United States Prevention, Pesticides EPA738-R-97-010
Environmental Protection And Toxic Substances April 1998
Agency (7508W)
&EPA Reregistration
Eligibility Decision (RED)
Diphenylamine
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, B.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency has completed its
reregistration eligibility review and decisions on the pesticide chemical case diphenylamine
which includes the active ingredient N-phenylbenzeneamine. The enclosed Reregistration
Eligibility Decision (RED), which was approved on September 30, 1997 contains the
Agency's evaluation of the data base of these chemicals, its conclusions of the potential human
health and environmental risks of the current product uses, and its decisions and conditions
under which these uses and products will be eligible for reregistration. The RED includes the
data and labeling requirements for products for reregistration. It may also include
requirements for additional data (generic) on the active ingredients to confirm the risk
assessments.
To assist you with a proper response, read the enclosed document entitled "Summary
of Instructions for Responding to the RED." This summary also refers to other enclosed
documents which include further instructions. You must follow all instructions and submit
complete and timely responses. The first set of required responses is due 90 days from the
receipt of this letter. The second set of required responses is due 8 months from the date
of this letter. Complete and timely responses will avoid the Agency taking the enforcement
action of suspension against your products.
Please note that the Food Quality Protection Act of 1996 (FQPA) became effective on
August 3, 1996, amending portions of both pesticide law (FIFRA) and the food and drug law
(FFDCA). This RED takes into account, to the extent currently possible, the new safety
standard set by FQPA for establishing and reassessing tolerances. However, it should be
noted that in continuing to make reregistration determinations during the early stages of FQPA
implementation, EPA recognizes that it will be necessary to make decisions relating to FQPA
before the implementation process is complete. In making these early case-by-case decisions,
EPA does not intend to set broad precedents for the application of FQPA. Rather, these early
determinations will be made on a case-by-case basis and will not bind EPA as it proceeds with
further policy development and any rulemaking that may be required.
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If EPA determines, as a result of this later implementation process, that any of the
determinations described in this RED are no longer appropriate, the Agency will pursue
whatever action may be appropriate, including but not limited to reconsideration of any
portion of this RED.
If you have questions on the product specific data requirements or wish to meet with
the Agency, please contact the Special Review and Reregistration Division representative C.P.
Moran at (703) 308-8590. Address any questions on required generic data to the Special
Review and Reregistration Division representative Ben Chamblis at (703)308-8174.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregistration Division
Enclosures
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SUMMARY OF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISION (RED)
1. DATA CALL-IN (PCI) OR "90-DAY RESPONSE" If generic data are required for
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 REQUESTS No time extension requests
will be granted for the 90-day response. Time extension requests may be submitted only with
respect to actual data submissions. Requests for time extensions for product specific data
should be submitted in the 90-day response. Requests for data waivers must be submitted as
part of the 90-day response. All data waiver and time extension requests must be accompanied
by a full justification. All waivers and time extensions must be granted by EPA in order to go
into effect.
3. APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE" You must
submit the following items for each product within eight months of the date of this letter
(RED issuance date).
a. Application for Reregistration (EPA Form 8570-1). Use only an original
application form. Mark it "Application for Reregistration." Send your Application for
Reregistration (along with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies of draft labeling which complies with the RED and current regulations
and requirements. Only make labeling changes which are required by the RED and current
regulations (40 CFR 156.10) and policies. Submit any other amendments (such as formulation
changes, or labeling changes not related to 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 from the
National Technical Information Service, publication #PB92-221811; telephone number 703-
487-4650).
c. Generic or Product Specific Data. Submit all data in a format which complies
with PR Notice 86-5, and/or submit citations of data already submitted and give the EPA
identifier (MRID) numbers. Before citing these studies, you must make sure that they meet
the Agency's acceptance criteria (attached to the DCI).
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d. Two copies of the Confidential Statement of Formula (CSF) for each basic and
each alternate formulation. The labeling and CSF which you submit for each product must
comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal
concentration. You have two options for submitting a CSF: (1) accept the standard certified
limits (see 40 CFR §158.175) or (2) provide certified limits that are supported by the analysis
of five batches. If you choose the second option, you must submit or cite the data for the five
batches along with a certification statement as described in 40 CFR §158.175(e). A copy of
the CSF is enclosed; follow the instructions on its back.
e. Certification With Respect to Data Compensation Requirements. Complete and
sign EPA form 8570-31 for each product.
4. COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE Comments
pertaining to the content of the RED may be submitted to the address shown in the Federal
Register Notice which announces the availability of this RED.
5. WHERE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES)
By U.S. Mail:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
By express:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
Arlington, VA 22202
6. EPA'S REVIEWS—EPA will screen all submissions for completeness; those which are not
complete will be returned with a request for corrections. EPA will try to respond to data
waiver and time extension requests within 60 days. EPA will also try to respond to all 8-
month submissions with a final reregistration determination within 14 months after the RED
has been issued.
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REREGISTRATION ELIGIBILITY DECISION
DIPHENYLAMINE
LISTB
CASE 2210
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
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TABLE OF CONTENTS
DIPHENYLAMINE REREGISTRATION ELIGIBILITY DECISION TEAM i
EXECUTIVE SUMMARY v
I. INTRODUCTION 1
II. CASE OVERVIEW 2
A. Chemical Overview 2
B. Use Profile 2
C. Estimated Usage of Pesticide 3
D. Data Requirements 4
E. Regulatory History 4
III. SCIENCE ASSESSMENT 5
A. Physical Chemistry Assessment 5
B. Human Health Assessment 5
1. Hazard Assessment 5
a. Acute Toxicity 5
b. Subchronic Toxicity 6
c. Chronic toxicity 8
d. Carcinogenicity 9
e. Developmental Toxicity 10
f. Reproductive Toxicity 11
g. Mutagenicity 12
h. Metabolism 13
2. Dose Response Assessment 14
a. Reference Dose 14
b. Carcinogenicity Classification and Risk Quantification . . 14
c. Other Toxic Endpoints 14
3. Exposure Assessment 15
a. Dietary Exposure 15
b. Occupational Exposure 19
4. Risk Characterization 22
a. Dietary Risk 22
(1) Acute Dietary Risk 22
(2) Chronic and Carcinogenic Dietary Risk 22
(3) Drinking Water Risk 23
b. Occupational and Residential Risk Characterization .... 23
5. FQPA Considerations 25
C. Environmental Assessment 28
1. Ecological Toxicity Data 28
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a. Toxicity to Terrestrial Animals 28
(1) Birds, Acute and Subacute 28
(2) Birds, Chronic 29
(3) Mammals, Acute and Chronic 29
(4) Insects 29
b. Toxicity to Aquatic Animals 29
(1) Freshwater Fish, Acute 30
(2) Freshwater Fish, Chronic 30
(3) Freshwater Invertebrates, Acute 30
(4) Freshwater Invertebrate, Chronic 30
2. Environmental Fate Characteristics of Diphenylamine Summary
31
3. Exposure and Risk Characterization 35
4. Endangered Species 35
5. Labelling 35
6. Data Requirements 35
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 36
A. Determination of Eligibility 36
B. Determination of Eligibility Decision 36
1. Eligibility Decision 36
2. Eligible and Ineligible Uses 37
C. Regulatory Position 37
1. FQPA Findings 37
2. Tolerance Reassessment 38
3. Tolerance Revocations and Import Tolerances 39
4. Summary of Risk Management Decisions 40
a. Human Health 40
(1) Dietary 40
(2) Worker (Mixer/Loader/Applicator) 40
b. Environmental 41
(1) Avian 41
(2) Mammals, Acute and Chronic 41
(3) Insects 41
(4) Freshwater Fish 41
(5) Aquatic invertebrates 42
(6) Estuarine and Marine Organisms 42
(7) Nontarget Plants (Terrestrial, Semi-Aquatic, and
Aquatic) 42
(8) Endangered Species 42
(9) Surface Water 42
(10) Ground Water 42
5. Restricted Use Classification 42
6. Reference Dose Exceedance 43
7. Endangered Species Statement 43
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8. Labeling Rationale 43
9. Spray Drift Advisory 44
V. ACTIONS REQUIRED OF REGISTRANTS 45
A. Manufacturing-Use Products 45
1. Additional Generic Data Requirements 45
2. Labeling Requirements for Manufacturing-Use Products 45
B. End-Use Products 46
1. Additional Product-Specific Data Requirements 46
2. Labeling Requirements for End-Use Products 47
C. Tolerance Revocation and Import Tolerances 51
D. Existing Stocks 51
VI. APPENDICES 53
APPENDIX A. Table of Use Patterns Subject to Reregistration 54
APPENDIX B. Table of the Generic Data Requirements and Studies Used to
Make the Reregistration Decision 57
APPENDIX C. Citations Considered to be Part of the Data Base Supporting the
Reregistration of Diphenylamine 61
APPENDIX D. Combined Generic and Product Specific Data Call-In ... 69
Attachment 1. Chemical Status Sheets 89
Attachment 2. Combined Generic and Product Specific Data Call-in
Response Forms (Form A inserts) Plus Instructions
91
Attachment 3. Generic and Product Specific Requirement Status and
Registrant's Response Forms (Form B inserts) and
Instructions 97
Attachment 4. EPA Batching of End-Use Products for Meeting Data
Requirements for Reregistration Ill
APPENDIX E. List of Available Related Documents 113
Attachment 1. List of All Registrants Sent This Data Call-in (insert)
Notice 114
Attachment 2. Cost Share, Data Compensation Forms, Confidential
Statement of Formula Form and Instructions ... 115
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DIPHENYLAMINE REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis Assessment
George Keitt
Alan Halverson
Biological Analysis Branch
Economic Analysis Branch
Environmental Fate and Effects Risk Assessment
Richard Lee
Jose Melendez
Mary Frankenberry
Miachel Rexrode
Health Effects Risk Assessment
Christina Swartz
Monica Spann
Stephen C. Dapson
Brian Steinwand
Robert Travaglini
Registration Support Risk Assessment
John Bazuin
Risk Management
Ben Chambliss, Team Leader
Environmental Risk Branch IV
Environmental Risk Branch IV
Environmental Risk Branch III
Environmental Risk Branch IV
Reregistration Support Chemistry Branch
Occupational and Residential Exposure Branch
Toxicology Branch II
Dietary Risk Analysis/SAB
Risk Characterization and Analysis Branch
Fungicide-Herbicide Branch
Reregistration Branch I
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11
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GLOSSARY OF TERMS AND ABBREVIATIONS
ADI Acceptable Daily Intake. A now defunct term for reference dose (RfD).
AE Acid Equivalent
a.i. Active Ingredient
ARC Anticipated Residue Contribution
CAS Chemical Abstracts Service
CI Cation
CNS Central Nervous System
CSF Confidential Statement of Formula
DFR Dislodgeable Foliar Residue
ORES Dietary Risk Evaluation System
DWEL Drinking Water Equivalent Level (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.
EEC Estimated Environmental Concentration. The estimated pesticide concentration in an environment,
such as a terrestrial ecosystem.
EP End-Use Product
EPA U.S. Environmental Protection Agency
FAO/WHO Food and Agriculture Organization/World Health Organization
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
FQPA Food Quality Protection Act
FOB Functional Observation Battery
GLC Gas Liquid Chromatography
GM Geometric Mean
GRAS Generally Recognized as Safe as Designated by FDA
HA Health Advisory (HA). The HA values are used as informal guidance to municipalities and other
organizations when emergency spills or contamination situations occur.
HOT Highest Dose Tested
LC50 Median Lethal Concentration. A statistically derived concentration of a substance that can be
expected to cause death in 50% of test animals. It is usually expressed as the weight of substance
per weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause death in 50%
of the test animals when administered by the route indicated (oral, dermal, inhalation). It is
expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
LDlo Lethal Dose-low. Lowest Dose at which lethality occurs.
LEL Lowest Effect Level
LOG Level of Concern
LOD Limit of Detection
LOEL Lowest Observed Effect Level
MATC Maximum Acceptable Toxicant Concentration
MCLG Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulate
contaminants in drinking water under the Safe Drinking Water Act.
pg/g Micrograms Per Gram
Mg/L Micrograms per liter
mg/L Milligrams Per Liter
MOE Margin of Exposure
MP Manufacturing-Use Product
MPI Maximum Permissible Intake
MRID Master Record Identification (number). EPA's system of recording and tracking studies submitted.
Ill
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GLOSSARY OF TERMS AND ABBREVIATIONS
N/A Not Applicable
NOEC No Observable Effect Concentration
NPDES National Pollutant Discharge Elimination System
NOEL No Observed Effect Level
NOAEL No Observed Adverse Effect Level
OP Organophosphate
OPP Office of Pesticide Programs
Pa pascal, the pressure exerted by a force of one newton acting on an area of one square meter.
PADI Provisional Acceptable Daily Intake
PAG Pesticide Assessment Guideline
PAM Pesticide Analytical Method
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
ppm Parts Per Million
PRN Pesticide Registration Notice
Q*j The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RBC Red Blood Cell
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose
RS Registration Standard
RUP Restricted Use Pesticide
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 A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
WP Wettable Powder
WPS Worker Protection Standard
IV
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EXECUTIVE SUMMARY
The U. S. Environmental Protection Agency has completed its reregistration eligibility
decision of the pesticide diphenylamine. This decision includes a comprehensive reassessment of
the required target data and the use patterns of currently registered products.
Diphenylamine is a plant growth regulator used post-harvest on apples to control storage
scald. This end-use pattern for the current formulations has been classified as indoor food use,
and applications include tank dipping, drenching, conveyor flooding, and spraying. It is
formulated as a wettable powder, as an emulsifiable concentrate, a soluble concentrate/liquid and
liquid ready-to-use. The Diphenylamine Task Force is supporting the reregistration of
diphenylamine for use only in the prevention of storage scald on apples prior to entering storage.
The Agency has concluded that all uses, as prescribed in this document, will not cause
unreasonable risks to humans or the environment. Therefore, all products containing
diphenylamine are eligible for reregistration.
In reaching the determination of safety for infants and children, the Agency found that the
toxicity data base for diphenylamine is complete, based on current requirements, and the effects
observed in pre- and post-natal studies do not indicate an increased sensitivity of infants and
children to diphenylamine. Therefore, an additional uncertainty factor to account for any special
sensitivity to infants and children was not warranted for diphenylamine and nitrosamine (TGAI
impurity) and was not used in the risk assesment.
In examining aggregate exposure, FQPA directs EPA to take into account available
information concerning exposures from pesticide residues in food and other exposures for which
there is reliable information. Since there are no data on diphenylamine in the Agency's Pesticides
in Ground Water Database or in the U.S. EPA's "STORET" database, and the limited use pattern
which is unlikely to result in DP A residues in drinking water, dietary risk from drinking water
will be assumed to be negligible. Diphenylamine is a food use chemical. There are no residential
(non-occupational) uses of diphenylamine; therefore, the considerations for aggregate exposure
are those only from food. Since the only aggregate concern is dietary and all chronic risk fall
below 100 % RfD, there is no aggregate chronic dietary risk concern for diphenylamine. An
acute dietary risk assessment was not conducted since no appropriate endpoint was identified in
the available studies.
EPA does not have, at this time, available data to determine whether diphenylamine has
a common mechanism of toxicity with other substances or how to include this pesticide in a
cumulative risk assessment. For the purposes of this reregistration decision, EPA has not
assumed that diphenylamine has a common mechanism of toxicity with other substances.
Because of minimal expected adverse risk on ecological systems and due to the unlikeliness
of exposure, risk to endangered species is not expected.
Before reregistering the products containing diphenylamine, the Agency is requiring that
product specific data, revised Confidential Statements of Formula (CSF) and revised labeling be
v
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submitted within eight months of the issuance of this document. These data include product
chemistry for each registration and acute toxicity testing. After reviewing these data and any
revised labels and finding them acceptable in accordance with Section 3(c)(5) of FIFRA, the
Agency will reregister a product. Those products which contain other active ingredients will be
eligible for reregistration only when the other active ingredients are determined to be eligible for
reregistration.
VI
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I. INTRODUCTION
In 1988, 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.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) (Public Law 104-
170) was signed into law. FQPA amends both the Federal Food, Drug, and Cosmetic Act
(FFDCA), 21 U.S.C. 301 et seq., and the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA), 7 U.S.C. 136 et seq. The FQPA amendments went into effect immediately. As a
result, EPA is embarking on an intense process, including consultation with registrants, States,
and other interested stakeholders, to make decisions on the new policies and procedures that will
be appropriate as a result of FQPA. This process will include a more in depth analysis of the new
safety standard and how it should be applied to both food and non-food pesticide applications.
The FQPA did not, however, amend any of the existing reregistration deadlines in section 4 of
FIFRA. The Agency will therefore continue its ongoing reregistration program while it continues
to determine how best to implement FQPA.
This document presents the Agency's decision regarding the reregistration eligibility of
the registered uses of diphenylamine (DPA). The document consists of six sections. Section I is
the introduction. Section II describes diphenylamine, 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 diphenylamine. Section
V discusses the reregistration requirements for diphenylamine. Finally, Section VI is the
Appendices which support this Reregistration Eligibility Decision. Additional details concerning
the Agency's review of applicable data are available on request.
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II. CASE OVERVIEW
A. Chemical Overview
The following active ingredient(s) are covered by this Reregistration Eligibility
Decision:
• Common Name: Diphenylamine (DPA)
• Chemical Name: N-phenylbenzeneamine
• CAS Registry Number: 122394
• OPP Chemical Code: 038501
• Empirical Formula: C12HUN
• Trade and Other Names: DPA, Shield DPA, Big Dipper, Decoscald 282, and
No Scald DPA 283
• Basic Manufacturer: Elf Atochem and Pace International
B. Use Profile
The following is information on the currently registered uses with an overview of
use sites and application methods. A detailed table of the uses of diphenylamine are in
Appendix A.
For Diphenylamine:
Type of Pesticide: plant growth regulator
Use Sites: apples
Target Pests: storage scald
Formulation Types emulsifiable concentrate, liquid ready-to-use
Registered: soluable concentrate, wettable powder
Methods and Rates of Application:
Equipment: drencher, tank
Method and Rate: Dip treatment, Post-harvest, Tank
2.666 lb/159 gal; 1.66 lb/100 gal
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Drench, Post-harvest, Drencher
2.6661b/159gal
Flood treatment, Post-harvest, Conveyer
1.661b/100gal
Spray, Post-harvest, Sprayer
1.661b/100gal
Spray, Post-harvest, Sprayer
2.6661b/159gal
post-harvest
C. Estimated Usage of Pesticide
This section summarizes the best estimates available for the pesticide uses of
diphenylamine. These estimates are derived from a variety of published and proprietary
sources available to the Agency. The data, reported on an aggregate and site (crop) basis,
reflect annual fluctuations in use patterns as well as the variability in using data from
various information sources.
Based on available pesticide usage and residue data for 1990 through 1994, an
annual estimate of the total domestic usage of diphenylamine is approximately one hundred
thousand pounds of active ingredient (a.i.) applied post-harvest to approximately 1.8
million tons of apples. The average treatment rate for post-harvest apples is about 0.04
pounds a.i. per ton. Much of the diphenylamine usage occurs in Washington, New York,
Michigan and California.
Table 1: Annual Usage of Diphenylamine Based on 1989-1994 Data
Post-Harvest Production Treated
Site
Apples,
U..S.
Apples, CA
Utilized
Production
(Tons)
5,367,600
461,670
Tons Treated
Likely
Average
1,775,630
51,120
Likely
Max
1,866,460
77,460
% of Crop Treated
Likely
Average
33
11
Likely
Max
35
17
LB AI Applied
Likely
Average
74,370
3,440
Likely
Max
94,370
5,840
Avg. Appl. Rates
Ibai/
ton/yr
0.042
0.067
# appl
/year
1
1
States of Most
Usage
(WA, NY, MI,
CA): 93%
CA: 100%
Notes:
- Percent of U.S. apples treated post-harvest estimated as: (total no. of detects of residues in 14 states)/(total sample size in 14
states)* 100.
- Pounds a.i. applied to U.S. aples post-harvest estimated as: (total no. of detects in 14 states)*(lbs. a.i. applied in CA)/(no. of
detects in C A).
- Data in the table may not exactly multiply or divide across because of rounding.
Sources:
- California EPA, California Use Reports, Annuals 1990-1994.
- US Department of Commerce/Bureau of the Census, 1992 Census of Agriculture, New Hampshire State and County Data.
- US EPA proprietary sources.
- USDA Pesticide Data Program (PDF) database, 1992 and 1993.
- USDA/ERS, Fruit and Tree Nuts, Situation and Outlook Report, August 1992.
- USDA/NASS, Noncitrus Fruits and Nuts, 1993 Preliminary and 1994 Summary.
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D. Data Requirements
Appendix B includes all data requirements identified by the Agency for the
currently registered uses of diphenylamine needed to support reregistration.
E. Regulatory History
The first product containing diphenylamine (DPA), Franklin Protec (Reg. No. 410-
12), was registered on 26 December 1947 by Franklin Laboratories, Inc. for use against
maggots and screw worms on horses. In early 1948, two other companies, CJ. Martin
Company and Texas Phenothiazine Company, registered one DPA product each, Martin's
Formula No. 62 Screwworm Smear for Horses and Mules (Reg. No. 299-2) and Dr.
Rogers's Screwworm Smear Formula No. 62 (Reg. No. 327-26), respectively, for screw
worm control on both horses and work mules. A DPA product, Diphenylamine 83-W
(Reg. No. 241-69), was first registered by American Cyanamid Company, for use against
storage scald on apples on February 14, 1962. A number of additional products were
subsequently registered for this site and pest between April, 1962 and the end of 1981.
In 1963, a DPA-containing product, Grosley's Original "No-roost" Bird Repellent (Reg.
No. 7682-1), was first registered by Aegis Labs, Inc. as a bird repellant for use in
residential outdoor and commercial areas, and bird roosting and nesting areas. A second
product, Tower Grezall NP-4 Bird Repellent (Reg. No. 10286-1) was registered by Tower
Oil Company for these purposes in 1968. In early 1985, the most recent new Section 3
DPA-containing product, DPA Oiled White Paper (Reg. No. 51650-1), was registered by
Compania Manufactura de Papeles y Cartones, S.A., for use on fruit wrappers against
fungi, a new pest use.
The only two DPA-containing Special Local Needs product registrations were
issued to Washington state in 1994 for use on apples. However, in early 1976 an old
Intrastate product was registered for screwworm control. These registrations have expired
and are no longer active.
Elimination of uses began in July, 1986 when Franklin Protec, the product with
the maggot control use was cancelled. In October, 1989 all of the products labeled for
screwworm control, the fungi in fruit wrapper use, and bird repellency were cancelled.
Currently only three DPA-containing products are active. One is a purified
technical product (Reg. No. 2792-47) for use in the formulation of other products, while
the other two products (Reg. No. 2792-45 and 64864-3) are registered for use against
storage scald on apples.
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III. SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
The physical and chemical characteristics of diphenylamine are described
below:
H
Empirical Formula: C12HUN
Molecular Weight: 169.22
CAS Registry No.: 122-39-4
ShaughnessyNo.: 038501
Below is a description of the physical and chemical properties of the
technical grade of diphenylamine.
Color:
Physical State:
Melting Point:
Solubility:
cream
solid flake with a sharp creosote odor
53-55°C
water at 0.038-0.042 mg/mL
acetonitrile at 808-897 mg/mL
methanol at 454-492 mg/mL
octanol at 204-237 mg/mL
hexane at 53-66 mg/mL
B.
Human Health Assessment
1.
Hazard Assessment
The toxicological database for diphenylamine is adequate to support a
reregistration eligibility.
a. Acute Toxicity
The Agency has characterized the acute toxicity of technical grade
diphenylamine based on laboratory data. Results of the acute toxicity studies
conducted with diphenylamine are summarized in Table 2:
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Table 2. Acute Toxicity Values of Diphenylamine.
Test
Oral LD50-rat
Dermal LD50— rabbit
Inhalation LC50~ rat
Eye irritation— rabbit"
Dermal irritation— rabbit"
Dermal sensitization guinea pig"
Purity (% a.i.)
99.9%
99.9%
EC-283 (31.0%)
99.9%
99.9%
99.9%
Results
LD50 = 2.72(2.49-2.98) g/kg
LD50 > 2 g/kg
LC50 = 1.46 mg/L
Slight eye irritation
Slight skin irritation
Not a dermal sensitizer
Cat
III
III
III
III
III
NA
1 Not required for TGAI, however, presented here for informational purposes.
b. Subchronic Toxicity
In a subchronic oral toxicity study, Sprague Dawley rats (10
rats/sex/group) received diphenylamine technical (> 99%) at dietary dose levels
of 0, 150, 1500, 7500, or 15000 ppm for 90 days (approximately 0, 7.5, 75, 375,
or 750 mg/kg/day). There were a number of significant dose-related effects. A
greenish tint to the animals' fur appeared first in the females (90%) in the 1500
ppm dose level group. Sixty percent of the males and 100% of the females showed
this same greenish tint at 7500 ppm. At the highest dose tested (15000 ppm) 70%
of the males and 100% and females the greenish tinted-hair respectively. Body
weights and body weight gains were reduced in both sexes in the 7500 and 15000
ppm dose groups throughout the time-course of the study without compromising
food consumption, therefore, suggesting decreased food efficiency. The darkening
of the urine was considered to be a significant treatment-related graded dose-
response effect. Compared to the concurrent controls, 60% of the males excreted
dark yellow urine at 7500 ppm, and 100% of the animals excreted dark yellow
urine at 15000 ppm. Pairwise, in the females at 7500 or 15000 ppm, the
percentage of rats that excreted dark yellow urine was 70% and 100% respectively.
In general, there were significant treatment-related effects on the
hematology parameters evaluated at terminal sacrifice that became apparent at a
lower dose level. These treatment-related effects on more parameters were
observed in females than in males when compared to the concurrent controls. The
hematological changes observed in males at 7500 and 15000 ppm were statistically
significant showing decreases in Red Blood Cell (RGB) and Hemoglobin (HGB)
counts, and increases in Mean Corpuscular Volume (MCV) and Mean Cell
Hematocrit (MCH). In females at 1500, 7500, and 15000 ppm, diphenylamine
caused decreases in RBC, HGB, and Hematocrit counts and increases in MCV and
MCH. The NOEL was 75 mg/kg/day for males and 7.5 mg/kg/day for females.
The LOEL was 375 mg/kg/day for males and 75 mg/kg/day for females based on
increased clinical signs of toxicity and alterations in hematological parameters
(MRID 42339701).
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In a subchronic toxicity study, pure-bred beagle dogs (4/sex/dose) received
gelatin capsules containing diphenylamine technical (> 99%) at dose levels of 0,
5, 25, or 50 mg/kg/day for at least 90 days. None of the dogs died during the
study. The statistically significant increases observed only in a few of the
hematology and clinical chemistry parameters were not considered to be
toxicologically or biologically relevant. The NOEL was equal to or greater than
50 mg/kg/day which was the Highest Dose Tested (HDT). A LOEL was not
established (MRID 42339801).
In a subchronic toxicity, CD-I mice (15/sex/dose) received technical
diphenylamine (>99%) in their diet at 0, 10, 525, 2625 or 5250 ppm for 90 days.
The dosages consumed in mg/kg/day for males and females, respectively, were 1.7
and 2.1 at 10 ppm, 93.8 and 107.0 at 525 ppm, 443.5 and 555.5 at 2625 ppm and
925.8 and 1100.7 at 5250 ppm. Slight treatment-related effects were observed at
525 ppm with the appearance of brownish-yellow pigment and extra-medullary
hematopoiesis in the liver and hemosiderosis, congestion and extramedullary
hematopoiesis in the spleen. As the dosage was increased, not only were the
incidence and severity of the lesions in the spleen and liver increased, but pigment
in kidneys, increased cellularity in the bone marrow, and cystitis (in the 5250 ppm
group) were also present. Treatment-related increases in relative organ weights
were seen in the liver and spleen in the highest dose groups (2625 and 5250 ppm).
Hematology parameters showing treatment-related effects included statistically
significant decreases in RBC count and hematocrit. Also statistically significant
increases in MCV, MCH and MCHC in the two highest dosage groups were
observed. The highest dosage group also showed a marked increase in
reticulocytes. In the 525 ppm group, there was a statistically significant increase
in MCHC. The systemic toxicity NOEL was 10 ppm (1.7 mg/kg/day for males
and 2.1 mg/kg/day for females) and the LOEL was 525 ppm (93.8 mg/kg/day for
males and 107.0 mg/kg/day for females) (MRID 42542801).
In a 21- day dermal toxicity study, New Zealand White rabbits
(5/sex/group) received repeated dermal applications (under occlusion) of
diphenylamine technical (100%) dissolved in distilled water at dose levels of 100,
500, or 1000 mg/kg for six hours a day for 21 consecutive days with terminal
sacrifice on day 22. Two additional groups of rabbits of each sex (5/sex) served
as the vehicle (distilled water) controls. No mortality was noted in the study.
Gross pathology was noted as dark-red foci in the stomachs of both sexes at the
500 and 1000 mg/kg/day groups. The systemic toxicity NOEL was 100
mg/kg/day and the LOEL was 500 mg/kg/day based on the effects in the stomach.
The dermal toxicity NOEL was greater than 1000 mg/kg/day (limit dose) (MRID
42304901).
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c. Chronic toxicity
In a combined chronic feeding/carcinogenicity study, Sprague-Dawley rats
received diphenylamine (>99.0%) at dose levels of 0, 200, 750, 3750 or 7500
ppm in males (equal to 8.1, 28.8, 146.7, or 302.1 mg/kg/day) and 0, 150, 500,
2500, or 5000 ppm in females (equal to 7.5, 24.9, 137.8, or 286.1 mg/kg/day) in
the diet for 2 years. A one year interim sacrifice of 10 animals per sex per dose
group was used. There was no treatment related mortality noted, however, the
study was terminated early due to increased mortality in the control and low dose
animals. No effects were noted in ophthalmic examinations. The only treatment
related clinical observation was a greenish tint to the hair coat in the urogenital or
ventral cervical area which was assumed to be due to an... oxidative product of the
interaction of the test article or a metabolite with urine or feces in the high mid and
high dose groups. Systemic toxicity was noted at the high mid and high dose
groups in both sexes as decreased mean body weights and body weight gains
(statically significant). Food consumption was increased in the same dose groups;
however, due to food spillage, when food consumption values exceeded two
standard deviations from the mean, they were not included in calculation of the
group mean food consumption. Treatment related effects were noted in
hematology involving red cell elements mainly in the high mid and high dose
groups. Increases in albumin levels, decreases in globulin levels and increased
albumin/globulin ratios were noted but, the biological relevance to these changes
is unknown since there was no related pathology. Some slight transient effects
were also noted in alkaline phosphatase and total bilirubin also in serum glutamic
oxaloacetic transaminase (SCOT) and serum glutamic pyruvic transaminase
(SGPT). Urinalysis did not reveal any specific treatment related effects except a
slight increase in ketones in the high dose due to incomplete or partial interference
of the test article causing a false positive reading. There was an increase in spleen
weights in both sexes in the high mid and high dose groups at the interim sacrifice
and terminal sacrifice. Gross necropsy observations revealed a roughened surface
to the kidneys in the high dose groups. Treatment related non-neoplastic
observations were splenic congestion, increased hemosiderosis and hematopoiesis
in the spleen, pigment deposits in the kidneys, and increased hematopoiesis in the
liver in the high mid and high dose groups. No treatment related increase in any
tumor type or site was seen in either sex at any dose level. Methemoglobin was
not measured in this study. For chronic toxicity the NOEL was 28.8 mg/kg/day
in males and 24.9 mg/kg/day in females and the LOEL was 146.7 mg/kg/day in
males and 137.8 mg/kg/day in females based on reduced mean body weight and
body weight gains, changes in hematological parameters, splenic and kidney
lesions and increased clinical signs of toxicity. There was no evidence of
carcinogenicity (MRID 43401401).
In a chronic toxicity study, beagle dogs received by capsule either 0, 10,
50, or 100 mg/kg/day of diphenylamine sodium salt (>99%) for 12 months.
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Systemic toxicity was noted at the 10 mg/kg/day dose group, lowest dose tested
(LDT), and above as alterations in clinical chemistry. There was a dose-related
increase in total bilirubin levels in both sexes for the 10 mg/kg/day, up to 75% for
the 50 mg/kg/day, up to 167%, p < 0.01 and for the 100 mg/kg/day groups, up
to 150%, p < 0.01. These increases showed statistical significance in both sexes
in the 10 mg/kg/day group at week 26 and in females only at week 39. Also, there
was a decrease in blood urea nitrogen (BUN) levels in females at 50 mg/kg/day
(16%) and 100 mg/kg/day (20%) groups at week 52. Cholesterol was increased
at 50 mg/kg/day and 100 mg/kg/day at all time points (4 to 68%; occasionally p
< 0.05), and albumin showed occasional increases, although no differences were
noted at the end of the study. Alterations seen in the hematological parameters
included: a treatment related decrease in red blood cells at 100 mg/kg/day (11%;
p < 0.05 in males at 52 weeks). Also, hemoglobin was slightly reduced in both
sexes at 100 mg/kg/day (males, 7-9%; females, 4-7%), hematocrit was slightly
reduced at 100 mg/kg/day males (5-9%), mean corpuscular volume was slightly
increased in both sexes at 100 mg/kg/day (males, 2-4%; females, 6%), and
platelets were increased in all treated males (3-35%; p < 0.05 to 0.01 at various
time points). The absolute and relative kidney weights were increased in males at
50 mg/kg/day (40/36%) and 100 mg/kg/day (18/10%) and in females at both 50
mg/kg/day (24/13%) and 100 mg/kg/day (13/9%). The absolute and relative liver
weights were increased at 50 mg/kg/day (males, 17/13%; females, 22/11%) and
100 mg/kg/day (males, 29/20%; females, 14/10%). The absolute and relative
spleen weights were increased in all treated females (9 to 38%/l 1 to 32%) and the
thyroid absolute and relative weights were decreased in 100 mg/kg/day females
(23/25%), and there were clinical signs where one 50 mg/kg/day and two 100
mg/kg/day animals had a greenish tint to the hair of the feet. Methemoglobin was
not measured in this study (see RfD section). For chronic toxicity a NOEL was
not achieved; the LOEL was 10 mg/kg/day (LDT) based on alterations in clinical
chemistry parameters (MRID 43000601).
d. Carcinogenicity
Diphenylamine
In a carcinogenicity study, CD-I mice (60 sex/group) were administered
diphenylamine (>99%) in the diet at levels of 0, 525, 2625 or 5250 ppm (males:
73.2, 368.0 and 755.7 mg/kg/day; females: 90.5, 455.2 or 936.6 mg/kg/day) for
18 months. There was a significant treatment-related increase in overall mortality
in the 2625 and 5250 ppm group males and females. The increased mortality was
due to cystitis in males and amyloidosis in females. A greenish staining of the hair
was the most frequently observed clinical sign with some of the 525 ppm group
and essentially all of the 2625 and 5250 ppm groups affected by the end of the
study. Mean body weight gain was significantly decreased in the 5250 ppm group
males at the majority of the time points in the study. Decreases were also
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occasionally recorded for the 2625 ppm group males. Changes in the hematology
parameters indicate that the chemical produced a regenerative anemia in the 2625
and 5250 ppm group males and females. On gross examination at the interim and
terminal necropsies, the liver and spleen of the 2625 and 5250 ppm group animals
were dark and enlarged. The absolute and relative weights of the liver and spleen
were also increased in these animals. On histopathology at the interim and terminal
necropsies, 525 ppm group and above had increased incidence of hemosiderosis
and congestion in the spleen, also the 2625 and 5250 ppm groups had increased
incidences and/or severity of hematopoiis in the spleen and liver, and pigment in
the reticuloendothelial cells of the liver. Pigment was also observed in the
convoluted epithelial cells of the kidney of these groups at the terminal necropsy.
The incidence of pyelonephritis in the 5250 ppm group males was marginally
increased. There were increased incidences of cystitis and dilatation of the urinary
bladder and balanoposthitis in the penis and preputial area of the 2625 and 5250
ppm groups at both of the necropsies. For the 5250 ppm group females, the
incidence of amyloidosis was increased in the thyroid, adrenals, kidneys (also in
the 2625 ppm group), stomach, small intestines, ovaries and uterus. For chronic
toxicity the NOEL was less than 525 ppm (73.2 mg/kg/day for males and 90.5
mg/kg/day for females), and the LOEL was equal to or less than 525 ppm (73.2
mg/kg/day for males and 90.5 mg/kg/day for females) based on histopathological
lesions in the spleen. There was no evidence of carcinogenicity (MRID 43369501).
Nitrosamine
Based on animal carcinogenicity data, N-nitrosodiphenylamine is classified
as a probable human carcinogen. Studies in rats and mice showed increased
incidence of bladder tumors in male and female rats and reticulum cell sarcomas
in mice as well as structural relationship to carcinogenic nitrosamines. The cancer
potency or Qj * was calculated to be 4.9 x 103 mg/kg/day.
e. Developmental Toxicity
In a developmental toxicity study, pregnant female Sprague-Dawley rats
(25/group) received diphenylamine (99.9%) in corn oil by oral gavage at dose
levels of 0, 10, 50, or 100 mg/kg/day from gestation day six through gestation day
15 inclusive; dams were sacrificed on gestation day 20. None of the rats died
during the study. Maternal toxicity was evidenced by increased splenic weights,
enlarged spleens and blackish-purple colored spleen in the dams at 100 mg/kg/day.
The maternal toxicity NOEL was 50 mg/kg/day and the LOEL was 100
mg/kg/day. No developmental toxicity was seen at any dose level. The
developmental toxicity NOEL was equal to or greater than 100 mg/kg/day (HDT);
a LOEL was not established (MRID 42292001).
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In a developmental toxicity study, pregnant New Zealand White rabbits
received either 0, 33, 100, or 300 mg/kg/day diphenylamine (99.9%) suspended
in 1% methylcellulose by oral gavage from gestation day 7 through 19, inclusive.
Animals came from 3 sources (vendors). Maternal toxicity was noted at 300 mg/kg
as decreases in food consumption and associated initial reductions in body weight
gain. The maternal toxicity NOEL was 100 mg/kg/day and the LOEL was 300
mg/kg/day based on decreased body weight gains and food consumption early
during the treatment period. No developmental toxicity was noted at any dose
level. The developmental toxicity NOEL was equal to or greater than 300
mg/kg/day (HDT); a LOEL was not established (MRID 00148521).
f. Reproductive Toxicity
In a two-generation reproductive toxicity study, Sprague-Dawley rats (28
per sex/group) received diphenylamine (99.8%) in the diet at dose levels of 0, 500,
1500, or 5000 ppm (0, 40, 115, or 399 mg/kg/day for F0 males and 0, 46, 131,
or 448 mg/kg/day for F0 females, respectively, during premating). Compound-
related systemic toxicity was observed in a dose related manner among both sexes
and generations at all dose levels. In general, females were more affected than
males and F1 animals were more affected than F0 animals. Clinical signs (bluish
colored fluid in the cage and bluish colored staining of the coat in both sexes, and
swelling of mammary gland(s) or palpable lateral-ventral masses, primarily in
females) were evident at 5000 ppm. Body weight was decreased at 1500 and 5000
ppm. At 5000 ppm, there was a 6-9% decrease in body weight values, as
compared to control, for F0 males, 5-8% for F0 females, 22-28% for F1 males, and
11-23% for Fj females. At 1500 ppm, there was a 5-8% decrease in body weight
values from controls for F0 females, 7-9% for F1 males, and 5% for F1 females.
Food consumption (g/animal/day) was also decreased at 1500 and 5000 ppm.
Kidney, spleen, and liver appeared to be the target organs as evidenced by weight
differences from control at 5000 ppm in males and at 1500 and 5000 ppm in
females and gross and microscopic findings at all dose levels in both sexes. Gross
findings included enlarged and blackish-purple spleens. Microscopic findings
included brown pigment in the proximal convoluted tubules of the kidney,
hepatocytic hypertrophy, brown pigments in the Kupffer cells of the liver,
congestion and hemosiderosis of the spleen. The systemic toxicity NOEL was less
than 500 ppm (40 mg/kg/day in males and 46 mg/kg/day in females). The LOEL
was less than or equal to 500 ppm based on gross pathological findings in the
spleen (enlarged, discolored), and on microscopic findings in the kidney (brown
pigment in the proximal convoluted tubule), liver (hepatic hypertrophy and brown
pigment in the Kupffer cells), and spleen (congestion and hemosiderosis).
Developmental toxicity was observed at 1500 and 5000 ppm, as evidenced
by significantly decreased body weight for F1 pups at 5000 ppm throughout
lactation (11-25 % less than control), for F2 pups at 5000 ppm from LD 4 through
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LD 21 (10%-29% less than control), and for F2 pups at 1500 ppm on LD 14 (10%)
and LD 21 (12%). The developmental toxicity NOEL was 500 ppm (46
mg/kg/day for maternal animals) and the LOEL was 1500 ppm (131 mg/kg/day
for maternal animals) based on decreased F2 pup body weight in late lactation.
Reproductive toxicity was noted as smaller litter sizes at birth (significant for the
F2 litters) in both generations at 5000 ppm. The reproductive toxicity NOEL was
1500 ppm (131 mg/kg/day for maternal animals) and the LOEL was 5000 ppm
(448 mg/kg/day for maternal animals), based upon decreased litter size in both
generations (MRID 42638101).
g. Mutagenicity
In a Salmonella typhimuriumfmammalian microsome plate incorporation
assay with tester strains TA1535, TA1537, TA1538, TA98, and TA100,
diphenylamine (99.9%) was found to be cytotoxic at doses >333 //g/plate -S9, and
>667 //g/plate +S9. At lower levels (6.67, 10.0, 33.3, 66.7, and 100 //g/plate -
S9; 10.0, 33.3, 66.7, 100, and 333 //g/plate +S9), there were no increases in
histidine-revertant colonies. Based on these findings, it was concluded that
diphenylamine was tested over an appropriate range of concentrations, and was not
mutagenic in this bacterial test system (MRID 42312101).
In a L5178Y TK + /- mouse lymphoma forward mutation assay,
diphenylamine (99.9%) was tested at dose levels of 5-80 //g/mL in DMSO both
with and without rat liver S9 metabolic activation. The test was positive in the
presence of exogenous metabolic activation. There were reproducible but not
dose-related increases in the mutation frequency at severely cytotoxic levels (40-70
//g/mL +S9) and moderately cytotoxic concentrations (20 and 30 //g/mL +S9).
Colony sizing analysis revealed a relatively equal distribution of large and small
colonies. Diphenylamine was non-mutagenic in the absence of S9 activation up to
a severely cytotoxic level (80 //g/mL). Thus, diphenylamine was considered to be
weakly mutagenic in this assay (MRID 42332101).
In a mouse micronucleus assay, the single oral gavage administration of
250, 500, or 1000 mg/kg (males) or 375, 750, or 1500 mg/kg (females)
diphenylamine (99.9%) did not significantly increase the frequency of
micronucleated polychromatic erythrocytes in bone marrow cells harvested from
ICR mice at 24, 48, or 72 hours postexposure. Dose selection for the
micronucleus assay was based on the findings of a preliminary acute dose range-
finding study which indicated that ~ 70% of the females administered 2750 mg/kg
of the test material died prior to the scheduled sacrifice. In agreement with the
preliminary results, mortality and other signs of compound toxicity (i.e.,
languidness, squinted eyes and/or rough fur) were seen in both sexes receiving the
high dose (1000 mg/kg; males; 1500 mg/kg; females) in the micronucleus assay.
The test was negative up to a lethal oral gavage dose (HTD: 1000 mg/kg; males;
1500 mg/kg; females) but there was no evidence of bone marrow cytotoxicity
(MRID 42312001).
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The acceptable mutagenicity studies discussed above satisfy the new initial
mutagenicity battery requirements for diphenylamine. However, the majority of
toxicology studies conducted with diphenylamine indicate that the liver is a target
organ. Therefore, the HED RfD/QA Peer Review Committee is requiring an in
vivo/in vitro rat hepatocyte unscheduled DNA synthesis (UDS) assay be performed
to determine if a potentially genotoxic concentration can be achieved in the liver.
The request for additional testing is in accordance with Agency current
mutagenicity guidelines. The outcome of this study will determine if any
additional mutagenicity studies are required for diphenylamine.
h. Metabolism
In a general metabolism study in the rat, 14C-Diphenylamine was
administered orally in corn oil to groups of male and female Sprague Dawley rats
(5/sex/group) at a low oral dose (5 mg/kg), repeated low oral dose (5 mg/kg x 14
days), and a single high oral dose (750 mg/kg).
Absorption of diphenylamine appeared rapid and complete for all dose
groups as judged from 24 hour excretion profiles. Terminal distribution data
showed no significant residual radioactivity in tissues 168 hours post-dose for both
the low and high oral dose groups. Urine was the major route for excretion of
diphenylamine derived radioactivity at both the low and high dose, with between
68-81% recovered for both sexes at the single and repeated low dose, and 73-74%
recovered at the single high dose. Male rats appeared to excrete a greater
percentage of diphenylamine derived radioactivity in urine at the low dose level,
while female rats showed greater excretion in feces at this dose. At the high dose,
the percentage eliminated in urine was equivalent in male and female rats.
Metabolites identified in urine in this study included dihydroxylated
conjugates of diphenylamine, monohydroxylated sulfate conjugates of
diphenylamine, and monohydroxylated glucuronide conjugates of diphenylamine.
Male rats appeared to show a much greater percentage of dihydroxylated
conjugates of diphenylamine in urine than female rats at both the single and
repeated low oral dose, but not at the single high dose. In contrast, females
showed higher urinary percentages of 4-hydroxydiphenylamine-O-sulfonic acid
than males at all dose levels. Fecal metabolites consisted of the parent chemical
and 4-hydroxydiphenylamine, which comprised only between 0.5-3% of the
administered dose in both sexes (MRID 42994801).
Based on the available data for diphenylamine, the rat metabolism study
with diphenylamine and the open literature data for diphenylamine and metabolites,
there is no evidence that the N-nitroso metabolite of diphenylamine would be
formed in rats or humans in vivo.
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2. Dose Response Assessment
a. Reference Dose
The HED Reference Dose (RfD)/Peer Review Committee (document dated
April 1, 1997) recommended that an RfD be established based on a chronic dog
study with a LOEL of 10 mg/kg/day. An Uncertainty Factor (UF) of 100 was
used to account for both the interspecies extrapolation and the intraspecies
variability. An additional UF of 3 was recommended to account for the lack of a
NOEL and the Committee's concern with respect to potential methemoglobinemia
which was not tested in this study. On this basis, the RfD was calculated to be
0.03 mg/kg/day.
It should be noted that the LOEL was established at 10 mg/kg/day, in both
males and females (based on hematological and clinical chemistry changes, and
clinical signs of toxicity). Due to the lack of information on methemoglobinemia,
the LOEL could not be verified and was considered tentative until this issue is
addressed. The Agency recommended that a subchronic study of sufficient
duration be conducted in dogs to investigate this possible methemoglobinemic
effect to accurately define the NOEL in the critical study. The registrant is
directed to contact the Agency before conducting such a study.
This chemical has been reviewed by the FAO/WHO joint committee
meeting on pesticide residue (JMPR) and an acceptable daily intake (ADI) of 0.02
mg/kg/day has been established by that Committee.
b. Carcinogenicity Classification and Risk Quantification
The HED Reference Dose (RfD)/Peer Review Committee (document dated
April 1, 1997) classified diphenylamine as "not likely" in reference to
carcinogenicity. This classification was based on the lack of evidence for
carcinogenicity in the two acceptable carcinogenicity studies in either male or
female CD-I mice or Sprague-Dawley rats.
c. Other Toxic Endpoints
The Agency's Health Effects Division's Toxicological Endpoint Selection
Committee (document dated February, 27 1997) concluded the following for
diphenylamine:
There are no dermal absorption data available; therefore, a default of 100%
dermal absorption is assumed.
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For acute dietary exposure (1 day) a risk assessment is not required since
no appropriate endpoint or NOEL could be identified from the available data. No
developmental toxicity was seen at doses greater than 100 mg/kg/day in rats or at
doses greater than 300 mg/kg/day in rabbits.
For short term (1-7 day) or intermediate term (1 week to several months), dermal
occupational:
In a 21 day dermal toxicity study, New Zealand White rabbits
(5/sex/group) received repeated dermal applications (under occlusion) of
diphenylamine Technical (100%) dissolved in distilled water at dose levels of 100,
500, or 1000 mg/kg for six hours a day for 21 consecutive days with terminal
sacrifice on day 22. Two additional groups of rabbits of each sex (5/sex) served
as the vehicle (distilled water) controls. None of the rabbits died, and with the
exception of dark-red foci in the stomachs of both sexes at the 500 and 1000
mg/kg/day groups, the results of this study were unremarkable. The systemic
toxicity NOEL was 100 mg/kg/day and the LOEL was 500 mg/kg/day based on
the effects in the stomach. The dermal toxicity NOEL was greater than 1000
mg/kg/day (limit dose).
The dose and endpoint for use in risk assessment is the systemic NOEL of
100 mg/kg/day with a LOEL of 500 mg/kg/day based on dark-red foci in the
stomachs of both sexes.
For chronic (several months to lifetime), dermal occupational exposures:
The dose and endpoint for use in risk assessment is the LOEL of < 10
mg/kg/day based on clinical chemistry observations based on a chronic dog study.
An extra uncertainty factor of 3 is added to the usual uncertainty factor of 100 due
to the lack of a NOEL in this study.
For inhalation (any duration) occupational exposures:
The requirement for an inhalation study was waived for the technical
product. The formulation is placed in Toxicity Category III. A separate inhalation
risk assessment is not required.
3. Exposure Assessment
This section describes the process the Agency used to estimate human
exposure to diphenylamine from the diet and from occupational use.
a. Dietary Exposure
A dietary risk assessment is required when a chemical is registered for use
on crops used either as food for people or feed for livestock. Diphenylamine
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meets this criteria. Diphenylamine is a plant growth regulator currently registered
in the U.S. for use on apples to prevent the appearance of the skin discoloration
known as storage scald. Diphenylamine is formulated for post-harvest treatment
on apples.
The residue chemistry data base identifying and quantifying the residues of
diphenylamine is adequate and supports reregistration of diphenylamine as a food
use pesticide on post-harvest treatment on apples. Tolerances are established for
diphenylamine residues in apples (10 ppm), milk (0 ppm), and meat (0 ppm) [40
CFR §180.190]. No food or feed additive tolerances have been established for
diphenylamine residues. The Agency has determined that the residue of concern
in plants and livestock is diphenylamine per se.
Directions For Use
A search of the Agency's Reference Files System (REFS) on 12/19/96
identified two end-use products containing diphenylamine that are registered to
members of the Diphenylamine Task Force. These end-use products, presented
below, include an EC and an SC formulation.
Table 3: End Use Products
EPA Reg No.
2792-45
64864-3
Formulation
2. 66 Ib/gal EC
1.241b/galSC/L
Label Date
4/91a
5/88
Trade Name
No Scald DPA EC-283
Shield Liquid DPA 15%
The 2.66 Ib/gal EC can be applied post-harvest to apples as a dip, spray,
or drench at concentrations of 1,000-2,200 ppm depending on apple variety, and
the 1.2 Ib/gal SC/L formulation can be applied post-harvest as a drench at the same
concentrations. The labels specify that contact time with the treatment solution
should not exceed 2 minutes and fruit should be thoroughly drained after
treatment. Each 100 gal of treatment solution can treat 30 bins (500-750 bushels)
of apples after which the treatment solution should be replaced. Labels indicate
that fruit should be treated within 7 days after harvest prior to being placed in
controlled atmosphere storage.
Nature of the Residue in Plants and Livestock
The qualitative nature of the residue in plants and livestock is adequately
understood based on acceptable apple, ruminant and poultry metabolism studies.
The Agency has concluded that the residue of concern in plants and livestock is
diphenylamine, perse (C. Swartz, 2/10/95).
Residue Analytical Methods
Adequate analytical methods are available for data collection and tolerance
enforcement in apples and apple processing fractions. A colorimetric method and
16
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a GLC/electron capture detector (ECD) method are listed in PAM, Vol. II (Section
180.190) as Method I and Method B, respectively, for the quantitation of
diphenylamine residues in apple commodities. Since Method I is a colorimetric
method, it is no longer suitable as an enforcement method. However, a GC/mass
selective detection (MSD) method for the quantitation of diphenylamine residues
in apples and processed fractions has been submitted along with a successful
independent method validation.
The GC/MSD method that was used to determine diphenylamine residues
in milk and livestock tissues is adequate for data collection; however, an
enforcement method must be provided. If the Task Force is proposing the
GC/MSD method as an enforcement method, an independent laboratory method
validation must be conducted as per PR Notice 96-1 (2/7/96).
Multiresidue Method Testing
The FDA PESTDATA database dated 1/94 (Pam Vol. I, Appendix I)
indicates that diphenylamine is completely recovered using FDA Multiresidue
Protocol D (PAM I Section 232.4) and that recovery of diphenylamine through
FDA Multiresidue Protocol E (fatty and nonfatty, PAM I Sections 211.1 and
212.1) is low (<50%).
Storage Stability Data
Adequate storage stability data are available to support the results of the
magnitude of the residue studies in apples, apple processed fractions, meat and
milk. Diphenylamine residues are stable at <-12° C for up to 155-167 days in
apples and apple pomace (wet and dry) and for up to 202 days in apple juice.
Diphenylamine residues are stable in frozen storage for up to 38 days in milk and
muscle and for up to 54 days in liver.
Magnitude of the Residue in Crop Plants
Adequate magnitude of the residue data are available to support the use on
apples. Acceptable residue data depicting diphenylamine residues in apples
following a single post-treatment application at the maximum use rate have been
submitted. These data indicate that the existing 10 ppm tolerance for
diphenylamine residues in apples is appropriate.
Magnitude of the Residue in Processed Food/Feed
Adequate processing data are available to support the use on apples.
Diphenylamine residues concentrated in wet pomace by a factor of 2.3-8.4X with
an average of 4.7X. Residues did not concentrate in juice. Based on the highest
17
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average field trial (HAFT) residue level of 5.86 ppm and the 4.7X average
concentration factor for wet pomace, residues in wet pomace are estimated to be
27.5 ppm. Since the residues in wet pomace are expected to be 2.8X higher than
the current 10 ppm tolerance for residues in apples, a 30 ppm tolerance for
diphenylamine residues in wet apple pomace must be proposed.
Magnitude of the Residue in Meat, Milk, Poultry, and Eggs
Adequate livestock feeding studies have been submitted to the Agency. The
ruminant feeding study indicates the need for tolerances for diphenylamine in milk
and animal commodities. A tolerance of 0.01 ppm is appropriate for residues in
milk, and meat, fat, and meat by-products (excluding liver) of cattle, goats,
horses, and sheep. The appropriate tolerance for diphenylamine residues in liver
of these animals is 0.1 ppm.
Poultry and swine feeding studies are not required since there are no
poultry or swine feed items associated with the use on apples, which is the only
food/feed use currently being supported in the U.S.
Magnitude of the Residue in Water, Fish, and Irrigated Crops
Diphenylamine is not registered for direct use on potable water or aquatic
food and feed crops; therefore, no residue chemistry data are required under these
guideline topics.
Magnitude of the Residue in Food-Handling Establishments
Diphenylamine is not registered for use in food-handling establishments;
therefore, no residue chemistry data are required under this guideline topic.
Confined Accumulation in Rotational Crops
Diphenylamine is not registered for use in the U.S. on any crops that are
subject to rotation; therefore, no residue chemistry data are required under this
guideline topic.
Field Accumulation in Rotational Crops
Diphenylamine is not registered for use in the U.S. on any rotated crops;
therefore, no residue chemistry data are required under this guideline topic.
Dietary Exposure from Drinking Water
Diphenylamine was not included in the list of pesticides to be analyzed in
well water/ground water in the Agency's Pesticides in Ground Water Database.
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The Agency's EFED database and its "STORET" database were searched
for monitoring data on diphenylamine residues in surface water. No data on
diphenylamine residues in surface water are available.
Based on the limited use pattern for diphenylamine as a post-harvest drench
on apples and the absence of detections in the ground water and surface water
databases, dietary exposure from drinking water is expected to be negligible.
b. Occupational Exposure
An occupational exposure assessment is required for an active ingredient
if (1) certain toxicological criteria are triggered and (2) there is potential exposure
to handlers (mixers, loaders, applicators, etc.) during use or to persons entering
treated sites after application is complete.
The Diphenylamine Task Force is only supporting the use in the prevention
of storage scald on apples prior to entering storage. No other uses are assessed in
this document. Application rates vary from 1,000 ppm to 2,200 ppm.
The registrant states that diphenylamine is applied to apples by a drive-
through and an automated bin drencher. The DP A Task Force submitted a study
on the two drenching process techniques for diphenylamine that were observed by
an assessor. The registrant asserts that the drive-through drenching sites represents
typical drenching operations. A typical description of the drive-through drenching
process for diphenylamine is as follows:
"The drive-through drencher process involved a truck loaded with apple bins to
pull into the drencher which is enclosed on the sides. The drencher is large
enough for a flat bed truck with apple bins stacked up to 3 layers high to pull
through. The truck cab is pulled beyond the application area before spraying
begins. The driver stays in the cab during the process. Once the truck is inside
the drencher, the operator turns on the spray nozzles from inside the drenching
area and steps away from the application area. The truck driver pulls through
slowly as the DPA material is applied to the apples using high-flow flood nozzles."
The assessor at the site observed that potential exposure could occur to
handlers when diphenylamine is loaded into the tank. The highest potential
exposure may occur from drift and over-spray from the drencher equipment onto
the persons present during application and also from routine cleaning of the
system.
Occupational-use products and homeowner-use products
At this time, products containing diphenylamine are intended for
occupational use only and not for homeowner use.
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Handler and Applicator Exposure
EPA has determined that there is a potential exposure scenario to the
drencher operator during usual use-patterns associated with diphenylamine. Based
on the use patterns, only one major exposure scenario was identified for
diphenylamine drencher operator (the person outside of the the truck who turns on
the spray nozzles).
Short-term and intermediate-term dermal exposures and risks (developed
using PHED Version 1.1 surrogate data) are presented in Table 5 (page 25). No
chemical-specific handler data were submitted. However, a surrogate PHED
exposure assessment was submitted to the Agency (MRID 44212501). Table 4
(page 21) summarizes the caveats and parameters specific to the exposure scenario
and corresponding risk assessment. No inhalation endpoints were identified;
therefore an inhalation risk assessment was not required. A chronic endpoint using
a LOEL of 10 mg/kg/day was identified. However, since no chronic exposure is
expected (i.e., seasonal apple treatments), no chronic risk assessment was
required.
The submitted surrogate assessment is limited to a mixer/loader PHED
exposure estimate. The submission also presented site specific observations on the
apple drenching process. These observations provided information on potential
exposures. It was reported that exposure may result from adding diphenylamine
to the tank and that the highest potential exposure may occur from the over-spray
from the drencher equipment and perhaps routine cleaning of the system. EPA has
modified this assessment to increase the number of observations in the
mixer/loader assessment and to adjust for potential exposure during the over-spray
from the drencher equipment. There are no known surrogate exposure data
available for drencher operators. Therefore, EPA has developed a screening level
assessment option to estimate potential exposure to a handler who both mixes/loads
diphenylamine into the drencher equipment and operates the drencher equipment,
and is potentially exposed to overspray. The option was developed by adding
mixer/loader exposure to exposure of a flagger during aerial spray applications.
The following use information was supplied in the surrogate PHED submission:
Concentrations of diphenylamine in the spray solution range from 1,000 ppm to
2,200 ppm.
Number of apple bins treated per day ranges from 300 to 660.
An average of 50 gallons of spray solution is applied per bin.
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EPA questions whether alternate methods of application are being used by
some apple growers/processors. For example, whether the drench is sometimes
applied during a conveyor belt operation. No data are available at this time
concerning these potential exposures. The Agency does not expect the exposure
for persons who may be handling the just treated apples and apple containers to
be greater than the exposure to the drenchers.
Potential daily dermal exposure is calculated using the following formula:
DailyDermalExposure(mgai/day) =UnitExposure(mgai/lbai)xUseRate(lbai/gal)xDailyAmountTreated(gal/day)
No dermal absorption adjustment is necessary, since the endpoints are based
on a dermal study.
These calculations of daily dermal exposure to diphenylamine by handlers are used
to calculate the daily dose to those handlers.
Table 4: Exposure Scenario Descriptions for the Use of Diphenylamine
Exposure
Scenario
(Number)
Data
Standard
Assumptions
(8-hr work day)
Comments
Mixer/Loader/Applicator Descriptors
Drencher
Operator
PHED
VI.1
Min.: 300
@ 50
gallons/bin
bins
660
@ 50
gallons/bin
bins
Mixer/Loader Baseline: "Best Available" grades: Hands and dermal =
acceptable grades. Hands = 53 replicates; dermal = 25 to 122 replicates.
High confidence in dermal data.
Mixer/Loader PPE: "Best Available" grades: Hands and dermal = acceptable
grades. Hands = 59 replicates; dermal = 25 to 122 replicates. High
confidence in dermal data.
Applicator (Flagger) Baseline and PPE: "Best Available" grades: Hands and
dermal = acceptable grades. Hands =16 replicates; dermal = 16 to 18
replicates. High confidence in dermal data.
PHED data used for baseline, no Protection Factors (PFs) were necessary. A
50 percent PF was used to add a layer of coveralls for the mixer/loader and
applicator PPE scenarios.
'Standard Assumptions based on an 8-hour work day as estimated by the Agency. Other data were not available.
b"Best Available" grades are defined by the Agency's SOP for meeting Subdivision U Guidelines. Best available grades
are assigned as follows: matrices with grades A and B data and a minimum of 15 replicates; if not available, then
grades A, B and C data and a minimum of 15 replicates; if not available, then all data regardless of the quality and
number of replicates. Data confidence are assigned as follows:
High = grades A and B and 15 or more replicates per body part
Medium = grades A, B, and C and 15 or more replicates per body part
Low = grades A, B, C, D and E or any combination of grades with less than 15 replicates
Post Application Exposure
At this time, EPA is not concerned about post-application exposures to
treated apples and apple containers. Available information show that post-
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application handling of the apples and apple bins are done by forklift machinery
thereby minimizing, if not eliminating, possible worker exposure.
4. Risk Characterization
a. Dietary Risk
(1) Acute Dietary Risk
A risk assessment was not conducted for acute dietary exposure since no
appropriate endpoint or NOEL could be identified from the available data. No
developmental toxicity was seen at doses greater than 100 mg/kg/day in rats or at
doses greater than 300 mg/kg/day in rabbits.
(2) Chronic and Carcinogenic Dietary Risk
An RfD is used to assess the dietary cancer risk for a chemical. The
chronic dog feeding study for diphenylamine was used to calculate the RfD.
Systemic toxicity was noted at the lowest dose tested (10 mg/kg/day). Uncertainty
factors of 10 each for both intra- and inter- species variability were applied as well
as an additional factor of 3 to account for the lack of a NOEL. The RfD was
calculated to be 0.03 mg/kg/day.
A Dietary Risk Evaluation System (ORES) chronic exposure analysis was
performed using tolerance level residues and 100 percent crop treated information
to estimate the Theoretical Maximum Residue Contribution (TMRC) for the
general population and 22 subgroups. The TMRC for the U.S. population utilized
32.12% of the RfD and 324.68% of the RfD for non-nursing infants (< 1 year
old). Anticipated residue data were used to calculate the Anticipated Residue
Concentration (ARC) for those same population subgroups for certain commodities
in order to refine the dietary risk assesment. The ARC for existing tolerances
utilizes 2% of the RfD for the general U.S. population and 20.1% of the RfD for
non-nursing infants (< 1 year old). Adding exposures from meat and milk which
currently have tolerances at 0 ppm results in an ARC of 2.27% of the RfD for the
general U.S. population and 20.8% of the RfD for non-nursing infants (< 1 year
old). Since all chronic risk falls below 100% of the RfD, there is no chronic
dietary risk concern for diphenylamine.
Diphenylamine is classified as "not likely" to be carcinogenic to humans
based on the lack of evidence for carcinogenicity in two studies. However,
diphenylnitrosamine, an impurity of technical grade diphenylamine has been
classified as a probable human carcinogen based on increased incidence of bladder
tumors in male and female rats, reticulum cell sarcomas in mice and structural
relationship to carcinogenic nitrosamines.
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A dietary risk assessment for diphenylnitrosamine, was conducted to
determine the cancer risk from exposure to the impurity. The nitrosamine level
of 10 ppm (0.00001) was multiplied by the ARC (0.000568 mg/kg/day) to obtain
the level of exposure. This was then multiplied by the Qx* or cancer potency of
4.9 X 103 mg/kg/day, as reported on IRIS for nitrosamines, to obtain the cancer
risk of 2.8 X 10n mg/kg/day. The chronic DRES analysis calculated an
anticipated residue contribution (ARC) for the total U.S. Population of 0.000568
mg/kg/day.
To calculate the cancer risk for the nitrosamine, the Agency multiplied the
ARC (0.000568 mg/kg/day) by 10 5 (because diphenylnitrosamine is 10 ppm or
10/1,000,000). This result was multiplied by the Qt* of 0.0049 mg/kg/day and
the lifetime (70 years) cancer risk was calculated to be 2.8 x 10 n.
0.000568 mg/kg/day x 105 = 5.6 x 109
5.6 x 109 x 4.9 x 103 = 2.8 x 10 n mg/kg/day
This value is well below the Agency's level of concern of 1 x 10 6 for
nitrosamine in the diet .
(3) Drinking Water Risk
Based on the absence of detections in the Agency's Pesticides in Ground
Water Database or in the U.S. EPA's "STORET" database, and the limited use
pattern, dietary risk from drinking water is assumed to be negligible.
b. Occupational and Residential Risk Characterization
Risk Estimates For Handler Exposures
Dermal
The daily dermal dose is calculated using a 70 kg body weight for short-
term exposure and a 70 kg body weight for intermediate-term exposure.
Daily Dermal Dose —— 1 = Daily Dermal Exposure —— 1 x
(Kg/Day] ' F ( Day }
Body Weight (Kg))
These calculations of daily dermal dose of diphenylamine received by
handlers are used to assess the dermal risk to those handlers. The short-term
dermal MOEs were calculated using a NOEL of 100 mg/kg/day. The short-term
and intermediate-term dermal MOEs were calculated using a NOEL of 100
mg/kg/day in the following formula:
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NOEL
MOE =
kg/day
Daily Dermal Dose
_Hi_\
kg/day)
Dermal Risk from Handler Exposures
Short-term and Intermediate-term
The calculations of short-term and intermediate-term dermal risk indicate
that the MOEs are more than 100 at baseline (i.e. clothing worn include long
pants, long sleeved shirt and no gloves for the exposure scenario combining open
mixing/loading and flagger) for the following scenarios:
- None for either minimum or maximum concentrations.
Table 5: Short-term and Intermediate-term Dermal Exposures and Risks to Diphenylamine
Exposure
Scenario
Baseline
Dermal Unit
Exposure
(mg/lb ai)a
Application
Rate
(Ib
ai/gallon)b
Daily
Gallons
Usetf
Amount of
ai Handled
per Day (Ib
ai)
Daily
Dermal
Exposure
(mg/day)d
Baseline
Dermal Dose
(mg/kg/day)e
Baseline
Dermal
MOEf
Risk Mitigation Measures
Additional PPE
Dermal
Unit Exp.
(mg/lb ai)g
PPE Dermal
Dose
(mg/kg/day)e
PPE
Dermal
MOEf
Mixer/Loader/Applicator Exposure/Risk
Drench
operator
Flagger
scenario:
2.91
Min.
0.0081
Max.
0.0181
15,000
33,000
121.5
597.3
354
1,738
5.1
24.8
20
4
0.05
0.09
0.43
1,111
233
" Baseline dermal unit exposure represents a combination of open mixing/loading liquid formulations (unit exposure = 2.9 mg/lb
ai) the exposure of a flagger (unit exposure = 0.01 mg/lb ai). Clothing worn includes long pants, long sleeved shirt, and no gloves.
b Spray solution concentrations are based on the label's minimum (Min. = 1,000 ppm) and the maximum (Max. = 2,200 ppm)
concentrations. Assessments have been calculated for both the minimum and maximum concentrations.
c The registrant reported a range of treatments per day as (Min.) 300 bins to (Max.) 660 bins with an average of 50 gallons per bin.
d Daily dermal exposure (mg/day) = Exposure (mg/lb ai) * Appl. rate (Ib ai/gallon) * Gallons treated.
e Dermal Dose (mg/kg/day) = Dermal Exposure (mg/day) / Body Weight (70 kg).
f Dermal MOE = NOEL (100 mg/kg/day) / Daily Dermal Dose (mg/kg/day).
g PPE dermal unit exposure represents a combination of open mixing/loading liquid formulations and the exposure of a flagger.
For the minimum and maximum application rate, the PPE scenario is single layer body covering and chemical-resistant gloves for
the mixing/loading portion of the operation and single layer body protection with no gloves during the application operation (unit
exposure = 0.043 mg/lb ai for the mixer/loader and 0.007 mg/lb ai for flaggers).
The calculations of short-term and intermediate-term dermal risk indicate
that the MOEs are more than 100 with additional PPE (single layer body covering
and chemical-resistant gloves for mixing/loading and single layer body covering
with no gloves during application)for the following scenarios:
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- minimum and maximum concentrations and minimum and maximum amounts
handled for the drencher operator.
The calculations of short-term and intermediate-term dermal risk indicate
that the MOEs are not more than 100 despite the maximum mitigation measure for
the following scenario:
- none
Dermal Risk - Diphenylnitrosamine
A worker risk assessment for nitrosamine, an impurity in technical grade
diphenylamine was calculated using the following assumptions. The product
contains 10 ppm of the impurity, a worker has 90 days of exposure per year and
a 35 year work life. Dermal absorption is assumed to be 100% and the Qx* is
0.0049 mg/kg\day. The worker risk range from 5.4 x 10 10 to 1.3 x 108 . The
worker risk from nitrosamine is below the Agency's level of concern
Additional Occupational Exposure Studies
Handler Studies
EPA is requiring the registrant to conduct a deposition study. The results
will be used to determine the need for additional dermal exposure studies for this
application scenario. These data are considered confirmatory. In addition, EPA
is requiring the registrant to submit more documentation regarding alternative
methods of drenching, particularly the automated bin drenching system and
conveyor belt drenching operations.
Post-Application Studies
There are no post-application studies required at this time since available
information show that handling of apples, apple containers, and other items wet
with diphenylamine to be tasks performed by forklift machinery, thereby
minimizing, if not eliminating, post-application worker exposure.
5. FQPA Considerations
The Food Quality Protection Act of 1996 (FQPA) amended the FFDCA by
setting a new safety standard for the establishment of tolerances. In determining
whether a tolerance meets the new safety standard, section 408(b)(2)(C) directs
EPA to consider information concerning the susceptability of infants and children
to pesticide residues in food, and available information concerning aggregate
exposure to infants and children of such residues, as well as the potential for
cumulative effects from pesticide residues and other substances that have a
common mechanism of toxicity.
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The FQPA amendments to section 408 (b) (2) (C) require EPA to apply an
additional 10-fold uncertainty (safety) factor unless reliable data demonstrate that
the additional factor is unnecessary to protect infants and children.
Section 408 (b) (2) (D) establishes factors that the Agency must consider in
determining whether the safety standard is met in deciding to issue or reassess
tolerances. These factors include the consideration of available information on the
aggregate exposures to the pesticide from dietary sources including drinking water
as well as non-occupational exposures such as those derived from pesticides used
in and around the home. The Agency must also consider the potential cumulative
effects of the pesticide for which a tolerance is being sought as well as other
substances that have a common mechanism of toxicity.
Because diphenylamine has food uses, specific consideration of the risks to
infants and children, as well as aggregate exposures and potential cumulative
effects is warranted.
Potential Risk to Infants and Children
In determining whether an additional uncertainty factor is or is not
appropriate for assessing risks to infants and children, EPA uses a weight of
evidence approach taking into account the completeness and adequacy of the
toxicity data base, the nature and severity of the effects observed in pre- and post-
natal studies, and other information such as epidemiological data.
For purposes of assessing the pre- and post-natal toxicity of diphenylamine,
EPA has evaluated two developmental and one reproduction study. Based on
current toxicological data requirements, the data base for diphenylamine, relative
to pre- and post-natal toxicity, is complete. However, as EPA fully implements
the requirements of FQPA, additional data related to the special sensitivity of
infants and children may be required.
The data provided no indication of increased sensitivity of rats or rabbits
to in utero and/or post-natal exposure to diphenylamine. The reproduction study
demonstrated that the offspring were less sensitive than the adults and there was
no developmental toxicity observed in either the rat or rabbit developmental studies
at any dose tested.
Uncertainty Factor
Based on the considerations outlined above, the Agency concludes that an
additional uncertainty factor to account for any special sensitivity to infants and
children is not warranted for diphenylamine or the impurity nitrosamine.
Aggregate Exposure
In examining aggregate exposure, FQPA directs EPA to take into account
available information concerning exposures from pesticide residues in food and
26
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other exposures for which there is reliable information. These other exposures
include drinking water and non-occupational exposures, e.g., to pesticides used in
and around the home. Risk assessments for aggregate exposure consider both
short-term and long-term (chronic) exposure scenarios including the toxic effects
which would likely be seen for each exposure duration.
Since there are no data on diphenylamine in the Agency's Pesticides in
Ground Water Database or in the U.S. EPA's "STORET" database, and the
limited use pattern, dietary risk from drinking water will assumed to be negligible.
Diphenylamine is a food use chemical. There are no residential (non-occupational)
uses of diphenylamine; therefore the considerations for aggregate exposure are
those only from food.
Acute Risk
As previously discussed, an acute dietary risk assessment was not conducted
since no appropriate endpoint or NOEL was identified in the available studies.
Chronic Risk
The chronic dietary risk evaluation indicated that exposure to
diphenylamine through food containing residues of this pesticide are below the
Agency's level of concern (i.e., the percent RfD utilized is only 20.8 percent for
non-nursing infants, the most sensitive subpopulation).
Cumulative Exposure To Substances with Common Mechanism of Toxicity.
Section 408(b)(2)(D)(v) of the Food Quality Protection Act requires that,
when considering whether to establish, modify, or revoke a tolerance, the Agency
consider "available information" concerning the cumulative effects of a particular
pesticide's residues and "other substances that have a common mechanism of
toxicity." The Agency believes that "available information" in this context might
include not only toxicity, chemistry, and exposure data, but also scientific policies
and methodologies for understanding common mechanisms of toxicity and
conducting cumulative risk assessments. For most pesticides, although the Agency
has some information in its files that may turn out to be helpful in eventually
determining whether a pesticide shares a common mechanism of toxicity with any
other substances, EPA does not at this time have the methodologies to resolve the
complex scientific issues concerning common mechanism of toxicity in a
meaningful way. EPA has begun a pilot process to study this issue further through
the examination of particular classes of pesticides. The Agency hopes that the
results of this pilot process will increase the Agency's scientific understanding of
this question such that EPA will be able to develop and apply scientific principles
for better determining which chemicals have a common mechanism of toxicity and
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evaluating the cumulative effects of such chemicals. The Agency anticipates,
however, that even as its understanding of the science of common mechanisms
increases, decisions on specific classes of chemicals will be heavily dependent on
chemical specific data, much of which may not be presently available.
Although at present, the Agency does not know how to apply the
information in its files concerning common mechanism issues to most risk
assessments, there are pesticides as to which the common mechanism issues can be
resolved. These pesticides include pesticides that are toxicologically dissimilar to
existing chemical substances (in which case the Agency can conclude that it is
unlikely that a pesticide shares a common mechanism of activity with other
substances) and pesticides that produce a common toxic metabolite (in which case
common mechanism of activity will be assumed).
EPA does not have, at this time, available data to determine whether
diphenylamine has a common mechanism of toxicity with other substances or how
to include this pesticide in a cumulative risk assessment. For the purposes of this
tolerance action, therefore, EPA has not assumed that diphenylamine has a
common mechanism of toxicity with other substances.
C. Environmental Assessment
1. Ecological Toxicity Data
Diphenylamine is moderately toxic to fish and aquatic invertebrates. It is
practically non-toxic to avian species on an acute and subacute basis. Since this
is an indoor food use chemical, and given the the limited volume and pattern of
DPA use, the likelihood of adverse effects on ecological systems is considered to
be minimal. No further data are required. Discharge of effluent containing
diphenylamine for manufacturing use is regulated by NPDES.
a. Toxicity to Terrestrial Animals
Only acute oral and subacute dietary studies are required for birds due to
the indoor-food end-use pattern. The results are discussed below.
(1) Birds, Acute and Subacute
An acute oral toxicity study using the technical grade of the active
ingredient (TGAI) is required to establish the toxicity of diphenylamine to birds.
The preferred test species is either mallard duck (a waterfowl) or bobwhite quail
(an upland gamebird). The result of this test is tabulated below.
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Table 6: Avian Acute Oral Toxicity
Species
Northern bobwhite quail
(Colinus virginianus)
%al
100
LD50 (mg/kg)
>2250
Toxicity Category
Practically nontoxic
MRID No. Author/Year
43878901
Palmer/Beavers 1995
Study Classification1
Core
1 Core (study satisfies guideline). Supplemental (study is scientifically sound, but does not satisfy guideline)
Since the LD50 is greater than 2250 mg/kg, diphenylamine is categorized
as practically non-toxic to avian species on an acute oral basis. Guideline 71-1 is
fulfilled (MRID 4387901).
A sub-acute dietary study using the TGAI is required to establish the
toxicity of diphenylamine to birds for the indoor-food end-use. The preferred test
species is either mallard duck or bobwhite quail. The result of this test is
tabulated below.
Table 7: Avian Subacute Dietary Toxicity
Species
Mallard duck
(Anas platyrhynchos)
%al
100
5-Day LC50 (ppm)1
>5205
Toxicity Category
Practically non-toxic
MRID No. Author/Year
43879101
Palmer/Beavers 1995
Study Classification
Core
Test organisms observed an additional three days while on untreated feed.
Since the LC50 is greater than 5205 ppm, diphenylamine is categorized as
practically non-toxic to avian species on a subacute dietary basis. Guideline (71-2)
is fulfilled (MRID 43879101).
(2) Birds, Chronic
Avian reproduction studies using the TGAI are not required for
diphenylamine because of the intended indoor-food end-use.
(3) Mammals, Acute and Chronic
Wild mammal studies using the TGAI are not required for diphenylamine
because of the intended indoor-food end-use.
(4)
Insects
A honey bee acute contact study using the TGAI is not required for
diphenylamine because its use will not result in honey bee exposure.
b. Toxicity to Aquatic Animals
Only acute studies are required for fish and aquatic invertebrates because
of the indoor-food end-use. The results are presented below:
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(1) Freshwater Fish, Acute
One freshwater fish toxicity study using the TGAI is required to establish
the toxicity of diphenylamine to fish for the indoor-food end-use. The preferred
test species is either rainbow trout (a coldwater fish) or bluegill sunfish (a
warmwater fish). The result of this test is tabulated below.
Table 8: Freshwater Fish Acute Toxicity
Species/
Flow-through or Static
Rainbow trout
(Oncorhynchus mykiss) static
%al
100
96-hour LC50 (ppm)
(measured/nominal)
2.2 (measured)
Toxicity
Category
Moderately
toxic
MRID No.
Author/Year
43879001
Drottar/Swigert 1995
Study
Classification
Core
Since the LC50 is 2.2 ppm, diphenylamine is categorized as moderately
toxic to freshwater fish on an acute basis. Guideline 72-1 is fulfilled (MRID
43879001).
(2) Freshwater Fish, Chronic
A freshwater fish early life-stage test using the TGAI is not required for
diphenylamine because of the intended indoor-food end-use, and its relative low
acute toxicity.
(3) Freshwater Invertebrates, Acute
A freshwater aquatic invertebrate toxicity test using the TGAI was required
to establish the toxicity of diphenylamine to aquatic invertebrates. The preferred
test species is Daphnia magna. The result of this test is tabulated below.
Table 9: Freshwater Invertebrate Acute Toxicity
Species/Static or
Flow-through
Waterflea
(Daphnia magna)
%ai
100
48-hour LC5tl/EC50 (ppm)
(measured)
1.2
Toxicity
Category
Moderately toxic
MRID No.
Author/Year
43878301
Drottar/Swigert 1995
Study
Classification
Core
Since the EC50 is 1.2 ppm, diphenylamine is categorized as moderately
toxic to aquatic invertebrates on an acute basis. Guideline 72-2 is fulfilled (MRID
43878301).
(4) Freshwater Invertebrate, Chronic
A freshwater aquatic invertebrate life-cycle test using the TGAI is not
required for diphenylamine because of the intended indoor-food end-use.
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2. Environmental Fate Characteristics of Diphenylamine Summary
Since this is an indoor-food end-use chemical, only hydrolysis data are
required. The available data indicate that diphenylamine is stable towards
hydrolysis at pH's 5,7, and 9. Based on limited laboratory data only, the Agency
concludes:
Diphenylamine has a moderate solubility in water (39.4 ppm), a relatively
high octanol/water partition coefficient (Kow=3,860), and a high vapor pressure
(6.39xl04torr).
Diphenylamine appears to be very labile in the environment, with aerobic
soil metabolism, and aqueous photolysis having important roles in the dissipation
of the molecule. Under aerobic soil metabolism conditions, diphenylamine is
rapidly transformed to dimers and polymers (half-life < 1 day). In addition, when
exposed to light in aqueous media, transformation is rapid (half-life 4.39 hours).
There is relatively little information about the transformation products
formed when diphenylamine is subjected to aerobic soil metabolism or aqueous
photolytic conditions. As mentioned earlier many of the ultimate transformation
products of diphenylamine are dimers and polymers with structures more complex
than that of diphenylamine. The rate of dissipation of such compounds is unknown
although it appears that they are much more stable than parent diphenylamine.In
aerobic soils it appears that the ultimate fate of the diphenylamine residues is
mineralization (formation of C02; 17.87% of the applied after 365 days), and soil
binding (unextracted residues 57.89% of the applied at 184 days).
The mobility of diphenylamine ranges from somewhat mobile (Kads= 151.57
in clay soil), to mobile (Kads = 21.43 for loamy sand, j^ =13.79 for loam,
Kads = 4.92 for silt loam, and I£js =16.44 for silty clay loam). Diphenylamine
residues (parent diphenylamine aged under aerobic soil metabolism conditions for
16.5-24.5 hours) were mobile in silt loam soil columns, and slightly mobile in
loamy sand, loam and clay soil columns.
Because this chemical is used indoors only, it is highly unlikely that it will
runoff to surface waters. However, if used outdoors there is a potential to reach
surface waters via dissolved runoff events occurring immediately after application.
The high rate of aqueous photolysis and the susceptibility of the chemical in
aerobic environments indicate that if it were to reach surface waters, however, the
chemical would be short lived.
Hydrolysis
[14C]-Diphenylamine (uniformly ring-labeled), at about 7 ppm, was
relatively stable towards hydrolysis in pH 5,7, and 9 buffered aqueous solutions
at 25±1°C. The registrant-calculated half-lives ranged from 316 to 358 days.
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Four minor degradates (<3.08% of the applied radioactivity) were detected in all
buffer solutions, but not identified. This study is acceptable and can be used to
satisfy the Hydrolysis data requirement. No additional data are required. (MRID
42660001)
The following studies are not required to satisfy the current data requirements for
diphenylamine; however, EFED reviewed the studies and included the information
in the chemical's database:
Photodegradation in Water
[U-14C]Diphenylamine, at 5 ppm, photolyzed with a registrant-calculated
half-life of 4.39 hours in a sterile aqueous pH 7 buffer solution that was irradiated
with a xenon lamp at 25°C for 192 hours. The major transformation products
observed were as follows:
Carbazole (Dl), reached a maximum of 51.74% of the applied at 10.5
hours, and decreased to non-detectable levels from 72 to 192 hours.
Hydroxydiphenylamine (OH-DPA, D2), averaged a maximum of 16.34%
of the applied at 36 hours and decreased to 6.83% by 192 hours.
A hydroxylated tricyclic compound (D3), was first detected at 4
hours(< 1% of the applied) and increased gradually to 93.18% at 192 hours (last
test interval).
Three other minor transformation products were observed, at < 5.87% of
the applied.
This study is acceptable and can be used to satisfy a Photolysis in Water
(guideline 161-2) data requirement. No additional data are required. (MRID
42958201)
Aerobic Soil Metabolism
[U-14C]Diphenylamine, at 10 ppm, dissipated with an observed half-life of
< 1 day in loam soil that was incubated in the dark at 24-26°C and 75% field
moisture capacity. Twelve [14C] compounds were isolated (<18.9% of the applied)
from the soil but could not be identified. Such compounds were characterized as
polymers, most of which contained dimeric diphenylamine with one additional unit
of aniline.
[14C02] averaged 17.87% of the applied by 365 days post-treatment.
Unextracted [14C] residues increased to >46.40% of the applied by 3 days post-
treatment and thereafter (maximum of 57.89% at 184 days).
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This study is acceptable and can be used to satisfy an Aerobic Soil
Metabolism (162-1) data requirement. No additional data are required. (MRID
42964201)
Anaerobic Aquatic Metabolism
This study is unacceptable, but does not have to be repeated. It cannot be
used to satisfy any data requirements for the following reasons:
o A number of samples (not identified by the registrant) appear to have
become aerobic during the study. This change confounded the analysis of
the information provided.
o The [14C] in the acetonitrile:methylene chloride extracts were assumed to
contain only the parent diphenylamines while the TLC analyses of the same
extracts showed the presence of various components. These components
were neither identified nor quantified.
[U-14C]Diphenylamine, at about 10 ppm, appears to dissipate slowly, with
a registrant calculated half-life of 60 days in anaerobic silty clay loam sediment
(flooded plus nitrogen atmosphere) incubated in the dark at 25°C for up to 1 year.
14C02 was <3.13% of the applied throughout the study. Unextracted [14C] residues
were 23.13-44.22% of the applied at 364 days. Up to 69.91% of the applied
radioactivity was volatilized and found in the rubber stoppers. (MRID 43080901)
Mobility-Leaching and Adsorption/Desorption
Based on batch equilibrium experiments, [U-14C]diphenylamine, at
approximately 0.10, 1.0, 5.0, and 10.0 jig/mL, was mobile in loamy sand soil,
loam soil, silt loam soil, and silty clay loam sediments, and somewhat mobile in
clay soil. Freundlich K values were as follows:
Table 10: Freundlich K values for Diphenylamine
Soil type
loamy sand
loam
silt loam
silty clay loam sediment
clay
Kads
21.43
13.79
4.92
16.44
151.57
Koc
3622
3962
1212
6593
5143
Kdes
34.67
23.51
8.73
39.58
306.56
This study is acceptable and can be used to partially satisfy a Mobility-
Leaching and Adsorption/Desorption (163-1) data requirement by providing
information about the mobility of unaged diphenylamine. No additional data are
required. (MRID 43412701)
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Mobility-Leaching and Adsorption/Desorption
Based on column leaching studies, unaged [14C]diphenylamine was
relatively mobile in columns of silt loam and loamy sand soil. It was somewhat
mobile in columns of loam soil and relatively immobile in columns of clay soil.
All columns were treated with about 500//g of [14C]diphenylamine and leached
with 20 inches of 0.01 M calcium chloride solution.
In the loamy sand, an average of 37.5% of the applied was found in the
treated soil layer. In the first two segments 61.66% was observed and in segments
3-5 <0.16% was observed. The leachate contained only 0.11% of the applied. In
the silt loam soil 23.71 - 27.26% of the applied was found in segments 1,2, and
the treated soil layer. 6.07% was found in segment 3, and <1.88% was found in
the leachates and segments 4 and 5. In the loam soil columns, the majority of the
radioactivity was in the treated segment, with 75.12% of the applied, followed by
segments 1 and 2, with 15.54% and 2.54%, respectively. Segments 3-5 and the
leachate contained <0.48% of the applied. In the clay soil, 88.77% of the applied
was in the treated segment, and <0.15% was observed in the other segments and
the leachate.
Based on column leaching experiments, [14C]diphenylamine residues were
mobile in silt loam soil columns, slightly mobile in loamy sand, loam and clay soil
columns. Prior to leaching, each column was topped with 50 g of soil that had
been treated with [U-14C] diphenylamine and incubated for 16.5-24.5 hours.
The loam, loamy sand, and clay soils had a similar radioactivity profile,
with 85.43-108.21% of the applied in the aged soil layer, 3.84-7.32% of the
applied in the first segment, 0.79-1.83% in the second segment, < 0.35% in
segments 3 to 5, and <1.06% in the leachate fractions. In the silt loam only, an
average of 35.62% of the applied radioactivity was in the aged soil, 17.40% was
in segment 1, 27.73% was in segment 2, 10.47% in segment 3, 1.57% in segment
4, 0.74% in segment 5, and 4.19% of the applied in the leachate.
In the soil columns, the following transformation products were observed:
N,N-Diphenylformamide (DPF),
4-nitro-N-phenylbenzenamine (NDPA),
diphenylamine dimer 1 (DPA-1), and
diphenylamine dimer 2 (DPA-2).
This study is acceptable and can be used to partially satisfy a Mobility-
Leaching and Adsorption/Desorption (163-1) data requirement by providing
information about the mobility of aged diphenylamine. No additional data are
required. (MRID 43413001)
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3. Exposure and Risk Characterization
Diphenylamine is moderately toxic to fish and aquatic invertebrates. It is
practically non-toxic to avian species on an acute and subacute basis. This is an
indoor food use chemical, and discharge of effluent containing diphenylamine for
manufacturing use is regulated by NPDES permit. EFED does not conduct risk
assessments for indoor use chemicals. However, given the limited volume and
pattern of diphenylamine use, the likelihood of adverse effects on ecological
systems is considered to be minimal.
4. Endangered Species
Because of minimal expected adverse risk on ecological systems due to the
unlikeliness of exposure, the usual statement concerning endangered species is not
necessary for diphenylamine.
5. Labelling
The "Environmental Hazards" section should include the following:
Manufacturing Use
"This pesticide is toxic to fish and aquatic invertebrates. Do not discharge effluent
containing this product into lakes, streams, ponds, estuaries, oceans or other
waters unless in accordance with the requirements of a National Pollutant
Discharge Elimination System (NPDES) permit and the permitting authority has
been notified in writing prior to discharge. Do not discharge effluent containing
this product to sewage systems without previously notifying the local sewage
treatment plant authority. For guidance contact your State Water Board or
Regional Office of the EPA."
End-Use Product
"This pesticide is toxic to fish and aquatic invertebrates. Do not contaminate water
by cleaning of equipment or disposing of equipment washwater or rinsate."
6. Data Requirements
All ecological toxicity and environmental fate data requirements for
diphenylamine are fulfilled.
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IV. RISK MANAGEMENT AND REREGISTRATION DECISION
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission
of relevant data concerning an active ingredient, whether products containing the active
ingredients are eligible for reregistration. The Agency has previously identified and
required the submission of the generic (i.e. active ingredient specific) data required to
support reregistration of products containing diphenylamine as active ingredients. The
Agency has completed its review of these generic data, and has determined that the data
are sufficient to support reregistration of all products containing diphenylamine. Appendix
B identifies the generic data requirements that the Agency reviewed as part of its
determination of reregistration eligibility of diphenylamine, and lists the submitted studies
that the Agency found acceptable.
The data identified in Appendix B were sufficient to allow the Agency to assess the
registered uses of diphenylamine and to determine that diphenylamine can be used without
resulting in unreasonable adverse effects to humans and the environment. The Agency
therefore finds that all products containing diphenylamine as the active ingredients are
eligible for reregistration. The reregistration of particular products is addressed in Section
V of this document.
The Agency made its reregistration eligibility determination based upon the target
data base required for reregistration, the current guidelines for conducting acceptable
studies to generate such data, published scientific literature, etc. and the data identified in
Appendix B. Although the Agency has found that all uses of diphenylamine are eligible
for reregistration, it should be understood that the Agency may take appropriate regulatory
action, and/or require the submission of additional data to support the registration of
products containing diphenylamine, if new information comes to the Agency's attention
or if the data requirements for registration (or the guidelines for generating such data)
change.
B. Determination of Eligibility Decision
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredients
diphenylamine, the Agency has sufficient information on the health effects of
diphenylamine and on its potential for causing adverse effects in fish and wildlife
and the environment. The Agency has determined that diphenylamine products,
labeled and used as specified in this Reregistration Eligibility Decision, will not
pose unreasonable risks or adverse effects to humans or the environment.
Therefore, the Agency concludes that products containing diphenylamine for all
uses are eligible for reregistration.
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2. Eligible and Ineligible Uses
The Agency has determined that the currently registered use of
diphenylamine is eligible for reregistration subject to conditions imposed in this
RED.
C. Regulatory Position
The following is a summary of the regulatory positions and rationales for
diphenylamine. Where labeling revisions are imposed, specific language is set
forth in Section V of this document.
1. FQPA Findings
Because diphenylamine has a food use, specific consideration of the risks
to infants and children, as well as aggregate exposures and potential cumulative
effects, is warranted.
In determining whether an additional uncertainty factor is or is not
appropriate for assessing risks to infants and children, EPA uses a weight of
evidence approach taking into account the completeness and adequacy of the
toxicity data base, the nature and severity of the effects observed in pre- and post-
natal studies, and other information such as epidemiological data.
For purposes of assessing the pre- and post-natal toxicity of diphenylamine,
EPA has evaluated two developmental and one reproduction study. Based on
current toxicological data requirements, the data base for diphenylamine, relative
to pre- and post-natal toxicity, is complete. However, as EPA fully implements
the requirements of FQPA, additional data related to the special sensitivity of
infants and children may be required.
The data provided no indication of increased sensitivity of rats or rabbits
to in utero and/or post-natal exposure to diphenylamine. The reproduction study
demonstrated that the offspring were less sensitive than the adults and there was
no developmental toxicity observed in either the rat or rabbit developmental studies
at any dose tested.
Based on the considerations outlined above, the Agency concludes that an
additional uncertainty factor to account for any special sensitivity to infants and
children is not warranted for diphenylamine.
There are no data or information to indicate that diphenylamine will
contaminate drinking water. Additionally, it is unlikely for this to occur given the
limited use pattern for this chemical. There are also no residential uses for
diphenylamine. Therefore, aggregate exposure is obtained only from the use on
apples.
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It is not appropriate to conduct an acute dietary risk assessment as no acute
endpoint or NOEL was identified in the available studies.
The chronic dietarty risk assessment using anticipated residues for some
commodities indicated that only 20.8 percent of the RfD is utilized for the most
sensitive subpopulation, non-nursing infants.
A dietary cancer risk asesment for the impurity diphenylnitrosamine was
also conducted and indicated that the estimated lifetime cancer risk is 2.8 x 10 n.
Both the non-cancer and cancer dietary risk assessments indicate that the
risk fall below the Agency's levels of concern.
EPA does not have, at this time, available data to determine whether
diphenylamine has a common mechanism of toxicity with other substances or how
to include this pesticide in a cumulative risk assessment. For the purposes of this
tolerance action, therefore, EPA has not assumed that diphenylamine has a
common mechanism of toxicity with other substances.
2. Tolerance Reassessment
A summary of the diphenylamine tolerance reassessment and recommended
modifications in commodity definitions are presented in Table 11.
Tolerances Listed Under 40 CFR §180.190:
Adequate residue data are available to determine the adequacy of the
established tolerances on apples, milk, and meat. The residue data support the
current tolerance of 10 ppm for residues in apples. Data indicate that tolerances
for residues in milk and meat, both currently 0 ppm, should be increased.
Separate tolerances of 0.01 ppm should be established for residues in milk and
meat, fat, and mbyp (excluding liver) of cattle, goats, horses, and sheep. Separate
tolerances of 0.1 ppm should be established for residues in liver of cattle, goats,
horses, and sheep.
New Tolerances Needed Under 40 CFR §180.190:
Data from an adequate apple processing study indicate that the registrants
should propose a tolerance of 30 ppm for diphenylamine residues in wet apple
pomace.
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Table 11: Tolerance Reassessment Summary for Diphenylamine.
Commodity
Current
Tolerance (ppm)
Tolerance
Reassessment (ppm)
Comment/ Correct Commodity Definition
Tolerances listed under 40 CFR §180.190:
Apples
Milk
Meat
10.0
0
0
10.0
0.01
0.01
Data from the ruminant study indicate that a higher tolerance is required.
Residue data from a ruminant feeding study indicate that a higher tolerance is
required. Separate tolerances must be established for meat, fat, and mbyp
(excluding liver) of cattle, goats, horses, and sheep.
Tolerances needed under 40 CFR §180.190:
Liver
Apple,
pomace, wet
None
None
0.1
30.0
Residue data from a ruminant feeding study indicate a tolerance is required.
Separate tolerances must be established for liver of cattle, goats, horses, and
sheep.
Residue data from an apple processing study indicate that a tolerance for
residues in wet apple pomace is required.
Dietary Exposure Assessment Summary
Adequate plant and livestock metabolism and residue data are available for
reregistration and risk assessment. Although additional data are required for the
livestock enforcement method, a risk assessment can be performed at this time.
The residue levels to be used in the risk assessment are shown in the tolerance
reassessment summary.
Codex Harmonization
The Codex Alimentarius Commission has established a maximum residue
limit (MRL) for diphenylamine residues in apples (see Guide to Codex Maximum
Limits For Pesticide Residues, Part A. 1-58, 1995). The Codex residue definition
and the U.S. tolerance expression for diphenylamine are currently compatible,
since each includes only the parent, diphenylamine. However, the Codex MRL
(CXL) for diphenylamine on apples is 5 mg/kg compared to the 10 ppm U.S.
tolerance for apples. Since available residue data, based on the current U.S. use
pattern, indicate that the 10 ppm tolerance is appropriate, harmonization of the
Codex MRL and U.S. tolerance is not possible at the present time.
3. Tolerance Revocations and Import Tolerances
At this time EPA, does not have any issues or recommendations for
diphenylamine relative to tolerance revocations or import tolerances.
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4. Summary of Risk Management Decisions
a. Human Health
(1) Dietary
Acute Dietary
An acute dietary risk assessment was not conducted since no appropriate
endpoint or NOEL could be identified from the available data. No developmental
toxicity was seen at doses greater than 100 mg/kg/day in rats or at doses greater
than 300 mg/kg/day in rabbits.
Chronic Dietary (including cancer)
The Agency has evaluated the chronic dietary risk associated with
consuming food containing residues of diphenylamine. Anticipated residues for
some commodities were used to estimate exposure. The RfD was determined to
be 0.03 mg/kg/day based on the LOEL observed in a chronic dog feeding study
and uncertainty factors of 10 for both intra- and inter species variability and 3 for
the lack of a NOEL. The percent RfD utilized for the most sensitive subpopulation
(non-nursing infants) was calculated to be 20.8 percent; well below the Agency's
level of concern.
No dietary cancer risk assessment was performed for diphenylamine since
available data indicate it is not carcinogenic. However, an impurity,
diphenylnitrosamine, has been determined to be carcinogenic and the dietary risk
is calculated to be 2.8 x 10 n for a lifetime of exposure. This level of risk is
considered to be negligible and not of concern.
(2) Worker (Mixer/Loader/Applicator)
Acute (Short-Term) and Intermediate Term
EPA has determined that there is potential exposure to pesticide handlers
from the use of diphenylamine as a drench on apples following harvest.
Exposure data for this use pattern are not available; consequently, the
Agency had to rely on surrogate data and adjust to fit the exposure scenario. MOEs
were calculated based on each for both minimum and maximum label rates. MOEs
were adequate when applicators were assumed to wear a single layer of clothing
(long sleeved shirt and long pants) and mixers/loaders were assumed to wear
chemical-resistant goves and a single layer of clothing. The Agency is requiring
the registrant, through this RED, to develop appropriate exposure data in order to
more accurately assess the risk associated with this use. This RED also requires
mixers/loaders to wear chemical-resistant gloves and single layer body covering.
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All applicators must wear single layer clothing in order to reduce potential
exposure. Given the range of exposure values based on the databases used and the
protective clothing that will be required to be worn when handling this pesticide,
the Agency believes that workers will be adequately protected. Exposures and
resultant risks will be assessed once the required data are available.
Post-Application
EPA has no concerns about post-application exposure at this time and no
data are required at this time.
b. Environmental
(1) Avian
Acute
Diphenylamine is practically non-toxic to avian species on an acute and sub-
acute basis. Since this is an indoor food use chemical, the Agency does not
conduct avian risk assessments for indoor use chemicals. However, given the
limited volume and pattern of diphenylamine use, the likelihood of adverse effects
on ecological systems is considered to be minimal. There are no further data
required.
Chronic
Diphenylamine does not represent a chronic risk to birds. Avian
reproduction studies using the TGAI are not required for diphenylamine because
of the indoor-food end-use.
(2) Mammals, Acute and Chronic
Diphenylamine does not represent an acute or chronic risk to mammals.
Wild mammal testing is not required for diphenylamine because of the intended
indoor-food end-use pattern.
(3) Insects
A honey bee acute contact study using the TGAI is not required for
diphenylamine because its use will not result in honey bee exposure.
(4) Freshwater Fish
Diphenylamine represents a relatively low acute toxicity to fresh water fish.
Hence, a freshwater fish early life-stage test using the TGAI is not required for
diphenylamine because of the intended indoor-food end-use.
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(5) Aquatic invertebrates
The acute toxicity to aquatic invertebrates is expected to be moderate. A
freshwater chronic aquatic invertebrate life-cycle test using the TGAI is not
required for diphenylamine because of the intended indoor-food end-use.
(6) Estuarine and Marine Organisms
Diphenylamine represents a relatively low toxicity to estuarine and marine
organisms. Estuarine and marine testing is not required for diphenylamine because
of the intended indoor-food end-use pattern.
(7) Nontarget Plants (Terrestrial, Semi-Aquatic, and
Aquatic)
Diphenylamine represents a relatively low toxicity to non-target plants.
Nontarget plant testing is not required for diphenylamine because of the intended
indoor-food end-use pattern.
(8) Endangered Species
The use of diphenylamine is expected to have minimal adverse effect on
ecological systems due to the unlikeliness of exposure..
(9) Surface Water
Since diphenylamine is used indoors only, it is highly unlikely that it will
runoff to surface waters. However, if used outdoors there is a potential to reach
surface waters via dissolved runoff events occurring immediately after application.
The high rate of aqueous photolysis and the susceptibility of the chemical in
aerobic environments indicate that if it were to reach surface waters, however, the
chemical would be short lived. Discharge of effluent containing diphenylamine for
manufacturing use is regulated by NPDES permit.
(10) Ground Water
Because of minimal expected adverse effect on ecological systems due to
the unlikeliness of exposure, the usual statement concerning groundwater is not
necessary for diphenylamine.
5. Restricted Use Classification
Restricted Use Classification is not applicable for current diphenylamine
use.
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6. Reference Dose Exceedance
Current diphenylamine usage does not exceed the reference dose limits
established by available data and current tolerances.
7. Endangered Species Statement
The Agency has developed a program ("The Endangered Species
Protection Program") to identify all pesticides whose use may cause adverse
impacts on endangered and threatened species and to implement mitigation
measures that will eliminate the adverse impacts. At present, the program is being
implemented on an interim basis as described in a Federal Register notice (54 FR
27984-28008, July 3, 1989), and is providing information to pesticide users to help
them protect these species on a voluntary basis. As currently planned, the final
program will call for label modifications referring to required limitations on
pesticide uses, typically as depicted in county-specific bulletins or by other site-
specific mechanisms as specified by state partners. A final program, which may
be altered from the interim program, will be described in a future Federal Register
notice. The Agency is not imposing label modifications at this time through the
RED. Rather, any requirements for product use modifications will occur in the
future under the Endangered Species Protection Program.
8. Labeling Rationale
The 1992 Worker Protection Standard for Agricultural Pesticides (WPS)
established certain worker-protection requirements (personal protective equipment,
restricted entry intervals, etc.) to be specified on the label of all products that
contain uses within the scope of the WPS. All currently registered uses of
diphenylamine are within the scope of the the WPS.
At this time, all products containing diphenylamine are intended primarily
for occupational use (i.e. mixed, loaded, and applied by commercial applicators
only; generally not available to homeowners). No registered use is likely to involve
applications at residential sites.
Requirements for Handlers
For each end-use product, personal protective equipment and engineering
control requirements for pesticide handlers are set during reregistration as follows:
• Based on risks posed to handlers by the active ingredient, EPA may
establish active-ingredient-specific (a-i specific) handler requirements for
end-use products containing that active ingredient. If such risks are
minimal, EPA may choose not to establish a-i-specific handler
requirements.
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• EPA establishes handler PPE requirements for most end-use products,
based on each product's acute toxicity characteristics.
• If A-I-specific requirements have been established, they must be compared
to the end-use-product-specific PPE. The more stringent choice for each
type of PPE (i.e., bodywear, hand protection, footwear, eyewear, etc.)
must be placed on the label of the end-use product. Engineering controls
are considered more stringent than PPE requirements.
Occupational-Use Products
EPA is establishing a-i-specific requirements for all occupational handlers
for diphenylamine. EPA has no data upon which to assess the risk to handlers
operating drenching equipment. In lieu of data, EPA roughly estimated potential
exposure and risk using a range-finding technique. Surrogate mixer/loader data
from PHED (ver. 1.1) was combined with flagger data in the assessment. These
surrogate exposure scenarios are assumed to more closely duplicate the exposures
to handlers involved in drive-thru drenching applicators than other exposure
scenarios for which data are available. Due to EPA's lack of data to assess
exposure to handlers participating in drenching operations, EPA is establishing
requirements of single layer body protection for the drench operator. Persons
involved in mixing, loading, and adjusting and maintaining the drench equipment
must wear chemical-resistant gloves and single layer body protection. Persons who
during the application remain inside the truck cab with the windows and doors
closed need not wear the required personal protective equipment. If, however,
drivers exit the truck cab in or immediately adjacent to the treatment area during
the application, they must wear the required PPE.
Post-Application/Entry Restrictions
Occupational-Use Products
At this time, EPA has no concerns about post-application exposures to
immediately following diphenylamine drenching of apples.
9. Spray Drift Advisory
The Agency has been working with the Spray Drift Task Force, EPA
Regional Offices and State Lead Agencies for pesticide regulation to develop the
best spray drift management practices. The Agency is now requiring interim
measures that must be placed on product labels/labeling as specified in Section V.
Once the Agency completes its evaluation of the new data base submitted by the
Spray Drift Task Force, a membership of U.S. pesticide registrants, the Agency
may impose further refinements in spray drift management practices to further
reduce off-target drift and risks associated with this drift.
44
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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. The DP A Task
Force has agreed to submit to the Agency for approval all label amendments by
January 1, 1998 on both the manufacturing-use product and end-use products.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of diphenylamine for the
above eligible use has been reviewed and determined to be substantially complete.
The following studies are required to be conducted on the generic active
ingredient:
- in vivo/in vitro Rat Hepatocyte Unscheduled DNA Synthesis (UDS) Assay
[Guideline 84-4]
- Subchronic Dog: to investigate methemoglobinemic effect [Guideline 82-1]
- Deposition Study
- UV/visible absorption [Guideline 830.7050]
- Registrant must either certify that the beginning materials and manufacturing
process for the TGAI have not changed, or must submit an updated product
chemistry package.
- An independent laboratory validation study is needed if the data collection
method for meat and milk is to be used as an enforcement method.
The DPA Task Force has agreed to conduct the deposition study and any
subsequent exposure studies required (based on the results of the deposition study)
as conditions of registration. Submission of the deposition study and the dermal
exposure study, if needed, will be included as a term and condition of all DPA
registrations. Consequently, failure to submit these studies in a timely manner will
result in automatic suspension of these registrations.
2. Labeling Requirements for Manufacturing-Use Products
The Agency is requiring that the diphenylamine manufacturing use labeling
be revised to include only the indoor-food end-use (specifically restricted to post-
harvest drenching treatment prior to storage). The "Environmental Hazards"
section must include the following:
45
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" This pesticide is toxic to fish and aquatic invertebrates. Do not
discharge effluent containing this product into lakes, streams,
ponds, estuaries, oceans or other waters unless in accordance with
the requirements of a National Pollutant Discharge Elimination
System (NPDES) permit and the permitting authority has been
notified in writing prior to discharge. Do not discharge effluent
containing this product to sewage systems without previously
notifying the local sewage treatment plant authority. For guidance
contact your State Water Board or Regional Office of the EPA."
To remain in complaince 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 a plant growth regulator used for reduction of scald on
apples in storage."
An MP registrant may, at his/her discretion, add one of the following
statements to an MP label under "Directions for Use" to permit the reformulation
of the product for a specific use or all additional uses supported by a formulator
or user group:
(a) "This product may be used to formulate products for specific use(s)
not listed on the MP label if the formulator, user group, or grower
has complied with U.S. EPA data submission requirements
regarding support of such use(s)."
(b) "This product may be used to formulate products for any additional
use(s) not listed on the MP label if the formulator, user group, or
grower has complied with U.S. EPA submission requirements
regarding support of such use(s)."
All products distributed or sold by registrants and distributors
(supplemental registrants) should bear labeling that is consistent with this notice
by January 1, 1998 and all products distributed or sold by persons other than
registrants or supplemental registrants after January 1, 1998 should bear
correct labeling.
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
46
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been made. Registrants must review previous data submissions to ensure that they
meet current EPA acceptance criteria and if not, commit to conduct new studies.
If a registrant believes that previously submitted data meet current testing
standards, then study MRID numbers should be cited according to the instructions
in the Requirement Status and Registrants Response Form provided for each
product.
2. Labeling Requirements for End-Use Products
The labels and labeling of all products must comply with EPA's current
regulations and requirements as specified in 40 CFR 156.10 and other applicable
notices. All end-use product labels [e.g. multiple active ingredient (MAI) labels,
SLN's, and products subject to generic data exemption] must be amended such that
they are consistent with the basic producer labels.
Diphenylamine labeling for end-use products must be revised to include
only the indoor-food end-use (specifically restricted to post-harvest drenching
treatment prior to storage). The "Environmental Hazards" section should include
the following:
" This pesticide is toxic to fish and aquatic invertebrates. Do not contaminate water
by cleaning of equipment or disposing of equipment washwater or rinsate."
Worker Protection Standard
Any product whose labeling reasonably permits use in the production of an
agricultural plant on any farm, forest, nursery, or greenhouse must comply with
the labeling requirements of PR Notice 93-7, "Labeling Revisions Required by the
Worker Protection Standard (WPS), and PR Notice 93-11, "Supplemental
Guidance for PR Notice 93-7, which reflect the requirements of EPA' s labeling
regulations for worker protection statements ( 4 0 CFR part 156, subpart K).
These labeling revisions are necessary to implement the Worker Protection
Standard for Agricultural Pesticides (40 CFR part 170) and must be completed in
accordance with, and within the deadlines specified in, PR Notices 93-7 and 93-11.
Unless otherwise specifically directed in this RED, all statements required by PR
Notices 93-7 and 93-11 are to be on the product label exactly as instructed in those
notices.
After April 21, 1994, except as otherwise provided in PR Notices 93-7 and
93-11, all products within the scope of those notices must bear WPS PR Notice
complying labeling when they are distributed or sold by the primary registrant or
any supplementally registered distributor.
After October 23, 1995, except as otherwise provided in PR Notices 93-7
and 93-11, all products within the scope of those notices must bear WPS PR Notice
complying labeling when they are distributed or sold by any person.
47
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The labels and labeling of all products must comply with EPA's current
regulations and requirements as specified in 40 CFR §156.10 and other applicable
notices.
PPE Requirements for Pesticide Handlers
For sole-active-ingredient end-use products that contain diphenylamine, the
product labeling must be revised to adopt the handler personal protective
equipment/engineering control requirements set forth in this section. Any
conflicting PPE requirements on the current labeling must be removed.
For multiple-active-ingredient end-use products that contain diphenylamine,
the handler personal protective equipment/engineering control requirements set
forth in this section must be compared to the requirements on the current labeling
and the more protective must be retained. For guidance on which requirements are
considered more protective, see PR Notice 93-7.
Products Intended Primarily for Occupational Use
Active-Ingredient-Specific PPE or Engineering Control Requirements
EPA is establishing the following active-ingredient specific PPE for all
handlers of diphenylamine end-use products.
"Handlers (including mixers, loaders, persons cleaning or maintaining the drencher
equipment, and persons handling treated apples or apple containers still wet with
drench) must wear:
—long-sleeved shirt and long pants
—chemical-resistant gloves*
Drenching applicators must wear:
—long-sleeved shirt and long pants
Exception: Persons who, during the application, remain inside the truck cab with
the windows and doors closed need not wear the PPE required for other handlers.
However, if such drivers exit the truck cab in or immediately adjacent to the
treatment area during the application, then they must wear the required PPE."
* For the glove statement, use the statement established for diphenylamine through
the instructions in Supplement Three of PR Notice 93-7.
PPE Requirements for End-use Product Labels
The PPE that would be established on the basis of the acute toxicity
category of the end-use product must be compared to the active-ingredient specific
48
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personal protective equipment specified above. The more protective PPE must be
placed on the product labeling. For guidance on which PPE is considered more
protective, see PR Notice 93-7.
Placement in Labeling
The personal protective equipment requirements must be placed on the end-
use product labeling in the location specified in PR Notice 93-7. The format and
language of the PPE requirements must be the same as is specified in PR Notice
93-7.
PPE Requirements for End-Use Product Labels
The PPE, if any, that would be established on the basis of the acute toxicity
category of each end-use product must be compared to the active-ingredient-
specific personal protective equipment specified above. The more protective PPE
must be placed on the product labeling. A requirement is considered more
protective than a recommendation (e.g., "must wear" is more protective than
"should wear"). For guidance on which PPE is considered more protective, see PR
Notice 93-7.
Placement in Labeling
The personal protective equipment requirements must be placed on the end-
use product labeling in the location specified in PR Notice 93-7. The format and
language of the PPE requirements must be the same as is specified in PR Notice
93-7.
Entry Restrictions
For sole-active-ingredient end-use products that contain diphenylamine, the
product labeling must be revised to adopt the entry restrictions set forth in this
section. Any conflicting entry restrictions on the current labeling must be removed.
For multiple-active-ingredient end-use products that contain diphenylamine,
the entry restrictions set forth in this section must be compared to the entry
restrictions on the current labeling and the more protective must be retained. A
specific time period in hours or days is considered more protective than "sprays
have dried" or "dusts have settled."
Products Intended Primarily for Occupational Use
Entry restrictions:
49
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The Agency is aware that all post-application handling of treated apples or
apple containers are to be conducted by forklift machinery. However, if for any
reason circumstanses arise whereby persons are manually handling treated apples
or apple containers that are still wet with drench, then they must wear the same
personal protective equipment as required for handlers. See section on handler
PPE above for the required PPE.
Other Labeling Requirements
The Agency is requiring the following labeling statements to be located on
all end-use products containing diphenylamine that are intended primarily for
occupational use.
Application Restrictions
"Do not apply this product in a way that will contact workers or other
persons, either directly or through drift. Only protected handlers may be in the
area during application."
User Safety Requirements
"Discard clothing or other absorbent materials that have been drenched or
heavily contaminated with this product's concentrate. Do not reuse them."
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no
such instructions for washables, use detergent and hot water. Keep and wash PPE
separately from other laundry."
User Safety Recommendations
• "Users should wash hands before eating, drinking, chewing gum,
using tobacco, or using the toilet."
• "Users should remove clothing immediately if pesticide gets inside.
Then wash thoroughly and put on clean clothing."
• "Users should remove PPE immediately after handling this product. Wash
the outside of gloves before removing. As soon as possible, wash
thoroughly and change into clean clothing."
Effluent Discharge Labeling Statements
Refer to subsection A. above for labeling requirements for effluent
discharge.
50
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C. Tolerance Revocation and Import Tolerances
No use of diphenylamine is being cancelled/voluntarily cancelled as part of EPA's
reregistration eligibility decision regarding this pesticide. It is EPA's policy to propose
revocation of a tolerance, and/or food/feed additive regulation, following the deletion of
a related food use from a registration, or following the cancellation of a related food-use
registration. As a result, any parties interested in supporting the tolerance/regulation for
import purposes in the absence of a registered U.S. use should notify EPA as soon as
possible.
In responding, EPA will provide detailed information on the outstanding data
requirements for these tolerances and/or regulations. The Agency will consider
commitments made to generate data to support such tolerances/regulations and the
timeliness of data submissions in its assessment of whether the tolerances/regulations
should be retained. Persons interested in establishing a new tolerance for import purposes
only, or retaining a current tolerance for import purposes following cancellation of the
related use, must submit a petition along with the appropriate fees and supporting data.
D. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling
until December 31, 1997. 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 diphenylamine
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.
51
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52
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VI. APPENDICES
53
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SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Max. Appl. Soil Max. # Apps Max. Dose [(AI Min.
/year
Geographic Limitations
Interv Entry Allowed
Intv.
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES
APPLE
Dip treatment, Postharvest, Dip tank
WP NA
RTU
WP
GI4
NA
54
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Report Run Date: 09/26/97 ) Time 10:49 LUIS 4.1 - Page:
PRD Report Date: 07/18/96
APPENDIX A REPORT
Case 2210 [Diphenylamine] Chemical 038501 [Diphenylamine]
4444444.
LEGEND
444444
Sort: Uses Eligible or Ineligible for Re-registration, Food/Feed or Non-Food/Non-Feed Uses, Alpha Site Name, Use Group Name, Alpha Application Type/Timing/Equipment
Description, Formulation, Maximum Application Rate Unit/Area Quantity, Minimum Application Rate
HEADER ABBREVIATIONS
Min. Appl. Rate (AI unless : Minimum dose for a single application to a single site. System calculated. Antimicrobial claims only.
noted otherwise)
Max. Appl. Rate (AI unless : Maximum dose for a single application to a single site. System calculated.
noted otherwise)
: Maximum dose for a single application to a single site as related to soil texture (Herbicide claims only) .
: Maximum number of Applications at Maximum Dosage Rate. Example: "4 applications per year" is expressed as "4/1 yr"; "4 applications per 3
years" is expressed as "4/3 yr"
: Maximum dose applied to a site over a single crop cycle or year. System calculated.
: Minimum Interval between Applications (days)
: Reentry Intervals
: LUIS contains all products that were active or suspended (and that were available from OPP Document Center) as of this date. Some products
registered after this date may have data included in this report, but LUIS does not guarantee that all products registered after this date
have data that has been captured.
SOIL TEXTURE FOR MAX APP. RATE
* : Non-specific
C : Coarse
M : Medium
F : Fine
O : Others
FORMULATION CODES
EC : EMULSIFIABLE CONCENTRATE
RTU : LIQUID-READY TO USE
SC/L : SOLUBLE CONCENTRATE/LIQUID
WP : WETTABLE POWDER
ABBREVIATIONS
AN : As Needed
NA : Not Applicable
NS : Not Specified (on label)
UC : Unconverted due to lack of data (on label), or with one of following units: bag, bait, bait block, bait pack, bait station, bait station(s), block, briquet,
briquets, bursts, cake, can, canister, capsule, cartridges, coil, collar, container, dispenser, drop, eartag, grains, lure, pack, packet, packets, pad, part,
parts, pellets, piece, pieces, pill, pumps, sec, sec burst, sheet, spike, stake, stick, strip, tab, tablet, tablets, tag, tape, towelette, tray, unit, --
APPLICATION RATE
: Dosage Can Not be Calculated
: No Calculation can be made
: PPM calculated by weight
: PPM Calculated by volume
: Unknown whether PPM is given by weight or by volume
55
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APPLICATION RATE (CONT.)
cwt : Hundred Weight
nnE-xx : nn times (10 power -xx); for instance, "1.234E-04" is equivalent to ".0001234"
USE LIMITATIONS CODES
A26 : minute(s) contact time (maximum).
A43 : seconds contact time (minimum).
C04 : Proper ventilation required.
C93 : Do not apply directly to water.
CAG : Do not apply where runoff is likely to occur.
CAL : Do not contaminate water, food or feed.
CCD : Do not make more than applications per year.
GD8 : Do not use treated apples in the manufacture of livestock feeds.
GD9 : Do not graze cover crops.
GI4 : Do not use treated apples in the manufacture of pomace for use in livestock feeds.
* NUMBER IN PARENTHESES REPRESENTS THE NUMBER OF TIME UNITS (HOURS,DAYS, ETC.) DESCRIBED IN THE LIMITATION.
UNIT DESCRIPTIONS
bu : bushel
gal : gallon
Ib : pound
tree : tree
56
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for active
ingredients within the case 2665 covered by this Reregistration Eligibility Decision Document.
It contains generic data requirements that apply to 2665 in all products, including data
requirements for which a "typical formulation" is the test substance.
The data table is organized in the following format:
1. Data Requirement (Column 1). The data requirements are listed in the order in which
they appear in 40 CFR Part 158. the reference numbers accompanying each test refer to the test
protocols set in the Pesticide Assessment Guidelines, which are available from the National
Technical Information Service, 5285 Port Royal Road, Springfield, VA 22161 (703) 487-4650.
2. Use Pattern (Column 2). This column indicates the use patterns for which the data
requirements apply. The following letter designations are used for the given use patterns:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
0 Indoor residential
3. Bibliographic citation (Column 3). If the Agency has acceptable data in its files, this
column lists the identifying number of each study. This normally is the Master Record
Identification (MRID) number, but may be a "GS" number if no MRID number has been
assigned. Refer to the Bibliography appendix for a complete citation of the study.
57
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APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of
Diphenylamine
REQUIREMENT
USE PATTERN
CITATION(S)
PRODUCT CHEMISTRY
61-1 Chemical Identity
61-2A Start. Mat. & Mnfg. Process
61-2B Formation of Impurities
62-1 Preliminary Analysis
62-3 Analytical Method
63-2 Color
63-3 Physical State
63-4 Odor
63-5 Melting Point
63-7 Density
63-8 Solubility
63-9 Vapor Pressure
63-10 Dissociation Constant
63-11 Octanol/Water Partition
63-12 pH
63-13 Stability
ECOLOGICAL EFFECTS
71-1A Acute Avian Oral - Quail/Duck
71-2B Avian Dietary - Duck
72-1C Fish Toxicity Rainbow Trout
72-2A Invertebrate Toxicity
TOXICOLOGY
all 43503901
all 43642001
all 43642001,43503901
all 42795501,43153301
all 42795501,43153301
all 42716501
all 42716501
all 42716501
all 42716501
all 42716501
all 42898801
all 42876201
all 42716401
all 42826601
all 42716501
all 42781501
all
all
all
all
43878901
43879101
43879001
43878301
81-1
Acute Oral Toxicity - Rat
all
41899401
58
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Data Supporting Guideline Requirements for the Reregistration of
Diphenylamine
REQUIREMENT
USE PATTERN
CITATION(S)
81-2 Acute Dermal Toxicity - Rabbit/Rat all
81-4 Primary Eye Irritation - Rabbit all
81-5 Primary Dermal Irritation - Rabbit all
81-6 Dermal Sensitization - Guinea Pig all
82-1A 90-Day Feeding - Rodent all
82-IB 90-Day Feeding - Non-rodent all
82-2 21-Day Dermal-Rabbit/Rat all
83-1A Chronic Feeding Toxicity - Rodent all
83-IB Chronic Feeding Toxicity - Non-Rodent all
83-2A Oncogenicity - Rat all
83-2B Oncogenicity - Mouse all
83-3A Developmental Toxicity - Rat all
83-3B Developmental Toxicity - Rabbit all
83-4 2-Generation Reproduction - Rat all
84-2A Gene Mutation (Ames Test) all
84-2B Structural Chromosomal Aberration all
84-4 Other Genotoxic Effects all
85-1 General Metabolism all
OCCUPATIONAL/RESIDENTIAL EXPOSURE
231 Estimation of Dermal Exposure at
Outdoor Sites
232 Estimation of Inhalation Exposure at
Outdoor Sites
ENVIRONMENTAL FATE
161-1 Hydrolysis
161-2 Photodegradation - Water
all
all
all
all
41899402
41899404
41899405
43540801
42339701
00148521
42304901
43401401, 43033601
43000601
43401401, 43033601
43369501, 43132401
44165401
00148521
42638101
42312101, 42311901
42311901, 42312001
42332101
42994801
44212501
44212501
42660001
42958201
59
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Data Supporting Guideline Requirements for the Reregistration of
Diphenylamine
REQUIREMENT
USE PATTERN
CITATION(S)
162-1 Aerobic Soil Metabolism
162-3 Anaerobic Aquatic Metabolism
163-1 Leaching/Adsorption/ Desorption
RESIDUE CHEMISTRY
171-4A Nature of Residue - Plants
171-4B Nature of Residue - Livestock
171-4C Residue Analytical Method - Plants
171-4D Residue Analytical Method - Animal
171-4E Storage Stability
171-4J Magnitude of Residues -
Meat/Milk/Poultry/Egg
171-4K Crop Field Trials
171-4L Processed Food
all 42964201
all 43080901
all 43412701,43413001
all 43156201,43370101,
42897301
all
all
all
all
all
all
all
43197101,
43428401,
43428403
43973201
43620901
43972601
43625501
43633601
43187501
43428402
60
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GUIDE TO APPENDIX C
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated
elsewhere in the Reregistration Eligibility Document. Primary sources for studies in
this bibliography have been the body of data submitted to EPA and its predecessor
agencies in support of past regulatory decisions. Selections from other sources
including the published literature, in those instances where they have been considered,
are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In the
case of published materials, this corresponds closely to an article. In the case of
unpublished materials submitted to the Agency, the Agency has sought to identify
documents at a level parallel to the published article from within the typically larger
volumes in which they were submitted. The resulting "studies" generally have a
distinct title (or at least a single subject), can stand alone for purposes of review and
can be described with a conventional bibliographic citation. The Agency has also
attempted to unite basic documents and commentaries upon them, treating them as a
single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted
numerically by Master Record Identifier, or "MRID number". This number is unique
to the citation, and should be used whenever a specific reference is required. It is not
related to the six-digit "Accession Number" which has been used to identify volumes of
submitted studies (see paragraph 4 (d) (4) below for further explanation). In a few
cases, entries added to the bibliography late in the review may be preceded by a nine
character temporary identifier. These entries are listed after all MRID entries. This
temporary identifying number is also to be used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry
consists of a citation containing standard elements followed, in the case of material
submitted to EPA, by a description of the earliest known submission. Bibliographic
conventions used reflect the standard of the American National Standards Institute
(ANSI), expanded to provide for certain special needs.
a Author. Whenever the author could confidently be identified, the Agency has
chosen to show a personal author. When no individual was identified, the
Agency has shown an identifiable laboratory or testing facility as the author.
When no author or laboratory could be identified, the Agency has shown the
first submitter as the author.
b. Document date. The date of the study is taken directly from the document.
When the date is followed by a question mark, the bibliographer has deduced
the date from the evidence contained in the document. When the date appears
61
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as (19??), the Agency was unable to determine or estimate the date of the
document.
c. Title. In some cases, it has been necessary for the Agency bibliographers to
create or enhance a document title. Any such editorial insertions are contained
between square brackets.
d. Trailing parentheses. For studies submitted to the Agency in the past, the
trailing parentheses include (in addition to any self-explanatory text) the
following elements describing the earliest known submission:
(1) Submission date. The date of the earliest known submission appears
immediately following the 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.
62
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BIBLIOGRAPHY
MRID
CITATION
00148521 Edwards, J.; Leeming, N.; Clark, R.; et al. (1983) Effect of Diphenylamine on
Pregnancy of the New Zealand White Rabbit: HRC Report No. PWT 1/2/83409.
Unpublished study prepared by Huntingdon Research Centre. 80 p.
00148523 Spanjers, M.; Til, H. (1982) Determination of the Acute Oral Toxicity of
Diphenylamine in Rats: Report No. V 82.263/220060. Unpublished study
prepared by Netherlands Organization for Applied Scientific Research. 14 p.
00148524 Van Beek, L.; Bruijntjes, J. (1982) Acute Dermal Toxicity Study with
Diphenylamine in Albino Rabbits: B82/993. Unpublished study prepared by
Institute CIVO-Toxicology and Nutrition TNO. 4 p.
00148525 Van Beek, L. (1982) Eye Irritation Test with Diphenylamine in Albino Rabbits:
B 82-61-23. Unpublished study prepared by CIVO-Toxicology and Nutrition
TNO. 7 p.
00148533 Decco Tiltbelt (1984) Current Practices and Residues: ?Diphenylamine in or on
Appleso. Unpublished compilation. 30 p.
41899401 Majnarich, J. (1991) Diphenylamine-Super Refined-Acute Oral to Toxicity, LD
50 (Rat): Lab Project Number: 022-91. Unpublished Study prepared by
Bioconsultants, Inc. 13 p.
41899402 Majnarich, J. (1991) Diphenylamine-Super Refined-Dermal LD 50. : Lab Project
Number: 024-91. Unpublished study prepared by Bioconsultants, Inc. 20 p.
41899403 Majnarich, J. (1991) Diphenylamine-Super Refined-Dermal Sensitization Study:
Lab Project Number: 023-91. Unpublished study prepared by Bioconsultants, Inc.
13 p.
41899404 Kreuzmann, J. (1991) Primary Eye Irritation Study in Rabbits Without Rinsing
With Diphenylamine Super-Refined: Lab Project Number 91-8052-21 (B).
Unpublished study prepared by Hill Top Biolabs, Inc. 32 p.
41899405 Kreuzmann, J. (1991) Primary Skin Irritation Study in Rabbits With
Diphenylamine Super-Refined: Lab Project Number: 91-8052-21 (A). Unpublished
study prepared by Hill Top Biolabs, Inc. 30 p.
42292001 Rodwell, D. (1992) Teratology Study in Rats with Diphenylamine (DPA): Final
Report: Lab Project Number: 3255.3. Unpublished study prepared by Springborn
Laboratories, Inc. 267 p.
63
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BIBLIOGRAPHY
MRID
CITATION
42304901 Siglin, J. (1992) 21-Day Dermal Toxicity Study in Rabbits with Diphenylamine
(DPA): Final Report: Lab Project Number: 3255. 1. Unpublished study prepared
by Springborn Labs, Inc. 257 p.
42312001 Murli, H. (1992) Mutagenicity Test on Diphenylamine in vivo Mammalian
Micronucleus Assay: Lab Project Number: 14902-0-455. Unpublished study
prepared by Hazleton Washington, Inc. 52 p.
42312101 Lawlor, T. (1992) Mutagenicity Test on Diphenylamine in the
Salmonella/Mammalian-Microsome Reverse Mutation Assay (Ames Test): Lab
Project Number: 14902-0-401. Unpublished study prepared by Hazleton
Washington, Inc. 67 p.
42332101 Cifone, M. (1992) Mutagenicity Test on Diphenylamine in the L5178Y
TK +/Mouse Lymphoma Forward Mutation Assay: Lab Project Number:
14902-0-431. Unpublished study prepared by Hazleton Washington, Inc. 74 p.
42339701 Krohmer, R. (1992) 90-Day Subchronic Toxicity Evaluation of Diphenylamine in
Rats: Lab Project Number: 426C-101-034-91. Unpublished study prepared by
T.P.S., Inc. 382 p.
42339801 Krohmer, R. (1992) 90 Day Evaluation of Diphenylamine in the Dog: Lab Project
Number: 426A-501-034-91. Unpublished study prepared by T.P.S., Inc. 308 p.
42542801 Botta, J. (1992) 90 Day Subchronic Toxicity Evaluation of Diphenylamine in the
Mouse: Lab Project Number: 426E-001-034-91. Unpublished study prepared by
TPS, Inc. 449 p.
42638101 Rodwell, D. (1993) Two Generation Reproduction Study in Rats with
Diphenylamine (DPA): Final Report: Lab Project Number: 3255.4. Unpublished
study prepared by Springborn Laboratories, Inc. 1185 p.
42660001 Baur, L. (1993) Hydrolysis of (carbon 14)-Ring-Diphenylamine in Water at pH 5,
7, and 9: Lab Project Number: XBL 92084: RPT00119. Unpublished study
prepared by XenoBiotic Labs, Inc. 82 p.
42897301 Kim-Kang, H. (1993) Metabolism of (carbon 14)-Diphenylamine in Stores
Apples-Nature of the Residue in Plants: Final Report: Lab No: XBL/91071:
RPT00124. Unpublished study prepared by XenoBiotic Laboratories, Inc. 300
P-
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BIBLIOGRAPHY
MRID
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42958201 Baur, L.; Robinson, R. (1993) Aqueous Photolysis of (carbon
14)-Ring-Diphenylamine: Lab Project Number: XBL 92087: RPT00123.
Unpublished study prepared by XenoBiotic Laboratories, Inc. 106 p.
42964201 Liu, D. (1993) Aerobic Soil Metabolism of (carbon 14)-Ring-Diphenylamine: Lab
Project Number: XBL 92082: RPT00139. Unpublished study prepared by
XenoBiotic Labs, Inc. 98 p.
42994801 Wu, D. (1993) Diphenylamine: Rat Metabolism Study: Final Report: Lab Project
Number: 92081: RPT00131. Unpublished study prepared by XenoBiotic
Laboratories, Inc. 342 p.
43000601 Botta, J. (1993) One Year Chronic Study of Diphenylamine in Dogs: Lab Project
Number: 426B-502-044-91. Unpublished study prepared by T.P.S., Inc. 624 p.
43080901 Liu, D. (1993) Anaerobic Aquatic Metabolism of (carbon
14)-Ring-Diphenylamine: Lab Project Number: 92083: RPT00140. Unpublished
study prepared by XenoBiotic Labs, Inc. 102 p.
43156201 Kim-Kang, H. (1994) Metabolism of (carbon 14)-Diphenylamine in Stored
Apples—Nature of the Residue in Plants: Addendum: Lab Project Number: XBL
91071: RPT00124. Unpublished study prepared by XenoBiotic Labs, Inc. 54 p.
43163501 Tshabalala, M. (1994) Determination of Diphenylamine Residues in Apples and
Processed Apple Fractions by Gas Chromatography (GC) with Mass-Selective
Detection (MSD): Final Report: Lab Project Number: HWI 6524-100:
MP-DPAP-MA. Unpublished study prepared by Hazleton Wisconsin, Inc. 37 p.
43187501 Kim-Kang, H. (1994) Metabolism of (carbon 14)Diphenylamine in the Laying
Hen: Lab Project Number: XBL 93041: RPT00161. Unpublished study prepared
by XenoBiotic Labs., Inc. 264 p.
43197101 Kim-Kang, H. (1994) Metabolism of (carbon 14)Diphenylamine in Lactating
Goats: Lab Project Number: XBL 92089: RPT00150: WIL-207001. Unpublished
study prepared by XenoBiotic Labs., Inc. and WIL Research Labs., Inc. 416 p.
43369501 Botta, J. (1994) 18 Month Oncogenicity Evaluation of Diphenylamine in the
Mouse: Lab Project Number: 426H/002/646/91. Unpublished study prepared by
T.P.S., Inc. 2348 p.
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43370101 Kim-Kang, H. (1994) Metabolism of (carbon 14)-Diphenylamine in Stored
Apples—Nature of the Residue in Plants: Addendum (to Original and Addendum
Reports): Lab Project Number: XBL 91071: RPT00124. Unpublished study
prepared by XenoBiotic Labs, Inc. 45 p.
43401401 Botta, J. (1994) 24 Month Combined Oncogenicity/Toxicity Evaluation of
Diphenylamine in Rats: Final Report: Lab Project Number: 426D-102-048-91.
Unpublished study prepared by T.P.S., Inc. 3421 p.
43412701 Reynolds, J. (1994) Adsorption and Desorption of (carbon
14)-Ring-Diphenylamine in Four Soils and One Sediment: Lab Project Number:
92086: RPT00163. Unpublished study prepared by XenoBiotic Lab., Inc. 123 p.
43413001 Kammerer, R. (1994) Aged Leaching of ((carbon 14)-Ring) Diphenylamine in
Four Soils: Lab Project Number: XBL94011: RPT00184. Unpublished study
prepared by XenoBiotic Lab., Inc. 139 p.
43428401 Tshabalala, M. (1994) Amendment No. 1 to the Report Determination of
Diphenylamine Residues in Apples and Processed Apple Fractions by Gas
Chromatography (GC) with Mass-Selective Detection (MSD): Lab Project
Number: HWI 6524-100. Unpublished study prepared by Hazleton Wisconsin,
Inc. 5 p.
43428402 Tshabalala, M. (1994) Amendment No. 2 to the Report Determination of
Diphenylamine Residues in Apples and Processed Apple Fractions by Gas
Chromatography (GC) with Mass-Selective Detection (MSD): Lab Project
Number: HWI 6524-100. Unpublished study prepared by Hazleton Wisconsin,
Inc. 5 p.
43428403 Clark, A. (1994) Validation of a Method for the Determination of Diphenylamine
Residues in Apples and Processed Apple Fractions by Gas Chromatography (GC)
with Mass-Selective Detection (MSD): Lab Project Number: 3716-F. Unpublished
study prepared by Midwest Research Institute. 67 p.
43540801 Kiplinger, G. (1995) Skin Sensitization Study of Diphenylamine Technical in
Albino Guinea Pigs: Final Report: Lab Project Number: WIL-256001.
Unpublished study prepared by WIL Research Labs, Inc. 49 p.
43620901 Johnson, G.; Strickland, M.(1995) Storage Stability of Residues of Diphenylamine
in/on Fresh Apples, Apple Juice, and Wet and Dried Pomace: Lab Project
Number: Final Report: 101/003: DPA/ 93/03. Unpublished study prepared by
Western EcoSystems Technology and Hazleton Wisconsin. 302 p.
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43625501 Johnson, G.; Strickland, M. (1995) Magnitude of Residues in/on Fresh and Stored
Apples After Post-harvest Treatment with Diphenylamine: Final Report: Lab
Project Number: DPA 93-01. Unpublished study prepared by Western Ecosystems
Technology (WEST, Inc.). 272 p.
43633601 Johnson, G.; Strickland, M. (1995) Magnitude of Residues in/on Apple Juice and
Wet and Dried Pomace Processed from Fruit Treated Post-Harvest with
Diphenylamine: Final Report: Lab Project Number: DPA 93-02: MP-DPAP-MA:
HWI 6524-103. Unpublished study prepared by Western Ecosystems Technology
(WEST, Inc.); Wm. J. Englar & Assoc.; and Hazleton Wisconsin. 406 p.
43878301 Drottar, K.; Swigert, J. (1995) Diphenylamine Technical: A 48-Hour
Flow-Through Acute Toxicity Test with the Cladoceran (Daphnia magna): Final
Report: Lab Project Number: SDR20: 436A-102: MP-DPAP-MA. Unpublished
study prepared by Wildlife International Ltd. 97 p.
43879001 Drottar, K.; Swigert, J. (1995) Diphenylamine Technical: A 96-Hour
Flow-Through Acute Toxicity Test with the Rainbow Trout (Oncorhynchus
mykiss): Final Report: Lab Project Number: SDR20: 436A-101:
436/100295/RBT-96H2/CHP105. Unpublished study prepared by Wildlife
International Ltd. 99 p.
43879101 Palmer, S.; Beavers, J. (1995) Diphenylamine: A Dietary LC50 Study with the
Mallard: Lab Project Number: DLR52: 436-101: 436/100295/MLCSDT.WC/
CHP105. Unpublished study prepared by Wildlife International Ltd. 74 p.
43972601 Keller, G.; Weber, K. (1996) Magnitude of the Residues of Diphenylamine in
Edible Tissues and Milk of Lactating Dairy Cows: Final Report: Lab Project
Number: CHW 6524-110. Unpublished study prepared by Corning Hazleton, Inc.
347 p.
43973201 Keller, G.; Weber, K. (1996) Validation of the Method for the Determination of
Diphenylamine Using Milk and Tissues From a Lactating Goat Metabolism Study:
Final Report: Lab Project Number: CHW 6524-112: CHW 6524-110.
Unpublished study prepared by Corning Hazleton Inc. 93 p.
44212501 Wise, J. (1997) Estimation of Dermal and Inhalation Exposure at Apple Drenching
Sites for Diphenylamine: Lab Project Number: S&A-970101: 97DPA0001:
970101. Unpublished study prepared by Seiler & Associates Inc. 46 p.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, B.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
GENERIC AND PRODUCT SPECIFIC
DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the
active ingredient identified in Attachment A of this Notice, the Data Call-In Chemical Status
Sheet, to submit certain data as noted herein to the U.S. Environmental Protection Agency
(EPA, the Agency). These data are necessary to maintain the continued registration of your
product(s) containing this active ingredient. Within 90 days after you receive this Notice you
must respond as set forth in Section III below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its
Attachments 1 through 7; or
2. Why you believe you are exempt from the requirements listed in this Notice and
in Attachment 3 (for both generic and product specific data), the Requirements
Status and Registrant's Response Form, (see section III-B); or
3. Why you believe EPA should not require your submission of data in the manner
specified by this Notice (see section III-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply
with its requirements or should be exempt or excused from doing so, then the registration of
your product(s) subject to this Notice will be subject to suspension. We have provided a list of
all of your products subject to this Notice in Attachment 2. All products are listed on both the
generic and product specific Data Call-in Response Forms. Also included is a list of all
registrants who were sent this Notice (Attachment 5).
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide, Fungicide
and Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
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information is authorized under the Paperwork Reduction Act by OMB Approval No.
2070-0107 and 2070-0057 (expiration date 3-31-99).
This Notice is divided into six sections and seven Attachments. The Notice itself
contains information and instructions applicable to all Data Call-In Notices. The Attachments
contain specific chemical information and instructions. The six sections of the Notice are:
Section I - Why You are Receiving this Notice
Section II - Data Required by this Notice
Section III - Compliance with Requirements of this Notice
Section IV - Consequences of Failure to Comply with this Notice
Section V - Registrants' Obligation to Report Possible Unreasonable Adverse Effects
Section VI - Inquiries and Responses to this Notice
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2 - Generic Data Call-In and Product Specific Data Call-In Response Forms with
Instructions (Form A)
3 - Generic Data Call-In and Product Specific Data Call-In Requirements Status
and Registrant's Response Forms with Instructions (Form B)
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - List of Registrants Receiving This Notice
6 - Cost Share and Data Compensation Forms
SECTION I. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient (s) and reevaluated the
data needed to support continued registration of the subject active ingredient(s). This
reevaluation identified additional data necessary to assess the health and safety of the continued
use of products containing this active ingredient(s). You have been sent this Notice because
you have product (s) containing the subject active ingredients.
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The data required by this Notice are specified in the Requirements Status and
Registrant's Response Forms: Attachment 3 (for both generic and product specific data
requirements). Depending on the results of the studies required in this Notice, additional
studies/testing may be required.
II-B. SCHEDULE FOR SUBMISSION OF DATA
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You are required to submit the data or otherwise satisfy the data requirements specified
in the Requirements Status and Registrant's Response Forms (Attachment 3) within the
timeframes provided.
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test
standards outlined in the Pesticide Assessment Guidelines for those studies for which
guidelines have been established.
These EPA Guidelines are available from the National Technical Information Service
(NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (Telephone number:
703-487-4650).
Protocols approved by the Organization for Economic Cooperation and Development
(OECD) are also acceptable if the OECD recommended test standards conform to those
specified in the Pesticide Data Requirements regulation (40 CFR § 158.70). When using the
OECD protocols, they should be modified as appropriate so that the data generated by the
study will satisfy the requirements of 40 CFR § 158. Normally, the Agency will not extend
deadlines for complying with data requirements when the studies were not conducted in
accordance with acceptable standards. The OECD protocols are available from OECD, 2001 L
Street, N.W., Washington, D.C. 20036 (Telephone number 202-785-6323; Fax telephone
number 202-785-0350).
All new studies and proposed protocols submitted in response to this Data Call-In
Notice must be in accordance with Good Laboratory Practices [40 CFR Part 160].
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(c)(2)(B) NOTICES ISSUED
BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede or
change the requirements of any previous Data Call-In(s), or any other agreements entered into
with the Agency pertaining to such prior Notice. Registrants must comply with the
requirements of all Notices to avoid issuance of a Notice of Intent to Suspend their affected
products.
SECTION III. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
You must use the correct forms and instructions when completing your response to this
Notice. The type of Data Call-In you must comply with (Generic or Product Specific) is
specified in item number 3 on the four Data Call-In forms (Attachments 2 and 3).
III-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice for generic and product
specific data must be submitted to the Agency within 90 days after your receipt of this Notice.
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Failure to adequately respond to this Notice within 90 days of your receipt will be a basis for
issuing a Notice of Intent to Suspend (NOIS) affecting your products. This and other bases for
issuance of NOIS due to failure to comply with this Notice are presented in Section IV-A and
IV-B.
III-B. OPTIONS FOR RESPONDING TO THE AGENCY
1. Generic Data Requirements
The options for responding to this Notice for generic data requirements are: (a)
voluntary cancellation, (b) delete use(s), (c) claim generic data exemption, (d) agree to satisfy
the generic data requirements imposed by this Notice or (e) request a data waiver (s).
A discussion of how to respond if you choose the Voluntary Cancellation option, the
Delete Use(s) option or the Generic Data Exemption option is presented below. A discussion
of the various options available for satisfying the generic data requirements of this Notice is
contained in Section III-C. A discussion of options relating to requests for data waivers is
contained in Section III-D.
Two forms apply to generic data requirements, one or both of which must be used in
responding to the Agency, depending upon your response. These two forms are the
Data-Call-in Response Form, and the Requirements Status and Registrant's Response Form,
(contained in Attachments 2 and 3, respectively).
The Data Call-In Response Forms must be submitted as part of every response to this
Notice. The Requirements Status and Registrant's Response Forms also must be submitted if
you do not qualify for a Generic Data Exemption or are not requesting voluntary cancellation
of your registration^). Please note that the company's authorized representative is required to
sign the first page of both Data Call-In Response Forms and the Requirements Status and
Registrant's Response Forms (if this form is required) and initial any subsequent pages. The
forms contain separate detailed instructions on the response options. Do not alter the printed
material. If you have questions or need assistance in preparing your response, call or write the
contact person (s) identified in Attachment 1.
a. Voluntary Cancellation -
You may avoid the requirements of this Notice by requesting voluntary cancellation of
your product (s) containing the active ingredient that is the subject of this Notice. If you wish
to voluntarily cancel your product, you must submit completed Generic and Product Specific
Data Call-In Response Forms (Attachment 2), indicating your election of this option.
Voluntary cancellation is item number 5 on both Data Call-In Response Form(s). If you
choose this option, these are the only forms that you are required to complete.
If you chose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice, which are contained in Section IV-C.
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b. Use Deletion -
You may avoid the requirements of this Notice by eliminating the uses of your product
to which the requirements apply. If you wish to amend your registration to delete uses, you
must submit the Requirements Status and Registrant's Response Form (Attachment 3), a
completed application for amendment, a copy of your proposed amended labeling, and all
other information required for processing the application. Use deletion is option number 7
under item 9 in the instructions for the Requirements Status and Registrant's Response Forms.
You must also complete a Data Call-in Response Form by signing the certification, item
number 8. Application forms for amending registrations may be obtained from the
Registration Support Branch, Registration Division, Office of Pesticide Programs, EPA, by
calling (703) 308-8358.
If you choose to delete the use(s) subject to this Notice or uses subject to specific data
requirements, further sale, distribution, or use of your product after one year from the due
date of your 90 day response, is allowed only if the product bears an amended label.
c. Generic Data Exemption -
Under section 3(c)(2)(D) of FIFRA, an applicant for registration of a product is
exempt from the requirement to submit or cite generic data concerning an active ingredient if
the active ingredient in the product is derived exclusively from purchased, registered pesticide
products containing the active ingredient. EPA has concluded, as an exercise of its discretion,
that it normally will not suspend the registration of a product which would qualify and
continue to qualify for the generic data exemption in section 3(c)(2)(D) of FIFRA. To qualify,
all of the following requirements must be met:
(i). The active ingredient in your registered product must be present solely because of
incorporation of another registered product which contains the subject active ingredient
and is purchased from a source not connected with you;
(ii). Every registrant who is the ultimate source of the active ingredient in your
product subject to this DCI must be in compliance with the requirements of this Notice
and must remain in compliance; and
(iii). You must have provided to EPA an accurate and current " Confidential Statement
of Formula" for each of your products to which this Notice applies.
To apply for the Generic Data Exemption you must submit a completed Data Call-in
Response Form, Attachment 2 and all supporting documentation. The Generic Data Exemption
is item number 6a on the Data Call-In Response Form. If you claim a generic data exemption
you are not required to complete the Requirements Status and Registrant's Response Form.
Generic Data Exemption cannot be selected as an option for responding to product specific
data requirements.
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If you are granted a Generic Data Exemption, you rely on the efforts of other persons
to provide the Agency with the required data. If the registrant^) who have committed to
generate and submit the required data fail to take appropriate steps to meet requirements or are
no longer in compliance with this Data Call-In Notice, the Agency will consider that both they
and you are not compliance and will normally initiate proceedings to suspend the registrations
of both your and their product(s), unless you commit to submit and do submit the required
data within the specified time. In such cases the Agency generally will not grant a time
extension for submitting the data.
d. Satisfying the Generic Data Requirements of this Notice
There are various options available to satisfy the generic data requirements of this
Notice. These options are discussed in Section III-C.l. of this Notice and comprise options 1
through 6 of item 9 in the instructions for the Requirements Status and Registrant's Response
Form and item 6b on the Data Call-in Response Form. If you choose item 6b (agree to satisfy
the generic data requirements), you must submit the Data Call-In Response Form and the
Requirements Status and Registrant's Response Form as well as any other information/data
pertaining to the option chosen to address the data requirement. Your response must be on the
forms marked "GENERIC" in item number 3.
e. Request for Generic Data Waivers.
Waivers for generic data are discussed in Section III-D.l. of this Notice and are
covered by options 8 and 9 of item 9 in the instructions for the Requirements Status and
Registrant's Response Form. If you choose one of these options, you must submit both forms
as well as any other information/data pertaining to the option chosen to address the data
requirement.
2. Product Specific Data Requirements
The options for responding to this Notice for product specific data are: (a) voluntary
cancellation, (b) agree to satisfy the product specific data requirements imposed by this Notice
or (c) request a data waiver (s).
A discussion of how to respond if you choose the Voluntary Cancellation option is
presented below. A discussion of the various options available for satisfying the product
specific data requirements of this Notice is contained in Section III-C.2. A discussion of
options relating to requests for data waivers is contained in Section III-D.2.
Two forms apply to the product specific data requirements one or both of which must
be used in responding to the Agency, depending upon your response. These forms are the
Data-Call-in Response Form, and the Requirements Status and Registrant's Response Form,
for product specific data (contained in Attachments 2 and 3, respectively). The Data Call-In
Response Form must be submitted as part of every response to this Notice. In addition, one
copy of the Requirements Status and Registrant's Response Form also must be submitted for
each product listed on the Data Call-In Response Form unless the voluntary cancellation option
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is selected. Please note that the company's authorized representative is required to sign the
first page of the Data Call-in Response Form and Requirements Status and Registrant's
Response Form (if this form is required) and initial any subsequent pages. The forms contain
separate detailed instructions on the response options. Do not alter the printed material. If you
have questions or need assistance in preparing your response, call or write the contact
person(s) identified in Attachment 1.
a. Voluntary Cancellation
You may avoid the requirements of this Notice by requesting voluntary cancellation of
your product(s) containing the active ingredient that is the subject of this Notice. If you wish
to voluntarily cancel your product, you must submit a completed Data Call-in Response Form,
indicating your election of this option. Voluntary cancellation is item number 5 on both the
Generic and Product Specific Data Call-in Response Forms. If you choose this
option, you must complete both Data Call-In response forms. These are the only forms that
you are required to complete.
If you choose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
b. Satisfying the Product Specific Data Requirements of this Notice.
There are various options available to satisfy the product specific data requirements of
this Notice. These options are discussed in Section III-C.2. of this Notice and comprise
options 1 through 6 of item 9 in the instructions for the product specific Requirements Status
and Registrant's Response Form and item numbers 7a and 7b (agree to satisfy the product
specific data requirements for an MUP or EUP as applicable) on the product specific Data
Call-In Response Form. Note that the options available for addressing product specific data
requirements differ slightly from those options for fulfilling generic data requirements.
Deletion of a use(s) and the low volume/minor use option are not valid options for fulfilling
product specific data requirements. It is important to ensure that you are using the correct
forms and instructions when completing your response to the Reregistration Eligibility
Decision document.
c. Request for Product Specific Data Waivers.
Waivers for product specific data are discussed in Section III-D.2. of this Notice and
are covered by option 7 of item 9 in the instructions for the Requirements Status and
Registrant's Response Form. If you choose this option, you must submit the Data Call-In
Response Form and the Requirements Status and Registrant's Response Form as well as any
other information/data pertaining to the option chosen to address the data requirement. Your
response must be on the forms marked "PRODUCT SPECIFIC" in item number 3.
III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
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1. Generic Data
If you acknowledge on the Generic Data Call-In Response Form that you agree to
satisfy the generic data requirements (i.e. you select item number 6b), then you must select
one of the six options on the Generic Requirements Status and Registrant's Response Form
related to data production for each data requirement. Your option selection should be entered
under item number 9, "Registrant Response." The six options related to data production are
the first six options discussed under item 9 in the instructions for completing the Requirements
Status and Registrant's Response Form. These six options are listed
immediately below with information in parentheses to guide you to additional instructions
provided in this Section. The options are:
(1) I will generate and submit data within the specified timeframe (Developing
Data)
(2) I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing
study that has been submitted but not reviewed by the Agency (Citing an
Existing Study)
Option 1. Developing Data
If you choose to develop the required data it must be in conformance with Agency
deadlines and with other Agency requirements as referenced herein and in the attachments. All
data generated and submitted must comply with the Good Laboratory Practice (GLP) rule (40
CFR Part 160), be conducted according to the Pesticide Assessment Guidelines (PAG) and be
in conformance with the requirements of PR Notice 86-5. In addition, certain studies require
Agency approval of test protocols in advance of study initiation. Those studies for which a
protocol must be submitted have been identified in the Requirements Status and Registrant's
Response Form and/or footnotes to the form. If you wish to use a protocol which differs from
the options discussed in Section II-C of this Notice, you must submit a detailed description of
the proposed protocol and your reason for wishing to use it. The Agency may choose to reject
a protocol not specified in Section II-C. If the Agency rejects your protocol you will be
notified in writing, however, you should be aware that rejection of a proposed protocol will
not be a basis for extending the deadline for submission of data.
A progress report must be submitted for each study within 90 days from the date you
are required to commit to generate or undertake some other means to address that study
requirement, such as making an offer to cost share or agreeing to share in the cost of
developing that study. This 90-day progress report must include the date the study was or will
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be initiated and, for studies to be started within 12 months of commitment, the name and
address of the laboratory(ies) or individuals who are or will be conducting the study.
In addition, if the time frame for submission of a final report is more than 1 year,
interim reports must be submitted at 12 month intervals from the date you are required to
commit to generate or otherwise address the requirement for the study. In addition to the other
information specified in the preceding paragraph, at a minimum, a brief description of current
activity on and the status of the study must be included as well as a full
description of any problems encountered since the last progress report.
The time frames in the Requirements Status and Registrant's Response Form are the
time frames that the Agency is allowing for the submission of completed study reports or
protocols. The noted deadlines run from the date of the receipt of this Notice by the registrant.
If the data are not submitted by the deadline, each registrant is subject to receipt of a Notice of
Intent to Suspend the affected registration(s).
If you cannot submit the data/reports to the Agency in the time required by this Notice
and intend to seek additional time to meet the requirements(s), you must submit a request to
the Agency which includes: (1) a detailed description of the expected difficulty and (2) a
proposed schedule including alternative dates for meeting such requirements on a step-by-step
basis. You must explain any technical or laboratory difficulties and provide documentation
from the laboratory performing the testing. While EPA is considering your request, the
original deadline remains. The Agency will respond to your request in writing. If EPA does
not grant your request, the original deadline remains. Normally, extensions can be requested
only in cases of extraordinary testing problems beyond the expectation or control of the
registrant. Extensions will not be given in submitting the 90-day responses. Extensions will
not be considered if the request for extension is not made in a timely fashion; in no event shall
an extension request be considered if it is submitted at or after the lapse of the subject
deadline.
Option 2. Agreement to Share in Cost to Develop Data
If you choose to enter into an agreement to share in the cost of producing the required
data but will not be submitting the data yourself, you must provide the name of the registrant
who will be submitting the data. You must also provide EPA with documentary evidence that
an agreement has been formed. Such evidence may be your letter offering to join in an
agreement and the other registrant's acceptance of your offer, or a written statement by the
parties that an agreement exists. The agreement to produce the data need not specify all of the
terms of the final arrangement between the parties or the mechanism to resolve the terms.
Section 3(c)(2)(B) provides that if the parties cannot resolve the terms of the agreement they
may resolve their differences through binding arbitration.
Option 3. Offer to Share in the Cost of Data Development
If you have made an offer to pay in an attempt to enter into an agreement or amend an
existing agreement to meet the requirements of this Notice and have been unsuccessful, you
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may request EPA (by selecting this option) to exercise its discretion not to suspend your
registration(s), although you do not comply with the data submission requirements of this
Notice. EPA has determined that as a general policy, absent other relevant considerations, it
will not suspend the registration of a product of a registrant who has in good faith sought and
continues to seek to enter into a joint data development/cost sharing program, but the other
registrant^) developing the data has refused to accept the offer. To qualify for this option, you
must submit documentation to the Agency proving that you have made an offer to another
registrant (who has an obligation to submit data) to share in the burden of developing that
data. You must also submit to the Agency a completed EPA Form 8570-32, Certification of
Offer to Cost Share in the Development of Data, Attachment 7. In addition, you must
demonstrate that the other registrant to whom the offer was made has not accepted your offer
to enter into a cost-sharing agreement by including a copy of your offer and proof of the other
registrant's receipt of that offer (such as a certified mail receipt). Your offer must, in addition
to anything else, offer to share in the burden of producing the data upon terms to be agreed to
or, failing agreement, to be bound by binding arbitration as provided by FIFRA section
3(c)(2)(B)(iii) and must not qualify this offer. The other registrant must also inform EPA of its
election of an option to develop and submit the data required by this Notice by submitting a
Data Call-in Response Form and a Requirements Status and Registrant's Response Form
committing to develop and submit the data required by this Notice.
In order for you to avoid suspension under this option, you may not withdraw your
offer to share in the burden of developing the data. In addition, the other registrant must fulfill
its commitment to develop and submit the data as required by this Notice. If the other
registrant fails to develop the data or for some other reason is subject to suspension, your
registration as well as that of the other registrant normally will be subject to initiation of
suspension proceedings, unless you commit to submit, and do submit, the required data in the
specified time frame. In such cases, the Agency generally will not grant a time extension for
submitting the data.
Option 4. Submitting an Existing Study
If you choose to submit an existing study in response to this Notice, you must
determine that the study satisfies the requirements imposed by this Notice. You may only
submit a study that has not been previously submitted to the Agency or previously cited by
anyone. Existing studies are studies which predate issuance of this Notice. Do not use this
option if you are submitting data to upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not acceptable, the
Agency will require you to comply with this Notice, normally without an extension of the
required date of submission. The Agency may determine at any time that a study is not valid
and needs to be repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of the
following three criteria must be clearly Met:
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a. You must certify at the time that the existing study is submitted that the raw
data and specimens from the study are available for audit and review and you
must identify where they are available. This must be done in accordance with
the requirements of the Good Laboratory Practice (GLP) regulation, 40 CFR
Part 160. As stated in 40 CFR 160.3 'Raw data' means any laboratory
worksheets, records, memoranda, notes, or exact copies thereof, that are the
result of original observations and activities of a study and are necessary for the
reconstruction and evaluation of the report of that study. In the event that exact
transcripts of raw data have been prepared (e.g., tapes which have been
transcribed verbatim, dated, and verified accurate by signature), the exact copy
or exact transcript may be substituted for the original source as raw data. 'Raw
data' may include photographs, microfilm or microfiche copies, computer
printouts, magnetic media, including dictated observations, and recorded data
from automated instruments." The term "specimens", according to 40 CFR
160.3, means "any material derived from a test system for examination or
analysis."
b. Health and safety studies completed after May 1984 also must also contain all
GLP-required quality assurance and quality control information, pursuant to the
requirements of 40 CFR Part 160. Registrants also must certify at the time of
submitting the existing study that such GLP information is available for post
May 1984 studies by including an appropriate statement on or attached to the
study signed by an authorized official or representative of the registrant.
c. You must certify that each study fulfills the acceptance criteria for the Guideline
relevant to the study provided in the FIFRA Accelerated Reregistration Phase 3
Technical Guidance and that the study has been conducted according to the
Pesticide Assessment Guidelines (PAG) or meets the purpose of the PAG (both
available from NTIS). A study not conducted according to the PAG may be
submitted to the Agency for consideration if the registrant believes that the
study clearly meets the purpose of the PAG. The registrant is referred to 40
CFR 158.70 which states the Agency's policy regarding acceptable protocols. If
you wish to submit the study, you must, in addition to certifying that the
purposes of the PAG are met by the study, clearly articulate the rationale why
you believe the study meets the purpose of the PAG, including copies of any
supporting information or data. It has been the Agency's experience that studies
completed prior to January 1970 rarely satisfied the purpose of the PAG and
that necessary raw data usually are not available for such studies.
If you submit an existing study, you must certify that the study meets all requirements
of the criteria outlined above.
If EPA has previously reviewed a protocol for a study you are submitting, you must
identify any action taken by the Agency on the protocol and must indicate, as part of your
certification, the manner in which all Agency comments, concerns, or issues were addressed
in the final protocol and study.
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If you know of a study pertaining to any requirement in this Notice which does not
meet the criteria outlined above but does contain factual information regarding unreasonable
adverse effects, you must notify the Agency of such a study. If such study is in the Agency's
files, you need only cite it along with the notification. If not in the Agency's files, you must
submit a summary and copies as required by PR Notice 86-5.
Option 5. Upgrading a Study
If a study has been classified as partially acceptable and upgradeable, you may submit
data to upgrade that study. The Agency will review the data submitted and determine if the
requirement is satisfied. If the Agency decides the requirement is not satisfied, you may still
be required to submit new data normally without any time extension. Deficient, but
upgradeable studies will normally be classified as supplemental. However, it is important to
note that not all studies classified as supplemental are upgradeable. If you have questions
regarding the classification of a study or whether a study may be upgraded, call or write the
contact person listed in Attachment 1. If you submit data to upgrade an existing study you
must satisfy or supply information to correct all deficiencies in the study identified by EPA.
You must provide a clearly articulated rationale of how the deficiencies have been remedied or
corrected and why the study should be rated as acceptable to EPA. Your submission must also
specify the MRID number (s) of the study which you are attempting to upgrade and must be in
conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified as
unacceptable and determined by the Agency as not capable of being upgraded.
This option also should be used to cite data that has been previously submitted to
upgrade a study, but has not yet been reviewed by the Agency. You must provide the MRID
number of the data submission as well as the MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above, apply to
all data submissions intended to upgrade studies. Additionally, your submission of data
intended to upgrade studies must be accompanied by a certification that you comply with each
of those criteria, as well as a certification regarding protocol compliance with Agency
requirements.
Option 6. Citing Existing Studies
If you choose to cite a study that has been previously submitted to EPA, that study
must have been previously classified by EPA as acceptable, or it must be a study which has
not yet been reviewed by the Agency. Acceptable toxicology studies generally will have been
classified as "core-guideline" or "core-minimum." For ecological effects studies, the
classification generally would be a rating of "core." For all other disciplines the classification
would be "acceptable." With respect to any studies for which you wish to select this option,
you must provide the MRID number of the study you are citing and, if the study has been
reviewed by the Agency, you must provide the Agency's classification of the study.
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If you are citing a study of which you are not the original data submitter, you must
submit a completed copy of EPA Form 8570-31, Certification with Respect to Data
Compensation Requirements.
2. Product Specific Data
If you acknowledge on the product specific Data Call-in Response Form that you agree
to satisfy the product specific data requirements (i.e. you select option 7a or 7b), then you
must select one of the six options on the Requirements Status and Registrant's Response Form
related to data production for each data requirement. Your option selection should be entered
under item number 9, "Registrant Response." The six options related to data production are
the first six options discussed under item 9 in the instructions for completing the Requirements
Status and Registrant's Response Form. These six options are listed immediately below with
information in parentheses to guide registrants to additional instructions provided in this
Section. The options are:
(1) I will generate and submit data within the specified time-frame (Developing
Data)
(2) I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing
study that has been
submitted but not reviewed by the Agency (Citing an Existing Study)
Option 1. Developing Data — The requirements for developing product specific data are the
same as those described for generic data (see Section III.C.I, Option 1) except that normally
no protocols or progress reports are required.
Option 2. Agree to Share in Cost to Develop Data — If you enter into an agreement to cost
share, the same requirements apply to product specific data as to generic data (see Section
III.C.I, Option 2). However, registrants may only choose this option for acute toxicity data
and certain efficacy data and only if EPA has indicated in the attached data tables that your
product and at least one other product are similar for purposes of depending on
the same data. If this is the case, data may be generated for just one of the products in the
group. The registration number of the product for which data will be submitted must be noted
in the agreement to cost share by the registrant selecting this option.
Option 3. Offer to Share in the Cost of Data Development —The same requirements for
generic data (Section III.C.L, Option 3) apply to this option. This option only applies to acute
toxicity and certain efficacy data as described in option 2 above.
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Option 4. Submitting an Existing Study — The same requirements described for generic data
(see Section III.C.l., Option 4) apply to this option for product specific data.
Option 5. Upgrading a Study — The same requirements described for generic data (see Section
III.C.l., Option 5) apply to this option for product specific data.
Option 6. Citing Existing Studies — The same requirements described for generic data (see
Section III.C.l., Option 6) apply to this option for product specific data.
Registrants who select one of the above 6 options must meet all of the requirements
described in the instructions for completing the Data Call-In Response Form and the
Requirements Status and Registrant's Response Form, and in the generic data requirements
section (III.C.l.), as appropriate.
III-D REQUESTS FOR DATA WAIVERS
1. Generic Data
There are two types of data waiver responses to this Notice. The first is a request for a
low volume/minor use waiver and the second is a waiver request based on your belief that the
data requirement(s) are not appropriate for your product.
a. Low Volume/Minor Use Waiver
Option 8 under item 9 on the Requirements Status and Registrant's Response
Form. Section 3(c)(2)(A) of FIFRA requires EPA to consider the appropriateness of
requiring data for low volume, minor use pesticides. In implementing this provision,
EPA considers low volume pesticides to be only those active ingredients whose total
production volume for all pesticide registrants is small. In determining whether to grant a low
volume, minor use waiver, the Agency will consider the extent, pattern and volume of use, the
economic incentive to conduct the testing, the importance of the pesticide, and the exposure
and risk from use of the pesticide. If an active ingredient is used for both high volume and low
volume uses, a low volume exemption will not be approved. If all uses of an active ingredient
are low volume and the combined volumes for all uses are also low, then an exemption may be
granted, depending on review of other information outlined below. An exemption will not be
granted if any registrant of the active ingredient elects to conduct the testing. Any registrant
receiving a low volume minor use waiver must remain within the sales figures in their forecast
supporting the waiver request in order to remain qualified for such waiver. If granted a
waiver, a registrant will be required, as a condition of the waiver, to submit annual sales
reports. The Agency will respond to requests for waivers in writing.
To apply for a low volume, minor use waiver, you must submit the following
information, as applicable to your product(s), as part of your 90-day response to this
Notice:
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(i). Total company sales (pounds and dollars) of all registered product(s)
containing the active ingredient. If applicable to the active ingredient, include foreign
sales for those products that are not registered in this country but are applied to sugar
(cane or beet), coffee, bananas, cocoa, and other such crops. Present the above
information by year for each of the past five years.
(ii) Provide an estimate of the sales (pounds and dollars) of the active
ingredient for each major use site. Present the above information by year for each of
the past five years.
(iii) Total direct production cost of product (s) containing the active ingredient
by year for the past five years. Include information on raw material cost, direct labor
cost, advertising, sales and marketing, and any other significant costs listed separately.
(iv) Total indirect production cost (e.g. plant overhead, amortized plant and
equipment) charged to product (s) containing the active ingredient by year for the past
five years. Exclude all non-recurring costs that were directly related to the active
ingredient, such as costs of initial registration and any data development.
(v) A list of each data requirement for which you seek a waiver. Indicate the
type of waiver sought and the estimated cost to you (listed separately for each data
requirement and associated test) of conducting the testing needed to fulfill each of these
data requirements.
(vi) A list of each data requirement for which you are not seeking any waiver
and the estimated cost to you (listed separately for each data requirement and associated
test) of conducting the testing needed to fulfill each of these data requirements.
(vii) For each of the next ten years, a year-by-year forecast of company sales
(pounds and dollars) of the active ingredient, direct production costs of product (s)
containing the active ingredient (following the parameters in item 2 above), indirect
production costs of product(s) containing the active ingredient (following the
parameters in item 3 above), and costs of data development pertaining to the active
ingredient.
(viii) A description of the importance and unique benefits of the active
ingredient to users. Discuss the use patterns and the effectiveness of the active
ingredient relative to registered alternative chemicals and non-chemical control
strategies. Focus on benefits unique to the active ingredient, providing information that
is as quantitative as possible. If you do not have quantitative data upon which to base
your estimates, then present the reasoning used to derive your estimates. To assist the
Agency in determining the degree of importance of the active ingredient in terms of its
benefits, you should provide information on any of the following factors, as applicable
to your product(s): (a) documentation of the usefulness of the active ingredient in
Integrated Pest Management, (b) description of the beneficial impacts on the
environment of use of the active ingredient, as opposed to its registered alternatives,
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(c) information on the breakdown of the active ingredient after use and on its
persistence in the environment, and (d) description of its usefulness against a pest(s) of
public health significance.
Failure to submit sufficient information for the Agency to make a determination
regarding a request for a low volume/minor use waiver will result in denial of the
request for a waiver.
b. Request for Waiver of Data
Option 9, under Item 9, on the Requirements Status and Registrant's Response
Form. This option may be used if you believe that a particular data requirement should
not apply because the requirement is inappropriate. You must submit a rationale
explaining why you believe the data requirements should not apply. You also must
submit the current label(s) of your product(s) and, if a current copy of your
Confidential Statement of Formula is not already on file you must submit a current
copy.
You will be informed of the Agency's decision in writing. If the Agency
determines that the data requirements of this Notice are not appropriate to your
product(s), you will not be required to supply the data pursuant to section 3(c)(2)(B). If
EPA determines that the data are required for your product(s), you must choose a
method of meeting the requirements of this Notice within the time frame provided by
this Notice. Within 30 days of your receipt of the Agency's written decision, you must
submit a revised Requirements Status and Registrant's Response Form indicating the
option chosen.
2. Product Specific Data
If you request a waiver for product specific data because you believe it is
inappropriate, you must attach a complete justification for the request including
technical reasons, data and references to relevant EPA regulations, guidelines or
policies. (Note: any supplemental data must be submitted in the format required by PR
Notice 86-5). This will be the only opportunity to state the reasons or provide
information in support of your request. If the Agency approves your waiver request,
you will not be required to supply the data pursuant to section 3(c)(2)(B) of FIFRA. If
the Agency denies your waiver request, you must choose an option for meeting the data
requirements of this Notice within 30 days of the receipt of the Agency's decision.
You must indicate and submit the option chosen on the product specific Requirements
Status and Registrant's Response Form. Product specific data requirements for product
chemistry, acute toxicity and efficacy (where appropriate) are required for all products
and the Agency would grant a waiver only under extraordinary circumstances. You
should also be aware that submitting a waiver request will not automatically extend the
due date for the study in question. Waiver requests submitted without adequate
supporting rationale will be denied and the original due date will remain in force.
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SECTION IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS
NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice due
to failure by a registrant to comply with the requirements of this Data Call-in Notice, pursuant
to FIFRA section 3 (c) (2) (B). Events which may be the basis for issuance of a Notice of Intent
to Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of
this Notice.
2. Failure to submit on the required schedule an acceptable proposed or final
protocol when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a
study as required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this
Notice.
5. Failure to take a required action or submit adequate information pertaining to
any option chosen to address the data requirements (e.g., any required action or
information pertaining to submission or citation of existing studies or offers,
arrangements, or arbitration on the sharing of costs or the formation of Task
Forces, failure to comply with the terms of an agreement or arbitration
concerning joint data development or failure to comply with any terms of a data
waiver).
6. Failure to submit supportable certifications as to the conditions of submitted
studies, as required by Section III-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in the cost
of developing data and provided proof of the registrant's receipt of such offer
or failure of a registrant on whom you rely for a generic data exemption either
to:
i. Inform EPA of intent to develop and submit the data required by this Notice
on a Data Call-In Response Form and a Requirements Status and Registrant's
Response Form.
ii. Fulfill the commitment to develop and submit the data as required by this
Notice; or
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iii. 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 following the issuance of this Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS
UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The grounds
for suspension include, but are not limited to, failure to meet any of the following:
1) EPA requirements specified in the Data Call-In Notice or other documents
incorporated by reference (including, as applicable, EPA Pesticide Assessment
Guidelines, Data Reporting Guidelines, and GeneTox Health Effects Test Guidelines)
regarding the design, conduct, and reporting of required studies. Such requirements
include, but are not limited to, those relating to test material, test procedures, selection
of species, number of animals, sex and distribution of animals, dose and effect levels to
be tested or attained, duration of test, and, as applicable, Good Laboratory Practices.
2) EPA requirements regarding the submission of protocols, including the
incorporation of any changes required by the Agency following review.
3) EPA requirements regarding the reporting of data, including the manner of
reporting, the completeness of results, and the adequacy of any required supporting (or
raw) data, including, but not limited to, requirements referenced or included in this
Notice or contained in PR 86-5. All studies must be submitted in the form of a final
report; a preliminary report will not be considered to fulfill the submission
requirement.
IV-C EXISTING STOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing
stocks of a pesticide product which has been suspended or cancelled if doing so would be
consistent with the purposes of the Act.
The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3 (c) (2) (B) data request is outstanding generally would
not be consistent with the Act's purposes. Accordingly, the Agency anticipates granting
registrants permission to sell, distribute, or use existing stocks of suspended product(s) only in
exceptional circumstances. If you believe such disposition of existing stocks of your product (s)
which may be suspended for failure to comply with this Notice should be permitted, you have
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the burden of clearly demonstrating to EPA that granting such permission would be consistent
with the Act. You also must explain why an "existing stocks" provision is necessary, including
a statement of the quantity of existing stocks and your estimate of the time required for their
sale, distribution, and use. Unless you meet this burden, the Agency will not consider any
request pertaining to the continued sale, distribution, or use of your existing stocks after
suspension.
If you request a voluntary cancellation of your product(s) as a response to this Notice
and your product is in full compliance with all Agency requirements, you will have, under
most circumstances, one year from the date your 90 day response to this Notice is due, to sell,
distribute, or use existing stocks. Normally, the Agency will allow persons other than the
registrant such as independent distributors, retailers and end users to sell, distribute or use
such existing stocks until the stocks are exhausted. Any sale, distribution or use of stocks of
voluntarily cancelled products containing an active ingredient for which the Agency has
particular risk concerns will be determined on a case-by-case basis.
Requests for voluntary cancellation received after the 90 day response period required
by this Notice will not result in the agency granting any additional time to sell, distribute, or
use existing stocks beyond a year from the date the 90 day response was due, unless you
demonstrate to the Agency that you are in full compliance with all Agency requirements,
including the requirements of this Notice. For example, if you decide to voluntarily cancel
your registration six months before a 3-year study is scheduled to be submitted, all progress
reports and other information necessary to establish that you have been conducting the study in
an acceptable and good faith manner must have been submitted to the Agency, before EPA
will consider granting an existing stocks provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE
UNREASONABLE ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6 (a) (2) states that if at any time after a
pesticide is registered a registrant has additional factual information regarding unreasonable
adverse effects on the environment by the pesticide, the registrant shall submit the information
to the Agency. Registrants must notify the Agency of any factual information they have, from
whatever source, including but not limited to interim or preliminary results of studies,
regarding unreasonable adverse effects on man or the environment. This requirement
continues as long as the products are registered by the Agency.
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by
this Notice, call the contact person(s) listed in Attachment 1, the Data Call-in Chemical Status
Sheet.
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All responses to this Notice must include completed Data Call-In Response Forms
(Attachment 2)and completed Requirements Status and Registrant's Response Forms
(Attachment 3), for both (generic and product specific data) and any other documents required
by this Notice, and should be submitted to the contact person(s) identified in Attachment 1. If
the voluntary cancellation or generic data exemption option is chosen, only the Generic and
Product Specific Data Call-in Response Forms need be submitted.
The Office of Compliance (OC) of the Office of Enforcement and Compliance
Assurance (OECA), EPA, will be monitoring the data being generated in response to this
Notice.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregistration Division
Attachments
The Attachments to this Notice are:
1 - Data Call-in Chemical Status Sheet
2 - Generic Data Call-in and Product Specific Data Call-in Response Forms with
Instructions
3 - Generic Data Call-In and Product Specific Data Call-In Requirements Status
and Registrant's Response Forms with Instructions
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - List of Registrants Receiving This Notice
6 - Confidential Statement of Formula, Cost Share and Data Compensation Forms
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DIPHENYLAMINE DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have product(s)
containing diphenylamine.
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
diphenylamine. This attachment is to be used in conjunction with (1) the Product Specific Data
Call-In Notice, (2) the Product Specific Data Call-In Response Form (Attachment 2), (3) the
Requirements Status and Registrant's Form (Attachment 3), (4) EPA's Grouping of End-Use
Products for Meeting Acute Toxicology Data Requirement (Attachment 4), (5) the EPA
Acceptance Criteria (Attachment 5), (6) a list of registrants receiving this DCI (Attachment 6) and
(7) the Cost Share and Data Compensation Forms in replying to this diphenylamine 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 diphenylamine are
contained in the Requirements Status and Registrant's Response, Attachment 3. The Agency has
concluded that additional data on diphenylamine are needed for specific products. These data are
required to be submitted to the Agency within the time frame listed. These data are needed to
fully complete the reregistration of all eligible diphenylamine products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding this product specific data requirements and procedures
established by this Notice, please contact CP Moran at (703) 308-8590.
All responses to this Notice for the Product Specific data requirements should be submitted
to:
CP Moran
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: 2665
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2665 DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Generic Data Call-In Notice because you have product(s)
containing diphenylamine.
This Generic Data Call-In Chemical Status Sheet, contains an overview of data required
by this notice, and point of contact for inquiries pertaining to the reregistration of diphenylamine.
This attachment is to be used in conjunction with (1) the Generic Data Call-In Notice, (2) the
Generic Data Call-In Response Form (Attachment 2), (3) the Requirements Status and Registrant's
Form (Attachment 2), (4) a list of registrants receiving this DCI (Attachment 4), (5) the EPA
Acceptance Criteria (Attachment 5), and (6) the Cost Share and Data Compensation Forms in
replying to this diphenylamine Generic Data Call In (Attachment F). Instructions and guidance
accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the generic database for
diphenylamine are contained in the Requirements Status and Registrant's Response, Attachment
C. The Agency has concluded that additional product chemistry data on diphenylamine are
needed. These data are needed to fully complete the reregistration of all eligible diphenylamine
products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic data requirements and procedures
established by this Notice, please contact Dennis Deziel at (703) 308-8180.
All responsades to this Notice for the generic data requirements should be submitted to:
Dennis Deziel, Chemical Review Manager
Reregistration Branch I
Special Review and Registration Division (H7508W)
Office of Pesticiafde Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: 2665
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Instructions For Completing The "Data Call-In Response Forms" For The Generic And
Product Specific Data Call-In
INTRODUCTION
These instructions apply to the Generic and Product Specific "Data Call-in Response Forms"
and are to be used by registrants to respond to generic and product specific Data Call-ins as
part of EPA's Reregistration Program under the Federal Insecticide, Fungicide, and
Rodenticide Act. If you are an end-use product registrant only and have been sent this DCI
letter as part of a RED document you have been sent just the product specific "Data Call-In
Response Forms." Only registrants responsible for generic data have been sent the generic
data response form. The type of Data Call-in (generic or product specific) is indicated in
item number 3 ("Date and Type of DCI") on each form.
Although the form is the same for both generic and product specific data, instructions for
completing these forms are different. Please read these instructions carefully before filling out
the forms.
EPA has developed these forms individually for each registrant, and has preprinted these
forms with a number of items. DO NOT use these forms for any other active ingredient.
Items 1 through 4 have been preprinted on the form. Items 5 through 7 must be completed by
the registrant as appropriate. Items 8 through 11 must be completed by the registrant before
submitting a response to the Agency.
The public reporting burden for this collection of information is estimated to average 15
minutes per response, including time for reviewing instructions, searching existing data
sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect of
this collection of information, including suggestions for reducing this burden, to Chief,
Information Policy Branch, Mail Code 2136, U.S. Environmental Protection Agency, 401 M
St., S.W., Washington, D.C. 20460; and to the Office of Management and Budget,
Paperwork Reduction Project 2070-0107, Washington, D.C. 20503.
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
Generic and Product Specific Data Call-in
Item 1. ON BOTH FORMS: This item identifies your company name, number and
address.
Item 2. ON BOTH FORMS: This item identifies the case number, case name, EPA
chemical number and chemical name.
Item 3. ON BOTH FORMS: This item identifies the type of Data Call-in. The date
of issuance is date stamped.
Item 4. ON BOTH FORMS: This item identifies the EPA product registrations
relevant to the data call-in. Please note that you are also responsible for
informing the Agency of your response regarding any product that you believe
may be covered by this Data Call-In but that is not listed by the Agency in Item
4. You must bring any such apparent omission to the Agency's attention within
the period required for submission of this response form.
Item 5. ON BOTH FORMS: Check this item for each product registration you wish to
cancel voluntarily. If a registration number is listed for a product for which you
previously requested voluntary cancellation, indicate in Item 5 the date of that
request. Since this Data Call-In requires both generic and product specific data,
you must complete item 5 on both Data Call-In response forms. You do not
need to complete any item on the Requirements Status and Registrant's
Response Forms.
Item 6a. ON THE GENERIC DATA FORM: Check this Item if the Data Call-in is for
generic data as indicated in Item 3 and you are eligible for a Generic Data
Exemption for the chemical listed in Item 2 and used in the subject product. By
electing this exemption, you agree to the terms and conditions of a Generic Data
Exemption as explained in the Data Call-In Notice.
If you are eligible for or claim a Generic Data Exemption, enter the EPA
registration Number of each registered source of that active ingredient that you
use in your product.
Typically, if you purchase an EPA-registered product from one or more other
producers (who, with respect to the incorporated product, are in compliance
with this and any other outstanding Data Call-In Notice), and incorporate that
product into all your products, you may complete this item for all products
listed on this form. If, however, you produce the active ingredient yourself, or
use any unregistered product (regardless of the fact that some of your sources
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are registered), you may not claim a Generic Data Exemption and you may not
select this item.
INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
Generic and Product Specific Data Call-in
Item 6b. ON THE GENERIC DATA FORM: Check this Item if the Data Call-in is for
generic data as indicated in Item 3 and if you are agreeing to satisfy the generic
data requirements of this Data Call-In. Attach the Requirements Status and
Registrant's Response Form that indicates how you will satisfy those
requirements.
NOTE: Item 6a and 6b are not applicable for Product Specific Data.
Item 7a. ON THE PRODUCT SPECIFIC DATA FORM: For each manufacturing use
product (MUP) for which you wish to maintain registration, you must agree to
satisfy the data requirements by responding "yes."
Item 7b. For each end use product (EUP) for which you wish to maintain registration,
you must agree to satisfy the data requirements by responding "yes."
FOR BOTH MUP and EUP products
You should also respond "yes" to this item (7a for MUP's and 7b for EUP's) if
your product is identical to another product and you qualify for a data
exemption. You must provide the EPA registration numbers of your source(s);
do not complete the Requirements Status and Registrant's Response form.
Examples of such products include repackaged products and Special Local
Needs (Section 24c) products which are identical to federally registered
products.
If you are requesting a data waiver, answer "yes" here; in addition, on the
"Requirements Status and Registrant's Response" form under Item 9, you must
respond with option 7 (Waiver Request) for each study for which you are
requesting a waiver.
NOTE: Item 7a and 7b are not applicable for Generic Data.
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
Generic and Product Specific Data Call-in
Item 8. ON BOTH FORMS: This certification statement must be signed by an
authorized representative of your company and the person signing must include
his/her title. Additional pages used in your response must be initialled and
dated in the space provided for the certification.
Item 9. ON BOTH FORMS: Enter the date of signature.
Item 10. ON BOTH FORMS: Enter the name of the person EPA should contact with
questions regarding your response.
Item 11. ON BOTH FORMS: Enter the phone number of your company contact.
Note: You may provide additional information that does not fit on this form in a signed letter that accompanies your response. For example, you
may wish to report that your product has already been transferred to another company or that you have already voluntarily cancelled this
product. For these cases, please supply all relevant details so that EPA can ensure that its records are correct.
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Instructions For Completing The "Requirements Status and Registrant's Response
Forms" For The Generic and Product Specific Data Call-In
INTRODUCTION
These instructions apply to the Generic and Product Specific "Requirements Status and
Registrant's Response Forms" and are to be used by registrants to respond to generic and
product specific Data Call-in's as part of EPA's reregistration program under the Federal
Insecticide, Fungicide, and Rodenticide Act. If you are an end-use product registrant only
and have been sent this DCI letter as part of a RED document you have been sent just the
product specific "Requirements Status and Registrant's Response Forms." Only registrants
responsible for generic data have been sent the generic data response forms. The type of
Data Call-in (generic or product specific) is indicated in item number 3 ("Date and Type
of DCI") on each form.
Although the form is the same for both product specific and generic data, instructions
for completing the forms differ slightly. Specifically, options for satisfying product specific
data requirements do not include (1) deletion of uses or (2) request for a low volume/minor
use waiver. Please read these instructions carefully before filling out the forms.
EPA has developed these forms individually for each registrant, and has preprinted
these forms to include certain information unique to this chemical. DO NOT use these forms
for any other active ingredient.
Items 1 through 8 have been preprinted on the form. Item 9 must be completed by the
registrant as appropriate. Items 10 through 13 must be completed by the registrant before
submitting a response to the Agency.
The public reporting burden for this collection of information is estimated to average
30 minutes per response, including time for reviewing instructions, searching existing data
sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect of
this collection of information, including suggestions for reducing this burden, to Chief,
Information Policy Branch, Mail Code 2136, U.S. Environmental Protection Agency, 401 M
St., S.W., Washington, D.C. 20460; and to the Office of Management and Budget,
Paperwork Reduction Project 2070-0107, Washington, D.C. 20503.
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
Generic and Product Specific Data Call-in
Item 1. ON BOTH FORMS: This item identifies your company name, number and
address.
Item 2. ON THE GENERIC DATA FORM: This item identifies the case number,
case name, EPA chemical number and chemical name.
ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the
case number, case name, and the EPA Registration Number of the product for
which the Agency is requesting product specific data.
Item 3. ON THE GENERIC DATA FORM: This item identifies the type of Data
Call-in. The date of issuance is date stamped.
ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the type
of Data Call-in. The date of issuance is also date stamped. Note the unique
identifier number (ID#) assigned by the Agency. This ID number must be used
in the transmittal document for any data submissions in response to this Data
Call-In Notice.
Item 4. ON BOTH FORMS: This item identifies the guideline reference number of
studies required. These guidelines, in addition to the requirements specified in
the Data Call-In Notice, govern the conduct of the required studies. Note that
series 61 and 62 in product chemistry are now listed under 40 CFR 158.155
through 158.180, Subpart c.
Item 5. ON BOTH FORMS: This item identifies the study title associated with the
guideline reference number and whether protocols and 1, 2, or 3-year progress
reports are required to be submitted in connection with the study. As noted in
Section III of the Data Call-In Notice, 90-day progress reports are required for
all studies.
If an asterisk appears in Item 5, EPA has attached information relevant to this
guideline reference number to the Requirements Status and Registrant's
Response Form.
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
Generic and Product Specific Data Call-in
Item 6. ON BOTH FORMS: This item identifies the code associated with the use
pattern of the pesticide. In the case of efficacy data (product specific
requirement), the required study only pertains to products which have the use
sites and/or pests indicated. A brief description of each code follows:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food crop
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
0 Indoor residential
Item 7. ON BOTH FORMS: This item identifies the code assigned to the substance
that must be used for testing. A brief description of each code follows:
EUP End-Use Product
MP Manufacturing-Use Product
MP/TGAI Manufacturing-Use Product and Technical Grade Active
Ingredient
PAI Pure Active Ingredient
PAI/M Pure Active Ingredient and Metabolites
PAI/PAIRA Pure Active Indredient or Pute Active
Ingredient Radiolabelled
PAIRA Pure Active Ingredient Radiolabelled
PAIRA/M Pure Active Ingredient Radiolabelled and Metabolites
PAIRA/PM Pure Active Ingredient Radiolabelled and Plant
Metabolites
TEP Typical End-Use Product
TEP % Typical End-Use Product, Percent Active Ingredient
Specified
TEP/MET Typical End-Use Product and Metabolites
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TEP/PAI/M Typical End-Use Product or Pure Active Ingredient and
Metabolites
TGAI Technical Grade Active Ingredient
TGAI/PAI Technical Grade Active Ingredient or Pure Active
Ingredient
TGAI/PAIRA Technical Grade Active Ingredient or Pure Active
Ingredient Radiolabelled
TGAI/TEP Technical Grade Active Ingredient or Typical End-Use
Product
MET Metabolites
IMP Impurities
DEGR Degradates
* See: guideline comment
Item 8. This item completed by the Agency identifies the time frame allowed for
submission of the study or protocol identified in item 5.
ON THE GENERIC DATA FORM: The time frame runs from the date of
your receipt of the Data Call-In notice.
ON THE PRODUCT SPECIFIC DATA FORM: The due date for
submission of product specific studies begins from the date stamped on the letter
transmitting the Reregistration Eligibility Decision document, and not from the
date of receipt. However, your response to the Data Call-In itself is due 90
days from the date of receipt.
Item 9. ON BOTH FORMS: Enter the appropriate Response Code or Codes to show
how you intend to comply with each data requirement. Brief descriptions of
each code follow. The Data Call-In Notice contains a fuller description of each
of these options.
Option 1. ON BOTH FORMS: (Developing Data) I will conduct a new study and
submit it within the time frames specified in item 8 above. By indicating
that I have chosen this option, I certify that I will comply with all the
requirements pertaining to the conditions for submittal of this study as
outlined in the Data Call-In Notice and that I will provide the protocols
and progress reports required in item 5 above.
Option 2. ON BOTH FORMS: (Agreement to Cost Share) I have entered into an
agreement with one or more registrants to develop data jointly. By
indicating that I have chosen this option, I certify that I will comply with
all the requirements pertaining to sharing in the cost of developing data
as outlined in the Data Call-In Notice.
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However, for Product Specific Data, I understand that this
option is available for acute toxicity or certain efficacy data ONLY if
the Agency indicates in an attachment to this notice that my product is
similar enough to another product to qualify for this option. I certify that
another party in the agreement is committing to submit or provide the
required data; if the required study is not submitted on time, my product
may be subject to suspension.
Option 3. ON BOTH FORMS: (Offer to Cost Share) I have made an offer to
enter into an agreement with one or more registrants to develop data
jointly. I am also submitting a completed "Certification of offer to Cost
Share in the Development of Data" form. I am submitting evidence that
I have made an offer to another registrant (who has an obligation to
submit data) to share in the cost of that data. I am including a copy of
my offer and proof of the other registrant's receipt of that offer. I am
identifying the party which is committing to submit or provide the
required data; if the required study is not submitted on time, my product
may be subject to suspension. I understand that other terms under Option
3 in the Data Call-in Notice apply as well.
However, for Product Specific Data, I understand that this
option is available only for acute toxicity or certain efficacy data and
only if the Agency indicates in an attachment to this Data Call-in Notice
that my product is similar enough to another product to qualify for this
option.
Option 4. ON BOTH FORMS: (Submitting Existing Data) I will submit an
existing study by the specified due date that has never before been
submitted to EPA. By indicating that I have chosen this option, I certify
that this study meets all the requirements pertaining to the conditions for
submittal of existing data outlined in the Data Call-In Notice and I have
attached the needed supporting information along with this response.
OptionS. ON BOTH FORMS: (Upgrading a Study) I will submit by the
specified due date, or will cite data to upgrade a study that EPA has
classified as partially acceptable and potentially upgradeable. By
indicating that I have chosen this option, I certify that I have met all the
requirements pertaining to the conditions for submitting or citing
existing data to upgrade a study described in the Data Call-In Notice. I
am indicating on attached correspondence the Master Record
Identification Number (MRID) that EPA has assigned to the data that I
am citing as well as the MRID of the study I am attempting to upgrade.
Option 6. ON BOTH FORMS: (Citing a Study) I am citing an existing study
that has been previously classified by EPA as acceptable, core, core
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minimum, or a study that has not yet been reviewed by the Agency. If
reviewed, I am providing the Agency's classification of the study.
However, for Product Specific Data, I am citing another
registrant's study. I understand that this option is available ONLY for
acute toxicity or certain efficacy data and ONLY if the cited study was
conducted on my product, an identical product or a product which the
Agency has "grouped" with one or more other products for purposes of
depending on the same data. I may also choose this option if I am citing
my own data. In either case, I will provide the MRID or Accession
number (s). If I cite another registrant's data, I will submit a completed
"Certification With Respect To Data Compensation Requirements"
form.
FOR THE GENERIC DATA FORM ONLY: The following three options
(Numbers 7,8, and 9) are responses that apply only to the "Requirements Status
and Registrant's Response Form" for generic data.
Option 7. (Deleting Uses) I am attaching an application for amendment to my
registration deleting the uses for which the data are required.
Option 8. (Low Volume/Minor Use Waiver Request) I have read the statements
concerning low volume-minor use data waivers in the Data Call-In
Notice and I request a low-volume minor use waiver of the data
requirement. I am attaching a detailed justification to support this waiver
request including, among other things, all information required to
support the request. I understand that, unless modified by the Agency in
writing, the data requirement as stated in the Notice governs.
Option 9. (Request for Waiver of Data) I have read the statements concerning data
waivers other than lowvolume minor-use data waivers in the Data
Call-In Notice and I request a waiver of the data requirement. I am
attaching a rationale explaining why I believe the data requirements do
not apply. I am also submitting a copy of my current labels. (You must
also submit a copy of your Confidential Statement of Formula if not
already on file with EPA). I understand that, unless modified by the
Agency in writing, the data requirement as stated in the Notice governs.
FOR PRODUCT SPECIFIC DATA: The following option (number 7) is a
response that applies to the "Requirements Status and Registrant's Response
Form" for product specific data.
Option 7. (Waiver Request) I request a waiver for this study because it is
inappropriate for my product. I am attaching a complete justification for
this request, including technical reasons, data and references to relevant
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EPA regulations, guidelines or policies. [Note: any supplemental data
must be submitted in the format required by P.R. Notice 86-5]. I
understand that this is my only opportunity to state the reasons or
provide information in support of my request. If the Agency approves
my waiver request, I will not be required to supply the data pursuant to
Section 3(c) (2) (B) of FIFRA. If the Agency denies my waiver request,
I must choose a method of meeting the data requirements of this Notice
by the due date stated by this Notice. In this case, I must, within 30
days-of my receipt of the Agency's written decision, submit a revised
"Requirements Status" form specifying the option chosen. I also
understand that the deadline for submission of data as specified by the
original Data Call-In notice will not change.
Item 10. ON BOTH FORMS: This item must be signed by an authorized representative
of your company. The person signing must include his/her title, and must initial
and date all other pages of this form.
Item 11. ON BOTH FORMS: Enter the date of signature.
Item 12. ON BOTH FORMS: Enter the name of the person EPA should contact with
questions regarding your response.
Item 13. ON BOTH FORMS: Enter the phone number of your company contact.
NOTE: You may provide additional information that does not fit on this form in a signed letter that accompanies this your response. For example, you
may wish to report that your product has already been transferred to another company or that you have already voluntarily cancelled this
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TRB'S BATCHING OF PRODUCTS CONTAINING DIPHENYLAMINE AS THE
ACTIVE INGREDIENT FOR MEETING ACUTE TOXICITY DATA REQUIREMENTS
FOR REREGISTRATION
In an effort to reduce the time, resources and number of animals needed to fulfill the acute
toxicity data requirements for reregistration of products containing diphenylamine as the active
ingredient, the Agency has batched products which can be considered similar for purposes of
acute toxicity. Factors considered in the sorting process include each product's active and inert
ingredients (identity, percent composition and biological activity), type of formulation (e.g.,
emulsifiable concentrate, aerosol, wettable powder, granular, etc.), and labeling (e.g., signal
word, use classification, precautionary labeling, etc.). Note that the Agency is not describing
batched products as "substantially similar" since some products within a batch may not be
considered chemically similar or have identical use patterns.
Using available information, batching has been accomplished by the process described in
the preceding paragraph. Notwith-standing the batching process, the Agency reserves the right
to require, at any time, acute toxicity data for an individual product should the need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or cite
a single battery of six acute toxicological studies to represent all the products within that batch.
It is the registrants' option to participate in the process with all other registrants, only some of the
other registrants, or only their own products within a batch, or to generate all the required acute
toxicological studies for each of their own products. If a registrant chooses to generate the data
for a batch, he/she must use one of the products within the batch as the test material. If a
registrant chooses to rely upon previously submitted acute toxicity data, he/she may do so
provided that the data base is complete and valid by today's standards (see acceptance criteria
attached), the formulation tested is considered by EPA to be similar for acute toxicity, and the
formulation has not been significantly altered since submission and acceptance of the acute toxicity
data. Regardless of whether new data is generated or existing data is referenced, registrants must
clearly identify the test material by EPA Registration Number. If more than one confidential
statement of formula (CSF) exists for a product, the registrant must indicate the formulation
actually tested by identifying the corresponding CSF.
In deciding how to meet the product specific data requirements, registrants must follow
the directions given in the Data Call-In Notice and its attachments appended to the RED. The DCI
Notice contains two response forms which are to be completed and submitted to the Agency within
90 days of receipt. The first form, "Data Call-In Response," asks whether the registrant will meet
the data requirements for each product. The second form, "Requirements Status and Registrant's
Response," lists the product specific data required for each product, including the standard six
acute toxicity tests. A registrant who wishes to participate in a batch must decide whether he/she
will provide the data or depend on someone else to do so. If a registrant supplies the data to
support a batch of products, he/she must select one of the following options: Developing Data
(Option 1), Submitting an Existing Study (Option 4), Upgrading an Existing Study (Option 5) or
Citing an Existing Study (Option 6). If a registrant depends on another's data, he/she must choose
among: Cost Sharing (Option 2), Offers to Cost Share (Option 3) or Citing an Existing Study
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(Option 6). If a registrant does not want to participate in a batch, the choices are Options 1, 4,
5 or 6. However, a registrant should know that choosing not to participate in a batch does not
preclude other registrants in the batch from citing his/her studies and offering to cost share
(Option 3) those studies.
Three products were found which contain diphenylamine as the active ingredient. All
three products have been placed into the "no batch" category based on the active/inert ingredients
and type of formulation. However, with the exception of eye and skin irritation data, EPA Reg.
Nos. 2792-45 and 64864-3 may be supported by acute toxicity data performed with the technical
[EPA Reg. No. 2792-47]. Eye and skin irritation data performed with EPA Reg. Nos. 2792-45
and 64864-3 [separately] are needed to support reregistration of these two products. Furthermore,
since the Agency has obtained Material Safety Data Sheets which designate diphenylamine as a
dermal sensitizer, dermal sensitization data are not required for any of these products. Each
product, however, will be required to include a label statement indicating that the product may
cause dermal sensitization following repeated exposure.
At a minimum, the acute data cited or submitted to support these products should meet the
acceptance criteria included in this document. In addition, the acute toxicity values for
diphenylamine [also included in this document] are for informational purposes only, and the data
supporting these values may or may not meet the acceptance criteria.
No Batch
EPA Reg. No.
2792-45
2792-47
64864-3
% Active Ingredient
31.0
99.9
15.0
Formulation Type
Liquid
Solid
Liquid
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The following is a list of available documents for diphenylamine that may further assist
you in responding to this Reregistration Eligibility Decision document. These documents may be
obtained by the following methods:
Electronic
File format: Portable Document Format (.PDF) Requires Adobe® Acrobat or compatible
reader. Electronic copies can be downloaded from the Pesticide Special Review
and Reregistration Information System at 703-308-7224. They also are available
on the Internet on EPA's gopher server using WWW (World Wide Web) on
WWW.EPA.GOV., or contact CP Moran at (703)-308-8590.
1. PR Notice 86-5.
2. PR Notice 91-2 (pertains to the Label Ingredient Statement).
3. A full copy of this RED document.
4. A copy of the fact sheet for diphenylamine.
The following documents are part of the Administrative Record for diphenylamine and
may included in the EPA's Office of Pesticide Programs Public Docket. Copies of these
documents are not available electronically, but may be obtained by contacting the person listed
on the Chemical Status Sheet.
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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Attachment 1. List of All Registrants Sent This Data Call-In (insert) Notice
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Instructions for Completing the Confidential Statement of Formula
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
common names for the trade names must be reported.
i. For the active ingredients, the percent purity of the source products must be
reported under column 10 and must be exactly the same as on the source product's
label.
j. 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 100 percent.
1. All items under columns 14.a. and 14.b. for the active ingredients must represent
pure active form.
m. The upper and lower certified limits for ail 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.
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118
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United States Environmental Protection Agency
Washington, B.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 developingdata.
My firm has offered in writing to enter into such an agreement. That offer was irrevocable and included 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
119
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120
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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
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
Product Name
Company Number
EPA Reg. No.
I Certify that:
1. For each study cited in support of registration or reregistratiion under the Federal Insecticide, Fungicide and Rodenticide 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
company(ies) that submitted data I have cited and have offered to: (a) Pay compensation for those data in accordance with sections
3(c)(1 )(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)(1)(F) of FIFRA for the studies I have cited in support of registration or
reregistration under FIFRA.
Signature
Date
Name and Title (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)(1)(F) and 3(c)(2)(D).
Signature
Date
Name and Title (Please Type or Print)
EPA Form 8570-31 (4-96)
121
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