United States Prevention, Pesticides EPA 738-R-94-025
Environmental Protection And Toxic Substances September 1994
Agency (7508W)
&EPA Reregistration
Eligibility Decision (RED)
M-CRESOL AND XYLENOL
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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 cases m-cresol and
xylenol. The enclosed Reregistration Eligibility Decision (RED) 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 ingredient(s) to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary
of Instructions for Responding to the RED". This summary also refers to other enclosed
documents which include further instructions. You must follow all instructions and submit
complete and timely responses. The first set of required responses are due 90 days from
the date of this letter. The second set of required responses are due 8 months from the
date of this letter. Complete and timely responses will avoid the Agency taking the
enforcement action of suspension against your products.
If you have questions on the product specific data requirements or wish to meet with
the Agency, please contact the Special Review and Reregistration Division representative
Franklin Gee at (703) 308-8008.
Sincerely yours,
Louis P. True, Jr., Acting 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, another DCI letter will be enclosed listing such requirements. If both generic
and product specific data are required, a combined Generic and Product Specific letter will
be enclosed describing such data. Complete the two response forms provided with each DCI
letter (or four forms for the combined) by following the instructions provided. You must
submit the response forms for each product and for each DCI within 90 days of the date
of this letter (RED issuance date); 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 data waivers must be submitted as part of the
90-day response. Requests for time extensions should be submitted in the 90-day response,
but certainly no later than the 8-month response date. All data waiver and time extension
requests must be accompanied by a full justification. All waivers and time extensions must be
granted by EPA in order to go into effect.
3. APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE" You must
submit the following items for each product within eight months of the date of this letter
(RED issuance date).
a. Application for Reregistration (EPA Form 8570-1). Use only an original
application form. Mark it "Application for Reregistration." Send your Application for
Reregistration (along with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies of draft labeling which complies with the RED and current regulations
and requirements. Only make labeling changes which are required by the RED and current
regulations (40 CFR 156.10) and policies. Submit any other amendments (such as formulation
changes, or labeling changes not related to reregistration) separately. You may delete uses
which the RED says are ineligible for reregistration. For further labeling guidance, refer to
the labeling section of the EPA publication " General Information on Applying for Registration
in the U.S., Second Edition, August 1992" (available from the National Technical Information
Service, publication #PB92-221811; telephone number 703-487-4650).
c. Generic or Product Specific Data. Submit all data in a format which complies
with PR Notice 86-5, and/or submit citations of data already submitted and give the EPA
identifier (MRID) numbers. Before citing these studies, you must make sure that they meet
the Agency's acceptance criteria (attached to the DCI).
d. Two copies of the Confidential Statement of Formula (CSF) for each basic and
each alternate formulation. The labeling and CSF which you submit for each product must
comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal
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.
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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
M-CRESOL AND XYLENOL
LISTD
CASES 4027 and 4098
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
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TABLE OF CONTENTS
M-CRESOL AND XYLENOL REREGISTRATION ELIGIBILITY DECISION TEAM
i
EXECUTIVE SUMMARY vi
I. INTRODUCTION 1
II. CASE OVERVIEW 2
A. Chemical Overview 2
B. Use Profile 3
C. Estimated Usage of Pesticide 4
D. Data Requirements 4
E. Regulatory History 4
III. SCIENCE ASSESSMENT 4
A. Physical Chemistry Assessment 4
B. Human Health Assessment 6
1. Toxicology Assessment 6
a. Acute Toxicity 7
b. Subchronic Toxicity 9
c. Developmental Toxicity 10
d. Reproductive Toxicity 11
e. Mutagenicity 11
f. Metabolism 12
g. Reference Dose 12
2. Exposure Assessment 12
a. Dietary Exposure 12
b. Occupational and Residential 12
3. Risk Assessment 13
a. Dietary 13
b. Occupational and Residential 13
C. Environmental Assessment 15
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 15
A. Determination of Eligibility 15
1. Eligibility Decision 16
2. Eligible and Ineligible Uses 16
B. Regulatory Position 16
1. Tolerance Reassessment 17
2. Labeling Rationale 17
a. General 17
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b. Worker Protection Standard and Personal Protective
Equipment (PPE) 17
V. ACTIONS REQUIRED BY REGISTRANTS 18
A. Manufacturing-Use Products 18
1. Additional Generic Data Requirements 18
B. End-Use Products 18
1. Additional Product-Specific Data Requirements 18
2. Labeling Requirements for End-Use Products 19
C. Existing Stocks 19
VI. APPENDICES 21
APPENDIX A. Table of Use Patterns Subject to Reregistration 23
APPENDIX B. Table of the Generic Data Requirements and Studies Used to
Make the Reregistration Decision 33
APPENDIX C. Citations Considered to be Part of the Data Base Supporting the
Reregistration of M-Cresol and Xylenol 53
APPENDIX D. List of Available Related Documents 59
APPENDIX E 63
PR Notice 86-5 65
PR Notice 91-2 83
APPENDIX F. Product Specific Data Call-in 89
Attachment 1. Chemical Status Sheet 103
Attachment 2. Product Specific Data Call-in Response Forms (Form A
inserts) Plus Instructions 105
Attachment 3. Product Specific Requirement Status and Registrant's
Response Forms (Form B inserts) and Instructions Ill
Attachment 4. EPA Batching of End-Use Products for Meeting Data
Requirements for Reregistration 117
Attachment 5. EPA Acceptance Criteria 121
Attachment 6. List of All Registrants Sent This Data Call-in (insert) Notice
135
Attachment 7. Cost Share Data Compensation Forms, Confidential
Statement of Formula Form and Instructions 137
APPENDIX G. FACT SHEET 147
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M-CRESOL AND XYLENOL REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis Division
Phyllis Johnson
James Saulmon
Ghulam Ali
Environmental Fate and Effects Division
William Schneider
Betsy Grim
Renee Lamb
Patricia Ott
Health Effects Division
Felecia Fort
Pat McLaughlin
Winston Dang
Arliene Aikens
Registration Division
Shyam B. Mathur
Amelia M. Acierto
Sidney Jackson
Denise Greenway
Special Review and Reregistration Division
Paul Lewis
Virginia Dietrich
Carol Stangel
Office of Compliance
Beverly Updike
Biological Analysis Branch
Biological Analysis Branch
Economic Analysis Branch
Science Analysis and Coordination Staff
Science Analysis and Coordination Staff
Ecological Effects Branch
Environmental Fate and Ground Water Branch
Reregistration Support Chemistry Branch
Toxicology Branch II
Occupational and Residential Exposure
Branch
Chemical Coordination Branch
Registration Support Branch
Registration Support Branch
Fungicide-Herbicide Branch
Fungicide-Herbicide Branch
Accelerated Reregistration Branch
Accelerated Reregistration Branch
Planning and Reregistration Branch
Office of General Counsel
Kevin Lee
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11
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GLOSSARY OF TERMS AND ABBREVIATIONS
AE Acid equivalent
a.i. Active Ingredient
CAS Chemical Abstracts Service
CSF Confidential Statement of Formula
DRES 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
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
GLC Gas Liquid Chromatography
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.
in
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GLOSSARY OF TERMS AND ABBREVIATIONS
LD
50
LDlo
LEL
LOG
LOEL
MCLG
MP
MPI
MOE
MRID
N/A
NPDES
NOEL
OPP
PADI
PAM
ppm
PR
Notice
Median Lethal Dose. A statistically derived single dose that can be expected to
cause death in 50% of the test animals when administered by the route indicated
(oral, dermal, inhalation). It is expressed as a weight of substance per unit
weight of animal, e.g., mg/kg.
Lethal Dose-low. Lowest Dose at which lethality occurs
Lowest Effect Level
Level of Concern
Lowest Observed Effect Level
Maximum Contaminant Level Goal (MCLG) The MCLG is used by the
Agency to regulate contaminants in drinking water under the Safe Drinking
Water Act.
Manufacturing-Use Product
Maximum Permissible Intake
Margin Of Exposure
Master Record Identification (number). EPA's system of recording and
tracking studies submitted.
Not Applicable
National Pollutant Discharge Elimination System
No Observed Effect Level
Office of Pesticide Programs
Provisional Acceptable Daily Intake
Pesticide Analytical Method
Parts Per Million
Notice that is published in the Public Register
IV
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GLOSSARY OF TERMS AND ABBREVIATIONS
Q*! The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer
Risk Model
RED Reregistration Eligibility Decision
RfD Reference Dose
RS Registration Standard
TD Toxic Dose. The dose at which a substance produces a toxic effect.
TC Toxic Concentration. The concentration at which a substance produces a toxic
effect.
TGAI Technical Grade Active Ingredient
TMRC Theoretical Maximum Residue Contribution
TLC Thin Layer Chromatography
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EXECUTIVE SUMMARY
The U.S. Environmental Protection Agency (hereafter referred to as the "Agency" or
"EPA") has completed its reregistration assessment of the available information on the
pesticidal active ingredients m-cresol and xylenol (2,4 xylenol). The two active ingredients
(i.e. two cases) are formulated together as one product that has bacteriostatic activity against
the causal agents for crown gall and olive knot and control of the genetic/physiological
disorder, burr knot. Use sites include fruit, ornamental and shade trees and ornamental
woody shrubs and vines. The Agency has reviewed the available data for m-cresol and
xylenol and has determined that the uses described and modified in this reregistration
eligibility decision document as currently registered will not cause unreasonable risk to
humans or the environment and that these uses are eligible for reregistration.
Before reregistering the products containing m-cresol and xylenol, the Agency is
requiring that product specific data, revised Confidential Statements of Formula (CSF) and
revised labeling be submitted within eight months of the issuance of this document. These data
include product chemistry for each registration and acute toxicity testing. After reviewing
these data and any revised labels and finding them acceptable in accordance with Section
3(c)(5) of FIFRA, the Agency will reregister a product. 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.
This document presents the Agency's decision regarding the reregistration eligibility of
the registered uses of m-cresol and xylenol. The document consists of six sections. Section I
is the introduction. Section II describes m-cresol and xylenol, 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 m-
cresol and xylenol. Section V discusses the reregistration requirements for m-cresol and
xylenol. 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 ingredients are covered by this Reregistration Eligibility
Document:
• Common Names: m-cresol and xylenol
Chemical Names:
m-cresol: 3-methyl phenol
xylenol: 2,4-dimethylphenol; 2,4 xylenol
Chemical Family: phenols
CAS Registry Number:
m-cresol: 108-39-4
xylenol: 105-67-9
OPP Chemical Code:
m-cresol: 22102
xylenol: 86804
Empirical Formula:
m-cresol: C7H80
xylenol: C8H100
Trade and Other Names: Gallex, as both active ingredients formulated
together
Basic Manufacturer: AgBioChem, Inc.
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B. Use Profile
The following is information on the current registered uses with an overview of
use sites and application methods. A detailed table of these uses of m-cresol and
xylenol is in Appendix A.
Type of Pesticide: bactericide/bacteriostat
Use sites: almond, apple, apricot, blueberry, cherry, filbert (hazelnut), grape,
nectarine, olive, oleander, ornamentals, peach, pear, pecan, plum, prune, and walnut
(English/black), fruit, nut, ornamental trees and vine crops in the field or greenhouse.
Diseases:
biotic - crown gall (Agrobacterium tumefacians) and olive knot (Pseudomonas
savastanoi).
abiotic - burr knot (genetic/physiological disorder).
Formulation Types Registered: Liquid-Ready to use (0.466% m-cresol and
0.463% xylenol)
Method and Rates of Application:
Equipment - paintbrush
Method, rate and timing - The product is applied as a brush-on
(painted) gall or tumor treatment for control of the bacterial diseases
crown gall and olive knot on certain fruit and nut trees and ornamentals
and the genetic/physiological disorder burr knot on apples. The end-use
product is painted on the gall and cut surfaces plus 1/2 inch of the
surrounding healthy bark. Treated galls below ground level are allowed
to dry one or more days before the soil is replaced. Treatment may be
repeated after 4 to 6 months, if any live galls are found upon
examination. Pesticide applications are to be made only on infected
areas and are typically done prior to budbreak in early spring or during
early summer. Treatment is made up to one half of the galled trunk per
application interval to prevent girdling and water deprivation of the host.
Use Practice Limitations: Gallex will injure tender foliage, stems and root
tissue of most plants. Do not allow rinse water from brushes and containers to
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contaminate streams, ponds and lakes, as water life may be affected. Do not
contaminate water, food, or feed by storage, spillage or disposal. Keep
container closed when not in use.
C. Estimated Usage of Pesticide
Due to a lack of usage data for m-cresol and xylenol, the Agency cannot
estimate the volume of use for these pesticides. However, it assumes the
volume is relatively low.
D. Data Requirements
Appendix B includes all data requirements identified by the Agency needed to
support reregistration for currently registered uses.
E. Regulatory History
M-cresol and xylenol were registered by the Agency for use in the United States
in 1980 for use as a bactericide for control of crown gall and olive knot on certain fruit
and nut trees and ornamentals and the genetic/physiological disorder burr knot on
apples. Currently, one product is registered which contains both m-cresol and xylenol.
III. SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
M-cresol
The crude chemical cresol can be a mixture of its isomers, namely o-
cresol, m-cresol and p-cresol. Each of these individual compounds can be
prepared and identified in the pure form.
Chemical name: 3-methyl phenol
Chemical formula: C7H80
Molecular weight: 108.14
Color: colorless or yellowish color
Physical State: liquid at room temperature
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Odor: phenolic odor
Melting Point: 11.5°C
Boiling Point: 202.2°C at 760 mm
Solubility: 2.5% in water, in solutions of alkali
hydroxides; miscible alcohol, chloroform
and ether.
Vapor Pressure: 0.18mmat25°C
Dissociation Constant: 9.8 x 10 n at 25°C
LogK0/w: 1.98
Specific gravity: 1.034 at 20°C
2,4-Xylenol (xylenol)
2,4-Xylenol is one of the six isomers of xylenol. It is derived from
cresylic acid or tar acid fraction of coal tar.
Chemical name: 2,4-dimethylphenol
Chemical formula: C8H100
Molecular weight: 122.17
Color: white
Physical state : crystalline solid
Odor: phenolic odor
Melting point: 26°C
Boiling point: 211°Cat760mm
Solubility: Slightly soluble in water (6.2 g/1000 ml at
25°C), soluble in organic solvents and
freely soluble in alcohol, chloroform,
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Vapor Pressure
Dissociation constant
Octanol/water
partition coefficient
Specific gravity
ether, benzene and sodium hydroxide
solution.
0.2 mm Hg at 25°C
pKa = 10.63
logP =2.35
0.97 at 20°C
B. Human Health Assessment
1. Toxicology Assessment
The Agency relied on data from the registrant and the published
literature for both chemicals. While the generic toxicological database
requirements for these two chemicals are limited to acute and subchronic
toxicology and mutagenicity because of the current use patterns, there are other
studies on developmental and reproductive toxicology and metabolism of m-
cresol which are also reported here. The toxicology data base on the active
ingredients, m-cresol and xylenol, is adequate and will support reregistration
eligibility.
In general, cresols are present at low concentration levels in various
environmental media including air, car exhaust, wood, and coal. There have
been reports that cresols may have tumor promoting activity. However, no
adequate studies are currently available on the carcinogenicity of cresols.
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a. Acute Toxicity
TECHNICAL M-CRESOL AND END-USE PRODUCT
TEST
Acute oral - rat
Acute oral - mouse
Acute oral - rabbit
Acute dermal - rat
Acute dermal - rabbit
Acute inhalation - rat
Eye irritation - rabbit
Skin irritation - rabbit
Skin irritation - rabbit
Dermal sensitization - guinea pig
TEST SUBSTANCE
m-cresol
m-cresol
m-cresol
m-cresol
m-cresol
m-cresol
m-cresol
m-cresol
m-cresol
end-use product
RESULTS
LD50 = 242 mg/kg
LD5n = 828 mg/kg
LD5n = 2050 mg/kg
LD5n = 11 00 mg/kg
LD5n = 2050 mg/kg
waived2
severe irritation
corrosive
severe irritation
sensitizer
CATE-
GORY1
II
III
III
II
III
—
I
I
I
—
1 Categories of acute toxicity:
Category I - high level of toxicity
Category II - moderate to high level of toxicity
Category III - low to moderate level of toxicity
Category IV - very low toxicity
2 Study not required because there is no registered manufacturing
product formulation has a low concentration of m-cresol, and the
a brush in the field or greenhouse.
M-Cresol
use product, the end-use
end-use product is applied by
For m-cresol, the literature reports that the acute oral toxicity LD50 was
242 mg/kg for rats and 828 mg/kg for mice. The oral LD50 for rabbits was
1400 mg/kg. The dermal LD50 was reported as 1100 mg/kg for rats and 2050
mg/kg for rabbits. M-cresol was also reported to cause severe dermal and eye
irritation, based on studies in which a 517 mg dose was placed on rabbit skin
for 24 hours and when a 103 mg dose was placed in rabbit eyes (Sax and
Lewis, 1989).
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TECHNICAL XYLENOL AND END-USE PRODUCT
TEST
Acute oral - rat
Acute oral - mouse
Acute dermal - rat
Acute dermal - mouse
Acute inhalation - rat
Skin irritation - rabbit
Skin irritation - rabbit
Dermal sensitization - guinea pig
TEST
SUBSTANCE
xylenol
xylenol
xylenol
xylenol
xylenol
xylenol
xylenol + m-cresol
(50/50 w/w)
end-use product
RESULTS
LD5n = 3200 mg/kg
LD5n = 809 mg/kg
LD5n = 1040 mg/kg
LD5n = 1040 mg/kg
waived2
corrosive
corrosive
sensitizer
CATE-
GORY1
III
III
II
II
__
I
I
—
1 Categories of acute toxicity:
Category I - high level of toxicity
Category II - moderate to high level of toxicity
Category III - moderate to low level of toxicity
Category IV - very low toxicity
2 Study not required because there is no registered manufacturing-use product, the end-use
product formulation has a low concentration of xylenol, and the end-use product is applied by
a brush in the field or greenhouse.
Xylenol
For xylenol, the literature reports that the acute oral toxicity LD50 was
3200 mg/kg for rats and 809 mg/kg for mice. The dermal LD50 was reported
as 1040 mg/kg for rats and 1040 mg/kg for mice and that xylenol was corrosive
to rabbit skin (Sax and Lewis, 1989).
Other Acute Studies
An eye irritation study in rabbits using 8.5% of each active ingredient
found slight eye irritation, which was toxicity category II (MRID 00138519).
A primary dermal irritation study of five variations of m-cresol and/or
xylenol was conducted with rabbits. The first test material, m-cresol, produced
necrotic and corrosive effects, as did the second test material, xylenol, and the
third, a 50/50 (w/w) mixture of these two chemicals. These results were in
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toxicity category I. The fourth test material was the final product, and the fifth
test material was the final product without m-cresol and xylenol; neither
produced skin irritation and were toxicity category IV (MRID 00138520).
A dermal sensitization study with guinea pigs found that the end-use
product did produce sensitization (MRID 00138521).
b. Subchronic Toxicity
Cresol
The National Toxicology Program (NTP) of the National Institutes of
Health conducted two 28-day feeding studies with m-cresol (Dietz, 1992).
F344/N rats and B6C3F1 mice were given 0, 300, 1,000, 3,000, 10,000, or
30,000 ppm of m-cresol in the diet. In the study on mice, the threshold NOEL
was 53 mg/kg/day in males and 66 mg/kg/day in females (300 ppm). The
LOEL was 1,000 ppm (approximately 200 mg/kg/day) based upon neurotoxic
signs. The effects at 30,000 ppm included mammary gland, ovarian and uterine
atrophy; increased brain weights in males; hypothermia in females; weight loss
and reduced weight gain; hunched posture, rough coat, thin appearance,
lethargy and tremors. At 10,000 ppm, both sexes displayed hunched posture
and rough coat. In addition, females exhibited labored breathing and sunken
eyes. There were increased relative kidney weights in males treated at 3,000
ppm and in females treated at 30,000 ppm; increased relative liver weights in
males at the three highest doses and all female dose groups; thin appearance in
300 ppm treated females. Some animals died at 10,000 ppm and 30,000 ppm
doses.
In the rat study using the same treatment regimen, weight gains were
reduced at the highest dose. The NOEL was 3,000 ppm (252 mg/kg/day for
both sexes) and the LOEL was 10,000 ppm (870 mg/kg/day for males and 862
mg/kg/day for females). Relative liver weights were increased at 10,000 and
30,000 ppm. Relative brain weight and relative kidney weight for the high dose
rats were increased. Uterine atrophy was seen at 30,000 ppm in rats.
NTP conducted 13-week feeding studies with rats and mice using a
60/40 mixture of m-cresol and p-cresol (Dietz, 1992). On the basis of these
and other studies, the NTP report indicated that the three isomers (ortho-, meta-
and para-) of cresol have similar toxicities. F344/N rats were given diets
containing 0, 1880, 3750, 7500, 15,000, or 30,000 ppm m/p cresol mixture.
B6C3F1 mice were given diets containing 0, 625, 1,250, 2,500, 5,000, or
10,000 ppm of the m/p-cresol mixture.
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In the above 13-week rat study, body weight for both sexes at the two
highest doses as well as weight gain for males at the highest dose and females at
the two highest doses were reduced. Rough coat and thin appearance were
noted at the high dose. Relative kidney weights were increased in males at the
three highest doses and high dose females. Both sexes at the three highest doses
had increased relative liver weights. Males at the two highest doses had
increased relative testis weights. Indications of decreased hepatocellular
function were found at the high dose. Dose-related hyperplasia of the nasal
respiratory epithelium was found at all doses. There was increased colloid in
thyroid follicles in males at the highest dose and females at the four highest
doses. Minimal hypocellularity of bone marrow and minimal uterine atrophy
were found in the two highest dose groups.
In the above 13-week mouse study, body weights for both sexes of high
dose animals and weight gain for high dose males were decreased. Relative
liver weights were increased for males at the two highest doses and high dose
females. Hyperplasia of the nasal respiratory epithelium occurred in males at
the two highest doses and females at the three highest doses.
Cresol and Xylenol
In a 21-day dermal study, the formulated product (0.46% m-
cresol/0.46% xylenol) was applied at 1.0 or 2.0 ml/kg/day and the formulated
product's diluent only was applied at 2.0 ml/kg/day to groups of New Zealand
white rabbits with abraded or intact skin. Both the formulated product and the
diluent produced severe dermal damage on both intact and abraded skin, along
with hyperplasia of regional lymph nodes and myeloid hyperplasia of the bone
marrow. While this study does not conform to the Agency's testing guidelines
for a 21-day dermal study, no further dermal studies are required since this
study demonstrated the formulated product to be corrosive to skin (MRID
00138524).
c. Developmental Toxicity
Cresol
In Sprague-Dawley rats, m-cresol was given by gavage on gestation days
6-15 at doses of 0, 30, 175, or 450 mg/kg/day. The only observation at the
mid dose was perioral wetness. At the high dose, which was the maternal
LOEL, there was reduced body weight gain, decreased gestational weight,
increased relative liver weight, hypoactivity, audible respiration, ataxia,
twitches, tremors, prone positioning, perioral wetness, and urogenital wetness.
The NOEL for maternal toxicity was 175 mg/kg/day. No developmental
toxicity was found and the developmental toxicity NOEL was at least 450
mg/kg/day for m-cresol (Bushy Run, 1988).
10
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d. Reproductive Toxicity
Cresol
In a two-generation reproduction toxicity study, m-cresol was given by
gavage to Sprague-Dawley rats. The doses were 0, 30, 175, or 450 mg/kg/day
of m-cresol. There was parental toxicity at all dose levels for the Fl generation
and at the high dose level for the FO generation, thus the parental NOEL was
less than 30 mg/kg/day. The LOEL was 30 mg/kg/day. The high dose groups
had reduced food consumption, weight suppression, clinical signs, and
mortality. Necropsy revealed brain hemorrhage, distentions of the intestines,
decreased numbers of sperm, atrophied seminal vesicles, and lung congestion.
The Fl mid dose group had perioral wetness and all Fl treated groups had
weight suppression. There were reductions in pup body weight gain and
reduced mean pup weight at the high dose. In addition, the Fl high dose group
had increased numbers of dead pups. The NOEL for offspring was 175
mg/kg/day (Bushy Run, 1989).
NTP reported a reproductive toxicity study in CD-I Swiss mice with a
mixture of 60% m-cresol and 40% p-cresol, using the reproductive assessment
by continuous breeding protocol (Izard et al, 1992). The doses were 0, 0.25,
1.0, or 1.5% in the feed, given for 14 weeks of cohabitation. For the FO
generation, live pup weight and the number of live pups per litter were
decreased in the high dose group, and the number of days to the fifth litter was
increased. Body weight and food consumption were decreased at 1.0 and 1.5%
doses. There were increased kidney and liver weights at the 1.5% dose, as well
as decreased epididymal and seminal vesicle weights. For the Fl generation,
pup growth and survival were decreased at the 1.5% level, with reduced size,
dehydration, lethargy, and rough coat. Both 1.0 and 1.5% doses had decreased
male body weight and male reproductive organ weights, but increased relative
liver and kidney weights. Females at the two highest doses had reduced body
weight, and all dosed female groups had increased kidney and liver weights plus
reduced ovarian weights. The NOEL for reproductive toxicity for the parent
generation was 1.0% (average 1389 mg/kg/day) and the LOEL was 1.5%
(average 1649 mg/kg/day). The NOEL for reproductive effects in Fl animals
was 0.25% (463 mg/kg/day) while the LOEL was 1.0% (1798 mg/kg/day),
based on body and organ weights.
e. Mutagenicity
Cresol
M-cresol was negative for gene mutation in Salmonella tests, with and
without activation and in mouse lymphoma tests, with and without activation
11
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(Hazleton, 1988a; Health and Human Services, 1992). It showed no effect on
unscheduled DNA synthesis in rat hepatocytes (Hazleton, 1988b). Chinese
hamster ovary cell tests for chromosomal aberrations were suggestive, but not
without activation (Hazleton, 1988c). The data were suggestive of cell
transformation without activation when m-cresol was tested using BALB/C-3T3
cells, with and without activation (Hazleton, 1988d). An in vivo assay for
chromosomal aberration in mouse bone marrow was negative (Hazleton, 1989).
Xylenol
Studies on the xylenol active ingredient are not required to fulfill this
guideline requirement.
f. Metabolism
Cresol
The NTP report on cresols discussed the available information on cresol
metabolism (Dietz, 1992). Generally, exogenous cresols are absorbed from the
gastrointestinal tract and subsequently conjugated with glucuronide or sulfate;
there is urinary excretion.
g. Reference Dose
Significant toxicological residues of m-cresol and xylenol are not
expected to occur in food/feed commodities from registered uses of the end-use
pesticide product. Therefore, reference doses are not required.
2. Exposure Assessment
a. Dietary Exposure
The uses of the active ingredients m-cresol and xylenol in the end-use
product include application only to the bases of fruit and nut trees. No dietary
exposure to residues m-cresol and xylenol are expected in food/feed
commodities.
b. Occupational and Residential
There is one registered product subject to reregistration for m-cresol and
xylenol. The two active ingredients in the end-use product are each present at
0.46%(w/w). The end-use product is formulated as a flowable emulsion. The
product label states applications can be made every four to six months or about
twice a year.
12
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For workers who apply the pesticide by paint brush and wear long pants,
long sleeves and no gloves, the unit of exposure is estimated at 290 mg/lb a.i.
handled (Ref: Surrogate Unit Exposure Values for REDs where clothing
scenario is long pants, long sleeves, no gloves, and the median Ib ai/handled
was 0.0253. March 9, 1994). For the purpose of estimating
occupational/residential exposures to the m-cresol and xylenol active ingredients
in the end-use pesticide product, it is assumed that one gallon (total weight = 9
Ib/gal) of this product is used per worker per day for 4 consecutive days and
that the worker is of average body weight (70 kg). Total worker exposure to
m-cresol and xylenol in the pesticide product is estimated to be 0.172
mg/kg/day of each chemical (see below).
Ibs. a.i. handled per day = 1 gal. X 0.0046 X 9 Ib = 0.0414 Ib a.i.
Total exposure per day = 290 mg/lb a.i. X 0.0414 Ib a.i. = 12.01 mg
Average worker body weight = 70 kg
Average exposure per worker per day = 12.01 mg / 70 kg/day = 0.172
mg/kg/day
3. Risk Assessment
a. Dietary
The current use pattern for the end-use product is not expected to result
in residues in/on food/feed crops. Therefore, a dietary risk assessment is not
required for the current use pattern for the two active ingredients in the
pesticide end-use product.
b. Occupational and Residential
Toxicity Endpoints
Toxicological endpoints of concern for technical m-cresol and xylenol
include acute and subchronic toxicological parameters. Acute dermal toxicity
of both chemicals was moderate (Toxicology Category II). Skin irritation for
both chemicals and eye irritation for m-cresol were high (Toxicology
Category I). Although acute oral toxicity of m-cresol and xylenol were
moderate, they are not a toxicological endpoint of concern because oral
exposure is not expected from the use pattern. Details of these endpoints are
presented above in the Toxicology Assessment section.
For the purposes of evaluating worker risk from the current use of this
pesticide end-use product, the active ingredient of concern in this pesticide
product is m-cresol due to the available data on this chemical. For technical m-
13
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cresol, the Agency concluded the short term occupational/residential exposure
NOEL for m-cresol is 175 mg/kg/day, based on maternal toxicity from the
developmental toxicity study described above. No developmental toxicity was
found; the NOEL was at least 450 mg/kg/day, for m-cresol. The intermediate
term exposure NOEL for m-cresol is 53 mg/kg/day, based on the 28-day
feeding study in male and female mice (Dietz, 1992). Comparable data for
xylenol were not available.
Acute toxicity data on the end-use product (Gallex), suggest it is not a
skin irritant (Toxicology Category IV). However, the end-use product is
considered to be a dermal sensitizer. In a 21-day dermal study (rabbit) which
compared the effects of the end-use product with the effects of end-use product
solvent alone, no toxic effects could be attributed to the active ingredients, m-
cresol and xylenol.
Occupational/Residential Risk
For the registered end-use product, one to two applications are made to
infected plant tissue. A maximum of four consecutive days of
occupational/residential use and applicator exposure are expected from available
information on the pesticide product use pattern. The NOEL for short term
exposure (7 consecutive days or less) is 175 mg/kg/day for m-cresol.
The Agency also considered intermediate term exposure (one week to
several months) for the end-use product. The Agency considered intermediate
term exposure in its risk assessment due to the potential that commercial
applicators may be exposed to the end-use product for this interval. However,
the Agency believes that short term exposure is more applicable for the risk
assessment due to the nature of the use pattern of the end-use product. The
intermediate term exposure (one week to several months) NOEL is 53
mg/kg/day. Similar toxicity data are not available for xylenol.
The Agency calculated margins of exposure (MOE) to compare the
NOEL from m-cresol to the estimates of exposure to applicators. On this basis,
the short term (1 to 7 days) occupational/residential MOE (margin of exposure)
is estimated to be 1017 and the intermediate term (one week to several months)
MOE is estimated to be 308.
MOE = NOEL •*• Exposure
Short term occupational/Residential
MOE = 175 mg/kg/day •*• 0.172 mg/kg/day =1017
14
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Intermediate term occupational/Residential
MOE = 53 mg/kg/day •*• 0.172 mg/kg/day = 308
Considering the estimated MOEs, the Agency does not expect significant
health risks from short term or intermediate occupational/residential exposures
to m-cresol from proper use of the end-use product.
However, data indicate that the end-use product is a dermal sensitizer.
In addition, uncertainty exists for acute dermal toxicity and acute eye irritation
from exposure to the end-use product. Toxicity tests using technical grade m-
cresol and xylenol demonstrated corrositivity and severe irritation for these
endpoints. The Agency is requiring data to address the dermal toxicity and eye
irritation potential of the formulated product. Use of PPE (protective eyewear,
chemical resistant gloves, long sleeves, long pants, shoes and socks) would
reduce exposure.
Post Application Risk
Based on the toxicity data and pesticide product use pattern, there are no
post-application worker exposure concerns.
C. Environmental Assessment
The Agency did not require registrants to submit any data about the
environmental fate or ecotoxicology of m-cresol and xylenol. The Agency
believes the current use pattern will result in very low environmental exposure
and the Agency presumes the volume of use is very low. Therefore, the
Agency did not conduct an environmental risk assessment for the use of these
two chemicals. Considering the limited exposure and the small amount thought
to be used, use of this product represents no threat to wildlife. Non-target
organisms, including endangered species, are not expected to be adversely
affected from this use.
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 m-cresol and
xylenol active ingredients. The Agency has completed its review of these generic data,
15
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and has determined that the data are sufficient to support reregistration of all products
containing m-cresol and xylenol. Appendix B identifies the generic data requirements
that the Agency reviewed as part of its determination of reregistration eligibility of m-
cresol and xylenol, 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 m-cresol and xylenol and to determine that m-cresol and xylenol
can be used without resulting in unreasonable adverse effects to humans and the
environment. The Agency therefore finds that all products containing m-cresol and
xylenol 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 and the data identified in Appendix B.
Although the Agency has found that all uses of m-cresol and xylenol are eligible for
reregistration as specified in this RED, 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 m-cresol and/or xylenol, if new
information comes to the Agency's attention or if the data requirements for registration
(or the guidelines for generating such data) change.
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredients m-
cresol and xylenol, the Agency has sufficient information on their health effects
and on their potential for causing adverse effects in fish and wildlife and the
environment. The Agency has determined that m-cresol and xylenol 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 m-cresol and xylenol
for all uses are eligible for reregistration.
2. Eligible and Ineligible Uses
The Agency has determined that all uses of m-cresol and xylenol are
eligible for reregistration.
B. Regulatory Position
The following is a summary of the regulatory positions and rationales for m-
cresol and xylenol. Where labeling revisions are imposed, specific language is set
forth in Section V of this document.
16
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1. Tolerance Reassessment
The Agency does not expect residues to be found in edible crops because
of the method of use. Since the Agency does not have dietary concerns with
either m-cresol or xylenol, an exemption from the requirements of tolerances
must be established for m-cresol and xylenol in or on raw agricultural
commodities from the registered use on food/feed crops. The Agency has
notified the registrant under separate cover of this requirement to file the
petition for exemption.
2. Labeling Rationale
a. General
The labels and labeling of all products must comply with EPA's
current regulations and requirements as specified in 40 CFR §156.10.
b. Worker Protection Standard and Personal Protective
Equipment (PPE)
For each end-use product, PPE requirements for pesticide
handlers will be set during reregistration in one of two ways:
• If the Agency has no special concerns about the acute or other
adverse effects of an active ingredient, the PPE for pesticide handlers
will be based on the acute toxicity or the end-use product. For
occupational-use products, PPE will be established using the process
described in PR Notice 93-7 or more recent guidelines.
• If the Agency has special concerns about an active ingredient due to
very high acute toxicity or to certain other adverse effects, such as
allergic effects or delayed effects (cancer, developmental toxicity,
reproductive effects, etc):
• In the RED for that active ingredient, the Agency may
establish minimum or "baseline" handler PPE requirements that
pertain to all or most occupational end-use products containing
that active ingredient.
•These minimum PPE requirements must be compared with the
PPE that would be designed on the basis of the acute toxicity of
each end-use product.
17
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• The more stringent choice of PPE (i.e., bodywear, hand
protection, footwear, eyewear, etc.) must be in place on the label
of the end-use product.
Because of the acute toxicity potential of the end-use product
(dermal sensitization and possible eye and skin irritation), the Agency is
requiring the use of PPE for applicators of the product. Protective
eyewear, chemical resistant gloves, long sleeves, long pants, shoes and
socks are being required.
Upon receipt and review of additional future data for the end-use
product or for new proposed products containing the subject active
ingredients, the Agency may determine that different PPE is more
appropriate.
V. ACTIONS REQUIRED BY REGISTRANTS
This section specifies the data requirements and responses necessary for the
reregistration of both manufacturing-use and end-use products.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of m-cresol and
xylenol for the above eligible uses has been reviewed and determined to be
substantially complete. No additional generic data are required at this time.
Also, currently, there are no registered manufacturing use products.
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed
product-specific data regarding the pesticide after a determination of eligibility
has been made. The product specific data requirements are listed in Appendix
G, the Product Specific Data Call-in Notice.
Registrants must review previous data submissions to ensure that they
meet current EPA acceptance criteria (Appendix F; Attachment E) and if not,
commit to conduct new studies. If a registrant believes that previously
submitted data meet current testing standards, then study MRID numbers should
18
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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
Because of the acute toxicity potential of the end-use product, the
Agency is requiring PPE for applicators. The following label statement is
required:
"Applicators and other handlers must wear: protective eyewear, chemical
resistant gloves, long sleeves, long pants, shoes and socks."
C. Existing Stocks
Registrants may generally distribute and sell products bearing old
labels/labeling for 26 months from the date of the issuance of this Reregistration
Eligibility Decision (RED). Persons other than the registrant may generally distribute
or sell such products for 50 months from the date of the issuance of this RED.
However, existing stocks time frames will be established case-by-case, depending on
the number of products involved, the number of label changes, and other factors. Refer
to "Existing Stocks of Pesticide Products; Statement of Policy"; Federal Register,
Volume 56, No. 123, June 26, 1991.
The Agency has determined that registrants may distribute and sell m-cresol and
xylenol 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.
19
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20
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VI. APPENDICES
21
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22
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APPENDIX A. Table of Use Patterns Subject to Reregistration
23
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24
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APPENDIX A
CASE 4027, [m-cresol] Chemical 022102
SITE Application Type, Application Form(s) Min. Appl. Max. Appl. Soil Max.
Timing, Application Equipment _ Rate (AI un- Rate (AI Tex. Apps
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. @ Max
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose Rate
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES
Maximum Dose Min. Restr. Geographic Limitations Use
/crop cycle Interv Entry Allowed Disallowed Limitations
or /year (days) Interv Codes
[day(s) ]
ALMOND
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
APPLE
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
APRICOT
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
BLUEBERRY
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
CHERRY
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
FILBERT (HAZELNUT)
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
Use Group: GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL FOOD+FEED CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL FOOD+FEED CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
-------
APPENDIX A
CASE 4027, [m-cresol] Chemical 022102
SITE Application Type, Application Form(s) Min. Appl .
Timing, Application Equipment Rate (AI un-
Surface Type (Antimicrobial only) & Effica- less noted
cy Influencing Factor (Antimicrobial only) otherwise)
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
GRAPES
Gall treatment.
Gall treatment.
Gall treatment.
Gall treatment.
NECTARINE
Gall treatment.
Gall treatment.
OLIVE
Gall treatment.
Gall treatment.
PEACH
Gall treatment.
Gall treatment.
PEAR
Gall treatment.
Gall treatment.
PECAN
Gall treatment.
Gall treatment.
PLUM
Gall treatment.
Gall treatment.
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
Max. Appl. Soil
Rate (AI Tex.
unless noted Max.
otherwise) Dose
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Max. Maximum Dose Min. Restr. Geographic Limitations Use
Apps /crop cycle Interv Entry Allowed Disallowed Limitations
@ Max or /year (days) Interv Codes
Rate [day (s) ]
GREENHOUSE FOOD CROP
NS NS 120
NS NS 120
TERRESTRIAL FOOD+FEED CROP
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
NS
NS
NS
NS
CROP
NS
NS
CROP
NS
NS
CROP
NS
NS
CROP
NS
NS
CROP
NS
NS
CROP
NS
NS
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
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APPENDIX A
CASE 4027, [m-cresol] Chemical 022102
SITE Application Type, Application Form(s) Min. Appl. Max. Appl. Soil Max.
Timing, Application Equipment _ Rate (AI un- Rate (AI Tex. Apps
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. @ Max
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose Rate
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Maximum Dose Min. Restr. Geographic Limitations Use
/crop cycle Interv Entry Allowed Disallowed Limitations
or /year (days) Interv Codes
[day(s) ]
PRUNE
Gall treatment., Dormant., Paintbrush. RTU NA
Gall treatment., Foliar., Paintbrush. RTU NA
WALNUT (ENGLISH/BLACK)
Gall treatment., Dormant., Paintbrush. RTU NA
Gall treatment., Foliar., Paintbrush. RTU NA
NON- FOOD/NON- FEED
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
ORNAMENTAL AND/OR SHADE TREES
Gall treatment., Dormant., Paintbrush. RTU NA
Gall treatment., Foliar., Paintbrush. RTU NA
ORNAMENTAL WOODY SHRUBS AND VINES
Gall treatment., Dormant., Paintbrush. RTU NA
Gall treatment., Foliar., Paintbrush. RTU NA
Use Group: TERRESTRIAL+GREENHOUSE NON-FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE NON-FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
-------
APPENDIX A _ CASE 4027, [m-Cresol] Chemical 022102 [m-cresol] LUIS 1.4 _ Page 4
HEADER ABBREVIATIONS
Max. Apps @ Max Rate : Maximum number of Applications at Maximum Dosage Rate
Min. Interv (days) : Minimum Interval between Applications (days)
Restr. Entry Interv (days) : Restricted Entry Interval (days)
SOIL TEXTURE FOR MAX APP. RATE
* : Non-specific
C : Coarse
M : Medium
F : Fine
O : Others
FORMULATION CODES
RTU : LIQUID-READY TO USE
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
DCNC : Dosage Can Not be Calculated
No Calc : No Calculation can be made
W : PPM calculated by weight
V : PPM Calculated by volume
cwt : Hundred Weight
nnE-xx : nn times (10 power -xx); for instance, "1.234E-04" is equivalent to ".0001234"
USE LIMITATIONS CODES
CAL : Do not contaminate water, food or feed.
CAM : Do not allow rinse water to contaminate streams, ponds and lakes, as water life may be endangered.
* NUMBER IN PARENTHESES REPRESENTS THE NUMBER OF TIME UNITS (HOURS,DAYS, ETC.) DESCRIBED IN THE LIMITATION.
-------
APPENDIX A _ CASE 4098, [Xylenol] Chemical 086804
SITE Application Type, Application Form(s) Min. Appl. Max. Appl. Soil Max.
Timing, Application Equipment _ Rate (AI un- Rate (AI Tex. Apps
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. @ Max
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose Rate
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES
Maximum Dose Min. Restr. Geographic Limitations Use
/crop cycle Interv Entry Allowed Disallowed Limitations
or /year (days) Interv Codes
[day(s) ]
ALMOND
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
APPLE
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
APRICOT
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
BLUEBERRY
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
CHERRY
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
FILBERT (HAZELNUT)
Gall treatment., Dormant., Paintbrush.
Gall treatment., Foliar., Paintbrush.
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
RTU NA
Use Group: GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL FOOD+FEED CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL FOOD+FEED CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
-------
APPENDIX A _ CASE 4098, [Xylenol] Chemical 086804 Page
SITE Application Type, Application Form(s) Min. Appl .
Timing, Application Equipment Rate (AI un-
Surface Type (Antimicrobial only) & Effica- less noted
cy Influencing Factor (Antimicrobial only) otherwise)
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
GRAPES
Gall treatment.
Gall treatment.
Gall treatment.
Gall treatment.
NECTARINE
Gall treatment.
Gall treatment.
OLIVE
Gall treatment.
Gall treatment.
PEACH
Gall treatment.
Gall treatment.
PEAR
Gall treatment.
Gall treatment.
PECAN
Gall treatment.
Gall treatment.
PLUM
Gall treatment.
Gall treatment.
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
. , Dormant .
. , Foliar. ,
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
, Paintbrush. RTU NA
Paintbrush. RTU NA
Max. Appl. Soil
Rate (AI Tex.
unless noted Max.
otherwise) Dose
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Use Group :
UC *
UC *
Max. Maximum Dose Min. Restr. Geographic Limitations Use
Apps /crop cycle Interv Entry Allowed Disallowed Limitations
@ Max or /year (days) Interv Codes
Rate [day (s) ]
GREENHOUSE FOOD CROP
NS NS 120
NS NS 120
TERRESTRIAL FOOD+FEED CROP
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
TERRESTRIAL+GREENHOUSE FOOD
NS NS 120
NS NS 120
NS
NS
NS
NS
CROP
NS
NS
CROP
NS
NS
CROP
NS
NS
CROP
NS
NS
CROP
NS
NS
CROP
NS
NS
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAL,
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
CAM
-------
APPENDIX A _ CASE 4098, [Xylenol] Chemical 086804
SITE Application Type, Application Form(s) Min. Appl. Max. Appl. Soil Max.
Timing, Application Equipment _ Rate (AI un- Rate (AI Tex. Apps
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. @ Max
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose Rate
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Maximum Dose Min. Restr. Geographic Limitations Use
/crop cycle Interv Entry Allowed Disallowed Limitations
or /year (days) Interv Codes
[day(s) ]
PRUNE
Gall treatment., Dormant., Paintbrush. RTU NA
Gall treatment., Foliar., Paintbrush. RTU NA
WALNUT (ENGLISH/BLACK)
Gall treatment., Dormant., Paintbrush. RTU NA
Gall treatment., Foliar., Paintbrush. RTU NA
NON- FOOD/NON- FEED
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
ORNAMENTAL AND/OR SHADE TREES
Gall treatment., Dormant., Paintbrush. RTU NA
Gall treatment., Foliar., Paintbrush. RTU NA
ORNAMENTAL WOODY SHRUBS AND VINES
Gall treatment., Dormant., Paintbrush. RTU NA
Gall treatment., Foliar., Paintbrush. RTU NA
Use Group: TERRESTRIAL+GREENHOUSE NON-FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
Use Group: TERRESTRIAL+GREENHOUSE NON-FOOD CROP
UC * NS NS 120 NS
UC * NS NS 120 NS
CAL, CAM
CAL, CAM
CAL, CAM
CAL, CAM
-------
APPENDIX A _ CASE 4098, [Xylenol] Chemical 086804 [2,4-Xylenol] Page 4
HEADER ABBREVIATIONS
Max. Apps @ Max Rate : Maximum number of Applications at Maximum Dosage Rate
Min. Interv (days) : Minimum Interval between Applications (days)
Restr. Entry Interv (days) : Restricted Entry Interval (days)
SOIL TEXTURE FOR MAX APP. RATE
* : Non-specific
C : Coarse
M : Medium
F : Fine
O : Others
FORMULATION CODES
RTU : LIQUID-READY TO USE
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
DCNC : Dosage Can Not be Calculated
No Calc : No Calculation can be made
W : PPM calculated by weight
V : PPM Calculated by volume
cwt : Hundred Weight
nnE-xx : nn times (10 power -xx); for instance, "1.234E-04" is equivalent to ".0001234"
USE LIMITATIONS CODES
CAL : Do not contaminate water, food or feed.
CAM : Do not allow rinse water to contaminate streams, ponds and lakes, as water life may be endangered.
* NUMBER IN PARENTHESES REPRESENTS THE NUMBER OF TIME UNITS (HOURS,DAYS, ETC.) DESCRIBED IN THE LIMITATION.
-------
APPENDIX B. Table of the Generic Data Requirements
and Studies Used to Make the Reregistration Decision
33
-------
34
-------
GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for active
ingredients within the case M-Cresol and Xylenol covered by this Reregistration Eligibility
Decision Document. It contains generic data requirements that apply to M-Cresol and Xylenol
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.
35
-------
36
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of M-CRESOL
REQUIREMENT
USE PATTERN
CITATION(S)
PRODUCT CHEMISTRY
61-1
61-2A
61-2B
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-6
63-7
63-8
63-9
63-10
63-11
63-12
63-13
Chemical Identity
Start. Mat. & Mnfg
Process
Formation of Impurities
Preliminary Analysis
Certification of limits
Analytical Method
Color
Physical State
Odor
Melting Point
Boiling Point
Density
Solubility
Vapor Pressure
Dissociation Constant
Octanol/Water Partition
PH
Stability
all
all
all
all
all
all
all
all
all
all
all
all
all
all
all
all
all
all
Satisfied
Satisfied
Satisifed
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
37
-------
Data Supporting Guideline Requirements for the Reregistration of M-CRESOL
REQUIREMENT
63-14
63-15
63-16
63-17
63-18
63-19
Oxidizing/Reducing Action
Flammability
Explodability
Storage stability
Viscosity
Miscibility
USE PATTERN
all
all
all
all
all
all
CITATION(S)
Satisfied
Satisifed
Satisfied
Satisfied
Satisfied
Satisfied
ECOLOGICAL EFFECTS
71-1A
71-1B
71-2A
71-2B
71-3
71-4A
71-4B
71-5A
71-5B
72-1A
Acute Avian Oral - Quail/Duck
Acute Avian Oral - Quail/Duck
TEP
Avian Dietary - Quail
Avian Dietary - Duck
Wild Mammal Toxicity
Avian Reproduction - Quail
Avian Reproduction - Duck
Simulated Field Study
Actual Field Study
Fish Toxicity Bluegill
A.B.C.H.I
A,B,C,H,I
A,B,C,H,I
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
38
-------
Data Supporting Guideline Requirements for the Reregistration of M-CRESOL
REQUIREMENT
72-1B
72-1C
72-1D
72-2A
72-2B
72-3A
72-3B
72-3C
72-3D
72-3E
72-3F
72-4A
72-4B
72-5
72-6
72-7A
Fish Toxicity Bluegill - TEP
Fish Toxicity Rainbow Trout
Fish Toxicity Rainbow Trout- TEP
Invertebrate Toxicity
Invertebrate Toxicity - TEP
Estuarine/Marine Toxicity - Fish
Estuarine/Marine Toxicity -
Mollusk
Estuarine/Marine Toxicity -
Shrimp
Estuarine/Marine Toxicity Fish-
TEP
Estuarine/Marine Toxicity Mollusk
-TEP
Estuarine/Marine Toxicity Shrimp
-TEP
Early Life Stage Fish
Life Cycle Invertebrate
Life Cycle Fish
Aquatic Organism Accumulation
Simulated Field - Aquatic
USE PATTERN
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
CITATION(S)
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
72-7B
Organisms
Actual Field - Aquatic Organisms
A,B,C,H,I
Waived
39
-------
Data Supporting Guideline Requirements for the Reregistration of M-CRESOL
REQUIREMENT
122-1A
122-1B
122-2
123-1A
123-1B
123-2
124-1
124-2
141-1
141-2
141-5
Seed Germination/Seedling
Emergence
Vegetative Vigor
Aquatic Plant Growth
Seed Germination/Seedling
Emergence
Vegetative Vigor
Aquatic Plant Growth
Terrestrial Field
Aquatic Field
Honey Bee Acute Contact
Honey Bee Residue on Foliage
Field Test for Pollinators
USE PATTERN
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
CITATION(S)
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
TOXICOLOGY
81-1
81-2
81-3
81-4
81-5
81-6
82-1A
Acute Oral Toxicity - Rat
Acute Dermal Toxicity -
Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit
Dermal Sensitization - Guinea Pig
90-Day Feeding - Rodent
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
Satified
Satified
Waived
00138519
00138520
00138521
Satified
40
-------
Data Supporting Guideline Requirements for the Reregistration of M-CRESOL
REQUIREMENT
82-2
83-3A
83-4
84-2A
84-2B
84-4
85-1
21 -Day Dermal - Rabbit/Rat
Developmental Toxicity - Rat
2-Generation Reproduction - Rat
Gene Mutation (Ames Test)
Structural Chromosomal
Aberration
Other Genotoxic Effects
General Metabolism
USE PATTERN
A.B.C.H.I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
CITATION(S)
00138524
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
OCCUPATIONAL/RESIDENTIAL EXPOSURE
231
232
233
234
Estimation of Dermal Exposure at
Outdoor Sites
Estimation of Inhalation Exposure
at Outdoor Sites
Estimation of Dermal Exposure at
Indoor Sites
Estimation of Inhalation Exposure
at Indoor Sites
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
Satisfied
Waived
Satisfied
Waived
ENVIRONMENTAL FATE
160-5
161-1
161-2
161-3
162-1
Chemical Identity
Hydrolysis
Photodegradation - Water
Photodegradation - Soil
Aerobic Soil Metabolism
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
Waived
Waived
Waived
Waived
Waived
41
-------
Data Supporting Guideline Requirements for the Reregistration of M-CRESOL
REQUIREMENT
162-2
162-3
162-4
163-1
163-2
163-3
164-1
164-2
164-3
165-1
RESIDUE
171-4A
171-4B
171-4C
171-4D
171-4E
171-4F
Anaerobic Soil Metabolism
Anaerobic Aquatic Metabolism
Aerobic Aquatic Metabolism
Leaching/Adsorption/Desorption
Volatility - Lab
Volatility - Field
Terrestrial Field Dissipation
Aquatic Field Dissipation
Forest Field Dissipation
Confined Rotational Crop
CHEMISTRY
Nature of Residue - Plants
Nature of Residue - Livestock
Residue Analytical Method - Plants
Residue Analytical Method -
Animal
Storage Stability
Magnitude of Residues - Potable
USE PATTERN
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
A,B,C,H,I
A.B.C.H.I
CITATION(S)
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
H2O
171-4G Magnitude of Residues in Fish
A.B.C.H.I
Waived
42
-------
Data Supporting Guideline Requirements for the Reregistration of M-CRESOL
REQUIREMENT
171-4H
171-41
171-4J
171-4K
171-4L
171-5
171-6
171-7
171-13
Magnitude of Residues - Irrigated
Crop
Magnitude of Residues - Food
Handling
Magnitude of Residues -
Meat/Milk/Poultry/Egg
Crop Field Trials
Processed Food
Reduction of Residues
Proposed Tolerance
Support for Tolerance
Analtyical Reference Standard
USE PATTERN
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
A.B.C.H.I
A.B.C.H.I
CITATION(S)
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
43
-------
44
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of XYLENOL
REQUIREMENT
USE PATTERN
CITATION(S)
PRODUCT CHEMISTRY
61-1
61-2A
61-2B
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-6
63-7
63-8
63-9
63-10
63-11
63-12
63-13
63-14
Chemical Identity
Start. Mat. & Mnfg. Process
Formation of Impurities
Preliminary Analysis
Certification of limits
Analytical Method
Color
Physical State
Odor
Melting Point
Boiling Point
Density
Solubility
Vapor Pressure
Dissociation Constant
Octanol/Water Partition
PH
Stability
Oxidizing/Reducing Action
all
all
all
all
all
all
all
all
all
all
all
all
all
all
all
all
all
all
all
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisified
Satisfied
Satisifed
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
Satisfied
45
-------
Data Supporting Guideline Requirements for the Reregistration of XYLENOL
REQUIREMENT
63-15
63-16
63-17
63-18
63-19
Flammability
Explodability
Storage stability
Viscosity
Miscibility
USE PATTERN
all
all
all
all
all
CITATION(S)
Satisfied
Satisfied
Satisifed
Satisfied
Satisfied
ECOLOGICAL EFFECTS
71-1A
71-1B
71-2A
71-2B
71-3
71-4A
71-4B
71-5A
71-5B
72-1A
72-1B
Acute Avian Oral - Quail/Duck
Acute Avian Oral - Quail/Duck
TEP
Avian Dietary - Quail
Avian Dietary - Duck
Wild Mammal Toxicity
Avian Reproduction - Quail
Avian Reproduction - Duck
Simulated Field Study
Actual Field Study
Fish Toxicity Bluegill
Fish Toxicity Bluegill - TEP
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
A.B.C.H.I
A.B.C.H.I
A.B.C.H.I
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
46
-------
Data Supporting Guideline Requirements for the Reregistration of XYLENOL
REQUIREMENT
72-1C
72-1D
72-2A
72-2B
72-3A
72-3B
72-3C
72-3D
72-3E
72-3F
72-4A
72-4B
72-5
72-6
72-7A
72-7B
122-1A
Fish Toxicity Rainbow Trout
Fish Toxicity Rainbow Trout- TEP
Invertebrate Toxicity
Invertebrate Toxicity - TEP
Estuarine/Marine Toxicity - Fish
Estuarine/Marine Toxicity -
Mollusk
Estuarine/Marine Toxicity -
Shrimp
Estuarine/Marine Toxicity Fish-
TEP
Estuarine/Marine Toxicity Mollusk
-TEP
Estuarine/Marine Toxicity Shrimp
-TEP
Early Life Stage Fish
Life Cycle Invertebrate
Life Cycle Fish
Aquatic Organism Accumulation
Simulated Field - Aquatic
Organisms
Actual Field - Aquatic Organisms
Seed Germination/Seedling
Emergence
USE PATTERN
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
CITATION(S)
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
47
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Data Supporting Guideline Requirements for the Reregistration of XYLENOL
REQUIREMENT
122-1B
122-2
123-1A
123-1B
123-2
124-1
124-2
141-1
141-2
141-5
Vegetative Vigor
Aquatic Plant Growth
Seed Germination/Seedling
Emergence
Vegetative Vigor
Aquatic Plant Growth
Terrestrial Field
Aquatic Field
Honey Bee Acute Contact
Honey Bee Residue on Foliage
Field Test for Pollinators
USE PATTERN
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
CITATION(S)
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
TOXICOLOGY
81-1
81-2
81-3
81-4
81-5
81-6
82-1A
82-1B
82-2
Acute Oral Toxicity - Rat
Acute Dermal Toxicity -
Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit
Dermal Sensitization - Guinea Pig
90-Day Feeding - Rodent
90-Day Feeding - Non-rodent
21 -Day Dermal - Rabbit/Rat
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
Satisfied
Satisfied
Waived
00138519
00138520
00138521
Waived
Waived
00138524
48
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Data Supporting Guideline Requirements for the Reregistration of XYLENOL
REQUIREMENT
84-2A
84-2B
84-4
Gene Mutation (Ames Test)
Structural Chromosomal
Aberration
Other Genotoxic Effects
USE PATTERN
A.B.C.H.I
A.B.C.H.I
A,B,C,H,I
CITATION(S)
Waived
Waived
Waived
OCCUPATIONAL/RESIDENTIAL EXPOSURE
231
232
233
234
Estimation of Dermal Exposure at
Outdoor Sites
Estimation of Inhalation Exposure
at Outdoor Sites
Estimation of Dermal Exposure at
Indoor Sites
Estimation of Inhalation Exposure
at Indoor Sites
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
Satisfied
Waived
Satisfied
Waived
ENVIRONMENTAL FATE
160-5
161-1
161-2
161-3
162-1
162-2
162-3
162-4
163-1
Chemical Identity
Hydrolysis
Photodegradation - Water
Photodegradation - Soil
Aerobic Soil Metabolism
Anaerobic Soil Metabolism
Anaerobic Aquatic Metabolism
Aerobic Aquatic Metabolism
Leaching/Adsorption/Desorption
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
49
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
-------
Data Supporting Guideline Requirements for the Reregistration of XYLENOL
REQUIREMENT
163-2
163-3
164-1
164-2
164-3
165-1
RESIDUE
171-4A
171-4B
171-4C
171-4D
171-4E
171-4F
171-4G
171-4H
171-41
171-4J
171-4K
Volatility - Lab
Volatility - Field
Terrestrial Field Dissipation
Aquatic Field Dissipation
Forest Field Dissipation
Confined Rotational Crop
CHEMISTRY
Nature of Residue - Plants
Nature of Residue - Livestock
Residue Analytical Method - Plants
Residue Analytical Method -
Animal
Storage Stability
Magnitude of Residues - Potable
H2O
Magnitude of Residues in Fish
Magnitude of Residues - Irrigated
Crop
Magnitude of Residues - Food
Handling
Magnitude of Residues -
Meat/Milk/Poultry/Egg
Crop Field Trials
USE PATTERN
A.B.C.H.I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
A,B,C,H,I
50
CITATION(S)
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
Waived
-------
Data Supporting Guideline Requirements for the Reregistration of XYLENOL
REQUIREMENT
USE PATTERN
CITATION(S)
171-4L Processed Food
171-5 Reduction of Residues
171-6 Proposed Tolerance
171-7 Support for Tolerance
171-13 Analtyical Reference Standard
A.B.C.H.I
A,B,C,H,I
A.B.C.H.I
A,B,C,H,I
A.B.C.H.I
Waived
Waived
Waived
Waived
Waived
51
-------
52
-------
APPENDIX C. Citations Considered to be Part of the Data
Base Supporting the Reregistration of M-Cresol and
Xylenol
53
-------
54
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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
55
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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.
56
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BIBLIOGRAPHY
MRID
CITATION
00138519 Goyings, L.; Burr, W.; Kaczkofsky, H. (1967) Bacticin: Eye Irritation Study
in the Rabbit: 231-9610-8. (Unpublished study received Aug 9, 1967 uder
1023-46; submitted by Upjohn Co., Kalamazoo, MI; CDL:005491-F)
00138520 Wazeter, F.; Buller, R.; Geil, R. (1966) Primary Skin Irritation in the Albino
Rabbit: Experimental Bactericide P: 400-011; 231-9610-1. (Unpublished study
received Aug 9, 1967 under 1023-46; prepared by International Research and
Development Corp., submitted by Upjohn Co.,Kalamazoo, MI;
CDL:005491-G)
00138521 Wazeter, F.; Buller, R.; Geil, R. (1966) Dermal Sensitization in the Guinea
Pig: Experimental Bactericide P: 400-012; 231-9610-2. (Unpublished study
received Aug 9, 1967 under 1023-46; prepared by International Research and
Development Corp., submitted by Upjohn Co., Kalamazoo, MI;
CDL:005491-H)
00138524 Wazeter, F.; Buller, R.; Geil, R.; et al. (1967) Three Week Repeat ed Dermal
Application in Albino Rabbits: 400-046; 231-9610-9. (Unpublished study
received Aug 9, 1967 under 1023-46; prepared by International Research and
Development Corp., submitted by Upjohn Co., Kalamazoo, MI;
CDL:005491-K)
Bushy Run Research Center. 1988. Developmental Toxicity Evaluation of o-,
m-, or p-Cresol Administered by Gavage to Sprague Dawley (CD) Rats.
Unpublished study submitted to EPA/OTS (Fiche no. OTS0517695).
Bushy Run Research Center. 1989. Two-Generation Reproduction Study of m-
Cresol (CAS No. 108-39-4) Administered by Gavage to Sprague-Dawley (CD)
Rats. Report No. 51-634. Unpublished study submitted to EPA/OTS by the
Chemical Manufacturers Assoc. Cresols Panel.
Dietz, D.D. 1992. CRC Handbook of Chemistry.
Hazleton Laboratories. 1988a. Mutagenicity Test on Meta-Cresol in a Mouse
Lymphoma Mutation Assay. Study No. 10003-0-431. Unpublished study
submitted to EPA/OTS.
57
-------
BIBLIOGRAPHY
MRID CITATION
Hazleton Laboratories. 1988b. Mutagenicity Test on Meta-Cresol in the Rat
Primary Hepatocyte Unscheduled DNA Synthesis Assay. Study No. 10002-0-
447. Unpublished study submitted to EPA/OTS.
Hazleton Laboratories. 1988c. Mutagenicity Test on Meta-Cresol in an in Vitro
Cytogenetic Assay Measuring Chromosomal Aberration Frequencies in Chinese
Hamster Ovary (CHO) Cells. Study No. 10003-0-437. Unpublished study
submitted to EPA/OTS.
Hazleton Laboratories. 1988d. Genetic Toxicology Test on Meta-Cresol in the
In Vitro Transformation of BALB/C-3T3 Cells Assay. Study No. 10002-0-441.
Unpublished study submitted to EPA/OTS.
Hazleton Laboratories. 1989. Mutagenicity Test on Cresol Program Panel
Sample #2 Meta-Cresol in the Mouse Bone Marrow Cytogenetic Assay. Study
No. 10002-0-451. Unpublished study submitted to EPA/OTS.
Health and Human Services. 1992. Toxicological Profile for Cresols. PHS. TP-
91/11.
Izard, M.K.; George, J.D.; Fail, P.A.; Grizzle, T.B. 1992. Reproductive
Toxicity of Meta-/Para-Cresol (MPCRE) in CD-I Swiss Mice. Study No.
NTP89-RACB-85. Study conducted for National Toxicology Program.
Ride, D. Handbook of Chemistry and Physics. 71st edition. (CRC Press, FL).
Sax, N.I., and Lewis, R.J. SR, (1989) Dangerous Properties of Industrial
Materials, 7th Edition. Van Nostrand Reinhold, NY.
Toxicity Studies of Cresols in F344/N Rats and B6C3F1 Mice. NTP TOX 9.
Studies conducted by the National Toxicology Program.
Windholz, S., Budavari, R. and E. Otterbein (eds.). Merck Index. 10th
edition. (Merck & Co., Inc. 1983).
58
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APPENDIX D. List of Available Related Documents
59
-------
60
-------
The following is a list of available documents related to M-Cresol and Xylenol. It's
purpose is to provide a path to more detailed information if it is needed. These accompanying
documents are part of the Administrative Record for M-Cresol and Xylenol and are included
in the EPA's Office of Pesticide Programs Public Docket.
1. Health and Environmental Effects Science Chapters
2. Detailed Label Usage Information System (LUIS) Report
3. M-Cresol and Xylenol RED Fact Sheet
4. PR Notice 86-5 (included in this appendix)
5. PR Notice 91-2 (included in this appendix) pertains to the Label Ingredient
Statement
61
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62
-------
APPENDIX E. PR Notices 86-5 and 91-2
63
-------
64
-------
PR Notice 86-5
65
-------
66
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
tpno1 WASHINGTON, D.C. 20460
July 29, 1986
OFFICE OF
PR NOTICE 86-5 PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
NOTICE TO PRODUCERS, FORMULATORS, DISTRIBUTORS
AND REGISTRANTS
Attention: Pers9ns responsible for Federal registration of
pesticides.
Subject: Standard format for data submitted under the
Federal Insecticide, Fungicide, and Rodenticide
Act (FIFRA) and certain provisions of the Federal
Food, Drug, and Cosmetic Act (FFDCA).
I. Purpose
To require data to be submitted to the Environmental
Protection Agency (EPA) in a standard format. This Notice also
provides additional guidance about, and illustrations of, the
required formats.
II. Applicability
This PR Notice applies to all data that are submitted to EPA
to satisfy data requirements for granting or maintaining
pesticide registrations, experimental use permits, tolerances,
and related approvals under certain provisions of FIFRA and
FFDCA. These data are defined in FIFRA §10(d)(1). This Notice
does not apply to commercial, financial, or production
information, which are, and must continue to be, submitted
differently under separate cover.
Ill. Effective Date
This notice is effective on November 1, 1986. Data formatted
according to this notice may be submitted prior to the effective
date. As of the effective date, submitted data packages that do
not conform to these requirements may be returned to the
submitter for necessary revision.
IV. Background
On September 26, 1984, EPA published proposed regulations in
the Federal Register (49 FR 37956) which include Requirements for
Data Submission (40 CFR §158.32), and Procedures for Claims of
Confidentiality of Data (40 CFR §158.33). These regulations
specify the format for data submitted to EPA under Section 3 of
FIFRA and Sections 408 and 409 of FFDCA, and procedures which
must be followed to make and substantiate claims of confiden-
tiality. No entitlements to data confidentiality are changed,
either by the proposed regulation or by this notice.
OPP is making these requirements mandatory through this
Notice to gain resource-saving benefits from their use before the
67
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entire proposed regulation becomes final. Adequate lead time is
being provided for submitters to comply with the new
requirements.
V. Relationship of this Notice to Other OPP Policy and Guidance
While this Notice contains requirements for organizing and
formatting submittals of supporting data, it does not address the
substance of test reports themselves. "Data reporting" guidance
is now under development in OPP, and will specify how the study
objectives, protocol, observations, findings, and conclusions are
organized and presented within the study report. The data
reporting guidance will be C9mpatible with submittal format
requirements described in this Notice.
OPP has also promulgated a policy (PR Notice 86-4 dated
April 15, 1986) that provides for early screening of certain
applications for registration under FIFRA §3. The objective of
the screen is to avoid the additional C9sts and prolonged delays
associated with handling significantly incomplete application
packages. As of the effective date of this Notice, the screen
will include in its criteria for acceptance of applicati9n
packages the data formatting requirements described herein.
OPP has also established a public docket which imposes
deadlines for inserting int9 the docket documents submitted in
connection with Special Reviews and Registration Standards (see
40 CFR §154.15 and §155.32). To meet these deadlines, OPP is
requiring an additional copy of any data submitted to the docket.
Please refer to Page 10 for more information about this
requirement.
For several years, OPP has required that each application
for registration or other action include a list 9f all applicable
data requirements and an indication of how each is satisfied--the
statement of the method of support f9r the application.
Typically, many requirements are satisfied by reference to data
previously submitted--either by the applicant or by another
party. That requirement is not altered by this notice, which
applies only to data submitted with an application.
VI. Format Requirements
A more detailed discussion of these format requirements
foll9ws the index on the next page, and samples of some of the
requirements are attached. Except for the language 9f the two
alternative forms of the Statement of Data Confidentiality Claims
(shown in Attachment 3) which cannot be altered, these samples
are illustrative. As long as the required information is
included and clearly identifiable, the form of the samples may be
altered to reflect the submitter's preference.
- INDEX-
Text Example
Page Page
A. Organization of the Submittal Package 3 17
B. Transmittal Document 4 11
C. Individual Studies 4
C. 1 Special Considerations for Identifying Studies . . 5
D. Organization of each Study Volume 6 17
D. 1 Study Title Page 7 12
68
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D. 2 Statement of Data Confidentiality Claims
(based on FIFRA §10 (d) (1)1 8 13
D. 3 Confidential Attachment 8 15
D. 4 Supplemental Statement of Data Confidentiality
Claims (other than those based on FIFRA §10(d)(1) ) 8 14
D. 5 Good Laboratory Practice Compliance Statement . . 9 16
E. Reference to Previously Submitted Data 9
F. Physical Format Requirements & Number of Copies .... 9
G. Special Requirements for Submitting Data to the Docket 10
A. Organization of Submittal Package
A "submittal package" consists of all studies submitted at
the same time f9r review in support of a single regulatory
action, along with a transmittal document and other related
administrative material (e.g. the method of support statement,
EPA Forms 8570-1, 8570-4, 8570-20, etc.) as appropriate.
Data submitters must organize each submittal package as
described in this Notice. The transmittal and any other admin-
istrative material must be grouped together in the first physical
volume. Each study included in the submittal package must then
be bound separately.
Submitters sometimes provide additional materials that are
intended to clarify, emphasize, or otherwise comment to help
Product Managers and reviewers better understand the submittal.
If such materials relate to one study, they should be
included as an appendix to that study.
- If such materials relate to more than one study (as for
example a summary of all studies in a discipline) or to the
submittal in general, they must be included in the submittal
package as a separate study (with title page and statement
of confidentiality claims).
B. Transmittal Document
The first item in each submittal package must be a trans-
mittal document. This document identifies the submitter or all
joint submitters; the regulatory action in support of which the
package is being submitted--!.e., a registration application,
petition, experimental use permit (EUPT, §3(c)(2)(B) data
call-in, §6(a)(2) submittal, 9r a special review; the transmittal
date; and a list of all individual studies included in the
gackage in the order of their appearance, showing (usually by
uideline reference number) the data requirement(s) addressed by
each one. The EPA-assigned number for the regulatory action
(e.g. the registration, EUP, or tolerance petition number) should
be included in the transmittal document as well, if it is known
to the submitter. See Attachment 1 for an example of an
acceptable transmittal document.
The list of included studies in the transmittal of a data
submittal package supporting a registration application should be
subdivided by discipline, reflecting the order in which data
requirements appear in 40 CFR 158.
The list of included studies in the transmittal of a data
submittal package supporting a petition for tolerance or an
69
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application for an EUP should be subdivided into sections A, B,
C,.... of the petition or application, as defined in 40 CFR 180.7
and 158.125, (petitions) or Pesticide Assessment Guidelines,
Subdivision I (EUPs) as appropriate.
When a submittal package supports a tolerance petiti9n and
an application for a registration or an EUP, list the petition
studies first, then the balance of the studies. Within these two
groups of studies follow the instructions above.
C. Individual Studies
A study is the report of a single scientific investigation,
including all supporting analyses required for logical complete-
ness. A study should be identifiable and distinguishable by a
C9nventional bibliographic citation including author, date, and
title. Studies generally correspond in scope to a single Guide-
line requirement for supporting data, with 39016 exceptions dis-
cussed in section C.I. Each study included in a submittal
Eackage must be bound as a separate entity. (See comments on
inding studies on page 9.)
Each study must be consecutively paginated, beginning from
the title page as page 1. The total number of pages in the com-
plete study must be shown on the study title page. In addition
(to ensure that inadvertently separated pages can be reassociated
with the proper study during handling or review) use either of
the following:
- Include the total number of pages in the complete study on
each page (i.e., 1 of 250, 2 of 250, ...250 of 250).
- Include a company name or mark and study number on each
page of the study, e g , Company Name-1986-23. Never reuse
a study number for marking the pages of subsequent studies.
When a single study is extremely long, binding it in mul-
tiple V9lumes is permissible so long as the entire study is pag-
inated in a single series, and each volume is plainly identified
by the study title and its position in the multi-volume sequence.
C.1 Special Considerations for Identifying Studies
Some studies raise special problems in study identification,
because they address Guidelines of broader than normal scope or
for other reasons.
a. Safety Studies. Several Guidelines require testing for
safety in more than one species. In these cases each species
tested should be reported as a separate study, and bound
separately.
Extensive supplemental reports of pathology reviews, feed
analyses, historical C9ntrol data, and the like are often assoc-
iated with safety studies. Whenever possible these should be
submitted with primary reports of the study, and bound with the
primary study as appendices. When such supplemental reports are
submitted independently of the primary report, take care to fully
identify the primary report to which they pertain.
Batteries of acute toxicity tests, performed on the same end
use product and covered by a single title page, may be bound
together and reported as a single study.
b. Product Chemistry Studies. All product chemistry data
within a submittal package submitted in support of an end-use
product produced from registered manufacturing-use products
should be bound as a single study under a single title page.
Product chemistry data submitted in support of a technical
product, other manufacturing-use product, an experimental use
permit, an import tolerance petition, or an end-use product
70
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produced from unregistered source ingredients, should be bound as
a single study for each Guideline series (61, 62, and 63) for
C9nventional pesticides, or for the equivalent subject range for
biorational pesticides. The first of the three studies in a
complete product chemistry submittal for a biochemical pesticide
would cover Guidelines 151-10, 151-11, and 151-12; the second
would cover Guidelines 151-13, 151-15, and 151-16; the third
would cover Guideline 151-17. The first study for a microbial
pesticide would cover Guidelines 151-20, 151-21, and 151-22; the
second W9uld cover Guidelines 151-23 and 151-25; the third would
cover Guideline 151-26.
Note particularly that product chemistry studies are likely
to contain Confidential Business Information as defined in FIFRA
§10(d)(1)(A), (B) , or (C), and if so must be handled as described
in section D.3. of this notice.
c. Residue Chemistry Studies. Guidelines 171-4, 153-3,
and 153-4 are extremely broad in scope; studies addressing
residue chemistry requirements must thus be defined at a level
below that of the Guideline code. The general principle,
h9wever, of limiting a study to the report of a single inves-
tigation still applies fully. Data should be treated as a single
study and bound separately for each analytical method, each
report of the nature of the residue in a single crop or animal
species, and for each report of the magnitude of residues
resulting from treatment of a single crop or from processing a
single crop. When more than one commodity is derived from a
single crop (such as beet tops and beet roots) residue data on
all such C9mmodities should be reported as a single study. When
multiple field trials are associated with a single crop, all such
trials should be reported as a single study.
D.
Organization of Each Study Volume
Each complete study must include all applicable elements in
the list below, in the order indicated. (Also see Page 17.)
Several of these elements are further explained in the following
paragraphs. Entries in the column headed "example" cite the
page number of this notice where the element is illustrated.
Element
Study Title Page
Statement of Data
Confidentiality
Claims
Certification of Good
Laboratory Practice
Flagging statements
Body of Study
Study Appendices
Cover Sheet to Confi-
dential Attachment
When Required Example
Always Page 12
One of the two alternative Page 13
forms of this statement
is always required
If study reports Iaborat9ry Page 16
work subject to GLP require-
ments
For certain t9xicology studies (When
flagging requirements are finalized.)
Always - with an English language
translation if required.
At submitter's option
If CBI is claimed under FIFRA
§10 (d) (1) (A) , (B) , or (C)
CBI Attachment
Supplemental Statement
of Data Confidentiality
Claims
If CBI is claimed under FIFRA
§10 (d) (1) (A) , (B) , or (C) Page 15
Only if confidentiality is Page 14
claimed on a basis other than
FIFRA §10(d)(1)(A), (B), or (C)
71
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D.I. Title Page
A title page is always required for each submitted study,
published or unpublished. The title page must always be freely
releasable to requestors; DO NOT INCLUDE CBI ON THE TITLE PAGE.
An example of an acceptable title page is on page 12 of this
notice. The following information must appear on the title page:
a. Study title. The study title should be as descriptive as
possible It must clearly identify the substance(s) tested and
correspond to the name of the data requirement as it appears in
the Guidelines.
b. Data requirement addressed. Include on the title page the
Guideline number(s) of the specific requirement(s) addressed by
the study.
c. Author(s). Cite only individuals with primary intellectual
responsibility for the C9ntent 9f the study. Identify them
plainly as authors, to distinguish them from the performing
laboratory, study sponsor, or other names that may also appear on
the title page.
d. Study Date. The title page must include a single date for
the study. If parts of the study were performed at different
times, use only the date of the latest element in the study.
e. Performing Laboratory IdentificatJ9n. If the study reports
work done by one or more laboratories,Include on the title page
the name and address of the performing laboratory or
laboratories, and the laboratory's internal project number(s) for
the work. Clearly distinguish the laboratory's project
identifier from any other reference numbers provided by the study
sponsor or submitter.
f. Supplemental Submissions. If the study is a commentary on
or supplement to another previously submitted study, or if it
responds to EPA questions raised with respect to an earlier
study, include 9n the title page elements a. through d. for the
previ9usly submitted study, along with the EPA Master Record
Identifier (MRID) or Accession number of the earlier study if you
know these numbers. (Supplements submitted in the same submittal
package as the primary study should be appended to and bound with
the primary stuay. Do not include supplements to more than one
study under a single title page).
g. Facts of Publication. If the study is a reprint of a pub-
lished d9cument, identity on the title page all relevant facts of
publication, such as the J9urnal title, volume, issue, inclusive
page numbers, and publication date.
D.2. Statements of Data Confidentiality Claims Under FIFRA
§10(d) (1) .
Each submitted study must be accompanied by one of the two
alternative forms of the statement of Data Confidentiality Claims
specified in the proposed regulation in §158.33 (b) and (c) (See
Attachment 3). These statements apply only to claims of data
confidentiality based on FIFRA §10(d)(1)(A), (B), or (C). Use
the appropriate alternative form of the statement either to
assert a claim of §10(d)(l) data confidentiality (§158.33(b)) or
to waive such a claim (§158.33(c)). In either case, the
statement must be signed and dated, and must include the typed
name and title of the official who signs it. Do not make CBI
72
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claims with respect to analytical methods associated with pet-
itions for tolerances or emergency exemptions (see NOTE Pg 13).
D.3. Confidential Attachment
If the claim is made that a study includes confidential
business information as defined by the criteria of FIFRA
§10(D)(1)(A), (B), or (C) (as described in D.2. above) all such
information must be excised from the body of the study and
confined to a separate study-specific Confidential Attachment.
Each passage of CBI so isolated must be identified by a reference
number cited within the body of the study at the point from which
the passage was excised (See Attachment 5).
The Confidential Attachment to a study must be identified by
a cover sheet fully identifying the parent study, and must be
clearly marked "Confidential Attachment." An appropriately
annotated photocopy of the parent study title page may be used as
this cover sheet. Paginate the Confidential Attachment
separately from the body of the study, beginning with page 1 of X
on the title page. Each passage confined t9 the Confidential
Attachment must be associated with a specific cross reference to
the page(s) in the main body of the study on which it is cited,
and with a reference to the applicable passage(s) of FIFRA
§10(d)(1) on which the confidentiality claim is based.
D.4. Supplemental Statement of Data Confidentiality Claims (See
Attachment 4)
If you wish to make a claim of confidentiality for any
)ortion of a submitted study other than described by FIFRA £
[I)(A), (B), or (C), the following provisions apply:
- The specific information to which the claim applies must
be clearly marked in the body of the study as subject to a
claim of confidentiality.
- A Supplemental Statement 9f Data Confidentiality Claims
must be submitted, identifying each passage claimed confi-
dential and describing in detail the basis for the claim.
A list of the points to address in such a statement is
included in Attachment 4 on Pg 14.
- The Supplemental Statement of Data Confidentiality Claims
must be signed and dated and must include the typed name and
title of the official who signed it.
D.5. Good Laboratory Practice Compliance Statement
This statement is required if the study contains laboratory
work subject to GLP requirements specified in 40 CFR 160. Sam-
ples of these statements are shown in Attachment 6.
E. Reference to Previously Submitted Data
DO NOT RESUBMIT A STUDY THAT HAS PREVIOUSLY BEEN SUBMITTED
FOR ANOTHER PURPOSE unless EPA specifically requests it. A copy
of the title page plus the MRID number (if known) is sufficient
to allow us t9 retrieve the study immediately for review. This
prevents duplicate entries in the Agency files, and saves you
the cost of sending more copies of the study. References to pre-
viously submitted studies smpuld not be included in the transmit-
tal document, but should be incorp9rated into the statement of
the method of support for the application.
F. Physical Format Requirements
All elements in the data submittal package must be on
uniform 8 1/2 by 11 inch white paper, printed 9n one side only in
black ink, with high contrast and good res9lution. Bindings for
individual studies must be secure, but easily removable to permit
73
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disassembly for microfilming. Check with EPA for special
instructions bef9re submitting data in any medium other than
paper, such as film or magnetic media.
Please be particularly attentive to the following points:
• Do not include frayed or torn pages.
• Do not include carbon copies, or copies in other than
black ink.
• Make sure that photocopies are clear, complete, and
fully readable.
• Do not include oversize computer printouts or fold-out
pages.
• Do not bind any documents with glue or binding tapes.
• Make sure that all pages of each study, including any
attachments or appendices, are present and in correct
sequence.
Number of Copies Required - All submittal packages except
those associated with a Registration Standard or Special Review
(See Part G below) must be provided In three complete, identical
copies. (The prop9sed regulati9ns specified two copies; three
are now being required to expedite and reduce the cost of
processing data into the OPP Pesticide Document Management System
and getting it into review.)
G. Special Requirements for Submitting Data to the Docket
Data submittal packages associated with a Registration Stan-
dard 9r Special Review must be provided in four C9pies, fr9m one
of which all material claimed as CBI has been excised. This
fourth copy will become part of the public docket for the RS or
SR case. If no claims of confidentiality are made for the study,
the fourth copy should be identical to the other three. When
portions of a study submitted in support of an RS or SR are
claimed as CBI, the first three copies will include the CBI
material as provided in section D of this notice. The following
special preparation is required for the fourth copy.
• Remove the "Supplemental Statement of Data
Confidentiality Claims".
• Remove the "Confidential Attachment".
• Excise from the body of the study any information you
claim as confidential, even if it does not fall within
the scope of FIFRA §10(d)(1)(A), (B), or (C). Do not
close up or paraphrase text remaining after this
excision.
• Mark the fourth copy plainly on both its cover and its
title page with the phrase "Public Docket Material -
contains no information claimed as confidential".
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V. For Further Information
For further information contact John Carley, Chief,
Information Services Branch, Program Management and Support
Division, (703) 305-5240.
/S/
James W. Akerman
Acting Director,
Registration Division
Attachment 1. Sample Transmittal Document
Attachment 2. Sample Title Page for a Newly Submitted Study
Attachment 3. Statements of Data Confidentiality Claims
Attachment 4. Supplemental Statement of Data Confidentiality
Claims
Attachment 5. Samples of Confidential Attachments
Attachment 6. Sample G9od Laboratory Practice Statements
Attachment 7. Format Diagrams for Submittal Packages and Studies
75
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ATTACHMENT 1
ELEMENTS TO BE INCLUDED IN THE TRANSMITTAL DOCUMENT*
1. Name and address of submitter (or all joint submitters**)
"Smith Chemical Corporation Jones Chemical Company
1234 West Smith Street -and- 5678 Wilson Blvd
Cincinnati, OH 98765 Covington, KY 56789
"Smith Chemical Corp will act as sole agent for all submitters.
2. Regulatory action in support of which this package is
submitted
Use the EPA identification number (e.g. 359-EUP-67) if you know
it. Otherwise describe the type of request (e.g. experimental
use permit, data call-in - of xx-xx-xx date).
3. Transmittal date
4. List of submitted studies
Vol 1. Administrative materials - forms, previous corres-
pondence with Project Managers, and so forth.
Vol 2. Title of first study in the submittal (Guideline
No.)
Vol n Title of nth study in the submittal (Guideline
No.)
* Applicants commonly provide this information in a tran-
smittal letter. This remains an acceptable practice so
long as all four elements are included.
* Indicate which of the J9int submitters is empowered to
act on behalf of all joint submitters in any matter
concerning data compensation or subsequent use or
release of the data.
Company Official:
Name Signature
Company Name
Company Contact:
Name Phone
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ATTACHMENT 2
SAMPLE STUDY TITLE PAGE FOR A NEWLY SUBMITTED STUDY
Study Title
(Chemical name) - Magnitude of Residue on Corn
Data Requirement
Guideline 171-4
Author
John C. Davis
Study Completed On
January 5, 1979
Performing Laboratory
ABC Agricultural Laboratories
940 West Bay Drive
Wilmington, CA 39897
Laboratory Project ID
ABC 47-79
Page 1 of X
(X is the total number of pages in the study)
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ATTACHMENT 3
STATEMENTS OF DATA CONFIDENTIALITY CLAIMS
1. No claim of confidentiality under FIFRA §10(d)(1)(A),(B), or (C).
STATEMENT OF NO DATA CONFIDENTIALITY CLAIMS
No claim of confidentiality is made for any information contained in this
study on the basis of its falling within the scope of FIFRA
6§10(d)(1)(A), (B), or (C).
Company
Company Agent: Typed Name Date:
Title Signature
2. Claim of confidentiality under FIFRA §10(d)(1)(A), (B), or (C).
Information claimed confidential on the basis of its falling within the
scope of FIFRA §10(d)(1)(A), (B), or (C) has been removed to a
confidential appendix, and is cited by cross-reference number in the body
of the study.
Company:
Company Agent: Typed Name Date:
Title Signature
STATEMENT OF DATA CONFIDENTIALITY CLAIMS
NOTE: Applicants for permanent or temporary tolerances should
note that it is OPP policy that no permanent tolerance, temporary
tolerance, or request for an emergency exemption incorporating an
analytical method, can be approved unless the applicant waives
all claims of confidentiality for the analytical method. These
analytical methods are published in the FDA Pesticide Analytical
Meth9ds Manual, and therefore cannot be claimed as confidential.
OPP implements this policy by returning submitted analytical
methods, for which confidentiality claims have been made, to the
submitter, to obtain the confidentiality waiver before they can
be processed.
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ATTACHMENT 4
SUPPLEMENTAL STATEMENT OF DATA CONFIDENTIALITY CLAIMS
For any portion of a submitted study that is not described
by FIFRA §10(d)(1)(A), (B), or (C), but for which y9u claim
C9nfidential treatment 9n another basis, the following informa-
tion must be included within a Supplemental Statement of Data
Confidentiality Claims:
• Identify specifically by page and line number(s) each
portion of the study for which you claim
confidentiality.
• Cite the reasons why the cited passage qualifies for
confidential treatment.
• Indicate the length of time--until a specific date or
event, or permanently--for which the information should
be treated as confidential.
• Identify the measures taken to guard against undesired
disclosure of this information.
• Describe the extent to which the information has been
disclosed, and what precautions have been taken in con-
nection with those disclosures.
• Encl9se C9pies of any pertinent determinations of
confidentiality made by EPA, other Federal agencies, of
courts concerning this information.
• If y9u assert that disclosure of this information would
be likely to result in substantial harmful effects to
you, describe th9se harmful effects and explain why
they should be viewed as substantial.
• If you assert that the informati9n in voluntarily sub-
mitted, indicate whether you believe disclosure of this
information might tend to lessen the availability to
EPA of similar information in the future, and if so,
how.
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ATTACHMENT 5
EXAMPLES OF SEVERAL CONFIDENTIAL ATTACHMENTS
Example 1. (Confidential word or phrase that has been deleted
from the study)
CROSS REFERENCE NUMBER 1 This cross reference number is used in the study in place of the
following paragraph (s) at the indicated volume and page
references.
DELETED WORDS OR PHRASE: Ethylene Glycol
PAGE LINES REASON FOR THE DELETION FIFRA
REFERENCE
6 14 Identity of Inert Ingredient §10(d)(C)
28 25
100 19
Example 2. (Confidential paragraph(s) that have been deleted from the study)
CROSS REFERENCE NUMBER 5 This cross reference number is used in the study in place of the
following paragraph (s) at the indicated volume and page
references.
DELETED PARAGRAPH(S) :
( )
( Reproduce the deleted paragraph (s) here )
PAGE LINES REASON FOR THE DELETION FIFRA REFERENCE
20. 2-17 Description of the quality control process § 1 0 (d) ( 1) (C)
Example 3. (Confidential pages that have been deleted from the study)
CROSS REFERENCE NUMBER 7 This cross reference number is used in the study in place of the
following paragraph (s) at the indicated volume and page
references.
DELETED PAGES(S): are attached immediately behind this page
PAGES REASON FOR THE DELETION FIFRA REFERENCE
35-41. Description of product manufacturing process § 10 (d) (1) (A)
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ATTACHMENT 6.
SAMPLE GOOD LABORATORY PRACTICE STATEMENTS
Example 1.
This study meets the requirements for 40 CFR Part 160
Submitter
Sponsor
Example 2.
This study does not meet the requirements of 40 CFR Part 160, and
differs in the following ways:
1.
2.
3.
Submitter
Sponsor
Study Director_
Example 3.
The submitter of this study was neither the sponsor of this study nor
conducted it, and does not know whether it has been conducted in
accordance with 40 CFR Part 160.
Submitter
81
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ATTACHMENT 7.
FORMAT OF THE SUBMITTAL PACKAGE
Transmittal Document
Related Administrative Materials
(e.g. Method of Support Statement, etc.)
Other materials about the submittal
(e.g., summaries of groups of studies
to aid in their review).
Studies submitted as unique
to the format below.
FORMAT OF SUBMITTED STUDIES
• Study title page.
Statement of Confidentiality Claims.
GLP and flagging* statements - as appropriate.
Body of the study, with English
language translation if required.
Appendices to the study.
Title Page of the Confidential
Attachment.
Confidential Attachment.
Supplemental Statement
of Confidentiality Claims
When flagging requirements
are finalised.
Documents which must be submitted as
appropriate to meet established requirements.
Documents submitted at submitter's option.
LEGEND
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PR Notice 91-2
83
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84
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, B.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
PR NOTICE 91-2
NOTICE TO MANUFACTURERS, PRODUCERS, FORMULATORS,
AND REGISTRANTS OF PESTICIDES
ATTENTION: Persons Responsible for Federal Registration of
Pesticide Products.
SUBJECT: Accuracy of Stated Percentages for Ingredients
Statement
I. PURPOSE:
The purpose of this notice is to clarify the Office of
Pesticide Program's P9licy with respect to the statement of
percentages in a pesticide's label's ingredient statement.
Specifically, the amount (percent by weight) of ingredient(s)
specified in the ingredient statement on the label must be stated
as the nominal concentration of such ingredient(s), as that term
is defined in 40 CFR 158.153(1). Accordingly, the Agency has
established the nominal concentration as the only acceptable
label claim for the amount of active ingredient in the product.
II. BACKGROUND
For some time the Agency has accepted two different methods
9f identifying on the label what percentage is claimed for the
ingredient(s) contained in a pesticide. Some applicants claimed a
percentage which represented a level between the upper and the
lower certified limits. This was referred to as the nominal
concentration. Other applicants claimed the lower limit as the
percentage of the ingredient(s) that would be expected to be
present in their product at the end of the product's shelf-life.
Unfortunately, this led to a great deal of confusion among the
regulated industry, the regulators, and the consumers as to
exactly how much of a given ingredient was in a given product.
The Agency has established the nominal concentration as the only
acceptable label claim for the amount of active ingredient in the
product.
Current regulations require that the percentage listed in
the active ingredient statement be as precise as possible
reflecting go9d manufacturing practices 40 CFR 156.10(g)(5). The
certified limits required for each active ingredient are intended
to encompass any such "good manufacturing practice" variations 40
CFR 158.175(c)(3).
The upper and lower certified limits, which must be proposed
in connection with a product's registration, represent the
amounts of an ingredient that may legally be present 40 CFR
158.175. The lower certified limit is used as the enforceable
lower limit for the product composition according to FIFRA
section 12(a)(1)(C), while the nominal concentration appearing on
the label would be the routinely achieved concentration used for
calculation of dosages and dilutions.
The nominal concentration would in fact state the greatest
degree of accuracy that is warranted with respect to actual
85
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product compositi9n because the nominal concentration would be
the amount of active ingredient typically found in the product.
It is imp9rtant for registrants to note that certified
limits for active ingredients are not considered to be trade
secret information under FIFRA section 10(b). In this respect the
certified limits will be routinely provided by EPA to States for
enforcement purposes, since the nominal concentration appearing
on the label may not represent the enforceable composition for
purposes of section 12(a)(1)(C).
III. REQUIREMENTS
As described below under Unit V. " COMPLIANCE SCHEDULE," all
currently registered products as well as all applications for new
registration must comply with this Notice by specifying the
nominal C9ncentrati9n expressed as a percentage by weight as the
label claim in the ingredient(s) statement and equivalence
statements if applicable (e.g., elemental arsenic, metallic zinc,
salt of an acid). In addition, the requirement for performing
sample analyses of five or more representative samples must be
fulfilled. C9pies of the raw analytical data must be submitted
with the nominal ingredient label claim. Further information
about the analysis requirement may be found in the 40 CFR
158.170. All products are required to pr9vide certified limits
for each active, inert ingredient, impurities of toxicological
significance(i.e., upper limit(s) 9nly) and on a case by case
basis as specified by EPA. These limits are to be set based on
representative sampling and chemical analysis(i.e., quality
control) of the product.
The format of the ingredient statement must conform to 40
CFR 156-Labeling Requirements For Pesticides and Devices.
After July 1, 1997, all pesticide ingredient Statements must
be changed to nominal concentration.
IV. PRODUCTS THAT REQUIRE EFFICACY DATA
All pesticides are required to be efficacious. Therefore,
the certified lower limits may not be lower then the minimum
level to achieve efficacy. This is extremely important for
products which are intended to C9ntrol pests which threaten the
public health, e.g., certain antimicrobial and rodenticide
products. Refer to 40 CFR 153.640.
In those cases where efficacy limits have been established,
the Agency will not accept certified lower limits which are below
that level for the shelf life of the product.
V. COMPLIANCE SCHEDULE
As described earlier, the purpose of this Notice is to make
the registration process more uniform and more manageable for
both the agency and the regulated community. It is the Agency's
intention to implement the requirements of this notice as
smoothly as possible so as not to disrupt or delay the Agency's
high priority programs, i.e., reregistration, new chemical, or
fast track (FIFRA section 3(c)(3)(B). Therefore,
applicants/registrants are expected to comply with the
requirements of this Notice as follows:
(1) Beginning July 1, 1991, all new product registrations
submitted to the Agency are to comply with the
requirements of this Notice.
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(2) Registrants having products subject to reregistration
under FIFRA section 4(a) are to comply with the
requirements of this Notice when specific products are
called in by the Agency under Phase V of the
Reregistration Program.
(3) All other products/applications that are not subject to
(1) and (2) ab9ve will have until July 1, 1997, to
comply with this Notice. Such applications should note
"Conversion to Nominal Concentrations on the
application form. These types Or amendments will not be
handled as "Fast Track" applications but will be
handled as routine requests.
VI. FOR FURTHER INFORMATION
Contact Tyrone Aiken for information or questions concerning
this notice on (703) 308-7031.
/s/
Anne E. Lindsay, Director
Registration Division (H-7505C)
87
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88
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APPENDIX F. Product Specific Data Call-in
89
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90
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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 1 of this N9tice, the Data Call-In Chemical Status
Sheet, to submit certain product specific data as noted herein to
the U.S. Environmental Protection Agency (EPA, the Agency).
These data are necessary t9 maintain the C9ntinued 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 A through G; or
2. Why you believe you are exempt from the requirements
listed in this Notice and in Attachment 3,
Requirements Status and Registrant's Response Form,
(see section III-B); or
3. Why you believe EPA should not require your submission
of product specific data in the manner specified by
this Notice (see section III-D).
If you do not respond to this Notice, or if you do not
satisfy EPA that you will comply with its requirements or should
be exempt or excused from doing so, then the registration of your
product(s) subject t9 this Notice will be subject t9 suspensi9n.
We have provided a list of all of your products subject to this
N9tice in Attachment 2, Data Call-In Response Form, as well as a
list of all registrants who were sent this Notice (Attachment 6).
The authority for this Notice is secti9n 3(c)(2)(B) of the
Federal Insecticide, Fungicide and Rodenticide Act as amended
(FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
information is authorized under the Paperwork Reduction Act by
OMB Approval No. 2070-0107 (expiration date 12-31-92) .
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
91
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Section V - Registrants' Obligation To Report
Possible Unreasonable Adverse Effects
Section VI - Inquiries And Responses To This Notice
The Attachments to this Notice are:
I - Data Call-In Chemical Status Sheet
2 - Product-Specific Data Call-In Response Form
3 - Requirements Status and Registrant's Resp9nse Form
4 - EPA Grouping of End-Use Products for Meeting Acute
Toxicology Data Requirements for Reregistration
5 - EPA Acceptance Criteria
6 - List of Registrants Receiving This Notice
7 - Cost Share and Data Compensation Forms, and Product
Specific Data Report Form
SECTION I. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active
ingredient and reevaluated the data needed to support continued
registration of the subject active ingredient. The Agency has
concluded that the only additional data necessary are product
specific data. No additional generic data requirements are being
imposed. You have been sent this Notice because you have
product(s) containing the subject active ingredient.
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The product specific data required by this Notice are
specified in Attachment 3, Requirements Status and Registrant's
Response Form. Depending on the results of the studies required in
this Notice, additional testing may be required.
II-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the
data requirements specified in Attachment 3, Requirements Status
and Registrant's Response Form, within the time frames provided.
II-C. TESTING PROTOCOL
All studies required under this Notice must be C9nducted in
accordance with test standards outlined in the Pesticide Assessment
Guidelines for those studies for which guidelines have been
established.
These EPA Guidelines are available from the National Technical
Information Service (NTIS), Attn: Order Desk, 5285 Port Royal Road,
Springfield, Va 22161 (tel: 703-487-4650).
Protocols approved by the Organization for Economic
Cooperation 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, 1750 Pennsylvania Avenue N.W.,
Washington, D.C. 20006.
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All new studies and proposed protocols submitted in response
to this Data Call-in Notice must be in accordance with Good
Laboratory Practices [40 CFR Part 160.3(a)(6)].
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(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
III-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice
for product specific data must be submitted to the Agency within 90
days after your receipt of. this Notice. Failure to adequately
respond to this Notice within 90 days of your receipt will be a
basis for issuing a Notice of Intent to Suspend (NOIS) affecting
your products. This and other bases for issuance of. NOIS due to
failure to comply with this Notice are presented in Section IV-A
and IV-B.
III-B. OPTIONS FOR RESPONDING TO THE AGENCY
The options for responding to this Notice for product specific
data are: (a) voluntary cancellation, (b) agree to satisfy the
product specific data requirements imposed by this notice or (c)
request a data waiver(s).
A discussion of how to respond if you chose the Voluntary
Cancellation option is presented below. A discussion of the
various options available for satisfying the product specific 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.
There are two forms that accompany this Notice of which,
depending upon your response, one or both must be used in your
response to the Agency. These forms are the Data-Call-in Response
Form, and the Requirements Status and Registrant's Response Form,
Attachment 2 and Attachment 3. The Data 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 must be submitted for each product listed on the Data
Call-In Response Form unless the V9luntary cancellation option is
selected or unless the product is identical to another (refer t9
the instructions for completing the Data Call-In Resp9nse Form in
Attachment 2). Please note that the company's authorized
representative is required to sign the first page of the Data Call-
in Response Form and Requirements Status and Registrant's Response
Form (if this f9rm is required) and initial any subsequent pages.
The forms contain separate detailed instructions on the response
options. 09 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.
1. Voluntary Cancellation - You may avoid the requirements of
this Notice by requesting voluntary cancellation of your product(s)
containing the active ingredient that is the subject of this
Notice. If you wish to voluntarily cancel your pr9duct, you must
submit a completed Data Call-In Response Form, indicating your
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election of this option. Voluntary cancellation is item number 5
9n the Data Call-In Response Form. If you choose this option, this
is the only form that you are required to complete.
If y9u chose to voluntarily cancel your product, further sale
and distribution of y9ur product after the effective date of
cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
2. Satisfying the Product Specific Data Requirements of this
Notice There are various options available to satisfy the product
specific data requirements of this Notice. These options are
discussed in Section III-C of this Notice and comprise options 1
through 6 on the Requirements Status and Registrant's Response Form
and item numbers 7a and 7b on the Data Call-In Response Form.
Deletion 9f a use(s) and the low volume/min9r use option are not
valid options for fulfilling product specific data requirements.
3. Request for Product Specific Data Waivers. Waivers for
product specific data are discussed in Section III-D of this Notice
and are covered by option 7 on the Requirements Status and
Registrant's Response Form. If you choose one of these 9ptions,
you must submit both forms as well as any other information/data
pertaining to the option chosen to address the data requirement.
III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-In Response Form that you
agree t9 satisfy the product specific data requirements (i.e. y9u
select item number 7a or 7b), then you must select one of the six
options on the Requirements Status and Registrant's Response Form
related to data production for each data requirement. Your option
selection should be entered under item number 9, "Registrant
Response." The six options related to data production are the
first six options discussed under item 9 in the instructions for
completing the Requirements Status and Registrant's Response Form.
These six options are listed immediately below with inf9rmation in
parentheses to guide registrants t9 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 rrrare
registrants to develop data jointly (Cost Sharing)
(3) I have made 9ffers 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 9r 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.
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The time frames in the Requirements Status and Registrant's
Response Form are the time frames that the Agency is allowing for
the submission of completed study reports. The noted deadlines run
from the date of the receipt of this Notice by the registrant. If
the data are not submitted by the deadline, each registrant is
subject t9 receipt of a Notice of Intent to Suspend the affected
registration(s).
If y9u 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), y9u 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. Y9u must
explain any technical or laboratory difficulties and provide
documentati9n 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 9nly in cases of extraordinary testing
problems bey9nd the expectati9n or C9ntrol 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
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. 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
ormed. 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 --
This option only applies to acute toxicity and certain efficacy
data as described in option 2 above. If you have made an offer to
pay in an attempt to enter into an agreement or amend an existing
agreement to meet the requirements of this N9tice and have been
unsuccessful, you may request EPA (by selecting this 9ption) to
exercise its discretion not to suspend your registration(s),
although you do not comply with the data submission requirements of
this Notice. EPA has determined that as a general policy, absent
other relevant considerations, it will not suspend the registration
of a product of a registrant who has in good faith sought and
continues to seek to enter into a joint data development/cost
sharing program, but the other registrant(s) developing the data
has refused to accept your offer. To qualify for this option, you
must submit documentati9n 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
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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 9ther 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 or failing agreement to be bound by
binding arbitrati9n as provided by FIFRA section 3 (c) (2) (B) (iiij
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 burdens of developing
the data. In addition, the other registrant must fulfill its
commitment to develop and submit the data as required by this
Notice. If the other registrant fails to develop the data or for
some other reason is subject to suspension, your registration as
well as that of the other registrant will normally be subject t9
initiation 9f suspensi9n proceedings, unless you C9mmit 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) .
should be aware that if the Agency determines that the
study is not acceptable, the Agency will require you t9 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 f9r submitting an
existing study, all of the following three criteria must be clearly
met :
a. You must certify at the time that the existing study is
submitted that the raw data and specimens from the study
are available for audit and review and you must identify
where they are available. This must be done in
accordance with the requirements of the Good Laboratory
Practice (GLP) regulation, 40 CFR Part 160. As stated in
40 CFR 160.3(j) " 'raw data' means any laboratory
worksheets, records, memoranda, notes, or exact C9pies
there9f, that are the result of original observations and
activities 9f 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
C9pies, computer printouts, magnetic media, including
dictated observations, and recorded data from automated
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instruments." The term "specimens", according to 40 CFR
160.3(k), means "any material derived from a test system
for examination or analysis."
b. Health and safety studies completed after May 1984 must
also contain all GLP-required quality assurance and
quality control information, pursuant to the requirements
of 40 CFR Part 160. Registrants must also certify at the
time of submitting the existing study that such GLP
information is available for post-May 1984 studies by
including an appropriate statement on or attached to the
study signed by an authorized official or representative
of the registrant.
c. You 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 are usually not available for
such studies.
If you submit an existing study, you must certify that the
study meets all requirements of the criteria outlined above.
If y9u 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, y9u 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 n9rmally 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 pers9n 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 sh9uld 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.
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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 should also 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
Opti9n 4 above, apply to all data submissions intended to upgrade
studies. Additionally y9ur 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" 9r "core minimum." For all other disciplines the
classification would be "acceptable." With respect to any studies
for which you wish to select this option you must provide the MRID
number of the study you are citing and, if the study has been
reviewed by the Agency, you must provide the Agency's
classification of the study.
If y9u are citing a study of which you are not the original
data submitter, you must submit a completed copy of EPA Form 8570-
31, Certification with Respect to Data Compensation Requirements.
Registrants who select one of the ab9ve 6 options must meet
all of the requirements described in the instructions for
completing the Data Call-In Response Form and the Requirements
Status and Registrant's Response Form, as appropriate.
III-D REQUESTS FOR DATA WAIVERS
If you request a waiver for product specific data because
you believe it is inappropriate, you must attach a complete
justification for the request, including technical reasons, data
and references to relevant EPA regulations, guidelines or policies.
(Note: any supplemental data must be submitted in the format
required by PR Notice 86-5). This will be the 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 9f this Notice within
30 days 9f the receipt of the Agency's decision. You must indicate
and submit the option chosen on the Requirements Status and
Registrant'sResponse 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 n9t automatically extend the
due date for the study in question. Waiver requests submitted
with9ut adequate supporting rationale will be denied and the
original due date will remain in force.
IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
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The Agency may issue a Notice of Intent t9 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
prop9sed 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 t9 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 C9Sts 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 9f a registrant on whom you rely for a generic
data exemption either to:
a. inform EPA of intent to develop and submit the data
required by this Notice on a Data Call-In Response
Form and a Requirements Status and Registrant's
Response Form,-
b. fulfill the commitment to develop and submit the
data as required by this Notice; or
c. otherwise take appropriate steps to meet the
requirements stated in this Notice, unless you
commit t9 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
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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 9f 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 rep9rt will not be considered to fulfill the
submission requirement.
IV-C EXISTING STOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale,
distribution and use of existing stocks of a pesticide product
which has been suspended or cancelled if doing so would be
consistent with the purposes of the Act.
The Agency has determined that such disposition by registrants
of existing stocks for a suspended registration when a section
3(c) (2) (B) data request is outstanding would generally not be
consistent with the Act's purposes. Acc9rdingly, the Agency
anticipates granting registrants permission to sell, distribute, or
use existing stocks of suspended product(s) 9nly in exceptional
circumstances. If you believe such disposition 9f existing stocks
of your product(s) which may be suspended for failure to comply
with this Notice should be permitted, y9u have the burden of
clearly demonstrating to EPA that granting such permission W9uld be
consistent with the Act. You must also explain why an "existing
stocks" provision is necessary, including a statement 9f the
quantity of existing stocks and your estimate of the time required
for their sale, distribution, and use. Unless y9u meet this burden
the Agency will n9t C9nsider 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 N9tice and your product is in full compliance
with all Agency requirements, you will have, under most
circumstances, one year from the date your 90 day response to this
Notice is due, to sell, distribute, or use existing stocks.
Normally, the Agency will allow persons other than the registrant
such as independent distributors, retailers and end users to sell,
distribute or use such existing stocks until the stocks are
exhausted. Any sale, distribution or use of stocks of voluntarily
cancelled products containing an active ingredient for which the
Agency has particular risk concerns will be determined on case-by-
case basis.
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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 y9u demonstrate to the Agency that you are in full
compliance with all Agency requirements, including the requirements
of this Notice. For example, if you decide to voluntarily cancel
your registration six months before a 3 year study is scheduled to
be submitted, all progress reports and other information necessary
to establish that you have been conducting the study in an
acceptable and good faith manner must have been submitted to the
Agency, before EPA will consider granting an existing stocks
provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE
UNREASONABLE ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states
that if at any time after a pesticide is registered a registrant
has additional factual information regarding unreasonable adverse
effects on the environment by the pesticide, the registrant shall
submit the information to the Agency. Registrants must notify the
Agency of any factual information they have, from whatever source,
including but not limited to interim or preliminary results of
studies, regarding unreasonable adverse effects on man or the
environment. This requirement continues as long as the products
are registered by the Agency.
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and
procedures established by this Notice, call the contact person(s)
listed in Attachment 1, the Data Call-In Chemical Status Sheet.
All responses to this Notice (other than voluntary
cancellation requests and generic data exemption claims) must
include a completed Data Call-In Response Form and a completed
Requirements Status and Registrant's Response Form (Attachment 2
and Attachment 3for 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 9ption is chosen, only the
Data Call-In Response Form need be submitted.
The Office of Compliance Monitoring (OCM) of the Office of
Pesticides and Toxic Substances (OPTS), EPA, will be monitoring the
data being generated in response to this Notice.
Sincerely yours,
Louis P. True, Jr., Acting Director
Special Review and
Reregistration Division
Attachments
1 - Data Call-In Chemical Status Sheet
2 - Product-Specific Data Call-In Response Form
3 - Requirements Status and Registrant's Resp9nse Form
4 - EPA Grouping of End-Use Products for Meeting Acute
Toxicology Data Requirements for Reregistration
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5 - EPA Acceptance Criteria
6 - List of Registrants Receiving This Notice
7 - Cost Share and Data Compensation Forms, and Product
Specific Data Report Form
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Attachment 1. Chemical Status Sheet
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M-CRESOL AND XYLENOL DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-in Notice
because you have product(s) containing M-Cresol and Xylenol.
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 M-Cresol
and Xylenol. 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 F9rm (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 M-Cresol
and Xylenol 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 M-Cresol and Xylenol are contained in the Requirements
Status and Registrant's Response, Attachment 3. The Agency has
concluded that additional data on M-Cresol and Xylenol are needed
for specific pr9ducts. 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 M-Cresol and
Xylenol products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic database of M-
Cresol and Xylenol, please contact Paul Lewis at (703) 308-8018.
If you have any questions regarding the product specific data
requirements and procedures established by this Notice, for
m-cresol contact Veronica Dutch at (703) 308-8585; for xylenol
contact Emily Mitchell at (703) 308-8583
All responses to this Notice for the Product Specific data
requirements should be submitted to:
Veronica Dutch and Emily Mitchell
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: M-Cresol and Xylenol
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Attachment 2. Product Specific Data Call-in
Response Forms (Form A inserts) Plus
Instructions
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORM FOR
PRODUCT SPECIFIC DATA
Item 1-4. Already completed by EPA.
Item 5. If you wish to voluntarily cancel your product, answer
"yes." If you choose this option, you will not have to
provide the data required by the Data Call-in Notice and
you will not have to complete any other forms. Further
sale and distribution of your product after the effective
date of cancellation must be in accordance with the
Existing Stocks provision of the Data Call-in Notice
(Section IV-C).
Item 6. Not applicable since this form calls in product specific
data only. However, if your product is identical to
another product and you qualify for a data exemption, you
must respond with "yes" to Item 7a (MUP) or 7B (EUP) on
this form, provide the EPA registration numbers of your
source(s); you would not complete the "Requirements Status
and Registrant's Response" form. Examples of such products
include repackaged products and Special Local Needs
(Section 24c) products which are identical to federally
registered products.
Item 7a. 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." 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. See Item
6 with regard to identical products and data exemptions.
Items 8-11. Self-explanatory.
NOTE: You may provide additional information that does not fit on
this form in a signed letter that accompanies this form.
For example, you may wish to report that your product has
already been transferred to another company or that you
have already voluntarily canceled this product. For these
cases, please supply all relevant details so that EPA can
ensure that its records are correct.
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INSTRUCTIONS FOR COMPLETING THE REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORM FOR PRODUCT SPECIFIC DATA
Item 1-3 Completed by EPA. Note the unique identifier number
assigned by EPA in Item 3. This number must be used in the
transmittal document for any data submissions in response
to this Data Call-in Notice.
Item 4. The guideline reference numbers of studies required to
support the product's continued registration are
identified. These guidelines, in addition to the
requirements specified in the Notice, govern the conduct 9f
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. The study title associated with the guideline reference
number is identified.
Item 6. The use pattern (s) of the pesticide ass9ciated with the
product specific requirements is (are) identified. For
most product specific data requirements, all use patterns
are covered by the data requirements. In the case of
efficacy data, the required studies only pertain to
products which have the use sites and/or pests indicated.
Item 7. The substance to be tested is identified by EPA. For
product specific data, the product as formulated for sale
and distribution is the test substance, except in rare
cases.
Item 8. The due date for submission of each study is identified.
It is normally based on 8 months after issuance of the
Reregistration Eligibility Document unless EPA determines
that a longer time period is necessary.
Item 9. Enter only one of the following response codes for each
data requirement to show how you intend to comply with the
data requirements listed in this table. Fuller
descriptions of each option are contained in the Data Call-
in Notice.
1. I will generate and submit data by the specified due date
(Developing Data). By indicating that I have chosen this
option, I certify that I will comply with all the
requirements pertaining to the conditions for submittal of
this study as outlined in the Data Call-in Notice. By the
specified due date, I will also submit: (1) a completed
"Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-29) and (2) two completed
and signed copies of the Confidential Statement of Formula
(EPA Form 8570-4).
2. I have entered into an agreement with one or more
registrants to develop data jointly (Cost Sharing). I am
submitting a copy of this agreement. I understand that
this option is available only for acute toxicity or certain
efficacy data and only if EPA indicates in an attachment to
this Notice that my product is similar enough to another
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 n9t submitted
on time, my product may be subject to suspension. By the
specified due date, I will also submit: (1) a completed
"Certification With Respect To Data Compensation
108
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Requirements" form (EPA Form 8570-29) and (2) two completed
and signed copies of the Confidential Statement of Formula
(EPA Form 8570-4).
3. I have made offers to share in the cost to develop data
(Offers to Cost Share). I understand that this option is
available only for acute toxicity or certain efficacy data
and only if EPA indicates in an attachment to this Data
Call-in Notice that my product is similar enough to another
product to qualify for this option. I am submitting
evidence that I have made an offer to another registrant
(who has an obligation to submit data) to share in the cost
of that data. I am also submitting a completed
"Certification of Offer to Cost Share in the Development
Data" form. I am including a copy of my offer and proof of
the other registrant's receipt of that offer. I am
identifying the party which is committing to submit or
provide the required data; if the required study is not
submitted on time, my product may be subject to suspension.
I understand that other terms under Option 3 in the Data
Call-in Notice (Section III-C.l.) apply as well. By the
specified due date, I will also submit: (1) a completed
"Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-29) and (2) two completed
and signed copies of the Confidential Statement of Formula
(EPA Form 8570-4).
4. By the specified due date, I will submit an existing study
that has not been submitted previously to the Agency by
anyone (Submitting an Existing Study). I certify that this
study will meet all the requirements for submittal of
existing data outlined in Option 4 in the Data Call-in
Notice (Section III-C.l.) and will meet the attached
acceptance criteria (for acute toxicity and product
chemistry data) . I will attach the needed supporting
information along with this response. I also certify that
I have determined that this study will fill the data
requirement for which I have indicated this choice. By the
specified due date, I will also submit a completed
"Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-29) to show what data
compensation option I have chosen. By the specified due
date, I will also submit: (1) a completed "Certification
With Respect To Data Compensation Requirements" form (EPA
Form 8570-29) and (2) two completed and signed copies of
the Confidential Statement of Formula (EPA Form 8570-4) .
5. By the specified due date, I will submit or cite data to
upgrade a study classified by the Agency as partially
acceptable and upgradable (Upgrading a Study). I will
submit evidence of the Agency's review indicating that the
study may be upgraded and what informati9n is required to
do so. I will provide the MRID or Accession number of the
study at the due date. I understand that the conditions
for this option outlined Option 5 in the Data Call-in
Notice (Section III-C.l.) apply. By the specified due
date, I will also submit: (1) a completed "Certification
With Respect To Data Compensation Requirements" form (EPA
Form 8570-29) and (2) two completed and signed copies of
the Confidential Statement of Formula (EPA Form 8570-4).
6. By the specified due date, I will cite an existing study
that the Agency has classified as acceptable or an existing
study that has been submitted but not reviewed by the
Agency (Citing an Existing Study). If I am citing another
109
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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 C9nducted on my product, an
identical product or a product which EPA has "grouped" with
one or more other products for purposes of depending on the
same data. I may also choose this option if I am citing my
own data. In either case, I will provide the MRID or
Accession number (s) for the cited data on a "Product
Specific Data Report" form or in a similar format. By the
specified due date, I will also submit: (1) a completed
"Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-29) and (2) two completed
and signed copies of the Confidential Statement of Formula
(EPA Form 8570-4).
7. I request a waiver for this study because it is
inappropriate for my product (Waiver Request). I am
attaching a complete justification for this request,
including technical reasons, data and references to
relevant EPA regulations, guidelines or policies. [Note:
any supplemental data must be submitted in the format
required by P.R. Notice 86-5]. I understand that this is
my only opportunity to state the reasons or provide
information in support of my request. If the Agency
approves my waiver request, I will not be required to
supply the data pursuant to Section 3(c)(2)(B) of FIFRA.
If the Agency denies my waiver request, I must choose a
method of meeting the data requirements of this Notice by
the due date stated by this N9tice. In this case, I must,
within 30 days of my receipt of the Agency's written
decision, submit a revised "Requirements Status and
Registrant's Response" Form indicating the 9ption chosen.
I also understand that the deadline for submission of data
as specified by the original data call-in notice will not
change. By the specified due date, I will also submit: (1)
a completed "Certification With Respect To Data
Compensation Requirements" form (EPA Form 8570-29) and (2)
two completed and signed copies of the Confidential
Statement of Formula (EPA Form 8570-4).
Items 10-13. Self-explanatory.
NOTE: You may provide additional information that does not fit on
this form in a signed letter that accompanies this form.
For example, you may wish to report that your product has
already been transferred to another company or that you
have already voluntarily canceled this product. For these
cases, please supply all relevant details so that EPA can
ensure that its records are correct.
110
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Attachment 3. Product Specific Requirement
Status and Registrant's Response Forms (Form
B inserts) and Instructions
111
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112
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND REGISTRANT'S
RESPONSE" FORM FOR PRODUCT SPECIFIC DATA
Item 1-3. Completed by EPA. Note the unique identifier number
assigned by EPA in item 3. This number must be used in the
transmittal document for any data submissions in response
to this Data Call-in Notice.
Item 4. The guidelines reference numbers of studies required to
support the product's continued registration are
identified. These guidelines, in addition to the
requirements specified in the Notice, govern the conduct 9f
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. The study title associated with the guideline reference
number is identified.
Item 6. The use patters (s) of the pesticide associated with the
product specific requirements is (are) identified. For
most product specific data requirements, all use patterns
are covered by the data requirements. In the case of
efficacy data, the required studies only pertain to
products which have the use sites and/ or pests indicated.
Item 7. The substance to be tested is identified by EPA. For
product specific data, the product as formulated for sale
and distribution is the test substance, except in rare
cases.
Item 8. The due date for submission of each study is identified.
It is normally based 9n 8 months after issuance of the
Reregistration Eligibility Documents unless EPA determines
that a longer time period is necessary.
Item 9. Enter Only one of the following response codes for each
data requirement to show how you intend to comply with the
data requirements listed in this table. Fuller
descriptions of each option are contained in the Data Call-
in Notice.
1. I will generate and submit data by the specified due
date (Developing Data). By indicating that I have chosen
this option, I certify that I will comply with all the
requirements pertaining to the conditions for submittal of
this study as outlined in the Data Call-in Notice.
2. I have entered into an agreement with one or more
registrants to develop data jointly (Cost Sharing). I am
submitting a copy of this agreement. I understand that
this option is available on for acute tpxicity or certain
efficacy data and only if EPA 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 prpvide
the required data; if the required study is not submitted
on time, my product my be subject to suspension.
3. I have made offers to share in the cost to develop
data (Offers to Cost Share). I understand that this option
is available only for acute toxicity or certain efficacy
data and only if EPA indicates in an attachment to this
Data Call-in Notice that my product is similar enough to
another product to qualify for this option. I am
113
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submitting evidence that I have made an offer to another
registrant (who has an obligation to submit data) to share
in the cost of that data. I am also submitting a completed
" Certification of offer to Cost Share in the Development
Data" form. I am including a copy of my offer and proof of
the other registrant's receipt of that offer. I am
identifying the party which is committing to submit or
provide the require data; if the required study is not
submitted on time, my product may be subject to suspension.
I understand that other terms under Option 3 in the Data
Call-in Notice (Section III-C.l.) apply as well.
4. By the specified due date, I will submit an existing
study that has not been submitted previously to the Agency
by anyone (submitting an Existing Study). I certify that
this study will meet all the requirements for submittal of
existing data outlined in option 4 in the Data Call-in
Notice (Section III-C.l.) and will meet the attached
acceptance criteria (for acute toxicity and product
chemistry data) . I will attach the needed supporting
information along with this response. I also certify that
I have determined that this study will fill the data
requirement for which I have indicated this choice.
5. By the specified due date, I will submit or cite data
to upgrade a study classified by the Agency as partially
acceptable and upgrade (upgrading a study). I will submit
evidence of the Agency's review indicating that the study
may be upgraded and what information is required to do so.
I will provide the MRID or Accession number of the study at
the due date. I understand that the conditions for this
Option outlined Option 5 in the Data Call-in Notice
(Section III-C.l.) apply.
6. By the specified due date, I will cite an existing
study that the Agency has classified as acceptable or an
existing study that has been submitted but not reviewed by
the Agency (Citing an Existing Study) . If 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 EPA has
"grouped" with one or more other products for purposes of
depending on the same data. I may also choose this option
if I am citing my own data. In either case, I will provide
the MRID or Accession number (s) number (s) for the cited
data on a "Product Specific Data Report" form or in a
similar f9rmat. If I cite an9ther registratrant's data, I
will submit a completed "Certification With Respect To Data
Compensation Requirements" form.
7. I request a waiver for this study because it is
inappropriate for my product (Waiver Request). I am
attaching a complete justification for this request,
including technical reasons, data and references to
relevant EPA regulations, guidelines or policies. [Note:
any supplemental data must be submitted in the format
required by P.R. Notice 86-5]. I understand that this is
my only opportunity to state the reasons or provide
information in support of my request. If the Agency
approves my waiver request, I will not be require to supply
the data pursuant t9 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
114
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30 days of my receipt of. the Agency's written decision,
submit a revised "Requirements Status chosen. I also
understand that the deadline for submission of data as
specified by the original data cal-in notice will not
change.
Items 10-13. Self-explanatory.
NOTE:You may provide additional information that does not fit on
this form in a signed letter that accompanies this form. For
example, you may wish to report that your product has already been
transferred to another company or that you have already voluntarily
cancelled this product. For these cases, please supply all relevant
details so that EPA can ensure that its records are correct.
115
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116
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Attachment 4. EPA Batching of End-Use
Products for Meeting Data Requirements for
Reregistration
117
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118
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No toxicological batching is required
119
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120
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Attachment 5. EPA Acceptance Criteria
121
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122
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SUBDIVISION D
Guideline Study Title
Series 61 Product Identity and Composition
Series 62 Analysis and Certification of Product Ingredients
Series 63 Physical and Chemical Characteristics
123
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61 Product Identity and Composition
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Name of technical material tested (include product name and trade name, if appropriate).
2. Name, nominal concentration, and certified limits (upper and lower) for each active ingredient and each
intentionally-added inert ingredient.
3. Name and upper certified limit for each impurity or each group of impurities present at _>_ 0.1% by weight and
for certain lexicologically significant impurities (e.g., dioxins, nitrosamines) present "af < 0.1%.
4. Purpose of each active ingredient and each intentionally-added inert.
5. Chemical name from Chemical Abstracts index of Nomenclature and Chemical Abstracts Service (CAS)
Registry Number for each active ingredient and, if available, for each intentionally-added inert.
6. Molecular, structural, and empirical formulas, molecular weight or weight range, and any company assigned
experimental or internal code numbers for each active ingredient.
7. Description of each beginning material in the manufacturing process.
EPA Registration Number if registered;
for other beginning materials, the following:
Name and address of manufacturer or supplier.
Brand name, trade name or commercial designation.
Technical specifications or data sheets by which manufacturer or supplier describes composition,
properties or toxicity.
8. Description of manufacturing process.
Statement of whether batch or continuous process.
Relative amounts of beginning materials and order in which they are added.
Description of equipment.
Description of physical conditions (temperature, pressure, humidity) controlled in each step and the
parameters that are maintained.
Statement of whether process involves intended chemical reactions.
Flow chart with chemical equations for each intended chemical reaction.
Duration of each step of process.
Description of purification procedures.
Description of measures taken to assure quality of final product.
9. Discussion of formation of impurities based on established chemical theory addressing (1) each impurity which
may be present at _>_ 0.1% or was found at _>_ 0.1% by product analyses and (2) certain lexicologically
significant impurities~(see #3).
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62 Analysis and Certification of Product Ingredients
ACCEPTANCE CRITERIA
The following criteria apply to the technical grade of the active ingredient being reregistered. Use a table to present the
information in items 6, Y, and 8.
Does your study meet the following acceptance criteria?
1. Five or more representative samples (batches in case of batch process) analyzed for each active ingredient and
all impurities present at > 0.1%.
2. Degree of accountability!^ closure _>_ ca 98%.
3. Analyses conducted for certain trace toxiclmpurities at lower than 0.1% (examples, nitrosamines in the case of
products containing dinitroanilines or containing secondary or tertiary amines/alkanolamines plus nitrites;
polyhalogenated dibenzodioxins and dibenzofurans). [Note that in the case of nitrosamines both fresh and stored
samples must be analyzed.].
4. Complete and detailed description of each step in analytical method used to analyze above samples.
5. Statement of precision and accuracy of analytical method used to analyze above samples.
6. Identities and quantities (including mean and standard deviation) provided for each analyzed ingredient.
7. Upper and lower certified limits proposed for each active ingredient and intentionally added inert along with
explanation of how the limits were determined.
8. Upper certified limit proposed for each impurity present at > 0.1% and for certain lexicologically significant
impurities at < 0.1% along with explanation of how limit determined.
9. Analytical methods to verify certified limits of each active ingredient and impurities (latter not required if exempt
from requirement of tolerance or if generally recognized as safe by FDA) are fully described.
10. Analytical methods (as discussed in 19) to verify certified limits validated as to their precision and accuracy.
125
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63 Physical and Chemical Characteristics
ACCEPTANCE CRITERIA
The following criteria apply to the technical grade of the active ingredient being reregistered.
Does your study meet the following acceptance criteria?
63-2 Color
Verbal description of coloration (or lack of it)
Any intentional coloration also reported in terms of Munsell color system
63-3 Physical State
Verbal description of physical state provided using terms such as "solid, granular, volatile liquid"
Based on visual inspection at about 20-25E C
63-4 Odor
Verbal description of odor (or lack of it) using terms such as "garlic-like, characteristic of aromatic
compounds"
Observed at room temperature
63-5 Melting Point
Reported in EC
Any observed decomposition reported
63-6 Boiling Point
Reported in EC
Pressure under which B.P. measured reported
Any observed decomposition reported
63-7 Density, Bulk Density, Specific Gravity
Measured at about 20-25E C
Density of technical grade active ingredient reported in g/ml or the specific gravity of liquids reported with
reference to water at 20E C. [Note: Bulk density of registered products may be reported in lbs/ft3 or
Ibs/gallon.]
63-8 Solubility
Determined in distilled water and representative polar and non-polar solvents, including those used in
formulations and analytical methods for the pesticide
Measured at about 20-25E C
Reported in g/100 ml (other units like ppm acceptable if sparingly soluble)
63-9 Vapor Pressure
Measured at 25E C (or calculated by extrapolation from measurements made at higher temperature if pressure
too low to measure at 25E C)
Experimental procedure described
Reported in mm Hg (torr) or other conventional units
63-10 Dissociation Constant
Experimental method described
Temperature of measurement specified (preferably about
20-25EC)
63-11 Octanol/water Partition Coefficient
Measured at about 20-25E C
Experimentally determined and description of procedure provided (preferred method-45 Fed. Register 77350)
Data supporting reported value provided
63-12 pH
Measured at about 20-25E C
Measured following dilution or dispersion in distilled water
63-13 Stability
Sensitivity to metal ions and metal determined
Stability at normal and elevated temperatures
Sensitivity to sunlight determined
126
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SUBDIVISION F
Guideline Study Tide
81-1 Acute Oral Toxicity in the Rat
81-2 Acute Dermal Toxicity in the Rat, Rabbit or Guinea Pig
81-3 Acute Inhalation Toxicity in the Rat
81-4 Primary Eye Irritation in the Rabbit
81-5 Primary Dermal Irritation Study
81-6 Dermal Sensitization in the Guinea Pig
127
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81-1 Acute Oral Toxicity in the Rat
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc).
2. At least 5 young adult rats/sex/group.
3.r Dosing, single oral may be administered over 24 hrs.
4.*^ Vehicle control if other than water.
5. Doses tested, sufficient to determine a toxicity category or a limit dose (5000 mg/kg).
6. Individual observations at least once a day.
7. Observation period to last at least 14 days, or until all test animals appear normal whichever is longer.
8. Individual daily observations.
9. Individual body weights.
10. Gross necropsy on all animals.
Criteria marked with an * are supplemental and may not be required for every study.
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81-2 Acute Dermal toxicity in the Rat, Rabbit or Guinea Pig
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc).
2. At least 5 animals/sex/group.
3.* Rats 200-300 gm, rabbits 2.0-3.0 kg or guinea pigs 350-450 gm.
4. Dosing, single dermal.
5. Dosing duration at least 24 hours.
6.^ Vehicle control, only if toxicity of vehicle is unknown.
7.~ Doses tested, sufficient to determine a toxicity category or a limit dose (2000 mg/kg).
8. Application site clipped or shaved at least 24 hours oefore dosing.
9. Application site at least 10% of body surface area.
10. Application site covered with a porous nonirritating cover to retain test material and to prevent
ingestion.
11. Individual observations at least once a day.
12. Observation period to last at least 14 days.
13. Individual body weights.
14. Gross necropsy on all animals.
Criteria marked with an * are supplemental and may not be required for every study.
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81-3 Acute Inhalation Toxicity in the Rat
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc).
2. Product is a gas, a solid which may produce a significant vapor hazard based on toxicity and expected use or
contains particles of inhalable size for man (aerodynamic diameter 15 pm or less).
3. At least 5 young adult rats/sex/group.
4. Dosing, at least 4 hours by inhalation.
5. Chamber air flow dynamic, at least 10 air changes/hour, at least 19% oxygen content.
6. Chamber temperature, 22E C (+_2°), relative humidity 40-60%.
7. Monitor rate of air flow.
8. Monitor actual concentrations of test material in breathing zone.
9. Monitor aerodynamic particle size for aerosols.
10. Doses tested, sufficient to determine a toxicity category or a limit dose (5 mg/L actual concentration of respirable
substance).
11. Individual observations at least once a day.
12. Observation period to last at least 14 days.
13. Individual body weights.
14. Gross necropsy on all animals.
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81-4 Primary Eye Irritation in the Rabbit
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc).
2. Study not required if material is corrosive, causes severe
dermal irritation or has a pH of < 2 or > 11.5.
3. 6 adult rabbits.
4. Dosing, instillation into the conjunctival sac of one eye
per animal.
5. Dose, 0.1 ml if a liquid; 0.1 ml or not more than 100 mg if a solid, paste or particulate substance.
6. Solid or granular test material ground to a fine dust.
7. Eyes not washed for at least 24 hours.
8. Eyes examined and graded for irritation before dosing and
at 1, 24, 48 and 72 hr, then daily until eyes are normal
or 21 days (whichever is shorter).
9.^ Individual daily observations.
Criteria marked with an * are supplemental and may not be required for every study.
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81-5 Primary Dermal Irritation Study
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc).
2. Study not required if material is corrosive or has a pH of < 2 or > 11.5.
3. 6 adult animals.
4. Dosing, single dermal.
5. Dosing duration 4 hours.
6. Application site shaved or clipped at least 24 hours prior to dosing.
7. Application site approximately 6 cm2.
8. Application site covered with a gauze patch held in place with nonirritating tape.
9. Material removed, washed with water, without trauma to application site.
10. Application site examined and graded for irritation at 1, 24, 48 and 72 hr, then daily until normal or 14 days
(whichever is shorter).
11.^ Individual daily observations.
Criteria marked with an * are supplemental and may not be required for every study.
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81-6 Dermal Sensitization in the Guinea Pig
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc).
2. Study not required if material is corrosive or has a
pHof <2or >11.5.
3. One offhe following methods is utilized:
Freund's complete adjuvant test
Guinea pig maximization test
Split adjuvant technique
Buehler test
Open epicutaneous test
Mauer optimization test
Footpad technique in guinea pig.
4. Complete description of test.
5.^ Reference for test.
6.~ Test followed essentially as described in reference document.
7. Positive control included (may provide historical data conducted within the last 6 months).
Criteria marked with an * are supplemental and may not be required for every study.
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134
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Attachment 6. List of All Registrants Sent This Data Call-In (insert) Notice
135
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136
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Attachment 7. Cost Share Data Compensation Forms, Confidential
Statement of Formula Form and Instructions
137
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138
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140
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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 laoel.
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.
141
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142
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&EPA
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION OF OFFER TO COST
SHARE IN THE DEVELOPMENT OF DATA
Form Approved
OMB No. 2070-0106
2070-0057
Approval Expires 3-31-96
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-223, 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:
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA), if necessary. However, my company would prefer to
enter into an agreement with one or more registrants to develop jointly or share in the cost of developing
data.
My firm has offered in writing to enter into such an agreement. That offer was irrevocable and included an
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 firm(s) 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 obsolete
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&EPA
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
OKI N*. 2070-0107
2070-0037
Approval Esplro* 3 31 96
Public reporting burden for this collection of information is estimated lo 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-223, 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 Namo
Product N«M
Company Numbar
BPA R*g. Ho.
I Certify that:
1. For each study cited in support of registration or reregisiratton 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 ^registration 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)(D) 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 tonn or attached
sheets, or indicated on the attached •Requirements Status and Registrants' Response Form,*
3. That I have previously complied with section 3(0(1 )(D) of FIFRA for the studies I have cited in support of
registration or ^registration under FIFRA.
Signature
Date
Name and Till* (Ploaao Typo or Print)
GENERAL OFFER TO PAY: I hereby offer and agree to pay compensation to other persons, with regard to tne
registration or reregrstratton of my products, to the extent required by FIFRA sections 3(C)(1)(D) and 3(c)(2)(D).
Signature
Date
Nama and Tltlo (Ploaaa Typo or Print)
EPA Form M70-J1 (4-90
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APPENDIX G. FACT SHEET
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United States
Environmental Protection
Prevention. Pesticides
And Toxic Substances
EPA-738-F-94-022
September 1994
&ERA R.E.D. FACTS
Pesticide
Reregistration
Use Profile
Regulatory
History
Human Health
Assessment
M-Cresol and Xylenol
All pesticides sold or distributed in the United States must be
registered by EPA, based on scientific studies showing that they can be used
without posing unreasonable risks to people or the environment. Because of
advances in scientific knowledge, the law requires that pesticides which
were first registered years ago be reregistered to ensure that they meet
today's more stringent standards.
In evaluating pesticides for reregistration, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency imposes
any regulatory controls that are needed to effectively manage each
pesticide's risks. EPA then reregisters pesticides that can be used without
posing unreasonable risks to human health or the environment.
When a pesticide is eligible for reregistration, EPA announces this and
explains why in a Reregistration Eligibility Decision (RED) document. This
fact sheet summarizes the information in the RED for m-cresol and xylenol,
cases 4027 and 4098, which are formulated together to produce a single
pesticide product called Gallex.
M-cresol and xylenol, when formulated together, have bacteriostatic
activity against the causal agents of crown gall and olive knot on fruit,
ornamental and shade trees and ornamental woody shrubs and vines and
control of the genetic/physiological disorder, burr knot, on apples. The
pesticide product that contains these two active ingredients, Gallex, is a
ready-to-use liquid that is brushed or painted onto the infected areas of trees
and ornamentals. Treatments may be made every 4 to 6 months, or about
twice a year. Although usage data are not available, EPA assumes that the
volume of use is relatively low.
M-cresol and xylenol were first registered for use as pesticides in the
U.S. in 1980. Their initial registration was for a use pattern similar to that
of the currently registered product, Gallex. Gallex contains the two active
ingredients at a very low concentration (only 0.46% of each).
Cresols (m-cresol and two other isomers) are present at low
concentrations in various environmental media including air, car exhaust,
wood and coal. Reports that cresols may have tumor promoting activity
have not been substantiated by scientific studies. Only acute and subchronic
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toxicity and mutagenicity studies are required for reregistration of m-cresol
and xylenol because of their current use patterns.
Toxicity
Technical grade m-cresol causes severe eye and skin irritation and has
been placed in Toxicity Category I, indicating the greatest degree of acute
toxicity, for these effects. Technical xylenol also is corrosive to the skin,
and has been placed in Toxicity Category I for this effect.
The end use product that contains both m-cresol and xylenol has been
found to cause slight eye irritation in rabbits and has been assigned to
Toxicity Category II for eye effects. It has been found to produce skin
sensitization in guinea pigs but does not cause skin irritation in rabbits.
Subchronic toxicity studies by the National Toxicology Program
(NTP) of the National Institutes of Health on m-cresol alone and with p-
cresol, a related isomer, indicated effects to the kidneys, liver and other
organs in rats and mice, particularly at high doses. A dermal study using
the formulated product on rabbits showed the product to be corrosive to
skin.
M-cresol does not cause developmental toxicity, but causes effects on
body and organ weights in reproductive toxicity studies using rats and mice.
M-cresol is not mutagenic, and is excreted through urine.
Dietary Exposure
Since m-cresol and xylenol are applied only to the bases of fruit and
nut trees, no residues are expected to remain in food or feed commodities.
The Agency is requesting the registrant seek an exemption from tolerance
(enforceable residue limit).
Occupational and Residential Exposure
Applicators may be exposed to m-cresol and xylenol when applying
the end-use product Gallex by paint brush to infected areas of trees and
ornamentals. Direct dermal and eye exposures to this product are
considered potentially significant because the active ingredients have a high
degree of acute toxicity to the eyes and skin. The formulated product
Gallex is also considered to be a dermal sensitizer. Use of personal
protective equipment (PPE) may mitigate the acute toxicity risks to
applicators.
Since no more than four consecutive days of occupational/residential
exposure are typically expected, a short term occupational/residential
margin of exposure (MOE) was calculated for m-cresol based on maternal
toxicity. The MOE for the end-use product, estimated to be 1,017, is
acceptable. The Agency also considered intermediate term exposure due to
the potential that commercial applicators may be exposed to the end-use
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product for this interval. The intermediate term exposure assessment was
based on a 28-day feeding study. The less likely intermediate term exposure
revealed a MOE for the end-use product at 308, an acceptable level. There
are no post-application worker exposure concerns.
Human Risk Assessment
Dietary exposure to m-cresol and xylenol is not a concern since
residues of these pesticides do not remain in the fruit or nuts of treated
trees. Applicators face acute toxicity hazards to the skin and eyes.
However, these risks will be mitigated by use of PPE, as required by the
RED. Considering Gallex's use pattern, the low concentration of each
active ingredient in the end use product, the toxicity characteristics of these
chemicals, and the acceptable MOE, EPA does not expect significant health
risks from short term or intermediate term residential/occupational exposure
to m-cresol and xylenol, when used properly as directed.
EPA did not conduct an environmental risk assessment for m-cresol
and xylenol and did not require any data on environmental fate or
ecotoxicity. The current use pattern of these pesticides and their low
volume of use will result in very low environmental exposure, resulting in
no threat to wildlife. Non-target organisms including endangered species
are not expected to be adversely affected from this use.
Additional Data EPA is requiring product specific data including product chemistry
RedUJr0d anc^ acute toxicity studies, a revised Confidential Statement of Formula and
revised labeling for reregistration of m-cresol and xylenol.
Product LabGling The label of the registered pesticide product containing m-cresol and
ChanCieS RGCIUirGd xylenol must comply with EPA's current pesticide labeling requirements.
In addition, Personal Protective Equipment (PPE) must be required on
product labeling, as follows:
"Applicators and other handlers must wear: protective eyewear,
chemical resistant gloves, long sleeves, long pants, shoes and socks."
Environmental
Assessment
Regulatory
Conclusion
Use of the currently registered pesticide product containing m-cresol
and xylenol in accordance with approved labeling will not pose unreasonable
risks or adverse effects to humans or the environment. Therefore, all uses
of these pesticides are eligible for reregistration. The product Gallex will
be reregistered once the required product specific data, Confidential
Statement of Formula and revised labeling are received and accepted by
EPA.
For MorG EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for m-cresol and xylenol during a 60-day time
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Information period, as announced in a Notice of Availability published in the Federal
Register. To obtain a copy of the RED document or to submit written
comments, please contact the Pesticide Docket, Public Response and
Program Resources Branch, Field Operations Division (7506C), Office of
Pesticide Programs (OPP), US EPA, Washington, DC 20460, telephone
703-305-5805.
Following the comment period, the m-cresol and xylenol RED
document will be available from the National Technical Information Service
(NTIS), 5285 Port Royal Road, Springfield, VA 22161, telephone
703-487-4650.
For more information about EPA's pesticide reregistration program,
the m-cresol and xylenol RED, or reregistration of the end-use product
containing m-cresol and xylenol, please contact the Special Review and
Reregistration Division (7508W), OPP, US EPA, Washington, DC 20460,
telephone 703-308-8000.
For information about the health effects of pesticides, or for assistance
in recognizing and managing pesticide poisoning symptoms, please contact
the National Pesticides Telecommunications Network (NPTN). Call toll-
free 1-800-858-7378, between 8:00 am and 6:00 pm Central Time, Monday
through Friday.
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