and the absence of dietary exposure for this pesticide.
5. Residential Exposure and Risk Characterization
DEET is a chemical that repels (but does not kill) insects. Most of the 200 or
so registered end-use products are intended for residential human use; there are a few
products registered for veterinary uses. Among the residential human (i.e., non-
veterinary) end-use products, all but four are products that are applied directly to the
skin and/or clothing. The four products that are not applied directly to skin include
two that have DEET imbedded in picnic tablecloths and two that have DEET
imbedded in a wristband.
DEET products that are applied directly to skin and/or clothing are available
in numerous formulation types (e.g., aerosol sprays, non-aerosol sprays, creams,
lotions, sticks, foams, and towelettes) and concentrations (products range from -4%
27
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a.i. to 100% a.i.)- Often, the lower concentration products (those less than 30% a.i.)
are formulated as sprays while-the higher concentration products (those greater than
50% a.i.) are formulated as creams or lotions.
' ' i
The following exposure and risk characterization is limited to the non-
veterinary uses of DEBT.
;>'",!!ซ: ;' ''..' ;.. ' !>,' ';. ..' V / .I' ',-'"' '"":'- : "i '':''; ' ':' '''.," ;: > ;. .'.' ;"',Y> ,1';f!.'
a. Residential Exposure
Tablecloths and Wristbands
Exposure to DEBT from these two product types will be via the
dermal route. Because the pesticide is imbedded into the matrix (i.e.,
tablecloth or wristband), the Agency expects that human exposure to the
active ingredient will be negligible.
Products Applied Directly to Skin and/or Clothing
Most DEBT end-use products are formulated as sprays, creams, etc.
that are intended to be applied directly to trie skin and/or clothing; thus, the
Agency assumes that the primary route of exposure will be dermal. The
Agency recognizes that exposure via the inhalation or oral route is possible.
However, such exposure would be accidental (e.g., spraying the product in
the eyes because the can was pointed the wrong way) or would result from
misuse (spraying in an enclosed area such as a tent). In any case, any
exposure via the inhalation or oral route will be much less than exposure via
'ijll ;. :'.'. the dermal route, ii:, .. , ' '
: DEBT products are used by both adults and children. Users of DEBT
are expected to be exposed to the product intermittently for days or weeks
(acute to subchronic exposure). The Agency considers acute to subchronic
exposure to be one to several weeks; chronic exposure is generally considered
to be over a long portion of an individual's lifetime and is continuous. Tne
Agency expects mat residential exposure to DEBT would be subchronic;
except in the most unusual circumstances (e.g., military personnel who are in
the field for an extended period of time), long-term exposure (chronic) is hot
expected.
iff
DEBT products are applied by spraying or spreading the material
directly onto the skin and/or clothing. In terms of pesticide exposure patterns,
that of DEBT is unusual in that it is one of the few residential-use pesticides
that is applied directly to skin. The amount typically absorbed is a function
of the product formulation and the area of the body to which it has been
28
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' applied. Products that are formulated by diluting concentrated DEBT with a
solvent such as ethanol have a greater dermal absorption than products that
are undiluted. This point is illustrated in the human dermal absorption study
(MRID 42578501). in which a 15% DEBT product yielded 20% dermal
absorption while an undiluted DEBT product yielded 12% "dermal absorption.
Dermal absorption of pesticides is approximately four times greater around
the ears than the forearm (Maibach, 1971).
In 1991, the DEBT registrants submitted a study to the Agency where
the amount of DEBT an individual typically applies to himself or to children
was measured. Assuming one application per day and standard body weights,
the following Daily Exposure estimates were derived (Table 3):
i , ' " " " ' " '
Table 3. Daily Exposure Estimates for DEET
Category of
Exposure
Adult Male
Adult Female
Child, 13-17
Child, ^ 12
AmtofDEET
per Application (rag)
952.25
649.31
1065.35
940.83
Body
weight (kg)
78.7
67.1
50.6
25
Daily Exposure
(mg/kg/day)
12.10 :
9.68
21.05
37.63
CATEGORY OF EXPOSURE. To differentiate among adult males, adult females, and children, the study
investigators provided exposure estimates for each of these sub-groups.
AMT. OF DEET USED PER APPLICATION. This is the total amount of product applied; it has been
corrected for the concentration of the product used. .
BODY WEIGHT. These are mean body weights; they were obtained from the "Exposure Factors Handbook."
DAILY EXPOSURE (mg/kg/day). This was derived using the formula':.
Daily Exposure = Amount of DEET per application (or day)
(mg/kg/day) Body weight (kg) ,
The Agency recognizes that there are many shortcomings with these exposure
data and that they may be underestimating exposure. For example, common sense
indicates that users of DEET may apply the product two or three times in a single day
(not just once), depending on the concentration of product being used and the level
of insect infestation. Also, these data do not consider exposure via the inhalation or
oral route (however, this omission is not expected to significantly underestimate
exposure as dermal exposure to DEET is so much greater than inhalation or oral).
However, even though there are weaknesses with these data, the Agency believes that
they are useful in that they provide an idea of the magnitude of DEBT exposure.
29
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b.
Risk Characterization
!;ง,;>
fl,
Based on the results of extensive toxicity testing, the Agency believes that the
Use of DEBT does not present a health concern to the general U.S. population. The
.' i-Eli ' I ", V, 1 ' I"' .Jl!!! . SI ,i * , - , , , y , , , -..III .,.. Si. , , ,. l.-T. f.... .; .-
toxicity of DEBT has been investigated since the 1940's when the U.S. Army first
MB , ...ir: ' ,' .,-,. ,:: ., ,.-ซ , .. _, ,H',,|,.. ,:, , .11,.' ' , :.!, MM . Mr,,, i ,:, ....,. .1-1 J- , Hi,.,: ,
developed and patented it for use by military personnel in insect-infested areas. In
acute toxicity testing using the technical grade material, DEBT exhibited relatively
jjiild effects. For example, in rabbits, eye and dermal irritation were exhibited;
however, both conditions cleared within a week. Also, the LD50 values were quite
1 ill i ', I" .II111..' / , , ซ,, -I II , Ill ., . j" ':,.., .,,.,,.. ,, ' -l|.|, i;.,,,, I", ,, <","i, ,, , , , ; ||,,, ' ,;;,| -lh ,lv
high, on the order of four grams of test material per kilogram of body weight.
In addition to acute effects, DEBT has also been tested for an entire battery
of subchronic and chronic toxicity effects. Although some minor effects were seen
a| the 4ฐงes tested, the data do not show DEBT to be carcinogenic, significantly
aevelopmentally toxic, nor mutagenic.
Even though the empirical testing does not demonstrate significant human
toxicity to DEBT, there are a few reports of individuals experiencing adverse effects
after using a DEBT product. Over the past 35 years, 14 people have reported having
a seizure as a result of being exposed to DEBT. Twelve of these individuals were
children and two were adults. Among these 14 incidents is the cluster of five that was
reported to the New York State (NYS) Department of Health in 1989. The Agency
has analyzed these incidents and cannot, at this time, conclude that these seizures are
directly related to DEBT exposure. However, neither can the Agency definitely
Conclude that they are not DEET-related. As noted in the Morbidity and Mortality
Weekly Report editorial on the five NYS cases in 1989, "Anecdotal reports of
Seizures are difficult to interpret. None of the recent cases in New York and
Connecticut have been clearly established as DEBT toxicity" (Oransky, 1989).. One
possible explanation for the seizures is coincidence. Seizure coinciding with DEBT
is not unexpected, given an estimated 15,000-20,000 afebrile seizures hi children
(ages zero-19 years) estimated annually and an estimated 17 million children using
DEBT 10 times a year.
External Review
The FIFRA Scientific Advisory Panel (SAP) generally agrees with EPA's
conclusion. In June 1997, OPP presented DEBT to the SAP; the Agency felt that it
would be wise to do so as DEBT is such a widely-used consumer pesticide. Three
questions were presented:
(1) Based on the currently available data on DEBT, OPP requests that the
members of the SAP comment on OPP's hazard characterization of
this chemical and the decision not to establish toxicity endpoints for
risk assessment.
1 "i
30
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(2) What do you think about our approach to and methodology for the
risk assessment and characterization?
-1
(3) What is your opinion of our interpretation of the incident information?
(EPA believes that the reported incidences are inconclusive).
In response to the first two questions, the Panel stated that it "agrees with the
Agency's hazard characterization and decision not to establish toxicity eridpoints to
be used for risk assessment, as exposure to DEBT does not result in clearly
characterized specific toxicological responses; to rationally choose toxicity endpoints
that reflect a consistent response to DEBT would be impossible." Additionally, the
Panel suggested that the EPA improve upon its exposure assessment by looking at
multiple applications, inhalation, and chronic exposure. With respect to the incident
information, the SAP indicated that it "agrees with the Agency's interpretation of the
incident information (that the reported incidences are inconclusive). There is no
compelling information that exposure to DEBT is causing an appreciable number of
seizures, and data from animal studies do not support or predict symptoms
experienced by children exposed to DEBT."
Conclusion
In summary, the Agency concludes that, based on the currently available
information, the use of DEBT as an insect repellent does not pose a significant health
risk to the general U.S. population for the following reasons:.
(1) DEBT is not believed to be acutely toxic nor carcinogenic, significantly
developmentally toxic nor mutagenic at the doses tested.
(2) The available data do not support a direct link between exposure to DEBT
and reported seizure incidences (14 cases). ,
However, because DEBT is: (1) so widely used among the U.S. population,
including children; (2). is one of the few residential-use pesticides that is applied
directly to the skin; and (3) has been thought to be associated with incidents of
seizure, the Agency believes that it is prudent to require unproved label warnings and
restrictions for DEBT products. The Agency believes, that such common sense
measures will be especially protective of children and other individuals who may be
more sensitive to chemical substances.
Finally, in a continuing effort to monitor and understand DEBT poisonings,
the Chemical Specialties Manufacturers Association (CSMA) has recently set up a
DEBT registry through PEGUSran independent research company in Utah. They
have made agreements with a number of Poison Control Centers (PCCs) to collect
31
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iriformation and follow-up on any serious DEET-related cases. The information will
be collected to determine whether any seizure type effects may have been related to
DEBT use.
C. Environmental Assessment
1. Ecological Toxicity Data
A limited set of tpxicity data are required for pesticides that have only indoor
uses. N,N-diethyl-meta-toluamide (DEBT) qualifies for a reduced data set, because
use patterns are limited to indoor nonfood and indoor residential. The data available
are adequate to assess the hazard of DEBT to nontarget terrestrial and aquatic
organisms.
" ' : !, tl . , ' '' ' , 1 . .1 ' '' , " i.' ' I! I' , " "I"!" '!"' ' ,.',"! ป'' '." " . . , ' ' ," "'Si,' I1
a. Toxicity to Terrestrial Animals
(1) Birds, Acute and Subacute
To establish me toxicityofT>EET to birds, the following test
is required using the technical grade material: a single-dose oral
(LD50) study on one avian species (preferably mallard or bobwhite
quail). Subacute dietary studies (LC50) on a waterfowl species and an
upland gamebird species are waived. Table 4 summarizes the avian
'. , " :"ji" . ,;'' '.; : 'apiite oral findings' for DEBT:
! "' Vti .- " ': ' I '"'"' ' ,' I- ..I ,',;, ' ,;" , ' : '" ,;,'" ." "!'' '" ;'''.':',, , , "' , ' ' !.,..'.. ',ป
,,'i,i|'l ' ' ' ''',,' f " . , ' ' '<"' , . ,i. '' . -Ill i. ,.,,.!!.," i" ', ' .' 1 ' ' . ' ,,., I" ,',' ,' " ''i, SlB' ,
Table 4: Avian Acute Oral Toxicity
Species
Northern Bobwhite
% A.I.
98.3
LDSO (mg/kg)
1375
MRTONo. Author/Year
41159701 (Grimes and Jabar, 1989)
Toxicity Category
slightly toxic
These results indicate that DEBT is slightly toxic to avian species on
an acute oral basis. The guideline requirement'for an acute oral
toxicity test is fulfilled. (MRID 41159701)
(2) Mammals
Wild mammal testing is required on a case-by-case basis,
depending on the results of the lower tier studies such as acute and
subacute testing, intended use pattern, and pertinent environmental
fate characteristics. In most cases, however, an acute oral LD50 from
the Agency's Health Effects Division (HED) is used to determine
toxicity to mammals. This LD50 is reported below.
32
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Table 5: Mammalian Acute Oral Toxicity
Species
Rat (smallmammal surrogate)
LD50(mg/kg)
3900(73.0%ai)
MRTONo.
41678101
Toxicity Category
practically nontoxic
the available mammalian 'data are sufficient to characterize DEBT as
practically nontoxic to small mammals on an acute oral basis.
b. Toxicity to Aquatic Animals
(1) Freshwater Fish
To establish the toxicity of DEBT to freshwater fish, the
minimum data required on the technical grade of the active ingredient
is one freshwater, fish toxicity study with a coldwater species
(preferably the rainbow trout). The following acute toxicity findings
with coldwater fish species apply to DEBT:
Table 6: Freshwater Fish Acute Toxicity
Species
Rainbow trout
% A.I.
95
LC50 ppm a.i.
75
MRID No.
00001026 (McCann, 1972)
Toxicity Category
slightly toxic
The results of the 96-hour acute toxicity study indicate that
DEBT is slightly toxic to fish. The guideline requirement is
fulfilled. (MRID 00001026) '
(2) Freshwater Invertebrates
The minimum testing required to assess the hazard of
a pesticide to freshwater invertebrates is a freshwater aquatic
invertebrate toxicity test, preferably using first instar Daphnia
magnet or early instar amphipods, stpneflies, mayflies, or
midges. The following acute toxicity findings apply to DEBT:
Table 7; Freshwater Invertebrate Toxicity
Species
Daphnia magna
% A.I.
100
EC50 (ppm)
75
MRID No. Author/Year
00243419
Toxicity Category
slightly toxic
There is sufficient information to characterize DEBT as
slightly, toxic to aquatic invertebrates. The guideline
requirement is fulfilled. (MRID 00243419)
2.
Environmental Fate
33
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a.
Environmental Fate Assessment
Because of its limited use pattern, the only environmental fate study
required for DEBT was hydrolysis. The registrant submitted a hydrolysis
study that satisfied this data requirement (MRID -40192701). That study
demonstrated that DEBT is stable tp hydrolysis in solutions initially buffered
to pH 5,7, and 9. It can be concluded that DEBT will be stable to hydrolysis
at pH levels found in the environment.
3. Exposure and Risk Characterization
a. Ecological Exposure and Risk Characterization
(1) Exposure and Risk to Nontarget Terrestrial Animals
Environmental risk assessments are not conducted for
pesticides with exclusively indoor use patterns. N,N-diethyl-m-
toluamide (DEET) is considered to be an "indoor residential" use
rather than an outdoor use because it is only applied directly to the
human body/clothing, cats, dogs, pet quarters, and
household/domestic dwellings. Application of DEBT to these sites is
not likely to adversely affect terrestrial wildlife or aquatic organisms.
'..'., , ' I, I ''"!!, ! " , I' '. " , ซ','',, I, .ill" '! *|r " '!! ,. " ' ,i ' ' .' ' ' I; ' . T .' ' ;. ,,ปซ', :'i v'l'.,
A limited set of toxicity data for indoor-use pesticides is
required to determine precautionary label statements and to assess
environmental hazards in case of spills. The available data
characterize DEBT as slightly toxic to birds, fish, and aquatic
invertebrates and as practically nontoxic to mammals.
(2) Endangered Species
Based on the current indoor-only use patterns and the
relatively low toxicity of DEET, risks to endangered species are not
anticipated.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
ii mi i
II 111 > III
A. Determination of Eligibility
I Ml * * I i j I
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether products containing the active
ingredient are eligible for reregistration. The Agency has previously identified and required
the submission of the generic (i.e. active ingredient specific) data required to support
34
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reregistratipn of products containing N,N-diethyl-meta-toluamide (DEBT) active ingredients.
The Agency has.completed its review of these generic data, and has determined that the data
are sufficient to support reregistration of most formulations/uses of DEBT under the
conditions specified in this RED. Appendix B identifies the generic data requirements that
the Agency reviewed as part of its determination of reregistration eligibility of DEBT, and
list? 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 DEBT and to determine that DEBT can be used without resulting in
unreasonable adverse effects to humans and the environment if used according to the labels
as amended by this RED. The Agency therefore finds that most products containing DEBT
as the active ingredient are eligible for reregistration under the conditions specified in this
RED. The Agency will defer its decision regarding the eligibility of products/formulations
that combine DEBT and sunscreen until an advisory panel has been convened and has made
specific recommendations to the Agency concerning the reregistration of these products.
DEBT products with labels that make child-safety claims are ineligible for reregistration, and
can only be reregistered when all child-safety claims (including trade names) are removed
from product labels. In order to be eligible for reregistration, DEBT products with cosmetic
claims must conform to the labeling requirements for these products as outlined in Section
V. of this document. .
. The Agency made its reregistration eligibility determination based upon the target data
base required for reregistration, the current guidelines for conducting acceptable studies to
generate such data, published scientific literature, etc. and the data identified in Appendix B.
The Agency has found that all uses of DEBT are eligible for reregistration under the
conditions specified in this RED, except for uses/formulations that Contain sunscreen and
uses/formulations that make child-safety claims. Child-safety claims must be removed from
end-use product labels in order for those products to be reregistered. It'should be understood
that the Agency may take additional appropriate regulatory action, and/or require the
submission pf additional data to support the registration of products containing DEBT, if new
information comes to the Agency's attention or if the data requirements for registration (or
the guidelines for generatirig such data) change.
B. Determination of Eligibility Decision
.' ' . ."' *
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredient DEBT, the
Agency has sufficient information on the health effects of DEBT and on its potential
for causing adverse effects in fish and wildlife and the environment. The Agency has
determined that DEBT products, labeled and used as specified in this Reregistration
Eligibility Decision, will not pose unreasonable risks to humans or the environment.
35
-------
'.ill V
1;,
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'w'lill'liii,' .'IS
The Agency is concerned in general with the use directions and label
pecautionS for all DEBT end-use products. EPA believes that it is prudent to
require consistent, protective, and common sense directions to prevent
oVerapplication and misuse. The Agency is particularly concerned with DEBT
registrations for which cosmetic claims are made, where DEBT is formulated with
sunscreen, and where labeling indicates that use is safe for children. Consequently,
|11 DEBT registrations (with the exception of the products containing sunscreens) are
eligible for reregistration as long as labeling is amended as specified below.
Although the scientific data reviewed for DEBT do not show it to be
carcinogenic, developmentally toxic, nor mutagenic, there have been seizure incidents
associated with DEBT use. The Agency has concerns regarding these seizures,
especially for children who are more susceptible to seizures in general and who
rjceiye a higher dose of DEBT due to a greater surface area to body weight ratio.
This concern is heightened due to the manner in which DEBT is applied: directly to
the skin. Therefore, the Agency is requiring label directions for the safe, effective
application and reapplication of all DEET-contaming products.
" ,!", In " ' ,.'!' ป' , ' " 7 'i ' ',,'',,', ' I '"' '" ' ' ' . !'','' ,'i " i ' ' ป'' i "'"'
l|J ,,"" ' " I ',ป,!. '' , , , if , ' I'l' ' i I1 'ii'1!."' ! ", , | 'ป ' ' I .' I1 i, i i,l' '' , ' III," i ' .Ill,",],
The Agency will defer its decision regarding the reregistration eligibility of
products/formulations that combine DEBT and sunscreen until the Agency has
solicited the views of various governmental agencies and other groups. Additionally,
the Agency will not act on any pending registration applications under section 3 until
tfrat time. As stated in the amended Reregistration Standard (dated March 1985), the,
Agency will not register products whose acute toxicity falls into Toxicity Category
I or II. Additionally, end-use products must not be corrosive tp the eye or cause
cbmeal involvement or irritation persisting for 21 days or more.
The Agency is concerned about consumer use of products mat combine
sunscreen arid DEBT, since directions to reapply sunscreens generously and
frequently may promote greater use of DEBT than needed for pesticidal efficacy and
thus pose unnecessary exposure to DEBT. DEBT labels currently recommend that
llnil'll | *,, ,11 ,|| n j ^ |iii,, j .. ".r ih,, ',,". ipi 4,1" ,,.', i I ,| f , ,, * i /I",, ]! m ,i| ,|, , . , ,i ,, ,, i ,|l , . , ,,*N|, ,, . ,| , " ,||i, ,,11, J, , 'I,,,!',! " ,|,|,, ||1, |>,
products be used sparingly and not be reapplied too often. Sunscreen products,
however, recommend frequent reapplication. No benefits attach to use of DEBT
more frequently than necessary to achieve its purpose. Products containing DEBT
which have cosmetic claims could encourage the user to apply the product for reasons
other than to repel insects resulting in unnecessary exposure. DEBT
uses/formulations whose labels make child-safety claims are ineligible for
reregistration. DEBT uses/formulations with labels that make cosmetic claims must
be labeled such that label statements and use directions regarding insect repellency
appear first and more prominently on the label than cosmetic claims.
Finally, brand names for certain DEBT products with 15% or less DEBT
Britain statements suph as "for kids" or "for use on children," Products with child
safety" claims are ineligible for reregistration because the Agency believes such claims
are false and misleading. The Agency is generally wary of safety claims and EPA
regulations specify that safety claims for pesticides are, on their face, false or
36
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misleading. 40 C.F.R. ง 156.10 (a) (5) (ix). However, the Agency does not believe
this regulation would necessarily bar a children's version of a personal use pesticide
if such product was formulated based on scientific testing. But that is not the case
here. The Agency believes there is no factual basis to support a claim that certain
DEBT products pose significantly lower risk to children. The children's safety claims
appear on certain DEBT products containing 15% or less DEBT and thus, the Agency
presumes, these claims are tied to the percentage of DEBT in the product. Yet, the
scientific data for DEBT do not support product label claims of safety for children
based on the percent active ingredient. In addition, there is no apparent correlation
between reported cases of seizure incidents and the concentration of DEBT that was
applied. Registrations for which the labeling is amended as specified below will be
considered to be eligible for reregistration.
2. Eligible and Ineligible Uses
The Agency has determined that all uses of DEBT are eligible for
reregistration except uses/formulations that contain sunscreen and uses/formulations
whose labels make child-safety claims. Products labels with cosmetic claims must be
revised to conform with the labeling requirements for those products outlined in
Section V. of this RED document.
C. Regulatory Position
The following is a summary of the regulatory positions and rationales for DEBT.
Where labeling revisions are imposed, specific language is set forth in Section V of this
document.
1. Labeling Rationale
Because DEBT is applied directly to skin and/or clothing being worn and
because of its association with seizure incidents, the Agency believes it is prudent to
require consistent, protective, common sense use directions and label precautions for
, . all DEBT end-use products to prevent over-application and misuse. Product labeling
requirements have been revised in accordance with this goal and are outlined in
Section V.JB. 2., "Labeling Requirements for DEBT End-Use Products."
Child-Safety Claims
Some DEBT formulations have label language and/or brand names that imply
that those formulations are better for use on children (e.g. "...for children," " ...for
kids.") The Agency considers these formulations/products to be ineligible for
reregistration. The scientific data reviewed by the Agency for DEBT do not support
the claim that certain concentration DEBT formulations are safer than others. Also,
there appears to be no correlation between the reported cases of seizure and the
- concentration of DEBT that was used. All direct or indirect claims of child, safety
must be removed from DEBT labeling for those products to be reregistered.
37
-------
;*" ' i .(: < :
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.
Hi: '. ซ,. ;,' '''' . :;;' ^ : : ;, ' ; ' i
,.\A'.'
Manufacturing-Use Products
t. Additional Generic Data Requirements
tie substantially complete. No additional generic data are being callecl-in for DEBT
' ''
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 use(s)[fill blank
only with those uses that are being supported by MP registrant]."
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
,, SfO^''.,. . , , ,,- ,., , :,' ... , .,..., ' '
(a) "This product may be used to formulate products for specific use(s)
not listed on me MP label if me formulator, user
complied with U.S. EPA submission requirements regarding support
of suchuse(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 support of such use(s)."
The Agency has determined that registrants may distribute and sell N,N-
diethy 1-m-toluamide products bearing old labels/labeling for 26 monthsirom 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
38
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label changes and existing stocks requirements applicable to products they sell or
distribute. .
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed
product-specific data regarding the pesticide after a determination of eligibility has
been made. The product specific data requirements are listed in Appendix G, the
Product Specific Data Call-In Notice. Note that product-specific efficacy data is
being called in for end-use products containing N,N-diethyl-m-toluamide (DEBT).
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.
i. . , - . '
2. Labeling Requirements for End-Use Products
All registrants of DEBT end-use products must comply with the labeling
statements listed below. >
ALL PRODUCTS
To be eligible for reregistration, the following statements are required on all
DEBT product labels:
1. Read and follow all directions and precautions on this product label.
2. Do not apply over cuts, wounds, or irritated skin.
3. Do not apply near eyes and mouth. Apply sparingly around ears.
' '4'. < ' Do not apply to children's hands.
5. Do not allow children to handle this product.
6. When using on children, apply to your own hands and then put it on
the child.
7. Use just enough repellent to coyer exposed skin, and/or clothing.
' ' '' ' ' 39 - , .
-------
I!"!*'
I*'ill!
ft >',;,., ,!!,: \ , ,'JM ' J'11,1
8. Do not use under clothing.
9. Avoid over-application of this product.
10. After returning indoors, wash treated skin with soap and water.
11. Wash treated clothing before wearing it again.
12. Use of this product may cause skin reactions in rare cases.
'"I'l'i i1 ,i" * i in
hi I i I II i I1 I ill
13. If you suspect a reaction to this product, discontinue use, wash treated
skin, and call your local poison control center.
14. If you go to a doctor, take this product with you.
fill I t ' ill
AEROSOL AND PUMP SPRAY FORMULATIONS
To be eligible for reregistration, the following additional statements/requirements are
required for all aerosol and pump spray formulations:
1. Do not spray in enclosed areas.
2. If used on the face, spray on hands first and tHen apply sparingly and avoid
eyes. Do not spray directly onto face.
3. To be eligible for reregistration, aerosol and pump spray formulations must
be packaged in containers utilizing a concave trigger to help aim product
or Other comparable mechanism that will ensure that the product will not be
inadvertently sprayed in the eyes.
OTHER LABELING REQUIREMENTS
1. Ingredients Statement for DEET Products
," " " ' ', ., ' . ' " , "" i,
The following label statement is required for all DEET products:
ACTIVE INGREDIENTS
DEET XX.XX%
2. Statement of Practical Treatment
"First Aid" must replace "Statement of Practical
Treatment" on all product labels.
.. , , 40 .'
-------
3. Telephone Number on all Product Labels
A toll-free telephone number must appear on all product labels for consumers
to call for additional product information and to report incidents.
s 4. , Dissolving Labels
Current labels on DEBT repellent products tend.to dissolve from contact with
the repellent (usually liquids). All reregistered DEBT product labels must use
materials that remain permanent and readable for the reasonable life of the
product. .;-,..
5. Cosmetic Claims
Cosmetic claims may be used in DEBT end-use labeling, however, the words
"INSECT REPELLENT" must be displayed prominently on the front panel
of all product labels, immediately after the brand name, in capital lettering,
. with large, contrasting, bold-faced type.
6. Child-Safety Claims
All direct or indirect claims of child safety must be removed from DEBT end-
use product labeling in order for those products to be eligible for
reregistration.
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 N,N-diethyl-m-
toluamide 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.
41
-------
"I I
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42-
-------
VI. APPENDICES
43
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for active ingredients within the CE
I)EET covered by this Reregistration Eligibility Decision Document. It contains generic data requirements that apply j
pEET in all products, including data requirements for which a "typical formulation" is the test substance.
i i in i i i1 i ' i i i ipi IP
The data table is organized in the following format:
I, ' "Ti lii i , . t , ,' '
1. Data Requirement (Column 1). The data requirements are listed in the order in which they appear in 40 CFR PJ
158, the reference numbers accompanying each test refer to the test protocols set in the Pesticide Assessment GuidelinJ
which are available fi[gm the JE^atipnal Technical Informatipn Service, 5285 Port Royal Road, Springfield, VA 22161 (7C
i i 487-4650. - ' ' ' '
1 I I II ill I ! I I I) II I | 1111 |
2. Use Pattern (Column 2). This column indicates the use patterns for which the data requirements apply.
following letter designations are used for the given use patterns:
A Terrestrial food
B _ Terrestrial feed i ^ , |4 . _ ^
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 i , ,
L Indoor food
M IndQ0/ non-food
N Indoor mecucaj
O Indoor residential
3. Bibliographic citation (Column 3). If the Agency has acceptable data in its files, this column lists the identifyil
number of each study. This normally is the Master Record Identification (MRID) number, but may be a "GS" number if]
MRID number has been assigned. Refer to the Bibliography appendix for a complete citation of the study.
5*0
-------
APPENDIX B
Data Supporting Guideline Requirements
for the Reregistration Of DEET
REQUIREMENT
USE PATTERN
CITATIQN(S)(MRID#)
PRODUCT CHEMISTRY
61-1
61-2A
61-2B
62-1
62-2
62-3
63-2
63-3
63-4
63-6
63-8
63-9
63-11
63-13
Chemical Identity
Start. Mat. & Mnfg. Process
Formation of Impurities
Preliminary Analysis
Certification of limits
-Analytical Method
Color
Physical State
Odor
Boiling Point
Solubility
Vapor Pressure
Octanol/Water Partition
Stability
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
.. . ALL
ALL
ALL
ALL
ALL
42910001
43241002
43241003'
43241004
43241001
43241005
43241006 '.'.'.
00001025
00001068
00001100
43241007
4321008
4321009
4321010
43241012
ECOLOGICAL EFFECTS
71-la
i 72-1C
72-2a
Acute Avian Oral - Quail/Duck
Fish Toxicity Rainbow Trout
Invertebrate Toxicity .
ABCDEFJK
ABCDEFJK,
ABCDEFJK
41159701
00001026
00243419
TOXICOLOGY
81-1
81-2
81-3 ,
81-4
81-5
81-6
Acute Oral Toxicity - Rat
Acute Dermal Toxicity - Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit .
Dermal Sensitization - Guinea Pig
ALL
ALL
ALL
ALL-
ALL .
00134359a
43763201
00134359b
00l34359c
00134359d
00l34359e
00134359f
51
-------
Data Supporting Guideline Requirements
for the Registration of DEBT
REQUIREMENT
82-iA::;:''::
82-1B
ii'i,! ' i'1 'ii ! nn1" i, Ll ' ' ,'!'i WJii !;,' .'"i . "
i,n !1|P ,13-1 A. ,
83-1B
"IS ' 1 Ml' ! i "" , i'1" ป, nniiM ill!'1' I,,!,!::"
i'!i!i!;::j;;'',l'83-2A
83-2B
83-3A
83-3B
: : :":" 83-4
:""": :: '":'83-5
84-2A
84-2B
:;''; 84-4
;:-.' 85-1 ' !l
E'iJ' 15-2 ,
90-pay Feeding - Rodent
1 i iiiii i i l
90-Day Feeding - Non-rodent
; "i , , i lll'll . if ' ; i" .. ..,' ,11; 'iii; ,.',. ;, 'i, : ; ', .' '', . ;"i
90-Day Dermal - micropig
;:'/' E-rat '. "
'. -rat
Chronic Feeding Toxicity - Rodent
11 , ..,! j'i"1 Illrflnnli ,, In1, li.PU'li I,. IN ,!!' ' ^ tr
Chronic Feeding Toxicity - Non-
,,.. '/in, , Si,1'.'!1' !M ' iHil1!!!!' ' i ,, ' ! ( ^^ H .,5
Rodent
Oncogenicity - Rat
Oncogenicity - Mouse
Developmental Toxicity - Rat
Developmental Toxicity - Rabbit
2-Generation Reproduction - Rat
Combined chronic/oncogenicity - rats
Gene Mutation (Ames Test)
Structural Chromosomal Aberration
Other Genotoxic Effects
General Metabolism
Dermal Penetration
USE PATTERN
ABDHL
ABDHL
ABDHL
ABDHL
ABDHL
ABDHL
ABDHL
ABDHL
ALL
- ALL
_' ALL'
ABDHL
CITATION(S)(MRID#)
40241703
42518101
41344101
41987401
1 43514201
.43514202 .
41987401
''40241702 ";
41199301 ' ' ' ""
' ""is'sYfeos '''''" 1"""" "'; if "" ; '":i
43320101 ^
43320101
41351501
41351401
42141101
40979001
43514202
41344801
41344401
41344301 ' . , ' ".".. ii'"'^'" '"'
"41994401' " ' ' ''
41994402
41994403
42578501
lElsrvlRONMENTAL FATE -
160-5
161-1
' ' ''..' SPECIAI
Chemical Identity
Hydrolysis
.STUDIES
ALL
ABCDEFGHI
' ' '
40192701
'; ' " p '' ' ' i"": " ' "'
158.75-s Human Use Exposure
41968001
52
-------
Data Supporting Guideline Requirements
for the Registration of DEET
REQUIREMENT
USE PATTERN CITATJON(S)(MRID#)
85-2-ss Dermal Absorption
. (human)
88-1-ss - Acute/Subacute neurotdxicity
42578501
41368401
41368501
53
-------
Mlili'T . "' 'Illlll
111
I
I'llli!
f
54
-------
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 Reregistration Eligibility Document. Primary, sources for studies in this bibliography
have been the body of data submitted to EPA and its predecessor agencies in support of
past regulatory decisions. Selections from other sources including the published literature,
in those instances,where they have been considered, are included."
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 Author. Whenever the author could confidently be identified, .the Agency has
chosen to show a personal author. When no individual was identified, the Agency
has shown an identifiable laboratory or testing facility as the author. When no
author or laboratory could be identified, the Agency has shown the first submitter
as the author.
b. Document date. The date of the study is taken directly from the document. When
the date is followed by a question mark, the bibliographer has deduced the date
from the evidence contained in the document. When the date appears as (19??),
the Agency was unable to determine or estimate the date of the document.
55
-------
if! ! '
lii ' '
c. Title. In some cases, it has been necessary for the Agency bibliographers to create
Or enhance a document title. Any such editorial insertions are contained between
square brackets.
ซ i ', ป ,i ' :'i>Ki i ii i' i i i, .' , !, , " ,|, . ', : ' / , ; | ' ':, ' J '". v ,>. '.v .i/;,,! , ," , 'j., i ;' >ป , " ,1,1,1 ,, i ,, ,\a, \, ,ป i,,,.:ri n j
d. Trailing parentheses. For studies submitted to the Agency in the past, the trailing
parentheses include (hi 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
ullmediately 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.
56
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BIBLIOGRAPHY
MRID
CITATION
00001026 McCann, J.A.'(1972) Fish Toxicity Laboratory Report: Toxicity of Hercules
-Metadelphene to Rainbow Trout: I.D. No. MB 154. (Unpublished study that includes
, bibliography, Statistical analy sis and graph, received 1972 under 891-12; prepared
by Animal Biology Laboratory, submitted by Hercules, Inc., Agricultural Chemicals,
Wilmington, Del; CDL:129780-A)
00134359 U.S. Army. Environmental Hygiene Agency. .1979. Preliminary Assessment of
Relative Toxicity of Insect Repellent N,N-diethyl-meta-toluamide. Special Study No.
75-51-0034,80. Appendix F: Acute oral LD50 determinations (17D-0005). ,
00134359 U.S. Army Environmental Hygiene Agency. 1979. Preliminary Assessment of
Relative Toxicity of Insect Repellent N,N-diethyl-meta-toluamide. Special Study No.
75-51-0034,80. App'endixE: Acute dermal LD50 determinations.
<,
00134359 U.S. Army Environmental Hygiene Agency. 1979. Preliminary Assessment of
Relative Toxicity of Insect Repellent N,N-diethyl-meta-toluamide. Special Study No.
75-51-0034,80. Appendix M: Inhalation toxicities of N,N-diethyl-meta-toluamide
(M-DET)(17D-0012).
00134359 U.S. Army Environmental Hygiene Agency. 1979. Preliminary Assessment of
Relative Toxicity of Insect Repellent N,N-diethyl-meta-toluamide. Special Study No.
75-51-0034,80. Appendix B: Protocol-Primary Eye Irritation (17D-0001).
00134359 U.S. Army Environmental Hygiene Agency. 1979. Preliminary Assessment of
Relative Toxieity of Insect Repellent N,N-diethyl-meta-toluamide. Special Study No.
, " 75-51-0034,80. Appendix A: Protocol-Primary Skin Irritation (17D-0000).
00134359 U.S. Army Environmental Hygiene Agency. 1979. Preliminary Assessment of
Relative Toxicity of InsectRepellentN,N-diethyl-meta-toluamide. Special Study No.
75-51-0034,80. Appendix H: Guinea pig dermal sensitization study on N,N-diethyl-
meta-toluamide (M-DEET).
00243419 Analytical Bio-Chemistry Laboratories (1985). Static Acute Toxicity TesttoDaphnia
magna 33909
40192701 Meinen, V. (1987),Diethyltoluamide Thirty Day Water Hydrolysis Test. Unpublished
study prepared by McLaughlhi Gormley King Co. 108 p.
57
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MRID
BIBLIOGRAPHY
CITATION
40241702 Johnson, D.E. 1987. Evaluation of DEBT in 90-day Subchronic Dermal Toxicity
Study in Rats. International Research and Development Corp., Study No.: IRDC-
5J5-OOJ3. June 5,1987, Subm
Specialties Manufacturers Association.
40241703 Johnson, D.E, 1987. Evaluation of DEBT in 90-day Oral Dose-Range Finding Study
in Rats. International Research and Development Corp., Study No.: IRDC-555-001.
June 1,1987. Submitted to U.S. EPA by DEBT Joint Venture/Chemical Specialties
Manufacturers Association.
s
40241704 Jjhnspn, D.E. 1987. Evaluation of DEBT in 90-day Oral Dose-Range Finding Study
inMice. International Research and Development Corp., Study No.: IRDC-555-002.
June 2,1987. Submitted to U.S. EPA by DEBT Joint Venture/Chemical Specialties
Manufacturers Association.
40979001 Schardein, J.L. 1989. Evaluation of DEBT in aTwo-Generation
Reproduction/Fertility Study in Rats. International Research and Development Corp.,
'Study No.: IRDC-555-004. January 23, "iW^V'Submitte<3fto1t/;ง1.1'iESA1t)y f)EET
Joint Venture/Chemical Specialties Manufacturers Association.
41159701 Grimes, J.; Jaber, M. (1989) An Evaluation of Deet in an Acute Oral Toxicity Study
with the Bobwhite: Final Report: Wildlife International Ltd. 20 p.
41199301 Goldenthal, E.I. 1989. Evaluation of DEET in a 90-day Toxicity Study in Castrated
Male Rats. International Research and Development Corp.; Lab. Project No. 555-
010, August 9, 1989. Submitted to U.S. EPA by DEET Joint Venture/Chemical
Specialties Manufacturers Association.
41344101 Goldenthal, E.I. 1989. Evaluation of DEET in a 90-day Dose-Range Finding Study
in Hamsters. International Research and Development Corp.; Study No. 555-012.
October ฃ5, 1989. Submitted to U.S. EPA by DEBT Joint Venture/Chemical
Specialties Manufacturers Association.
41344301 Cuiren,R.D. 1989. Unscheduled DNA Synthesis Assay in Rat Primary Hepatocytes
with a Confirmatory Assay. Microbiological Associates, Inc.; Study No.
T8728.380009. December 22, 1989. Submitted to U.S. EPA by DEET Joint
Venture/Chemical Specialties Manufacturers Association.
58
11 I ' ,,,:" i,1 I!!' Hi .,.'' : ,! I llflllliJ>' BjK ! ', '!!""
J '
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BIBLIOGRAPHY
MRID
CITATION
41344401 Putman, D.L. and Morris, M.J. 1989. Chromosome Aberrations in Chinese Hamster
Ovary (CHO) cells. Microbiological Associates, Inc.; Study No. T8728.337.
December 28, 1989. Submitted to US EPA by DEBT Joint Venture/Chemical
Specialties Manufacturers Association.
41344801 San, R.H.C. and Schadly, M.B., 1989. Salmonella/mamrnalian-microsome plate
" incorporation mutagenicity assay (Ames Test) with a confirmatory assay.
Microbiological Associates, Inc.; Study No. T8728.501014. December 28, 1989.
Submitted to US EPA by DEBT Joint Venture/Chemical Specialties Manufacturers
Association.
>
41351401 Neeper-Bradley, T.L. 1990. Developmental toxicity, evaluation- of DEBT
administered by gavage to CDฎ (Sprague Dawley) rat. Bushy Run Research Center;
Study No.: 52r603. January 4, 1990, Submitted to USEPA by DEBT Joint
Venture/Chemical Specialties Manufacturers Association.
41351501 Goldenthal, E.I. 1990. Evaluation of DEBT in an eighteen-month oncogenicity study
in mice. International Research and Development, Corp.; Study No. 555-005.
Submitted to EPA by DEBT Joint Venture/Chemical Specialties Manufacturers
Association. -! -
' ฐ ' C*" ' '
41368401 Schardein, J.L. 1990. Neurotoxicity evaluation in rats following multigeneration
exposure to DEBT. International Research and Development Corp.; Study No.: 555-
015. January 23, 1990. Submitted to USEPA by DEBT Joint Venture/Chemical
Specialties Manufacturers Association.
41368501 Schardein, J.L. 1990. Neurotoxicity evaluation in rats following acute oral exposure
to DEBT. International Research and Development Corp.; Study No.: 555-017.
January 23, 1990. Submitted to USEPA by DEBT Joint Venture/Chemical
Specialties Manufacturers Association.
41678101 Gabriel,D. (1990) MGK Intermediate 2007 Code No. 356-90: Acute
Oral Toxicity, LD50-Rats: Lab Project Number: 90-6978A. Unpublished study
prepared by Biosearch Inc. 21 p. >
41987401 Goldenthal, E.I. 1991. Evaluation of DEBT in a 90-day subchronie dermal toxicity
study in micropigs. International Research and Development, Corp.; Study No. 555-
- - '. 018. Submitted to EPA by DEBT Joint Venture/Chemical Specialties Manufacturers
- Association. ,
41994401 Selim, S. 1991. Pharmacokinetics and comparative absorption study of
59
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MRID
41994402
42141101
42518101
42578501
43320101
43514201
43514202
BIBLIOGRAPHY
CITATION
N,N-dimethyl-ni-toluamide (DEBT) in the rat. Biological Test Center, Study No.
P01836. Submitted to US EPA by DEET Joint Venture/ Chemical Specialties
Manufacturers Association.
Selim, S. 1991. Addendum to Report Entitled 'Tharmacokinetics and comparative
absorption study of N,N-dimethyl-m-toluamide (DEET) in the rat." Biological Test
Center, Study No.: Addendum P01836. Submitted to US EPA by DEBT Joint,
Yenture/Chemical Specialties Manufacturers Association.
Chun, J.S. and Neeper-Bradiey, T.U. 1991. Developmental toxicity evaluation of
DEBT administered by gavage to New Zealand white rabbits. Bushy Run Research
Center; Study No. 54-597. December 6,1991. Submitted to US EPA by DEBT Joint
Venture/Chemical Specialties Manufacturers Association. Supplemental Study
(44279903). '
Goldenthal, E.I, 1992. Evaluation of DEET in a multistrain 90-day dietary renal
toxicity study in rats. International Research and Development Corp.; Study No. 555-
022. October 14, 1992. Submitted.'to US EPA.byDEET Joint Venture/Chemical
Specialties Manufacturers Association. Supplemental Study (44279901).
Selim, S. 1992. Absorption and mass balance of 14C-DEET after topical
administration to healthy volunteers. Biological Test Center. Study No. P891002.
December 3, 1992. Submitted to US EPA by DEET Joint Venture/Chemical
Specialties Manufacturers Association.
Goldenthal, E.I. 1994- Evaluation of DEET in a one-year chronic oral toxicity study
in dogs. International Research and Development Corp.; Study No. 555-02L
January 30, 1994! Submitted to EPA by 3^ Specialties
Manufacturers Association, ,. , ' _ ,,,,,', ',,,,'...' '. ,.'. ,,,,,,,.,,,',,. ',', ,., .I,,,,.
Goldenthal, E.I, 1994. Evaluation of DEBT in an eight week oral gelatin capsule .
toxicity study in dogs. International Research and Development Corp.; Study No.
555-027- January 3, 1995. Submitted to EPA by DEBT Joint Venture/Chemical '
Specialties Manufacturers Association.
Goldenthal, E.I. 1994. Evaluation of DEET in an eight-week dietary toxicity study
in dogs. International Research and Development Corp.; Study No. 555-020.
II i I i * , 11
1 i !"' ! - i"'
60
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BIBLIOGRAPHY
MRID
CITATION
January 3, 1995. Submitted to EPA by DEBT Joint Venture/Chemical Specialties
Manufacturers Association. ,
43514203 Goldenthal, E.I. 1995. Evaluation of DEET in a two-year dietary and oncogenicity
, study in rats. International Research and Development Corp.; Study No^ 555-023.
January 3,1995. Submitted to US EPA by DEET Joint Venture/Chemical Specialties
Manufacturers Association.
43763201 McCain, W.C. 1995. Executive summary: Acute oral toxicity study of
pyridostigmine bromide, permethrin, and DEET in laboratory rat. U.S. Army Center
for Health Promotion and Preventive Medicine; Study No. 75-48-2665.' June 21,
1995. Distributed to HED/OPP/US EPA.
Other References
Boomsa, J.C. and Parthasarathy, M. 1990. "Human Use & Exposure To, Insect Repellents
Containing DEET." Subitted to the U.S. EPA by the DEET Joint Venture/Chemical Specialties
Manufacturers Association. September 14, 1990.
Oransky, S., Roseman, B., Fish, D., Gentile, M.S., Melius, J., and Carter, M.L. 1989. "Seizures
Temporally Associated with Use of DEET Insect Repellent - New York and Connecticut." Mortality
and Morbidity Weekly Review.. 38:678-680. :
U.S. EPA. 1980. Pesticide Registration Standard for N,N-diethyl-m-toluamide (DEET). Office of
Pesticides and Toxic Substances Special Pesticides Review Division. US EPA, Washington, DC.
December 1980.
U.S. EPA. 1989. Recognition and Management of Pesticide Poisonings. 4th Edition.
EPA-540/9-88-001. March 1989.
U.S. EPA. 1990. "Exposure Factors Handbook." March 1990.
U.S. EPA. 1991. "Alphas-Globulin: Association with chemically induced renal toxicity and
neoplasia in the male rats." Risk Assessment Forum.. US EPA/6253-91/019F; September 1991.
U.S. EPA. 1996. Memorandum from George Ghali, Ph.D. to Rick Keigwin. "RfD Peer Review
Report of DEET (N,N-diethyl-m-toluidine)." January 4, 1996.
61
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MRID
BIBLIOGRAPHY
CITATION
Yeltri, J.C., Osimitz, T.G., Bradford, D.C., and Page, B.C. 1994. Retrospective analysis of calls to
Poison Control Centers resulting from exposure to the insect repellent N,N-diethyl-m-toluarnide
-''." ClMcal Toxicology, 32(T):i-i6. "" ' " ':-
62
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C 20460
DATA CALL-IN NOTICE
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
., - NOV -4 1998
CERTIFIED. MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the active
ingredient identified in Attachment 1 of this Notice, the Data Call-In Chemical Status Sheet, to
submit certain product specific data as noted herein to the U.S. Environmental Protection Agency
(EPA, the Agency). These data are necessary to maintain the continued registration of your
product(s) containing this active ingredient. Within 90 days after you receive this Notice you must
respond as set forth in Section III below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its
Attachments 1 through 6; or . \
2. ' Why you believe you are exempt from the requirements listed in this Notice and in
Attachment 3, Requirements Status and Registrant's Response Form, (see section
3.
Why you believe EPA should not require your submission of product specific 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
63
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iiiiiiif
IHilllll! HI) 'Il'lll
iii;! y wjmw iiiiiซ!;i isi wm BIII uume siiniiiii s; wii fr-mm; RIP"
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, Data Call-In Response Form, as well as a list
of all registrants who were sent this Notice (Attachment 6).
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide, Fungicide and
Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
information is authorized under the Paperwork Reduction Act by OMB Approval No. 2070-0107
ind 2070-6057(expiration date03-31-99)'.'
This Notice is divided into six sections and six Attachments. The Notice itself contains
information and instructions applicable to all Data Call-In Notices. The Attachments contain
specific chemical information and instructions. The six sections of the Notice are:
Section I - Why You Are Receiving This Notice
Section II - Data Required By This Notice
Section III - Compliance With Requirements Of This Notice
: Section IV- Consequences Of Failure To Comply With This Notice
Section V - Registrants'Obligation. To Report Possible Unreasonable Adverse
" : , Effects ' ,
Section VI - Inquiries And Responses To This Notice
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet ,
2 - Product-Specific Data Call-In Response Form
3 - Requirements Status and Registrant's Response Form
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - List of Registrants Receiving This Notice
Share and Data Compensation Forms
SECTION I. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient and reevaluated the data
needed to support continued registration of the subject active ingredient. The Agency has
concluded that the only additional data necessary are product specific data. No additional generic
data requirements are being imposed. You have been sent this Notice because you have product(s)
containing the subject active ingredient.
"in (nil ' ' . ' i i ii I1.
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
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The product specific data-required by this Notice are specified in Attachment 3, Requirements
Status and Registrant's Response Form. Depending on the results of the studies required in this
Notice, additional testing may be required.. ; =
II-JB. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements specified in
Attachment 3, Requirements Status and Registrant's Response Form, within the time frames provided.
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test standards
outlined in the Pesticide Assessment Guidelines for those studies for which guidelines have been
established.
These EPA Guidelines are available from the National Technical Information Service (NTIS),
Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (tel: 703-487-4650).
Protocols approved by the Organization for Economic Cooperation arid Development (OECD)
are also acceptable if the OECD-recommended test standards conform to those specified in the
Pesticide Data Requirements regulation (40 CFR ง 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 ง 158. Normally, the Agency will not extend deadlines for complying with data
requirements when the studies .were not conducted in accordance with acceptable standards. The
OECD protocols are available from OECD, 2001 L Street, N.W., Washington, D.C. 20036
(Telephone number 202-785-6323; Fax telephone number 202-785-0350).
All new studies and proposed protocols submitted in response to this Data Call-In Notice
must be in accordance with Good Laboratory Practices [40 CFR Part 160.3(a)(6)]. ,
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(W2)rB) 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-Infs). or any other agreements entered into with the Agency
pertaining to such prior Notice. Registrants must comply with the requirements of all Notices to
avoid issuance of a Notice of Intent to Suspend their affected products.
SECTION III. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
III-A. SCHEDULE FOR RESPONDING TO THE AGENCY ,
The appropriate responses initially required by this Notice for 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 .
' , " . 65 : . . -. '
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I
Suspend (NOIS) affecting your products. This and other bases for issuance of NOIS due to failure to
comply with this Notice are presented in Section IV-A and IV-B.
III-B. OPTIONS FOR RESPONDING TO THE AGENCY
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 chose the Voluntary Cancellation option is presented
below. A discussion of the" various satisfying the product specific data
requirements of this Notice is contained in Section ill-C A discussion of options relating to requests
for data waivers is contained in Section III-D.
There are two forms that accompany this Notice of which, depending upon your response, one
or both must be used in your response to the Agency. These forms are the Data-Call-in Response
Form, and the Requirements Status and Registrant's Response Form. Attachment 2 and Attachment 3.
The Data Sali-ln 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 must be submitted for
each product listed on the Data Call-In Response Form unless the voluntary cancellation option is
selected or unless the product is identical to another (refer to the instructions for completing the Data
Call-in Response Form in Attachment 2). Please note that the company's authorized representative is
required to sign the first page of the Data Call-In Response Form arid 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 riot 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.
mill i mi1! i ซ i * I 1 < ,
1. 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 Form, indicating your election of this option. Voluntary cancellation is item number 5 on
Jhe, Data Call-In Response Form. If you choose this option, |his is the only form 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.
2. Satisfying the Product Specific Data Requirements of this Notice There are various options
available to satisfy the product specific data requirements of this Notice. These options are discussed
in Section. III.-C of this Notice and comprise options 1 through 6 on the Requirements Status and
Registrant's Response Form and item numbers 7a and 7b on the Data Call-In Response Form.
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Deletion of a use(s) and the low volume/minor use option are not valid options for fulfilling product
specific data requirements. ,
3. Request for Product Specific Data Waivers. Waivers for product specific data are discussed
in Section III-D of this Notice and are covered by option 7 on 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.
III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-In Response Form that you agree to satisfy the product
specific data requirements (i.e. you select item number 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)
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.
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. 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 jexplain
67 .
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any technical or laboratory difficulties and provide documentation from the laboratory performing the
ilsting. 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.
Mprrnally, 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
feshion;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 - Registrants may onjy_ 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
lustration 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. If you choose to enter into an agreement to share in
the cost of producing the required data but will not be submitting the data yourself, you must provide
the name of the registrant who will be submitting the data. You must also provide EPA with
documentary evidence that an agreement has been formed. Such evidence may be your letter offering
to join in an agreement and the other registrant's acceptance of your offer, or a written statement by
the parties that an agreement exists. The agreementto 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.
QptJon ฃ Offer to Share in the Cost of Data Development -- This option only applies to acute
toxicity and certain efficacy data as described in option 2 above. 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 registrants) developing the data has refused to accept your 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 copyof your offer and proof of the other registrant's receipt of that offer (such as a
mail receipt). Your offer must, in addition to anything else, offer to share in the burden of
JSlsp inl>rm EPA of its election of an option to develop and submit the data required by this Notice by
f Sifctfttflng 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.
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In order for you to avoid suspension under this option, you may not withdraw your offer to
share in the burdens 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 will normally 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.VSubmitting an Existing Study -- If you choose to submit an existing study hv
response to this Notice, you must determine that the study satisfies the requirements imposed by this
Notice. You may only submit a study that has not been previously submitted to the Agency or
previously cited by anyone. Existing studies are studies which predate issuance of this Notice. Do
not use this option if you are submitting data to upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not acceptable, the:
Agency will require you to comply with this Notice, normally without an extension of the required
date of submission. The Agency may determine at any time that a study is not valid and needs to be
repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of the ,
following three criteria must be clearly met: .
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(j) " 'raw'data' means any laboratory worksheets, records, memoranda, notes, or
exact copies thereof, that are the result of original observations and activities of a
study and are necessary for the reconstruction and evaluation of the report of that
' study. In the event that exact transcripts of raw data have been prepared (e.g., tapes
which have been transcribed verbatim, dated, and verified accurate by signature), the
exact copy or exact transcript may be substituted for the1 original source as raw data.
'Raw data' may include photographs, microfilm or microfiche copies, computer
printouts, magnetic media, including dictated observations, and recorded data from
.automated instruments." The term "specimens", according to 40 CFR 160.3(k), means
"any material derived from a test system for examination or analysis."
b Health and safety studies completed after May 1984 must also contain all GLP-
required quality assurance and quality control information, pursuant to the
requirements of 40 CFR Part 160. Registrants must also 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 musit certify that e^ch study fulfills the acceptance criteria for the Guideline
relevant to the study provided in the FIFRA Accelerated Reregistration Phase 3
'69..
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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.
A?s|sm^ _ _^_d ^^.^ to ^ pAG may be submitted to the A
for consideration if the registrant believes that the study clearly meets the purpose of
me PAG The registrant is referred to 40 CFR 158.70 which states the Agency's policy
regarding acceptable protocols. If you wish to submit the study, you must, in addition
to certifying that the purposes of the PAG are met by the study clearly articulate the
rat^nafe 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 ^P6^6*^165
completed prior to January 1970 rarely satisfied the purpose of the PAG and that
necessary raw data are usually not available for such studies.
If you submit an existing study, you must certify that the study meets all requirements of the
criteria outlined above.
If youknow of astudy pertaining to any requirement In mis Notice which does not meet the
criteria outlined above but does contain factual information regarding unreasonable adverse effects
^mos||dg>v|b ^^ studyisintheAgency,sflles, you need only cite
no^SriSfflfcatio\L If not in the Agency's files, you must submit a summary and copies as
required by PR Notice 86-5.
a Study - If a study has been classified as partially acceptable and
upgrade that study. The Agency will review the data submitted
a .
quirement is satisfied. If the Agency decides the requirement is not satisfied,
be required to submit new data normally without any time extension. Deficient, but
aWe sLdls will normally be classified as supplemental. However, it is important to note that
nol suTdieJ classified as supplemental are upgradeable. If you have questions regarding the
dass SiSป ofSy or whSher a study may be upgraded, call or write the contact persor i listed _m
u submit data to upgrade an existing study you must satisfy or supply information
^slnthes^dyidQnmedbyEPA. You must provide a clearly articulated
eficiencies have been remedied or corrected and why the study should be rated
. YoursubmissionmustalsospecifytheMRIDnumbe^
you are attempting to upgrade and must be in conformance with PR Notice 86-5.
a study classified as unacceptable
Do not submit
and determined by the Agency as not capable of being upgraded.
This Option should also be used to cite data that has been previously submitted to upgrade a
study bufSlefbeenreviewedby 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 submittiri aS existing study, as specified in Option 4 above, apply to aU
, ons Sended to upgrade studies. Additionally your submission of data intended to upgrade
es rTt be" corned by a certification that you comply with each of those criteria as well as a
certification regarding pf otbcol compliance with Agency requirements.
70
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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 all other disciplines the
classification would be "acceptable." With respect to any studies for which you wish to select this
option you must provide the MRID number of the study you are citing and, if the study has been
reviewed by the Agency, you must provide the Agency's classification of the study. .
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.
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, as appropriate. ,
, ' . - i
TTT-n RF.OT TRSTS FOR DATA WAIVERS ..'".
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 My. opportunity to
state the reasons or provide information in support of your request. If the Agency^proves your
waiver request, you will not be required to supply the data pursuant to section 3(c)(2)(B) oi Mi- KA. it
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 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 tor
the study in question. Waiver requests submitted without adequate supporting rationale will be
denied and the original due date will remain in force.
IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE _ ~
TV-A NOTTCF. OF INTENT TO SUSPEND - . '
The Agency may issue aNotice 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.
71
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i.jWS'Wt'*!r I
.S1,!1 ป 1.1 'I1/ MA" i,*!"!'!!!!,' !i Mi,!1
2.
3.
4.
5.
6.
7.
8.
Failure to submit on the required schedule an acceptable proposed or final protocpl
when such is required to be submitted to the Agency for review.
11 ,' ' ' , ' , ' .JM
Failure to submit on the required schedule an adequate progress report on a study as
required by this Notice.
Failure to submit on the required schedule acceptable data as required by this Notice.
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).
il 111II i I li \iiiB1!,' ,..:.'!'!.?. ' i":,,i.,B1'!1;';!'>,:;" , iir',}:*'"' iil's ',?ซ' j'S'XiB
Failure to submit supportable certifications as to the conditions of submitted studies,
as required by Section III-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:
a. 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: .
b. fulfill the commitment to develop and submit the data as required by this
Notice; or
* i ' .
"!
c. otherwise take appropriate steps to meet the requirements stated in this Notice,
unless you commit to submit and do submit the required data in the specified
time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any time
fQjJowing the issuance of this Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS
UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The grounds for
suspension include, but are not limited to, failure to meet any of the following:
72
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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 would generally 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 must also
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.
If you request a voluntary cancellation of your product(s) as a response to this Notice and your
product is in full compliance with all Agency requirements, you will have, under most circumstances,
one year from the date your 90 day response to this Notice is due, to sell, distribute, or use existing
stocks. Normally, the Agency will allow persons other than the registrant such as independent
distributors, retailers and end users to sell, distribute or use such existing stocks until the stocks are
exhausted. Any sale, distribution or use of stocks of voluntarily cancelled, products containing an
active ingredient for which the Agency has particular risk concerns will be determined on case-by-
case basis.
73
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1(1 111
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 yTar from the cfate the 90 day response was due unless you demonstrate to the
Agency that you are in full compliance with all Agency requirements, including the requirements of
this Notice. For example, if you decide to voluntarily cancel your registration six months before a 3
year study is scheduled to be submitted, all progress reports and other information necessary to
establish that you have been conducting the study in an acceptable and good faith manner must have
been submitted to the Agency" before EPA will consider granting an existing stocks provision.
t
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.
^egis'trants'must notify"tEe"'Agency"of any factual information they have, from whatever source,
including but not limited to interim or preliminary results of studies, regarding unreasonable adverse
effects on man or the environment. This requirement continues as long as the products are registered
by the Agency.
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by this
Notice, call the contact person(s) listed in Attachment 1, the Data Call-In Chemical Status Sheet.
74
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All responses to this Notice (other than voluntary cancellation requests and genenc data
claims) must include a completed Data r.ซ11-Tn Response Form and a completed
. Resnonse Form (Attachment 2 and Attachment 3 for product
status ana jxegistraiu 5 rv^opum^ *. \jj.m ^ -~- : -
and any other documents required by this Notice, and should be submitted to the
identified in Attachment 1. If the voluntary cancellation or genenc data exemption
jl rh^ ^iy
-------
DEBT DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You haye been sent this Product Specific Data Call-In Notice because you have product(s)
containing DEBT.
I ;, ii.,1,11! ..... i. lilllll!\4':cl!>) ...... '"i1 ', 'J> it. ...... ..'Ill; Hill! ll.il 'Hi! .'Mil: iM" J'jrtl ....... Hi.;" ,::!'. ......... * "i** ':! '" .: I" ';=,ซ<" ..... ' ป' ..... I ..... t. '.ป ......... .' ;" >"' ..... ' ...... "' ...... ......................... 'i .............. > J "V .............. J
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 DEET. 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 Pom (Attachment 3), (4) EPA's Grouping of End-Use Products for Meeting Acute
Toxicology Data Requirement (Attachment 4), (5) the EPA Acceptance Criteria (Attachment 5), (6) a
list of registrants receiving this DCI (Attachment 6) and (7) the Cost Share and Data Compensation
Forms in replying to this DEBT Product Specific Data Call-In (Attachment 7). Instructions and
guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for DEET are contained in
the Requirements Status and Registrant's Response. Attachment 3. The Agency has concluded that
additional "(fata "on DEET are Heeded for specific products. These data are required to be submitted to
the Agency within the time "faaas s listed. These data are needed to fully complete the reregistration of"
all eligible DEBT products.
INQUIRIES AND RESPONSES TO THIS NOTICE
ill i mi i ii i i, i 1 1 i in 1 1 ill
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: DEET
76
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORM FOR
PRODUCT SPECIFIC DATA
Item 1-4. - Already completed'by EPA. . '
Item 5. If youvvdsh to voluntarily cancel your product, answer "yes." If you choose this option,
, you will not have to provide the data required by the Data Call-in Notice and you will
not have to complete any other forms. Further sale and distribution of your product after
the effective date of cancellation must be in accordance.with,the Existing Stocks
provision of the Data Call-In Notice (Section IV-G).
Item 6. Not applicable since this form calls in product specific data only. However, if your
product is identical to another product arid you qualify for a data exemption, you must
respond with "yes" to Item 7a (MUP) or 7B (EUP) on this form, provide the EPA
registration numbers of your source(s); you would not complete the "Requirements
Status and Registrant's Response" form. Examples of such products include repackaged
products arid Special Local Needs (Section 24c) products which are identical to
- federally, registered products.
Item7a. . 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 me data requirements by responding "yes." If you are requesting a data
waiver, answer "yes" here; in additipn, 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. See Item 6 with regard to identical
products and data exemptions.
Items 8-11. Self-explanatory. '
* .
NOTE: You may provide additional information that does not fit on this form in a signed letter
that accompanies this form. For example, you may wish to report that your product has
already been transferred to another company or that you have already voluntarily
canceled this product. For these cases, please supply all relevant details so that EPA can
ensure that its records are correct.
77
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Item 1-3
Item 4.
INSTRUCTIONS, FOR COMPLETING THE REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORM FOR PRODUCT SPECIFIC DATA
Completed by EPA. Note the unique identifier number assigned by EPA in Item
3. This number must be used in the transmittal document for any data
submissions in response to this Data Call-In Notice.
The guideline reference numbers of studies required to support the product's
continued registration are identified. These guidelines, in addition to the requirements
specified in the 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
158.1 80, SubpartC.
ป ' 'i'lilill ,,ii ' hi"''!| ' "IP:". ' i' "II1"'" J" ': ,;.." ili n/ 1! ...... ,', "l" r '" 'i, I '|. i i I'J . " ..... ', : ' '. ,'," >' J"1 /'"'liMn1:, i " " '.,. 't,, i1 ' " '"'I!..'1 ': i.1"', ' ,' ' ' ป " '.I ' M'l.Milllii'iliii ป ,,11:11
Item 5.
Item 6.
! i;
Item?.
'Item''!
KM-;.
1.
2.
The study title associated with the guideline reference number is identified.
The use pattem(s) of the pesticide associated with the product specific requirements
is (are) identified. For most product specific data requirements, all use patterns are
covered by the data requirements. In the case of efficacy data, the required studies
only pertain to products which have the use sites and/or pests indicated.
The substance to be tested is identified by EPA. For product specific data, the
product as formulated for sale and distribution is the test substance, except in rare
cases.
due date for submission of each study is identified. It is normally based on 8
: 'Ifo&fiis after issuance' of the Reregistration iEligibility Document unless EPA"'
determines that a longer time period is necessary.
" if 11 . 'I'"1'1'; "':,ii !,'n';i-:,Elli'' vS"!!!"!;'!,1 '':," "',:ป,"* s < vi,r,!'/ . ., I-B, '>'',>, >., KM : ...tin" ...:![,; 'in11,/1 '" i!'!":. ,' .r..'1' 'fit. 'BIS*;! it*;
'!, (ilii ;, ii,' J": !,;.';; ', '': ',.'.<'' *', -,[ "ii ;'' ",.,:, ii:.' ii [';;', >, v. S;'<;!' ,:,! i, j i'j", - i .',; ,\ ; i:? ";i|: ' ii"',i:. j ''iii .:' tft,' :>': , ,'i a -:.. ' ilia ",';ซ:, i:, i- ปi,'. .iJsli '';'iii 'iliiiiiii1 iiii:
Enter,only _one of the fpUpwing response codes for each data requirement to
:: 'show how you intend to comply with the data requirements listed in this table.
I^ujlei; descriptions of each option are contained in the Data Call-in Notice.
j wi|J generate and submit data by the specified due date (Developing Data). 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. By the specified due date, I will also submit: (1) a completed
'"'Certification With Respect To Data Compensation Requirements'' form (EPA
Form 8570-29) and (2) two completed and signed copies of the Confidential
Statement of Formula (EPA Form 8570-4).
I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing). I am submitting a copy of this agreement. I understand[thatthis
option is available only for acute toxicity or certain efficacy data and only if EPA
indicates in an attachment to this Notice that my product is similar enough to another
80
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4.
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. By the specified due
date, I will also submit: (1) a completed "Certification With Respect To Data
Compensation Requirements" form (EPA Form 8570-29) and (2) two completed
and signed copies of the Confidential Statement of Formula (EPA Form 8570-4).
I have made offers to share in the cost to develop data (Offers to Cost Share). I
understand that this option is available only for acute toxiciry or certain efficacy data
and only if EPA indicates, in an attachment to this Data Call-in Notice that my
product is similar enough to another product to qualify for this option. 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 also submitting a
completed "Certification of Offer to Cost Share in the Development Data" form.
I am including a copy of my offer and proof of the other registrant's receipt of that
offer. I am identifying the party which is committing to submit or provide the
required data; if the required study is not submitted on time, my product may be
subject to suspension. I understand that other terms under Option 3 in the Data Call-
in Notice (Section III-C.l.) apply as well. By the specified due date, I will also
submit: (1) a completed "Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570r29) and (2) two completed and signed
copies of the Confidential Statement of Formula (EPA Form 8570-4).
By the .specified due date, I will submit an existing study that has not been submitted
previously to the Agency by anyone (Submitting an Existing Study). I certify that
this study will meet all the requirements for submittal of existing data outlined in
Option 4 in the Data Call-In Notice (Section III-C.l.) and will meet the attached
acceptance criteria (for acute toxicity and product chemistry data). I will attach the
needed supporting information along with this response. I also certify that I have
determined that this study will fill the data requirement for which I have indicated this
choice. By the specified due date, I will also submit a completed "Certification
With Respect To Data Compensation Requirements" form (EPA Form 8570-29)
to show what data compensation option I have chosen. By the specified due date, I
will also submit: (1), a completed "Certification With Respect To Data
Compensation Requirements" form (EPA Form 8570-29) and (2) two completed
and signed copies of the Confidential Statement of Formula (EPA Form 8570-4).
By the specified due date, I will submit or cite data to upgrade a study, classified by
the Agency as partially acceptable and upgradable (Upgrading a Study). I will
submit evidence of the Agency's review indicating that the study may be upgraded
and what information is required to do so. I will provide the MRID or Accession
number of the study at the due date. I understand mat the conditions for this option
outlined Option 5 in the Data Call-In Notice (Section III-C. 1.) apply. By the specified
due date, I will also submit: (1) a completed "Certification With Respect To Data
81
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ii i n mi i inn i i in i n i i iniiinn i n
Compensation Requirements" form (EPA Form 8570-29) and (2) two completed
and signed copies of the Confidential Statement of Formula (EPA Form 8570-4).
6. By the specified due date, I will cite an existing study that the Agency has classified
as acceptable or an existing study that has been submitted but not reviewed by the
"' _ " ^ency\(Citing^ [If JJain,citing\aiiother registrant's, study7i"
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 EPA 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) for the cited
data on a "Product Specific Data Report" form or in a similar format. By the
specified due date, I will also submit: (1) a completed "Certification With Respect
To Data Compensation Requirements" form (EPA Form 8570-29) and (2) two
completed and signed copies of the Confidential Statement of Formula (EPA
Form 8570-4).
7. I request a waiver for this study because it is inappropriate for my product (Waiver
Request). I am attaching a complete justification for mis request, including technical
reasons, data and references to relevant EPA regulations, guidelines or policies.
[Note: any supplemental data must be submitted in the format required by P.R. Notice
86-5]. I understand that this is my only opportunity to state the reasons or provide
information in support of my request. If the Agency approves my waiver request, I
will not be required to supply the data pursuant to Section 3(c)(2)(B) of FIFRA. If
the Agency denies my "waiver request, I must choose a method of meeting the data
requirements of this Notice by the due date stated by this Notice. In this case, I must,
within 30 days of my receipt of the Agency's written decision, submit a revised
"Requirements Status and Registrant's Response" Form indicating 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. By the specified due date, I will also submit: (1)
a completed "Certification With Respect To Data Compensation Requirements"
form (EPA Form 8570-29) and (2) two completed and signed copies of the
Confidential Statement of Formula (EPA Form 8570-4).
Items 10-13. Self-explanatory.
NOTE:
You may provide additional information that does not fit on this form in a signed
letter that accompanies this form. For example, you may wish to report that your
product has already been transferred to another company or that you have already
voluntarily canceled this product. For these cases, please supply all relevant details
so that EPA can ensure that its records are correct.
82
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Form Approved
OMB Ho. 2070-0107
2070-0057
Approval Expires 03-31-99
United States Environmental Protection Agency
Washington, D. C. 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE
INSTRUCTIONS: Please type or print in ink. Please read carefully the attached instructions and supply the information requested on this form.
Use additional sheet (s) if necessary.
3. Date and Type of DCI
PRODUCT SPECIFIC
ID# NNNNNN-RD-NNNN
2. Case If and Name
0002 Deet
EPA Reg. No. NNNNNN-NNNNN
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EPA'S BATCHING OF DIETHYLTOLUAMIDE (DEET) PRODUCTS FOR MEETING ACUTE
TOXICITY DATA REQUIREMENTS FOR RJEREGI STRATI ON
In an effort to reduce the time, resources and number of animals needed to fulfill the acute
toxicity data requirements for reregistration of products containing DEET as the active ingredient,
theAgency "HasBatchedjprbHucts'wiuch"can be'considered"similarfor purposes of acute toxicity.
Factors .considexed.in.thesorting process include each product's active and inert ingredients (identity,
percent composition and biological activity), type of formulation (e.g., emulsifiable concentrate,
aerosol, wettable powder, granular, etc.), and labeling (e.g., signal word, use classification,
precautionary labeling, etc.). Note that the Agency is not describing batched products as
"substantially similar" since some products within a batch may not be considered chemically similar
or have identical use patterns.
Using available information, batching has been accomplished by the process described in the
preceding paragraph. Notwithstanding the batching process, the Agency reserves the right to require,
at any time, acute toxicity data for an individual product should the need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or cite
a single battery of six acute lexicological studies to represent all the products within that batch. It is
the registrants' option to participate in the process with all other registrants, only some of the other
registrants, or only their own products within a batch, or to generate all the required acute
toxicological studies for each of their own products. If a registrant chooses to generate the data for
a batch, he/she must use one of the products within the batch as the test material. If a registrant
chooses to rely upon previously submitted acute toxicity data, he/she may do so provided that the
data base is complete and valid by today's standards (see acceptance criteria attached), the
formulation tested is considered by EPA to be similar for acute toxicity, and the formulation has not
been significantly altered since submission and acceptance of the acute toxicity data. Regardless of
whether new data is generated or existing data is referenced, registrants must clearly identify the test
material by EPA Registration Number. If more than one confidential statement of formula (CSF)
exists for a product, the registrant must indicate the formulation actually tested by identifying the
corresponding CSF.
In deciding how to meet the product specific data requirements, registrants must follow the
directions given in the Data (jall-ln Notice and its attachments appended to the RED The DCI Notice
contains two response forms which are to be completed and submitted to the Agency within 90 days
of receipt. The first form, "f)a^ Call-In Response," asks whether the registrant will meet the data
requirements for each product. The second form, "Requirements Status and Registrant's Response,"
lists the product specific data required for each product, including the standard six acute toxicity tests.
A registrant who wislieii'tb participate in a:'b'a'tch must decide whether he/she will provide the data
or depend oh" s'omeone else to doso. If a regjstran1: Supplies the data to support a batch of products,
he/she must select one of the following options: Developing Data (Option 1), Submitting an Existing
Study (Option 4), Upgrading an Existing Study (Option 5) or Citing an Existing Study (Option 6).
If a registrant depends on another's data, he/she must choose among: Cost Sharing (Option 2), Offers
|p Cpst Share (Option 3) or Citing an Existing Study (Option 6). If a registrant does not want to
participate in a batch, the choices are Options 1, 4, 5 or 6. However, a registrant should know that
f f 7' ;:";:' -;:; *' ;': '*'"_'"'' 3',* 3 !!!'"'"''.'"'.'. 7"'. If'! M'ฐ,. ".I."., . I" .' "I'.'""..'.. . '. , ,1'. I. 11',.'. '.. '.'..". Z" "I
i:!iซ.ii>i nr w ' mat %'. <',>: i>fj '. >,sm H ' ซ"':; **',;::"i:<..' i >:ซ:;>>''*' :".>'?:..;<<. ;.'':Vv..i ;(;; xr:< '.. it* ..."01: r;"i.;:-,'i.1!;.v> ซ. ', !:,' (, ,:;*ป^v^
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-------
choosing not to participate in a batch does not preclude other registrants in the batch from citing
his/her studies and offering to cost share (Option 3) those studies. -
Two hundred and thirty nine products were found which contain DEBT as the active
ingredient: The products have been placed into twenty-six batches and a "no batch" category in
accordance with the active and inert ingredients, -type of formulation and current labeling. Table 1
identifies the batched products. Table 2 lists the products which have been placed in the "no batch"
category. Products which have previous acute data reviews on file with the Agency have been
identified with an asterisk The studies addressed in these reviews, however, may or may not be
acceptable under current acceptance criteria. The following explains how acceptable data may be
bridged to support products between batches and sub-batches:
Batch IB -Can rely on batch 1A data except for eye irritation. Need separate eye study for each
product in IB. ... - ' ' ,
Batch 1C-Can rely on batch 1A data.
Batch ID -Can rely on category 3/4 batch 1A data. ; . , ;
Batch IE -Can rely on batch 1A data except for eye irritation. Need separate eye study for each
product in IE. . .
Batch IF-Can rely on batch 1A data.
Batch 1G-Can rely on category 3/4 batch 1A data.
Batch 2B -Can rely on data from batch 2A except for eye irritation. Need separate eye study for each
product hi 2B.
Batch 2C-Can rely on data from batch 2A.
Batch 3B -Can rely on data from batch 3A except for eye irritation. Need separate eye study for each
product in 3B.
Batch 4B -Can rely on category 3/4 data from batch 4A. -
Batch 4C -Can rely on data from batch 4A except for eye irritation. Need separate eye study for each
product in 4C.
Batch 5B -Can rely on category 3/4 data from batch 5A except for eye irritation. Need separate eye
study for each product.
. - i
Batch 6B -Can-rely on data from batch 6A except for eye irritation. Need separate eye study for each
product. .
89
-------
Batch 7B -Can rely on data from batch 7 A except for eye irritation. Need separate eye study for each
let.
Batch 7C -Can rely on data from batch 7A except for acute dermal toxicity.
Batch 1 IB-Can rely on category 3/4 data from batch 11 A.
Batch1 SB-Can rely on category 3/4 data from batch 15A.-
Batch 16B-Can rely on category 3/4 data from batch 16A.
Batch 1 SB-Can rely on data from batch 18A except for eye irritation. Need separate eye study for
each product in 18B.
Batch19B-Can rely on data from batch 19A except for eye irritation. Need separate eye study for
each groduct in 19B.
Batch 20A-May be supported by data on source components.
Ill If,'111 I JIIIJI11 'I1,,'' ,lr,i'i Ilk, IP , II IIIIIIIK f .i,lll'!!l, H ' .Wil'IIM II! nil, ill1',,,:' *N ,! I!' I IT , fl ป , v . ., ~. I '"i!l;, s f i ,| J',. iiii' |j^Ltt, iir" i iM::! ^ilK'I'd?i 4 \S^^ ; \l!'|l!4ln' o''^:, ^'i:^
Batch 21B-Can rely on data from batch 21A except for eye irritation. Need separate eye study for
each product in 21B.
Batch 22B-Can rely on data from batch 22A except for eye irritation. Need separate eye study for
each product hi 22B.
Batch 22C-Can rely on data supporting batch 22A.
y
Batch 22D-Can rely on category 3/4 data from batch 22A except for eye studies. Need separate eye
studies for each product in 22D.
Batch 23- Needs separate eye irritation study for each product.
Batch 24A-Needs separate eye irritation study for each product.
Batch 24B-Can rely on category 3/4 data from batch 24A except for eye irritation. Need separate
eye study for each product.
Batch 25 -Can rely on category 3/4 data from batch 22A except for eye irritation. Need separate eye
study for each product.
Batch 26B-Can rely on data from batch 26A except for eye irritation. Need separate eye study for
ซ'., eac'hproduct. . .
90
-------
Batch 26C-Can rely on category 3/4 data from batch 26A except for eye irritation. Need separate
eye study for each product. . . ~
Batch 26D-Can rely on category 3/4 data from batch 26A except for eye irritation. Need separate
eye study for each product. .
Table 1
Batch
1A
EPA Reg. No.
121-17
121-25
305-30
1021-891
2217-779
3095-27 ,
4822-215
4822-216
4822-276
*6148-8
7754-36
8340-39 .
10807-160
11715-185.
34797-32
41878-2
46075-1
48139-5
50830-1
51147-1
53356-3
54287-2
56575-7
62424-1
62446-1
65636-58
67405-2
67867-1
68688-20
69421-28
% Active Ingredient
95.0
95.0
95.0
95.0
95.0
95.0
95.0
-94,5
. 95.0
95.0
95.0
95.0
95.0
95.0 ,
95.0
95.0
95.0
95.0
95.0
95.0
95.0
95.0
, 95.0
95.0
95.0 ,
95.0
95.0
95.0
95.0 .- . .
95.0
Formulation Type
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid v
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
. Liquid
Liquid
Liquid >
Liquid
Liquid
-r Liquid
Liquid
Liquid ,
Liquid
91
-------
Batch
IB
EPA Reg. No.
11715-22
28293-101
48139-4
% Active Ingredient
71.25
71.25
76.0
Formulation Type
Aerosol
Aerosol
Aerosol
Batch
1C
EPA Reg. No.
8668-3
67200-3
67200-4
69152-1
69152-2
% Active Ingredient
78.0
9.5
9-9.5
10.0
10.0
Formulation Type
Towelette
Wristband
Tablecloth
Wristband
Tablecloth
:,:: ..1 . '
, ";'ii ,,<1 '
Batch
ID
Batch
IE
Batch
IF
Batch
1G
EPA Reg. No.
3282-55
EPA Reg. No.
4822-174
EPA Reg. No.
8668-3
EPA Reg. No.
54287-5
% Active Ingredient
42.75
% Active Ingredient
14.25
% Active Ingredient
78.0
% Active Ingredient
30.0
Formulation Type
Liquid
Formulation Type
Aerosol
Formulation Type
Towelette
Formulation Type
Liquid
Batch
2A
EPA Reg. No.
305-29
901-37
4822-217
*4822-244
28293-114
39494-1
46075-2
53356-2
66733-5
% Active Ingredient ,
55.0
71.25
71.25
71.27
71.25
71.0
71.25
71.25
71.25
Formulation Type
Towelettes
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Batch
2B
EPA Reg. No.
4822-241
% Active Ingredient
71.25
Formulation Type
Aerosol
92
-------
Batch
2C
EPA Reg. No.
305-29
% Active Ingredient
. " 52.25 '
Formulation Type
Towelette
Batch
3A,
' EPA Reg. No.
4822-7
4822-242
4822-243
19713-314 ,
56575-10
% Active Ingredient
' -- '47.5. .
38.0
47.5
50.0
47.5
Formulation Type
Liquid
Liquid
Liquid
Liquid
Liquid
Batch
3B
EPA Reg. No.
*305-32
305-33
305-46
*4822-239
4822-240
4822-398
6148-10
% Active Ingredient
38.0
52.25
38.0
38.0
47.5
38.0
38:0
Formulation Type
Aerosol
Aerosol
Aerosol
Aerosol
Aerosol '
Aerosol
Aerosol
Batch
4A
EP,A Reg. No.
*4822-253
*4822-254
% Active Ingredient
, . 33.25 " ...-''
28.5 ''
Formulation Type
Liquid
Liquid
Batch
4B
EPA Reg. No.
*4822-258
% Active Ingredient
23.75
Formulation Type
Towelette
Batch
, 4C
EPA Reg. No.
* 121-45
121-46
121-67
305-49
- 305-52
4758-81
4822-197
*4822-204
4822-397
% Active Ingredient
28.5
28.5
28.5
29.0
' 27.0 ;
28.5
33.25
28.5
28.5
Formulation Type
Aerosol
Aerosol
Aerosol
Aerosol
, Aerosol
Aerosol
' Aerosol .
Aerosol
Aerosol ._,
93
-------
, "11, - ,,
1 ' >
III 1 1 1 iป !r: III1,,'!,;,.:,, ,,r ,ji";! ", 11 JIB 1 >i ill1 11 ' ?, i'1 , ,, ",'; ' ,ซ I,,',!,11,1;,,!,,'!!!!!1,,! ,
Batch EPA Reg. No.
*4822-205
5A , 4822-207
i 11556-114
Batch EPA Reg. No.
* 121-31
' *121-33
' 30548
305-50
305-51
4822-10
SB *4822-51
i 4822-119
! 4822-167
4822-380
4822401
--
r i
! { 7056-20
Batch EPA Reg. No.
*4822-368
1 HI i i mi : 4822495
Ill | Illllllllllllll III Mill! i>,!,.
Ji'1, 6A , 4822415 2V1I
j 4822417
1 46515-46
Batch ' EPA Reg. No.
* 121-50
I 121-51
6B
4822-366
4822-396
Batch EPA Reg. No.
* 121-54
7A 121-56
> ,. .iv.;; ' !.:.. '. i ,11, ซ. .-,".M !
;,,,, ; ./I.;,.;,,;,. ;;, sii,^,;,, .uyjf.-u *-,'.*. ,ซ;;; ,' ;. ".;
% Active Ingredient
,,:.: ...14.25
..',.',,. 19-Q ."
21.8
! % Active Ingredient
, ' 21.85
21.85
! , 15.0 : :
, 23.0
; 25.0 .
14.25
17.1 ;
| 19.0
: 23.8
i 14-25 j
i ' . 23.8 i
! .' , ' 14.25 |
; 14.25 i
, ,
; % Active Ingredient j
[ , ' , 6.65
, ,, , , 6.65,; , , j
, 4,75 ,
1 , 4.75 ', ' |
, 6.65, ;
j ; : ; ; ; j-
% Active Ingredient i
9.5
9:5 . t
6.65
, 6.65 1
k 1
% Active Ingredient '
; . i
6.79
;.,. ...I- !:ซ\,-v;:' :;,"";ซ ':,ป: :"::, I,,;;, :ri::,,:1: s-J:^1
' "y ': f,|, , '"! " "'',ป
:,;,,,";,;,;, ;:;: .,-",,;,,;,;.,: ^/hM'-rimiirrfiiiwu'^^
*
Formulation Type
Liquid .
Liquid
Liquid
1 i
Formulation Type
Aerosol
Aerpspl [
Aerosol
. Aerosol
Aerosol j
Aerosol
Aerosol
Aerosol |
'. : " 1 ' '' ,
Aerosol j
Aerosol i
- p i i '
Aerosol '
Aerosol |
Aerosol
Formulation Type
Liquid '
Liquid
Liquid
. , , ." *" ' .::::.-" ; ..;,"l.l.."..;.::t:;. :::;:,;; ':";;:':::.." . ";,
Liquid
Liquid
Formulation Type
Aerosol
Aerosol
- i
Aerosol (
Aerosol j
'
Formulation Type
1
Liquid
Towelette |
9.5
Liquid
11
iiiiii
94
IIIIIII I IIP IIII ill I
-------
Batch t EPA Reg. No.
121-62
121-63
7B
121-64
i - 121-65
Batch ! EPA Reg. No.
1 ' ".."121-52
i 121-53
7C '
. ;' ., 121-55
i 121-72
- ^ '
Batch EPA Reg. No.
' - 498-122
'8
- .*498-154
Batch EPA Reg. No.
' ' . ". 121-29
^ 121-34
.9 4822-160
*4822-206
4822-399
Batch EPA Reg. No.
121-60
121-61
*4822-362
' .
10 ' .' 4822^-373
' i 4822-414
4822-416
, i .4822-424
Batch EPA Reg. No.
121-66
11A i 121-68
! 121-69 .
11B ' . 121-77
% Active Ingredient
9.5
9.5
9.5 '
. 9.5 .'.
% Active Ingredient
' -.. 9-5
' . 9.5,
.- . -,9-5
9.5
.
% Active Ingredient
14.25.
x 14.25 -
% Active Ingredient
- 2L85
21.85
17.10 "
' ', 23.75
23.7.5
---.'.
% Active Ingredient
7.125
. 7.125
. 7.125
7.125
4.75:
.': ' 4.75
. . . - J.125'
% Active Ingredient
28.5 .
21.85
21.85
. 6.65 ^
i Formulation Type
" Aerosol
; ' Aerosol
Aerosol
. .j - . Aerosol
; Formulation Type
; Liquid
! - Liquid
Liquid
h : Liquid
Formulation Type
: , Aerosol
Aerosol
{
Formulation Type
. t . .
Liquid
! Liquid :
'.' ' Liquid
1 . Liquid
Liquid
&
Formulation Type '
Liquid
1 Liquid
Liquid !
I Liquid
! Liquid ;
: .Liquid ;
Liquid
Formulation Type
Aerosol
Aerosol
Aerosol
Aerosol
95
-------
1
" . . - ป
.ill, I1.. 1 'I ! "' '.'I? ;,;!!!(. ' '"
:
au ซ":',!', '",,; ;.. ,',;,! ''
in" a.!"1 " i, ,
in ii
. |, i mil i i i
Batch EPA Reg. No.
69298-1
12 69298-2
68298-3
^Batch EPA Reg. No.
121-18 ;
13 ' 121-20
121-59 ;
i Batch EPA Reg. No.
j *66306-1 '
66306-3
14
66306-5
i '
! 66306-4 | "
% Active
in in '
Ingredient
23.75
11.875
10.83
;
% Active
31
.31
Ingredient
.35
.35
28.5
% Active
Ingredient
19.00
19.00
9.
19
50
.00
i I- i
Formulation Type
; < Liquid
Liquid
Liquid
Formulation Type
Solid
Solid
Solid
Formulation Type '
Liquid '
Liquid
Liquid
Liquid '
Batch EPA Reg. No.
i 3.ฐ5-41 i
} 305-43 !
15A
305-44 j.
305-45 [
;
Batch .EPA Reg. No. j "
! * 121-70 '
15B ; 305-42 '. I ".
*64583-l !
Batch EPA Reg. No. |
i
' I,'' ...'i , I 121-16 ".. "I , ".,
IfiA ' "
i ..;ป. i .':,, "., .: !'!! , J -,A's' vx I1 '
1 tl'.vi , -,,i. !;.;,,i"i. . tir - iiwiiii', : f-4-v r- ,, m ป !
% Active
9
19
^ ,19
19
Ingredient
.5 ; ; ;
.do
.00
.00
'
% Active Ingredient
9
9
Formulation Type
Liquid
Liquid
Liquid 1
Liquid
Formulation Type
5 | Liquid
5
9.5
% Active Ingredient
DEBT 33.25 j
N-pctyl 1.0 ;
Di-N-propyl 1.0 "
:,:'.' ' ,, DEBT
33.25
N-octyi 1.6 !
Di-N-propyl 1.0 '
Liquid
Liquid !'
i
Formulation Type
Liquid
Liquid \
' * ; r
,
Batch EPA Reg. No. !
% Active Ingredient i
::; "": -'-'" : ';'' : ' '"':"*121-30 ' , j- 33.25 ' 1
*I21-32 . ;
121-57 :
1 ,121-58 ' !
33.
28
28
25 i
.5 i
.5 !
Formulation Type '
'"lI'M
Liquid
Liquid
Liquid
Liquid
96
-------
Batch EPA Reg. No.
58007-1
17
58001-4-
% Active ^ngredient ;
'
'
31.50 , . ' :
'28.4
Formulation Type
Liquid
Liquid
' - '
Batch EPA Reg. No.
; 121-27
----- "_ ,'
1KA '
'. ' , * 121-41
% Active Ingredient
DEBT 17.1
N-octyl 1.0"
Di-N-propyl
DEBT 17.1
N-octyl 1.0
- Di-N-propyl
1.0 ' i
1.0
Formulation Type
Liquid
Liquid
Batch . EPA Reg. No.
18B ; 121-15
! '
121-21
% Active Ingredient j
DEBT 17.1
N-octyl 1.0
Di-N-Propyl
DEET 17.1
N-octyl 1.0
Di-N-propyl
! .
i
i.o ;
1 ' i
1-0 ;- . j
Formulation Type
~
Aerosol
\, .
Aerosol
...
Batch ; EPA Reg. No.
2596-114
19A
2596-115
2596-120
ion
2596-121
% Active Ingredient
Esfenvalerate.il .DEBT 10.0^ \
/Esfenvalerate .11 DEBT 10.0 |
Esfenvalerate 0.025 DEET . 3.99 ;
Esfenvalerate 0.025 DEET 3.9? . ;
Formulation Type
Aerosol
' Aerosol '.
Aerosol
Aerosol
Htch EPA Reg. No.
j 1021-567
1021-1276
OflA
1021-1290.
! . ' ' ' - '
-1021-1312
% Active Ingredient i
: DEBT 66.50 . ' ;
N-octyl 20.00 ,
Di-N-propyl 10.00 ' . '
DEET 86.00 * !
, N-octyl 8.00
Di-N-propyl 6.00
DEET 73.07 !
N-octyl 15.38
Di-N-propyl 7.70
, DEBT ' 76.00 !
N-octyl 12.00' '!
Di-N-propyl 8.00 !
Formulation Type
Liquid
. 'i
Liquid i
Liquid '
, !
, Liquid
Batch EPA Reg. No.
20B . 102'l-737
. . %' Active Ingredient ;
- DEET 84^45 1
N-octyl 11.11 ' :
Formulation Type j
Liquid ;
97
-------
n 1 in i miiw in mi
111 111
Batch EPA Reg. No.
* 99-123
21 A ' 10404-25
2217-780
1
Batch EPA Reg. No.
3546-28
01 15 ,
10806-86
Batch EPA Reg. No.
305-40
t
r
769-606
1021-535
in in in in
! 56058-4"
77 A
56058-5
54287-11
in i i i nil i
l|l III I L i i"
56575-9
111 i ill III i i 1 IL
65636-86
% Active Ingredient
DEBT 36.53
N-octyl 7.69
Di-N-propyl 3.85
DEBT 38,0 '
N-octyl 6.0
Di-N-propyl 2.0
:DEET 33.25
N-octyl 10,0
Di-N-propyl 5.0
% Active Ingredient
DEBT 26.60
N-octyl 8.00
Di-N-propyl 4.00
DEBT 26.60
N-octyl 8.00
Di-N-propyl 4.00
1 % Active Ingredient
DEBT 16.62
N-octyl 5.00
Di-N-propyl 2.50
DEBT 16.62
N-octyl 5.00
Di-N-propyl 2.50
DEBT 16.625
N-octyl 5.00
Di-N-propyl 2.50
DEBT " 23.75 ' J ,
N-octyl 5.00
1 Di-N-propyl 2.50
DEBT 16.625
N-octyl 5.000
Di-N-propyl 2.500
DEBT 16.625
N-octyl 5.000
Di-N-propyl 2.500
DEBT 23.75 ..", ;;. :,"
N-octyl 5.00
Di-N-propyl 2.50
DEBT 16.62
N-octyl 5.00
Di-N-propyl 2.50
i
Formulation Type
Liquid
Liquid
,
i -
1 Liquid
I ''
j Formulation Type
! Aerosol
[ i ,i ..,,', ,
i i
! . . ' i
Aerosol
i , ......
| Formulation Type
i,
f
) Liquid
: Liquid ,
, v,.f ,
1 Liquid
i ! ' f.
! '. ' wr. T :,.; t
Liquid 1
".:;... r:: :::.:: ;; ;..; :.: : (
.: I.'.:,"...:: ': ::..'."
Liquid
Liquid ,
" - " . [
Liquid
I
i
,. . 1 ; ,i , |||
. Liquid :
'i i-
iillill
98
-------
Batch EPA Reg. No.
67405-1
OO A
Z//V
68688-42
I - .
Batch ; EPA Reg. No.
! " 7405-60
, - . ' ( ' ' .,
*
1
22B ! 7754-40 .
11715-86
i
Batch ; EPA Reg. No.
' ' ' - \ ,
22C 11715-242 -
Batch EPA Reg. No.
22D ' , 9444-26
Batch EPA Reg. No.
. '69421-55 .
!
23 10807-29
. ' ..
-'. , 10900-74
' . ' .
.
% Active Ingredient
DEET 16.625
N-octyl 5.000
. Di-N-propyl 2.500
: DEET 16.62
N-octyl ,5.00
. Di-N-propyl 2.50
% Active Ingredient
, DEET 9.975
N-octyl 3.000
Di-N-propyl 1.500
DEET. 6.65
N-octyl 2.00
Di-N-propyl 1.00
. DEET 13.66
. ' . N-octyl 3.84
Di-N-propyl 0.96
% Active Ingredient
. , , DEET 15.43
N-octyl 4.34
Di-N-propyl 1.08
% Active Ingredient
DEET 6.65
N-octyl 2.00
Di-N-propyl 1.00
% Active Ingredient
DEET 6.65
.'-. N-octyl 2.00 ,
Di-N-propyl 1,00
DEET 6.65
N-octyl 2.00 ,
Di-N-propyl 1.00
- DEET 9.975
N-octyl 3.000
.Di-N-propyl 1.500
Formulation Type
Liquid
Liquid
Formulation Type
Aerosol
Aerosol
Aerosol
* ' .
,
Formulation Type
.-...'
Towelette
Formulation Type
Aerosol
,
Formulation Type
Aerosol
tAerosol
Aerosol .
99
-------
Ill, IJiilL ,niu III II M itS'S &;::(
Batch EPA Reg. No.
" 3282-38
i
24 A 7754-41
' 69421-53
L Batch " EPA Reg. No.
I
305-39
| 334-561 "
1
I"
I
498-148
* 1021-1600
10807-127
f
24B 10900-72
i t
i
, i
11715-85
. 13283-12
I
1 34702-5
1
j 44446-48
, 46813-22
,;i, Jl ' , >!( J,; ;,; , ; .( ;"p I :'?. " i , : ,S ! sM <*;(,>! -Wl ' '-i "! -if >%'.X3
% Active Ingredient
DEET 25.0 (
N-octyi 5.0
Di-N-propyl 1.25 ;
, DEET ,23.75," ' ; ' !
( N-octyl 5.00
* Di-N-propyl 2.50 '
DEET 23.75 ,:,
N-octyl 5.66 V
Di-N-propyl 2.50 !
' ., ' . ' "
1 '
, % Active Ingredient
DEET 25.50
N-octyl 7.67 ' '
; Di-N-propyl 3.84 \
DEET 23.75
N-octyl 5.00
Di-N-propyl 2.50
1 ฃ~p 23_75; i
N-octyl 5.00
Di-N-propyl 2.50
DE'lET 23.75 ' ' !'
N-octyl 5.00
Di-N-propyl 2.50
DEET 23.75
N-octyi 5.66 !
Di-N-propyl 2.50 ,;
DEET 23.75 :
N-octyl 5.00' - :
Di-N-propyl 2.50
DEET 27.32 . ', ;
N-octyl 7.67
Di-N-propyl 1.92
DEET 27.32 ' !
N-octyl 7.67 .
Di-N-propyl 1.92 j
DEET 23.75 . i
N-octyl 5.00 !
Di-N-propyl 2.50
DEET 22.56
N-octyl 5.66
Di-N-propyl 2.50
DEET 23S75 ','
N-octyl 5.00
Di-N-propyl 2.50 |
li,!:!!1;,,'!;1 ;,:;'!(; , ^4i^t!MT .'ir^MliSiJfii'BiiiiiiK'JWM
Formulation Type j
Aerosol
Aerosol
', " , i
' i
Aerosol I
Formulation Type
Aerosol
Aerosol
Aerosol
Aerosol
(
r
Aerosol
t
Aerosol | , ,
Aerosol
,,| , .
Aerosol > , . . .
1
Aerosol
- Aerosol , ,]
Aerosol
100
-------
Batch " EPA Reg. No.
; . 56058-6
"MP
' i ' .-'
i 58284-20
Batch EPA Reg. No.
1685-72
i?1
. '-. " i ' 2915-47
.' ' i . . - .
Batch | EPA Reg. No.
26A' ' - 48139-6
Batch i EPA Reg. No.
. 305-31
-'..'. 6148-9
i . .
Batch EPA Reg. No.
26C 1 . 1270-107
Batch | EPA Reg. No.
26D ; ' . 478-40
% Active Ingredient
! DEBT 23.75
N-octyl 5.00 '-,'.
Di-N-propyl 2.50
DEET 23.75
N-octyl 5.00
Di-N-propyl 2.50
% Active Ingredient
DEBT 4.38
N-octyl 1.30
Di-N-propyl 0.65
; ' DEBT "8,0
N-octyl 0.54
Di-N-propyl 0.54
% Active Ingredient
DEBT 28.5.
% Active Ingredient
DEET. 33.25 . .
DEBT 25.0
- .
% Active Ingredient
DEBT; 15,0
% Active Ingredient
DEET 15.0
; Formulation Type
Aerosol
1
i
! Aerosol.
; Formulation Type
_. Aerosol
Aerosol
i Formulation Type
| Liquid
Formulation Type
j Aerosol
i . , Aerosol
i Formulation Type
! . '
i . Aerosol
1 ,- - : -
\ Formulation Type
i Aerosol
The following table lists products that were either considered not to be similar or the Agency
lacked sufficient information for decision making and were not placed in any batch. The-registrants
of these products are responsible for meeting the acute toxicity data requirements separately.
Table 2 (No Batch)
EPA Reg. No.
121-74
. . 305-28 .
498-4 L
| % Active Ingredient
i , DEET
; DEET.
: DEET
; . N-oetyl
! " Di-N-propyl
9.5
52.25
16.62
5.00
2.50
; Formulation Type [
| Liquid ,
'i . Liquid ;
i
i Aerosol ]
! .1
i . ' - . , i
101
-------
11 nun i i i ป""' ' '-'.,''
EPA Reg. No.
498-175
*29 15-40
r-
3095-23
4822-UAI
:;-',4758778 ,
3862-102
4972-32
1
6148-11
10806-34
28293-113
44599-1
44599-2
46813-46
*50830-3
54287-6
*54287-8
*58007-2
IP i i ii iiiiiii 1 1 iiiiiii i ii i MI in ii i 111 in
*58007-3
:::', :: 61553-1
:.":'.-. :. . " " "66306-5
66306-7
% Active Ingredient
DEET
N-octyl
Di-N-propyl
DEBT "
N-octyl
DEET
N-octyl
Di-N-propyl
DEET
DEET
Butoxypolypropylene
glycol
DEET
DEET
N-octyl
} Di-N-propyl
DEET
,! DEBT
N-octyl
] Di-N-propyl
DEET
DEET
DEET
l'"|l::=:;::' .'DEBT
N-octyl
DEET
N-octyl
Di-N-propyl
" DEET
N-octyl
DEET
N-octyl
Di-N-propyl
DEET
II 1 1 II P III I'! ป' f '"!' '"''
DEET
i DEBT
'. N-octyl '
Di-N-propyl
DEBT
DEET
24.46
5.0
2.5 .
7.0
2.50
22.80
1.72
3.00
7.5
28.5
15.0
14.25
9.975
3.000
1.50
io.o "
9,975
3.000
1.50
14.25
9.50
19.00
"8:45 .
1.11
25.00
5.00
3.00
19.06
5.00
16.625
5,000
2.50.0
9.02
23.75
,11.2
3.2
0.8
950
' 19.95
102
Formulation Type
; Liquid
Liquid
i Liquid
Liquid
t i '
i
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1 Aerosol
I ' ;
; Aerosol
i
1 *
[ Liquid
i
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I '' ' ! ' '
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, Liquid
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' t ' " ' ' '
i ; _ ;
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i . . .
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; ii,,sji:.i;r,iii "3i< . &. iซ,iri i mi .1 :i i ,, i :tt it1! -i . , ,; i i -r. K if'\jn /if -r i, ' : ( |l|!l,i ' (iwiKW '.'("Mitt "'t 'm
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i . , i
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Liciuid
( Liquid
111 111111 111 111 111 111 111 I 111 IIIIIII 11 IIIIIII
-------
103
-------
Cost Share, Data Compensation Forms, Confidential Statement of Formula Form and
Instructions
The Confidential Statement of Formula (CSF) Form 8570-4 must be used. Two legible, signed
copies of the form are required. Following are basic instructions:
a. All the blocks on the form must be filled in and answered completely.
b. If any block is not applicable, mark it N/A.
' ' ' < ,
c. The CSF must be signed, dated and the telephone number of the responsible party
must be provided.
d. All applicable information which is on the product specific data submission must
also be reported on the CSF.
e. All weights reported under item 7 must be in pounds per gallon for liquids and
pounds per cubic feet for solids.
f. Flashpoint must be in degrees Fahrenheit and flame extension in inches.
g. For all active ingredients, the EPA Registration Numbers for the currently registered
source products must be reported under column 12.
h. The Chemical Abstracts Service (CAS) Numbers for all actives and inerts and all
I.
j-
m.
common names for the trade names must be reported.
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For the active ingredients, the percent purity of the source products must be reported
tinder column 10 and must be exactly the same as on the source product's label.
All the weights in columns 13.a. and 13.b. must be in pounds, kilograms, or grams.
In no case will volumes be accepted. Do not mix English and metric system units
(i.e., pounds and kilograms).
k. All the items under column 13 .b. must total 1QO percent.
1. All items under columns 14.a. and 14.b. for the active ingredients must represent
.'.' .'pure" active:
The upper and lower certified limits for aT-1 active and inert ingredients must follow
the 40 CFR 158.175 instructions. An explanation must be provided if the proposed
limits are different than standard certified limits.
n. When new CSFs are submitted and approved, all previously submitted CSFs become
obsolete for that specific formulation.
104
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106
-------
United States Environmental Protection Agency
Washington, D.C, 20460;
Certification of Offer-to Cost
Share in the Development of Data
Form Approved
OMB No. 2070-0106,
2070-0057
Approval Expires
3-31-99
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, PM-233, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460; and to the Office of
Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill in blanks below:
Company Name
Company Number
Product Name
EPA Reg. No.
I Certify that:
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA), if necessary. However my company would prefer to
enter into an agreement with one or more registrants to develop jointly or share in the cost of developing
data.
; ' - *,
My firm has offered in writing to enter into such an agreement. That offer was irrevocable and included an
an offer to be bound by arbitration decision under section 3(c)(2)(B)(iii) of FIFRA if final agreement on all
terms could not be reached otherwise. This offer was made to the following firms on the following
date(s):
Name of Firm(s)
Date of Offer
Certification:
I certify that I am duly authorized to represent the company named above, and that the statements that I have made on
this form and all attachments therein are true, accurate, and complete. I acknowledge that any knowingly false or
misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature of Company's Authorized Representative
Date
Name and Title (Please Type or Print)
EPA Form 8570-32 (5/91) Replaces EPA form 8580 which is obselete
107
-------
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'i,ii ,., i aiiiiii'iiLii1,!1!!!:1' .i,,!:1;. >,
| ijjllljjljjji'illjl lij; :"i'' ''ijluY
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mir , i1 "lij, :nr K nm I
^^^^ HllllFii*111'l;1"';',;;;ii
lll,lil"i!i,il lnl,'' f!" '"i '/'I i!;!1'1'1'1' ' i ' V :,; ''f1, '" ''.""nlJ11','1'" '''''".'i!"!''1'
".i'l!1!'!, II, ,ซ ',' 1,l!"1 ||l||||vi,:'"|i. I" ',;, ., 1" Hi) ' ,!, ป!!' i.1;,'1!'' ' ,', "III
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108
-------
Form Approved OMB No. 2070-0060
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
401 Wl Street, S.W.
WASHINGTON, D.C. 20460
Paperwork Reduction Act Notice: The public reporting burden for this collection of information is estimated to average 1.25 hours per response for
registration,and 0.25 hours per response for reregistration and special review activities, including time for reading the instructions and completing the
necessary forms. Send comments regarding burden estimate or any other aspect of this collection of information, including suggestions for reducing the
burden to: Director, OPPE Information Management Division (2137), U.S. Environmental Protection Agency, 401 M Street, S.W., Washington, DC 20460.
Do not send the completed form to this address. - .
Certification with Respect to Citation of Data
Applicant's/Registrant's Name, Address; and Telephone Number
Active Ingredient(s) and/or representative test compound(s)
General Use Pattern(s) (list all those claimed for this product using 40 CFR Part 158)
EPA Registration Number/File Symbol
Date -
Product Name
NOTE: If your product is a 100% repackaging of another purchased EPA-registered product labeled for all the same uses on your label, you do not need to
submit this form. You must submit the Formuiator's Exemption Statement (EPA Form 8570-27).
D
I am responding to a Data-Call-in Notice, and have included with this form a list of companies sent offers of compensation (the Data Matrix form
should be used for this purpose). . .
SECTION I: METHOD OF DATA SUPPORT (Check one method only)
D
I am using the cite-all method of support, and have included with this
form a list of companies sent offers of compensation (the Data,Matrix
form should be used for this purpose)!
n
I am using the selective method of support (or cite-all option
under the selective method), and have included with this form a
completed list of data requirements (the Data Matrix form must
be used).
SECTION II: GENERAL OFFER TO PAY
[Required if using the cite-all method or when using the cite-all option under the selective method to satisfy one or more data requirements]
| I I hereby offer and agree to pay compensation, to other persons, with regard to the approval of this application, to the extent required by FIFRA.
SECTION III: CERTIFICATION
I certify that this application for registration, this form for reregistration, or this Data-Call-in response is supported by all data submitted or cited in
the application for registration, the form for reregistration, or the Data-Call-in response. In addition, if the cite-all option or cite-all option under the selective
method is indicated in Section I, this application is supported by all data in the Agency's files that (1) concern the properties .or effects of this product or an
identical or substantially similar product, or one or more of the ingredients in this product; and (2) is a type of data that would be required to be submitted
under the data requirements in effect on the date of approval of this application if the application sought the initial registration of a product of identical or
similar composition and uses. .' ,
I certify that for each exclusive'use study cited in support of this registration or reregistration, that I am the original data submitter or that I have
obtained the written permission of the original data submitter to cite that study.
I certify that for each study cited in support of this registration or reregistration that is not an exclusive use study, either: (a) I am the original data
submitter; (b) I have obtained the permission of the original data submitter to use the study in support of this application; (c) all periods of eligibility for
compensation have expired for the study; (d) the study is in the public literature; or (e) I have notified in writing the company that submitted the study and
have offered (I) to pay compensation to the extent required by sections 3(c)(1 )(F) and/or 3(c)(2)(B) of FIFRA; and (ii) to commence negotiations to determim
the amount and terms of compensation, if any, to be paid for the use of the study.-
I certify that in all instances where an offer of compensation is required, copies, of all offers to pay compensation and evidence of their delivery in
accordance with sections 3(c)(1)(F) and/or 3(c)(2)(B) of FIFRA are available and will be submitted to the Agency upon request. Should I fail to produce sucl
evidence to the Agency upon request, I understand that the Agency may initiate action to deny, cancel or suspend the registration of my product in
conformity with FIFRA.
I certify that the statements I have made on this form and all attachments to it are true, accurate, and complete. I acknowledge that any
knowingly false or misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature
Date
Typed or Printed
Name and Title
EPA Form 8570-34 (9-97) Electronic and Paper versions available. Submit only Paper version.
-------
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DATA MATRIX
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INSTRUCTIONS FOR DATA MATRIX
in ill i iiii n in i in mi 111 in Miiiiiiii in i in in ii i in in i n MI n in in i i ( i i in ill 11(111 i in iiiiiiiii i ii ii ' in mil in iiiiiii iiiiiii iiiiiii i
INSTRUCTIONS: Identify all data submitted or cited and all submitters from whom permission has been received or to whom offers to pay
have been sent by entering sufficient information in the attached matrix (photocopy and attach additional pages as necessary). Complete
all columns; omission of essential information will delay approval of the registration/reregistration. On each page enter the date,
Applicant's/Registrant's name, EPA Registration Number or application file symbol of the product, ingredient, page number, and total
number of pages.
The Data Compensation Form entitled "Certification with Respect to Citation of Data" and the Data Matrix will be publicly available, except
for the Guideline Reference Number, Guideline Study Name, and MRID Number columns after the registration/reregistration of this product
has been granted or once this form is received in response to a Data-Call-in Notice. However, the information in the Guideline Reference
Number, Guideline Study Name, and MRID Number columns is available through the Freedom of Information Act in association with the
EPA Registration Number.
Ingredient; Identify the active ingredients) in this product for which data are cited. The active ingredients) are to be identified by entering
the chemical name and the CAS registry number. Begin a new page for each .separate active ingredient for which data are cited. If bridging
data from ง relatedjฑem|cal or representative test compound are cited, enter the identity of that chemical/representative test compound
including the EPA Registration Number/File Symbol if appropriate.
'I'ilij! ,:!i'i iil'1
II 1
if the cite-all method is used for all data supporting this particular ingredient, enter "CITE-ALL" in the Guideline Reference Number
column and leave the Guideline Study Name column blank. If the cite-all method is used for a particular Guideline Reference Number enter
"CITE-ALL" in the MRlD Number column on the line for that Guideline Reference Number. In either case, enter all submitters to whom
offers to pay have been sent on subsequent lines. [Note: if the selective method of support is used and written authorization (letter of
permission) is provided, the individual Guideline Reference Number, Guideline Study Name, and MRID Number columns must still be
completed.] Otherwise:"
Number: Enter on separate lines in numerical order the Guideline Reference Numbers from 40 CFR Part 158 for
all studies cited to support the registration/reregistration for this ingredient.
-GuldelJpeJฃtudvJtemjg: For each Guideline Reference Number cited, enter the corresponding Guideline Study Name.
MRID Number For each individual study cited in support of a Guideline Reference Number and Guideline Study Name, enter the Master
BfifiPjrd Identification (MRID) Number listed in the Pesticide Document Management System (PDMS). Enter only one MRID Number on
each line. Note that more than one MRID Number may be required per Guideline Reference Number. Note: Occasionally a study required
to maintain a registration/reregistration is not associated with a Guideline Reference Number and Guideline Study Name. In such case,
enler the pRID Number(s) for the study(ies).
Submitter: Using the most recent Data Submitters List, identify the Original Data Submitter with their current address for each study cited.
The EPA assigned company number or other abbreviation may be used. Clearly explain any variations (alternate addresses, data owners
not on the Data Submitters List, etc.) in footnotes to this table.
Status: Enter one of the following codes for each study cited, as appropriate:
OWN: I am the Original Data Submitter for this study.
EXC: rhaye'pbtiined" written" permissibn' of the Original "Data 'Submitter' to cjje fnjs exclusive-use study in support of this"
'application. ' '
I have obtained the permission of the Original Data Submitter to use this study in support of this application.
The study was submitted more than 15 years ago and all periods of compensation have expired.
The study is in the public literature.
I have notified in writing the Original Data Submitter or, if the cite-all method is used, all companies listed in the most
current Data Submitters Uงt for this ingredient, and have offered (a) to pay compensation in accordance with FIFRA
sections 3(cj(1)(F) and/or 3(c)(2)(B), and (b) to commence negotiations to determine the amount and terms of
compensation, if any, to be paid for the use of the study(ies).
This Guideline data requirement is a data gap as defined in 40 CFR sections 152.83(a) and 152.96.
I am taking the formulator's exemption for this ingredient only. Other columns of this line should be marked "NA".
However, if this product is to be registered/reregistered for additional uses for which the purchased EPA registered
ingredient is not supported, additional data must be submitted or cited here to support those uses.
If additional explanation is needed, enter a footnote number in this column and attach the corresponding explanation.
PER:
OLD:
PL*
i * **
PAY:
GAP:
FOR:
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United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
#
Form Approved
OMB No. 2070-0107,
2070-0057
Approval Expires
3-31-99 K'
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, Regulatory Information Division, Mail Code 2137, U.S. Environmental Protection
Agency, 401 M St., S.W., Washington, DC 20460; and to the Office of Management and Budget, Paperwork Reduction Project
(2070-0106), Washington, DC 20503.
Please fill in blanks below.
CompanyName
Product Name
Company Number
EPA Reg. No.
I Certify that:
1. For each study cited in support of registration or reregistration under the Federal Insecticide, Fungicide and Rbdenticide Act
(FIFRA) that is an exclusive use study, I am the original data submitter, or I have obtained the written permission of the original
data submitter to cite that study.
2. That for each study cited in support of registration or reregistration under FIFRA that is NOT an exclusive use study, I am the
original data submitter, or I have obtained the written permission of the original data submitter, or I have notified in writing the
compahy(ies) that submitted data I have cited and have offered to: (a) Pay compensation for those data in accordance with sections
3(c)(l)(F) and 3(c)(2)(D) of FIFRA; and (b) Commence negotiation to determine which data are subject to the compensation
requirement of FIFRA and the amount of compensation due, if any. The companies I have notified are: (check one)
[ ] The companies who have submitted the studies listed on the back of this form or attached sheets, or indicated on the attached "Requirements
Status and Registrants' Response Form," . , .
3. That I have previously complied with section 3(c)(l )(F) of FIFRA for the studies I have cited in support of registration or reregistration
under FIFRA.
Signature
Date
Name andTitle (Please Type or Print)
GENERAL OFFER TO PAY: I hereby offer and agree to pay compensation to other persons, with regard to the registration or
reregistration of my products, to the extent required by FIFRA section 3(c)(l)(F) and 3(c)(2)(D).
Signature
Date
Name and Title (Please Type or Print)
IPA Form 8570-31 (4-96)
115
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List of Available Related Documents
The following is a list of available documents for DEBT that my further assist you in
responding to this Reregistration Eligibility Decision document. These documents may be obtained
by the following methods:
Electronic
Tl II I II Illll I nil I II III I III I I I II II I II II ,,M' ,."!! till, ,,1,1'i' '' : .i;,!,11!!,!!!1!:.!.!,,1'':!,'' II. ''i.ilW ,: lUll'S*,!1 ฅ" M1'1-" ;r,n ..-Il :,r 'til 'ปซ" ,: ,' V'Sihliii '<::,'ซ '"I" Mi"1:!!!!!! 'fJiilii'sESIiJiJillllirtJ
ile format: Portable Document Format (.PDF) Requires Adobeฎ Acrobat or compatible reader.
Electronic copies can be downloaded from the Pesticide Special Review and
Reregistration Information System at 703-308-7224. They also are ayailable on lie
Internet using ftp on FTP.EPA.GOV, or using WWW (World Wide Web) on
WWW.EPA.GOV., or contact Linda Werrell at (703)-308-8033.
1, PR Notice 86-5.
2. PR Notice 91-2 (pertains to the Label Ingredient Statement).
< ,,",,, in u< s, , ปi , ...j.n' ,, in ,'..' ,,,,: i ',,', , ..PI,,!! ,, :.,!,, ,! ,,,i ,',,' 'ซ," r : rj ,: I* , , , ,'<', !""ซ -
3. Afiillcopy of this RED document.
4. A copy of the fact sheet for DEBT.
li'lii,,1' '! u i"u,ii! l ilii!'
The following documents are part of the Administrative Record for DEBT and may included
in the EPA's Office of Pesticide Programs Public Docket;. Copies of these documents are not
ayailable electronically, but may be obtained by contacting the person listed on the Chemical Status
Sheet !, ; .,..
'i . " '
1. Health and Environmental Effects Science Chapters.
2. Detailed Label Usage Information System (LUIS) Report. ".
The following Agency reference documents are not available electronically, but may be
obtained by contacting the person listed on the Chemical Status Sheet of this RED document.
1. The Label Review Manual.
2. EPA Acceptance Criteria
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